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1

Contactin-1 regulates myelination and nodal/paranodal domain organization in the central nervous system.  

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Myelin, a multilayered membrane sheath formed by oligodendrocytes around axons in the CNS, enables rapid nerve impulse conduction and sustains neuronal health. The signals exchanged between axons and oligodendrocytes in myelin remain to be fully elucidated. Here we provide genetic evidence for multiple and critical functions of Contactin-1 in central myelin. We document dynamic Contactin-1 expression on oligodendrocytes in vivo, and progressive accumulation at nodes of Ranvier and paranodes during postnatal mouse development. Nodal and paranodal expression stabilized in mature myelin, but overall membranous expression diminished. Contactin-1-deficiency disrupted paranodal junction formation as evidenced by loss of Caspr, mislocalized potassium Kv1.2 channels, and abnormal myelin terminal loops. Reduced numbers and impaired maturation of sodium channel clusters accompanied this phenotype. Histological, electron microscopic, and biochemical analyses uncovered significant hypomyelination in Contactin-1-deficient central nerves, with up to 60% myelin loss. Oligodendrocytes were present in normal numbers, albeit a minor population of neuronal/glial antigen 2-positive (NG2(+)) progenitors lagged in maturation by postnatal day 18, when the mouse null mutation was lethal. Major contributing factors to hypomyelination were defects in the generation and organization of myelin membranes, as judged by electron microscopy and quantitative analysis of oligodendrocyte processes labeled by GFP transgenically expressed from the proteolipid protein promoter. These data reveal that Contactin-1 regulates both myelin formation and organization of nodal and paranodal domains in the CNS. These multiple roles distinguish central Contactin-1 functions from its specific role at paranodes in the periphery, and emphasize mechanistic differences in central and peripheral myelination. PMID:24385581

Çolako?lu, Gülsen; Bergstrom-Tyrberg, Ulrika; Berglund, Erik O; Ranscht, Barbara

2014-01-21

2

Paranodal myelin retraction in relapsing experimental autoimmune encephalomyelitis visualized by coherent anti-Stokes Raman scattering microscopy  

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How demyelination is initiated is a standing question for pathology of multiple sclerosis. By label-free coherent anti-Stokes Raman scattering (CARS) imaging of myelin lipids, we investigate myelin integrity in the lumbar spinal cord tissue isolated from naïve SJL mice, and from mice at the onset, peak acute, and remission stages of relapsing experimental autoimmune encephalomyelitis (EAE). Progressive demyelinating disease is initially characterized by the retraction of paranodal myelin both at the onset of disease and at the borders of acute demyelinating lesions. Myelin retraction is confirmed by elongated distribution of neurofascin proteins visualized by immunofluorescence. The disruption of paranodal myelin subsequently exposes Kv1.2 channels at the juxtaparanodes and lead to the displacement of Kv1.2 channels to the paranodal and nodal domains. Paranodal myelin is partially restored during disease remission, indicating spontaneous myelin regeneration. These findings suggest that paranodal domain injury precedes formation of internodal demyelinating lesions in relapsing EAE. Our results also demonstrate that CARS microscopy is an effective readout of myelin disease burden.

Fu, Yan; Frederick, Terra J.; Huff, Terry B.; Goings, Gwendolyn E.; Miller, Stephen D.; Cheng, Ji-Xin

2011-10-01

3

Paranodal myelin retraction in relapsing experimental autoimmune encephalomyelitis visualized by coherent anti-Stokes Raman scattering microscopy  

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How demyelination is initiated is a standing question for pathology of multiple sclerosis. By label-free coherent anti-Stokes Raman scattering (CARS) imaging of myelin lipids, we investigate myelin integrity in the lumbar spinal cord tissue isolated from naïve SJL mice, and from mice at the onset, peak acute, and remission stages of relapsing experimental autoimmune encephalomyelitis (EAE). Progressive demyelinating disease is initially characterized by the retraction of paranodal myelin bot...

Fu, Yan; Frederick, Terra J.; Huff, Terry B.; Goings, Gwendolyn E.; Miller, Stephen D.; Cheng, Ji-xin

2011-01-01

4

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

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

Cheng, Ji-xin

2011-01-01

5

Sulfatide decrease in myelin influences formation of the paranodal axo-glial junction and conduction velocity in the sciatic nerve.  

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Cerebroside sulfotransferase (CST) catalyzes the production of sulfatide, which is one of the major glycolipids in myelin. Homozygous CST knockout mice were shown to be completely deficient in sulfatide. They were born healthy but began to display progressive neurological deficits from 6 weeks of age. Severe abnormalities of paranodal regions and changes in axonal ion channel distribution were prominent in both the central and peripheral nervous systems. But whether partial decreases in myelin sulfatide levels influence paranodal formation, as well as nerve conduction velocity (NCV), is largely unknown. To determine the functional significance of sulfatide content in myelin, we performed electrophysiological, morphological, and biochemical analyses using heterozygote, homozygote, and wild-type mouse peripheral nerves and compared the results with individual sulfatide content. NCVs were significantly reduced in homozygote animals compared with wild-type mice. In contrast, these values were markedly varied in individual heterozygote mice. On the basis of NCV values, we divided heterozygous mice into two groups: mice with mild but significant reduction of NCV and those with normal NCV. Teased nerve fibers obtained from individual mouse sciatic nerves were immunostained, and Na(+) channel and Caspr cluster lengths were measured to determine abnormal levels of junctional formation at the paranode. Furthermore, sulfatide content in each sciatic nerve was examined by thin layer chromatography. The results demonstrated significant correlations among sulfatide level, severity of paranodal abnormality, and reduction of NCV. Thus, the fine regulation of myelin sulfatide content by CST is important for normal function of myelinated axons. PMID:23322453

Hayashi, Akiko; Kaneko, Naoki; Tomihira, Chiaki; Baba, Hiroko

2013-04-01

6

Age-dependent redistribution and hypersialylation of the central myelin paranodal loop membrane protein Opalin in the mouse brain.  

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Opalin/Tmem10 is a myelin-associated sialylglycoprotein that is specific to only the mammalian central nervous system. However, little is known about the properties or function of this protein. Here, we analyzed the expression and glycosylation patterns of Opalin in the postnatal mouse brain. Immunolocalization patterns of Opalin were similar to those of myelin basic protein in juvenile and adolescent mice. On the other hand, in the adult mouse brain, decreasing immunoreactivity for Opalin was observed in the hindbrain region especially in the cerebellar white matter compared with the corpus callosum in the forebrain. In addition, Opalin showed increasing molecular size with mouse aging. This age-dependent increase in Opalin molecular weight was mainly owing to hypersialylation of O-glycans. These results indicate that the regional redistribution and the degree of sialylation of Opalin protein are age-dependently regulated in mouse brains. PMID:25153515

Sato, Yumi; Yoshikawa, Fumio; Sadakata, Tetsushi; Shinoda, Yo; Koebis, Michinori; Furuichi, Teiichi

2014-10-01

7

Early myelin breakdown following sural nerve crush: a freeze-fracture study  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in english In this study we describe the early changes of the myelin sheath following surgical nerve crush. We used the freeze-fracture technique to better evaluate myelin alterations during an early stage of Wallerian degeneration. Rat sural nerves were experimentally crushed and animals were sacrificed by tr [...] anscardiac perfusion 30 h after surgery. Segments of the nerves were processed for routine transmission electron microscopy and freeze-fracture techniques. Our results show that 30 h after the lesion there was asynchrony in the pattern of Wallerian degeneration, with different nerve fibers exhibiting variable degrees of axon disruption. This was observed by both techniques. Careful examination of several replicas revealed early changes in myelin membranes represented by vacuolization and splitting of consecutive lamellae, rearrangement of intramembranous particles and disappearance of paranodal transverse bands associated or not with retraction of paranodal myelin terminal loops from the axolemma. These alterations are compatible with a direct injury to the myelin sheath following nerve crush. The results are discussed in terms of a similar mechanism underlying both axon and myelin breakdown.

A.M.B., Martinez; S., Canavarro.

1477-14-01

8

Early myelin breakdown following sural nerve crush: a freeze-fracture study  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in english In this study we describe the early changes of the myelin sheath following surgical nerve crush. We used the freeze-fracture technique to better evaluate myelin alterations during an early stage of Wallerian degeneration. Rat sural nerves were experimentally crushed and animals were sacrificed by tr [...] anscardiac perfusion 30 h after surgery. Segments of the nerves were processed for routine transmission electron microscopy and freeze-fracture techniques. Our results show that 30 h after the lesion there was asynchrony in the pattern of Wallerian degeneration, with different nerve fibers exhibiting variable degrees of axon disruption. This was observed by both techniques. Careful examination of several replicas revealed early changes in myelin membranes represented by vacuolization and splitting of consecutive lamellae, rearrangement of intramembranous particles and disappearance of paranodal transverse bands associated or not with retraction of paranodal myelin terminal loops from the axolemma. These alterations are compatible with a direct injury to the myelin sheath following nerve crush. The results are discussed in terms of a similar mechanism underlying both axon and myelin breakdown.

A.M.B., Martinez; S., Canavarro.

9

Early myelin breakdown following sural nerve crush: a freeze-fracture study  

Directory of Open Access Journals (Sweden)

Full Text Available In this study we describe the early changes of the myelin sheath following surgical nerve crush. We used the freeze-fracture technique to better evaluate myelin alterations during an early stage of Wallerian degeneration. Rat sural nerves were experimentally crushed and animals were sacrificed by transcardiac perfusion 30 h after surgery. Segments of the nerves were processed for routine transmission electron microscopy and freeze-fracture techniques. Our results show that 30 h after the lesion there was asynchrony in the pattern of Wallerian degeneration, with different nerve fibers exhibiting variable degrees of axon disruption. This was observed by both techniques. Careful examination of several replicas revealed early changes in myelin membranes represented by vacuolization and splitting of consecutive lamellae, rearrangement of intramembranous particles and disappearance of paranodal transverse bands associated or not with retraction of paranodal myelin terminal loops from the axolemma. These alterations are compatible with a direct injury to the myelin sheath following nerve crush. The results are discussed in terms of a similar mechanism underlying both axon and myelin breakdown.

A.M.B. Martinez

2000-12-01

10

Myelination and myelin disorders  

International Nuclear Information System (INIS)

The first part of this thesis contains the results of a study into the capabilities of MR in the assessment of normal cerebral development. The process of normal myelination under the age of 1 year is divided into stages with specific MRI characteristics. An indication of normal age limits for each stage is given. The relationships between changes in signal intensities and biochemical background, and between progress of myelination and psychomotor development are discussed. The latter in the light of a study performed in hydrocephalic children, prior to and repeatedly after shunt implantation. Normal changes in 1H and 31P spectra of the brain in infants and children are described. The relationship between observed spectral changes and cerebral maturational processes is discussed. The second part deals with assessment of myelin disorders with MRI. Basic information about demyelinating disorders and biochemical background are reviewed. A new classification of myelin disorders, underlying the development of an MRI pattern recognition scheme, is proposed based on the most recent scientific developments. Common histological characteristics are described for all main categories of myelin disorders. Extensive information is presented about MRI patterns of abnormalities in patients in whom the disease is predominantly or exclusively located in the white matter. On the basis of the data of these patients a global MRI pattern recognition scheme has been deMRI pattern recognition scheme has been developed covering all white matter disorders that were encountered. Also an example of an in-depth pattern recognition in a circumscribed category of disorders is presented. Finally a study of MRS in demyelinating disorders as opposed to neuronal disorders is described. While MRI provides information about the extent of the process of demyelination and about the disease category, MRS turns out to provide information about the severity of the demyelination and of the concomitant neuronal damage. (H.W.). 725 refs.; 53 figs.; 16 tabs

11

Myelin membrane wrapping of CNS axons by PI(3,4,5)P3-dependent polarized growth at the inner tongue.  

Science.gov (United States)

Central nervous system myelin is a multilayered membrane sheath generated by oligodendrocytes for rapid impulse propagation. However, the underlying mechanisms of myelin wrapping have remained unclear. Using an integrative approach of live imaging, electron microscopy, and genetics, we show that new myelin membranes are incorporated adjacent to the axon at the innermost tongue. Simultaneously, newly formed layers extend laterally, ultimately leading to the formation of a set of closely apposed paranodal loops. An elaborated system of cytoplasmic channels within the growing myelin sheath enables membrane trafficking to the leading edge. Most of these channels close with ongoing development but can be reopened in adults by experimentally raising phosphatidylinositol-(3,4,5)-triphosphate levels, which reinitiates myelin growth. Our model can explain assembly of myelin as a multilayered structure, abnormal myelin outfoldings in neurological disease, and plasticity of myelin biogenesis observed in adult life. PMID:24439382

Snaidero, Nicolas; Möbius, Wiebke; Czopka, Tim; Hekking, Liesbeth H P; Mathisen, Cliff; Verkleij, Dick; Goebbels, Sandra; Edgar, Julia; Merkler, Doron; Lyons, David A; Nave, Klaus-Armin; Simons, Mikael

2014-01-16

12

Neuron-oligodendrocyte myelination co-culture derived from embryonic rat spinal cord and cerebral cortex.  

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An in vitro myelination model derived from rat central nervous system (CNS) remains to be established. Here, we describe a simple and reproducible myelination culture method using dissociated neuron-oligodendrocyte (OL) co-cultures from either the embryonic day 16 (E16) rat spinal cord or cerebral cortex. The dissociated cells are plated directly on poly-L-lysine-coated cover slips and maintained in a modified myelination medium that supports both OL and neuron differentiation. The spinal cord derived OL progenitor cells develop quickly into myelin basic protein (MBP)+ mature OLs and start to myelinate axons around 17 days in vitro (DIV17). Myelination reaches its peak around six weeks (DIV40) and the typical nodes of Ranvier are revealed by paranodal proteins Caspr and juxaparanodal protein Kv1.2 immunoreactivity. Electron microscopy (EM) shows typical myelination cytoarchitecture and synaptic organization. In contrast, the cortical-derived co-culture requires triiodothyronine (T3) in the culture medium for myelination. Finally, either hypomyelination and/or demyelination can be induced by exposing proinflammatory cytokines or demyelinating agents to the co-culture, suggesting the feasibility of this modified in vitro myelination model for myelin-deficit investigation. PMID:22574274

Pang, Yi; Zheng, Baoying; Kimberly, Simpson L; Cai, Zhengwei; Rhodes, Philip G; Lin, Rick C S

2012-01-01

13

Protein 4.1B Contributes to the Organization of Peripheral Myelinated Axons  

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Neurons are characterized by extremely long axons. This exceptional cell shape is likely to depend on multiple factors including interactions between the cytoskeleton and membrane proteins. In many cell types, members of the protein 4.1 family play an important role in tethering the cortical actin-spectrin cytoskeleton to the plasma membrane. Protein 4.1B is localized in myelinated axons, enriched in paranodal and juxtaparanodal regions, and also all along the internodes, but not at nodes of Ranvier where are localized the voltage-dependent sodium channels responsible for action potential propagation. To shed light on the role of protein 4.1B in the general organization of myelinated peripheral axons, we studied 4.1B knockout mice. These mice displayed a mildly impaired gait and motility. Whereas nodes were unaffected, the distribution of Caspr/paranodin, which anchors 4.1B to the membrane, was disorganized in paranodal regions and its levels were decreased. In juxtaparanodes, the enrichment of Caspr2, which also interacts with 4.1B, and of the associated TAG-1 and Kv1.1, was absent in mutant mice, whereas their levels were unaltered. Ultrastructural abnormalities were observed both at paranodes and juxtaparanodes. Axon calibers were slightly diminished in phrenic nerves and preterminal motor axons were dysmorphic in skeletal muscle. ?II spectrin enrichment was decreased along the axolemma. Electrophysiological recordings at 3 post-natal weeks showed the occurrence of spontaneous and evoked repetitive activity indicating neuronal hyperexcitability, without change in conduction velocity. Thus, our results show that in myelinated axons 4.1B contributes to the stabilization of membrane proteins at paranodes, to the clustering of juxtaparanodal proteins, and to the regulation of the internodal axon caliber. PMID:21966409

Devaux, Jerome; Carnaud, Michele; Levasseur, Gregoire; Niwa-Kawakita, Michiko; Harroch, Sheila; Girault, Jean-Antoine; Giovannini, Marco; Goutebroze, Laurence

2011-01-01

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Ermin, a myelinating oligodendrocyte-specific protein that regulates cell morphology.  

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Oligodendrocytes form an insulating multilamellar structure of compact myelin around axons, thereby allowing rapid propagation of action potentials. Despite the considerable clinical importance of myelination, little is known about the molecular mechanisms that enable oligodendrocytes to generate their specialized membrane wrapping. Here, we used microarray expression profiling of oligodendrocyte-ablated mutant mice to identify new glial molecules that are involved in CNS myelination. This effort resulted in the identification of Ermin, a novel cytoskeletal molecule that is exclusively expressed by oligodendrocytes. Ermin appears at a late stage during myelination, and in the mature nerves, it is localized to the outer cytoplasmic lip of the myelin sheath and the paranodal loops. In cultured oligodendrocytes, Ermin becomes visible in well differentiated MBP-positive cells, where it is concentrated at the tip of F-actin-rich processes (termed "Ermin spikes"). Ectopic expression of Ermin, but not of a mutant protein lacking its actin-binding domain, induced the formation of numerous cell protrusions and a pronounced change in cell morphology. Our results demonstrate that Ermin is a novel marker of myelinating oligodendroglia and suggest that it plays a role in cytoskeletal rearrangements during the late wrapping and/or compaction phases of myelinogenesis. PMID:16421295

Brockschnieder, Damian; Sabanay, Helena; Riethmacher, Dieter; Peles, Elior

2006-01-18

15

CSF myelin basic protein  

Science.gov (United States)

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

16

Defects in myelination, paranode organization and Purkinje cell innervation in the ether lipid-deficient mouse cerebellum  

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Ether lipids (ELs), particularly plasmalogens, are essential constituents of the mammalian central nervous system. The physiological role of ELs, in vivo, however is still enigmatic. In the present study, we characterized a mouse model carrying a targeted deletion of the peroxisomal dihydroxyacetonephosphate acyltransferase gene that results in the complete lack of ELs. Investigating the cerebellum of these mice, we observed: (i) defects in foliation patterning and delay in precursor granule ...

Teigler, Andre; Komljenovic, Dorde; Draguhn, Andreas; Gorgas, Karin; Just, Wilhelm W.

2009-01-01

17

Myelin formation and remodeling.  

Science.gov (United States)

Myelin is a multilayer wrapping of insulation formed by glial cells around axons that is essential for rapid impulse transmission, but how glial cells accomplish this cellular choreography has long intrigued researchers. In this issue of Cell, Snaidero et al., provide new insights into how myelin forms and is remodeled. PMID:24439366

Fields, R Douglas

2014-01-16

18

Disruption of paranodal axo-glial interaction and/or absence of sulfatide causes irregular type I inositol 1,4,5-trisphosphate receptor deposition in cerebellar Purkinje neuron axons.  

Science.gov (United States)

Paranodal axo-glial junctions (PNJs) play an essential role in the organization and maintenance of molecular domains in myelinated axons. To understand the importance of PNJs better, we investigated cerebroside sulfotransferase (CST; a sulfatide synthetic enzyme)-deficient mice, which partially lack PNJs in both the central nervous system (CNS) and the peripheral nervous system (PNS). Previously, we reported that axonal mitochondria at the nodes of Ranvier in the PNS were large and swollen in CST-deficient mice. Although we did not observed significant defects in the nodal regions in several areas of the CNS, myelinated internodal regions showed many focal swellings in Purkinje cell axons in the cerebellum, and the number and the size of swellings increased with age. In the present analysis of various stages of the swellings in 4-12-week-old mutant mice, calbindin-positive axoplasm swellings started to appear at an early stage. After that, accumulation of neurofilament and mitochondria gradually increased, whereas deposition of amyloid precursor protein became prominent later. Ultrastructural analysis showed accumulations of tubular structures closely resembling smooth endoplasmic reticulum (ER). Staining of cerebellar sections of the mutant mice for type I inositol 1,4,5-trisphosphate receptor (IP3 R1) revealed high immunoreactivity within the swellings. This IP3 R1 deposition was the initial change and was not observed in development prior to the onset of myelination. This suggests that local calcium regulation through ER was involved in these axonal swellings. Therefore, in addition to the biochemical composition of the internodal myelin sheath, PNJs might also affect maintenance of axonal homeostasis in Purkinje cells. © 2014 Wiley Periodicals, Inc. PMID:25093737

Ishibashi, Tomoko; Kodama, Akiko; Baba, Hiroko

2015-01-01

19

Glycans of myelin proteins.  

Science.gov (United States)

Human P0 is the main myelin glycoprotein of the peripheral nervous system. It can bind six different glycans, all linked to Asn(93) , the unique glycosylation site. Other myelin glycoproteins, also with a single glycosylation site (PMP22 at Asn(36) , MOG at Asn(31) ), bind only one glycan. The MAG has 10 glycosylation sites; the glycoprotein OMgp has 11 glycosylation sites. Aside from P0, no comprehensive data are available on other myelin glycoproteins. Here we review and analyze all published data on the physicochemical structure of the glycans linked to P0, PMP22, MOG, and MAG. Most data concern bovine P0, whose glycan moieties have an MW ranging from 1,294.56 Da (GP3) to 2,279.94 Da (GP5). The pI of glycosylated P0 protein varies from pH 9.32 to 9.46. The most charged glycan is MS2 containing three sulfate groups and one glucuronic acid; whereas the least charged one is the BA2 residue. All glycans contain one fucose and one galactose. The most mannose rich are the glycans MS2 and GP4, each of them has four mannoses; OPPE1 contains five N-acetylglucosamines and one sulfated glucuronic acid; GP4 contains one sialic acid. Furthermore, human P0 variants causing both gain and loss of glycosylation have been described and cause peripheral neuropathies with variable clinical severity. In particular, the substitution T(95) ?M is a very common in Europe and is associated with a late-onset axonal neuropathy. Although peripheral myelin is made up largely of glycoproteins, mutations altering glycosylation have been described only in P0. This attractive avenue of research requires further study. © 2014 Wiley Periodicals, Inc. PMID:25213400

Sedzik, Jan; Jastrzebski, Jan Pawel; Grandis, Marina

2015-01-01

20

Human fetal myelinated organotypic cultures.  

Science.gov (United States)

We have previously reported the establishment of organotypic cultures derived from human fetal brain tissue. Although these cultures permit the testing of multiple hypotheses about normal human neurodevelopment and neuropathologic conditions, they have the limitation of not being myelinated and therefore preclude the study of questions related to myelinogenesis and diseases of myelin. In the current communication, we describe recent developments that allow us to overcome this limitation and permit the establishment of a myelinated organotypic culture model. Sections of dorsal column dissected from the lumbar spinal cord of human fetuses ranging in age 21-23 weeks of gestation were placed in culture. The explants were maintained for up to 12 weeks during which time they were characterized and shown to express a number of CNS cell-type-specific markers including glial fibrillary acidic protein (astrocytes), nerve growth factor receptor and neurofilament protein (neurons), CD68 (microglia), and myelin basic protein, HNK-1 and galactocerebroside (oligodendrocytes). In addition, lectin histochemistry using Ricinus communis agglutinin-1 detected microglia and endothelial cells. Upon explantation, abundant myelin was seen by electron microscopy in the cultures. Although during the culture period there was degradation of myelin, there was also evidence of maintenance of intact myelin sheaths around small caliber axons and de novo myelin synthesis. This model system may permit the further use of human organotypic cultures to investigate issues related to neurodevelopment and to pathologic conditions including those relevant to dysmyelination and demyelination. PMID:1493548

Lyman, W D; Hatch, W C; Pousada, E; Stephney, G; Rashbaum, W K; Weidenheim, K M

1992-12-18

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

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Niemann-Pick disease type C (NPC disease) is an incurable, neurodegenerative, autosomal recessive disease caused by mutations in either the NPC1 or NPC2 gene. These mutations affect the intracellular trafficking of lipids and cholesterol resulting in the intralysosomal accumulation of unesterified cholesterol and glycosphingolipids, and clinical signs of ataxia and impaired motor and intellectual development with death frequently occurring in adolescence. The incidence of peripheral neuropathy in NPC patients is not known. We investigated peripheral nerves in the naturally-occurring feline model of NPC disease which has proven critical for understanding both disease pathogenesis and for evaluating experimental therapies. Electrodiagnostic studies revealed significantly slowed motor and sensory nerve conduction velocities in affected cats in the absence of altered M-wave amplitude. Histology showed demyelination characterized by thin myelin sheaths, membranous debris, myelin figures, lipid vacuolization of Schwann cell cytoplasm, and expanded paranodal areas. Axonal degeneration was not identified. A shift to small myelinated fibers was noted in affected cats and significant decreases in fiber diameter, axonal diameter, and myelin thickness was found. These changes were similar to those described in the murine model as well as in the rare patient in which nerve biopsy was performed. Characterization of the demyelinating neuropathy is necessary in NPC disease due to the clinical trial in patients scheduled for 2013 where cyclodextrin will be delivered into the cerebral ventricles in an attempt to control the CNS aspects of this disease. PMID:23399903

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

2013-01-01

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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

23

In Vivo Evidence That TRAF4 Is Required for Central Nervous System Myelin Homeostasis  

Science.gov (United States)

Tumor Necrosis Factor Receptor-Associated Factors (TRAFs) are major signal transducers for the TNF and interleukin-1/Toll-like receptor superfamilies. However, TRAF4 does not fit the paradigm of TRAF function in immune and inflammatory responses. Its physiological and molecular functions remain poorly understood. Behavorial analyses show that TRAF4-deficient mice (TRAF4-KO) exhibit altered locomotion coordination typical of ataxia. TRAF4-KO central nervous system (CNS) ultrastructure shows strong myelin perturbation including disorganized layers and disturbances in paranode organization. TRAF4 was previously reported to be expressed by CNS neurons. Using primary cell culture, we now show that TRAF4 is also expressed by oligodendrocytes, at all stages of their differentiation. Moreover, histology and electron microscopy show degeneration of a high number of Purkinje cells in TRAF4-KO mice, that was confirmed by increased expression of the Bax pro-apoptotic marker (immunofluorescence), TUNEL analysis, and caspase-3 activation and PARP1 cleavage (western blotting). Consistent with this phenotype, MAG and NogoA, two myelin-induced neurite outgrowth inhibitors, and their neuron partners, NgR and p75NTR were overexpressed (Q-RT-PCR and western blotting). The strong increased phosphorylation of Rock2, a RhoA downstream target, indicated that the NgR/p75NTR/RhoA signaling pathway, known to induce actin cytoskeleton rearrangement that favors axon regeneration inhibition and neuron apoptosis, is activated in the absence of TRAF4 (western blotting). Altogether, these results provide conclusive evidence for the pivotal contribution of TRAF4 to myelination and to cerebellar homeostasis, and link the loss of TRAF4 function to demyelinating or neurodegenerative diseases. PMID:22363515

Blaise, Sebastien; Kneib, Marie; Rousseau, Adrien; Gambino, Frederic; Chenard, Marie-Pierre; Messadeq, Nadia; Muckenstrum, Martine; Alpy, Fabien; Tomasetto, Catherine; Humeau, Yann; Rio, Marie-Christine

2012-01-01

24

Accelerated myelination associated with venous congestion  

International Nuclear Information System (INIS)

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

25

Accelerated myelination associated with venous congestion  

Energy Technology Data Exchange (ETDEWEB)

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

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

2006-04-15

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Metabolites of 5-fluorouracil, alpha-fluoro-beta-alanine and fluoroacetic acid, directly injure myelinated fibers in tissue culture.  

Science.gov (United States)

The neurotoxicity of two 5-fluorouracil (5-FU) derivatives, tegafur (FT) and carmofur (HCFU), which selectively induce leukoencephalopathy involving the cerebral white matter in humans and vacuolation of myelinated fibers in dogs and cats, was examined in vitro. The common metabolites of these drugs, alpha-fluoro-beta-alanine (FBAL) and fluoroacetic acid (FA), were added to the medium of cultured murine cerebellar myelinated fibers. On day 1 of exposure to 7 microM FBAL and FA, which corresponds to their blood concentrations 2 h after oral administration of 10 mg.kg-1 HCFU to dogs that induced central nervous system vacuolation after 30 days, partial splits of the myelinic intraperiod line were observed by electron microscopy. On days 4-7, phase contrast microscopy revealed spindle-shaped swelling and granulation of myelin and electron microscopy demonstrated prominent dissociation of the myelinic intraperiod line with monolocular and multilocular vacuolation. More severe changes, such as myelin loss, were found in cultures exposed to a higher concentration (70 microM) of FBAL and FA, but no remarkable neuronal, astrocytic or oligodendrocytic changes occurred. Quantitative evaluation of myelin injury by electron microscopy revealed significant toxicity of FBAL and FA, at concentrations of 7 and 70 microM, on day 4. However, groups treated with 0.7 microM FBAL and FA, 5-FU (7 microM) and controls exposed to beta-alanine and acetic acid concentrations of 0.7, 7 and 70 microM showed no marked injury. We concluded that these anticancer drug metabolites injure myelin fibers directly, resulting in vacuolation due to myelin splitting and destruction. PMID:8811119

Akiba, T; Okeda, R; Tajima, T

1996-07-01

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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...

28

Myelin-associated glycoprotein and its axonal receptors  

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Myelin-associated glycoprotein (MAG) is expressed on the innermost myelin membrane wrap, directly apposed to the axon surface. While it is not required for myelination, MAG enhances long-term axon-myelin stability, helps to structure nodes of Ranvier, and regulates the axon cytoskeleton. In addition to its role in axon-myelin stabilization, MAG inhibits axon regeneration after injury; MAG and a discrete set of other molecules on residual myelin membranes at injury sites actively signal axons ...

Schnaar, Ronald L.; Lopez, Pablo H. H.

2009-01-01

29

Motor skill learning requires active central myelination.  

Science.gov (United States)

Myelin-forming oligodendrocytes (OLs) are formed continuously in the healthy adult brain. In this work, we study the function of these late-forming cells and the myelin they produce. Learning a new motor skill (such as juggling) alters the structure of the brain's white matter, which contains many OLs, suggesting that late-born OLs might contribute to motor learning. Consistent with this idea, we show that production of newly formed OLs is briefly accelerated in mice that learn a new skill (running on a "complex wheel" with irregularly spaced rungs). By genetically manipulating the transcription factor myelin regulatory factor in OL precursors, we blocked production of new OLs during adulthood without affecting preexisting OLs or myelin. This prevented the mice from mastering the complex wheel. Thus, generation of new OLs and myelin is important for learning motor skills. PMID:25324381

McKenzie, Ian A; Ohayon, David; Li, Huiliang; de Faria, Joana Paes; Emery, Ben; Tohyama, Koujiro; Richardson, William D

2014-10-17

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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

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

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Full Text Available Abstract Background Traumatic injury to axons produces breakdown of axons and myelin at the site of the lesion and then further distal to this where Wallerian degeneration develops. The rapid removal of degenerated myelin by phagocytosis is advantageous for repair since molecules in myelin impede regeneration of severed axons. Thus, revealing mechanisms that regulate myelin phagocytosis by macrophages and microglia is important. We hypothesize that myelin regulates its own phagocytosis by simultaneous activation and down-regulation of microglial and macrophage responses. Activation follows myelin binding to receptors that mediate its phagocytosis (e.g. complement receptor-3, which has been previously studied. Down-regulation, which we test here, follows binding of myelin CD47 to the immune inhibitory receptor SIRP? (signal regulatory protein-? on macrophages and microglia. Methods CD47 and SIRP? expression was studied by confocal immunofluorescence microscopy, and myelin phagocytosis by ELISA. Results We first document that myelin, oligodendrocytes and Schwann cells express CD47 without SIRP? and further confirm that microglia and macrophages express both CD47 and SIRP?. Thus, CD47 on myelin can bind to and subsequently activate SIRP? on phagocytes, a prerequisite for CD47/SIRP?-dependent down-regulation of CD47+/+ myelin phagocytosis by itself. We then demonstrate that phagocytosis of CD47+/+ myelin is augmented when binding between myelin CD47 and SIRP? on phagocytes is blocked by mAbs against CD47 and SIRP?, indicating that down-regulation of phagocytosis indeed depends on CD47-SIRP? binding. Further, phagocytosis in serum-free medium of CD47+/+ myelin is augmented after knocking down SIRP? levels (SIRP?-KD in phagocytes by lentiviral infection with SIRP?-shRNA, whereas phagocytosis of myelin that lacks CD47 (CD47-/- is not. Thus, myelin CD47 produces SIRP?-dependent down-regulation of CD47+/+ myelin phagocytosis in phagocytes. Unexpectedly, phagocytosis of CD47-/- myelin by SIRP?-KD phagocytes, which is not altered from normal when tested in serum-free medium, is augmented when serum is present. Therefore, both myelin CD47 and serum may each promote SIRP?-dependent down-regulation of myelin phagocytosis irrespective of the other. Conclusions Myelin down-regulates its own phagocytosis through CD47-SIRP? interactions. It may further be argued that CD47 functions normally as a marker of "self" that helps protect intact myelin and myelin-forming oligodendrocytes and Schwann cells from activated microglia and macrophages. However, the very same mechanism that impedes phagocytosis may turn disadvantageous when rapid clearance of degenerated myelin is helpful.

Reichert Fanny

2011-03-01

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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...

2011-01-01

33

Myelination of rodent hippocampal neurons in culture  

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Axons of various hippocampal neurons are myelinated mainly postnatally, which is important for the proper function of neural circuits. Demyelination in the hippocampus has been observed in patients with multiple sclerosis, Alzheimer’s disease or temporal lobe epilepsy. However, very little is known about the mechanisms and exact functions of the interaction between the myelin-making oligodendrocytes and the axons within the hippocampus. This is mainly attributable to the lack of a system su...

Gardner, Asa; Jukkola, Peter; Gu, Chen

2012-01-01

34

Ephaptic coupling of myelinated nerve fibers  

DEFF Research Database (Denmark)

Numerical predictions of a simple myelinated nerve fiber model are compared with theoretical results in the continuum and discrete limits, clarifying the nature of the conduction process on an isolated nerve axon. Since myelinated nerve fibers are often arranged in bundles, this model is used to study ephaptic (nonsynaptic) interactions between impulses on parallel fibers, which may play a functional role in neural processing. (C) 2001 Published by Elsevier Science B.V.

Scott, Alwyn C.

2001-01-01

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Myelination of the nervous system: mechanisms and functions.  

Science.gov (United States)

Myelination of axons in the nervous system of vertebrates enables fast, saltatory impulse propagation, one of the best-understood concepts in neurophysiology. However, it took a long while to recognize the mechanistic complexity both of myelination by oligodendrocytes and Schwann cells and of their cellular interactions. In this review, we highlight recent advances in our understanding of myelin biogenesis, its lifelong plasticity, and the reciprocal interactions of myelinating glia with the axons they ensheath. In the central nervous system, myelination is also stimulated by axonal activity and astrocytes, whereas myelin clearance involves microglia/macrophages. Once myelinated, the long-term integrity of axons depends on glial supply of metabolites and neurotrophic factors. The relevance of this axoglial symbiosis is illustrated in normal brain aging and human myelin diseases, which can be studied in corresponding mouse models. Thus, myelinating cells serve a key role in preserving the connectivity and functions of a healthy nervous system. PMID:25288117

Nave, Klaus-Armin; Werner, Hauke B

2014-10-11

36

Developmental dissociation of myelin synthesis and "myelin-associated" enzyme activities in the shiverer mouse.  

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Developmental changes in three enzymes associated with myelin lipids were studied in the shiverer mouse, a murine mutant showing a severe deficiency of CNS myelin. Age-related changes in cerebroside sulfotransferase (measured in brain) and arylsulfatase A and cerebroside B-galactosidase (measured in brain and liver) were the same for shiverer and control mice. The shiverer mouse, therefore, demonstrates a dissociation between the genetic mechanisms regulating myelination in the CNS and developmental changes in enzyme activities thought to be closely related to the synthesis of myelin. In addition, we found no defect in the shiverer mouse in the incorporation of glycine-labeled basic protein into CNS myelin, indicating an important metabolic difference between the morphologically similar shiverer and quaking mutants. PMID:6110194

Bird, T D; Farrell, D F; Stranahan, S; Austin, E

1980-08-01

37

MMP-28 as a regulator of myelination  

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

Dotzlaf Joseph E

2008-09-01

38

Myelination of rodent hippocampal neurons in culture.  

