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Sample records for paranodal myelin splitting

  1. Cytoskeletal transition at the paranodes: the Achilles’ heel of myelinated axons

    OpenAIRE

    Sousa, Aurea D.; Bhat, Manzoor A.

    2007-01-01

    Myelination organizes axons into distinct domains that allow nerve impulses to propagate in a saltatory manner. The edges of the myelin sheath are sealed at the paranodes by axon–glial junctions that have a crucial role in organizing the axonal cytoskeleton. Here we propose a model in which the myelinated axons depend on the axon–glial junctions to stabilize the cytoskeletal transition at the paranodes. Thus paranodal regions are likely to be particularly susceptible to damage induced by ...

  2. Opalin, a Transmembrane Sialylglycoprotein Located in the Central Nervous System Myelin Paranodal Loop Membrane*S?

    Science.gov (United States)

    Yoshikawa, Fumio; Sato, Yumi; Tohyama, Koujiro; Akagi, Takumi; Hashikawa, Tsutomu; Nagakura-Takagi, Yuko; Sekine, Yukiko; Morita, Noriyuki; Baba, Hiroko; Suzuki, Yutaka; Sugano, Sumio; Sato, Akira; Furuichi, Teiichi

    2008-01-01

    In contrast to compact myelin, the series of paranodal loops located in the outermost lateral region of myelin is non-compact; the intracellular space is filled by a continuous channel of cytoplasm, the extracellular surfaces between neighboring loops keep a definite distance, but the loop membranes have junctional specializations. Although the proteins that form compact myelin have been well studied, the protein components of paranodal loop membranes are not fully understood. This report describes the biochemical characterization and expression of Opalin as a novel membrane protein in paranodal loops. Mouse Opalin is composed of a short N-terminal extracellular domain (amino acid residues 1–30), a transmembrane domain (residues 31–53), and a long C-terminal intracellular domain (residues 54–143). Opalin is enriched in myelin of the central nervous system, but not that of the peripheral nervous system of mice. Enzymatic deglycosylation showed that myelin Opalin contained N- and O-glycans, and that the O-glycans, at least, had negatively charged sialic acids. We identified two N-glycan sites at Asn-6 and Asn-12 and an O-glycan site at Thr-14 in the extracellular domain. Site-directed mutations at the glycan sites impaired the cell surface localization of Opalin. In addition to the somata and processes of oligodendrocytes, Opalin immunoreactivity was observed in myelinated axons in a spiral fashion, and was concentrated in the paranodal loop region. Immunogold electron microscopy demonstrated that Opalin was localized at particular sites in the paranodal loop membrane. These results suggest a role for highly sialylglycosylated Opalin in an intermembranous function of the myelin paranodal loops in the central nervous system. PMID:18490449

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

    Science.gov (United States)

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

    2014-01-21

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

  4. 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.

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

    Science.gov (United States)

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

    2013-04-01

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

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

    OpenAIRE

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

    2004-01-01

    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...

  7. Myelination and myelin disorders

    Energy Technology Data Exchange (ETDEWEB)

    Knaap, M.S. van der.

    1991-05-28

    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 {sup 1}H and {sup 31}P 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 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.

  8. 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

  9. Nodes of Ranvier and Paranodes in Chronic Acquired Neuropathies

    OpenAIRE

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

    2011-01-01

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

  10. 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

    2014-12-01

    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

  11. 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

  12. Localization of aquaporin 1 water channel in the Schmidt-Lanterman incisures and the paranodal regions of the rat sciatic nerve.

    Science.gov (United States)

    Segura-Anaya, E; Martínez-Gómez, A; Dent, M A R

    2015-01-29

    Aquaporin 1 (AQP1) is a member of a family of small, integral membrane water-transporting proteins, which facilitate water movement across cell membranes in response to osmotic gradients. Several papers have studied the expression and function of the AQPs in the central nervous system. However, little is known about the AQPs in the peripheral nervous system (PNS). In the PNS, AQP1, AQP2 and AQP4 have been reported in both peripheral neurons and glial cells. In this work we studied the expression and localization of AQP1 in the rat sciatic nerve. We found that from the four AQPs we studied (AQP1, AQP2, AQP4 and AQP9) only AQP1 is expressed in the nerve by reverse transcription polymerase chain reaction (RT-PCR). AQP1 is also observed at the protein level by Western blot analysis. We also studied the localization of AQP1 in the sciatic nerve by immunohistochemistry. The results show that AQP1 is present in both myelinating and non-myelinating Schwann cells. In myelin internodes AQP1 is enriched in the Schmidt-Lanterman incisures and in some internodes it is also present in the abaxonal membrane. At the nodes of Ranvier, AQP1 co-localizes with actin in the paranodal regions of the nerve. Therefore, AQP1 might play an important role in myelin homeostasis maintaining the thermodynamic equilibrium across the plasma membrane in myelinated axons during electrical activity. Also the expression of AQP1 in non-myelinating Schwann cells supports the involvement of AQP1 in pain perception. PMID:25451277

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

    Science.gov (United States)

    Kutuzov, N. P.; Brazhe, A. R.; Yusipovich, A. I.; Maksimov, G. V.; Dracheva, O. E.; Lyaskovskiy, V. L.; Bulygin, F. V.; Rubin, A. B.

    2013-07-01

    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.

  14. CSF myelin basic protein

    Science.gov (United States)

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

  15. Caspr and caspr2 are required for both radial and longitudinal organization of myelinated axons.

    Science.gov (United States)

    Gordon, Aaron; Adamsky, Konstantin; Vainshtein, Anya; Frechter, Shahar; Dupree, Jeffrey L; Rosenbluth, Jack; Peles, Elior

    2014-11-01

    In myelinated peripheral axons, Kv1 potassium channels are clustered at the juxtaparanodal region and at an internodal line located along the mesaxon and below the Schmidt-Lanterman incisures. This polarized distribution is controlled by Schwann cells and requires specific cell adhesion molecules (CAMs). The accumulation of Kv1 channels at the juxtaparanodal region depends on the presence of Caspr2 at this site, as well as on the presence of Caspr at the adjacent paranodal junction. However, the localization of these channels along the mesaxonal internodal line still persists in the absence of each one of these CAMs. By generating mice lacking both Caspr and Caspr2 (caspr(-/-)/caspr2(-/-)), we now reveal compensatory functions of the two proteins in the organization of the axolemma. Although Kv1 channels are clustered along the inner mesaxon and in a circumferential ring below the incisures in the single mutants, in sciatic nerves of caspr(-/-)/caspr2(-/-) mice, these channels formed large aggregates that were dispersed along the axolemma, demonstrating that internodal localization of Kv1 channels requires either Caspr or Caspr2. Furthermore, deletion of both Caspr and Caspr2 also resulted in widening of the nodes of Ranvier, suggesting that Caspr2 (which is present at paranodes in the absence of Caspr) can partially compensate for the barrier function of Caspr at this site even without the formation of a distinct paranodal junction. Our results indicate that Caspr and Caspr2 are required for the organization of the axolemma both radially, manifested as the mesaxonal line, and longitudinally, demarcated by the nodal domains. PMID:25378149

  16. 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.

  17. Synthesis and incorporation of myelin polypeptides into CNS myelin

    OpenAIRE

    1982-01-01

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

  18. 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

  19. Repetitive propagation of action potentials destabilizes the structure of the myelin sheath. A dynamic x-ray diffraction study.

    Science.gov (United States)

    Padrón, R; Mateu, L

    1982-01-01

    Time courses of myelin lattice swelling in toad sciatic nerves preexposed to different treatments were determined by x-ray diffraction using a one-dimensional position-sensitive detector. In the nerves supramaximally stimulated for 1 h at 200 Hz, the subsequent process of myelin swelling occurred 45.0 +/- 7.3 min (n = 24) sooner than in resting controls. Sciatic nerves incubated for 1 h in a Ringer's solution deprived of divalent cations (Ca++ and Mg++) exhibited a kinetics of swelling similar to that shown by the stimulated nerves, that is, 52.5 +/- 14.2 min (n = 6) sooner than controls preincubated for the same time in normal Ringer's solution (with divalent cations). The fact that both pretreatments supramaximal stimulation and removal of divalent cations from the perfusion solution produced a similar effect; namely, a decrease of the myelin lattice stability against swelling in distilled water, suggests that the repetitive propagation of action potentials could modify the ionic composition at either the intraperiod channel or the paranodal axoglial junction complexes. PMID:6810970

  20. 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

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

    OpenAIRE

    Lugt, Jaco J.; Venter, I.

    2007-01-01

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

  2. Control of Schwann cell myelination

    OpenAIRE

    Jessen, Kristja?n R.; Mirsky, Rhona

    2010-01-01

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

  3. Accelerated myelination associated with venous congestion

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-04-15

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

  4. Accelerated myelination associated with venous congestion

    International Nuclear Information System (INIS)

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

  5. Myelination in very low birth weight infants

    International Nuclear Information System (INIS)

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

  6. 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.

  7. Signals to promote myelin formation and repair

    OpenAIRE

    Taveggia, Carla; Feltri, Maria Laura; Wrabetz, Lawrence

    2010-01-01

    The myelin sheath wraps large axons in both the CNS and the PNS, and is a key determinant of efficient axonal function and health. Myelin is targeted in a series of diseases, notably multiple sclerosis (MS). In MS, demyelination is associated with progressive axonal damage, which determines the level of patient disability. Few treatments are available for combating myelin damage in MS and related disorders. These treatments, which largely comprise anti-inflammatory drugs, only show limited ef...

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

    Science.gov (United States)

    van der Lugt, J J; Venter, I

    2007-01-01

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

  9. Detection of Myelination Using a Novel Histological Probe

    OpenAIRE

    Xiang, Zhongmin; Nesterov, Evgueni E.; Skoch, Jesse; Lin, Tong; Hyman, Bradley T.; Swager, Timothy M.; Bacskai, Brian J.; Reeves, Steven A.

    2005-01-01

    Current methods for myelin staining in tissue sections include both histological and immunohistochemical techniques. Fluorescence immunohistochemistry, which uses antibodies against myelin components such as myelin basic protein, is often used because of the convenience for multiple labeling. To facilitate studies on myelin, this paper describes a quick and easy method for direct myelin staining in rodent and human tissues using novel near-infrared myelin (NIM) dyes that are comparable to oth...

  10. Inborn errors of brain myelin formation.

    Science.gov (United States)

    Boespflug-Tanguy, Odile

    2013-01-01

    Inborn errors of brain myelin formation or hypomyelinating leukodystrophies (HLD) represent a heterogeneous group of white matter diseases related to a primitive impairment of oligodendrocytes to produce myelin in the central nervous system (CNS). Cerebral magnetic resonance imaging (MRI) allows an assessment of the myelination pattern. The clinical presentation is related to the degree of hypomyelination and its consequences on axonal functions. When the gene defect interferes with the active infantile phase of myelination, the consequences might be severe, with delayed and loss of psychomotor development, absence of myelin signal on cerebral MRI and of identifiable waves on cerebral evoked potentials, as described by Pelizaeus and Merzbacher (PMD). When the pathophysiological mechanism is less severe, myelin production is maintained, although signs of progressive axonopathy are observed, related to progressive spastic paraplegia (SPG) associated with cognitive or behavioral disturbances. HLDs have been classified according to gene defects or associated signs. The X-linked HDL1 (PMD and SPG2) is related to the gene that controls the production of the major CNS myelin proteins, the proteolipid proteins (PLP). The gap junction protein, gamma 2 gene (GJC2) encoding oligodendrocyte-specific connexin, has been shown to be involved in the autosomal recessive HLD2 (PMLD1 and SPG44). PMID:23622380

  11. Hypomyelinated mutant mice. II. Myelination in vitro.

    Science.gov (United States)

    Billings-Gagliardi, S; Adcock, L H; Schwing, G B; Wolf, M K

    1980-10-27

    Organotypic cultures of cerebellum from hypomyelinated mutant mice provide a powerful experimental system for studying the cell biology of the mutant diseases. We have examined the extent to which the culture system reproduces the diseases of three well-known mutants, qk, jpmsd, and jp. Quantitation of myelin profiles per sq. mm of section demonstrates that in vitro, as in situ, qk produces the most myelin jpmsd an intermediate amount, and jp the least. Myelin in qk cultures is unique in being invisible by light microscopy of the living culture. Hypomyelination of jp may be more severe in vitro than in situ. Cultures of jpmsd exhibit many of the ultrastructural features of cerebellar abnormalities that occur in situ: degree of hypomyelination, clustering of myelin segments, scarcity of oligodendrocytes, absence of nodes of Ranvier but presence of heminodes, and apparent structural integrity of the myelin sheaths. Correspondence between in vitro and in situ ultrastructure is more difficult to assess for jp, because the available sample of jp myelin in vitro is too small, and for qk, because the abnormalities observed in situ resemble nonspecific abnormalities of normal myelin in vitro. PMID:7417802

  12. Nonenzymatic glycosylation of bovine myelin basic protein

    Energy Technology Data Exchange (ETDEWEB)

    Hitz, J.B.

    1987-01-01

    In the CNS myelin sheath the nonenzymatic glycosylation reaction (at the early stage of the Amadori product) occurs only with the myelin basic protein and not with the other myelin proteins. This was observed in isolated bovine myelin by in vitro incubation with (/sup 14/C)-galactose and (/sup 14/C)-glucose. The respective in-vitro incorporation rates for purified bovine myelin basic protein with D-galactose, D-glucose and D-mannose were 7.2, 2.4 and 2.4 mmoles/mole myelin basic protein per day at 37/sup 0/C. A more rapid, HPLC method was devised and characterized to specifically analyze for the Amadori product. The HPLC method was correlated to the (/sup 14/C)-sugar incorporation method for myelin basic protein under a set of standard reaction conditions using (/sup 14/C)-glucose and (/sup 14/C)-mannose with HPLC values at 1/6 and 1/5 of the (/sup 14/C)-sugar incorporation method. A novel myelin basic protein purification step has been developed that yields a relativity proteolytic free preparation that is easy to work with, being totally soluble at a neutral pH. Nine new spots appear for a trypsinized glycosylated MBP in the paper peptide map of which eight correspond to positions of the (/sup 3/H)-labeled Amadori product in affinity isolated peptides. These studies provide a general characterization of and a structural basis for investigations on nonenzymatically glycosylated MBP as well as identifying MBP as the only nonenzymatically glycosylated protein in the CNS myelin sheath which may accumulate during aging, diabetes, and demyelinating diseases in general.

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

    Directory of Open Access Journals (Sweden)

    Reichert Fanny

    2011-03-01

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

  14. CNS myelin sheath is stochastically built by homotypic fusion of myelin membranes within the bounds of an oligodendrocyte process.

    Science.gov (United States)

    Szuchet, Sara; Nielsen, Lauren L; Domowicz, Miriam S; Austin, Jotham R; Arvanitis, Dimitrios L

    2015-04-01

    Myelin - the multilayer membrane that envelops axons - is a facilitator of rapid nerve conduction. Oligodendrocytes form CNS myelin; the prevailing hypothesis being that they do it by extending a process that circumnavigates the axon. It is pertinent to ask how myelin is built because oligodendrocyte plasma membrane and myelin are compositionally different. To this end, we examined oligodendrocyte cultures and embryonic avian optic nerves by electron microscopy, immuno-electron microscopy and three-dimensional electron tomography. The results support three novel concepts. Myelin membranes are synthesized as tubules and packaged into "myelinophore organelles" in the oligodendrocyte perikaryon. Myelin membranes are matured in and transported by myelinophore organelles within an oligodendrocyte process. The myelin sheath is generated by myelin membrane fusion inside an oligodendrocyte process. These findings abrogate the dogma of myelin resulting from a wrapping motion of an oligodendrocyte process and open up new avenues in the quest for understanding myelination in health and disease. PMID:25682762

  15. Unwrapping Myelination by MicroRNAs

    OpenAIRE

    Xuelian, He; Yu, Yang; Awatramani, Rajeshwar; Lu, Q. Richard

    2011-01-01

    Myelination of axons by oligodendrocytes and Schwann cells in the central and peripheral nervous system, respectively, is essential for normal neuronal functions, and its failure results in devastating demyelinating diseases. During development, both oligodendrocyte and Schwann cell precursors undergo a temporally well-defined series of molecular and structural changes, ultimately culminating in the cessation of proliferation and the elaboration of a highly complex myelin sheath. Recent studi...

  16. Signals to promote myelin formation and repair.

    Science.gov (United States)

    Taveggia, Carla; Feltri, Maria Laura; Wrabetz, Lawrence

    2010-05-01

    The myelin sheath wraps large axons in both the CNS and the PNS, and is a key determinant of efficient axonal function and health. Myelin is targeted in a series of diseases, notably multiple sclerosis (MS). In MS, demyelination is associated with progressive axonal damage, which determines the level of patient disability. The few treatments that are available for combating myelin damage in MS and related disorders, which largely comprise anti-inflammatory drugs, only show limited efficacy in subsets of patients. More-effective treatment of myelin disorders will probably be accomplished by early intervention with combinatorial therapies that target inflammation and other processes-for example, signaling pathways that promote remyelination. Indeed, evidence suggests that such pathways might be impaired in pathology and, hence, contribute to the failure of remyelination in such diseases. In this article, we review the molecular basis of signaling pathways that regulate myelination in the CNS and PNS, with a focus on signals that affect differentiation of myelinating glia. We also discuss factors such as extracellular molecules that act as modulators of these pathways. Finally, we consider the few preclinical and clinical trials of agents that augment this signaling. PMID:20404842

  17. Radioimmunoassay for central nervous system myelin-specific proteolipid protein

    International Nuclear Information System (INIS)

    A double-antibody radioimmunoassay (RIA) has been developed with antisera to purified rat brain myelin proteolipid protein (PLP). The addition of Triton X-100 allowed antibody-antigen interaction and immune precipitation in the presence of sodium dodecyl sulfate (SDS). The RIA will accurately measure 8-80 ng of PLP in buffer or human serum. The RIA is highly specific for myelin PLP and does not cross-react with material in tissues (heart, kidney, muscle, testicle, and intestine) other than the central nervous system. The antibodies to rat myelin PLP cross-react with PLP from bovine brain homogenate or myelin. Myelin PLP was found to account for 55 and 52% of total myelin protein from bovine and rat brain, respectively. Furthermore, there is a higher concentration of PLP in white than in gray matter corresponding to the degree of myelination. Unlike myelin basic protein, myelin PLP was undetectable in both bovine and rat peripheral nervous system. (author)

  18. Molecular organisation in central nerve myelin.

    Science.gov (United States)

    Crang, A J; Rumsby, M G

    1978-01-01

    Pertinent data from the literature and in press is summarised and used to construct a model for the molecular arrangement of lipid and protein in the lamellae of compact central nerve myelin. For the lipid phase of myelin the available data is best interpreted in terms of a bilayer arrangement while physical studies suggest that the lipids are in an intermediate fluid state maintained by the presence of cholesterol and water in the system. Lipids will interact to maintain this condition. The proteins of myelin differ in their membrane locations. The high molecular weight proteins are considered to be intrinsic components with at least part of their polypeptide chains in the lipid phase. The proteolipid protein is also intrinsic and may be completely buried in the lipid phase. The basic protein of myelin is an extrinsic component and must be localised at the surface of the lipid phase at either the external or cytoplasmic face of the lamellae. Present results suggest an elusive location at the cytoplasmic apposition region. The lipid-interacting properties of the basic protein are segregated on the polypeptide chain of the molecule and this may be important for the possible role of the basic protein in bridging adjacent lamellae at the cytoplasmic apposition. It is speculated that association of the proteolipid protein with the basic protein in a 1:1 molar ratio would form an effective lipid-complexing nucleus in the lipid rich myelin lamellae but experimental data to support this idea is lacking at present. PMID:80940

  19. Split Decomp

    Science.gov (United States)

    Tony Weisstein (Truman State University; Biology)

    2007-04-20

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

  20. A myelin-specific contrast agent for magnetic resonance imaging of myelination.

    Science.gov (United States)

    Frullano, Luca; Wang, Changning; Miller, Robert H; Wang, Yanming

    2011-02-16

    Myelination is one of the most fundamental biological processes in the development of vertebrate nervous systems. Abnormal or disrupted myelination occurs in many acquired or inherited neurodegenerative diseases, including multiple sclerosis (MS) and various leukodystrophies. To date, magnetic resonance imaging (MRI) has been the primary tool for diagnosing and monitoring the progression of MS and related diseases; however, any change in signal intensity of conventional MRI reflects a change only in tissue water content, which is a nonspecific measure of the overall changes in macroscopic tissue injury. Thus, the use of MRI as a primary measure of disease activity was shown to be disassociated from the clinical outcome due to the lack of specificity for myelination. In order to increase the MRI specificity for myelin pathologies, we designed and synthesized the first Gd-based T(1) MR contrast agent (MIC) that binds to myelin with high specificity. In this Communication, we demonstrate that MIC localizes in brain regions in proportion to the extent of myelination. In addition, MIC possesses promising MR contrast properties, which allow for direct detection of myelin distribution through T(1) mapping in the mouse brain. PMID:21265506

  1. Myelin Abnormalities without Oligodendrocyte Loss in Periventricular Leukomalacia

    OpenAIRE

    Billiards, Saraid S.; Haynes, Robin L.; Folkerth, Rebecca D.; Borenstein, Natalia S.; Trachtenberg, Felicia L.; Rowitch, David H.; Ligon, Keith L.; Volpe, Joseph J.; Kinney, Hannah C.

    2008-01-01

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

  2. Myelin figures: the buckling and flow of wet soap

    OpenAIRE

    Zou, Ling-nan

    2009-01-01

    Myelin figures are interfacial structures formed when certain surfactants swell in excess water. Here, I present data and model calculations suggesting myelin formation and growth is due to the fluid flow of surfactant, driven by the hydration gradient at the dry surfactant/water interface; a simple model based on this idea qualitatively reproduces the various myelin growth behaviors observed in different experiments. From a detailed experimental observation of how myelins d...

  3. Myelin-associated glycoprotein and myelinating Schwann cell-axon interaction in chronic B,B'-iminodipropionitrile neuropathy

    OpenAIRE

    1984-01-01

    The myelin-associated glycoprotein (MAG) is a heavily glycosylated integral membrane glycoprotein which is a minor component of isolated rat peripheral nervous system (PNS) myelin. Immunocytochemically MAG has been localized in the periaxonal region of PNS myelin sheaths. The periaxonal localization and biochemical features of MAG are consistent with the hypothesis that MAG plays a role in maintaining the periaxonal space of myelinated fibers. To test this hypothesis, MAG was localized immuno...

  4. Complement activation by isolated myelin: activation of the classical pathway in the absence of myelin-specific antibodies.

    OpenAIRE

    Vanguri, P.; Koski, C. L.; Silverman, B.; Shin, M. L.

    1982-01-01

    Many pathological conditions of the central nervous system involve damage to and removal of myelin membrane. Very little is known about initiation of this membrane damage and the mechanisms of disposal of the damaged tissue. We are interested in the interaction between complement (the components of complement are designated C1, C2, C3, etc.) and myelin membranes and the possible role of complement in amplifying myelin damage and in the disposal of damaged myelin in vivo, because activation of...

  5. Adult myelination: wrapping up neuronal plasticity

    OpenAIRE

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

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Daldrup, H.E.; Schuierer, G.; Link, T.M.; Moeller, H.; Bick, U.; Peters, P.E. [Institute of Clinical Radiology, Westfaelische Wilhelms Universitaet, D-48149 Muenster (Germany); Kurlemann, G. [Department of Pediatrics, Westfaelische Wilhelms Universitaet, D-48149 Muenster (Germany)

    1997-12-01

    The aim of our work was to determine the efficacy of turbo inversion recovery spin echo (TIRSE) pulse sequences in differentiating patients with normal and abnormal myelination. Twenty neurological normal children (aged 5 months to 12 years) as well as 65 children presenting clinically with neurologic developmental deficits (aged 2 months to 10 years) were examined using TIRSE, T1-weighted SE, and T2-weighted turbo SE pulse sequences. Contrast-to-noise-ratio (CNR) between myelinated white and gray matter was compared for the different pulse sequences. In addition, two readers analyzed all images qualitatively by consensus. The CNR values were significantly higher on TIRSE images as compared with conventional images (p < 0.05). Forty-two neurologically abnormal patients displayed a normal myelination on all sequences, whereas 23 showed an abnormal myelination. The TIRSE sequence provided a sensitive and specific depiction of an abnormal myelination in all of these patients. The TIRSE sequence provided additional information to conventional pulse sequences in determining myelination disorders in children, especially in children older than 2 years. (orig.) With 9 figs., 25 refs.

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

    Science.gov (United States)

    Daldrup, H E; Schuierer, G; Link, T M; Moeller, H; Bick, U; Kurlemann, G; Peters, P E

    1997-01-01

    The aim of our work was to determine the efficacy of turbo inversion recovery spin echo (TIRSE) pulse sequences in differentiating patients with normal and abnormal myelination. Twenty neurological normal children (aged 5 months to 12 years) as well as 65 children presenting clinically with neurologic developmental deficits (aged 2 months to 10 years) were examined using TIRSE, T1-weighted SE, and T2-weighted turbo SE pulse sequences. Contrast-to-noise-ratio (CNR) between myelinated white and gray matter was compared for the different pulse sequences. In addition, two readers analyzed all images qualitatively by consensus. The CNR values were significantly higher on TIRSE images as compared with conventional images (p < 0. 05). Forty-two neurologically abnormal patients displayed a normal myelination on all sequences, whereas 23 showed an abnormal myelination. The TIRSE sequence provided a sensitive and specific depiction of an abnormal myelination in all of these patients. The TIRSE sequence provided additional information to conventional pulse sequences in determining myelination disorders in children, especially in children older than 2 years. PMID:9369518

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

    International Nuclear Information System (INIS)

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

  9. Polarity development in oligodendrocytes: sorting and trafficking of myelin components.

    Science.gov (United States)

    Maier, Olaf; Hoekstra, Dick; Baron, Wia

    2008-05-01

    In vertebrates, myelination is required for the saltatory signal conductance along the axon. At the onset of myelination, the myelinating cells, i.e., oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system, are heavily engaged in the biogenesis of membranes that are wrapped around the axon to form the myelin sheath. Although the membrane of the myelin sheath is continuous with the plasma membrane surrounding the cell body, the composition of both membrane domains is clearly distinct implying that myelinating cells are polarized cells. The coordinated manner of myelin sheath formation requires the existence of sorting and trafficking pathways to establish and maintain this highly polarized phenotype. Although in vitro data show that the formation of myelin-like membranes is an intrinsic property of oligodendrocytes, exogenous factors modulate myelination and are required for the subcompartmentation and compaction of the myelin sheath in vivo. In this paper, we discuss the sorting and trafficking of myelin proteins and lipids in oligodendrocytes in relation to polarity development and maintenance, including the role of exogenous factors, and give examples how the perturbation of trafficking pathways may contribute to the development of demyelinating diseases of the central nervous system. PMID:18172773

  10. Myelination in very low birth weight infants; Evaluation by MRI

    Energy Technology Data Exchange (ETDEWEB)

    Noma, Kazuko; Tamai, Hiroshi; Shimada, Seiichi; Funato, Masahisa (Yodogawa Christian Hospital, Osaka (Japan))

    1991-07-01

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

  11. 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.

  12. Progesterone synthesis in the nervous system: implications for myelination and myelin repair

    Directory of Open Access Journals (Sweden)

    MichaelSchumacher

    2012-02-01

    Full Text Available Progesterone is well known as a female reproductive hormone and in particular for its role in uterine receptivity, implantation and the maintenance of pregnancy. However, neuroendocrine research over the past decades has established that progesterone has multiple functions beyond reproduction. Within the nervous system, its neuromodulatory and neuroprotective effects are much studied. Although progesterone has been shown to also promote myelin repair, its influence and that of other steroids on myelination and remyelination is relatively neglected. Reasons for this are that hormonal influences are still not considered as a central problem by most myelin biologists, and that neuroendocrinologists are not sufficiently concerned with the importance of myelin in neuron functions and viability. The effects of progesterone in the nervous system involve a variety of signaling mechanisms. The identification of the classical intracellular progesterone receptors as therapeutic targets for myelin repair suggests new health benefits for synthetic progestins, specifically designed for contraceptive use and hormone replacement therapies. There are also major advantages to use natural progesterone in neuroprotective and myelin repair strategies, because progesterone is converted to biologically active metabolites in nervous tissues and interacts with multiple target proteins. The delivery of progesterone however represents a challenge because of its first-pass metabolism in digestive tract and liver. Recently, the intranasal route of progesterone administration has received attention for easy and efficient targeting of the brain. Progesterone in the brain is derived from the steroidogenic endocrine glands or from local synthesis by neural cells. Stimulating the formation of endogenous progesterone is currently explored as an alternative strategy for neuroprotection, axonal regeneration and myelin repair.

  13. 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.

  14. Determination of the sequential degradation of myelin proteins by macrophages.

    Science.gov (United States)

    van der Goes, Annette; Boorsma, Wiebe; Hoekstra, Karin; Montagne, Lisette; de Groot, Corline J A; Dijkstra, Christine D

    2005-04-01

    Demonstration of different myelin proteins (myelin basic protein [MBP], proteolipid protein [PLP] and myelin oligodendrocyte glycoprotein [MOG]) is used as a tool to determine the stage of MS lesions in autopsy tissue. Since such tissue can never be obtained at well-defined stages of lesion formation, the time course of myelin degradation in MS lesions can only be estimated. In order to obtain a more precise indication on the sequence of events of myelin degradation in MS lesions, the breakdown of human myelin by human monocytes was studied in vitro. Human monocytes were fed with myelin; next cytocentrifuge preparations were made on several time points (day 0 until day 6). The cytospots were immunocytochemically stained with mono- and polyclonal antibodies directed against various myelin proteins (MOG, MBP, PLP). We found that MOG is degraded after 1 day, whereas PLP and MBP can be detected for a longer period, 2 and 3 days, respectively. The exact time frame of myelin degradation in our in vitro assay cannot be extrapolated to the MS lesion formation in vivo, but our data allow conclusions on the sequence of events as well as a rough indication of the time frame of myelin degradation by macrophages in MS lesions. PMID:15748939

  15. Nogo-A and myelin-associated glycoprotein differently regulate oligodendrocyte maturation and myelin formation.

    Science.gov (United States)

    Pernet, Vincent; Joly, Sandrine; Christ, Franziska; Dimou, Leda; Schwab, Martin E

    2008-07-16

    Nogo-A is one of the most potent oligodendrocyte-derived inhibitors for axonal regrowth in the injured adult CNS. However, the physiological function of Nogo-A in development and in healthy oligodendrocytes is still unknown. In the present study, we investigated the role of Nogo-A for myelin formation in the developing optic nerve. By quantitative real-time PCR, we found that the expression of Nogo-A increased faster in differentiating oligodendrocytes than that of the major myelin proteins MBP (myelin basic protein), PLP (proteolipid protein)/DM20, and CNP (2',3'-cyclic nucleotide 3'-phosphodiesterase). The analysis of optic nerves and cerebella of mice deficient for Nogo-A (Nogo-A(-/-)) revealed a marked delay of oligodendrocyte differentiation, myelin sheath formation, and axonal caliber growth within the first postnatal month. The combined deletion of Nogo-A and MAG caused a more severe transient hypomyelination. In contrast to MAG(-/-) mice, Nogo-A(-/-) mutants did not present abnormalities in the structure of myelin sheaths and Ranvier nodes. The common binding protein for Nogo-A and MAG, NgR1, was exclusively upregulated in MAG(-/-) animals, whereas the level of Lingo-1, a coreceptor, remained unchanged. Together, our results demonstrate that Nogo-A and MAG are differently involved in oligodendrocyte maturation in vivo, and suggest that Nogo-A may influence also remyelination in pathological conditions such as multiple sclerosis. PMID:18632947

  16. Interactions of dicyclohexylcarbodiimide with myelin proteolipid.

    OpenAIRE

    Lin, L. F.; Lees, M. B.

    1982-01-01

    Dicyclohexylcarbodiimide (DCCD) is known to bind preferentially to a proteolipid subunit of proton-translocating systems and thereby to inhibit proton transport. In the present study we show that, in an aqueous medium, DCCD binds to the bovine white matter proteolipid apoprotein, the major protein of central nervous system myelin. The binding is dependent on time, temperature, and concentration and is not inhibited by the hydrophilic carbodiimide 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide...

  17. Jimpy mouse myelin revisited with freeze-fracture.

    Science.gov (United States)

    Privat, A; Drian, M J; Escaig, J

    1979-02-15

    Corpus callosum, cerebellum, and spinal cord from Jimpy mice, and control littermates, 15 and 21 days old, were prepared for freeze-fracture in a "cryofract" apparatus. The few myelinated axons in the Jimpy exhibited a striking paucity of particles in myelin P faces, though tight junctions were present. In addition, small maculae of particles were found on these P faces. Peripheral myelin appeared normal, both for the quantity and disposition of particles on their P faces. PMID:419935

  18. Brain gangliosides in axon-myelin stability and axon regeneration

    OpenAIRE

    Schnaar, Ronald L.

    2009-01-01

    Gangliosides, sialic acid-bearing glycosphingolipids, are expressed at high abundance and complexity in the brain. Altered ganglioside expression results in neural disorders, including seizures and axon degeneration. Brain gangliosides function, in part, by interacting with a ganglioside-binding lectin, myelin-associated glycoprotein (MAG). MAG, on the innermost wrap of the myelin sheath, binds to gangliosides GD1a and GT1b on axons. MAG-ganglioside binding ensures optimal axon-myelin cell-ce...

