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Sample records for paranodal myelin splitting

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

    OpenAIRE

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

    2014-01-01

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

  2. HDAC1/2-Dependent P0 Expression Maintains Paranodal and Nodal Integrity Independently of Myelin Stability through Interactions with Neurofascins

    Science.gov (United States)

    Brgger, Valrie; Engler, Stefanie; Pereira, Jorge A.; Ruff, Sophie; Horn, Michael; Welzl, Hans; Mnger, Emmanuelle; Vaqui, Adrien; Sidiropoulos, Pris N. M.; Egger, Boris; Yotovski, Peter; Filgueira, Luis; Somandin, Christian; Lhmann, Tessa C.; DAntonio, Maurizio; Yamaguchi, Teppei; Matthias, Patrick; Suter, Ueli; Jacob, Claire

    2015-01-01

    The pathogenesis of peripheral neuropathies in adults is linked to maintenance mechanisms that are not well understood. Here, we elucidate a novel critical maintenance mechanism for Schwann cell (SC)axon interaction. Using mouse genetics, ablation of the transcriptional regulators histone deacetylases 1 and 2 (HDAC1/2) in adult SCs severely affected paranodal and nodal integrity and led to demyelination/remyelination. Expression levels of the HDAC1/2 target gene myelin protein zero (P0) were reduced by half, accompanied by altered localization and stability of neurofascin (NFasc)155, NFasc186, and loss of Caspr and septate-like junctions. We identify P0 as a novel binding partner of NFasc155 and NFasc186, both in vivo and by in vitro adhesion assay. Furthermore, we demonstrate that HDAC1/2-dependent P0 expression is crucial for the maintenance of paranodal/nodal integrity and axonal function through interaction of P0 with neurofascins. In addition, we show that the latter mechanism is impaired by some P0 mutations that lead to late onset Charcot-Marie-Tooth disease. PMID:26406915

  3. 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 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

  4. 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.

  5. Assembly of juxtaparanodes in myelinating DRG culture: Differential clustering of the Kv1/Caspr2 complex and scaffolding protein 4.1B.

    Science.gov (United States)

    Hivert, Bruno; Pinatel, Delphine; Labasque, Marilyne; Tricaud, Nicolas; Goutebroze, Laurence; Faivre-Sarrailh, Catherine

    2016-05-01

    The precise distribution of ion channels at the nodes of Ranvier is essential for the efficient propagation of action potentials along myelinated axons. The voltage-gated potassium channels Kv1.1/1.2 are clustered at the juxtaparanodes in association with the cell adhesion molecules, Caspr2 and TAG-1 and the scaffolding protein 4.1B. In the present study, we set up myelinating cultures of DRG neurons and Schwann cells to look through the formation of juxtaparanodes in vitro. We showed that the Kv1.1/Kv1.2 channels were first enriched at paranodes before being restricted to distal paranodes and juxtaparanodes. In addition, the Kv1 channels displayed an asymmetric expression enriched at the distal juxtaparanodes. Caspr2 was strongly co-localized with Kv1.2 whereas the scaffolding protein 4.1B was preferentially recruited at paranodes while being present at juxtaparanodes too. Kv1.2/Caspr2 but not 4.1B, also transiently accumulated within the nodal region both in myelinated cultures and developing sciatic nerves. Studying cultures and sciatic nerves from 4.1B KO mice, we further showed that 4.1B is required for the proper targeting of Caspr2 early during myelination. Moreover, using adenoviral-mediated expression of Caspr-GFP and photobleaching experiments, we analyzed the stability of paranodal junctions and showed that the lateral stability of paranodal Caspr was not altered in 4.1B KO mice indicating that 4.1B is not required for the assembly and stability of the paranodal junctions. Thus, developing an adapted culture paradigm, we provide new insights into the dynamic and differential distribution of Kv1 channels and associated proteins during myelination. GLIA 2016;64:840-852. PMID:26840208

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

    Energy Technology Data Exchange (ETDEWEB)

    Denninger, Andrew R. [Boston College, Chestnut Hill, MA 02467 (United States); Demé, Bruno; Cristiglio, Viviana [Institut Laue–Langevin (ILL), CS 20156, F-38042 Grenoble CEDEX 9 (France); LeDuc, Géraldine [European Synchrotron Radiation Facility (ESRF), CS 40220, F-38043 Grenoble CEDEX 9 (France); Feller, W. Bruce [NOVA Scientific Inc., Sturbridge, MA 01566 (United States); Kirschner, Daniel A., E-mail: kirschnd@bc.edu [Boston College, Chestnut Hill, MA 02467 (United States)

    2014-12-01

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

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

    International Nuclear Information System (INIS)

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

  8. Altered potassium channel distribution and composition in myelinated axons suppresses hyperexcitability following injury

    Science.gov (United States)

    Calvo, Margarita; Richards, Natalie; Schmid, Annina B; Barroso, Alejandro; Zhu, Lan; Ivulic, Dinka; Zhu, Ning; Anwandter, Philipp; Bhat, Manzoor A; Court, Felipe A; McMahon, Stephen B; Bennett, David LH

    2016-01-01

    Neuropathic pain following peripheral nerve injury is associated with hyperexcitability in damaged myelinated sensory axons, which begins to normalise over time. We investigated the composition and distribution of shaker-type-potassium channels (Kv1 channels) within the nodal complex of myelinated axons following injury. At the neuroma that forms after damage, expression of Kv1.1 and 1.2 (normally localised to the juxtaparanode) was markedly decreased. In contrast Kv1.4 and 1.6, which were hardly detectable in the naïve state, showed increased expression within juxtaparanodes and paranodes following injury, both in rats and humans. Within the dorsal root (a site remote from injury) we noted a redistribution of Kv1-channels towards the paranode. Blockade of Kv1 channels with α-DTX after injury reinstated hyperexcitability of A-fibre axons and enhanced mechanosensitivity. Changes in the molecular composition and distribution of axonal Kv1 channels, therefore represents a protective mechanism to suppress the hyperexcitability of myelinated sensory axons that follows nerve injury. DOI: http://dx.doi.org/10.7554/eLife.12661.001 PMID:27033551

  9. 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. Normal value ranges may vary ...