Science.gov (United States)

Axons of various hippocampal neurons are myelinated mainly postnatally, which is important for the proper function of neural circuits. Demyelination in the hippocampus has been observed in patients with multiple sclerosis, Alzheimer's disease or temporal lobe epilepsy. However, very little is known about the mechanisms and exact functions of the interaction between the myelin-making oligodendrocytes and the axons within the hippocampus. This is mainly attributable to the lack of a system suitable for molecular studies. We recently established a new myelin coculture from embryonic day (E) 18 rat embryos consisting of hippocampal neurons and oligodendrocytes, with which we identified a novel intra-axonal signaling pathway regulating the juxtaparanodal clustering of Kv1.2 channels. Here we describe the detailed protocol for this new coculture. It takes about 5 weeks to set up and use the system. This coculture is particularly useful for studying myelin-mediated regulation of ion channel trafficking and for understanding how neuronal excitability and synaptic transmission are regulated by myelination. PMID:22955693

Gardner, Asa; Jukkola, Peter; Gu, Chen

2012-10-01

39

Split Supersymmetry  

International Nuclear Information System (INIS)

The naturalness criterion applied to the cosmological constant implies a new-physics threshold at 10-3 eV. Either the naturalness criterion fails, or this threshold does not influence particle dynamics at higher energies. It has been suggested that the Higgs naturalness problem may follow the same fate. We investigate this possibility and, abandoning the hierarchy problem, we use unification and dark matter as the only guiding principles. The structure of Split Supersymmetry and its phenomenological consequences are briefly discussed

40

Splitting Descartes  

DEFF Research Database (Denmark)

Kognition og Pædagogik vol. 48:10-18. 2003 Short description : The cognitivistic paradigm and Descartes' view of embodied knowledge. Abstract: That the philosopher Descartes separated the mind from the body is hardly news: He did it so effectively that his name is forever tied to that division. But what exactly is Descartes' point? How does the Kartesian split hold up to recent biologically based learning theories?

Schilhab, Theresa

2007-01-01

 
 
 
 
41

Cytoplasmic domains of the myelin-associated glycoprotein  

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Abstract The function of the vertebrate nervous system is based on the rapid and accurate transmission of electrical impulses. The myelin sheath is a lipid-rich membrane that envelops the axon, preventing the leakage of the nervous impulse to the environment. Myelin is formed when the plasma membrane of a myelinating glial cell differentiates and wraps around an axon. The compaction of myelin leads to the extrusion of most of the glial cell cytoplasm from the structure. ...

Kursula, Petri

2000-01-01

42

Distinct endocytic recycling of myelin proteins promotes oligodendroglial membrane remodeling.  

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The central nervous system myelin sheath is a multilayered specialized membrane with compacted and non-compacted domains of defined protein composition. How oligodendrocytes regulate myelin membrane trafficking and establish membrane domains during myelination is largely unknown. Oligodendroglial cells respond to neuronal signals by adjusting the relative levels of endocytosis and exocytosis of the major myelin protein, proteolipid protein (PLP). We investigated whether endocytic trafficking is common to myelin proteins and analyzed the endocytic fates of proteins with distinct myelin subdomain localization. Interestingly, we found that PLP, myelin-associated glycoprotein (MAG) and myelin-oligodendrocyte glycoprotein (MOG), which localize to compact myelin, periaxonal loops and abaxonal loops, respectively, exhibit distinct endocytic fates. PLP was internalized via clathrin-independent endocytosis, whereas MAG was endocytosed by a clathrin-dependent pathway, although both proteins were targeted to the late-endosomal/lysosomal compartment. MOG was also endocytosed by a clathrin-dependent pathway, but in contrast to MAG, trafficked to the recycling endosome. Endocytic recycling resulted in the association of PLP, MAG and MOG with oligodendroglial membrane domains mimicking the biochemical characteristics of myelin domains. Our results suggest that endocytic sorting and recycling of myelin proteins may assist plasma membrane remodeling, which is necessary for the morphogenesis of myelin subdomains. PMID:18303048

Winterstein, Christine; Trotter, Jacqueline; Krämer-Albers, Eva-Maria

2008-03-15

43

Immunohistochemical detection of myelin basic protein is a sensitive marker of myelination in second trimester human fetal spinal cord.  

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The Luxol fast blue (LFB) technique is widely used for the assessment of myelination. Lectin histochemistry using peanut agglutinin (PNA) has also been employed for this purpose. Recently, immunohistochemical methods using antibodies to several myelin-related proteins have been adopted to study myelination in humans. However, the relative sensitivities of these different methods for the detection of early myelination in the human fetal central nervous system have not been determined. Vibratome sections of cervical spinal cord from 15 human abortuses ranging in age from 15 to 24 gestational weeks (GW) were probed with immunohistochemical methods using antibodies to myelin basic protein (MBP), 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), and myelin-associated glycoprotein (MAG). In addition, LFB and PNA histochemistry was employed. The degree of myelination observed in immunohistochemically stained sections was compared to that found in corresponding LFB- and PNA-stained paraffin-embedded tissues. The intensity of myelination was graded by two observers on a scale of 0 (none), +1 (mild), +2 (moderate), and +3 (marked). At all ages examined, the MBP immunohistochemical method revealed more myelin than LFB or MAG staining. CNPase could not be reliably detected until after 18 GW. Peanut agglutinin stained myelin, but subpial astrocytes and the intervening neuropil were also stained. These results suggest that MBP is a more sensitive marker for early human fetal myelination than CNPase, MAG, PNA or LFB. PMID:7509848

Bodhireddy, S R; Lyman, W D; Rashbaum, W K; Weidenheim, K M

1994-03-01

44

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

45

Axon-glia interaction and membrane traffic in myelin formation  

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

Eva-Maria Krämer-Albers

2014-01-01

46

Axon-glia interaction and membrane traffic in myelin formation.  

Science.gov (United States)

In vertebrate nervous systems myelination of neuronal axons has evolved to increase conduction velocity of electrical impulses with minimal space and energy requirements. Myelin is formed by specialized glial cells which ensheath axons with a lipid-rich insulating membrane. Myelination is a multi-step process initiated by axon-glia recognition triggering glial polarization followed by targeted myelin membrane expansion and compaction. Thereby, a myelin sheath of complex subdomain structure is established. Continuous communication between neurons and glial cells is essential for myelin maintenance and axonal integrity. A diverse group of diseases, from multiple sclerosis to schizophrenia, have been linked to malfunction of myelinating cells reflecting the physiological importance of the axon-glial unit. This review describes the mechanisms of axonal signal integration by oligodendrocytes emphasizing the central role of the Src-family kinase Fyn during central nervous system (CNS) myelination. Furthermore, we discuss myelin membrane trafficking with particular focus on endocytic recycling and the control of proteolipid protein (PLP) transport by soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. Finally, PLP mistrafficking is considered in the context of myelin diseases. PMID:24431989

White, Robin; Krämer-Albers, Eva-Maria

2014-01-01

47

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

48

Strategies for achieving and monitoring myelin repair.  

Science.gov (United States)

A number of factors more or less unique to multiple sclerosis have suggested that this disease may be particularly amenable to cell-based reparative therapies. The relatively focussed damage to oligodendrocytes and myelin at least in early disease implies that only a single population of cells need be replaced-and that the daunting problem of re-establishing connectivity does not apply. The presence of significant though partial spontaneous myelin repair in multiple sclerosis proves there to be no insurmountable barrier to remyelination intrinsic to the CNS: the therapeutic challenge becomes that of supplementing this spontaneous process, rather than creating repair de novo. Finally, the large body of available knowledge concerning the biology of oligodendrocytes, and the success of experimental myelin repair, have allowed cautious optimism that future prospects for such therapies are not unrealistic. Nonetheless, particular and significant problems are not hard to list: the occurrence of innumerable lesions scattered throughout the CNS, axon loss, astrocytosis, and a continuing inflammatory process, to name but a few. Here we review the progress and the areas where difficulties have yet to be resolved in efforts to develop remyelinating therapies for multiple sclerosis. PMID:17345032

Rice, Claire; Scolding, Neil

2007-03-01

49

Myelin structures formed by thermotropic smectic liquid crystals.  

Science.gov (United States)

We report on transient structures, formed by thermotropic smectic-A liquid crystals, resembling the myelin figures of lyotropic lamellar liquid crystals. The thermotropic myelin structures form during the solubilization of a smectic-A droplet in an aqueous phase containing a cationic surfactant at concentrations above the critical micelle concentration. Similar to the lyotropic myelin figures, the thermotropic myelins appear in an optical microscope as flexible tubelike structures growing at the smectic/aqueous interface. Polarizing microscopy and confocal fluorescence microscopy show that the smectic layers are parallel to the tube surface and form a cylindrically bent arrangement around a central line defect in the tube. We study the growth behavior of this new type of myelins and discuss similarities to and differences from the classical lyotropic myelin figures. PMID:24274621

Peddireddy, Karthik; Kumar, Pramoda; Thutupalli, Shashi; Herminghaus, Stephan; Bahr, Christian

2013-12-17

50

Effect of electroconvulsive therapy on serum myelin basic protein immunoreactivity.  

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A sensitive radioimmunoassay that can detect brain damage in cases of head injury and stroke was applied to blood samples from 13 patients before and after they received multiple treatments with electroconvulsive therapy for psychiatric disorder. None of the patients showed a significant increase in serum myelin basic protein immunoreactivity. As increased serum myelin basic protein immunoreactivity may reflect myelin damage it is apparent that in these patients electroconvulsive therapy did ...

Hoyle, N. R.; Pratt, R. T.; Thomas, D. G.

1984-01-01

51

Strategies for myelin regeneration: lessons learned from development.  

Science.gov (United States)

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 certain common mechanisms with developmental myelination, knowledge from study of developmental myelination contributes greatly to emerging myelin regeneration therapies, best evidenced as the recently developed human anti-Nogo receptor interacting protein-1 (LINGO-1) monoclonal antibodies to treat MS patients in clinical trials. PMID:25221590

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

2014-07-15

52

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

53

Human brain myelination and amyloid beta deposition in Alzheimer's disease.  

Science.gov (United States)

We hypothesized that myelin breakdown in vulnerable late-myelinating regions releases oligodendrocyte- and myelin-associated iron that promotes amyloid beta (A beta) oligomerization, its associated toxicity, and the deposition of oligomerized A beta and iron in neuritic plaques observed in Alzheimer's disease (AD). The model was tested by using published maps of cortical myelination from 1901 and recent in vivo imaging maps of A beta deposits in humans. The data show that in AD, radiolabeled ligands detect A beta deposition in a distribution that matches the map of late-myelinating regions. Furthermore, the strikingly lower ability of this imaging ligand to bind A beta in animal models is consistent with the much lower levels of myelin and associated iron levels in rodents when compared with humans. The hypotheses derived from the "myelin model" are testable with current imaging methods and have important implications for therapeutic interventions that should be expanded to include novel targets such as oligodendrocytes, myelin, and brain iron. PMID:18596894

Bartzokis, George; Lu, Po H; Mintz, Jim

2007-04-01

54

Proposed Evolutionary Changes In The Role Of Myelin  

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

JaySCoggan

2013-11-01

55

Unconventional myosin ID is expressed in myelinating oligodendrocytes.  

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Myelin is a dynamic multilamellar structure that ensheathes axons and is crucial for normal neuronal function. In the central nervous system (CNS), myelin is produced by oligodendrocytes that wrap many layers of plasma membrane around axons. The dynamic membrane trafficking system, which relies on motor proteins, is required for myelin formation and maintenance. Previously, we found that myosin ID (Myo1d), a class I myosin, is enriched in the rat CNS myelin fraction. Myo1d is an unconventional myosin and has been shown to be involved in membrane trafficking in the recycling pathway in an epithelial cell line. Western blotting revealed that Myo1d expression begins early in myelinogenesis and continues to increase into adulthood. The localization of Myo1d in CNS myelin has not been reported, and the function of Myo1d in vivo remains unknown. To demonstrate the expression of Myo1d in CNS myelin and to begin to explore the function of Myo1d in myelination, we produced a new antibody against Myo1d that has a high titer and specificity for rat Myo1d. By using this antibody, we demonstrated that Myo1d is expressed in rat CNS myelin and is especially abundant in abaxonal and adaxonal regions (the outer and inner cytoplasm-containing loops, respectively), but that expression is low in peripheral nervous system myelin. In culture, Myo1d was expressed in mature rat oligodendrocytes. Furthermore, an increase in expression of Myo1d during maturation of CNS white matter (cerebellum and corpus callosum) was demonstrated by histological analysis. These results suggest that Myo1d may be involved in the formation and/or maintenance of CNS myelin. PMID:24903835

Yamazaki, Reiji; Ishibashi, Tomoko; Baba, Hiroko; Yamaguchi, Yoshihide

2014-10-01

56

Myelin gene regulatory factor is required for maintenance of myelin and mature oligodendrocyte identity in the adult CNS.  

Science.gov (United States)

Although the transcription factors required for the generation of oligodendrocytes and CNS myelination during development have been relatively well established, it is not known whether continued expression of the same factors is required for the maintenance of myelin in the adult. Here, we use an inducible conditional knock-out strategy to investigate whether continued oligodendrocyte expression of the recently identified transcription factor myelin gene regulatory factor (MRF) is required to maintain the integrity of myelin in the adult CNS. Genetic ablation of MRF in mature oligodendrocytes within the adult CNS resulted in a delayed but severe CNS demyelination, with clinical symptoms beginning at 5 weeks and peaking at 8 weeks after ablation of MRF. This demyelination was accompanied by microglial/macrophage infiltration and axonal damage. Transcripts for myelin genes, such as proteolipid protein, MAG, MBP, and myelin oligodendrocyte glycoprotein, were rapidly downregulated after ablation of MRF, indicating an ongoing requirement for MRF in the expression of these genes. Subsequently, a proportion of the recombined oligodendrocytes undergo apoptosis over a period of weeks. Surviving oligodendrocytes gradually lose the expression of mature markers such as CC1 antigen and their association with myelin, without reexpressing oligodendrocyte progenitor markers or reentering the cell cycle. These results demonstrate that ongoing expression of MRF within the adult CNS is critical to maintain mature oligodendrocyte identity and the integrity of CNS myelin. PMID:22956843

Koenning, Matthias; Jackson, Stacey; Hay, Curtis M; Faux, Clare; Kilpatrick, Trevor J; Willingham, Melanie; Emery, Ben

2012-09-01

57

New insights into signaling during myelination in zebrafish  

Science.gov (United States)

Myelin is a vertebrate adaptation that allows for the rapid propagation of action potentials along axons. Specialized glial cells – oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS) – form myelin by repeatedly wrapping axon segments. Debilitating diseases result from the disruption of myelin, including Multiple Sclerosis and Charcot-Marie-Tooth peripheral neuropathies. The process of myelination involves extensive communication between glial cells and the associated neurons, and the last few years have seen important progress in understanding the molecular basis of the signals that coordinate the development of these fascinating cells. This review highlights recent advances in myelination deriving from studies in the zebrafish model system, with a primary focus on the PNS. While Neuregulin1-ErbB signaling has long been known to play important roles in peripheral myelin development, work in zebrafish has elucidated its roles in Schwann cell migration and radial sorting of axons sorting in vivo. Forward genetic screens in zebrafish have also uncovered new genes required for development of myelinated axons, including gpr126, which encodes a G-protein coupled receptor required for Schwann cells to progress beyond the promyelinating stage. In addition, work in zebrafish uncovered new roles for Schwann cells themselves, including in regulating the boundary between the PNS and CNS and positioning a nerve after its initial outgrowth. PMID:22074600

Raphael, Alya R.; Talbot, William S.

2014-01-01

58

Stimulation of adult oligodendrogenesis by myelin-specific T cells  

DEFF Research Database (Denmark)

In multiple sclerosis (MS), myelin-specific T cells are normally associated with destruction of myelin and axonal damage. However, in acute MS plaque, remyelination occurs concurrent with T-cell infiltration, which raises the question of whether T cells might stimulate myelin repair. We investigated the effect of myelin-specific T cells on oligodendrocyte formation at sites of axonal damage in the mouse hippocampal dentate gyrus. Infiltrating T cells specific for myelin proteolipid protein stimulated proliferation of chondroitin sulfate NG2-expressing oligodendrocyte precursor cells early after induction via axonal transection, resulting in a 25% increase in the numbers of oligodendrocytes. In contrast, T cells specific for ovalbumin did not stimulate the formation of new oligodendrocytes. In addition, infiltration of myelin-specific T cells enhanced the sprouting response of calretinergic associational/commissural fibers within the dentate gyrus. These results have implications for the perception of MS pathogenesis because they show that infiltrating myelin-specific T cells can stimulate oligodendrogenesis in the adult central nervous system.

Hvilsted Nielsen, Helle; Toft-Hansen, Henrik

2011-01-01

59

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

Science.gov (United States)

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

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

2014-06-01

60

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

 
 
 
 
61

A role for nociceptive, myelinated nerve fibers in itch sensation.  

Science.gov (United States)

Despite its clinical importance, the underlying neural mechanisms of itch sensation are poorly understood. In many diseases, pruritus is not effectively treated with antihistamines, indicating the involvement of nonhistaminergic mechanisms. To investigate the role of small myelinated afferents in nonhistaminergic itch, we tested, in psychophysical studies in humans, the effect of a differential nerve block on itch produced by intradermal insertion of spicules from the pods of a cowhage plant (Mucuna pruriens). Electrophysiological experiments in anesthetized monkey were used to investigate the responsiveness of cutaneous, nociceptive, myelinated afferents to different chemical stimuli (cowhage spicules, histamine, capsaicin). Our results provide several lines of evidence for an important role of myelinated fibers in cowhage-induced itch: (1) a selective conduction block in myelinated fibers substantially reduces itch in a subgroup of subjects with A-fiber-dominated itch, (2) the time course of itch sensation differs between subjects with A-fiber- versus C-fiber-dominated itch, (3) cowhage activates a subpopulation of myelinated and unmyelinated afferents in monkey, (4) the time course of the response to cowhage is different in myelinated and unmyelinated fibers, (5) the time of peak itch sensation for subjects with A-fiber-dominated itch matches the time for peak response in myelinated fibers, and (6) the time for peak itch sensation for subjects with C-fiber-dominated itch matches the time for the peak response in unmyelinated fibers. These findings demonstrate that activity in nociceptive, myelinated afferents contributes to cowhage-induced sensations, and that nonhistaminergic itch is mediated through activity in both unmyelinated and myelinated afferents. PMID:22016517

Ringkamp, Matthias; Schepers, Raf J; Shimada, Steven G; Johanek, Lisa M; Hartke, Timothy V; Borzan, Jasenka; Shim, Beom; LaMotte, Robert H; Meyer, Richard A

2011-10-19

62

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

63

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

64

Myelin imaging in amyotrophic and primary lateral sclerosis.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Primary lateral sclerosis (PLS) has been regarded as a rare, extreme form of amyotrophic lateral sclerosis (ALS). Like ALS, it is a clinical diagnosis without established biomarkers. We sought to explore loss of cerebral myelin in relation to clinical features, including cognitive impairment, in cases of both ALS and PLS. A novel MRI sequence (mcDESPOT) sensitive to water pools within myelin and intra- and extra-cellular spaces was applied to 23 ALS patients, seven PLS patients and 12 healthy...

Kolind, S.; Sharma, R.; Knight, S.; Johansen-berg, H.; Talbot, K.; Turner

2013-01-01

65

Rapid myelin water content mapping on clinical MR systems.  

Science.gov (United States)

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(1), T(2)(*) and total water content. Employing the multiexponential T(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(2)(*) curve was compromised to 10 echo times with a TE(max) of approx. 40ms. Therefore, pool amplitudes were determined using a quadratic optimisation approach. The optimisation was constrained by including à 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(1), T(2)(*), total and myelin water content is feasible on almost any modern MR scanner in less than 10 minutes. PMID:22019512

Tonkova, Vyara; Arhelger, Volker; Schenk, Jochen; Neeb, Heiko

2012-06-01

66

Rapid myelin water content mapping on clinical MR systems  

International Nuclear Information System (INIS)

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 T1, T*2 and total water content. Employing the multiexponential T*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*2 curve was compromised to 10 echo times with a T 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 T1, T*2, total and myelin water content is feasible on almost any modern MR scanner in less than 10 minutes. (orig.)

67

Effects of hemicranial irradiation on myelination in the neonatal rat  

International Nuclear Information System (INIS)

Neonatal rats, aged 4 to 15 days, received single doses of X-irradiation to the right hemicranium. Doses of 5, 7.5, 10 and 15 Gy were administered with linear accelerator. The rats were sacrificed at 14, 21, 28 and 35 days of age and examined for histological changes and immunohistochemically. No remarkable neurological abnormality was noted at the time of sacrifice. With conventional stains there was a dose-dependent decrease in the number of glial cells in the corpus callosum of the irradiated hemisphere, while neurons and blood vessels showed no abnormal changes. Myelin was identified using immunohistochemistry for myelin basic protein and myelin-associated glycoprotein. As compared with unirradiated hemisphere, irradiated hemisphere showed delayed myelination. The antiserum to the large isoform of myelin-associated glycoprotein (L-MAG) stained the cytoplasm of oligodendroglia in 2 to 3 weeks after birth. A smaller number of L-MAG-positive cells were observed in the irradiated hemisphere. This immunohistochemical method appears to be a sensitive histopathological indicator of radiation effect on oligodendroglias. The permeability of the blood-brain barrier (BBB) to sodium fluorescein was investigated and breakdown of the BBB was not observed in the irradiated hemisphere. These results suggest that delayed myelination in this study was due to a direct radiation effect on oligodendroglias. (author)

68

Interleukin-11 potentiates oligodendrocyte survival and maturation, and myelin formation.  

Science.gov (United States)

Mechanisms that regulate oligodendrocyte survival and myelin formation are an intense focus of research into myelin repair in the lesions of multiple sclerosis (MS). Although demyelination and oligodendrocyte loss are pathological hallmarks of the disease, increased oligodendrocyte numbers and remyelination are frequently observed in early lesions, but these diminish as the disease course progresses. In the current study, we used a microarray-based approach to investigate genes regulating repair in MS lesions, and identified interleukin-11 (IL-11) as an astrocyte-derived factor that potentiates oligodendrocyte survival and maturation, and myelin formation. IL-11 was induced in human astrocyte cultures by the cytokines IL-1beta and TGFbeta1, which are both prominently expressed in MS plaques. In MS tissue samples, IL-11 was expressed by reactive astrocytes, with expression particularly localized at the myelinated border of both active and silent lesions. Its receptor, IL-11R alpha, was expressed by oligodendrocytes. In experiments in human cultures in vitro, IL-11R alpha localized to immature oligodendrocytes, and its expression decreased during maturation. In cultures treated with IL-11, we observed a significant increase in oligodendrocyte number, and this was associated with enhanced oligodendrocyte survival and maturation. Importantly, we also found that IL-11 treatment was associated with significantly increased myelin formation in rodent CNS cocultures. These data are the first to implicate IL-11 in oligodendrocyte viability, maturation, and myelination. We suggest that this pathway may represent a potential therapeutic target for oligodendrocyte protection and remyelination in MS. PMID:17122042

Zhang, Yueting; Taveggia, Carla; Melendez-Vasquez, Carmen; Einheber, Steven; Raine, Cedric S; Salzer, James L; Brosnan, Celia F; John, Gareth R

2006-11-22

69

Abnormal myelination in ring chromosome 18 syndrome.  

Science.gov (United States)

Partial deletion of genetic material from the long arm of chromosome 18 results in a syndrome with multisystemic involvement, including dysmorphic features, intellectual disability, cardiac malformations, endocrine abnormalities, immunodeficiency, musculoskeletal deformities, and variable neurologic manifestations. Hypomyelination has been reported in patients with chromosome 18q- and postulated to be secondary to deletion of the gene coding for myelin basic protein found at 18q23. Little however is reported on cerebral anomalies seen in patients with ring chromosome 18, an analogous syndrome but with expectedly more severe phenotype secondary to the combined deletions of genetic material from both the short (p-) and long arm (q-) of chromosome 18. We are reporting a case of a girl with ring chromosome 18 and deletions involving 18p11.32-18p11.21 and 18q21.31-18q23. The abnormalities observed on magnetic resonance imaging are discussed with a specific focus on the evolution and significance of associated white matter changes. PMID:22290857

Benini, Ruba; Saint-Martin, Christine; Shevell, Michael I; Bernard, Genevieve

2012-08-01

70

Structural and dynamical properties of reconstituted myelin sheaths in the presence of myelin proteins MBP and P2 studied by neutron scattering.  

Science.gov (United States)

The myelin sheath is a tightly packed, multilayered membrane structure wrapped around selected nerve axons in the central and the peripheral nervous system. Because of its electrical insulation of the axons, which allows fast, saltatory nerve impulse conduction, myelin is crucial for the proper functioning of the vertebrate nervous system. A subset of myelin-specific proteins is well-defined, but their influence on membrane dynamics, i.e. myelin stability, has not yet been explored in detail. We investigated the structure and the dynamics of reconstituted myelin membranes on a pico- to nanosecond timescale, influenced by myelin basic protein (MBP) and myelin protein 2 (P2), using neutron diffraction and quasi-elastic neutron scattering. A model for the scattering function describing molecular lipid motions is suggested. Although dynamical properties are not affected significantly by MBP and P2 proteins, they act in a highly synergistic manner influencing the membrane structure. PMID:24651633

Knoll, Wiebke; Peters, Judith; Kursula, Petri; Gerelli, Yuri; Ollivier, Jacques; Demé, Bruno; Telling, Mark; Kemner, Ewout; Natali, Francesca

2014-01-21

71

MicroRNA and transcriptional crosstalk in myelinating glia.  

Science.gov (United States)

Several recent studies have addressed the important role of microRNA in regulation of differentiation of myelinating glia. While Schwann cells and oligodendrocytes in the peripheral and central nervous systems, respectively, exhibit significant morphological and regulatory differences, some aspects of transcriptional and microRNA regulation are shared between these two cell types. This review focuses on the intersection of microRNAs with transcriptional regulation in Schwann cell and oligodendrocyte differentiation. In particular, several microRNAs have been shown to modulate expression of critical transcription factors, and in turn, the regulation of microRNA expression is enmeshed within transcriptional networks that coordinate both coding gene and noncoding RNA profiles of myelinating cells. These hubs of regulation control both myelin gene expression as well as the cell cycle transitions of Schwann cells and oligodendrocytes as they terminally differentiate. In addition, some studies have begin to highlight the combinatorial effects of different microRNAs that establish the narrow range of gene regulation required for efficient and stable myelin formation. Overall, the integration of microRNA and transcriptional aspects will help elucidate mechanistic control of the myelination process. PMID:24979526

Svaren, John

2014-11-01

72

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

73

48 echo T2 myelin imaging of white matter in first-episode schizophrenia: Evidence for aberrant myelination  

Science.gov (United States)

Myelin water imaging provides a novel strategy to assess myelin integrity and corresponding clinical relationships in psychosis, of particular relevance in frontal white matter regions. In the current study, T2 myelin water imaging was used to assess the myelin water fraction (MWF) signal from frontal areas in a sample of 58 individuals experiencing first-episode psychosis (FEP) and 44 healthy volunteers. No differences in frontal MWF were observed between FEP subjects and healthy volunteers; however, differences in normal patterns of associations between frontal MWF and age, education and IQ were seen. Significant positive relationships between frontal MWF and age, North American Adult Reading Test (NAART) IQ, and years of completed education were observed in healthy volunteers. In contrast, only the relationship between frontal MWF and NAART IQ was significant after Bonferroni correction in the FEP group. Additionally, significant positive relationships between age and MWF in the anterior and posterior internal capsules, the genu, and the splenium were observed in healthy volunteers. In FEP subjects, only the relationship between age and MWF in the splenium was statistically significant. Frontal MWF was not associated with local white matter volume. Altered patterns of association between age, years of education, and MWF in FEP suggest that subtle disturbances in myelination may be present early in the course of psychosis. PMID:25379454

Lang, Donna J.M.; Yip, Eugene; MacKay, Alexander L.; Thornton, Allen E.; Vila-Rodriguez, Fidel; MacEwan, G. William; Kopala, Lili C.; Smith, Geoffrey N.; Laule, Cornelia; MacRae, Cassie B.; Honer, William G.

2014-01-01

74

Delayed myelination in a mouse model of fragile X syndrome.  

Science.gov (United States)

Fragile X Syndrome is the most common inherited cause of autism. Fragile X mental retardation protein (FMRP), which is absent in fragile X, is an mRNA binding protein that regulates the translation of hundreds of different mRNA transcripts. In the adult brain, FMRP is expressed primarily in the neurons; however, it is also expressed in developing glial cells, where its function is not well understood. Here, we show that fragile X (Fmr1) knockout mice display abnormalities in the myelination of cerebellar axons as early as the first postnatal week, corresponding roughly to the equivalent time in human brain development when symptoms of the syndrome first become apparent (1-3 years of age). At postnatal day (PND) 7, diffusion tensor magnetic resonance imaging showed reduced volume of the Fmr1 cerebellum compared with wild-type mice, concomitant with an 80-85% reduction in the expression of myelin basic protein, fewer myelinated axons and reduced thickness of myelin sheaths, as measured by electron microscopy. Both the expression of the proteoglycan NG2 and the number of PDGFR?+/NG2+ oligodendrocyte precursor cells were reduced in the Fmr1 cerebellum at PND 7. Although myelin proteins were still depressed at PND 15, they regained wild-type levels by PND 30. These findings suggest that impaired maturation or function of oligodendrocyte precursor cells induces delayed myelination in the Fmr1 mouse brain. Our results bolster an emerging recognition that white matter abnormalities in early postnatal brain development represent an underlying neurological deficit in Fragile X syndrome. PMID:23740941

Pacey, Laura K K; Xuan, Ingrid C Y; Guan, Sihui; Sussman, Dafna; Henkelman, R Mark; Chen, Yan; Thomsen, Christian; Hampson, David R

2013-10-01

75

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

76

Nail Splitting (Onychoschizia)  

Science.gov (United States)

... Nail splitting may also be caused by nail cosmetics (hardeners, polish, polish removers/solvents), nail procedures, and occupational exposure to various chemicals (alkalis, acids, cement, solvents, thioglycolates, salt, sugar solutions). ...

77

Activation of NF-?B in Schwann Cells Is Dispensable for Myelination In Vivo  

Science.gov (United States)

Peripheral myelination is a dynamic process orchestrated by axons and Schwann cells. Although the signaling mechanisms governing myelination are not fully understood, NF-?B activation in Schwann cells has been implicated as a key regulator in vitro. Using a mouse model, we show that nuclear factor ?B activation in Schwann cells is not required for myelination in vivo. PMID:23761888

Morton, Paul D.; Dellarole, Anna; Theus, Michelle H.; Walters, Winston M.; Berge, Summer S.

2013-01-01

78

Activation of NF-?B in Schwann cells is dispensable for myelination in vivo.  

Science.gov (United States)

Peripheral myelination is a dynamic process orchestrated by axons and Schwann cells. Although the signaling mechanisms governing myelination are not fully understood, NF-?B activation in Schwann cells has been implicated as a key regulator in vitro. Using a mouse model, we show that nuclear factor ?B activation in Schwann cells is not required for myelination in vivo. PMID:23761888

Morton, Paul D; Dellarole, Anna; Theus, Michelle H; Walters, Winston M; Berge, Summer S; Bethea, John R

2013-06-12

79

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

80

Promoting myelin repair and return of function in multiple sclerosis  

Science.gov (United States)

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. Conduction block in demyelinated axons underlies early neurological symptoms, but axonal transection and neuronal loss are believed to be responsible for more permanent chronic deficits. Several therapies are approved for treatment of relapsing-remitting MS, all of which are immunoregulatory and clinically proven to reduce the rate of lesion formation and exacerbation. However, existing approaches are only partially effective in preventing the onset of disability in MS patients, and novel treatments to protect myelin-producing oligodendrocytes and enhance myelin repair may improve long-term outcomes. Studies in vivo in genetically modified mice have assisted in the characterization of mechanisms underlying the generation of neuropathology in MS patients, and have identified potential avenues for oligodendrocyte protection and myelin repair. However, no treatments are yet approved that target these areas directly, and in addition, the relationship between demyelination and axonal transection in the lesions of the disease remain unclear. Here, we review translational research targeting oligodendrocyte protection and myelin repair in models of autoimmune demyelination, and their potential relevance as therapies in MS patients. PMID:21864535

Zhang, Jingya; Kramer, Elisabeth G.; Asp, Linnea; Dutta, Dipankar J.; Navrazhina, Kristina; Pham, Trinh; Mariani, John N.; Argaw, Azeb Tadesse; Melendez-Vasquez, Carmen V.; John, Gareth R.

2011-01-01

 
 
 
 
81

Peripheral nervous system plasmalogens regulate Schwann cell differentiation and myelination.  

Science.gov (United States)

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

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

2014-06-01

82

DIMINISHED DEGRADATION OF MYELIN BASIC PROTEIN BY ANTI-SULFATIDE ANTIBODY AND INTERFERON-? IN MYELIN FROM GLIA MATURATION FACTOR-DEFICIENT MICE  

Science.gov (United States)

In this study we show the effect of anti-sulfatide (RmAb) antibodies and inflammatory cytokines, TNF-? and IFN-? in inducing myelin basic protein (MBP) degradation in myelin isolated from control wild type (WT) and glia maturation factor (GMF)-deficient (GMF-KO) mice. GMF was not detected in isolated myelin from WT and GMF-KO mice although it is present in brains of WT mice. Our results show that calcium dependent neutral protease activity caused significantly elevated degradation of 18.5 and/or 17.5 kDa isoforms of MBP in WT-myelin treated with RmAb or IFN-?. In contrast, MBP degradation in isolated myelin from GMF-KO mice remained unaffected following treatment with RmAb, IFN-?, or GM-CSF. Neither the 14 kDa isoform of MBP or proteolipid protein (PLP) showed an elevated degradation compared to controls. A virtual absence of GM-CSF, TNF-? and IFN-? in GMF-KO brain compared to WT was also evident when the animals were challenged with MOG 35-55. Additionally, the myelin from GMF-KO mice showed difference in distribution of myelin oligodendrocyte glycoprotein (MOG) and ?-tubulin in a sucrose density gradient myelin-axolemmal fractions compared to WT. Taken together, our data suggests a role for GMF in the biochemical organization of myelin and thereby its effect on MBP degradation induced by RmAb and IFN-?. PMID:17383764

Menon, Krishnakumar; Wu, Yanghong; Haas, Joel; Sahu, Shailendra K.; Yang, Baoli; Zaheer, Asgar

2007-01-01

83

Split Special Lagrangian Geometry  

CERN Document Server

One purpose of this article is to draw attention to the seminal work of J. Mealy in 1989 on calibrations in semi-riemannian geometry where split SLAG geometry was first introduced. The natural setting is provided by doing geometry with the complex numbers C replaced by the double numbers D, where i with i^2 = -1 is replaced by tau with tau^2 = 1. A rather surprising amount of complex geometry carries over, almost untouched, and this has been the subject of many papers. We briefly review this material and, in particular, we discuss Hermitian D-manifolds with trivial canonical bundle, which provide the background space for the geometry of split SLAG submanifolds. A removable singularities result is proved for split SLAG subvarieties. It implies, in particular, that there exist no split SLAG cones, smooth outside the origin, other than planes. This is in sharp contrast to the complex case. Parallel to the complex case, space-like Lagrangian submanifolds are stationary if and only if they are theta-split SLAG for...

Harvey, F Reese

2010-01-01

84

Aspects of Split Supersymmetry  

Energy Technology Data Exchange (ETDEWEB)

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 supersymmetry breaking is directly communicated at tree level to the visible sector via renormalizable interactions. Next, we discuss possible low-energy signals for Split Supersymmetry. The absence of new light scalars removes all the phenomenological difficulties of low-energy supersymmetry, associated with one-loop flavor and CP-violating effects. However, the electric dipole moments of leptons and quarks do arise at two loops, and are automatically at the level of present limits with no need for small phases, making them accessible to several ongoing new-generation experiments. We also study proton decay in the context of Split Supersymmetry, and point out scenarios where the dimension-six induced decays may be observable. Finally, we show that the novel spectrum of Split Supersymmetry opens up new possibilities for the generation of dark matter, as the decays of ultraheavy gravitinos in the early universe typically increase the abundance of the lightest neutralino above its usual freeze-out value. This allows for lighter gauginos and Higgsinos, more accessible both to the LHC and to dark-matter detection experiments.

Arkani-Hamed, N. [Jefferson Laboratory of Physics, Harvard University, Cambridge, MA 02138 (United States); Dimopoulos, S. [Physics Department, Stanford University, Stanford, CA 94305 (United States); Giudice, G.F. [CERN, Theory Division, CH-1211 Geneva 23 (Switzerland); Romanino, A. [CERN, Theory Division, CH-1211 Geneva 23 (Switzerland)]. E-mail: andrea.romanino@cern.ch

2005-03-07

85

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.