  19. Strategies for myelin regeneration: lessons learned from development.

    Science.gov (United States)

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

    2014-07-15

    Myelin regeneration is indispensably important for patients suffering from several central nervous system (CNS) disorders such as multiple sclerosis (MS) and spinal cord injury (SCI), because it is not only essential for restoring neurophysiology, but also protects denuded axons for secondary degeneration. Understanding the cellular and molecular mechanisms underlying remyelination is critical for the development of remyelination-specific therapeutic approaches. As remyelination shares certain common mechanisms with developmental myelination, knowledge from study of developmental myelination contributes greatly to emerging myelin regeneration therapies, best evidenced as the recently developed human anti-Nogo receptor interacting protein-1 (LINGO-1) monoclonal antibodies to treat MS patients in clinical trials. PMID:25221590

  20. Split engine

    Energy Technology Data Exchange (ETDEWEB)

    Ueno, M.; Hori, K.

    1984-08-21

    A split engine comprising a plurality of cylinders which are divided into a first cylinder group and a second cylinder group. The second cylinder group is connected to the outside air via a second intake passage. The first cylinder group is connected to a first intake passage which is, in turn, connected to the second intake passage via a shut-off valve. The first intake passage is connected to the exhaust passage of the engine via an exhaust-gas recirculation passage. When the level of the load of the engine becomes high, the exhaust-gas recirculation passage is shut off, and the shut-off valve is initially opened at a high speed and then opened at a low speed.

  1. 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

  2. Myelin-associated proteins labelled by slow axonal transport

    International Nuclear Information System (INIS)

    This paper deals with the problem of protein metabolism and provides evidence that the neuronal contribution to myelin metabolism may be restricted to lipids only. On the other hand this line of research led to the partial characterization of a group of neuronal proteins probably involved in axo-glial interactions subserving the onset of myelination and the structural maintenance of the mature myelin sheath. Intraocular injection of radioactive amino acids allows the study of the anterograde transport of labelled proteins along retinofugal fibres which are well myelinated. Myelin extracted from the optic nerve and tract under these conditions also contains labelled proteins. Three hypotheses are available to explain this phenomenon. To offer an explanation for this phenomenon the work was planned as follows. a) Characterization of the spatio-temporal pattern of labelling of myelin, in order to define the experimental conditions (survival time and region of the optic pathway to be studied) necessary to obtain maximal labelling. b) Characterization (by gel electrophoresis) of the myelin-associated proteins which become labelled by axonal transport, in order to work on a consistent pattern of labelling. c) Investigation of the possible mechanism responsible for the labelling of myelin-associated proteins. (Auth.)

  3. 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.

  4. Oligodendrocytes and myelination: the role of iron.

    Science.gov (United States)

    Todorich, Bozho; Pasquini, Juana M; Garcia, Corina I; Paez, Pablo M; Connor, James R

    2009-04-01

    Iron is an essential trophic factor that is required for oxygen consumption and ATP production. Thus it plays a key role in vital cell functions. Although the brain has a relatively high rate of oxygen consumption compared to other organs, oligodendrocytes are the principal cells in the CNS that stain for iron under normal conditions. The importance of iron in myelin production has been demonstrated by studies showing that decreased availability of iron in the diet is associated with hypomyelination. The timing of iron delivery to oligodendrocytes during development is also important because hypomyelination and the associated neurological sequelae persist long after the systemic iron deficiency has been corrected. Therefore, identifying the molecular roles of iron in oligodendrocyte development and myelin production, and the mechanisms and timing of iron acquisitions are important prerequisites to developing effective therapies for dysmyelinating disorders. It is the purpose of this review to give a comprehensive overview of the existing literature on role of iron in oligodendrocytes and the mechanisms of iron acquisition and intracellular handling. PMID:18837051

  5. Brittle Splitting Nails (Onychoschizia)

    Science.gov (United States)

    ... Category: Share: Yes No, Keep Private Brittle Splitting Nails Share | Onychoschizia or splitting of the fingernails is ... term onychoschizia includes splitting, brittle, soft or thin nails. Onychoschizia is more common in women. Only very ...

  6. 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.

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

    Science.gov (United States)

    Jacobs, Erin C; Reyes, Samuel D; Campagnoni, Celia W; Irene Givogri, M; Kampf, Kathy; Handley, Vance; Spreuer, Vilma; Fisher, Robin; Macklin, Wendy; Campagnoni, Anthony T

    2009-01-01

    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. PMID:19715557

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

    Directory of Open Access Journals (Sweden)

    Melikulov A.Kh.

    2014-03-01

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

  9. Stimulation of adult oligodendrogenesis by myelin-specific T cells

    DEFF Research Database (Denmark)

    Hvilsted Nielsen, Helle; Toft-Hansen, Henrik

    2011-01-01

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

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

    Science.gov (United States)

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

    2011-10-19

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

  11. CNS live imaging reveals a new mechanism of myelination: the liquid croissant model.

    Science.gov (United States)

    Sobottka, Bettina; Ziegler, Urs; Kaech, Andres; Becher, Burkhard; Goebels, Norbert

    2011-12-01

    The overall morphology and with it associated the formation of myelin is generally thought to be resolved. Based on electron microscopic findings more than half a century ago, the current model of myelination describes all myelin membranes to run in parallel with the longitudinal axis of the axon and to form a smooth surface, reminiscent of a rolled up carpet. However, different studies in the past demonstrated a distinct myelin morphology with an uneven myelin surface contour that challenges the established concept. Even though the current model of myelination has since been recognized as insufficient, CNS myelin formation has not yet been investigated in real-time with the requisite technique and resolution. We therefore traced myelin growth in murine organotypic cerebellar slice cultures using high-resolution confocal live imaging, light and electron microscopy and assessed myelin morphology in young and adult mice by confocal microscopy. Our data verify that the myelin surface is indeed not smooth but runs in a bidirectional, regularly spaced coil along the axon in both young and adult mice. Time-lapse imaging revealed that the growth of coiled myelin turns emerges during myelin formation. We therefore propose the "liquid croissant" model as a new concept of myelination that overcomes not only some of the incongruences of previous myelination theories, but potentially also explains the development of certain myelin pathologies observed in remyelination and axonopathies. PMID:21887712

  12. Dynamics of oligodendrocyte generation and myelination in the human brain.

    Science.gov (United States)

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

    2014-11-01

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

  13. Oligodendrocyte differentiation and myelination defects in OMgp null mice.

    Science.gov (United States)

    Lee, Xinhua; Hu, Yinghui; Zhang, Yiping; Yang, Zhongshu; Shao, Zhaohui; Qiu, Mengsheng; Pepinsky, Blake; Miller, Robert H; Mi, Sha

    2011-04-01

    OMgp is selectively expressed in CNS by oligodendrocyte. However, its potential role(s) in oligodendrocyte development and myelination remain unclear. We show that OMgp null mice are hypomyelinated in their spinal cords, resulting in slower ascending and descending conduction velocities compared to wild-type mice. Consistent with the hypomyelination, in the MOG induced EAE model, OMgp null mice show a more severe EAE clinical disease and slower nerve conduction velocity compared to WT animals. The contribution of OMgp to oligodendrocyte differentiation and myelination was verified using cultured oligodendrocytes from null mice. Oligodendrocytes isolated from OMgp null mice show a significant decrease in the number of MBP(+) cells and in myelination compared to wild-type mice. The dramatic effects of the OMgp KO in oligodendrocyte maturation in vivo and in vitro reveal a new and important function for OMgp in regulating CNS myelination. PMID:21352918

  14. The thrombin receptor is a critical extracellular switch controlling myelination.

    Science.gov (United States)

    Yoon, Hyesook; Radulovic, Maja; Drucker, Kristen L; Wu, Jianmin; Scarisbrick, Isobel A

    2015-05-01

    Hemorrhagic white matter injuries in the perinatal period are a growing cause of cerebral palsy yet no neuroprotective strategies exist to prevent the devastating motor and cognitive deficits that ensue. We demonstrate that the thrombin receptor (protease-activated receptor 1, PAR1) exhibits peak expression levels in the spinal cord at term and is a critical regulator of the myelination continuum from initiation to the final levels achieved. Specifically, PAR1 gene deletion resulted in earlier onset of spinal cord myelination, including substantially more Olig2-positive oligodendrocytes, more myelinated axons, and higher proteolipid protein (PLP) levels at birth. In vitro, the highest levels of PAR1 were observed in oligodendrocyte progenitor cells (OPCs), being reduced with differentiation. In parallel, the expression of PLP and myelin basic protein (MBP), in addition to Olig2, were all significantly higher in cultures of PAR1-/- oligodendroglia. Moreover, application of a small molecule inhibitor of PAR1 (SCH79797) to OPCs in vitro increased PLP and MBP expression. Enhancements in myelination associated with PAR1 genetic deletion were also observed in adulthood as evidenced by higher amounts of MBP and thickened myelin sheaths across large, medium, and small diameter axons. Enriched spinal cord myelination in PAR1-/- mice was coupled to increases in extracellular-signal-regulated kinase 1/2 and AKT signaling developmentally. Nocturnal ambulation and rearing activity were also elevated in PAR1-/- mice. These studies identify the thrombin receptor as a powerful extracellular regulatory switch that could be readily targeted to improve myelin production in the face of white matter injury and disease. GLIA 2015;63:846-859. PMID:25628003

  15. Evaluating dermal myelinated nerve fibers in skin biopsy

    OpenAIRE

    Myers, M. Iliza; Peltier, Amanda C.; Li, Jun

    2012-01-01

    Although there has been extensive research on small, unmyelinated fibers in the skin, little research has investigated dermal myelinated fibers in comparison. Glabrous, non-hairy skin contains mechanoreceptors that afford a vantage point for observation of myelinated fibers that have previously been seen only with invasively obtained nerve biopsies. This review discusses current morphometric and molecular expression data of normative and pathogenic glabrous skin obtained by various processing...

  16. Clozapine promotes glycolysis and myelin lipid synthesis in cultured oligodendrocytes

    OpenAIRE

    Steiner, Johann; Martins-de-souza, Daniel; Schiltz, Kolja; Sarnyai, Zoltan; Westphal, Sabine; Isermann, Berend; Dobrowolny, Henrik; Turck, Christoph W.; Bogerts, Bernhard; Bernstein, Hans-gert; Horvath, Tamas L.; Schild, Lorenz; Keilhoff, Gerburg

    2014-01-01

    Clozapine displays stronger systemic metabolic side effects than haloperidol and it has been hypothesized that therapeutic antipsychotic and adverse metabolic effects of these drugs are related. Considering that cerebral disconnectivity through oligodendrocyte dysfunction has been implicated in schizophrenia, it is important to determine the effect of these drugs on oligodendrocyte energy metabolism and myelin lipid production. Effects of clozapine and haloperidol on glucose and myelin lipid ...

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

    OpenAIRE

    Jacobs, Erin C.; Reyes, Samuel D.; Campagnoni, Celia W.; Irene Givogri, M.; Kampf, Kathy; Handley, Vance; Spreuer, Vilma; Fisher, Robin; Macklin, Wendy; Campagnoni, Anthony T.

    2009-01-01

    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 mo...

  18. Thermocouple split follower

    Science.gov (United States)

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

    1980-01-01

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

  19. Thermocouple split follower

    International Nuclear Information System (INIS)

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

  20. Synergistic interactions of lipids and myelin basic protein

    Science.gov (United States)

    Hu, Yufang; Doudevski, Ivo; Wood, Denise; Moscarello, Mario; Husted, Cynthia; Genain, Claude; Zasadzinski, Joseph A.; Israelachvili, Jacob

    2004-09-01

    This report describes force measurements and atomic force microscope imaging of lipid-protein interactions that determine the structure of a model membrane system that closely mimics the myelin sheath. Our results suggest that noncovalent, mainly electrostatic and hydrophobic, interactions are responsible for the multilamellar structure and stability of myelin. We find that myelin basic protein acts as a lipid coupler between two apposed bilayers and as a lipid "hole-filler," effectively preventing defect holes from developing. From our protein-mediated-adhesion and force-distance measurements, we develop a simple quantitative model that gives a reasonably accurate picture of the molecular mechanism and adhesion of bilayer-bridging proteins by means of noncovalent interactions. The results and model indicate that optimum myelin adhesion and stability depend on the difference between, rather than the product of, the opposite charges on the lipid bilayers and myelin basic protein, as well as on the repulsive forces associated with membrane fluidity, and that small changes in any of these parameters away from the synergistically optimum values can lead to large changes in the adhesion or even its total elimination. Our results also show that the often-asked question of which membrane species, the lipids or the proteins, are the "important ones" may be misplaced. Both components work synergistically to provide the adhesion and overall structure. A better appreciation of the mechanism of this synergy may allow for a better understanding of stacked and especially myelin membrane structures and may lead to better treatments for demyelinating diseases such as multiple sclerosis. lipid-protein interactions | myelin membrane structure | membrane adhesion | membrane regeneration/healing | demyelinating diseases

  1. In vivo acylation of proteolipid protein and DM-20 in myelin and myelin subfractions of developing rat brain: immunoblot identification of acylated PLP and DM-20

    International Nuclear Information System (INIS)

    The acylation of proteolipid protein (PLP) was examined in myelin and myelin subfractions from rat brain during the active period of myelination. Proteolipid protein and DM-20 in myelin and myelin subfractions were readily acylated in developing rat brain 22 hours after intracerebral injection of [3H]palmitic acid. No differences in the relative specific activity of PLP in myelin from 9-, 15-, and 30-day-old rat brains was observed; however, the relative specific activity of PLP in the heavy myelin subfraction tended to be higher than that in the light myelin subfraction. The acylation of PLP was confirmed by fluorography of immuno-stained cellulose nitrate sheets, clearly establishing that the acylated protein is in fact the oligodendroglial cell- and myelin-specific protein, PLP. Since PLP is acylated in the 9-day-old animal, when little compact myelin is present, it is possible that the acylation of PLP is a prerequisite for the incorporation of this protein into the myelin membrane

  2. PIKE is essential for oligodendroglia development and CNS myelination.

    Science.gov (United States)

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

    2014-02-01

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

  3. Topology and organization of bovine brain myelin proteolipid

    International Nuclear Information System (INIS)

    Myeline proteolipid protein (PLP), the mayor myeline protein in the central nervous system in an extremely hydrophobic membrane protein. Its relative abundance in myelin and lack of known enzymatic activity suggest that it may play an important role in the development and maintenance of the multilamellar structure of myelin. On the basis of primary sequence data, two conformational models of PLP have been proposed. To test these models, the author have attempted to locate thiol groups and disulfide bonds of PLP to determine which extramembrane fragments are located at the exterior and which at the interior faces of myelin membrane. 14C-Carboxamidomethylated PLP was fragmented by chymotrypsin, and the resulting mixture was separated by reverse-phase high performance liquid chromatography. All of the purified 14C-labeled peptides and disulfide containing peptides were further characterized by amino acid analysis. Two thiol groups (Cys-32 and Cys-34) and one disulfide bond between Cys-200 and Cys-219 were found. Unfortunately much of the fragmented protein proved intractable and the status of the other Cys residues was not determined

  4. Ephrin-B3 is a myelin-based inhibitor of neurite outgrowth

    OpenAIRE

    Benson, M. Douglas; Romero, Mario I.; Lush, Mark E.; Lu, Q. Richard; Henkemeyer, Mark; Parada, Luis F.

    2005-01-01

    The inability of CNS axons to regenerate after traumatic spinal cord injury is due, in part, to the inhibitory effects of myelin. The three major previously identified constituents of this activity (Nogo, myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein) were isolated based on their potent inhibition of axon outgrowth in vitro. All three myelin components transduce their inhibitory signals through the same Nogo receptor/p75 neurotrophin receptor/LINGO-1 (NgR1/p75/LINGO-...

  5. ANALYSIS OF PERIPHERAL NERVE EXPRESSION PROFILES IDENTIFIES A NOVEL MYELIN GLYCOPROTEIN, MP11

    OpenAIRE

    Ryu, Elizabeth J.; Yang, Mao; Gustin, Jason A.; Chang, Li-wei; Freimuth, Robert R.; Nagarajan, Rakesh; Milbrandt, Jeffrey

    2008-01-01

    The myelin sheath insulates axons and allows for rapid saltatory conduction in the nervous system of all vertebrates. The formation of peripheral myelin requires expression of the transcription factor, Egr2 which is responsible for inducing such essential myelin-associated genes as Mpz, Mbp, Pmp22 and Mag. Using microarray analysis to compare gene expression patterns in peripheral nerve during development, re-myelination after nerve injury, and in a congenital hypomyelinating mouse model, we ...

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

    OpenAIRE

    Kegel, L.

    2013-01-01

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

  7. Assembly of Myelin by Association of Proteolipid Protein with Cholesterol- and Galactosylceramide-Rich Membrane Domains

    OpenAIRE

    Simons, Mikael; Kra?mer, Eva-maria; Thiele, Christoph; Stoffel, Wilhelm; Trotter, Jacqueline

    2000-01-01

    Myelin is a specialized membrane enriched in glycosphingolipids and cholesterol that contains a limited spectrum of proteins. We investigated the assembly of myelin components by oligodendrocytes and analyzed the role of lipid–protein interactions in this process. Proteolipid protein (PLP), the major myelin protein, was recovered from cultured oligodendrocytes from a low-density CHAPS-insoluble membrane fraction (CIMF) enriched in myelin lipids. PLP associated with the CIMF after leaving th...

  8. 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.)

  9. Evaluation of dermal myelinated nerve fibers in diabetes mellitus

    OpenAIRE

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

    2013-01-01

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

  10. Development and maturation of central nervous system myelin: Comparison of immunohistochemical localization of proteolipid protein and basic protein in myelin and oligodendrocytes

    OpenAIRE

    Hartman, Boyd K.; Agrawal, Harish C.; Agrawal, Daya; Kalmbach, Sandra

    1982-01-01

    The immunohistochemical localization of two myelin specific proteins—basic protein (BP) and proteolipid protein (PLP)—was compared during the process of myelination. Although both proteins were present in oligodendrocytes, (i) neither protein was observed in oligodendrocytes not already closely associated with nerve fibers exhibiting a fluorescent coating; (ii) in any discrete anatomical area oligodendrocytes were positive for BP before PLP was visible; and (iii) as myelination progressed...

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

    DEFF Research Database (Denmark)

    DrØjdahl, Nina; Nielsen, Helle Hvilsted

    2010-01-01

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

  12. Mammalian target of rapamycin promotes oligodendrocyte differentiation, initiation and extent of CNS myelination.

    Science.gov (United States)

    Wahl, Stacey E; McLane, Lauren E; Bercury, Kathryn K; Macklin, Wendy B; Wood, Teresa L

    2014-03-26

    Prior studies support a role for mammalian target of rapamycin (mTOR) signaling in oligodendrocyte differentiation and myelination. Here we use Cre-recombinase driven by the CNP promoter to generate a mouse line with oligodendrocyte-specific knockdown of mTOR (mTOR cKO) in the CNS. We provide evidence that mTOR is necessary for proper oligodendrocyte differentiation and myelination in the spinal cord. Specifically, the number of mature oligodendrocytes was reduced, and the initiation and extent of myelination were impaired during spinal cord development. Consistent with these data, myelin protein expression, including myelin basic protein, proteolipid protein, myelin oligodendrocyte glycoprotein, and myelin-associated glycoprotein, was delayed in the spinal cord. Hypomyelination of the spinal cord persisted into adulthood, as did the reduction in numbers of mature oligodendrocytes. In the cortex, the structure of myelin appeared normal during development and in the adult; however, myelin protein expression was delayed during development and was abnormal in the adult. Myelin basic protein was significantly reduced in all regions at postnatal day 25. These data demonstrate that mTOR promotes oligodendrocyte differentiation and CNS myelination in vivo and show that the requirement for mTOR varies by region with the spinal cord most dependent on mTOR. PMID:24671992

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    Anthony T Campagnoni

    2010-02-01

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

  15. 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.

  16. Inefficient transcription of the myelin basic protein gene possibly causes hypomyelination in myelin-deficient mutant mice.

    Science.gov (United States)

    Okano, H; Miura, M; Moriguchi, A; Ikenaka, K; Tsukada, Y; Mikoshiba, K

    1987-02-01

    A hereditary dysmyelination mutation, named myelin deficient (mld), is considered to be allelic to shiverer, a deletion mutation of the myelin basic protein (MBP) gene. The present study showed that MBP expression is greatly reduced in mld, but that it is still detectable. Northern blot analysis revealed that the pronounced decrease in the MBP level in mld resulted from a reduced mRNA level and was not caused by deletion of a large portion of the MBP gene as in shiverer. Southern blot studies with BamHI-digested chromosomal DNA suggested some part of the MBP gene, at least the 5'-portion, was duplicated in mld. These results indicated that the mld and shiverer mutations were different from each other, even though genetic allelism between the two was reconfirmed. We also examined the developmental pattern of the gene expression of MBP and that of another protein, myelin proteolipid protein (PLP), specifically expressed in the oligodendrocyte, in mld by RNA dot blot study. The mRNA level of MBP in mld was greatly reduced during the active myelination stages, gradually increasing and remaining constant in the later stages. The PLP-mRNA content in mld was almost normal (60-80% that of control) at any stage of development. All these findings imply that the primary defect in mld is due to reduced transcriptional activity of the MBP gene. PMID:2432182

  17. 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.

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

    Science.gov (United States)

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

    2013-11-20

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

  19. The temporal progression of the myelination defect in the taiep rat.

    Science.gov (United States)

    Lunn, K F; Clayton, M K; Duncan, I D

    1997-05-01

    The Sprague Dawley myelin mutant, the taiep rat, demonstrates a defect in CNS myelination which worsens with age and which is associated with abnormal accumulations of microtubules in oligodendrocytes. Quantitative and qualitative electron microscopic studies of myelin development and oligodendrocyte morphology were used to describe the temporal development of the defect in this mutant, in three regions of the CNS. The results indicate that the time of onset of myelination is similar in mutant and control rats, however the amount of myelin formed is reduced in the mutant, compared to controls, and there is a loss of myelin from the taiep CNS as the animals age. Thus the myelination defect in taiep has features of both hypomyelination and demyelination. Oligodendrocyte microtubule abnormalities were noted in each region of the taiep CNS at the time of onset of myelination. The earliest changes seen were close associations of oligodendrocyte microtubules with endoplasmic reticulum, with marked accumulations of microtubules filling the cytoplasm of oligodendrocytes from older taiep rats. These findings suggest that the microtubule abnormality in the taiep mutant inhibits both the initial formation and the long-term maintenance of myelin by the oligodendrocyte. In addition, there is also evidence to suggest that although the microtubule abnormality is present in oligodendrocytes throughout the taiep CNS, it results in a more marked defect in the myelination of axons of small diameter. PMID:9192292

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

    OpenAIRE

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

    2011-01-01

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

  1. Structural parameters of the myelin transmembrane proteolipid in reverse micelles.

    OpenAIRE

    Binks, B. P.; Chatenay, D.; Nicot, C.; Urbach, W.; Waks, M.

    1989-01-01

    The Folch-Pi proteolipid is the most abundant structural protein from the central nervous system myelin. This protein-lipid complex, normally insoluble in water, requires only a small amount of water for solubilization in reverse micelles of sodium bis (2-ethylhexyl) sulfosuccinate (AOT) in isooctane. The characterization of the proteolipid-free and proteolipid-containing micelles was undertaken by light scattering and fluorescence recovery after fringe pattern photobleaching (FRAPP) experime...

  2. The Role of TSC in Oligodendrocyte Differentiation and Myelination

    OpenAIRE

    Han, Juliette

    2012-01-01

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

  3. Strategies for myelin regeneration: lessons learned from development

    OpenAIRE

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

    2014-01-01

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

  4. Rapid morphological fusion of severed myelinated axons by polyethylene glycol.

    OpenAIRE

    Krause, T. L.; Bittner, G. D.

    1990-01-01

    We are able to morphologically fuse the severed halves of an invertebrate-myelinated axon by application of polyethylene glycol (PEG) to closely apposed cut ends. Morphological fusion of the medial giant axon (MGA) of the earthworm Lumbricus terrestris is defined as axoplasmic and axolemmal continuity in serial longitudinal sections of MGAs taken through the fusion site as viewed with light or electron microscopes. Morphological continuity is also shown by the transfer of Lucifer yellow dye b...

  5. Myelin-associated changes in mouse brain following irradiation

    International Nuclear Information System (INIS)

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

  6. Proliferation of Schwann cells induced by axolemmal and myelin membranes

    International Nuclear Information System (INIS)

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

  7. Negative regulation of central nervous system myelination by polysialylated-neural cell adhesion molecule

    OpenAIRE

    Charles, P.; Hernandez, M. P.; Stankoff, B.; Aigrot, M. S.; Colin, C.; Rougon, G.; Zalc, B.; Lubetzki, C.

    2000-01-01

    Many factors have been shown to promote myelination, but few have been shown to be inhibitory. Here, we show that polysialylated-neural cell adhesion molecule (PSA-NCAM) can negatively regulate myelin formation. During development, PSA-NCAM is first expressed on all growing fibers; then, axonal expression is down-regulated and myelin deposition occurs only on PSA-NCAM-negative axons. Similarly, in cocultures of oligodendrocytes and neurons, PSA-NCAM expression on axons is initially high, but ...

  8. Schwann cells of the myelin-forming phenotype express neurofilament protein NF-M

    OpenAIRE

    1992-01-01

    Immature Schwann cells of the rat sciatic nerve can differentiate into myelin-forming or non-myelin-forming cells. The factors that influence this divergent development are unknown but certain markers such as galactocerebroside distinguish the two cell populations at an early stage of Schwann cell differentiation. Because myelination requires extensive changes in cell morphology, we have investigated the composition and structure of the Schwann cell cytoskeleton at a time when these cells bec...

  9. The QKI-PLP pathway controls SIRT2 abundance in CNS myelin

    OpenAIRE

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

    2011-01-01

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

  10. Split Special Lagrangian Geometry

    CERN Document Server

    Harvey, F Reese

    2010-01-01

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

  11. Distances of Heegaard splittings

    CERN Document Server

    Abrams, A; Schleimer, Saul

    2003-01-01

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

  12. A Mutation in the Canine Gene Encoding Folliculin-Interacting Protein 2 (FNIP2) Associated With a Unique Disruption in Spinal Cord Myelination

    OpenAIRE

    Pemberton, Trevor J.; Choi, Sunju; Mayer, Joshua A.; Li, Fang-yuan; Gokey, Nolan; Svaren, John; Safra, Noa; Bannasch, Danika L.; Sullivan, Katrina; Breuhaus, Babetta; Patel, Pragna I.; Duncan, Ian D.

    2014-01-01

    Novel mutations in myelin and myelin-associated genes have provided important information on oligodendrocytes and myelin and the effects of their disruption on the normal developmental process of myelination of the central nervous system (CNS). We report here a mutation in the folliculin-interacting protein 2 (FNIP2) gene in the Weimaraner dog that results in hypomyelination of the brain and a tract-specific myelin defect in the spinal cord. This myelination disruption results in a notable tr...

  13. [Split-liver transplantation].

    Science.gov (United States)

    Loss, M; Obed, A; Schlitt, H J

    2008-02-01

    Split-liver transplantation is now established as a safe and successful technique that extends the donor pool for patients of all ages and thus reduces waiting-list mortality, although it can not solve the problem of organ shortage alone. Split-liver transplantation additionally represents an alternative to living liver transplantation without a potential risk of harm to the donor. Careful selection of donor and recipient, high technical and surgical skill, and experience are necessary to achieve results comparable to those of whole organ transplantation. PMID:18209986

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

    Science.gov (United States)

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

    2008-06-27

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

  15. Split dynamics plasma simulations

    International Nuclear Information System (INIS)

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

  16. 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.

  17. Cleavage of Myelin Associated Glycoprotein by Matrix Metalloproteinases

    OpenAIRE

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

    2007-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Wei-Chin; Liao, Jiunn-Der [Department of Materials Science and Engineering, National Cheng Kung University, 1 University Road, Tainan 70101, Taiwan (China); Lin, Chou-Ching K [Department of Neurology, National Cheng Kung University, 1 University Road, Tainan 70101, Taiwan (China); Ju, Ming-Shaung, E-mail: jdliao@mail.ncku.edu.tw [Department of Mechanical Engineering, National Cheng Kung University, 1 University Road, Tainan 70101, Taiwan (China)

    2011-07-08

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

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

    Science.gov (United States)

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

    2011-07-01

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

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

    International Nuclear Information System (INIS)

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

  1. 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.)

  2. Neuropathy-Associated Egr2 Mutants Disrupt Cooperative Activation of Myelin Protein Zero by Egr2 and Sox10?

    OpenAIRE

    Leblanc, Scott E.; Ward, Rebecca M.; Svaren, John

    2007-01-01

    Dominant mutations in the early growth response 2 (Egr2/Krox20) transactivator, a critical regulator of peripheral myelin development, have been associated with peripheral myelinopathies. These dominant mutants interfere with the expression of genes required for myelination by Schwann cells, including that for the most abundant peripheral myelin protein, Myelin protein zero (Mpz). In this study, we show that Egr2 mutants specifically affect an Egr2-responsive element within the Mpz first intr...

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

    OpenAIRE

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

    2011-01-01

    Abstract Background The sphingolipids galactosylceramide (GalCer) and sulfatide are major myelin components and are thought to play important roles in myelin function. The importance of GalCer and sulfatide has been validated using UDP-galactose:ceramide galactosyltransferase-deficient (Cgt-/-) mice, which are impaired in myelin maintenance. These mice, however, are still able to form compact myelin. Loss of GalCer and sulfatide in these mice is accompanied by up-regulation of 2-hydroxylated ...

  4. The initial events in myelin synthesis: orientation of proteolipid protein in the plasma membrane of cultured oligodendrocytes

    OpenAIRE

    1989-01-01

    Proteolipid protein (PLP) is the most abundant transmembrane protein in myelin of the central nervous system. Conflicting models of PLP topology have been generated by computer predictions based on its primary sequence and experiments with purified myelin. We have examined the initial events in myelin synthesis, including the insertion and orientation of PLP in the plasma membrane, in rat oligodendrocytes which express PLP and the other myelin-specific proteins when cultured without neurons (...

  5. Unmasking of an unusual myelin basic protein epitope during the process of myelin degeneration in humans: a potential mechanism for the generation of autoantigens.

    OpenAIRE

    Matsuo, A.; Lee, G. C.; Terai, K.; Takami, K.; Hickey, W. F.; Mcgeer, E. G.; Mcgeer, P. L.

    1997-01-01

    A rabbit antiserum (anti-EP), induced against a synthetic peptide corresponding to residues 68 to 86 of guinea pig myelin basic protein, powerfully immunostained abnormal-appearing oligodendrocytic processes and cell bodies in demyelinating areas associated with multiple sclerosis plaques. However, it failed to recognize any structures in normal human, rat, or guinea pig brain. The antiserum recognized the synthetic peptide QDENPVV, which corresponds to human myelin basic protein residues 82 ...

  6. 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.

  7. Human Neural Stem Cells Induce Functional Myelination in Mice with Severe Dysmyelination

    Science.gov (United States)

    Uchida, Nobuko; Chen, Kevin; Dohse, Monika; Hansen, Kelly D.; Dean, Justin; Buser, Joshua R.; Riddle, Art; Beardsley, Douglas J.; Wan, Ying; Gong, Xi; Nguyen, Thuan; Cummings, Brian J.; Anderson, Aileen J.; Tamaki, Stanley J.; Tsukamoto, Ann; Weissman, Irving L.; Matsumoto, Steven G.; Sherman, Larry S.; Kroenke, Christopher D.; Back, Stephen A.

    2013-01-01

    Shiverer-immunodeficient (Shi-id) mice demonstrate defective myelination in the central nervous system (CNS) and significant ataxia by 2 to 3 weeks of life. Expanded, banked human neural stem cells (HuCNS-SCs) were transplanted into three sites in the brains of neonatal or juvenile Shi-id mice, which were asymptomatic or showed advanced hypomyelination, respectively. In both groups of mice, HuCNS-SCs engrafted and underwent preferential differentiation into oligodendrocytes. These oligodendrocytes generated compact myelin with normalized nodal organization, ultrastructure, and axon conduction velocities. Myelination was equivalent in neonatal and juvenile mice by quantitative histopathology and high-field ex vivo magnetic resonance imaging, which, through fractional anisotropy, revealed CNS myelination 5 to 7 weeks after HuCNS-SC transplantation. Transplanted HuCNS-SCs generated functional myelin in the CNS, even in animals with severe symptomatic hypomyelination, suggesting that this strategy may be useful for treating dysmyelinating diseases. PMID:23052293

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-09-01

    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.)

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

    International Nuclear Information System (INIS)

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

  10. 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.)

  11. Statistical physics approach to quantifying differences in myelinated nerve fibers

    Science.gov (United States)

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

    2014-01-01

    We present a new method to quantify differences in myelinated nerve fibers. These differences range from morphologic characteristics of individual fibers to differences in macroscopic properties of collections of fibers. Our method uses statistical physics tools to improve on traditional measures, such as fiber size and packing density. As a case study, we analyze cross–sectional electron micrographs from the fornix of young and old rhesus monkeys using a semi-automatic detection algorithm to identify and characterize myelinated axons. We then apply a feature selection approach to identify the features that best distinguish between the young and old age groups, achieving a maximum accuracy of 94% when assigning samples to their age groups. This analysis shows that the best discrimination is obtained using the combination of two features: the fraction of occupied axon area and the effective local density. The latter is a modified calculation of axon density, which reflects how closely axons are packed. Our feature analysis approach can be applied to characterize differences that result from biological processes such as aging, damage from trauma or disease or developmental differences, as well as differences between anatomical regions such as the fornix and the cingulum bundle or corpus callosum. PMID:24676146

  12. 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...

