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Sample records for paranodal myelin splitting

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

    OpenAIRE

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

    2014-01-01

    Myelin is a multilayered membrane sheath that encircles axons to enable rapid information processing and protect neurons. Formation of myelin requires communication between axons and oligodendrocytes, the myelin-forming cells in the CNS. Here we identify Contactin-1 as a critical signal for axon–glia communication in CNS myelin. Gene ablation in mice shows that Contactin-1 is necessary for myelin sheath formation by oligodendrocytes and establishment of paranodal axoglial junctions that regul...

  2. Gangliosides contribute to stability of paranodal junctions and ion channel clusters in myelinated nerve fibers.

    Science.gov (United States)

    Susuki, Keiichiro; Baba, Hiroko; Tohyama, Koujiro; Kanai, Kazuaki; Kuwabara, Satoshi; Hirata, Koichi; Furukawa, Keiko; Furukawa, Koichi; Rasband, Matthew N; Yuki, Nobuhiro

    2007-05-01

    Paranodal axo-glial junctions are important for ion channel clustering and rapid action potential propagation in myelinated nerve fibers. Paranode formation depends on the cell adhesion molecules neurofascin (NF) 155 in glia, and a Caspr and contactin heterodimer in axons. We found that antibody to ganglioside GM1 labels paranodal regions. Autoantibodies to the gangliosides GM1 and GD1a are thought to disrupt nodes of Ranvier in peripheral motor nerves and cause Guillain-Barré syndrome, an autoimmune neuropathy characterized by acute limb weakness. To elucidate ganglioside function at and near nodes of Ranvier, we examined nodes in mice lacking gangliosides including GM1 and GD1a. In both peripheral and central nervous systems, some paranodal loops failed to attach to the axolemma, and immunostaining of Caspr and NF155 was attenuated. K(+) channels at juxtaparanodes were mislocalized to paranodes, and nodal Na(+) channel clusters were broadened. Abnormal immunostaining at paranodes became more prominent with age. Moreover, the defects were more prevalent in ventral than dorsal roots, and less frequent in mutant mice lacking the b-series gangliosides but with excess GM1 and GD1a. Electrophysiological studies revealed nerve conduction slowing and reduced nodal Na(+) current in mutant peripheral motor nerves. The amounts of Caspr and NF155 in low density, detergent insoluble membrane fractions were reduced in mutant brains. These results indicate that gangliosides are lipid raft components that contribute to stability and maintenance of neuron-glia interactions at paranodes. PMID:17352383

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

    Science.gov (United States)

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

    2011-10-01

    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.

  4. Nodes of Ranvier act as barriers to restrict invasion of flanking paranodal domains in myelinated axons.

    Science.gov (United States)

    Thaxton, Courtney; Pillai, Anilkumar M; Pribisko, Alaine L; Dupree, Jeffrey L; Bhat, Manzoor A

    2011-01-27

    Accumulation of voltage-gated sodium (Na(v)) channels at nodes of Ranvier is paramount for action potential propagation along myelinated fibers, yet the mechanisms governing nodal development, organization, and stabilization remain unresolved. Here, we report that genetic ablation of the neuron-specific isoform of Neurofascin (Nfasc(NF¹??)) in vivo results in nodal disorganization, including loss of Na(v) channel and ankyrin-G (AnkG) enrichment at nodes in the peripheral nervous system (PNS) and central nervous system (CNS). Interestingly, the presence of paranodal domains failed to rescue nodal organization in the PNS and the CNS. Most importantly, using ultrastructural analysis, we demonstrate that the paranodal domains invade the nodal space in Nfasc(NF¹??) mutant axons and occlude node formation. Our results suggest that Nfasc(NF¹??)-dependent assembly of the nodal complex acts as a molecular boundary to restrict the movement of flanking paranodal domains into the nodal area, thereby facilitating the stereotypic axonal domain organization and saltatory conduction along myelinated axons. PMID:21262464

  5. Spatiotemporal ablation of myelinating glia-specific neurofascin (Nfasc NF155) in mice reveals gradual loss of paranodal axoglial junctions and concomitant disorganization of axonal domains.

    Science.gov (United States)

    Pillai, Anilkumar M; Thaxton, Courtney; Pribisko, Alaine L; Cheng, Jr-Gang; Dupree, Jeffrey L; Bhat, Manzoor A

    2009-06-01

    The evolutionary demand for rapid nerve impulse conduction led to the process of myelination-dependent organization of axons into distinct molecular domains. These domains include the node of Ranvier flanked by highly specialized paranodal domains where myelin loops and axolemma orchestrate the axoglial septate junctions. These junctions are formed by interactions between a glial isoform of neurofascin (Nfasc(NF155)) and axonal Caspr and Cont. Here we report the generation of myelinating glia-specific Nfasc(NF155) null mouse mutants. These mice exhibit severe ataxia, motor paresis, and death before the third postnatal week. In the absence of glial Nfasc(NF155), paranodal axoglial junctions fail to form, axonal domains fail to segregate, and myelinated axons undergo degeneration. Electrophysiological measurements of peripheral nerves from Nfasc(NF155) mutants revealed dramatic reductions in nerve conduction velocities. By using inducible PLP-CreER recombinase to ablate Nfasc(NF155) in adult myelinating glia, we demonstrate that paranodal axoglial junctions disorganize gradually as the levels of Nfasc(NF155) protein at the paranodes begin to drop. This coincides with the loss of the paranodal region and concomitant disorganization of the axonal domains. Our results provide the first direct evidence that the maintenance of axonal domains requires the fence function of the paranodal axoglial junctions. Together, our studies establish a central role for paranodal axoglial junctions in both the organization and the maintenance of axonal domains in myelinated axons. PMID:19185024

  6. Glial ankyrins facilitate paranodal axoglial junction assembly.

    Science.gov (United States)

    Chang, Kae-Jiun; Zollinger, Daniel R; Susuki, Keiichiro; Sherman, Diane L; Makara, Michael A; Brophy, Peter J; Cooper, Edward C; Bennett, Vann; Mohler, Peter J; Rasband, Matthew N

    2014-12-01

    Neuron-glia interactions establish functional membrane domains along myelinated axons. These include nodes of Ranvier, paranodal axoglial junctions and juxtaparanodes. Paranodal junctions are the largest vertebrate junctional adhesion complex, and they are essential for rapid saltatory conduction and contribute to assembly and maintenance of nodes. However, the molecular mechanisms underlying paranodal junction assembly are poorly understood. Ankyrins are cytoskeletal scaffolds traditionally associated with Na(+) channel clustering in neurons and are important for membrane domain establishment and maintenance in many cell types. Here we show that ankyrin-B, expressed by Schwann cells, and ankyrin-G, expressed by oligodendrocytes, are highly enriched at the glial side of paranodal junctions where they interact with the essential glial junctional component neurofascin 155. Conditional knockout of ankyrins in oligodendrocytes disrupts paranodal junction assembly and delays nerve conduction during early development in mice. Thus, glial ankyrins function as major scaffolds that facilitate early and efficient paranodal junction assembly in the developing CNS. PMID:25362471

  7. Spectrins and ankyrinB constitute a specialized paranodal cytoskeleton.

    Science.gov (United States)

    Ogawa, Yasuhiro; Schafer, Dorothy P; Horresh, Ido; Bar, Vered; Hales, Kimberly; Yang, Yang; Susuki, Keiichiro; Peles, Elior; Stankewich, Michael C; Rasband, Matthew N

    2006-05-10

    Paranodal junctions of myelinated nerve fibers are important for saltatory conduction and function as paracellular and membrane protein diffusion barriers flanking nodes of Ranvier. The formation of these specialized axoglial contacts depends on the presence of three cell adhesion molecules: neurofascin 155 on the glial membrane and a complex of Caspr and contactin on the axon. We isolated axonal and glial membranes highly enriched in these paranodal proteins and then used mass spectrometry to identify additional proteins associated with the paranodal axoglial junction. This strategy led to the identification of three novel components of the paranodal cytoskeleton: ankyrinB, alphaII spectrin, and betaII spectrin. Biochemical and immunohistochemical analyses revealed that these proteins associate with protein 4.1B in a macromolecular complex that is concentrated at central and peripheral paranodal junctions in the adult and during early myelination. Furthermore, we show that the paranodal localization of ankyrinB is disrupted in Caspr-null mice with aberrant paranodal junctions, demonstrating that paranodal neuron-glia interactions regulate the organization of the underlying cytoskeleton. In contrast, genetic disruption of the juxtaparanodal protein Caspr2 or the nodal cytoskeletal protein betaIV spectrin did not alter the paranodal cytoskeleton. Our results demonstrate that the paranodal junction contains specialized cytoskeletal components that may be important to stabilize axon-glia interactions and contribute to the membrane protein diffusion barrier found at paranodes. PMID:16687515

  8. Proteomic analysis of optic nerve lipid rafts reveals new paranodal proteins.

    Science.gov (United States)

    Ogawa, Yasuhiro; Rasband, Matthew N

    2009-11-15

    Neuron-glia interactions at paranodal junctions play important roles in action potential propagation. Among their many functions, they contribute to the passive electrical properties of myelinated nerve fibers and actively regulate the polarized distribution of ion channels along axons. Despite their importance, relatively little is known about the molecules responsible for paranode formation and function. Paranodal junction formation apparently depends on interactions among three cell adhesion molecules: caspr and contactin on the axon and neurofascin 155 (NF-155) on the glial membrane. Using Caspr-null paranodal mutant mice, we demonstrate that loss of paranodal junctions causes failure of NF-155 to partition into lipid rafts, indicating that proteins located at paranodal junctions have biochemical characteristics of lipid raft-associated proteins. Based on this property of paranodal junctions, mass spectrometry of lipid rafts isolated from a pure white matter tract (optic nerve) was used to search for new paranodal proteins. Because we used a relatively crude biochemical preparation, we identified several hundred different proteins. Among these, we found all previously described paranodal proteins. Further analysis based on antibody staining of central and peripheral nerves revealed beta-adducin, septin 2, and sh3p8 as putative paranodal proteins. We describe the localization of these proteins in relation to other markers of nodes, paranodes, and juxtaparanodes in adult and developing nerve fibers. Finally, we describe their distribution in dysmyelinating TremblerJ mice, a model for the peripheral neuropathy Charcot-Marie-Tooth disease. PMID:19156860

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

    Science.gov (United States)

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

    2010-02-01

    Stability of the myelin-axon unit is achieved, at least in part, by specialized paranodal junctions comprised of the neuronal heterocomplex of contactin and contactin-associated protein and the myelin protein neurofascin 155. In multiple sclerosis, normal distribution of these proteins is altered, resulting in the loss of the insulating myelin and consequently causing axonal dysfunction. Previously, this laboratory reported that mice lacking the myelin-enriched lipid sulphatide are characterized by a progressive deterioration of the paranodal structure. Here, it is shown that this deterioration is preceded by significant loss of neurofascin 155 clustering at the myelin paranode. Interestingly, prolonged electrophoretic separation revealed the existence of two neurofascin 155 bands, neurofascin 155 high and neurofascin 155 low, which are readily observed following N-linked deglycosylation. Neurofascin 155 high is observed at 7 days of age and reaches peak expression at one month of age, while neurofascin 155 low is first observed at 14 days of age and constantly increases until 5 months of age. Studies using conditional neurofascin knockout mice indicated that neurofascin 155 high and neurofascin 155 low are products of the neurofascin gene and are exclusively expressed by oligodendrocytes within the central nervous system. Neurofascin 155 high is a myelin paranodal protein while the distribution of neurofascin 155 low remains to be determined. While neurofascin 155 high levels are significantly reduced in the sulphatide null mice at 15 days, 30 days and 4 months of age, neurofascin 155 low levels remain unaltered. Although maintained at normal levels, neurofascin 155 low is incapable of preserving paranodal structure, thus indicating that neurofascin 155 high is required for paranodal stability. Additionally, comparisons between neurofascin 155 high and neurofascin 155 low in human samples revealed a significant alteration, specifically in multiple sclerosis plaques. PMID:20129933

  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. Disruption of myelination by diagnostic US

    International Nuclear Information System (INIS)

    In order to test for possible effects of US on myelination, the authors exposed 20 unanesthetized rat pups to US intensities consistent with those used for imaging a human fetus in utero. The rats were 3-5 days old and at a stage of myelination similar to that of a human fetus of about 4-5 months. Then animals were exposed for 30 minutes to the beam from a 3.5-MHz transducer (ADR 2130 real-time linear array, SPTA intensity of 0.4 mW/cm/sup 2/ and SATA intensity of 0.05 mW/cm/sup 2/). Control animals were bound and placed in the tank but not exposed for 30 minutes, and taken straight from the cage. Some animals were killed and tissues were processed for electron microscopy immediately after exposure, others were killed after recovery periods of up to 24 hours. Enlargements of the periaxonal space was visible with separation of adjacent paranodal loops and disruption of Schwann cell-axonal junctions in all exposed animals. Paranodal demyelination was also noted in several nodes. Nodes exhibiting this microedematous morphology were apparent even after a 24-hour recovery period but were not found in control preparations

  12. In vivo deletion of immunoglobulin domains 5 and 6 in neurofascin (Nfasc) reveals domain-specific requirements in myelinated axons.

    Science.gov (United States)

    Thaxton, Courtney; Pillai, Anilkumar M; Pribisko, Alaine L; Labasque, Marilyne; Dupree, Jeffrey L; Faivre-Sarrailh, Catherine; Bhat, Manzoor A

    2010-04-01

    The formation of paranodal axo-glial junctions is critical for the rapid and efficient propagation of nerve impulses. Genetic ablation of genes encoding the critical paranodal proteins Caspr, contactin (Cont), and the myelinating glia-specific isoform of Neurofascin (Nfasc(NF155)) results in the disruption of the paranodal axo-glial junctions, loss of ion channel segregation, and impaired nerve conduction, but the mechanisms regulating their interactions remain elusive. Here, we report that loss of immunoglobulin (Ig) domains 5 and 6 in Nfasc(NF155) in mice phenocopies complete ablation of Nfasc(NF155). The mutant mice lack paranodal septate junctions, resulting in the diffusion of Caspr and Cont from the paranodes, and redistribution of the juxtaparanodal potassium channels toward the nodes. Although critical for Nfasc(NF155) function, we find that Ig5-6 are dispensable for nodal Nfasc(NF186) function. Moreover, in vitro binding assays using Ig5-6 deletion constructs reveal their importance for the association of Nfasc(NF155) with Cont. These findings provide the first molecular evidence demonstrating domain-specific requirements controlling the association of the paranodal tripartite complex in vivo. Our studies further emphasize that in vivo structure/function analysis is necessary to define the unique protein-protein interactions that differentially regulate the functions of Neurofascins during axonal domain organization. PMID:20371806

  13. Disposition of axonal caspr with respect to glial cell membranes: Implications for the process of myelination.

    Science.gov (United States)

    Pedraza, Liliana; Huang, Jeffrey K; Colman, David

    2009-11-15

    Neurofascin-155 (NF155) and caspr are transmembrane proteins found at discrete locations early during development of the nervous system. NF155 is present in the oligodendrocyte cell body and processes, whereas caspr is on the axonal surface. In mature nerves, these proteins are clustered at paranodes, flanking the node of Ranvier. To understand how NF155 and caspr become localized to the paranodal regions of myelinated nerves, we have studied their distribution over time in myelinating cultures. Our observations indicate that these two proteins are recruited to the cell surface at the contact zone between axons and oligodendrocytes, where they trans-interact. This association explains the early pattern of caspr distribution, a helical coil that winds around the axon, resembling the turns of the myelin sheath. Caspr, an axonal membrane protein, therefore seems to move in register with the overlying myelinating cell via its interactions with myelin proteins. We suggest that NF155 is the glial cell membrane protein responsible for caspr distribution. The pair act as interacting partners on either side of the axoglial contact area. Most likely, there are other proteins on the axonal surface whose distribution is equally influenced by interaction with the nascent myelin sheath. The fact that caspr follows the movement of the spiraling membrane has a direct affect on the interpretation of the way in which myelin is formed. PMID:19170162

  14. A novel Caspr mutation causes the shambling mouse phenotype by disrupting axoglial interactions of myelinated nerves.

    Science.gov (United States)

    Sun, Xiao-yang; Takagishi, Yoshiko; Okabe, Erina; Chishima, Yûko; Kanou, Yasuhiko; Murase, Shiori; Mizumura, Kazue; Inaba, Mie; Komatsu, Yukio; Hayashi, Yoshitaka; Peles, Elior; Oda, Sen-ichi; Murata, Yoshiharu

    2009-11-01

    The neurological mouse mutation shambling (shm) exhibits ataxia and hindlimb paresis. Positional cloning of shm showed that it encodes contactin-associated protein (Caspr), which is required for formation of the paranodal junction in myelinated nerves. The shm mutation is a TT insertion in the Caspr gene that results in a frame shift and a premature stop codon at the COOH-terminus. The truncated Caspr protein that is generated lacks the transmembrane and cytoplasmic domains. Here, we found that the nodal/paranodal axoplasm of shm mice lack paranodal junctions and contain large mitochondria and abnormal accumulations of cytoplasmic organelles that indicate altered axonal transport. Immunohistochemical analysis of mutant mice showed reduced expression of Caspr, contactin, and neurofascin 155, which are thought to form a protein complex in the paranodal region; protein 4.1B, however, was normally distributed. The mutant mice had aberrant localization of voltage-gated ion channels on the axolemma of nodal/paranodal regions. Electrophysiological analysis demonstrated that the velocity of saltatory conduction was reduced in sciatic nerves and that the visual response was attenuated in the primary visual cortex. These abnormalities likely contribute to the neurological phenotype of the mutant mice. PMID:19816196

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2014-01-01

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

  17. Diagnostic levels of ultrasound may disrupt myelination.

    Science.gov (United States)

    Ellisman, M H; Palmer, D E; André, M P

    1987-10-01

    Neonatal rats 3 to 5 days of age were exposed to the ultrasound beam from a medical ultrasound imaging system. Dorsal nerve roots were examined by electron microscopy. Comparison between exposed and sham-exposed controls revealed disruption of the nodes of Ranvier attributable to ultrasound. Morphologic changes ranged from vacuole formation in the paranodal region to frank demyelination and were still evident after 24 h of recovery. Rats of this age are at a stage of myelination similar to that of a human fetus 4 to 5 months. The ultrasound intensities used in this study are consistent with those used for human imaging (SPTA 0.135 mW/cm2, SATA 0.045 mW/cm2, SPTP 8.7 W/cm2, SPPA 1.9 W/cm2), but the relevance of these findings to clinical ultrasound will require further study. PMID:3308504

  18. Is myelin a mitochondrion?

    OpenAIRE

    Harris, Julia J; Attwell, David

    2013-01-01

    It has been hypothesized that myelin acts like a mitochondrion, generating ATP across the membranes of its sheath. By calculating the proton motive force across the myelin membrane based on known values for the pH and membrane potential of the oligodendrocyte, we find that insufficient energy could be harvested from proton flow across the myelin membrane to synthesize ATP. In fact, if the respiratory chain were present in the myelin membrane, then the ATP synthase would function in reverse, h...

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

    International Nuclear Information System (INIS)

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

  20. Oligodendrocytes assist in the maintenance of sodium channel clusters independent of the myelin sheath

    Science.gov (United States)

    DUPREE, JEFFREY L.; MASON, JEFFREY L.; MARCUS, JILL R.; STULL, MICHAEL; LEVINSON, ROCK; MATSUSHIMA, GLENN K.; POPKO, BRIAN

    2006-01-01

    To ensure rapid and efficient impulse conduction, myelinated axons establish and maintain specific protein domains. For instance, sodium (Na+) channels accumulate in the node of Ranvier; potassium (K+) channels aggregate in the juxtaparanode and neurexin/caspr/paranodin clusters in the paranode. Our understanding of the mechanisms that control the initial clustering of these proteins is limited and less is known about domain maintenance. Correlative data indicate that myelin formation and/ or mature myelin-forming cells mediate formation of all three domains. Here, we test whether myelin is required for maintaining Na+ channel domains in the nodal gap by employing two demyelinating murine models: (1) cuprizone ingestion, which induces complete demyelination through oligodendrocyte toxicity; and (2) ceramide galactosyltransferase deficient mice, which undergo spontaneous adult-onset demyelination without oligodendrocyte death. Our data indicate that the myelin sheath is essential for long-term maintenance of sodium channel domains; however, oligodendrocytes, independent of myelin, provide a partial protective influence on the maintenance of nodal Na+ channel clusters. Thus, we propose that multiple mechanisms regulate the maintenance of nodal protein organization. Finally, we present evidence that following the loss of Na+ channel clusters the chronological progression of expression and reclustering of Na+ channel isoforms during the course of CNS remyelination recapitulates development. PMID:18634596

  1. Oligodendrocytes assist in the maintenance of sodium channel clusters independent of the myelin sheath.

    Science.gov (United States)

    Dupree, Jeffrey L; Mason, Jeffrey L; Marcus, Jill R; Stull, Michael; Levinson, Rock; Matsushima, Glenn K; Popko, Brian

    2004-08-01

    To ensure rapid and efficient impulse conduction, myelinated axons establish and maintain specific protein domains. For instance, sodium (Na+) channels accumulate in the node of Ranvier; potassium (K+) channels aggregate in the juxtaparanode and neurexin/caspr/paranodin clusters in the paranode. Our understanding of the mechanisms that control the initial clustering of these proteins is limited and less is known about domain maintenance. Correlative data indicate that myelin formation and/or mature myelin-forming cells mediate formation of all three domains. Here, we test whether myelin is required for maintaining Na+ channel domains in the nodal gap by employing two demyelinating murine models: (1) cuprizone ingestion, which induces complete demyelination through oligodendrocyte toxicity; and (2) ceramide galactosyltransferase deficient mice, which undergo spontaneous adult-onset demyelination without oligodendrocyte death. Our data indicate that the myelin sheath is essential for long-term maintenance of sodium channel domains; however, oligodendrocytes, independent of myelin, provide a partial protective influence on the maintenance of nodal Na+ channel clusters. Thus, we propose that multiple mechanisms regulate the maintenance of nodal protein organization. Finally, we present evidence that following the loss of Na+ channel clusters the chronological progression of expression and reclustering of Na+ channel isoforms during the course of CNS remyelination recapitulates development. PMID:18634596

  2. Myelinated nerve fibres and the fate of lanthanum tracer: an in vivo study.

    Science.gov (United States)

    Mackenzie, M L; Shorer, Z; Ghabriel, M N; Allt, G

    1984-01-01

    The permeability of the marginal tight junctional system of myelin was tested in the rat employing the electron-dense tracer lanthanum nitrate. Lanthanum was either included in the fixative used for vascular perfusion (at a concentration of 20 mM) or was microinjected in vivo into the sural or tibial nerve (5, 10 and 20 mM). After 5-60 minutes, the microinjected nerves were fixed either by immersion or vascular perfusion. Lanthanum tracer was present in the intraperiod line gap of myelin, irrespective of the mode of application of the tracer, the method of fixation or the time of exposure to lanthanum. However, the tracer was present more extensively when included in the fixative compared with in vivo microinjection. Internodally, lanthanum was usually restricted to the inner, or more commonly, the outer lamellae of larger fibres, while all lamellae were usually penetrated by tracer in smaller fibres. Paranodally, compact myelin was more extensively penetrated. The periaxonal space (between axon and Schwann cell) was readily accessible to tracer. It is concluded that the marginal tight junctional system of myelin is apparently of the 'leaky' type and is permeable to ions. The findings have implications for the electrophysiology and pathophysiology of the myelinated nerve fibre. PMID:6368509

  3. The "Lillie transition": models of the onset of saltatory conduction in myelinating axons.

    Science.gov (United States)

    Young, Robert G; Castelfranco, Ann M; Hartline, Daniel K

    2013-06-01

    Almost 90 years ago, Lillie reported that rapid saltatory conduction arose in an iron wire model of nerve impulse propagation when he covered the wire with insulating sections of glass tubing equivalent to myelinated internodes. This led to his suggestion of a similar mechanism explaining rapid conduction in myelinated nerve. In both their evolution and their development, myelinating axons must make a similar transition between continuous and saltatory conduction. Achieving a smooth transition is a potential challenge that we examined in computer models simulating a segmented insulating sheath surrounding an axon having Hodgkin-Huxley squid parameters. With a wide gap under the sheath, conduction was continuous. As the gap was reduced, conduction initially slowed, owing to the increased extra-axonal resistance, then increased (the "rise") up to several times that of the unmyelinated fiber, as saltatory conduction set in. The conduction velocity slowdown was little affected by the number of myelin layers or modest changes in the size of the "node," but strongly affected by the size of the "internode" and axon diameter. The steepness of the rise of rapid conduction was greatly affected by the number of myelin layers and axon diameter, variably affected by internode length and little affected by node length. The transition to saltatory conduction occurred at surprisingly wide gaps and the improvement in conduction speed persisted to surprisingly small gaps. The study demonstrates that the specialized paranodal seals between myelin and axon, and indeed even the clustering of sodium channels at the nodes, are not necessary for saltatory conduction. PMID:23306554

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

    Science.gov (United States)

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

    2011-06-01

    White matter injury characterized by damage to myelin is an important process in hypoxic-ischemic brain damage (HIBD). Because the oligodendrocyte-specific isoform of neurofascin, neurofascin 155 (NF155), and its association with lipid rafts are essential for the establishment and stabilization of the paranodal junction, which is required for tight interaction between myelin and axons, we analyzed the effect of monosialotetrahexosyl ganglioside (GM1) on NF155 expression and its association with lipid rafts after HIBD in Sprague-Dawley rats, weighing 12-15 g, on day 7 post-partum (P7; N = 20 per group). HIBD was induced on P7 and the rats were divided into two groups: one group received an intraperitoneal injection of 50 mg/kg GM1 three times and the other group an injection of saline. There was also a group of 20 sham-operated rats. After sacrifice, the brains of the rats were removed on P30 and studied by immunochemistry, SDS-PAGE, Western blot analysis, and electron microscopy. Staining showed that the saline group had definite rarefaction and fragmentation of brain myelin sheaths, whereas the GM1 group had no obvious structural changes. The GM1 group had 1.9-2.9-fold more GM1 in lipid rafts than the saline group (fraction 3-6; all P < 0.05) and 0.5-2.4-fold higher expression of NF155 in lipid rafts (fraction 3-5; all P < 0.05). Injection of GM1 increased the content of GM1 in lipid rafts as well as NF155 expression and its lipid raft association in HIBD rat brains. GM1 may repair the structure of lipid rafts, promote the association of NF155 (or other important proteins) with lipid rafts, stabilize the structure of paranodes, and eventually prevent myelin sheath damage, suggesting a novel mechanism for its neuroprotective properties. PMID:21670940

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

    Directory of Open Access Journals (Sweden)

    Y.P. Zhang

    2011-06-01

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

  6. Myelin Loss and Axonal Ion Channel Adaptations Associated with Gray Matter Neuronal Hyperexcitability

    Science.gov (United States)

    Hamada, Mustafa S.

    2015-01-01

    Myelination and voltage-gated ion channel clustering at the nodes of Ranvier are essential for the rapid saltatory conduction of action potentials. Whether myelination influences the structural organization of the axon initial segment (AIS) and action potential initiation is poorly understood. Using the cuprizone mouse model, we combined electrophysiological recordings with immunofluorescence of the voltage-gated Nav1.6 and Kv7.3 subunits and anchoring proteins to analyze the functional and structural properties of single demyelinated neocortical L5 axons. Whole-cell recordings demonstrated that neurons with demyelinated axons were intrinsically more excitable, characterized by increased spontaneous suprathreshold depolarizations as well as antidromically propagating action potentials ectopically generated in distal parts of the axon. Immunofluorescence examination of demyelinated axons showed that ?IV-spectrin, Nav1.6, and the Kv7.3 channels in nodes of Ranvier either dissolved or extended into the paranodal domains. In contrast, while the AIS in demyelinated axons started more closely to the soma, ankyrin G, ?IV-spectrin, and the ion channel expression were maintained. Structure–function analysis and computational modeling, constrained by the AIS location and realistic dendritic and axonal morphologies, confirmed that a more proximal onset of the AIS slightly reduced the efficacy of action potential generation, suggesting a compensatory role. These results suggest that oligodendroglial myelination is not only important for maximizing conduction velocity, but also for limiting hyperexcitability of pyramidal neurons. PMID:25948275

  7. Myelin loss and axonal ion channel adaptations associated with gray matter neuronal hyperexcitability.

    Science.gov (United States)

    Hamada, Mustafa S; Kole, Maarten H P

    2015-05-01

    Myelination and voltage-gated ion channel clustering at the nodes of Ranvier are essential for the rapid saltatory conduction of action potentials. Whether myelination influences the structural organization of the axon initial segment (AIS) and action potential initiation is poorly understood. Using the cuprizone mouse model, we combined electrophysiological recordings with immunofluorescence of the voltage-gated Nav1.6 and Kv7.3 subunits and anchoring proteins to analyze the functional and structural properties of single demyelinated neocortical L5 axons. Whole-cell recordings demonstrated that neurons with demyelinated axons were intrinsically more excitable, characterized by increased spontaneous suprathreshold depolarizations as well as antidromically propagating action potentials ectopically generated in distal parts of the axon. Immunofluorescence examination of demyelinated axons showed that ?IV-spectrin, Nav1.6, and the Kv7.3 channels in nodes of Ranvier either dissolved or extended into the paranodal domains. In contrast, while the AIS in demyelinated axons started more closely to the soma, ankyrin G, ?IV-spectrin, and the ion channel expression were maintained. Structure-function analysis and computational modeling, constrained by the AIS location and realistic dendritic and axonal morphologies, confirmed that a more proximal onset of the AIS slightly reduced the efficacy of action potential generation, suggesting a compensatory role. These results suggest that oligodendroglial myelination is not only important for maximizing conduction velocity, but also for limiting hyperexcitability of pyramidal neurons. PMID:25948275

  8. Early events in node of Ranvier formation during myelination and remyelination in the PNS.

    Science.gov (United States)

    Schafer, Dorothy P; Custer, Andrew W; Shrager, Peter; Rasband, Matthew N

    2006-05-01

    Action potential conduction velocity increases dramatically during early development as axons become myelinated. Integral to this process is the clustering of voltage-gated Na(+) (Nav) channels at regularly spaced gaps in the myelin sheath called nodes of Ranvier. We show here that some aspects of peripheral node of Ranvier formation are distinct from node formation in the CNS. For example, at CNS nodes, Nav1.2 channels are detected first, but are then replaced by Nav1.6. Similarly, during remyelination in the CNS, Nav1.2 channels are detected at newly forming nodes. By contrast, the earliest Nav-channel clusters detected during developmental myelination in the PNS have Nav1.6. Further, during PNS remyelination, Nav1.6 is detected at new nodes. Finally, we show that accumulation of the cell adhesion molecule neurofascin always precedes Nav channel clustering in the PNS. In most cases axonal neurofascin (NF-186) accumulates first, but occasionally paranodal neurofascin is detected first. We suggest there is heterogeneity in the events leading to Nav channel clustering, indicating that multiple mechanisms might contribute to node of Ranvier formation in the PNS. PMID:16652168

  9. Fyn tyrosine kinase participates in the compact myelin sheath formation in the central nervous system.

    Science.gov (United States)

    Seiwa, C; Sugiyama, I; Yagi, T; Iguchi, T; Asou, H

    2000-05-01

    The cellular mechanisms for spiral wrapping and compaction of myelin sheaths by oligodendrocytes are not known yet. In this study, we examined the role of fyn tyrosine kinase, which could be responsible for molecular events during the stage of myelination in the CNS. Western blot and immunohistochemical analyses revealed that fyn-deficient mice have significantly lower levels of myelin basic protein (MBP), which is required for intracellular membrane adhesion parts so-called major dense line (MDL) and thought to be essential for the stability of myelin sheath. Electron microscopy verified that the myelin ultrastructure could be used to distinguish fyn-deficient mice from wild-type mice, showing a thin and redundant myelin sheath in the corpus callosum. Further, the electron-dense 'major' line in myelin from the purified myelin fractions remained condensed, and myelin compaction was split opened in fyn-deficient mice. To determine whether there was a change in the microheterogeneity of MBP due to a post-translational event we first investigated peptidylarginine deiminase (PAD), which is an enzyme that converts arginine residues in peptides to citrulline residues. PAD immunoreactivity was observed both in the myelin from fyn-deficient and wild-type mice. By Western blot analysis we found an increase of the citrullined form of MBP. In addition, MBP from fyn-deficient mice did weakly induce vesicle aggregation properties of MBP-mediated adhesion. We concluded that although oligodendrocytes from fyn-deficient mice are able to wrap around the axon, they are unable to form compact myelin due to decreased MBP level and the presence of increased citrullinated MBP. PMID:10802341

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

    Scientific Electronic Library Online (English)

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

    2011-06-01

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

  11. Effect of posttranslational modifications to myelin basic protein on its ability to aggregate acidic lipid vesicles.

    Science.gov (United States)

    Boggs, J M; Yip, P M; Rangaraj, G; Jo, E

    1997-04-22

    When isolated from central nervous system myelin, myelin basic protein (MBP) exhibits charge microheterogeneity due to posttranslational deamidation, phosphorylation, and deimination of arginine to citrulline. These modifications are known to decrease the ability of MBP to aggregate acidic lipid vesicles and thus could regulate the ability of MBP to mediate adhesion between the intracellular surfaces of myelin. The effects of salt (KCl) concentration and the protein to lipid ratio on the ability of charge isomers of MBP to aggregate large unilamellar vesicles (LUVs) were investigated. Increased salt concentration from 10 to 100 mM caused increasing aggregation of LUVs by low concentrations of all charge isomers but did not eliminate the differences in their abilities to aggregate. All isomers were bound equally up to about 100 mM K+ but were dissociated at higher K+ concentrations. The degree of dissociation increased with increasing net negative charge of the isomer. At high concentrations all charge isomers except the form in which six arginine residues are converted to citrulline (C8) aggregated LUVs of phosphatidylcholine/phosphatidylserine (PC/PS) 8:2 (mol/mol) similarly and salt increased the aggregation to the same degree for all. There was less difference in the ability of the charge isomers, including C8, to aggregate LUVs with a lipid composition resembling that of the cytoplasmic leaflet of myelin (Cyt-LUVs) than for PC/PS LUVs. Furthermore, high salt concentrations (400 mM) did not dissociate any of the charge isomers from the Cyt-LUVs. These results suggest that the reason for inhibition of aggregating ability by charge modification is not increased charge repulsion of the protein but rather its reduced multivalency of net positive charge. They indicate further that the lipid composition of the cytoplasmic leaflet is ideally suited to permit MBP-mediated adhesion and that charge modifications of MBP would probably not affect adhesion of the intracellular surfaces of compact myelin where MBP concentration is high. However, charge modifications might affect adhesion in cytoplasm-containing regions of myelin such as the paranodal loops, where MBP concentration is low and where K+ concentration may vary in the range of 60-75 mM. PMID:9125528

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

    Science.gov (United States)

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

    1991-05-01

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

  13. Schwann cell myelination requires Dynein function

    Directory of Open Access Journals (Sweden)

    Langworthy Melissa M

    2012-11-01

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

  14. Myelin alters the inflammatory phenotype of macrophages by activating PPARs

    OpenAIRE

    BOGIE, Jeroen; JORISSEN, Winde; Mailleux, Jo; VANMIERLO, Tim; Van Horssen, Jack; HELLINGS, Niels; Stinissen, Piet; Hendriks, J.J.A.; Nijland, Philip G; Zelcer, Noam

    2013-01-01

    Background Foamy macrophages, containing myelin degradation products, are abundantly found in active multiple sclerosis (MS) lesions. Recent studies have described an altered phenotype of macrophages after myelin internalization. However, mechanisms by which myelin affects the phenotype of macrophages and how this phenotype influences lesion progression remain unclear. Results We demonstrate that myelin as well as phosphatidylserine (PS), a phospholipid found in myelin, reduce nitri...

  15. Tracing immature myelin in acute disseminated encephalomyelitis.

    Science.gov (United States)

    Anlar, Banu; Karli-O?uz, Kader; Yurtyapan, Osman Yücel; Senbil, Nesrin; Hergüner, Ozlem; Altunba?ak, Sakir; Sönmez, F Müjgan; Ozdemir-Geyik, Pinar

    2006-01-01

    Inherent abnormalities of myelin have been suggested in the pathogenesis of multiple sclerosis (MS). We investigated myelin in acute disseminated encephalomyelitis (ADEM) patients by magnetic resonance spectroscopy (MRS) and cerebrospinal fluid (CSF) analysis for citrulline, a marker of immature myelin. A citrulline peak was observed in the normal appearing white matter of 7/15 patients and of 1/10 age-matched neurological controls (p=0.08). CSF citrulline was elevated in 4/6 patients. Alterations in the composition of myelin might predispose to or follow acute inflammatory disorders of the central nervous system. PMID:17172061

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

    OpenAIRE

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

    2011-01-01

    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 sim...

  17. Conduction failure in myelinated and non-myelinated axons at low temperatures

    Science.gov (United States)

    Franz, D. N.; Iggo, A.

    1968-01-01

    1. The effects of low temperature on conduction in single myelinated and non-myelinated axons of the feline saphenous nerve were examined and compared. Nerves were cooled by a conventional thermode, but thermal gradients were minimized by an insulating layer of agar-saline gel over the nerve and the face of the thermode. 2. The mean blocking temperature of thirty-one non-myelinated axons, 2·7° C, was significantly lower than that of 111 myelinated axons, 7·2° C. No evidence for a differential block of myelinated axons according to their normal conduction velocity could be demonstrated. 3. Reductions in the proportional conduction velocities of both myelinated and non-myelinated axons were nearly identical between 17 and 37° C. However, below 17° C the rate at which the proportional conduction velocity of the non-myelinated axons fell during cooling was significantly less than for the myelinated axons and was sufficient to account for their lower blocking temperatures. As a result, critical minimum conduction velocities were reached at higher temperatures in myelinated axons than in non-myelinated axons. 4. The conduction velocity of successive impulses in a train slowed progressively to a constant value which depended on the frequency of stimulation. Consequently, the early impulses were separated by intervals that exceeded those between stimuli and were not affected by temperatures that blocked later impulses. The pattern of block was consistent with an increasing refractoriness of the axons as the temperature fell. 5. The maximal frequency of discharge that myelinated axons could carry at temperatures between normal and 12° C was related directly to fibre size. Non-myelinated axons could conduct low frequency trains of impulses at temperatures that blocked such activity in myelinated axons. In all axons, high frequency trains of impulses could be completely blocked at temperatures which permitted lower frequency trains to pass uninterrupted. 6. Hysteresis in the blocking temperatures of axons was related to the hysteresis in their conduction velocities. PMID:5723515

  18. Axon-glia interaction and membrane traffic in myelin formation

    OpenAIRE

    Eva-Maria Krämer-Albers; Robin White

    2014-01-01

    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...

  19. Astrocyte phenotypes and their relationship to myelination.

    Science.gov (United States)

    Nash, Besma; Ioannidou, Kalliopi; Barnett, Susan C

    2011-07-01

    Astrocytes are one of the major glial cell types that maintain homeostasis in the undamaged CNS. After injury and disease, astrocytes become reactive and prevent regeneration; however, it has also been suggested that astrocytes can become activated and promote regeneration. Thus, it is hypothesised that astrocytes have an important role in modulating CNS repair. This review will focus on the variable phenotypic state of astrocytes that range from inactive/quiescent to reactive, and relate these to their ability to influence myelination. Using myelinating cultures plated on astrocytes we propose a possible mechanism for oligodendrocyte precursor cell interaction with the axon, leading to myelination. The phenotypic status of astrocytes is an intriguing and widely discussed issue, which is critical for understanding the mechanisms involved in CNS injury and its subsequent repair. PMID:21496013

  20. Myelination: all about Rac 'n' roll.

    Science.gov (United States)

    Chan, Jonah R

    2007-06-18

    During the development of the peripheral nervous system, Schwann cells select individual axons from a nerve bundle and establish a one-to-one relationship through a process termed "radial sorting". Recent findings identify the Rho family GTPase Rac1 as the downstream effector molecule responsible for process extension and lamellipodia formation in Schwann cells, allowing for proper radial sorting and myelination. These findings begin to shed light on our understanding of the distinct and yet essential molecular mechanisms involved in developmental processes preceding myelination. PMID:17576794

  1. On the resemblance of synapse formation and CNS myelination.

    Science.gov (United States)

    Almeida, R G; Lyons, D A

    2014-09-12

    The myelination of axons in the central nervous system (CNS) is essential for nervous system formation, function and health. CNS myelination continues well into adulthood, but not all axons become myelinated. Unlike the peripheral nervous system, where we know of numerous axon-glial signals required for myelination, we have a poor understanding of the nature or identity of such molecules that regulate which axons are myelinated in the CNS. Recent studies have started to elucidate cell behavior during myelination in vivo and indicate that the choice of which axons are myelinated is made prior to myelin sheath generation. Here we propose that interactions between axons and the exploratory processes of oligodendrocyte precursor cells (OPCs) lead to myelination and may be similar to those between dendrites and axons that prefigure and lead to synapse formation. Indeed axons and OPCs form synapses with striking resemblance to those of neurons, suggesting a similar mode of formation. We discuss families of molecules with specific functions at different stages of synapse formation and address studies that implicate the same factors during axon-OPC synapse formation and myelination. We also address the possibility that the function of such synapses might directly regulate the myelinating behavior of oligodendrocyte processes in vivo. In the future it may be of benefit to consider these similarities when taking a candidate-based approach to dissect mechanisms of CNS myelination. PMID:24035825

  2. Autoantibodies against myelin antigens in patients with neuromyelitis optica

    Directory of Open Access Journals (Sweden)

    Kota Moriguchi

    2013-06-01

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

  3. Localization of basic proteins in human myelin.

    Science.gov (United States)

    McLaurin, J; Ackerley, C A; Moscarello, M A

    1993-08-15

    The myelin basic protein (MBPs) represent a family of proteins (charge isomers) which account for 35% of the total myelin protein. Localization studies have been inconclusive because MBP is not a single protein. Antibodies obtained by injection of MBP into animals recognized all members of the MBP family. In the studies reported here, we have fractionated the MBPs into specific components or charge isomers. One of these which contains citrulline accounts for about 20% of the total MBP. We report the localization of this single MBP to the intraperiod line of myelin by immunoelectron microscopy. For these studies several specific antibodies were used including antibodies raised against total MBP, specific MBP peptides, and against a tetracitrulline peptide. This latter antibody was specific for component 8 (C-8) of MBP. Since C-8 is the only MBP which contains citrulline it was used to localize this particular form of MBP principally to the intraperiod line by immunogold electron microscopy, while antibody against total MBP (consisting of all charge isomers C-1-->C-8) labelled both the major dense line and the intraperiod line. When the anti-citrulline antibody was used with a 3 nm gold conjugated Fab fragments prepared from the secondary antibody, 66.5% of the gold particles were localized to the intraperiod line, while 11.2% of gold particles were localized to the major dense line. On the other hand, with the monoclonal anti-MBP antibodies reactive with residues 69-74, 59.4% of the gold particles were localized to the major dense line and 23.6% of gold particles at the intraperiod line. Other supporting evidence includes increased labelling of myelin by 125I labelled anti-citrulline IgG when isolated myelin was swollen, a process known to take place at the intraperiod line. Gold particles were demonstrated at the intraperiod line in swollen and recompacted myelin. C-8 was shown to associate preferentially with lipids asymmetrically localized to the intraperiod line. PMID:7692076

  4. Axon-glia interaction and membrane traffic in myelin formation

    Directory of Open Access Journals (Sweden)

    Eva-Maria Krämer-Albers

    2014-01-01

    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.

  5. Zebrafish myelination: a transparent model for remyelination?

    OpenAIRE

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

    2008-01-01

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

  6. Myelination: all about Rac ‘n’ roll

    OpenAIRE

    Chan, Jonah R

    2007-01-01

    During the development of the peripheral nervous system, Schwann cells select individual axons from a nerve bundle and establish a one-to-one relationship through a process termed “radial sorting”. Recent findings identify the Rho family GTPase Rac1 as the downstream effector molecule responsible for process extension and lamellipodia formation in Schwann cells, allowing for proper radial sorting and myelination. These findings begin to shed light on our understanding of the distinct and ...

  7. Plasmalogen phospholipids protect internodal myelin from oxidative damage.

    Science.gov (United States)

    Luoma, Adrienne M; Kuo, Fonghsu; Cakici, Ozgur; Crowther, Michelle N; Denninger, Andrew R; Avila, Robin L; Brites, Pedro; Kirschner, Daniel A

    2015-07-01

    Reactive oxygen species (ROS) are implicated in a range of degenerative conditions, including aging, neurodegenerative diseases, and neurological disorders. Myelin is a lipid-rich multilamellar sheath that facilitates rapid nerve conduction in vertebrates. Given the high energetic demands and low antioxidant capacity of the cells that elaborate the sheaths, myelin is considered intrinsically vulnerable to oxidative damage, raising the question whether additional mechanisms prevent structural damage. We characterized the structural and biochemical basis of ROS-mediated myelin damage in murine tissues from both central nervous system (CNS) and peripheral nervous system (PNS). To determine whether ROS can cause structural damage to the internodal myelin, whole sciatic and optic nerves were incubated ex vivo with a hydroxyl radical-generating system consisting of copper (Cu), hydrogen peroxide (HP), and ortho-phenanthroline (OP). Quantitative assessment of unfixed tissue by X-ray diffraction revealed irreversible compaction of myelin membrane stacking in both sciatic and optic nerves. Incubation in the presence of the hydroxyl radical scavenger sodium formate prevented this damage, implicating hydroxyl radical species. Myelin membranes are particularly enriched in plasmalogens, a class of ether-linked phospholipids proposed to have antioxidant properties. Myelin in sciatic nerve from plasmalogen-deficient (Pex7 knockout) mice was significantly more vulnerable to Cu/OP/HP-mediated ROS-induced compaction than myelin from WT mice. Our results directly support the role of plasmalogens as endogenous antioxidants providing a defense that protects ROS-vulnerable myelin. PMID:25801291

  8. Transcriptional upregulation of myelin components in spontaneous myelin basic protein-deficient mice.

    Science.gov (United States)

    Staats, Kim A; Pombal, Diana; Schönefeldt, Susann; Van Helleputte, Lawrence; Maurin, Hervé; Dresselaers, Tom; Govaerts, Kristof; Himmelreich, Uwe; Van Leuven, Fred; Van Den Bosch, Ludo; Dooley, James; Humblet-Baron, Stephanie; Liston, Adrian

    2015-05-01

    Myelin is essential for efficient signal transduction in the nervous system comprising of multiple proteins. The intricacies of the regulation of the formation of myelin, and its components, are not fully understood. Here, we describe the characterization of a novel myelin basic protein (Mbp) mutant mouse, mbp(jive), which spontaneously occurred in our mouse colony. These mice displayed the onset of a shaking gait before 3 weeks of age and seizure onset before 2 months of age. Due to a progressive increase of seizure intensity, mbp(jive) mice experienced premature lethality at around 3 months of age. Mbp mRNA transcript or protein was undetectable and, accordingly, genetic analysis demonstrated a homozygous loss of exons 3 to 6 of Mbp. Peripheral nerve conductance was mostly unimpaired. Additionally, we observed grave structural changes in white matter predominant structures were detected by T1, T2 and diffusion weighted magnetic resonance imaging. We additionally observed that Mbp-deficiency results in an upregulation of Qkl, Mag and Cnp, suggestive of a regulatory feedback mechanism whereby compensatory increases in Qkl have downstream effects on Mag and Cnp. Further research will clarify the role and specifications of this myelin feedback loop, as well as determine its potential role in therapeutic strategies for demyelinating disorders. PMID:25708149

  9. Splitting Descartes

    DEFF Research Database (Denmark)

    Schilhab, Theresa

    2007-01-01

    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?