86

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

DEFF Research Database (Denmark)

Axons are linked to induction of myelination during development and to the maintenance of myelin and myelinated tracts in the adult CNS. Currently, it is unknown whether and how axonal plasticity in adult CNS impacts the myelinating cells and their precursors. In this article, we report that newly formed axonal sprouts are able to induce a protracted myelination response in adult CNS. We show that newly formed axonal sprouts, induced by lesion of the entorhino-hippocampal perforant pathway, have the ability to induce a myelination response in stratum radiatum and lucidum CA3. The lesion resulted in significant recruitment of newly formed myelinating cells, documented by incorporation of the proliferation marker bromodeoxyuridine into chondroitin sulphate NG2 expressing cells in stratum radiatum and lucidum CA3 early after lesion, and the occurrence of a 28% increase in the number of oligodendrocytes, of which some had incorporated bromodeoxyuridine, 9 weeks post-lesion. Additionally, a marked increase (41%) in myelinated fibres was detected in silver stained sections. Interestingly, these apparently new fibres achieved the same axon diameter as unlesioned mice but myelin thickness remained thinner than normal, suggesting that the sprouting axons in stratum radiatum and lucidum CA3 were not fully myelinated 9 weeks after lesion. Our combined results show that sprouting axons provide a strong stimulus to oligodendrocyte lineage cells to engage actively in the myelination processes in the adult CNS.

DrØjdahl, Nina; Nielsen, Helle Hvilsted

2010-01-01

87

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

88

The multiple roles of myelin protein genes during the development of the oligodendrocyte  

Directory of Open Access Journals (Sweden)

Full Text Available It has become clear that the products of several of the earliest identified myelin protein genes perform functions that extend beyond the myelin sheath. Interestingly, these myelin proteins, which comprise proteolipid protein, 2?,3?-cyclic nucleotide 3?-phosphodiesterase and the classic and golli MBPs (myelin basic proteins, play important roles during different stages of oligodendroglial development. These non-myelin-related functions are varied and include roles in the regulation of process outgrowth, migration, RNA transport, oligodendrocyte survival and ion channel modulation. However, despite the wide variety of cellular functions performed by the different myelin genes, the route by which they achieve these many functions seems to converge upon a common mechanism involving Ca2+ regulation, cytoskeletal rearrangements and signal transduction. In the present review, the newly emerging functions of these myelin proteins will be described, and these will then be discussed in the context of their contribution to oligodendroglial development.

Anthony T Campagnoni

2010-02-01

89

Boring split links  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

90

Split Injection Gas Chromatography  

Science.gov (United States)

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

2011-05-11

91

Activation of MAPK overrides the termination of myelin growth and replaces Nrg1/ErbB3 signals during Schwann cell development and myelination  

Science.gov (United States)

Myelination depends on the synthesis of large amounts of myelin transcripts and proteins and is controlled by Nrg1/ErbB/Shp2 signaling. We developed a novel pulse labeling strategy based on stable isotope labeling with amino acids in cell culture (SILAC) to measure the dynamics of myelin protein production in mice. We found that protein synthesis is dampened in the maturing postnatal peripheral nervous system, and myelination then slows down. Remarkably, sustained activation of MAPK signaling by expression of the Mek1DD allele in mice overcomes the signals that end myelination, resulting in continuous myelin growth. MAPK activation leads to minor changes in transcript levels but massively up-regulates protein production. Pharmacological interference in vivo demonstrates that the effects of activated MAPK signaling on translation are mediated by mTOR-independent mechanisms but in part also by mTOR-dependent mechanisms. Previous work demonstrated that loss of ErbB3/Shp2 signaling impairs Schwann cell development and disrupts the myelination program. We found that activated MAPK signaling strikingly compensates for the absence of ErbB3 or Shp2 during Schwann cell development and myelination. PMID:24493648

Sheean, Maria E.; McShane, Erik; Cheret, Cyril; Walcher, Jan; Muller, Thomas; Wulf-Goldenberg, Annika; Hoelper, Soraya; Garratt, Alistair N.; Kruger, Markus; Rajewsky, Klaus; Meijer, Dies; Birchmeier, Walter; Lewin, Gary R.; Selbach, Matthias; Birchmeier, Carmen

2014-01-01

92

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

Science.gov (United States)

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

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

2001-01-01

93

The heme precursor delta-aminolevulinate blocks peripheral myelin formation  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

94

Compaction and particle segregation in myelin membrane arrays  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Compacted membrane arrays are formed in the nerve myelin sheath by lowering the water activity (through evaporation or immersion in hypertonic solutions of nonelectrolytes or monovalent salts) or by binding specific cations (Ca(++), La(+++), and tetracaine at concentrations above 5-10 mM). X-ray diffraction observations on intact, hydrated nerves treated to induce compaction provide a control to assess the significance of structural changes seen by freeze-fracture electron microscopy. Compact...

Hollingshead, Cj; Caspar, Dld; Melchior, V.; Kirschner, Da

1981-01-01

95

Proliferation of Schwann cells induced by axolemmal and myelin membranes  

International Nuclear Information System (INIS)

Purified Schwann Cells were cultured from neonatal rat sciatic nerve using a modification of the method of Brockes. Schwann cells and contaminating fibroblasts were unambiguously identified using fluorescent antibodies of 2'3' cyclic nucleotide 3'-phosphodiesterase and the thy 1.1 antigen respectively. The Schwann cells were quiescent unless challenged with mitogens. They proliferated rapidly in response to the soluble mitogen, cholera toxin, or to membrane fractions from rat CNS or PNS, prepared by the method of DeVries. Mitogenic activity was present in both axolemmal and myelin enriched fractions and promoted a 10-15 fold increase in the rate of 3H-thymidine uptake. The axolemmal mitogen was sensitive to heat (800C for 10 minutes), trypsin digestion (0.05% x 30 mins) or to treatment with endoglycosidase D, suggesting that it could be a glycoprotein. Fifty percent of the axolemmal mitogenic activity was solubilized in 1% octyl-glucoside. The solubilized material, however, was very unstable and further purification was not possible. The myelin associated mitogenic activity was markedly different. It was resistant to freeze thaw cycles, trypsin digestion of endoglycosidase treatment and the activity was actually enhanced by heating at 1000C for two hours. It is proposed that the axolemmal activity is responsible for Schwann cell proliferation during development and that the myelin associated activity promotes Schwann cell proliferation during Wallerian degeneration

96

Myelin-associated changes in mouse brain following irradiation  

International Nuclear Information System (INIS)

The goals of this study were to quantify myelin-associated changes in the brain following single doses of radiation and to determine their relationship to the dose limits that this tissue can tolerate. Mice developed a transient loss of balance 1 month after 60 Gy doses 250 kVp X-rays to the brain and 3-4 months after 30-45 Gy radiation, but not after lower doses. The symptoms were transient and lasted ? 1 month. The ED50/300 for radiation-induced brain death, which occurred largely between 200 and 240 days, was 32.4 Gy (29.1, 35.5 Gy, 95% confidence limit of mean). At the time that animals developed neurological symptoms, 3-4 months after irradiation with doses of 30-45 Gy, biochemical assays of myelin-associated proteins showed decreases in 2',3' -cyclic nucleotide phosphohydrolase (CNPase) and myelin basic protein (MBP) levels that were not seen with lower radiation doses. By 120-180 days, further dose-dependent decreases in both CNPase and MBP levels were found after 20-45 Gy irradiation that preceded and correlated with death. The correlation of the decrease in CNPase and MBP levels with the incidence of transient neurological malfunction and animal death, together with histological evidence, suggests that demyelination is responsible for these phenomena. (author)

97

A functional role for EGFR signaling in myelination and remyelination.  

Science.gov (United States)

Cellular strategies for oligodendrocyte regeneration and remyelination involve characterizing endogenous neural progenitors that are capable of generating oligodendrocytes during normal development and after demyelination, and identifying the molecular signals that enhance oligodendrogenesis from these progenitors. Using both gain- and loss-of-function approaches, we explored the role of epidermal growth factor receptor (EGFR) signaling in adult myelin repair and in oligodendrogenesis. We show that 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) promoter-driven overexpression of human EGFR (hEGFR) accelerated remyelination and functional recovery following focal demyelination of mouse corpus callosum. Lesion repopulation by Cspg4+ (also known as NG2) Ascl1+ (also known as Mash1) Olig2+ progenitors and functional remyelination were accelerated in CNP-hEGFR mice compared with wild-type mice. EGFR overexpression in subventricular zone (SVZ) and corpus callosum during early postnatal development also expanded this NG2+Mash1+Olig2+ progenitor population and promoted SVZ-to-lesion migration, enhancing oligodendrocyte generation and axonal myelination. Analysis of hypomorphic EGFR-mutant mice confirmed that EGFR signaling regulates oligodendrogenesis and remyelination by NG2+Mash1+Olig2+ progenitors. EGFR targeting holds promise for enhancing oligodendrocyte regeneration and myelin repair. PMID:17618276

Aguirre, Adan; Dupree, Jeff L; Mangin, J M; Gallo, Vittorio

2007-08-01

98

Proliferation of Schwann cells induced by axolemmal and myelin membranes  

Energy Technology Data Exchange (ETDEWEB)

Purified Schwann Cells were cultured from neonatal rat sciatic nerve using a modification of the method of Brockes. Schwann cells and contaminating fibroblasts were unambiguously identified using fluorescent antibodies of 2'3' cyclic nucleotide 3'-phosphodiesterase and the thy 1.1 antigen respectively. The Schwann cells were quiescent unless challenged with mitogens. They proliferated rapidly in response to the soluble mitogen, cholera toxin, or to membrane fractions from rat CNS or PNS, prepared by the method of DeVries. Mitogenic activity was present in both axolemmal and myelin enriched fractions and promoted a 10-15 fold increase in the rate of /sup 3/H-thymidine uptake. The axolemmal mitogen was sensitive to heat (80/sup 0/C for 10 minutes), trypsin digestion (0.05% x 30 mins) or to treatment with endoglycosidase D, suggesting that it could be a glycoprotein. Fifty percent of the axolemmal mitogenic activity was solubilized in 1% octyl-glucoside. The solubilized material, however, was very unstable and further purification was not possible. The myelin associated mitogenic activity was markedly different. It was resistant to freeze thaw cycles, trypsin digestion of endoglycosidase treatment and the activity was actually enhanced by heating at 100/sup 0/C for two hours. It is proposed that the axolemmal activity is responsible for Schwann cell proliferation during development and that the myelin associated activity promotes Schwann cell proliferation during Wallerian degeneration.

Dinneen, M..

1985-01-01

99

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

International Nuclear Information System (INIS)

The aim of this investigation was to study binding of ALA by brain myelin under normal conditions and under the influence of lead and benzene. Rabbits of three different groups were given an intercranial injection of 14C-ALA (50 microCi) in physiological saline in a volume of 0.25 ml. The myelin fraction was obtained by differential centrifugation and the 14C-ALA in it was assayed on an LKB liquid scintillation counter. By determining the quantity of exogenous 14C-ALA bound with myelin, the authors found that myelin of white matter in the brain contains more of the acid than myelin of the gray matter. Data on binding of 14C-ALA calculated per milligram of each group of myelin proteins isolated is given

100

Natural electromagnetic waveguide structures based on myelin sheath in the neural system  

CERN Document Server

The saltatory propagation of action potentials on myelinated axons is conventionally explained by the mechanism employing local circuit ionic current flows between nodes of Ranvier. Under this framework, the myelin sheath with up to 100 layers of membrane only serves as the insulating shell. The speed of action potentials is measured to be as fast as 100 m/s on myelinated axons, but ions move in fluids at just 100 nm/s in a 1 V/m electric field. We show here the action potentials, in the form of electromagnetic (EM) pulses, can propagate in natural EM waveguide structures formed by the myelin sheath merged in fluids. The propagation time is mainly cost on the duration for triggering EM pulses at nodes of Ranvier. The result clearly reveals the evolution of axons from the unmyelinated to the myelinated, which has remarkably enhanced the propagation efficiency by increasing the thickness of myelin sheath.

Xue, Jiongwei

2012-01-01

 
 
 
 
101

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

Energy Technology Data Exchange (ETDEWEB)

The aim of this investigation was to study binding of ALA by brain myelin under normal conditions and under the influence of lead and benzene. Rabbits of three different groups were given an intercranial injection of /sup 14/C-ALA (50 microCi) in physiological saline in a volume of 0.25 ml. The myelin fraction was obtained by differential centrifugation and the /sup 14/C-ALA in it was assayed on an LKB liquid scintillation counter. By determining the quantity of exogenous /sup 14/C-ALA bound with myelin, the authors found that myelin of white matter in the brain contains more of the acid than myelin of the gray matter. Data on binding of /sup 14/C-ALA calculated per milligram of each group of myelin proteins isolated is given.

Muzyka, V.I.; Bogovskii, L.A.

1986-03-01

102

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

103

Neuron-oligodendrocyte myelination co-culture derived from embryonic rat spinal cord and cerebral cortex  

Digital Repository Infrastructure Vision for European Research (DRIVER)

An in vitro myelination model derived from rat central nervous system (CNS) remains to be established. Here, we describe a simple and reproducible myelination culture method using dissociated neuron-oligodendrocyte (OL) co-cultures from either the embryonic day 16 (E16) rat spinal cord or cerebral cortex. The dissociated cells are plated directly on poly-L-lysine-coated cover slips and maintained in a modified myelination medium that supports both OL and neuron differentiation. The spinal cor...

Pang, Yi; Zheng, Baoying; Kimberly, Simpson L.; Cai, Zhengwei; Rhodes, Philip G.; Lin, Rick C. S.

2012-01-01

104

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

105

The phosphoinositide signaling cycle in myelin requires cooperative interaction with the axon.  

Science.gov (United States)

Previous studies on the origin of myelin phosphoinositides involved in signaling mechanisms indicated axon to myelin transfer of phosphatidylinositol followed by myelin-localized incorporation of axon-derived phosphate groups into phosphatidylinositol 4-monophosphate and phosphatidylinositol 4,5-bisphosphate. This is in agreement with other studies showing the presence of phosphorylating activity in myelin that converts phosphatidylinositol into the mono-and diphospho derivatives. It was also found that the second messenger, inositol 1,4,5-trisphosphate, is hydrolyzed to inositol 1,4-bisphosphate by a myelin-localized enzyme. The present study was undertaken to determine the locus of the remaining reactions leading to formation of free inositol and completion of the cycle by resynthesis of phosphatidylinositol. The latter reaction was found to occur preferentially in isolated axons, and to a limited extent if at all in myelin. On the other hand, hydrolytic reactions which sequentially convert inositol 1,4,5-trisphosphate to inositol 1,4-bisphosphate, inositol 1-phosphate, and free inositol were found to occur more prominently in myelin. Thus, restoration of phosphoinositides following signal-induced breakdown of PIP2 in myelin is seen as requiring metabolic interplay between myelin and axon. PMID:9972871

Chakraborty, G; Drivas, A; Ledeen, R

1999-02-01

106

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, Alexey; Maksimov, G. V.

2011-01-01

107

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

108

X-ray studies on the bilayer structure of trypsin-treated rat brain myelin  

International Nuclear Information System (INIS)

Trypsin-treated rat brain myelin was subjected to biochemical and x-ray studies. Untreated myelin gave rise to a pattern of three rings with a fundamental repeat period of 155 A consisting of two bilayers per repeat period, whereas myelin treated with trypsin showed a fundamental repeat period of 75 A with one bilayer per repeat period. The integrated raw intensity of the h = 4 reflection with respect to the h = 2 reflection is 0.38 for untreated myelin. The corresponding value reduced to 0.23, 0.18, 0.17 for myelin treated with 5, 10, 40 units of trypsin per mg of myelin, respectively, for 30 min at 30 degC. The decrease in relative raw intensity of the higher-order reflection relative to the lower-order reflection is suggestive of a disordering of the phosphate groups upon trypsin treatment or an increased mosaicity of the membrane or a combination of both these effects. However, trypsin treatment does not lead to a complete breakdown of the membrane. The integrated intensity of the h = 1 reflection, though weak, is above the measurable threshold for untreated myelin, whereas the corresponding intensity is below the measurable threshold for trypsin-treated myelin, indicating a possible asymmetric to symmetric transition of the myelin bilayer structure about its centre after trypsin treatment. (author). 24 refs., 4 figs., 1 tab

109

Early myelination in the human fetal lumbosacral spinal cord: characterization by light and electron microscopy.  

Science.gov (United States)

Myelination in the human central nervous system is well documented after 20 weeks of gestation (WOG). However, earlier stages of this process have not been described in detail, although it is assumed that human myelinogenesis is similar to that observed in other animals. We used light and electron microscopy to study myelination in the human lumbosacral spinal cord during the second trimester of gestation. The kinetics of myelin-associated gene expression were analyzed by immunocytochemistry using antibodies to the myelin markers myelin basic protein (MBP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase). These studies show that in 12-13 WOG specimens, occasional MBP-positive processes are found in developing white matter in areas distinct from the root entry zones. At this time, ultrastructural study revealed early investment of axons by glial processes and rare compacted myelin. CNPase staining was qualitatively and quantitatively less than that of MBP. The numbers of MBP- and CNPase-positive myelin sheaths increased with time, and by 24 WOG many were evident in all areas of the spinal cord except in the corticospinal tracts. Ultrastructural study of corresponding areas revealed many thin lamellae of compact myelin. This study provides initial normative data for early human myelination in the lumbosacral spinal cord and may serve as a baseline for future developmental and pathological studies. PMID:1538238

Weidenheim, K M; Kress, Y; Epshteyn, I; Rashbaum, W K; Lyman, W D

1992-03-01

110

Split Trees, Cuttings and Explosions  

Digital Repository Infrastructure Vision for European Research (DRIVER)

This thesis is based on four papers investigating properties of split trees and also introducing new methods for studying such trees. Split trees comprise a large class of random trees of logarithmic height and include e.g., binary search trees, m-ary search trees, quadtrees, median of (2k+1)-trees, simplex trees, tries and digital search trees. Split trees are constructed recursively, using “split vectors”, to distribute n “balls” to the vertices/nodes. The vertices of a split tree m...

Holmgren, Cecilia

2010-01-01

111

The expression patterns of nogo-A, myelin associated glycoprotein and oligodendrocyte myelin glycoprotein in the retina after ocular hypertension : the expression of myelin proteins in the retina in glaucoma  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Nogo-A, a major myelin inhibitory protein, inhibits axon growth and synaptic function in the central nervous system. Glaucoma is a progressive neuropathy as a result of retinal ganglion cell (RGC) death. Synaptic degeneration is thought to be an early pathology of neurodegeneration in glaucoma and precedes RGC loss. Here experimental ocular hypertension model was induced in adult rats with laser coagulation of the episcleral and limbal veins. The expression of Nogo-A, myelin-associated glycop...

Liao, Xx; Chen, D.; Shi, J.; Sun, Yq; Sun, Sj; So, Kf; Fu, Ql

2011-01-01

112

Evaluation of white matter myelin water fraction in chronic stroke?  

Science.gov (United States)

Multi-component T2 relaxation imaging (MCRI) provides specific in vivo measurement of myelin water content and tissue water environments through myelin water fraction (MWF), intra/extra-cellular water fraction (I/EWF) and intra/extracellular and global geometric mean T2 (GMT2) times. Quantitative MCRI assessment of tissue water environments has provided new insights into the progression and underlying white matter pathology in neural disorders such as multiple sclerosis. It has not previously been applied to investigate changes in white matter in the stroke-affected brain. Thus, the purposes of this study were to 1) use MCRI to index myelin water content and tissue water environments in the brain after stroke 2) evaluate relationships between MWF and diffusion behavior indexed by diffusion tensor imaging-based metrics and 3) examine the relationship between white matter status (MWF and fractional anisotropy) and motor behavior in the chronic phase of stroke recovery. Twenty individuals with ischemic stroke and 12 matched healthy controls participated. Excellent to good test/re-test and inter-rater reliability was observed for region of interest-based voxelwise MWF data. Reduced MWF was observed in whole-cerebrum white matter (p MWF in healthy controls. The stroke group also demonstrated increased I/EWF, I/E GMT2 and global GMT2 times for whole-cerebrum white matter. Measures of diffusion behavior were also significantly different in the stroke group across each region investigated (p MWF was not significantly correlated with specific tensor-based measures of diffusion in the PLIC for either group. Fractional anisotropy in the ipsilesional PLIC correlated with motor behavior in chronic stroke. These results provide novel insights into tissue-specific changes within white matter after stroke that may have important applications for the understanding of the neuropathology of stroke. PMID:24179808

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

2013-01-01

113

Evaluation of white matter myelin water fraction in chronic stroke.  

Science.gov (United States)

Multi-component T2 relaxation imaging (MCRI) provides specific in vivo measurement of myelin water content and tissue water environments through myelin water fraction (MWF), intra/extra-cellular water fraction (I/EWF) and intra/extracellular and global geometric mean T2 (GMT2) times. Quantitative MCRI assessment of tissue water environments has provided new insights into the progression and underlying white matter pathology in neural disorders such as multiple sclerosis. It has not previously been applied to investigate changes in white matter in the stroke-affected brain. Thus, the purposes of this study were to 1) use MCRI to index myelin water content and tissue water environments in the brain after stroke 2) evaluate relationships between MWF and diffusion behavior indexed by diffusion tensor imaging-based metrics and 3) examine the relationship between white matter status (MWF and fractional anisotropy) and motor behavior in the chronic phase of stroke recovery. Twenty individuals with ischemic stroke and 12 matched healthy controls participated. Excellent to good test/re-test and inter-rater reliability was observed for region of interest-based voxelwise MWF data. Reduced MWF was observed in whole-cerebrum white matter (p MWF in healthy controls. The stroke group also demonstrated increased I/EWF, I/E GMT2 and global GMT2 times for whole-cerebrum white matter. Measures of diffusion behavior were also significantly different in the stroke group across each region investigated (p MWF was not significantly correlated with specific tensor-based measures of diffusion in the PLIC for either group. Fractional anisotropy in the ipsilesional PLIC correlated with motor behavior in chronic stroke. These results provide novel insights into tissue-specific changes within white matter after stroke that may have important applications for the understanding of the neuropathology of stroke. PMID:24179808

Borich, M R; Mackay, A L; Vavasour, I M; Rauscher, A; Boyd, L A

2013-01-01

114

Active gene repression by the Egr2.NAB complex during peripheral nerve myelination.  

Science.gov (United States)

The Egr2/Krox20 transactivator is required for activation of many myelin-associated genes during peripheral nerve myelination by Schwann cells. However, recent work has indicated that Egr2 not only activates genes required for peripheral nerve myelination but may also be involved in gene repression. The NAB (NGFI-A/Egr-binding) corepressors interact with Egr2 and are required for proper coordination of myelin formation. Therefore, NAB proteins could mediate repression of some Egr2 target genes, although direct repression by Egr2 or NAB proteins during myelination has not been demonstrated. To define the physiological role of NAB corepression in gene repression by Egr2, we tested whether the Egr2.NAB complex directly repressed specific target genes. A screen for NAB-regulated genes identified several (including Id2, Id4, and Rad) that declined during the course of peripheral nerve myelination. In vivo chromatin immunoprecipitation analysis of the myelinating sciatic nerve was used to show developmental association of both Egr2 and NAB2 on the Id2, Id4, and Rad promoters as they were repressed during the myelination process. In addition, NAB2 represses transcription by interaction with the chromodomain helicase DNA-binding protein 4 (CHD4) subunit of the nucleosome remodeling and deacetylase chromatin remodeling complex, and we demonstrate that CHD4 occupies NAB-repressed promoters in a developmentally regulated manner in vivo. These results illustrate a novel aspect of genetic regulation of peripheral nerve myelination by showing that Egr2 directly represses genes during myelination in conjunction with NAB corepressors. Furthermore, repression of Id2 was found to augment activation of Mpz (myelin protein zero) expression. PMID:18456662

Mager, Gennifer M; Ward, Rebecca M; Srinivasan, Rajini; Jang, Sung-Wook; Wrabetz, Lawrence; Svaren, John

2008-06-27

115

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

116

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

Science.gov (United States)

Axon-to-myelin transfer of lipids precursors have been studied in the rabbit optic system by intraocular injection of [32P]orthophosphate, [14C]glycerol and [3H]glycerol. Choline and ethanolamine phosphoglycerides and myelin showed increasing [32P]-radioactivity between 7 and 21 days following injection, while [3H]- and [14C]-radioactivities remained relative constant. The latter radioactivities decreased, however, in all the axon- and axolemma-enriched fractions during the same period. These findings supported the concept that a portion of substances undergoing axonal transport enters the pool of myelin lipids by two mechanisms: transcellular transfer of intact lipid and axon-myelin transfer of precursors which are re-utilized for lipid biosynthesis by myelin-localized enzymes. The present study shows that inorganic phosphate, possibly generated by catabolic activity within the axon, is able to enter myelin and participate in the re-utilization mechanism as previously described for serine, choline and acyl chains. The relative invariance of the 3H:14C ratio suggested that the majority of glycerol is not re-utilized in this manner but probably enters myelin through transfer of intact lipid. These and earlier results suggest a possible form of metabolic dependence of myelin on tropine substances from the axon. PMID:6192870

Ledeen, R W; Haley, J E

1983-06-20

117

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

Science.gov (United States)

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.

Huang, Wei-Chin; Liao, Jiunn-Der; Lin, Chou-Ching K.; Ju, Ming-Shaung

2011-07-01

118

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

International Nuclear Information System (INIS)

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

119

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

Directory of Open Access Journals (Sweden)

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

AlanPeters

2009-07-01

120

Targeting of myelin protein zero in a spontaneous autoimmune polyneuropathy.  

Science.gov (United States)

Elimination of the costimulatory molecule B7-2 prevents autoimmune diabetes in NOD mice, but leads to the development of a spontaneous autoimmune polyneuropathy (SAP), which resembles the human disease chronic inflammatory demyelinating polyneuropathy (CIDP). In this study, we examined the immunopathogenic mechanisms in this model, including identification of SAP Ags. We found that B7-2-deficient NOD mice exhibit changes in cytokine and chemokine gene expression in spleens over time. There was an increase in IL-17 and a decrease in IL-10 transcript levels at 4 mo (preclinical phase), whereas IFN-gamma expression peaked at 8 mo (clinical phase). There was also an increase in transcript levels of Th1 cytokines, CXCL10, and RANTES in sciatic nerves of mice that developed SAP. Splenocytes from SAP mice exhibited proliferative and Th1 cytokine responses to myelin P0 (180-199), but not to other P0 peptides or P2 (53-78). Adoptive transfer of P0-reactive T cells generated from SAP mice induced neuropathy in four of six NOD.SCID mice. Data from i.v. tolerance studies indicate that myelin P0 is one of the autoantigens targeted by T cells in SAP in this model. The expression of P0 by peri-islet Schwann cells provides a potential mechanism linking islet autoimmunity and inflammatory neuropathy. PMID:19050296

Kim, Hye-Jung; Jung, Cha-Gyun; Jensen, Mark A; Dukala, Danuta; Soliven, Betty

2008-12-15

 
 
 
 
121

Japanese neuropathy patients with peripheral myelin protein-22 gene aneuploidy  

Energy Technology Data Exchange (ETDEWEB)

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

122

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

123

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.)

124

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.)

125

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

Energy Technology Data Exchange (ETDEWEB)

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.)

Carmody, Dennis P. [Robert Wood Johnson Medical School, New Brunswick, NJ (United States); Dunn, Stanley M.; Boddie-Willis, Akiza S. [The State University of New Jersey, Rutgers, New Brunswick, NJ (United States); DeMarco, J. Kevin [Laurie Imaging Center, New Brunswick, NJ (United States); Lewis, Michael [Robert Wood Johnson Medical School, New Brunswick, NJ (United States); Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Institute for the Study of Child Development, New Brunswick (United States)

2004-09-01

126

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

127

Photon splitting cross sections  

International Nuclear Information System (INIS)

The differential cross section for photon splitting (scattering of one photon into two photons) in a Coulomb field, obtained earlier by Shima, has been integrated numerically to yield various differential cross sections. Energy spectra differential with respect to the energy of one of the outgoing photons are presented for several values of the primary photon energy. Selected examples of recoil-momentum distributions and some interesting doubly or multiply differential cross sections are also given. Values for the total cross section are obtained essentially for all energies. The screening effect caused by atomic electrons is also taken into account, and is found to be important for high energies, as in e-e+ pair production Comparisons with various approximate results obtained by previous authors mostly show fair agreement. We also discuss the possibilities for experimental detection and find the most promising candidate to be a measurement of both photons, and their energies, at a moderately high energy. (Auth.)

128

Myelin contains neutral sphingomyelinase activity that is stimulated by tumor necrosis factor-alpha.  

Science.gov (United States)

Purified myelin from mouse brain was found to contain two forms of neutral sphingomyelinase, one Mg2+ dependent and the other Mg2+ independent. The former had a pH optimum of 7.5 and Km of 0.35 mM, whereas the corresponding values for the latter were pH 8.0 and Km 3.03 mM. Specific activity of the Mg(2+)-dependent enzyme showed a rostral-caudal gradient, ranging from 75 nmol/mg protein/hr in myelin from cerebral hemispheres to 21 nmol/mg protein/hr in myelin from spinal cord. Relative specific activity was approximately 20% that of brain stem or cerebral hemisphere homogenate. Treatment of myelin with taurocholate or high salt concentration did not significantly reduce activity of the Mg(2+)-dependent enzyme. The activity of that enzyme did not change with time or in the presence or absence of protease inhibitors; by contrast, that of Mg(2+)-independent enzyme decreased sharply in the absence of protease inhibitors but rose in their presence. To test for the effect of tumor necrosis factor-alpha (TNF alpha) on myelin sphingomyelinase, mouse brain myelin was labeled in vivo by intracerebral injection of [3H]acetate into 18-20-day-old mice. After 40 hr, brain stems were removed, minced, and treated with TNF alpha in Krebs-Ringer solution, after which myelin was immediately isolated. Separation and counting of individual lipids revealed TNF alpha treatment to cause increased labeling of myelin ceramide and cholesterol ester with concomitant decrease in myelin sphingomyelin. Western blotting of myelin proteins using antibodies to the two TNF alpha receptors as probes revealed the presence of the p75 receptor. Implications of these findings in relation to possible mechanisms of autoimmune demyelination are discussed. PMID:9364332

Chakraborty, G; Ziemba, S; Drivas, A; Ledeen, R W

1997-11-01

129

NF-?B signaling regulates myelination in the CNS  

Directory of Open Access Journals (Sweden)

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

130

Altered brain myelin sheath morphology after rewarming in situ.  

Science.gov (United States)

In this study cerebral ultrastructure was examined in an in vivo rat model, after rewarming from profound hypothermia (15-13 degrees C). Animals held at 37 degrees C served as controls. After rewarming, brains were examined by electron microscope. Micrographs were taken randomly, analyzed anonymously, and quantified by morphometry. Serum analysis of the stress marker S-100beta was carried out in identical groups. The most striking findings in rewarmed animals, when compared to controls, were alterations of myelin sheaths (p<.008) and elevated S-100beta (p<.0001). This indicates that cells in the central nervous system are susceptible to injury in an experimental model of accidental hypothermia and rewarming. PMID:20192705

Dietrichs, E S; Lindal, S; Naesheim, T; Ingebrigtsen, T; Tveita, T

2010-04-01

131

Split SUSY Radiates Flavor  

CERN Document Server

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

132

From Pet to Split  

CERN Document Server

Various forms of the polynomial ergodic theorem (PET) which attracted substantial attention in ergodic theory study the limits of expressions having the form $1/N\\sum_{n=1}^NT^{q_1(n)}f_1... T^{q_\\ell (n)}f_\\ell$ where $T$ is a weakly mixing measure preserving transformation, $f_i$'s are bounded measurable functions and $q_i$'s are polynomials taking on integer values on the integers. Motivated partially by these results we obtain a central limit theorem for expressions of the form $1/\\sqrt{N}\\sum_{n=1}^N (X_1(q_1(n))X_2(q_2(n))... X_\\ell(q_\\ell(n))-a_1a_2... a_\\ell)$ (sum-product limit theorem--SPLIT) where $X_i$'s are fast $\\alpha$-mixing bounded stationary processes, $a_j=EX_j(0)$ and $q_i$'s are positive functions taking on integer values on integers with some growth conditions which are satisfied, for instance, when $q_i$'s are polynomials of growing degrees. This result can be applied to the case when $X_i(n)=T^nf_i$ where $T$ is a mixing subshift of finite type, a hyperbolic diffeomorphism or an expand...

Kifer, Yuri

2008-01-01

133

Split-ball resonator  

CERN Document Server

We introduce a new concept of split-ball resonator and demonstrate a strong omnidirectional magnetic dipole response for both gold and silver spherical plasmonic nanoparticles with nanometer-scale cuts. Tunability of the magnetic dipole resonance throughout the visible spectral range is demonstrated by a change of the depth and width of the nanoscale cut. We realize this novel concept experimentally by employing the laser-induced transfer method to produce near-perfect spheres and helium ion beam milling to make cuts with the nanometer resolution. Due to high quality of the spherical particle shape, governed by strong surface tension forces during the laser transfer process, and the clean, straight side walls of the cut made by helium ion milling, magnetic resonance is observed at 600 nm in gold and at 565 nm in silver nanoparticles. Structuring arbitrary features on the surface of ideal spherical resonators with nanoscale dimensions provides new ways of engineering hybrid resonant modes and ultra-high near-f...

Kuznetsov, Arseniy I; Fu, Yuan Hsing; Viswanathan, Vignesh; Rahmani, Mohsen; Valuckas, Vytautas; Kivshar, Yuri; Pickard, Daniel S; Lukiyanchuk, Boris

2014-01-01

134

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

135

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

136

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

137

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

138

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

Directory of Open Access Journals (Sweden)

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

139

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

140

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

Science.gov (United States)

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

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

2011-11-01

 
 
 
 
141

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

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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

2014-01-01

142

Progesterone and nestorone promote myelin regeneration in chronic demyelinating lesions of corpus callosum and cerebral cortex.  

Science.gov (United States)

Multiple Sclerosis affects mainly women and consists in intermittent or chronic damages to the myelin sheaths, focal inflammation, and axonal degeneration. Current therapies are limited to immunomodulators and antiinflammatory drugs, but there is no efficient treatment for stimulating the endogenous capacity of myelin repair. Progesterone and synthetic progestins have been shown in animal models of demyelination to attenuate myelin loss, reduce clinical symptoms severity, modulate inflammatory responses and partially reverse the age-dependent decline in remyelination. Moreover, progesterone has been demonstrated to promote myelin formation in organotypic cultures of cerebellar slices. In the present study, we show that progesterone and the synthetic 19-nor-progesterone derivative Nestorone® promote the repair of severe chronic demyelinating lesions induced by feeding cuprizone to female mice for up to 12 weeks. Progesterone and Nestorone increase the density of NG2(+) oligodendrocyte progenitor cells and CA II(+) mature oligodendrocytes and enhance the formation of myelin basic protein (MBP)- and proteolipid protein (PLP)-immunoreactive myelin. However, while demyelination in response to cuprizone was less marked in corpus callosum than in cerebral cortex, remyelination appeared earlier in the former. The remyelinating effect of progesterone was progesterone receptor (PR)-dependent, as it was absent in PR-knockout mice. Progesterone and Nestorone also decreased (but did not suppress) neuroinflammatory responses, specifically astrocyte and microglial cell activation. Therefore, some progestogens are promising therapeutic candidates for promoting the regeneration of myelin. GLIA 2015;63:104-117. PMID:25092805

El-Etr, Martine; Rame, Marion; Boucher, Celine; Ghoumari, Abdel M; Kumar, Narender; Liere, Philippe; Pianos, Antoine; Schumacher, Michael; Sitruk-Ware, Regine

2015-01-01

143

Astrocytes regulate myelin clearance through recruitment of microglia during cuprizone-induced demyelination.  