  13. 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.

  14. Rotational Splitting of Pulsational Modes

    CERN Document Server

    Deupree, Robert

    2010-01-01

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

  15. ROTATIONAL SPLITTING OF PULSATION MODES

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2014-12-16

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

  17. 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

  18. 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; Claude Boccara, A.; 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.

  19. The lysosomal sialic acid transporter sialin is required for normal CNS myelination.

    Science.gov (United States)

    Prolo, Laura M; Vogel, Hannes; Reimer, Richard J

    2009-12-01

    Salla disease and infantile sialic acid storage disease are autosomal recessive lysosomal storage disorders caused by mutations in the gene encoding sialin, a membrane protein that transports free sialic acid out of the lysosome after it is cleaved from sialoglycoconjugates undergoing degradation. Accumulation of sialic acid in lysosomes defines these disorders, and the clinical phenotype is characterized by neurodevelopmental defects, including severe CNS hypomyelination. In this study, we used a sialin-deficient mouse to address how loss of sialin leads to the defect in myelination. Behavioral analysis of the sialin(-/-) mouse demonstrates poor coordination, seizures, and premature death. Analysis by histology, electron microscopy, and Western blotting reveals a decrease in myelination of the CNS but normal neuronal cytoarchitecture and normal myelination of the PNS. To investigate potential mechanisms underlying CNS hypomyelination, we studied myelination and oligodendrocyte development in optic nerves. We found reduced numbers of myelinated axons in optic nerves from sialin(-/-) mice, but the myelin that was present appeared grossly normal. Migration and density of oligodendrocyte precursor cells were normal; however, a marked decrease in the number of postmitotic oligodendrocytes and an associated increase in the number of apoptotic cells during the later stages of myelinogenesis were observed. These findings suggest that a defect in maturation of cells in the oligodendrocyte lineage leads to increased apoptosis and underlies the myelination defect associated with sialin loss. PMID:20007460

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Shu Yang

    2011-05-01

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

  2. 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

  3. Transport of the major myelin proteolipid protein is directed by VAMP3 and VAMP7.

    Science.gov (United States)

    Feldmann, Anke; Amphornrat, Jesa; Schönherr, Madeleine; Winterstein, Christine; Möbius, Wiebke; Ruhwedel, Torben; Danglot, Lydia; Nave, Klaus-Armin; Galli, Thierry; Bruns, Dieter; Trotter, Jacqueline; Krämer-Albers, Eva-Maria

    2011-04-13

    CNS myelination by oligodendrocytes requires directed transport of myelin membrane components and a timely and spatially controlled membrane expansion. In this study, we show the functional involvement of the R-soluble N-ethylmaleimide-sensitive factor attachment protein receptor (R-SNARE) proteins VAMP3/cellubrevin and VAMP7/TI-VAMP in myelin membrane trafficking. VAMP3 and VAMP7 colocalize with the major myelin proteolipid protein (PLP) in recycling endosomes and late endosomes/lysosomes, respectively. Interference with VAMP3 or VAMP7 function using small interfering RNA-mediated silencing and exogenous expression of dominant-negative proteins diminished transport of PLP to the oligodendroglial cell surface. In addition, the association of PLP with myelin-like membranes produced by oligodendrocytes cocultured with cortical neurons was reduced. We furthermore identified Syntaxin-4 and Syntaxin-3 as prime acceptor Q-SNAREs of VAMP3 and VAMP7, respectively. Analysis of VAMP3-deficient mice revealed no myelination defects. Interestingly, AP-3?-deficient mocha mice, which suffer from impaired secretion of lysosome-related organelles and missorting of VAMP7, exhibit a mild dysmyelination characterized by reduced levels of select myelin proteins, including PLP. We conclude that PLP reaches the cell surface via at least two trafficking pathways with distinct regulations: (1) VAMP3 mediates fusion of recycling endosome-derived vesicles with the oligodendroglial plasma membrane in the course of the secretory pathway; (2) VAMP7 controls exocytosis of PLP from late endosomal/lysosomal organelles as part of a transcytosis pathway. Our in vivo data suggest that exocytosis of lysosome-related organelles controlled by VAMP7 contributes to myelin biogenesis by delivering cargo to the myelin membrane. PMID:21490207

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

    Directory of Open Access Journals (Sweden)

    Martin Roland

    2011-09-01

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

  5. Interactions of Sox10 and Egr2 in Myelin Gene Regulation

    OpenAIRE

    Jones, Erin A.; Jang, Sung-wook; Mager, Gennifer M.; Chang, Li-wei; Srinivasan, Rajini; Gokey, Nolan G.; Ward, Rebecca M.; Nagarajan, Rakesh; Svaren, John

    2007-01-01

    Myelination in the PNS is accompanied by a large induction of the Myelin Protein Zero (Mpz) gene to produce the most abundant component in peripheral myelin. Analyses of knockout mice have shown that the EGR2/Krox20 and SOX10 transcription factors are required for Mpz expression. Our recent work has shown that the dominant EGR2 mutations associated with human peripheral neuropathies cause disruption of EGR2/SOX10 synergy at specific sites, including a conserved enhancer element in the first i...

  6. 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...

  7. 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

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

    OpenAIRE

    Dante Mantini; Nicole Wenderoth

    2014-01-01

    Despite recent advancements in MR imaging, non-invasive mapping of myelin in the brain still remains an open issue. Here we attempted to provide a potential solution. Specifically, we developed a processing workflow based on T1-w and T2-w MR data to generate an optimized myelin enhanced contrast image. The workflow allows whole brain mapping using the T1-w/T2-w technique, which was originally introduced as a non-invasive method for assessing cortical myelin content. The hallmark of our approa...

  9. Study of the expression of myelin proteolipid protein (lipophilin) using a cloned complementary DNA.

    OpenAIRE

    Naismith, A. L.; Hoffman-chudzik, E.; Tsui, L. C.; Riordan, J. R.

    1985-01-01

    We have prepared a ?gt10 cDNA library with the mRNA isolated from fetal calf brains which were actively myelinating. Using two oligonucleotides made according to the known amino acid sequence of myelin proteolipid protein (PLP or lipophilin), we have isolated several cDNA clones for this major intrinsic membrane protein of myelin. One of these clones, designated as pLP1, is found to contain 444 bp of coding sequence for the C-terminal half of PLP and 486 bp of 3? untranslated sequence. Usi...

  10. Myelin proteolipid protein (PLP and DM-20) transcripts are deleted in jimpy mutant mice.

    OpenAIRE

    Morello, D.; Dautigny, A.; Pham-dinh, D.; Jolle?s, P.

    1986-01-01

    The myelin-associated proteolipid protein, PLP, is one of the two major components of the central nervous system (CNS) myelin. We analyze, by using a rat PLP cDNA and S1 nuclease protection experiments, the PLP transcripts in the mouse brain and show that the PLP gene encodes two different but related mRNA transcripts, the PLP and the DM-20 transcripts. On the other hand, we demonstrate that in the jimpy mutant, which is characterized by an abnormal CNS myelination, both these transcripts are...

  11. Effects of osmolality on PLP-null myelin structure: Implications re axon damage

    OpenAIRE

    Rosenbluth, Jack; Schiff, Rolf; Lam, Pokman

    2008-01-01

    In order to test the adhesiveness of PLP-null compact myelin lamellae we soaked aldehyde-fixed CNS specimens from PLP-null and control mice overnight in distilled water, in Ringer’s solution or in Ringer’s solution with added 1M sucrose. Subsequent examination of the tissue by EM showed that both PLP-null and control white matter soaked in Ringer remained largely compact. After the distilled water soak, control myelin was virtually unchanged, but PLP-null myelin showed some decompaction, ...

  12. Divalent cations induce a compaction of intrinsically disordered myelin basic protein.

    Science.gov (United States)

    Baran, Christian; Smith, Graham S T; Bamm, Vladimir V; Harauz, George; Lee, Jeremy S

    2010-01-01

    Central nervous system myelin is a dynamic entity arising from membrane processes extended from oligodendrocytes, which form a tightly-wrapped multilamellar structure around neurons. In mature myelin, the predominant splice isoform of classic MBP is 18.5kDa. In solution, MBP is an extended, intrinsically disordered protein with a large effective protein surface for myriad interactions, and possesses transient and/or induced ordered secondary structure elements for molecular association or recognition. Here, we show by nanopore analysis that the divalent cations copper and zinc induce a compaction of the extended protein in vitro, suggestive of a tertiary conformation that may reflect its arrangement in myelin. PMID:19903451

  13. Geometrical splitting in Monte Carlo

    International Nuclear Information System (INIS)

    A statistical model is presented by which a direct statistical approach yielded an analytic expression for the second moment, the variance ratio, and the benefit function in a model of an n surface-splitting Monte Carlo game. In addition to the insight into the dependence of the second moment on the splitting parameters the main importance of the expressions developed lies in their potential to become a basis for in-code optimization of splitting through a general algorithm. Refs

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

    Science.gov (United States)

    Laulumaa, Saara; Kursula, Petri; Natali, Francesca

    2015-01-01

    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.

  15. 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.

  16. Ethanol down regulates the expression of myelin proteolipid protein in the rat hippocampus

    OpenAIRE

    Lee, Dong Hoon; Jeong, Jin Young; Kim, Yoon Sook; Kim, Joon Soo; Cho, Yong Woon; Roh, Gu Seob; Kim, Hyun Joon; Kang, Sang Soo; Cho, Gyeong Jae; Choi, Wan Sung

    2010-01-01

    It is well known that chronic ethanol treatment affects the synthesis of RNA and protein in the brain and the maintenance and function of nervous system. The changes in myelination-related genes are most prominent in human alcoholics. Previously, our cDNA microarray study showed altered Proteolipid protein (PLP), a major protein of central myelin. The present study aimed to gain more understanding of the expression of PLP after chronic ethanol treatment. Male Sprague-Dawley rats were daily tr...

  17. Microfluidic compartmentalized co-culture platform for CNS axon myelination research

    OpenAIRE

    Park, Jaewon; Koito, Hisami; Li, Jianrong; Han, Arum

    2009-01-01

    This paper presents a circular microfluidic compartmentalized co-culture platform that can be used for central nervous system (CNS) axon myelination research. The microfluidic platform is composed of a soma compartment and an axon/glia compartment connected through arrays of axon-guiding microchannels. Myelin-producing glia, oligodendrocytes (OLs), placed in the axon/glia compartment, interact with only axons but not with neuronal somata confined to the soma compartment, reminiscent to in viv...

  18. The NURD chromatin remodeling complex is required for peripheral nerve myelination

    OpenAIRE

    Hung, Holly; Kohnken, Rebecca; Svaren, John

    2012-01-01

    Several key transcription factors and coregulators important to peripheral nerve myelination have been identified, but the contributions of specific chromatin remodeling complexes to peripheral nerve myelination have not been analyzed. Chromodomain helicase DNA-binding protein 4 (Chd4) is the core catalytic subunit of the Nucleosome Remodeling and Deacetylase (NuRD) chromatin remodeling complex. Previous studies have shown Chd4 interacts with Nab (NGFI-A/Egr-binding) corepressors, which are r...

  19. Inhibition of Myelin Membrane Sheath Formation by Oligodendrocyte-derived Exosome-like Vesicles*

    OpenAIRE

    Bakhti, Mostafa; Winter, Christine; Simons, Mikael

    2010-01-01

    Myelin formation is a multistep process that is controlled by a number of different extracellular factors. During the development of the central nervous system (CNS), oligodendrocyte progenitor cells differentiate into mature oligodendrocytes that start to enwrap axons with myelin membrane sheaths after receiving the appropriate signal(s) from the axon or its microenvironment. The signals required to initiate this process are unknown. Here, we show that oligodendrocytes secrete small membrane...

  20. Differential aggregation of the Trembler and Trembler J mutants of peripheral myelin protein 22

    OpenAIRE

    Tobler, Andreas R.; Liu, Ning; Mueller, Lukas; Shooter, Eric M.

    2001-01-01

    Mutations in the gene encoding the peripheral myelin protein 22 (PMP22), a tetraspan protein in compact peripheral myelin, are one of the causes of inherited demyelinating peripheral neuropathy. Most PMP22 mutations alter the trafficking of the PMP22 protein in Schwann cells, and this different trafficking has been proposed as the underlying mechanism of the disease. To explore this problem further, we compared the aggregation of wild-type Pmp22 with those of the t...

  1. Thermally induced photon splitting

    CERN Document Server

    Elmfors, P; Elmfors, Per; Skagerstam, Bo-Sture

    1998-01-01

    We calculate thermal corrections to the non-linear QED effective action for low-energy photon interactions in a background electromagnetic field. The high-temperature expansion shows that at $T \\gg m$ the vacuum contribution is exactly cancelled to all orders in the external field except for a non-trivial two-point function contribution. The high-temperature expansion derived reveals a remarkable cancellation of infrared sensitive contributions. As a result photon-splitting in the presence of a magnetic field is suppressed in the presence of an electron-positron QED-plasma at very high temperatures. In a cold and dense plasma a similar suppression takes place. At the same time Compton scattering dominates for weak fields and the suppression is rarely important in physical situations.

  2. Positronium Hyperfine Splitting

    CERN Document Server

    Miyazaki, Akira

    2010-01-01

    Positronium is an ideal system for the research of QED in the bound state. The hyperfine splitting of positronium (Ps-HFS: about 203 GHz) is a good tool to test QED and also sensitive to new physics beyond the Standard Model. Previous experimental results show 3.9\\,$\\sigma$ (15 ppm) discrepancy from the QED $\\mathrm{O}\\left(\\alpha ^3 \\ln{1/\\alpha}\\right)$ prediction. We point out probable common systematic errors in all previous experiments. I measure the Ps-HFS in two different ways. (1) A prototype run without RF system is described first. (2) I explain a new direct Ps-HFS measurement without static magnetic field. The present status of the optimization studies and current design of the experiment are described. We are now taking data of a test experiment for the observation of the direct transition.

  3. Fuel pin bundle splitting

    International Nuclear Information System (INIS)

    The patent describes the splitting of a bundle of nuclear fuel pins into smaller bundles, during the dismantling of a fuel element, in preparation for the reprocessing of the spent fuel. The size of the small bundles are such that they are suitable for cropping in an easily maintainable shearing machine. The cropping of fuel pins into short sections exposes the irradiated fuel to be reprocessed. The invention involves feeding a number of blades into the exposed end of a fuel pin bundle. The bundle is forced out of the containing sheath by a ram, and the fuel pins are forced to pass either side of theblades, there by the bundle is sorted into a number of smaller bundles. (U.K.)

  4. Erythropoietin treatment alleviates ultrastructural myelin changes induced by murine cerebral malaria

    DEFF Research Database (Denmark)

    Hempel, Casper; Hyttel, Poul

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Andreana Benitez

    2014-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2014-01-01

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

  8. Phylogeny of proteolipid proteins: divergence, constraints, and the evolution of novel functions in myelination and neuroprotection.

    Science.gov (United States)

    Möbius, Wiebke; Patzig, Julia; Nave, Klaus-Armin; Werner, Hauke B

    2008-05-01

    The protein composition of myelin in the central nervous system (CNS) has changed at the evolutionary transition from fish to tetrapods, when a lipid-associated transmembrane-tetraspan (proteolipid protein, PLP) replaced an adhesion protein of the immunoglobulin superfamily (P0) as the most abundant constituent. Here, we review major steps of proteolipid evolution. Three paralog proteolipids (PLP/DM20/DMalpha, M6B/DMgamma and the neuronal glycoprotein M6A/DMbeta) exist in vertebrates from cartilaginous fish to mammals, and one (M6/CG7540) can be traced in invertebrate bilaterians including the planktonic copepod Calanus finmarchicus that possess a functional myelin equivalent. In fish, DMalpha and DMgamma are coexpressed in oligodendrocytes but are not major myelin components. PLP emerged at the root of tetrapods by the acquisition of an enlarged cytoplasmic loop in the evolutionary older DMalpha/DM20. Transgenic experiments in mice suggest that this loop enhances the incorporation of PLP into myelin. The evolutionary recruitment of PLP as the major myelin protein provided oligodendrocytes with the competence to support long-term axonal integrity. We suggest that the molecular shift from P0 to PLP also correlates with the concentration of adhesive forces at the radial component, and that the new balance between membrane adhesion and dynamics was favorable for CNS myelination. PMID:19497142

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

    Science.gov (United States)

    Vela, J M; González, B; Castellano, B

    1998-03-01

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

  10. 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.

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

    Science.gov (United States)

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

    2014-06-01

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

  12. 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

  13. A New Flux Splitting Scheme

    Science.gov (United States)

    Liou, Meng-Sing; Steffen, Christopher J.

    1993-07-01

    A new flux splitting scheme is proposed. The scheme is remarkably simple and yet its accuracy rivals, and in some cases surpasses, that of Roe's solver in the Euler and Navier-Stokes solutions carried out in this study, The scheme is robust and converges as fast as the Roe splitting. We propose an appropriately defined cell-face advection Mach number using values from the two straddling cells via associated characteristic speeds. This interface Mach number is then used to determine the upwind extrapolation for the convective quantities. Accordingly, the name of the scheme is coined as the advection upstream splitting method (AUSM). We also introduce a new pressure splitting which is shown to behave successfully, yielding much smoother results than other existing pressure splittings. Of particular interest is the supersonic blunt body problem in which the Roe scheme gives anomalous solutions. The AUSM produces correct solutions without difficulty for a wide range of flow conditions as well as grids.

  14. Requirement of cAMP Signaling for Schwann Cell Differentiation Restricts the Onset of Myelination

    Science.gov (United States)

    Bacallao, Ketty; Monje, Paula V.

    2015-01-01

    Isolated Schwann cells (SCs) respond to cAMP elevation by adopting a differentiated post-mitotic state that exhibits high levels of Krox-20, a transcriptional enhancer of myelination, and mature SC markers such as the myelin lipid galactocerebroside (O1). To address how cAMP controls myelination, we performed a series of cell culture experiments which compared the differentiating responses of isolated and axon-related SCs to cAMP analogs and ascorbate, a known inducer of axon ensheathment, basal lamina formation and myelination. In axon-related SCs, cAMP induced the expression of Krox-20 and O1 without a concomitant increase in the expression of myelin basic protein (MBP) and without promoting axon ensheathment, collagen synthesis or basal lamina assembly. When cAMP was provided together with ascorbate, a dramatic enhancement of MBP expression occurred, indicating that cAMP primes SCs to form myelin only under conditions supportive of basal lamina formation. Experiments using a combination of cell permeable cAMP analogs and type-selective adenylyl cyclase (AC) agonists and antagonists revealed that selective transmembrane AC (tmAC) activation with forskolin was not sufficient for full SC differentiation and that the attainment of an O1 positive state also relied on the activity of the soluble AC (sAC), a bicarbonate sensor that is insensitive to forskolin and GPCR activation. Pharmacological and immunological evidence indicated that SCs expressed sAC and that sAC activity was required for morphological differentiation and the expression of myelin markers such as O1 and protein zero. To conclude, our data indicates that cAMP did not directly drive myelination but rather the transition into an O1 positive state, which is perhaps the most critical cAMP-dependent rate limiting step for the onset of myelination. The temporally restricted role of cAMP in inducing differentiation independently of basal lamina formation provides a clear example of the uncoupling of signals controlling differentiation and myelination in SCs. PMID:25705874

  15. Accumulation of diabetic rat peripheral nerve myelin by macrophages increases with the presence of advanced glycosylation endproducts

    OpenAIRE

    1984-01-01

    We have previously shown that increased nonenzymatic glycosylation occurs in peripheral nervous tissue of diabetic humans and animals, primarily on the PO-protein of peripheral nerve myelin. The pathophysiologic mechanism by which this biochemical alteration leads to myelin breakdown and removal is not as yet understood. In the present study we show that advanced glycosylation end-product (AGE) adducts that form during long-term exposure of peripheral nerve myelin proteins to glucose in vitro...

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

    OpenAIRE

    Pham-dinh, D.; Popot, J. L.; Boespflug-tanguy, O.; Landrieu, P.; Deleuze, J. F.; Boue?, J.; Jolle?s, 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 ...

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

    OpenAIRE

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

    2010-01-01

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

  18. Anti-myelin-associated glycoprotein polyneuropathy coexistent with CREST syndrome.

    Science.gov (United States)

    Andreadou, E; Zouvelou, V; Karandreas, N; Kilidireas, C

    2012-01-01

    Clinical involvement of the peripheral nervous system in the calcinosis cutis, raynaud's phenomenon, esophageal dismotility, sclerodactyly and telangiectasia (CREST) variant of systemic sclerosis occurs infrequently and is characterized by axonal degeneration due to necrotizing vasculitis. We report a female patient with a known history of CREST syndrome, which developed a slowly progressive, distal symmetric demyelinating sensorimotor polyneuropathy (PN), with tremor and ataxia as prominent features, compatible with anti-myelin associated glycoprotein (MAG) PN. The diagnosis of PN was established by the presence of monoclonal immunoglobulin M anti-MAG antibodies (Thin-Layer Chromatography, Western Blot and enzyme-linked immunoabsorbent assay). Given the evidence that in CREST activation of T-helper cells is observed and that anti-MAG antibodies, despite the fact that they are T-cell-independent, may be influenced by an increase in T-helper function, the coexistence of these two rare autoimmune disorders in the same patient may not be incidental but related to the underlying immunological mechanisms involved. PMID:22387650

  19. 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.)

  20. Organotypic slice cultures to study oligodendrocyte dynamics and myelination.

    Science.gov (United States)

    Hill, Robert A; Medved, Jelena; Patel, Kiran D; Nishiyama, Akiko

    2014-01-01

    NG2 expressing cells (polydendrocytes, oligodendrocyte precursor cells) are the fourth major glial cell population in the central nervous system. During embryonic and postnatal development they actively proliferate and generate myelinating oligodendrocytes. These cells have commonly been studied in primary dissociated cultures, neuron cocultures, and in fixed tissue. Using newly available transgenic mouse lines slice culture systems can be used to investigate proliferation and differentiation of oligodendrocyte lineage cells in both gray and white matter regions of the forebrain and cerebellum. Slice cultures are prepared from early postnatal mice and are kept in culture for up to 1 month. These slices can be imaged multiple times over the culture period to investigate cellular behavior and interactions. This method allows visualization of NG2 cell division and the steps leading to oligodendrocyte differentiation while enabling detailed analysis of region-dependent NG2 cell and oligodendrocyte functional heterogeneity. This is a powerful technique that can be used to investigate the intrinsic and extrinsic signals influencing these cells over time in a cellular environment that closely resembles that found in vivo. PMID:25177825

  1. Strength-duration characteristics of myelinated and non-myelinated bulbospinal axons in the cat spinal cord.

    Science.gov (United States)

    West, D C; Wolstencroft, J H

    1983-04-01

    Strength-duration characteristics for the stimulation of 131 raphespinal and reticulospinal axons in the spinal cord were determined using two types of stimulating electrode. Conduction velocity of these fibres ranged from 0.86 to 63 m/s. With silver wire (250 micron diameter) stimulating electrodes, chronaxies were: 0.18 +/- 0.06 ms for axons conducting between 16 and 63 m/s, 0.4 +/- 0.22 ms for axons conducting between 5 and 15 m/s and 2.06 +/- 0.79 ms for those with conduction velocity less than 5 m/s. There was an inverse relationship between chronaxie and conduction velocity. Rheobase values ranged from 7.4 to 400 microA but were independent of conduction velocity. Chronaxies obtained with wire electrodes were compared with those from stimulation of the same fibre through saline-filled micropipettes (2-12 micron tip diameter). Rheobase values with the micropipettes ranged from 1.6 to 20 microA, indicating a close proximity of the pipette to the axon. For these axons, chronaxies from metal wire electrodes ranged from 0.12 to 2.4 ms and for micropipettes from 0.04 to 0.65 ms. In almost all cases, chronaxies for micropipette stimulation were lower than those for metal wire electrodes. Furthermore, with micropipettes chronaxies were independent of conduction velocity. The results are shown to be related to differences in time constant of the activated region of axon and charge requirements of threshold activation. The two stimulating conditions, i.e. micro-electrodes compared with wire electrodes, are analogous to the theoretical point stimulated cable and uniformly polarized membrane cases. The results are discussed in relation to the possibility of determination of fibre type from stimulation characteristics. A distinction between chronaxies of myelinated and non-myelinated fibres can be made using wire electrodes of 250 micron diameter, but not with micro-stimulation, as with micropipettes (2-12 micron diameter). PMID:6875936

  2. Crystal structure of the extracellular domain of human myelin protein zero

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-03-27

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

  3. miR-32 and its target SLC45A3 regulate the lipid metabolism of oligodendrocytes and myelin

    OpenAIRE

    Shin, Daesung; Howng, Shen Yi B.; Pta?c?ek, Louis J.; Fu, Ying-hui

    2012-01-01

    Oligodendrocytes generate large amounts of myelin by extension of their cell membranes. Though lipid is the major component of myelin, detailed lipid metabolism in the maintenance of myelin is not understood. We reported previously that miR-32 might be involved in myelin maintenance (Shin et al., 2009). Here we demonstrate a novel role for miR-32 in oligodendrocyte function and development through the regulation of SLC45A3 (solute carrier family 45, member 3) and other downstream targets such...

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

    Science.gov (United States)

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

    2015-01-01

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

  5. 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.

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

    DEFF Research Database (Denmark)

    Laursen, Lisbeth Schmidt; Chan, Colin W

    2011-01-01

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

  7. [Choledocholithiasis--therapeutic splitting].

    Science.gov (United States)

    Boeckl, O; Sungler, P; Heinerman, P M; Lexer, G

    1994-05-01

    Despite new developments like chemolitholysis and extracorporeal shock wave lithotripsy, conventional cholecystectomy was the "gold standard" in the treatment of gallstones. The range of indications and the operative strategy were well standardized, although the management of common bile duct stones in gallstone disease was still under debate. For high-risk and elder patients endoscopic retrograde cholangio-pancreatography (ERCP), papillotomy and stone extraction was established, in younger patients the best management was questionable. According to better and more accurate preoperative tests like ultrasound and the ample evidence of the function of the papilla after endoscopic papillotomy the trend seemed to be the preoperative endoscopic bile duct clearance in all patients, just when the "bushfire" of laparoscopic cholecystectomy arised and until then praised standards were thrown overboard because of technical difficulties. Routine intraoperative cholangiography (IOC) was replaced by indicated selective IOC due to the lack of talent of many surgeons. Only the therapeutic concept of the removal of the stone-bearing gallbladder survived all new concepts and the debate of whether to perform routine IOC and whether to clear the bile ducts--pre-, intra- or postoperatively or primarily or secondarily convert to open cholecystectomy and bile duct revision. In the eye of a new "gold standard" and according to the literature and our own results we should standardize our management especially in the era of laparoscopic cholecystectomy as "therapeutical splitting" with indicated and selective preoperative ERCP and bile duct clearance offers the best results and facilitates minimally invasive surgery. PMID:8050295

  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. Environmental tobacco smoke in the early postnatal period induces impairment in brain myelination.

    Science.gov (United States)

    Torres, Larissa H; Annoni, Raquel; Balestrin, Natalia T; Coleto, Priscila L; Duro, Stephanie O; Garcia, Raphael C T; Pacheco-Neto, Maurílio; Mauad, Thais; Camarini, Rosana; Britto, Luiz R G; Marcourakis, Tania

    2014-09-01

    Environmental tobacco smoke (ETS) is associated with high morbidity and mortality, mainly in children. However, few studies focus on the brain development effects of ETS exposure. Myelination mainly occurs in the early years of life in humans and the first three postnatal weeks in rodents and is sensitive to xenobiotics exposure. This study investigated the effects of early postnatal ETS exposure on myelination. BALB/c mice were exposed to ETS generated from 3R4F reference research cigarettes from the third to the fourteenth days of life. The myelination of nerve fibers in the optic nerve by morphometric analysis and the levels of Olig1 and myelin basic protein (MBP) were evaluated in the cerebellum, diencephalon, telencephalon, and brainstem in infancy, adolescence, and adulthood. Infant mice exposed to ETS showed a decrease in the percentage of myelinated fibers in the optic nerve, compared with controls. ETS induced a decrease in Olig1 protein levels in the cerebellum and brainstem and an increase in MBP levels in the cerebellum at infant. It was also found a decrease in MBP levels in the telencephalon and brainstem at adolescence and in the cerebellum and diencephalon at adulthood. The present study demonstrates that exposure to ETS, in a critical phase of development, affects the percentage of myelinated fibers and myelin-specific proteins in infant mice. Although we did not observe differences in the morphological analysis in adolescence and adulthood, there was a decrease in MBP levels in distinctive brain regions suggesting a delayed effect in adolescence and adulthood. PMID:25182420

  11. The T3-induced gene KLF9 regulates oligodendrocyte differentiation and myelin regeneration.

    Science.gov (United States)

    Dugas, Jason C; Ibrahim, Adiljan; Barres, Ben A

    2012-05-01

    Hypothyroidism is a well-described cause of hypomyelination. In addition, thyroid hormone (T3) has recently been shown to enhance remyelination in various animal models of CNS demyelination. What are the ways in which T3 promotes the development and regeneration of healthy myelin? To begin to understand the mechanisms by which T3 drives myelination, we have identified genes regulated specifically by T3 in purified oligodendrocyte precursor cells (OPCs). Among the genes identified by genomic expression analyses were four transcription factors, Kruppel-like factor 9 (KLF9), basic helix-loop-helix family member e22 (BHLHe22), Hairless (Hr), and Albumin D box-binding protein (DBP), all of which were induced in OPCs by both brief and long term exposure to T3. To begin to investigate the role of these genes in myelination, we focused on the most rapidly and robustly induced of these, KLF9, and found it is both necessary and sufficient to promote oligodendrocyte differentiation in vitro. Surprisingly, we found that loss of KLF9 in vivo negligibly affects the formation of CNS myelin during development, but does significantly delay remyelination in cuprizone-induced demyelinated lesions. These experiments indicate that KLF9 is likely a novel integral component of the T3-driven signaling cascade that promotes the regeneration of lost myelin. Future analyses of the roles of KLF9 and other identified T3-induced genes in myelination may lead to novel insights into how to enhance the regeneration of myelin in demyelinating diseases such as multiple sclerosis. PMID:22472204

  12. Abnormal morphology of myelin and axon pathology in murine models of multiple sclerosis.

    Science.gov (United States)

    Bando, Yoshio; Nomura, Taichi; Bochimoto, Hiroki; Murakami, Koichi; Tanaka, Tatsuhide; Watanabe, Tsuyoshi; Yoshida, Shigetaka

    2015-02-01

    Demyelination and axonal damage are responsible for neurological deficits in multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system. However, the pathology of axonal damage in MS is not fully understood. In this study, histological analysis of morphological changes of axonal organelles during demyelination in murine models was investigated by scanning electron microscopy (SEM) using an osmium-maceration method. In cuprizone-induced demyelination, SEM showed typical morphology of demyelination in the corpus callosum of mouse brain. In contrast, SEM displayed variations in ultrastructural abnormalities of myelin structures and axonal organelles in spinal cord white matter of experimental autoimmune encephalomyelitis (EAE) mice, an animal model of MS. Myelin detachment and excessive myelin formation were observed as typical morphological myelin abnormalities in EAE. In addition, well-developed axoplasmic reticulum-like structures and accumulated mitochondria were observed in tortuous degenerating/degenerated axons and the length of mitochondria in axons of EAE spinal cord was shorter compared with naïve spinal cord. Immunohistochemistry also revealed dysfunction of mitochondrial fusion/fission machinery in EAE spinal cord axons. Moreover, the number of Y-shaped mitochondria was significantly increased in axons of the EAE spinal cord. Axonal morphologies in myelin basic protein-deficient shiverer mice were similar to those in EAE. However, shiverer mice had "tortuous" (S-curve shaped mitochondria) and larger mitochondria compared with wild-type and EAE mice. Lastly, analysis of human MS patient autopsied brains also demonstrated abnormal myelin structures in demyelinating lesions. These results indicate that morphological abnormalities of myelin and axonal organelles play important role on the pathogenesis of axonal injury in demyelinating diseases. PMID:25595039

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

    International Nuclear Information System (INIS)

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

  14. Kähler manifolds with split tangent bundle

    OpenAIRE

    Brunella, Marco; Pereira, Jorge Vitorio; Touzet, Fre?de?ric

    2006-01-01

    We study in this paper compact kaeler manifolds whose tangent bundle splits as a sum of subbundles. Under some suitable assumption, this infetitesimal splitting G is retated whith a splitting of the universal covering .