  10. Uncompacted Myelin Lamellae and Nodal Ion Channel Disruption in POEMS Syndrome.

    Science.gov (United States)

    Hashimoto, Rina; Koike, Haruki; Takahashi, Mie; Ohyama, Ken; Kawagashira, Yuichi; Iijima, Masahiro; Sobue, Gen

    2015-12-01

    To elucidate the significance of uncompacted myelin lamellae (UML) and ion channel disruption at the nodes of Ranvier in the polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, we evaluated sural nerve biopsy specimens from 33 patients with POEMS syndrome and from 7 control patients. Uncompacted myelin lamellae distribution was assessed by electron microscopy and immunofluorescence microscopy. In the POEMS patient biopsies, UML were seen more frequently in small versus large myelinated fibers. Paranodes and Schmidt-Lanterman incisures, where normal physiologic UM is located, were frequently associated with UM. Widening of the nodes of Ranvier (i.e. segmental demyelination) was not associated with UML. There was axonal hollowing with neurofilament condensation at Schmidt-Lanterman incisures with abnormal UML, suggesting axonal damage at those sites in the POEMS patient biopsies. Myelin sheath irregularity was conspicuous in large myelinated fibers and was associated with abnormally widened bizarrely shaped Schmidt-Lanterman incisures. Indirect immunofluorescent studies revealed abnormalities of sodium (pan sodium) and potassium (KCNQ2) channels, even at nonwidened nodes of Ranvier. Thus, UML was not apparently associated with segmental demyelination but seemed to be associated with axonal damage. These observations suggest that nodal ion channel disruption may be associated with functional deficits in POEMS syndrome patient nerves. PMID:26574667

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

    Science.gov (United States)

    Ishibashi, Tomoko; Kodama, Akiko; Baba, Hiroko

    2015-01-01

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

  12. Major myelin protein gene (P0) mutation causes a novel form of axonal degeneration.

    Science.gov (United States)

    Li, Jun; Bai, Yunhong; Ianakova, Emilia; Grandis, Marina; Uchwat, Fred; Trostinskaia, Anna; Krajewski, Karen M; Garbern, James; Kupsky, William J; Shy, Michael E

    2006-09-10

    Mutations in the major peripheral nervous system (PNS) myelin protein, myelin protein zero (MPZ), cause Charcot-Marie-Tooth Disease type 1B (CMT1B), typically thought of as a demyelinating peripheral neuropathy. Certain MPZ mutations, however, cause adult onset neuropathy with minimal demyelination but pronounced axonal degeneration. Mechanism(s) for this phenotype are unknown. We performed an autopsy of a 73-year-old woman with a late-onset neuropathy caused by an H10P MPZ mutation whose nerve conduction studies suggested severe axonal loss but no demyelination. The autopsy demonstrated axonal loss and reorganization of the molecular architecture of the axolemma. Segmental demyelination was negligible. In addition, we identified focal nerve enlargements containing MPZ and ubiquitin either in the inner myelin intralaminar and/or periaxonal space that separates axons from myelinating Schwann cells. Taken together, these data confirmed that a mutation in MPZ can cause axonal neuropathy, in the absence of segmental demyelination, thus uncoupling the two pathological processes. More important, it also provided potential molecular mechanisms as to how the axonal degeneration occurred: either by disruption of glial-axon interaction by protein aggregates or by alterations in the molecular architecture of internodes and paranodes. This report represents the first study in which the molecular basis of axonal degeneration in the late-onset CMT1B has been explored in human tissue. PMID:16856127

  13. Glycosphingolipid synthesis in cerebellar Purkinje neurons: roles in myelin formation and axonal homeostasis.

    Science.gov (United States)

    Watanabe, Shun; Endo, Shogo; Oshima, Eriko; Hoshi, Tomiko; Higashi, Hideyoshi; Yamada, Kazuyuki; Tohyama, Koujiro; Yamashita, Tadashi; Hirabayashi, Yoshio

    2010-08-01

    Glycosphingolipids (GSLs) occur in all mammalian plasma membranes. They are most abundant in neuronal cells and have essential roles in brain development. Glucosylceramide (GlcCer) synthase, which is encoded by the Ugcg gene, is the key enzyme driving the synthesis of most neuronal GSLs. Experiments using conditional Nestin-Cre Ugcg knockout mice have shown that GSL synthesis in vivo is essential, especially for brain maturation. However, the roles of GSL synthesis in mature neurons remain elusive, since Nestin-Cre is expressed in neural precursors as well as in postmitotic neurons. To address this problem, we generated Purkinje cell-specific Ugcg knockout mice using mice that express Cre under the control of the L7 promoter. In these mice, Purkinje cells survived for at least 10-18 weeks after Ugcg deletion. We observed apparent axonal degeneration characterized by the accumulation of axonal transport cargos and aberrant membrane structures. Dendrites, however, were not affected. In addition, loss of GSLs disrupted myelin sheaths, which were characterized by detached paranodal loops. Notably, we observed doubly myelinated axons enveloped by an additional concentric myelin sheath around the original sheath. Our data show that axonal GlcCer-based GSLs are essential for axonal homeostasis and correct myelin sheath formation. PMID:20544855

  14. Diffusion of myelin water.

    Science.gov (United States)

    Andrews, Trevor J; Osborne, Michael T; Does, Mark D

    2006-08-01

    We studied compartmentally specific characteristics of water diffusion in excised frog sciatic nerve by combining T1 or T2 selective acquisitions with pulse-gradient spin-echo (PGSE) diffusion weighting, with the specific objective of characterizing myelin water diffusion. Combining a PGSE with a Carr-Purcell-Meiboom-Gill (CPMG) acquisition provided apparent diffusion coefficients (ADCs) for each of the three T2 components found in nerve, including the short-lived component believed to be derived from myelin water. Double-inversion-recovery (DIR) preparation provided an alternate means of discriminating myelin water, and in combination with PGSE provided somewhat different measures of ADC. The DIR measures yielded myelin water ADCs of 0.37 microm2/ms (parallel to nerve) and 0.13 microm2/ms (perpendicular to nerve). These ADC estimates were postulated to be more accurate than those based on T2 discrimination, although the difference between the two findings is not clear. PMID:16767712

  15. Glycans of myelin proteins.

    Science.gov (United States)

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

    2015-01-01

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

  16. Myelin glycolipids and their functions.

    Science.gov (United States)

    Stoffel, W; Bosio, A

    1997-10-01

    During myelination, oligodendrocytes in the CNS and Schwann cells in the PNS synthesise myelin-specific proteins and lipids for the assembly of the axon myelin sheath. A dominant class of lipids in the myelin bilayer are the glycolipids, which include galactocerebroside (GalC), galactosulfatide (sGalC) and galactodiglyceride (GalDG). A promising approach for unravelling the roles played by various lipids in the myelin membrane involves knocking out the genes encoding important enzymes in lipid biosynthesis. The recent ablation of the ceramide galactosyltransferase ( cgt) gene in mice is the first example. The cgt gene encodes a key enzyme in glycolipid biosynthesis. Its absence causes glycolipid deficiency in the lipid bilayer, breakdown of axon insulation and loss of saltatory conduction. Additional knock-out studies should provide important insights into the various functions of glycolipids in myelinogenesis and myelin structure. PMID:9384539