  10. 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

  11. Proposed Evolutionary Changes In The Role Of Myelin

    Directory of Open Access Journals (Sweden)

    JaySCoggan

    2013-11-01

    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.

  12. Cortical maturation and myelination in healthy toddlers and young children.

    Science.gov (United States)

    Deoni, Sean C L; Dean, Douglas C; Remer, Justin; Dirks, Holly; O'Muircheartaigh, Jonathan

    2015-07-15

    The maturation of cortical structures, and the establishment of their connectivity, are critical neurodevelopmental processes that support and enable cognitive and behavioral functioning. Measures of cortical development, including thickness, curvature, and gyrification have been extensively studied in older children, adolescents, and adults, revealing regional associations with cognitive performance, and alterations with disease or pathology. In addition to these gross morphometric measures, increased attention has recently focused on quantifying more specific indices of cortical structure, in particular intracortical myelination, and their relationship to cognitive skills, including IQ, executive functioning, and language performance. Here we analyze the progression of cortical myelination across early childhood, from 1 to 6years of age, in vivo for the first time. Using two quantitative imaging techniques, namely T1 relaxation time and myelin water fraction (MWF) imaging, we characterize myelination throughout the cortex, examine developmental trends, and investigate hemispheric and gender-based differences. We present a pattern of cortical myelination that broadly mirrors established histological timelines, with somatosensory, motor and visual cortices myelinating by 1year of age; and frontal and temporal cortices exhibiting more protracted myelination. Developmental trajectories, defined by logarithmic functions (increasing for MWF, decreasing for T1), were characterized for each of 68 cortical regions. Comparisons of trajectories between hemispheres and gender revealed no significant differences. Results illustrate the ability to quantitatively map cortical myelination throughout early neurodevelopment, and may provide an important new tool for investigating typical and atypical development. PMID:25944614

  13. Myelin-phagocytosing macrophages modulate autoreactive T cell proliferation

    Directory of Open Access Journals (Sweden)

    Hellings Niels

    2011-07-01

    Full Text Available Abstract Introduction Multiple sclerosis (MS is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS in which macrophages play a central role. Initially, macrophages where thought to be merely detrimental in MS, however, recent evidence suggests that their functional phenotype is altered following myelin phagocytosis. Macrophages that have phagocytosed myelin may be less inflammatory and may exert beneficial effects. The presence of myelin-containing macrophages in CNS-draining lymph nodes and perivascular spaces of MS patients suggests that these cells are ideally positioned to exert an immune regulatory role. Therefore we evaluated in this study the effect of myelin-phagocytosing macrophages on lymphocyte reactivity. Methods Thioglycolate-elicited rat peritoneal macrophages were loaded with myelin and cocultured with myelin-basic protein (MBP or ovalbumin (OVA reactive lymphocytes. Lymphocyte proliferation was determined by CFSE-labeling. The role of nitric oxide in regulating lymphocyte proliferation was assessed by addition of an inhibitor of inducible nitric oxide synthase to the coculture. In vivo immune regulation was investigated by treating MBP- and OVA-immunized animals subcutaneously with myelin. Cognate antigen specific lymphocyte proliferation and nitric oxide production were determined 9d post-immunization. Results In this study we demonstrate that myelin-phagocytosing macrophages inhibit TCR-triggered lymphocyte proliferation in an antigen-independent manner. The observed immune suppression is mediated by an increase in NO production by myelin-phagocytosing macrophages upon contact with lymphocytes. Additionally, myelin delivery to primarily CD169+ macrophages in popliteal lymph nodes of OVA-immunized animals results in a reduced cognate antigen specific proliferation. In contrast to OVA-immunized animals, lymphocytes from MBP-immunized animals displayed an increased proliferation after stimulation with their cognate antigen, indicating that myelin-phagocytosing macrophages have dual effects depending on the specificity of surrounding lymphocytes. Conclusions Collectively our data show that myelin phagocytosis leads to an altered macrophage function that inhibits lymphocyte proliferation. Additionally, results from this study indicate that myelin-phagocytosing macrophages fulfill a dual role in vivo. On one hand they aggravate autoimmunity by activating myelin-reactive lymphocytes and on the other hand they suppress lymphocyte reactivity by producing NO.

  14. Inefficient clearance of myelin debris by microglia impairs remyelinating processes.

    Science.gov (United States)

    Lampron, Antoine; Larochelle, Antoine; Laflamme, Nathalie; Préfontaine, Paul; Plante, Marie-Michèle; Sánchez, Maria Gabriela; Yong, V Wee; Stys, Peter K; Tremblay, Marie-Ève; Rivest, Serge

    2015-04-01

    An imbalance between remyelinating and demyelinating rates underlies degenerative processes in demyelinating diseases such as multiple sclerosis. An optimal therapeutic strategy would be to stimulate remyelination while limiting demyelination. Although accumulation of myelin debris impairs remyelination, the mechanisms regulating the clearance of such debris by mononuclear phagocytic cells are poorly understood. We demonstrate that after cuprizone intoxication, CCR2-dependent infiltration of mouse bone marrow-derived cells is abundant in demyelinating areas, but that these cells do not impact demyelination. However, in CX3CR1-deficient mice, the clearance of myelin debris by microglia was blocked greatly, affecting the integrity of the axon and myelin sheaths and thus preventing proper remyelination. These results highlight the crucial role played by CX3CR1 in myelin removal and show that there can be no efficient remyelination after a primary demyelinating insult if myelin clearance by microglia is impaired. PMID:25779633

  15. Split quasicocycles

    OpenAIRE

    Rolli, Pascal

    2013-01-01

    Let E be a linear isometric representation of a group \\Gamma. In this paper we construct and study a family of quasicocycles \\Gamma -> E that arise from splittings \\Gamma = A * B. Under certain assumptions on A, B and E the bounded cohomology classes associated to these quasicocycles form an infinite-dimensional subspace of H^2_b(\\Gamma,E). This is in particular the case when \\Gamma is free and E finite-dimensional or of the type l^p(\\Gamma). For the trivial target E = R we ...

  16. Targeted overexpression of a golli–myelin basic protein isoform to oligodendrocytes results in aberrant oligodendrocyte maturation and myelination

    Directory of Open Access Journals (Sweden)

    Erin C Jacobs

    2009-09-01

    Full Text Available Recently, several in vitro studies have shown that the golli–myelin basic proteins regulate Ca2+ homoeostasis in OPCs (oligodendrocyte precursor cells and immature OLs (oligodendrocytes, and that a number of the functions of these cells are affected by cellular levels of the golli proteins. To determine the influence of golli in vivo on OL development and myelination, a transgenic mouse was generated in which the golli isoform J37 was overexpressed specifically within OLs and OPCs. The mouse, called JOE (J37-overexpressing, is severely hypomyelinated between birth and postnatal day 50. During this time, it exhibits severe intention tremors that gradually abate at later ages. After postnatal day 50, ultrastructural studies and Northern and Western blot analyses indicate that myelin accumulates in the brain, but never reaches normal levels. Several factors appear to underlie the extensive hypomyelination. In vitro and in vivo experiments indicate that golli overexpression causes a significant delay in OL maturation, with accumulation of significantly greater numbers of pre-myelinating OLs that fail to myelinate axons during the normal myelinating period. Immunohistochemical studies with cell death and myelin markers indicate that JOE OLs undergo a heightened and extended period of cell death and are unable to effectively myelinate until 2 months after birth. The results indicate that increased levels of golli in OPC/OLs delays myelination, causing significant cell death of OLs particularly in white matter tracts. The results provide in vivo evidence for a significant role of the golli proteins in the regulation of maturation of OLs and normal myelination.

  17. Effects of galactolipid elimination on oligodendrocyte development and myelination.

    Science.gov (United States)

    Marcus, J; Dupree, J L; Popko, B

    2000-06-01

    The galactolipids galactocerebroside and sulfatide, which require the enzyme UDP-galactose:ceramide galactosyltransferase (CGT) for their synthesis, are among the most prevalent molecules in the myelin sheath. Numerous studies, mainly using antibody perturbation methods in vitro, have suggested that these molecules are crucial mediators of oligodendrocyte differentiation and myelin formation. Although we have previously demonstrated that myelin formation occurs in CGT null mutant mice, which are incapable of synthesizing the myelin galactolipids, here we show that there are developmental alterations in the CNS of these animals. There is a significant decrease in the number of myelinated axon segments in the mutant spinal cord despite normal levels of myelin gene-specific mRNAs and proteins. Also, there is an increased cellularity in the mature mutant spinal cord and the distinctive morphology of the additional cells suggests that they are actively myelinating oligodendrocytes. Using in situ hybridization techniques, we show that there is a 50% increase in the number of oligodendrocytes in the mutant spinal cord. The data suggest that galactolipids play an important developmental role in regulating the maturation program and final number of oligodendrocytes. PMID:10797612

  18. Low-density lipoprotein receptor-related protein 1 is an essential receptor for myelin phagocytosis

    OpenAIRE

    Gaultier, Alban; Wu, Xiaohua; Le Moan, Natacha; Takimoto, Shinako; Mukandala, Gatambwa; Akassoglou, Katerina; Campana, W. Marie; Gonias, Steven L.

    2009-01-01

    Multiple sclerosis (MS) is an autoimmune disease in which myelin is progressively degraded. Because degraded myelin may both initiate and accelerate disease progression, clearing degraded myelin from extracellular spaces may be critical. In this study, we prepared myelin vesicles (MV) from rat brains as a model of degraded myelin. Murine embryonic fibroblasts (MEFs) rapidly internalized MVs, which accumulated in lysosomes only when these cells expressed low-density lip...

  19. Analysis of Gpr126 function defines distinct mechanisms controlling the initiation and maturation of myelin

    OpenAIRE

    Glenn, Thomas D.; Talbot, William S.

    2013-01-01

    In peripheral nerves, Schwann cells form the myelin sheath, which allows the efficient propagation of action potentials along axons. The transcription factor Krox20 regulates the initiation of myelination in Schwann cells and is also required to maintain mature myelin. The adhesion G protein-coupled receptor (GPCR) Gpr126 is essential for Schwann cells to initiate myelination, but previous studies have not addressed the role of Gpr126 signaling in myelin maturation and maintenance. Through an...

  20. Mapping early stage of myelin degradation at nanoscale resolution

    CERN Document Server

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

    2013-01-01

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

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

    OpenAIRE

    Schulte, S. (Sebastian); Stoffel, W.

    1993-01-01

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

  2. Myelin-Associated Glycoprotein Gene and Brain Morphometry in Schizophrenia

    OpenAIRE

    JamesKennedy; JasonPLerch; ArashNazeri

    2012-01-01

    Myelin and oligodendrocyte disruption may be a core feature of schizophrenia pathophysiology. The purpose of the present study was to localize the effects of previously identified risk variants in the myelin associated glycoprotein gene on brain morphometry in schizophrenia patients and healthy controls. 45 schizophrenia patients and 47 matched healthy controls underwent clinical, structural magnetic resonance imaging, and genetics procedures. Gray and white matter cortical lobe volumes alon...

  3. Myelin vs axon abnormalities in white matter in bipolar disorder.

    Science.gov (United States)

    Lewandowski, Kathryn E; Ongür, Dost; Sperry, Sarah H; Cohen, Bruce M; Sehovic, Selma; Goldbach, Jacqueline R; Du, Fei

    2015-04-01

    White matter (WM) abnormalities are among the most commonly reported neuroimaging findings in bipolar disorder. Nonetheless, the specific nature and pathophysiology of these abnormalities remain unclear. Use of a combination of magnetization transfer ratio (MTR) and diffusion tensor spectroscopy (DTS) permits examination of myelin and axon abnormalities separately. We aimed to examine myelination and axon geometry in euthymic patients with bipolar disorder with psychosis (BDP) by combining these two complementary noninvasive MRI techniques. We applied a combined MRI approach using MTR to study myelin content and DTS to study metabolite (N-acetylaspartate, NAA) diffusion within axons in patients with BDP (n=21) and healthy controls (n=24). Data were collected from a 1 × 3 × 3-cm voxel within the right prefrontal cortex WM at 4 Tesla. Clinical and cognitive data were examined in association with MTR and DTS data. MTR was significantly reduced in BDP, suggesting reduced myelin content. The apparent diffusion coefficient of NAA did not differ from healthy controls, suggesting no changes in axon geometry in patients with BDP. These findings suggest that patients with BDP exhibit reduced myelin content, but no changes in axon geometry compared with controls. These findings are in contrast with our recent findings, using the same techniques, in patients with schizophrenia (SZ), which suggest both myelination and axon abnormalities in SZ. This difference may indicate that alterations in WM in BDP may have unique causes and may be less extensive than WM abnormalities seen in SZ. PMID:25409595

  4. Myelin Recovery in Multiple Sclerosis: The Challenge of Remyelination

    Directory of Open Access Journals (Sweden)

    Edward L. Hogan

    2013-08-01

    Full Text Available Multiple sclerosis (MS is the most common demyelinating and an autoimmune disease of the central nervous system characterized by immune-mediated myelin and axonal damage, and chronic axonal loss attributable to the absence of myelin sheaths. T cell subsets (Th1, Th2, Th17, CD8+, NKT, CD4+CD25+ T regulatory cells and B cells are involved in this disorder, thus new MS therapies seek damage prevention by resetting multiple components of the immune system. The currently approved therapies are immunoregulatory and reduce the number and rate of lesion formation but are only partially effective. This review summarizes current understanding of the processes at issue: myelination, demyelination and remyelination—with emphasis upon myelin composition/ architecture and oligodendrocyte maturation and differentiation. The translational options target oligodendrocyte protection and myelin repair in animal models and assess their relevance in human. Remyelination may be enhanced by signals that promote myelin formation and repair. The crucial question of why remyelination fails is approached is several ways by examining the role in remyelination of available MS medications and avenues being actively pursued to promote remyelination including: (i cytokine-based immune-intervention (targeting calpain inhibition, (ii antigen-based immunomodulation (targeting glycolipid-reactive iNKT cells and sphingoid mediated inflammation and (iii recombinant monoclonal antibodies-induced remyelination.

  5. Lipid domains control myelin basic protein adsorption and membrane interactions between model myelin lipid bilayers

    Science.gov (United States)

    Lee, Dong Woog; Banquy, Xavier; Kristiansen, Kai; Kaufman, Yair; Boggs, Joan M.; Israelachvili, Jacob N.

    2014-01-01

    The surface forces apparatus and atomic force microscope were used to study the effects of lipid composition and concentrations of myelin basic protein (MBP) on the structure of model lipid bilayers, as well as the interaction forces and adhesion between them. The lipid bilayers had a lipid composition characteristic of the cytoplasmic leaflets of myelin from “normal” (healthy) and “disease-like” [experimental allergic encephalomyelitis (EAE)] animals. They showed significant differences in the adsorption mechanism of MBP. MBP adsorbs on normal bilayers to form a compact film (3–4 nm) with strong intermembrane adhesion (?0.36 mJ/m2), in contrast to its formation of thicker (7–8 nm) swelled films with weaker intermembrane adhesion (?0.13 mJ/m2) on EAE bilayers. MBP preferentially adsorbs to liquid-disordered submicron domains within the lipid membranes, attributed to hydrophobic attractions. These results show a direct connection between the lipid composition of membranes and membrane–protein adsorption mechanisms that affects intermembrane spacing and adhesion and has direct implications for demyelinating diseases. PMID:24516125

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

    OpenAIRE

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

    2013-01-01

    Unilateral extensive myelination of the peripapillary nerve fibers may be associated with anisometropic myopia, strabismus, and reduced vision. Myelination of optic nerve fibers terminate at lamina cribrosa. Yet in some patients, myelination progresses into the peripapillary retinal nerve fibers and may affect the visual acuity. In this report, we described 4 patients. All patients presented extensive peripapillary myelinated nerve fibers associated with myopic anisometropia. After routine op...

  7. Rapid myelin water content mapping on clinical MR systems

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-07-01

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

  8. Role of the Thyroid System in Myelination and Neural Connectivity.

    Science.gov (United States)

    Calzà, Laura; Fernández, Mercedes; Giardino, Luciana

    2015-07-01

    The role of thyroid hormone on brain development is dramatically illustrated by "cretinism," a severe mental retardation due to iodine deficiency and maternal hypothyroidism during gestation. In the last decades, the molecular bases of the cellular action of thyroid hormone in the nervous tissue have been at least partially elucidated, and the emerged picture is much more complex than expected. In this article, the main mechanisms determining thyroid hormone availability, nuclear and membrane receptor occupancy and downstream action, gene expression, and nongenomic mechanism are reviewed, focusing on myelination and myelin turnover. © 2015 American Physiological Society. Compr Physiol 5:1405-1421, 2015. PMID:26140723

  9. Bilateral Hypermetropia, Myelinated Retinal Nerve Fibers, and Amblyopia

    OpenAIRE

    Shenoy Radha; Bialasiewicz Alexander; Al Barwani B

    2011-01-01

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

  10. Bilateral hypermetropia, myelinated retinal nerve fibers, and amblyopia

    Directory of Open Access Journals (Sweden)

    Shenoy Radha

    2011-01-01

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

  11. Galactolipids are molecular determinants of myelin development and axo-glial organization.

    Science.gov (United States)

    Marcus, Jill; Popko, Brian

    2002-12-19

    Myelination is a developmentally regulated process whereby myelinating glial cells elaborate large quantities of a specialized plasma membrane that ensheaths axons. The myelin sheath contains an unusual lipid composition in that the glycolipid galactosylceramide (GalC) and its sulfated form sulfatide constitute a large proportion of the total lipid mass. These glycolipids have been implicated in a range of developmental processes such as cell differentiation and myelination initiation, but analyses of mice lacking UDP-galactose:ceramide galactosyltransferase (CGT), the enzyme required for myelin galactolipid synthesis, have more recently demonstrated that the galactolipids more subtly regulate myelin formation. The CGT mutants display a delay in myelin maturation and axo-glial interactions develop abnormally. By interbreeding the CGT mutants with mice that lack myelin-associated glycoprotein, it has been shown that these specialized myelin lipids and proteins act in concert to promote axo-glial adhesion during myelinogenesis. The analysis of the CGT mutants is helping to clarify the roles myelin galactolipids play in regulating the development, and ultimately the function of the myelin sheath. PMID:12417425

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

    Directory of Open Access Journals (Sweden)

    DouglasFields

    2009-06-01

    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.

  13. 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.

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

    OpenAIRE

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

    2012-01-01

    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 expressio...

  15. Noise-assisted spike propagation in myelinated neurons

    OpenAIRE

    Ochab-Marcinek, Anna; Schmid, Gerhard; Goychuk, Igor; Hänggi, Peter

    2008-01-01

    We consider noise-assisted spike propagation in myelinated axons within a multi-compartment stochastic Hodgkin-Huxley model. The noise originates from a finite number of ion channels in each node of Ranvier. For the subthreshold internodal electric coupling, we show that (i) intrinsic noise removes the sharply defined threshold for spike propagation from node to node, and (ii) there exists an optimum number of ion channels which allows for the most efficient signal propagati...

  16. Neurotoxocarosis alters myelin protein gene transcription and expression.

    Science.gov (United States)

    Heuer, Lea; Beyerbach, Martin; Lühder, Fred; Beineke, Andreas; Strube, Christina

    2015-06-01

    Neurotoxocarosis is an infection of the central nervous system caused by migrating larvae of the common dog and cat roundworms (Toxocara canis and Toxocara cati), which are zoonotic agents. As these parasites are prevalent worldwide and neuropathological and molecular investigations on neurotoxocarosis are scare, this study aims to characterise nerve fibre demyelination associated with neurotoxocarosis on a molecular level. Transcription of eight myelin-associated genes (Cnp, Mag, Mbp, Mog, Mrf-1, Nogo-A, Plp1, Olig2) was determined in the mouse model during six time points of the chronic phase of infection using qRT-PCR. Expression of selected proteins was analysed by Western blotting or immunohistochemistry. Additionally, demyelination and neuronal damage were investigated histologically. Significant differences (p???0.05) between transcription rates of T. canis-infected and uninfected control mice were detected for all analysed genes while T. cati affected five of eight investigated genes. Interestingly, 2', 3 ´-cyclic nucleotide 3'-phosphodiesterase (Cnp) and myelin oligodendrocyte glycoprotein (Mog) were upregulated in both T. canis- and T. cati-infected mice preceding demyelination. Later, CNPase expression was additionally enhanced. As expected, myelin basic protein (Mbp) was downregulated in cerebra and cerebella of T. canis-infected mice when severe demyelination was present 120 days post infectionem (dpi). The transcriptional pattern observed in the present study appears to reflect direct traumatic and hypoxic effects of larval migration as well as secondary processes including host immune reactions, demyelination and attempts to remyelinate damaged areas. PMID:25773181

  17. Synthesis of myelin glycosphingolipids by isolated oligodendrocytes in tissue culture

    International Nuclear Information System (INIS)

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

  18. Splitting of Singularities

    CERN Document Server

    Jiang, G; Jiang, Guangfeng; Tibar, Mihai

    2000-01-01

    We study one parameter deformations of a pair consisting of an analytic singular space $X_0$ and a function $f_0$ on it, in case this defines an isolated singularity. We prove, under general conditions, a bouquet decomposition of the Milnor fibre when the isolated singularity splits in the deformation and the invariance of the Milnor fibration if there is no splitting.

  19. The evolution of vertebrate and invertebrate myelin: a theoretical computational study.

    Science.gov (United States)

    Castelfranco, Ann M; Hartline, Daniel K

    2015-06-01

    Multilayered, lipid-rich myelin increases nerve impulse conduction velocity, contributes to compact nervous systems, and reduces metabolic costs of neural activity. Based on the hypothesis that increased impulse conduction velocity provides a selective advantage that drives the evolution of myelin, we simulated a sequence of plausible intermediate stages of myelin evolution, each of which providing an enhancement of conduction speed. We started with the expansion of insulating glial coverage, which led first to a single layer of myelin surrounding the axon and then to multiple myelin wraps with well-organized nodes. The myelinated fiber was modeled at three levels of complexity as the hypothesized evolutionary progression became more quantitatively exacting: 1) representing the fiber as a mathematically-tractable uniform active cylinder with the effect of myelination approximated by changing its specific capacitance (C m ); 2) representing it as a chain of simple, cable-model compartments having alternating nodal and internodal parameters subject to optimization, and 3) representing it in a double cable model with the axon and myelin sheath treated separately. Conduction velocity was optimized at each stage. To maintain optimal conduction velocities, increased myelin coverage of axonal surface must be accompanied by an increase in channel density at the evolving nodes, but along with increases in myelin thickness, a reduction in overall average channel density must occur. Leakage under the myelin sheath becomes more of a problem with smaller fiber diameters, which may help explain the tendency for myelin to occur preferentially in larger nerve fibers in both vertebrates and invertebrates. PMID:25832903

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

    OpenAIRE

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

    1981-01-01

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

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

    OpenAIRE

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

    2011-01-01

    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 ...

  2. Coded Splitting Tree Protocols

    DEFF Research Database (Denmark)

    SØrensen, Jesper Hemming; Stefanovic, Cedomir

    2013-01-01

    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.

  3. The polarity protein Par-3 directly interacts with p75NTR to regulate myelination.

    Science.gov (United States)

    Chan, Jonah R; Jolicoeur, Christine; Yamauchi, Junji; Elliott, Jimmy; Fawcett, James P; Ng, Benjamin K; Cayouette, Michel

    2006-11-01

    Cell polarity is critical in various cellular processes ranging from cell migration to asymmetric cell division and axon and dendrite specification. Similarly, myelination by Schwann cells is polarized, but the mechanisms involved remain unclear. Here, we show that the polarity protein Par-3 localizes asymmetrically in Schwann cells at the axon-glial junction and that disruption of Par-3 localization, by overexpression and knockdown, inhibits myelination. Additionally, we show that Par-3 directly associates and recruits the p75 neurotrophin receptor to the axon-glial junction, forming a complex necessary for myelination. Together, these results point to a critical role in the establishment of cell polarity for myelination. PMID:17082460

  4. Probe split graphs

    Directory of Open Access Journals (Sweden)

    Van Bang Le

    2007-01-01

    Full Text Available An undirected graph G=(V,E is a probe split graph if its vertex set can be partitioned into two sets, N (non-probes and P (probes where N is independent and there exists E' ? N× N such that G'=(V,E? E' is a split graph. Recently Chang et al. gave an O(V 4 (V+E time recognition algorithm for probe split graphs. In this article we give O(V 2 +VE time recognition algorithms and characterisations by forbidden induced subgraphs both for the case when the partition into probes and non-probes is given, and when it is not given.

  5. Aspects of Split Supersymmetry

    OpenAIRE

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

    2004-01-01

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

  6. Polarized Antenna Splitting Functions

    International Nuclear Information System (INIS)

    We consider parton showers based on radiation from QCD dipoles or 'antennae'. These showers are built from 2 ? 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.

  7. 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.)

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

    Science.gov (United States)

    Osaguona, Vivian B; Uhumwangho, Odarosa M

    2014-11-01

    Myelinated retinal nerve fibres (MRNF) are rare congenital anomalies. They may present in a syndrome characterised by ipsilateral myelinated retinal nerve fibres, myopia and amblyopia. We report a case of this rare condition with unilateral extensive MRNF, axial myopia, amblyopia and strabismus in a Nigerian girl. PMID:25538374

  9. Oligodendrocyte Development and Myelin Biogenesis: Parsing Out the Roles of Glycosphingolipids

    Science.gov (United States)

    Nicole Jackman (University of Connecticut Medical School Neuroscience)

    2009-10-01

    The myelin sheath is an extension of the oligoddendrocyte (OL) plasma membrane enriched in lipids that ensheaths the axons of the central and peripheral nervous system. Here, we review the involvement of glycosphingolipids in myelin/OL functions, including the regulation of OL differentiation, lipid raft-mediated trafficking and signaling, and neuronglia interactions.

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

    Directory of Open Access Journals (Sweden)

    Kazuaki Nakamura

    2012-07-01

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

  11. Modifications of myelin basic protein in DM20 transgenic mice are similar to those in myelin basic protein from multiple sclerosis.

    OpenAIRE

    Mastronardi, F G; Mak, B; Ackerley, C.A.; Roots, B I; Moscarello, M.A.

    1996-01-01

    Transgenic mice containing different numbers of transgenes (2-70) of the myelin proteolipid protein DM20 were phenotypically normal up to 3 mo of age, after which the mice containing 70 copies of the transgene spontaneously demyelinated and died at 10-12 mo. Since we demonstrated that demyelination in multiple sclerosis involved specific chemical changes in myelin basic protein (MBP), we investigated the MBP in our transgenic line for similar changes. Both the total amount of MBP in brain and...

  12. 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.)

  13. Autoantibodies to Non-myelin Antigens as Contributors to the Pathogenesis of Multiple Sclerosis.

    Science.gov (United States)

    Levin, Michael C; Lee, Sangmin; Gardner, Lidia A; Shin, Yoojin; Douglas, Joshua N; Cooper, Chelsea

    2013-06-30

    For years, investigators have sought to prove that myelin antigens are the primary targets of autoimmunity in multiple sclerosis (MS). Recent experiments have begun to challenge this assumption, particularly when studying the neurodegenerative phase of MS. T-lymphocyte responses to myelin antigens have been extensively studied, and are likely early contributors to the pathogenesis of MS. Antibodies to myelin antigens have a much more inconstant association with the pathogenesis of MS. Recent studies indicate that antibodies to non-myelin antigens such as neurofilaments, neurofascin, RNA binding proteins and potassium channels may contribute to the pathogenesis of MS. The purpose of this review is to analyze recent studies that examine the role that autoantibodies to non-myelin antigens might play in the pathogenesis of MS. PMID:24363960

  14. Aspects of Split Supersymmetry

    CERN Document Server

    Arkani-Hamed, N; Giudice, Gian Francesco; Romanino, A

    2005-01-01

    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 ongo...

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

    Science.gov (United States)

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

    2014-12-01

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

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

    Science.gov (United States)

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

    2008-04-01

    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

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

    Science.gov (United States)

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

    2011-11-01

    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

  18. 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

  19. 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.

  20. Propagation of Action Potentials in Myelinated vs. Unmyelinated Neurons

    Science.gov (United States)

    PhD Barbara E. Goodman (University of South Dakota School of Medicine Division of Basic Biomedical Sciences)

    2002-09-01

    For invertebrates, propagation of action potentials down unmyelinated axons is sufficient for rapid conduction. For faster propagation velocities, the axon becomes larger in diameter. However, increasing the speed of action potentials by increasing the diameter of the axon is not feasible in vertebrates. Squid giant axons are up to 1 mm in diameter and have very rapid propagation velocities. Mammalian nerves have about 400 fibers in the same cross-sectional area as the squid giant axon. Thus, if each of the fibers were as large as the squid giant axon, each mammalian nerve would be approximately 2 cm in diameter! Thus, vertebrates have evolved another mechanism for increasing nerve conduction: wrapping the axons in insulating membranes of a myelin sheath. Some axons have as many as 150 wraps of Schwann cells around them, thereby increasing the effective thickness of the axonal membrane 100-fold and eliminating ion leaks across cell membranes except at the periodic gaps called Nodes of Ranvier.

  1. NF-?B signaling regulates myelination in the CNS

    Directory of Open Access Journals (Sweden)

    Thomas Blank

    2014-05-01

    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.

  2. [Myelin basic protein in cerebrospinal fluid in neurosyphilis (author's transl)].

    Science.gov (United States)

    Prange, H; Kohlschütter, A; Ritter, G

    1980-08-01

    Myelin basic protein (MBP) was demonstrated in the CSF of 15 out of 41 patients with assumed or ascertained neurosyphilis using a radio-immunoassay. In parenchymatous syphilis (progressive paralysis, tabes dorsalis) more than 50% of patients had MBP-positive CSF independent of immunological findings and previous treatment. CSF of patients with meningovascular neurosyphilis was mostly negative, only in 2 cases with acute symptoms was MBP demonstrable. In one of these patients MBP was no longer demonstrable in the CSF 6 months after treatment. The frequent occurrence of MBP in CSF in parenchymatous neurosyphilis can be taken as evidence of persistence of demyelinising activity even in cases where immunological finding point to "syphilis satis curata" (sufficiently treated syphilis). PMID:6159144

  3. Myelinating cocultures of purified oligodendrocyte lineage cells and retinal ganglion cells.

    Science.gov (United States)

    Watkins, Trent A; Scholze, Anja R

    2014-10-01

    In this article, we introduce methods for generating rapidly myelinating cocultures with reaggregates of purified retinal ganglion cells and optic nerve oligodendrocyte precursor cells. This coculture system facilitates the study of complex central nervous system neuronal-glial interactions and myelination. It enables control of the extracellular environment and allows the use of transfected, virally infected, mutant, or knockout neurons and/or glial cell types. It is therefore possible to assess the role of various signaling pathways and genes in myelination and node of Ranvier formation. PMID:25275113

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

    Science.gov (United States)

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

    2003-01-01

    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

  5. PMP22 expression in dermal nerve myelin from patients with CMT1A

    OpenAIRE

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

    2009-01-01

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

  6. Myelin Activates FAK/Akt/NF-?B Pathways and Provokes CR3-Dependent Inflammatory Response in Murine System

    Science.gov (United States)

    Sun, Xin; Wang, Xi; Chen, Tianxiang; Li, Tianyi; Cao, Kai; Lu, Andrew; Chen, Yongxiong; Sun, Dongming; Luo, Jianhong; Fan, Jianqing; Young, Wise; Ren, Yi

    2010-01-01

    Inflammatory response following central nervous system (CNS) injury contributes to progressive neuropathology and reduction in functional recovery. Axons are sensitive to mechanical injury and toxic inflammatory mediators, which may lead to demyelination. Although it is well documented that degenerated myelin triggers undesirable inflammatory responses in autoimmune diseases such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), there has been very little study of the direct inflammatory consequences of damaged myelin in spinal cord injury (SCI), i.e., there is no direct evidence to show that myelin debris from injured spinal cord can trigger undesirable inflammation in vitro and in vivo. Our data showed that myelin can initiate inflammatory responses in vivo, which is complement receptor 3 (CR3)-dependent via stimulating macrophages to express pro-inflammatory molecules and down-regulates expression of anti-inflammatory cytokines. Mechanism study revealed that myelin-increased cytokine expression is through activation of FAK/PI3K/Akt/NF-?B signaling pathways and CR3 contributes to myelin-induced PI3K/Akt/NF-?B activation and cytokine production. The myelin induced inflammatory response is myelin specific as sphingomyelin (the major lipid of myelin) and myelin basic protein (MBP, one of the major proteins of myelin) are not able to activate NF-?B signaling pathway. In conclusion, our results demonstrate a crucial role of myelin as an endogenous inflammatory stimulus that induces pro-inflammatory responses and suggest that blocking myelin-CR3 interaction and enhancing myelin debris clearance may be effective interventions for treating SCI. PMID:20186338

  7. Impossibility of obtaining split links from split links via twistings

    OpenAIRE

    Ozawa, Makoto

    2001-01-01

    We show that if a split link is obtained from a split link $L$ in $S^3$ by $1/n$-Dehn surgery along a trivial knot $C$, then the link $L\\cup C$ is splittable. That is to say, it is impossible to obtain a split link from a split link via a non-trivial twisting. As its corollary, we completely determine when a trivial link is obtained from a trivial link via a twisting.

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

    Directory of Open Access Journals (Sweden)

    Laulumaa Saara

    2015-01-01

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

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

    DEFF Research Database (Denmark)

    Podbielska, Maria; Levery, Steven B

    2011-01-01

    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.

  10. Split Hamiltonian Monte Carlo

    OpenAIRE

    Shahbaba, Babak; Lan, Shiwei; Johnson, Wesley O.; Neal, Radford M.

    2011-01-01

    We show how the Hamiltonian Monte Carlo algorithm can sometimes be speeded up by "splitting" the Hamiltonian in a way that allows much of the movement around the state space to be done at low computational cost. One context where this is possible is when the log density of the distribution of interest (the potential energy function) can be written as the log of a Gaussian density, which is a quadratic function, plus a slowly varying function. Hamiltonian dynamics for quadrat...

  11. Splitting Extended Supersymmetry

    OpenAIRE

    Antoniadis, Ignatios(Department of Physics, CERN Theory Division, Geneva 23, CH-1211, Switzerland); Benakli, Karim; Delgado, Antonio; Quiros, Mariano; Tuckmantel, Marc

    2005-01-01

    We show how splitting supersymmetry reconciles a class of intersecting brane models with unification. The gauge sector in these models arises in multiplets of extended supersymmetry while matter states are in N=1 representations. A deformation of the angles between the branes gives large masses to squarks and sleptons, as well as supersymmetry breaking contributions to other string states. The latter generate at one-loop heavy Dirac masses for Winos and gluinos and can induc...

  12. Bisphenol-a impairs myelination potential during development in the hippocampus of the rat brain.

    Science.gov (United States)

    Tiwari, Shashi Kant; Agarwal, Swati; Chauhan, Lalit Kumar Singh; Mishra, Vijay Nath; Chaturvedi, Rajnish Kumar

    2015-06-01

    Myelin is the functional implication of oligodendrocytes (OLs), which is involved in insulation of axons and promoting rapid propagation of action potential in the brain. OLs are derived from oligodendrocyte progenitor cells (OPCs), which proliferate, differentiate, and migrate throughout the central nervous system. Defects in myelination process lead to the onset of several neurological and neurodegenerative disorders. Exposure to synthetic xenoestrogen bisphenol-A (BPA) causes cognitive dysfunction, impairs hippocampal neurogenesis, and causes onset of neurodevelopmental disorders. However, the effects of BPA on OPC proliferation, differentiation and myelination, and associated cellular and molecular mechanism(s) in the hippocampus of the rat brain are still largely unknown. We found that BPA significantly decreased bromodeoxyuridine (BrdU)-positive cell proliferation and number and size of oligospheres. We observed reduced co-localization of BrdU with myelination markers CNPase and platelet-derived growth factor receptor-? (PDGFR-?), suggesting impaired proliferation and differentiation of OPCs by BPA in culture. We studied the effects of BPA exposure during prenatal and postnatal periods on cellular and molecular alteration(s) in the myelination process in the hippocampus region of the rat brain at postnatal day 21 and 90. BPA exposure both in vitro and in vivo altered proliferation and differentiation potential of OPCs and decreased the expression of genes and levels of proteins that are involved in myelination. Ultrastructural electron microscopy analysis revealed that BPA exposure caused decompaction of myelinated axons and altered g-ratio at both the developmental periods as compared to control. These results suggest that BPA exposure both during prenatal and postnatal periods alters myelination in the hippocampus of the rat brain leading to cognitive deficits. PMID:25084756

  13. Peripheral myelin protein 22 is a constituent of intercellular junctions in epithelia

    OpenAIRE

    Notterpek, Lucia; Roux, Kyle J.; Amici, Stephanie A.; Yazdanpour, Amy; Rahner, Christoph; Fletcher, Brad S.

    2001-01-01

    Alterations in peripheral myelin protein 22 (PMP22) gene expression are associated with a host of heritable demyelinating peripheral neuropathies, yet the function of the protein remains unknown. PMP22 expression is highest in myelinating Schwann cells of peripheral nerves; however, significant levels of PMP22 mRNAs can be detected in a variety of non-neural tissue, including epithelia. To date, PMP22 protein expression and localization in non-neural tissues have not b...

  14. Molecules affecting myelin stability: a novel hypothesis regarding the pathogenesis of multiple sclerosis.

    Science.gov (United States)

    Mastronardi, Fabrizio G; Moscarello, Mario A

    2005-05-01

    In this Mini-Review we present a new hypothesis in support of the neurodegenerative theory as a mechanism for the pathogenesis of multiple sclerosis (MS). The pathogenesis of MS results from changes in two distinct CNS compartments. These are the "myelin" and "nonmyelin" compartments. The myelin compartment is where primary demyelination, amidst attempts at remyelination, is superseded in the CNS by ongoing disease. Recent evidence obtained via magnetic resonance imaging and spectroscopy techniques supports the view that the normal-appearing white matter (NAWM) in the MS brain is altered. Several biochemical changes in NAWM have been determined. These include the cationicity of myelin basic protein (MBP) as a result of the action of peptidyl argininedeiminase (PAD) activity converting arginyl residues to citrulline. The accompanying loss of positive charge makes myelin susceptible to vesiculation and MBP more susceptible to proteolytic activity. An increase of MBP autocatalysis in the MS brain might also contribute to the generation of immunodominant epitopes. Accompanying the destruction of myelin in the myelin compartment is the activation of astrocytes and microglia. These contribute to the inflammatory response and T-cell activation leading to autoimmunity. The complex environment that exists in the demyelinating brain also affects the "nonmyelin" compartment. The inappropriate up-regulation of molecules, including those of the Jagged-1-Notch-1 signal transduction pathway, affects oligodendrocyte precursor cell (OPC) differentiation. Other effectors of oligodendrocyte maturation include stathmin, a microtubule-destabilizing protein, which prevents healing in the demyelinating brain. The hypothesis we present suggests a therapeutic strategy that should 1) target the effectors within the myelin compartment and 2) enable resident OPC maturation in the nonmyelin compartment, allowing for effective repair of myelin loss. The net effect of this new therapeutic strategy is the modification of the disease environment and the stimulation of healing and repair. PMID:15704220

  15. 17?-Estradiol restores excitability of a sexually dimorphic subset of myelinated vagal afferents in ovariectomized rats

    OpenAIRE

    Qiao, Guo-fen; Li, Bai-Yan; Lu, Yan-jie; Fu, Yi-li; Schild, John H.

    2009-01-01

    We recently identified a myelinated vagal afferent subpopulation (Ah type) far more prevalent in female than male rats and showed that this difference extends to functionally specific visceral sensory afferents, baroreceptors of the aortic arch. Excitability of myelinated Ah-type afferents is markedly reduced after ovariectomy (OVX). Here we tested the hypothesis that 17?-estradiol can selectively restore excitability of these sex-specific vagal afferents. Acutely isolated vagal afferent neu...

  16. Gpr126 Functions in Schwann Cells to Control Differentiation and Myelination via G-Protein Activation

    OpenAIRE

    Mogha, Amit; Benesh, Andrew E.; Patra, Chinmoy; Engel, Felix B.; Schöneberg, Torsten; Liebscher, Ines; Monk, Kelly R

    2013-01-01

    The myelin sheath surrounding axons ensures that nerve impulses travel quickly and efficiently, allowing for the proper function of the vertebrate nervous system. We previously showed that the adhesion G-protein-coupled receptor (aGPCR) Gpr126 is essential for peripheral nervous system myelination, although the molecular mechanisms by which Gpr126 functions were incompletely understood. aGPCRs are a significantly understudied protein class, and it was unknown whether Gpr126 couples to G-prote...

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

    OpenAIRE

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

    2004-01-01

    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...

  18. Complement receptor-3 negatively regulates the phagocytosis of degenerated myelin through tyrosine kinase Syk and cofilin

    Directory of Open Access Journals (Sweden)

    Hadas Smadar

    2012-07-01

    Full Text Available Abstract Background Intact myelin, which normally surrounds axons, breaks down in Wallerian degeneration following axonal injury and during neurodegenerative diseases such as multiple sclerosis. Clearance of degenerated myelin by phagocytosis is essential since myelin impedes repair and exacerbates damage. CR3 (complement receptor-3 is a principal phagocytic receptor in myelin phagocytosis. We studied how tyrosine kinase Syk (spleen tyrosine kinase and cofilin control phagocytosis of degenerated myelin by CR3 in microglia and macrophages. Syk is a non-receptor tyrosine kinase that CR3 recruits to convey cellular functions. Cofilin is an actin-depolymerizing protein that controls F-actin (filamentous actin remodeling (i.e., disassembly and reassembly by shifting between active unphosphorylated and inactive phosphorylated states. Results Syk was continuously activated during prolonged phagocytosis. Phagocytosis increased when Syk activity and expression were reduced, suggesting that normally Syk down regulates CR3-mediated myelin phagocytosis. Levels of inactive p-cofilin (phosphorylated cofilin decreased transiently during prolonged phagocytosis. In contrast, p-cofilin levels decreased continuously when Syk activity and expression were continuously reduced, suggesting that normally Syk advances the inactive state of cofilin. Observations also revealed inverse relationships between levels of phagocytosis and levels of inactive p-cofilin, suggesting that active unphosphorylated cofilin advances phagocytosis. Active cofilin could advance phagocytosis by promoting F-actin remodeling, which supports the production of membrane protrusions (e.g., filopodia, which, as we also revealed, are instrumental in myelin phagocytosis. Conclusions CR3 both activates and downregulates myelin phagocytosis at the same time. Activation was previously documented. We presently demonstrate that downregulation is mediated through Syk, which advances the inactive phosphorylated state of cofilin. Self-negative control of phagocytosis by the phagocytic receptor can be useful in protecting phagocytes from excessive phagocytosis (i.e., “overeating” during extended exposure to particles that are destined for ingestion.

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

    OpenAIRE

    Ryder, Sean P.; Williamson, James R.

    2004-01-01

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

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

    Directory of Open Access Journals (Sweden)

    William L. Maxwell

    2013-09-01

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

  1. Neuroactive steroid treatment modulates myelin lipid profile in diabetic peripheral neuropathy.

    Science.gov (United States)

    Mitro, Nico; Cermenati, Gaia; Brioschi, Elisabetta; Abbiati, Federico; Audano, Matteo; Giatti, Silvia; Crestani, Maurizio; De Fabiani, Emma; Azcoitia, Inigo; Garcia-Segura, Luis Miguel; Caruso, Donatella; Melcangi, Roberto Cosimo

    2014-09-01

    Diabetic peripheral neuropathy causes a decrease in the levels of dihydroprogesterone and 5?-androstane-3?,17?-diol (3?-diol) in the peripheral nerves. These two neuroactive steroids exert protective effects, by mechanisms that still remain elusive. We have previously shown that the activation of Liver X Receptors improves the peripheral neuropathic phenotype in diabetic rats. This protective effect is accompanied by the restoration to control values of the levels of dihydroprogesterone and 3?-diol in peripheral nerves. In addition, activation of these receptors decreases peripheral myelin abnormalities by improving the lipid desaturation capacity, which is strongly blunted by diabetes, and ultimately restores the myelin lipid profile to non-diabetic values. On this basis, we here investigate whether dihydroprogesterone or 3?-diol may exert their protective effects by modulating the myelin lipid profile. We report that both neuroactive steroids act on the lipogenic gene expression profile in the sciatic nerve of diabetic rats, reducing the accumulation of myelin saturated fatty acids and promoting desaturation. These changes were associated with a reduction in myelin structural alterations. These findings provide evidence that dihydroprogesterone and 3?-diol are protective agents against diabetic peripheral neuropathy by regulating the de novo lipogenesis pathway, which positively influences myelin lipid profile. PMID:24607810

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

    Science.gov (United States)

    Anderton, S M; Wraith, D C

    1998-04-01

    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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-10-11

    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.

  4. Almost split sequences and approximations

    CERN Document Server

    Liu, Shiping; Paquette, Charles

    2012-01-01

    Let A be an exact category, that is, an extension-closed full subcategory of an abelian category. Firstly, we give some necessary and sufficient conditions for A to have almost split sequences. Then, we study when an almost split sequence in A induces an almost split sequence in an exact subcategory C of A. In case A has almost split sequences and C is Hom-finite Krull-Schmidt, this provides a necessary and sufficient condition for C to have almost split sequences. Finally, we show two applications of these results.

  5. Organisation and control of neuronal connectivity and myelination by cell adhesion molecule neurofascin.

    Science.gov (United States)

    Ebel, Julia; Beuter, Simone; Wuchter, Jennifer; Kriebel, Martin; Volkmer, Hansjürgen

    2014-01-01

    The neuronal cell adhesion molecule neurofascin is expressed in highly complex temporally and spatially regulated patterns. Accordingly, many different functions have been described including control of neurite outgrowth, clustering of protein complexes at the axon initial segments as well as at the nodes of Ranvier and axoglial contact formation at paranodal segments. At the molecular level, neurofascin provides a link between extracellular interactions of many different interaction partners and cytoskeletal components or signal transduction. Such interactions are subject to intimate regulation by alternative splicing and posttranslational modification. The versatile functional aspects of neurofascin interactions pose it at a central position for the shaping and maintenance of neural circuitry and synaptic contacts which are implicated in nervous system disorders. PMID:25300139

  6. A tale of two citrullines--structural and functional aspects of myelin basic protein deimination in health and disease.

    Science.gov (United States)

    Harauz, George; Musse, Abdiwahab A

    2007-02-01

    Myelin basic protein (MBP) binds to negatively charged lipids on the cytosolic surface of oligodendrocyte membranes and is responsible for adhesion of these surfaces in the multilayered myelin sheath. The pattern of extensive post-translational modifications of MBP is dynamic during normal central nervous system (CNS) development and during myelin degeneration in multiple sclerosis (MS), affecting its interactions with the myelin membranes and with other molecules. In particular, the degree of deimination (or citrullination) of MBP is correlated with the severity of MS, and may represent a primary defect that precedes neurodegeneration due to autoimmune attack. That the degree of MBP deimination is also high in early CNS development indicates that this modification plays major physiological roles in myelin assembly. In this review, we describe the structural and functional consequences of MBP deimination in healthy and diseased myelin. PMID:16900293

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

    OpenAIRE

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

    2009-01-01

    The bHLH transcription factor Olig1 promotes oligodendrocyte maturation and is required for myelin repair. In this report, we characterize an Olig1-regulated G-protein coupled receptor GPR17 whose function is to oppose the action of Olig1. GPR17 is restricted to oligodendrocyte lineage cells but downregulated during the peak period of myelination and in adulthood. Transgenic mice with sustained GPR17 expression in oligodendrocytes exhibit stereotypic features of myelinating disorders in the C...

  8. Adduction of cholesterol 5,6-secosterol aldehyde to membrane-bound myelin basic protein exposes an immunodominant epitope.