  15. Split-illumination electron holography

    International Nuclear Information System (INIS)

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

  16. Generalized Split-Octonion Electrodynamics

    CERN Document Server

    Chanyal, B C; Negi, O P S

    2010-01-01

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

  17. Apparatus Splits Glass Tubes Longitudinally

    Science.gov (United States)

    Shaw, Ernest; Manahan, Robert O'neil

    1993-01-01

    Tubes split into half cylinders by hot-wire/thermal-shock method. Tube to be cut placed on notched jig in apparatus. Nichrome wire stretched between arms of pivoted carriage and oriented parallel to notch. Wire heated by electrical current while resting on tube. After heating for about 1 minute for each millimeter of thickness of glass, tube quenched in water and split by resulting thermal shock. Apparatus used to split tubes in sizes ranging from 3/8 in. in diameter by 1 in. long to 1 1/2 in. in diameter by 4 in. long.

  18. 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

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

    Directory of Open Access Journals (Sweden)

    Crutcher Keith A

    2001-05-01

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

  20. A dual tyrosine-leucine motif mediates myelin protein P0 targeting in MDCK cells.

    Science.gov (United States)

    Kidd, Grahame J; Yadav, Vijay K; Huang, Ping; Brand, Stacey L; Low, Seng Hui; Weimbs, Thomas; Trapp, Bruce D

    2006-08-01

    Differential targeting of myelin proteins to multiple, biochemically and functionally distinct Schwann cell plasma membrane domains is essential for myelin formation. In this study, we investigated whether the myelin protein P0 contains targeting signals using Madin-Darby canine kidney (MDCK) cells. By confocal microscopy, P0 was localized to MDCK cell basolateral membranes. C-terminal deletion resulted in apical accumulation, and stepwise deletions defined a 15-mer region that was required for basolateral targeting. Alanine substitutions within this region identified the YAML sequence as a functional tyrosine-based targeting signal, with the ML sequence serving as a secondary leucine-based signal. Replacement of the P0 ectodomain with green fluorescent protein altered the distribution of constructs lacking the YAML signal. Coexpression of the myelin-associated glycoprotein did not alter P0 distribution in MDCK cells. The results indicate that P0 contains a hierarchy of targeting signals, which may contribute to P0 localization in myelinating Schwann cells and the pathogenesis in human disease. PMID:16788992

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

    International Nuclear Information System (INIS)

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

  2. Prolonged Sox4 expression in oligodendrocytes interferes with normal myelination in the central nervous system.

    Science.gov (United States)

    Potzner, Michaela R; Griffel, Carola; Lütjen-Drecoll, Elke; Bösl, Michael R; Wegner, Michael; Sock, Elisabeth

    2007-08-01

    The highly related transcription factors Sox4 and Sox11 are both expressed in oligodendrocyte precursors. Yet whether they have a function in oligodendrocyte development is unknown. By overexpressing Sox4 under the control of 3.1 kb of 5' flanking sequences of the myelin basic protein gene in transgenic mice, we extended Sox4 expression in the oligodendrocyte lineage from oligodendrocyte precursors to cells undergoing terminal differentiation. As a consequence of transgene expression, mice develop the full spectrum of phenotypic traits associated with a severe hypomyelination during the first postnatal weeks. Myelin gene expression was severely reduced, and myelin dramatically thinned in several central nervous system (CNS) regions. Despite these disturbances in CNS myelination, the number of oligodendrocytic cells remained unaltered. Considering that apoptosis rates were normal and proliferation only slightly increased, oligodendrocytes likely persist in a premyelinating to early myelinating state. This shows that prolonged Sox4 expression in cells of the oligodendrocyte lineage is incompatible with the acquisition of a fully mature phenotype and argues that the presence of Sox4, and possibly Sox11, in oligodendrocyte precursors may normally prevent premature differentiation. PMID:17515609

  3. Hindshaker, a novel myelin mutant showing hypomyelination preferentially affecting the spinal cord.

    Science.gov (United States)

    King, H; McCulloch, M C; Barrie, J A; Kyriakides, E; Beechey, C V; Cattanach, B M; Griffiths, I R

    1997-08-01

    Animals with spontaneous mutations affecting myelin formation have provided useful information about the genetic and cellular mechanisms regulating normal and abnormal myelination. In this paper we describe a novel murine mutation termed hindshaker (hsh), which is inherited in an autosomal recessive manner. Affected mice are characterised by a variable tremor of the hind end which commences at about 2 weeks of age and largely disappears in animals older than 6 weeks. There is hypomyelination affecting predominantly the spinal cord, although the optic nerves and brain are involved to a much lesser degree. The defect of thinly myelinated and naked axons is maximal at 20 days of age and largely resolves with time so that in the adult most axons are myelinated. The myelin structure appears normal and immunostains for the major proteins. Although the distribution of oligodendrocytes in the spinal cord is similar to normal during the period of hypomyelination, there are fewer mature cells. The hsh mutation appears to delay the maturation of oligodendrocytes, particularly in the spinal cord. Additionally, there is a considerable variation in phenotypic expression and in penetrance when the mutation is expressed on different genetic backgrounds, suggesting the hsh locus is subject to the influence of modifying gene(s). Identification of the hsh gene should identify a factor important in the development of oligodendrocytes, particularly those in the spinal cord. PMID:9350807

  4. Structural features of the Nogo receptor signaling complexes at the neuron/myelin interface.

    Science.gov (United States)

    Saha, Nayanendu; Kolev, Momchil; Nikolov, Dimitar B

    2014-10-01

    Upon spinal cord injury, the central nervous system axons are unable to regenerate, partially due to the repulsive action of myelin inhibitors, such as the myelin-associated glycoprotein (MAG), Nogo-A and the oligodendrocyte myelin glycoprotein (OMgp). These inhibitors bind and signal through a single receptor/co-receptor complex that comprises of NgR1/LINGO-1 and either p75 or TROY, triggering intracellular downstream signaling that impedes the re-growth of axons. Structure-function analysis of myelin inhibitors and their neuronal receptors, particularly the NgRs, have provided novel information regarding the molecular details of the inhibitor/receptor/co-receptor interactions. Structural and biochemical studies have revealed the architecture of many of these proteins and identified the molecular regions important for assembly of the inhibitory signaling complexes. It was also recently shown that gangliosides, such as GT1b, mediate receptor/co-receptor binding. In this review, we highlight these studies and summarize our current understanding of the multi-protein cell-surface complexes mediating inhibitory signaling events at the neuron/myelin interface. PMID:24956133

  5. Knockdown of Lingo1b protein promotes myelination and oligodendrocyte differentiation in zebrafish.

    Science.gov (United States)

    Yin, Wu; Hu, Bing

    2014-01-01

    Demyelinating diseases include multiple sclerosis, which is a neurodegenerative disease characterized by immune attacks on the central nervous system (CNS), resulting in myelin sheath damage and axonal loss. Leucine-rich repeat and immunoglobulin domain-containing neurite outgrowth inhibitory protein (Nogo) receptor-interacting protein-1 (LINGO-1) have been identified as a negative regulator of oligodendrocytes differentiation. Targeted LINGO-1 inhibition promotes neuron survival, axon regeneration, oligodendrocyte differentiation, and remyelination in diverse animal models. Although studies in rodent models have extended our understanding of LINGO-1, its roles in neural development and myelination in zebrafish (Danio rerio) are not yet clear. In this study, we cloned the zebrafish homolog of the human LINGO-1 and found that lingo1b regulated myelination and oligodendrocyte differentiation. The expression of lingo1b started 1 (mRNA) and 2 (protein) days post-fertilization (dpf) in the CNS. Morpholino oligonucleotide knockdown of lingo1b resulted in developmental abnormalities, including less dark pigment, small eyes, and a curly spinal cord. The lack of lingo1b enhanced myelination and oligodendrocyte differentiation during embryogenesis. Furthermore, immunohistochemistry and movement analysis showed that lingo1b was involved in the axon development of primary motor neurons. These results suggested that Lingo1b protein functions as a negative regulator of myelination and oligodendrocyte differentiation during zebrafish development. PMID:24262204

  6. 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.

  7. Maturation-dependent apoptotic cell death of oligodendrocytes in myelin-deficient rats.

    Science.gov (United States)

    Grinspan, J B; Coulalaglou, M; Beesley, J S; Carpio, D F; Scherer, S S

    1998-12-01

    Mutations in the proteolipid protein gene (PLP/plp), which encodes the major intrinsic membrane protein in central nervous system (CNS) myelin, cause inherited dysmyelination in mammals. One of these mutants, the myelin-deficient (md) rat, has severe dysmyelination that is associated with oligodendrocyte cell death. Using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling (TUNEL) assay, which labels apoptotic cells, we find that cell death is increased in multiple white matter tracts of md rats. The tracts that myelinate the earliest show the earliest increase in cell death, and cell death persists for at least 22 days, the lifespan of these mutant animals. In all tracts, and at all developmental ages examined, apoptotic cells expressed the markers of mature oligodendrocytes, such as myelin basic protein, myelin-associated glycoprotein, and the Rip antigen, but not chondroitin sulfate proteoglycan, a marker of oligodendrocyte precursors. Mature oligodendrocytes fail to accumulate in md brain because they die before they fully mature. PMID:9843153

  8. Ultrastructure of tubular myelin and lamellar bodies in fast-frozen adult rat lung.

    Science.gov (United States)

    Williams, M C

    1982-12-01

    In order to study the structure of membranes of tubular myelin and lamellar bodies (pulmonary surfactant), tissue from adult rat lung was prepared for freeze fracture by the rapid freezing method of Heuser et al. which requires no prior fixation or cryoprotection. Other tissues were freeze substituted and thin sectioned. A layer of tissue 50-100 mu thick was well preserved, but alveoli were partially collapsed. Freeze-fractured lamellar bodies were composed of tightly packed stacks of smooth lamellae about 100 A thick. Cross-fractures through tubular myelin exposed membranes organized into the square lattice described earlier. Fractures parallel to the longitudinal axis exposed particles arranged in rows which coincided with the corners. Membrane faces between the rows were smooth. These observations suggest (1) that in vivo the content of lamellar bodies is most likely arranged in layers, (2) that tubular myelin is present in tissues unexposed to fixatives or lipid solvents, (3) that smooth-surfaced lamellar body membranes become particulate when they form tubular myelin, and (4) that chemical fixation does not alter the general appearance of tubular myelin but it may affect lattice dimensions. PMID:6897776

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

    Directory of Open Access Journals (Sweden)

    Gieselmann Volkmar

    2011-03-01

    Full Text Available Abstract Background The sphingolipids galactosylceramide (GalCer and sulfatide are major myelin components and are thought to play important roles in myelin function. The importance of GalCer and sulfatide has been validated using UDP-galactose:ceramide galactosyltransferase-deficient (Cgt-/- mice, which are impaired in myelin maintenance. These mice, however, are still able to form compact myelin. Loss of GalCer and sulfatide in these mice is accompanied by up-regulation of 2-hydroxylated fatty acid containing (HFA-glucosylceramide in myelin. This was interpreted as a partial compensation of the loss of HFA-GalCer, which may prevent a more severe myelin phenotype. In order to test this hypothesis, we have generated Cgt-/- mice with an additional deletion of the fatty acid 2-hydroxylase (Fa2h gene. Results Fa2h-/-/Cgt-/- double-deficient mice lack sulfatide, GalCer, and in addition HFA-GlcCer and sphingomyelin. Interestingly, compared to Cgt-/- mice the amount of GlcCer in CNS myelin was strongly reduced in Fa2h-/-/Cgt-/- mice by more than 80%. This was accompanied by a significant increase in sphingomyelin, which was the predominant sphingolipid in Fa2h-/-/Cgt-/- mice. Despite these significant changes in myelin sphingolipids, compact myelin was formed in Fa2h-/-/Cgt-/- mice, and g-ratios of myelinated axons in the spinal cord of 4-week-old Fa2h-/-/Cgt-/- mice did not differ significantly from that of Cgt-/- mice, and there was no obvious phenotypic difference between Fa2h-/-/Cgt-/- and Cgt-/- mice Conclusions These data show that compact myelin can be formed with non-hydroxylated sphingomyelin as the predominant sphingolipid and suggest that the presence of HFA-GlcCer and HFA-sphingomyelin in Cgt-/- mice does not functionally compensate the loss of HFA-GalCer.

  10. Interplay between LXR and Wnt/?-catenin signaling in the negative regulation of peripheral myelin genes by oxysterols.

    Science.gov (United States)

    Makoukji, Joelle; Shackleford, Ghjuvan'Ghjacumu; Meffre, Delphine; Grenier, Julien; Liere, Philippe; Lobaccaro, Jean-Marc A; Schumacher, Michael; Massaad, Charbel

    2011-06-29

    Oxysterols are reactive molecules generated from the oxidation of cholesterol. Their implication in cholesterol homeostasis and in the progression of neurodegenerative disorders is well known, but few data are available for their functions in the peripheral nervous system. Our aim was to study the influence of oxysterols on myelin gene expression and myelin sheath formation in peripheral nerves. We show by gas chromatography/mass spectrometry that Schwann cells and sciatic nerves contain 24(S)-hydroxycholesterol, 25-hydroxycholesterol, and 27-hydroxycholesterol and that they express their biosynthetic enzymes and receptors (liver X receptors LXR? and LXR?). We demonstrate that oxysterols inhibit peripheral myelin gene expression [myelin protein zero (MPZ) and peripheral myelin protein-22 (PMP22)] in a Schwann cell line. This downregulation is mediated by either LXR? or LXR?, depending on the promoter context, as suggested by siRNA strategy and chromatin immunoprecipitation assays in Schwann cells and in the sciatic nerve of LXR knock-out mice. Importantly, the knock-out of LXR in mice results in thinner myelin sheaths surrounding the axons. Oxysterols repress myelin genes via two mechanisms: by binding of LXRs to myelin gene promoters and by inhibiting the Wnt/?-catenin pathway that is crucial for the expression of myelin genes. The Wnt signaling components (Disheveled, TCF/LEF, ?-catenin) are strongly repressed by oxysterols. Furthermore, the recruitment of ?-catenin at the levels of the MPZ and PMP22 promoters is decreased. Our data reveal new endogenous mechanisms for the negative regulation of myelin gene expression, highlight the importance of oxysterols and LXR in peripheral nerve myelination, and open new perspectives of treating demyelinating diseases with LXR agonists. PMID:21715627

  11. 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.

  12. Characterization of dodecylphosphocholine/myelin basic protein complexes

    International Nuclear Information System (INIS)

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

  13. Lattice splitting under intermittent flows

    OpenAIRE

    Schla?pfer, Markus; Trantopoulos, Konstantinos

    2010-01-01

    We study the splitting of regular square lattices subject to stochastic intermittent flows. Various flow patterns are produced by different groupings of the nodes, based on their random alternation between two possible states. The resulting flows on the lattices decrease with the number of groups according to a power law. By Monte Carlo simulations we reveal how the time span until the occurrence of a splitting depends on the flow patterns. Increasing the flow fluctuation fr...

  14. Autophagy promotes oligodendrocyte survival and function following dysmyelination in a long-lived myelin mutant.

    Science.gov (United States)

    Smith, Chelsey M; Mayer, Joshua A; Duncan, Ian D

    2013-05-01

    The Long-Evans shaker (les) rat has a mutation in myelin basic protein that results in severe CNS dysmyelination and subsequent demyelination during development. During this time, les oligodendrocytes accumulate cytoplasmic vesicles, including lysosomes and membrane-bound organelles. However, the mechanism and functional relevance behind these oligodendrocyte abnormalities in les have not been investigated. Using high-magnification electron microscopy, we identified the accumulations in les oligodendrocytes as early and late autophagosomes. Additionally, immunohistochemistry and Western blots showed an increase in autophagy markers in les. However, autophagy did not precede the death of les oligodendrocytes. Instead, upregulating autophagy promoted membrane extensions in les oligodendrocytes in vitro. Furthermore, upregulating autophagy in les rats via intermittent fasting increased the proportion of myelinated axons as well as myelin sheath thickness in les and control rats. Overall, this study provides insight into the abnormalities described in les as well as identifying a novel mechanism that promotes the survival and function of oligodendrocytes. PMID:23637198

  15. X-ray diffraction study of the kinetics of myelin lattice swelling. Effect of divalent cations.

    Science.gov (United States)

    Padrón, R; Mateu, L; Kirschner, D A

    1979-01-01

    The time-course of myelin lattice swelling and its reversal in dissected peripheral nerves was determined by small-angle x-ray diffraction using a position-sensitive proportional detector. The process of swelling can take place either in several hours or in less than 1 h depending on pretreatment of the nerves. The reversal of swelling was always completed within 1 h. The rapid structural transitions involved the disordering of membrane pairs as indicated by the transient appearance of a continuous intensity distribution similar to the membrane pair transform for myelin. The slow transitions involved the gradual replacement of the discrete reflections from the native structure by the reflections from the swollen lattice. Myelin membrane arrays reformed in normal Ringer's solution were much more stable to subsequent swelling than arrays reformed in Ca+2 and Mg+2-free Ringer's. These results suggest that these ions participate in stabilizing the interactions between the external surfaces of adjacent membrane pairs. PMID:122265

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

    International Nuclear Information System (INIS)

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

  17. Wnt/beta-catenin signaling is an essential and direct driver of myelin gene expression and myelinogenesis.

    Science.gov (United States)

    Tawk, Marcel; Makoukji, Joelle; Belle, Martin; Fonte, Cosima; Trousson, Amalia; Hawkins, Thomas; Li, Huiliang; Ghandour, Said; Schumacher, Michael; Massaad, Charbel

    2011-03-01

    Wnt/?-catenin signaling plays a major role in the development of the nervous system and contributes to neuronal plasticity. However, its role in myelination remains unclear. Here, we identify the Wnt/?-catenin pathway as an essential driver of myelin gene expression. The selective inhibition of Wnt components by small interfering RNA or dominant-negative forms blocks the expression of myelin protein zero (MPZ) and peripheral myelin protein 22 (PMP22) in mouse Schwann cells and proteolipid protein in mouse oligodendrocytes. Moreover, the activation of Wnt signaling by recombinant Wnt1 ligand increases by threefold the transcription of myelin genes and enhances the binding of ?-catenin to T-cell factor/lymphoid-enhancer factor transcription factors present in the vicinity of the MPZ and PMP22 promoters. Most important, loss-of-function analyses in zebrafish embryos show, in vivo, a key role for Wnt/?-catenin signaling in the expression of myelin genes and in myelin sheath compaction, both in the peripheral and central nervous systems. Inhibition of Wnt/?-catenin signaling resulted in hypomyelination, without affecting Schwann cell and oligodendrocyte generation or axonal integrity. The present findings attribute to Wnt/?-catenin pathway components an essential role in myelin gene expression and myelinogenesis. PMID:21389228

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2014-07-24

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

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

    Science.gov (United States)

    DeFelici, M.; Felici, R.; Ferrero, C.; Tartari, A.; Gambaccini, M.; Finet, S.

    2008-10-01

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

  1. Erythropoietin treatment alleviates ultrastructural myelin changes induced by murine cerebral malaria

    Directory of Open Access Journals (Sweden)

    Hempel Casper

    2012-06-01

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

  2. The antiaging protein Klotho enhances oligodendrocyte maturation and myelination of the CNS.

    Science.gov (United States)

    Chen, Ci-Di; Sloane, Jacob A; Li, Hu; Aytan, Nurgul; Giannaris, Eustathia L; Zeldich, Ella; Hinman, Jason D; Dedeoglu, Alpaslan; Rosene, Douglas L; Bansal, Rashmi; Luebke, Jennifer I; Kuro-o, Makoto; Abraham, Carmela R

    2013-01-30

    We have previously shown that myelin abnormalities characterize the normal aging process of the brain and that an age-associated reduction in Klotho is conserved across species. Predominantly generated in brain and kidney, Klotho overexpression extends life span, whereas loss of Klotho accelerates the development of aging-like phenotypes. Although the function of Klotho in brain is unknown, loss of Klotho expression leads to cognitive deficits. We found significant effects of Klotho on oligodendrocyte functions, including induced maturation of rat primary oligodendrocytic progenitor cells (OPCs) in vitro and myelination. Phosphoprotein analysis indicated that Klotho's downstream effects involve Akt and ERK signal pathways. Klotho increased OPC maturation, and inhibition of Akt or ERK function blocked this effect on OPCs. In vivo studies of Klotho knock-out mice and control littermates revealed that knock-out mice have a significant reduction in major myelin protein and gene expression. By immunohistochemistry, the number of total and mature oligodendrocytes was significantly lower in Klotho knock-out mice. Strikingly, at the ultrastructural level, Klotho knock-out mice exhibited significantly impaired myelination of the optic nerve and corpus callosum. These mice also displayed severe abnormalities at the nodes of Ranvier. To decipher the mechanisms by which Klotho affects oligodendrocytes, we used luciferase pathway reporters to identify the transcription factors involved. Together, these studies provide novel evidence for Klotho as a key player in myelin biology, which may thus be a useful therapeutic target in efforts to protect brain myelin against age-dependent changes and promote repair in multiple sclerosis. PMID:23365232

  3. Rectangle condition for irreducibility of Heegaard splittings

    CERN Document Server

    Lee, Jung Hoon

    2008-01-01

    Casson and Gordon gave the rectangle condition for strong irreducibility of Heegaard splittings [1]. We give a weak version of rectangle condition for irreducibility of Heegaard splittings. As an application, we give an example of an irreducible genus three Heegaard splitting of a 3-manifold which is not a minimal genus Heegaard splitting.

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2000-07-01

    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.)

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

    Science.gov (United States)

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

    2005-10-01

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

  7. Mammalian Target of Rapamycin Promotes Oligodendrocyte Differentiation, Initiation and Extent of CNS Myelination

    OpenAIRE

    Wahl, Stacey E.; Mclane, Lauren E.; Bercury, Kathryn K.; Macklin, Wendy B.; Wood, Teresa L.

    2014-01-01

    Prior studies support a role for mammalian target of rapamycin (mTOR) signaling in oligodendrocyte differentiation and myelination. Here we use Cre-recombinase driven by the CNP promoter to generate a mouse line with oligodendrocyte-specific knockdown of mTOR (mTOR cKO) in the CNS. We provide evidence that mTOR is necessary for proper oligodendrocyte differentiation and myelination in the spinal cord. Specifically, the number of mature oligodendrocytes was reduced, and the initiation and exte...

  8. 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 de...

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

    OpenAIRE

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

    2009-01-01

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

  10. 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.)

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

    OpenAIRE

    Palazuelos, Javier; Klingener, Michael; Aguirre, Adan

    2014-01-01

    Research on myelination has focused on identifying molecules capable of inducing oligodendrocyte (OL) differentiation in an effort to develop strategies that promote functional myelin regeneration in demyelinating disorders. Here, we show that transforming growth factor ? (TGF?) signaling is crucial for allowing oligodendrocyte progenitor (OP) cell cycle withdrawal, and therefore, for oligodendrogenesis and postnatal CNS myelination. Enhanced oligodendrogenesis and subcortical white matter ...

  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. 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.

  14. Cosmological limits on photon splitting

    International Nuclear Information System (INIS)

    General conservation laws and symmetries permit one photon to split into three all traveling in the original direction. But QED predicts that this process has vanishing probability. Observations of the 3-K microwave background and optical line spectra of quasars can be used to test this over cosmic length scales. We discuss photon splitting within the framework of a Lorentz-covariant, phenomenological theory. This theory predicts (a) spectral broadening, (b) frequency-dependent red-shift, and (c) multiple red-shifts for each source. Because these effects do not show up, we can set observational limits on the parameters that govern the splitting. In particular, the 3-K background implies that a photon of arbitrary wavelength lambda propagating in flat space (i.e., without cosmological reddening) must have a decay lifetime larger than (6 cm/lambda)t, where t is the present age of the universe

  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. Hyperfine splitting in lithiumlike bismuth

    International Nuclear Information System (INIS)

    Uncertainties involving the distribution of nuclear magnetism that affect the interpretation of ground-state hyperfine splitting (hfs) in hydrogenlike ions can be avoided by also measuring hyperfine splitting in lithiumlike ions. Because a recent experiment looking for hfs in lithiumlike bismuth at the predicted value of 0.7971(2) eV had negative results, we have repeated the calculation using a QED approach based on both screened potentials and the Coulomb potential. We find 0.79715(13) eV, in good agreement with the previous calculation

  17. 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.)

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

    Science.gov (United States)

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

    2014-09-12

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

  19. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-09-15

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

  1. Emerging functions of myelin-associated proteins during development, neuronal plasticity, and neurodegeneration.

    Science.gov (United States)

    Llorens, Franc; Gil, Vanessa; del Río, José Antonio

    2011-02-01

    Adult mammalian central nervous system (CNS) axons have a limited regrowth capacity following injury. Myelin-associated inhibitors (MAIs) limit axonal outgrowth, and their blockage improves the regeneration of damaged fiber tracts. Three of these proteins, Nogo-A, MAG, and OMgp, share two common neuronal receptors: NgR1, together with its coreceptors [p75(NTR), TROY, and Lingo-1]; and the recently described paired immunoglobulin-like receptor B (PirB). These proteins impair neuronal regeneration by limiting axonal sprouting. Some of the elements involved in the myelin inhibitory pathways may still be unknown, but the discovery that blocking both PirB and NgR1 activities leads to near-complete release from myelin inhibition, sheds light on one of the most competitive and intense fields of neuroregeneration study in recent decades. In parallel with the identification and characterization of the roles and functions of these inhibitory molecules in axonal regeneration, data gathered in the field strongly suggest that most of these proteins have roles other than axonal growth inhibition. The discovery of a new group of interacting partners for myelin-associated receptors and ligands, as well as functional studies within or outside the CNS environment, highlights the potential new physiological roles for these proteins in processes, such as development, neuronal homeostasis, plasticity, and neurodegeneration. PMID:21059749

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

    Energy Technology Data Exchange (ETDEWEB)

    Alberghina, M.; Viola, M.; Giuffrida, A.M.

    1982-02-01

    The contribution of the axonal transport to the biosynthesis of myelin phospholipids was investigated in the rabbit optic pathway. A double labeling technique was used. The same animals were injected with one isotope intravitreally and the other intraventricularly. This procedure allows double labeling of the optic nerves, optic tracts, lateral geniculate bodies (LGB), and superior colliculus (SC). The precursors simultaneously injected were: (1-/sup 14/C)palmitate (15 microCi intravitreally in both eyes or 50 microCi intraventricularly) and (2-/sup 3/H)glycerol (50 microCi intravitreally in both eyes of 100 microCi intraventricularly). Twenty four hours and 10 days after the injections, myelin was purified from pooled optic nerves and optic tracts as well as from pooled LGBs or SCs. The phospholipids were extracted and then separated by thin-layer chromatography; the specific radioactivity of the various classes of phospholipids was determined. Using both administration routes of C- or /sup 3/H-precursors, the distribution of label and specific radioactivity of myelin phospholipids in the retina and in all other optic structures were very similar. Phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine + phosphoinositol were preferentially labeled with both precursors. These results suggest that, in the rabbit optic pathway the phospholipids synthesized in the retinal ganglion cells and transported along the axons, could undergo transaxonal transfer into myelin.

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

    International Nuclear Information System (INIS)

    The contribution of the axonal transport to the biosynthesis of myelin phospholipids was investigated in the rabbit optic pathway. A double labeling technique was used. The same animals were injected with one isotope intravitreally and the other intraventricularly. This procedure allows double labeling of the optic nerves, optic tracts, lateral geniculate bodies (LGB), and superior colliculus (SC). The precursors simultaneously injected were: [1-14C]palmitate (15 microCi intravitreally in both eyes or 50 microCi intraventricularly) and [2-3H]glycerol (50 microCi intravitreally in both eyes of 100 microCi intraventricularly). Twenty four hours and 10 days after the injections, myelin was purified from pooled optic nerves and optic tracts as well as from pooled LGBs or SCs. The phospholipids were extracted and then separated by thin-layer chromatography; the specific radioactivity of the various classes of phospholipids was determined. Using both administration routes of C- or 3H-precursors, the distribution of label and specific radioactivity of myelin phospholipids in the retina and in all other optic structures were very similar. Phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine + phosphoinositol were preferentially labeled with both precursors. These results suggest that, in the rabbit optic pathway the phospholipids synthesized in the retinal ganglion cells and transported along the axons, could undergo transaxona along the axons, could undergo transaxonal transfer into myelin

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

    Directory of Open Access Journals (Sweden)

    M. Firouzi

    2003-07-01

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

  5. Myelin basic protein induces hexagonal phase formation in dispersions of diacylphosphatidic acid.

    Science.gov (United States)

    Smith, R; Cornell, B A

    1985-08-27

    31P nuclear magnetic resonance and low-angle X-ray diffraction measurements have shown that the basic protein of myelin caused diacylphosphatidic acid dispersions to change from a lamellar to a hexagonal lipid organisation. Several other basic proteins failed to effect a similar phase change, and had little influence on phospholipid headgroup structure and motion. PMID:2411291

  6. Comparison of myelination between large and small pig fetuses during late gestation

    Science.gov (United States)

    We compared myelination of the cerebellum, brain stem, and spinal cord in the largest and smallest pig fetuses within a litter during late gestation. Gilts were killed on days 92, 100, and 110 of gestation and these neural tissues were obtained from the largest and smallest fetuses in each litter. M...

  7. 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

  8. 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.

  9. 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.

  10. 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)

  11. Transcriptional expression of myelin basic protein in oligodendrocytes depends on functional syntaxin 4: a potential correlation with autocrine signaling.

    Science.gov (United States)

    Bijlard, Marjolein; Klunder, Bert; de Jonge, Jenny C; Nomden, Anita; Tyagi, Sanjay; de Vries, Hans; Hoekstra, Dick; Baron, Wia

    2015-02-01

    Myelination of axons by oligodendrocytes is essential for saltatory nerve conduction. To form myelin membranes, a coordinated synthesis and subsequent polarized transport of myelin components are necessary. Here, we show that as part of the mechanism to establish membrane polarity, oligodendrocytes exploit a polarized distribution of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) machinery components syntaxins 3 and 4, localizing to the cell body and the myelin membrane, respectively. Our data further reveal that the expression of myelin basic protein (MBP), a myelin-specific protein that is synthesized "on site" after transport of its mRNA, depends on the correct functioning of the SNARE machinery, which is not required for mRNA granule assembly and transport per se. Thus, downregulation and overexpression of syntaxin 4 but not syntaxin 3 in oligodendrocyte progenitor cells but not immature oligodendrocytes impeded MBP mRNA transcription, thereby preventing MBP protein synthesis. The expression and localization of another myelin-specific protein, proteolipid protein (PLP), was unaltered. Strikingly, conditioned medium obtained from developing oligodendrocytes was able to rescue the block of MBP mRNA transcription in syntaxin 4-downregulated cells. These findings indicate that the initiation of the biosynthesis of MBP mRNA relies on a syntaxin 4-dependent mechanism, which likely involves activation of an autocrine signaling pathway. PMID:25512606

  12. Acceleration of conduction velocity linked to clustering of nodal components precedes myelination.

    Science.gov (United States)

    Freeman, Sean A; Desmazières, Anne; Simonnet, Jean; Gatta, Marie; Pfeiffer, Friederike; Aigrot, Marie Stéphane; Rappeneau, Quentin; Guerreiro, Serge; Michel, Patrick Pierre; Yanagawa, Yuchio; Barbin, Gilles; Brophy, Peter J; Fricker, Desdemona; Lubetzki, Catherine; Sol-Foulon, Nathalie

    2015-01-20

    High-density accumulation of voltage-gated sodium (Nav) channels at nodes of Ranvier ensures rapid saltatory conduction along myelinated axons. To gain insight into mechanisms of node assembly in the CNS, we focused on early steps of nodal protein clustering. We show in hippocampal cultures that prenodes (i.e., clusters of Nav channels colocalizing with the scaffold protein ankyrinG and nodal cell adhesion molecules) are detected before myelin deposition along axons. These clusters can be induced on purified neurons by addition of oligodendroglial-secreted factor(s), whereas ankyrinG silencing prevents their formation. The Nav isoforms Nav1.1, Nav1.2, and Nav1.6 are detected at prenodes, with Nav1.6 progressively replacing Nav1.2 over time in hippocampal neurons cultured with oligodendrocytes and astrocytes. However, the oligodendrocyte-secreted factor(s) can induce the clustering of Nav1.1 and Nav1.2 but not of Nav1.6 on purified neurons. We observed that prenodes are restricted to GABAergic neurons, whereas clustering of nodal proteins only occurs concomitantly with myelin ensheathment on pyramidal neurons, implying separate mechanisms of assembly among different neuronal subpopulations. To address the functional significance of these early clusters, we used single-axon electrophysiological recordings in vitro and showed that prenode formation is sufficient to accelerate the speed of axonal conduction before myelination. Finally, we provide evidence that prenodal clusters are also detected in vivo before myelination, further strengthening their physiological relevance. PMID:25561543

  13. Myelin repair is accelerated by inactivating CXCR2 on nonhematopoietic cells.

    Science.gov (United States)

    Liu, LiPing; Darnall, Lindsey; Hu, Taofang; Choi, Karen; Lane, Thomas E; Ransohoff, Richard M

    2010-07-01

    Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS and remyelination in MS ultimately fails. Although strategies to promote myelin repair are eagerly sought, mechanisms underlying remyelination in vivo have been elusive. CXCR2 is expressed on neutrophils and oligodendrocyte lineage cells in the CNS. CXCR2-positive neutrophils facilitate inflammatory demyelination in demyelination models such as experimental autoimmune encephalomyelitis (EAE) and cuprizone intoxication. Systemic injection of a small molecule CXCR2 antagonist at the onset of EAE decreased demyelinated lesions. These results left the cellular target of the CXCR2 antagonist uncertain and did not clarify whether CXCR2 blockade prevented demyelination or promoted remyelination. Here, we show that the actions of CXCR2 on nonhematopoietic cells unexpectedly delay myelin repair. Bone marrow chimeric mice (Cxcr2(+/-)-->Cxcr2(-/-) and Cxcr2(+/-)-->Cxcr2(+/+)) were subjected to two distinct models of myelin injury. In all cases, myelin repair was more efficient in Cxcr2(+/-)-->Cxcr2(-/-) animals. Oligodendrocyte progenitor cells (OPCs) in demyelinated lesions of Cxcr2(+/-)-->Cxcr2(-/-) mice proliferated earlier and more vigorously than in tissues from Cxcr2(+/-)--> Cxcr2(+/+) animals. In vitro demyelinated CNS slice cultures also showed better myelin repair when CXCR2 was blocked with neutralizing antibodies or was genetically deleted. Our results suggest that CXCR2 inactivation permits optimal spatiotemporal positioning of OPCs in demyelinating lesions to receive local proliferative and differentiating signals. Given that CXCR2 exerts dual functions that promote demyelination and decrease remyelination by actions toward hematopoietic cells and nonhematopoietic cells, respectively, our findings identify CXCR2 as a promising drug target for clinical demyelinating disorders. PMID:20610741

  14. 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.