  17. Magnetic resonance imaging and myelin

    International Nuclear Information System (INIS)

    Postnatal development of the brain is characterized by growth and by myelination. Myelination of the brain normally extends from birth until about two years of age. MRI changes corresponding to the various myelination stages are due mainly to changes in the water content of the cerebral parenchyma. Myelination kinetics follow a fairly precise timetable, with variations across areas of the brain. Abnormalities of white matter are responsible for relatively stereotyped, nonspecific manifestations, which are mainly due to an increase in the amount of water contained in diseased white matter, whatever the cause of the disorder. Interpretation is based on the location, distribution, and progression of lesions. (authors). 7 refs., 5 figs

  18. F3/contactin, a neuronal cell adhesion molecule implicated in axogenesis and myelination.

    Science.gov (United States)

    Falk, Julien; Bonnon, Carine; Girault, Jean-Antoine; Faivre-Sarrailh, Catherine

    2002-10-01

    A general feature of the cell adhesion molecules belonging to the immunoglobulin family (Ig-CAMs) is to display a modular structure that provides a framework for multiple binding sites for other recognition molecules. Among this family, F3/contactin is a glycan phosphatidyl-inositol (GPI)-anchored molecule expressed by neurons that displays the distinctiveness to exert heterophilic but no homophilic binding activities. The Ig domains of F3/contactin were shown to interact with the L1 family of Ig-CAMs, including L1, NrCAM, and neurofascin. Binding between F3/contactin and NrCAM is known to modulate axonal elongation of the cerebellar granule cells and to control sensory axon guidance. F3/contactin mediates neuron-glial contacts through its association with extracellular matrix components (tenascin-R, tenascin-C) and RPTPbeta/phosphacan, influencing axonal growth and fasciculation. Another major role of F3/contactin is to organize axonal subdomains at the node of Ranvier of myelinated fibers in interplay with other Ig-CAMs, through its binding with caspr/paranodin at paranodes and the voltage-gated sodium channels in the nodal region. The F3/contactin deficient mice display a severe ataxia correlated with defects in axonal and dendritic projections in the cerebellum. These mice also display defects in nerve influx conduction due to the disruption of the axo-glial contacts at paranodes. Finally, the recent identification of a Drosophila homologue of F3/contactin indicated that this family of GPI-anchored CAMs plays a conserved function in axonal insulation. PMID:12500940

  19. Dynamic properties of a reconstituted myelin sheath

    OpenAIRE

    Knoll, W.; Natali, F.; Peters, J; Nanekar, R. (Rahul); Wang, C; Kursula, P.

    2010-01-01

    Myelin is a multilamellar membrane which, wrapping the nerve axons, increases the efficiency of nervous signal transmission. Indeed, the molecular components of the myelin sheath interact tightly with each other and molecules on the axonal surface to drive myelination, to keep both myelin and the axon intact, and to transduce signals from myelin to the axon and vice versa. Myelin is strongly affected in human demyelinating diseases in both the central and peripheral nervous system (CNS and PN...

  20. Nuc-ErbB3 regulates H3K27me3 levels and HMT activity to establish epigenetic repression during peripheral myelination.

    Science.gov (United States)

    Ness, Jennifer K; Skiles, Amanda A; Yap, Eng-Hui; Fajardo, Eduardo J; Fiser, Andras; Tapinos, Nikos

    2016-06-01

    Nuc-ErbB3 an alternative transcript from the ErbB3 locus binds to a specific DNA motif and associates with Schwann cell chromatin. Here we generated a nuc-ErbB3 knockin mouse that lacks nuc-ErbB3 expression in the nucleus without affecting the neuregulin-ErbB3 receptor signaling. Nuc-ErbB3 knockin mice exhibit hypermyelination and aberrant myelination at the paranodal region. This phenotype is attributed to de-repression of myelination associated gene transcription following loss of nuc-ErbB3 and histone H3K27me3 promoter occupancy. Nuc-ErbB3 knockin mice exhibit reduced association of H3K27me3 with myelination-associated gene promoters and increased RNA Pol-II rate of transcription of these genes. In addition, nuc-ErbB3 directly regulates levels of H3K27me3 in Schwann cells. Nuc-ErbB3 knockin mice exhibit significant decrease of histone H3K27me3 methyltransferase (HMT) activity and reduced levels of H3K27me3. Collectively, nuc-ErbB3 is a master transcriptional repressor, which regulates HMT activity to establish a repressive chromatin landscape on promoters of genes during peripheral myelination. GLIA 2016;64:977-992. PMID:27017927

  1. Developmental impairment of compound action potential in the optic nerve of myelin mutant taiep rats.

    Science.gov (United States)

    Roncagliolo, Manuel; Schlageter, Carol; León, Claudia; Couve, Eduardo; Bonansco, Christian; Eguibar, José R

    2006-01-01

    The taiep rat is a myelin mutant with an initial hypomyelination, followed by a progressive demyelination of the CNS. The neurological correlates start with tremor, followed by ataxia, immobility episodes, epilepsy and paralysis. The optic nerve, an easily-isolable central tract fully myelinated by oligodendrocytes, is a suitable preparation to evaluate the developmental impairment of central myelin. We examined the ontogenic development of optic nerve compound action potentials (CAP) throughout the first 6 months of life of control and taiep rats. Control optic nerves (ON) develop CAPs characterized by three waves. Along the first month, the CAPs of taiep rats showed a delayed maturation, with lower amplitudes and longer latencies than controls; at P30, the conduction velocity has only a third of the normal value. Later, as demyelination proceeds, the conduction velocity of taiep ONs begins to decrease and CAPs undergo a gradual temporal dispersion. CAPs of control and taiep showed differences in their pharmacological sensitivity to TEA and 4-AP, two voltage dependent K+ channel-blockers. As compared with TEA, 4-AP induced a significant increase of the amplitudes and a remarkable broadening of CAPs. After P20, unlike controls, the greater sensitivity to 4-AP exhibited by taiep ONs correlates with the detachment and retraction of paranodal loops suggesting that potassium conductances could regulate the excitability as demyelination of CNS axons progresses. It is concluded that the taiep rat, a long-lived mutant, provides a useful model to study the consequences of partial demyelination and the mechanisms by which glial cells regulate the molecular organization and excitability of axonal membranes during development and disease. PMID:16360123