    OpenAIRE

    Cygan, NK; Scheinost, JC; Butters, TD; Wentworth, P

    2011-01-01

    Myelin degradation in the central nervous system (CNS) is a clinical hallmark of multiple sclerosis (MS). A reduction in the net positive charge of myelin basic protein (MBP) via deimination of arginine to citrulline has been shown to correlate strongly with disease severity and has been linked to myelin instability and a defect that precedes neurodegeneration and leads to autoimmune attack. Recently, we have shown that lipid-derived aldehydes, such as cholesterol 5,6-secosterols atheronal A ...

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

    OpenAIRE

    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

    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 ...

  10. Radioimmunoassay of myelin basic protein. A methodological evaluation

    International Nuclear Information System (INIS)

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

  11. Kif1b is essential for mRNA localization in oligodendrocytes and development of myelinated axons

    OpenAIRE

    Lyons, David A.; Naylor, Stephen G.; Scholze, Anja; Talbot, William S.

    2009-01-01

    The kinesin motor protein Kif1b has previously been implicated in the axonal transport of mitochondria and synaptic vesicles1,2. More recently kif1b has been linked with susceptibility to Multiple Sclerosis (MS) 3. Here we show that Kif1b is required for the localization of myelin basic protein mRNA to processes of myelinating oligodendrocytes in zebrafish. We observe the ectopic appearance of myelin-like membrane in kif1b mutants, coincident with the ectopic localization of myelin proteins i...

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

    Science.gov (United States)

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

    2014-11-01

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

  13. 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)

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

    2004-03-01

    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

  14. Comet LINEAR Splits Further

    Science.gov (United States)

    2001-05-01

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

  15. Exposure to serotonin adversely affects oligodendrocyte development and myelination in vitro.

    Science.gov (United States)

    Fan, Lir-Wan; Bhatt, Abhay; Tien, Lu-Tai; Zheng, Baoying; Simpson, Kimberly L; Lin, Rick C S; Cai, Zhengwei; Kumar, Praveen; Pang, Yi

    2015-05-01

    Serotonin (5-hydroxytryptamine, 5-HT) has been implicated to play critical roles in early neural development. Recent reports have suggested that perinatal exposure to selective serotonin reuptake inhibitors (SSRIs) resulted in cortical network miswiring, abnormal social behavior, callosal myelin malformation, as well as oligodendrocyte (OL) pathology in rats. To gain further insight into the cellular and molecular mechanisms underlying SSRIs-induced OL and myelin abnormalities, we investigated the effect of 5-HT exposure on OL development, cell death, and myelination in cell culture models. First, we showed that 5-HT receptor 1A and 2A subtypes were expressed in OL lineages, using immunocytochemistry, Western blot, as well as intracellular Ca(2+) measurement. We then assessed the effect of serotonin exposure on the lineage development, expression of myelin proteins, cell death, and myelination, in purified OL and neuron-OL myelination cultures. For pure OL cultures, our results showed that 5-HT exposure led to disturbance of OL development, as indicated by aberrant process outgrowth and reduced myelin proteins expression. At higher doses, such exposure triggered a development-dependent cell death, as immature OLs exhibited increasing susceptibility to 5-HT treatment compared to OL progenitor cells (OPC). We showed further that 5-HT-induced immature OL death was mediated at least partially via 5-HT2A receptor, since cell death could be mimicked by 5-HT2A receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride, (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride, but atten-uated by pre-treatment with 5-HT2A receptor antagonist ritanserin. Utilizing a neuron-OL myelination co-culture model, our data showed that 5-HT exposure significantly reduced the number of myelinated internodes. In contrast to cell injury observed in pure OL cultures, 5-HT exposure did not lead to OL death or reduced OL density in neuron-OL co-cultures. However, abnormal patterns of contactin-associated protein (Caspr) clustering were observed at the sites of Node of Ranvier, suggesting that 5-HT exposure may affect other axon-derived factors for myelination. In summary, this is the first study to demonstrate that manipulation of serotonin levels affects OL development and myelination, which may contribute to altered neural connectivity noted in SSRIs-treated animals. The current in vitro study demonstrated that exposure to high level of serotonin (5-HT) led to aberrant oligodendrocyte (OL) development, cell injury, and myelination deficit. We propose that elevated extracellular serotonin levels in the fetal brain, such as upon the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy, may adversely affect OL development and/or myelination, thus contributing to altered neural connectivity seen in Autism Spectrum Disorders. OPC = oligodendrocyte progenitor cell. PMID:25382136

  16. Regulation of Peripheral Nerve Myelin Maintenance by Gene Repression through Polycomb Repressive Complex 2.

    Science.gov (United States)

    Ma, Ki H; Hung, Holly A; Srinivasan, Rajini; Xie, Huafeng; Orkin, Stuart H; Svaren, John

    2015-06-01

    Myelination of peripheral nerves by Schwann cells requires coordinate regulation of gene repression as well as gene activation. Several chromatin remodeling pathways critical for peripheral nerve myelination have been identified, but the functions of histone methylation in the peripheral nerve have not been elucidated. To determine the role of histone H3 Lys27 methylation, we have generated mice with a Schwann cell-specific knock-out of Eed, which is an essential subunit of the polycomb repressive complex 2 (PRC2) that catalyzes methylation of histone H3 Lys27. Analysis of this mutant revealed no significant effects on early postnatal development of myelin. However, its loss eventually causes progressive hypermyelination of small-diameter axons and apparent fragmentation of Remak bundles. These data identify the PRC2 complex as an epigenomic modulator of mature myelin thickness, which is associated with changes in Akt phosphorylation. Interestingly, we found that Eed inactivation causes derepression of several genes, e.g., Sonic hedgehog (Shh) and Insulin-like growth factor-binding protein 2 (Igfbp2), that become activated after nerve injury, but without activation of a primary regulator of the injury program, c-Jun. Analysis of the activated genes in cultured Schwann cells showed that Igfbp2 regulates Akt activation. Our results identify an epigenomic pathway required for establishing thickness of mature myelin and repressing genes that respond to nerve injury. PMID:26041929

  17. Functional inflammatory profiles distinguish myelin-reactive T cells from patients with multiple sclerosis.

    Science.gov (United States)

    Cao, Yonghao; Goods, Brittany A; Raddassi, Khadir; Nepom, Gerald T; Kwok, William W; Love, J Christopher; Hafler, David A

    2015-05-13

    Myelin-reactive T cells have been identified in patients with multiple sclerosis (MS) and healthy subjects with comparable frequencies, but the contribution of these autoreactive T cells to disease pathology remains unknown. A total of 13,324 T cell libraries generated from blood of 23 patients and 22 healthy controls were interrogated for reactivity to myelin antigens. Libraries derived from CCR6(+) myelin-reactive T cells from patients with MS exhibited significantly enhanced production of interferon-? (IFN-?), interleukin-17 (IL-17), and granulocyte-macrophage colony-stimulating factor (GM-CSF) compared to healthy controls. Single-cell clones isolated by major histocompatibility complex/peptide tetramers from CCR6(+) T cell libraries also secreted more proinflammatory cytokines, whereas clones isolated from controls secreted more IL-10. The transcriptomes of myelin-specific CCR6(+) T cells from patients with MS were distinct from those derived from healthy controls and, notably, were enriched in T helper cell 17 (TH17)-induced experimental autoimmune encephalitis gene signatures, and gene signatures derived from TH17 cells isolated other human autoimmune diseases. These data, although not causal, imply that functional differences between antigen-specific T cells from MS and healthy controls are fundamental to disease development and support the notion that IL-10 production from myelin-reactive T cells may act to limit disease progression or even pathogenesis. PMID:25972006

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

    DEFF Research Database (Denmark)

    Lozeron, Pierre; Krarup, Christian

    2004-01-01

    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.

  19. Association of myelin basic protein with detergent micelles.

    Science.gov (United States)

    Smith, R; McDonald, B J

    1979-06-13

    Equilibrium measurements of the binding of central nervous system myelin basic protein to sodium dodecyl sulphate, sodium deoxycholate and lysophosphatidylcholine have been obtained by gel permeation chromatography and dialysis. This protein associates with large amounts of each of these surfactants: the apparent saturation weight ratios (surfactant/protein) being 3.58 +/- 0.12 and 2.30 +/- 0.15 for dodecyl sulphate at ionic strengths 0.30 and 0.10, respectively 1.34 +/- 0.10 for deoxycholate (at 0.12 ionic strength) and 4.0 +/- 0.5 for lysophosphatidylcholine. Binding to the ionic surfactants increases markedly close to their critical micelle concentrations. Sedimentation analysis shows that at 0.30 ionic strenght in excess dodecyl sulphate the protein is monomeric. It becomes dimeric when the binding ratio falls below 1 at a free detergent concentration of approximately 0.25 mM: below this concentration much of the protein and deterent forms an insoluble complex. The amount of dodecyl sulphate bound at high concentrations and at both above-mentioned ionic strengths corresponds closely to that expected for interaction of a single poly-peptide with two micelles. Variability of deoxycholate micelle size on interaction with other molecules precludes a similar analysis for this surfactant. Association was observed only with single micelles of lysophosphatidylcholine. The results provide strong evidence for dual lipid-binding sites on basic protein and indicate that lipid bilayer cross-linking by this protein may be effected by single molecules. PMID:88232

  20. Axon-myelin transfer of phospholipid components in the course of their axonal transport as visualized by radioautography

    International Nuclear Information System (INIS)

    To determine whether or not a transfer of phospholipids takes place between the axon and its myelin sheath, the preganglionic axons of the chicken ciliary ganglion were loaded by transported radioactive phospholipids after an intracerebral injection of [3H]choline or [3H]glycerol. The eventual appearance of label in the myelin sheath was analyzed by radioautography. (Auth.)

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

    Science.gov (United States)

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

    2013-07-01

    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

  2. Astrocytes, but not olfactory ensheathing cells or Schwann cells, promote myelination of CNS axons in vitro.

    Science.gov (United States)

    Sorensen, Annette; Moffat, Keith; Thomson, Christine; Barnett, Susan C

    2008-05-01

    We have examined the interaction between olfactory ensheathing cells (OECs), Schwann cells (SC), oligodendrocytes, and CNS axons using cultures generated from embryonic rat spinal cord. Oligodendrocyte process extension and myelination in these cultures was poor if the cells were plated on OECs or SCs. Myelin internodes and nodes of Ranvier formed frequently if these cultures were plated onto monolayers of neurosphere-derived astrocytes (NsAs). In the myelinated fibers generated on NsAs, Nav channels, caspr, and neurofascin molecules were correctly assembled at the nodes of Ranvier. The density of neurites, survival, and antigenic differentiation of oligodendrocytes was similar on OEC and NsAs monolayers. However, on OEC monolayers, despite a transient increase in the number of endogenous oligodendrocytes, there was a decrease in oligodendrocyte process extension and axonal ensheathment when compared with cultures plated on NsAs monolayers. To determine if these changes were due to axonal or glial factors, spinal cord oligodendrocytes were plated onto monolayers of OECs, NsAs, and poly-L-lysine in the absence of neurons. In these cultures, process extension and myelin-like membrane formation by oligodendrocytes was improved on monolayers of OEC. This suggests that inhibition of process extension is mediated via cross-talk between OECs and neurites. In cultures containing axons plated on OEC monolayers, oligodendrocyte process formation, axonal ensheathment, and myelination occurred albeit lower if the cultures were supplemented with NsAs conditioned medium. These data suggest OECs can permit neurite extension and oligodendrocyte proliferation, but lack secreted factor(s) and possible cell-cell contact that is necessary for oligodendrocyte process extension and myelination. PMID:18293402

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

    OpenAIRE

    Dave Kunjan R; Pandya Jignesh D; Katyare Surendra S

    2004-01-01

    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 decr...

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

    Science.gov (United States)

    Watkins, Trent A; Scholze, Anja R

    2014-10-01

    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

  5. Dicer1 and miR-219 Are Required for Normal Oligodendrocyte Differentiation and Myelination

    OpenAIRE

    Dugas, Jason C.; Cuellar, Trinna L.; Scholze, Anja; Ason, Brandon; Ibrahim, Adiljan; Emery, Ben; Zamanian, Jennifer L.; Foo, Lynette C.; Mcmanus, Michael T.; Barres, Ben A.

    2010-01-01

    To investigate the role of microRNAs in regulating oligodendrocyte (OL) differentiation and myelination, we utilized transgenic mice in which microRNA processing was disrupted in OL precursor cells (OPCs) and OLs by targeted deletion of Dicer1. We found that inhibition of OPC-OL miRNA processing disrupts normal CNS myelination, and that OPCs lacking mature miRNAs fail to differentiate normally in vitro. We identified three miRNAs, miR-219, miR-138, and miR-338, that are induced 10–100x duri...

  6. 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.)

  7. Monoclonal antibody specific for myelin glycoprotein P0: derivation and characterization.

    OpenAIRE

    Franko, M. C.; Koski, C. L.; Gibbs, C. J.; Mcfarlin, D. E.; Gajdusek, D. C.

    1982-01-01

    A monoclonal antibody was produced against the major structural glycoprotein (P0) of human peripheral nervous system myelin. The hybridomas were generated by fusion of mouse myeloma line NS-1 with spleen cells of C3H mice immunized with purified human peripheral nervous system myelin. Hybridomas were screened by a two-step solid-phase radioimmunoassay, with P0 adsorbed on microtiter plates and with addition of 125I-labeled rabbit anti-mouse IgG as the second step. One derived clone, designate...

  8. Split-ball resonator

    CERN Document Server

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

    2014-01-01

    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...

  9. Split supersymmetry radiates flavor

    Science.gov (United States)

    Baumgart, Matthew; Stolarski, Daniel; Zorawski, Thomas

    2014-09-01

    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.

  10. Dipole Splitting Algorithm

    CERN Document Server

    Hasegawa, K

    2014-01-01

    The Catani-Seymour dipole subtraction is a general and powerful procedure to calculate the QCD next-to-leading order corrections for collider observables. We clearly define a practical algorithm to use the dipole subtraction. The algorithm is named as the Dipole Splitting Algorithm (DSA). The DSA is applied to arbitrary process by following the well defined steps. The results of the created subtraction terms can be summarized in a compact form at tables. We give a template for the summary tables. One advantage of the DSA is to allow the straightforward proof of the consistency of the created subtraction terms. The proof algorithm is presented in the accompany paper. We demonstrate the DSA at two example processes, $pp \\to \\mu^{-}\\mu^{+}$ and $pp \\to 2\\,jets$. Further as a confirmation of the DSA it is shown that the analytical results obtained by the DSA at the Drell-Yan process exactly agree with the well-known results by the traditional method.

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

    OpenAIRE

    Kazuaki Nakamura; Masahiro Maeda; Hideki Tsumura; Naoko Onami; Motoshi Nagao; Yuki Miyamoto; Tomohiro Torii; Akito Tanoue; Junji Yamauchi

    2012-01-01

    During development of the peripheral nervous system (PNS), Schwann cells (SCs) wrap individual axons to form myelin sheaths, which act as surrounding insulators and markedly enhance the propagation of the action potential. In peripheral neuropathies such as Guillain-Barré syndrome (GBS) and inherited demyelinating Charcot-Marie-Tooth (CMT) disease and diabetic neuropathies, chronic demyelination and defective remyelination are repeated, causing more severe neuropathies. It is thus thought th...

  12. ISR split-field magnet

    CERN Multimedia

    1975-01-01

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

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

    Directory of Open Access Journals (Sweden)

    RadmilaFilipovic

    2009-06-01

    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.

  14. AGC1 Deficiency Causes Infantile Epilepsy, Abnormal Myelination, and Reduced N-Acetylaspartate

    OpenAIRE

    Falk, Marni J.; Li, Dong; Gai, Xiaowu; Mccormick, Elizabeth; Place, Emily; Lasorsa, Francesco M.; Otieno, Frederick G.; Hou, Cuiping; Kim, Cecilia E.; Abdel-magid, Nada; Vazquez, Lyam; Mentch, Frank D.; Chiavacci, Rosetta; Liang, Jinlong; Liu, Xuanzhu

    2014-01-01

    Background: Whole exome sequencing (WES) offers a powerful diagnostic tool to rapidly and efficiently sequence all coding genes in individuals presenting for consideration of phenotypically and genetically heterogeneous disorders such as suspected mitochondrial disease. Here, we report results of WES and functional validation in a consanguineous Indian kindred where two siblings presented with profound developmental delay, congenital hypotonia, refractory epilepsy, abnormal myelination, fluct...

  15. Glutathione deficit impairs myelin maturation: relevance for white matter integrity in schizophrenia patients.

    Science.gov (United States)

    Monin, A; Baumann, P S; Griffa, A; Xin, L; Mekle, R; Fournier, M; Butticaz, C; Klaey, M; Cabungcal, J H; Steullet, P; Ferrari, C; Cuenod, M; Gruetter, R; Thiran, J P; Hagmann, P; Conus, P; Do, K Q

    2014-08-26

    Schizophrenia pathophysiology implies both abnormal redox control and dysconnectivity of the prefrontal cortex, partly related to oligodendrocyte and myelin impairments. As oligodendrocytes are highly vulnerable to altered redox state, we investigated the interplay between glutathione and myelin. In control subjects, multimodal brain imaging revealed a positive association between medial prefrontal glutathione levels and both white matter integrity and resting-state functional connectivity along the cingulum bundle. In early psychosis patients, only white matter integrity was correlated with glutathione levels. On the other side, in the prefrontal cortex of peripubertal mice with genetically impaired glutathione synthesis, mature oligodendrocyte numbers, as well as myelin markers, were decreased. At the molecular levels, under glutathione-deficit conditions induced by short hairpin RNA targeting the key glutathione synthesis enzyme, oligodendrocyte progenitors showed a decreased proliferation mediated by an upregulation of Fyn kinase activity, reversed by either the antioxidant N-acetylcysteine or Fyn kinase inhibitors. In addition, oligodendrocyte maturation was impaired. Interestingly, the regulation of Fyn mRNA and protein expression was also impaired in fibroblasts of patients deficient in glutathione synthesis. Thus, glutathione and redox regulation have a critical role in myelination processes and white matter maturation in the prefrontal cortex of rodent and human, a mechanism potentially disrupted in schizophrenia.Molecular Psychiatry advance online publication, 26 August 2014; doi:10.1038/mp.2014.88. PMID:25155877

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

    International Nuclear Information System (INIS)

    Highlights: ? Lysolecithin-induced demyelination elevated EpoR expression in OPCs. ? In association with elevated EpoR, EPO increased OPCs proliferation. ? EPO enhanced the oligodendrogenesis via activation of JAK2 pathway. ? 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.

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

    Directory of Open Access Journals (Sweden)

    Goh Eyleen LK

    2008-10-01

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

  18. Does Data Splitting Improve Prediction?

    OpenAIRE

    Faraway, Julian J.

    2013-01-01

    Data splitting divides data into two parts. One part is reserved for model selection. In some applications, the second part is used for model validation but we use this part for estimating the parameters of the chosen model. We focus on the problem of constructing reliable predictive distributions for future observed values. We judge the predictive performance using log scoring. We compare the full data strategy with the data splitting strategy for prediction. We show how th...

  19. Split Inteins: Nature's Protein Ligases

    OpenAIRE

    Shah, Neel H.; Muir, Tom W

    2011-01-01

    Split inteins carry out a naturally occurring process known as protein trans-splicing, where two protein fragments bind to form a catalytically competent enzyme, then catalyze their own excision and the ligation of their flanking sequences. In the past thirteen years since their discovery, chemists and biologists have utilized split inteins in exogenous contexts for a number of biotechnological applications centered around the formation of native peptide bonds. While many protein trans-splici...

  20. Splitting methods for Levitron Problems

    OpenAIRE

    Geiser, Juergen; Lueskow, Karl

    2012-01-01

    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 split...

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

    Directory of Open Access Journals (Sweden)

    Kucharova Karolina

    2011-11-01

    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.

  2. 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)

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

    Directory of Open Access Journals (Sweden)

    Strichartz Gary R

    2007-07-01

    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.

  4. The p38? mitogen-activated protein kinase is a key regulator of myelination and remyelination in the CNS.

    Science.gov (United States)

    Chung, S-H; Biswas, S; Selvaraj, V; Liu, X-B; Sohn, J; Jiang, P; Chen, C; Chmilewsky, F; Marzban, H; Horiuchi, M; Pleasure, D E; Deng, W

    2015-01-01

    The p38? mitogen-activated protein kinase (MAPK) is one of the serine/threonine kinases regulating a variety of biological processes, including cell-type specification, differentiation and migration. Previous in vitro studies using pharmacological inhibitors suggested that p38 MAPK is essential for oligodendrocyte (OL) differentiation and myelination. To investigate the specific roles of p38? MAPK in OL development and myelination in vivo, we generated p38? conditional knockout (CKO) mice under the PLP and nerve/glial antigen 2 (NG2) gene promoters, as these genes are specifically expressed in OL progenitor cells (OPCs). Our data revealed that myelin synthesis was completely inhibited in OLs differentiated from primary OPC cultures derived from the NG2 Cre-p38? CKO mouse brains. Although an in vivo myelination defect was not obvious after gross examination of these mice, electron microscopic analysis showed that the ultrastructure of myelin bundles was severely impaired. Moreover, the onset of myelination in the corpus callosum was delayed in the knockout mice compared with p38? fl/fl control mice. A delay in OL differentiation in the central nervous system was observed with concomitant downregulation in the expression of OPC- and OL-specific genes such as Olig1 and Zfp488 during early postnatal development. OPC proliferation was not affected during this time. These data indicate that p38? is a positive regulator of OL differentiation and myelination. Unexpectedly, we observed an opposite effect of p38? on remyelination in the cuprizone-induced demyelination model. The p38? CKO mice exhibited better remyelination capability compared with p38? fl/fl mice following demyelination. The opposing roles of p38? in myelination and remyelination could be due to a strong anti-inflammatory effect of p38? or a dual reciprocal regulatory action of p38? on myelin formation during development and on remyelination after demyelination. PMID:25950478

  5. Cholesterol 5,6-secosterol Aldehyde Adduction to Membrane-Bound Myelin Basic Protein Exposes an Immunodominant Epitope†

    OpenAIRE

    Cygan, Natalie K.; Scheinost, Johanna C.; Butters, Terry D; Wentworth, Paul

    2011-01-01

    Myelin degradation in the CNS is a clinical hallmark of multiple sclerosis (MS). A reduction in the net positive charge of myelin basic protein (MBP) via deimination of arginine to citrulline, has been shown to correlate strongly with disease severity and has been linked to myelin instability and a defect that precedes neurodegeneration and leads to autoimmune attack. Recently, we have shown that lipid-derived aldehydes, such as the cholesterol 5,6-secosterols atheronal-A (1a) and atheronal-B...

  6. Rashba spin splitting in symmetric structures

    OpenAIRE

    Tenev, Tihomir G.

    2013-01-01

    It is widely believed that Rasba spin splitting occurs only in systems lacking space inversion invariance. In this letter we present analytical analysis which suggests that non-zero Rashba spin splitting occurs in systems possessing space inversion invariance. We present numerical simulations which confirm that non-zero Rashba spin splitting occurs in symmetric structures but this splitting is several orders of magnitude smaller than the Rashba spin splitting due to broken s...

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

    OpenAIRE

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

    2013-01-01

    In the injured adult mammalian central nervous system (CNS), products are generated that inhibit neuronal sprouting and regeneration. In recent years, most attention has focused on the myelin-associated inhibitory proteins (MAIs) Nogo-A, OMgp, and myelin-associated glycoprotein (MAG). Binding of MAIs to neuronal cell-surface receptors leads to activation of RhoA, growth cone collapse, and neurite outgrowth inhibition. In the present study, we identify low-density lipoprotein (LDL) receptor-re...

  8. 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

  9. Hyperfine splitting of hydrogenlike thallium

    International Nuclear Information System (INIS)

    The dynamic correlation model was used to calculate nuclear ground-state wave functions of 203Tl, 205Tl, and 207Tl. The ground states of these isotopes are characterized by strong mixing amplitudes of the valence 3s1/2-1 hole with the intrinsic vacuum states (valence hole coupled to core excitations). Nuclear magnetic moments, radii, and the 1s hyperfine-structure splitting energy for the hydrogenlike ions were calculated. Experimental magnetic moments and radii of the nuclear ground states are well reproduced. The hyperfine-structure splitting of the hydrogenlike Tl isotopes have not been measured so far, hence, the obtained values are only compared with predictions of other theoretical calculations. The difference in the 1s hyperfine-structure splitting between 203Tl80+ and 205Tl80+ is found to be 0.026 eV, which corresponds to a 3.1 nm shift in the transiton wavelength

  10. Lattice splitting under intermittent flows

    CERN Document Server

    Schläpfer, Markus

    2010-01-01

    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.

  11. Splitting methods for Levitron Problems

    CERN Document Server

    Geiser, Juergen

    2012-01-01

    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.

  12. Testing Split Supersymmetry with Inflation

    CERN Document Server

    Craig, Nathaniel

    2014-01-01

    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...

  13. Geometrical Applications of Split Octonions

    CERN Document Server

    Gogberashvili, Merab

    2015-01-01

    Physical signals and space-time intervals are described in terms of split octonions. Geometrical symmetries are represented by the automorphism group of the algebra - the real non-compact form of Cartan's smallest exceptional group G2. This group generates specific rotations of (3+4)-vector parts of split octonions with three extra time-like coordinates and in certain limits reduces to standard Lorentz group. In this picture several physical characteristics of ordinary (3+1)-dimensional theory (such as: number of spatial dimensions, existence of maximal velocities, the uncertainty principle, some quantum numbers) are naturally emerge from the properties of the algebra.

  14. Splitting strings on integrable backgrounds

    International Nuclear Information System (INIS)

    We use integrability to construct the general classical splitting string solution on R x S3. Namely, given any incoming string solution satisfying a necessary self-intersection property at some given instant in time, we use the integrability of the worldsheet ?-model to construct the pair of outgoing strings resulting from a split. The solution for each outgoing string is expressed recursively through a sequence of dressing transformations, the parameters of which are determined by the solutions to Birkhoff factorization problems in an appropriate real form of the loop group of SL2(C). (orig.)

  15. 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)

  16. Splitting strings on integrable backgrounds

    Energy Technology Data Exchange (ETDEWEB)

    Vicedo, Benoit

    2011-05-15

    We use integrability to construct the general classical splitting string solution on R x S{sup 3}. Namely, given any incoming string solution satisfying a necessary self-intersection property at some given instant in time, we use the integrability of the worldsheet {sigma}-model to construct the pair of outgoing strings resulting from a split. The solution for each outgoing string is expressed recursively through a sequence of dressing transformations, the parameters of which are determined by the solutions to Birkhoff factorization problems in an appropriate real form of the loop group of SL{sub 2}(C). (orig.)

  17. Akt signals through the mammalian target of rapamycin, mTOR, pathway to regulate central nervous system myelination

    OpenAIRE

    Narayanan, S. Priyadarshini; Flores, Ana I.; Wang, Feng; Macklin, Wendy B.

    2009-01-01

    Mammalian target of rapamycin (mTOR), a well known Akt substrate, regulates multiple cellular functions including cell growth and protein synthesis. The current study identifies a novel role of the Akt/mTOR pathway as a regulator of central nervous system myelination. Previously, we showed that overexpressing constitutively active Akt in oligodendrocytes in a transgenic mouse model induces enhanced central nervous system myelination, with no changes in the proliferation or survival of oligode...

  18. Myelin repair in vivo is increased by targeting oligodendrocyte precursor cells with nanoparticles encapsulating leukaemia inhibitory factor (LIF).

    Science.gov (United States)

    Rittchen, Sonja; Boyd, Amanda; Burns, Alasdair; Park, Jason; Fahmy, Tarek M; Metcalfe, Su; Williams, Anna

    2015-07-01

    Multiple sclerosis (MS) is a progressive demyelinating disease of the central nervous system (CNS). Many nerve axons are insulated by a myelin sheath and their demyelination not only prevents saltatory electrical signal conduction along the axons but also removes their metabolic support leading to irreversible neurodegeneration, which currently is untreatable. There is much interest in potential therapeutics that promote remyelination and here we explore use of leukaemia inhibitory factor (LIF), a cytokine known to play a key regulatory role in self-tolerant immunity and recently identified as a pro-myelination factor. In this study, we tested a nanoparticle-based strategy for targeted delivery of LIF to oligodendrocyte precursor cells (OPC) to promote their differentiation into mature oligodendrocytes able to repair myelin. Poly(lactic-co-glycolic acid)-based nanoparticles of ?120 nm diameter were constructed with LIF as cargo (LIF-NP) with surface antibodies against NG-2 chondroitin sulfate proteoglycan, expressed on OPC. In vitro, NG2-targeted LIF-NP bound to OPCs, activated pSTAT-3 signalling and induced OPC differentiation into mature oligodendrocytes. In vivo, using a model of focal CNS demyelination, we show that NG2-targeted LIF-NP increased myelin repair, both at the level of increased number of myelinated axons, and increased thickness of myelin per axon. Potency was high: a single NP dose delivering picomolar quantities of LIF is sufficient to increase remyelination. Impact statement Nanotherapy-based delivery of leukaemia inhibitory factor (LIF) directly to OPCs proved to be highly potent in promoting myelin repair in vivo: this delivery strategy introduces a novel approach to delivering drugs or biologics targeted to myelin repair in diseases such as MS. PMID:25934281

  19. Deletion of Jun Proteins in Adult Oligodendrocytes Does Not Perturb Cell Survival, or Myelin Maintenance In Vivo

    OpenAIRE

    Schreiner, Bettina; Ingold-Heppner, Barbara; Pehl, Debora; Locatelli, Giuseppe; Berrit-Schönthaler, Helia; Becher, Burkhard

    2015-01-01

    Oligodendrocytes, the myelin-forming glial cells of the central nervous system (CNS), are fundamental players in rapid impulse conduction and normal axonal functions. JunB and c-Jun are DNA-binding components of the AP-1 transcription factor, which is known to regulate different processes such as proliferation, differentiation, stress responses and death in several cell types, including cultured oligodendrocyte/lineage cells. By selectively inactivating Jun B and c-Jun in myelinating oligoden...

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

    OpenAIRE

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

    2013-01-01

    Protective properties of moderate wine consumption against cancers, cardiovascular, metabolic and degenerative diseases have been reported in various clinical studies. Here, we analysed the effect of red wine (RW) and white wine (WW) on myelination using an in vitro embryonic co-culture mouse model. The total amount of myelin was found to be significantly increased after RW and WW treatment, while only RW significantly increased the number of internodes. Both types of wine increased rat Schwa...

  1. Damage to the Optic Chiasm in Myelin Oligodendrocyte Glycoprotein–Experimental Autoimmune Encephalomyelitis Mice

    Science.gov (United States)

    Herrera, Sheryl L; Palmer, Vanessa L; Whittaker, Heather; Smith, Blair Cardigan; Kim, Annie; Schellenberg, Angela E; Thiessen, Jonathan D; Buist, Richard; Del Bigio, Marc R; Martin, Melanie

    2014-01-01

    Optic chiasm lesions in myelin oligodendrocyte glycoprotein (MOG)–experimental autoimmune encephalomyelitis (EAE) mice were characterized using magnetic resonance imaging (MRI) and validated using electron microscopy (EM). MR images were collected from 3 days after induction to remission, approximately 20 days after induction. Hematoxylin and eosin, solochrome cyanin–stained sections, and EM images were obtained from the optic chiasms of some mice approximately 4 days after disease onset when their scores were thought to be the highest. T2-weighted imaging and apparent diffusion coefficient map hyperintensities corresponded to abnormalities in the optic chiasms of EAE mice. Mixed inflammation was concentrated at the lateral surface. Degeneration of oligodendrocytes, myelin, and early axonal damage were also apparent. A marked increase in chiasm thickness was observed. T2-weighted and diffusion-weighted MRI can detect abnormalities in the optic chiasms of MOG-EAE mice. MRI is an important method in the study of this model toward understanding optic neuritis. PMID:25520558

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

    Directory of Open Access Journals (Sweden)

    Dave Kunjan R

    2004-06-01

    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.

  3. Myelinated retinal nerve fibers (MRNF) – Dilemmas related to their influence on visual function

    Science.gov (United States)

    Grzybowski, Andrzej; Winiarczyk, Iwona

    2013-01-01

    Myelinated nerve fibers (MNF) occur in less than 1% of the population, however, they might be responsible for diagnostic dilemmas in cases with visual loss. The case report of an aged pseudophakic patient with visual deterioration in the right eye and MNF in both eyes is presented. The documentation provided by the patient proved recent several examinations of both fundi, and all of them were described as normal. Physical examination revealed the posterior capsule opacification in the right eye, white lesions on the retina of the right eye around the optic disk, and in the left eye – the peripheral, which could correspond to the myelinated fibers. Although visual field changes and OCTs corresponded to the NMF, it turned out, however, that visual acuity loss was in fact caused by PCO and was reversed by the YAG capsulotomy procedure. This case shows some problems related to MNF diagnosis and evaluation of their influence on visual function. PMID:25859147

  4. Myelinated retinal nerve fibers (MRNF) - Dilemmas related to their influence on visual function.

    Science.gov (United States)

    Grzybowski, Andrzej; Winiarczyk, Iwona

    2015-01-01

    Myelinated nerve fibers (MNF) occur in less than 1% of the population, however, they might be responsible for diagnostic dilemmas in cases with visual loss. The case report of an aged pseudophakic patient with visual deterioration in the right eye and MNF in both eyes is presented. The documentation provided by the patient proved recent several examinations of both fundi, and all of them were described as normal. Physical examination revealed the posterior capsule opacification in the right eye, white lesions on the retina of the right eye around the optic disk, and in the left eye - the peripheral, which could correspond to the myelinated fibers. Although visual field changes and OCTs corresponded to the NMF, it turned out, however, that visual acuity loss was in fact caused by PCO and was reversed by the YAG capsulotomy procedure. This case shows some problems related to MNF diagnosis and evaluation of their influence on visual function. PMID:25859147

  5. Ubiquitin-independent proteosomal degradation of myelin basic protein contributes to development of neurodegenerative autoimmunity.

    Science.gov (United States)

    Belogurov, Alexey; Kuzina, Ekaterina; Kudriaeva, Anna; Kononikhin, Alexey; Kovalchuk, Sergey; Surina, Yelena; Smirnov, Ivan; Lomakin, Yakov; Bacheva, Anna; Stepanov, Alexey; Karpova, Yaroslava; Lyupina, Yulia; Kharybin, Oleg; Melamed, Dobroslav; Ponomarenko, Natalia; Sharova, Natalia; Nikolaev, Eugene; Gabibov, Alexander

    2015-05-01

    Recent findings indicate that the ubiquitin-proteasome system is involved in the pathogenesis of cancer as well as autoimmune and several neurodegenerative diseases, and is thus a target for novel therapeutics. One disease that is related to aberrant protein degradation is multiple sclerosis, an autoimmune disorder involving the processing and presentation of myelin autoantigens that leads to the destruction of axons. Here, we show that brain-derived proteasomes from SJL mice with experimental autoimmune encephalomyelitis (EAE) in an ubiquitin-independent manner generate significantly increased amounts of myelin basic protein peptides that induces cytotoxic lymphocytes to target mature oligodendrocytes ex vivo. Ten times enhanced release of immunogenic peptides by cerebral proteasomes from EAE-SJL mice is caused by a dramatic shift in the balance between constitutive and ?1i(high) immunoproteasomes in the CNS of SJL mice with EAE. We found that during EAE, ?1i is increased in resident CNS cells, whereas ?5i is imported by infiltrating lymphocytes through the blood-brain barrier. Peptidyl epoxyketone specifically inhibits brain-derived ?1i(high) immunoproteasomes in vitro (kobs/[I] = 240 M(-1)s(-1)), and at a dose of 0.5 mg/kg, it ameliorates ongoing EAE in vivo. Therefore, our findings provide novel insights into myelin metabolism in pathophysiologic conditions and reveal that the ?1i subunit of the immunoproteasome is a potential target to treat autoimmune neurologic diseases.-Belogurov Jr., A., Kuzina, E., Kudriaeva, A., Kononikhin, A., Kovalchuk, S., Surina, Y., Smirnov, I., Lomakin, Y., Bacheva, A., Stepanov, A., Karpova, Y., Lyupina, Y., Kharybin, O., Melamed, D., Ponomarenko, N., Sharova, N., Nikolaev, E., Gabibov, A. Ubiquitin-independent proteosomal degradation of myelin basic protein contributes to development of neurodegenerative autoimmunity. PMID:25634956

  6. The Role of Endothelin Receptor A during Myelination of Developing Oligodendrocytes

    OpenAIRE

    Jung, Kyung Jin; Kim, Dong Woon; Lee, Ha Na; Lee, Young Sook; Lee, Sung Joong; Che, Jeong-Hwan; Lee, Young Ho; Kang, Byeong-Cheol

    2010-01-01

    Endothelin (ET)-1 and its receptors (ETA and ETB receptor) are present in the central nervous system. ET exerts biological effects on gliogenesis and glial cell functions. In order to define a possible mechanism of ETA receptor signaling, the distribution of the ETA receptor in developing oligodendrocytes and the effects of ET-1 on the myelination of oligodendrocytes were examined. ETA receptor immunoreactivity was confined to the perivascular elements of the blood vessels during early postna...

  7. Steroid responsive polyneuropathy in a family with a novel myelin protein zero mutation

    OpenAIRE

    Donaghy, M.; Sisodiya, S.; Kennett, R.; Mcdonald, B.; Haites, N.; Bell, C.

    2000-01-01

    OBJECTIVE—To report a novel hereditary motor and sensory neuropathy (HMSN) phenotype, with partial steroid responsiveness, caused by a novel dominant mutation in the myelin protein zero (MPZ) gene. Most MPZ mutations lead to the HMSN type I phenotype, with recent reports of Déjérine-Sottas, congenital hypomyelination, and HMSN II also ascribed to MPZ mutations. Differing phenotypes may reflect the effect of particular mutations on MPZ structure and adhesivity.?...

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

    OpenAIRE

    Lee, Jae K.; Zheng, Binhai

    2011-01-01

    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 ...

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

    Energy Technology Data Exchange (ETDEWEB)

    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

    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.

  10. 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)

  11. An autometallographic technique for myelin staining in formaldehyde-fixed tissue

    OpenAIRE

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

    2003-01-01

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

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

    OpenAIRE

    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

    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...

  13. THEORETICAL PRINCIPLES UNDERLYING OPTICAL STIMULATION OF MYELINATED AXONS EXPRESSING CHANNELRHODOPSIN-2

    OpenAIRE

    Arlow, R. L.; Foutz, T. J.; Mcintyre, C. C.

    2013-01-01

    Numerous clinical conditions can be treated by neuromodulation of the peripheral nervous system (PNS). Typical electrical PNS therapies activate large diameter axons at lower electrical stimulus thresholds than small diameter axons. However, recent animal experiments with peripheral optogenetic neural stimulation (PONS) of myelinated axons expressing channelrhodopsin-2 (ChR2) have shown that this technique activates small diameter axons at lower irradiances than large diameter axons. We hypot...

  14. Adult brain retains the potential to generate oligodendroglial progenitors with extensive myelination capacity

    OpenAIRE

    Zhang, Su-Chun; Ge, Bin; Duncan, Ian D.

    1999-01-01

    Remyelination of focal areas of the central nervous system (CNS) in animals can be achieved by transplantation of glial cells, yet the source of these cells in humans to similarly treat myelin disorders is limited at present to fetal tissue. Multipotent precursor cells are present in the CNS of adult as well as embryonic and neonatal animals and can differentiate into lineage-restricted progenitors such as oligodendroglial progenitors (OPs). The OPs present in adults have a different phenotyp...

  15. Identification of Naturally Occurring Fatty Acids of the Myelin Sheath That Resolve Neuroinflammation

    OpenAIRE

    Ho, Peggy P.; Kanter, Jennifer L.; Johnson, Amanda M.; Srinagesh, Hrishikesh K.; Chang, Eun-ju; Purdy, Timothy M.; Haren, Keith P.; Wikoff, William R.; Kind, Tobias; Khademi, Mohsen; Matloff, Laura Y.; Narayana, Sirisha; Hur, Eun Mi; Lindstrom, Tamsin M.; He, Zhigang

    2012-01-01

    Lipids comprise 70% of the myelin sheath, and autoantibodies against lipids may contribute to the demyelination that characterizes multiple sclerosis (MS). We used lipid antigen microarrays and lipid mass spectrometry to identify bona fide lipid targets of the autoimmune response in MS brain, and an animal model of MS to explore the role of the identified lipids in autoimmune demyelination. We found that autoantibodies in MS target a phosphate group in phosphatidylserine and oxidized phosphat...

  16. Neuroglialpharmacology: myelination as a shared mechanism of action of psychotropic treatments.

    Science.gov (United States)

    Bartzokis, George

    2012-06-01

    Current psychiatric diagnostic schema segregate symptom clusters into discrete entities, however, large proportions of patients suffer from comorbid conditions that fit neither diagnostic nor therapeutic schema. Similarly, psychotropic treatments ranging from lithium and antipsychotics to serotonin reuptake inhibitors (SSRIs) and acetylcholinesterase inhibitors have been shown to be efficacious in a wide spectrum of psychiatric disorders ranging from autism, schizophrenia (SZ), depression, and bipolar disorder (BD) to Alzheimer's disease (AD). This apparent lack of specificity suggests that psychiatric symptoms as well as treatments may share aspects of pathophysiology and mechanisms of action that defy current symptom-based diagnostic and neuron-based therapeutic schema. A myelin-centered model of human brain function can help integrate these incongruities and provide novel insights into disease etiologies and treatment mechanisms. Available data are integrated herein to suggest that widely used psychotropic treatments ranging from antipsychotics and antidepressants to lithium and electroconvulsive therapy share complex signaling pathways such as Akt and glycogen synthase kinase-3 (GSK3) that affect myelination, its plasticity, and repair. These signaling pathways respond to neurotransmitters, neurotrophins, hormones, and nutrition, underlie intricate neuroglial communications, and may substantially contribute to the mechanisms of action and wide spectra of efficacy of current therapeutics by promoting myelination. Imaging and genetic technologies make it possible to safely and non-invasively test these hypotheses directly in humans and can help guide clinical trial efforts designed to correct myelination abnormalities. Such efforts may provide insights into novel avenues for treatment and prevention of some of the most prevalent and devastating human diseases. PMID:22306524

  17. Conformational epitopes of myelin oligodendrocyte glycoprotein are targets of potentially pathogenic antibody responses in multiple sclerosis

    OpenAIRE

    Menge Til; Lalive Patrice H; -christian, Von Bu?dingen H.; Genain Claude P

    2011-01-01

    Abstract Background Myelin/oligodendrocyte glycoprotein (MOG) is a putative autoantigen in multiple sclerosis (MS). Establishing the pathological relevance and validity of anti-MOG antibodies as biomarkers has yielded conflicting reports mainly due to different MOG isoforms used in different studies. Because epitope specificity may be a key factor determining anti-MOG reactivity we aimed at identifying a priori immunodominant MOG epitopes by monoclonal antibodies (mAbs) and at assessing clini...

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

    OpenAIRE

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

    2005-01-01

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

  19. Process outgrowth in oligodendrocytes is mediated by CNP, a novel microtubule assembly myelin protein

    OpenAIRE

    Lee, John; Gravel, Michel; Zhang, Rulin; Thibault, Pierre; Braun, Peter E.

    2005-01-01

    Oligodendrocytes (OLs) extend arborized processes that are supported by microtubules (MTs) and microfilaments. Little is known about proteins that modulate and interact with the cytoskeleton during myelination. Several lines of evidence suggest a role for 2?,3?-cyclic nucleotide 3?-phosphodiesterase (CNP) in mediating process formation in OLs. In this study, we report that tubulin is a major CNP-interacting protein. In vitro, CNP binds preferentially to tubulin heterodimers compared wit...

  20. Modifications of myelin basic protein in DM20 transgenic mice are similar to those in myelin basic protein from multiple sclerosis.