  15. LINGO-1, a transmembrane signaling protein, inhibits oligodendrocyte differentiation and myelination through intercellular self-interactions.

    Science.gov (United States)

    Jepson, Scott; Vought, Bryan; Gross, Christian H; Gan, Lu; Austen, Douglas; Frantz, J Daniel; Zwahlen, Jacque; Lowe, Derek; Markland, William; Krauss, Raul

    2012-06-22

    Overcoming remyelination failure is a major goal of new therapies for demyelinating diseases like multiple sclerosis. LINGO-1, a key negative regulator of myelination, is a transmembrane signaling protein expressed in both neurons and oligodendrocytes. In neurons, LINGO-1 is an integral component of the Nogo receptor complex, which inhibits axonal growth via RhoA. Because the only ligand-binding subunit of this complex, the Nogo receptor, is absent in oligodendrocytes, the extracellular signals that inhibit myelination through a LINGO-1-mediated mechanism are unknown. Here we show that LINGO-1 inhibits oligodendrocyte terminal differentiation through intercellular interactions and is capable of a self-association in trans. Consistent with previous reports, overexpression of full-length LINGO-1 inhibited differentiation of oligodendrocyte precursor cells (OPCs). Unexpectedly, treatment with a soluble recombinant LINGO-1 ectodomain also had an inhibitory effect on OPCs and decreased myelinated axonal segments in cocultures with neurons from dorsal root ganglia. We demonstrated LINGO-1-mediated inhibition of OPCs through intercellular signaling by using a surface-bound LINGO-1 construct expressed ectopically in astrocytes. Further investigation showed that the soluble LINGO-1 ectodomain can interact with itself in trans by binding to CHO cells expressing full-length LINGO-1. Finally, we observed that soluble LINGO-1 could activate RhoA in OPCs. We propose that LINGO-1 acts as both a ligand and a receptor and that the mechanism by which it negatively regulates OPC differentiation and myelination is mediated by a homophilic intercellular interaction. Disruption of this protein-protein interaction could lead to a decrease of LINGO-1 inhibition and an increase in myelination. PMID:22514275

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

    Science.gov (United States)

    Ganzetti, Marco; Wenderoth, Nicole; Mantini, Dante

    2014-01-01

    Despite recent advancements in MR imaging, non-invasive mapping of myelin in the brain still remains an open issue. Here we attempted to provide a potential solution. Specifically, we developed a processing workflow based on T1-w and T2-w MR data to generate an optimized myelin enhanced contrast image. The workflow allows whole brain mapping using the T1-w/T2-w technique, which was originally introduced as a non-invasive method for assessing cortical myelin content. The hallmark of our approach is a retrospective calibration algorithm, applied to bias-corrected T1-w and T2-w images, that relies on image intensities outside the brain. This permits standardizing the intensity histogram of the ratio image, thereby allowing for across-subject statistical analyses. Quantitative comparisons of image histograms within and across different datasets confirmed the effectiveness of our normalization procedure. Not only did the calibrated T1-w/T2-w images exhibit a comparable intensity range, but also the shape of the intensity histograms was largely corresponding. We also assessed the reliability and specificity of the ratio image compared to other MR-based techniques, such as magnetization transfer ratio (MTR), fractional anisotropy (FA), and fluid-attenuated inversion recovery (FLAIR). With respect to these other techniques, T1-w/T2-w had consistently high values, as well as low inter-subject variability, in brain structures where myelin is most abundant. Overall, our results suggested that the T1-w/T2-w technique may be a valid tool supporting the non-invasive mapping of myelin in the brain. Therefore, it might find important applications in the study of brain development, aging and disease. PMID:25228871

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

    Directory of Open Access Journals (Sweden)

    Dante Mantini

    2014-09-01

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

  18. 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.

  19. 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

  20. Solar p-mode frequency splittings

    International Nuclear Information System (INIS)

    I discuss here new measurements of solar p-mode frequency splitting, based on 100 days of solar Doppler observations from Big Bear Solar Observatory. Because of the long observing run, the splitting measurements have significantly smaller uncertainties than previously published values. In addition, splittings were determined accurately for individual mode multiplets for the first time, and show a dependence of splitting on radial order n as well as degree l

  1. 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...

  2. Relations between meson and baryon hyperfine splittings

    International Nuclear Information System (INIS)

    The recent treatment of hyperfine splittings in meson spectroscopy by Frank and O'Donnell is generalized and applied to baryons by the use of techniques developed for treating hyperfine interactions in atomic physics. Predictions of the N-?, ?*-? and ?*-? splittings using meson splittings as input are in good agreement with experiment, showing that the same constituent quark model describes both mesons and baryons. (orig.)

  3. Salt splitting using ceramic membranes

    International Nuclear Information System (INIS)

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

  4. Stability of split Stirling refrigerators

    Energy Technology Data Exchange (ETDEWEB)

    Waele, A T A M de; Liang, W [Department of Applied Physics, Eindhoven University of Technology, Eindhoven (Netherlands)

    2009-02-01

    In many thermal systems spontaneous mechanical oscillations are generated under the influence of large temperature gradients. Well-known examples are Taconis oscillations in liquid-helium cryostats and oscillations in thermoacoustic systems. In split Stirling refrigerators the compressor and the cold finger are connected by a flexible tube. The displacer in the cold head is suspended by a spring. Its motion is pneumatically driven by the pressure oscillations generated by the compressor. In this paper we give the basic dynamic equations of split Stirling refrigerators and investigate the possibility of spontaneous mechanical oscillations if a large temperature gradient develops in the cold finger, e.g. during or after cool down. These oscillations would be superimposed on the pressure oscillations of the compressor and could ruin the cooler performance.

  5. The Stationary Set Splitting Game

    OpenAIRE

    Larson, Paul; Shelah, Saharon

    2010-01-01

    The \\emph{stationary set splitting game} is a game of perfect information of length $\\omega_{1}$ between two players, \\unspls and \\spl, in which \\unspls chooses stationarily many countable ordinals and \\spls tries to continuously divide them into two stationary pieces. We show that it is possible in ZFC to force a winning strategy for either player, or for neither. This gives a new counterexample to $\\Sigma^{2}_{2}$ maximality with a predicate for the nonstationary ideal on ...

  6. Empirical Methods for Compound Splitting

    OpenAIRE

    Koehn, Philipp; Knight, Kevin

    2003-01-01

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

  7. Finite bias Cooper pair splitting

    OpenAIRE

    Hofstetter, L.; Csonka, S.; Baumgartner, A.; Fülöp; D Hollosy, S.; Nyga?rd, J.; Scho?nenberger, C.

    2011-01-01

    In a device with a superconductor coupled to two parallel quantum dots (QDs) the electrical tunability of the QD levels can be used to exploit non-classical current correlations due to the splitting of Cooper pairs. We experimentally investigate the effect of a finite potential difference across one quantum dot on the conductance through the other completely grounded QD in a Cooper pair splitter fabricated on an InAs nanowire. We demonstrate that the electrical transport thr...

  8. Optimal Transport with Proximal Splitting

    OpenAIRE

    Papadakis, Nicolas; Peyre?, Gabriel; Oudet, Edouard

    2013-01-01

    This article reviews the use of first order convex optimization schemes to solve the discretized dynamic optimal transport problem, initially proposed by Benamou and Brenier. We develop a staggered grid discretization that is well adapted to the computation of the $L^2$ optimal transport geodesic between distributions defined on a uniform spatial grid. We show how proximal splitting schemes can be used to solve the resulting large scale convex optimization problem. A specifi...

  9. 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...

  10. Phosphorylation of Highly Conserved Neurofilament Medium KSP Repeats Is Not Required for Myelin-Dependent Radial Axonal Growth

    OpenAIRE

    Garcia, Michael L.; Rao, Mala V.; Fujimoto, Jiro; Garcia, Virginia B.; Shah, Sameer B.; Crum, John; Gotow, Takahiro; Uchiyama, Yasuo; Ellisman, Mark; Calcutt, Nigel A.; Cleveland, Don W.

    2009-01-01

    Neurofilament medium (NF-M) is essential for the acquisition of normal axonal caliber in response to a myelin-dependent “outside-in” trigger for radial axonal growth. Removal of the tail domain and lysine-serine-proline (KSP) repeats of NF-M, but not neurofilament heavy, produced axons with impaired radial growth and reduced conduction velocities. These earlier findings supported myelin-dependent phosphorylation of NF-MKSP repeats as an essential component of axonal growth. As a direct te...

  11. 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...

  12. A Study of Molecular Mimicry and Immunological Cross-reactivity between Hepatitis B Surface Antigen and Myelin Mimics

    OpenAIRE

    Diego Vergani; Giorgina Mieli-Vergani; Harold Baum; Yun Ma; Heather Smith; Dimitrios-Petrou Bogdanos

    2005-01-01

    On the basis of the reported association between hepatitis B vaccination (HBvacc) and autoimmune demyelinating complications such as multiple sclerosis (MS), we have looked for aminoacid similarities between the small hepatitis B virus surface antigen (SHBsAg), and the MS-autoantigens myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) that could serve as targets of immunological cross-reactivity. Twenty-mer...

  13. Label-free in vivo imaging of myelinated axons in health and disease with spectral confocal reflectance microscopy

    OpenAIRE

    Schain, Aaron J.; Hill, Robert A.; Grutzendler, Jaime

    2014-01-01

    We report a new technique for high-resolution in vivo imaging of myelinated axons in the brain, spinal cord and peripheral nerve that requires no fluorescent labeling. This method, based on spectral confocal reflectance microscopy (SCoRe), uses a conventional laser scanning confocal system to generate images by merging the simultaneously reflected signals from multiple lasers of different wavelengths. Striking color patterns unique to individual myelinated fibers are generat...

  14. Structured Functional Domains of Myelin Basic Protein: Cross Talk between Actin Polymerization and Ca2+-Dependent Calmodulin Interaction

    OpenAIRE

    Bamm, Vladimir v; De avila, Miguel; Smith, Graham s T.; Ahmed, Mumdooh a M.; Harauz, George

    2011-01-01

    The 18.5-kDa myelin basic protein (MBP), the most abundant isoform in human adult myelin, is a multifunctional, intrinsically disordered protein that maintains compact assembly of the sheath. Solution NMR spectroscopy and a hydrophobic moment analysis of MBP's amino-acid sequence have previously revealed three regions with high propensity to form strongly amphipathic ?-helices. These regions, located in the central, N- and C-terminal parts of the protein, have been shown to play a role in ...

  15. Fuzzy complexes of myelin basic protein: NMR spectroscopic investigations of a polymorphic organizational linker of the central nervous system1

    OpenAIRE

    Libich, David S.; Ahmed, Mumdooh A. M.; Zhong, Ligang; Bamm, Vladimir V.; Ladizhansky, Vladimir; Harauz, George

    2010-01-01

    The classic 18.5 kDa isoform of myelin basic protein (MBP) is central to maintaining the structural homeostasis of the myelin sheath of the central nervous system. It is an intrinsically disordered, promiscuous, multifunctional, peripheral membrane protein, whose conformation adapts to its particular environment. Its study requires the selective and complementary application of diverse approaches, of which solution and solid-state NMR spectroscopy are the most powerful to elucidate site-speci...

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

    OpenAIRE

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

    2014-01-01

    Neurons in the CNS do not regenerate following injury; regeneration is blocked by inhibitory proteins in myelin, such as myelin-associated glycoprotein (MAG). Elevating neuronal levels of the second messenger cAMP overcomes this blocked axonal outgrowth. One way to elevate cAMP is pretreating neurons with neurotrophins, such as brain-derived neurotrophic factor (BDNF). However, pleiotropic effects and poor bioavailability make exogenous administration of neurotrophins in vivo problematic; the...

  17. Components of Myelin Damage and Repair in the Progression of White Matter Pathology After Mild Traumatic Brain Injury

    Science.gov (United States)

    Mierzwa, Amanda J.; Marion, Christina M.; Sullivan, Genevieve M.; McDaniel, Dennis P.; Armstrong, Regina C.

    2015-01-01

    Abstract White matter tracts are highly vulnerable to damage from impact-acceleration forces of traumatic brain injury (TBI). Mild TBI is characterized by a low density of traumatic axonal injury, whereas associated myelin pathology is relatively unexplored. We examined the progression of white matter pathology in mice after mild TBI with traumatic axonal injury localized in the corpus callosum. Adult mice received a closed-skull impact and were analyzed from 3 days to 6 weeks post-TBI/sham surgery. At all times post-TBI, electron microscopy revealed degenerating axons distributed among intact fibers in the corpus callosum. Intact axons exhibited significant demyelination at 3 days followed by evidence of remyelination at 1 week. Accordingly, bromodeoxyuridine pulse-chase labeling demonstrated the generation of new oligodendrocytes, identified by myelin proteolipid protein messenger RNA expression, at 3 days post-TBI. Overall oligodendrocyte populations, identified by immunohistochemical staining for CC1 and/or glutathione S-transferase pi, were similar between TBI and sham mice by 2 weeks. Excessively long myelin figures, similar to redundant myelin sheaths, were a significant feature at all post-TBI time points. At 6 weeks post-TBI, microglial activation and astrogliosis were localized to areas of axon and myelin pathology. These studies show that demyelination, remyelination, and excessive myelin are components of white matter degeneration and recovery in mild TBI with traumatic axonal injury. PMID:25668562

  18. Distribution of monocarboxylate transporters in the peripheral nervous system suggests putative roles in lactate shuttling and myelination.

    Science.gov (United States)

    Domènech-Estévez, Enric; Baloui, Hasna; Repond, Cendrine; Rosafio, Katia; Médard, Jean-Jacques; Tricaud, Nicolas; Pellerin, Luc; Chrast, Roman

    2015-03-11

    Lactate, a product of glycolysis, has been shown to play a key role in the metabolic support of neurons/axons in the CNS by both astrocytes and oligodendrocytes through monocarboxylate transporters (MCTs). Despite such importance in the CNS, little is known about MCT expression and lactate function in the PNS. Here we show that mouse MCT1, MCT2, and MCT4 are expressed in the PNS. While DRG neurons express MCT1, myelinating Schwann cells (SCs) coexpress MCT1 and MCT4 in a domain-specific fashion, mainly in regions of noncompact myelin. Interestingly, SC-specific downregulation of MCT1 expression in rat neuron/SC cocultures led to increased myelination, while its downregulation in neurons resulted in a decreased amount of neurofilament. Finally, pure rat SCs grown in the presence of lactate exhibited an increase in the level of expression of the main myelin regulator gene Krox20/Egr2 and the myelin gene P0. These data indicate that lactate homeostasis participates in the regulation of the SC myelination program and reveal that similar to CNS, PNS axon-glial metabolic interactions are most likely mediated by MCTs. PMID:25762662

  19. Isoelectric focusing of membrane proteins: high resolution separation of myelin proteins.

    Science.gov (United States)

    Persson, H; Corneliuson, O

    1989-11-01

    A mixture of the nonionic detergent Triton X-100, the zwitterionic detergent 3-[(cholamidopropyl)dimethylammonio]-1-propanesulphonate (CHAPS), 9M urea and carrier ampholytes was found comparable to media containing sodium dodecyl sulfate in the capacity for solubilization of myelin proteins, including the highly hydrophobic proteolipid protein. The solubilized sample was incorporated into the polymerization mixture before moulding an ultrathin gel, with heat convection characteristics allowing a high wattage to be applied, thus allowing fast separation with high resolving power. Since the most basic protein in myelin focuses at a pH greater than 10, fast separation is essential in order to minimize decay of the cathodic end of the pH gradient. PMID:2515057

  20. 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.

  1. Voltage-gated Ca(++) entry promotes oligodendrocyte progenitor cell maturation and myelination in vitro.

    Science.gov (United States)

    Cheli, V T; Santiago González, D A; Spreuer, V; Paez, P M

    2015-03-01

    We have previously shown that the expression of voltage-operated Ca(++) channels (VOCCs) is highly regulated in the oligodendroglial lineage and is essential for proper oligodendrocyte progenitor cell (OPC) migration. Here we assessed the role of VOCCs, in particular the L-type, in oligodendrocyte maturation. We used pharmacological treatments to activate or block voltage-gated Ca(++) uptake and siRNAs to specifically knock down the L-type VOCC in primary cultures of mouse OPCs. Activation of VOCCs by plasma membrane depolarization increased OPC morphological differentiation as well as the expression of mature oligodendrocyte markers. On the contrary, inhibition of L-type Ca(++) channels significantly delayed OPC development. OPCs transfected with siRNAs for the Cav1.2 subunit that conducts L-type Ca(++) currents showed reduce Ca(++) influx by ~75% after plasma membrane depolarization, indicating that Cav1.2 is heavily involved in mediating voltage-operated Ca(++) entry in OPCs. Cav1.2 knockdown induced a decrease in the proportion of oligodendrocytes that expressed myelin proteins, and an increase in cells that retained immature oligodendrocyte markers. Moreover, OPC proliferation, but not cell viability, was negatively affected after L-type Ca(++) channel knockdown. Additionally, we have tested the ability of L-type VOCCs to facilitate axon-glial interaction during the first steps of myelin formation using an in vitro co-culture system of OPCs with cortical neurons. Unlike control OPCs, Cav1.2 deficient oligodendrocytes displayed a simple morphology, low levels of myelin proteins expression and appeared to be less capable of establishing contacts with neurites and axons. Together, this set of in vitro experiments characterizes the involvement of L-type VOCCs on OPC maturation as well as the role played by these Ca(++) channels during the early phases of myelination. PMID:25542980

  2. 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)

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

    OpenAIRE

    Mader Simone; Gredler Viktoria; Schanda Kathrin; Rostasy Kevin; Dujmovic Irena; Pfaller Kristian; Lutterotti Andreas; Jarius Sven; Di Pauli Franziska; Kuenz Bettina; Ehling Rainer; Hegen Harald; Deisenhammer Florian; Aboul-Enein Fahmy; Storch Maria K

    2011-01-01

    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...

  4. Identity of Myelinated Cutaneous Sensory Neurons Projecting to Nocireceptive Laminae Following Nerve Injury in Adult Mice

    OpenAIRE

    Woodbury, C. Jeffery; Kullmann, Florenta A.; Mcilwrath, Sabrina L.; Koerber, H. Richard

    2008-01-01

    It is widely thought that, after peripheral injury, some low-threshold mechanoreceptive (LTMR) afferents “sprout” into pain-specific laminae (I–II) of the dorsal horn and are responsible for chronic pain states such as mechanical allodynia. Although recent studies have questioned this hypothesis, they fail to account for a series of compelling results from single-fiber analyses showing extensive projections from large-diameter myelinated afferents into nocireceptive layers after nerve i...

  5. Autophagy Promotes Oligodendrocyte Survival and Function following Dysmyelination in a Long-Lived Myelin Mutant

    OpenAIRE

    Smith, Chelsey M.; Mayer, Joshua A.; Duncan, Ian D.

    2013-01-01

    The Long–Evans shaker (les) rat has a mutation in myelin basic protein that results in severe CNS dysmyelination and subsequent demyelination during development. During this time, les oligodendrocytes accumulate cytoplasmic vesicles, including lysosomes and membrane-bound organelles. However, the mechanism and functional relevance behind these oligodendrocyte abnormalities in les have not been investigated. Using high-magnification electron microscopy, we identified the accumulations in les...

  6. Macrophages in spinal cord injury: Phenotypic and functional change from exposure to myelin debris.

    Science.gov (United States)

    Wang, Xi; Cao, Kai; Sun, Xin; Chen, Yongxiong; Duan, Zhaoxia; Sun, Li; Guo, Lei; Bai, Paul; Sun, Dongming; Fan, Jianqing; He, Xijing; Young, Wise; Ren, Yi

    2015-04-01

    Macrophage activation and persistent inflammation contribute to the pathological process of spinal cord injury (SCI). It was reported that M2 macrophages were induced at 3-7 days after SCI but M2 markers were reduced or eliminated after 1 week. By contrast, M1 macrophage response is rapidly induced and then maintained at injured spinal cord. However, factors that modulate macrophage phenotype and function are poorly understood. We developed a model to distinguish bone-marrow derived macrophages (BMDMs) from residential microglia and explored how BMDMs change their phenotype and functions in response to the lesion-related factors in injured spinal cord. Infiltrating BMDMs expressing higher Mac-2 and lower CX3CR1 migrate to the epicenter of injury, while microglia expressing lower Mac-2 but higher CX3CR1 distribute to the edges of lesion. Myelin debris at the lesion site switches BMDMs from M2 phenotype towards M1-like phenotype. Myelin debris activates ATP-binding cassette transporter A1 (ABCA1) for cholesterol efflux in response to myelin debris loading in vitro. However, this homeostatic mechanism in injured site is overwhelmed, leading to the development of foamy macrophages and lipid plaque in the lesion site. The persistence of these cells indicates a pro-inflammatory environment, associated with enhanced neurotoxicity and impaired wound healing. These foamy macrophages have poor capacity to phagocytose apoptotic neutrophils resulting in uningested neutrophils releasing their toxic contents and further tissue damage. In conclusion, these data demonstrate for the first time that myelin debris generated in injured spinal cord modulates macrophage activation. Lipid accumulation following macrophage phenotype switch contributes to SCI pathology. GLIA 2015;63:635-651. PMID:25452166

  7. 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.

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

    OpenAIRE

    Altaf, Faris M.

    2012-01-01

    The objectives were to study the ultrastructural changes in the myelinated nerve fibers in an animal model of galactosaemia. The study was done in the Anatomy Department, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia. Twenty-four adult male albino rats were used (6 control and 12 experimental animals). Galactosaemia was induced by adding 40% D-galactose to the rats' diet for 2 months. Sciatic nerves of the control and experimental animals were removed and processed for ele...

  9. Myelin Basic Protein-Specific T Lymphocytes Proliferation and Programmed Cell Death in Demyelinating Diseases

    OpenAIRE

    Saresella, Marina; Marventano, Ivana; Guerini, Franca Rosa; Zanzottera, Milena; Delbue, Serena; Marchioni, Enrico; Maserati, Renato; Longhi, Renato; Ferrante, Pasquale; Clerici, Mario

    2008-01-01

    A dynamic equilibrium between proliferation and programmed cell death (PCD) of auto reactive T-lymphocytes plays a pivotal role in the prevention of autoimmune diseases. We analyzed T lymphocytes myelin basic protein (MBP)-specific PCD and proliferation in demyelinating diseases. Results showed that MBP-specific PCD was significantly decreased in CD4+ and CD8+ T lymphocytes of progressive multifocal leukoencephalopathy (PML), not determined leukoencephalopathy (NDLE), and acute MS (AMS) patie...

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

    OpenAIRE

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

    2014-01-01

    In inflammatory demyelinating diseases such as multiple sclerosis (MS), myelin degradation results in loss of axonal function and eventual axonal degeneration. Differentiation of resident oligodendrocyte precursor cells (OPCs) leading to remyelination of denuded axons occurs regularly in early stages of MS but halts as the pathology transitions into progressive MS. Pharmacological potentiation of endogenous OPC maturation and remyelination is now recognized as a promising th...

  11. Prolonged Sox4 Expression in Oligodendrocytes Interferes with Normal Myelination in the Central Nervous System? †

    OpenAIRE

    Potzner, Michaela R.; Griffel, Carola; Lu?tjen-drecoll, Elke; Bo?sl, Michael R.; Wegner, Michael; Sock, Elisabeth

    2007-01-01

    The highly related transcription factors Sox4 and Sox11 are both expressed in oligodendrocyte precursors. Yet whether they have a function in oligodendrocyte development is unknown. By overexpressing Sox4 under the control of 3.1 kb of 5? flanking sequences of the myelin basic protein gene in transgenic mice, we extended Sox4 expression in the oligodendrocyte lineage from oligodendrocyte precursors to cells undergoing terminal differentiation. As a consequence of transgene expression, mice ...

  12. 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...

  13. Galectin-3 drives oligodendrocyte differentiation to control myelin integrity and function

    OpenAIRE

    Pasquini, L. A.; Millet, V.; Hoyos, H. C.; Giannoni, J. P.; Croci, D. O.; Marder, M.; Liu, F. T.; Rabinovich, G. A.; Pasquini, J. M.

    2011-01-01

    Galectins control critical pathophysiological processes, including the progression and resolution of central nervous system (CNS) inflammation. In spite of considerable progress in dissecting their role within lymphoid organs, their functions within the inflamed CNS remain elusive. Here, we investigated the role of galectin–glycan interactions in the control of oligodendrocyte (OLG) differentiation, myelin integrity and function. Both galectin-1 and -3 were abundant in astrocytes and microg...

  14. 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

  15. Interaction of myelin basic protein with actin in the presence of dodecylphosphocholine micelles.

    Science.gov (United States)

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

    2010-08-17

    The 18.5 kDa myelin basic protein (MBP), the most abundant splice isoform in human adult myelin, is a multifunctional, intrinsically disordered protein that maintains compact assembly of the myelin sheath in the central nervous system. Protein deimination and phosphorylation are two key posttranslational modifications whose balance determines local myelin microdomain stability and function. It has previously been shown that MBP in solution causes both polymerization of G-actin to F-actin and bundling of the microfilaments, and binds them to a negatively charged membrane. However, the binding parameters, and the roles of different possible interacting domains of membrane-associated MBP, have not yet been investigated. Here, we compared the interaction of unmodified (rmC1) and pseudodeiminated (rmC8) recombinant murine MBP (full-length charge variants), and of two terminal deletion variants (rmDeltaC and rmDeltaN), with actin in the presence of DPC (dodecylphosphocholine) to mimic a membrane environment. Our results show that although both charge variants polymerized and bundled actin, the maximal polymerization/bundling due to rmC1 occurred at a lower molar ratio compared to rmC8. In the presence of DPC, rmC1 appeared to be more active than rmC8 in its ability to polymerize and bundle actin, and the binding affinity of both charge variants to G-actin became higher. Moreover, of the two deletion variants studied in the presence of DPC, the one lacking the C-terminal domain (rmDeltaC) was more active compared to the variant lacking the N-terminal domain (rmDeltaN) but exhibited weaker binding to actin. Thus, whereas the N-terminal domain of MBP can be more important for the MBP's actin polymerization activity and membrane-association, the C-terminal domain can regulate its interaction with actin. PMID:20593886

  16. Tolerance Induction and Autoimmune Encephalomyelitis Amelioration After Administration of Myelin Basic Protein–derived Peptide

    OpenAIRE

    Marusic, Suzana; Tonegawa, Susumu

    1997-01-01

    Experimental autoimmune encephalomyelitis (EAE), a demyelinating disease of the central nervous system, is an animal model of paralyzing human disease, multiple sclerosis. EAE is readily induced by immunization with myelin basic protein (MBP) in mice transgenic for an ?? T cell receptor (TCR) that is specific for MBP. Subcutaneous injection of p17 (a peptide consisting of 17 NH2-terminal aminoacids of MBP) in complete Freund's adjuvant (CFA) causes paralysis. Induction of paralysis is ...

  17. THE ANTI-AGING PROTEIN KLOTHO ENHANCES OLIGODENDROCYTE MATURATION AND MYELINATION OF THE CENTRAL NERVOUS SYSTEM

    OpenAIRE

    Chen, Ci-di; Sloane, Jacob A.; Li, Hu; Aytan, Nurgul; Giannaris, Eustathia L.; Zeldich, Ella; Hinman, Jason D.; Dedeoglu, Alpaslan; Rosene, Douglas L.; Bansal, Rashmi; Luebke, Jennifer; Kuro-o, Makoto; Abraham, Carmela R.

    2013-01-01

    We have previously shown that myelin abnormalities and loss characterize the normal aging process of the brain and that an age-associated reduction in Klotho is conserved across species. Predominantly generated in brain and kidney, Klotho overexpression extends life span, whereas loss of Klotho accelerates the development of aging-like phenotypes. While the function of Klotho in brain is unknown, loss of Klotho expression leads to cognitive deficits. In the present study, we found significant...

  18. Aging of myelinating glial cells predominantly affects lipid metabolism and immune response pathways.

    Science.gov (United States)

    Verdier, Valérie; Csárdi, Gábor; de Preux-Charles, Anne-Sophie; Médard, Jean-Jacques; Smit, August B; Verheijen, Mark H G; Bergmann, Sven; Chrast, Roman

    2012-05-01

    Both the central and the peripheral nervous systems are prone to multiple age-dependent neurological deficits, often attributed to still unknown alterations in the function of myelinating glia. To uncover the biological processes affected in glial cells by aging, we analyzed gene expression of the Schwann cell-rich mouse sciatic nerve at 17 time points throughout life, from day of birth until senescence. By combining these data with the gene expression data of myelin mouse mutants carrying deletions of either Pmp22, SCAP, or Lpin1, we found that the majority of age-related transcripts were also affected in myelin mutants (54.4%) and were regulated during PNS development (59.5%), indicating a high level of overlap in implicated molecular pathways. The expression profiles in aging copied the direction of transcriptional changes observed in neuropathy models; however, they had the opposite direction when compared with PNS development. The most significantly altered biological processes in aging involved the inflammatory/immune response and lipid metabolism. Interestingly, both these pathways were comparably changed in the aging optic nerve, suggesting that similar biological processes are affected in aging of glia-rich parts of the central and peripheral nervous systems. Our comprehensive comparison of gene expression in three distinct biological conditions including development, aging, and myelin disease thus revealed a previously unanticipated relationship among themselves and identified lipid metabolism and inflammatory/immune response pathways as potential therapeutical targets to prevent or delay so far incurable age-related and inherited forms of neuropathies. PMID:22337502

  19. 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.?...