  2. PERIPHERAL MYELIN PROTEIN-22 IS EXPRESSED IN CNS MYELIN

    OpenAIRE

    De Gasperi, Rita; Gama Sosa, Miguel A.; Naumowicz, Zuzanna; Hof, Patrick R; Notterpek, Lucia; Davis, Kenneth L; Buxbaum, Joseph D.; Elder, Gregory A

    2010-01-01

    Myelin abnormalities exist in schizophrenia leading to the hypothesis that oligodendrocyte dysfunction plays a role in the pathophysiology of the disease. The expression of the mRNA for the peripheral myelin protein-22 (PMP-22) is decreased in schizophrenia and recent genetic evidence suggests a link between PMP-22 and schizophrenia. While PMP-22 mRNA is found in both rodent and human brain it has been generally thought that no protein expression occurs. Here we show that PMP-22 protein is pr...

  3. 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)

  4. 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.

  5. Split hypergraphs

    CERN Document Server

    Timar, Adam

    2011-01-01

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

  6. The acquisition of myelin: a success story.

    Science.gov (United States)

    Zalc, Bernard

    2006-01-01

    The myelin sheath, and hence the myelin-forming cells (i.e. Schwann cells in the PNS and oligodendrocytes in the CNS), have been a crucial acquisition of vertebrates. The major function of myelin is to increase the velocity of propagation of nerve impulses. Invertebrate axons are ensheathed by glial cells, but do not have a compact myelin. As a consequence, action potentials along invertebrate axons propagate at about 1 m/s, or less. This is sufficient, however, for the survival of small animals (between 0.1 and 30cm). Among invertebrates, only the cephalopods are larger. By increasing their axonal diameter to 1 mm or more, cephalopods have been able to increase the speed of propagation of action potentials and therefore adapt nerve conduction to their larger body size. However, due to the physical constraint imposed by the skull and vertebrae, vertebrates had to find an alternative solution. This was achieved by introducing the myelin sheath, which leads action potentials to propagate at speeds of 50-100m/s without increasing the diameter of their axons. Not all vertebrate axons, however, are myelinated. In the protovertebrates (lancelets, hagfishes, lampreys), which belong to the agnathes (jawless fishes), axons are not ensheathed by myelin. Among living vertebrates, the most ancient myelinated species are the cartilaginous fishes (sharks, rays), suggesting that acquisition of myelin is concomitant with the acquisition of a hinged-jaw, i.e. the gnathostoma. The close association between the apparition of a hinged-jaw and the myelin sheath has led to speculation that among the devonian fishes that have disappeared today, the jawless conodonts and ostracoderms were not myelinated, and that myelin was first acquired by the oldest gnathostomes: the placoderms. I also question where myelin first appeared: the PNS, the CNS or both? I provide evidence that, in fact, it is not the type of myelin-forming cell that is crucial, but the appearance of axonal signals, rendering axons receptive to inducing an ensheathing glial cell to wrap around the axon. Under certain circumstances or in some species, invertebrate ensheathing glial cells wrap around axon to form a pseudo-myelin sheath. Therefore, to form myelin it was not compulsory to 'invent' a new cell type. Hence my conclusion that myelination has most probably started simultaneously in the PNS and the CNS, using pre-existing ensheathing glial cells. PMID:16805421

  7. MRI assessment of myelination: an age standardization

    International Nuclear Information System (INIS)

    777 cerebral MRI examinations of children aged 3 days to 14 years were staged for myelination to establish an age standardization. Staging was performed using a system proposed in a previous paper, separately ranking 10 different regions of the brain. Interpretation of the results led to the identification of foue clinical diagnoses that are frequently associated with delays in myelination: West syndrome, cerebral palsy, developmental retardation, and congenital anomalies. In addition, it was found that assessment of myelination in children with head injuries was not practical as alterations in MRI signal can simulate earlier stages of myelination. Age limits were therefore calculated from the case material after excluding all children with these conditions. When simplifications of the definition of the stages are applied, these age limits for the various stages of myelination of each of the 10 regions of the brain make the staging system applicable for routine assessment of myelination. (orig.)

  8. Labelled splitting

    OpenAIRE

    Fietzke, A.; Weidenbach, C.

    2008-01-01

    We define a superposition calculus with explicit splitting and an explicit, new backtracking rule on the basis of labelled clauses. For the first time we show a superposition calculus with explicit backtracking rule sound and complete. The new backtracking rule advances backtracking with branch condensing known from SPASS. An experimental evaluation of an implementation of the new rule shows that it improves considerably the previous SPASS splitting implementation. Finally, we discuss the rel...

  9. Nonenzymatic glycosylation of bovine myelin basic protein

    International Nuclear Information System (INIS)

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

  10. Magnetic resonance imaging and myelin; Imagerie par resonance magnetique et myeline

    Energy Technology Data Exchange (ETDEWEB)

    Adamsbaum, C.; Andre, C. [Hopital Saint-Vincent-de-Paul, 75 - Paris (France); Rolland, Y. [CMC, 78 -Saint-Quentin-en-Yvelines (France)

    1995-09-01

    Postnatal development of the brain is characterized by growth and by myelination. Myelination of the brain normally extends from birth until about two years of age. MRI changes corresponding to the various myelination stages are due mainly to changes in the water content of the cerebral parenchyma. Myelination kinetics follow a fairly precise timetable, with variations across areas of the brain. Abnormalities of white matter are responsible for relatively stereotyped, nonspecific manifestations, which are mainly due to an increase in the amount of water contained in diseased white matter, whatever the cause of the disorder. Interpretation is based on the location, distribution, and progression of lesions. (authors). 7 refs., 5 figs.

  11. Proposed evolutionary changes in the role of myelin

    OpenAIRE

    Stiefel, Klaus M.; Torben-Nielsen, Benjamin; Coggan, Jay S

    2013-01-01

    Myelin is the multi-layered lipid sheet periodically wrapped around neuronal axons. It is most frequently found in vertebrates. Myelin allows for saltatory action potential (AP) conduction along axons. During this form of conduction, the AP travels passively along the myelin-covered part of the axon, and is recharged at the intermittent nodes of Ranvier. Thus, myelin can reduce the energy load needed and/or increase the speed of AP conduction. Myelin first evolved during the Ordovician period...