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Recent evidence suggests that astrocytes play an important role in regulating de- and remyelination in multiple sclerosis. The role of astrocytes is controversial, and both beneficial as well as detrimental effects are being discussed. We performed loss-of-function studies based on astrocyte depletion in a cuprizone-induced rodent model of demyelination. This led to strong astrogliosis accompanied by microgliosis and demyelination in C57BL/6 wild-type mice. Ablation of astrocytes in glial fibrillary acidic protein-thymidine kinase transgenic mice was associated with a failure of damaged myelin removal and a consecutive delay in remyelination. Despite oligodendrocyte death, myelin was still present, but ultrastructual investigations showed that the myelin structure was loosened and this damaged myelin did not protect axons. These alterations were associated with a decrease in microglial activation. Thus, our results show that astrocyte loss does not prevent myelin damage, but clearance of damaged myelin through recruitment of microglia is impaired. Further studies suggest that this process is regulated by the chemokine CXCL10. As a consequence of the delayed removal of myelin debris, remyelination and oligodendrocyte precursor cell proliferation were impaired. Experiments omitting the influence of myelin debris demonstrated an additional beneficial effect of astrocytes on oligodendrocyte regeneration during remyelination. In conclusion, these data demonstrate for the first time in vivo that astrocytes provide the signal environment that forms the basis for the recruitment of microglia to clear myelin debris, a process required for subsequent repair mechanisms. This is of great importance to understanding regenerative processes in demyelinating diseases such as multiple sclerosis. PMID:23266461

Skripuletz, Thomas; Hackstette, Diane; Bauer, Katharina; Gudi, Viktoria; Pul, Refik; Voss, Elke; Berger, Katharina; Kipp, Markus; Baumgärtner, Wolfgang; Stangel, Martin

2013-01-01

144

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

145

MR imaging of the various stages of normal myelination during the first year of life  

International Nuclear Information System (INIS)

The normal process of myelination of the brain mainly occurs during the first year of life. This process as known from histology can be visualized by MRI. Because of the very long T1 and T2 of immature brain tissue it is necessary to use adjusted pulse sequences with a long TR in order to obtain sufficient tissue contrast. With long TR SE images five stages can be recognized in the process of normal myelination and brain maturation. During the first month of life long TR short TE SE images show what are believed to be myelinated structures by correlation with published histological studies with a high signal intensity, unmyelinated white matter with a low signal intensity and gray matter with an intermediate signal intensity. The signal intensity of unmyelinated and myelinated white matter is reversed on long TR long TE SE images. In the course of a few weeks the signal intensity of unmyelinated white matter becomes high and the signal intensity of myelinated white matter becomes low also on long TR short TE SE images. These changes are believed to be caused by a loss of water and a change in chemical composition of brain tissue just prior to the onset of a wave of myelination. With progression of myelination the signal intensity of white matter changes from high to intermediate to low. These changes result in stages of isointensity, first in the central parts of the brain, later in the lobar parts. At the end of the first year the adult contrast pattern is reached inr the adult contrast pattern is reached in all parts of the brain. IR images are also able to depict the progress of myelination, but appear to be less sensitive to subtle changes in the degree of myelination. The precise normal values for the five stages depend on the magnetic field strength and the pulse sequences used. (orig.)

146

Purinergic signaling mediated by P2X7 receptors controls myelination in sciatic nerves.  

Science.gov (United States)

Adenosine-5'-triphosphate, the physiological ligand of P2X receptors, is an important factor in peripheral nerve development. P2X7 receptor is expressed in Schwann cells (SCs), but the specific effects of P2X7 purinergic signaling on peripheral nerve development, myelination, and function are largely unknown. In this study, sciatic nerves from P2X7 knockout mice were analyzed for altered expression of myelin-associated proteins and for alterations in nerve morphology. Immunohistochemical analyses revealed that, in the wild-type peripheral nerves, the P2X7 receptor was localized mainly in myelinating SCs, with only a few immunopositive nonmyelinating SCs. Complete absence of P2X7 receptor protein was confirmed in the sciatic nerves of the knockout mice by Western blot and immunohistochemistry. Western blot analysis revealed that expression levels of the myelin proteins protein zero and myelin-associated glycoprotein are reduced in P2X7 knockout nerves. In accordance with the molecular results, transmission electron microscopy analyses revealed that P2X7 knockout nerves possess significantly more unmyelinated axons, contained in a higher number of Remak bundles. The myelinating/nonmyelinating SC ratio was also decreased in knockout mice, and we found a significantly increased number of irregular fibers compared with control nerves. Nevertheless, the myelin thickness in the knockout was unaltered, suggesting a stronger role for P2X7 in determining SC maturation than in myelin formation. In conclusion, we present morphological and molecular evidence of the importance of P2X7 signaling in peripheral nerve maturation and in determining SC commitment to a myelinating phenotype. PMID:24903685

Faroni, A; Smith, R J P; Procacci, P; Castelnovo, L F; Puccianti, E; Reid, A J; Magnaghi, V; Verkhratsky, A

2014-10-01

147

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

International Nuclear Information System (INIS)

High-affinity muscarinic cholinergic receptors were detected in myelin purified from rat brain stem with use of the radioligands 3H-N-methylscopolamine (3H-NMS), 3H-quinuclidinyl benzilate (3H-QNB), and 3H-pirenzepine. 3H-NMS binding was also present in myelin isolated from corpus callosum. In contrast, several other receptor types, including alpha 1- and alpha 2-adrenergic receptors, present in the starting brain stem, were not detected in myelin. Based on Bmax values from Scatchard analyses, 3H-pirenzepine, a putative M1 selective ligand, bound to about 25% of the sites in myelin labeled by 3H-NMS, a nonselective ligand that binds to both M1 and M2 receptor subtypes. Agonist affinity for 3H-NMS binding sites in myelin was markedly decreased by Gpp(NH)p, indicating that a major portion of these receptors may be linked to a second messenger system via a guanine-nucleotide regulatory protein. Purified myelin also contained adenylate cyclase activity; this activity was stimulated several fold by forskolin and to small but significant extents by prostaglandin E1 and the beta-adrenergic agonist isoproterenol. Myelin adenylate cyclase activity was inhibited by carbachol and other muscarinic agonists; this inhibition was blocked by the antagonist atropine. Levels in myelin of muscarinic receptors were 20-25% and those of forskolin-stimulated adenylate cyclase 10% of the valuesulated adenylate cyclase 10% of the values for total particulate fraction of whole brain stem. These levels in myelin are appreciably greater than would be predicted on the basis of contamination. Also, additional receptors and adenylate cyclase, added by mixing nonmyelin tissue with whole brain stem, were quantitatively removed during the purification procedure

148

Diabetes-induced myelin abnormalities are associated with an altered lipid pattern: protective effects of LXR activation[S  

Science.gov (United States)

Diabetic peripheral neuropathy (DPN) is characterized by myelin abnormalities; however, the molecular mechanisms underlying such deficits remain obscure. To uncover the effects of diabetes on myelin alterations, we have analyzed myelin composition. In a streptozotocin-treated rat model of diabetic neuropathy, analysis of sciatic nerve myelin lipids revealed that diabetes alters myelin's phospholipid, FA, and cholesterol content in a pattern that can modify membrane fluidity. Reduced expression of relevant genes in the FA biosynthetic pathway and decreased levels of the transcriptionally active form of the lipogenic factor sterol-regulatory element binding factor-1c (SREBF-1c) were found in diabetic sciatic nerve. Expression of myelin's major protein, myelin protein zero (P0), was also suppressed by diabetes. In addition, we confirmed that diabetes induces sciatic nerve myelin abnormalities, primarily infoldings that have previously been associated with altered membrane fluidity. In a diabetic setting, synthetic activator of the nuclear receptor liver X receptor (LXR) increased SREBF-1c function and restored myelin lipid species and P0 expression levels to normal. These LXR-modulated improvements were associated with restored myelin structure in sciatic nerve and enhanced performance in functional tests such as thermal nociceptive threshold and nerve conduction velocity. These findings demonstrate an important role for the LXR-SREBF-1c axis in protection from diabetes-induced myelin abnormalities. PMID:22158827

Cermenati, Gaia; Abbiati, Federico; Cermenati, Solei; Brioschi, Elisabetta; Volonterio, Alessandro; Cavaletti, Guido; Saez, Enrique; De Fabiani, Emma; Crestani, Maurizio; Garcia-Segura, Luis M.; Melcangi, Roberto C.; Caruso, Donatella; Mitro, Nico

2012-01-01

149

Delayed myelination in a rhizomelic chondrodysplasia punctata case: MR spectroscopy findings.  

Science.gov (United States)

Rhizomelic chondrodysplasia punctata is a member of genetic peroxisomal disorders. Delayed myelination, which is probably related to the inadequacy of plasmalogens biosynthesis, is an important feature of this disorder. Direct assessment of neuropathologic aspects of RCDP syndrome such as neuronal degeneration and delayed myelination is possible with MR spectroscopy. In this report, MR spectroscopy findings (decreased Cho/Cr and increased Ins-Gly/Cr ratios and increased levels of mobile lipids) of a rhizomelic chondrodysplasia punctata case supporting delayed myelination are presented. This is the second report of MR spectroscopy examination of the specific brain metabolic changes associated with rhizomelic chondrodysplasia punctata. PMID:12620550

Alkan, Alpay; Kutlu, Ramazan; Yakinci, Cengiz; Sigirci, Ahmet; Aslan, Mehmet; Sarac, Kaya

2003-01-01

150

Generalized Split-Octonion Electrodynamics  

CERN Document Server

Starting with the usual definitions of octonions and split octonions in terms of Zorn vector matrix realization, we have made an attempt to write the consistent form of generalized Maxwell's equations in presence of electric and magnetic charges (dyons). We have thus written the generalized potential, generalized field, and generalized current of dyons in terms of split octonions and accordingly the split octonion forms of generalized Dirac Maxwell's equations are obtained in compact and consistent manner. This theory reproduces the dynamic of electric (magnetic) in the absence of magnetic (electric) charges.

Chanyal, B C; Negi, O P S

2010-01-01

151

Photocatalytic water splitting  

Science.gov (United States)

New photocatalystic materials Ti-In oxy(nitride) and nanosized Ru-loaded strontium titanate doped with Rh (Ru/SrTiO3:Rh) have been synthesized. The textural and surface characteristic properties were studied by nitrogen BET analysis, diffuse reflectance UV-vis spectroscopy, X-ray photoelectron spectroscopy, transmission electron microscopy, scanning electron microscopy and powder XRD. The photocatalytic properties were enhanced by the binary metal oxides of titanium dioxide and indium oxide. The XRD patterns confirmed the oxygen exchange between two metal oxides during the synthesis. Moreover, the presence of titanium dioxide can help the stabilization of InN during hot NH3(g) treatment. On the other hand, the particle sizes of aerogel prepared Ru/SrTiO3:Rh varied from 12 to 25 nm depended on different Rh doping. A mixture of ethanol and toluene was found to be the best binary solvent for supercritical drying, which yielded a SrTiO3 sample with a surface area of 130 m2/g and an average crystallite size of 6 nm. Enhanced photocatalytic hydrogen production under UV-vis light irradiation was achieved by ammonolysis of intimately mixed titanium dioxide and indium oxide at high temperatures. Gas chromatography monitored steadily the formation of hydrogen when sacrificial (methanol or ethanol) were present. XRD patterns confirmed that the photocatalysts maintain crystalline integrity before and after water splitting experiments. Moreover, the presence of InN may be crucial for the increase of hydrogen production activities. These Ru/SrTiO3:Rh photocatalysts have been studied for photocatalytic hydrogen production under visible light. The band gap of the bulk SrTiO 3 (3.2 eV) does not allow response to visible light. However, after doping with rhodium and loaded with ruthenium, the modified strontium titanates can utilize light above 400 nm due to the formation of valence band or electron donor levels inside of the band gap. Moreover, the surface areas of these photocatalysts are much larger than conventional solid-state synthesized samples (1--2 m2/g), which yielded more Ru loading and reaction sites. The aerogel and hydrothermal synthesized samples required basic (alkaline) conditions for hydrogen generation facilitation compared with acidic conditions for conventional solid-state samples.

Kuo, Yenting

152

Focally folded myelin in Charcot-Marie-Tooth type 1B disease is associated with Asn131Lys mutation in myelin protein zero gene: short report.  

Science.gov (United States)

Charcot-Marie-Tooth disease type 1B (CMT1B) is a demyelinating neuropathy inherited as an autosomal dominant trait. The majority of CMT1B cases are caused by mutations in the myelin protein zero (P0) gene (MPZ). Only a few mutations in MPZ gene have been reported to be associated with focally folded myelin sheaths. We have studied five patients from one family with five generations, affected by CMT1B disease. The morphological studies of sural nerve biopsy performed in the proband revealed fibers with focally folded myelin. DNA sequencing analysis showed the Asn131Lys mutation in the MPZ gene in three members of the affected family. PMID:12940837

Kocha?ski, A; Drac, H; Jedrzejowska, H; Hausmanowa-Petrusewicz, I

2003-09-01

153

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.

154

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

155

The MR evaluation of normal children and disorders of neuronal migration and myelination  

International Nuclear Information System (INIS)

Magnetic resonance imaging (MRI) scans were available for review in 10 healthy children (aged one month-4 years) and 5 pediatric patients with disorders of neuronal migration and myelination during the developing process (aged 2-10 years). Such disorders in the 5 patients were megalencephaly, pachygyria, heterotopia, delayed myelination, and dysmyelinating disease. In the heathy group, myelination was matured during the first two years on MRI. This was depicted earlier on T1-weighted images than T2-weighted images (7 months vs one year and 9 months after birth). Abnormality in myelination was clearly visualized on T2-weighted images. Furthermore, MRI had the ability to detect morphologically the associated brain malformations. Thus, MRI may be a promising diagnostic procedure of choice in pediatric brain abnormality. (N.K.)

156

Soluble Mannosylated Myelin Peptide Inhibits the Encephalitogenicity of Autoreactive T Cells during Experimental Autoimmune Encephalomyelitis  

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We have previously shown that immunization with a mannosylated myelin peptide in complete adjuvant induces tolerance instead of disease in experimental autoimmune encephalomyelitis (EAE), a rodent model for multiple sclerosis. In this report we demonstrate that treatment with a soluble mannosylated epitope of proteolipid protein (M-PLP139-151) significantly inhibits disease mediated by autoreactive myelin-specific T cells during EAE. Treatment with M-PLP139-151, applied in different EAE model...

Kel, Junda; Oldenampsen, Judith; Luca, Mariken; Drijfhout, Jan Wouter; Koning, Frits; Nagelkerken, Lex

2007-01-01

157

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

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

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

2009-01-01

158

Function and distribution of three types of rectifying channel in rat spinal root myelinated axons  

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1. The nature, distribution and function of rectifying channels in rat spinal root myelinated axons has been assessed with selective blocking agents and a variety of intracellular and extracellular recording techniques. 2. The electrotonic responses of roots poisoned with tetrodotoxin (TTX) to constant current pulses had fast (rise time much less than 1 ms) and slow components, which were interpreted in terms of Barrett & Barrett's (1982) revised cable model for myelinated nerve. Depolarizati...

Baker, M.; Bostock, Hugh; Grafe, Peter; Martius, P.

1987-01-01

159

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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 chan...

Carmody, Dennis P.; Dunn, Stanley M.; Boddie-willis, Akiza S.; Demarco, J. Kevin; Lewis, Michael

2004-01-01

160

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

Zhang, Chuan-li; Rodenkirch, Lance; Schultz, Justin R.; Chiu, Shing Yan

2012-01-01

 
 
 
 
161

Quantification of myelin basic protein in the human fetal spinal cord during the midtrimester of gestation.  

Science.gov (United States)

The amount of myelin basic protein (MBP) was quantified in human fetal spinal cords from 12 to 24 gestational weeks (GW). MBP expression was determined by Northern blot, quantitative immunoblot, and immunocytochemistry. The development of compact myelin was analyzed by electron microscopy. Thirty-eight human fetal spinal cords were obtained after elective termination of intrauterine pregnancies from healthy women. Northern blot analysis showed a 15.8-fold increase in MBP mRNA between 12 and 18 GW. From 18 to 24 GW, MBP mRNA increased by 2.2-fold. The mRNA data paralleled immunoblot results that showed a 90.5-fold increase in MBP (0.147 ng/mg to 13.3 ng/mg tissue) between 12 and 18 GW and an approximately 11.5-fold increase between 18 and 24 GW (13.3 ng/mg to 154 ng/mg tissue). Immunocytochemical analysis also showed increased staining for MBP with advancing gestational age. At 12 GW, MBP immunoreactivity was observed in all three spinal cord funiculi. By 18 GW, MBP was expressed throughout the spinal cord white matter with the exception of the lateral corticospinal tracts and in the rostral levels of the fasciculus gracilis. With respect to myelin, at 12 GW, rare, noncompacted myelin lamellae were observed by electron microscopy. By 18 GW, discrete areas of compact myelin were observed in areas that showed MBP immunoreactivity, and at 24 GW, compact myelin was prominent throughout the white matter of the spinal cord. This study demonstrates a quantitative increase in MBP expression that is associated with myelin formation during the second trimester of human gestation. This information may provide normative data that can aid in the diagnosis of myelin disorders of the preterm, neonatal, and pediatric spinal cord. PMID:8951645

Grever, W E; Chiu, F C; Tricoche, M; Rashbaum, W K; Weidenheim, K M; Lyman, W D

1996-12-01

162

The molecular architecture of myelinated peripheral nerves is supported by calorie restriction with aging  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Peripheral nerves from aged animals exhibit features of degeneration, including marked fiber loss, morphological irregularities in myelinated axons and notable reduction in the expression of myelin proteins. To investigate how protein homeostatic mechanisms change with age within the peripheral nervous system, we isolated Schwann cells from the sciatic nerves of young and old rats. The responsiveness of cells from aged nerves to stress stimuli is weakened, which in part may account for the ob...

Rangaraju, Sunitha; Hankins, David; Madorsky, Irina; Madorsky, Evgenia; Lee, Wei-hua; Carter, Christy S.; Leeuwenburgh, Christiaan; Notterpek, Lucia

2009-01-01

163

Myelin water imaging reflects clinical variability in multiple sclerosis.  

Science.gov (United States)

Whilst MRI is routinely used for the assessment and diagnosis of multiple sclerosis, there is poor correspondence between clinical disability in primary progressive multiple sclerosis (PPMS) patients and conventional MRI markers of disease activity (e.g., number of enhancing lesions). As PPMS patients show diffuse and global myelin loss, the aim of this study was to evaluate the efficacy of whole-brain myelin water fraction (MWF) imaging in PPMS. Specifically, we sought to use full-brain analysis techniques to: 1) determine the reproducibility of MWF estimates in PPMS brain; 2) compare MWF values in PPMS brain to healthy controls; and 3) establish the relationship between MWF and clinical disability, regionally and globally throughout the brain. Seventeen PPMS patients and seventeen age-matched controls were imaged using a whole-brain multi-component relaxation imaging technique to measure MWF. Analysis of MWF reduction was performed on three spatial levels: 1) histogram; 2) white matter skeleton; and 3) voxel-wise at the single-subject level. From histogram analysis, PPMS patients had significantly reduced global normal appearing white matter MWF (6%, p=0.04) compared to controls. Focal lesions showed lower MWF values than white matter in controls (61%, pMWF was diffusely reduced throughout the PPMS brain, with significant correlations between reduced MWF and increased clinical disability (more severe symptoms), as measured by the Expanded Disability Status Scale, within the corpus callosum and frontal, temporal, parietal and occipital white matter. Correlations with the more specific mental and sensory functional system scores were localized to clinically eloquent locations: reduced MWF was significantly associated with increased mental scores in anterior regions (i.e., frontal lobes and genu of the corpus callosum), and increased sensory scores in more posterior regions closer to the sensory cortex. Individual patient MWF maps were also compared to a normative population atlas, which highlighted areas of statistical difference between the individual patient and the population mean. A significant correlation was found between the volume of significantly reduced MWF and clinical disability (p=0.008, R=0.58). Our results show that clinical disability is reflected in particular regions of cerebral white matter that are consistent between subjects, and illustrates a method to examine tissue alteration throughout the brain of individual patients. These results strongly support the use of MWF imaging to evaluate disease activity in PPMS. PMID:22155325

Kolind, Shannon; Matthews, Lucy; Johansen-Berg, Heidi; Leite, M Isabel; Williams, Steven C R; Deoni, Sean; Palace, Jackie

2012-03-01

164

Neuroanatomical localization of myelin basic protein in the late first and early second trimester human foetal spinal cord and brainstem.  

Science.gov (United States)

The temporal and spatial expression of myelin basic protein in the first and second trimester human foetal spinal cord and brainstem from 9 to 20 gestational weeks was determined by immunocytochemistry in sections of cervical, thoracic and lumbosacral levels from 41 human foetal spinal cords and ten brainstems. Myelin basic protein-positive oligodendrocytes were observed peripheral to the ependyma at 9-10 gestational weeks. Oligodendrocytes expressing myelin basic protein were seen at 10-12 gestational weeks in the anterior and lateral funiculi. Myelin basic protein was detected later in the posterior funiculi than in the anterolateral white matter and most spinal cord tracts could not be identified by means of variation in myelin basic protein expression. Myelin basic protein was found in the midline of the brainstem at ten gestational weeks and spread laterally during the second trimester. We conclude that in the human foetal spinal cord, myelin basic protein is present by 10 gestational weeks in the anterolateral cervical spinal cord and midline of the brainstem. It is expressed in a rostral-to-caudal and anterolateral-to-posterior manner in most tracts of the spinal cord. However, an exception to these findings is that the fasciculus gracilis, upon developing into a defined region, had more myelin basic protein-positive cells at the lumbar level than in more rostral regions. Definition of the kinetics of myelin basic protein expression in the normal human foetal spinal cord provides a baseline for study of aberrant myelination and demyelination. PMID:7691995

Weidenheim, K M; Epshteyn, I; Rashbaum, W K; Lyman, W D

1993-07-01

165

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

Science.gov (United States)

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

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

2014-06-01

166

Hierarchy in the ability of T cell epitopes to induce peripheral tolerance to antigens from myelin.  

Science.gov (United States)

Nasal administration of peptide antigens has been shown to induce T cell tolerance. We have investigated the potential for peptide therapy of the autoimmune response to myelin antigens in experimental autoimmune encephalomyelitis (EAE). Three major encephalitogenic epitopes were studied for their ability to induce nasal tolerance to myelin antigens. These included epitopes Ac1-9 and 89-101 of myelin basic protein (MBP) and 139-151 from proteolipid protein (PLP). Peptide Ac1-9 from MBP effectively suppressed responses to both MBP epitopes, following immunization with whole myelin (linked suppression). The N-terminal epitope failed, however, to modify the response to epitope 139-151 of PLP. The second MBP epitope (89-101) was poorly tolerogenic for the immune response to any naturally processed myelin epitope. By contrast, PLP[139-151] was able to induce bystander suppression of T cells responsive to both itself and the two epitopes from MBP. Furthermore, this epitope suppressed EAE induced with peptides derived from MBP and was capable of treating ongoing disease. The mechanism of bystander suppression, mediated by PLP[139-151], did not correlate with an overt switch from the T helper 1 to the T helper 2 phenotype. These results demonstrate how a complex autoimmune disease may be controlled by treatment with a single peptide epitope and reveal a hierarchy in the suppressive properties of different myelin antigens. PMID:9565365

Anderton, S M; Wraith, D C

1998-04-01

167

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

168

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

169

Influence of myelinated retinal nerve fibers on scanning laser polarimetry using variable and enhanced corneal compensation methods.  

Science.gov (United States)

Five eyes with myelinated retinal nerve fibers were imaged using a scanning laser polarimeter with variable corneal compensation and with enhanced corneal compensation (a new research software). Using variable corneal compensation, areas of myelinated retinal nerve fibers uniformly appeared as areas of increased retardation. Using enhanced corneal compensation software, the same myelinated retinal nerve fiber areas adjacent to the optic nerve head appeared as areas of clinically significant thinning of the retinal nerve fiber layer in the superior and inferior quadrants, and as areas of increased retinal nerve fiber layer thickness nasally and temporally. Wedge-shaped myelinated retinal nerve fibers along a retinal nerve fiber bundle and discontinuous to the optic nerve head caused increased retardation with both compensation methods. The results show that influence of myelinated retinal nerve fibers on scanning laser polarimetric results varies according to the compensation method and the retinal location of the myelinated retinal nerve fibers. PMID:16898400

Tóth, Márta; Holló, Gábor

2006-01-01

170

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

171

Splitting methods for Levitron Problems  

CERN Document Server

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

Geiser, Juergen

2012-01-01

172

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

173

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

174

Structural characterization of the human cerebral myelin sheath by small angle x-ray scattering  

International Nuclear Information System (INIS)

Myelin is a multi-lamellar membrane surrounding neuronal axons and increasing their conduction velocity. When investigated by small-angle x-ray scattering (SAXS), the lamellar quasi-periodical arrangement of the myelin sheath gives rise to distinct peaks, which allow the determination of its molecular organization and the dimensions of its substructures. In this study we report on the myelin sheath structural determination carried out on a set of human brain tissue samples coming from surgical biopsies of two patients: a man around 60 and a woman nearly 90 years old. The samples were extracted either from white or grey cerebral matter and did not undergo any manipulation or chemical-physical treatment, which could possibly have altered their structure, except dipping them into a formalin solution for their conservation. Analysis of the scattered intensity from white matter of intact human cerebral tissue allowed the evaluation not only of the myelin sheath periodicity but also of its electronic charge density profile. In particular, the thicknesses of the cytoplasm and extracellular regions were established, as well as those of the hydrophilic polar heads and hydrophobic tails of the lipid bilayer. SAXS patterns were measured at several locations on each sample in order to establish the statistical variations of the structural parameters within a single sample and among different samples. This work demonstrates that a detailed structural analysis of the myelin sheath structural analysis of the myelin sheath can also be carried out in randomly oriented samples of intact human white matter, which is of importance for studying the aetiology and evolution of the central nervous system pathologies inducing myelin degeneration.

175

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

176

Impairment of heme synthesis in myelin as potential trigger of multiple sclerosis.  

Science.gov (United States)

The pathogenesis of multiple sclerosis (MS), a disease characterized by demyelination and subsequent axonal degeneration, is as yet unknown. Also, the nature of the disease is as yet not established, since doubts have been cast on its autoimmune origin. Genetic and environmental factors have been implied in MS, leading to the idea of an overall multifactorial origin. An unexpected role in energizing the axon has been reported for myelin, supposed to be the site of consumption of most of oxygen in brain. Myelin would be able to perform oxidative phosphorylation to supply the axons with ATP, thanks to the expression therein of mitochondrial F(o)F(1)-ATP synthase, and respiratory chains. Interestingly, myelin expresses the pathway of heme synthesis, hence of cytochromes, that rely on heme group, in turn depending on Fe availability. Poisoning by these pollutants shares the common characteristic to bring about demyelination both in animal models and in man. Carbon monoxide (CO) and lead poisoning which cause functional imbalance of the heme group, as well as of heme synthesis, cause myelin damage. On the other hand, a lack of essential metals such as iron and copper, produces dramatic myelin decrease. Myelin is a primary target, of iron shortage, indicating that in myelin Fe-dependent processes are more active than in other tissues. The predominant spread of MS in industrialized countries where pollution by heavy metals, and CO poisoning is widespread, suggests a relationship among toxic action of metal pollutants and MS. According to the present hypothesis, MS can be primarily triggered by environmental factors acting on a genetic susceptibility, while the immune response may be a consequence of a primary oxidative damage due to reactive oxygen species produced consequently to an imbalance of cytochromes and respiratory chains in the sheath. PMID:22398388

Morelli, Alessandro; Ravera, Silvia; Calzia, Daniela; Panfoli, Isabella

2012-06-01

177

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)

178

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

179

Internal nanosecond dynamics in the intrinsically disordered myelin basic protein.  

Science.gov (United States)

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

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

2014-05-14

180

A novel mutation, Thr65Ala, in the MPZ gene in a patient with Charcot-Marie-Tooth type 1B disease with focally folded myelin.  

Science.gov (United States)

Charcot-Marie-Tooth type 1B disease is a demyelinating neuropathy caused by mutations in the Myelin Protein Zero gene. It is inherited in an autosomal dominant fashion. So far only a few patients with a focally folded myelin phenotype on nerve biopsy have been shown to have mutations in the Myelin Protein Zero gene. In this report we describe a Polish patient with Charcot-Marie-Tooth type 1B disease. Sural nerve biopsy demonstrated focally folded myelin. Molecular genetic analysis of the coding region of the Myelin Protein Zero gene revealed a novel mutation, Thr65Ala, in exon 2 of the Myelin Protein Zero gene. PMID:15036333

Kochanski, A; Drac, H; Kabzi?ska, D; Hausmanowa-Petrusewicz, I

2004-03-01

 
 
 
 
181

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. PMID:25104411

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

2014-08-01

182

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

Science.gov (United States)

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

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

2012-12-13

183

Induction of Oligodendrocyte Differentiation and In Vitro Myelination by Inhibition of Rho-Associated Kinase  

Science.gov (United States)

In inflammatory demyelinating diseases such as multiple sclerosis (MS), myelin degradation results in loss of axonal function and eventual axonal degeneration. Differentiation of resident oligodendrocyte precursor cells (OPCs) leading to remyelination of denuded axons occurs regularly in early stages of MS but halts as the pathology transitions into progressive MS. Pharmacological potentiation of endogenous OPC maturation and remyelination is now recognized as a promising therapeutic approach for MS. In this study, we analyzed the effects of modulating the Rho-A/Rho-associated kinase (ROCK) signaling pathway, by the use of selective inhibitors of ROCK, on the transformation of OPCs into mature, myelinating oligodendrocytes. Here we demonstrate, with the use of cellular cultures from rodent and human origin, that ROCK inhibition in OPCs results in a significant generation of branches and cell processes in early differentiation stages, followed by accelerated production of myelin protein as an indication of advanced maturation. Furthermore, inhibition of ROCK enhanced myelin formation in cocultures of human OPCs and neurons and remyelination in rat cerebellar tissue explants previously demyelinated with lysolecithin. Our findings indicate that by direct inhibition of this signaling molecule, the OPC differentiation program is activated resulting in morphological and functional cell maturation, myelin formation, and regeneration. Altogether, we show evidence of modulation of the Rho-A/ROCK signaling pathway as a viable target for the induction of remyelination in demyelinating pathologies. PMID:25289646

Taylor, Christopher; Pereira, Albertina; Seng, Michelle; Tham, Chui-Se; Izrael, Michal; Webb, Michael

2014-01-01

184

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

185

Oligodendrocyte-encoded HIF function couples postnatal myelination and white matter angiogenesis.  

Science.gov (United States)

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

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

2014-07-17

186

Induction of oligodendrocyte differentiation and in vitro myelination by inhibition of rho-associated kinase.  

Science.gov (United States)

In inflammatory demyelinating diseases such as multiple sclerosis (MS), myelin degradation results in loss of axonal function and eventual axonal degeneration. Differentiation of resident oligodendrocyte precursor cells (OPCs) leading to remyelination of denuded axons occurs regularly in early stages of MS but halts as the pathology transitions into progressive MS. Pharmacological potentiation of endogenous OPC maturation and remyelination is now recognized as a promising therapeutic approach for MS. In this study, we analyzed the effects of modulating the Rho-A/Rho-associated kinase (ROCK) signaling pathway, by the use of selective inhibitors of ROCK, on the transformation of OPCs into mature, myelinating oligodendrocytes. Here we demonstrate, with the use of cellular cultures from rodent and human origin, that ROCK inhibition in OPCs results in a significant generation of branches and cell processes in early differentiation stages, followed by accelerated production of myelin protein as an indication of advanced maturation. Furthermore, inhibition of ROCK enhanced myelin formation in cocultures of human OPCs and neurons and remyelination in rat cerebellar tissue explants previously demyelinated with lysolecithin. Our findings indicate that by direct inhibition of this signaling molecule, the OPC differentiation program is activated resulting in morphological and functional cell maturation, myelin formation, and regeneration. Altogether, we show evidence of modulation of the Rho-A/ROCK signaling pathway as a viable target for the induction of remyelination in demyelinating pathologies. PMID:25289646

Pedraza, Carlos E; Taylor, Christopher; Pereira, Albertina; Seng, Michelle; Tham, Chui-Se; Izrael, Michal; Webb, Michael

2014-01-01

187

Balanced mTORC1 activity in oligodendrocytes is required for accurate CNS myelination.  

Science.gov (United States)

The mammalian target of rapamycin (mTOR) pathway integrates multiple signals and regulates crucial cell functions via the molecular complexes mTORC1 and mTORC2. These complexes are functionally dependent on their raptor (mTORC1) or rictor (mTORC2) subunits. mTOR has been associated with oligodendrocyte differentiation and myelination downstream of the PI3K/Akt pathway, but the functional contributions of individual complexes are largely unknown. We show, by oligodendrocyte-specific genetic deletion of Rptor and/or Rictor in the mouse, that CNS myelination is mainly dependent on mTORC1 function, with minor mTORC2 contributions. Myelin-associated lipogenesis and protein gene regulation are strongly reliant on mTORC1. We found that also oligodendrocyte-specific overactivation of mTORC1, via ablation of tuberous sclerosis complex 1 (TSC1), causes hypomyelination characterized by downregulation of Akt signaling and lipogenic pathways. Our data demonstrate that a delicately balanced regulation of mTORC1 activation and action in oligodendrocytes is essential for CNS myelination, which has practical overtones for understanding CNS myelin disorders. PMID:24948799

Lebrun-Julien, Frédéric; Bachmann, Lea; Norrmén, Camilla; Trötzmüller, Martin; Köfeler, Harald; Rüegg, Markus A; Hall, Michael N; Suter, Ueli

2014-06-18

188

Splitting criterion for reflexive sheaves  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The purpose of this paper is to study the structure of reflexive sheaves over projective spaces through hyperplane sections. We give a criterion for a reflexive sheaf to split into a direct sum of line bundles. An application to the theory of free hyperplane arrangements is also given.

Abe, Takuro; Yoshinaga, Masahiko

2005-01-01

189

Water splitting: Catalyst or spectator?  

Science.gov (United States)

The deposition of cobalt-phosphate onto photocatalytic haematite improves its ability to split water and thus create clean hydrogen fuel. The source of this improvement is, however, not yet understood, and now two separate studies suggest different roles for the deposited cobalt-phosphate.

Gamelin, Daniel R.

2012-12-01

190

Splitting the superstring vacuum degeneracy  

International Nuclear Information System (INIS)

A general method is presented for calculating the energy splitting of gauge field vacua to the one-loop level on compact, multiply-connected manifolds. Two explicit examples are given in which non-zero gauge vacua have the lowest energy, and the gauge group is spontaneously broken. (orig.)

191

Evolution kernels from splitting amplitudes  

International Nuclear Information System (INIS)

We recalculate the next-to-leading order Altarelli-Parisi kernel using a method which relates it to the splitting amplitudes describing the collinear factorization properties of scattering amplitudes. The method breaks up the calculation of the kernel into individual pieces which have an independent physical interpretation

192

Evolution Kernels from Splitting Amplitudes  

CERN Document Server

We recalculate the next-to-leading order Altarelli-Parisi kernel using a method which relates it to the splitting amplitudes describing the collinear factorization properties of scattering amplitudes. The method breaks up the calculation of the kernel into individual pieces which have an independent physical interpretation.

Kosower, D A; Kosower, David A.; Uwer, Peter

2003-01-01

193

Cool covered sky-splitting spectrum-splitting FK  

Science.gov (United States)

Placing a plane mirror between the primary lens and the receiver in a Fresnel Köhler (FK) concentrator gives birth to a quite different CPV system where all the high-tech components sit on a common plane, that of the primary lens panels. The idea enables not only a thinner device (a half of the original) but also a low cost 1-step manufacturing process for the optics, automatic alignment of primary and secondary lenses, and cell/wiring protection. The concept is also compatible with two different techniques to increase the module efficiency: spectrum splitting between a 3J and a BPC Silicon cell for better usage of Direct Normal Irradiance DNI, and sky splitting to harvest the energy of the diffuse radiation and higher energy production throughout the year. Simple calculations forecast the module would convert 45% of the DNI into electricity.

Mohedano, Rubén; Miñano, Juan C.; Benitez, Pablo; Buljan, Marina; Chaves, Julio; Falicoff, Waqidi; Hernandez, Maikel; Sorgato, Simone

2014-09-01

194

MR imaging evaluation of early myelination patterns in normal and developmentally delayed infants  

International Nuclear Information System (INIS)

The gray-white matter differentiation of myelination patterns in 64 normal and developmentally delayed children (aged 4 days to 36 months) was evaluated using either 0.3-T or 0.35-T imaging systems and T2-weighted pulse sequences (spin echo 2,000/80-84). Progression of myelination was correlated with mapping of myelination using stained pathologic sections. Gray-white matter patterns observed were defined as (1) infantile, (2) isointense, and (3) early adult. In children scanned sequentially, progression through these patterns was demonstrated. In developmentally delayed children, the infantile and isointense patterns persisted in the age distribution of the normal and developmentally delayed children (P values: infantiles, <.025; isointense, <.01; early adult, <.05)

195

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

Energy Technology Data Exchange (ETDEWEB)

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

196

Myelin loss and oligodendrocyte pathology in white matter tracts following traumatic brain injury in the rat.  