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

    OpenAIRE

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

    2011-01-01

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

  1. Cloning of Human Myelin Protein Zero-like Genes by Bioinformatics Strategy.

    Science.gov (United States)

    Tang, Dong-Sheng; Yu, Kuan-Ping; Tang, Xi-Xiang; Zhang, Hua-Li; Pan, Qian; Dai, He-Ping; Xia, Jia-Hui

    2000-01-01

    To clone novel myelin protein related genes, two human ESTs, which shared significant similarity with the human myelin protein zero gene, were found by the comparison of homologue between the cDNA coding region sequences of MPZ gene and the EST database of NCBI. An 801 bp EST contig was assembled, which was 100% identical with a 128 kb genomic sequence, mapped to 1q24. A 435 bp open reading frame (ORF) within the 801 bp contig was shown by computer analysis. Two primers designed according to the sequence of the contig, were coupled with the primers(lambdagt10-5 and gt10-5) on the sequences flanking cloning site of the cDNA library vector to amplify the cDNA library sequences by nested PCR. New primers, designed based on novel cDNA sequences, were used for the PCR amplification with lambdagt10-5 and gt10-5 in the same way as above. Finally, the human myelin protein zero like gene isoform I and II (MPZL1a, MPZL1b GenBank AF095727, AF092424) were cloned. Comparison of gene and protein structures between MPZL1 and MPZ revealed that MPZL1 is the second member of MPZ family. Mutation analysis of MPZL1 gene was performed in 24 Charcot-Marie-Tooth disease (CMT) families and 26 nonsyndrome deafness families, but no mutation was found. PMID:12075424

  2. Kir4.1 potassium channel subunit is crucial for oligodendrocyte development and in vivo myelination.

    Science.gov (United States)

    Neusch, C; Rozengurt, N; Jacobs, R E; Lester, H A; Kofuji, P

    2001-08-01

    To understand the cellular and in vivo functions of specific K(+) channels in glia, we have studied mice with a null mutation in the weakly inwardly rectifying K(+) channel subunit Kir4.1. Kir4.1-/- mice display marked motor impairment, and the cellular basis is hypomyelination in the spinal cord, accompanied by severe spongiform vacuolation, axonal swellings, and degeneration. Immunostaining in the spinal cord of wild-type mice up to postnatal day 18 reveals that Kir4.1 is expressed in myelin-synthesizing oligodendrocytes, but probably not in neurons or glial fibrillary acidic protein-positive (GFAP-positive) astrocytes. Cultured oligodendrocytes from developing spinal cord of Kir4.1-/- mice lack most of the wild-type K(+) conductance, have depolarized membrane potentials, and display immature morphology. By contrast, cultured neurons from spinal cord of Kir4.1-/- mice have normal physiological characteristics. We conclude that Kir4.1 forms the major K(+) conductance of oligodendrocytes and is therefore crucial for myelination. The Kir4.1 knock-out mouse is one of the few CNS dysmyelinating or demyelinating phenotypes that does not involve a gene directly involved in the structure, synthesis, degradation, or immune response to myelin. Therefore, this mouse shows how an ion channel mutation could contribute to the polygenic demyelinating diseases. PMID:11466414

  3. RA-RAR-? counteracts myelin-dependent inhibition of neurite outgrowth via Lingo-1 repression.

    Science.gov (United States)

    Puttagunta, Radhika; Schmandke, André; Floriddia, Elisa; Gaub, Perrine; Fomin, Natalie; Ghyselinck, Norbert B; Di Giovanni, Simone

    2011-06-27

    After an acute central nervous system injury, axonal regeneration is limited as the result of a lack of neuronal intrinsic competence and the presence of extrinsic inhibitory signals. The injury fragments the myelin neuronal insulating layer, releasing extrinsic inhibitory molecules to signal through the neuronal membrane-bound Nogo receptor (NgR) complex. In this paper, we show that a neuronal transcriptional pathway can interfere with extrinsic inhibitory myelin-dependent signaling, thereby promoting neurite outgrowth. Specifically, retinoic acid (RA), acting through the RA receptor ? (RAR-?), inhibited myelin-activated NgR signaling through the transcriptional repression of the NgR complex member Lingo-1. We show that suppression of Lingo-1 was required for RA-RAR-? to counteract extrinsic inhibition of neurite outgrowth. Furthermore, we confirm in vivo that RA treatment after a dorsal column overhemisection injury inhibited Lingo-1 expression, specifically through RAR-?. Our findings identify a novel link between RA-RAR-?-dependent proaxonal outgrowth and inhibitory NgR complex-dependent signaling, potentially allowing for the development of molecular strategies to enhance axonal regeneration after a central nervous system injury. PMID:21690307

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

    Science.gov (United States)

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

    2015-01-01

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

  5. 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

  6. Unstable split mode laser resonator

    International Nuclear Information System (INIS)

    An unstable laser resonator system which provides an output beam with enhanced power, energy distribution and optical characteristics is disclosed. Two separate regions of gain medium each of which has the maximum dimensions permitted by the physical constraints of superfluorescent and excited population decay characteristics resonate in a split mode optical cavity having a common interlocked region of resonance which incorporates the contributions of each gain medium and combines the composite intracavity mode prior to output coupling from the resonator. The resonator system produces a coherent, phase-locked, high power, symmetric output beam. Optical cavities based on both spherical and cylindrical optics are discussed

  7. Induced Secondary Structure and Polymorphism in an Intrinsically Disordered Structural Linker of the CNS: Solid-State NMR and FTIR Spectroscopy of Myelin Basic Protein Bound to Actin

    OpenAIRE

    Ahmed, Mumdooh A. M.; Bamm, Vladimir V.; Shi, Lichi; Steiner-mosonyi, Marta; Dawson, John F.; Brown, Leonid; Harauz, George; Ladizhansky, Vladimir

    2008-01-01

    The 18.5 kDa isoform of myelin basic protein (MBP) is a peripheral membrane protein that maintains the structural integrity of the myelin sheath of the central nervous system by conjoining the cytoplasmic leaflets of oligodendrocytes and by linking the myelin membrane to the underlying cytoskeleton whose assembly it strongly promotes. It is a multifunctional, intrinsically disordered protein that behaves primarily as a structural stabilizer, but with elements of a transient or induced seconda...

  8. 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.

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

    Science.gov (United States)

    Hung, Holly; Kohnken, Rebecca; Svaren, John

    2012-02-01

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

  10. Multiple sclerosis: altered expression of 70- and 27-kDa heat shock proteins in lesions and myelin.

    Science.gov (United States)

    Aquino, D A; Capello, E; Weisstein, J; Sanders, V; Lopez, C; Tourtellotte, W W; Brosnan, C F; Raine, C S; Norton, W T

    1997-06-01

    Recent studies have implicated heat shock proteins (HSP) in the pathogenesis of the multiple sclerosis (MS) lesion. Expression of the 73 kDa constitutive HSP (HSC70), the 72 kDa stress-inducible HSP (HSP70), and the 27 kDa small HSP (HSP27) was analyzed in white matter and myelin from central nervous system (CNS) tissue of MS and normal subjects using a combination of immunocytochemistry and quantitative immunoblotting. Plaques of all types were sharply defined by reduced immunostaining for HSC70, and shown by immunoblotting to contain 30 to 50% less HSC70 than surrounding white matter or normal tissue. In contrast, HSP27 was markedly enhanced 2.5- to 4-fold in plaque regions, especially in fibrous astrocytes and in hyperplastic interfascicular oligodendrocytes at the lesion edge. HSP70 was less abundant than HSC70, and no significant differences in HSP70 levels were noted between MS and normal white matter. Myelin isolated from active plaques contained 3- to 4-fold more HSC70 than normal myelin. Pronounced expression of HSP70 and HSP27 was also found in MS myelin, although neither protein was detected in normal myelin. Thus, white matter undergoing immune-mediated destruction in MS was associated with altered distribution and expression of HSC70 and HSP27. These changes may initially serve to protect myelin from further destruction and facilitate repair; however, enhanced expression of HSC70, HSP70, and HSP27 in myelin may subsequently present as additional immune targets involved in the progression of disease. PMID:9184657

  11. Controllable valley splitting in silicon quantum devices

    CERN Document Server

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

    2006-01-01

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

  12. 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

  13. The Problem of Split Comets Revisited

    Science.gov (United States)

    Sekanina, Z.

    1996-01-01

    The results from studies of D/Shoemaker-Levy 9 and other recent split comets and comet pairs lead to the recognition of fundamental differences between breakup products of the tidally and nontidally split comets and to the conclusive indentification of the so-called dissipating comets as secondary nuclei of previously split comets, whose separately arriving principal nulei had in most cases been missed.

  14. No Effect of Genetic Deletion of Contactin-Associated Protein (CASPR) on Axonal Orientation and Synaptic Plasticity

    OpenAIRE

    Pillai, Anilkumar M.; Garcia-fresco, German P.; Sousa, Aurea D.; Dupree, Jeffrey L.; Philpot, Benjamin D.; Bhat, Manzoor A.

    2007-01-01

    Myelinated axons are endowed with a specialized domain structure that is essential for saltatory action potential conduction. The paranodal domain contains the axoglial junctions and displays a unique ultrastructure that resembles the invertebrate septate junctions (SJs). Biochemical characterizations of the paranodal axoglial SJs have identified several molecular components that include Caspr and contactin (Cont) on the axonal side and neurofascin 155 kDa (NF155) isoform on the glial side. A...

  15. Zeeman splitting in ballistic hole quantum wires

    CERN Document Server

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

    2006-01-01

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

  16. 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.

  17. 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

  18. Myocilin is involved in NgR1/Lingo-1-mediated oligodendrocyte differentiation and myelination of the optic nerve.

    Science.gov (United States)

    Kwon, Heung Sun; Nakaya, Naoki; Abu-Asab, Mones; Kim, Hong Sug; Tomarev, Stanislav I

    2014-04-16

    Myocilin is a secreted glycoprotein that belongs to a family of olfactomedin domain-containing proteins. Although myocilin is detected in several ocular and nonocular tissues, the only reported human pathology related to mutations in the MYOCILIN gene is primary open-angle glaucoma. Functions of myocilin are poorly understood. Here we demonstrate that myocilin is a mediator of oligodendrocyte differentiation and is involved in the myelination of the optic nerve in mice. Myocilin is expressed and secreted by optic nerve astrocytes. Differentiation of optic nerve oligodendrocytes is delayed in Myocilin-null mice. Optic nerves of Myocilin-null mice contain reduced levels of several myelin-associated proteins including myelin basic protein, myelin proteolipid protein, and 2'3'-cyclic nucleotide 3'-phosphodiesterase compared with those of wild-type littermates. This leads to reduced myelin sheath thickness of optic nerve axons in Myocilin-null mice compared with wild-type littermates, and this difference is more pronounced at early postnatal stages compared with adult mice. Myocilin also affects differentiation of oligodendrocyte precursors in vitro. Its addition to primary cultures of differentiating oligodendrocyte precursors increases levels of tested markers of oligodendrocyte differentiation and stimulates elongation of oligodendrocyte processes. Myocilin stimulation of oligodendrocyte differentiation occurs through the NgR1/Lingo-1 receptor complex. Myocilin physically interacts with Lingo-1 and may be considered as a Lingo-1 ligand. Myocilin-induced elongation of oligodendrocyte processes may be mediated by activation of FYN and suppression of RhoA GTPase. PMID:24741044

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

    Science.gov (United States)

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

    2014-06-30

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

  20. 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.

  1. Salt splitting with ceramic membranes

    International Nuclear Information System (INIS)

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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Ectrodactyly/split hand feet malformation

    OpenAIRE

    Jindal Geetanjali; Parmar Veena; Gupta Vipul

    2009-01-01

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

  7. Locally unknotted spines of Heegaard splittings

    OpenAIRE

    Johnson, Jesse

    2004-01-01

    We show that under reasonable conditions, the spines of the handlebodies of a strongly irreducible Heegaard splitting will intersect a closed ball in a graph which is isotopic into the boundary of the ball. This is in some sense a generalization of the results by Scharlemann on how a strongly irreducible Heegaard splitting surface can intersect a ball.

  8. Uptake and Presentation of Myelin Basic Protein by Normal Human B Cells

    OpenAIRE

    Brimnes, Marie Klinge; Hansen, Bjarke Endel; Nielsen, Leif Kofoed; Dziegiel, Morten Hanefeld; Nielsen, Claus Henrik

    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 ...

  9. 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...

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

    OpenAIRE

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

    1993-01-01

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

  11. Characterization of binding properties of the myelin-associated glycoprotein to extracellular matrix constituents.

    OpenAIRE

    Fahrig, T.; Landa, C.; Pesheva, P.; Ku?hn, K.; Schachner, M.

    1987-01-01

    The myelin-associated glycoprotein (MAG) can be obtained from adult mouse brain from detergent-lysates of a crude membrane fraction as a 96-100 kd form (detergent solubilized MAG), and from 100,000 g supernatants of homogenates as a 90-96 kd form (soluble MAG). The soluble form distributes into the Triton X-114-poor aqueous phase, while detergent-solubilized MAG predominantly enters the Triton X-114-rich phase. Both molecular forms bind to heparin in hypo- and isotonic buffers. Soluble MAG bi...

  12. Characterization of myelin proteolipid mRNAs in normal and jimpy mice.

    OpenAIRE

    Gardinier, M. V.; Macklin, W. B.; Diniak, A. J.; Deininger, P. L.

    1986-01-01

    A clone specific for the rat myelin proteolipid protein (PLP) was isolated from a cDNA library made in pUC18 from 17-day-old rat brain stem mRNA. This clone corresponded to the carboxyl-terminal third of the PLP-coding region. The clone was used to identify PLP-specific mRNAs in mouse brain and to establish the time course of PLP mRNA expression during mouse brain development. Three PLP-specific mRNAs were seen, approximately 1,500, 2,400, and 3,200 bases in length, of which the largest was t...

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

    OpenAIRE

    Mason, K.; Mcconnell, H. M.

    1994-01-01

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

  14. MCT8 deficiency: extrapyramidal symptoms and delayed myelination as prominent features.

    Science.gov (United States)

    Tonduti, Davide; Vanderver, Adeline; Berardinelli, Angela; Schmidt, Johanna L; Collins, Christin D; Novara, Francesca; Genni, Antonia Di; Mita, Alda; Triulzi, Fabio; Brunstrom-Hernandez, Janice E; Zuffardi, Orsetta; Balottin, Umberto; Orcesi, Simona

    2013-06-01

    Monocarboxylate transporter 8 (MCT8) deficiency is an X-linked disorder resulting from an impairment of the transcellular transportation of thyroid hormones. Within the central nervous system thyroid hormone transport is normally mediated by MCT8. Patients are described as affected by a static or slowly progressive clinical picture which consists of variable degrees of mental retardation, hypotonia, spasticity, ataxia and involuntary movements, occasionally paroxysmal. The authors describe the clinical and neuroradiological picture of 3 males patients with marked delayed brain myelination and in which the clinical picture was dominated by early onset nonparoxysmal extrapyramidal symptoms. In one subject a novel mutation is described. PMID:22805248

  15. 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...

  16. On non-compact Heegaard splittings

    CERN Document Server

    Taylor, S

    2006-01-01

    A Heegaard splitting of an open 3-manifold is the partition of the manifold into two non-compact handlebodies which intersect on their common boundary. This paper proves several non-compact analogues of theorems about compact Heegaard splittings. The main theorem is: if N is a compact, connected, orientable 3-manifold with non-empty boundary, containing no S^2 components, and if M is obtained from N by removing the boundary then any two Heegaard splittings of M are properly ambient isotopic. This is a non-compact analogue of the classifications of splittings of (closed surface) x I and (closed surface) x S^1 by Scharlemann-Thompson and Schultens. Work of Frohman-Meeks and a non-compact analogue of the Casson-Gordon theorem on weakly reducible Heegaard splittings are key tools.

  17. Quasiperiodic Tip Splitting in Directional Solidification

    CERN Document Server

    Utter, B C; Bodenschatz, E

    2001-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Henry Michael A

    2012-03-01

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

  19. 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

  20. Repetitive propagation of action potentials destabilizes the structure of the myelin sheath. A dynamic x-ray diffraction study.

    OpenAIRE

    Padro?n, R.; Mateu, L.

    1982-01-01

    Time courses of myelin lattice swelling in toad sciatic nerves preexposed to different treatments were determined by x-ray diffraction using a one-dimensional position-sensitive detector. In the nerves supramaximally stimulated for 1 h at 200 Hz, the subsequent process of myelin swelling occurred 45.0 +/- 7.3 min (n = 24) sooner than in resting controls. Sciatic nerves incubated for 1 h in a Ringer's solution deprived of divalent cations (Ca++ and Mg++) exhibited a kinetics of swelling simila...

  1. Mapping Human Cortical Areas in vivo Based on Myelin Content as Revealed by T1- and T2-weighted MRI

    OpenAIRE

    Glasser, Matthew F.; Essen, David C.

    2011-01-01

    Non-invasively mapping the layout of cortical areas in humans is a continuing challenge for neuroscience. We present a new method of mapping cortical areas based on myelin content as revealed by T1-weighted (T1w) and T2-weighted (T2w) MRI. The method is generalizable across different 3T scanners and pulse sequences. We use the ratio of T1w/T2w image intensities to eliminate the MR-related image intensity bias and enhance the contrast to noise ratio for myelin. Data from each subject was mappe...

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

    OpenAIRE

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

    2008-01-01

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

  3. Molecular dissection of the myelin-associated glycoprotein receptor complex reveals cell type–specific mechanisms for neurite outgrowth inhibition

    OpenAIRE

    Venkatesh, Karthik; Chivatakarn, Onanong; Sheu, Shey-shing; Giger, Roman J.

    2007-01-01

    Neuronal Nogo66 receptor-1 (NgR1) binds the myelin inhibitors NogoA, OMgp, and myelin-associated glycoprotein (MAG) and has been proposed to function as the ligand-binding component of a receptor complex that also includes Lingo-1, p75NTR, or TROY. In this study, we use Vibrio cholerae neuraminidase (VCN) and mouse genetics to probe the molecular composition of the MAG receptor complex in postnatal retinal ganglion cells (RGCs). We find that VCN treatment is not sufficient to release MAG inhi...

  4. 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.

  5. Lightweight electrical connector split backshell

    Science.gov (United States)

    Goldman, Elliot (Inventor)

    2009-01-01

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

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

    Scientific Electronic Library Online (English)

    Francisco J, Rivera; Ludwig, Aigner.

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

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

    Science.gov (United States)

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

    2009-05-01

    Although the myelin proteolipid protein gene (Plp1) is highly expressed in the central nervous system encoding the most abundant myelin protein in oligodendrocytes, it is also expressed in other tissues, including testis. Transgenic studies with mice that harbor Plp1-lacZ fusion genes suggest that Leydig cells are the source of Plp1 gene expression in testis. However, virtually nothing is known about Plp1 gene regulation in Leydig cells, which is the focus of this study. The first intron contains both positive and negative regulatory elements that are important in regulating Plp1 gene expression in oligodendrocytes. To test whether these elements are functional in Leydig cells, a battery of Plp1-lacZ fusion genes with partial deletion of Plp1 intron 1 sequence was transfected into the mouse Leydig cell line, TM3. Results presented here suggest that an enhancer, which is very potent in oligodendrocytes, is only nominally active in TM3 cells. The intron also contains several negative regulatory elements that are operative in TM3 cells. Moreover a new exon (exon 1.2) was identified within the first 'intron' resulting in novel splice variants in TM3 cells. Western blot analysis suggests that these splice variants, along with those containing another alternatively spliced exon (exon 1.1) derived from intron 1 sequence, give rise to multiple Plp1 gene products in the mouse testis. PMID:19232385

  8. Temporal and spatial expression analysis of peripheral myelin protein 22 (Pmp22) in developing Xenopus.

    Science.gov (United States)

    Tae, Hyun-Jin; Rahman, Md Mahfujur; Park, Byung-Yong

    2015-01-01

    Peripheral myelin protein 22 (Pmp22), a member of the junction protein family Claudin/EMP/PMP22, contributes to the formation and maintenance of myelin sheaths in the peripheral nervous system. Apart from the establishment and maintenance of peripheral nerves, Pmp22 and its family member have also participated in a broad range of more general processes including cell cycle regulation and apoptosis during development. Pmp22 has been identified from several vertebrate species including mouse, human and zebrafish. However, Pmp22 has not been identified from Xenopus embryos yet. In this paper, we cloned Pmp22 from Xenopus laevis and evaluated its expression during embryogenesis. We found that Pmp22 was initially expressed in the mesoderm and cement gland during the neurula stage. At early tailbud stage, strong expression of Pmp22 was detected in the trigeminal and profundal ganglia as well as developing somites and branchial arches. Later in development, Pmp22 was expressed specifically in cranio-facial cartilage, roof plate and floor plate of the developing brain, otic vesicle and lens. Pmp22 is also strongly expressed in the developing trachea and lungs. Based on its expression in facial tissues, we propose that Pmp22 may be involved in the formation of head structure in addition to the maintenance of functional peripheral nerves in Xenopus embryos. PMID:25616247

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

    Science.gov (United States)

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

    2007-02-01

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

  10. 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.

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

    International Nuclear Information System (INIS)

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

  12. Physicochemical characterization of dodecylphosphocholine/palmitoyllysophosphatidic acid/myelin basic protein complexes

    International Nuclear Information System (INIS)

    The stoichiometry of dodecylphosphocholine/palmitoyllysophosphatidic acid/myelin basic protein complexes and the location of the protein in the micelles have been investigated by electron paramagnetic resonance, ultracentrifugation, small-angle X-ray scattering, 31P, 13C, and 1H nuclear magnetic resonance spectroscopy, and electron microscopy. Ultracentrifugation measurements indicated that well-defined complexes are formed by association of one protein molecule with approximately 133 detergent molecules. The spin-labels 5-, 12-, and 16-doxylstearate have been incorporated into detergent/protein aggregates. Electron paramagnetic resonance spectral parameters and 13C and 1H nuclear magnetic resonance relaxation times showed that the addition of myelin basic protein does not affect the environment and location of the labels or the organization of the micelles. Electron micrographs of the complexes taken by using the freeze-fracture technique revealed the presence of particles with an estimated radius about three times the radius of the micelles measured by small-angle X-ray scattering. The structural integrity of the complexes appears to be based on intramolecular protein interactions as well as protein-detergent interactions

  13. 2S Hyperfine splitting of muonic hydrogen

    CERN Document Server

    Martynenko, A P

    2004-01-01

    Corrections of orders alpha^5, alpha^6 are calculated in the hyperfine splitting of the 2S state in the muonic hydrogen. The nuclear structure effects are taken into account in the one- and two-loop Feynman amplitudes by means of the proton electromagnetic form factors. Total numerical value of the 2S state hyperfine splitting 22.8148 meV in the (\\mu p) can be considered as reliable estimation for the corresponding experiment with the accuracy 10^{-5}. The value of the Sternheim's hyperfine splitting interval [8\\Delta E^{HFS}(2S)-\\Delta E^{HFS}(1S)] is obtained with the accuracy 10^{-6}.

  14. Semi-strong split domination in graphs

    Directory of Open Access Journals (Sweden)

    Anwar Alwardi

    2014-06-01

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

  15. Consumption Growth, Household Splits and Civil War

    OpenAIRE

    Verwimp, Philip; Bundervoet, Tom

    2008-01-01

    We analyse the effect of civil war on household welfare. Using Burundian panel data for the 1998-2007 period in which we re-interviewed original as well as newly formed households (split-offs), we show that headcount poverty decreased by 3.5 % points when split-off households are taken into account and 1% when splits are left out. Poverty is persistent while prosperity is not, in particular in war-affected areas. We find that 25 war-related deaths or wounded at the village level reduce consum...

  16. Solar p-mode frequency splittings

    International Nuclear Information System (INIS)

    Measurements of solar p-mode frequency splittings based on 100 days of solar Doppler observations are presented. The measurements have a high S/N ratio and show the dependence of splitting on radial order as well as spherical harmonic degree. The data confirm that the solar rotation rate is not constant on cylinders but is more closely represented as having only slight variation with radius throught the convection zone. Also, it is shown that the frequency splitting vary with solar cycle. 18 references

  17. Photoinduced water splitting with oxotitanium tetraphenylporphyrin.

    Science.gov (United States)

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

    2014-08-01

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

  18. 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

  19. Structural basis of photosynthetic water-splitting

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-12-10

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

  20. Solar activity and oscillation frequency splittings

    Science.gov (United States)

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

    1993-01-01

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

  1. Split-SUSY versus SUSY GUTs

    International Nuclear Information System (INIS)

    Gauge coupling unification is one of main motivations in the split-SUSY scenario, in which the existence of grand unified theories (GUTs) is assumed. We examine how to realize a split-SUSY mass spectrum in the context of GUTs and find that the construction of split-SUSY GUTs is by no means straightforward. With R-symmetry breaking sources in the GUT sector, GUT particles play the role of messengers in the gauge mediation scenario, and their contributions to gaugino masses can be large. We find an upper bound on soft scalar masses of O(1010) GeV from the condition of consistency in constructing the split-SUSY GUT. Also, we discuss an attempt to construct R-symmetric GUT models. (author)

  2. Recent advances in muonium hyperfine splitting calculations

    International Nuclear Information System (INIS)

    Recent advances in the theoretical calculation of ground state muonium hyperfine splitting are described. The role of the known nonrelativistic Coulomb Green's function as the basis of approximation schemes is emphasized

  3. 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)

  4. Expression of common acute lymphoblastic leukemia antigen (CD 10) by myelinated fibers of the peripheral nervous system.

    Science.gov (United States)

    Cadoni, A; Mancardi, G L; Zaccheo, D; Nocera, A; Barocci, S; Bianchini, D; Schenone, A; Capello, E; Zicca, A

    1993-06-01

    The common acute lymphoblastic leukemia antigen (CALLA), CD10, is a 100-kDa surface glycoprotein endowed with neutral endopeptidase activity, shared by a number of hemopoietic and non-hemopoietic cells. In this report, immunohistochemical and Western blot techniques, using different anti-CD10 monoclonal antibodies, were utilized to demonstrate that CD10 is also expressed by myelin sheaths of the human peripheral nervous system (PNS), but not of the central nervous system. CD10-positive immunoreactivity appeared to be localized in the outer and inner borders of myelinated fibers, in nodes of Ranvier and in the Schmidt-Lantermann clefts, thus showing a distribution pattern very similar to that of myelin-associated glycoprotein (MAG). The above findings suggest that CD10 antigen, through its enzymatic activity, may have a functional role in the assembly and maintenance of PNS myelin. In addition, it is not known whether CD10, similarly to MAG, may be a target antigen in some PNS immune-mediated disorders. PMID:8392520

  5. A Dual Role of erbB2 in Myelination and in Expansion of the Schwann Cell Precursor Pool

    Science.gov (United States)

    Garratt, Alistair N.; Voiculescu, Octavian; Topilko, Piotr; Charnay, Patrick; Birchmeier, Carmen

    2000-01-01

    Neuregulin-1 provides an important axonally derived signal for the survival and growth of developing Schwann cells, which is transmitted by the ErbB2/ErbB3 receptor tyrosine kinases. Null mutations of the neuregulin-1, erbB2, or erbB3 mouse genes cause severe deficits in early Schwann cell development. Here, we employ Cre-loxP technology to introduce erbB2 mutations late in Schwann cell development, using a Krox20-cre allele. Cre-mediated erbB2 ablation occurs perinatally in peripheral nerves, but already at E11 within spinal roots. The mutant mice exhibit a widespread peripheral neuropathy characterized by abnormally thin myelin sheaths, containing fewer myelin wraps. In addition, in spinal roots the Schwann cell precursor pool is not correctly established. Thus, the Neuregulin signaling system functions during multiple stages of Schwann cell development and is essential for correct myelination. The thickness of the myelin sheath is determined by the axon diameter, and we suggest that trophic signals provided by the nerve determine the number of times a Schwann cell wraps an axon. PMID:10704452

  6. Myelin proteolipid protein (Plp) intron 1 DNA is required to temporally regulate Plp gene expression in the brain.

    Science.gov (United States)

    Li, Shenyang; Moore, Christopher L; Dobretsova, Anna; Wight, Patricia A

    2002-10-01

    The myelin proteolipid protein (Plp) gene encodes the most abundant protein found in mature CNS myelin. Expression of the gene is regulated spatiotemporally, with maximal expression occurring in oligodendrocytes during the myelination period of CNS development. Plp gene expression is tightly controlled. Misregulation of the gene in humans can result in the dysmyelinating disorder Pelizaeus-Merzbacher disease, and in transgenic mice carrying a null mutation or extra copies of the gene can result in a variety of conditions, from late onset demyelination and axonopathy, to severe early onset dysmyelination. In this study we have examined the effects of Plp intron 1 DNA in mediating proper developmental expression of Plp-lacZ fusion genes in transgenic mice. Our results reveal the importance of Plp intron 1 sequences in instigating the expected surge in Plp-lacZ gene activity during (and following) the active myelination period of brain development. Transgene expression was also detected in the testis (Leydig cells), however, the presence or absence of Plp intron 1 sequences had no effect on the temporal profile in the testis. Surprisingly, expression of the transgene missing Plp intron 1 DNA was always higher in the testis, as compared to the brain, in all of the transgenic lines generated. PMID:12358743

  7. Stereological investigation of the age-related changes of the myelinated fibers in the hippocampus of male rats.

    Science.gov (United States)

    Lu, Wei; Yang, Shu; Chen, Lin; Qiu, Xuan; Huang, Chun-Xia; Wu, Hong; Li, Chen; Yang, Jun-Qing; Zhang, Lei; Chao, Feng-Lei; Tang, Yong

    2014-08-01

    The decline of hippocampus-dependent learning and memory during normal aging is not associated with neuron death and synapse loss. Until now, age-related changes in the myelinated fibers of the hippocampus have not been investigated. Therefore, in this study, the myelinated fibers in the hippocampi of young (6 months), middle-aged (18 months), and old-aged (28 months) male Sprague-Dawley rats were studied with transmission electron microscope and stereological methods, following spatial learning tests in a Morris water maze. The results showed that hippocampus-dependent spatial learning was impaired in old-aged rats but that the total volume, length, and mean diameter of the myelinated fibers in the hippocampus, as well as the hippocampal volume, remained constant during the normal aging process. Our results suggest that the age-related decline in hippocampus-dependent spatial learning is not attributable to myelinated fiber changes in the hippocampus and that other, undetermined factors are responsible. PMID:24782353

  8. Rumpshaker mouse: a new X-linked mutation affecting myelination: evidence for a defect in PLP expression.

    Science.gov (United States)

    Griffiths, I R; Scott, I; McCulloch, M C; Barrie, J A; McPhilemy, K; Cattanach, B M

    1990-04-01

    This report describes a new X-linked mutation in mice, named rumpshaker (rsh) which is associated with hypomyelination of the central nervous system. Myelination commences appropriately but the majority of sheaths fail to develop normally. Oligodendrocytes are increased in number and have prominent Golgi apparatus, rough endoplasmic reticulum and free ribosomes. Occasional cisternae of rough endoplasmic reticulum are distended. Some dense lamellar inclusions occur in oligodendrocytes but overall, degenerative changes and cell death are uncommon. Immunostaining demonstrates a major defect in expression of PLP DM-20. Using site-specific antisera directed at different portions of the PLP/DM-20 molecule, the major defect appears to be with PLP where virtually no myelin sheaths are positive. Antiserum against the C-terminal common to PLP and DM-20 shows reduced but definite myelin staining. Genetic analysis indicates a locus at or close to the PLP/jimpy (jp) locus. The rsh mutation, however, differs from jp in that affected mice have normal longevity, can breed, produce substantially more myelin and have increased numbers of oligodendrocytes. PMID:1694232

  9. Enriched environment increases myelinated fiber volume and length in brain white matter of 18-month female rats.

    Science.gov (United States)

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

    2015-04-23

    Cognition and memory decline with normal aging, which could be partly attributed to the degeneration of brain white matter. Previous studies demonstrated that exposure to an enriched environment (EE) could protect cognition and memory from aging. However, if or how EE might affect the brain white matter has not been thoroughly investigated. In the current study, 24 middle-aged (14-month-old) female Sprague -Dawley (SD) rats were randomly assigned to EE or standard environment (SE) for 4 months. At the end of the environment intervention, the Morris water maze tests were performed. Then, 5 rats were randomly selected from each group for stereological assessment of the brain white matter and its myelinated fibers. The results revealed that middle-aged rats living in EE displayed better spatial learning than SE controls. The white matter volume was 124.6±7.8mm(3) in EE rats, which was significantly enlarged compared with 84.8±3.4mm(3) in SE rats. Likewise, the myelinated fiber volume was markedly increased from 56.6±1.7mm(3) in SE rats to 87.2±9.0mm(3) in EE rats; so was the myelinated fiber length from 83.5±6.6km in SE rats to 119.0±10.0km in EE rats. Our data suggested that EE could protect brain white matter and its myelinated fibers of female rats at middle age. PMID:25796176

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

    Science.gov (United States)

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

    2008-10-01

    Oligodendrocyte-myelin glycoprotein (OMgp) is a myelin component that has been shown in vitro to inhibit neurite outgrowth by binding to the Nogo-66 receptor (NgR1)/Lingo-1/Taj (TROY)/p75 receptor complex to activate the RhoA pathway. To investigate the effects of OMgp on axon regeneration in vivo, OMgp(-/-) mice on a mixed 129/Sv/C57BL/6 (129BL6) or a C57BL/6 (BL6) genetic background were tested in two spinal cord injury (SCI) models - a severe complete transection or a milder dorsal hemisection. OMgp(-/-) mice on the mixed 129BL6 genetic background showed greater functional improvement compared to OMgp(+/+) littermates, with increased numbers of cholera toxin B-labeled ascending sensory axons and 5-HT(+) descending axons and less RhoA activation after spinal cord injury. Myelin isolated from OMgp(-/-) mice (129BL6) was significantly less inhibitory to neurite outgrowth than wild-type (wt) myelin in vitro. However, OMgp(-/-) mice on a BL/6 genetic background showed neither statistically significant functional recovery nor axonal sprouting following dorsal hemisection. PMID:18692574

  11. Myelin-oligodendrocyte glycoprotein is a member of a subset of the immunoglobulin superfamily encoded within the major histocompatibility complex

    Energy Technology Data Exchange (ETDEWEB)

    Pham-Dinh, D.; Dautigny, A. (Institut des Neurosciences, Paris (France)); Mattei, M.G.; Roeckel, N. (Institut National de la Sante et de la Recherche Medicale Unite, Marseille (France)); Nussbaum, J.H.; Roussel, G. (Centre National de la Recherche Scientifique Unite, Strasbourg (France)); Pontarotti, P. (Centre Natinal de la Recherche Scientifique Unite, Toulouse (France)); Mather, I.H. (Univ. of Maryland, College Park, MD (United States)); Artzt, K. (Univ. of Texas, Austin, TX (United States)); Lindahl, K.F. (Univ. of Texas Southwestern Medical Center, Dallas, TX (United States))

    1993-09-01

    Myelin/oligodendrocyte glycoprotein (MOG) is found on the surface of myelinating oligodendrocytes and external lamellae of myelin sheaths in the central nervous system, and it is target antigen in experimental autoimmune encephalomyelitis and multiple sclerosis. The authors have isolated bovine, mouse, and rat MOG cDNA clones and shown that the developmental pattern of MOG expression in the rat central nervous system coincides with the late stages of myelination. The amino-terminal, extracellular domain of MOG has characteristics of an immunoglobulin variable domain and is 46% and 41% identical with the amino terminus of bovine butyrophilin (expressed in the lactating mammary gland) and B-G antigens of the chicken major histocompatibility complex (MHC), respectively; these proteins thus form a subset of the immunoglobulin superfamily. The homology between MOG and B-G extends beyond their structure and genetic mapping to their ability to induce strong antibody responses and has implications for the role of MOG in pathological, autoimmune conditions. The authors colocalized the MOG and BT genes to the human MHC on chromosome 6p21.3-p22. The mouse MOG gene was mapped to the homologous band C of chromosome 17, within the M region of the mouse MHC. 38 refs., 6 figs.