    Science.gov (United States)

    Mastronardi, F G; Mak, B; Ackerley, C A; Roots, B I; Moscarello, M A

    1996-01-15

    Transgenic mice containing different numbers of transgenes (2-70) of the myelin proteolipid protein DM20 were phenotypically normal up to 3 mo of age, after which the mice containing 70 copies of the transgene spontaneously demyelinated and died at 10-12 mo. Since we demonstrated that demyelination in multiple sclerosis involved specific chemical changes in myelin basic protein (MBP), we investigated the MBP in our transgenic line for similar changes. Both the total amount of MBP in brain and the MBP mRNA levels were unaffected at the different ages. All the isoforms (14-21 kD) of MBP were present, but the microheterogeneity (a posttranslational event) was changed resulting in a higher proportion of the less cationic components reminiscent of the changes in MBP found in multiple sclerosis. An increased amount of the citrullinated form of MBP was found by Western blot analysis. Immunogold labeling of cryosections of brain revealed a greater density of particles with the anticitrulline antibody at 10 mo and that the levels of peptidylarginine deiminase (which deiminates protein-bound arginine to citrulline) were increased. This stable transgenic line represents a useful animal model for the human disease multiple sclerosis. PMID:8567954

  1. ISA ''split pole'' injection magnet

    International Nuclear Information System (INIS)

    The conceptual design for a shutterless ''split pole'' vertical deflecting dipole magnet for ISA beam injection is presented. Preliminary results of field mesh calculations are given together with measured data for a simple dc model. The results warrant proceeding with the further design and construction of a fast pulsed ferrite vertical injection kicker model for the ISA

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

    Directory of Open Access Journals (Sweden)

    Yamada,Teruo

    1980-02-01

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

  3. Peripheral myelin protein 22 is a constituent of intercellular junctions in epithelia.

    Science.gov (United States)

    Notterpek, L; Roux, K J; Amici, S A; Yazdanpour, A; Rahner, C; Fletcher, B S

    2001-12-01

    Alterations in peripheral myelin protein 22 (PMP22) gene expression are associated with a host of heritable demyelinating peripheral neuropathies, yet the function of the protein remains unknown. PMP22 expression is highest in myelinating Schwann cells of peripheral nerves; however, significant levels of PMP22 mRNAs can be detected in a variety of non-neural tissue, including epithelia. To date, PMP22 protein expression and localization in non-neural tissues have not been studied in detail. In adult rat liver and intestine, and cultured epithelial cells, we detected PMP22-like immunoreactivity associated with markers of the tight junctional complex, including zonula occludens 1 (ZO-1) and occludin. Upon disruption of intercellular contacts, PMP22 was internalized into vesicles that were immunoreactive for both anti-occludin and anti-PMP22 antibodies. Nonionic detergent extraction of cultured epithelial cells did not solubilize PMP22, as the majority of the protein remained in the detergent insoluble fraction, as did ZO-1 and occludin. We also observed the targeting of exogenous myc-tagged PMP22 to apical cell junctions in polarized epithelia and to anti-ZO-1 antibody immunoreactive cell contacts of L fibroblasts. These studies support a role for PMP22 at intercellular junctions of epithelia and may indicate a similar function in myelinating Schwann cells. Furthermore, our findings could provide an explanation for certain phenotypes of PMP22 neuropathy mice that cannot be accounted for by dysmyelination. PMID:11717414

  4. Vitamin D3 potentiates myelination and recovery after facial nerve injury.

    Science.gov (United States)

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

    2014-09-27

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

  5. NKCC1 Activation Is Required for Myelinated Sensory Neurons Regeneration through JNK-Dependent Pathway.

    Science.gov (United States)

    Mòdol, Laura; Santos, Daniel; Cobianchi, Stefano; González-Pérez, Francisco; López-Alvarez, Víctor; Navarro, Xavier

    2015-05-13

    After peripheral nerve injury, axons are able to regenerate, although specific sensory reinnervation and functional recovery are usually worse for large myelinated than for small sensory axons. The mechanisms that mediate the regeneration of different sensory neuron subpopulations are poorly known. The Na(+)-K(+)-Cl(-) cotransporter 1 (NKCC1) is particularly relevant in setting the intracellular chloride concentration. After axotomy, increased NKCC1 phosphorylation has been reported to be important for neurite outgrowth of sensory neurons; however, the mechanisms underlying its effects are still unknown. In the present study we used in vitro and in vivo models to assess the differential effects of blocking NKCC1 activity on the regeneration of different types of dorsal root ganglia (DRGs) neurons after sciatic nerve injury in the rat. We observed that blocking NKCC1 activity by bumetanide administration induces a selective effect on neurite outgrowth and regeneration of myelinated fibers without affecting unmyelinated DRG neurons. To further study the mechanism underlying NKCC1 effects, we also assessed the changes in mitogen-activated protein kinase (MAPK) signaling under NKCC1 modulation. The inhibition of NKCC1 activity in vitro and in vivo modified pJNK1/2/3 expression in DRG neurons. Together, our study identifies a mechanism selectively contributing to myelinated axon regeneration, and point out the role of Cl(-) modulation in DRG neuron regeneration and in the activation of MAPKs, particularly those belonging to the JNK family. PMID:25972170

  6. Dicer1 and miR-219 Are required for normal oligodendrocyte differentiation and myelination.

    Science.gov (United States)

    Dugas, Jason C; Cuellar, Trinna L; Scholze, Anja; Ason, Brandon; Ibrahim, Adiljan; Emery, Ben; Zamanian, Jennifer L; Foo, Lynette C; McManus, Michael T; Barres, Ben A

    2010-03-11

    To investigate the role of microRNAs in regulating oligodendrocyte (OL) differentiation and myelination, we utilized transgenic mice in which microRNA processing was disrupted in OL precursor cells (OPCs) and OLs by targeted deletion of Dicer1. We found that inhibition of OPC-OL miRNA processing disrupts normal CNS myelination and that OPCs lacking mature miRNAs fail to differentiate normally in vitro. We identified three miRNAs (miR-219, miR-138, and miR-338) that are induced 10-100x during OL differentiation; the most strongly induced of these, miR-219, is necessary and sufficient to promote OL differentiation, and partially rescues OL differentiation defects caused by total miRNA loss. miR-219 directly represses the expression of PDGFRalpha, Sox6, FoxJ3, and ZFP238 proteins, all of which normally help to promote OPC proliferation. Together, these findings show that miR-219 plays a critical role in coupling differentiation to proliferation arrest in the OL lineage, enabling the rapid transition from proliferating OPCs to myelinating OLs. PMID:20223197

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

    Science.gov (United States)

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

    2012-09-01

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

  8. Age-related microstructural differences quantified using myelin water imaging and advanced diffusion MRI.

    Science.gov (United States)

    Billiet, Thibo; Vandenbulcke, Mathieu; Mädler, Burkhard; Peeters, Ronald; Dhollander, Thijs; Zhang, Hui; Deprez, Sabine; Van den Bergh, Bea R H; Sunaert, Stefan; Emsell, Louise

    2015-06-01

    Age-related microstructural differences have been detected using diffusion tensor imaging (DTI). Although DTI is sensitive to the effects of aging, it is not specific to any underlying biological mechanism, including demyelination. Combining multiexponential T2 relaxation (MET2) and multishell diffusion MRI (dMRI) techniques may elucidate such processes. Multishell dMRI and MET2 data were acquired from 59 healthy participants aged 17-70 years. Whole-brain and regional age-associated correlations of measures related to multiple dMRI models (DTI, diffusion kurtosis imaging [DKI], neurite orientation dispersion and density imaging [NODDI]) and myelin-sensitive MET2 metrics were assessed. DTI and NODDI revealed widespread increases in isotropic diffusivity with increasing age. In frontal white matter, fractional anisotropy linearly decreased with age, paralleled by increased "neurite" dispersion and no difference in myelin water fraction. DKI measures and neurite density correlated well with myelin water fraction and intracellular and extracellular water fraction. DTI estimates remain among the most sensitive markers for age-related alterations in white matter. NODDI, DKI, and MET2 indicate that the initial decrease in frontal fractional anisotropy may be due to increased axonal dispersion rather than demyelination. PMID:25840837

  9. Myocilin mediates myelination in the peripheral nervous system through ErbB2/3 signaling.

    Science.gov (United States)

    Kwon, Heung Sun; Johnson, Thomas V; Joe, Myung Kuk; Abu-Asab, Mones; Zhang, Jun; Chan, Chi Chao; Tomarev, Stanislav I

    2013-09-13

    The glaucoma-associated gene, myocilin, is expressed in ocular and non-ocular tissues including the peripheral nervous system, but its functions in these tissues remain poorly understood. We demonstrate that in sciatic nerve, myocilin is expressed in Schwann cells with high concentrations at the nodes of Ranvier. There, myocilin interacts with gliomedin, neurofascin, and NrCAM, which are essential for node formation and function. Treatment of isolated dorsal root ganglion cultures with myocilin stimulates clustering of the nodal proteins neurofascin and sodium channel Nav1.2. Sciatic nerves of myocilin null mice express reduced levels of several myelin-associated and basal membrane proteins compared with those of wild-type littermates. They also demonstrate reduced myelin sheath thickness and partial disorganization of the nodes. Myocilin signaling through ErbB2/3 receptors may contribute to these observed effects. Myocilin binds to ErbB2/ErbB3, activates these receptors, and affects the downstream PI3K-AKT signaling pathway. These data implicate a role for myocilin in the development and/or maintenance of myelination and nodes of Ranvier in sciatic nerve. PMID:23897819

  10. Cool covered sky-splitting spectrum-splitting FK

    International Nuclear Information System (INIS)

    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

  11. Cool covered sky-splitting spectrum-splitting FK

    Energy Technology Data Exchange (ETDEWEB)

    Mohedano, Rubén; Chaves, Julio; Falicoff, Waqidi; Hernandez, Maikel; Sorgato, Simone [LPI, Altadena, CA, USA and Madrid (Spain); Miñano, Juan C.; Benitez, Pablo [LPI, Altadena, CA, USA and Madrid, Spain and Universidad Politécnica de Madrid (UPM), Madrid (Spain); Buljan, Marina [Universidad Politécnica de Madrid (UPM), Madrid (Spain)

    2014-09-26

    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.

  12. Cool covered sky-splitting spectrum-splitting FK

    Science.gov (United States)

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

    2014-09-01

    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.

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

    Scientific Electronic Library Online (English)

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

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

  14. Annular ray-splitting billiard

    Science.gov (United States)

    Kohler, A.; Blümel, R.

    1998-02-01

    We define and investigate in detail the annular ray-splitting (RS) billiard. We test the scaled RS correction to the Weyl formula using ? 10 5 states of a separable RS billiard. In the case of a mixed phase space a limiting nearest neighbour distribution exists only for a scaled spectrum, as computed here for the annular RS billiard. A circular, flat microwave cavity containing a teflon disk insert is proposed as an experimental realization of the annular RS billiard.

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

    Science.gov (United States)

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

    2014-04-01

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

  16. Splitting Supersymmetry in String Theory

    CERN Document Server

    Antoniadis, Ignatios

    2005-01-01

    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...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-12-01

    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.

  18. 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

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

    Science.gov (United States)

    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

    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

  20. YY1 negatively regulates mouse myelin proteolipid protein (Plp1 gene expression in oligodendroglial cells

    Directory of Open Access Journals (Sweden)

    Patricia A Wight

    2011-11-01

    Full Text Available YY1 (Yin and Yang 1 is a multifunctional, ubiquitously expressed, zinc finger protein that can act as a transcriptional activator, repressor, or initiator element binding protein. Previous studies have shown that YY1 modulates the activity of reporter genes driven by the myelin PLP (proteolipid protein (PLP1/Plp1 promoter. However, it is known that Plp1 intron 1 DNA contains regulatory elements that are required for the dramatic increase in gene activity, coincident with the active myelination period of CNS (central nervous system development. The intron in mouse contains multiple prospective YY1 target sites including one within a positive regulatory module called the ASE (anti-silencer/enhancer element. Results presented here demonstrate that YY1 has a negative effect on the activity of a Plp1-lacZ fusion gene [PLP(+Z] in an immature oligodendroglial cell line (Oli-neu that is mediated through sequences present in Plp1 intron 1 DNA. Yet YY1 does not bind to its alleged site in the ASE (even though the protein is capable of recognizing a target site in the promoter, indicating that the down-regulation of PLP(+Z activity by YY1 in Oli-neu cells does not occur through a direct interaction of YY1 with the ASE sequence. Previous studies with Yy1 conditional knockout mice have demonstrated that YY1 is essential for the differentiation of oligodendrocyte progenitors. Nevertheless, the current study suggests that YY1 functions as a repressor (not an activator of Plp1 gene expression in immature oligodendrocytes. Perhaps YY1 functions to keep the levels of PLP in check in immature cells before vast quantities of the protein are needed in mature myelinating oligodendrocytes.

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

    Directory of Open Access Journals (Sweden)

    Han Ruolan

    2008-04-01

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

  2. PROBING MYELIN AND AXON ABNORMALITIES SEPARATELY IN PSYCHIATRIC DISORDERS USING MRI TECHNIQUES

    Directory of Open Access Journals (Sweden)

    DostOngur

    2013-04-01

    Full Text Available In this manuscript we present novel MRI approaches to dissecting axon vs. myelin abnormalities in psychiatric disorders. Existing DTI approaches are not able to provide specific information on these subcellular elements but novel approaches are beginning to do so. We review two approaches (magnetization transfer ratio - MTR; and diffusion tensor spectroscopy - DTS and the theoretical framework for interpreting data derived from these approaches. Work is ongoing to collect data that will answer some relevant questions using these techniques in schizophrenia and related conditions.

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

    OpenAIRE

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

    2008-01-01

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

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

    DEFF Research Database (Denmark)

    Jensen, N A; Pedersen, Karen-Marie

    1998-01-01

    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.

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

    CERN Document Server

    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

    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...

  6. Split quaternion nonlinear adaptive filtering.

    Science.gov (United States)

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

    2010-04-01

    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

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

    Directory of Open Access Journals (Sweden)

    T. Kameswara Rao

    2014-06-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Falzon, G [Physics and Electronics, School of Biological, Biomedical and Molecular Sciences, University of New England, Armidale, NSW 2351 (Australia); Pearson, S [Physics and Electronics, School of Biological, Biomedical and Molecular Sciences, University of New England, Armidale, NSW 2351 (Australia); Murison, R [School of Mathematics, Statistics and Computer Science, University of New England, Armidale, NSW 2351 (Australia); Hall, C [School of Physics, Monash University, Victoria 3800 (Australia); Siu, K [School of Physics, Monash University, Victoria 3800 (Australia); Round, A [European Molecular Biology Laboratory, Hamburg Outstation, Notkestrasse 85, 22603 Hamburg (Germany); Schueltke, E [Division of Neurosurgery, University of Sakatchewan, Saskatoon S7N 5E5 (Canada); Kaye, A H [Department of Surgery, University of Melbourne, Parkville, 3050 (Australia); Lewis, R [Monash Centre for Synchrotron Science, Monash University, Victoria 3800 (Australia)

    2007-11-07

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

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

    OpenAIRE

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

    2007-01-01

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

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

    International Nuclear Information System (INIS)

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

  11. 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

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

    Directory of Open Access Journals (Sweden)

    Hayashi Nobuhiro

    2008-02-01

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

  13. Regulation of neuronal nitric oxide synthase by histone, protamine, and myelin basic protein.

    Science.gov (United States)

    Hu, J; Fridlund, J; el-Fakahany, E E

    1995-04-01

    We examined the effects of endogenous basic proteins rich in the amino acid L-arginine on neuronal NO synthase activity by monitoring cyclic GMP formation in intact neuron-like neuroblastoma N1E-115 cells. Histone, protamine and myelin basic protein significantly stimulated cyclic GMP formation, both in a time- and concentration-dependent manner. These effects were blocked by hemoglobin and NO synthase inhibitors. Removal of the extracellular/intracellular Ca2+ gradient by a Ca2+ chelator completely abolished the cyclic GMP responses elicited by histone and protamine, suggesting that influx of extracellular Ca2+ might be involved in their activation of NO synthase. The effects of myelin basic protein on cyclic GMP formation, however, appeared to be due to Ca2+ release from intracellular stores. In cytosolic preparations of rat cerebellum, these basic proteins inhibited the metabolism of L-arginine into L-citrulline by NO synthase. We conclude from our findings that endogenous basic proteins might be involved in the regulation of neuronal NO synthase activity. Their effects on the enzyme could be either stimulatory or inhibitory, depending on whether the basic proteins exert their effects extracellularly or intracellularly, respectively. PMID:7544448

  14. Adult mesenchymal stem cell therapy for myelin repair in Multiple Sclerosis

    Scientific Electronic Library Online (English)

    Francisco J, Rivera; Ludwig, Aigner.

    Full Text Available Multiple sclerosis (MS) is a demyelinating immune-mediated disease of the central nervous system (CNS). It is the most frequent neurological disease in young adults and affects over 2 million people worldwide. Current treatments reduce the relapse rate and the formation of inflammatory lesions in 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.

  15. Supplementation with complex milk lipids during brain development promotes neuroplasticity without altering myelination or vascular density

    Directory of Open Access Journals (Sweden)

    Rosamond B. Guillermo

    2015-03-01

    Full Text Available Background: Supplementation with complex milk lipids (CML during postnatal brain development has been shown to improve spatial reference learning in rats. Objective: The current study examined histo-biological changes in the brain following CML supplementation and their relationship to the observed improvements in memory. Design: The study used the brain tissues from the rats (male Wistar, 80 days of age after supplementing with either CML or vehicle during postnatal day 10–80. Immunohistochemical staining of synaptophysin, glutamate receptor-1, myelin basic protein, isolectin B-4, and glial fibrillary acidic protein was performed. The average area and the density of the staining and the numbers of astrocytes and capillaries were assessed and analysed. Results: Compared with control rats, CML supplementation increased the average area of synaptophysin staining and the number of GFAP astrocytes in the CA3 sub-region of the hippocampus (p<0.01, but not in the CA4 sub-region. The supplementation also led to an increase in dopamine output in the striatum that was related to nigral dopamine expression (p<0.05, but did not alter glutamate receptors, myelination or vascular density. Conclusion: CML supplementation may enhance neuroplasticity in the CA3 sub-regions of the hippocampus. The brain regions-specific increase of astrocyte may indicate a supporting role for GFAP in synaptic plasticity. CML supplementation did not associate with postnatal white matter development or vascular remodelling.

  16. Additive operator-difference schemes splitting schemes

    CERN Document Server

    Vabishchevich, Petr N

    2013-01-01

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

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

    OpenAIRE

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

    2014-01-01

    Splitting is a conventional process in most of Indian languages according to their grammar rules. It is called ‘pada vicchEdanam’ (a Sanskrit term for word splitting) and is widely used by most of the Indian languages. Splitting plays a key role in Machine Translation (MT) particularly when the source language (SL) is an Indian language. Though this splitting may not succeed completely in extracting the root words of which the compound is formed, but it shows considerable impact in Natura...

  18. Salt splitting with ceramic membranes

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-10-01

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

  19. Salt splitting using ceramic membranes

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-10-01

    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.

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

    CERN Document Server

    Gao, Changjun; Shen, You-Gen

    2015-01-01

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

  1. Myelin Activates FAK/Akt/NF-?B Pathways and Provokes CR3-Dependent Inflammatory Response in Murine System

    OpenAIRE

    Sun, Xin; Xi WANG; Chen, Tianxiang; Li, Tianyi; CAO Kai; Lu, Andrew; Chen, Yongxiong; Sun, Dongming; Luo, Jianhong; Fan, Jianqing; Young, Wise; Ren, Yi

    2010-01-01

    Inflammatory response following central nervous system (CNS) injury contributes to progressive neuropathology and reduction in functional recovery. Axons are sensitive to mechanical injury and toxic inflammatory mediators, which may lead to demyelination. Although it is well documented that degenerated myelin triggers undesirable inflammatory responses in autoimmune diseases such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), there has been v...

  2. Kif1b is essential for mRNA localization in oligodendrocytes and development of myelinated axons

    Science.gov (United States)

    Lyons, David A.; Naylor, Stephen G.; Scholze, Anja; Talbot, William S.

    2009-01-01

    The kinesin motor protein Kif1b has previously been implicated in the axonal transport of mitochondria and synaptic vesicles1,2. More recently kif1b has been linked with susceptibility to Multiple Sclerosis (MS) 3. Here we show that Kif1b is required for the localization of myelin basic protein mRNA to processes of myelinating oligodendrocytes in zebrafish. We observe the ectopic appearance of myelin-like membrane in kif1b mutants, coincident with the ectopic localization of myelin proteins in kif1b mutant oligodendrocyte cell bodies. These observations suggest the hypothesis that oligodendrocytes localize certain mRNA molecules, namely those encoding small basic proteins such as mbp, to prevent aberrant effects of these proteins elsewhere in the cell. We also find that Kif1b is required for outgrowth of some of the longest axons in the peripheral and central nervous systems. Our data demonstrate new functions of kif1b in vivo and provide insights into its possible roles in Multiple Sclerosis. PMID:19503091

  3. PTEN inhibitor bisperoxovanadium protects oligodendrocytes and myelin and prevents neuronal atrophy in adult rats following cervical hemicontusive spinal cord injury.

    Science.gov (United States)

    Walker, Chandler L; Xu, Xiao-Ming

    2014-06-24

    Cervical spinal cord injury (SCI) damages axons and motor neurons responsible for ipsilateral forelimb function and causes demyelination and oligodendrocyte death. Inhibition of the phosphatase and tensin homologue, PTEN, promotes neural cell survival, neuroprotection and regeneration in vivo and in vitro. PTEN inhibition can also promote oligodendrocyte-mediated myelination of axons in vitro likely through Akt activation. We recently demonstrated that acute treatment with phosphatase PTEN inhibitor, bisperoxovanadium (bpV)-pic reduced tissue damage, neuron death, and promoted functional recovery after cervical hemi-contusion SCI. Evidence suggests bpV can promote myelin stability; however, bpV effects on myelination and oligodendrocytes in contusive SCI models are unclear. We hypothesized that bpV could increase myelin around the injury site through sparing or remyelination, and that bpV treatment may promote increased numbers of oligodendrocytes. Using histological and immunofluorescence labeling, we found that bpV treatment promoted significant spared white matter (30%; pvehicle-treatment (1.0 ± 0.02 vs. Veh: 0.77 ± 0.02) relative to Sham neuron size. This study provides key insight into additional cell and tissue effects that could contribute to bpV-mediated functional recovery observed after contusive cervical SCI. PMID:24582904

  4. Antenna splitting functions for massive particles

    International Nuclear Information System (INIS)

    An antenna shower is a parton shower in which the basic move is a color-coherent 2?3 parton splitting process. In this paper, we give compact forms for the spin-dependent antenna splitting functions involving massive partons of spin 0 and spin 1/2.

  5. Antenna Splitting Functions for Massive Particles

    OpenAIRE

    Andrew J. Larkoski; Peskin, Michael E.

    2011-01-01

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

  6. Highly deiminated isoform of myelin basic protein from multiple sclerosis brain causes fragmentation of lipid vesicles.

    Science.gov (United States)

    Boggs, J M; Rangaraj, G; Koshy, K M; Ackerley, C; Wood, D D; Moscarello, M A

    1999-08-15

    Myelin basic protein (MBP) occurs as a number of charge isomers due to phosphorylation, deamidation, and deimination of arginine to citrulline. All of these modifications decrease the net positive charge of the protein and its ability to cause aggregation of negatively charged lipid vesicles. This is used as a model system for the ability of MBP to cause adhesion of the cytosolic surfaces of myelin. Therefore, the effect of two deiminated forms of MBP on lipid vesicles was compared with that of the unmodified, most positively charged isomer, C1, to determine how loss of positively charged arginines would affect the function of MBP. The deiminated forms were the isomer isolated from normal human brains, in which only 6 Arg are deiminated to citrulline (MBP-Cit(6)), and an isomer isolated from the brain of a patient who died with acute, fulminating multiple sclerosis (Marburg type), in which 18 of the 19 Arg were deiminated (MBP-Cit(18)). Whereas C1 caused aggregation of lipid vesicles, resulting in an increase in absorbance due to light scattering, MBP-Cit(18) caused a decrease in absorbance of the lipid vesicles. Size exclusion chromatography and negative staining electron microscopy showed that this was due to fragmentation of the large multilayered vesicles into much smaller vesicles. MBP-Cit(6) caused less aggregation of lipid vesicles than did C1. However, no fragmentation of the vesicles into smaller ones in the presence of C1 and MBP-Cit(6) was detected by size exclusion chromatography or electron microscopy. The membrane fragmentation caused by MBP-Cit(18) is dramatically different from the effects of other forms of MBP from normal brain and may indicate a pathogenic effect of this charge isomer, which may have contributed to the severity of the Marburg type of multiple sclerosis. Alternatively, the deimination may have been a secondary effect resulting from the disease process. Regardless of the role of MBP-Cit(18) in multiple sclerosis, the effect of this modification indicates that, when most of the arginines of MBP are modified to an uncharged amino acid, the protein acquires properties similar to an apolipoprotein; thus, it may take up an amphipathic structure when bound to lipid. A partly amphipathic character may also be related to the role of MBP-Cit(6) in normal immature myelin, where it is the predominant charge isomer. PMID:10440902

  7. Split donor centers and split excitons in a semiconductor heterostructure

    Science.gov (United States)

    Gribnikov, Z. S.; Haddad, G. I.

    2005-10-01

    The first subject considered in the article is a donor center embedded in a thin heterostructural barrier separating a semiconductor medium into two halves. As a result of the small thickness of this barrier, the wave function of an electron bound by the donor center shifts almost completely into both halves of the surrounding semiconductor medium. The ground and first excited electron states of such a donor center are separated from each other by a narrow energy gap determined by the symmetric-antisymmetric tunnel splitting. Such structures can be implemented in both GaAs/AlXGa1-XAs and Si/GeXSi1-X material systems. The second considered subject is an exciton formed in analogous heterostructures when the staggered band alignment takes place between the heterobarrier and semiconductor medium. As a result of such band alignment, the hole participating in the exciton creation is located in the formed quantum well and the electron, which is the hole's opponent, is separated into halves (on different sides of the quantum well) as before. Unlike the donor center, the exciton can be shifted and localized in arbitrary positions along the staggered ``barrier-well'' boundary by inhomogeneous electric fields of external controlling gates.

  8. Magnetization transfer ratio does not correlate to myelin content in the brain in the MOG-EAE mouse model.

    Science.gov (United States)

    Fjær, Sveinung; Bø, Lars; Myhr, Kjell-Morten; Torkildsen, Øivind; Wergeland, Stig

    2015-01-01

    Magnetization transfer ratio (MTR) is a magnetic resonance imaging (MRI) method which may detect demyelination not detected by conventional MRI in the central nervous system of patients with multiple sclerosis (MS). A decrease in MTR value has previously been shown to correlate to myelin loss in the mouse cuprizone model for demyelination. In this study, we investigated the sensitivity of MTR for demyelination in the myelin oligodendrocyte (MOG) 1-125 induced experimental autoimmune encephalomyelitis (EAE) mouse model. A total of 24 female c57Bl/6 mice were randomized to a control group (N?=?6) or EAE (N?=?18). MTR images were obtained at a preclinical 7 Tesla Bruker MR-scanner before EAE induction (baseline), 17-19 days (midpoint) and 31-32 days (endpoint) after EAE induction. Mean MTR values were calculated in five regions of the brain and compared to weight, EAE severity score and myelin content assessed by immunostaining for proteolipid protein and luxol fast blue, lymphocyte and monocyte infiltration and iron deposition. Contrary to what was expected, MTR values in the EAE mice were higher than in the control mice at the midpoint and endpoint. No significant difference in myelin content was found according to histo- or immunohistochemistry. Changes in MTR values did not correlate to myelin content, iron content, lymphocyte or monocyte infiltration, weight or EAE severity scores. This suggest that MTR measures of brain tissue can give significant differences between control mice and EAE mice not caused by demyelination, inflammation or iron deposition, and may not be useful surrogate markers for demyelination in the MOG1-125 mouse model. PMID:25744931

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

    OpenAIRE

    1985-01-01

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

  10. Instability of Myelin Tubes under Dehydration deswelling of layered cylindrical structures

    CERN Document Server

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

    2001-01-01

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

  11. Instability of myelin tubes under dehydration: Deswelling of layered cylindrical structures

    Science.gov (United States)

    Chen, C.-M.; Schmidt, C. F.; Olmsted, P. D.; Mackintosh, F. C.

    2001-11-01

    We report experimental observations of an undulational instability of myelin figures. Motivated by this, we examine theoretically the deformation and possible instability of concentric, cylindrical, multilamellar membrane structures. Under conditions of osmotic stress (swelling or dehydration), we find a stable, deformed state in which the layer deformation is given by ?R~rBA/(hB), where BA is the area compression modulus, B is the interlayer compression modulus, and h is the repeat distance of layers. Also, above a finite threshold of dehydration (or osmotic stress), we find that the system becomes unstable to undulations, first with a characteristic wavelength of order ?d0, where ? is the standard smectic penetration depth and d0 is the thickness of dehydrated region.

  12. Rapid release and unusual stability of immunodominant peptide 45-89 from citrullinated myelin basic protein.

    Science.gov (United States)

    Cao, L; Goodin, R; Wood, D; Moscarello, M A; Whitaker, J N

    1999-05-11

    Myelin basic protein (MBP) exists in a population of isoforms and isomers. The 18.5 kDa MBP-C1, the main human adult isoform, has 170 residues and is relatively unmodified, whereas the same isoform can be citrullinated on six arginine residues to create the MBP-C8 (MBP Cit6) isomer. MBP Cit6 dominates in MS brain, accounting for 45% rather than 25% of the population of MBP isomers. In the fulminant form of MS, known as Marburg's Disease, 18 of the 19 arginines in MBP are citrullinated (MBP Cit18). Citrullination of MBP could lead to instability of myelin or limited remyelination. In this investigation, the susceptibilities to degradation by cathepsin D of MBP Cit6 and MBP-C1, both from normal and MS brain tissue, and Marburg MBP Cit18 were compared. The pattern of digestion was similar, and no differences of corresponding isomers in normal and MS brain were noted. However, normal MBP Cit6 was degraded 10-fold more rapidly than MBP-C1, and MBP Cit18 was degraded even more rapidly. MBP peptide 45-89 was preserved regardless of isomer type or source. Its generation was directly related to the citrulline content of the MBP substrate being 4 times faster in normal MBP Cit6 and 35 times faster in Marburg MBP Cit18 than in normal MBP-C1. Peptide 45-89 from a citrullinated MBP exhibited more deamidation, and, regardless of source, showed an alpha-helix structure in a lipid mimetic environment. We postulate that the generation of MBP peptides, including those that are dominant and encephalitogenic, is directly related to deimination of arginine to citrulline in MBP. PMID:10320343

  13. Enhanced T cell responsiveness to citrulline-containing myelin basic protein in multiple sclerosis patients.

    Science.gov (United States)

    Tranquill, L R; Cao, L; Ling, N C; Kalbacher, H; Martin, R M; Whitaker, J N

    2000-08-01

    Myelin basic protein (MBP), a candidate autoantigen in multiple sclerosis (MS), exists in different isoforms and charge isomers generated by differential splicing of exons and by a combination of posttranslational modifications, respectively. These various isoforms and charge isomers of MBP vary in abundance and most likely serve different functions during myelinogenesis and remyelination. The least cationic among the charge isomers of MBP is citrullinated and is referred to as MBP-C8. MBP-C8 is relatively increased in the population of MBP isomers in more developmentally immature myelin and in MS brain tissue. In a previous study, we found that MBP-C8-reactive T cells could be detected in CD4+ T cell lines (TCL) generated with MBP from both MS patients and normal controls. Here, we examined the frequency and peptide specificity of MBP-C8-specific TCL generated with MBP-C8 in MS patients and controls. Ten subjects grouped in five sets, each an MS patient and a control, were studied. In all cases, the MS patient had either a higher overall number of MBP-C8-responding lines, responded with greater sensitivity to the MBP-C8 antigen or both. Few lines responded to the MBP-C8 peptides but, if they did, they appeared to be specific to the carboxyl-half of the MBP-C8 molecule. Given the large amounts of citrullinated MBP in MS brain tissue, a preferential T cell response to MBP-C8 may be involved in the induction and perpetuation of this disease. Multiple Sclerosis (2000) 6 220 - 225 PMID:10962541

  14. The isolation, characterization, and lipid-aggregating properties of a citrulline containing myelin basic protein.

    Science.gov (United States)

    Wood, D D; Moscarello, M A

    1989-03-25

    Human myelin basic protein was fractionated into its various charge isomers by CM52 cation exchange chromatography. Approximately 25-30% of the total charge applied to the column appeared in the void volume. This material termed "C-8," was further purified by reversed phase high performance liquid chromatography. Amino acid analyses of C-8 revealed low Arg (7 residue % in C-8 compared to 11-12 residue % in C-1) and increased Glx residues. The low Arg was accounted for by a corresponding amount of citrulline. Sequence analysis after chemical fragmentation (cyanogen bromide and BNPS-skatole) and enzymatic (cathepsin D and carboxypeptidase S-1) digestion localized the citrulline at residues 25, 31, 122, 130, 159, and 170 of the amino acid sequence. The effect of this loss of positive charge on the ability of the protein to aggregate lipid vesicles was demonstrated with vesicles composed of phosphatidylcholine (92.2 mol %) and phosphatidylserine (7.8 mol %). C-1 was the most effective charge isomer, and C-8 was the least effective. The ability of these charge isomers to aggregate vesicles correlated with the net positive charge on each. Vesicles composed of phosphatidylcholine alone were not aggregated by lipophilin or any of the charge isomers. However, when lipophilin was incorporated into phosphatidylcholine vesicles (50% w/w), small, optically clear suspensions of vesicles were formed. None of C-1, C-2, or C-3 aggregated these vesicles, but C-8 produced rapid vesicle aggregation. Since the substitution of citrulline for Arg would generate several relatively long apolar sequences, these would enhance the ability of C-8 to interact with the hydrophobic lipophilin molecule, promoting vesicle aggregation by hydrophobic interactions. The mechanism by which citrulline is generated in myelin is not known, although enzymatic conversion has been described in other systems. Studies are underway to elucidate the mechanism by which this post-translational modification is generated. PMID:2466844

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

    International Nuclear Information System (INIS)

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

  16. Innovative solar thermochemical water splitting.

    Energy Technology Data Exchange (ETDEWEB)

    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

    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.

  17. Deimination of myelin basic protein. 1. Effect of deimination of arginyl residues of myelin basic protein on its structure and susceptibility to digestion by cathepsin D.

    Science.gov (United States)

    Pritzker, L B; Joshi, S; Gowan, J J; Harauz, G; Moscarello, M A

    2000-05-01

    The effect of deimination of arginyl residues in bovine myelin basic protein (MBP) on its susceptibility to digestion by cathepsin D has been studied. Using bovine component 1 (C-1) of MBP, the most unmodified of the components with all 18 arginyl residues intact, we have generated a number of citrullinated forms by treatment of the protein with purified peptidylarginine deiminase (PAD) in vitro. We obtained species containing 0-9.9 mol of citrulline/mol of MBP. These various species were digested with cathepsin D, a metalloproteinase which cleaves proteins at Phe-Phe linkages. The rate of digestion compared to component 1 was only slightly affected when 2.7 or 3.8 mol of citrulline/mol of MBP was present. With 7.0 mol of citrulline/mol of MBP, a large increase in the rate of digestion occurred. No further increase was observed with 9.9 mol of citrulline/mol of MBP. The immunodominant peptide 43-88 (bovine sequence) was released slowly when 2.7 and 3.8 mol of citrulline/mol of MBP was present, but it was released rapidly when 7.0 mol of citrulline/mol of MBP was present. The dramatic change in digestion with 7.0 mol of citrulline/mol of MBP or more could be explained by a change in three-dimensional structure. Molecular dynamics simulation showed that increasing the number of citrullinyl residues above 7 mol/mol of MBP generated a more open structure, consistent with experimental observations in the literature. We conclude that PAD, which deiminates arginyl residues in proteins, decreases both the charge and compact structure of MBP. This structural change allows better access of the Phe-Phe linkages to cathepsin D. This scheme represents an effective way of generating the immunodominant peptide which sensitizes T-cells for the autoimmune response in demyelinating disease. PMID:10820008

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

    DEFF Research Database (Denmark)

    Moisini, Ioana; Nguyen, Phuong

    2008-01-01

    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

  19. The solar internal rotation from GOLF splittings

    OpenAIRE

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

    1998-01-01

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

  20. Split-coil-system SULTAN

    International Nuclear Information System (INIS)

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

  1. Existence Theorem for Split Involution Constraint Algebra

    Science.gov (United States)

    Batalin, I. A.; Lyakhovich, S. L.; Tyutin, I. V.

    The existence theorem is proven for the generating equations of the split involution constraint algebra. The structure of the general solution is established, and the characteristic arbitrariness in generating functions is described.

  2. Existence Theorem for Split Involution Constraint Algebra

    CERN Document Server

    Batalin, I A; Tyutin, I V

    2000-01-01

    Existence theorem is proven for the generating equations of the split involution constraint algebra. The structure of the general solution is established, and the characteristic arbitrariness in generating functions is described.

  3. Existence Theorem for Split Involution Constraint Algebra

    OpenAIRE

    Batalin, I. A.; Lyakhovich, S. L.; Tyutin, I. V.

    1998-01-01

    Existence theorem is proven for the generating equations of the split involution constraint algebra. The structure of the general solution is established, and the characteristic arbitrariness in generating functions is described.

  4. Dominated splittings for flows with singularities

    International Nuclear Information System (INIS)

    We obtain sufficient conditions for an invariant splitting over a compact invariant subset of a C1 flow Xt to be dominated. In particular, we reduce the requirements to obtain sectional hyperbolicity and hyperbolicity. (paper)

  5. Structural basis of photosynthetic water-splitting

    International Nuclear Information System (INIS)

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

  6. Curcumin Treatment Abrogates Endoplasmic Reticulum Retention and Aggregation-Induced Apoptosis Associated with Neuropathy-Causing Myelin Protein Zero–Truncating Mutants

    OpenAIRE

    Khajavi, Mehrdad ; Inoue, Ken ; Wiszniewski, Wojciech ; Ohyama, Tomoko ; Snipes, G. Jackson ; Lupski, James R. 

    2005-01-01

    Mutations in MPZ, the gene encoding myelin protein zero (MPZ), the major protein constituent of peripheral myelin, can cause the adult-onset, inherited neuropathy Charcot-Marie-Tooth disease, as well as the more severe, childhood-onset Dejerine-Sottas neuropathy and congenital hypomyelinating neuropathy. Most MPZ-truncating mutations associated with severe forms of peripheral neuropathy result in premature termination codons within the terminal or penultimate exons that are not subject to non...

  7. Replacement of split-pin assemblies in nuclear reactors

    International Nuclear Information System (INIS)

    This patent describes a pin-insertion/torque tool for the replacement of old split-pin assemblies. Each of the new split-pin assemblies including a new split-pin having times and a new nut for securing the new split pin in the guide tube, a new nut being inserted in the guide tube in position to receive a split pin. The the pin-insertion/torque tool including a blade means for engaging a new split pin with the blade with the tines of the new split pins straddling the blade, means, connected to the blade, for advancing the split-pin into the guide tube into threading engagement with the new nut positioned to receive a new split pin and means, to be connected to the nut for securing the new nut onto the new split pin while the split pin is engaged by the blade

  8. Determination of structure coefficients from splitting matrices

    OpenAIRE

    Gilbert, F.; Woodhouse, Jh

    2000-01-01

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

  9. A splitting method for stochastic programs

    OpenAIRE

    Pennanen, Teemu; Kallio, Markku

    2002-01-01

    This paper derives a new splitting-based decomposition algorithm for convex stochastic programs. It combines certain attractive features of the progressive hedging algorithm of Rockafellar and Wets, the dynamic splitting algorithm of Salinger and Rockafellar and an algorithm of Korf. We give two derivations of our algorithm. The first one is very simple, and the second one yields a preconditioner that can be used to speed up the convergence.

  10. Ink Film Splitting Acoustics in Offset Printing

    OpenAIRE

    Voltaire, Joakim

    2006-01-01

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

  11. Ray splitting in paraxial optical cavities

    OpenAIRE

    Puentes, G.; Aiello, A.; Woerdman, J. P.

    2003-01-01

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

  12. Observers and Splitting Structures in Relativistic Electrodynamics

    OpenAIRE

    Auchmann, Bernhard; Kurz, Stefan

    2014-01-01

    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 re...

  13. Mutual synergistic protein folding in split intein

    OpenAIRE

    Yuchuan Zheng; Qin Wu; Chunyu Wang; Min?qun Xu; Yangzhong Liu

    2012-01-01

    Inteins are intervening protein sequences that undergo self-excision from a precursor protein with the concomitant ligation of the flanking polypeptides. Split inteins are expressed in two separated halves, and the recognition and association of two halves are the first crucial step for initiating trans-splicing. In the present study, we carried out the structural and thermodynamic analysis on the interaction of two halves of DnaE split intein from Synechocystis sp. PCC6803. Both isolated hal...

  14. Antenna Splitting Functions for Massive Particles

    International Nuclear Information System (INIS)

    An antenna shower is a parton shower in which the basic move is a color-coherent 2 ? 3 parton splitting process. In this paper, we give compact forms for the spin-dependent antenna splitting functions involving massive partons of spin 0 and spin 1/2. 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.

  15. Spin-dependent antenna splitting functions

    International Nuclear Information System (INIS)

    We consider parton showers based on radiation from QCD dipoles or 'antennas'. These showers are built from 2?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.

  16. Split-Quaternions and the Dirac Equation

    CERN Document Server

    Antonuccio, Francesco

    2014-01-01

    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.

  17. Kondo spin splitting with slave boson

    Scientific Electronic Library Online (English)

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

    2006-09-01

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

  18. Application of Operator Splitting Methods in Finance

    OpenAIRE

    Hout, Karel In T.; Toivanen, Jari

    2015-01-01

    Financial derivatives pricing aims to find the fair value of a financial contract on an underlying asset. Here we consider option pricing in the partial differential equations framework. The contemporary models lead to one-dimensional or multidimensional parabolic problems of the convection-diffusion type and generalizations thereof. An overview of various operator splitting methods is presented for the efficient numerical solution of these problems. Splitting schemes o...

  19. Manipulating the electron current through a splitting

    OpenAIRE

    Harmer, M.; Mikhailova, A.; Pavlov, B. S.

    2007-01-01

    The description of electron current through a splitting is a mathematical problem of electron transport in quantum networks. For quantum networks constructed on the interface of narrow-gap semiconductors the relevant scattering problem for the multi-dimensional Schoedinger equation may be substituted by the corresponding problem on a one-dimensional linear graph with proper selfadjoint boundary conditions at the nodes. However, realistic boundary conditions for splittings ha...

  20. Spin-Dependent Antenna Splitting Functions

    OpenAIRE

    Andrew J. Larkoski; Peskin, Michael E.

    2009-01-01

    We consider parton showers based on radiation from QCD dipoles or `antennae'. These showers are built from 2->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.

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

    Science.gov (United States)

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

    2009-02-01

    Failure of oligodendrocyte precursor cell (OPC) differentiation contributes significantly to failed myelin sheath regeneration (remyelination) in chronic demyelinating diseases. Although the reasons for this failure are not completely understood, several lines of evidence point to factors present following demyelination that specifically inhibit differentiation of cells capable of generating remyelinating oligodendrocytes. We have previously demonstrated that myelin debris generated by demyelination inhibits remyelination by inhibiting OPC differentiation and that the inhibitory effects are associated with myelin proteins. In the present study, we narrow down the spectrum of potential protein candidates by proteomic analysis of inhibitory protein fractions prepared by CM and HighQ column chromatography followed by BN/SDS/SDS-PAGE gel separation using Nano-HPLC-ESI-Q-TOF mass spectrometry. We show that the inhibitory effects on OPC differentiation mediated by myelin are regulated by Fyn-RhoA-ROCK signalling as well as by modulation of protein kinase C (PKC) signalling. We demonstrate that pharmacological or siRNA-mediated inhibition of RhoA-ROCK-II and/or PKC signalling can induce OPC differentiation in the presence of myelin. Our results, which provide a mechanistic link between myelin, a mediator of OPC differentiation inhibition associated with demyelinating pathologies and specific signalling pathways amenable to pharmacological manipulation, are therefore of significant potential value for future strategies aimed at enhancing CNS remyelination. PMID:19208690

  2. Intersectional Cre Driver Lines Generated Using Split-Intein Mediated Split-Cre Reconstitution

    OpenAIRE

    Ping Wang; Tianrui Chen; Katsuyasu Sakurai; Bao-Xia Han; Zhigang He; Guoping Feng; Fan Wang

    2012-01-01

    Tissue and cell type highly specific Cre drivers are very rare due to the fact that most genes or promoters used to direct Cre expressions are generally expressed in more than one tissues and/or in multiple cell types. We developed a split-intein based split-Cre system for highly efficient Cre-reconstitution through protein splicing. This split-intein-split-Cre system can be used to intersect the expression patterns of two genes or promoters to restrict full-length Cre reconstitution in their...

  3. Normal centrolineal myelination of the callosal splenium reflects the development of the cortical origin and size of its commissural fibers

    Energy Technology Data Exchange (ETDEWEB)

    Whitehead, Matthew T. [University of Tennessee Health Science Center, Department of Radiology, Memphis, TN (United States); Le Bonheur Children' s Hospital, Le Bonheur Neuroscience Institute, Memphis, TN (United States); Children' s National Medical Center, Department of Radiology, Washington, DC (United States); Raju, Anand; Choudhri, Asim F. [University of Tennessee Health Science Center, Department of Radiology, Memphis, TN (United States); Le Bonheur Children' s Hospital, Le Bonheur Neuroscience Institute, Memphis, TN (United States)

    2014-04-15

    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.)

  4. Intraoperative values of S-100 protein, myelin basic protein, lactate, and albumin in the CSF and serum of neurosurgical patients

    OpenAIRE

    Vries, J.; Thijssen, W.; Snels, S.; Menovsky, T.; Peer, N.; Lamers, K.

    2001-01-01

    OBJECTIVES—To assess the concentrations of S-100 protein, myelin basic protein (MBP), and lactate, and the (CSF)/serum albumin ratio (Qalb) during intracranial neurosurgical procedures.?METHODS—Samples of CSF from 91 patients with various CNS diseases were obtained by aspiration of cisternal CSF at the beginning of surgery (before starting surgical manipulation of the brain) and concentrations of S-100 protein, MBP, and lactate, and Qalb were determined. At the same...

  5. Expression of Myelin Genes: A Comparative Analysis of Oli-neu and N20.1 Oligodendroglial Cell Lines

    OpenAIRE

    Pereira, Glauber B.; Dobretsova, Anna; Hamdan, Hamdan; Wight, Patricia A.

    2011-01-01

    The use of immortalized cells has been instrumental as a tool in which to study gene regulation. However it is crucial to understand the status of a given cell line, especially when investigating the regulation of genes whose expression is developmentally regulated. Several immortalized cell lines have been derived from primary cultures of mouse oligodendrocytes. Two such cell lines – N20.1 and Oli-neu – were characterized here in terms of their relative expression of myelin genes at both the...

  6. Cryoelectron microscopy of protein-lipid complexes of human myelin basic protein charge isomers differing in degree of citrullination.

    Science.gov (United States)

    Beniac, D R; Wood, D D; Palaniyar, N; Ottensmeyer, F P; Moscarello, M A; Harauz, G

    2000-02-01

    Myelin basic protein (MBP) is considered to be essential for the maintenance of stability of the myelin sheath. Reduction in cationicity of MBP, especially due to conversion of positively charged arginine residues to uncharged citrulline (Cit), has been found to be associated with multiple sclerosis (MS). Here, the interactions of an anionic phosphatidylserine/monosialoganglioside-G(M1) (4:1, w:w) lipid monolayer with 18.5-kDa MBP preparations from age-matched adult humans without MS (no Cit residues), with chronic MS (6 Cit), and with acute Marburg-type MS (18 Cit) were studied by transmission and ultralow dose scanning transmission electron microscopy under cryogenic conditions. Immunogold labeling and single particle electron crystallography were used to define the nature of the complexes visualized. These electron microscopical analyses showed that the three different MBP charge isomers all formed uniformly sized and regularly shaped protein-lipid complexes with G(M1), probably as hexamers, but exhibited differential association with and organization of the lipid. The least cationic Marburg MBP-Cit(18) formed the most open protein-lipid complex. The data show a disturbance in lipid-MBP interactions at the ultrastructural level that is related to degree of citrullination, and which may be involved in myelin degeneration in multiple sclerosis. PMID:10675299

  7. Fibroblast growth factor signalling in multiple sclerosis: inhibition of myelination and induction of pro-inflammatory environment by FGF9.

    Science.gov (United States)

    Lindner, Maren; Thümmler, Katja; Arthur, Ariel; Brunner, Sarah; Elliott, Christina; McElroy, Daniel; Mohan, Hema; Williams, Anna; Edgar, Julia M; Schuh, Cornelia; Stadelmann, Christine; Barnett, Susan C; Lassmann, Hans; Mücklisch, Steve; Mudaliar, Manikhandan; Schaeren-Wiemers, Nicole; Meinl, Edgar; Linington, Christopher

    2015-07-01

    Remyelination failure plays an important role in the pathophysiology of multiple sclerosis, but the underlying cellular and molecular mechanisms remain poorly understood. We now report actively demyelinating lesions in patients with multiple sclerosis are associated with increased glial expression of fibroblast growth factor 9 (FGF9), which we demonstrate inhibits myelination and remyelination in vitro. This inhibitory activity is associated with the appearance of multi-branched 'pre-myelinating' MBP(+)/PLP(+) oligodendrocytes that interact with axons but fail to assemble myelin sheaths; an oligodendrocyte phenotype described previously in chronically demyelinated multiple sclerosis lesions. This inhibitory activity is not due to a direct effect of FGF9 on cells of the oligodendrocyte lineage but is mediated by factors secreted by astrocytes. Transcriptional profiling and functional validation studies demonstrate that these include effects dependent on increased expression of tissue inhibitor of metalloproteinase-sensitive proteases, enzymes more commonly associated with extracellular matrix remodelling. Further, we found that FGF9 induces expression of Ccl2 and Ccl7, two pro-inflammatory chemokines that contribute to recruitment of microglia and macrophages into multiple sclerosis lesions. These data indicate glial expression of FGF9 can initiate a complex astrocyte-dependent response that contributes to two distinct pathogenic pathways involved in the development of multiple sclerosis lesions. Namely, induction of a pro-inflammatory environment and failure of remyelination; a combination of effects predicted to exacerbate axonal injury and loss in patients. PMID:25907862

  8. Pelizaeus-Merzbacher disease: a valine to phenylalanine point mutation in a putative extracellular loop of myelin proteolipid.

    Science.gov (United States)

    Pham-Dinh, D; Popot, J L; Boespflug-Tanguy, O; Landrieu, P; Deleuze, J F; Boué, J; Jollès, P; Dautigny, A

    1991-01-01

    In the central nervous system, myelin proteolipid protein isoforms (PLP and DM20) play an essential structural role in myelination. It has been shown in several species that myelination is impaired by molecular defects resulting from single base mutations in the PLP gene. We have used DNA amplification by polymerase chain reaction to study the PLP gene coding regions from 17 patients in 15 unrelated families with similar Pelizaeus-Merzbacher phenotype. In one case amplification of peripheral nerve PLP/DM20 cDNAs revealed that a silent T----C transition was unrelated to the disease. In one family a nonsilent mutation was identified that leads to a phenylalanine substitution for valine-218 in PLP/DM20 proteins. We investigated the inheritance of the mutant allele in 19 subjects of this four-generation family and found a strict cosegregation of the Phe218 substitution with transmission and expression of the disease. The effect of the Val218----Phe mutation is discussed in the frame of a recently suggested topological model of PLP/DM20, according to which Val218 is part of an extracellular loop that connects the last two of four membrane-spanning alpha-helices. Images PMID:1715570

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

    DEFF Research Database (Denmark)

    Jensen, N A; Pedersen, Karen-Marie

    1998-01-01

    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.