Science.gov (United States)

Axonal injury is an important contributor to the behavioral deficits observed following traumatic brain injury (TBI). Additionally, loss of myelin and/or oligodendrocytes can negatively influence signal transduction and axon integrity. Apoptotic oligodendrocytes, changes in the oligodendrocyte progenitor cell (OPC) population and loss of myelin were evaluated at 2, 7 and 21 days following TBI. We used the central fluid percussion injury model (n = 18 and three controls) and the lateral fluid percussion injury model (n = 15 and three controls). The external capsule, fimbriae and corpus callosum were analysed. With Luxol Fast Blue and RIP staining, myelin loss was observed in both models, in all evaluated regions and at all post-injury time points, as compared with sham-injured controls (P ? 0.05). Accumulation of ?-amyloid precursor protein was observed in white matter tracts in both models in areas with preserved and reduced myelin staining. White matter microglial/macrophage activation, evaluated by isolectin B4 immunostaining, was marked at the early time points. In contrast, the glial scar, evaluated by glial fibrillary acidic protein staining, showed its highest intensity 21 days post-injury in both models. The number of apoptotic oligodendrocytes, detected by CC1/caspase-3 co-labeling, was increased in both models in all evaluated regions. Finally, the numbers of OPCs, evaluated with the markers Tcf4 and Olig2, were increased from day 2 (Olig2) or day 7 (Tcf4) post-injury (P ? 0.05). Our results indicate that TBI induces oligodendrocyte apoptosis and widespread myelin loss, followed by a concomitant increase in the number of OPCs. Prevention of myelin loss and oligodendrocyte death may represent novel therapeutic targets for TBI. PMID:23458840

Flygt, J; Djupsjö, A; Lenne, F; Marklund, N

2013-07-01

197

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

198

Alcohol Binge Drinking during Adolescence or Dependence during Adulthood Reduces Prefrontal Myelin in Male Rats.  

Science.gov (United States)

Teen binge drinking is associated with low frontal white matter integrity and increased risk of alcoholism in adulthood. This neuropathology may result from alcohol exposure or reflect a pre-existing condition in people prone to addiction. Here we used rodent models with documented clinical relevance to adolescent binge drinking and alcoholism in humans to test whether alcohol damages myelinated axons of the prefrontal cortex. In Experiment 1, outbred male Wistar rats self-administered sweetened alcohol or sweetened water intermittently for 2 weeks during early adolescence. In adulthood, drinking behavior was tested under nondependent conditions or after dependence induced by 1 month of alcohol vapor intoxication/withdrawal cycles, and prefrontal myelin was examined 1 month into abstinence. Adolescent binge drinking or adult dependence induction reduced the size of the anterior branches of the corpus callosum, i.e., forceps minor (CCFM), and this neuropathology correlated with higher relapse-like drinking in adulthood. Degraded myelin basic protein in the gray matter medial to the CCFM of binge rats indicated myelin was damaged on axons in the mPFC. In follow-up studies we found that binge drinking reduced myelin density in the mPFC in adolescent rats (Experiment 2) and heavier drinking predicted worse performance on the T-maze working memory task in adulthood (Experiment 3). These findings establish a causal role of voluntary alcohol on myelin and give insight into specific prefrontal axons that are both sensitive to alcohol and could contribute to the behavioral and cognitive impairments associated with early onset drinking and alcoholism. PMID:25355229

Vargas, Wanette M; Bengston, Lynn; Gilpin, Nicholas W; Whitcomb, Brian W; Richardson, Heather N

2014-10-29

199

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

International Nuclear Information System (INIS)

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: 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.)

200

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

International Nuclear Information System (INIS)

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

 
 
 
 
201

Measurement of myelin in the preterm brain: multi-compartment diffusion imaging and multi-component T2 relaxometry.  

Science.gov (United States)

Measurements of myelination and indicators of myelination status in the preterm brain could be predictive of later neurological outcome. Quantitative imaging of myelin could thus serve to develop predictive biomarkers; however, accurate estimation of myelin content is difficult. In this work we show that measurement of the myelin water fraction (MWF) is achievable using widely available pulse sequences and state-of-the-art algorithmic modelling of the MR imaging. We show results of myelin water fraction measurement at both 30 (4 infants) and 40 (2 infants) weeks equivalent gestational age (EGA) and show that the spatial pattern of myelin is different between these ages. Furthermore we apply a multi-component fitting routine to multi-shell diffusion weighted data to show differences in neurite density and local spatial arrangement in grey and white matter. Finally we combine these results to investigate the relationships between the diffusion and myelin measurements to show that MWF in the preterm brain may be measured alongside multi-component diffusion characteristics using clinically feasible MR sequences. PMID:24579158

Melbourne, Andrew; Eaton-Rosen, Zach; Bainbridge, Alan; Kendall, Giles S; Cardoso, Manuel Jorge; Robertson, Nicola J; Marlow, Neil; Ourselin, Sebastien

2013-01-01

202

Murine cathepsin D deficiency is associated with dysmyelination/myelin disruption and accumulation of cholesteryl esters in the brain.  

Science.gov (United States)

Cathepsin D (CTSD) deficiencies are fatal neurological diseases that in human infants and in sheep are characterized by extreme loss of neurons and myelin. To date, similar morphological evidence for myelin disruption in CTSD knockout mice has not been reported. Here, we show that CTSD deficiency leads to pronounced myelin changes in the murine brain: myelin-related proteolipid protein and myelin basic protein were both markedly reduced at postnatal day 24, and the amount of lipids characteristically high in myelin (e.g. plasmalogen-derived alkenyl chains and glycosphingolipid-derived 20- and 24-carbon acyl chains) were significantly lowered compared with controls. These changes were accompanied by ultrastructural alterations of myelin, including significant thinning of myelin sheaths. Furthermore, in CTSD knockout brains there was a pronounced accumulation of cholesteryl esters and abnormal levels of proteins related to cholesterol transport, with an increased content of apolipoprotein E and a reduced content of ATP-binding cassette transporter A1. These results provide evidence for dysmyelination and altered trafficking of cholesterol in brains of CTSD knockout mice, and warrant further studies on the role of lipid metabolism in the pathogenesis of CTSD deficiencies. PMID:19845830

Mutka, Aino-Liisa; Haapanen, Aleksi; Käkelä, Reijo; Lindfors, Maria; Wright, Ann K; Inkinen, Teija; Hermansson, Martin; Rokka, Anne; Corthals, Garry; Jauhiainen, Matti; Gillingwater, Thomas H; Ikonen, Elina; Tyynelä, Jaana

2010-01-01

203

Proteolipid protein cannot replace P0 protein as the major structural protein of peripheral nervous system myelin.  

Science.gov (United States)

The central nervous system (CNS) of terrestrial vertebrates underwent a prominent molecular change when proteolipid protein (PLP) replaced P0 protein as the most abundant protein of CNS myelin. However, PLP did not replace P0 in peripheral nervous system (PNS) myelin. To investigate the possible consequences of a PLP to P0 shift in PNS myelin, we engineered mice to express PLP instead of P0 in PNS myelin (PLP-PNS mice). PLP-PNS mice had severe neurological disabilities and died between 3 and 6 months of age. Schwann cells in sciatic nerves from PLP-PNS mice sorted axons into one-to-one relationships but failed to form myelin internodes. Mice with equal amounts of P0 and PLP had normal PNS myelination and lifespans similar to wild-type (WT) mice. When PLP was overexpressed with one copy of the P0 gene, sciatic nerves were hypomyelinated; mice displayed motor deficits, but had normal lifespans. These data support the hypothesis that while PLP can co-exist with P0 in PNS myelin, PLP cannot replace P0 as the major structural protein of PNS myelin. GLIA 2015;63:66-77. PMID:25066805

Yin, Xinghua; Kiryu-Seo, Sumiko; Kidd, Grahame J; Feltri, M Laura; Wrabetz, Lawrence; Trapp, Bruce D

2015-01-01

204

Myelinating cocultures of rat retinal ganglion cell reaggregates and optic nerve oligodendrocyte precursor cells.  

Science.gov (United States)

This protocol describes the generation of a rapidly myelinating central nervous system coculture for the study of complex neuronal-glial interactions in vitro. Postnatal rat retinal ganglion cells (RGCs) purified by immunopanning are promoted to cluster into reaggregates and then allowed to extend dense beds of radial axons for 10-14 d. Subsequently, rodent oligodendrocyte precursor cells are purified by immunopanning, transfected if desired, and seeded on top of the RGC reaggregates. Under the conditions described here, compact myelin can be observed within 6 d. PMID:25275100

Watkins, Trent A; Scholze, Anja R

2014-01-01

205

Myelin basic protein synthesis is regulated by small non-coding RNA 715.  

Science.gov (United States)

Oligodendroglial Myelin Basic Protein (MBP) synthesis is essential for myelin formation in the central nervous system. During oligodendrocyte differentiation, MBP mRNA is kept in a translationally silenced state while intracellularly transported, until neuron-derived signals initiate localized MBP translation. Here we identify the small non-coding RNA 715 (sncRNA715) as an inhibitor of MBP translation. SncRNA715 localizes to cytoplasmic granular structures and associates with MBP mRNA transport granule components. We also detect increased levels of sncRNA715 in demyelinated chronic human multiple sclerosis lesions, which contain MBP mRNA but lack MBP protein. PMID:22744314

Bauer, Nina M; Moos, Christina; van Horssen, Jack; Witte, Maarten; van der Valk, Paul; Altenhein, Benjamin; Luhmann, Heiko J; White, Robin

2012-09-01

206

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.)

207

Castration attenuates myelin repair following lysolecithin induced demyelination in rat optic chiasm: an evaluation using visual evoked potential, marker genes expression and myelin staining.  

Science.gov (United States)

Multiple sclerosis (MS) is a demyelinating disease that affects the central nervous system. MS is the most common neurological disorder in young adults with a greater incidence among females. Male gonadal hormones have a protective effect on neural system development and myelin maturation. In this study, we investigate the effect of castration on lysolecithin-induced demyelination and remyelination processes using visual evoked potentials, in addition to measuring the expressions of Olig2, MBP, Nogo-A and GFAP mRNAs as oligodendrocyte or astrocyte markers; and histological assessments by myelin-specific staining. We observed more expanded demyelination with delayed repair process in castrated rats. Expression levels of the aforementioned marker genes confirmed histological and electrophysiological observations. Our results showed a pivotal role for endogenous male hormones in the context of demyelinating insults. It may also account for the different prognosis of MS between male and female genders and provide new insights for therapeutic treatments. PMID:21626170

Sherafat, Mohammad Amin; Javan, Mohammad; Mozafari, Sabah; Mirnajafi-Zadeh, Javad; Motamedi, Fereshteh

2011-10-01

208

Gluino decays in Split Supersymmetry  

International Nuclear Information System (INIS)

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

209

Gluino decays in Split Supersymmetry  

Energy Technology Data Exchange (ETDEWEB)

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

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

2005-10-17

210

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

International Nuclear Information System (INIS)

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

211

Testing split supersymmetry with inflation  

Science.gov (United States)

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 (LSS) surveys. In the event of a detection, we forecast our ability to find evidence for superpartners through the scaling behavior in the squeezed limit of the bispectrum.

Craig, Nathaniel; Green, Daniel

2014-07-01

212

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

213

Two-party information splitting  

Science.gov (United States)

Consider the very general process where the state of a quantum system is encoded into a (possibly larger) quantum system, which is then physically split into pieces A and B. One can ask: how much information does A have (about the original state), how much does B have, and how are they related? We find a deterministic trade-off between the quantum information in A and that in B. One can go a step further and consider different types of information (e.g. the X, Y, and Z components of angular momentum), asking how much each party has of each information type. While classical information can be copied to both A and B, we find a trade-off inequality for an information type in A and a mutually-unbiased type in B, e.g. I(X,A)+I(Z,B)<=1 for X-information in A and Z-information in B. Even more intriguing is our finding that, for certain information measures, the information splitting between A and B, I(W,A)-I(W,B), is invariant to the information type W. The fundamental phenomena of measurement and decoherence can be viewed as information splitting processes between the system and the apparatus (or environment), so our results are applicable to these phenomena.

Coles, Patrick; Yu, Li; Gheorghiu, Vlad; Griffiths, Robert

2010-03-01

214

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

215

MYELIN BASIC PROTEIN-MRNA USED TO MONITOR TRIMETHYLTIN TOXIC NEUROPATHY IN RATS  

Science.gov (United States)

Trimethyltin (TMT) is an alkyltin that selectively targets neurons of the limbic system. ene probe (i.e., mRNA) for myelin basic protein (MBP) was used to monitor this toxic neuropathy. prague Dawley rats, were dosed (IP) acutely with hydroxide at neuropathic (8.0 mg/kg) or non-n...

216

Struktur-Funktionsanalyse des Myelin Oligodendrozyten Glykoproteins durch Gen-Ablation mittels homologer Rekombination  

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Generierung einer MOG (Myelin Oligodendrozyten Glykoprotein)-defizienten Mauslinie mittels homologer Rekombination. Die Gen Ablation wurde durch Southern, Northern und Western Blotting bestätigt. Es wurden weitere Versuche durchgeführt (Lipidanalyse mittels Dünnschicht, Elektronenmikroskopie des Gehirns und Rückenmarks, Verhaltenstests). Die Ablation des MOG-Gens zeigte keinen Phänotyp. Die außerdem generierten Tripelmutanten (defizient in MOG, PLP und MBP) zeigten ebenfalls keinen erke...

Hoch, Lennart Von

2004-01-01

217

Rapamycin improves peripheral nerve myelination while it fails to benefit neuromuscular performance in neuropathic mice.  

Science.gov (United States)

Charcot--Marie-Tooth disease type 1A (CMT1A) is a hereditary peripheral neuropathy characterized by progressive demyelination and distal muscle weakness. Abnormal expression of peripheral myelin protein 22 (PMP22) has been linked to CMT1A and is modeled by Trembler J (TrJ) mice, which carry the same leucine to proline substitution in PMP22 as affected pedigrees. Pharmacologic modulation of autophagy by rapamycin in neuron-Schwann cell explant cultures from neuropathic mice reduced PMP22 aggregate formation and improved myelination. Here we asked whether rapamycin administration by food supplementation, or intraperitoneal injection, could alleviate the neuropathic phenotype of affected mice and improve neuromuscular performance. Cohorts of male and female wild type (Wt) and TrJ mice were assigned to placebo or rapamycin treatment starting at 2 or 4months of age and tested monthly on the rotarod. While neither long-term feeding (8 or 10months) on rapamycin-enriched diet, or short-term injection (2months) of rapamycin improved locomotor performance of the neuropathic mice, both regimen benefited peripheral nerve myelination. Together, these results indicate that while treatment with rapamycin benefits the myelination capacity of neuropathic Schwann cells, this intervention does not improve neuromuscular function. The observed outcome might be the result of the differential response of nerve and skeletal muscle tissue to rapamycin. PMID:25014022

Nicks, Jessica; Lee, Sooyeon; Harris, Andrew; Falk, Darin J; Todd, Adrian G; Arredondo, Karla; Dunn, William A; Notterpek, Lucia

2014-10-01

218

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

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

RadmilaFilipovic

2009-06-01

219

THE EFFECTS OF NERVE GROWTH FACTOR ON MYELINATION OF REGENERATED FIBERS IN RAT  

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Full Text Available The effect of nerve growth factor (NGF on regeneration of rat sciatic nerves in adult rat was studied. The sciatic nerve was cut out across a 6?mm gap, then the proximal and distal stumps were inserted into the silicone tube chamber. 7s NGF was extracted from submaxillary gland and then was injected into the silicone in experimental group. After seven months nerve was transected and stained with toluidine blue. Semithin sections (1 µm from middle of silicone (control group, without NGF showed that regenerated axons (mostly unmyelinated were dispersed randomly, and they were not grouped into bundles. In this group some of the myelinated fibers were degenerated and macrophages or in other word, schwann cells contained a large amount of these degenerated sheaths. Semithin section of experimental group (with NGF showed numerous regenerated axons (myelinated that were grouped into small bundles. Schwann cells in experimental group were large and eucromatin and some of them were divided. These data indicate that NGF causes myelinated axons, regenerate and making new myelinated sheaths.

M. Firouzi

2003-07-01

220

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.)

 
 
 
 
221

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

222

Changes in the anisotropy of oriented membrane dynamics induced by myelin basic protein  

International Nuclear Information System (INIS)

We report recent results showing the evidence of the effect induced by physiological amounts of myelin basic protein (MBP) on the dynamics of dimyristoyl L-a-phosphatidic acid (DMPA) membranes. Incoherent elastic neutron scattering scans, performed over a wide temperature range, have shown that the anisotropy of motions in oriented membranes is significantly enhanced by the presence of MBP. (orig.)

223

In vivo longitudinal Myelin Water Imaging in rat spinal cord following dorsal column transection injury.  

Science.gov (United States)

Longitudinal Myelin Water Imaging was carried out in vivo to characterize white matter damage following dorsal column transection (DC Tx) injury at the lumbar level L1 of rat spinal cords. A transmit-receive implantable coil system was used to acquire multiple spin-echo (MSE) quantitative T2 data from the lumbar spinal cords of 16 rats at one week pre-injury as well as 3 and 8weeks post-injury (117 microns in-plane resolution and 1.5mm slice thickness). In addition, ex vivo MSE and DTI data were acquired from cords fixed and excised at 3 or 8weeks post injury using a solenoid coil. The MSE data were used to generate Myelin Water Fractions (MWFs) as a surrogate measure of myelin content, while DTI data were acquired to study damage to the axons. Myelin damage was assessed histologically with Eriochrome cyanine (EC) and Myelin Basic Protein in degenerated myelin (dgen-MBP) staining, and axonal damage was assessed by neurofilament-H in combination with neuron specific beta-III-tubulin (NF/Tub) staining. These MRI and histological measures of injury were studied in the dorsal column at 5mm cranial and 5mm caudal to injury epicenter. MWF increased significantly at 3weeks post-injury at both the cranial and caudal sites, relative to baseline. The values on the cranial side of injury returned to baseline at 8weeks post-injury but remained elevated on the caudal side. This trend was found in both in vivo and ex vivo data. This MWF increase was likely due to the presence of myelin debris, which were cleared by 8 weeks on the cranial, but not the caudal, side. Both EC and dgen-MBP stains displayed similar trends. MWF showed significant correlation with EC staining (R=0.63, p=0.005 in vivo and R=0.74, p=0.0001 ex vivo). MWF also correlated strongly with the dgen-MBP stain, but only on the cranial side (R=0.64, p=0.05 in vivo; R=0.63, p=0.038 ex vivo). This study demonstrates that longitudinal MWI in vivo can accurately characterize white matter damage in DC Tx model of injury in the rat spinal cord. PMID:24462106

Kozlowski, Piotr; Rosicka, Paulina; Liu, Jie; Yung, Andrew C; Tetzlaff, Wolfram

2014-04-01

224

Reduced inflammation accompanies diminished myelin damage and repair in the NG2 null mouse spinal cord  

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Full Text Available Abstract Background Multiple sclerosis (MS is a demyelinating disease in which blood-derived immune cells and activated microglia damage myelin in the central nervous system. While oligodendrocyte progenitor cells (OPCs are essential for generating oligodendrocytes for myelin repair, other cell types also participate in the damage and repair processes. The NG2 proteoglycan is expressed by OPCs, pericytes, and macrophages/microglia. In this report we investigate the effects of NG2 on these cell types during spinal cord demyelination/remyelination. Methods Demyelinated lesions were created by microinjecting 1% lysolecithin into the lumbar spinal cord. Following demyelination, NG2 expression patterns in wild type mice were studied via immunostaining. Immunolabeling was also used in wild type and NG2 null mice to compare the extent of myelin damage, the kinetics of myelin repair, and the respective responses of OPCs, pericytes, and macrophages/microglia. Cell proliferation was quantified by studies of BrdU incorporation, and cytokine expression levels were evaluated using qRT-PCR. Results The initial volume of spinal cord demyelination in wild type mice is twice as large as in NG2 null mice. However, over the ensuing 5 weeks there is a 6-fold improvement in myelination in wild type mice, versus only a 2-fold improvement in NG2 null mice. NG2 ablation also results in reduced numbers of each of the three affected cell types. BrdU incorporation studies reveal that reduced cell proliferation is an important factor underlying NG2-dependent decreases in each of the three key cell populations. In addition, NG2 ablation reduces macrophage/microglial cell migration and shifts cytokine expression from a pro-inflammatory to anti-inflammatory phenotype. Conclusions Loss of NG2 expression leads to decreased proliferation of OPCs, pericytes, and macrophages/microglia, reducing the abundance of all three cell types in demyelinated spinal cord lesions. As a result of these NG2-dependent changes, the course of demyelination and remyelination in NG2 null mice differs from that seen in wild type mice, with both myelin damage and repair being reduced in the NG2 null mouse. These studies identify NG2 as an important factor in regulating myelin processing, suggesting that therapeutic targeting of the proteoglycan might offer a means of manipulating cell behavior in demyelinating diseases.

Kucharova Karolina

2011-11-01

225

CBM split title in Alberta  

Energy Technology Data Exchange (ETDEWEB)

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

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

2006-07-01

226

Hyperfine splitting in noncommutative spaces  

Energy Technology Data Exchange (ETDEWEB)

We study the hyperfine splitting in the framework of the noncommutative quantum mechanics (NCQM) developed in the literature. The results show deviations from the usual quantum mechanics. We show that the energy difference between two excited F=I+1/2 and the ground F=I-1/2states in a noncommutative space (NCS) is bigger than the one in the commutative case, so the radiation wavelength in NCSs must be shorter than the radiation wavelength in commutative spaces. We also find an upper bound for the noncommutativity parameter.

Alavi, S A [Department of Physics, Tarbiat Moallem University of Sabzevar, PO Box 397, Sabzevar (Iran, Islamic Republic of)], E-mail: alavi@sttu.ac.ir

2008-07-15

227

Hyperfine splitting in noncommutative spaces  

International Nuclear Information System (INIS)

We study the hyperfine splitting in the framework of the noncommutative quantum mechanics (NCQM) developed in the literature. The results show deviations from the usual quantum mechanics. We show that the energy difference between two excited F=I+1/2 and the ground F=I-1/2states in a noncommutative space (NCS) is bigger than the one in the commutative case, so the radiation wavelength in NCSs must be shorter than the radiation wavelength in commutative spaces. We also find an upper bound for the noncommutativity parameter

228

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

229

Immune cells contribute to myelin degeneration and axonopathic changes in mice overexpressing proteolipid protein in oligodendrocytes.  

Science.gov (United States)

Overexpression of the major myelin protein of the CNS, proteolipid protein (PLP), leads to late-onset degeneration of myelin and pathological changes in axons. Based on the observation that in white matter tracts of these mutants both CD8+ T-lymphocytes and CD11b+ macrophage-like cells are numerically elevated, we tested the hypothesis that these cells are pathologically involved in the primarily genetically caused neuropathy. Using flow cytometry of mutant brains, CD8+ cells could be identified as activated effector cells, and confocal microscopy revealed a close association of the T-cells with MHC-I+ (major histocompatibility complex class I positive) oligodendrocytes. Crossbreeding the myelin mutants with mice deficient in the recombination activating gene-1 (RAG-1) lacking mature T- and B-lymphocytes led to a reduction of the number of CD11b+ cells and to a substantial alleviation of pathological changes. In accordance with these findings, magnetic resonance imaging revealed less ventricular enlargement in the double mutants, partially because of more preserved corpora callosa. To investigate the role of CD8+ versus CD4+ T-lymphocytes, we reconstituted the myelin-RAG-1 double mutants with bone marrow from either CD8-negative (CD4+) or CD4-negative (CD8+) mice. The severe ventricular enlargement was only found when the double mutants were reconstituted with bone marrow from CD8+ mice, suggesting that the CD8+ lymphocytes play a critical role in the immune-related component of myelin degeneration in the mutants. These findings provide strong evidence that a primary glial damage can cause secondary immune reactions of pathological significance as it has been suggested for some forms of multiple sclerosis and other leukodystrophies. PMID:16885234

Ip, Chi Wang; Kroner, Antje; Bendszus, Martin; Leder, Christoph; Kobsar, Igor; Fischer, Stefan; Wiendl, Heinz; Nave, Klaus-Armin; Martini, Rudolf

2006-08-01

230

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

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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.

DanteMantini

2014-09-01

231

Peripheral nervous system manifestations in a Sandhoff disease mouse model: nerve conduction, myelin structure, lipid analysis  

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Full Text Available Abstract Background Sandhoff disease is an inherited lysosomal storage disease caused by a mutation in the gene for the ?-subunit (Hexb gene of ?-hexosaminidase A (?? and B (??. The ?-subunit together with the GM2 activator protein catabolize ganglioside GM2. This enzyme deficiency results in GM2 accumulation primarily in the central nervous system. To investigate how abnormal GM2 catabolism affects the peripheral nervous system in a mouse model of Sandhoff disease (Hexb-/-, we examined the electrophysiology of dissected sciatic nerves, structure of central and peripheral myelin, and lipid composition of the peripheral nervous system. Results We detected no significant difference in signal impulse conduction velocity or any consistent change in the frequency-dependent conduction slowing and failure between freshly dissected sciatic nerves from the Hexb+/- and Hexb-/- mice. The low-angle x-ray diffraction patterns from freshly dissected sciatic and optic nerves of Hexb+/- and Hexb-/- mice showed normal myelin periods; however, Hexb-/- mice displayed a ~10% decrease in the relative amount of compact optic nerve myelin, which is consistent with the previously established reduction in myelin-enriched lipids (cerebrosides and sulfatides in brains of Hexb-/- mice. Finally, analysis of lipid composition revealed that GM2 content was present in the sciatic nerve of the Hexb-/- mice (undetectable in Hexb+/-. Conclusion Our findings demonstrate the absence of significant functional, structural, or compositional abnormalities in the peripheral nervous system of the murine model for Sandhoff disease, but do show the potential value of integrating multiple techniques to evaluate myelin structure and function in nervous system disorders.

Strichartz Gary R

2007-07-01

232

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

Science.gov (United States)

The elaboration of the myelinated white matter is essential for normal neurodevelopment, establishing and mediating rapid communication pathways throughout the brain. These pathways facilitate the synchronized communication required for higher order behavioral and cognitive functioning. Altered neural messaging (or 'disconnectivity') arising from abnormal white matter and myelin development may underlie a number of neurodevelopmental psychiatric disorders. Despite the vital role myelin plays, few imaging studies have specifically examined its maturation throughout early infancy and childhood. Thus, direct investigations of the relationship(s) between evolving behavioral and cognitive functions and the myelination of the supporting neural systems have been sparse. Further, without knowledge of the 'normative' developmental time-course, identification of early abnormalities associated with developmental disorders remains challenging. In this work, we examined the use of longitudinal (T(1)) and transverse (T(2)) relaxation time mapping, and myelin water fraction (MWF) imaging to investigate white matter and myelin development in 153 healthy male and female children, 3 months through 60 months in age. Optimized age-specific acquisition protocols were developed using the DESPOT and mcDESPOT imaging techniques; and mean T(1), T(2) and MWF trajectories were determined for frontal, temporal, occipital, parietal and cerebellar white matter, and genu, body and splenium of the corpus callosum. MWF results provided a spatio-temporal pattern in-line with prior histological studies of myelination. Comparison of T(1), T(2) and MWF measurements demonstrates dissimilar sensitivity to tissue changes associated with neurodevelopment, with each providing differential but complementary information. PMID:22884937

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

2012-11-15

233

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)

234

Signature splitting in 135Pr  

International Nuclear Information System (INIS)

In-beam spectroscopic study of 135Pr was made using 91 MeV 120Sn(19F,4n) reaction. A strong negative parity proton band based on the h/sub 11/2-/ 1/2[550] configuration with ? = -1/2 was observed. Possibly ? = +1/2 unfavored band is observed. Also two positive parity proton bands are observed most likely based on the g/sub 7/2+/ 5/2[413] configurations with ? = +-1/2. In all cases (except for the (?,?) = (-,+1/2) band) the backbending is caused by alignment of two h/sub 11/2-/ 9/2[514] quasi-neutrons. For the strongly decoupled ?(-) bands the observed signature splitting decreases with increasing rotational frequency. The signature splitting of the positive parity bands increases with rotational frequency and then inverts above the backbending. This is interpreted to be caused by the quasi-neutrons, which drive the ?-deformation to the negative values. 18 refs., 6 figs

235

Corneal cross-linking for the treatment of keratoconus in a patient with ipsilateral myelinated retinal nerve fiber layer.  

Science.gov (United States)

Keratoconus associated with myelinated retinal nerve fibers is not frequent and the relationship between the two pathologies is difficult to explain, therefore studies and further investigation are required. The etiology of each condition may suggest the role of genetic factors. Follow-up is important to evaluate the progression of keratoconus and myelination. Here we describe the unusual coexistence of keratoconus and ipsilateral myelinated retinal nerve fiber layer and, for the first time, the corneal cross-linking treatment in this condition. PMID:21475609

Leozappa, M; Ciani, S; Ferrari, T Micelli

2011-01-01

236

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

International Nuclear Information System (INIS)

The major myelin protein, P0, has been shown to have decreased levels of expression and altered oligosaccharide processing after the disruption of Schwann cell-axon interaction. We show here that lysosomal degradation of the glycoprotein shortly after its synthesis accounts for much of its decreased expression in the permanently transected adult rat sciatic nerve, a denervated preparation where there is no axonal regeneration or myelin assembly. If [3H]mannose incorporation into sciatic nerve endoneurial slices is examined in the presence of the lysosomotropic agent, NH4Cl, a marked increase in the level of newly synthesized P0 is seen. Pulse-chase analysis of [3H]mannose-labeled P0 in the presence of NH4Cl indicates that this increase is a consequence of inhibition of P0 degradation that normally occurs 1-2 h after biosynthesis in the transected nerve. P0 degradation can also be inhibited if lysosomal function is disturbed by dilation of secondary lysosomes with L-methionine methyl ester. The addition of deoxymannonojirimycin or swainsonine (SW), inhibitors of oligosaccharide-processing mannosidases I and II, respectively, also results in a decrease in P0 degradation. This inhibition is presumably caused by a blockage of transport to the lysosomes due to altered processing of the glycoprotein, although the direct inhibition of lysosomal mannosidases cannot be excluded. In contrast to the transected nerve, addition of NH4Cl or SW has no effect on P0 levels in the crushed nerve, where myelin assembly occurs. The delivery of P0 to the lysosomes of the transected nerve Schwann cells does not appear to be triggered by the mannose-6-phosphate transport system involved in acid hydrolase routing

237

Excitonic exchange splitting in bulk semiconductors  

International Nuclear Information System (INIS)

We present an approach to calculate the excitonic fine-structure splittings due to electron-hole short-range exchange interactions using the local-density approximation pseudopotential method, and apply it to bulk semiconductors CdSe, InP, GaAs, and InAs. Comparing with previous theoretical results, the current calculated splittings agree well with experiments. Furthermore, we provide an approximate relationship between the short-range exchange splitting and the exciton Bohr radius, which can be used to estimate the exchange splitting for other materials. The current calculation indicates that a commonly used formula for exchange splitting in quantum dot is not valid. Finally, we find a very large pressure dependence of the exchange splitting: a factor of 4.5 increase as the lattice constant changes by 3.5%. This increase is mainly due to the decrease of the Bohr radius via the change of electron effective mass. copyright 1999 The American Physical Society

238

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

239

Development of concepts for hydraulic splitting cylinders  

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The assignment is to develop a concept for the company Emstone AB’s hydraulic splitting cylinders that, to date, has not been out on the market. This product splits rocks through hydraulic pressure and targeted splitting effect. It’s seen as a sustainable alternative to the traditional blast with dynamite. Since this technique is so new there exists no construction at present, which can easily transport cylinders with one hand. The major contribution of this report is to describe and anal...

Cheung, Sai-kit

2009-01-01

240

Quasiperiodic Tip Splitting in Directional Solidification  

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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

 
 
 
 
241

Stock splits on the Athens Stock exchange  

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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

242

Photon-splitting cross sections  

International Nuclear Information System (INIS)

The differential cross section for photon splitting (scattering of one photon into two photons) in a Coulomb field, obtained earlier by Shima, has been integrated numerically to yield various differential cross sections. Energy spectra differential with respect to the energy of one of the outgoing photons are presented for several values of the primary photon energy. Selected examples of recoil momentum distributions and some interesting doubly or multiply differential cross sections are also given. Values for the total cross section are obtained essentially for all energies. The screening effect caused by atomic electrons is also taken into account, and is found to be important for high energies, as in e+e- pair production. Comparisons with various approximate results obtained by previous authors mostly show fair agreement. We also discuss the possibilities for experimental detection and find the most promising candidate to be a measurement of both photons, and their energies, at a moderately high energy

243

Beam Splitting in Induced Inhomogeneous Media  

International Nuclear Information System (INIS)

We study the spatial behavior of a deflected beam in a coherent ?-type three-level atomic medium with an inhomogeneous control laser. When the Rabi coupling by the control laser is in a Gaussian profile, the spatial-dependent refraction index of the atomic medium will result in a beam splitting as well as the deflection of the slow probe light under electromagnetically induced transparency. In terms of the phase difference between the two splitting beams and the position of the splitting, the possible interpretation of the splitting is given in theory. (fundamental areas of phenomenology(including applications))

244

Intervalley splittings of Si quantum wells  

Science.gov (United States)

Intervalley splittings of Si quantum wells are studied using a multivalley effective mass theory and a finite element method. It is found that the contributions to the valley splitting mainly come from the quantum well interfaces and the external field. Especially the derivatives of the confinement potential which appears in the valley coupling Hamiltonian cause the periodic oscillation of the splitting with the well width. Theoretical predictions are in reasonably good agreement with the recent experimental observation of valley splitting in a SiO2/Si/SiO2 quantum well, which proves the validity of our approach.

Park, S.-H.; Lee, Y. Y.; Ahn, Doyeol

2008-08-01

245

Salt splitting using ceramic membranes  

Energy Technology Data Exchange (ETDEWEB)

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{sup +2}, Cs{sup +}). The charge balance in the anode compartment is maintained by generating H{sup +} from the electrolysis of water. The charge balance in the cathode is maintained by generating OH{sup {minus}}, either from the electrolysis of water or from oxygen and water using an oxygen cathode. The normal gaseous products of the electrolysis of water are oxygen at the anode and hydrogen at the cathode. Potentially flammable gas mixtures can be prevented by providing adequate volumes of a sweep gas, using an alternative reductant or destruction of the hydrogen as it is generated. As H{sup +} 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.

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

1997-10-01

246

Myelin disorders: Causes and perspectives of Charcot-Marie-Tooth neuropathy.  

Science.gov (United States)

Charcot-Marie-Tooth (CMT) disease is a common hereditary neuropathy that causes progressive distally pronounced muscle weakness and can lead to life-long disability in patients. In most cases, the disorder has been associated with a partial duplication of human chromosome 17 (CMT1A), causing 1.5-fold overexpression of the peripheral myelin protein 22 kDa (PMP22). Increased PMP22 gene dosage results in demyelination, secondary axonal loss, and neurogenic muscle atrophy. Experimental therapeutic approaches based on the role of progesterone and ascorbic acid in myelin formation recently have reached preclinical proof-of-principle trials in rodents. It was shown that progesterone receptor antagonists can reduce PMP22 overexpression and clinical severity in a CMT1A rat model. Furthermore, ascorbic acid treatment reduced premature death and demyelination in a CMT1A mouse model. Thus, basic research has opened up new vistas for the understanding and treatment of hereditary neuropathies. PMID:16632877

Meyer zu Hörste, Gerd; Prukop, Thomas; Nave, Klaus-Armin; Sereda, Michael W

2006-01-01

247

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

248

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

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Effect of long-term (90–100 days exposure of rats to soluble salt of aluminum (AlCl3 on myelin lipid profile was examined. The long-term exposure to AlCl3 resulted in a 60 % decrease in the total phospholipid (TPL content while the cholesterol (CHL content increased by 55 %. Consequently the TPL / CHL molar ratio decreased significantly by 62 %. The phospholipid composition of the myelin membrane changed drastically; the proportion of practically all the phospholipid classes decreased by 32 to 60 % except for phosphatidylcholine (PC and phosphatidylethanolamine (PE. Of the latter two, proportion of PC was unchanged while PE increased in proportion by 47 %. Quantitatively, all phospholipid classes decreased by from 42 to 76% with no change in the PE content. However the membrane fluidity was not altered in Al-treated rats. Many of the changes we observe here show striking similarities with the reported phospholipid profiles of Alzheimer brains.

Dave Kunjan R

2004-06-01

249

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)

250

In vivo multi-slice mapping of myelin water content using T2* decay.  