  12. Myelination Delay and Allan-Herndon-Dudley Syndrome Caused by a Novel Mutation in the SLC16A2 Gene.

    Science.gov (United States)

    Piana, Roberta La; Vanasse, Michel; Brais, Bernard; Bernard, Genevieve

    2014-11-01

    Allan-Herndon-Dudley syndrome is an X-linked disease caused by mutations in the solute carrier family 16 member 2 (SLC16A2) gene. As SLC16A2 encodes the monocarboxylate transporter 8 (MCT8), a thyroid hormone transporter, patients with Allan-Herndon-Dudley syndrome present a specific altered thyroid hormone profile. Allan-Herndon-Dudley syndrome has been associated with myelination delay on the brain magnetic resonance imaging (MRI) of affected subjects. We report a patient with Allan-Herndon-Dudley syndrome characterized by developmental delay, hypotonia, and delayed myelination caused by a novel SLC16A2 mutation (p.L291R). The thyroid hormones profile in our patient was atypical for Allan-Herndon-Dudley syndrome. The follow-up examinations showed that the progression of the myelination was not accompanied by a clinical improvement. Our paper suggests that SLC16A2 mutations should be investigated in patients with myelination delay even when the thyroid function is not conclusively altered. PMID:25380603

  13. On generalizations of separating and splitting families

    OpenAIRE

    Condon, Daniel; Coskey, Samuel; Serafin, Luke; Stockdale, Cody

    2014-01-01

    The work in this article concerns two different types of families of finite sets: separating families and splitting families. These families have applications in combinatorial search, coding theory, and cryptography as well as many other fields. We define generalizations of these two notions, naming them $n$-separating families and $n$-splitting families. We discuss the basic properties of these notions and compare them with existing notions of separation. We also give lower...

  14. Ectrodactyly/split hand feet malformation

    Directory of Open Access Journals (Sweden)

    Jindal Geetanjali

    2009-01-01

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

  15. 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...

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

  17. 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.

  18. Valley splitting in strained silicon quantum wells

    OpenAIRE

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

    2003-01-01

    A theory based on localized-orbital approaches is developed to describe the valley splitting observed in silicon quantum wells. The theory is appropriate in the limit of low electron density and relevant for proposed quantum computing architectures. The valley splitting is computed for realistic devices using the quantitative nanoelectronic modeling tool NEMO. A simple, analytically solvable tight-binding model is developed, it yields much physical insight, and it reproduces...

  19. Molecular characterization of myelin protein zero in Xenopus laevis peripheral nerve

    Science.gov (United States)

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

    2007-12-01

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

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

    International Nuclear Information System (INIS)

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

  1. Analysis of congenital hypomyelinating Egr2Lo/Lo nerves identifies Sox2 as an inhibitor of Schwann cell differentiation and myelination

    OpenAIRE

    Le, Nam; Nagarajan, Rakesh; Wang, James Y. T.; Araki, Toshiyuki; Schmidt, Robert E.; Milbrandt, Jeffrey

    2005-01-01

    Egr2 is a transcription factor required for peripheral nerve myelination in rodents, and mutations in Egr2 are associated with congenital hypomyelinating neuropathy (CHN) in humans. To further study its role in myelination, we generated mice harboring a hypomorphic Egr2 allele (Egr2Lo) that survive for up to 3 weeks postnatally, a period of active myelination in rodents. These Egr2Lo/Lo mice provided the opportunity to study the molecular effects of Egr2 deficiency on Schwann cell biology, an...

  2. Expression of Proteolipid Protein Gene in Spinal Cord Stem Cells and Early Oligodendrocyte Progenitor Cells Is Dispensable for Normal Cell Migration and Myelination

    OpenAIRE

    Harlow, Danielle E.; Saul, Katherine E.; Culp, Cecilia M.; Vesely, Elisa M.; Macklin, Wendy B.

    2014-01-01

    Plp1 gene expression occurs very early in development, well before the onset of myelination, creating a conundrum with regard to the function of myelin proteolipid protein (PLP), one of the major proteins in compact myelin. Using PLP-EGFP mice to investigate Plp1 promoter activity, we found that, at very early time points, PLP-EGFP was expressed in Sox2+ undifferentiated precursors in the spinal cord ventricular zone (VZ), as well as in the progenitors of both neuronal and glial lineages. As ...

  3. Protein membrane interaction: effect of myelin basic protein on the dynamics of oriented lipids

    Science.gov (United States)

    Natali, F.; Relini, A.; Gliozzi, A.; Rolandi, R.; Cavatorta, P.; Deriu, A.; Fasano, A.; Riccio, P.

    2003-08-01

    We have studied the effect of physiological amounts of myelin basic protein (MBP) on pure dimyristoyl L-?-phosphatidic acid (DMPA) oriented membranes. The investigation has been carried out using several complementary experimental methods to provide a detailed characterization of the proteo-lipid complexes. In particular, taking advantage of the power of the quasi-elastic neutron scattering (QENS) technique as optimal probe in biology, a significant effect is suggested to be induced by MBP on the anisotropy of lipid dynamics across the liquid-gel phase transition. Thus, the enhancement of the spatially restricted, vertical translation motion of DMPA is suggested to be the main responsible for the increased contribution of the out of plane lipid dynamics observed at 340 K.

  4. Protein-membrane interaction: effect of myelin basic protein on the dynamics of oriented lipids

    International Nuclear Information System (INIS)

    We have studied the effect of physiological amounts of myelin basic protein (MBP) on pure dimyristoyl L-?-phosphatidic acid (DMPA) oriented membranes. The investigation has been carried out using several complementary experimental methods to provide a detailed characterization of the proteo-lipid complexes. In particular, taking advantage of the power of the quasi-elastic neutron scattering (QENS) technique as optimal probe in biology, a significant effect is suggested to be induced by MBP on the anisotropy of lipid dynamics across the liquid-gel phase transition. Thus, the enhancement of the spatially restricted, vertical translation motion of DMPA is suggested to be the main responsible for the increased contribution of the out of plane lipid dynamics observed at 340 K

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

    Science.gov (United States)

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

    2013-01-01

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

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

    International Nuclear Information System (INIS)

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

  7. Misincorporation of the proline homologue Aze (azetidine-2-carboxylic acid) into recombinant myelin basic protein.

    Science.gov (United States)

    Bessonov, Kyrylo; Bamm, Vladimir V; Harauz, George

    2010-04-01

    We have evaluated the effects of the proline homologue Aze (1) (azetidine-2-carboxylic acid) on growth of Escherichia coli strains used to over-express recombinant forms of murine myelin basic protein (rmMBP), and on the degree of misincorporation. Addition of Aze to minimal media resulted in severe diminution of growth rate, but rmMBP could still be produced and purified. Mass spectrometry indicated that a detectable proportion of the rmMBP produced had incorporated Aze instead of proline (Pro), to a maximum of three of eleven possible sites. Molecular modelling of a proline-rich region of rmMBP illustrated that the misincorporation of Aze at any site would cause a severe bend in the polypeptide chain, and that multiple Pro-->Aze substitutions would completely disrupt a poly-proline type II structure that has been conjectured to be functionally significant. PMID:20064647

  8. 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))

  9. 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

  10. Self-induced spectral splits in supernova neutrino fluxes

    OpenAIRE

    Raffelt, Georg G.; Smirnov, Alexei Yu

    2007-01-01

    In the dense-neutrino region above the neutrino sphere of a supernova (r > 400 km), neutrino-neutrino refraction causes collective flavor transformations. They can lead to "spectral splits" where an energy E_split splits the transformed spectrum sharply into parts of almost pure but different flavors. Unless there is an ordinary MSW resonance in the dense-neutrino region, E_split is determined by flavor-lepton number conservation alone. Spectral splits are created by an adia...

  11. Wave Splitting in Direct and Inverse Scattering Problems

    OpenAIRE

    Gustafsson, Mats

    2000-01-01

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

  12. 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...

  13. Structural insight into the function of myelin basic protein as a ligand for integrin ?M?2

    DEFF Research Database (Denmark)

    Stapulionis, Romualdas; Oliveira, Cristiano

    2008-01-01

    Multiple sclerosis (MS) is an inflammatory disease where phagocytic cells infiltrate the nerve tissue and act as terminal agents in destruction of the myelin sheath. However, the mechanism that triggers the ability of these cells to recognize myelin remains obscure. We show that myelin basic protein (MBP), a major autoantigen in MS, is a potent and specific ligand for the integrin ?M?2 (Mac-1, CD11b/CD18) expressed mainly on phagocytic cells. MBP undergoes a dramatic conformational change when liberated from the lipid-rich environment of the myelin sheath. The MS drug glatiramer acetate mimics the conformationally labile regions of MBP, interacts in the unfolded state strongly with ?M?2, and inhibits the MBP binding to ?M?2. Our study reveals a link between MBP, glatiramer acetate, and the ?M?2 integrin, and suggests a new model for MS pathogenesis based on the recognition of unfolded MBP by the ?M?2 integrin.

  14. Localization in splitting of matter waves

    International Nuclear Information System (INIS)

    In this paper we present an analysis of how matter waves, guided as propagating modes in potential structures, are split under adiabatic conditions. The description is formulated in terms of localized states obtained through a unitary transformation acting on the mode functions. The mathematical framework results in coupled propagation equations that are decoupled in the asymptotic regions as well before as after the split. The resulting states have the advantage of describing propagation in situations, for instance matter-wave interferometers, where local perturbations make the transverse modes of the guiding potential unsuitable as a basis. The different regimes of validity of adiabatic propagation schemes based on localized versus delocalized basis states are also outlined. Nontrivial dynamics for superposition states propagating through split potential structures is investigated through numerical simulations. For superposition states the influence of longitudinal wave-packet extension on the localization is investigated and shown to be accurately described in quantitative terms using the adiabatic formulations presented here

  15. High efficiency beam splitting for H- accelerators

    International Nuclear Information System (INIS)

    Beam splitting for high energy accelerators has typically involved a significant loss of beam and radiation. This paper reports on a new method of splitting beams for H- accelerators. This technique uses a high intensity flash of light to strip a fraction of the H- beam to H0 which are then easily separated by a small bending magnet. A system using a 900-watt (average electrical power) flashlamp and a highly efficient collector will provide 10-3 to 10-2 splitting of a 50 MeV H- beam. Results on the operation and comparisons with stripping cross sections are presented. Also discussed is the possibility for developing this system to yield a higher stripping fraction

  16. 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%.

  17. NF-M is an essential target for the myelin-directed “outside-in” signaling cascade that mediates radial axonal growth

    OpenAIRE

    Garcia, Michael L.; Lobsiger, Christian S.; Shah, Sameer B.; Deerinck, Tom J.; Crum, John; Young, Darren; Ward, Christopher M.; Crawford, Thomas O.; Gotow, Takahiro; Uchiyama, Yasuo; Ellisman, Mark H.; Calcutt, Nigel A.; Cleveland, Don W.

    2003-01-01

    Neurofilaments are essential for acquisition of normal axonal calibers. Several lines of evidence have suggested that neurofilament-dependent structuring of axoplasm arises through an “outside-in” signaling cascade originating from myelinating cells. Implicated as targets in this cascade are the highly phosphorylated KSP domains of neurofilament subunits NF-H and NF-M. These are nearly stoichiometrically phosphorylated in myelinated internodes where radial axonal growth takes place, but n...

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

    OpenAIRE

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

    2005-01-01

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

  19. Rumpshaker: an X-linked mutation causing hypomyelination: developmental differences in myelination and glial cells between the optic nerve and spinal cord.

    Science.gov (United States)

    Fanarraga, M L; Griffiths, I R; McCulloch, M C; Barrie, J A; Kennedy, P G; Brophy, P J

    1992-01-01

    The X-linked mutation rumpshaker (rsh), which is probably an allele of jimpy (jp), causes hypomyelination in the CNS of mice. This study examines the developmental expression of the morphology, glial cells, and immunostaining of myelin proteins in the optic nerve and spinal cord. The optic nerve contains varying numbers of amyelinated and myelinated fibres. The majority of such sheaths are of normal thickness whereas in the spinal cord most axons are associated with a disproportionately thin sheath which changes little in thickness during development. In the optic nerve glial cell numbers are elevated in mutants during early and peak myelination but then fall slightly below normal in adults. In contrast, the number of glial cells is consistently elevated after 16 days of age in the spinal cord. The majority of the alterations to total glial cells are due to corresponding changes in the oligodendrocyte population. Immunostaining intensity is somewhat reduced for myelin basic protein (MBP) and the C-terminal common to proteolipid protein (PLP) and DM-20 and profoundly decreased for the PLP-specific peptide. Glial fibrillary acidic protein (GFAP) is increased in rsh. It is probable that some of the variation in myelination between optic nerve and cord in rsh is related to the difference in axon diameter in the two locations, as there are adequate numbers of oligodendrocytes at the time of myelination. However, the effect of the mutation on cell development in the brain and the spinal cord may be different. The immunostaining indicates a marked deficiency in PLP in myelin but suggests that DM-20 levels may be relatively normal. rsh shows several major differences from jp and other X-linked myelin mutants, particularly in relation to oligodendrocyte numbers, and will be useful to elucidate the role of the PLP gene in influencing oligodendrocyte differentiation and survival. PMID:1375190

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

    OpenAIRE

    Dupin, E.; Baroffio, A.; Dulac, C; Cameron-curry, P.; Le Douarin, N. M.

    1990-01-01

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

  1. Dynamical Doublet-Triplet Higgs Mass Splitting

    OpenAIRE

    Kitano, Ryuichiro; Okada, Nobuchika

    2001-01-01

    We propose a new mechanism towards the solution to the doublet-triplet Higgs mass splitting problem in the supersymmetric grand unified theory. Our model is based on the gauge group $SU(5)_H \\times SU(5)_{GUT}$, where $SU(5)_H$ and $SU(5)_{GUT}$ are a new strong gauge interaction and the ordinary grand unified gauge group, respectively. The doublet-triplet Higgs mass splitting is realized through the quantum deformation of moduli space caused by the strong $SU(5)_H$ gauge dy...

  2. Macroscopic tunnel splittings in superconducting phase qubits

    CERN Document Server

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

    2004-01-01

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

  3. The transversely split gracilis twin free flaps

    Directory of Open Access Journals (Sweden)

    Upadhyaya Divya

    2010-01-01

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

  4. 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.

  5. Medium-induced splitting kernels from SCETG

    Science.gov (United States)

    Ovanesyan, Grigory

    2013-05-01

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

  6. Lecture notes on generalized Heegaard splittings

    CERN Document Server

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

    2005-01-01

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

  7. 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.

  8. Tunneling and Energy Splitting in Ising Models

    CERN Document Server

    Jansen, K; Jansen, Karl; Shen, Yue

    1993-01-01

    The energy splitting $E_{0a}$ in two and four dimensional Ising models is measured in a cylindrical geometry on finite lattices. By comparing to exact results in the two dimensional Ising model we demonstrate that $E_{0a}$ can be extracted very reliably from Monte Carlo calculations in practice. In four dimensions we compare the measured $E_{0a}$ with two different theoretical predictions on the finite size behavior of the energy splitting. We find that our numerical data are in favor of the predictions based on the semiclassical dilute instanton gas approximation.

  9. Linear birefringence in split-ring resonators.

    Science.gov (United States)

    Iyer, Srinivasan; Popov, Sergei; Friberg, Ari T

    2012-06-01

    We study polarization-dependent transmission of light through arrays of single-slit split-ring resonator (SSRR) based systems at normal incidence using finite integration time domain (FITD) and finite element methods (FEM). It is found that a conventional planar array of SSRRs acts as an effective optical wave plate at certain polarizations of incident light. The effect is attributed to the intrinsic linear birefringence of individual SSRRs. A comparison is made with other split-ring resonator-based systems exhibiting wave-plate-like properties due to inter-SSRR coupling. PMID:22660115

  10. A Mutation in the Canine Gene Encoding Folliculin-Interacting Protein 2 (FNIP2) Associated With a Unique Disruption in Spinal Cord Myelination

    Science.gov (United States)

    Mayer, Joshua A.; Li, Fang-Yuan; Gokey, Nolan; Svaren, John; Safra, Noa; Bannasch, Danika L.; Sullivan, Katrina; Breuhaus, Babetta; Patel, Pragna I.; Duncan, Ian D.

    2014-01-01

    Novel mutations in myelin and myelin-associated genes have provided important information on oligodendrocytes and myelin and the effects of their disruption on the normal developmental process of myelination of the central nervous system (CNS). We report here a mutation in the folliculin-interacting protein 2 (FNIP2) gene in the Weimaraner dog that results in hypomyelination of the brain and a tract-specific myelin defect in the spinal cord. This myelination disruption results in a notable tremor syndrome from which affected dogs recover with time. In the peripheral tracts of the lateral and ventral columns of the spinal cord, there is a lack of mature oligodendrocytes. A genome-wide association study of DNA from three groups of dogs mapped the gene to canine chromosome 15. Sequencing of all the genes in the candidate region identified a frameshift mutation in the FNIP2 gene that segregated with the phenotype. While the functional role of FNIP2 is not known, our data would suggest that production of truncated protein results in a delay or failure of maturation of a subpopulation of oligodendrocytes. PMID:24272703

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

    Science.gov (United States)

    Palazuelos, Javier; Klingener, Michael; Aguirre, Adan

    2014-06-01

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

  12. Severe demyelination but no astrocytopathy in clinically definite neuromyelitis optica with anti-myelin-oligodendrocyte glycoprotein antibody.

    Science.gov (United States)

    Ikeda, Kensuke; Kiyota, Naoki; Kuroda, Hiroshi; Sato, Douglas Kazutoshi; Nishiyama, Shuhei; Takahashi, Toshiyuki; Misu, Tatsuro; Nakashima, Ichiro; Fujihara, Kazuo; Aoki, Masashi

    2015-04-01

    We report a patient with neuromyelitis optica (NMO) presenting anti-myelin-oligodendrocyte glycoprotein (MOG)-seropositive, in whom biomarkers of demyelination and astrocyte damage were measured during an acute attack. A 31-year-old man developed right optic neuritis followed by longitudinally extensive transverse myelitis, fulfilling the criteria for definite NMO. He was anti-MOG-seropositive and anti-aquaporin-4 seronegative. The myelin basic protein level was markedly elevated whereas glial fibrillary acidic protein was not detectable in cerebrospinal fluid during an acute attack. His symptoms quickly improved after high-dose methylprednisolone therapy. This case suggests that NMO patients with anti-MOG may have severe demyelination in the absence of astrocyte injury. PMID:25257613

  13. Fuzzy complexes of myelin basic protein: NMR spectroscopic investigations of a polymorphic organizational linker of the central nervous system1

    Science.gov (United States)

    Libich, David S.; Ahmed, Mumdooh A.M.; Zhong, Ligang; Bamm, Vladimir V.; Ladizhansky, Vladimir; Harauz, George

    2012-01-01

    The classic 18.5 kDa isoform of myelin basic protein (MBP) is central to maintaining the structural homeostasis of the myelin sheath of the central nervous system. It is an intrinsically disordered, promiscuous, multifunctional, peripheral membrane protein, whose conformation adapts to its particular environment. Its study requires the selective and complementary application of diverse approaches, of which solution and solid-state NMR spectroscopy are the most powerful to elucidate site-specific features. We review here several recent solution and solid-state NMR spectroscopic studies of 18.5 kDa MBP, and the induced partial disorder-to-order transitions that it has been demonstrated to undergo when complexed with calmodulin, actin, and phospholipid membranes. PMID:20453917

  14. Fuzzy complexes of myelin basic protein: NMR spectroscopic investigations of a polymorphic organizational linker of the central nervous system.

    Science.gov (United States)

    Libich, David S; Ahmed, Mumdooh A M; Zhong, Ligang; Bamm, Vladimir V; Ladizhansky, Vladimir; Harauz, George

    2010-04-01

    The classic 18.5 kDa isoform of myelin basic protein (MBP) is central to maintaining the structural homeostasis of the myelin sheath of the central nervous system. It is an intrinsically disordered, promiscuous, multifunctional, peripheral membrane protein, whose conformation adapts to its particular environment. Its study requires the selective and complementary application of diverse approaches, of which solution and solid-state NMR spectroscopy are the most powerful to elucidate site-specific features. We review here several recent solution and solid-state NMR spectroscopic studies of 18.5 kDa MBP, and the induced partial disorder-to-order transitions that it has been demonstrated to undergo when complexed with calmodulin, actin, and phospholipid membranes. PMID:20453917

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-06-20

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

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

    OpenAIRE

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

    2008-01-01

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

  17. Expansion of NF-M carboxy terminus increases axonal diameter independent of increases in conduction velocity or myelin thickness

    OpenAIRE

    Barry, Devin M.; Stevenson, William; Bober, Brian G.; Wiese, Peter J.; Dale, Jeffrey M.; Barry, Garet S.; Byers, Nathan S.; Strope, Jonathan D.; Chang, Rakwoo; Schulz, David J.; Shah, Sameer; Calcutt, Nigel A.; Gebremichael, Yeshitila; Garcia, Michael L.

    2012-01-01

    Maturation of the peripheral nervous system requires specification of axonal diameter, which, in turn, has a significant influence on nerve conduction velocity. Radial axonal growth initiates with myelination, and is dependent upon the C-terminus region of neurofilament medium (NF-M). Molecular phylogenetic analysis in mammals suggested that expanded NF-M C-termini correlated with larger diameter axons. We utilized gene targeting and computational modeling to test this new hypothesis. Increas...

  18. An essential role of MAG in mediating axon-myelin attachment in Charcot-Marie-Tooth 1A disease

    OpenAIRE

    Kinter, Jochen; Lazzati, Thomas; Schmid, Daniela; Zeis, Thomas; Erne, Beat; Lu?tzelschwab, Roland; Steck, Andreas J.; Pareyson, Davide; Peles, Elior; Schaeren-wiemers, Nicole

    2012-01-01

    Charcot-Marie-Tooth disease type 1A (CMT1A) is a hereditary demyelinating peripheral neuropathy caused by the duplication of the PMP22 gene. Demyelination precedes the occurrence of clinical symptoms that correlate with axonal degeneration. It was postulated that a disturbed axon-glia interface contribute to altered myelination consequently leading to axonal degeneration. In this study, we examined the expression of MAG and Necl4, two critical adhesion molecules that are present at the axon-g...

  19. 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.)

  20. Myocilin Is Involved in NgR1/Lingo-1-Mediated Oligodendrocyte Differentiation and Myelination of the Optic Nerve

    OpenAIRE

    Kwon, Heung Sun; Nakaya, Naoki; Abu-asab, Mones; Kim, Hong Sug; Tomarev, Stanislav I.

    2014-01-01

    Myocilin is a secreted glycoprotein that belongs to a family of olfactomedin domain-containing proteins. Although myocilin is detected in several ocular and nonocular tissues, the only reported human pathology related to mutations in the MYOCILIN gene is primary open-angle glaucoma. Functions of myocilin are poorly understood. Here we demonstrate that myocilin is a mediator of oligodendrocyte differentiation and is involved in the myelination of the optic nerve in mice. Myocilin is expressed ...

  1. Dominant-negative action of the jimpy mutation in mice complemented with an autosomal transgene for myelin proteolipid protein.

    OpenAIRE

    Schneider, A. M.; Griffiths, I. R.; Readhead, C.; Nave, K. A.

    1995-01-01

    Mutations in genes encoding membrane proteins have been associated with cell death of unknown cause from invertebrate development to human degenerative diseases. A point mutation in the gene for myelin proteolipid protein (PLP) underlies oligodendrocyte death and dysmyelination in jimpy mice, an accurate model for Pelizaeus-Merzbacher disease. To distinguish the loss of PLP function from other effects of the misfolded protein, we took advantage of the X chromosomal linkage of the gene and hav...

  2. Targeting Myelin Proteolipid Protein to the MHC Class I Pathway by Ubiquitination Modulates the Course of Experimental Autoimmune Encephalomyelitis

    OpenAIRE

    Theil, Diethilde J.; Libbey, Jane E.; Rodriguez, Fernando; Whitton, J. Lindsay; Tsunoda, Ikuo; Derfuss, Tobias J.; Fujinami, Robert S.

    2008-01-01

    Relapsing-remitting experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis model, is induced in mice by injection of myelin proteolipid protein (PLP) encephalitogenic peptide, PLP139–151, in adjuvant. In this study, prior to EAE induction, mice were vaccinated with a bacterial plasmid encoding a PLP-ubiquitin fusion (pCMVUPLP). During the relapse phase of EAE, clinical signs, histopathologic changes, in vitro lymphoproliferation to PLP139–151 and interferon-? levels were r...

  3. Mielinização, desmielinização e remielinização no sistema nervoso central / Myelination, demyelination and remyelination in the central nervous system

    Scientific Electronic Library Online (English)

    Dominguita Lühers, Graça.

    1988-09-01

    Full Text Available As bainhas de mielina que envolvem axônios no SNC são feitas e mantidas por oligodendrócitos. Estas células gliais formam um número variável de segmentos de mielina (internódulos): entre 1 e 200, de modo que quando uma célula é lesada junto com ela podem ser destruídos numerosos internódulos, consti [...] tuindo um processo desmielinizante. Como conseqüência da destruição da célula-bainha e internódulos relacionados há uma resposta celular rápida e abundante. Esta resposta é feita por fagócitos residentes (microglia) e hematógenos. Ambas as células fagocitam os detritos celulares e de. mielina, deixando os axônios desmielinizados. Estes axônios podem permanecer desprovidos de suas bainhas e aglutinados, podem ser separados por processos de astrócitos ou podem ser remielinizados. A ocorrência do processo de remielinização depende da intensidade e tempo de exposição ao agente desmielinizante. A remielinização, com total restabelecimento da condução, pode ser realizada por oligodendrócito ou por célula de Schwann que invade o SNC sempre que os astrócitos são destruídos. Abstract in english The myelin sheaths that surround axons in the CNS are made and maintained by oligodendrocytes. These glial cells can form variable numbers of myelin segments (internodules): from 1 to 200 so that when one oligodendrocyte is destroyed with preservation of the axon, many internodules can be lost, cons [...] tituting a demyelinating process. As a consequence of the destruction of myelin and sheath cells a rapid and abundant cell response takes place. The response is made up by resident (microglia) and haematogenous phagocytes which phagocytose myelin and cellular debris leaving the axons demyelinated. Demyelinated axons may either stay demyelinated and clumped together or they may be separated by astrocytic processes, yet they can be remyelinated. The occurrence of remyelination depends upon the intensity and time of exposition to the demyelinating agent. Remyelination in the CNS with complete restoration of conduction may be made by oligodendrocytes or Schwann cells which invade the CNS when astrocytes are destroyed.

  4. Slowed Conduction and Thin Myelination of Peripheral Nerves Associated with Mutant Rho Guanine-Nucleotide Exchange Factor 10

    OpenAIRE

    Verhoeven, Kristien; De jonghe, Peter; Van de putte, Tom; Nelis, Eva; Zwijsen, An; Verpoorten, Nathalie; De vriendt, Els; Jacobs, An; Van gerwen, Veerle; Francis, Annick; Ceuterick, Chantal; Huylebroeck, Danny; Timmerman, Vincent

    2003-01-01

    Slowed nerve-conduction velocities (NCVs) are a biological endophenotype in the majority of the hereditary motor and sensory neuropathies (HMSN). Here, we identified a family with autosomal dominant segregation of slowed NCVs without the clinical phenotype of HMSN. Peripheral-nerve biopsy showed predominantly thinly myelinated axons. We identified a locus at 8p23 and a Thr109Ile mutation in ARHGEF10, encoding a guanine-nucleotide exchange factor (GEF) for the Rho family of GTPase proteins (Rh...

  5. Controlled Splitting of an Atomic Wave Packet

    International Nuclear Information System (INIS)

    We propose a simple scheme capable of adiabatically splitting an atomic wave packet using two independent translating traps. Implemented with optical dipole traps, our scheme allows a high degree of flexibility for atom interferometry arrangements and highlights its potential as an efficient and high fidelity atom optical beam splitter

  6. 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).

  7. Conversion efficiency in a solar splitting system

    Science.gov (United States)

    Kurin, S. Yu; Doronin, V. D.; Ivanov, S. A.; Helava, H. I.; Papchenko, B. P.; Antipov, A. A.; Usikov, A. S.; Makarov, Yu N.

    2014-12-01

    In this paper we report on concentrator photovoltaic system made by splitting the solar system based on separate Si, GaAs, and InGaN solar cells. The SSCPV module was fabricated and conversion efficiency up to 24.8% was achieved for the concentration factor of 12.8 that is in correlation with theoretical predictions.

  8. Polynomial splittings of Casson-Gordon invariants

    Science.gov (United States)

    Kim, Se-Goo

    2005-01-01

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

  9. Uniruled varieties with splitting tangent bundle

    OpenAIRE

    Hoering, Andreas

    2005-01-01

    Beauville asked if a compact Kaehler manifold with splitting tangent bundle has a universal covering that is a product of manifolds. We use Mori theory and elementary results about holomorphic foliations to study this problem for projective uniruled varieties. In particular we obtain an affirmative answer for rationally connected varieties in any dimension and uniruled varieties in dimension 4.

  10. Unified Split Octonion Formulation of Dyons

    CERN Document Server

    Bisht, P S; Negi, O P S; Dangwal, Shalini

    2006-01-01

    Demonstrating the split octonion formalism for unified fields of dyons (electromagnetic fields) and gravito-dyons (gravito-Heavisidian fields of linear gravity), relevant field equations are derived in compact, simpler and manifestly covariant forms. It has been shown that this unified model reproduces the dynamics of structure of fields associated with individual charges (masses) in the absence of others.

  11. 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.

  12. Anomalous Kondo Spin Splitting in Quantum Dots

    CERN Document Server

    Hualde, J M A; Anda, E V

    2006-01-01

    The Zeeman splitting of localized electrons in a quantum dot in the Kondo regime is studied using a new slave-boson formulation. Our results show that the Kondo peak splitting depends on the gate potential applied to the quantum dot and on the topology of the system. A common fact of any geometry is that the differential susceptibility shows a strong non linear behavior. It was shown that there exist a critical field above which the Kondo resonance is splitted out. This critical field rapidly diminishes when the gate potential is lowered, as a consequence of the reduction of the Kondo temperature and a subsequent strong enhancement in the differential susceptibility occurring at low fields. The critical field is also strong depedent on the topology of the circuit. Above this critical field the Zeeman splitting depends linearly upon the magnetic field and does not extrapolate to zero at zero field. The magnitude of the Y-intercept coordinate depends on the gate potential but the slope of this function is not r...

  13. Source splitting via the point source method

    International Nuclear Information System (INIS)

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

  14. Splitting the Kemmer-Duffin-Petiau Equations

    CERN Document Server

    Okninski, A

    2003-01-01

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

  15. 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...

  16. Structure of split supersymmetry and simple models

    International Nuclear Information System (INIS)

    We derive in detail a condition on the Higgs mass parameters that is necessary for the recently proposed ''split supersymmetry'' (split SUSY) scenario to provide a realistic magnitude of tan ?. The nature of this condition can be understood by showing how the Higgs sector of the minimal supersymmetric Standard Model reduces to that of the Standard Model in the heavy limit of the soft supersymmetry breaking Higgs mass parameters. Based on this condition, we present some simple supersymmetry breaking models that each provides a realistic split-SUSY mass spectrum, in accordance with the scale of the gravitino mass (m3/2) in relation to those of the soft scalar mass (m tilde) and the gaugion mass (M1/2) employed in each, namely m3/2?m tilde, m tilde ? m3/2 ?M1/2 ? and M1/2 ? m3/2, respectively, with the relation m tilde >> M1/2 of the split-SUSY mass spectrum. (author)

  17. 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.

  18. 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

  19. Evidence for locus heterogeneity in human autosomal dominant split hand/split foot malformation.

    OpenAIRE

    Palmer, S. E.; Scherer, S. W.; Kukolich, M.; Wijsman, E. M.; Tsui, L. C.; Stephens, K.; Evans, J. P.

    1994-01-01

    Split hand/split foot (SHSF; also known as ectrodactyly) is a human developmental disorder characterized by missing central digits and other distal limb malformations. An association between SHSF and cytogenetically visible rearrangements of chromosome 7 at bands q21-q22 provides compelling evidence for the location of a causative gene at this location, and the locus has been designated SHFD1. In the present study, marker loci were localized to the SHFD1 critical region through the analysis o...

  20. Extensions of the CQ Algorithm for the split feasibility and split equality problems (10th draft)

    OpenAIRE

    Byrne, Charles L.; Moudafi, Abdellatif

    2012-01-01

    The convex feasibility problem (CFP) is to find a member of the intersection of finitely many closed convex sets in Euclidean space. When the intersection is empty, one can minimize a proximity function to obtain an approximate solution to the problem. The split feasibility problem (SFP) and the split equality problem (SEP) are generalizations of the CFP. The approximate SFP (ASFP) and approximate SEP (ASEP) involve finding only approximate solutions to the SFP and SEP, respectively. We prese...

  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. Purification and spectroscopic characterization of the recombinant BG21 isoform of murine golli myelin basic protein.