  10. On the additive splitting procedures and their computer realization

    DEFF Research Database (Denmark)

    Farago, I.; Thomsen, Per Grove

    2008-01-01

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

  11. Adduction of cholesterol 5,6-secosterol aldehyde to membrane-bound myelin basic protein exposes an immunodominant epitope.

    Science.gov (United States)

    Cygan, Natalie K; Scheinost, Johanna C; Butters, Terry D; Wentworth, Paul

    2011-03-29

    Myelin degradation in the central nervous system (CNS) is a clinical hallmark of multiple sclerosis (MS). A reduction in the net positive charge of myelin basic protein (MBP) via deimination of arginine to citrulline has been shown to correlate strongly with disease severity and has been linked to myelin instability and a defect that precedes neurodegeneration and leads to autoimmune attack. Recently, we have shown that lipid-derived aldehydes, such as cholesterol 5,6-secosterols atheronal A (1a) and atheronal B (1b), modulate the misfolding of certain proteins such as apolipoprotein B(100), ?-amyloid, ?-synuclein, and ?- and ?-antibody light chains in a process involving adduction of the hydrophobic aldehyde to lysine side chains, resulting in a decrease in the net positive charge of the protein. In this study, we show that the presence of either atheronal A (1a) or atheronal B (1b) in large unilamellar vesicles (cyt-LUVs) with the lipid composition found in the cytosolic myelin sheath and bovine MBP (bMBP) leads to an atheronal concentration-dependent increase in the surface exposure of the immunodominant epitope (V86-T98) as determined by antibody binding. Other structural changes in bMBP were also observed; specifically, 1a and 1b induce a decrease in the surface exposure of L36-P50 relative to control cyt-LUVs as measured both by antibody binding and by a reduction in the level of cathepsin D proteolysis of F42 and F43. Structure-activity relationship studies with analogues of 1a and 1b point to the aldehyde moiety of both compounds being critical to their effects on bMBP structure. The atheronals also cause a reduction in the size of the bMBP-cyt-LUV aggregates, as determined by fluorescence microscopy and dynamic light scattering. These results suggest that formation of an imine between inflammatory-derived aldehydes, which effectively reduces the cationic nature of MBP, can lead to structural changes in MBP and a decrease in myelin stability akin to deimination and as such may make a hitherto unknown contribution to the onset and progression of MS. PMID:21314187

  12. Multiple epitopes in a dodecapeptide of myelin basic protein determined bymonoclonal antibodies

    International Nuclear Information System (INIS)

    Three custom synthesized myelin basic protein (MBP) peptides, bovine peptide 79-88, human peptide 80-89, and human peptide 82-91, were used to produce four murine monoclonal antibodies (MAb) that were selected on the basis of reaction in a solid phase radioimmunoassay (SRIA) with human MBP. The MAb were compared with respect to antigen specificity against intact MBP and 10 overlapping MBP peptides. One MAb recognized an epitope near the amino-terminus of bovine MBP peptide 79-88. A second MAb was directed towards an epitope that is more reactive in human MBP peptide 45-89 than in intact MBP, but is not recognized in any of the small MBP peptides examined. The third MAb detected an epitope near the middle of human MBP peptide 80-89, whereas the fourth MAb reacted with the carboxyl-terminal portion of human MBP peptide 82-91. Epitopes recognized in SRIA were sometimes not detected by the same MAb in a fluid phase double antibody radioimmunoassay. These results demonstrate the multiplicity of potential epitopes in a dodecapeptide of MBP and do not support the concept of a single, dominant epitope in the region of MBP peptide 80-89

  13. Analysis of chemokines and receptors expression profile in the myelin mutant taiep rat.

    Science.gov (United States)

    Soto-Rodriguez, Guadalupe; Gonzalez-Barrios, Juan-Antonio; Martinez-Fong, Daniel; Blanco-Alvarez, Victor-Manuel; Eguibar, Jose R; Ugarte, Araceli; Martinez-Perez, Francisco; Brambila, Eduardo; Millán-Perez Peña, Lourdes; Pazos-Salazar, Nidia-Gary; Torres-Soto, Maricela; Garcia-Robles, Guadalupe; Tomas-Sanchez, Constantino; Leon-Chavez, Bertha Alicia

    2015-01-01

    Taiep rat has a failure in myelination and remyelination processes leading to a state of hypomyelination throughout its life. Chemokines, which are known to play a role in inflammation, are also involved in the remyelination process. We aimed to demonstrate that remyelination-stimulating factors are altered in the brainstem of 1- and 6-month-old taiep rats. We used a Rat RT(2) Profiler PCR Array to assess mRNA expression of 84 genes coding for cytokines, chemokines, and their receptors. We also evaluated protein levels of CCL2, CCR1, CCR2, CCL5, CCR5, CCR8, CXCL1, CXCR2, CXCR4, FGF2, and VEGFA by ELISA. Sprague-Dawley rats were used as a control. PCR Array procedure showed that proinflammatory cytokines were not upregulated in the taiep rat. In contrast, some mRNA levels of beta and alpha chemokines were upregulated in 1-month-old rats, but CXCR4 was downregulated at their 6 months of age. ELISA results showed that CXCL1, CCL2, CCR2, CCR5, CCR8, and CXCR4 protein levels were decreased in brainstem at the age of 6 months. These results suggest the presence of a chronic neuroinflammation process with deficiency of remyelination-stimulating factors (CXCL1, CXCR2, and CXCR4), which might account for the demyelination in the taiep rat. PMID:25883747

  14. Localization of methylated arginine in the A1 protein from myelin.

    Science.gov (United States)

    Brostoff, S; Eylar, E H

    1971-04-01

    Methylated arginine residues are found at only one site (position 107) of the polypeptide chain of the A1 protein, as shown by analysis of tryptic and peptic peptides; these analyses show 0.2 mole of N(G)-dimethylarginine and 0.4-0.8 mole of N(G)-monomethylarginine per mole of A1 protein. The methylated arginine residues appeared to be relatively resistant to tryptic attack. Both methylated derivatives were isolated from an enzymatic digest of the A1 protein; they were identified by chromatography, electrophoresis, and degradation to citrulline, methylamine, and ornithine on alkaline hydrolysis. The phylogenetic importance of the methylated derivatives was shown by their presence in the human, monkey, bovine, rabbit, guinea pig, rat, chicken, and turtle A1 proteins at the analogous position to that of the bovine sequence: [Formula: see text] We postulate that the methylated arginine residues may serve an important role in the myelin membrane in situ by stabilization of a double-chain structure for the A1 protein; such a double-chain conformation is induced by a (proline)(3) sequence located nearby. PMID:4994464

  15. IgG reactivity against citrullinated myelin basic protein in multiple sclerosis.

    Science.gov (United States)

    de Seze, J; Dubucquoi, S; Lefranc, D; Virecoulon, F; Nuez, I; Dutoit, V; Vermersch, P; Prin, L

    2001-07-01

    An increased level of citrullinated myelin basic protein (MBP-C8) has been reported in the brains of multiple sclerosis (MS) patients. However, the involvement of the immune response to post-translational modified MBP in the pathophysiology of MS remains speculative. The aim of this study was to compare the levels of immunoglobulin G antibodies to several MBP epitopes, before and after citrullination, in the cerebrospinal fluid (CSF) and sera of MS patients using enzyme-linked immunosorbent assay (ELISA). We analyzed antibody reactivity against various MBP-peptides in the CSF and sera of 60 MS patients, and 30 patients with other neurological diseases (OND) as controls. The peptides tested were: MBP(75-98) (peptide 1), native (peptide 2) and citrullinated (peptide 3) MBP(108-126) (ARG(122)-->Cit(122)), and native (peptide 4) and citrullinated (peptide 5) MBP(151-170) (ARG(159, 170)-->Cit(159, 170)). All selected peptides could support an immune reactivity in CSF and sera of MS and OND patients. A higher reactivity against peptide 4 was found in the CSF of MS patients compared with OND patients (Pcitrullinated peptides (peptides 3 and 5). However, we observed that the citrullination state of peptide 2 modified the patterns of immune reactivity more markedly in MS patients (Pcitrullinated forms. PMID:11431015

  16. Acute multiple sclerosis (Marburg type) is associated with developmentally immature myelin basic protein.

    Science.gov (United States)

    Wood, D D; Bilbao, J M; O'Connors, P; Moscarello, M A

    1996-07-01

    We have studied a case of acute, fulminating multiple sclerosis (MS) (Marburg type) at the pathological and biochemical levels. Postmortem examination of the brain revealed extensive areas of gross rarefaction in the hemispheric white matter. Histologically, well-demarcated areas of demyelination with a large influx of macrophages and a subtle perivascular infiltration of lymphocytes were seen with relative preservation of the axis cylinders. Myelin basic protein (MBP) was isolated and purified [correction of purifed] from noninvolved white matter. It was slightly larger in molecular weight than MBP from normal brain or from chronic MS brain. The increase in mass was accounted for, in part, by the deimination of 18 of 19 arginyl residues to citrulline, making the patient's MBP much less cationic than MBP from normal white matter. When expressed as the ratio of least cationic form of MBP to the most cationic (C-8/C-1), the normal ratio was 0.82, chronic MS 2.5, and the patient in this study 6.7. Because the ratio of 6.7 was similar to 7.5 found for a 15-month-old infant, MBP was considered to be of the immature form. The data are consistent with a genetic factor influencing the charge microheterogeneity of MBP. The resulting less cationic MBP cannot carry out its normal function of compacting multilayers. PMID:8687186

  17. Loss of myelin basic protein cationicity in DM20 transgenic mice is dosage dependent.

    Science.gov (United States)

    Mastronardi, F G; Ackerley, C A; Roots, B I; Moscarello, M A

    1996-05-15

    Demyelination in the transgenic mice depended on the dosage of the cDNA for DM20, in which low copy numbers (two to four and 17 copies of the minigene) showed no signs of demyelination. However when transgenic mice with 17 copies were made homozygous with 34 copies of the DM20 minigene (ND3A hm.) demyelination was observed at around 12 to 16 months compared with ND4 mice having 70 copies of the transgene which had an earlier onset of demyelinating symptoms at 3 months, demonstrating a transgene dosage effect. The process by which demyelination was initiated was associated with changes in myelin basic protein. An increased abundance of less cationic MBP (C-8) isomers occurred prior to demyelination. This increase was also associated with increased activity of peptidylarginine deiminase, the enzyme which converts arginine to citrulline in proteins, thereby providing a mechanism for generating less cationic forms of MBP. These data support a dosage effect of the DM20 transgene. PMID:8739149

  18. An immunochemical comparison of human myelin basic protein and its modified, citrullinated form, C8.

    Science.gov (United States)

    Whitaker, J N; Kirk, K A; Herman, P K; Zhou, S R; Goodin, R R; Moscarello, M A; Wood, D D

    1992-02-01

    An immunochemical analysis was conducted to compare the C1 isomer of human myelin basic protein (MBP) with the newly described and less cationic, citrullinated isomer of MBP referred to as C8. Ten polyclonal antisera directed at multiple epitopes or restricted regions of MBP were used in radioimmunoassays to examine MBP-C1 and MBP-C8. Antisera reactive with MBP peptide 1-14 clearly distinguished MBP-C1 from MBP-C8. Antisera to human MBP peptides 10-19 and 90-170, but not to MBP peptide 69-89, showed modest differences between MBP-C1 and MBP-C8. The MBP-C8s from multiple sclerosis (MS) and non-MS brain reacted essentially the same. With murine monoclonal antibodies and enzyme-linked immunosorbent assay (ELISA), differences between MBP-C8 and other isomers were shown for anti-MBP 10-19 but not for anti-MBP 1-9 or anti-MBP 80-89. These findings imply differences in sequence or conformation in the structure of MBP-C7 compared to MBP-C1, most notably near the amino terminus. PMID:1370666

  19. Characterization of fatty acid binding by the P2 myelin protein

    International Nuclear Information System (INIS)

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

  20. Process outgrowth in oligodendrocytes is mediated by CNP, a novel microtubule assembly myelin protein

    Science.gov (United States)

    Lee, John; Gravel, Michel; Zhang, Rulin; Thibault, Pierre; Braun, Peter E.

    2005-01-01

    Oligodendrocytes (OLs) extend arborized processes that are supported by microtubules (MTs) and microfilaments. Little is known about proteins that modulate and interact with the cytoskeleton during myelination. Several lines of evidence suggest a role for 2?,3?-cyclic nucleotide 3?-phosphodiesterase (CNP) in mediating process formation in OLs. In this study, we report that tubulin is a major CNP-interacting protein. In vitro, CNP binds preferentially to tubulin heterodimers compared with MTs and induces MT assembly by copolymerizing with tubulin. CNP overexpression induces dramatic morphology changes in both glial and nonglial cells, resulting in MT and F-actin reorganization and formation of branched processes. These morphological effects are attributed to CNP MT assembly activity; branched process formation is either substantially reduced or abolished with the expression of loss-of-function mutants. Accordingly, cultured OLs from CNP-deficient mice extend smaller outgrowths with less arborized processes. We propose that CNP is an important component of the cytoskeletal machinery that directs process outgrowth in OLs. PMID:16103231

  1. 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)

  2. Novel Characteristics of Split Trees by use of Renewal Theory

    OpenAIRE

    Holmgren, Cecilia

    2010-01-01

    We investigate characteristics of random split trees introduced by Devroye; split trees include for example binary search trees, $m$-ary search trees, quadtrees, median of $(2k+1)$-trees, simplex trees, tries and digital search trees. More precisely: We introduce the use of renewal theory in the studies of split trees, and use this theory to prove several results about split trees. A split tree of cardinality $n$ is constructed by distributing $n$ "balls" (which often repres...

  3. Observers and splitting structures in relativistic electrodynamics

    Science.gov (United States)

    Auchmann, B.; Kurz, S.

    2014-10-01

    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.

  4. Spin-orbit splitting of image states

    CERN Document Server

    McLaughlan, J R; Crampin, S

    2004-01-01

    We quantify the effect of the spin-orbit interaction on the Rydberg-like series of image state electrons at the (111) and (001) surface of Ir, Pt and Au. Using relativistic multiple-scattering methods we find Rashba-like dispersions with Delta E(K)=gamma K with values of gamma for n=1 states in the range 38-88 meV Angstrom. Extending the phase-accumulation model to include spin-orbit scattering we find that the splittings vary like 1/(n+a)^3 where a is the quantum defect and that they are related to the probability of spin-flip scattering at the surface. The splittings should be observable experimentally being larger in magnitude than some exchange-splittings that have been resolved by inverse photoemission, and are comparable to linewidths from inelastic lifetimes.

  5. SKS splitting measurements with horizontal component misalignment

    Science.gov (United States)

    Tian, Xiaobo; Zhang, Jianli; Si, Shaokun; Wang, Jingbo; Chen, Yun; Zhang, Zhongjie

    2011-04-01

    The measurement of SKS splitting parameters is widely used for the study of deformation in the upper mantle, but the misalignment of the station horizontal components, for example misorientation of the sensors, may result in false measurements. In this paper, we suggest that the splitting analysis should be repeated with different assumed angles of misalignment. Two criteria can be applied to correct the measurement of the SKS splitting parameters: (1) the horizontal rotating angle should produce the global minimum transverse energy, as determined using the least transverse energy method; (2) there should be consistent results between the least transverse energy method and the minimum eigenvalue method. Model tests show that the method is suitable for complex anisotropy models, such as two-layer anisotropy.

  6. Reflection hologram solar spectrum-splitting filters

    Science.gov (United States)

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

    2012-10-01

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

  7. 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)

  8. Splitting methods for the nonlocal Fowler equation

    CERN Document Server

    Bouharguane, Afaf

    2011-01-01

    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.

  9. Sunspot splitting triggering an eruptive flare

    OpenAIRE

    Louis, Rohan E.; Puschmann, Klaus G.; Kliem, Bernhard; Balthasar, Horst; Denker, Carsten

    2013-01-01

    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 mix...

  10. Hyperfine splitting in lithium-like bismuth

    International Nuclear Information System (INIS)

    High-precision measurements of the hyperfine splitting values on Li- and H-like bismuth ions, combined with precise atomic structure calculations allow us to test QED-effects in the regime of the strongest magnetic fields that are available in the laboratory. Performing laser spectroscopy at the experimental storage ring (ESR) at GSI Darmstadt, we have now succeeded in measuring the hyperfine splitting in Li-like bismuth. Probing this transition has not been easy because of its extremely low fluorescence rate. Details about this challenging experiment will be given and the achieved experimental accuracy are presented.

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

    Directory of Open Access Journals (Sweden)

    Sand Jette C

    2010-04-01

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

  12. A critical review of pro-cognitive drug targets in psychosis: Convergence on myelination and inflammation.

    Directory of Open Access Journals (Sweden)

    Rune A.Kroken

    2014-02-01

    Full Text Available Antipsychotic drugs have thus far focused on dopaminergic antagonism at the D2 receptors, as counteracting the hyperdopaminergia in nigrostriatal and mesolimbic projections has been considered mandatory for the antipsychotic action of the drugs. Current drugs effectively target the positive symptoms of psychosis such as hallucinations and delusions in the majority of patients, whereas effect sizes are smaller for negative symptoms and cognitive dysfunctions. With the understanding that neurocognitive dysfunction associated with schizophrenia have a greater impact on functional outcome than the positive symptoms, the focus in pharmacotherapy for schizophrenia has shifted to the potential effect of future drugs on cognitive enhancement. A major obstacle is, however, that the biological underpinnings of cognitive dysfunction remain largely unknown. With the availability of increasingly sophisticated techniques in molecular biology and brain imaging, this situation is about to change, with major advances being made in identifying the neuronal substrates underlying schizophrenia, and putative pro-cognitive drug targets may be revealed. In relation to cognitive effects, this review focuses on evidence from basic neuroscience and clinical studies, taking two separate perspectives. One perspective is the identification of previously under-recognized treatment targets for existing antipsychotic drugs, including myelination and mediators of inflammation. A second perspective is the development of new drugs or novel treatment targets for well-known drugs which act on recently discovered treatment targets for cognitive enhancement, and which may complement the existing drugs. This might pave the way for personalized treatment regimens for patients with schizophrenia aimed at improved functional outcome. The review also aims at identifying major current constraints for pro-cognitive drug development for patients with schizophrenia.

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

    Science.gov (United States)

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

    2010-03-15

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

  14. Uptake and presentation of myelin basic protein by normal human B cells

    DEFF Research Database (Denmark)

    Brimnes, Marie Klinge; Hansen, Bjarke Endel

    2014-01-01

    B cells may play both pathogenic and protective roles in T-cell mediated autoimmune diseases such as multiple sclerosis (MS). These functions relate to the ability of B cells to bind and present antigens. Under serum-free conditions we observed that 3-4% of circulating B cells from healthy donors were capable of binding the MS-associated self-antigen myelin basic protein (MBP) and of presenting the immunodominant peptide MBP85-99, as determined by staining with the mAb MK16 recognising the peptide presented by HLA-DR15-positive cells. In the presence of serum, however, the majority of B cells bound MBP in a complement-dependent manner, and almost half of the B cells became engaged in presentation of MBP85-99. Even though complement receptor 1 (CR1, CD35) and CR2 (CD21) both contributed to binding of MBP to B cells, only CR2 was important for the subsequent presentation of MBP85-99. A high proportion of MBP85-99 presenting B cells expressed CD27, and showed increased expression of CD86 compared to non-presenting B cells. MBP-pulsed B cells induced a low frequency of IL-10-producing CD4+ T cells in 3 out of 6 donors, indicating an immunoregulatory role of B cells presenting MBP-derived peptides. The mechanisms described here refute the general assumption that B-cell presentation of self-antigens requires uptake via specific B-cell receptors, and may be important for maintenance of tolerance as well as for driving T-cell responses in autoimmune diseases.

  15. How big is the myelinating orchestra? Cellular diversity within the oligodendrocyte lineage: facts and hypotheses.

    Directory of Open Access Journals (Sweden)

    Giulio Srubek Tomassy

    2014-07-01

    Full Text Available Since monumental studies from scientists like His, Ramón y Cajal, Lorente de Nó and many others have put down roots for modern neuroscience, the scientific community has spent a considerable amount of time, and money, investigating any aspect of the evolution, development and function of neurons. Today, the complexity and diversity of myriads of neuronal populations is still focus of extensive studies in hundreds of laboratories around the world. However, our prevalent neuron-centric perspective has dampened the efforts in understanding glial cells, even though their active participation in the brain physiology and pathophysiology has been increasingly recognized over the years. Among all glial cells of the central nervous system (CNS, oligodendrocytes (OLs are a particularly specialized type of cells that provide fundamental support to neuronal activity by producing the myelin sheath. Despite their functional relevance, the developmental mechanisms regulating the generation of OLs are still poorly understood. In particular, it is still not known whether these cells share the same degree of heterogeneity of their neuronal companions and whether multiple subtypes exist within the lineage. Here, we will review and discuss current knowledge about OL development and function in the brain and spinal cord. We will try to address some specific questions: do multiple OL subtypes exist in the CNS? What is the evidence for their existence and those against them? What are the functional features that define an oligodendrocyte? We will end our journey by reviewing recent advances in human pluripotent stem cell differentiation towards OLs. This exciting field is still at its earliest days, but it is quickly evolving with improved protocols to generate functional OLs from different spatial origins. As stem cells constitute now an unprecedented source of human OLs, we believe that they will become an increasingly valuable tool for deciphering the complexity of human OL identity.

  16. Conformational epitopes of myelin oligodendrocyte glycoprotein are targets of potentially pathogenic antibody responses in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Menge Til

    2011-11-01

    Full Text Available Abstract Background Myelin/oligodendrocyte glycoprotein (MOG is a putative autoantigen in multiple sclerosis (MS. Establishing the pathological relevance and validity of anti-MOG antibodies as biomarkers has yielded conflicting reports mainly due to different MOG isoforms used in different studies. Because epitope specificity may be a key factor determining anti-MOG reactivity we aimed at identifying a priori immunodominant MOG epitopes by monoclonal antibodies (mAbs and at assessing clinical relevance of these epitopes in MS. Methods Sera of 325 MS patients, 69 patients with clinically isolated syndrome and 164 healthy controls were assayed by quantitative, high-throughput ELISA for reactivity to 3 different MOG isoforms, and quantitative titers correlated with clinical characteristics. mAbs defined unique immunodominant epitopes distinct to each of the isoforms. Results In the majority of human samples anti-MOG levels were skewed towards low titers. However, in 8.2% of samples high-titer anti-MOG antibodies were identified. In contrast to anti-MOG reactivity observed in a mouse model of MS, in patients with MS these never reacted with ubiquitously exposed epitopes. Moreover, in patients with relapsing-remitting MS high-titer anti-MOG IgG correlated with disability (EDSS; Spearman r = 0.574; p = 0.025. Conclusions Thus high-titer reactivity likely represents high-affinity antibodies against pathologically relevant MOG epitopes, that are only present in a small proportion of patients with MS. Our study provides valuable information about requirements of anti-MOG reactivity for being regarded as a prognostic biomarker in a subtype of MS.

  17. A HISTOLOGICAL COMPARISON OF MYELINATED NERVE FIBERS BETWEEN THE EXTERNAL AND EXTREME CAPSULES IN HUMAN BRAIN

    Directory of Open Access Journals (Sweden)

    HAGHIR H

    2001-01-01

    Full Text Available Introduction: To recognize the myelinated nerve fibers of the external and extreme capsules in human brain. Materials and Methods: 10 adult and normal brains (20 hemispheres from both sexes were studied using 15 mm serial secions in all three cardinal planes after fixation and processing. These sections were stained by Klüver – Barrera and Heidenhin – Woelcke methods. Results: Some fibers from different parts of the cortex through corona radiata entered the dorsal border of the external capsule, These fibers moved ventraly and ventrocaudaly toward the ventral border of the external capsule, and most of them entered the cerebral peduncles trans -, sub-, or retrolenticularly. Some fibers passed through dorsal part of putamen and connected the external capsule with posterior limb of the internal capsule. Some fibers passed between rostrum of corpus callosum and venteral part of the external capsule. Some fibers traced from the external capsule to posterior bundle of the anterior commissure; some of them entered the commissure but others terminated in nucleus basalis (Meynert neurons. Some fibers passed through rostral part of the external and extreme capsules.Most of the fibers of the extreme capsule interconnected the temporal and frontoparietal operculi with the insular gyri, or with each other. A group of the extreme capsule fibers connected the adjacent insular gyri with each other. Some fibers exchanged between the extreme capsule and the claustrum. There were fibers which went between the external and extreme capsules through the dorsal claustrum. Conclusion: It is concluded that the external capsule contains all three groups of fibers, but it is mainly projectional; on the other hand, the extreme capsule is mainly associational. Thus, in our opinion, these two capsules should be classified in different groups.

  18. Cell-free synthesis of the four mouse myelin basic proteins

    International Nuclear Information System (INIS)

    A homologous in vitro protein synthesizing system from mouse brain was developed to test the hypothesis that a precursor-product relationship exists among the 4 forms of the mouse myelin basic proteins (MBP). This system consists of free polysomes, pH 5 enzymes and initiation factors. The incorporation of L-35S-met into the 4 MBPs (14K, 17K, 18.5K, and 21.5K) was detected by immunoprecipitation of the in vitro products of synthesis followed by polyacrylamide gel electrophoresis in sodium dodecyl sulfate (SDS). The 4 MBPs were identified by their cross-reactivity with purified MBP antibodies and their apparent molecular weights in SDS gels. Using the brain cell-free system three types of experiments were carried out which suggested that no metabolic relationship exists among the 4 forms of MBPs: (1) In a time-course experiment, the incorporation of L-35S-met into all 4 MBPs increased in proportion to the incubation time. (2) In pulse-labeling experiments, the incorporation of L-35S-met into 4 MBPs was stopped was stopped by the addition of puromycin or a 600-fold excess of unlabeled L-met after 2.5 min of incubation. (3) When polysomes were separated into 5 fractions of different size classes and incubated in the in vitro system, the relative proportion of each of the 4 MBPs differed with ribosomal fraction examined. Mouse strain mRNA was translated in rabbit reticulocyte lysates which were supplemented with pH 5 enzymes and initiation lemented with pH 5 enzymes and initiation factors. A time-course study and pulse labeling experiments were performed as in the homologous system. The results of these studies provided further evidence that the 4 MBPs are the primary translation products of independent mRNAs and are not metabolically related

  19. Spin splitting in 2D monochalcogenide semiconductors

    CERN Document Server

    Do, Dat T; Lai, Chih-Wei

    2015-01-01

    We report ab initio calculations of the spin splitting of the uppermost valence band (UVB) and the lowermost conduction band (LCB) in bulk and atomically thin GaS, GaSe, GaTe, and InSe. These layered monochalcogenides appear in four major polytypes ($\\epsilon$, $\\beta$, $\\gamma$, and $\\delta$) depending on the stacking order, except for the monoclinic GaTe. Bulk and few-layer $\\epsilon$- and $\\gamma$-type, as well as odd-number few-layer $\\beta$-type GaS, GaSe, and InSe crystals are noncentrosymmetric. The spin splittings of the UVB and the LCB near the $\\Gamma$ point in the Brillouin zone are finite, but still smaller than those in a zinc-blende semiconductor, such as GaAs. On the other hand, the spin splitting is zero in centrosymmetric bulk and even-number few-layer $\\beta$-type GaS, GaSe, and InSe, owing to the constraint of spatial inversion symmetry. By contrast, GaTe exhibits zero spin splitting because it is centrosymmetric down to a single layer. The electron and hole spin relaxation times in these s...

  20. Frobenius splitting of certain rings of invariants

    CERN Document Server

    Lakshmibai, V; Sankaran, P

    2009-01-01

    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.

  1. Czech, Slovak science ten years after split

    CERN Multimedia

    2003-01-01

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

  2. Decoherence-induced wave packet splitting

    CERN Document Server

    Chough, Y T; Kim, S W; Youn, S H; An, K; Chough, Young-Tak; Nha, Hyunchul; Kim, Sang Wook; Youn, Sun-Hyun; An, Kyungwon

    2001-01-01

    We provide an intuitive interpretation of the optical Stern-Gerlach effect (OSGE) in the dressed-state point of view. We also analyze the effect of atomic damping in an experiment on the OSGE. We show that the atomic damping also causes the wave packet splitting, in a non-mechanical fashion, as opposed to the coherent process that is mechanical.

  3. Split-Care Patients and Their Caregivers

    Science.gov (United States)

    Baruch, Rachel Levine; Vishnevsky, Bella; Kalman, Thomas

    2015-01-01

    Abstract This study assessed the experiences of patients receiving split-care treatment, focusing on communication between the two treating professionals and its impact on patient satisfaction. Studies have documented that for more than 20% of patients, no communication occurs between providers, and the present study provides further data. Split-care patients completed a 23-item questionnaire on SurveyMonkey via Mechanical Turk, a crowd-sourcing Website, assessing patients’ split-care experiences, including whether their providers had communicated and the impact of communication on patients’ satisfaction with treatment. Of respondents who knew if their providers communicated, 30% reported that no communication occurred. Similarly, 30% and 36% of respondents were never asked by their psychotherapist or psychopharmacologist, respectively, for permission to speak to the other professional. Non-communication yielded significantly lower patient satisfaction with treatment. This study replicates the high frequency of non-communication between providers of split care and has great implications for the impact of communication on treatment compliance and outcome. PMID:25938507

  4. Forward-Backward Splitting with Bregman Distances

    OpenAIRE

    Nguyen, Quang

    2015-01-01

    We propose a forward-backward splitting algorithm based on Bregman distances for composite minimization problems in general reflexive Banach spaces. The convergence is established using the notion of variable quasi-Bregman monotone sequences. Various examples are discussed, including some in Euclidean spaces, where new algorithms are obtained.

  5. Splitting up Beta’s change

    OpenAIRE

    Suarez, Ronny

    2014-01-01

    In this paper we estimated IBM beta from 2000 to 2013, then using differential equation mathematical formula we split up the annual beta’s change attributed to the volatility market effect, the stock volatility effect, the correlation effect and the jointly effect of these variables.

  6. Isospin Splittings of Doubly Heavy Baryons

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-08-18

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

  7. Planar microfluidic drop splitting and merging.

    Science.gov (United States)

    Collignon, Sean; Friend, James; Yeo, Leslie

    2015-03-31

    Open droplet microfluidic platforms offer attractive alternatives to closed microchannel devices, including lower fabrication cost and complexity, significantly smaller sample and reagent volumes, reduced surface contact and adsorption, as well as drop scalability, reconfigurability, and individual addressability. For these platforms to be effective, however, they require efficient schemes for planar drop transport and manipulation. While there are many methods that have been reported for drop transport, it is far more difficult to carry out other drop operations such as dispensing, merging and splitting. In this work, we introduce a novel alternative to merge and, more crucially, split drops using laterally-offset modulated surface acoustic waves (SAWs). The energy delivery into the drop is divided into two components: a small modulation amplitude excitation to initiate weak rotational flow within the drop followed by a short burst in energy to induce it to stretch. Upon removal of the SAW energy, capillary forces at the center of the elongated drop cause the liquid in this capillary bridge region to drain towards both ends of the drop, resulting in its collapse and therefore the splitting of the drop. This however occurs only below a critical Ohnesorge number, which is a balance between the viscous forces that retard the drainage and the sufficiently large capillary forces that cause the liquid bridge to pinch. We show the possibility of reliably splitting drops into two equal sized droplets with an average deviation in their volumes of only around 4% and no greater than 10%, which is comparable to the 7% and below splitting deviation obtained with electrowetting drop splitting techniques. In addition, we also show that it is possible to split the drop asymmetrically to controllably and reliably produce droplets of different volumes. Such potential as well as the flexibility in tuning the device to operate on drops of different sizes without requiring electrode reconfiguration, i.e., the use of different devices, as is required in electrowetting-therefore makes the present method an attractive alternative to electrowetting schemes. PMID:25738425

  8. Comet Splitting - Observations and Model Scenarios

    Science.gov (United States)

    Boehnhardt, Hermann

    2000-10-01

    Splitting events affect cometary nuclei to a different level of severity ranging from complete disruption of the nucleus (e.g., C/1999 S4 LINEAR) to separation of major fragments (e.g., 73P/Schwassmann-Wachmann 3) and spill-offs of smaller boulders (e.g., C/2001 A2 LINEAR).Fragmentation of comets produces secondary products over a wide range of sizes (from cometesimals to sub-micron dust). It is detectable through the presence of fragments (with own comae and tails) in the coma of the parent nucleus, through outbursts in its activity and through arc-lets (“coma wings”)associated with fragments. The secondaries have different life times and show different non-gravitational forces. Nucleus splitting is also considered to generate whole families of comets (Kreutz group) or — if gravitational bound — multiple nuclei (e.g., C/1995 O1 Hale-Bopp). It may explain the striae phenomena seen in dust tails of bright comets (C/1995 O1 Hale-Bopp) and the detection of chains of impact craters onother bodies in the solar system. As process of significant mass loss it is relevant for the scenario of nucleus extinction, at the same time it also plays a role for the number statistics of existing (observable) comets and for the size distribution of comet nuclei. Various model scenarios for nucleus splitting are proposed: tidal disruption, rotational splitting, break-up due to internal gas pressure, fragmentation due to collision with other bodies. Only in one case, Comet D/1993 F1Shoemaker-Levy 9, the physical process of fragmentation could be undoubtedly identified. In any case, comet splitting provides important insights inthe internal structure, surface layering and chemistry of comet nuclei.

  9. Síndrome de mielinización de fibras nerviosas retinales, miopía y ambliopía / Syndrome of myelinated retinal nerve fibers, myopia and amblyopia

    Scientific Electronic Library Online (English)

    Daniel, López Felipe; Teresita de Jesús, Méndez Sánchez.

    Full Text Available Las fibras de mielina intraoculares se presentan desde el nacimiento y suelen localizarse alrededor de la papila. El síndrome de mielinización de las fibras nerviosas retinales fue descrito por Virchow por primera vez en 1856. Este aparece como parches estriados, blanco o blanco grisáceos con los bo [...] rdes imprecisos y plumosos siguiendo una configuración coincidente con la distribución de las fibras nerviosas retinales. Se presenta una paciente femenina de 4 años que es traída a consulta por desviación del ojo derecho. En el examen oftalmológico se detecta una agudeza visual con corrección de 0,1 y la oftalmoscopia confirma la mielinización de las fibras nerviosas retinales. En estos pacientes se asocia frecuentemente la miopía y ambliopía. A pesar de los pobres resultados visuales y ante la ausencia de otras terapias disponibles existe tendencia a tratamiento agresivo para la ambliopía, aunque en la literatura esto es aún controversial. Abstract in english The intraocular myelin fibers emerge since one's birth and it is usually located around the papilla. The syndrome of myelinated retinal nerve fibers was described for the first time by Virchow in 1856. This appears in the form of grooved patches, white or grayish white with imprecise and feathery bo [...] rders following a coincident configuration with the distribution of the retinal nerve fibers. A four years-old girl who was taken to the doctor's office because she presented with right eye deviation. In the ophthalmologic exam, the best corrected visual acuity was 0.1 and the ophthalmoscopy confirmed myelinated retinal nerve fibers. Myopia and amblyopia were often associated in these patients. In spite of the poor visual results and the lack of other available therapies, specialists tend to apply aggressive treatment for amblyopia, although this procedure is still controversial in the medical literature.

  10. Atomic resolution view into the structure–function relationships of the human myelin peripheral membrane protein P2

    Energy Technology Data Exchange (ETDEWEB)

    Ruskamo, Salla [University of Oulu, Oulu (Finland); University of Oulu, Oulu (Finland); Yadav, Ravi P. [Banaras Hindu University, Varanasi (India); Helmholtz Centre for Infection Research (CSSB-HZI), German Electron Synchrotron (DESY), Hamburg (Germany); Sharma, Satyan; Lehtimäki, Mari [University of Oulu, Oulu (Finland); University of Oulu, Oulu (Finland); Laulumaa, Saara [University of Oulu, Oulu (Finland); University of Oulu, Oulu (Finland); Helmholtz Centre for Infection Research (CSSB-HZI), German Electron Synchrotron (DESY), Hamburg (Germany); Aggarwal, Shweta; Simons, Mikael [Max Planck Institute for Experimental Medicine, Göttingen (Germany); Bürck, Jochen; Ulrich, Anne S. [Karlsruhe Institute for Technology (KIT), Karlsruhe (Germany); Juffer, André H. [University of Oulu, Oulu (Finland); University of Oulu, Oulu (Finland); Kursula, Inari [University of Oulu, Oulu (Finland); Helmholtz Centre for Infection Research (CSSB-HZI), German Electron Synchrotron (DESY), Hamburg (Germany); Kursula, Petri, E-mail: petri.kursula@oulu.fi [University of Oulu, Oulu (Finland); University of Oulu, Oulu (Finland); Helmholtz Centre for Infection Research (CSSB-HZI), German Electron Synchrotron (DESY), Hamburg (Germany); University of Hamburg, Hamburg (Germany)

    2014-01-01

    The structure of the human myelin peripheral membrane protein P2 has been refined at 0.93 Å resolution. In combination with functional experiments in vitro, in vivo and in silico, the fine details of the structure–function relationships in P2 are emerging. P2 is a fatty acid-binding protein expressed in vertebrate peripheral nerve myelin, where it may function in bilayer stacking and lipid transport. P2 binds to phospholipid membranes through its positively charged surface and a hydrophobic tip, and accommodates fatty acids inside its barrel structure. The structure of human P2 refined at the ultrahigh resolution of 0.93 Å allows detailed structural analyses, including the full organization of an internal hydrogen-bonding network. The orientation of the bound fatty-acid carboxyl group is linked to the protonation states of two coordinating arginine residues. An anion-binding site in the portal region is suggested to be relevant for membrane interactions and conformational changes. When bound to membrane multilayers, P2 has a preferred orientation and is stabilized, and the repeat distance indicates a single layer of P2 between membranes. Simulations show the formation of a double bilayer in the presence of P2, and in cultured cells wild-type P2 induces membrane-domain formation. Here, the most accurate structural and functional view to date on P2, a major component of peripheral nerve myelin, is presented, showing how it can interact with two membranes simultaneously while going through conformational changes at its portal region enabling ligand transfer.

  11. Atomic resolution view into the structure–function relationships of the human myelin peripheral membrane protein P2

    International Nuclear Information System (INIS)

    The structure of the human myelin peripheral membrane protein P2 has been refined at 0.93 Å resolution. In combination with functional experiments in vitro, in vivo and in silico, the fine details of the structure–function relationships in P2 are emerging. P2 is a fatty acid-binding protein expressed in vertebrate peripheral nerve myelin, where it may function in bilayer stacking and lipid transport. P2 binds to phospholipid membranes through its positively charged surface and a hydrophobic tip, and accommodates fatty acids inside its barrel structure. The structure of human P2 refined at the ultrahigh resolution of 0.93 Å allows detailed structural analyses, including the full organization of an internal hydrogen-bonding network. The orientation of the bound fatty-acid carboxyl group is linked to the protonation states of two coordinating arginine residues. An anion-binding site in the portal region is suggested to be relevant for membrane interactions and conformational changes. When bound to membrane multilayers, P2 has a preferred orientation and is stabilized, and the repeat distance indicates a single layer of P2 between membranes. Simulations show the formation of a double bilayer in the presence of P2, and in cultured cells wild-type P2 induces membrane-domain formation. Here, the most accurate structural and functional view to date on P2, a major component of peripheral nerve myelin, is presented, showing how it can interact with two membranes simultaneously while going through conformational changes at its portal region enabling ligand transfer

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

    DEFF Research Database (Denmark)

    Rosberg, Mette Romer; Alvarez, Susana

    2013-01-01

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

  13. Effects of short- and long-term Schwann cell denervation on peripheral nerve regeneration, myelination, and size.

    Science.gov (United States)

    Sulaiman, O A; Gordon, T

    2000-12-01

    Poor functional recovery after peripheral nerve injury has been generally attributed to inability of denervated muscles to accept reinnervation and recover from denervation atrophy. However, deterioration of the Schwann cell environment may play a more vital role. This study was undertaken to evaluate the effects of chronic denervation on the capacity of Schwann cells in the distal nerve stump to support axonal regeneration and to remyelinate regenerated axons. We used a delayed cross-suture anastomosis technique in which the common peroneal (CP) nerve in the rat was denervated for 0-24 weeks before cross-suture of the freshly axotomized tibial (TIB) and chronically denervated CP nerve stumps. Motor neurons were backlabeled with either fluoro-ruby or fluorogold 12 months later, to identify and count TIB motor neurons that regenerated axons into chronically denervated CP nerve stumps. Number, size, and myelination of regenerated sensory and motor axons were determined using light and electron microscopy. We found that short-term denervation of < or =4 weeks did not affect axonal regeneration but more prolonged denervation profoundly reduced the numbers of backlabeled motor neurons and axons in the distal nerve stump. Yet, atrophic Schwann cells retained their capacity to remyelinate regenerated axons. In fact, the axons were larger and well myelinated by long-term chronically denervated Schwann cells. These findings demonstrate a progressive inability of chronically denervated Schwann cells to support axonal regeneration and yet a sustained capacity to remyelinate the axons which do regenerate. Thus, axonal interaction can effectively switch the nonmyelinating phenotype of atrophic Schwann cells back into the myelinating phenotype. PMID:11102965

  14. Targeting Insulin-Like Growth Factor-1 Signaling into the Central Nervous System for Promoting Myelin Repair

    Directory of Open Access Journals (Sweden)

    Nadine Wilczak

    2008-01-01

    Full Text Available Multiple sclerosis (MS is the most common demyelinating disease of the central nervous system (CNS. Without myelin, nerve impulses in the CNS are slowed or stopped, leading to a constellation of neurological symptoms. Demyelination also provides a permitting condition for irreversible axonal damage. Remyelination of MS lesions largely fails, although oligodendrocyte precursors and premyelinating oligodendrocytes (myelin forming cells are present in many demyelinated plaques. Insulin-like growth factor (IGF-1 is a growth factor that should provide the appropriate signals to promote repair of MS lesions, because it acts as a survival factor for cells of the oligodendrocyte lineage and stimulates myelin synthesis. In a pilot study on MS patients, no detectable remyelinating effects in the CNS were observed following subcutaneous administration of IGF-1. A number of reasons might explain a lack of beneficial effects: a it is unlikely that subcutaneous administration of IGF-1 provides sufficient passage across the blood-brain-barrier and into the CNS, b the biological actions of IGF-1 are tightly regulated by several insulin-like growth factor binding proteins (IGFBPs, which become upregulated in the demyelinated lesions and may prevent access of IGF-1 to its receptor, c IGF-1 not only acts on oligodendrocytes, but also stimulates the proliferation of astrocytes, which form the glial scar that impedes repair processes. In this review, we will discuss strategies to enhance IGF-1 signaling in the CNS utilizing a alternative routes of administration, b IGF analogues that displace IGF-1 from regulatory IGFBPs and c strategies to selectively target IGF-1 to oligodendrocytes.

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

    Science.gov (United States)

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

    2013-06-01

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

  16. Stimulation of bovine brain phospholipase C activity by myelin basic protein requires arginyl residues in peptide linkage.

    Science.gov (United States)

    Tompkins, T A; Moscarello, M A

    1993-05-01

    We reported previously a highly purified phosphatidylinositol-specific phospholipase C (PI-PLC) from bovine brain and from human myelin which was stimulated by myelin basic protein. In this paper we report that the stimulation of the PI-PLC activity by myelin basic protein (MBP) requires arginine residues in peptide linkage. MBP and poly-L-arginine were able to stimulate the PI-PLC activity by 250% while other basic poly amino acids were unable to stimulate the PI-PLC activity. Neither free arginine nor benzoyl-arginine ethylester was able to stimulate the activity of the enzyme. These results suggested a requirement for the guanidino group of arginine and arginine in peptidyl linkage. The arginyl residues of MBP were modified chemically with 1,2-cyclohexanedione, or enzymatically by cholera toxin which ADP-ribosylated arginyl groups, or by peptidylarginine deiminase which converted the guanidino group of arginine to the ureido group of citrulline. ADP-ribosylation did not affect the stimulation while the 1,2-cyclohexanedione modified MBP and the peptidylarginine deiminase-treated MBP showed a reduced ability to stimulate the PI-PLC activity which correlated with the number of arginyl residues modified. Sequence analysis of the peptidylarginine deiminase-treated MBP established that specific arginyl residues had been converted to citrulline to a greater extent than others. When 70% of Arg 25 and Arg31 were converted to citrulline little stimulatory activity remained, whereas the conversion of 100% of Arg 170 did not affect the ability of C1 to stimulate the enzyme. A role for "active" arginine in this MBP peptide is suggested by our data. PMID:7683860

  17. Mannan-conjugated myelin peptides prime non-pathogenic Th1 and Th17 cells and ameliorate experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Tseveleki, Vivian; Tselios, Theodore; Kanistras, Ioannis; Koutsoni, Olga; Karamita, Maria; Vamvakas, Sotiris-Spyros; Apostolopoulos, Vasso; Dotsika, Eleni; Matsoukas, John; Lassmann, Hans; Probert, Lesley

    2015-05-01

    Antigen presenting cells (APC) are critical for regulating immune responses. We tested mannan-peptide conjugates for targeting myelin peptides to APC to induce T cell tolerance and resistance to experimental autoimmune encephalomyelitis (EAE). Myelin peptides conjugated to mannan in oxidized (OM) or reduced (RM) forms protected mice against EAE in prophylactic and therapeutic protocols, with OM-conjugated peptides giving best results. Protection was peptide-specific and associated with reduced antigen-specific T cell proliferation, but not alterations in Th1, Th17 and Treg cell differentiation or T cell apoptosis compared to EAE controls. Bone marrow-derived dendritic cells (DC) loaded with OM-MOG showed up-regulated expression of co-stimulatory molecules, reduced PD-L1 expression and enhanced CD40-inducible IL-12 and IL-23 production compared to MOG DC, features consistent with immunogenic DC. OM-MOG induced active T cell tolerance because i.d. administration or passive transfer of OM-MOG DC suppressed ongoing EAE, while OM-MOG-vaccinated mice did not reduce the proliferation of transferred MOG-specific T cells. As in vivo, MOG-specific T cells cultured with OM-MOG DC showed reduced proliferation and equal Th1 and Th17 cell differentiation compared to those with MOG DC, but surprisingly cytokine production was unresponsive to CD40 engagement. Impaired effector T cell function was further evidenced in spinal cord sections from OM-MOG-vaccinated EAE mice, where markedly reduced numbers of CD3(+) T cells were present, restricted to leptomeninges and exceptional parenchymal lesions. Our results show that mannan-conjugated myelin peptides protect mice against EAE through the expansion of antigen-specific Th1 and Th17 cells with impaired proliferation responses and APC-induced co-stimulatory signals that are required for licensing them to become fully pathogenic T cells. PMID:25447934

  18. Differential proliferative responses of cultured Schwann cells to axolemma- and myelin-enriched fractions. I. Biochemical studies

    OpenAIRE

    1984-01-01

    Cultured rat Schwann cells were treated for 72 h with axolemma- and myelin-enriched fractions prepared from rat brainstem. [3H]Thymidine was added to the cultures 48 h before the termination of the experiment. Although, both fractions produced a dose-dependent uptake of label into Schwann cells, the shape of the dose response curves and rates at which [3H]thymidine was incorporated were different. The axolemma-enriched fraction produced a sigmoid dose response curve with a Hill coefficient of...