Science.gov (United States)

Quantitative assessment of the myelin water content in the brain can substantially improve our understanding of white matter diseases such as multiple sclerosis. In this study, in vivo myelin water content was estimated using T(2)* relaxation with multi-slice acquisitions in magnetic resonance imaging (MRI). The main advantages of using T(2)* relaxation are (1) a low specific absorption rate (SAR), which is especially beneficial for imaging at high field strengths, (2) a short first-echo time (approximately 2 ms) and short echo spacing (approximately 1 ms), which allows for the acquisition of multiple sampling points during the fast decay of the myelin water signal, and (3) fast multi-slice acquisitions. High-resolution and multi-slice myelin water fraction (MWF) maps were obtained in a clinically acceptable scan time at 3T. Five healthy adults were scanned with a multi-gradient-echo sequence to acquire T(2)* signal decay data. Images with a dimension of 256x256 at eight slice locations were acquired in 8.5 min with a signal-to-noise ratio (SNR) of 94.8 in the first-echo images. The SNR was further increased by using an anisotropic diffusion filter. Local field gradients (LFG) were estimated from the acquired multi-slice data, and the LFG-induced signal decays were corrected with a first-order approximation of LFG using the sinc function. The corrected T(2)* signal decays were analyzed with a three-pool model to quantify MWF. Our results demonstrate the feasibility of in vivo multi-slice mapping of MWF using multi-compartmental analysis of the T(2)* signal decay. PMID:20398770

Hwang, Dosik; Kim, Dong-Hyun; Du, Yiping P

2010-08-01

251

T2-relaxometry for myelin water fraction xtraction using wald distribution and extended phase graph.  

Science.gov (United States)

Quantitative assessment of myelin density in the white matter is an emerging tool for neurodegenerative disease related studies such as multiple sclerosis and Schizophrenia. For the last two decades, T2 relaxometry based on multi-exponential fitting to a single slice multi-echo sequence has been the most common MRI technique for myelin water fraction (MWF) mapping, where the short T2 is associated with myelin water. However, modeling the spectrum of the relaxations as the sum of large number of impulse functions with unknown amplitudes makes the accuracy and robustness of the estimated MWF's questionable. In this paper, we introduce a novel model with small number of parameters to simultaneously characterize transverse relaxation rate spectrum and B1 inhomogeneity at each voxel. We use mixture of three Wald distributions with unknown mixture weights, mean and shape parameters to represent the distribution of the relative amount of water in between myelin sheets, tissue water, and cerebrospinal fluid. The parameters of the model are estimated using the variable projection method and are used to extract the MWF at each voxel. In addition, we use Extended Phase Graph (EPG) method to compensate for the stimulated echoes caused by B1 inhomogeneity. To validate our model, synthetic and real brain experiments were conducted where we have compared our novel algorithm with the non-negative least squares (NNLS) as the state-of-the-art technique in the literature. Our results indicate that we can estimate MWF map with substantially higher accuracy as compared to the NNLS method. PMID:25320793

Akhondi-Asl, Alireza; Afacan, Onur; Mulkern, Robert V; Warfield, Simon K

2014-01-01

252

Clustering and Activity Tuning of Kv1 Channels in Myelinated Hippocampal Axons*  

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Precise localization of axonal ion channels is crucial for proper electrical and chemical functions of axons. In myelinated axons, Kv1 (Shaker) voltage-gated potassium (Kv) channels are clustered in the juxtaparanodal regions flanking the node of Ranvier. The clustering can be disrupted by deletion of various proteins in mice, including contactin-associated protein-like 2 (Caspr2) and transient axonal glycoprotein-1 (TAG-1), a glycosylphosphatidylinositol-anchored cell adhesion molecule. Howe...

Gu, Chen; Gu, Yuanzheng

2011-01-01

253

ADAM22, A KV1 CHANNEL INTERACTING PROTEIN, RECRUITS MAGUKS TO JUXTAPARANODES OF MYELINATED AXONS  

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Clustered Kv1 K+ channels regulate neuronal excitability at juxtaparanodes of myelinated axons, axon initial segments (AIS), and cerebellar basket cell terminals (BCTs). These channels are part of a larger protein complex that includes cell adhesion molecules and scaffolding proteins. To identify proteins that regulate assembly, clustering, and/or maintenance of axonal Kv1 channel protein complexes, we immunoprecipitated Kv1.2 ? subunits, then used mass-spectrometry to identify interacting p...

Ogawa, Yasuhiro; Oses-prieto, Juan; Kim, Moon Young; Horresh, Ido; Peles, Elior; Burlingame, Alma L.; Trimmer, James S.; Meijer, Dies; Rasband, Matthew N.

2010-01-01

254

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

255

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2012-01-13

256

Functional activation of myelin-specific T cells by virus-induced molecular mimicry.  

Science.gov (United States)

Molecular mimicry is the process by which T cells activated in response to determinants on an infecting microorganism cross-react with self epitopes, leading to an autoimmune disease. Normally, infection of SJL/J mice with the BeAn strain of Theiler's murine encephalomyelitis virus (TMEV) results in a persistent CNS infection, leading to a chronic progressive, CD4(+) T cell-mediated demyelinating disease. Myelin damage is initiated by T cell responses to virus persisting in CNS APCs, and progressive demyelinating disease (50 days postinfection) is perpetuated by myelin epitope-specific CD4(+) T cells activated by epitope spreading. We developed an infectious model of molecular mimicry by inserting a sequence encompassing the immunodominant myelin epitope, proteolipid protein (PLP) 139-151, into the coding region of a nonpathogenic TMEV variant. PLP139-TMEV-infected mice developed a rapid onset paralytic inflammatory, demyelinating disease paralleled by the activation of PLP139-151-specific CD4(+) Th1 responses within 10-14 days postinfection. The current studies demonstrate that the early onset demyelinating disease induced by PLP139-TMEV is the direct result of autoreactive PLP139-151-specific CD4(+) T cell responses. PLP139-151-specific CD4(+) T cells from PLP139-TMEV-infected mice transferred demyelinating disease to naive recipients and PLP139-151-specific tolerance before infection prevented clinical disease. Finally, infection with the mimic virus at sites peripheral to the CNS induced early demyelinating disease, suggesting that the PLP139-151-specific CD4(+) T cells could be activated in the periphery and traffic to the CNS. Collectively, infection with PLP139-151 mimic encoding TMEV serves as an excellent model for molecular mimicry by inducing pathologic myelin-specific CD4(+) T cells via a natural virus infection. PMID:12193746

Olson, Julie K; Eagar, Todd N; Miller, Stephen D

2002-09-01

257

Quaking I controls a unique cytoplasmic pathway that regulates alternative splicing of myelin-associated glycoprotein.  

Science.gov (United States)

Precise control of alternative splicing governs oligodendrocyte (OL) differentiation and myelination in the central nervous system (CNS). A well-known example is the developmentally regulated expression of splice variants encoding myelin-associated glycoprotein (MAG), which generates two protein isoforms that associate with distinct cellular components crucial for axon-glial recognition during myelinogenesis and axon-myelin stability. In the quakingviable (qk(v)) hypomyelination mutant mouse, diminished expression of isoforms of the selective RNA-binding protein quaking I (QKI) leads to severe dysregulation of MAG splicing. The nuclear isoform QKI-5 was previously shown to bind an intronic element of MAG and modulate alternative exon inclusion from a MAG minigene reporter. Thus, QKI-5 deficiency was thought to underlie the defects of MAG splicing in the qk(v) mutant. Surprisingly, we found that transgenic expression of the cytoplasmic isoform QKI-6 in the qk(v) OLs completely rescues the dysregulation of MAG splicing without increasing expression or nuclear abundance of QKI-5. In addition, cytoplasmic QKI-6 selectively associates with the mRNA that encodes heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), a well-characterized splicing factor. Furthermore, QKI deficiency in the qk(v) mutant results in abnormally enhanced hnRNPA1 translation and overproduction of the hnRNPA1 protein but not hnRNPA1 mRNA, which can be successfully rescued by the QKI-6 transgene. Finally, we show that hnRNPA1 binds MAG pre-mRNA and modulates alternative inclusion of MAG exons. Together, these results reveal a unique cytoplasmic pathway in which QKI-6 controls translation of the splicing factor hnRNPA1 to govern alternative splicing in CNS myelination. PMID:20956316

Zhao, Lixia; Mandler, Mariana D; Yi, Hong; Feng, Yue

2010-11-01

258

Endoplasmic reticulum stress modulates the response of myelinating oligodendrocytes to the immune cytokine interferon-?  

Digital Repository Infrastructure Vision for European Research (DRIVER)

I*nterferon-? (IFN-?) is believed to contribute to immune-mediated demyelinating disorders by targeting the myelin-producing oligodendrocyte, a cell known to be highly sensitive to the disruption of protein synthesis and to the perturbation of the secretory pathway. We found that apoptosis induced by IFN-? in cultured rat oligodendrocytes was associated with endoplasmic reticulum (ER) stress. ER stress also accompanied oligodendrocyte apoptosis and hypomyelination in transgenic mice that i...

Lin, Wensheng; Harding, Heather P.; Ron, David

2005-01-01

259

Visualizing the Entire Cortical Myelination Pattern in Marmosets with Magnetic Resonance Imaging  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Myeloarchitecture, the pattern of myelin density across the cerebral cortex, has long been visualized in histological sections to identify distinct anatomical areas of the cortex. In humans, two-dimensional (2D) magnetic resonance imaging (MRI) has been used to visualize myeloarchitecture in select areas of the cortex, such as the stripe of Gennari in the primary visual cortex and Heschl’s gyrus in the primary auditory cortex. Here, we investigated the use of MRI contrast based on longitudi...

Bock, Nicholas A.; Kocharyan, Ara; Liu, Junjie V.; Silva, Afonso C.

2009-01-01

260

Early Oligodendrocyte/Myelin Pathology in Alzheimer’s Disease Mice Constitutes a Novel Therapeutic Target  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The detection of myelin disruptions in Alzheimer’s disease (AD)–affected brain raises the possibility that oligodendrocytes undergo pathophysiological assault over the protracted course of this neurodegenerative disease. Oligodendrocyte compromise arising from direct toxic effects imparted by pathological amyloid-? peptides and/or through signals derived from degenerating neurons could play an important role in the disease process. We previously demonstrated that 3×Tg-AD mice, which har...

Desai, Maya K.; Mastrangelo, Michael A.; Ryan, Deborah A.; Sudol, Kelly L.; Narrow, Wade C.; Bowers, William J.

2010-01-01

 
 
 
 
261

Role of myelin-associated inhibitors in axonal repair after spinal cord injury  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Myelin-associated inhibitors of axon growth, including Nogo, MAG and OMgp, have been the subject of intense research. A myriad of experimental approaches have been applied to investigate the potential of targeting these molecules to promote axonal repair after spinal cord injury. However, there are still conflicting results on their role in axon regeneration and therefore a lack of a cohesive mechanism on how these molecules can be targeted to promote axon repair. One major reason may be the ...

Lee, Jae K.; Zheng, Binhai

2012-01-01

262

Isolation and long-term expansion of functional, myelinating oligodendrocyte progenitor cells from neonatal rat brain.  

Science.gov (United States)

Oligodendrocytes are the myelinating cells of the central nervous system (CNS). The isolation of purified oligodendrocyte progenitor cells (OPCs) in large numbers has been sought after as a source of cells for repair following CNS-demyelinating diseases and injuries, such as multiple sclerosis (MS) and spinal cord injury (SCI). Methods for isolation of OPCs from rodent neonatal brains are well established and have formed the basis for research in myelin repair within the CNS for many years. However, long-term maintenance of OPCs has been a challenge owing to small cellular yields per animal and spontaneous differentiation within a short period of time. Much effort has been devoted to achieving long-term culture and maintenance of OPCs, but little progress has been made. Here, protocols are presented for preparation of highly enriched rat OPC populations and for their long-term maintenance as oligospheres using mixed-glial-conditioned medium. Functional myelinating oligodendrocytes can be achieved from such protocols, when co-cultured with primary neurons. This approach is an extension of our normal shaking method for isolating OPCs, and incorporates some adaptations from previous OPC culture methods. © 2014 by John Wiley & Sons, Inc. PMID:25366898

Zhu, Bangfu; Zhao, Chao; Young, Fraser I; Franklin, Robin J M; Song, Bing

2014-01-01

263

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

264

Multi-slice Myelin Water Imaging for Practical Clinical Applications at 3.0 T  

Science.gov (United States)

Myelin water imaging is a promising, noninvasive technique for evaluating white matter diseases such as multiple sclerosis and other leukoencephalopathies (LE), and monitoring myelination in early childhood. Unfortunately, poor image quality and a long acquisition time are major obstacles to practical clinical applications. In this study, a novel postprocessing method with an efficient multi-slice acquisition scheme, called T2 spectrum analysis using a weighted regularized non-negative least squares algorithm and non-local mean filter (T2SPARC), is presented to overcome these obstacles and achieve a shorter acquisition time, higher image quality, and large volume coverage. In vivo results from healthy volunteers and a patient with LE showed that the T2SPARC method can generate robust and high-quality myelin water fraction (MWF) maps of 10 slices within 11 minutes. This method also yields some useful byproducts such as intra- and extracellular water fraction (IEWF) and long T2 tissue water fraction (LWF) maps, which can quantify lesions in different brain diseases. PMID:23132434

Guo, Junyu; Ji, Qing; Reddick, Wilburn E.

2012-01-01

265

A tissue-relaxation-dependent neighboring method for robust mapping of the myelin water fraction.  

Science.gov (United States)

Quantitative assessment of the myelin content in white matter (WM) using MRI has become a useful tool for investigating myelin-related diseases, such as multiple sclerosis (MS). Myelin water fraction (MWF) maps can be estimated pixel-by-pixel by a determination of the T? or T?* spectrum from signal decay measurements at each individual image pixel. However, detection of parameters from the measured decay curve, assuming a combination of smooth multi-exponential curves, results in a nonlinear and seriously ill-posed problem. In this paper, we propose a new method to obtain a stable MWF map robust to the presence of noise while sustaining sufficient resolution, which uses weighted combinations of measured decay signals in a spatially independent neighborhood to combine tissues with similar relaxation parameters. To determine optimal weighting factors, we define a spatially independent neighborhood for each pixel and a distance with respect to decay rates that effectively includes pixels with similar decay characteristics, and which therefore have similar relaxation parameters. We recover the MWF values by using optimally weighted decay curves. We use numerical simulations and in vitro and in vivo experimental brain data scanned with a multi-gradient-echo sequence to demonstrate the feasibility of our proposed algorithm and to highlight its advantages compared to the conventional method. PMID:23384527

Kwon, Oh In; Woo, Eung Je; Du, Yiping P; Hwang, Dosik

2013-07-01

266

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

267

Transferring Goods or Splitting a Resource Pool  

Science.gov (United States)

We investigated the consequences for exchange outcomes of the violation of an assumption underlying most social psychological research on exchange. This assumption is that the negotiated direct exchange of commodities between two actors (pure exchange) can be validly represented as two actors splitting a fixed pool of resources (split pool…

Dijkstra, Jacob; Van Assen, Marcel A. L. M.

2008-01-01

268

Anisotropic Spin Splitting in Step Quantum Wells  

International Nuclear Information System (INIS)

By the method of finite difference, the anisotropic spin splitting of the AlxGa1–xAs/GaAs/AlyGa1–yAs/AlxGa1–xAs step quantum wells (QWs) are theoretically investigated considering the interplay of the bulk inversion asymmetry and structure inversion asymmetry induced by step quantum well structure and external electric field. We demonstrate that the anisotropy of the total spin splitting can be controlled by the shape of the QWs and the external electric field. The interface related Rashba effect plays an important effect on the anisotropic spin splitting by influencing the magnitude of the spin splitting and the direction of electron spin. The Rashba spin splitting presents in the step quantum wells due to the interface related Rashba effect even without external electric field or magnetic field. (condensed matter: electronicstructure, electrical, magnetic, and opticalproperties)

269

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

270

Lightweight electrical connector split backshell  

Science.gov (United States)

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

Goldman, Elliot (Inventor)

2009-01-01

271

The nucleosome remodeling and deacetylase chromatin remodeling (NuRD) complex is required for peripheral nerve myelination.  

Science.gov (United States)

Several key transcription factors and coregulators important to peripheral nerve myelination have been identified, but the contributions of specific chromatin remodeling complexes to peripheral nerve myelination have not been analyzed. Chromodomain helicase DNA-binding protein 4 (Chd4) is the core catalytic subunit of the nucleosome remodeling and deacetylase (NuRD) chromatin remodeling complex. Previous studies have shown Chd4 interacts with Nab (NGFI-A/Egr-binding) corepressors, which are required for early growth response 2 (Egr2/Krox20), to direct peripheral nerve myelination by Schwann cells. In this study, we examined the developmental importance of the NuRD complex in peripheral nerve myelination through the generation of conditional Chd4 knock-out mice in Schwann cells (Chd4(loxP/loxP); P0-cre). Chd4 conditional null mice were found to have delayed myelination, radial sorting defects, hypomyelination, and the persistence of promyelinating Schwann cells. Loss of Chd4 leads to elevated expression of immature Schwann cell genes (Id2, c-Jun, and p75), and sustained expression of the promyelinating Schwann cell gene, Oct6/Scip, without affecting the levels of Egr2/Krox20. Furthermore, Schwann cell proliferation is upregulated in Chd4-null sciatic nerve. In vivo chromatin immunoprecipitation studies reveal recruitment of Chd4 and another NuRD component, Mta2, to genes that are positively and negatively regulated by Egr2 during myelination. Together, these results underscore the necessity of Chd4 function to guide proper terminal differentiation of Schwann cells and implicate the NuRD chromatin remodeling complex as a requisite factor in timely and stable peripheral nerve myelination. PMID:22302795

Hung, Holly; Kohnken, Rebecca; Svaren, John

2012-02-01

272

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

Science.gov (United States)

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

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

2014-01-01

273

Complement regulatory molecules on human myelin and glial cells: differential expression affects the deposition of activated complement proteins.  

Science.gov (United States)

The expression of decay-accelerating factor CD55, membrane cofactor protein CD46, and CD59 was studied on Schwann cells cultured from human sural nerve and myelin membranes prepared from human cauda equina and spinal cord. These proteins are regulatory membrane molecules of the complement system. CD55 and CD46 are inhibitors of C3 and C5 convertases and CD59 inhibits C8 and C9 incorporation into C5b-9 complex and C9-C9 polymerization. The presence of these proteins was assessed by using antibodies to each of the proteins by fluorescent microscopy, fluorescence-activated cell sorter analysis, and also sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blot analysis. Schwann cells in culture expressed CD55, CD46, and CD59. It is interesting that only CD59 was detected on myelin from both central and peripheral nerve tissue. The ability of these proteins to limit C3 peptide deposition and C9 polymerization in myelin was studied by western blot analysis. C3b deposition was readily detected on antibody-sensitized myelin incubated with normal human serum used as a source of complement but not with EDTA-treated or heat-inactivated serum. C3b deposition was not affected by anti-CD55 antibody. On the other hand, poly-C9 formation in myelin, which was maximum when 50% normal human serum was used, was increased four-to fivefold when myelin was preincubated with anti-CD59. Our data suggest that complement activation on myelin is down-regulated at the step of the assembly of terminal complement complexes, including C5b-9, due to the presence of CD59. PMID:8522968

Koski, C L; Estep, A E; Sawant-Mane, S; Shin, M L; Highbarger, L; Hansch, G M

1996-01-01

274

A combinatorial network of evolutionarily conserved myelin basic protein regulatory sequences confers distinct glial-specific phenotypes.  

Science.gov (United States)

Myelin basic protein (MBP) is required for normal myelin compaction and is implicated in both experimental and human demyelinating diseases. In this study, as an initial step in defining the regulatory network controlling MBP transcription, we located and characterized the function of evolutionarily conserved regulatory sequences. Long-range human-mouse sequence comparison revealed over 1 kb of conserved noncoding MBP 5' flanking sequence distributed into four widely spaced modules ranging from 0.1 to 0.4 kb. We demonstrate first that a controlled strategy of transgenesis provides an effective means to assign and compare qualitative and quantitative in vivo regulatory programs. Using this strategy, single-copy reporter constructs, designed to evaluate the regulatory significance of modular and intermodular sequences, were introduced by homologous recombination into the mouse hprt (hypoxanthine-guanine phosphoribosyltransferase) locus. The proximal modules M1 and M2 confer comparatively low-level oligodendrocyte expression primarily limited to early postnatal development, whereas the upstream M3 confers high-level oligodendrocyte expression extending throughout maturity. Furthermore, constructs devoid of M3 fail to target expression to newly myelinating oligodendrocytes in the mature CNS. Mutation of putative Nkx6.2/Gtx sites within M3, although not eliminating oligodendrocyte targeting, significantly decreases transgene expression levels. High-level and continuous expression is conferred to myelinating or remyelinating Schwann cells by M4. In addition, when isolated from surrounding MBP sequences, M3 confers transient expression to Schwann cells elaborating myelin. These observations define the in vivo regulatory roles played by conserved noncoding MBP sequences and lead to a combinatorial model in which different regulatory modules are engaged during primary myelination, myelin maintenance, and remyelination. PMID:14614079

Farhadi, Hooman F; Lepage, Pierre; Forghani, Reza; Friedman, Hana C H; Orfali, Wayel; Jasmin, Luc; Miller, Webb; Hudson, Thomas J; Peterson, Alan C

2003-11-12

275

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

International Nuclear Information System (INIS)

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

276

Photoinduced water splitting with oxotitanium tetraphenylporphyrin.  

Science.gov (United States)

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

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

2014-08-01

277

The development of myelin in the spinal cord of the North American opossum and its possible role in loss of rubrospinal plasticity. A study using myelin basic protein and galactocerebroside immuno-histochemistry.  

Science.gov (United States)

The aims of this study were to observe the timing and sequence of myelin formation in the opossum's spinal cord by using myelin basic protein (MBP) immuno-histochemistry and to determine whether the onset of myelination, as demonstrated by the presence of MBP or galactocerebroside (GalC)-like immuno-reactivity (LI), correlates temporally with the end of the critical period for rubrospinal plasticity. Rubral axons grow around a lesion of their pathway during early development but they do not do so at later stages of development or in the adult animal. MBP-LI was first observed in the opossum's spinal cord at postnatal day 15 and its development in most tracts followed rostral to caudal gradients. MBP-LI occurred in some tracts before others, however, regardless of level. MBP- and GalC-LI first appeared in the lateral funiculus, the location of rubrospinal axons, around the end of the critical period for rubrospinal plasticity and it was found in the dorsal horn, an area traversed by rerouted axons in the plasticity experiments, shortly thereafter. Since there is a rough temporal correlation between the development of myelin, as demonstrated by the presence of MBP and GalC immuno-reactivity, and the end of the critical period for rubrospinal plasticity, it is possible that myelin proteins which inhibit axonal elongation contribute to loss of that plasticity. PMID:7680969

Ghooray, G T; Martin, G F

1993-03-19

278

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

279

Poincaré Map Based on Splitting Methods  

International Nuclear Information System (INIS)

Firstly, by using the Liouville formula, we prove that the Jacobian matrix determinants of splitting methods are equal to that of the exact Sow. However, for the explicit Runge–Kutta methods, there is an error term of order p + 1 for the Jacobian matrix determinants. Then, the volume evolution law of a given region in phase space is discussed for different algorithms. It is proved that splitting methods can exactly preserve the sum of Lyapunov exponents invariable. Finally, a Poincaré map and its energy distribution of the Duffing equation are computed by using the second-order splitting method and the Heun method (a second-order Runge–Kutta method). Computation illustrates that the results by splitting methods can properly represent systems' chaotic phenomena. (general)

280

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

 
 
 
 
281

GENERAL: Poincaré Map Based on Splitting Methods  

Science.gov (United States)

Firstly, by using the Liouville formula, we prove that the Jacobian matrix determinants of splitting methods are equal to that of the exact Sow. However, for the explicit Runge-Kutta methods, there is an error term of order p + 1 for the Jacobian matrix determinants. Then, the volume evolution law of a given region in phase space is discussed for different algorithms. It is proved that splitting methods can exactly preserve the sum of Lyapunov exponents invariable. Finally, a Poincaré map and its energy distribution of the Duffing equation are computed by using the second-order splitting method and the Heun method (a second-order Runge-Kutta method). Computation illustrates that the results by splitting methods can properly represent systems' chaotic phenomena.

Gang, Tie-Qiang; Chen, Li-Jie; Mei, Feng-Xiang

2008-11-01

282

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

283

Interleukin-2 receptors and interleukin-2-mediated signaling in myelin: activation of diacylglycerol kinase and phosphatidylinositol 3-kinase.  

Science.gov (United States)

Myelin was previously shown to possess neurotransmitter and cytokine receptors that trigger well-defined signaling mechanisms within the multilamellar structure. The present study reveals the presence of an interleukin-2 (IL-2) receptor in isolated mouse CNS myelin that responds to recombinant mouse IL-2 by activating diacylglycerol kinase (DAGK) and phosphoinositide 3-kinase (PI3K); additional evidence suggests participation by protein tyrosine kinase. Activation of myelin DAGK by IL-2 occurred in brain stem tissue mince and was blocked by chelerythrin chloride, indicating an essential role for myelin-localized protein kinase C. Two inhibitors of PI3K, wortmannin and LY294002, blocked endogenous PI3K as well as that enhanced by IL-2. Activation of PI3K by IL-2 was also blocked by tyrphostin A25, a selective inhibitor of PTK, suggesting activation of the latter by IL-2 is upstream to PI3K activation. This reaction resulted in tyrosine phosphorylation of a protein tentatively identified as the p85 subunit of PI3K. Developmental changes were noted in that receptor density and signaling activity were robust during the period of rapid myelination and declined rapidly thereafter. PMID:14643763

Chakraborty, G; Reddy, R; Drivas, A; Ledeen, R W

2003-01-01

284

Temporal and spatial expression of major myelin proteins in the human fetal spinal cord during the second trimester  

Energy Technology Data Exchange (ETDEWEB)

Immunohistochemical identification of myelin basic protein (MBP) is a sensitive method for assessing myelination in the human fetal central nervous system (CNS). However, the temporospatial relationship of expression of two other major myelin proteins, proteolipid protein (PLP) and myelin-associated glycoprotein (MAG) to that of MBP during fetal development has not been assessed in human tissues. Vibratome sections of cervical, thoracic and lumbosacral levels from 37 normal spinal cords of {le} 10 to 24 gestational week (GW) fetuses were analyzed using immunohistochemical methods. Using light microscopy, MBP was the first oligodendrocyte marker detected, present by 10 GW at more rostral levels. PLP and MAG were detected rostrally between 12 to 14 GW. All myelin proteins were expressed in anterior to posterior and rostral to caudal gradients. By the late second trimester, expression of MBP, PLP and MAG was noted in all locations in the spinal white matter except for the corticospinal tract. Expression of MAG was particularly marked in the posterior root entry zone and propriospinal tracts. The results suggest that PLP and MAG are expressed later than MBP but follow similar spatial gradients. 44 refs., 11 figs., 2 tabs.

Weidenheim, K.M.; Bodhireddy, S.R.; Rashbaum, W.K.; Lyman, W.D. [Albert Einstein College of Medicine, Bronx, NY (United States)

1996-06-01

285

Temporal and spatial expression of major myelin proteins in the human fetal spinal cord during the second trimester.  

Science.gov (United States)

Immunohistochemical identification of myelin basic protein (MBP) is a sensitive method for assessing myelination in the human fetal central nervous system (CNS). However, the temporospatial relationship of expression of two other major myelin proteins, proteolipid protein (PLP) and myelin-associated glycoprotein (MAG) to that of MBP during fetal development has not been assessed in human tissues. Vibratome sections of cervical, thoracic and lumbosacral levels from 37 normal spinal cords of < or = 10 to 24 gestational week (GW) fetuses were analyzed using immunohistochemical methods. Using light microscopy, MBP was the first oligodendrocyte marker detected, present by 10 GW at more rostral levels. PLP and MAG were detected rostrally between 12 to 14 GW. All myelin proteins were expressed in anterior to posterior and rostral to caudal gradients. By the late second trimester, expression of MBP, PLP and MAG was noted in all locations in the spinal white matter except for the corticospinal tract. Expression of MAG was particularly marked in the posterior root entry zone and propriospinal tracts. The results suggest that PLP and MAG are expressed later than MBP but follow similar spatial gradients. PMID:8642400

Weidenheim, K M; Bodhireddy, S R; Rashbaum, W K; Lyman, W D

1996-06-01

286

CNS myelin induces regulatory functions of DC-SIGN-expressing, antigen-presenting cells via cognate interaction with MOG.  

Science.gov (United States)

Myelin oligodendrocyte glycoprotein (MOG), a constituent of central nervous system myelin, is an important autoantigen in the neuroinflammatory disease multiple sclerosis (MS). However, its function remains unknown. Here, we show that, in healthy human myelin, MOG is decorated with fucosylated N-glycans that support recognition by the C-type lectin receptor (CLR) DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) on microglia and DCs. The interaction of MOG with DC-SIGN in the context of simultaneous TLR4 activation resulted in enhanced IL-10 secretion and decreased T cell proliferation in a DC-SIGN-, glycosylation-, and Raf1-dependent manner. Exposure of oligodendrocytes to proinflammatory factors resulted in the down-regulation of fucosyltransferase expression, reflected by altered glycosylation at the MS lesion site. Indeed, removal of fucose on myelin reduced DC-SIGN-dependent homeostatic control, and resulted in inflammasome activation, increased T cell proliferation, and differentiation toward a Th17-prone phenotype. These data demonstrate a new role for myelin glycosylation in the control of immune homeostasis in the healthy human brain through the MOG-DC-SIGN homeostatic regulatory axis, which is comprised by inflammatory insults that affect glycosylation. This phenomenon should be considered as a basis to restore immune tolerance in MS. PMID:24935259

García-Vallejo, J J; Ilarregui, J M; Kalay, H; Chamorro, S; Koning, N; Unger, W W; Ambrosini, M; Montserrat, V; Fernandes, R J; Bruijns, S C M; van Weering, J R T; Paauw, N J; O'Toole, T; van Horssen, J; van der Valk, P; Nazmi, K; Bolscher, J G M; Bajramovic, J; Dijkstra, C D; 't Hart, B A; van Kooyk, Y

2014-06-30

287

Wave-equation shear wave splitting tomography  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The main focus of this paper is the development of a theoretical framework for the tomographic inversion of (broad-band) shear wave splitting measurements in terms of anisotropic structure in the upper mantle. We show that the partial differential equations (PDEs) that govern wave equation shearwave splitting tomography are, upon linearization with the Born approximation, similar in structure to the equations that describe wave equation transmission and reflection tomography. F...

Long, M. L.; Hoop, M. V.; Hilst, R. D.

2008-01-01

288

On p-symmetric Heegaard splittings  

CERN Document Server

We show that every p-fold strictly-cyclic branched covering of a b-bridge link in $S^3$ admits a p-symmetric Heegaard splitting - in the sense of Birman and Hilden - of genus $g=(b-1)(p-1)$. This gives a complete converse of one of the results of the two authors. Moreover, we introduce the concept of weakly p-symmetric Heegaard splittings and prove similar results in this more general context.

Mulazzani, M

2000-01-01

289

Ectrodactyly/split hand feet malformation  

Directory of Open Access Journals (Sweden)

Full Text Available Split-hand/split-foot malformation is a rare limb malformation with median clefts of the hands and feet and aplasia/hypoplasia of the phalanges, metacarpals and metatarsals. When present as an isolated anomaly, it is usually inherited as an autosomal dominant form. We report a case of autosomal recessive inheritance and discuss the antenatal diagnosis, genetic counseling and treatment for the malformation.

Jindal Geetanjali

2009-01-01

290

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

291

Macroscopic tunnel splittings in superconducting phase qubits  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

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

2004-01-01

292

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

293

Evaluating parametric holonomic sequences using rectangular splitting  

Digital Repository Infrastructure Vision for European Research (DRIVER)

We adapt the rectangular splitting technique of Paterson and Stockmeyer to the problem of evaluating terms in holonomic sequences that depend on a parameter. This approach allows computing the $n$-th term in a recurrent sequence of suitable type using $O(n^{1/2})$ "expensive" operations at the cost of an increased number of "cheap" operations. Rectangular splitting has little overhead and can perform better than either naive evaluation or asymptotically faster algorithms f...

Johansson, Fredrik

2013-01-01

294

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

CERN Document Server

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

Iida, Y; Yokoyama, T

2012-01-01

295

Cleavage of Neuregulin-1 by BACE1 or ADAM10 Protein Produces Differential Effects on Myelination*  

Science.gov (United States)

Neuregulin-1 (Nrg1) is encoded by a single gene and exists in naturally secreted and transmembrane isoforms. Nrg1 exerts its signaling activity through interaction with its cognate ErbB receptors. Multiple membrane-anchored Nrg1 isoforms, present in six different membrane topologies, must be processed by a protease to initiate a signaling cascade. Here, we demonstrate that BACE1 and ADAM10 can process type I and III Nrg1 at two adjacent sites. Our cleavage site mapping experiments showed that the BACE1 cleavage site is located eight amino acids downstream of the ADAM10 cleavage site, and this order of cleavage is the opposite of amyloid precursor protein cleavage by these two enzymes. Cleavages were further confirmed via optimized electrophoresis. Cleavage of type I or III Nrg1 by ADAM10 and BACE1 released a signaling-capable N-terminal fragment (ntf), either Nrg1-ntf? or Nrg1-ntf?, which could similarly activate an ErbB receptor as evidenced by increased phosphorylation of Akt and ERK, two downstream signaling molecules. Although both Nrg1-ntf? and Nrg1-ntf? could initiate a common signaling cascade, inhibition or down-regulation of ADAM10 alone in a co-culture system did not affect normal myelination, whereas specific inhibition of BACE1 impaired normal myelination. Thus, processing of Nrg1 by BACE1 appears to be more critical for regulating myelination. Our results imply that a significant inhibition of BACE1 could potentially impair Nrg1 signaling activity in vivo. PMID:21576249

Luo, Xiaoyang; Prior, Marguerite; He, Wanxia; Hu, Xiangyou; Tang, Xiaoying; Shen, Weizhen; Yadav, Satya; Kiryu-Seo, Sumiko; Miller, Robert; Trapp, Bruce D.; Yan, Riqiang

2011-01-01

296

Excitatory glycine responses of CNS myelin mediated by NR1/NR3 ‘NMDA’ receptor subunits  

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NMDA receptors are typically excited by a combination of glutamate and glycine. Here we describe excitatory responses in CNS myelin that are gated by a glycine agonist alone and mediated by NR1/NR3 ‘NMDA receptor’ subunits. Response properties include activation by d-serine, inhibition by the glycine-site antagonist CNQX, and insensitivity to the glutamate-site antagonist d-APV. d-Serine responses were abrogated in NR3A-deficient mice. Our results suggest the presence of functional NR1/NR...

Pin?a-crespo, Juan C.; Talantova, Maria; Micu, Ileana; States, Bradley; Chen, H. -s Vincent; Tu, Shichun; Nakanishi, Nobuki; Tong, Gary; Zhang, Dongxian; Heinemann, Stephen F.; Zamponi, Gerald W.; Stys, Peter K.; Lipton, Stuart A.

2010-01-01

297

Relationship between temperature and stimulation frequency in conduction block of amphibian myelinated axon  

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The temperature-frequency relationship in nerve conduction block induced by high-frequency, biphasic electrical current was investigated by computer simulation using an amphibian myelinated axon model based on Frankenhaeuser-Huxley (FH) equations. For an axon of diameter 10 µm, the minimal blocking frequency was changed from 6 kHz to 3 kHz as the temperature was decreased from 37 °C to 15 °C. The maximal blocking temperature below which the axon could be blocked was increased from 22 °C t...

Tai, Changfeng; Wang, Jicheng; Roppolo, James R.; Groat, William C.

2009-01-01

298

Lethal recessive myelin toxicity of prion protein lacking its central domain  

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PrPC-deficient mice expressing prion protein variants with large amino-proximal deletions (termed PrP?F) suffer from neurodegeneration, which is rescued by full-length PrPC. We now report that expression of PrP?CD, a PrP variant lacking 40 central residues (94–134), induces a rapidly progressive, lethal phenotype with extensive central and peripheral myelin degeneration. This phenotype was rescued dose-dependently by coexpression of full-length PrPC or PrPC lacking all octarepeats. Expres...

Baumann, Frank; Tolnay, Markus; Brabeck, Christine; Pahnke, Jens; Kloz, Ulrich; Niemann, Hartmut H.; Heikenwalder, Mathias; Ru?licke, Thomas; Bu?rkle, Alexander; Aguzzi, Adriano

2007-01-01

299

Increased charge displacement in the membrane of myelinated nerve at reduced extracellular pH.  

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Asymmetry currents were measured in nodes of myelinated nerve fibers from Rana esculenta at extracellular pH values of 5.2, 7.0, and 8.1 by averaging the currents during and after 1-ms depolarizing and hyperpolarizing voltage pulses. The charge displacement in the nodal membrane was obtained by numerical integration of the asymmetry currents. Lowering the pH from 7.0 to 5.2 significantly slows down the kinetics of the fast charge displacement during depolarization but hardly affects the kinet...