    Science.gov (United States)

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

    2007-02-01

    A recombinant form of the murine Golli-myelin basic protein (MBP) isoform BG21 (rmBG21) has been expressed in E. coli, and isolated to 96% purity via metal chelation chromatography. Characteristic yields were 6-8 mg protein per liter of culture in either minimal M9 or standard Luria-Bertani media. Circular dichroism spectroscopy showed that rmBG21 had a large proportion of random coil in aqueous solution, but gained alpha-helix in the presence of monosialoganglioside G(M1) and PI(4)P, as well as in the membrane-mimetic solvent trifluoroethanol. Bioinformatics analyses of the amino acid sequence of rmBG21 predicted an N-terminal calmodulin (CaM)-binding site. It was determined by fluorescence spectroscopy and dynamic light scattering that rmBG21 and CaM interacted weakly in a 1:1 ratio in a Ca(2+)-dependent manner. Solution NMR spectra of uniformly [(13)C(15)N]-labeled protein in aqueous buffer were consistent with it being an extended protein; spectral quality was independent of temperature. Thus, like "classic" MBP and the Golli-MBP isoform J37, rmBG21 is intrinsically disordered, implying multi functionality, and that its conformation depends on its environment and bound ligands. PMID:17131428

  3. A Structural Analysis of DNA Binding by Myelin Transcription Factor 1 Double Zinc Fingers*

    Science.gov (United States)

    Gamsjaeger, Roland; O'Connell, Mitchell R.; Cubeddu, Liza; Shepherd, Nicholas E.; Lowry, Jason A.; Kwan, Ann H.; Vandevenne, Marylene; Swanton, Michael K.; Matthews, Jacqueline M.; Mackay, Joel P.

    2013-01-01

    Myelin transcription factor 1 (MyT1/NZF2), a member of the neural zinc-finger (NZF) protein family, is a transcription factor that plays a central role in the developing central nervous system. It has also recently been shown that, in combination with two other transcription factors, the highly similar paralog MyT1L is able to direct the differentiation of murine and human stem cells into functional neurons. MyT1 contains seven zinc fingers (ZFs) that are highly conserved throughout the protein and throughout the NZF family. We recently presented a model for the interaction of the fifth ZF of MyT1 with a DNA sequence derived from the promoter of the retinoic acid receptor (RARE) gene. Here, we have used NMR spectroscopy, in combination with surface plasmon resonance and data-driven molecular docking, to delineate the mechanism of DNA binding for double ZF polypeptides derived from MyT1. Our data indicate that a two-ZF unit interacts with the major groove of the entire RARE motif and that both fingers bind in an identical manner and with overall two-fold rotational symmetry, consistent with the palindromic nature of the target DNA. Several key residues located in one of the irregular loops of the ZFs are utilized to achieve specific binding. Analysis of the human and mouse genomes based on our structural data reveals three putative MyT1 target genes involved in neuronal development. PMID:24097990

  4. A structural analysis of DNA binding by myelin transcription factor 1 double zinc fingers.

    Science.gov (United States)

    Gamsjaeger, Roland; O'Connell, Mitchell R; Cubeddu, Liza; Shepherd, Nicholas E; Lowry, Jason A; Kwan, Ann H; Vandevenne, Marylene; Swanton, Michael K; Matthews, Jacqueline M; Mackay, Joel P

    2013-12-01

    Myelin transcription factor 1 (MyT1/NZF2), a member of the neural zinc-finger (NZF) protein family, is a transcription factor that plays a central role in the developing central nervous system. It has also recently been shown that, in combination with two other transcription factors, the highly similar paralog MyT1L is able to direct the differentiation of murine and human stem cells into functional neurons. MyT1 contains seven zinc fingers (ZFs) that are highly conserved throughout the protein and throughout the NZF family. We recently presented a model for the interaction of the fifth ZF of MyT1 with a DNA sequence derived from the promoter of the retinoic acid receptor (RARE) gene. Here, we have used NMR spectroscopy, in combination with surface plasmon resonance and data-driven molecular docking, to delineate the mechanism of DNA binding for double ZF polypeptides derived from MyT1. Our data indicate that a two-ZF unit interacts with the major groove of the entire RARE motif and that both fingers bind in an identical manner and with overall two-fold rotational symmetry, consistent with the palindromic nature of the target DNA. Several key residues located in one of the irregular loops of the ZFs are utilized to achieve specific binding. Analysis of the human and mouse genomes based on our structural data reveals three putative MyT1 target genes involved in neuronal development. PMID:24097990

  5. Post-translational Modifications of Chicken Myelin Basic Protein Charge Components

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-07-11

    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 posttranslational modifications for each of the three charge components C1-C3. With the exception of N-terminal acetylation, the post-translational modifications were partial.

  6. 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

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

    International Nuclear Information System (INIS)

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

  8. The sodium channel isoform transition at developing nodes of ranvier in the peripheral nervous system: dependence on a Genetic program and myelination-induced cluster formation.

    Science.gov (United States)

    Luo, Songjiang; Jaegle, Martine; Li, Roy; Ehring, George R; Meijer, Dies; Levinson, Simon R

    2014-12-15

    Among sodium channel isoforms, Nav 1.6 is selectively expressed at nodes of Ranvier in both the CNS and the PNS. However, non-Nav 1.6 isoforms such as Nav 1.2 are also present at the CNS nodes in early development but gradually diminish later. It has been proposed that myelination is part of a glia-neuron signaling mechanism that produces this change in nodal isoform expression. The present study used isoform-specific antibodies to demonstrate that, in the PNS, four other neuronal sodium channel isoforms were also clustered at nodes in early development but eventually disappeared during maturation. To study possible roles of myelination in such transitions, we investigated the nodal expression of selected isoforms in the sciatic nerve of the transgenic mouse Oct6(?SCE/?geo) , whose PNS myelination is delayed in the first postnatal week but eventually resumes. We found that delayed myelination retarded the formation of nodal channel clusters and altered the expression-elimination patterns of sodium channel isoforms, resulting in significantly reduced expression levels of non-Nav 1.6 isoforms in such delayed nodes. However, delayed myelination did not significantly affect the gene expression, protein synthesis, or axonal trafficking of any isoform studied. Rather, we found evidence for a developmentally programmed increase in neuronal Nav 1.6 expression with constant or decreasing neuronal expression of other isoforms that were unaffected by delayed myelination. Thus our results suggest that, in the developmental isoform switch of the PNS, myelination does not play a signaling role as that proposed for the CNS but rather serves only to form nodal clusters from existing isoform pools. PMID:25048219

  9. Iwasawa decompositions of split Kac-Moody groups

    OpenAIRE

    Medts, Tom; Ko?hl, Ralf; Horn, Max

    2007-01-01

    We characterize all fields F for which a group with an F-locally split root group datum admits an Iwasawa decomposition. This class of groups in particular includes the split semisimple algebraic groups and the split Kac-Moody groups.

  10. Solitary waves of the splitted RLW equation

    Science.gov (United States)

    Zaki, S. I.

    2001-07-01

    A combination of the splitting method and the cubic B-spline finite elements is used to solve the non-linear regularized long wave (RLW) equation. This approach involves a Bubnov-Galerkin method with cubic B-spline finite elements so that there is continuity of the dependent variable and its first derivative throughout the solution region. Time integration of the resulting systems is effected using a Crank-Nicholson approximation. In simulations of the migration of a single solitary wave this algorithm is shown to have higher accuracy and better conservation than a recent splitting difference scheme based on cubic spline interpolation functions, for different amplitudes ranging from a very small ( ?0.03) to a considerably high amplitudes ( ?0.3). The development of an undular bore is modeled.

  11. A split SUSY model from SUSY GUT

    CERN Document Server

    Wang, Fei; Yang, Jin Min

    2015-01-01

    We propose to split the sparticle spectrum from the hierarchy between the GUT scale and the Planck scale. A realistic split supersymmetric model, which gives non-universal gaugino masses, is built with proper high dimensional operators in the framework of SO(10) GUT. Based on a calculation of two-loop beta functions for gauge couplings (taking into account all threshold corrections), we check the gauge coupling unification and dark matter constraints (relic density and direct detections). We find that our scenario can achieve the gauge coupling unification and satisfy the dark matter constraints in some part of parameter space. We also examine the sensitivity of the future XENON1T experiment and find that the currently allowed parameter space in our scenario can be covered for a neutralino dark matter below about 1.0 TeV.

  12. Timelike single-logarithm-resummed splitting functions

    Energy Technology Data Exchange (ETDEWEB)

    Albino, S.; Bolzoni, P.; Kniehl, B.A. [Hamburg Univ. (Germany). 2. Inst. fuer Theoretische Physik; Kotikov, A.V. [Hamburg Univ. (Germany). 2. Inst. fuer Theoretische Physik; Joint Inst. of Nuclear Research, Moscow (Russian Federation). Bogoliubov Lab. of Theoretical Physics

    2011-08-15

    We calculate the single logarithmic contributions to the quark singlet and gluon matrix of timelike splitting functions at all orders in the modified minimal-subtraction (MS) scheme. We fix two of the degrees of freedom of this matrix from the analogous results in the massive-gluon regularization scheme by using the relation between that scheme and the MS scheme. We determine this scheme transformation from the double logarithmic contributions to the timelike splitting functions and the coefficient functions of inclusive particle production in e{sup +}e{sup -} annihilation now available in both schemes. The remaining two degrees of freedom are fixed by reasonable physical assumptions. The results agree with the fixed-order results at next-to-next-to-leading order in the literature. (orig.)

  13. Timelike single-logarithm-resummed splitting functions

    International Nuclear Information System (INIS)

    We calculate the single logarithmic contributions to the quark singlet and gluon matrix of timelike splitting functions at all orders in the modified minimal-subtraction (MS) scheme. We fix two of the degrees of freedom of this matrix from the analogous results in the massive-gluon regularization scheme by using the relation between that scheme and the MS scheme. We determine this scheme transformation from the double logarithmic contributions to the timelike splitting functions and the coefficient functions of inclusive particle production in e+e- annihilation now available in both schemes. The remaining two degrees of freedom are fixed by reasonable physical assumptions. The results agree with the fixed-order results at next-to-next-to-leading order in the literature. (orig.)

  14. 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.

  15. 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.

  16. Splitting TCP Connections Adaptively Inside Networks

    Science.gov (United States)

    Shimamura, Masayoshi; Ikenaga, Takeshi; Tsuru, Masato

    The explosive growth of Internet usage has caused problems for the current Internet in terms of traffic congestion within networks and performance degradation of end-to-end flows. Therefore, a reconsideration of the current Internet has begun and is being actively discussed worldwide with the goals of enabling efficient share of limited network resources (i.e., the link bandwidth) and improved performance. To directly address the inefficiency of TCP's congestion mitigation solely on the end-to-end basis, in this paper we propose an adaptive split connection scheme on advanced relay nodes; this scheme dynamically splits end-to-end TCP connections on the basis of congestion status in output links. Through simulation evaluations, we examine the effectiveness and potential of the proposed scheme.

  17. A split SUSY model from SUSY GUT

    Science.gov (United States)

    Wang, Fei; Wang, Wenyu; Yang, Jin Min

    2015-03-01

    We propose to split the sparticle spectrum from the hierarchy between the GUT scale and the Planck scale. A split supersymmetric model, which gives non-universal gaugino masses, is built with proper high dimensional operators in the framework of SO(10) GUT. Based on a calculation of two-loop beta functions for gauge couplings (taking into account all weak scale threshold corrections), we check the gauge coupling unification and dark matter constraints (relic density and direct detections). We find that our scenario can achieve the gauge coupling unification and satisfy the dark matter constraints in some part of parameter space. We also examine the sensitivity of the future XENON1T experiment and find that the currently allowed parameter space in our scenario can be covered for a neutralino dark matter below about 1.0 TeV.

  18. Spin Polarization of the Split Kondo State

    Science.gov (United States)

    von Bergmann, Kirsten; Ternes, Markus; Loth, Sebastian; Lutz, Christopher P.; Heinrich, Andreas J.

    2015-02-01

    Spin-resolved scanning tunneling microscopy is employed to quantitatively determine the spin polarization of the magnetic field-split Kondo state. Tunneling conductance spectra of a Kondo-screened magnetic atom are evaluated within a simple model taking into account inelastic tunneling due to spin excitations and two Kondo peaks positioned symmetrically around the Fermi energy. We fit the spin state of the Kondo-screened atom with a spin Hamiltonian independent of the Kondo effect and account for Zeeman splitting of the Kondo peak in the magnetic field. We find that the width and the height of the Kondo peaks scales with the Zeeman energy. Our observations are consistent with full spin polarization of the Kondo peaks, i.e., a majority spin peak below the Fermi energy and a minority spin peak above.

  19. Flux-splitting schemes for parabolic problems

    Science.gov (United States)

    Vabishchevich, P. N.

    2012-08-01

    Splitting with respect to space variables can be used in solving boundary value problems for second-order parabolic equations. Classical alternating direction methods and locally one-dimensional schemes could be examples of this approach. For problems with rapidly varying coefficients, a convenient tool is the use of fluxes (directional derivatives) as independent variables. The original equation is written as a system in which not only the desired solution but also directional derivatives (fluxes) are unknowns. In this paper, locally one-dimensional additional schemes (splitting schemes) for second-order parabolic equations are examined. By writing the original equation in flux variables, certain two-level locally one-dimensional schemes are derived. The unconditional stability of locally one-dimensional flux schemes of the first and second approximation order with respect to time is proved.

  20. Split rank of triange and quadrilateral inequalities

    OpenAIRE

    Louveaux, Quentin

    2009-01-01

    A simple relaxation consisting of two rows of a simplex tableau is a mixed-integer set with two equations, two free integer variables, and nonnegative continuous variables. Recently, Andersen et al. and Cornue?jols and Margot showed that the facet- defining inequalities of this set are either split cuts or intersection cuts obtained from lattice-free triangles and quadrilaterals. From an example given by Cook, Kannan and Schrijver it is known that one particular class of facet-defining trian...

  1. Molecular catalytic system for efficient water splitting

    OpenAIRE

    Joya, Khurram Saleem

    2011-01-01

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

  2. Controllable valley splitting in silicon quantum devices

    OpenAIRE

    Goswami, Srijit; Slinker, K. A.; Friesen, Mark; Mcguire, L. M.; Truitt, J. L.; Tahan, Charles; Klein, L. J.; Chu, J. O.; Mooney, P. M.; Weide, D. W.; Joynt, Robert; Coppersmith, S. N.; Eriksson, Mark A.

    2006-01-01

    Silicon has many attractive properties for quantum computing, and the quantum dot architecture is appealing because of its controllability and scalability. However, the multiple valleys in the silicon conduction band are potentially a serious source of decoherence for spin-based quantum dot qubits. Only when these valleys are split by a large energy does one obtain well-defined and long-lived spin states appropriate for quantum computing. Here we show that the small valley s...

  3. Intervalley splittings of Si quantum wells

    OpenAIRE

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

    2007-01-01

    Multi-valley effective mass theory for silicon quantum well structure is studied taking into account the external fields and the quantum interfaces. It is found that the phenomenological delta function potential, employed to explain the valley splitting caused by the quantum well interface in the previous work [Ref. 10], can be derived self-consistently from the multi-valley effective mass theory. Finite element method is used to solve the multi-valley effective equations. T...

  4. Almost split sequences for Knorr lattices

    OpenAIRE

    Poulton, Andrew

    2013-01-01

    Let $O$ be a complete d.v.r. and $G$ a finite group. We give two applications of an adjunction in the stable category of $OG$. The first application gives necessary and sufficient conditions for the middle term of an almost split sequence terminating in a Knorr lattice to be indecomposable. The second characterises the stable endomorphism rings of Heller lattices of kG-modules.

  5. A thermodynamically compatible splitting procedure in hyperelasticity

    Science.gov (United States)

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

    2014-08-01

    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.

  6. Graduate Program in Astrophysics in Split

    OpenAIRE

    Krajnovic, Davor

    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 skil...

  7. 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.

  8. Multiplet mass splitting in a gravitational field

    International Nuclear Information System (INIS)

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

  9. Penalized Split Criteria for Interpretable Trees

    OpenAIRE

    Goldstein, Alex; Buja, Andreas

    2013-01-01

    This paper describes techniques for growing classification and regression trees designed to induce visually interpretable trees. This is achieved by penalizing splits that extend the subset of features used in a particular branch of the tree. After a brief motivation, we summarize existing methods and introduce new ones, providing illustrative examples throughout. Using a number of real classification and regression datasets, we find that these procedures can offer more inte...

  10. 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

  11. Dark Matter in split extended supersymmetry

    OpenAIRE

    Provenza, A.; Quiros, M.; Ullio, P.

    2006-01-01

    We consider the split extended (N=2) supersymmetry scenario recently proposed by Antoniadis et al. [hep-ph/0507192] as a realistic low energy framework arising from intersecting brane models. While all scalar superpartners and charged gauginos are naturally at a heavy scale, the model low energy spectrum contains a Higgsino-like chargino and a neutralino sector made out of two Higgsino and two Bino states. We show that the lightest neutralino is a viable dark matter candidat...

  12. Phase Splitting for Periodic Lie Systems

    CERN Document Server

    Flores-Espinoza, R; Vorobjev, Yurii

    2009-01-01

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

  13. Split angular momentum in noncommutative phase space

    International Nuclear Information System (INIS)

    In the very tiny string scale, the effect of noncommutativity of space may appear. The expression of angular momentum in Schwinger representation is briefly reviewed first, then the quantum mechanics algebra in noncommutative phase space is discussed; moreover, the angular momentum in noncommutative phase space is represented in terms of creation and annihilation operations of commutative space. At last, the angular momentum splitting effect is discussed in detail. (authors)

  14. Plasmonic resonance in planer split ring trimer

    Science.gov (United States)

    Xu, Haiqing; Li, Hongjian; Xiao, Gang

    2014-12-01

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

  15. 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...

  16. Resolving contact conflict for double patterning split

    Science.gov (United States)

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

    2009-10-01

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

  17. On the invariants of the splitting algebra

    CERN Document Server

    Thorup, Anders

    2011-01-01

    For a given monic polynomial $p(t)$ of degree $n$ over a commutative ring $k$, the splitting algebra is the universal $k$-algebra in which $p(t)$ has $n$ roots, or, more precisely, over which $p(t)$ factors, $p(t)=(t-\\xi_1)...(t-\\xi_n)$. The symmetric group $S_r$ for $1\\le r\\le n$ acts on the splitting algebra by permuting the first $r$ roots $\\xi_1,...,\\xi_r$. We give a natural, simple condition on the polynomial $p(t)$ that holds if and only if there are only trivial invariants under the actions. In particular, if the condition on $p(t)$ holds then the elements of $k$ are the only invariants under the action of $S_n$. We show that for any $n\\ge 2$ there is a polynomial $p(t)$ of degree $n$ for which the splitting algebra contains a nontrivial element invariant under $S_n$. The examples violate an assertion by A. D. Barnard from 1974.

  18. 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.

  19. The isomorphism problem for almost split Kac-Moody groups

    CERN Document Server

    Hainke, Guntram

    2011-01-01

    We consider the isomorphism problem for almost split Kac--Moody groups, which have been constructed by R\\'emy via Galois descent from split Kac-Moody groups as defined by Tits. We show that under certain technical assumptions, any isomorphism between two such groups must preserve the canonical subgroup structure, i.e. the twin root datum associated to these groups, which generalizes results of Caprace in the split case. An important technical tool we use is the existence of maximal split subgroups inside almost split Kac-Moody groups, which generalizes the corresponding result of Borel-Tits for reductive algebraic groups.

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Van Broeckhoven Christine

    2002-11-01

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

  2. 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.

  3. 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.

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

    Science.gov (United States)

    Kroken, Rune A; Løberg, Else-Marie; Drønen, Tore; Grüner, Renate; Hugdahl, Kenneth; Kompus, Kristiina; Skrede, Silje; Johnsen, Erik

    2014-01-01

    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. PMID:24550848

  5. Ascl1/Mash1 Promotes Brain Oligodendrogenesis during Myelination and Remyelination

    Science.gov (United States)

    Nakatani, Hiroko; Clavairoly, Adrien; Maire, Cécile L.; Viadieu, Arthur; Kerninon, Christophe; Delmasure, Aurélie; Frah, Magali; Weber, Melanie; Nakafuku, Masato; Zalc, Bernard; Thomas, Jean-Léon; Guillemot, François; Nait-Oumesmar, Brahim; Parras, Carlos

    2013-01-01

    Oligodendrocytes are the myelin-forming cells of the CNS. They differentiate from oligodendrocyte precursor cells (OPCs) that are produced from progenitors throughout life but more actively during the neonatal period and in response to demyelinating insults. An accurate regulation of oligodendrogenesis is required to generate oligodendrocytes during these developmental or repair processes. We hypothesized that this regulation implicates transcription factors, which are expressed by OPCs and/or their progenitors. Ascl1/Mash1 is a proneural transcription factor previously implicated in embryonic oligodendrogenesis and operating in genetic interaction with Olig2, an essential transcriptional regulator in oligodendrocyte development. Herein, we have investigated the contribution of Ascl1 to oligodendrocyte development and remyelination in the postnatal cortex. During the neonatal period, Ascl1 expression was detected in progenitors of the cortical subventricular zone and in cortical OPCs. Different genetic approaches to delete Ascl1 in cortical progenitors or OPCs reduced neonatal oligodendrogenesis, showing that Ascl1 positively regulated both OPC specification from subventricular zone progenitors as well as the balance between OPC differentiation and proliferation. Examination of remyelination processes, both in the mouse model for focal demyelination of the corpus callosum and in multiple sclerosis lesions in humans, indicated that Ascl1 activity was upregulated along with increased oligodendrogenesis observed in remyelinating lesions. Additional genetic evidence indicated that remyelinating oligodendrocytes derived from Ascl1+ progenitors/OPCs and that Ascl1 was required for proper remyelination. Together, our results show that Ascl1 function modulates multiplesteps of OPC development in the postnatal brain and in response to demyelinating insults. PMID:23739972

  6. Evaluation of salt split technique of immunofluorescence in bullous pemphigoid.

    Science.gov (United States)

    Satyapal, Seema; Amladi, Sangeeta; Jerajani, H R

    2002-01-01

    Recent studies suggest that salt split skin is a more sensitive substrate than intact skin for immunofluorescence diagnosis of bullous pemphigoid. We undertook this study to define the role of salt split technique of immunofluorescence findings in 32 clinical and histopathology confirmed cases of bullous pemphigoid. Both direct and indirect immunofluorescences were performed using normal and split skin. Direct immunofluorescence positivity of 100% was noted with both routine and salt split method. Additional immunoreactant deposition was noted with direct method on split skin in 5 cases. Patterns of fluorescence in the latter were roof (40.60%), floor (9.4%) and combined roof and floor (50%). On indirect immunofluorescence, positivity was almost doubled with salt split technique ( 68%) as compared to routine method (36%). Thus, salt split technique was equivalent to routine on direct method in positivity with additional immunoreactant deposits noted in some and had double the sensitivity of the indirect method in detecting immunofluorescence in bullous pemphigoid. PMID:17656991

  7. 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

  8. Copper accumulation and lipid oxidation precede inflammation and myelin lesions in N,N-diethyldithiocarbamate peripheral myelinopathy

    International Nuclear Information System (INIS)

    Dithiocarbamates have a wide spectrum of applications in industry, agriculture and medicine with new applications being actively investigated. One adverse effect of dithiocarbamates is the neurotoxicity observed in humans and experimental animals. Results from previous studies have suggested that dithiocarbamates elevate copper and promote lipid oxidation within myelin membranes. In the current study, copper levels, lipid oxidation, protein oxidative damage and markers of inflammation were monitored as a function of N,N-diethyldithiocarbamate (DEDC) exposure duration in an established model for DEDC-mediated myelinopathy in the rat. Intra-abdominal administration of DEDC was performed using osmotic pumps for periods of 2, 4, and 8 weeks. Metals in brain, liver and tibial nerve were measured using ICP-MS and lipid oxidation assessed through HPLC measurement of malondialdehyde in tibial nerve, and GC/MS measurement of F2 isoprostanes in sciatic nerve. Protein oxidative injury of sciatic nerve proteins was evaluated through quantification of 4-hydroxynonenal protein adducts using immunoassay, and inflammation monitored by quantifying levels of IgGs and activated macrophages using immunoassay and immunohistochemistry methods, respectively. Changes in these parameters were then correlated to the onset of structural lesions, determined by light and electron microscopy, to delineate the temporal relationship of copper accumulation and oxidative stress in peripheramulation and oxidative stress in peripheral nerve to the onset of myelin lesions. The data provide evidence that DEDC mediates lipid oxidation and elevation of total copper in peripheral nerve well before myelin lesions or activated macrophages are evident. This relationship is consistent with copper-mediated oxidative stress contributing to the myelinopathy

  9. 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.

  10. 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 SciELO Cuba | Language: Spanish Abstract in spanish 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.

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

    Science.gov (United States)

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

    2010-01-01

    Myelin basic protein (MBP) maintains the tight multilamellar compaction of the myelin sheath in the central nervous system through peripheral binding of adjacent lipid bilayers of oligodendrocytes. Myelin instability in multiple sclerosis (MS) is associated with the loss of positive charge in MBP as a result of posttranslational enzymatic deimination. A highly-conserved central membrane-binding fragment (murine N81-PVVHFFKNIVTPRTPPP-S99, identical to human N83-S101) represents a primary immunodominant epitope in MS. Previous low-resolution electron paramagnetic resonance measurements on the V83-T92 fragment, with Cys-mutations and spin-labeling that scanned the epitope, were consistent with it being a membrane-associated amphipathic ?-helix. Pseudodeimination at several sites throughout the protein, all distal to the central segment, disrupted the ?-helix at its amino-terminus and exposed it to proteases, representing a potential mechanism in the autoimmune pathogenesis of MS. Here, we have used magic-angle spinning solid-state NMR spectroscopy to characterize more precisely the molecular conformation and dynamics of this central immunodominant epitope of MBP in a lipid milieu, without Cys-substitution. Our solid-state NMR measurements have revealed that the ?-helix present within the immunodominant epitope is shorter than originally modeled, and is independent of the pseudodeimination, highlighting the importance of the local hydrophobic effects in helix formation and stability. The main effect of pseudodeimination is to cause the cytoplasmic exposure of the fragment, potentially making it more accessible to proteolysis. These results are the first, to our knowledge, to provide atomic-level detail of a membrane-anchoring segment of MBP, and direct evidence of decreased MBP-membrane interaction after posttranslational modification. PMID:20713009

  12. Solid-state NMR spectroscopy of membrane-associated myelin basic protein--conformation and dynamics of an immunodominant epitope.

    Science.gov (United States)

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

    2010-08-01

    Myelin basic protein (MBP) maintains the tight multilamellar compaction of the myelin sheath in the central nervous system through peripheral binding of adjacent lipid bilayers of oligodendrocytes. Myelin instability in multiple sclerosis (MS) is associated with the loss of positive charge in MBP as a result of posttranslational enzymatic deimination. A highly-conserved central membrane-binding fragment (murine N81-PVVHFFKNIVTPRTPPP-S99, identical to human N83-S101) represents a primary immunodominant epitope in MS. Previous low-resolution electron paramagnetic resonance measurements on the V83-T92 fragment, with Cys-mutations and spin-labeling that scanned the epitope, were consistent with it being a membrane-associated amphipathic alpha-helix. Pseudodeimination at several sites throughout the protein, all distal to the central segment, disrupted the alpha-helix at its amino-terminus and exposed it to proteases, representing a potential mechanism in the autoimmune pathogenesis of MS. Here, we have used magic-angle spinning solid-state NMR spectroscopy to characterize more precisely the molecular conformation and dynamics of this central immunodominant epitope of MBP in a lipid milieu, without Cys-substitution. Our solid-state NMR measurements have revealed that the alpha-helix present within the immunodominant epitope is shorter than originally modeled, and is independent of the pseudodeimination, highlighting the importance of the local hydrophobic effects in helix formation and stability. The main effect of pseudodeimination is to cause the cytoplasmic exposure of the fragment, potentially making it more accessible to proteolysis. These results are the first, to our knowledge, to provide atomic-level detail of a membrane-anchoring segment of MBP, and direct evidence of decreased MBP-membrane interaction after posttranslational modification. PMID:20713009

  13. 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.

  14. Modeling the action-potential-sensitive nonlinear-optical response of myelinated nerve fibers and short-term memory

    Science.gov (United States)

    Shneider, M. N.; Voronin, A. A.; Zheltikov, A. M.

    2011-11-01

    The Goldman-Albus treatment of the action-potential dynamics is combined with a phenomenological description of molecular hyperpolarizabilities into a closed-form model of the action-potential-sensitive second-harmonic response of myelinated nerve fibers with nodes of Ranvier. This response is shown to be sensitive to nerve demyelination, thus enabling an optical diagnosis of various demyelinating diseases, including multiple sclerosis. The model is applied to examine the nonlinear-optical response of a three-neuron reverberating circuit—the basic element of short-term memory.

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

    OpenAIRE

    Van Broeckhoven Christine; Nelis Eva; Fuchs Christina; Oezbey Sevinc; Ekici Arif B; Schachner Melitta; Rautenstrauss Bernd

    2002-01-01

    Abstract Background Mutations in P0, the major protein of the myelin sheath in peripheral nerves, cause the inherited peripheral neuropathies Charcot-Marie-Tooth disease type 1B (CMT1B), Dejerine-Sottas syndrome (DSS) and congenital hypomyelination (CH). We reported earlier a de novo insertional mutation c.662_663GC (Ala221fs) in a DSS patient. The c.662_663GC insertion results in a frame shift mutation Ala221fs altering the C-terminal amino acid sequence. The adhesion-relevant intracellular ...

  16. Gait Abnormalities and Progressive Myelin Degeneration in a New Murine Model of Pelizaeus-Merzbacher Disease with Tandem Genomic Duplication

    OpenAIRE

    Clark, Kristi; Sakowski, Lauren; Sperle, Karen; Banser, Linda; Landel, Carlisle P.; Bessert, Denise A.; Skoff, Robert P.; Hobson, Grace M.

    2013-01-01

    Pelizaeus-Merzbacher disease (PMD) is a hypomyelinating leukodystrophy caused by mutations of the proteolipid protein 1 gene (PLP1), which is located on the X chromosome and encodes the most abundant protein of myelin in the central nervous sytem. Approximately 60% of PMD cases result from genomic duplications of a region of the X chromosome that includes the entire PLP1 gene. The duplications are typically in a head-to-tail arrangement, and they vary in size and gene content. Although rodent...

  17. Magnesium-dependent non-specific binding of [125I]prolactin to myelinated tracts in the rat central nervous system

    International Nuclear Information System (INIS)

    An in vitro autoradiographic assay was used in identifying a magnesium-dependent, non-specific binding of [125I] prolactin to myelinated fiber tracts in the rat brain. Frozen tissue sections were incubated for 18 h at 4 degrees C in media which included [125I]prolactin alone or with a 500 fold excess of unlabelled prolactin. Magnesium in the incubation medium caused a non-specific binding of radiolabelled prolactin to the myelinated fiber tracts in the brain. In contrast, calcium did not facilitate prolactin non-specific binding to myelin. Hence, calcium should optimize the detection of specific prolactin binding sites in the brain by in vitro autoradiographic or radioreceptor assays

  18. Antibody that neutralizes myelin-associated inhibitors of axon growth does not interfere with recognition of target-specific guidance information by rat retinal axons.

    Science.gov (United States)

    Bähr, M; Schwab, M E

    1996-06-01

    During development, many CNS projection neurons establish topographically ordered maps in their target regions. Myelin-associated inhibitors of neurite growth contribute to the confinement of fiber tracts during development and limit plastic changes after CNS projections have been formed. Neutralization of myelin-associated growth inhibitors leads to an expansion of the retinal innervation of the superior colliculus (SC). In the lesioned adult mammalian CNS, these long projection neurons are usually unable to regrow axons over long distances after lesion due to myelin-associated inhibitors, which interfere with axonal growth in vivo and in vitro. Application of a specific antibody directed against myelin-inhibitors (IN-1) promotes regrowth of corticospinal tract or retinal ganglion cell axons. In the present study, we asked whether application of an antibody to myelin-associated growth inhibitors would lead to disturbances of target-specific axon guidance. To examine this issue, we used an in vitro model, the "stripe assay", to examine the behavior of rat retinal ganglion cell axons on membranes from embryonic and deafferented adult rat SC. On membrane preparations from embryonic rat SC, retinal fibers avoid posterior tectal membranes, possibly due to the presence of a repulsive factor. Nasal retinal axons show a random growth pattern. On membranes prepared from the deafferented adult rat SC, temporal and nasal axons prefer to grow on membranes prepared from their specific target region, which suggests the involvement of target-derived attractive guidance components. The results of the present study show that retinal axons grow significantly faster in the presence of IN-1 antibody that neutralizes myelin-associated growth inhibitors present in the membrane preparations from the adult rat SC. IN-1 antibody, however, does not interfere with specific axonal guidance. This suggests that axonal guidance and specific target finding are independently regulated in retinal axons. PMID:8738756

  19. 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.

  20. Groundstate splitting around rotating mini Blackholes

    CERN Document Server

    Sturm, I

    2007-01-01

    In this letter we present the result of a spin-dependent groundstate-energy calculation for fermionic boundstates in the spacetime around a rotating blackhole. Using a slow rotation approximation and a minimax variational approach we find boundstate energies of 0 to 5 percent of the fermions flatspace restmass. The groundstate displays a spin-dependent splitting with an energy difference of about 10 percent of the binding energy. For a dilute gas of primordial mini blackholes with gravitationally bound electrons spin-flip transitions could possibly give rise to observable signatures in the observed soft X-ray spectrum for sources at cosmological distances.