  19. Mutation analysis of the nerve specific promoter of the peripheral myelin protein 22 gene in CMT1 disease and HNPP.

    OpenAIRE

    Nelis, E.; De Jonghe, P; De Vriendt, E; Patel, P. I.; Martin, J. J.; Van Broeckhoven, C

    1998-01-01

    We analysed the nerve specific promoter of the peripheral myelin protein 22 gene (PMP22) in a set of 15 unrelated patients with Charcot-Marie-Tooth type 1 disease (CMT1) and 16 unrelated patients with hereditary neuropathy with liability to pressure palsies (HNPP). In these patients no duplication/deletion nor a mutation in the coding region of the CMT1/ HNPP genes was detected. In one autosomal dominant CMT1 patient, we identified a base change in the non-coding exon 1A of PMP22 which, howev...

  20. Na(v)1.8 channelopathy in mutant mice deficient for myelin protein zero is detrimental to motor axons

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Alvarez Herrero, Susana

    2011-01-01

    Myelin protein zero mutations were found to produce Charcot–Marie–Tooth disease phenotypes with various degrees of myelin impairment and axonal loss, ranging from the mild ‘demyelinating’ adult form to severe and early onset forms. Protein zero deficient homozygous mice () show a severe and progressive dysmyelinating neuropathy from birth with compromised myelin compaction, hypomyelination and distal axonal degeneration. A previous study using immunofluorescence showed that motor nerves deficient of myelin protein zero upregulate the NaV1.8 voltage gated sodium channel isoform, which is normally present only in restricted populations of sensory axons. The aim of this study was to investigate the function of motor axons in protein zero-deficient mice with particular emphasis on ectopic NaV1.8 voltage gated sodium channel. We combined ‘threshold tracking’ excitability studies with conventional nerve conduction studies, behavioural studies using rotor-rod measurements, and histological measures to assess membrane dysfunction and its progression in protein zero deficient homozygous mutants as compared with age-matched wild-type controls. The involvement of NaV1.8 was investigated by pharmacologic block using the subtype-selective NaV1.8 blocker A-803467 and chronically in NaV1.8 knock-outs. We found that in the context of dysmyelination, abnormal potassium ion currents and membrane depolarization, the ectopic NaV1.8 channels further impair the motor axon excitability in protein zero deficient homozygous mutants to an extent that precipitates conduction failure in severely affected axons. Our data suggest that a NaV1.8 channelopathy contributed to the poor motor function of protein zero deficient homozygous mutants, and that the conduction failure was associated with partially reversible reduction of the electrically evoked muscle response and of the clinical function as indicated by the partial recovery of function at rotor-rod measurements. As a consequence of these findings of partially reversible dysfunction, we propose that the NaV1.8 voltage gated sodium channel should be considered as a novel therapeutic target for Charcot–Marie–Tooth disease.

  1. Splitting, splitting and splitting again: A brief history of the development of regional government in Indonesia since independence

    Directory of Open Access Journals (Sweden)

    Anne Booth

    2011-04-01

    Full Text Available The paper reviews the changes in the structure and role of provincial and sub-provincial governments in Indonesia since independence. Particular attention is paid to the process of splitting both provinces and districts (kabupaten and kota into smaller units. The paper points out that this process has been going on since the 1950s, but has accelerated in the post-Soeharto era. The paper examines why the splitting of government units has occurred in some parts of the Outer Islands to a much greater extent than in Java, and also examines the implications of developments since 1999 for the capacity of local government units to deliver basic services such as health and education.

  2. Mapping class groups of Heegaard splittings of surface bundles

    CERN Document Server

    Johnson, Jesse

    2012-01-01

    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.

  3. On split products of quaternion algebras with involution

    OpenAIRE

    Mahmoudi, M. G.; Nokhodkar, A. -H.

    2013-01-01

    The question of whether a split tensor product of quaternion algebras with involution over a field of characteristic two can be expressed as a tensor product of split quaternion algebras with involution, is shown to have an affirmative answer.

  4. Focal cerebral ischemia induces increased myelin basic protein and growth-associated protein-43 gene transcription in peri-infarct areas in the rat brain

    DEFF Research Database (Denmark)

    Gregersen, R; Christensen, Thomas

    2001-01-01

    Although oligodendrocytes are vulnerable to focal cerebral ischemia, remyelination of denuded or regenerating axons in the peri-infarct area has been observed in the central nervous system. We studied the expression of myelin basic protein (MBP), a major component of central nervous system myelin, in peri-infarct areas in adult rat brain after transient middle cerebral artery occlusion (MCAO) and correlated it to the expression of the growth-associated protein-43 (GAP-43), a marker for axonal regeneration and sprouting, using non-radioactive in situ hybridization techniques. Within the infarct, MBP messenger RNA (mRNA) had disappeared by 24 h, whereas myelin protein, identified by MBP and myelin oligodendrocyte glycoprotein (MOG) immunohistochemistry, appeared structurally intact until day 3. Peri-infarct oligodendrocytes increased their expression of MBP mRNA from 24 h to maximal levels at day 7, corresponding to the appearance of process-bearing MBP and occasional MOG-immunoreactive oligodendrocytes in parallel sections. Quantitative analysis revealed significant increases in the density of oligodendrocytes (up to 7.6-fold) and in the level of MBP mRNA expressed by individual cells. Parallel sections showed that increased expression of GAP-43 mRNA in neurons was concomitant to MBP mRNA upregulation in oligodendrocytes. While the mechanisms regulating oligodendrocyte survival and myelination signals are not clear at this point, axonal sprouting could putatively serve as a stimulus for the upregulation of oligodendrocyte cell numbers, differentiation state, and/or active myelination in the peri-infarct areas.

  5. Technical Note: Watershed strategy for oceanic mesoscale eddy splitting

    OpenAIRE

    Li, Q. Y.; Sun, L

    2014-01-01

    To identify oceanic mononuclear mesoscale eddies, a threshold-free splitting method was developed based on the watershed. Because oceanic eddies are similar to plateaus and basins in the map of the sea level anomaly (SLA) data, the natural divisions of the basins are the watersheds between them. The splitting algorithm is based on identifying these watersheds by finding the path of steepest descent. Compared to previous splitting methods, the proposed split...

  6. 7 CFR 51.2731 - U.S. Spanish Splits.

    Science.gov (United States)

    2010-01-01

    ...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”...

  7. Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders

    Directory of Open Access Journals (Sweden)

    Mader Simone

    2011-12-01

    Full Text Available Abstract Background Serum autoantibodies against the water channel aquaporin-4 (AQP4 are important diagnostic biomarkers and pathogenic factors for neuromyelitis optica (NMO. However, AQP4-IgG are absent in 5-40% of all NMO patients and the target of the autoimmune response in these patients is unknown. Since recent studies indicate that autoimmune responses to myelin oligodendrocyte glycoprotein (MOG can induce an NMO-like disease in experimental animal models, we speculate that MOG might be an autoantigen in AQP4-IgG seronegative NMO. Although high-titer autoantibodies to human native MOG were mainly detected in a subgroup of pediatric acute disseminated encephalomyelitis (ADEM and multiple sclerosis (MS patients, their role in NMO and High-risk NMO (HR-NMO; recurrent optic neuritis-rON or longitudinally extensive transverse myelitis-LETM remains unresolved. Results We analyzed patients with definite NMO (n = 45, HR-NMO (n = 53, ADEM (n = 33, clinically isolated syndromes presenting with myelitis or optic neuritis (CIS, n = 32, MS (n = 71 and controls (n = 101; 24 other neurological diseases-OND, 27 systemic lupus erythematosus-SLE and 50 healthy subjects for serum IgG to MOG and AQP4. Furthermore, we investigated whether these antibodies can mediate complement dependent cytotoxicity (CDC. AQP4-IgG was found in patients with NMO (n = 43, 96%, HR-NMO (n = 32, 60% and in one CIS patient (3%, but was absent in ADEM, MS and controls. High-titer MOG-IgG was found in patients with ADEM (n = 14, 42%, NMO (n = 3, 7%, HR-NMO (n = 7, 13%, 5 rON and 2 LETM, CIS (n = 2, 6%, MS (n = 2, 3% and controls (n = 3, 3%, two SLE and one OND. Two of the three MOG-IgG positive NMO patients and all seven MOG-IgG positive HR-NMO patients were negative for AQP4-IgG. Thus, MOG-IgG were found in both AQP4-IgG seronegative NMO patients and seven of 21 (33% AQP4-IgG negative HR-NMO patients. Antibodies to MOG and AQP4 were predominantly of the IgG1 subtype, and were able to mediate CDC at high-titer levels. Conclusions We could show for the first time that a subset of AQP4-IgG seronegative patients with NMO and HR-NMO exhibit a MOG-IgG mediated immune response, whereas MOG is not a target antigen in cases with an AQP4-directed humoral immune response.

  8. Immunological analysis of the amino terminal and the C8 isomer of human myelin basic protein.

    Science.gov (United States)

    Zhou, S R; Whitaker, J N; Wood, D D; Moscarello, M A

    1993-07-01

    The citrullination and N-terminus acylation of myelin basic protein (MBP) increases the heterogeneity among the MBP isoforms. The present study was undertaken to further characterize the immune response to the citrullinated form (C8) of MBP as well as to the variably acylated N-terminus of MBP. Six well-characterized murine monoclonal antibodies (mAbs) to human MBP-C8 or MBP peptides (four mAbs to MBP acetyl 1-9, one mAb to MBP 10-19 and one mAb to MBP 80-89), one murine T cell line (PL11) to human MBP peptide acetyl 1-9 and one Lewis rat T cell line (RT-1) to guinea pig (GP) MBP peptide 68-88 were used to assess reactivity with MBP-C1, MBP-C8, and MBP peptides including a series of MBP peptide 1-21 containing 0, 2, 4, 6, 8 or 10 carbon fatty acids. Enzyme-linked immunosorbent assay (ELISA) results revealed that all of the mAbs reacted with human MBP-C1 and MBP-C8 except anti-MBP 10-19 and anti-MBP-C8. The former reacted only with MBP-C1 and the latter only with MBP-C8. The presence and length of acylation of MBP peptide 1-21 modified reactivity. Three mAbs to MBP acetyl 1-9 reacted only with acetyl 1-21, and one mAb anti-MBP actyl 1-9 reacted with all of MBP 1-21 preparations whether acylated or not. mAb anti-MBP-C8 generally reacted better with acylated MBP 1-21 having longer fatty acids. The PL11 T cell line strongly proliferated to human MBP-C1, MBP-C8 and MBP acetyl 1-9, responded, but less well, to MBP 1-21 with longer fatty acids and failed to respond to nonacylated MBP peptide 1-21. The RT-1 cell line responded strongly to GP MBP peptide 68-88, marginally to MBP-C8 and failed to respond to MBP-C1 or any of the other MBP peptides. Specific immune responses to different MBP charge isomers and different N-terminal acylating groups of MBP may play a role in immune-mediated demyelination. PMID:7689598

  9. Post-translational modifications of chicken myelin basic protein charge components.

    Science.gov (United States)

    Kim, Jeongkwon; Zhang, Rui; Strittmatter, Eric F; Smith, Richard D; Zand, Robert

    2009-02-01

    Purified myelin basic protein (MBP) from various species contains several post-translationally modified forms termed charge components or charge isomers. Chicken MBP contains four charge components denoted as C1, C2, C3 and C8. (The C8 isomer is a complex mixture and was not investigated in this study.) These findings are in contrast to those found for human, bovine and other mammalian MBP's. Mammalian MBP's, each of which contain seven or eight charge components depending on the analysis of the CM-52 chromatographic curves and the PAGE gels obtained under basic pH conditions. Chicken MBP components C1, C2 and C3 were treated with trypsin and endoproteinase Glu-C. The resulting digests were analyzed by capillary liquid chromatography combined with either an ion trap tandem mass spectrometer or with a Fourier transform ion cyclotron resonance mass spectrometer. This instrumentation permitted establishing the amino acid composition and the determination of the post-translational modifications for each of the three charge components C1-C3. With the exception of N-terminal acetylation, the post-translational modifications were partial. The C1 component lacks any phosphorylated sites, a finding in agreement with the analysis of other MBP species. It also had a single methylation at R105 as did the components C2 and C3. The C2 component contains ten phosphorylated sites (S7, S18, S33, S64, S73, T96, S113, S141, S164, and S168), and modified arginine to citrulline residues at R24, and R165. Component C3 contains eight phosphorylated sites (S7, S33, S64, T96, S113, S141, S164, and S168), and citrulline residues at Arginine 41, R24 and R165. Partial deamidation of glutamine residues Q71, Q101 and Q146 were present in addition to asparagine N90 that was found in all three charge components. The glutamine at residue 3 is partially deamidated in isomers C1 and C2, whereas glutamine 74 and asparagine 83 were found not to be deamidated. Comparison of the PTM's of MBP's isolated from several vertebrate species reveals marked differences in their phosphate content. Chicken MBP does not share any phosphorylated sites with dogfish MBP; However, it does contain phosphorylated serine and threonine residues in common with mammalian MBP. PMID:18618245

  10. Self-gravitating splitting thin shells

    Science.gov (United States)

    Ramirez, Marcos A.

    2015-04-01

    In this paper we show that thin shells in spherically symmetric spacetimes, whose matter content is described by a pair of non-interacting spherically symmetric matter fields, generically exhibit instability against an infinitesimal separation of its constituent fields. We give explicit examples and construct solutions that represent a shell that splits into two shells. Then we extend those results for five-dimensional Schwarzschild–AdS bulk spacetimes, which is a typical scenario for brane-world models, and show that the same kind of stability analysis and splitting solution can be constructed. We find that a widely proposed family of brane-world models are extremely unstable in this sense. Finally, we discuss possible interpretations of these features and their relation to the initial value problem for concentrated sources.

  11. Photoelectrochemical water splitting materials, processes and architectures

    CERN Document Server

    Lewerenz, Hans-Joachim

    2013-01-01

    There has been a resurgence of interest in light-induced water splitting as the search for storable carbon neutral energy becomes more urgent. Although the history of the basic idea dates back more than four decades, efficient, economical and stable integrated devices have yet to be realized. In the continuing quest for such devices, the field of photoelectrochemistry is entering a new phase where the extraordinary interdisciplinary of the research and development efforts are opening new avenues. This aspect of current research effort is reflected in the chapters of this book, which encompass present thinking in the various disciplines such as materials science, photo-electrochemistry and interfaces that can contribute to realization of viable solar fuel generators. This book presents a blend of the background science and recent advances in the field of photoelectrochemical water splitting, and includes aspects that point towards medium to long term future realization. The content of the book goes beyond the ...

  12. Granular Flows in Split Bottom Geometries

    Science.gov (United States)

    Dijksman, Joshua A.; van Hecke, Martin

    2009-06-01

    There is a simple and general experimental protocol to generate slow granular flows that exhibit wide shear zones, qualitatively different from the narrow shear bands usually observed. The essence is to drive the granular medium not from the sidewalls, but to split the bottom of the container that supports the grains in two parts that slide past each other. Here we discuss main features of granular flows in so-called split bottom geometries. We focuss on reviewing the results for dry, slow granular flow. New developments, on faster flows, on flows of particles submerged in fluids, and on flows accompanied by weak vibration will be briefly outlined—these new developments will be discussed in more details in the accompanying talk at P&G 2009.

  13. Splitting Technique Initialization in Local PCA

    Directory of Open Access Journals (Sweden)

    Alok Sharma

    2006-01-01

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

  14. Evolution of Advection Upstream Splitting Method Schemes

    Science.gov (United States)

    Liou, Meng-Sing

    2010-01-01

    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

  15. Achronal limits, Lorentzian spheres, and splitting

    CERN Document Server

    Galloway, Gregory J

    2012-01-01

    In the early 80's S.-T. Yau posed the problem of establishing the rigidity of the Hawking-Penrose singularity theorems. Approaches to this problem have involved the introduction of Lorentzian Busemann functions and the study of the geometry of their level sets - the horospheres. The regularity theory in the Lorentzian case is considerably more complicated and less complete than in the Riemannian case. In this paper we introduce a broad generalization of the notion of horosphere in Lorentzian geometry and take a completely different (and highly geometric) approach to regularity. These generalized horospheres are defined in terms of 'achronal limits', and the improved regularity we obtain is based on regularity properties of achronal boundaries. We establish a splitting result for generalized horospheres, which when specialized to 'Cauchy horospheres' yields new results on the Bartnik splitting conjecture, a concrete realization of the problem posed by Yau. Our methods are also applied to spacetimes with positi...

  16. Meshed split skin graft for extensive vitiligo

    Directory of Open Access Journals (Sweden)

    Srinivas C

    2004-05-01

    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.

  17. Isospin breaking in octet baryon mass splittings

    Energy Technology Data Exchange (ETDEWEB)

    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

    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.

  18. Thick Brane Split Caused by Spacetime Torsion

    OpenAIRE

    Yang, Jie; Li, Yun-liang; Zhong, Yuan; Li, Yang

    2012-01-01

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

  19. Split Involution Coupled to Actual Gauge Symmetry

    OpenAIRE

    Batalin, I. A.; Lyakhovich, S. L.; Tyutin, I. V.

    1994-01-01

    The split involution quantization scheme, proposed previously for pure second--class constraints only, is extended to cover the case of the presence of irreducible first--class constraints. The explicit Sp(2)--symmetry property of the formalism is retained to hold. The constraint algebra generating equations are formulated and the Unitarizing Hamiltonian is constructed. Physical operators and states are defined in the sense of the new equivalence criterion that is a natural ...

  20. Splittings of Non-Finitely Generated Groups

    OpenAIRE

    Lassonde, Robin M.

    2011-01-01

    In geometric group theory one uses group actions on spaces to gain information about groups. One natural space to use is the Cayley graph of a group. The Cayley graph arguments that one encounters tend to require local finiteness, and hence finite generation of the group. In this paper, I take the theory of intersections of splittings of finitely generated groups (as developed by Scott, Scott-Swarup, and Niblo-Sageev-Scott-Swarup), and rework it to remove finite generation a...

  1. Photon splitting in a laser field

    OpenAIRE

    Di Piazza, A.; Milstein, A. I.; Keitel, C. H.

    2007-01-01

    Photon splitting due to vacuum polarization in a laser field is considered. Using an operator technique, we derive the amplitudes for arbitrary strength, spectral content and polarization of the laser field. The case of a monochromatic circularly polarized laser field is studied in detail and the amplitudes are obtained as three-fold integrals. The asymptotic behavior of the amplitudes for various limits of interest are investigated also in the case of a linearly polarized l...

  2. Near-unity Cooper pair splitting efficiency

    OpenAIRE

    Schindele, J.; Baumgartner, A.; Schönenberger, C.

    2012-01-01

    The two electrons of a Cooper pair in a conventional superconductor form a singlet and therefore a maximally entangled state. Recently, it was demonstrated that the two particles can be extracted from the superconductor into two spatially separated contacts via two quantum dots (QDs) in a process called Cooper pair splitting (CPS). Competing transport processes, however, limit the efficiency of this process. Here we demonstrate efficiencies up to 90%, significantly larger th...

  3. Localised bending modes in split ring resonators

    International Nuclear Information System (INIS)

    We present band diagrams for in-plane elastic waves propagating within a doubly periodic structure involving split ring resonators (SRR). From the Navier equations we derive that the lowest resonant frequencies are associated with localised bending modes solutions of a fourth-order differential equation in thin-bridges, which are responsible for the appearance of a low frequency stop band. Potential applications lie in the design of earthquake resistant systems

  4. A thermodynamically compatible splitting procedure in hyperelasticity

    International Nuclear Information System (INIS)

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

  5. The Psi '- eta /sub c/' hyperfine splitting

    CERN Document Server

    Martin, A

    1982-01-01

    The hyperfine splitting of the radially excited states psi ' and eta /sub c/' is studied within the framework of potential models. Some rigorous results are derived and some phenomenological approaches are commented on. The recent experimental result M( psi ')-M( eta /sub c /')=93 MeV favours very short-range spin-spin forces and seems, on the other hand, difficult to accommodate if there is a sizeable effect of virtual D meson pairs on the charmonium mass spectrum.

  6. Splitting and focusing of neutrino collective states

    OpenAIRE

    Marklund, Mattias; Shukla, Padma K.; Stenflo, Lennart

    2003-01-01

    It is shown that the collective nonlinear interactions between intense neutrino or anti-neutrino fluxes and a dense neutrino plasma are governed by a multi-dimensional coupled cubic Schr\\"odinger equation in which the interaction potential is positive or negative depending on the neutrino type. The cubic Schr\\"odinger equation describes the splitting and focusing of intense neutrino beams due to the nonlinear excitations associated with the modifications of the individual ne...

  7. Traceless protein splicing utilizing evolved split inteins

    OpenAIRE

    Lockless, Steve W.; Muir, Tom W

    2009-01-01

    Split inteins are parasitic genetic elements frequently found inserted into reading frames of essential proteins. Their association and excision restore host protein function through a protein self-splicing reaction. They have gained an increasingly important role in the chemical modification of proteins to create cyclical, segmentally labeled, and fluorescently tagged proteins. Ideally, inteins would seamlessly splice polypeptides together with no remnant sequences and at high efficiency. He...

  8. Nanostructured hematite for photoelectrochemical water splitting

    Science.gov (United States)

    Ling, Yichuan

    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.

  9. Nf1 Loss and Ras Hyperactivation in Oligodendrocytes Induce NOS-Driven Defects in Myelin and Vasculature

    Directory of Open Access Journals (Sweden)

    Debra A. Mayes

    2013-09-01

    Full Text Available Patients with neurofibromatosis type 1 (NF1 and Costello syndrome Rasopathy have behavioral deficits. In NF1 patients, these may correlate with white matter enlargement and aberrant myelin. To model these features, we induced Nf1 loss or HRas hyperactivation in mouse oligodendrocytes. Enlarged brain white matter tracts correlated with myelin decompaction, downregulation of claudin-11, and mislocalization of connexin-32. Surprisingly, non-cell-autonomous defects in perivascular astrocytes and the blood-brain barrier (BBB developed, implicating a soluble mediator. Nitric oxide (NO can disrupt tight junctions and gap junctions, and NO and NO synthases (NOS1–NOS3 were upregulated in mutant white matter. Treating mice with the NOS inhibitor NG-nitro-L-arginine methyl ester or the antioxidant N-acetyl cysteine corrected cellular phenotypes. CNP-HRasG12V mice also displayed locomotor hyperactivity, which could be rescued by antioxidant treatment. We conclude that Nf1/Ras regulates oligodendrocyte NOS and that dysregulated NO signaling in oligodendrocytes can alter the surrounding vasculature. The data suggest that antioxidants may improve some behavioral deficits in Rasopathy patients.

  10. PAR-1 activation by SFLLRNP decreases myelin deposition on lumbar motor neuron axons as assessed with cupric silver staining

    Directory of Open Access Journals (Sweden)

    Candice Meuleners

    2010-01-01

    Full Text Available Working through protease-activated receptors (PARs, serine proteases have been shown to play important roles in neuronal and glial cell survival during development and in neurodegeneration. Past studies in chick embryos have shown that PAR-1 activation during the period of lumbar motor neuron programmed cell death (PCD leads to a decreased number of surviving motor neurons by embryonic day 10 (E10. Retrospective analysis of these tissues revealed increased thionin staining in the white matter of these spinal cords, interesting because thionin does not normally stain myelinated areas. We hypothesized that PAR-1 activation decreases myelin deposition in developing spinal cords. To activate PAR-1, embryos were treated with the amino acid sequence SFLLRNP for five consecutive days beginning on E5. Embryos were sacrificed on E10, prepared for histology, and stained with cupric silver. The ventral hemispheres of lumbar sections were examined for the degree of demyelination as characterized by punctate or linear silver markings in the white matter. Experimental embryos were found to exhibit statistically more punctate markings and linear markings. This study shows that in addition to decreasing motor neuron survival, PAR-1 activation potentially decreases the conducting ability and viability of the surviving motor neurons.

  11. New Insights in the Pathogenesis of Multiple Sclerosis—Role of Acrolein in Neuronal and Myelin Damage

    Directory of Open Access Journals (Sweden)

    Riyi Shi

    2013-10-01

    Full Text Available Multiple sclerosis (MS is an autoimmune disease of the central nervous system (CNS characterized by an inappropriate inflammatory reaction resulting in widespread myelin injury along white matter tracts. Neurological impairment as a result of the disease can be attributed to immune-mediated injury to myelin, axons and mitochondria, but the molecular mechanisms underlying the neuropathy remain incompletely understood. Incomplete mechanistic knowledge hinders the development of therapies capable of alleviating symptoms and slowing disease progression in the long-term. Recently, oxidative stress has been implicated as a key component of neural tissue damage prompting investigation of reactive oxygen species (ROS scavengers as a potential therapeutic option. Despite the establishment of oxidative stress as a crucial process in MS development and progression, ROS scavengers have had limited success in animal studies which has prompted pursuit of an alternative target capable of curtailing oxidative stress. Acrolein, a toxic ?-unsaturated aldehyde capable of initiating and perpetuating oxidative stress, has been suggested as a viable point of intervention to guide the development of new treatments. Sequestering acrolein using an FDA-approved compound, hydralazine, offers neuroprotection resulting in dampened symptom severity and slowed disease progression in experimental autoimmune encephalomyelitis (EAE mice. These results provide promise for therapeutic development, indicating the possible utility of neutralizing acrolein to preserve and improve neurological function in MS patients.

  12. Normal variation of focal T2 Hyperintensities in anterior parietal periventricular white matter: Another 'Terminal Zones of Myelination'

    International Nuclear Information System (INIS)

    It has been known that there are several areas of T2 hyperintensity in normal white matter of brain, such as terminal zones of myelination, ependymitis granularis, ones of posterior internal capsule, and perivascular space. The aim of our study is to demonstrate another region of T2 hyperintensities in normal pediatric age group. We have studied brain MR for 10 normal volunteers and 35 patients without having intracranial lesions in pediatric age group(3-19 years). In 5 among 45 cases, focal T2 hyperintensities were seen in the parietal periventricular white matter beneath the postcentral gyri. They were noted as poorly defined, 5-10 mm sized areas of increased signal intensities on T2-weighted axial images. They were also characterized by bilateral, posteromedially oriented, short band-like or oval areas. Interestingly, they were directly continuous with the T2 hyperintensity of posterior internal capsule. In spite of the relatively highly frequency in the pediatric population as in our study, this finding has not been reported in the asymptomatic adults. The results show that the bilateral anterior parietal hyperintense areas may be another terminal zones of delayed myelination affecting the parietopontine tract. They should be differentiated from pathologic T2 hyperintensities by their characteristic findings

  13. Deletion of Jun proteins in adult oligodendrocytes does not perturb cell survival, or myelin maintenance in vivo.

    Science.gov (United States)

    Schreiner, Bettina; Ingold-Heppner, Barbara; Pehl, Debora; Locatelli, Giuseppe; Berrit-Schönthaler, Helia; Becher, Burkhard

    2015-01-01

    Oligodendrocytes, the myelin-forming glial cells of the central nervous system (CNS), are fundamental players in rapid impulse conduction and normal axonal functions. JunB and c-Jun are DNA-binding components of the AP-1 transcription factor, which is known to regulate different processes such as proliferation, differentiation, stress responses and death in several cell types, including cultured oligodendrocyte/lineage cells. By selectively inactivating Jun B and c-Jun in myelinating oligodendrocytes in vivo, we generated mutant mice that developed normally, and within more than 12 months showed normal ageing and survival rates. In the adult CNS, absence of JunB and c-Jun from mature oligodendrocytes caused low-grade glial activation without overt signs of demyelination or secondary leukocyte infiltration into the brain. Even after exposure to toxic or autoimmune oligodendrocyte insults, signs of altered oligodendrocyte viability were mild and detectable only upon cuprizone treatment. We conclude that JunB and c-Jun expression in post-mitotic oligodendrocytes is mostly dispensable for the maintainance of white matter tracts throughout adult life, even under demyelinating conditions. PMID:25774663

  14. Split-Doa10: A Naturally Split Polytopic Eukaryotic Membrane Protein Generated by Fission of a Nuclear Gene

    OpenAIRE

    Stuerner, Elisabeth; Kuraku, Shigehiro; Hochstrasser, Mark; Kreft, Stefan G

    2012-01-01

    Large polytopic membrane proteins often derive from duplication and fusion of genes for smaller proteins. The reverse process, splitting of a membrane protein by gene fission, is rare and has been studied mainly with artificially split proteins. Fragments of a split membrane protein may associate and reconstitute the function of the larger protein. Most examples of naturally split membrane proteins are from bacteria or eukaryotic organelles, and their exact history is usually poorly understoo...

  15. Circular Permutation Prediction Reveals a Viable Backbone Disconnection for Split Proteins: An Approach in Identifying a New Functional Split Intein

    OpenAIRE

    Lee, Yun-Tzai; Su, Tz-Hsiang; Lo, Wei-Cheng; Lyu, Ping-Chiang; Sue, Shih-Che

    2012-01-01

    Split-protein systems have emerged as a powerful tool for detecting biomolecular interactions and reporting biological reactions. However, reliable methods for identifying viable split sites are still unavailable. In this study, we demonstrated the feasibility that valid circular permutation (CP) sites in proteins have the potential to act as split sites and that CP prediction can be used to search for internal permissive sites for creating new split proteins. Using a protein ligase, intein, ...

  16. Mutual synergistic protein folding in split intein

    Directory of Open Access Journals (Sweden)

    Yuchuan Zheng

    2012-07-01

    Full Text Available Inteins are intervening protein sequences that undergo self-excision from a precursor protein with the concomitant ligation of the flanking polypeptides. Split inteins are expressed in two separated halves, and the recognition and association of two halves are the first crucial step for initiating trans-splicing. In the present study, we carried out the structural and thermodynamic analysis on the interaction of two halves of DnaE split intein from Synechocystis sp. PCC6803. Both isolated halves (IN and IC are disordered and undergo conformational transition from disorder to order upon association. ITC (isothermal titration calorimetry reveals that the highly favourable enthalpy change drives the association of the two halves, overcoming the unfavourable entropy change. The high flexibility of two fragments and the marked thermodynamic preference provide a robust association for the formation of the well-folded IN/IC complex, which is the basis for reconstituting the trans-splicing activity of DnaE split intein.

  17. P-wave Cooper pair splitting

    Directory of Open Access Journals (Sweden)

    Henning Soller

    2012-07-01

    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.

  18. Splitting neutrino masses and showering into Sky

    CERN Document Server

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

    2006-01-01

    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...

  19. Sunspot splitting triggering an eruptive flare

    CERN Document Server

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

    2013-01-01

    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...

  20. Photon splitting in soft gamma repeaters

    CERN Document Server

    Baring, M G

    1995-01-01

    The exotic quantum process of photon splitting has great potential to explain the softness of emission in soft gamma repeaters (SGRs) if they originate in neutron stars with surface fields above the quantum critical field B_{\\rm cr}=4.413\\times 10^{13}Gauss. Splitting becomes prolific at such field strengths: its principal effect is to degrade photon energies, initiating a cascade that softens gamma-ray spectra. Uniform field cascade calculations have demonstrated that emission could be softened to the observed SGR energies for fields exceeding about 10^{14}Gauss. Recently, we have determined splitting attenuation lengths and maximum energies for photon escape in neutron star environments including the effects of magnetospheric dipole field geometry. Such escape energies \\erg_{esc} suitably approximate the peak energy of the emergent spectrum, and in this paper we present results for \\erg_{esc} as a function of photon emission angles for polar cap and equatorial emission regions. The escape energy is extremel...

  1. Consimilarity of Split Quaternion Matrices and a Solution of the Split Quaternion Matrix Equation X-AX_B=C

    OpenAIRE

    Kosal, Hidayet Huda; Akyigit, Mahmut; Tosun, Murat

    2014-01-01

    In this paper, the consimilarity of complex matrices is generalized for the split quaternions. In this regard, coneigenvalue and coneigenvector are de?ned for split quaternion matrices. Also, the existence of solution to the split quaternion matrix equation X-AXB = C is characterized and the solution of the equation in the explicit form are derived via its real representation.

  2. The isolation and characterization of four myelin basic proteins from the unbound fraction during CM52 chromatography.

    Science.gov (United States)

    Boulias, C; Pang, H; Mastronardi, F; Moscarello, M A

    1995-09-10

    The unbound fraction from CM52 columns was used as the source of at least four additional myelin basic protein (MBP) molecules. From this fraction we routinely obtained two major fractions called C8-A and C8-B. The C8-A and C8-B fractions were further purified on HPLC. Each contained two proteins in the 17- to 18-kDa range which we called C8-A(H) (higher M(r)), C8-A(L) (lower M(r)), C8-B(H), and C8-B(L). The citrulline values (calculated as citrulline plus ornithine) were high in three of the four proteins, which was accompanied by a compensatory decrease in the arginine values. The compositions clearly identified these four proteins with the citrullinated form of MBP. Western blot analysis showed that both H and L forms reacted with anti MBP antibodies. Partial sequence analysis after cyanogen bromide cleavage, showed that the sequences of both proteins in the C8-B fraction (C8-B(H) and C8-B(L)) were identical to the 18.5-kDa isoform of MBP. Mass spectrometry by electrospray ionization of the C8-B(H) and C8-B(L) provided us with accurate masses of 18,558.08 +/- 8.13 and 17,266.63 +/- 2.24, respectively. We concluded that the H and L proteins from the C8-B fractions were MBPs. Although similar detailed analyses of the C8-A(H) and C8-A(L) have not been done they are also considered to be MBP on the basis of the immunoreactivity with anti MBP antibodies. The origins of these proteins is not known at this time and their functional significance is obscure. The possibility that they are found in early forms of myelin, as components of transitional membranes between oligodendrocytes and myelin or are involved in remyelination, cannot be discounted. PMID:7574672

  3. Wave-equation shear wave splitting tomography

    Science.gov (United States)

    Long, Maureen D.; de Hoop, Maarten V.; van der Hilst, Robert D.

    2008-01-01

    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 shear wave splitting tomography are, upon linearization with the Born approximation, similar in structure to the equations that describe wave equation transmission and reflection tomography. For full broad-band analysis these PDEs can be evaluated numerically, but we show here the leading order asymptotic (i.e. `ray born') behaviour of the associated finite-frequency sensitivity kernels. For simplicity we assume that the anisotropic model is invariant in one horizontal direction. This 2.5-D geometry is well suited for studying upper-mantle anisotropy associated with subduction of lithospheric plates if the trench-slab system is approximately 2-D. With the so-called splitting intensity as the metric for data fit, and under the assumption of weak anisotropy, we derive expressions for the sensitivity kernels. We focus on two anisotropic parameters that describe tilted transverse isotropy: the dip ?0 of the symmetry axis with respect to the horizontal plane and the anellipticity parameter ?A, which represents the strength of the anisotropy. We illustrate the finite-frequency effects both for homogeneous and heterogeneous (anisotropic) background models. The sensitivity kernels in heterogeneous media are calculated for initial models obtained from numerical modelling of flow and finite strain beneath the Ryukyu arc. Kernels calculated in heterogeneous media differ substantially from those in a homogeneous background. This demonstrates the importance of iterative model (and kernel) assessment for reaching the full (resolution) potential of finite frequency tomography.

  4. Hyperfine splitting in hydrogen with form factors

    CERN Document Server

    Daza, F Garcia; Nowakowski, M

    2010-01-01

    Proton structure corrections to the hyperfine splittings in hydrogen are evaluated using the Breit potential with electromagnetic form factors. In contrast to other methods, several new features emerge: the Breit potential with $q^2$-dependent form factors is just an extension of the standard Breit equation which gives the hyperfine Hamiltonian. Order $\\alpha^5$ corrections are obtained from a one-photon exchange amplitude and time-independent perturbation theory. Structure corrections to $D_{21} = 8 E^{2S}_{hfs} - E^{1S}_{hfs}$ start at order $\\alpha^6$. QED corrections are comparable to structure corrections which must be evaluated ab initio.

  5. Dark Matter Generation and Split Supersymmetry

    OpenAIRE

    Kaplan, Jared

    2006-01-01

    We analyze a simple Split Supersymmetry scenario where fermion masses come from anomaly mediation, yielding m_s ~ 1000 TeV, m_{3/2} ~ 100 TeV, and m_f ~ 1 TeV. We consider non-thermal dark matter production in the presence of moduli, and we find that the decay chains of moduli to LSPs and moduli to gravitinos to LSPs generate dark matter more efficiently than perturbative freeze-out, allowing for a light, LHC visible spectrum. These decaying moduli can also weaken cosmologic...

  6. Split involution coupled to actual gauge symmetry

    CERN Document Server

    Batalin, I A; Tyutin, I V; Batalin, I A; Lyakhovich, S L; Tyutin, I V

    1994-01-01

    The split involution quantization scheme, proposed previously for pure second--class constraints only, is extended to cover the case of the presence of irreducible first--class constraints. The explicit Sp(2)--symmetry property of the formalism is retained to hold. The constraint algebra generating equations are formulated and the Unitarizing Hamiltonian is constructed. Physical operators and states are defined in the sense of the new equivalence criterion that is a natural counterpart to the Dirac's weak equality concept as applied to the first--class quantities.

  7. Heat transfer with a split water channel

    International Nuclear Information System (INIS)

    The heat transfer problem associated with the incidence of synchrotron radiation upon a vacuum chamber wall cooled by a single water channel was previously studied, and a numerical solution to the potential problem was found using the two-dimensional magnet program POISSON. Calculations were extended to consider the case of a split water channel using POISSON to solve the potential problem for a given choice of parameters. By optimizing the dimensions, boiling of the water can be avoided. A copper chamber is a viable solution to the heat transfer problem at a beam port

  8. Comparing Electrochemical and Biological Water Splitting

    DEFF Research Database (Denmark)

    Rossmeisl, Jan; Dimitrievski, Kristian

    2007-01-01

    On the basis of density functional theory calculations, we compare the free energies of key intermediates in the water splitting reaction over transition metal oxide surfaces to those of the Mn cluster in photo system II. In spite of the very different environments in the enzyme system and on the inorganic catalyst surface of an acidic electrolysis cell, the thermochemical features of the catalysts can be directly compared. We suggest a simple test for a thermochemically optimal catalyst. We show that, although both the RuO2 surface and the Mn cluster in photo system II are quite close to optimal, the biological catalyst appears to be best.

  9. Basic dynamics of split Stirling refrigerators

    Science.gov (United States)

    de Waele, A. T. A. M.; Liang, W.

    2008-09-01

    The basic features of the split Stirling refrigerator, driven by a linear compressor, are described. Friction of the compressor piston and of the regenerator, and the viscous losses due to the gas flow through the regenerator matrix are taken into account. The temperature at the cold end is an input parameter. The general equations are derived which are subsequently treated in the harmonic approximation. Examples are given of application of the relations for describing optimum-performance conditions as well as the interrelationship between cooler and heat-engine operation.

  10. The second order pole over split quaternions

    Science.gov (United States)

    Libine, Matvei

    2015-04-01

    This is an addition to a series of papers [1, 2, 3, 4], where we develop quaternionic analysis from the point of view of representation theory of the conformal Lie group and its Lie algebra. In this paper we develop split quaternionic analogues of certain results from [4]. Thus we introduce a space of functions Dh ? Da with a natural action of the Lie algebra gl(2, HC) ? sl(4, C), decompose Dh ? Da into irreducible components and find the gl(2, Hc)- equivariant projectors onto each of these irreducible components.

  11. Miniaturized Planar Split-Ring Resonator Antenna

    OpenAIRE

    Kim, Oleksiy S.; Breinbjerg, Olav

    2009-01-01

    A miniaturized planar antenna based on a broadside-coupled split ring resonator excited by an arc-shaped dipole is presented. The excitation dipole acts as a small tuning capacitor in series with a parallel RLC circuit represented by the SRR. The antenna resonance frequency and dimensions a essentially determined by the SRR, while by varying the dipole arm length the input resistance is changed in a wide range, thus matching the antenna to a feed line and compensating for simulation and ma...

  12. Alteration of split renal function during Captopril treatment

    International Nuclear Information System (INIS)

    Two different methods to evaluate the alteration of split renal function following continued Captopril treatment were studied in a total of 21 patients with hypertension. Eight patients with renovascular hypertension (five with unilateral renal artery stenosis and three with bilateral renal artery stenoses), three patients with diabetic nephropathy, one patient with primary aldosteronism, and nine patients with essential hypertension were included. The studies were performed the day prior to receiving Captopril (baseline), and 6th or 7th day following continued Captopril treatment (37.5 mg or 75 mg/day). Split effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) after injections of I-131 hippuran and Tc-99m DTPA were measured using kidney counting corrected for depth and dose, described by Schlegel and Gates. In the patients with renovascular hypertension, split GFR in the stenotic kidney was significantly decreased 6th or 7th day following continued Captopril treatment compared to a baseline value. And split ERPF in the stenotic kidney was slightly increased although significant increase of split ERPF was not shown. In the patients with diabetic nephropathy, primary aldosteronism or essential hypertension, on the other hand, split GFR was not changed and split ERPF was slightly increased. These findings suggest that the Captopril induced alterations of split renal function may be of importance for the diagnosis of renovascular hypertension. For thiosis of renovascular hypertension. For this purpose, split GFR determination is more useful than split ERPF determination. (author)

  13. Endogenous Interferon-?-Inducible Gene Expression and Interferon-?-Treatment Are Associated with Reduced T Cell Responses to Myelin Basic Protein in Multiple Sclerosis

    DEFF Research Database (Denmark)

    Börnsen, Lars; Romme Christensen, Jeppe

    2015-01-01

    Autoreactive CD4+ T-cells are considered to play a major role in the pathogenesis of multiple sclerosis. In experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, exogenous and endogenous type I interferons restrict disease severity. Recombinant interferon-? is used for treatment of multiple sclerosis, and some untreated multiple sclerosis patients have increased expression levels of type I interferon-inducible genes in immune cells. The role of endogenous type I interferons in multiple sclerosis is controversial: some studies found an association of high expression levels of interferon-?-inducible genes with an increased expression of interleukin-10 and a milder disease course in untreated multiple sclerosis patients, whereas other studies reported an association with a poor response to treatment with interferon-?. In the present study, we found that untreated multiple sclerosis patients with an increased expression of interferon-?-inducible genes in peripheral blood mononuclear cells and interferon-?-treated multiple sclerosis patients had decreased CD4+ T-cell reactivity to the autoantigen myelin basic protein ex vivo. Interferon-?-treated multiple sclerosis patients had increased IL10 and IL27 gene expression levels in monocytes in vivo. In vitro, neutralization of interleukin-10 and monocyte depletion increased CD4+ T-cell reactivity to myelin basic protein while interleukin-10, in the presence or absence of monocytes, inhibited CD4+ T-cell reactivity to myelin basic protein. Our findings suggest that spontaneous expression of interferon-?-inducible genes in peripheral blood mononuclear cells from untreated multiple sclerosis patients and treatment with interferon-? are associated with reduced myelin basic protein-induced T-cell responses. Reduced myelin basic protein-induced CD4+ T-cell autoreactivity in interferon-?-treated multiple sclerosis patients may be mediated by monocyte-derived interleukin-10.

  14. A small direct tandem duplication of the myelin protein zero gene in a patient with Dejerine-Sottas disease phenotype.

    Science.gov (United States)

    Tachi, N; Kozuka, N; Ohya, K; Chiba, S; Yamashita, S

    1998-04-01

    We present a male patient with Dejerine-Sottas disease phenotype, who had a small direct tandem duplication of the Po gene. The pathology of the sural nerve showed hypomyelinated fibers with absence of active demyelination and onion-bulb formations composed of two parallel layers of basement membrane, consistent with congenital hypomyelination neuropathy (CHN). However, his clinical features were more severe than those of previously reported CHN patients. A GGCA insertion was identified at the position of nucleotide 560 in the myelin protein zero (Po) gene. This insertional mutation was located in exon 4 coding for the transmembrane domain of the Po gene and caused a shift of reading frame, creating a stop codon. The mutation of the transmembrane domain probably has the largest impact on Po function. The mutation was not identified in both parents. PMID:9588852

  15. Vibration Analysis of a Split Path Gearbox

    Science.gov (United States)

    Krantz, Timothy L.; Rashidi, Majid

    1995-01-01

    Split path gearboxes can be attractive alternatives to the common planetary designs for rotorcraft, but because they have seen little use, they are relatively high risk designs. To help reduce the risk of fielding a rotorcraft with a split path gearbox, the vibration and dynamic characteristics of such a gearbox were studied. A mathematical model was developed by using the Lagrangian method, and it was applied to study the effect of three design variables on the natural frequencies and vibration energy of the gearbox. The first design variable, shaft angle, had little influence on the natural frequencies. The second variable, mesh phasing, had a strong effect on the levels of vibration energy, with phase angles of 0 deg and 180 deg producing low vibration levels. The third design variable, the stiffness of the shafts connecting the spur gears to the helical pinions, strongly influenced the natural frequencies of some of the vibration modes, including two of the dominant modes. We found that, to achieve the lowest level of vibration energy, the natural frequencies of these two dominant modes should be less than those of the main excitation sources.

  16. Oseledets' splitting of standard-like maps

    Science.gov (United States)

    Sala, M.; Artuso, R.

    2015-02-01

    For the class of differentiable maps of the plane and, in particular, for standard-like maps (McMillan form), a simple relation is shown between the directions of the local invariant manifolds of a generic point and its contribution to the finite-time Lyapunov exponents (FTLE) of the associated orbit. By computing also the point-wise curvature of the manifolds, we produce a comparative study between local Lyapunov exponent, manifold's curvature and splitting angle between stable/unstable manifolds. Interestingly, the analysis of the Chirikov-Taylor standard map suggests that the positive contributions to the FTLE average mostly come from points of the orbit where the structure of the manifolds is locally hyperbolic: where the manifolds are flat and transversal, the one-step exponent is predominantly positive and large; this behaviour is intended in a purely statistical sense, since it exhibits large deviations. Such phenomenon can be understood by analytic arguments which, as a by-product, also suggest an explicit way to point-wise approximate the splitting.

  17. Mild-split SUSY with flavor

    CERN Document Server

    Eliaz, Latif; Gudnason, Sven Bjarke; Tsuk, Eitan

    2013-01-01

    In the framework of a gauge mediated quiver-like model, the standard model flavor texture can be naturally generated. The model - like the MSSM - has furthermore a region in parameter space where the lightest Higgs mass is fed by heavy stop loops, which in turn sets the average squark mass scale near 10-20 TeV. We perform a careful flavor analysis to check whether this type of mild-split SUSY passes all flavor constraints as easily as envisioned in the original type of split SUSY. Interestingly, it turns out to be on the border of several constraints, in particular, the branching ratio of mu -> e gamma and, if order one complex phases are assumed, also epsilon_K neutron and electron EDM. Furthermore, we consider unification as well as dark matter candidates, especially the gravitino. Finally, we provide a closed-form formula for the soft masses of matter in arbitrary representations of any of the gauge groups in a generic quiver-like model with a general messenger sector.

  18. Mild-split SUSY with flavor

    Science.gov (United States)

    Eliaz, Latif; Giveon, Amit; Gudnason, Sven Bjarke; Tsuk, Eitan

    2013-10-01

    In the framework of a gauge mediated quiver-like model, the standard model flavor texture can be naturally generated. The model — like the MSSM — has furthermore a region in parameter space where the lightest Higgs mass is fed by heavy stop loops, which in turn sets the average squark mass scale near 10 - 20TeV. We perform a careful flavor analysis to check whether this type of mild-split SUSY passes all flavor constraints as easily as envisioned in the original type of split SUSY. Interestingly, it turns out to be on the border of several constraints, in particular, the branching ratio of ? ? e? and, if order one complex phases are assumed, also ? K , neutron and electron EDM. Furthermore, we consider unification as well as dark matter candidates, especially the gravitino. Finally, we provide a closed-form formula for the soft masses of matter in arbitrary representations of any of the gauge groups in a generic quiver-like model with a general messenger sector.