Neumcke, B.; Schwarz, W.; Sta?mpfli, R.

1980-01-01

300

Immunodominant fragments of myelin basic protein initiate T cell-dependent pain  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background The myelin sheath provides electrical insulation of mechanosensory A?-afferent fibers. Myelin-degrading matrix metalloproteinases (MMPs damage the myelin sheath. The resulting electrical instability of A?-fibers is believed to activate the nociceptive circuitry in A?-fibers and initiate pain from innocuous tactile stimulation (mechanical allodynia. The precise molecular mechanisms, responsible for the development of this neuropathic pain state after nerve injury (for example, chronic constriction injury, CCI, are not well understood. Methods and results Using mass spectrometry of the whole sciatic nerve proteome followed by bioinformatics analyses, we determined that the pathways, which are classified as the Infectious Disease and T-helper cell signaling, are readily activated in the nerves post-CCI. Inhibition of MMP-9/MMP-2 suppressed CCI-induced mechanical allodynia and concomitant TNF-? and IL-17A expression in nerves. MMP-9 proteolysis of myelin basic protein (MBP generated the MBP84-104 and MBP68-86 digest peptides, which are prominent immunogenic epitopes. In agreement, the endogenous MBP69-86 epitope co-localized with MHCII and MMP-9 in Schwann cells and along the nodes of Ranvier. Administration of either the MBP84-104 or MBP68-86 peptides into the naïve nerve rapidly produced robust mechanical allodynia with a concomitant increase in T cells and MHCII-reactive cell populations at the injection site. As shown by the genome-wide expression profiling, a single intraneural MBP84-104 injection stimulated the inflammatory, immune cell trafficking, and antigen presentation pathways in the injected naïve nerves and the associated spinal cords. Both MBP84-104-induced mechanical allodynia and characteristic pathway activation were remarkably less prominent in the T cell-deficient athymic nude rats. Conclusions These data implicate MBP as a novel mediator of pain. Furthermore, the action of MMPs expressed within 1?day post-injury is critical to the generation of tactile allodynia, neuroinflammation, and the immunodominant MBP digest peptides in nerve. These MBP peptides initiate mechanical allodynia in both a T cell-dependent and -independent manner. In the course of Wallerian degeneration, the repeated exposure of the cryptic MBP epitopes, which are normally sheltered from immunosurveillance, may induce the MBP-specific T cell clones and a self-sustaining immune reaction, which may together contribute to the transition of acute pain into a chronic neuropathic pain state.

Liu Huaqing

2012-06-01

 
 
 
 
301

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

302

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

303

Peroxisome proliferator-activated receptor gamma-coactivator-1 alpha coordinates sphingolipid metabolism, lipid raft composition and myelin protein synthesis.  

Science.gov (United States)

Peroxisome proliferator-activated receptor gamma-coactivator-1 alpha (PGC1a) is involved in energy and lipid metabolism, and its loss leads to neurodegenerative changes in the striatum. Here we performed lipidomic analysis on brain extracts from PGC1a mutant and wild-type mice. We found increased phosphatidylcholine and decreased ceramides in the brain of PGC1a-deficient mice. An analysis of lipid raft fractions revealed increased ceramide, glucocylceramides and GM1 ganglioside in the PGC1a mutants. In the cerebellum, we observed a decrease in proteins associated with myelination, but were unable to detect any morphological abnormalities in compact myelin formation in PGC1a mutants compared with wild-type mice. Although PGC1a is involved in lipid biosynthesis, we concluded that altered lipid composition in the PGC1a mutant did not directly affect central nervous system myelin morphology. PMID:23763823

Camacho, Alberto; Huang, Jeffrey K; Delint-Ramirez, Ilse; Yew Tan, Chong; Fuller, Maria; Lelliott, Christopher J; Vidal-Puig, Antonio; Franklin, Robin J M

2013-09-01

304

Unmyelinated nerve fibers in the human dental pulp express markers for myelinated fibers and show sodium channel accumulations  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background The dental pulp is a common source of pain and is used to study peripheral inflammatory pain mechanisms. Results show most fibers are unmyelinated, yet recent findings in experimental animals suggest many pulpal afferents originate from fibers that are myelinated at more proximal locations. Here we use the human dental pulp and confocal microscopy to examine the staining relationships of neurofilament heavy (NFH, a protein commonly expressed in myelinated afferents, with other markers to test the possibility that unmyelinated pulpal afferents originate from myelinated axons. Other staining relationships studied included myelin basic protein (MBP, protein gene product (PGP 9.5 to identify all nerve fibers, tyrosine hydroxylase (TH to identify sympathetic fibers, contactin-associated protein (caspr to identify nodal sites, S-100 to identify Schwann cells and sodium channels (NaChs. Results Results show NFH expression in most PGP9.5 fibers except those with TH and include the broad expression of NFH in axons lacking MBP. Fibers with NFH and MBP show NaCh clusters at nodal sites as expected, but surprisingly, NaCh accumulations are also seen in unmyelinated fibers with NFH, and in fibers with NFH that lack Schwann cell associations. Conclusions The expression of NFH in most axons suggests a myelinated origin for many pulpal afferents, while the presence of NaCh clusters in unmyelinated fibers suggests an inherent capacity for the unmyelinated segments of myelinated fibers to form NaCh accumulations. These findings have broad implications on the use of dental pulp to study pain mechanisms and suggest possible novel mechanisms responsible for NaCh cluster formation and neuronal excitability.

Henry Michael A

2012-03-01

305

Measurement of myelin basic protein by radioimmunoassay in closed head trauma, multiple sclerosis and other neurological diseases  

International Nuclear Information System (INIS)

A double antibody sequential radioimmunoassay for human myelin basic protein (MBP) has been developed. The assay utilizes a rabbit antibody to human MBP and purified rabbit MBP as the radiolabelled antigen. This assay was used to analyze cerebrospinal fluid (CSF) from 22 patients with severe head injury, 61 other cases of various neurological disorders, and 106 normal controls. The results showed that closed head trauma caused moderate to severe elevations in CSF MBP, and elevated CSF MBP was detectable in several diseases which involve CNS myelin

306

Myelin-associated neurite growth-inhibitory proteins and suppression of regeneration of immature mammalian spinal cord in culture.  

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Neurite outgrowth across spinal cord lesions in vitro is rapid in preparations isolated from the neonatal opossum Monodelphis domestica up to the age of 12 days. At this age oligodendrocytes, myelin, and astrocytes develop and regeneration ceases to occur. The role of myelin-associated neurite growth-inhibitory proteins, which increase in concentration at 10-13 days, was investigated in culture by applying the antibody IN-1, which blocks their effects. In the presence of IN-1, 22 out of 39 pr...

Varga, Z. M.; Schwab, M. E.; Nicholls, J. G.

1995-01-01

307

Amyloid precursor protein is enriched in axolemma and periaxolemmal-myelin and associated clathrin-coated vesicles.  

Science.gov (United States)

The amyloid precursor protein (APP) is widely distributed within the CNS, where it is expressed in both neurons and glia. We have isolated axolemma and periaxolemmal-myelin from rat brain and have determined by Western blot that APPs, Mr 100-110 kDa, are major constituents of these membrane. Isolation of axolemma, periaxolemmal-myelin, and compact myelin show that while APP represents 1 and 0.6% of the proteins of these respective membranes, it is absent from compact myelin. These results indicate that APP transported down the axon is deposited at sites in the axolemma as well as the synapse, and that within the myelin complex, APP is targeted to the periaxolemmal domain. Both axolemma and periaxolemmal-myelin contained a 10.5 kDa APP peptide which, based on reactivity with anti-C-terminal APP antibodies but not with anti-N-terminal antibody, appears to be a membrane-associated C-terminal fragment. Western blots with antibodies to Alzheimer precursor-like proteins (APLP) indicate that APP immune reactivity is not a result of cross reactivity with APLPs. Isolation of axolemma from human autopsy material showed nearly identical results with a clear enrichment, relative to homogenate, of APP Mr 100-110 and the 10.5 kDa C-terminal peptide. The demonstration of APP in axolemma and periaxolemmal-myelin was replicated in membrane isolated from bovine brain. Bovine studies were extended to analysis of white matter clathrin-coated vesicles; these data show that coated vesicles isolated from white matter, under conditions that previous studies indicate are largely endocytic vesicles, contain levels of APP comparable to that found in axolemma and periaxolemmal-myelin. In addition, these vesicles contain cysteinyl and aspartyl proteases. Incubation of axolemma with cathepsin B at pH 6.0 caused a rapid loss in the immune reactivity of APP Mr 100-110 and Mr 10.5 when analyzed with antibodies to APP672-695. This appears to be the result of hydrolysis within the epitope and not proteolysis of APP or the C-terminal peptide, since no loss of reactivity was observed when analyzed with antibodies to sites more distal to the C-terminus. Thus, cathepsin B hydrolyses membrane bound APP close to the C-terminus and may be a useful tool for altering C-terminal APP function. PMID:8176757

Sapirstein, V S; Durrie, R; Berg, M J; Marks, N

1994-02-15

308

Effect of prenatal neutron irradiation on expression of myelin genes and glycoprotein genes in developing rat brain  

International Nuclear Information System (INIS)

The effect of prenatal neutron irradiation on the expression of myelin genes and glycoprotein genes in the brain of rats is studied. The observed postradiation enhancement of the expression of glial and neuronal genes involved in the process of myelinization and differentiation in the central nervous system, is related to a necessity to compensate the functional disorders of the brain caused by radiation death of neuroblasts. A specific molecular mechanism of compensation reaction of brain cells of prenatally irradiated rats is described for the first time; the mechanism consists in the activation of the expression of specific glial genes and genes of neuronal surface glycoproteins

309

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.)

310

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

311

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

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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.

Adamsbaum, C. [Service de Radiologie, Hopital St. Vincent de Paul, Paris (France); Pinton, F. [Centre d`Energie Atomique, BRIPP, SHFJ, Orsay (France); Rolland, Y. [Service de Radiologie, Hopital St. Vincent de Paul, Paris (France); Chiron, C. [Service de Neurologie, Hopital St. Vincent de Paul, Paris (France); Dulac, O. [Service de Neurologie, Hopital St. Vincent de Paul, Paris (France); Kalifa, G. [Service de Radiologie, Hopital St. Vincent de Paul, Paris (France)

1996-11-01

312

Identification of the glycosylation pattern of meat proteins in tissues from bovine myelin.  

Science.gov (United States)

A variant form of Creutzfeld-Jacob disease in humans is associated with the consumption of food contaminated with the bovine central neural system. This has focused attention on the need for procedures to detect tissues of the neural system in meat and meat products. A method was developed for the identification of myelin glycoproteins in bovine neural tissue. The glycosylated structures of glycoproteins in different protein mixtures from central nervous system (CNS) and peripheral nervous system (PNS) isolated from bovine myelin were identified by the specific lectin-glycoprotein reactions. Digoxigenin-labeled lectins bonded to the terminal glycoconjugate sequences of nine CNS glycoproteins ranging from 15 to 200 kDa and four PNS glycoproteins ranging from 22 to 105 kDa. Datura stramonium (DSA) recognized the epitope Galbeta1-4GlcNAc by two CNS and three PNS glycoproteins. Maackia amurensis (MAA) recognized the epitope NeuAcalpha2-3Gal by four CNS and two PNS glycoproteins. The peanut Arachis hypogaea (PNA) reacted with the high molecular CNS glycoprotein (200 kDa) with the sequence Galbeta1-3GalNAc. Galanthus nivalis (GNA) bonded to mannose subunits linked alpha1-3 and alpha1-6 by six CNS glycoproteins with molecular weights between 17 and 200 kDa. Four of these glycoproteins were recognized from monoclonal antibodies against the "HNK-1 epitope". PMID:20513571

Katsiferis, Theofanis; Wiethölter, Horst

2010-08-01

313

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.

314

Direct profiling of myelinated and demyelinated regions in mouse brain by imaging mass spectrometry  

Science.gov (United States)

One of the newly developed imaging mass spectrometry (IMS) technologies utilizes matrix-assisted laser desorption/ionization (MALDI) mass spectrometry to map proteins in thin tissue sections. In this study, we evaluated the power of MALDI IMS as we developed it in our (Bruker) MALDI TOF (Reflex IV) and TOF-TOF (Ultraflex II) systems to study myelin patterns in the mouse central nervous system under normal and pathological conditions. MALDI IMS was applied to assess myelin basic protein (MBP) isoform-specific profiles in different regions throughout the mouse brain. The distribution of ions of m/z 14,144 and 18,447 displayed a striking resemblance with white matter histology and were identified as MBP isoform 8 and 5, respectively. In addition, we demonstrated a significant reduction of the MBP-8 peak intensity upon MALDI IMS analysis of focal ethidium bromide-induced demyelinated brain areas. Our MS images were validated by immunohistochemistry using MBP antibodies. This study underscores the potential of MALDI IMS to study the contribution of MBP to demyelinating diseases.

Ceuppens, Ruben; Dumont, Debora; van Brussel, Leen; van de Plas, Babs; Daniels, Ruth; Noben, Jean-Paul; Verhaert, Peter; van der Gucht, Estel; Robben, Johan; Clerens, Stefan; Arckens, Lutgarde

2007-02-01

315

Intelligent data splitting for volume data  

Science.gov (United States)

We describe a system that automatically extracts body sections of interest from volume data sets obtained from major medical modalities. This is critical as an effort to save storage and transmission bandwidth and improve data sharing efficiency. The data to be split is stored in a series of files, and each of the files contains one axial slice image. This is how the DICOM data is stored. The splitting of volume data will therefore be applied in the axial direction. The core of the system is an algorithm module that automatically detects lines of separation in the axial direction of the data. Afterwards, the system will copy the files that contain the desired section of slice images to the destination, according to the detected separation lines. To obtain the split lines, features are extracted from human anatomies that are specific to each body section. The method and principle can be applied to major modalities where the extraction of various data sections is needed.

Shen, Hong; Bartsch, Ernst

2006-03-01

316

Observers and splitting structures in relativistic electrodynamics  

Science.gov (United States)

We introduce a relativistic splitting structure as a means to map fields and equations of electromagnetism from curved four-dimensional space–time to three-dimensional observer?s space. We focus on a minimal set of mathematical structures that are directly motivated by the language of the physical theory. Space–time, world-lines, time translation, space platforms and time synchronization all find their mathematical counterparts. The splitting structure is defined without recourse to coordinates or frames. This is noteworthy since, in much of the prevalent literature, observers are identified with adapted coordinates and frames. Among the benefits of the approach is a concise and insightful classification of splitting structures that is juxtaposed to a classification of observers. The application of the framework to the Ehrenfest paradox and Schiff?s ‘Question in General Relativity’ further illustrates the advantages of the framework, enabling a compact, yet profound analysis of the problems at hand.

Auchmann, B.; Kurz, S.

2014-10-01

317

Memory B cells from a subset of treatment-naïve relapsing-remitting multiple sclerosis patients elicit CD4(+) T-cell proliferation and IFN-? production in response to myelin basic protein and myelin oligodendrocyte glycoprotein.  

Science.gov (United States)

Recent evidence suggests that B- and T-cell interactions may be paramount in relapsing-remitting MS (RRMS) disease pathogenesis. We hypothesized that memory B-cell pools from RRMS patients may specifically harbor a subset of potent neuro-APC that support neuro-Ag reactive T-cell proliferation and cytokine secretion. To test this hypothesis, we compared CD80 and HLA-DR expression, IL-10 and lymphotoxin-? secretion, neuro-Ag binding capacity, and neuro-Ag presentation by memory B cells from RRMS patients to naïve B cells from RRMS patients and to memory and naïve B cells from healthy donors (HD). We identified memory B cells from some RRMS patients that elicited CD4(+) T-cell proliferation and IFN-? secretion in response to myelin basic protein and myelin oligodendrocyte glycoprotein. Notwithstanding the fact that the phenotypic parameters that promote efficient Ag presentation were observed to be similar between RRMS and HD memory B cells, a corresponding capability to elicit CD4(+) T-cell proliferation in response to myelin basic protein and myelin oligodendrocyte glycoprotein was not observed in HD memory B cells. Our results demonstrate for the first time that the memory B-cell pool in RRMS harbors neuro-Ag specific B cells that can activate T cells. PMID:20812237

Harp, Christopher T; Ireland, Sara; Davis, Laurie S; Remington, Gina; Cassidy, Bonnie; Cravens, Petra D; Stuve, Olaf; Lovett-Racke, Amy E; Eagar, Todd N; Greenberg, Benjamin M; Racke, Michael K; Cowell, Lindsay G; Karandikar, Nitin J; Frohman, Elliot M; Monson, Nancy L

2010-10-01

318

Splitting methods for the nonlocal Fowler equation  

CERN Document Server

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

Bouharguane, Afaf

2011-01-01

319

Explicit Dehn filling and Heegaard splittings  

CERN Document Server

We prove an explicit, quantitative criterion that ensures the Heegaard surfaces in Dehn fillings behave "as expected." Given a cusped hyperbolic manifold X, and a Dehn filling whose meridian and longitude curves are longer than 2pi(2g-1), we show that every genus g Heegaard splitting of the filled manifold comes from a splitting of the original manifold X. The analogous statement holds for fillings of multiple boundary tori. This gives an effective version of a theorem of Moriah-Rubinstein and Rieck-Sedgwick.

Futer, David

2012-01-01

320

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

 
 
 
 
321

Macroscopic tunnel splittings in superconducting phase qubits  

CERN Document Server

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

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

2004-01-01

322

On geometrical splitting in nonanalog Monte Carlo  

International Nuclear Information System (INIS)

A very general geometrical procedure is considered, and it is shown how the free flights, the statistical weights and the contribution of particles participating in splitting are to be chosen in order to reach unbiased estimates in games where the transition kernels are nonanalog. Equations governing the second moment of the score and the number of flights to be stimulated are derived. It is shown that the post-splitting weights of the fragments are to be chosen equal to reach maximum gain in variance. Conditions are derived under which the expected number of flights remains finite. Simplified example illustrate the optimization of the procedure (author)

323

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

324

Detection and processing of peripheral myelin protein PMP22 in cultured Schwann cells.  

Science.gov (United States)

Peripheral myelin protein, 22 kDa (PMP22), is a myelin molecule associated with Schwann cells in peripheral nerves (Snipes, G. J., Suter, U., Welcher, A. A., and Shooter, E. M. (1992) J. Cell Biol. 117, 225-238). Mutations affecting the PMP22 gene have been implicated in the trembler mutation in mice (Suter, U., Welcher, A. A., Ozcelik, T., Snipes, G. J., Kosaras, B., Francke, U., Billings-Gagliardi, S., Sidman, R. L., and Shooter, E. M. (1992) Nature 356, 241-244; Suter, U., Moskow, J. J., Welcher, A. A., Snipes, G. J., Kosaras, B., Sidman, R. L., Buchberg, A. M., and Shooter, E. M. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 4382-4386) and Charcot-Marie-Tooth Disease in humans (Patel, P. I., Roa, B. B., Welcher, A. A., Schoener-Scott, R., Trask, B. J., Pentao, L., Snipes, G. J., Garcia, C. A., Francke, U., Shooter, E. M., Lupski, J. R., and Suter, U. (1992) Nature genet. 1, 159-165). In this report, we have studied PMP22 production in cultured rat Schwann cells. Schwann cells contain a 1.8-kilobase mRNA transcript coding for PMP22, and its production is up-regulated in vitro by forskolin. Metabolic labeling combined with immunoprecipitation methods using antibodies raised against synthetic peptides of PMP22 reveal that Schwann cells generate the protein from an 18-kDa precursor form which is post-translationally modified by N-linked glycosylation. A second molecule (molecular mass, 48 kDa) that reacted with PMP22 antibodies was also detected in Schwann cells but is not related chemically to PMP22 as determined by pulse-chase labeling. Metabolic labeling of rat sciatic nerve and Western blot analyses of purified rat sciatic nerve myelin reveal that deglycosylation of PMP22 gives rise to an 18-kDa protein similar in size to that in Schwann cells. These results indicate that cultured Schwann cells may provide a good model in which to investigate the production and function of PMP22 and to establish the cellular basis for the protein's involvement in inherited peripheral neuropathies. PMID:8486695

Pareek, S; Suter, U; Snipes, G J; Welcher, A A; Shooter, E M; Murphy, R A

1993-05-15

325

Supporting Students' Constructions of the Splitting Operation  

Science.gov (United States)

Previous research has demonstrated the effectiveness of particular instructional practices that support students' constructions of the partitive unit fraction scheme and measurement concepts for fractions. Another body of research has demonstrated the power of a particular mental operation--the splitting operation--in supporting students'…

Norton, Anderson; Wilkins, Jesse L. M.

2013-01-01

326

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

327

Splitting the Kemmer-Duffin-Petiau Equations  

Digital Repository Infrastructure Vision for European Research (DRIVER)

We study internal structure of the Kemmer-Duffin-Petiau equations for spin-0 and spin-1 mesons. We demonstrate, that the Kemmer-Duffin-Petiau equations can be splitted into constituent equations, describing particles with definite mass and broken Lorentz symmetry. We also show that solutions of the three component constituent equations fulfill the Dirac equation.

Okninski, Andrzej

2003-01-01

328

Frobenius splitting of certain rings of invariants  

CERN Document Server

Two classical rings of invariants are shown to be Frobenius split: for the special linear group acting on the direct sum of several copies of the defining representation and several copies of the dual of the defining representation; and for the special orthogonal group acting on several copies of the defining representation.

Lakshmibai, V; Sankaran, P

2009-01-01

329

On the tuning condition of split supersymmetry  

Energy Technology Data Exchange (ETDEWEB)

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{beta} and on the physical Higgs mass.

Delgado, A. [CERN, Theory Division, CH-1211 Geneva 23 (Switzerland)]. E-mail: antonio.delgado@cern.ch; Giudice, G.F. [CERN, Theory Division, CH-1211 Geneva 23 (Switzerland)

2005-10-27

330

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

331

Crystal-field splitting in Pr dideuteride  

International Nuclear Information System (INIS)

From inelastic neutron scattering experiments, it is concluded that the crystal-field splitting in PrD/sub 1.95/ is 41 meV. Because of this high value, the antiferromagnetic ordering below T/sub N/ = 2.3 K is ascribed to a magnetic ground state, probably GAMMA5, of the Pr3+ ions

332

Efficient Generation of Myelinating Oligodendrocytes from Primary Progressive Multiple Sclerosis Patients by Induced Pluripotent Stem Cells  

Science.gov (United States)

Summary Multiple sclerosis (MS) is a chronic demyelinating disease of unknown etiology that affects the CNS. While current therapies are primarily directed against the immune system, the new challenge is to address progressive MS with remyelinating and neuroprotective strategies. Here, we develop a highly reproducible protocol to efficiently derive oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes from induced pluripotent stem cells (iPSCs). Key elements of our protocol include adherent cultures, dual SMAD inhibition, and addition of retinoids from the beginning of differentiation, which lead to increased yields of OLIG2 progenitors and high numbers of OPCs within 75 days. Furthermore, we show the generation of viral and integration-free iPSCs from primary progressive MS (PPMS) patients and their efficient differentiation to oligodendrocytes. PPMS OPCs are functional, as demonstrated by in vivo myelination in the shiverer mouse. These results provide encouraging advances toward the development of autologous cell therapies using iPSCs. PMID:25254339

Douvaras, Panagiotis; Wang, Jing; Zimmer, Matthew; Hanchuk, Stephanie; O'Bara, Melanie A.; Sadiq, Saud; Sim, Fraser J.; Goldman, James; Fossati, Valentina

2014-01-01

333

Robust myelin quantitative imaging from multi-echo T2 MRI using edge preserving spatial priors.  

Science.gov (United States)

Demyelinating diseases such as multiple sclerosis cause changes in the brain white matter microstructure. Multi-exponential T2 relaxometry is a powerful technology for detecting these changes by generating a myelin water fraction (MWF) map. However, conventional approaches are subject to noise and spatial in-consistence. We proposed a novel approach by imposing spatial consistency and smoothness constraints. We first introduce a two-Gaussian model to approximate the T2 distribution. Then an expectation-maximization framework is introduced with an edge-preserving prior incorporated. Three-dimensional multi-echo MRI data sets were collected from three patients and three healthy volunteers. MWF maps obtained using the conventional, Spatially Regularized Non-negative Least Squares (srNNLS) algorithm as well as the proposed algorithm are compared. The proposed method provides MWF maps with improved depiction of brain structures and significantly lower coefficients of variance in various brain regions, PMID:24505719

Shen, Xiaobo; Nguyen, Thanh D; Gauthier, Susan A; Raj, Ashish

2013-01-01

334

Myelin protein zero Arg36Gly mutation with very late onset and rapidly progressive painful neuropathy.  

Science.gov (United States)

Mutations in myelin protein zero (MPZ) protein result in a wide spectrum of peripheral neuropathies, from congenital hypomyelinating to late onset sensory and motor axonal forms. In some patients, neuropathic pain can be a prominent symptom, making the diagnosis challenging mainly in those with other risk factors for neuropathy. We describe a 77-year-old woman with impaired glucose tolerance presenting with rapidly progressive axonal neuropathy leading to excruciating pain and severe weakness of lower limbs within 2?years from the onset. Her son abruptly complained of similar painful symptoms at the age of 47 years. Molecular analysis revealed a novel heterozygous missense mutation (c.106A>G) in MPZ exon 2, causing the substitution of arginine-36 with glycine in the extracellular domain. Our observation suggests that MPZ-related neuropathy should be considered in the diagnostic work up of patients with painful axonal neuropathy even presenting with rapid progression and at a very late age of onset. PMID:23279346

Dacci, Patrizia; Taroni, Franco; Bella, Eleonora Dalla; Milani, Micaela; Pareyson, Davide; Morbin, Michela; Lauria, Giuseppe

2012-12-01

335

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

Science.gov (United States)

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

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

2011-02-01

336

Myelin protein zero Val102fs mutation manifesting with isolated spinal root hypertrophy.  

Science.gov (United States)

The Val102fs mutation of the myelin protein zero gene (MPZ) has been associated with Charcot-Marie-Tooth disease type 1B (CMT1B). Here we describe an unusual presentation of the Val102fs mutation characterized by symptoms of spinal root hypertrophy with no overt peroneal muscular atrophy. Two sisters aged 41 and 35 years complained of neck pain and presented only pes cavus or deep-tendon hyporeflexia. In both of them magnetic resonance imaging revealed non-enhancing hypertrophy of spinal roots misdiagnosed as neurofibromatosis; neurophysiology disclosed a demyelinating neuropathy and addressed the correct molecular diagnosis. This report adds new data concerning the clinical presentations of MPZ mutations. PMID:19906531

Marchini, Corrado; Marsala, Sandro Zambito; Bendini, Matteo; Taioli, Federica; Damante, Giuseppe; Lonigro, Incoronata Renata; Fabrizi, Gian Maria

2009-12-01

337

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

338

Redirecting Therapeutic T Cells against Myelin-Specific T Lymphocytes Using a Humanized Myelin Basic Protein-HLA-DR2-{zeta} Chimeric Receptor.  

DEFF Research Database (Denmark)

Therapies that Ag-specifically target pathologic T lymphocytes responsible for multiple sclerosis (MS) and other autoimmune diseases would be expected to have improved therapeutic indices compared with Ag-nonspecific therapies. We have developed a cellular immunotherapy that uses chimeric receptors to selectively redirect therapeutic T cells against myelin basic protein (MBP)-specific T lymphocytes implicated in MS. We generated two heterodimeric receptors that genetically link the human MBP(84-102) epitope to HLA-DR2 and either incorporate or lack a TCRzeta signaling domain. The Ag-MHC domain serves as a bait, binding the TCR of MBP-specific target cells. The zeta signaling region stimulates the therapeutic cell after cognate T cell engagement. Both receptors were well expressed on primary T cells or T hybridomas using a tricistronic (alpha, beta, green fluorescent protein) retroviral expression system. MBP-DR2-zeta-, but not MBP-DR2, modified CTL were specifically stimulated by cognate MBP-specific T cells,proliferating, producing cytokine, and killing the MBP-specific target cells. The receptor-modified therapeutic cells were active in vivo as well, eliminating Ag-specific T cells in a humanized mouse model system. Finally, the chimeric receptor-modified CTL ameliorated or blocked experimental allergic encephalomyelitis (EAE) disease mediated by MBP(84-102)/DR2-specific T lymphocytes. These results provide support for the further development of redirected therapeutic T cells able to counteract pathologic, self-specific T lymphocytes, and specifically validate humanized MBP-DR2-zeta chimeric receptors as a potential therapeutic in MS. Udgivelsesdato: 2008-Mar-1

Moisini, Ioana; Nguyen, Phuong

2008-01-01

339

Generation of a dual-functional split-reporter protein for monitoring membrane fusion using self-associating split GFP.  

Science.gov (United States)

Split reporter proteins capable of self-association and reactivation have applications in biomedical research, but designing these proteins, especially the selection of appropriate split points, has been somewhat arbitrary. We describe a new methodology to facilitate generating split proteins using split GFP as a self-association module. We first inserted the entire GFP module at one of several candidate split points in the protein of interest, and chose clones that retained the GFP signal and high activity relative to the original protein. Once such chimeric clones were identified, a final pair of split proteins was generated by splitting the GFP-inserted chimera within the GFP domain. Applying this strategy to Renilla reniformis luciferase, we identified a new split point that gave 10 times more activity than the previous split point. The process of membrane fusion was monitored with high sensitivity using a new pair of split reporter proteins. We also successfully identified new split points for HaloTag protein and firefly luciferase, generating pairs of self-associating split proteins that recovered the functions of both GFP and the original protein. This simple method of screening will facilitate the designing of split proteins that are capable of self-association through the split GFP domains. PMID:22942393

Ishikawa, Hirohito; Meng, Fanxia; Kondo, Naoyuki; Iwamoto, Aikichi; Matsuda, Zene

2012-12-01

340

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

Directory of Open Access Journals (Sweden)

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

Anil Sharma, Vijay Raina.

1999-01-01

 
 
 
 
341

A leucine-to-proline mutation in the putative first transmembrane domain of the 22-kDa peripheral myelin protein in the trembler-J mouse.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Peripheral myelin protein PMP-22 is a potential growth-regulating myelin protein that is expressed by Schwann cells and predominantly localized in compact peripheral myelin. A point mutation in the Pmp-22 gene of inbred trembler (Tr) mice was identified and proposed to be responsible for the Tr phenotype, which is characterized by paralysis of the limbs as well as tremors and transient seizures. In support of this hypothesis, we now report the fine mapping of the Pmp-22 gene to the immediate ...

Suter, U.; Moskow, J. J.; Welcher, A. A.; Snipes, G. J.; Kosaras, B.; Sidman, R. L.; Buchberg, A. M.; Shooter, E. M.

1992-01-01

342

Mapping class groups of Heegaard splittings of surface bundles  

CERN Document Server

Every surface bundle with genus $g$ fiber has a canonical Heegaard splitting of genus $2g+1$. We classify the mapping class groups of such Heegaard splittings in the case when the surface bundle has a sufficiently complicated monodromy map.

Johnson, Jesse

2012-01-01

343

26 CFR 1.482-6 - Profit split method.  

Science.gov (United States)

...of this section. (B) Comparability. The first step of the residual profit split relies on market benchmarks of profitability. Thus, the comparability considerations that are relevant for the first step of the residual profit split are...

2010-04-01

344

Evolution of Advection Upstream Splitting Method Schemes  

Science.gov (United States)

This paper focuses on the evolution of advection upstream splitting method(AUSM) schemes. The main ingredients that have led to the development of modern computational fluid dynamics (CFD) methods have been reviewed, thus the ideas behind AUSM. First and foremost is the concept of upwinding. Second, the use of Riemann problem in constructing the numerical flux in the finite-volume setting. Third, the necessity of including all physical processes, as characterised by the linear (convection) and nonlinear (acoustic) fields. Fourth, the realisation of separating the flux into convection and pressure fluxes. The rest of this review briefly outlines the technical evolution of AUSM and more details can be found in the cited references. Keywords: Computational fluid dynamics methods, hyperbolic systems, advection upstream splitting method, conservation laws, upwinding, CFD

Liou, Meng-Sing

2010-01-01

345

Meshed split skin graft for extensive vitiligo  

Directory of Open Access Journals (Sweden)

Full Text Available A 30 year old female presented with generalized stable vitiligo involving large areas of the body. Since large areas were to be treated it was decided to do meshed split skin graft. A phototoxic blister over recipient site was induced by applying 8 MOP solution followed by exposure to UVA. The split skin graft was harvested from donor area by Padgett dermatome which was meshed by an ampligreffe to increase the size of the graft by 4 times. Significant pigmentation of the depigmented skin was seen after 5 months. This procedure helps to cover large recipient areas, when pigmented donor skin is limited with minimal risk of scarring. Phototoxic blister enables easy separation of epidermis thus saving time required for dermabrasion from recipient site.

Srinivas C

2004-05-01

346

Isospin breaking in octet baryon mass splittings  

Energy Technology Data Exchange (ETDEWEB)

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

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

2012-06-15

347

Splitting Triplet and Doublet in Extra Dimensions  

CERN Document Server

A novel mechanism to realize the triplet-doublet splitting in supersymmetric SU(5) grand unified theories is proposed in the framework of higher dimensional theories where chiral multiplets are localized due to kink configuration of a SU(5) singlet. An adjoint Higgs field which spontaneously breaks the SU(5) gauge symmetry is assumed to be involved with the localization process, splitting the wave functions of the color-triplet Higgs from its doublet counterpart. The resulting effective four-dimensional theory does not possess manifest SU(5) invariance. By adjusting couplings, the doublet mass can be exponentially suppressed. We also show that dimension 5 proton decay from triplet Higgs exchange can be suppressed to a negligible level.

Kakizaki, M; Kakizaki, Mitsuru; Yamaguchi, Masahiro

2002-01-01

348

Artificial photosynthesis for solar water-splitting  

Science.gov (United States)

Hydrogen generated from solar-driven water-splitting has the potential to be a clean, sustainable and abundant energy source. Inspired by natural photosynthesis, artificial solar water-splitting devices are now being designed and tested. Recent developments based on molecular and/or nanostructure designs have led to advances in our understanding of light-induced charge separation and subsequent catalytic water oxidation and reduction reactions. Here we review some of the recent progress towards developing artificial photosynthetic devices, together with their analogies to biological photosynthesis, including technologies that focus on the development of visible-light active hetero-nanostructures and require an understanding of the underlying interfacial carrier dynamics. Finally, we propose a vision for a future sustainable hydrogen fuel community based on artificial photosynthesis.

Tachibana, Yasuhiro; Vayssieres, Lionel; Durrant, James R.

2012-08-01

349

Splitting of high power, cw proton beams  

Science.gov (United States)

A simple method for splitting a high power, continuous wave (cw) proton beam in two or more branches with low losses has been developed in the framework of the EURISOL (European Isotope Separation On-Line Radioactive Ion Beam Facility) design study. The aim of the system is to deliver up to 4 MW of H- beam to the main radioactive ion beam production target, and up to 100 kW of proton beams to three more targets, simultaneously. A three-step method is used, which includes magnetic neutralization of a fraction of the main H- beam, magnetic splitting of H- and H0, and stripping of H0 to H+. The method allows slow raising and individual fine adjustment of the beam intensity in each branch.

Facco, Alberto; Paparella, Rita; Berkovits, Dan; Yamane, Isao

2007-09-01

350

Isospin breaking in octet baryon mass splittings  

International Nuclear Information System (INIS)

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

351

Comparative proteomics of the Mycobacterium leprae binding protein myelin P0: its implication in leprosy and other neurodegenerative diseases.  