  12. Ephaptic coupling of myelinated nerve fibers

    DEFF Research Database (Denmark)

    Binczak, S.; Eilbeck, J. C.; Scott, Alwyn C.

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

  13. Split symmetries

    CERN Document Server

    Buchmuller, Wilfried; Ruehle, Fabian; Schweizer, Julian

    2015-01-01

    We consider six-dimensional supergravity with gauge group $SO(10)\\times U(1)_A$, compactified on the orbifold $T^2 / \\mathbb{Z}_2$. Three quark-lepton generations arise as zero modes of a bulk $\\bf16$-plet due to magnetic flux of the anomalous $U(1)_A$. Boundary conditions at the four fixed points break $SO(10)$ to subgroups whose intersection is the Standard Model gauge group. The gauge and Higgs sector consist of "split" $SO(10)$ multiplets. As consequence of the $U(1)_A$ flux, squarks and sleptons are much heavier than gauge bosons, Higgs bosons, gauginos and higgsinos. We thus obtain a picture similar to "split supersymmetry." The flavor structure of the quark and lepton mass matrices is determined by the symmetry breaking at the orbifold fixed points.

  14. Split symmetries

    Science.gov (United States)

    Buchmuller, Wilfried; Dierigl, Markus; Ruehle, Fabian; Schweizer, Julian

    2015-11-01

    We consider six-dimensional supergravity with gauge group SO (10) × U(1)A, compactified on the orbifold T2 /Z2. Three quark-lepton generations arise as zero modes of a bulk 16-plet due to magnetic flux of the anomalous U(1)A. Boundary conditions at the four fixed points break SO (10) to subgroups whose intersection is the Standard Model gauge group. The gauge and Higgs sector consist of "split" SO (10) multiplets. As a consequence of the U(1)A flux, squarks and sleptons are much heavier than gauge bosons, Higgs bosons, gauginos and higgsinos. We thus obtain a picture similar to "split supersymmetry". The flavor structure of the quark and lepton mass matrices is determined by the symmetry breaking at the orbifold fixed points.

  15. Splitting Descartes

    DEFF Research Database (Denmark)

    Schilhab, Theresa

    2007-01-01

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

  16. Human habenula segmentation using myelin content.

    Science.gov (United States)

    Kim, Joo-Won; Naidich, Thomas P; Ely, Benjamin A; Yacoub, Essa; De Martino, Federico; Fowkes, Mary E; Goodman, Wayne K; Xu, Junqian

    2016-04-15

    The habenula consists of a pair of small epithalamic nuclei located adjacent to the dorsomedial thalamus. Despite increasing interest in imaging the habenula due to its critical role in mediating subcortical reward circuitry, in vivo neuroimaging research targeting the human habenula has been limited by its small size and low anatomical contrast. In this work, we have developed an objective semi-automated habenula segmentation scheme consisting of histogram-based thresholding, region growing, geometric constraints, and partial volume estimation steps. This segmentation scheme was designed around in vivo 3T myelin-sensitive images, generated by taking the ratio of high-resolution T1w over T2w images. Due to the high myelin content of the habenula, the contrast-to-noise ratio with the thalamus in the in vivo 3T myelin-sensitive images was significantly higher than the T1w or T2w images alone. In addition, in vivo 7T myelin-sensitive images (T1w over T2*w ratio images) and ex vivo proton density-weighted images, along with histological evidence from the literature, strongly corroborated the in vivo 3T habenula myelin contrast used in the proposed segmentation scheme. The proposed segmentation scheme represents a step toward a scalable approach for objective segmentation of the habenula suitable for both morphological evaluation and habenula seed region selection in functional and diffusion MRI applications. PMID:26826517

  17. Myelin-based inhibitors of oligodendrocyte myelination: clues from axonal growth and regeneration.

    Science.gov (United States)

    Mei, Feng; Christin Chong, S Y; Chan, Jonah R

    2013-04-01

    The differentiation of and myelination by oligodendrocytes (OLs) are exquisitely regulated by a series of intrinsic and extrinsic mechanisms. As each OL can make differing numbers of myelin segments with variable lengths along similar axon tracts, myelination can be viewed as a graded process shaped by inhibitory/inductive cues during development. Myelination by OLs is a prime example of an adaptive process determined by the microenvironment and architecture of the central nervous system (CNS). in this review, we discuss how myelin formation by OLs may be controlled by the heterogeneous microenvironment of the CNS. Then we address recent findings demonstrating that neighboring OLs may compete for available axon space, and highlight our current understanding of myelin-based inhibitors of axonal regeneration that are potentially responsible for the reciprocal dialogue between OLs and determine the numbers and lengths of myelin internodes. Understanding the mechanisms that control the spatiotemporal regulation of myelinogenic potential during development may provide valuable insight into therapeutic strategies for promoting remyelination in an inhibitory microenvironment. PMID:23516141

  18. Astrocytic TIMP-1 Promotes Oligodendrocyte Differentiation and Enhances CNS Myelination

    OpenAIRE

    Moore, Craig S.; Milner, Richard; NISHIYAMA, AKIKO; Frausto, Ricardo F.; SERWANSKI, DAVID R.; Pagarigan, Roberto R.; Whitton, J. Lindsay; Miller, Robert H.; CROCKER, STEPHEN J.

    2011-01-01

    Tissue inhibitor of metalloproteinase-1 (TIMP-1) is an extracellular protein and endogenous regulator of matrix metalloproteinases (MMPs) secreted by astrocytes in response to CNS myelin injury. We have previously reported that adult TIMP-1KO mice exhibit poor myelin repair following demyelinating injury. This observation led us to hypothesize a role for TIMP-1 in oligodendrogenesis and CNS myelination. Herein, we demonstrate that compact myelin formation is significantly delayed in TIMP-1KO ...

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

    DEFF Research Database (Denmark)

    Hvilsted Nielsen, Helle; Toft-Hansen, Henrik; Lambertsen, Kate Lykke; Owens, Trevor; Finsen, Bente

    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...... 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....

  20. Myelin proteomics : molecular anatomy of an insulating sheath

    OpenAIRE

    Jahn, Olaf; Tenzer, Stefan; Werner, Hauke B.

    2009-01-01

    Fast-transmitting vertebrate axons are electrically insulated with multiple layers of nonconductive plasma membrane of glial cell origin, termed myelin. The myelin membrane is dominated by lipids, and its protein composition has historically been viewed to be of very low complexity. In this review, we discuss an updated reference compendium of 342 proteins associated with central nervous system myelin that represents a valuable resource for analyzing myelin biogenesis and white matter homeost...