  19. Strong CP, Flavor, and Twisted Split Fermions

    Energy Technology Data Exchange (ETDEWEB)

    Harnik, Roni; Perez, Gilad; Schwartz, Matthew D.; Shirman, Yuri

    2004-11-10

    We present a natural solution to the strong CP problem in the context of split fermions. By assuming CP is spontaneously broken in the bulk, a weak CKM phase is created in the standard model due to a twisting in flavor space of the bulk fermion wavefunctions. But the strong CP phase remains zero, being essentially protected by parity in the bulk and CP on the branes. As always in models of spontaneous CP breaking, radiative corrections to theta bar from the standard model are tiny, but even higher dimension operators are not that dangerous. The twisting phenomenon was recently shown to be generic, and not to interfere with the way that split fermions naturally weaves small numbers into the standard model. It follows that out approach to strong CP is compatible with flavor, and we sketch a comprehensive model. We also look at deconstructed version of this setup which provides a viable 4D model of spontaneous CP breaking which is not in the Nelson-Barr class.

  20. Distributed transform coding via source-splitting

    Science.gov (United States)

    Yahampath, Pradeepa

    2012-12-01

    Transform coding (TC) is one of the best known practical methods for quantizing high-dimensional vectors. In this article, a practical approach to distributed TC of jointly Gaussian vectors is presented. This approach, referred to as source-split distributed transform coding (SP-DTC), can be used to easily implement two terminal transform codes for any given rate-pair. The main idea is to apply source-splitting using orthogonal-transforms, so that only Wyner-Ziv (WZ) quantizers are required for compression of transform coefficients. This approach however requires optimizing the bit allocation among dependent sets of WZ quantizers. In order to solve this problem, a low-complexity tree-search algorithm based on analytical models for transform coefficient quantization is developed. A rate-distortion (RD) analysis of SP-DTCs for jointly Gaussian sources is presented, which indicates that these codes can significantly outperform the practical alternative of independent TC of each source, whenever there is a strong correlation between the sources. For practical implementation of SP-DTCs, the idea of using conditional entropy constrained (CEC) quantizers followed by Slepian-Wolf coding is explored. Experimental results obtained with SP-DTC designs based on both CEC scalar quantizers and CEC trellis-coded quantizers demonstrate that actual implementations of SP-DTCs can achieve RD performance close to the analytically predicted limits.

  1. Adsorption Mechanism of Myelin Basic Protein on Model Substrates and Its Bridging Interaction between the Two Surfaces.

    Science.gov (United States)

    Lee, Dong Woog; Banquy, Xavier; Kristiansen, Kai; Min, Younjin; Ramachandran, Arun; Boggs, Joan M; Israelachvili, Jacob N

    2015-03-17

    Myelin basic protein (MBP) is an intrinsically disordered (unstructured) protein known to play an important role in the stability of myelin's multilamellar membrane structure in the central nervous system. The adsorption of MBP and its capacity to interact with and bridge solid substrates has been studied using a surface forces apparatus (SFA) and a quartz crystal microbalance with dissipation (QCM-D). Adsorption experiments show that MBP molecules adsorb to the surfaces in a swollen state before undergoing a conformational change into a more compact structure with a thickness of ?3 nm. Moreover, this compact structure is able to interact with nearby mica surfaces to form adhesive bridges. The measured adhesion force (energy) between two bridged surfaces is 1.0 ± 0.1 mN/m, (Ead = 0.21 ± 0.02 mJ/m(2)), which is slightly smaller than our previously reported adhesion force of 1.7 mN/m (Ead = 0.36 mJ/m(2)) for MBP adsorbed on two supported lipid bilayers (Lee et al., Proc. Natl. Acad. Sci. U.S.A. 2014, 111, E768-E775). The saturated surface concentration of compact MBP on a single SiO2 surface reaches a stable value of 310 ± 10 ng/cm(2) regardless of the bulk MBP concentration. A kinetic three-step adsorption model was developed that accurately fits the adsorption data. The developed model is a general model, not limited to intrinsically disordered proteins, that can be extended to the adsorption of various chemical compounds that undergo chemical reactions and/or conformational changes upon adsorbing to surfaces. Taken together with our previously published data (Lee et al., Proc. Natl. Acad. Sci. U.S.A. 2014, 111, E768-E775), the present results confirm that conformational changes of MBP upon adsorption are a key for strong adhesion, and that such conformational changes are strongly dependent on the nature of the surfaces. PMID:25706854

  2. The English split infinitive: A comparative study of learner corpora

    Directory of Open Access Journals (Sweden)

    Phoocharoensil, Supakorn

    2013-01-01

    Full Text Available The split infinitive in English has been controversial for over a century. Whilst a prescriptive grammar rule forbids infinitive splitting, it seems that modern grammar academics, as well as users, accept and allow for its occurrence. The approval of split-infinitive structure has also been clearly substantiated by plenty of convincing linguistic evidence: real data from native-speaker corpora confirms its existence in different varieties of English. The present study, using the data collected from Thai Learner English Corpus (TLEC, shows that professional English learners evidently produce a greater number of split infinitives than intermediate learners, whose proficiency level is lower. According to a comparative study of the two learner corpora, the higher the proficiency level of the learner, the greater of the production of the split infinitives, and low-proficiency learners seem to use split infinitives in a more specific context.

  3. Ultrasensitive detection of mode splitting in active optical microcavities

    International Nuclear Information System (INIS)

    Scattering-induced mode splitting in active microcavities is demonstrated. Below the lasing threshold, quality factor enhancement by optical gain allows resolving, in the wavelength-scanning transmission spectrum, of resonance dips of the split modes which otherwise would not be detected in a passive resonator. In the lasing regime, mode splitting manifests itself as two lasing modes with extremely narrow linewidths. Mixing these lasing modes in a detector leads to a heterodyne beat signal whose frequency corresponds to the mode-splitting amount. Lasing regime not only allows ultra-high sensitivity for mode-splitting measurements but also provides an easily accessible scheme by eliminating the need for wavelength scanning around resonant modes. Mode splitting in active microcavities has an immediate impact in enhancing the sensitivity of subwavelength scatterer detection and in studying light-matter interactions in a strong-coupling regime.

  4. Split renal function measured by triphasic helical CT

    International Nuclear Information System (INIS)

    Purpose: To present a method for calculating split renal function solely from routine triphasic helical computed tomography (CT). Subjects and methods: We retrospectively included 26 adult patients who received renal scintigraphy and triphasic CT within 4 weeks in the years 2003 and 2004. All scans were performed using a standard abdominal protocol. Split renal function was calculated as relative single-kidney glomerular filtration rate (GFR) using a simplified 'two-point Patlak plot' technique. As a reference method, split renal function was determined from renal scintigraphy using the standard technique. Results: Linear correlation between the two methods was r = 0.91, split renal function (CT) = 0.0266 + 0.9573 x split renal function (scintigraphy). Conclusion: Split renal function can be measured accurately by minimally extended triphasic CT

  5. Conditional Lot Splitting to Avoid Setups While Reducing Flow Time

    Directory of Open Access Journals (Sweden)

    Jacob V. Simons Jr

    2012-11-01

    Full Text Available Previous research has clearly and consistently shown that flow time advantages accrue from splitting production lots into smaller transfer batches or sub-lots. Less extensively discussed, and certainly undesired, is the fact that lot splitting may dramatically increase the number of setups required, making it impractical in some settings. This paper describes and demonstrates a primary cause of these “extra” setups. It then proposes and evaluates decision rules which selectively invoke lot splitting in an attempt to avoid extra setups. For the closed job shop environment tested, our results indicate that conditional logic can achieve a substantial portion of lot splitting’s flow time improvement while avoiding the vast majority of the additional setups which would be caused by previously tested lot splitting schemes.

  6. Vertical lid split approach for optic nerve sheath decompression

    OpenAIRE

    Prabhakaran Venkatesh; Selva Dinesh

    2009-01-01

    We describe a vertical lid split orbitotomy approach to perform optic nerve sheath fenestration which was done in a patient with idiopathic intracranial hypertension. A vertical lid split incision was used to enter the superomedial orbit and approach the optic nerve sheath. This approach resulted in a successful nerve sheath fenestration, with improvement in the patient?s symptoms. The vertical lid split incision provides access to the optic nerve sheath with minimal morbidity and may ...

  7. Management of trichiasis with lid margin split and cryotherapy

    Science.gov (United States)

    Khafagy, Amr; Mostafa, Mostafa Mahmoud; Fooshan, Fathi

    2012-01-01

    Purpose To evaluate outcomes of lid margin split with cryotherapy to the anterior lid lamella for treating trichiasis. Methods This prospective study included 20 eyelids of ten patients with trichiasis who were treated with lid margin split and cryotherapy. All patients were followed up for 6 months. Results Eighteen eyelids (90%) were successfully treated, and two eyelids (10%) developed recurrence within the follow-up period. Conclusion Lid margin split with cryotherapy is an effective and safe method for treating trichiasis. PMID:23185112

  8. Towards Highly Efficient Bias-Free Solar Water Splitting:

    OpenAIRE

    Abdi, F. F.

    2013-01-01

    Solar water splitting has attracted significant attention due to its potential of converting solar to chemical energy. It uses semiconductor to convert sunlight into electron-hole pairs, which then split water into hydrogen and oxygen. The hydrogen can be used as a renewable fuel, or it can serve as a feedstock material to form hydrocarbons. However, the development of an adequate semiconductor material for solar water splitting still remains a challenge. This thesis work aimed at developing ...

  9. A contribution to the calculation of a safe deltoid split

    OpenAIRE

    Gulihar Abhinav; Balasubramanian Sivaraman; Nixon Matthew; Taylor Grahame J

    2008-01-01

    Purpose : Traditional teaching suggests that a safe deltoid split should extend no more than 5 cm from the lateral edge of the acromion. However, there are reports of nerves lying within this distance. Our aim was to redefine the safe maximum split and also to study the influence of arm length and position. Materials and Methods: Thirty cadaveric shoulders were dissected using the deltoid-splitting approach and the acromion-axillary nerve distance was measured in the neutral position, in ...

  10. Fast complementation of split fluorescent protein triggered by DNA hybridization

    OpenAIRE

    Demidov, Vadim V.; Nikolay V. Dokholyan; Witte-Hoffmann, Carlos; Chalasani, Poornima; Yiu, Hung-Wei; DING, FENG; Yu, Yong; Cantor, Charles R.; Broude, Natalia E.

    2006-01-01

    Fluorescent proteins have proven to be excellent reporters and biochemical sensors with a wide range of applications. In a split form, they are not fluorescent, but their fluorescence can be restored by supplementary protein–protein or protein–nucleic acid interactions that reassemble the split polypeptides. However, in prior studies, it took hours to restore the fluorescence of a split fluorescent protein because the formation of the protein chromophore slowly occurred de novo concurrent...

  11. Photon splitting and Compton scattering in strongly magnetized hot plasma

    OpenAIRE

    Chistyakov, M. V.; Rumyantsev, D. A.; Stus', N. S.

    2012-01-01

    The process of photon splitting is investigated in the presence of strongly magnetized electron-positron plasma. The amplitude of the process is calculated in general case of plasma with nonzero chemical potential and temperature. The polarization selection rules and corresponding partial amplitudes for allowed splitting channels are obtained in the case of charge-symmetric plasma. It is found that the new splitting channel forbidden in magnetized vacuum becomes allowed. The...

  12. Reconfigurable Delay Lines with Split-Ring Resonators

    Directory of Open Access Journals (Sweden)

    Radovan Bojani?

    2011-12-01

    Full Text Available In this paper we proposed anovel multiband delay line which consists of two types of split-ring resonators: the broadiside coupled and the single split-ring resonator. Proposeddelay line exhibits two left-handed bands that can be shifted by twisting the split rings for certain angle or by changing their lengths. This delay line is suitable for design of multiband frequency scanning antennas since can provide phase shift of 70 degrees per 100MHz of frequency shift. Reconfigurability of the proposed delay line is demonstrated with two novel configurations obtained by switching ON/OFF a PIN diode placed at the upper split-ring resonator.

  13. The split pulses from actively Q-switched fiber lasers

    International Nuclear Information System (INIS)

    The split pulse or multi-peak pulse is a unique phenomenon in actively Q-switched fiber lasers. The dynamics of generating the split pulse has been debated with many theories. In this paper, a numerical model is set up to investigate the nature of the split pulse by analyzing the distribution and evolution of the signal and inverted population along the fiber. The impacts of pumping power, fiber length and rise time of the modulator are shown. Based on the numerical simulation, the mechanism is concluded on, and methods for controlling the shape of the pulse to form a narrower high-power split pulse are proposed. (paper)

  14. Electrochemical Water-Splitting Based on Hypochlorite Oxidation.

    Czech Academy of Sciences Publication Activity Database

    Minhová Macounová, Kate?ina; Simic, N.; Ahlberg, E.; Krtil, Petr

    -, - (2015). ISSN 0002-7863 Institutional support: RVO:61388955 Keywords : electrochemistry * hypochlorite oxidation * water-splitting Subject RIV: CG - Electrochemistry Impact factor: 11.444, year: 2013

  15. (Split-)octonions, generalized supersymmetries and M-theory

    International Nuclear Information System (INIS)

    In this talk I discuss the results of a joint paper with Z. Kuznetsova, where the split-division algebras are introduced to construct generalized supersymmetries in different space-time signatures. In particular, in D=11 dimensions, it is shown that split-octonions allow to introduce a split-octonionic M-algebra which extends to the (6,5) signature the properties of the 11-dimensional octonionic M-algebras, only existing in (10,1) and (2,9) signatures. The three space-times above form a triality-related set of (split-)octonionic, eleven dimensional, spacetimes. (author)

  16. Splitting Neutrino masses and Showering into Sky

    Science.gov (United States)

    Fargion, D.; D'Armiento, D.; Lanciano, O.; Oliva, P.; Iacobelli, M.; de Sanctis Lucentini, P. G.; Grossi, M.; de Santis, M.

    2007-06-01

    Neutrino masses might be as light as a few time the atmospheric neutrino mass splitting. The relic cosmic neutrinos may cluster in wide Dark Hot Local Group Halo. 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 water and ice it leads to isotropic light explosions. In air, Glashow's anti-neutrino showers lead to collimated and directional air-showers offering a new Neutrino Astronomy. Because of neutrino flavor mixing, astrophysical energetic tau neutrino above tens GeV must arise over atmospheric background. At TeV range is difficult to disentangle tau neutrinos from other atmospheric flavors. 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 shapes. Such air-showers secondaries release amplified and beamed gamma bursts (like observed TGF), made also by muon and electron pair bundles, with their accompanying rich Cherenkov flashes. Also planet's largest (Saturn, Jupiter) atmosphere limbs offer an ideal screen for UHE GZK and Z-burst tau neutrino, because their largest sizes. Titan thick atmosphere and small radius are optimal for discovering up-going resonant Glashow resonant anti-neutrino electron showers. Detection from Earth of Tau, anti-Tau, anti-electron neutrino induced Air-showers by twin Magic Telescopes on top mountains, or space based detection on balloons and satellites arrays facing the atmosphere's limbs are the simplest and cheapest way toward UHE Neutrino Astronomy Horizons.

  17. Rapid disruption of axon-glial integrity in response to mild cerebral hypoperfusion.

    Science.gov (United States)

    Reimer, Michell M; McQueen, Jamie; Searcy, Luke; Scullion, Gillian; Zonta, Barbara; Desmazieres, Anne; Holland, Philip R; Smith, Jessica; Gliddon, Catherine; Wood, Emma R; Herzyk, Pawel; Brophy, Peter J; McCulloch, James; Horsburgh, Karen

    2011-12-01

    Myelinated axons have a distinct protein architecture essential for action potential propagation, neuronal communication, and maintaining cognitive function. Damage to myelinated axons, associated with cerebral hypoperfusion, contributes to age-related cognitive decline. We sought to determine early alterations in the protein architecture of myelinated axons and potential mechanisms after hypoperfusion. Using a mouse model of hypoperfusion, we assessed changes in proteins critical to the maintenance of paranodes, nodes of Ranvier, axon-glial integrity, axons, and myelin by confocal laser scanning microscopy. As early as 3 d after hypoperfusion, the paranodal septate-like junctions were damaged. This was marked by a progressive reduction of paranodal Neurofascin signal and a loss of septate-like junctions. Concurrent with paranodal disruption, there was a significant increase in nodal length, identified by Nav1.6 staining, with hypoperfusion. Disruption of axon-glial integrity was also determined after hypoperfusion by changes in the spatial distribution of myelin-associated glycoprotein staining. These nodal/paranodal changes were more pronounced after 1 month of hypoperfusion. In contrast, the nodal anchoring proteins AnkyrinG and Neurofascin 186 were unchanged and there were no overt changes in axonal and myelin integrity with hypoperfusion. A microarray analysis of white matter samples indicated that there were significant alterations in 129 genes. Subsequent analysis indicated alterations in biological pathways, including inflammatory responses, cytokine-cytokine receptor interactions, blood vessel development, and cell proliferation processes. Our results demonstrate that hypoperfusion leads to a rapid disruption of key proteins critical to the stability of the axon-glial connection that is mediated by a diversity of molecular events. PMID:22159130

  18. Excitons confined by split-gate potentials

    Science.gov (United States)

    Cocoletzi, Gregorio H.; Ulloa, Sergio E.

    1994-03-01

    Quasi-one-dimensional excitons in a GaAs-AlxGa1-xAs quantum well are studied; they are produced by an applied twin-split-gate potential which confines the particles laterally and allows free motion in one dimension. A variational approach is used to calculate the binding energies Eex and oscillator strength fex of these excitonic transitions as functions of the applied voltage and width of the induced potential wells. In the limit of high electrostatic confinement the excitons are strongly polarized and the system resembles a type II structure where electron and hole are spatially separated. The resulting Eex and fex show a strong dependence on applied voltage and structure width. Strong oscillations are found, which should be observed experimentally, as a consequence of subtle competition between confinement and Coulomb attraction.

  19. Vortex Splitting in Subcritical Nonlinear Schrodinger Equation

    CERN Document Server

    Berloff, Natalia G

    2008-01-01

    Vortices and axisymmetric vortex rings are considered in the framework of the subcritical nonlinear Schrodinger equations. The higher order nonlinearity present in such systems models many-body interactions in superfluid systems and allows one to study the effects of negative pressure on vortex dynamics. We find the critical pressure for which the straight-line vortex becomes unstable to radial expansion of the core. The energy of the straight-line vortices and energy, impulse and velocity of vortex rings are calculated. The effect of a varying pressure on the vortex core is studied. It is shown that under the action of the periodically varying pressure field a vortex ring may split into many vortex rings and the conditions for which this happens are elucidated. These processes are also relevant to experiments in Bose-Einstein condensates where the strength and the sign of two-body interactions can be changed via Feshbach resonance.

  20. Graduate Program in Astrophysics in Split

    CERN Document Server

    Krajnovic, D

    2006-01-01

    Beginning in autumn 2008 the first generation of astronomy master students will start a 2 year course in Astrophysics offered by the Physics department of the University of Split, Croatia (http://fizika.pmfst.hr/astro/english/index.html). This unique master course in South-Eastern Europe, following the Bologna convention and given by astronomers from international institutions, offers a series of comprehensive lectures designed to greatly enhance students' knowledge and skills in astrophysics, and prepare them for a scientific career. An equally important aim of the course is to recognise the areas in which astronomy and astrophysics can serve as a national asset and to use them to prepare young people for real life challenges, enabling graduates to enter the modern society as a skilled and attractive work-force. In this contribution, I present an example of a successful organisation of international astrophysics studies in a developing country, which aims to become a leading graduate program in astrophysics ...

  1. Electrically small split ring resonator antennas

    Science.gov (United States)

    Alici, Kamil Boratay; Ozbay, Ekmel

    2007-04-01

    We studied electrically small resonant antennas composed of split ring resonators (SRR) and monopoles. The antennas considered have the same ring radius, but slightly different geometry. The resonance frequency depends on the geometry of the SRRs. Two SRR antennas are designed. The first one, which operates at 3.62 GHz, is demonstrated theoretically and experimentally. The size of this antenna is Q Q (min Q =1.78). The second one is a rather small SRR antenna in which the capacitance between the rings is increased. The size is reduced to 0.074?0×0.079?0. This structure is called serrated SRR (SSRR). Both antennas have similar far-field patterns but the efficiency of the SSRR antenna is less.

  2. Molecular concepts of water splitting. Nature's approach

    International Nuclear Information System (INIS)

    Based on studies of natural systems, much has also been learned concerning the design principles required for biomimetic catalysis of water splitting and hydrogen evolution. In summary, these include use of abundant and inexpensive metals, the effective protection of the active sites in functional environments, repair/replacement of active components in case of damage, and the optimization of reaction rates. Biomimetic chemistry aims to mimic all these features; many labs are working toward this goal by developing new approaches in the design and synthesis of such systems, encompassing not only the catalytic center, but also smart matrices and assembly via self-organization. More stable catalysts that do not require self-repair may be obtained from fully artificial (inorganic) catalytic systems that are totally different from the biological ones and only apply some basic principles learned from nature. Metals other than Mn/Ca, Fe, and Ni could be used (e.g. Co) in new ligand spheres and other matrices. For light harvesting, charge separation/stabilization, and the effective coupling of the oxidizing/reducing equivalents to the redox catalysts, different methods have been proposed - for example, covalently linked molecular donor-acceptor systems, photo-voltaic devices, semiconductor-based systems, and photoactive metal complexes. The aim of all these approaches is to develop catalytic systems that split water with sunlight into hydrogen and oxygen while displaying high efficiency and long-term stability. Such a system - either biological, biomimetic, or bioinspired - has the potential to be used on a large scale to produce 'solar fuels' (e.g. hydrogen or secondary products thereof). (orig.)

  3. A contribution to the calculation of a safe deltoid split

    Directory of Open Access Journals (Sweden)

    Gulihar Abhinav

    2008-01-01

    Full Text Available Purpose : Traditional teaching suggests that a safe deltoid split should extend no more than 5 cm from the lateral edge of the acromion. However, there are reports of nerves lying within this distance. Our aim was to redefine the safe maximum split and also to study the influence of arm length and position. Materials and Methods: Thirty cadaveric shoulders were dissected using the deltoid-splitting approach and the acromion-axillary nerve distance was measured in the neutral position, in abduction, and in adduction. This was correlated to upper arm length. Deltoid splits were measured at the end of 13 deltoid-splitting shoulder operations. Results : The mean acromion-axillary nerve distance was 6.0 cm (SD 0.6; range 4.5-6.5. Abduction brought the nerve closer by 1.5 cm. There was a strong correlation with upper arm length (r = 0.82 but the presence of high individual variability did not allow calculation of a safe deltoid split. The mean deltoid split in 13 open shoulder operations was 3.4 cm. Conclusions : Taking the mean acromion-axillary nerve distance minus three standard deviations as the safe deltoid split would protect 99.7% of nerves. Therefore we recommend that the maximum deltoid split should be 4.2 cm; this distance would be sufficient to preserve all nerves in our study as well as all those reported by other authors. Splitting the deltoid in abduction should be avoided. Clinical Relevance: The traditional 5-cm deltoid split is probably too generous. We believe 4.2 cm is a safer limit.

  4. A contribution to the calculation of a safe deltoid split

    Science.gov (United States)

    Abhinav, Gulihar; Sivaraman, Balasubramanian; Matthew, Nixon; Grahame J.S., Taylor

    2008-01-01

    Purpose: Traditional teaching suggests that a safe deltoid split should extend no more than 5 cm from the lateral edge of the acromion. However, there are reports of nerves lying within this distance. Our aim was to redefine the safe maximum split and also to study the influence of arm length and position. Materials and Methods: Thirty cadaveric shoulders were dissected using the deltoid-splitting approach and the acromion-axillary nerve distance was measured in the neutral position, in abduction, and in adduction. This was correlated to upper arm length. Deltoid splits were measured at the end of 13 deltoid-splitting shoulder operations. Results: The mean acromion-axillary nerve distance was 6.0 cm (SD 0.6; range 4.5–6.5). Abduction brought the nerve closer by 1.5 cm. There was a strong correlation with upper arm length (r = 0.82) but the presence of high individual variability did not allow calculation of a safe deltoid split. The mean deltoid split in 13 open shoulder operations was 3.4 cm. Conclusions: Taking the mean acromion-axillary nerve distance minus three standard deviations as the safe deltoid split would protect 99.7% of nerves. Therefore we recommend that the maximum deltoid split should be 4.2 cm; this distance would be sufficient to preserve all nerves in our study as well as all those reported by other authors. Splitting the deltoid in abduction should be avoided. Clinical Relevance: The traditional 5-cm deltoid split is probably too generous. We believe 4.2 cm is a safer limit. PMID:20300314

  5. Operator splittings and spatial approximations for evolution equations

    CERN Document Server

    Bátkai, András; Nickel, Gregor

    2008-01-01

    The convergence of various operator splitting procedures, such as the sequential, the Strang and the weighted splitting, is investigated in the presence of a spatial approximation. To this end a variant of Chernoff's product formula is proved. The methods are applied to abstract partial delay differential equations.

  6. Hyperfine and ?-doubling splitting in excited rotational levels of CH

    International Nuclear Information System (INIS)

    The ?-doubling and hyperfine splittings in the 2Pi1/2, J=1/2,3/2, and 5/2, and 2Pi3/2, J=3/2 and 5/2 levels of the CH radical have been calculated using a combination of calculated molecular parameters and observed spectral frequencies. The accuracy of the calculated splittings is discussed

  7. Splitting of a turbulent puff in pipe flow

    Energy Technology Data Exchange (ETDEWEB)

    Shimizu, Masaki; Kawahara, Genta [Graduate School of Engineering Science, Osaka University, Toyonaka, 560-8531 (Japan); Manneville, Paul [LadHyX, CNRS-UMR 7646, Ecole Polytechnique, F-91128, Palaiseau (France); Duguet, Yohann, E-mail: shimizu@me.es.osaka-u.ac.jp [LIMSI-CNRS, UPR 3251, Université Paris-Sud, F-91403 Orsay (France)

    2014-12-01

    The transition to turbulence of the flow in a pipe of constant radius is numerically studied over a range of Reynolds numbers where turbulence begins to expand by puff splitting. We first focus on the case Re=2300 where splitting occurs as discrete events. Around this value only long-lived pseudo-equilibrium puffs can be observed in practice, as typical splitting times become very long. When Re is further increased, the flow enters a more continuous puff splitting regime where turbulence spreads faster. Puff splitting presents itself as a two-step stochastic process. A splitting puff first emits a chaotic pseudopod made of azimuthally localized streaky structures at the downstream (leading) laminar–turbulent interface. This structure can later expand azimuthally as it detaches from the parent puff. Detachment results from a collapse of turbulence over the whole cross-section of the pipe. Once the process is achieved a new puff is born ahead. Large-deviation consequences of elementary stochastic processes at the scale of the streak are invoked to explain the statistical nature of splitting and the Poisson-like distributions of splitting times reported by Avila et al (2011 Science 333 192–6). (paper)

  8. Severe demyelinating hypertrophic polyneuropathy caused by a de novo frameshift mutation within the intracellular domain of myelin protein zero (MPZ/P0).

    Science.gov (United States)

    Zschüntzsch, Jana; Dibaj, Payam; Pilgram, Sara; Kötting, Judith; Gerding, Wanda M; Neusch, C

    2009-06-15

    Hereditary motor and sensory neuropathy (HMSN), also known as Charcot-Marie-Tooth disease (CMT) is a group of clinically and genetically heterogeneous neuropathies classically divided into demyelinating (CMT1) and axonal forms (CMT2). The most common demyelinating form is CMT1A with an underlying duplication in the gene coding for the peripheral myelin protein 22 (PMP22). Less frequently, mutations in the myelin protein zero gene (MPZ/P(0)) account for demyelinating CMT1B, Dejerine-Sottas syndrome (DSS), or congenital hypomyelinating neuropathy (CHN). Here, we report a patient with a severe, early-onset hypertrophic and dysmyelinating neuropathy. The patient exhibits a novel frameshift mutation with an insertion of a single T-nucleotide on position c.618_619 of the MPZ gene resulting in a premature stop M207fsX38. PMID:19344920

  9. Particle splitting in smoothed particle hydrodynamics based on Voronoi diagram

    CERN Document Server

    Chiaki, Gen

    2015-01-01

    We present a novel method for particle splitting in smoothed particle hydrodynamics simulations. Our method utilizes the Voronoi diagram for a given particle set to determine the position of fine daughter particles. We perform several test simulations to compare our method with a conventional splitting method in which the daughter particles are placed isotropically over the local smoothing length. We show that, with our method, the density deviation after splitting is reduced by a factor of about two compared with the conventional method. Splitting would smooth out the anisotropic density structure if the daughters are distributed isotropically, but our scheme allows the daughter particles to trace the original density distribution with length scales of the mean separation of their parent. We apply the particle splitting to simulations of the primordial gas cloud collapse. The thermal evolution is accurately followed to the hydrogen number density of 10^12 /cc. With the effective mass resolution of ~10^-4 Msu...

  10. Photon splitting and Compton scattering in strongly magnetized hot plasma

    CERN Document Server

    Chistyakov, M V; Stus', N S

    2012-01-01

    The process of photon splitting is investigated in the presence of strongly magnetized electron-positron plasma. The amplitude of the process is calculated in general case of plasma with nonzero chemical potential and temperature. The polarization selection rules and corresponding partial amplitudes for allowed splitting channels are obtained in the case of charge-symmetric plasma. It is found that the new splitting channel forbidden in magnetized vacuum becomes allowed. The absorption rates of the photon splitting are calculated with taking into account of the photon dispersion and wave function renormalization. In addition, the comparison of photon splitting and Compton scattering process is made. The influence of the reactions under consideration on the radiation transfer in the framework of magnetar model of SGR burst is discussed.

  11. Shear wave splitting and shear wave splitting tomography of the southern Puna plateau

    Science.gov (United States)

    Calixto, Frank J.; Robinson, Danielle; Sandvol, Eric; Kay, Suzanne; Abt, David; Fischer, Karen; Heit, Ben; Yuan, Xiaohui; Comte, Diana; Alvarado, Patricia

    2014-11-01

    We have investigated the seismic anisotropy beneath the Central Andean southern Puna plateau by applying shear wave splitting analysis and shear wave splitting tomography to local S waves and teleseismic SKS, SKKS and PKS phases. Overall, a very complex pattern of fast directions throughout the southern Puna plateau region and a circular pattern of fast directions around the region of the giant Cerro Galan ignimbrite complex are observed. In general, teleseismic lag times are much greater than those for local events which are interpreted to reflect a significant amount of sub and inner slab anisotropy. The complex pattern observed from shear wave splitting analysis alone is the result of a complex 3-D anisotropic structure under the southern Puna plateau. Our application of shear wave splitting tomography provides a 3-D model of anisotropy in the southern Puna plateau that shows different patterns depending on the driving mechanism of upper-mantle flow and seismic anisotropy. The trench parallel a-axes in the continental lithosphere above the slab east of 68W may be related to deformation of the overriding continental lithosphere since it is under compressive stresses which are orthogonal to the trench. The more complex pattern below the Cerro Galan ignimbrite complex and above the slab is interpreted to reflect delamination of continental lithosphere and upwelling of hot asthenosphere. The a-axes beneath the Cerro Galan, Cerro Blanco and Carachi Pampa volcanic centres at 100 km depth show some weak evidence for vertically orientated fast directions, which could be due to vertical asthenospheric flow around a delaminated block. Additionally, our splitting tomographic model shows that there is a significant amount of seismic anisotropy beneath the slab. The subslab mantle west of 68W shows roughly trench parallel horizontal a-axes that are probably driven by slab roll back and the relatively small coupling between the Nazca slab and the underlying mantle. In contrast, the subslab region (i.e. depths greater than 200 km) east of 68W shows a circular pattern of a-axes centred on a region with small strength of anisotropy (Cerro Galan and its eastern edge) which suggest the dominant mechanism is a combination of slab roll back and flow driven by an overlying abnormally heated slab or possibly a slab gap. There seems to be some evidence for vertical flow below the slab at depths of 200-400 km driven by the abnormally heated slab or slab gap. This cannot be resolved by the tomographic inversion due to the lack of ray crossings in the subslab mantle.

  12. Variations in the Electrostatic Landscape of Class II Human Leukocyte Antigen Molecule Induced by Modifications in the Myelin Basic Protein Peptide: A Theoretical Approach

    OpenAIRE

    Agudelo, William A.; Galindo, Johan F.; Ortiz, Marysol; Villaveces, Jose? L.; Daza, Edgar E.; Patarroyo, Manuel E.

    2009-01-01

    The receptor-ligand interactions involved in the formation of the complex between Class II Major Histocompatibility Complex molecules and antigenic peptides, which are essential for establishing an adaptive immunological response, were analyzed in the Class II Human Leukocyte Antigen (HLA) - Myelin Basic Protein (MBP) peptide complex (HLA-DR?1*1501-MBP) using a multipolar molecular electrostatic potential approach. The Human Leukocyte Antigen - peptide complex system was divided into four po...

  13. Neuron-Specific Enolase, but Not S100B or Myelin Basic Protein, Increases in Peripheral Blood Corresponding to Lesion Volume after Cortical Impact in Piglets

    OpenAIRE

    Costine, Beth A.; Quebeda-clerkin, Patricia B.; Dodge, Carter P.; Harris, Brent T.; Hillier, Simon C.; Duhaime, Ann-christine

    2012-01-01

    A peripheral indicator of the presence and magnitude of brain injury has been a sought-after tool by clinicians. We measured neuron-specific enolase (NSE), myelin basic protein (MBP), and S100B, prior to and after scaled cortical impact in immature pigs, to determine if these purported markers increase after injury, correlate with the resulting lesion volume, and if these relationships vary with maturation. Scaled cortical impact resulted in increased lesion volume with increasing age. Concen...

  14. Effect of phosphorylation of myelin basic protein by MAPK on its interactions with actin and actin binding to a lipid membrane in vitro.

    Science.gov (United States)

    Boggs, Joan M; Rangaraj, Godha; Gao, Wen; Heng, Yew-Meng

    2006-01-17

    Myelin basic protein (MBP) binds to negatively charged lipids on the cytosolic surface of oligodendrocyte membranes and is most likely responsible for adhesion of these surfaces in the multilayered myelin sheath. It can also polymerize actin, bundle F-actin filaments, and bind actin filaments to lipid bilayers through electrostatic interactions. MBP consists of a number of posttranslationally modified isomers of varying charge, some resulting from phosphorylation at several sites by different kinases, including mitogen-activated protein kinase (MAPK). Phosphorylation of MBP in oligodendrocytes occurs in response to various extracellular stimuli. Phosphorylation/dephosphorylation of MBP also occurs in the myelin sheath in response to electrical activity in the brain. Here we investigate the effect of phosphorylation of MBP on its interaction with actin in vitro by phosphorylating the most highly charged unmodified isomer, C1, at two sites with MAPK. Phosphorylation decreased the ability of MBP to polymerize actin and to bundle actin filaments but had no effect on the dissociation constant of the MBP-actin complex or on the ability of Ca2+-calmodulin to dissociate the complex. The most significant effect of phosphorylation on the MBP-actin complex was a dramatic reduction in its ability to bind to negatively charged lipid bilayers. The effect was much greater than that reported earlier for another charge isomer of MBP, C8, in which six arginines were deiminated to citrulline, resulting in a reduction of net positive charge of 6. These results indicate that although average electrostatic forces are the primary determinant of the interaction of MBP with actin, phosphorylation may have an additional effect due to a site-specific electrostatic effect or to a conformational change. Thus, phosphorylation of MBP, which occurs in response to various extracellular signals in both myelin and oligodendrocytes, attenuates the ability of MBP to polymerize and bundle actin and to bind it to a negatively charged membrane. PMID:16401070

  15. Chronic postnatal administration of methylmalonic acid provokes a decrease of myelin content and ganglioside N-acetylneuraminic acid concentration in cerebrum of young rats

    Directory of Open Access Journals (Sweden)

    Brusque A.M.

    2001-01-01

    Full Text Available Levels of methylmalonic acid (MMA comparable to those of human methylmalonic acidemia were achieved in blood (2-2.5 mmol/l and brain (1.35 µmol/g of rats by administering buffered MMA, pH 7.4, subcutaneously twice a day from the 5th to the 28th day of life. MMA doses ranged from 0.76 to 1.67 µmol/g as a function of animal age. Control rats were treated with saline in the same volumes. The animals were sacrificed by decapitation on the 28th day of age. Blood was taken and the brain was rapidly removed. Medulla, pons, the olfactory lobes and cerebellum were discarded and the rest of the brain ("cerebrum" was isolated. Body and "cerebrum" weight were measured, as well as the cholesterol and triglyceride concentrations in blood and the content of myelin, total lipids, and the concentrations of the lipid fractions (cholesterol, glycerolipids, phospholipids and ganglioside N-acetylneuraminic acid (ganglioside-NANA in the "cerebrum". Chronic MMA administration had no effect on body or "cerebrum" weight, suggesting that the metabolites per se neither affect the appetite of the rats nor cause malnutrition. In contrast, MMA caused a significant reduction of plasma triglycerides, but not of plasma cholesterol levels. A significant diminution of myelin content and of ganglioside-NANA concentration was also observed in the "cerebrum". We propose that the reduction of myelin content and ganglioside-NANA caused by MMA may be related to the delayed myelination/cerebral atrophy and neurological dysfunction found in methylmalonic acidemic children.

  16. Chronic postnatal administration of methylmalonic acid provokes a decrease of myelin content and ganglioside N-acetylneuraminic acid concentration in cerebrum of young rats

    Scientific Electronic Library Online (English)

    A.M., Brusque; L., Rotta; L.F., Pettenuzzo; D., Junqueira; C.V., Schwarzbold; A.T., Wyse; C.M.D., Wannmacher; C.S., Dutra-Filho; M., Wajner.

    2001-02-01

    Full Text Available Levels of methylmalonic acid (MMA) comparable to those of human methylmalonic acidemia were achieved in blood (2-2.5 mmol/l) and brain (1.35 µmol/g) of rats by administering buffered MMA, pH 7.4, subcutaneously twice a day from the 5th to the 28th day of life. MMA doses ranged from 0.76 to 1.67 µmol [...] /g as a function of animal age. Control rats were treated with saline in the same volumes. The animals were sacrificed by decapitation on the 28th day of age. Blood was taken and the brain was rapidly removed. Medulla, pons, the olfactory lobes and cerebellum were discarded and the rest of the brain ("cerebrum") was isolated. Body and "cerebrum" weight were measured, as well as the cholesterol and triglyceride concentrations in blood and the content of myelin, total lipids, and the concentrations of the lipid fractions (cholesterol, glycerolipids, phospholipids and ganglioside N-acetylneuraminic acid (ganglioside-NANA)) in the "cerebrum". Chronic MMA administration had no effect on body or "cerebrum" weight, suggesting that the metabolites per se neither affect the appetite of the rats nor cause malnutrition. In contrast, MMA caused a significant reduction of plasma triglycerides, but not of plasma cholesterol levels. A significant diminution of myelin content and of ganglioside-NANA concentration was also observed in the "cerebrum". We propose that the reduction of myelin content and ganglioside-NANA caused by MMA may be related to the delayed myelination/cerebral atrophy and neurological dysfunction found in methylmalonic acidemic children.

  17. Historical note: an analysis of a 17th century illustration of a child with split hand/split foot malformation

    OpenAIRE

    Ohry, Avi; Frydman, Moshe

    2010-01-01

    In one of Philipp Jakob Sachs von Lewenhaimb’s (1627–1672) books, one may find perhaps the first illustration of a child with the split hand/split foot malformation. A short historical note and some clinical genetic data are given.

  18. Deimination of myelin basic protein. 2. Effect of methylation of MBP on its deimination by peptidylarginine deiminase.

    Science.gov (United States)

    Pritzker, L B; Joshi, S; Harauz, G; Moscarello, M A

    2000-05-01

    Deimination of myelin basic protein (MBP) has been implicated in the chemical pathogenesis of multiple sclerosis (MS). Degradation of bovine MBP by cathepsin D, a myelin-associated protease, was increased when 6 arginyl residues were deiminated and became very rapid when all 18 arginyl residues were deiminated. Since MBP contains a number of modifications, including methylation, phosphorylation, etc., we studied the effect of methylation, an irreversible modification, to determine how this modification affected deimination. Methylation of Arg 106 in bovine MBP (Arg 107 in human), a naturally occurring modification of MBP, has been shown to affect the deimination of arginyl residues in the present study. Since fractionation of MBP into unmethylated, monomethylated, and dimethylated species cannot be done readily on a preparative scale, mass spectrometry with the Q-TOF instrument resolved these species readily since each differed from the other by 14 atomic mass units (amu). Examination of five different hMBP samples, two from normal brain and three from MS brain, revealed that increased deimination of arginyl residues correlated with a decreased methylation of Arg 107 (human sequence). To study this process in vitro, bovine MBP (bMBP) was used. Component 1 (C-1) is the most cationic of the MBP "charge isomers" and the most unmodified, in which all arginyl residues are intact. It was deiminated to various extents with purified bovine brain peptidylarginine deiminase, generating a number of species containing 0-13.7 mol of citrulline/mol of bMBP. Mass spectrometry of each of these species permitted us to determine the influence of methylation of Arg 106 (bovine sequence) on deimination by this enzyme. We found that bMBP with unmethylated arginine was deiminated at a rate of 0.081 mol of citrulline/min, with monomethylarginine, 0.068 mol of citrulline/min, and with dimethylarginine, 0.036 mol of citrulline/min. We suggest that the methylated arginyl residue becomes sequestered in the hydrophobic beta-sheet structure and disrupts the three-dimensional structure of the protein so that other arginyl residues are less accessible to peptidylarginine deiminase. PMID:10820009

  19. mTORC1 Controls PNS Myelination along the mTORC1-RXR?-SREBP-Lipid Biosynthesis Axis in Schwann Cells

    Directory of Open Access Journals (Sweden)

    Camilla Norrmén

    2014-10-01

    Full Text Available Myelin formation during peripheral nervous system (PNS development, and reformation after injury and in disease, requires multiple intrinsic and extrinsic signals. Akt/mTOR signaling has emerged as a major player involved, but the molecular mechanisms and downstream effectors are virtually unknown. Here, we have used Schwann-cell-specific conditional gene ablation of raptor and rictor, which encode essential components of the mTOR complexes 1 (mTORC1 and 2 (mTORC2, respectively, to demonstrate that mTORC1 controls PNS myelination during development. In this process, mTORC1 regulates lipid biosynthesis via sterol regulatory element-binding proteins (SREBPs. This course of action is mediated by the nuclear receptor RXR?, which transcriptionally regulates SREBP1c downstream of mTORC1. Absence of mTORC1 causes delayed myelination initiation as well as hypomyelination, together with abnormal lipid composition and decreased nerve conduction velocity. Thus, we have identified the mTORC1-RXR?-SREBP axis controlling lipid biosynthesis as a major contributor to proper peripheral nerve function.

  20. Inactivation of Fibroblast Growth Factor Receptor Signaling in Myelinating Glial Cells Results in Significant Loss of Adult Spiral Ganglion Neurons Accompanied by Age-Related Hearing Impairment

    Science.gov (United States)

    Wang, S. J.; Furusho, M.; D’Sa, C.; Kuwada, S.; Conti, L.; Morest, D. K.; Bansal, R.

    2010-01-01

    Hearing loss has been attributed to many factors, including degeneration of sensory neurons in the auditory pathway and demyelination along the cochlear nerve. Fibroblast growth factors (FGFs), which signal through four receptors (Fgfrs), are produced by auditory neurons and play a key role in embryonic development of the cochlea and in neuroprotection against sound-induced injury. However, the role of FGF signaling in the maintenance of normal auditory function in adult and aging mice remains to be elucidated. Furthermore, the contribution of glial cells, which myelinate the cochlear nerves, is poorly understood. To address these questions, we generated transgenic mice in which Fgfr1 and Fgfr2 were specifically inactivated in Schwann cells and oligodendrocytes but not in neurons. Adult mutant mice exhibited late onset of hearing impairment, which progressed markedly with age. The hearing impairment was accompanied by significant loss of myelinated spiral ganglion neurons. The pathology extended into the cochlear nucleus, without apparent loss of myelin or of the deletion-bearing glial cells themselves. This suggests that perturbation of FGF receptor-mediated glial function leads to the attenuation of glial support of neurons, leading to their loss and impairment of auditory functions. Thus, FGF/FGF receptor signaling provides a potentially novel mechanism of maintaining reciprocal interactions between neurons and glia in adult and aging animals. Dysfunction of glial cells and FGF receptor signaling may therefore be implicated in neurodegenerative hearing loss associated with normal aging. PMID:19598249

  1. Intraventricular Hemorrhage Induces Deposition of Proteoglycans in Premature Rabbits, but Their In Vivo Degradation with Chondroitinase Does Not Restore Myelination, Ventricle Size and Neurological Recovery

    Science.gov (United States)

    Vinukonda, Govindaiah; Zia, Muhammad T.; Bhimavarapu, Bala B. R.; Hu, Furong; Feinberg, Michelle; Bokhari, Aquiba; Ungvari, Zoltan; Fried, Victor A.; Ballabh, Praveen

    2013-01-01

    Intraventricular hemorrhage (IVH) results in white matter injury and hydrocephalus in premature infants. Chondroitin sulfate proteoglycans (CSPGs)--neuorcan, brevican, versican, aggrecan and phosphacan—are unregulated in the extracellular matrix after brain injury, and their degradation enhances plasticity of the brain. Therefore, we hypothesized that CSPG levels were elevated in the forebrain of premature infants with IVH and that in vivo degradation of CSPGs would enhance maturation of oligodendrocyte, augment myelination, promote neurological recovery, and minimize hydrocephalus. We found that levels of neurocan, brevican, aggrecan, phosphacan, and versican were elevated, whereas NG2 expression was reduced in premature rabbit pups and human infants with IVH compared to controls. Intracerebroventricular chondroitinase ABC (ChABC) reduced the expression of neuorcan, brevican, versican and aggrecan, but not NG2. However, ChABC treatment did not enhance maturation of oligodendrocytes, myelination, or neurological recovery in the pups with IVH. Moreover, ChABC did not reduce gliosis or ventriculomegaly. Our results demonstrate that IVH induces distinct changes in the components of CSPGs, and that reversing these changes by in vivo ChABC treatment neither promotes clinical recovery, myelination, nor reduces ventriculomegaly in preterm rabbit pups. PMID:23474192

  2. Citrulline-containing myelin basic protein is recognized by T-cell lines derived from multiple sclerosis patients and healthy individuals.