Science.gov (United States)

Mycobacterium leprae, the causative agent of leprosy invades Schwann cells of the peripheral nerves leading to nerve damage and disfigurement, which is the hallmark of the disease. Wet experiments have shown that M. leprae binds to a major peripheral nerve protein, the myelin P zero (P0). This protein is specific to peripheral nerve and may be important in the initial step of M. leprae binding and invasion of Schwann cells which is the feature of leprosy. Though the receptors on Schawann cells, cytokines, chemokines and antibodies to M. leprae have been identified the molecular mechanism of nerve damage and neurodegeneration is not clearly defined. Recently pathogen and host protein/nucleotide sequence similarities (molecular mimicry) have been implicated in neurodegenerative diseases. The approach of the present study is to utilise bioinformatic tools to understand leprosy nerve damage by carrying out sequence and structural similarity searches of myelin P0 with leproma and other genomic database. Since myelin P0 is unique to peripheral nerve, its sequence and structural similarities in other neuropathogens have also been noted. Comparison of myelin P0 with the M. leprae proteins revealed two characterised proteins, Ferrodoxin NADP reductase and a conserved membrane protein, which showed similarity to the query sequence. Comparison with the entire genomic database (www.ncbi.nlm.nih.gov) by basic local alignment search tool for proteins (BLASTP) and fold classification of structure-structure alignment of proteins (FSSP) searches revealed that myelin P0 had sequence/structural similarities to the poliovirus receptor, coxsackie-adenovirus receptor, anthrax protective antigen, diphtheria toxin, herpes simplex virus, HIV gag-1 peptide, and gp120 among others. These proteins are known to be associated directly or indirectly with neruodegeneration. Sequence and structural similarities to the immunoglobin regions of myelin P0 could have implications in host-pathogen interactions, as it has homophilic adhesive properties. Although these observed similarities are not highly significant in their percentage identity, they could be functionally important in molecular mimicry, receptor binding and cell signaling events involved in neurodegeneration. PMID:15019586

Vardhini, Deena; Suneetha, Sujai; Ahmed, Niyaz; Joshi, D S M; Karuna, S; Magee, X; Vijayalakshmi, D S R; Sridhar, V; Karunakar, K V; Archelos, Juan J; Suneetha, Lavanya M

2004-03-01

352

Nanostructured hematite for photoelectrochemical water splitting  

Science.gov (United States)

Solar water splitting is an environmentally friendly reaction of producing hydrogen gas. Since Honda and Fujishima first demonstrated solar water splitting in 1972 by using semiconductor titanium dioxide (TiO2) as photoanode in a photoelectrochemical (PEC) cell, extensive efforts have been invested into improving the solar-to-hydrogen (STH) conversion efficiency and lower the production cost of photoelectrochemical devices. In the last few years, hematite (alpha-Fe2O3) nanostructures have been extensively studied as photoanodes for PEC water splitting. Although nanostructured hematite can improve its photoelectrochemical water splitting performance to some extent, by increasing active sites for water oxidation and shortening photogenerated hole path length to semiconductor/electrolyte interface, the photoactivity of pristine hematite nanostructures is still limited by a number of factors, such as poor electrical conductivities and slow oxygen evolution reaction kinetics. Previous studies have shown that tin (Sn) as an n-type dopant can substantially enhance the photoactivity of hematite photoanodes by modifying their optical and electrical properties. In this thesis, I will first demonstrate an unintentional Sn-doping method via high temperature annealing of hematite nanowires grown on fluorine-doped tin oxide (FTO) substrate to enhance the donor density. In addition to introducing extrinsic dopants into semiconductors, the carrier densities of hematite can also be enhanced by creating intrinsic defects. Oxygen vacancies function as shallow donors for a number of hematite. In this regard, I have investigated the influence of oxygen content on thermal decomposition of FeOOH to induce oxygen vacancies in hematite. In the end, I have studied low temperature activation of hematite nanostructures.

Ling, Yichuan

353

Monocular SLAM with conditionally independent split mapping.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The recovery of structure from motion in real time over extended areas demands methods that mitigate the effects of computational complexity and arithmetical inconsistency. In this paper, we develop SCISM, an algorithm based on relative frame bundle adjustment, which splits the recovered map of 3D landmarks and keyframes poses so that the camera can continue to grow and explore a local map in real time while, at the same time, a bulk map is optimized in the background. By temporarily excludin...

Holmes, Sa; Murray, Dw

2013-01-01

354

Monocular SLAM with Conditionally Independent Split Mapping.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The recovery of structure from motion in real time over extended areas demands methods that mitigate the effects of computational complexity and arithmetical inconsistency. In this paper we develop SCISM, an algorithm based on relative frame bundle adjustment, which splits the recovered map of 3D landmarks and keyframes poses so that the camera can continue to grow and explore a local map in real-time while, at the same time, a bulk map is optimized in the background. By temporarily excluding...

Holmes, Sa; Murray, Dw

2012-01-01

355

Metric geometries over the split quaternions  

Digital Repository Infrastructure Vision for European Research (DRIVER)

We give an overview of some recent results in hypersymplectic and para-quaternionic Kähler geometry, and introduce the notion of split three-Sasakian manifold. In particular, we discuss the twistor spaces and Swann bundles of para-quaternionic Kähler manifolds. These are used to classify examples with a fully homogeneous action of a semi-simple Lie group, and to construct distinct para-quaternionic Kähler metrics from indefinite real analytic conformal manifolds. We also indicate how the t...

Dancer, As; Jørgensen, Hr; Swann, Af

2005-01-01

356

Multiplet mass splitting in a gravitational field  

International Nuclear Information System (INIS)

An expression for the mass splitting of particles belonging to the same spin multiplet defined in a space-time of general relativity is derived. The geometrical symmetry is a subgroup of SO(r,s), 9 >=r > 3, 5 >=s >=1, the mass operator being proportional to the second order Casimir operator of that subgroup. A brief analysis of the calculated values as compared to the experimental data is included. (Author)

357

Electromagnetic Mass Splittings in Heavy Mesons  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The electromagnetic contribution to the isomultiplet mass splittings of heavy mesons is reanalyzed within the framework of the heavy mass expansion. It is shown that the leading term in the expansion is given to a good approximation by the elastic term. $1/m_{Q}$-corrections can only be estimated, the main source of uncertainty now being inelastic contributions. The $1/m_{Q}$-corrections to the elastic term turn out to be relatively small in both D and B pseudoscalar mesons.

Goity, J. L.

1992-01-01

358

Phase splitting for periodic Lie systems  

Energy Technology Data Exchange (ETDEWEB)

In the context of the Floquet theory, using a variation of parameter argument, we show that the logarithm of the monodromy of a real periodic Lie system with appropriate properties admits a splitting into two parts called dynamic and geometric phases. The dynamic phase is intrinsic and linked to the Hamiltonian of a periodic linear Euler system on the co-algebra. The geometric phase is represented as a surface integral of the symplectic form of a co-adjoint orbit.

Flores-Espinoza, R; Vorobiev, Yu M [Departamento de Matematicas, Universidad de Sonora (Mexico); De Lucas, J, E-mail: rflorese@gauss.mat.uson.m, E-mail: delucas@impan.gov.p, E-mail: yurimv@guaymas.uson.m [Departamento de Fisica Teorica, Universidad de Zaragoza (Spain)

2010-05-21

359

Phase splitting for periodic Lie systems  

Science.gov (United States)

In the context of the Floquet theory, using a variation of parameter argument, we show that the logarithm of the monodromy of a real periodic Lie system with appropriate properties admits a splitting into two parts called dynamic and geometric phases. The dynamic phase is intrinsic and linked to the Hamiltonian of a periodic linear Euler system on the co-algebra. The geometric phase is represented as a surface integral of the symplectic form of a co-adjoint orbit.

Flores-Espinoza, R.; de Lucas, J.; Vorobiev, Yu M.

2010-05-01

360

Phase splitting for periodic Lie systems  

International Nuclear Information System (INIS)

In the context of the Floquet theory, using a variation of parameter argument, we show that the logarithm of the monodromy of a real periodic Lie system with appropriate properties admits a splitting into two parts called dynamic and geometric phases. The dynamic phase is intrinsic and linked to the Hamiltonian of a periodic linear Euler system on the co-algebra. The geometric phase is represented as a surface integral of the symplectic form of a co-adjoint orbit.

 
 
 
 
361

Resolving contact conflict for double patterning split  

Science.gov (United States)

Double patterning (DP) is one of the main options to print devices with half pitch less than 45nm. The basis of DP is to decompose a design into two masks. In this work we focus on the decomposition of the contact pattern layer. Contacts with pitch less than a split pitch are assigned to opposite masks corresponding to different exposures. However, there exist contact pattern configurations for which features can not be assigned to opposite masks. Such contacts are flagged as color conflicts. With the help of design of manufacturing (DFM), the contact conflicts can be reduced through redesign. However, even the state of the art DFM redesign solution will be limited by area constraints and will introduce delays to the design flow. In this paper, we propose an optical method for contact conflicts treatment. We study the impact of the split on imaging by comparing inverse lithography technology (ILT), optical proximity correction (OPC) and source mask co-optimization (SMO) techniques. The ability of these methods to solve some split contacts conflicts in double patterning are presented.

Zeggaoui, N.; Farys, V.; Trouiller, Y.; Yesilada, E.; Robert, F.; Belledent, J.; Besacier, M.

2009-10-01

362

Splitting neutrino masses and showering into Sky  

CERN Document Server

Neutrino masses might be as light as a few time the atmospheric neutrino mass splitting. High Energy ZeV cosmic neutrinos (in Z-Showering model) might hit relic ones at each mass in different resonance energies in our nearby Universe. This non-degenerated density and energy must split UHE Z-boson secondaries (in Z-Burst model) leading to multi injection of UHECR nucleons within future extreme AUGER energy. Secondaries of Z-Burst as neutral gamma, below a few tens EeV are better surviving local GZK cut-off and they might explain recent Hires BL-Lac UHECR correlations at small angles. A different high energy resonance must lead to Glashow's anti-neutrino showers while hitting electrons in matter. In air, Glashow's anti-neutrino showers lead to collimated and directional air-showers offering a new Neutrino Astronomy. At greater energy around PeV, Tau escaping mountains and Earth and decaying in flight are effectively showering in air sky. These Horizontal showering is splitting by geomagnetic field in forked sha...

Fargion, D; Iacovelli, M; Lanciano, O; Oliva, P; De Lucentini, P G S; Grossi, M; De Santis, M

2006-01-01

363

P-wave Cooper pair splitting  

Directory of Open Access Journals (Sweden)

Full Text Available Background: Splitting of Cooper pairs has recently been realized experimentally for s-wave Cooper pairs. A split Cooper pair represents an entangled two-electron pair state, which has possible application in on-chip quantum computation. Likewise the spin-activity of interfaces in nanoscale tunnel junctions has been investigated theoretically and experimentally in recent years. However, the possible implications of spin-active interfaces in Cooper pair splitters so far have not been investigated.Results: We analyze the current and the cross correlation of currents in a superconductor–ferromagnet beam splitter, including spin-active scattering. Using the Hamiltonian formalism, we calculate the cumulant-generating function of charge transfer. As a first step, we discuss characteristics of the conductance for crossed Andreev reflection in superconductor–ferromagnet beam splitters with s-wave and p-wave superconductors and no spin-active scattering. In a second step, we consider spin-active scattering and show how to realize p-wave splitting using only an s-wave superconductor, through the process of spin-flipped crossed Andreev reflection. We present results for the conductance and cross correlations.Conclusion: Spin-activity of interfaces in Cooper pair splitters allows for new features in ordinary s-wave Cooper pair splitters, that can otherwise only be realized by using p-wave superconductors. In particular, it provides access to Bell states that are different from the typical spin singlet state.

Henning Soller

2012-07-01

364

Plasmonic resonance in planer split ring trimer  

Science.gov (United States)

We have numerically investigated the plasmon properties supported by asymmetry planer split ring trimer structures. We investigate the modification of gap distance, thickness and gap width on the transmission properties of the weak coupling model (g is larger than or equal to 120 nm, d=48 nm, t is larger than 30 nm, w1=200 nm, and w2=40 nm), as the coupling becomes weaker, the first peak sharply attenuates, the second peak slightly decreases, the transmission dip in the near-infrared region becomes shallow, and they are very sensitive to the gap distance between two small split ring pairs and the thickness and gap width of the big split ring. We also study the change of gap distance on the strong coupling model (g is smaller than or equal to 40 nm, d=24 nm, t=10 nm, w1=80 nm, and w2=20 nm), there exists a new Fano resonance peak, the strongest peak in visible region becomes symmetry, while the peak in near-infrared region becomes asymmetry. The resonator design strategy opens up a rich pathway for the implementation of optimized optical properties for specific applications.

Xu, Haiqing; Li, Hongjian; Xiao, Gang

2014-12-01

365

Sunspot splitting triggering an eruptive flare  

CERN Document Server

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

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

2013-01-01

366

26 CFR 1.7872-15 - Split-dollar loans.  

Science.gov (United States)

...paid. (3) Split-dollar demand loans. In the case of a split-dollar demand loan, the amount of interest...this section is equal to the aggregate of— (i) For each year that the split-dollar demand loan was outstanding in...

2010-04-01

367

7 CFR 51.2731 - U.S. Spanish Splits.  

Science.gov (United States)

...2010-01-01 2010-01-01 false U.S. Spanish Splits. 51.2731 Section 51.2731...United States Standards for Grades of Shelled Spanish Type Peanuts Grades § 51.2731 U.S. Spanish Splits. “U.S. Spanish Splits”...

2010-01-01

368

Staining myelin and myelin-like degradation products in the spinal cords of chronic experimental allergic encephalomyelitis (Cr-EAE) rats using Sudan black B staining of glycol methacrylate-embedded material.  

Science.gov (United States)

A high-resolution light-microscopical (HRLM) technique is described to visualize myelin, and macrophages containing degradation products of myelin, in the spinal cords of chronic relapsing experimental allergic encephalomyelitis (Cr-EAE) rats. This HRLM technique was developed to optimalize the correlation between nuclear magnetic resonance (NMR) characteristics and histopathological images in this well-established animal model for multiple sclerosis (MS). Spinal cords were fixed by perfusion with a combination of cacodylate-buffered glutaraldehyde and formaldehyde, post-fixed in Dalton's fixative (containing osmium tetroxide), rinsed in water, processed in ethanol, acetone, and embedded in glycol methacrylate resin (Technovit 7100/HistoResin). Semi-thin sections were stained with Sudan Black B and counterstained with Cresyl Fast Violet, resulting in black staining of myelin and its degradation products, with blue/violet staining of demyelinated axons and other tissue elements. These dyes were selected with the aid of a numerical model of staining, which took both access and lipophilicity into account. The staining procedure is simple and highly reproducible. The resulting images are contrast rich, and combine excellent morphology with a high degree of lipid retention. PMID:1283436

Gerrits, P O; Brekelmans-Bartels, M; Mast, L; Gravenmade, E J; Horobin, R W; Holstege, G

1992-01-01

369

The Lateral Membrane Organization and Dynamics of Myelin Proteins PLP and MBP Are Dictated by Distinct Galactolipids and the Extracellular Matrix  

Science.gov (United States)

In the central nervous system, lipid-protein interactions are pivotal for myelin maintenance, as these interactions regulate protein transport to the myelin membrane as well as the molecular organization within the sheath. To improve our understanding of the fundamental properties of myelin, we focused here on the lateral membrane organization and dynamics of peripheral membrane protein 18.5-kDa myelin basic protein (MBP) and transmembrane protein proteolipid protein (PLP) as a function of the typical myelin lipids galactosylceramide (GalC), and sulfatide, and exogenous factors such as the extracellular matrix proteins laminin-2 and fibronectin, employing an oligodendrocyte cell line, selectively expressing the desired galactolipids. The dynamics of MBP were monitored by z-scan point fluorescence correlation spectroscopy (FCS) and raster image correlation spectroscopy (RICS), while PLP dynamics in living cells were investigated by circular scanning FCS. The data revealed that on an inert substrate the diffusion rate of 18.5-kDa MBP increased in GalC-expressing cells, while the diffusion coefficient of PLP was decreased in sulfatide-containing cells. Similarly, when cells were grown on myelination-promoting laminin-2, the lateral diffusion coefficient of PLP was decreased in sulfatide-containing cells. In contrast, PLP's diffusion rate increased substantially when these cells were grown on myelination-inhibiting fibronectin. Additional biochemical analyses revealed that the observed differences in lateral diffusion coefficients of both proteins can be explained by differences in their biophysical, i.e., galactolipid environment, specifically with regard to their association with lipid rafts. Given the persistence of pathological fibronectin aggregates in multiple sclerosis lesions, this fundamental insight into the nature and dynamics of lipid-protein interactions will be instrumental in developing myelin regenerative strategies. PMID:25003183

Ozgen, Hande; Schrimpf, Waldemar; Hendrix, Jelle; de Jonge, Jenny C.; Lamb, Don C.; Hoekstra, Dick; Kahya, Nicoletta; Baron, Wia

2014-01-01

370

Effect of Cytosolic Extract of Alternaria Alaternata Fungus on Monocyte-Derived Dendritic Cell Phagocytosis Ability and T-Lymphocyte Proliferation in the Presence of Myelin Basic Protein  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Background: Multiple sclerosis (MS) is an autoimmune disease with impairment in function of CNS, meanwhile macrophages and dendritic cells (DC) can cause inflammation and damage to the myelin of nerve cells by releasing Reactive oxygen species (ROS) and other harmful substances when these cells get matured. We investigated the effect of Alternaria alternata (A. alternata) extract on phagocytic T cell stimulation activity of DC pulsed with Myelin Basic Protein (MBP) as a laboratory model of MS...

Alireza Loghmani; Nowruz Delirezh; Abdolghaffar Ownagh; Hadi Mohebalian

2013-01-01

371

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

372

The lateral membrane organization and dynamics of myelin proteins PLP and MBP are dictated by distinct galactolipids and the extracellular matrix.  

Science.gov (United States)

In the central nervous system, lipid-protein interactions are pivotal for myelin maintenance, as these interactions regulate protein transport to the myelin membrane as well as the molecular organization within the sheath. To improve our understanding of the fundamental properties of myelin, we focused here on the lateral membrane organization and dynamics of peripheral membrane protein 18.5-kDa myelin basic protein (MBP) and transmembrane protein proteolipid protein (PLP) as a function of the typical myelin lipids galactosylceramide (GalC), and sulfatide, and exogenous factors such as the extracellular matrix proteins laminin-2 and fibronectin, employing an oligodendrocyte cell line, selectively expressing the desired galactolipids. The dynamics of MBP were monitored by z-scan point fluorescence correlation spectroscopy (FCS) and raster image correlation spectroscopy (RICS), while PLP dynamics in living cells were investigated by circular scanning FCS. The data revealed that on an inert substrate the diffusion rate of 18.5-kDa MBP increased in GalC-expressing cells, while the diffusion coefficient of PLP was decreased in sulfatide-containing cells. Similarly, when cells were grown on myelination-promoting laminin-2, the lateral diffusion coefficient of PLP was decreased in sulfatide-containing cells. In contrast, PLP's diffusion rate increased substantially when these cells were grown on myelination-inhibiting fibronectin. Additional biochemical analyses revealed that the observed differences in lateral diffusion coefficients of both proteins can be explained by differences in their biophysical, i.e., galactolipid environment, specifically with regard to their association with lipid rafts. Given the persistence of pathological fibronectin aggregates in multiple sclerosis lesions, this fundamental insight into the nature and dynamics of lipid-protein interactions will be instrumental in developing myelin regenerative strategies. PMID:25003183

Ozgen, Hande; Schrimpf, Waldemar; Hendrix, Jelle; de Jonge, Jenny C; Lamb, Don C; Hoekstra, Dick; Kahya, Nicoletta; Baron, Wia

2014-01-01

373

The contribution of myelin to magnetic susceptibility-weighted contrasts in high-field MRI of the brain.  

Science.gov (United States)

T(2)*-weighted gradient-echo MRI images at high field (? 7T) have shown rich image contrast within and between brain regions. The source for these contrast variations has been primarily attributed to tissue magnetic susceptibility differences. In this study, the contribution of myelin to both T(2)* and frequency contrasts is investigated using a mouse model of demyelination based on a cuprizone diet. The demyelinated brains showed significantly increased T(2)* in white matter and a substantial reduction in gray-white matter frequency contrast, suggesting that myelin is a primary source for these contrasts. Comparison of in-vivo and in-vitro data showed that, although tissue T(2)* values were reduced by formalin fixation, gray-white matter frequency contrast was relatively unaffected and fixation had a negligible effect on cuprizone-induced changes in T(2)* and frequency contrasts. PMID:22056461

Lee, Jongho; Shmueli, Karin; Kang, Byeong-Teck; Yao, Bing; Fukunaga, Masaki; van Gelderen, Peter; Palumbo, Sara; Bosetti, Francesca; Silva, Afonso C; Duyn, Jeff H

2012-02-15

374

Observation of Splitting of EPR Spectral Lines without Any Concomitant Splitting in Energy Levels.  

Science.gov (United States)

Splitting of spectral lines is generally associated with corresponding splitting of appropriate energy levels. However, here we report our observation of the splittings of hyperfine lines in the time-resolved EPR spectrum of a stable free radical that participates in the quenching of an excited molecule. The observed splitting does not arise from any splitting of the energy levels of the radical, nor due to Torrey oscillations but is a culmination of a detailed interplay of photophysical and magnetic resonance dynamics of the quenching process. In particular, sequential quenching of an excited singlet and triplet states by the free radical, generation of opposite electron spin polarization, and time-dependent EPR line width evolving according to the Bloch equations contribute to the appearance of unusual lineshapes of the observed EPR spectrum. This effect is sufficiently general and should always be observable in the time-resolved EPR experiments on free radicals involved in photophysical quenching of excited molecules. We also point out that this effect cannot be seen in Fourier transform EPR spectroscopy. PMID:25211527

Rane, Vinayak; Das, Ranjan

2014-09-25

375

Local synthesis and dual actions of progesterone in the nervous system: neuroprotection and myelination.  

Science.gov (United States)

Progesterone (PROG) is synthesized in the brain, spinal cord and peripheral nerves. Its direct precursor pregnenolone is either derived from the circulation or from local de novo synthesis as cytochrome P450scc, which converts cholesterol to pregnenolone, is expressed in the nervous system. Pregnenolone is converted to PROG by 3beta-hydroxysteroid dehydrogenase (3beta-HSD). In situ hybridization studies have shown that this enzyme is expressed throughout the rat brain, spinal cord and dorsal root ganglia (DRG) mainly by neurons. Macroglial cells, including astrocytes, oligodendroglial cells and Schwann cells, also have the capacity to synthesize PROG, but expression and activity of 3beta-HSD in these cells are regulated by cellular interactions. Thus, Schwann cells convert pregnenolone to PROG in response to a neuronal signal. There is now strong evidence that P450scc and 3beta-HSD are expressed in the human nervous system, where PROG synthesis also takes place. Although there are only a few studies addressing the biological significance of PROG synthesis in the brain, the autocrine/paracrine actions of locally synthesized PROG are likely to play an important role in the viability of neurons and in the formation of myelin sheaths. The neuroprotective effects of PROG have recently been documented in a murine model of spinal cord motoneuron degeneration, the Wobbler mouse. The treatment of symptomatic Wobbler mice with PROG for 15 days attenuated the neuropathological changes in spinal motoneurons and had beneficial effects on muscle strength and the survival rate of the animals. PROG may exert its neuroprotective effects by regulating expression of specific genes in neurons and glial cells, which may become hormone-sensitive after injury. The promyelinating effects of PROG were first documented in the mouse sciatic nerve and in co-cultures of sensory neurons and Schwann cells. PROG also promotes myelination in the brain, as shown in vitro in explant cultures of cerebellar slices and in vivo in the cerebellar peduncle of aged rats after toxin-induced demyelination. Local synthesis of PROG in the brain and the neuroprotective and promyelinating effects of this neurosteroid offer interesting therapeutic possibilities for the prevention and treatment of neurodegenerative diseases, for accelerating regenerative processes and for preserving cognitive functions during aging. PMID:15135772

Schumacher, Michael; Guennoun, Rachida; Robert, Françoise; Carelli, Claude; Gago, Nathalie; Ghoumari, Abdel; Gonzalez Deniselle, Maria C; Gonzalez, Susana L; Ibanez, Chrystelle; Labombarda, Florencia; Coirini, Héctor; Baulieu, Etienne-Emile; De Nicola, Alejandro F

2004-06-01

376

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.)

377

Mechanism of Conduction Block in Amphibian Myelinated Axon Induced by Biphasic Electrical Current at Ultra-High Frequency  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The mechanism of axonal conduction block induced by ultra-high frequency (?20 kHz) biphasic electrical current was investigated using a lumped circuit model of the amphibian myelinated axon based on Frankenhaeuser-Huxley (FH) equations. The ultra-high frequency stimulation produces constant activation of both sodium and potassium channels at the axonal node under the block electrode causing the axonal conduction block. This blocking mechanism is different from the mechanism when the stimula...

Tai, Changfeng; Guo, Dong; Wang, Jicheng; Roppolo, James R.; Groat, William C.

2011-01-01

378

ADAM22, a Kv1 channel-interacting protein, recruits membrane-associated guanylate kinases to juxtaparanodes of myelinated axons  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Clustered Kv1 K+channels regulate neuronal excitability at juxtaparanodes of myelinated axons, axon initial segments, and cerebellar basket cell terminals (BCTs). These channels are part of a larger protein complex that includes cell adhesion molecules and scaffolding proteins. To identify proteins that regulate assembly, clustering, and/or maintenance of axonal Kv1 channel protein complexes, we immunoprecipitated Kv1.2 ?subunits, and then used mass spectrometry to identify interacting prote...

Ogawa, Y.; Oses-prieto, J.; Kim, M. Y.; Horresh, I.; Peles, E.; Burlingame, A. L.; Trimmer, J. S.; Meijer, D. N.; Rasband, M. N.

2010-01-01

379

One-sided and two-sided Heegaard splittings  

CERN Document Server

We define a notion of Hempel distance for one-sided Heegaard splittings and show that the existence of alternate surfaces restricts distance for one-sided splittings in a manner similar to Hartshorn's and Scharlemann-Tomova's results for two-sided splittings. We also show that every geometrically compressible one-sided Heegaard surface in a non-Haken 3-manifold is stabilized, and show that the mapping class group of the two-sided Heegaard splitting induced by a high distance one-sided splitting is isomorphic to the fundamental group of the one-sided surface.

Johnson, Jesse

2011-01-01

380

TGF? signaling regulates the timing of CNS myelination by modulating oligodendrocyte progenitor cell cycle exit through SMAD3/4/FoxO1/Sp1.  

Science.gov (United States)

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

Palazuelos, Javier; Klingener, Michael; Aguirre, Adan

2014-06-01

 
 
 
 
381

Failure of central nervous system myelination in MBP/c-myc transgenic mice: evidence for c-myc cytotoxicity  

DEFF Research Database (Denmark)

c-myc is a member of the helix-loop-helix/leucine zipper family of proteins that modulate the transcriptional activity of specific target genes. Although aberrant c-myc expression has been reported to play a role in multistage carcinogenesis in astrocytic gliomas, little is known about the effects of the expression of c-myc on oligodendrocytes. Using transgenic animals expressing a human c-myc oncogene under transcriptional control of the myelin basic protein gene, we investigated the effect of overexpression of this oncogene in oligodendrocytes. The MBP/c-myc transgenic mice developed severe neurological disturbances characterized by action tremors and recurrent seizures, and premature death during postnatal weeks three to five. Affected transgenic mice of various strains had severely hypomyelinated central nervous systems and expressed low levels of c-myc, myelin basic protein (MBP) and proteolipid protein (PLP) mRNAs in the brain. These c-myc transgenic mice also exhibited an increased number of TUNEL positive nuclei, which in most cases were located in cells that expressed c-myc, as judged by double immunohistochemistry. There was no evidence of brain tumors in the c-myc transgenic mice, including heterozygous mice from two strains that had normal lifespans. These observations indicate that the myelin deficiency observed in the MBP/c-myc transgenic animals results from a cytotoxic effect of the c-myc transgene.

Jensen, N A; Pedersen, Karen-Marie

1998-01-01

382

Regulatory role of vitamin D in T-cell reactivity against myelin peptides in relapsing-remitting multiple sclerosis patients  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Low levels of plasma 25-hydroxyvitaminD (25(OHD are associated with a higher incidence of multiple sclerosis (MS due to the immune suppressive properties of vitamin D. The aim of this study was to determine the correlation between plasma 25(OHD concentrations and clinical and immunological variables in a cohort of multiple sclerosis patients. Methods Plasma 25(OHD concentrations were evaluated in summer and winter in 15 primary progressive MS (PPMS patients, 40 relapsing- remitting MS (RRMS patients and 40 controls (HC. Protocol variables included demographic and clinical data, radiological findings and immunological variables (oligoclonal bands, HLADR15 and T-lymphocyte proliferation to a definite mix of 7 myelin peptides. Results During the winter, plasma concentrations were significantly lower in RRMS patients compared to HC, whereas no differences were found in summer. No relationships were found between plasma 25(OHD concentrations and clinical or radiological variables. RRMS patients with a positive T-cell proliferation to a mix of myelin peptides (n?=?31 had lower 25(OHD concentrations. Conclusions 25(OHD is an immunomodulatory molecule that might have a regulatory role in T-cell proliferation to myelin peptides in RRMS patients.

Grau-López Laia

2012-09-01

383

Splitting in dual-phase 590 high strength steel plates  

Energy Technology Data Exchange (ETDEWEB)

The influence of splitting on Charpy impact energy was investigated by analyzing the primary fracture (from the Charpy V-notch) and splitting (secondary fracture) surfaces at different test temperatures quantitatively. The morphology of splitting at the primary fracture surface of Charpy impact specimens made of dual-phase (DP) 590 hot-rolled steel in TL direction at +60 deg. C and -30 deg. C were surveyed by scanning electron microscope (SEM). The broken Charpy impact specimens in both TL and LT directions at different test temperatures were studied by examining sliced images obtained from micro-radiography imaging system. Three-dimension (3D) and plane sliced images of specimens were analyzed using GEHC microview software. Results show that fracture appearance inside the splitting is cleavage. The length and depth of the splitting increased with decreasing test temperature. Splitting width decreased first then the trend becomes irregular when test temperature falls due to variation of steel ductility and reaction between splitting and the primary crack. The surface areas of splitting and primary crack changed with test temperature as well. Splitting area increased with decreasing test temperature, while the surface area of the primary crack decreased as the test temperature was lowered. Influence of splitting on the impact energy in upper shelf of DP590 hot-rolled steel is small. In the ductile-to-brittle transition temperature (DBTT) range, splitting tends to increase the Charpy impact energy and consequently reduced the DBTT of DP590 hot-rolled steel.

Yang Min [School of Materials Science and Engineering, Shandong University, Jinan, Shandong 250061 (China); Department of Mechanical Engineering, University of South Carolina, 300 Main Street, Columbia, SC 29208 (United States); Chao, Yuh J. [Department of Mechanical Engineering, University of South Carolina, 300 Main Street, Columbia, SC 29208 (United States)], E-mail: chao@sc.edu; Li Xiaodong [Department of Mechanical Engineering, University of South Carolina, 300 Main Street, Columbia, SC 29208 (United States); Immel, David [Savannah River National Laboratory, Aiken, SC (United States); Tan Jinzhu [College of Mechanical and Power Engineering, Nanjing University of Technology, Nanjing, Jiangsu 210009 (China); Department of Mechanical Engineering, University of South Carolina, 300 Main Street, Columbia, SC 29208 (United States)

2008-12-15

384

Evaluation of salt split technique of immunofluorescence in bullous pemphigoid  

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Full Text Available Recent studies suggest that salt split skin is a more sensitive substrate than intact skin for immunofluorescence diagnosis of bullous pemphigoid. We undertook this study to define the role of salt split technique of immunofluorescence findings in 32 clinical and histopothology confirmed cases of bullous pemphigoid. Both direct and indirect immunofluorescences were performed using normal and split skin. Direct immunofluorescence positivity of 100% was noted with both routine and salt split method. Additional immunoreadont deposition was noted with direct method on split skin in 5 cases. Patterns of fluorescence in the latter were roof (40.60%, floor (9.4% and combined roof and floor (50%. On indirect immunofluorescence, positivity was almost doubled with salt split technique ( 68% as compared to routine method (36%. Thus, salt split technique was equivalent to routine on direct method in positivity with additional immunoreactant deposits noted in some and had double the sensitivity of the indirect method in detecting immunofluorescence in bullous pemphigoid.

Satyapal Seema

2002-11-01

385

ERP evidence for the split fovea theory.  

Science.gov (United States)

According to the 'bilateral representation theory', a complete copy of the words presented foveally is received simultaneously in the left and right visual cortices. However, a growing body of observations, which has led to the 'split fovea theory', proposes a functional split of the foveal area between the two hemispheres. In the present study we tested these two accounts using an adapted version of the Reicher-Wheeler paradigm. Ten control participants and ten participants with developmental dyslexia undergoing electroencephalographic recordings were asked to identify one of five letters in a string. The target letter was systematically presented at fixation but the horizontal positioning of the letter string was varied such that the stimulus fluctuated in both the visual hemifields over the experiment. ERP results showed that letter strings encompassing the foveal field were not sent to both cerebral hemispheres simultaneously when fixation coincided with extreme letter positions (i.e., first or last). Indeed, the P1 peak was delayed in this case, which was interpreted as the result of a transfer of visual information from the contralateral hemisphere via the splenium of the corpus callosum. Consistent with the 'split fovea theory', this result suggests that a minimal amount of graphic input is necessary to induce a P1 event. The interhemispheric transfer time (IHTT) deducted from peak-to-peak P1 latency delays ranged from 26 to 42 ms. As previously observed, the IHTT was significantly faster for right-to-left than left-to-right transfer in the control group. IHTT was marginally shorter in control participants as compared to participants with developmental dyslexia, and the faster transfer to the left hemisphere seen in the former was not found in the latter. PMID:17956755

Martin, Clara D; Thierry, Guillaume; Démonet, Jean-François; Roberts, Mark; Nazir, Tatjana

2007-12-14

386

Dysmyelinating and demyelinating Charcot-Marie-Tooth disease associated with two myelin protein zero gene mutations.  

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Mutations in the myelin protein zero (MPZ) gene are the third most frequent cause of hereditary motor and sensory neuropathies (HMSN), also called Charcot-Marie-Tooth disorders (CMT). Only in case of recurrent mutations occurring in the MPZ gene is it possible to draw phenotype-genotype correlations essential for establishing the prognosis and outcomes of CMT1. We have surveyed a cohort of 67 Polish patients from CMT families with demyelinating neuropathy for mutations in the MPZ gene. In this study, we report two CMT families in which the Ile135Thr and Pro132Leu mutations have been identified for the MPZ gene. These MPZ gene mutations had not been identified hitherto in the Polish population. The Pro132Leu mutation segregates with a severe early-onset dysmyelinating-hypomyelinating neuropathy, whereas the Ile135Thr substitution is associated with the classical phenotype of CMT1. To the best of our knowledge, we present here, for the first time, morphological data obtained in two sural nerve biopsies pointing to a hypomyelination-dysmyelination process in a family harboring the Pro132Leu mutation in the MPZ gene. PMID:21107784

Drac, Hanna; Kabzi?ska, Dagmara; Moszy?ska, Izabela; Strugalska-Cynowska, Halina; Hausmanowa-Petrusewicz, Irena; Kocha?ski, Andrzej

2011-05-01

387

Ventriculomegaly, delayed myelination, white matter hypoplasia, and "periventricular" leukomalacia: how are they related?  

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Preterm infants, including some who have sustained intracranial hemorrhage, appear to be at increased risk of lateral ventricular enlargement. Although some occurrences might be due to an impairment of cerebrospinal fluid flow or absorption, many instances of ventriculomegaly without accompanying macrocephaly reflect diffuse white matter damage resulting in diminished (i.e., hypoplastic) white matter or an inadequate density of axons. Perinatally acquired widespread white matter damage is sometimes associated with the focal white matter necrosis. We hypothesize that in some infants both ventriculomegaly and delayed myelination are consequences of disturbances to myelinogenesis that result from an impairment of cells destined to become oligodendroglia or of disturbances to rapidly growing axons. The vulnerability of developing white matter in preterm newborns might, in part, reflect the diminished availability of growth/ survival factors, or a vulnerability to toxins or physiologic perturbations. Awareness that some ventriculomegaly reflects widely distributed white matter damage should prevent overtreatment of what might appear to be hydrocephalus, but is not due to impaired cerebrospinal fluid dynamics. Increased understanding of the phenomena leading to ventriculomegaly related to paucity of white matter should lead to successful efforts to prevent white matter damage in preterm newborns. PMID:8888047

Leviton, A; Gilles, F

1996-09-01

388

Myelin basic protein determination in cerebro-spinal fluid of children with tuberculous meningitis  

International Nuclear Information System (INIS)

Myelin basic protein (MBP), an indicator of neural tissue damage in cerebro-spinal fluid, was studied in patients with tuberculous meningitis (TBM). MBP levels were elevated in 62% of the cases of TBM, the levels being 13.3+-18.8 ng/mL, compared with control levels of 1.34+-0.55 ng/mL(p<0.001). MBP level was related to certain clinical features of the disease, such as level of consciousness, neurological characteristics associated with signs of raised intracranial tension and the presence of arteritis associated with hydrocephalus. However, its greatest significance was its correlation with the progress of disease. Persistence of high levels of MBP over a period of a few weeks was associated with little or no improvement in the clinical state of the patient or a higher mortality rate. Return to normal levels of MBP indicated a more favourable outcome of disease. Hence MBP estimation gave not only an indicator of the degree of neurological damage but also an important marker to evaluate patients' progress and response to treatment. (author)