  1. CNS Myelin Sheath Lengths Are an Intrinsic Property of Oligodendrocytes

    OpenAIRE

    Bechler, MarieE.; Byrne, Lauren; ffrench-Constant, Charles

    2015-01-01

    Since Ro-Hortegas description of oligodendrocyte morphologies nearly a century ago, many studies have observed myelin sheath-length diversity between CNS regions [13]. Myelin sheath length directly impacts axonal conduction velocity by influencing the spacing between nodes of Ranvier. Such differences likely affect neural signal coordination and synchronization [4]. What accounts for regional differences in myelin sheath lengths is unknown; are myelin sheath lengths determined solely by ax...

  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 develop from a plan...

  3. Altered PLP1 splicing causes hypomyelination of early myelinating structures

    DEFF Research Database (Denmark)

    Kevelam, Sietske H; Taube, Jennifer R; van Spaendonk, Rosalina M L; Bertini, Enrico; Sperle, Karen; Tarnopolsky, Mark; Tonduti, Davide; Valente, Enza Maria; Travaglini, Lorena; Sistermans, Erik A; Bernard, Geneviève; Catsman-Berrevoets, Coriene E; van Karnebeek, Clara D M; Østergaard, John R; Friederich, Richard L; Fawzi Elsaid, Mahmoud; Schieving, Jolanda H; Tarailo-Graovac, Maja; Orcesi, Simona; Steenweg, Marjan E; van Berkel, Carola G M; Waisfisz, Quinten; Abbink, Truus E M; van der Knaap, Marjo S; Hobson, Grace M; Wolf, Nicole I

    2015-01-01

    regulating PLP1/DM20 alternative splicing. Splicing studies in fibroblasts and transfected cells confirmed a decreased PLP1/DM20 ratio. INTERPRETATION: Brain structures that normally myelinate early are poorly myelinated in HEMS, while they are the best myelinated structures in Pelizaeus-Merzbacher disease...

  4. 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.)

  5. 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.

  6. Schwann cell myelination of the myelin deficient rat spinal cord following X-irradiation

    International Nuclear Information System (INIS)

    The myelin-deficient (md) rat is an X-linked myelin mutant that has an abnormality of oligodendrocytes and a severe paucity of myelin throughout the CNS. This lack of myelin makes it an ideal model in which to study the cellular interactions that occur when foreign myelinating cells are induced in the milieu of this nonmyelinated CNS. In this study, Schwann cells were induced in the lumbosacral spinal cord by exposing it to radiation, a technique demonstrated repeatedly in other nonmutant strains of rats. Md rats and their age-matched littermates were irradiated (3,000 to 4,000 R) at 3 days of age and perfused 16-22 days later after pulse labeling with tritiated thymidine. In the md rat, Schwann cell invasion progressed from the area of the spinal cord-nerve root junction and extended into the dorsal columns and adjacent gray matter. Autoradiographic evidence revealed that many of these cells incorporated 3H-thymidine, indicating that they were undergoing proliferation. Ultrastructural observations showed that there was an integration of these intraspinal Schwann cells with the cells normally occurring in this environment, i.e., oligodendrocytes and astrocytes. The extent of migration and division of Schwann cells, as well as their interactions with glial cells, were similar to those seen in the nonmutant irradiated littermates. These studies provide conclusive evidence that md rat axons are normal with respect to their ability to provide trophic and mitogenic signals to myelinating cells

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

    Science.gov (United States)

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

    2011-01-01

    Schwann cells elaborate myelin sheaths around axons by spirally wrapping and compacting their plasma membranes. Although actin remodeling plays a crucial role in this process, the effectors that modulate the Schwann cell cytoskeleton are poorly defined. Here, we show that the actin cytoskeletal regulator, neural Wiskott-Aldrich syndrome protein (N-WASp), is upregulated in myelinating Schwann cells coincident with myelin elaboration. When N-WASp is conditionally deleted in Schwann cells at the onset of myelination, the cells continue to ensheath axons but fail to extend processes circumferentially to elaborate myelin. Myelin-related gene expression is also severely reduced in the N-WASp-deficient cells and in vitro process and lamellipodia formation are disrupted. Although affected mice demonstrate obvious motor deficits these do not appear to progress, the mutant animals achieving normal body weights and living to advanced age. Our observations demonstrate that N-WASp plays an essential role in Schwann cell maturation and myelin formation. PMID:21385763

  8. 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.

  9. Myelination, oligodendrocytes, and serious mental illness.

    Science.gov (United States)

    Haroutunian, V; Katsel, P; Roussos, P; Davis, K L; Altshuler, L L; Bartzokis, G

    2014-11-01

    Historically, the human brain has been conceptually segregated from the periphery and further dichotomized into gray matter (GM) and white matter (WM) based on the whitish appearance of the exceptionally high lipid content of the myelin sheaths encasing neuronal axons. These simplistic dichotomies were unfortunately extended to conceptually segregate neurons from glia, cognition from behavior, and have been codified in the separation of clinical and scientific fields into medicine, psychiatry, neurology, pathology, etc. The discrete classifications have helped obscure the importance of continual dynamic communication between all brain cell types (neurons, astrocytes, microglia, oligodendrocytes, and precursor (NG2) cells) as well as between brain and periphery through multiple signaling systems. The signaling systems range from neurotransmitters to insulin, angiotensin, and multiple kinases such a glycogen synthase kinase 3 (GSK-3) that together help integrate metabolism, inflammation, and myelination processes and orchestrate the development, plasticity, maintenance, and repair that continually optimize function of neural networks. A more comprehensive, evolution-based, systems biology approach that integrates brain, body, and environmental interactions may ultimately prove more fruitful in elucidating the complexities of human brain function. The historic focus on neurons/GM is rebalanced herein by highlighting the importance of a systems-level understanding of the interdependent age-related shifts in both central and peripheral homeostatic mechanisms that can lead to remarkably prevalent and devastating neuropsychiatric diseases. Herein we highlight the role of glia, especially the most recently evolved oligodendrocytes and the myelin they produce, in achieving and maintaining optimal brain function. The human brain undergoes exceptionally protracted and pervasive myelination (even throughout its GM) and can thus achieve and maintain the rapid conduction and synchronous timing of neural networks on which optimal function depends. The continuum of increasing myelin vulnerability resulting from the human brain's protracted myelination underlies underappreciated communalities between different disease phenotypes ranging from developmental ones such as schizophrenia (SZ) and bipolar disorder (BD) to degenerative ones such as Alzheimer's disease (AD). These shared vulnerabilities also expose significant yet underexplored opportunities for novel treatment and prevention approaches that have the potential to considerably reduce the tremendous burden of neuropsychiatric disease. PMID:25056210

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    Robin White

    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.