    Science.gov (United States)

    Martin, R; Whitaker, J N; Rhame, L; Goodin, R R; McFarland, H F

    1994-01-01

    The cause of MS is uncertain, but an autoimmune disorder of the CNS is likely, and myelin basic protein (MBP) is a candidate antigen. MBP exists in different isoforms, generated by differential splicing of exons, and in charge isomers, generated by posttranslational modifications. Different isoforms and charge isomers presumably subserve different functions, and they vary in abundance in immature myelin found during myelinogenesis and remyelination compared with mature myelin. The 18.5-kd isomer is most abundant in normal human adults and consequently has been used almost exclusively for immunologic studies in MS. In the present study, we examined a different but abundant charge isomer of MBP, termed MBP-C8, to determine whether it could be recognized by MBP-specific cytotoxic and proliferative T-cell lines (TCL) and whether a T-cell response directed exclusively against citrulline-containing residues of MBP-C8 exists in MS patients and healthy controls. We showed that citrulline affects antigen recognition by some TCL that are specific for areas of MBP that contain the citrulline residues. Following stimulation with MBP-C8, MBP-C8-specific TCL could be generated from both MS patients and controls. T-cell responses against antigens that appear during myelinogenesis and during remyelination may be important in inducing and perpetuating an autoimmune response involved in the pathogenesis of MS. PMID:7507225

  3. Split-Field Magnet facility upgraded

    CERN Multimedia

    1977-01-01

    The Split Field Magnet (SFM) was the largest spectrometer for particles from beam-beam collisions in the ISR. It could determine particle momenta in a large solid angle, but was designed mainly for the analysis of forward travelling particles.As the magnet was working on the ISR circulating beams, its magnetic field had to be such as to restore the correct proton orbit.The SFM, therefore, produced zero field at the crossing point and fields of opposite signs upstream and downstream of it and was completed by 2 large and 2 small compensator magnets. The gradient effects were corrected by magnetic channels equipped with movable flaps. The useful magnetic field volume was 28 m3, the induction in the median plane 1.14 T, the gap heigth 1.1 m, the length 10.5 m, the weight about 1000 ton. Concerning the detectors, the SFM was the first massive application of multiwire proportional chambers (about 70000 wires) which filled the main and the large compensator magnets. In 1976 an improved programme was started with tw...

  4. Vertex Splitting and Upper Embeddable Graphs

    CERN Document Server

    Dong, Guanghua; Huang, Yuanqiu; Ren, Han; Liu, Yanpei

    2012-01-01

    The weak minor G of a graph G is the graph obtained from G by a sequence of edge-contraction operations on G. A weak-minor-closed family of upper embeddable graphs is a set G of upper embeddable graphs that for each graph G in G, every weak minor of G is also in G. Up to now, there are few results providing the necessary and sufficient conditions for characterizing upper embeddability of graphs. In this paper, we studied the relation between the vertex splitting operation and the upper embeddability of graphs; provided not only a necessary and sufficient condition for characterizing upper embeddability of graphs, but also a way to construct weak-minor-closed family of upper embeddable graphs from the bouquet of circles; extended a result in J: Graph Theory obtained by L. Nebesk{\\P}y. In addition, the algorithm complex of determining the upper embeddability of a graph can be reduced much by the results obtained in this paper.

  5. Probing split supersymmetry with cosmic rays

    International Nuclear Information System (INIS)

    A striking aspect of the recently proposed split supersymmetry is the existence of heavy gluinos which are metastable because of the very heavy squarks which mediate their decay. In this paper we correlate the expected flux of these particles with the accompanying neutrino flux produced in inelastic pp collisions in distant astrophysical sources. We show that an event rate at the Pierre Auger Observatory of approximately 1 yr-1 for gluino masses of about 500 GeV is consistent with existing limits on neutrino fluxes. Such an event rate requires powerful cosmic ray engines able to accelerate particles up to extreme energies, somewhat above 5x1013 GeV. The extremely low inelasticity of the gluino-containing hadrons in their collisions with the air molecules makes possible a distinct characterization of the showers induced in the atmosphere. Should such anomalous events be observed, we show that their cosmogenic origin, in concert with the requirement that they reach the Earth before decay, leads to a lower bound on their proper lifetime of the order of 100 years, and consequently, to a lower bound on the scale of supersymmetry breaking, ?SUSY>2.6x1011 GeV. Obtaining such a bound is not possible in collider experiments

  6. Descent Assisted Split Habitat Lunar Lander Concept

    Science.gov (United States)

    Mazanek, Daniel D.; Goodliff, Kandyce; Cornelius, David M.

    2008-01-01

    The Descent Assisted Split Habitat (DASH) lunar lander concept utilizes a disposable braking stage for descent and a minimally sized pressurized volume for crew transport to and from the lunar surface. The lander can also be configured to perform autonomous cargo missions. Although a braking-stage approach represents a significantly different operational concept compared with a traditional two-stage lander, the DASH lander offers many important benefits. These benefits include improved crew egress/ingress and large-cargo unloading; excellent surface visibility during landing; elimination of the need for deep-throttling descent engines; potentially reduced plume-surface interactions and lower vertical touchdown velocity; and reduced lander gross mass through efficient mass staging and volume segmentation. This paper documents the conceptual study on various aspects of the design, including development of sortie and outpost lander configurations and a mission concept of operations; the initial descent trajectory design; the initial spacecraft sizing estimates and subsystem design; and the identification of technology needs

  7. Markov branching in the vertex splitting model

    International Nuclear Information System (INIS)

    We study a special case of the vertex splitting model which is a recent model of randomly growing trees. For any finite maximum vertex degree D, we find a one parameter model, with parameter ? element of [0,1] which has a so-called Markov branching property. When D=? we find a two parameter model with an additional parameter ? element of [0,1] which also has this feature. In the case D = 3, the model bears resemblance to Ford's ?-model of phylogenetic trees and when D=? it is similar to its generalization, the ??-model. For ? = 0, the model reduces to the well known model of preferential attachment. In the case ? > 0, we prove convergence of the finite volume probability measures, generated by the growth rules, to a measure on infinite trees which is concentrated on the set of trees with a single spine. We show that the annealed Hausdorff dimension with respect to the infinite volume measure is 1/?. When ? = 0 the model reduces to a model of growing caterpillar graphs in which case we prove that the Hausdorff dimension is almost surely 1/? and that the spectral dimension is almost surely 2/(1 + ?). We comment briefly on the distribution of vertex degrees and correlations between degrees of neighbouring vertices

  8. Stratification-induced scale splitting in convection

    Science.gov (United States)

    Shcheritsa, O. V.; Getling, A. V.; Mazhorova, O. S.

    2015-02-01

    The coexistence of motions on various scales is a remarkable feature of solar convection, which should be taken into account in analyses of the dynamics of magnetic fields. Therefore, it is important to investigate the factors responsible for the observed multiscale structure of solar convection. In this study, an attempt is made to understand how the scales of convective motions are affected by the particularities of the static temperature stratification of a fluid layer. To this end, simple models are considered. The equations of two-dimensional thermal convection are solved numerically for a plane horizontal fluid layer heated from below, in an extended Boussinesq approximation that admits thermal-diffusivity variations. These variations specify the stratification of the layer. The static temperature gradient in a thin sublayer near the upper surface of the layer is assumed to be many times larger than in the remainder of the layer. In some cases, distributed heat sinks are assumed to produce a stably stratified region overlying the convective layer. Manifestations of the scale-splitting effect are noted, which depend on the boundary conditions and stratification; it becomes more pronounced with the increase of the Rayleigh number. Small-scale convection cells are advected by larger-scale flows. In particular, the phase trajectories of fluid particles indicate the presence of complex attractors, which reflect the multiscale structure of the flow. The effect of the stably stratified upper sublayer on the flow scales is also considered.

  9. Touching Syllable Segmentation using Split Profile Algorithm

    Directory of Open Access Journals (Sweden)

    L.Pratap Reddy

    2010-05-01

    Full Text Available The most challenging task of a character recognition system is associated with segmentation of individual components of the script with maximum efficiency. This process is relatively easy with regard to stroke based and standard scripts. Cursive scripts are more complex possessing a large number of overlapping and touching objects, where in the statistical behavior of the topological properties are to be studied extensively for achieving highest accuracy. Certain amount of similarity exists between unconstrained hand written text as well as South Indian scripts in terms of topology, component combinations, overlapping and merging characteristics. The concept of syllables and their formulations is an additive complexity with regard to Indian scripts. In this paper the statistical behavior of the cursive script, Telugu, is presented. The topological properties in terms of zones, component combinations, behavioural aspects of syllables are studied and adopted in the segmentation process. The statistical behaviour of cursive components are evaluated. Split Profile Algorithm is proposed while handling touching components. The proposed algorithm is evaluated on different fonts and sizes. The performance of the proposed algorithm is compared with two approaches methods viz aspect ratio and syllable width approaches.

  10. Image Segmentation Using Two Step Splitting Function

    Directory of Open Access Journals (Sweden)

    Gopal Kumar Jha

    2013-12-01

    Full Text Available Image processing and computer vision is widely using Level Set Method (LSM. In conventional level set formulation, irregularities are developed during evolution of level set function, which cause numerical errors and eventually destroy the stability of the evolution. Therefore a numerical remedy called re-initialization is typically applied periodically to replace the degraded level set function. However re –initialization raises serious problem that is when and how it should be performed and also affects numerical accuracy in an undesirable way. To overcome this drawback of re-initialization process, a new variation level set formulation called Distance regularization level set evolution (DRLSE is introduced in which the regularity of the level set function is internally maintained during the level set evolution. DRLSE allows more general and effective initialization of the level set function. But DRLSE uses relatively large number of steps to ensure efficient numerical accuracy. Here in this thesis we are implementing faster and equally efficient computation technique called two step splitting method (TSSM. TSSM is physio-chemical reaction diffusion equation in which firstly LSE equation get iterated and then regularize the level set function from the first step to ensure the stability and hence re-initialization is completely eliminated from LSE which also satisfy DRLSE.

  11. Split-course radiotherapy: where do we stand?

    International Nuclear Information System (INIS)

    Background: Split-course radiotherapy is only rarely applied in curative radiotherapy and there might be a number of arguments to believe that continuous radiotherapy is superior to split-course treatment. In order to point out the evidence current treatment practice is based on, the available randomized trials and some prominent retrospective analyses on split-course radiotherapy were critically assessed. Material and Methods: The analysis of the clinical results was based on published data only. Publications were searched in a Medline database. Results: Assessment of 13 randomized trials, including the data of 2,112 patients, revealed no significant difference between continuous-course and split-course radiotherapy. Astonishingly, the outcome of 77 radiotherapy studies on split-course, most of which are retrospective, seems to depend on the year of publication, suggesting publication bias. Conclusions: No clinically relevant difference between continuous and split-course radiotherapy could be found. This, of course, does not proof that there are indeed no differences but the data do not allow to draw clear-cut conclusions in favor of or against split-course radiotherapy due to methodological shortcomings of the studies. (orig.)

  12. Split octonion reformulation of generalized linear gravitational field equations

    Science.gov (United States)

    Chanyal, B. C.

    2015-05-01

    In this paper, we describe the properties of split octonions and their connection with the 2 × 2 Zorn vector matrix containing both scalar and vector components. Starting with a brief description of gravito-dyons, we reformulate the generalized linear gravitational field equations of gravito-dyons in terms of split octonion. We express the generalized gravito-Heavisidian (GH) potentials, fields, and various wave equations of gravito-dyons in terms of split octonions variables. Accordingly, we demonstrate the work-energy theorem of classical mechanics reproducing the continuity equation for the case of gravito-dyons in terms of split octonions. Further, we discuss the split octonionic form of linear momentum conservation law for gravito-dyons in the case of linear gravitational theory. We have summarized the various split octonion equations for the case of the generalized GH-field of gravito-dyons and the generalized electromagnetic field of dyons. The unified fields of dyons and gravito-dyons have been demonstrated and corresponding field equations are discussed in unique and consistent manner in terms of split octonions.

  13. The Japan Stock Split Bubble and the Livedoor Shock

    Directory of Open Access Journals (Sweden)

    Youki Kohsaka

    2014-04-01

    Full Text Available Livedoor, a famous Japanese IT company, experienced rapid growth through the overuse of a stock split strategy. Because of this strategy, the company faced a criminal investigation for suspicion of account rigging in January 2006. In this paper, I examine whether the Japanese stock split bubble burst not only because of system reform to make newly issued shares tradable on their ex-dates, but also because of the Livedoor shock. To explore this possibility, I evaluated data that were classified into specific categories: stock splits under the old system’s conditions that prevented the trade of newly issued shares for about 50 days following the ex-date, stock splits under the new system’s conditions, and news announced before and after the Livedoor shock. I estimated abnormal returns for each stock on their respective announcement dates. Results demonstrate that under the old system, trading restrictions for newly issued shares caused increases in stock prices, but the Livedoor shock stalled these increases for split stocks. These results suggest that the stock split bubble burst not only because of system reform but also because of changes in investor sentiment with regard to split stocks.

  14. Myelin paucity of the superior cerebellar peduncle in individuals with Friedreich ataxia: an MRI magnetization transfer imaging study.

    Science.gov (United States)

    Corben, Louise A; Kashuk, Saman R; Akhlaghi, Hamed; Jamadar, Sharna; Delatycki, Martin B; Fielding, Joanne; Johnson, Beth; Georgiou-Karistianis, Nellie; Egan, Gary F

    2014-08-15

    The dentate nucleus (DN) is the major relay station for neural connection between the cerebellum and cerebrum via the thalamus, and is a significant component of the neuropathological profile of Friedreich ataxia (FRDA). We have previously shown that the size of the superior cerebellar peduncle (SCP), which links the DN to cortical and subcortical structures via the thalamus, is significantly reduced in individuals with FRDA compared to control participants. This study used magnetization transfer imaging (MTI) to examine and contrast the integrity of white matter (WM) in the SCP and the corpus callosum (CC) (control region) in ten individuals with FRDA and ten controls. Individuals with FRDA demonstrated a significant reduction in the magnetization transfer ratio (MTR) in the SCP compared to control participants. However, there was no significant difference between groups in MTR in the CC. When comparing regions within groups, there was a significant reduction in MTR in the SCP compared to CC in participants with FRDA only. We suggest that the reduction in MTR in the SCP may be indicative of lack of myelin secondary to axonal loss and oligodendroglial dysfunction in WM tracts in individuals with FRDA. PMID:24930398

  15. Binding of methylmercury and methylmercury-thiol complexes by myelin isolated from mice of differing selenium status

    International Nuclear Information System (INIS)

    The chemical form of methylmercury found in the body provides evidence of the intimate involvement of glutathione and glutathione metabolites with methylmercury. The involvement of glutathione in converting protein bound methylmercury to low molecular weight methylmercury-selenium compounds was shown earlier. The effectiveness of selenium in modifying mercury metabolism has attracted increasing attention. After finding that concurrent equimolar selenite injections increased the uptake of mercury but did not alter the mercury distribution in the brain and that selenium reversed the effect of mercury upon glutathione peroxidase, Prohaska and Ganther suggested a complex of mercury and selenium may be involved in the interaction of mercury and selenium. However, considering that the protective effect of selenium is exerted within the tissue without decreasing the concentration or amount of mercury in the tissue, selenium is probably not simply chelating the bulk of brain mercury. The purpose of the following experiments was to determine the binding characteristics of thiol-metabolites of methylmercury to myelin isolated from the central nervous system. The possible alteration of such binding by dietary selenium was also investigated

  16. Neuronal expression of the transcription factor serum response factor modulates myelination in a mouse multiple sclerosis model.

    Science.gov (United States)

    Anastasiadou, Sofia; Liebenehm, Sophie; Sinske, Daniela; Meyer Zu Reckendorf, Christopher; Moepps, Barbara; Nordheim, Alfred; Knöll, Bernd

    2015-06-01

    In multiple sclerosis (MS), neurons in addition to inflammatory cells are now considered to mediate disease origin and progression. So far, molecular and cellular mechanisms of neuronal MS contributions are poorly understood. Herein we analyzed whether neuron-restricted signaling by the neuroprotective transcription factor serum response factor (SRF) modulates de- and remyelination in a rodent MS model. In the mouse cuprizone model, neuron- (Srf (flox/flox;CaMK) (CreERT2) ) but not glia-specific (Srf (flox/flox;Plp) (CreERT2) ) SRF depletion impaired demyelination suggesting impaired debris clearance by astrocytes and microglia. This supports an important role of SRF expression in neurons but not oligodendrocytes in de- and remyelination. During remyelination, NG2- and OLIG2-positive cells of the oligodendrocyte lineage as well as de novo mRNA synthesis of myelin genes were also reduced in neuron-specific Srf mutants. Using the stripe assay, we demonstrate that cortices of cuprizone-fed wild-type mice elicited astrocyte and microglia activation whereas this was abrogated in cuprizone-fed neuron-specific Srf mutants. We identified CCL chemokines (e.g. CCL2) as neuron-derived SRF-regulated paracrine signals rescuing immune cell activation upon neuronal SRF deletion. In summary, we uncovered important roles of neurons and neuronally expressed SRF in MS associated de- and remyelination. GLIA 2015;63:958-976. PMID:25639799

  17. Compensatory Upregulation of Myelin Protein Zero-Like 2 Expression in Spermatogenic Cells in Cell Adhesion Molecule-1-Deficient Mice

    International Nuclear Information System (INIS)

    The cell adhesion molecule-1 (Cadm1) is a member of the immunoglobulin superfamily. In the mouse testis, Cadm1 is expressed in the earlier spermatogenic cells up to early pachytene spermatocytes and also in elongated spermatids, but not in Sertoli cells. Cadm1-deficient mice have male infertility due to defective spermatogenesis, in which detachment of spermatids is prominent while spermatocytes appear intact. To elucidate the molecular mechanisms of the impaired spermatogenesis caused by Cadm1 deficiency, we performed DNA microarray analysis of global gene expression in the testis compared between Cadm1-deficient and wild-type mice. Out of the 25 genes upregulated in Cadm1-deficient mice, we took a special interest in myelin protein zero-like 2 (Mpzl2), another cell adhesion molecule of the immunoglobulin superfamily. The levels of Mpzl2 mRNA increased by 20-fold and those of Mpzl2 protein increased by 2-fold in the testis of Cadm1-deficient mice, as analyzed with quantitative PCR and western blotting, respectively. In situ hybridization and immunohistochemistry demonstrated that Mpzl2 mRNA and protein are localized in the earlier spermatogenic cells but not in elongated spermatids or Sertoli cells, in both wild-type and Cadm1-deficient mice. These results suggested that Mpzl2 can compensate for the deficiency of Cadm1 in the earlier spermatogenic cells

  18. Purification of a new clathrin assembly protein from bovine brain coated vesicles and its identification as myelin basic protein.

    Science.gov (United States)

    Prasad, K; Barouch, W; Martin, B M; Greene, L E; Eisenberg, E

    1995-12-22

    The multimeric clathrin assembly proteins AP-1 and AP-2 with molecular masses of approximately 270 kDa and the monomeric clathrin assembly proteins AP180 and auxilin with molecular masses of approximately 90 kDa catalyze the assembly of clathrin into artificial clathrin baskets under physiological conditions. We have now identified a much smaller approximately 20-kDa clathrin assembly protein in 0.5 M Tris, pH 7.0, extracts of bovine-brain coated vesicles and purified it to near homogeneity. A polyclonal antibody against this protein did not cross-react with any of the other assembly proteins, and sequencing data suggest that this new protein is similar or identical to myelin basic protein (MBP). At a molar ratio of 3 molecules per clathrin triskelion, MBP catalyzes polymerization of clathrin into artificial baskets that appear structurally similar to the baskets assembled by the other assembly proteins. In addition, like the other baskets, the clathrin-MBP baskets are uncoated by hsp70. MBP represents a significant fraction of the total assembly protein activity present in 0.5 M Tris, pH 7.0, extracts of coated vesicles. It is not clear if it acts as an assembly protein in vivo, but because it is well characterized and easily available, MBP will be a useful protein to investigate the mechanism of clathrin assembly and disassembly in vitro. PMID:8530487

  19. Microscopic origin of the relativistic splitting of surface states

    Science.gov (United States)

    Krasovskii, E. E.

    2014-09-01

    Spin-orbit splitting of surface states is analyzed within and beyond the Rashba model using as examples the (111) surfaces of noble metals, Ag2Bi surface alloy, and topological insulator Bi2Se3. The ab initio analysis of relativistic velocity proves the Rashba model to be fundamentally inapplicable to real crystals. The splitting is found to be primarily due to a spin-orbit induced in-plane modification of the wave function, namely, to its effect on the nonrelativistic Hamiltonian. The usual Rashba splitting—given by charge distribution asymmetry—is an order of magnitude smaller.

  20. Point-splitting regularization for gauge theories: quantum electrodynamics

    International Nuclear Information System (INIS)

    As a method of regularization, point splitting has played an essential role in the recent theoretical determination of the masses of the Higgs boson and the top quark. It is the purpose of this paper to put this point-splitting regularization on a firm basis. The result turns out to be extremely simple: Replace the usual vertex factor -ie?? in quantum electrodynamics by -ie(??-p/(p.?)??), where p is the momentum of the photon line, and ?? is the distance for point splitting. No additional vertices are needed. (orig.)

  1. Single and Double Perturbative Splitting Diagrams in Double Parton Scattering

    CERN Document Server

    Gaunt, Jonathan R

    2012-01-01

    We discuss the role of two different types of diagram in the proton-proton double parton scattering (DPS) cross section - single and double perturbative splitting graphs. Using explicit calculations of simple graphs from these classes we show that the treatment of these graphs by the 'double PDF' framework for describing the DPS cross section, introduced a number of years ago by Snigirev and collaborators, is unsatisfactory. We suggest that a contribution from single perturbative splitting graphs should be included in the DPS cross section, albeit with a different geometrical prefactor to the contribution from 'zero perturbative splitting' graphs.

  2. Scatterer induced mode splitting in poly(dimethylsiloxane) coated microresonators

    CERN Document Server

    He, Lina; Zhu, Jiangang; Yang, Lan; 10.1063/1.3435480

    2010-01-01

    We investigate scatterer induced mode splitting in a composite microtoroidal resonator (Q ~ 10^6) fabricated by coating a silica microtoroid (Q ~ 10^7) with a thin poly(dimethylsiloxane) layer. We show that the two split modes in both coated and uncoated silica microtoroids respond in the same way to the changes in the environmental temperature. This provides a self-referencing scheme which is robust to temperature perturbations. Together with the versatile functionalities of polymer materials, mode splitting in polymer and polymer coated microresonators offers an attractive sensing platform that is robust to thermal noise.

  3. A Splitting Algorithm for Directional Regularization and Sparsification

    DEFF Research Database (Denmark)

    Rakêt, Lars Lau; Nielsen, Mads

    2012-01-01

    We present a new split-type algorithm for the minimization of a p-harmonic energy with added data fidelity term. The half-quadratic splitting reduces the original problem to two straightforward problems, that can be minimized efficiently. The minimizers to the two sub-problems can typically be computed pointwise and are easily implemented on massively parallel processors. Furthermore the splitting method allows for the computation of solutions to a large number of more advanced directional regularization problems. In particular we are able to handle robust, non-convex data terms, and to define a 0-harmonic regularization energy where we sparsify directions by means of an L0 norm.

  4. Two-Loop g -> gg Splitting Amplitudes in QCD

    OpenAIRE

    Bern, Zvi; Lance J. Dixon; Kosower, David A.

    2004-01-01

    Splitting amplitudes are universal functions governing the collinear behavior of scattering amplitudes for massless particles. We compute the two-loop g -> gg splitting amplitudes in QCD, N=1, and N=4 super-Yang-Mills theories, which describe the limits of two-loop n-point amplitudes where two gluon momenta become parallel. They also represent an ingredient in a direct x-space computation of DGLAP evolution kernels at next-to-next-to-leading order. To obtain the splitting am...

  5. Quantum information splitting using multi-partite cluster states

    CERN Document Server

    Muralidharan, Sreraman

    2008-01-01

    We provide various schemes for the splitting up of Quantum information into parts using the four and five partite cluster states. Explicit protocols for the Quantum information splitting (QIS) of single and two qubit states are illustrated. It is found that the four partite cluster state can be used for the QIS of an entangled state and the five partite cluster state can be used for QIS of an arbitrary two qubit state. We propose a conjecture about the maximum number of protocols that can be constructed for the information splitting of an arbitrary $n$ qubit state among two parties using an $N$ qubit entangled channel.

  6. Effects of Coulomb interactions on the splitting of luminescence lines

    CERN Document Server

    Rodríguez, B A; Rodriguez, Boris A.; Gonzalez, Augusto

    2005-01-01

    We study the splitting between the right-hand and left-hand circularly polarized luminescence lines in a quantum dot under relatively weak confinement regime and resonant high-power excitation. When the dot is populated with an even number of electron-hole pairs (biexciton and higher excitations), the splitting measures basically the Zeeman energy. However, in the odd number of pairs case, we have, in addition to the Zeeman and Overhauser shifts, a contribution to the splitting coming from Coulomb interactions. This contribution is of the order of a few meV, and shows distinct signatures of shell-filling in the quantum dot.

  7. NNLO time-like splitting functions in QCD

    International Nuclear Information System (INIS)

    We review the status of the calculation of the time-like splitting functions for the evolution of fragmentation functions to the next-to-next-to-leading order in perturbative QCD. By employing relations between space-like and time-like deep-inelastic processes, all quark-quark and the gluon-gluon time-like splitting functions have been obtained to three loops. The corresponding quantities for the quark-gluon and gluon-quark splitting at this order are presently still unknown except for their second Mellin moments. (orig.)

  8. Autocorrelation function of level velocities for ray-splitting billiards

    Science.gov (United States)

    Hlushchuk, Y.; Kohler, A.; Bauch, Sz.; Sirko, L.; Blümel, R.; Barth, M.; Stöckmann, H.-J.

    2000-01-01

    We study experimentally and theoretically the autocorrelation function of level velocities c(x) and the generalized conductance C(0) for classically chaotic ray-splitting systems. Experimentally, a Sinai ray-splitting billiard was simulated by a thin microwave rectangular cavity with a quarter-circle Teflon insert. For the theoretical estimates of the autocorrelator c(x) and the conductance C(0) we made parameter-dependent quantum calculations of eigenenergies of an annular ray-splitting billiard. Our experimental and numerical results are compared to theoretical predictions of systems based on the Gaussian orthogonal ensemble in random matrix theory.

  9. Partially secret broadcasting, partially secret splitting with quantum entanglement

    International Nuclear Information System (INIS)

    In this paper, we propose a classical secret broadcasting and splitting joint protocol in a quantum scenario. With those genuinely entangled states, the boss can always broadcast some of his secrets and split some others to multi-receivers at the same time. The efficiency of the joint protocol is also compared with that of two separate ones which realise classical secret broadcasting and classical secret splitting respectively, and based on the comparison we can see the promising advantage of our joint protocol is that it can realise the two tasks more efficiently and more conveniently. (general)

  10. To Split or Not to Split, That Is the Question in Some Shallow Water Equations

    CERN Document Server

    Martínez, Vicente

    2012-01-01

    In this paper we analyze the use of time splitting techniques for solving shallow water equation. We discuss some properties that these schemes should satisfy so that interactions between the source term and the shock waves are controlled. This paper shows that these schemes must be well balanced in the meaning expressed by Greenberg and Leroux [5]. More speci?cally, we analyze in what cases it is enough to verify an Approximate C-property and in which cases it is required to verify an Exact C-property (see [1], [2]). We also include some numerical tests in order to justify our reasoning.

  11. Comparison of morbidity following the removal of mandibular third molar by lingual split, surgical bur and simplified split bone technique

    Directory of Open Access Journals (Sweden)

    Praveen G

    2007-01-01

    Full Text Available Background: The methods frequently used for surgical removal of impacted third molars are bur technique, lingual split and simplified split bone technique. The morbidity rates following the use of these different surgical techniques are not completely resolved. The use of a surgical method with minimum postoperative complication is needed. Aim: This study was conducted to compare the morbidity rates of the three different surgical techniques and their efficacy with regard to postoperative pain, swelling, labial and lingual sensation. Materials and Methods: Ninety patients with a symptomatic impacted mandibular third molar with the age range of 14-62 years were divided into three groups of 30 patients each for surgical bur technique, lingual split technique and simplified split bone technique. All patients were operated by the same surgeon under local anesthesia (2% lignocaine in the dental chair. The severity of pain and swelling was recorded on a visual analogue scale and the presence or absence of sensory disturbance at 6, 24, 48 hours and seven days after operation. The pain was scored according to a visual analogue 4-point scale. Patients were asked to indicate which side was more swollen and to record this assessment on the swelling scale. Results: Lingual split technique was more painful than the other two techniques. Surgical bur technique had more swelling than the other two techniques. Labial and lingual sensations were not altered in all the techniques. Conclusion: The simplified split bone technique had the least morbidity than the lingual split and surgical bur technique.

  12. Grafting of burns with widely meshed autograft split skin and Langerhans cell-depressed allograft split skin overlay

    Energy Technology Data Exchange (ETDEWEB)

    Alsbjoern, B.F.S.; Sorensen, B.

    1986-12-01

    Extensively burned patients suffer from lack of sufficient autologous donor skin. Meshing and wide expansion of the obtained split skin has met the requirement to a large degree. However, the wider the expansion, the less chance of a proper take. By covering widely expanded autografts with viable cadaver split skin, the take has been improved. If the epidermal Langerhans cells in the cadaver split skin are depressed by ultraviolet B light and glucocorticosteroids before grafting, a prolonged allograft take can be achieved and the healing of the underlying autografts is ensured for an extended period. Grafting results in 6 patients with extensive burns are reported.

  13. Grafting of burns with widely meshed autograft split skin and Langerhans cell-depressed allograft split skin overlay

    International Nuclear Information System (INIS)

    Extensively burned patients suffer from lack of sufficient autologous donor skin. Meshing and wide expansion of the obtained split skin has met the requirement to a large degree. However, the wider the expansion, the less chance of a proper take. By covering widely expanded autografts with viable cadaver split skin, the take has been improved. If the epidermal Langerhans cells in the cadaver split skin are depressed by ultraviolet B light and glucocorticosteroids before grafting, a prolonged allograft take can be achieved and the healing of the underlying autografts is ensured for an extended period. Grafting results in 6 patients with extensive burns are reported

  14. Mini-Split Heat Pumps Multifamily Retrofit Feasibility Study

    Energy Technology Data Exchange (ETDEWEB)

    Dentz, J.; Podorson, D.; Varshney, K.

    2014-05-01

    Mini-split heat pumps can provide space heating and cooling in many climates and are relatively affordable. These and other features make them potentially suitable for retrofitting into multifamily buildings in cold climates to replace electric resistance heating or other outmoded heating systems. This report investigates the suitability of mini-split heat pumps for multifamily retrofits. Various technical and regulatory barriers are discussed and modeling was performed to compare long-term costs of substituting mini-splits for a variety of other heating and cooling options. A number of utility programs have retrofit mini-splits in both single family and multifamily residences. Two such multifamily programs are discussed in detail.

  15. Geometrical tuning of nanoscale split-ring resonators

    DEFF Research Database (Denmark)

    Jeppesen, Claus; Kristensen, Anders

    2010-01-01

    We investigate the capacitance tuning of nanoscale split-ring resonators. An LC-model predicts a simple dependence of resonance frequency on slit aspect ratio. Experimental and numerical data follow the predictions of the LC-model.

  16. Mathematical aspects of laser beam shaping and splitting.

    Energy Technology Data Exchange (ETDEWEB)

    Dickey, Fred McCartney (FMD Consulting, LLC, Springfield MO); Romero, Louis Anthony

    2010-05-01

    We will discuss general mathematical ideas arising in the problems of Laser beam shaping and splitting. We will be particularly concerned with questions concerning the scaling and symmetry of such systems.

  17. Visualization of the sequence of a couple splitting outside shop

    DEFF Research Database (Denmark)

    Nielsen, SØren Zebitz

    Visualization of tracks of couple walking together before splitting and one goes into shop the other waits outside. The visualization represents the sequence described in figure 7 in the publication 'Taking the temperature of pedestrian movement in public spaces'

  18. Vacuum Photon Splitting in Lorentz-Violating Quantum Electrodynamics

    OpenAIRE

    Kostelecky, Alan; Pickering, Austin

    2002-01-01

    Radiative corrections arising from Lorentz violation in the fermion sector induce a nonzero amplitude for vacuum photon splitting. At one loop, the on-shell amplitude acquires both CPT-even and CPT-odd contributions forbidden in conventional electrodynamics.

  19. Polarized beam splitting by total internal reflection in ?-quartz

    International Nuclear Information System (INIS)

    By incidence of a laser beam, polarized beam splitting was observed by total internal reflection in the right-angle prism of ?-quartz. Divergent beams are formed after total internal reflection. The transmitted beams propagate in different directions in the plane of incidence, at different angles of reflection. Two split beams are linearly polarized waves, vibrating perpendicular (s-wave) and parallel (p-wave) to the plane of incidence, respectively. At total internal reflection from the direction of optic axis in a birefringent direction, the intensities of the two split beams depend on the propagation distance in the direction of optic axis. The polarized beam splitting is found to depend on the optic activity and birefringence of ?-quartz

  20. The Multivariate Split Normal Distribution and Asymmetric Principal Components Analysis

    OpenAIRE

    Villani, Mattias; Larsson, Rolf

    2004-01-01

    The multivariate split nomal distribution extends the usual multivariate normal distribution by a set of parameters which allows for skewness in the form of contraction/dilation along a subset of the prinicpal axis. The paper derives some properties for this distribution, including its moment generating function, multivariate skewness and kurtosis. Maximum likelihood estimation is discussed and a complete Bayesian analysis of the multivariate split normal distribution is developed.

  1. A Splitting Criteria Based on Similarity in Decision Tree Learning

    OpenAIRE

    Xinmeng Zhang; Shengyi Jiang

    2012-01-01

    Decision trees are considered to be the most effective and widely used data mining technique for classification, their representation is intuitive and generally easy to be comprehended by humans. The most critical issue in the learning process of decision trees is the splitting criteria. In this paper, We firstly provide the definition of similarity computation that usually used in data clustering and apply it to the learning process of decision trees. Then, we propose a novel splitting crite...

  2. Enhancement of Optical Nonlinearities Via Whispering Gallery Mode Splitting

    Science.gov (United States)

    Chang, Hongrok; Smith, David D.; Fuller, Kirk A.; Curreri, Peter A. (Technical Monitor)

    2002-01-01

    An iterative method is applied to the analysis of N coupled ring-resonators, and the results are compared with multilayered spheres. Splitting of the whispering gallery modes into N higher-Q modes occurs when the round-trip phase shifts in each ring (or layer) are equal, in agreement with results for planar resonators. This mode-splitting is, therefore, a universal phenomenon for resonant structures, and can lead to reduced thresholds for nonlinear optical effects.

  3. An equivariant generalization of the Miller splitting theorem

    OpenAIRE

    Ullman, Harry

    2011-01-01

    Let G be a compact Lie group. We build a tower of G-spectra over the suspension spectrum of the space of linear isometries from one G-representation to another. The stable cofibres of the maps running down the tower are certain interesting Thom spaces. We conjecture that this tower provides an equivariant extension of Miller's stable splitting of Stiefel manifolds. We provide a cohomological obstruction to the tower producing a splitting in most cases; however, this obstruct...

  4. Split Octonion electrodynamics and unified fields of dyons

    International Nuclear Information System (INIS)

    Split octonion electrodynamics has been developed in terms of Zorn's vector matrix realization by reformulating electromagnetic potential, current, field tensor and other dynamical quantities. Corresponding field equation (Unified Maxwell's equations) and equation of motion have been reformulated by means of split octonion and its Zorn vector realization in unique, simpler and consistent manner. It has been shown that this theory reproduces the dyon field equations in the absence of gravito-dyons and vice versa

  5. Distributed Verification of Rare Properties using Importance Splitting Observers

    OpenAIRE

    Jegourel, Cyrille; Legay, Axel; Sedwards, Sean; Traonouez, Louis-Marie

    2015-01-01

    Rare properties remain a challenge for statistical model checking (SMC) due to the quadratic scaling of variance with rarity. We address this with a variance reduction framework based on lightweight importance splitting observers. These expose the model-property automaton to allow the construction of score functions for high performance algorithms. The confidence intervals defined for importance splitting make it appealing for SMC, but optimising its performance in the sta...

  6. Calculation of hyperfine splitting in mesons using configuration interaction approach

    CERN Document Server

    Lengyel, V; Haysak, I I; Shpenik, A; Fekete, Yu.

    2001-01-01

    The spin - spin mass splitting of light, heavy and mixed mesons are described within a good accuracy in the potential model with screened potential. We conclude that the long - distance part of the potential cannot be pure scalar and that a vector - scalar mixture is favoured. With the same parameters which gives correct average mass spectrum excellent spin - spin splittings of heavy quarkonia is obtained. The results are obtained by going beyond usually used perturbation method, namely using configuration interaction approach.

  7. Applications and characteristics of polished polarization-splitting couplers

    Science.gov (United States)

    Lefevre, Herve C.; Simonpietri, Pascal; Martin, Philippe

    1991-01-01

    All-fiber polarization splitting was demonstrated using the stress release created by side polishing in stress-induced high birefringence fibers. This technique provides a very low loss (less than 0. 1 dB) and a broad wavelength range of operation (100 nm around 1500 nm). We report here about the detailled characteristics of the component and we present statistics about the 50 polarization splitting couplers that we have manufactured so far. We also describe typical applications of such a device.

  8. Counting with Combined Splitting and Capture-Recapture Methods

    CERN Document Server

    Dupuis, Paul; Ridder, Ad; Rubinstein, Reuven; Vaisman, Radislav

    2011-01-01

    We apply the splitting method to three well-known counting problems, namely 3-SAT, random graphs with prescribed degrees, and binary contingency tables. We present an enhanced version of the splitting method based on the capture-recapture technique, and show by experiments the superiority of this technique for SAT problems in terms of variance of the associated estimators, and speed of the algorithms.

  9. Thermal management of liquid direct cooled split disk laser

    Science.gov (United States)

    Yang, Huomu; Feng, Guoying; Zhou, Shouhuan

    2015-02-01

    The thermal effects of a liquid direct cooled split disk laser are modeled and analytically solved. The analytical solutions with the consideration of longitudinal cooling liquid temperature rise have been given to describe the temperature distribution in the split disk and cooling liquid based on the hydrodynamics and heat transfer. The influence of cooling liquid, liquid flowing velocity, thickness of cooling channel and of disk gain medium can also be got from the analytical solutions.

  10. Key Issues in Vowel Based Splitting of Telugu Bigrams

    OpenAIRE

    Kameswara Rao; Prasad, Dr. T. V

    2014-01-01

    Splitting of compound Telugu words into its components or root words is one of the important, tedious and yet inaccurate tasks of Natural Language Processing (NLP). Except in few special cases, at least one vowel is necessarily involved in Telugu conjunctions. In the result, vowels are often repeated as they are or are converted into other vowels or consonants. This paper describes issues involved in vowel based splitting of a Telugu bigram into proper root words using Telugu grammar conjunct...

  11. Defense on Split-Network Attack in Wireless Sensor Network

    OpenAIRE

    Ma Li; Du Chunlai; hang Jianshun

    2012-01-01

    Wireless Sensor Network is an open self-organized network, which faces serious challenge. Whole network can be split up into many separate subnets which cannot communicate with each other because some vital sensor nodes are attacked. A defense scheme which based on frequency hopping and fast network integration wasproposed to react against split-network attack. Frequency hopping makes the communication frequency of the network escape from attack frequency while fast network integration makes ...

  12. SMART: Unique Splitting-While-Merging Framework for Gene Clustering

    OpenAIRE

    Fa, Rui; Roberts, David J.; Nandi, Asoke K.

    2014-01-01

    Successful clustering algorithms are highly dependent on parameter settings. The clustering performance degrades significantly unless parameters are properly set, and yet, it is difficult to set these parameters a priori. To address this issue, in this paper, we propose a unique splitting-while-merging clustering framework, named “splitting merging awareness tactics” (SMART), which does not require any a priori knowledge of either the number of clusters or even the possible range of this ...

  13. Equivariant scanning and stable splittings of configuration spaces

    OpenAIRE

    Manthorpe, Richard; Tillmann, Ulrike

    2012-01-01

    We give a definition of the scanning map for configuration spaces that is equivariant under the action of the diffeomorphism group of the underlying manifold. We use this to extend the Bödigheimer-Madsen result for the stable splittings of the Borel constructions of certain mapping spaces from compact Lie group actions to all smooth actions. Moreover, we construct a stable splitting of configuration spaces which is equivariant under smooth group actions, completing a zig-zag of equivariant s...

  14. Evaluation of pressure beneath a split above elbow plaster cast.

    OpenAIRE

    Walker, R W; Draper, E; Cable, J.

    2000-01-01

    It has previously been shown that splitting a plaster cast after manipulation of, or surgery on, a limb leads to a decrease in pressure beneath the cast by accommodating the swelling that may occur. However, it is not known whether the axis along which the cast is split influences the amount of swelling that can occur before a critical pressure is reached. We investigated this with reference to above elbow plaster casts.

  15. Design, selection, and characterization of a split chorismate mutase

    OpenAIRE

    Müller, Manuel M; Kries, Hajo; Csuhai, Eva; Kast, Peter; Hilvert, Donald

    2010-01-01

    Split proteins are versatile tools for detecting protein–protein interactions and studying protein folding. Here, we report a new, particularly small split enzyme, engineered from a thermostable chorismate mutase (CM). Upon dissecting the helical-bundle CM from Methanococcus jannaschii into a short N-terminal helix and a 3-helix segment and attaching an antiparallel leucine zipper dimerization domain to the individual fragments, we obtained a weakly active heterodimeric mutase. Using combin...

  16. Scatterer induced mode splitting in poly(dimethylsiloxane) coated microresonators

    OpenAIRE

    He, Lina; Ozdemir, Sahin Kaya; Zhu, Jiangang; Yang, Lan

    2010-01-01

    We investigate scatterer induced mode splitting in a composite microtoroidal resonator (Q ~ 10^6) fabricated by coating a silica microtoroid (Q ~ 10^7) with a thin poly(dimethylsiloxane) layer. We show that the two split modes in both coated and uncoated silica microtoroids respond in the same way to the changes in the environmental temperature. This provides a self-referencing scheme which is robust to temperature perturbations. Together with the versatile functionalities o...

  17. Hydrogen Production from Semiconductor-based Photocatalysis via Water Splitting

    Directory of Open Access Journals (Sweden)

    Jeffrey C. S. Wu

    2012-10-01

    Full Text Available Hydrogen is the ideal fuel for the future because it is clean, energy efficient, and abundant in nature. While various technologies can be used to generate hydrogen, only some of them can be considered environmentally friendly. Recently, solar hydrogen generated via photocatalytic water splitting has attracted tremendous attention and has been extensively studied because of its great potential for low-cost and clean hydrogen production. This paper gives a comprehensive review of the development of photocatalytic water splitting for generating hydrogen, particularly under visible-light irradiation. The topics covered include an introduction of hydrogen production technologies, a review of photocatalytic water splitting over titania and non-titania based photocatalysts, a discussion of the types of photocatalytic water-splitting approaches, and a conclusion for the current challenges and future prospects of photocatalytic water splitting. Based on the literatures reported here, the development of highly stable visible–light-active photocatalytic materials, and the design of efficient, low-cost photoreactor systems are the key for the advancement of solar-hydrogen production via photocatalytic water splitting in the future.

  18. A Frequency Splitting Method For CFM Imaging

    DEFF Research Database (Denmark)

    Udesen, Jesper; Gran, Fredrik

    2006-01-01

    The performance of conventional CFM imaging will often be degraded due to the relatively low number of pulses (4-10) used for each velocity estimate. To circumvent this problem we propose a new method using frequency splitting (FS). The FS method uses broad band chirps as excitation pulses instead of narrow band pulses as in conventional CFM imaging. By appropriate filtration, the returned signals are divided into a number of narrow band signals which are approximately disjoint. After clutter filtering the velocities are found from each frequency band using a conventional autocorrelation estimator. Finally the velocity estimates from each frequency band are averaged to obtain an improved velocity estimate. The FS method has been evaluated in simulations using the Field II program and in flow phantom experiments using the experimental ultrasound scanner RASMUS. In both simulations and experiments, a 5 MHz linear array transducer was used to scan a vessel situated at 30 mm depth with a maximum flow velocity of 0.1 m/s. The pulse repetition frequency was 1.8 kHz and the angle between the flow and the beam was 60 deg. A 15 mus chirp was used as excitation pulse and 40 independent velocity estimates were obtained using the FS method with 10 pulse transmissions used for each estimate. For comparison, a 8 cycles sinusoid pulse at 5 MHz was used to acquire 40 independent velocity estimates, each derived from 10 pulse emissions. Here the velocity was found using a conventional autocorrelation estimator. In the simulation, the relative mean standard deviation of the velocity estimates over the vessel was 2.43% when using the FD method and the relative mean absolute bias was 1.84%. For the reference 8 oscillation pulse, the relative mean standard deviation over the vessel was 4.91 % and the relative mean absolute bias was 1.78%. In the experiments the relative mean standard deviation of the velocity estimates over the vessel was 2.41 % when using the FD method and the relative- mean absolute bias was 1.56%. For the reference 8 oscillation pulse, the relative mean standard deviation over the vessel was 4.76% and the relative mean absolute bias was 3.12%.

  19. Synthesis of myelin, particulate, and soluble protein subfractions of rat sciatic nerve during the early stage of Wallerian degeneration: a comparison of metabolic studies using double and single isotope methods and recovery

    International Nuclear Information System (INIS)

    The recovery, electrophoretic composition and synthesis of the myelin, particulate protein and soluble protein subfractions of rat sciatic nerve were compared in normal, sham-operated, and degenerating rat sciatic nerve at one, three and five days after neurotomy. Both single and double isotope methods were used to measure changes in synthesis in vitro and double isotope methods were used in vivo. The wet weights of nerves undergoing Wallerian degeneration for 5 days increased by 40 percent compared to normal and sham-operated nerves. The recovery, specific radioactivity, and synthesis of the myelin was reduced. The effect on myelin protein synthesis was similar in vitro and in vivo. The myelin loss was relatively constant in amount (30-40 microgram) regardless of differences in nerve sizes of young and old rats, consequently the percentage of myelin loss was inversely proportional to nerve size. The recovery of particulate protein increased, its rate of synthesis remained unchanged, and accordingly the specific radioactivity was decreased. The recovery, specific radioactivity, and the rate of synthesis of the soluble protein fraction were all elevated. The protein composition of the three fractions, as analyzed qualitatively by polyacrylamide disc gel electrophoresis, remained essentially unchanged through five days of degeneration. With regard to comparisons of the single and double isotope methods, results shows that the latter are more ideally suited to measuring tter are more ideally suited to measuring changes in synthesis during the non-steady state conditions that are characteristics of rapid degeneration

  20. Costimulatory molecule CD40 is essential for myelin protein 0 peptide 106-125-induced experimental autoimmune neuritis in mice.

    Science.gov (United States)

    Brunn, Anna; Utermöhlen, Olaf; Mihelcic, Mirna; Saupe, Lisa; Fiocco, Zeno; Schmidt, Annika; Carstov, Mariana; Montesinos-Rongen, Manuel; Deckert, Martina

    2014-05-01

    Myelin protein 0 peptide 106-125-induced murine experimental autoimmune neuritis (EAN) is a CD4-positive T cell-mediated monophasic axonal inflammatory neuropathy; interferon-? is the key proinflammatory mediator. Experimental autoimmune neuritis is well suited for elucidating pathogenetic mechanisms underlying human acute axonal Guillain-Barré syndrome. Here, the functional role of the costimulatory molecule CD40 was defined by characterization of EAN in CD40-deficient mice. In contrast to immunized C57BL/6 mice, CD40-deficient mice were resistant to EAN owing to impaired priming of CD4-positive T-effector cells. To determine whether CD40 is a suitable candidate for the treatment of EAN, we administered monoclonal anti-CD40 antibody either before immunization or upon onset of neurologic signs. Prophylactic anti-CD40 treatment completely abolished CD4-positive T-cell priming. Therapeutic application of anti-CD40 prevented full activation of CD4-positive T cells that were in the process of priming and suppressed production of interferon-? in peripheral lymph nodes, spleen, and serum, and of interleukin-6, interleukin-12p40, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, which are associated with activation of the nuclear factor-?B signaling pathway. This resulted in enhanced recovery by early generation of CD25-positive, Foxp3-positive, CD4-positive regulatory T cells. Thus, these experiments highlight the crucial role of CD40 as an important costimulatory molecule in EAN and suggest that it has potential as a therapeutic target in human neuritis. PMID:24709684