  12. Uncompacted myelin lamellae in peripheral nerve biopsy.

    Science.gov (United States)

    Vital, Claude; Vital, Anne; Bouillot, Sandrine; Favereaux, Alexandre; Lagueny, Alain; Ferrer, Xavier; Brechenmacher, Christiane; Petry, Klaus G

    2003-01-01

    Since 1979, the authors have studied 49 peripheral nerve biopsies presenting uncompacted myelin lamellae (UML). Based on the ultrastructural pattern of UML they propose a 3-category classification. The first category includes cases displaying regular UML, which was observed in 43 cases; it was more frequent in 9 cases with polyneuropathy organomegaly endocrinopathy m-protein skin changes (POEMS) syndrome as well as in 1 case of Charcot-Marie-Tooth 1B with a novel point mutation in the P0 gene. The second category consists of cases showing irregular UML, observed in 4 cases with IgM monoclonal gammopathy and anti-myelin-associated glycoprotein (MAG) activity. This group included 1 benign case and 3 B-cell malignant lymphomas. The third category is complex UML, which was present in 2 unrelated patients with an Arg 98 His missense mutation in the P0 protein gene. Irregular and complex UML are respectively related to MAG and P0, which play a crucial role in myelin lamellae compaction and adhesion. PMID:12554530

  13. Myelin figures: The buckling and flow of wet soap

    Science.gov (United States)

    Zou, Ling-Nan

    2009-06-01

    Myelin figures are interfacial structures formed when certain surfactants swell in excess water. Here, I present data and model calculations suggesting the formation and growth of myelins 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 various myelin growth behaviors observed in different experiments. From a detailed experimental observation of how myelins develop from a planar precursor structure, I identify a mechanical instability that may underlie myelin formation. These results indicate the mixed mechanical character of the surfactant lamellar structure, where fluid and elastic properties coexist, is what enables the formation and growth of myelins.

  14. Myelination of the brain in MRI: a staging system

    International Nuclear Information System (INIS)

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

  15. Proteomic mapping provides powerful insights into functional myelin biology

    OpenAIRE

    Taylor, Christopher M.; Marta, Cecilia B.; Claycomb, Robert J.; Han, David K.; Rasband, Matthew N; Coetzee, Timothy; Pfeiffer, Steven E.

    2004-01-01

    Myelin is a dynamic, functionally active membrane necessary for rapid action potential conduction, axon survival, and cytoarchitecture. The number of debilitating neurological disorders that occur when myelin is disrupted emphasizes its importance. Using high-resolution 2D gel electrophoresis, mass spectrometry, and immunoblotting, we have developed an extensive proteomic map of proteins present in myelin, identifying 98 proteins corresponding to at least 130 of the ?200 spots on the map. Thi...

  16. Effect of electroconvulsive therapy on serum myelin basic protein immunoreactivity.

    OpenAIRE

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

    1984-01-01

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

  17. The molecular physiology of the axo-myelinic synapse.

    Science.gov (United States)

    Micu, Ileana; Plemel, Jason R; Lachance, Celia; Proft, Juliane; Jansen, Andrew J; Cummins, Karen; van Minnen, Jan; Stys, Peter K

    2016-02-01

    Myelinated axons efficiently transmit information over long distances. The apposed myelin sheath confers favorable electrical properties, but restricts access of the axon to its extracellular milieu. Therefore, axonal metabolic support may require specific axo-myelinic communication. Here we explored activity-dependent glutamate-mediated signaling from axon to myelin. 2-Photon microscopy was used to image Ca(2+) changes in myelin in response to electrical stimulation of optic nerve axons ex vivo. We show that optic nerve myelin responds to axonal action potentials by a rise in Ca(2+) levels mediated by GluN2D and GluN3A-containing NMDA receptors. Glutamate is released from axons in a vesicular manner that is tetanus toxin-sensitive. The Ca(2+) source for vesicular fusion is provided by ryanodine receptors on axonal Ca(2+) stores, controlled by L-type Ca(2+) channels that sense depolarization of the internodal axolemma. Genetic ablation of GluN2D and GluN3A subunits results in greater lability of the compact myelin. Our results support the existence of a novel synapse between the axon and its myelin, suggesting a means by which traversing action potentials can signal the overlying myelin sheath. This may be an important physiological mechanism by which an axon can signal companion glia for metabolic support or adjust properties of its myelin in a dynamic manner. The axo-myelinic synapse may contribute to learning, while its disturbances may play a role in the pathophysiology of central nervous system disorders such as schizophrenia, where subtle abnormalities of myelinated white matter tracts have been shown in the human, or to frank demyelinating disorders such as multiple sclerosis. PMID:26515690

  18. 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

  19. Proteomic mapping provides powerful insights into functional myelin biology.

    Science.gov (United States)

    Taylor, Christopher M; Marta, Cecilia B; Claycomb, Robert J; Han, David K; Rasband, Matthew N; Coetzee, Timothy; Pfeiffer, Steven E

    2004-03-30

    Myelin is a dynamic, functionally active membrane necessary for rapid action potential conduction, axon survival, and cytoarchitecture. The number of debilitating neurological disorders that occur when myelin is disrupted emphasizes its importance. Using high-resolution 2D gel electrophoresis, mass spectrometry, and immunoblotting, we have developed an extensive proteomic map of proteins present in myelin, identifying 98 proteins corresponding to at least 130 of the approximately 200 spots on the map. This proteomic map has been applied to analyses of the localization and function of selected proteins, providing a powerful tool to investigate the diverse functions of myelin. PMID:15070771

  20. Mapping infant brain myelination with magnetic resonance imaging.

    Science.gov (United States)

    Deoni, Sean C L; Mercure, Evelyne; Blasi, Anna; Gasston, David; Thomson, Alex; Johnson, Mark; Williams, Steven C R; Murphy, Declan G M

    2011-01-12

    Myelination, the elaboration of myelin surrounding neuronal axons, is essential for normal brain function. The development of the myelin sheath enables rapid synchronized communication across the neural systems responsible for higher order cognitive functioning. Despite this critical role, quantitative visualization of myelination in vivo is not possible with current neuroimaging techniques including diffusion tensor and structural magnetic resonance imaging (MRI). Although these techniques offer insight into structural maturation, they reflect several different facets of development, e.g., changes in axonal size, density, coherence, and membrane structure; lipid, protein, and macromolecule content; and water compartmentalization. Consequently, observed signal changes are ambiguous, hindering meaningful inferences between imaging findings and metrics of learning, behavior or cognition. Here we present the first quantitative study of myelination in healthy human infants, from 3 to 11 months of age. Using a new myelin-specific MRI technique, we report a spatiotemporal pattern beginning in the cerebellum, pons, and internal capsule; proceeding caudocranially from the splenium of the corpus callosum and optic radiations (at 3-4 months); to the occipital and parietal lobes (at 4-6 months); and then to the genu of the corpus callosum and frontal and temporal lobes (at 6-8 months). Our results also offer preliminary evidence of hemispheric myelination rate differences. This work represents a significant step forward in our ability to appreciate the fundamental process of myelination, and provides the first ever in vivo visualization of myelin maturation in healthy human infancy. PMID:21228187

  1. Myelin membrane assembly is driven by a phase transition of myelin basic proteins into a cohesive protein meshwork.

    Science.gov (United States)

    Aggarwal, Shweta; Snaidero, Nicolas; Pähler, Gesa; Frey, Steffen; Sánchez, Paula; Zweckstetter, Markus; Janshoff, Andreas; Schneider, Anja; Weil, Marie-Theres; Schaap, Iwan A T; Görlich, Dirk; Simons, Mikael

    2013-01-01

    Rapid conduction of nerve impulses requires coating of axons by myelin. To function as an electrical insulator, myelin is generated as a tightly packed, lipid-rich multilayered membrane sheath. Knowledge about the mechanisms that govern myelin membrane biogenesis is required to understand myelin disassembly as it occurs in diseases such as multiple sclerosis. Here, we show that myelin basic protein drives myelin biogenesis using weak forces arising from its inherent capacity to phase separate. The association of myelin basic protein molecules to the inner leaflet of the membrane bilayer induces a phase transition into a cohesive mesh-like protein network. The formation of this protein network shares features with amyloid fibril formation. The process is driven by phenylalanine-mediated hydrophobic and amyloid-like interactions that provide the molecular basis for protein extrusion and myelin membrane zippering. These findings uncover a physicochemical mechanism of how a cytosolic protein regulates the morphology of a complex membrane architecture. These results provide a key mechanism in myelin membrane biogenesis with implications for disabling demyelinating diseases of the central nervous system. PMID:23762018

  2. Stereological methods for estimating the myelin sheaths of the myelinated fibers in white matter

    DEFF Research Database (Denmark)

    Li, Chen; Yang, Shu; Chen, Lin; Lu, Wei; Tang, Yong; Gundersen, Hans Jrgen Gottlieb; Qiu, Xuan

    2009-01-01

    . Isotropic, uniform random (IUR) sections were ensured by the use of the isector technique. One section with the thickness of 60 nm was cut from the center of each epon block. Eight to 10 fields of vision were randomly photographed under a transmission electron microscope. The total length of the myelinated...

  3. Transmembrane domain of myelin protein zero can form dimers: possible implications for myelin construction.

    Science.gov (United States)

    Plotkowski, Megan L; Kim, Sanguk; Phillips, Martin L; Partridge, Anthony W; Deber, Charles M; Bowie, James U

    2007-10-30

    Myelin protein zero (MPZ) is the major integral membrane protein of peripheral nerve myelin in higher vertebrates, mediating homoadhesion of the multiple, spiraling wraps of the myelin sheath. Previous studies have shown that full-length MPZ can form dimers and tetramers, and biochemical studies on the extracellular domain (ECD) indicate that it can form a tetramer, albeit very weakly. On the basis of cross-linking studies and equilibrium sedimentation of a transmembrane (TM) domain peptide (MPZ-TM), we find that the MPZ-TM can form homodimers. We further characterized the dimer by measuring the effects of alanine and leucine substitutions on the ability of the TM to dimerize in Escherichia coli membranes. Our results indicate that the primary packing interface for the MPZ TM homodimer is a glycine zipper (GxxxGxxxG) motif. We also find that the G134R mutation, which lies within the glycine zipper packing interface and causes Charcot-Marie-Tooth disease type 1B, severely inhibits dimerization, suggesting that dimerization of the TM domain may be important for the normal functioning of MPZ. By combining our new results with prior work, we suggest a new model for an MPZ lattice that may form during the construction of myelin. PMID:17915947

  4. Neuroactive steroids and peripheral myelin proteins.

    Science.gov (United States)

    Magnaghi, V; Cavarretta, I; Galbiati, M; Martini, L; Melcangi, R C

    2001-11-01

    The present review summarizes observations obtained in our laboratories which underline the importance of neuroactive steroids (i.e., progesterone (PROG), dihydroprogesterone (5alpha-DH PROG), tetrahydroprogesterone (3alpha, 5alpha-TH PROG), testosterone (T), dihydrotestosterone (DHT) and 5alpha-androstan-3alpha,17beta-diol (3alpha-diol)) in the control of the gene expression of myelin proteins (i.e. glycoprotein Po (Po) and the peripheral myelin protein 22 (PMP22)) in the peripheral nervous system. Utilizing different in vivo (aged and adult male rats) and in vitro (Schwann cell cultures) experimental models, we have observed that neuroactive steroids are able to stimulate the mRNA levels of Po and PMP22. The effects of these neuroactive steroids, which are able to interact with classical (progesterone receptor, PR, and androgen receptor, AR) and non-classical (GABA(A) receptor) steroid receptors is further supported by our demonstration in sciatic nerve and/or Schwann cells of the presence of these receptors. On the basis of the observations obtained in the Schwann cells cultures, we suggest that the stimulatory effect of neuroactive steroids on Po is acting through PR, while that on PMP22 needs the GABA(A) receptor. The present findings might be of importance for the utilization of specific receptor ligands as new therapeutical approaches for the rebuilding of the peripheral myelin, particularly in those situations in which the synthesis of Po and PMP22 is altered (i.e. demyelinating diseases like Charcot-Marie-Tooth type 1A and type 1B, hereditary neuropathy with liability to pressure palsies and the Djrine-Sottas syndrome, aging, and after peripheral injury). PMID:11744100

  5. Measuring longitudinal myelin water fraction in new multiple sclerosis lesions

    Directory of Open Access Journals (Sweden)

    Wendy S. Vargas

    2015-01-01

    Conclusions: FAST T2 provides a clinically feasible method to quantify MWF in new MS lesions. The observed influence of baseline MWF, which represents a combined effect of both resolving edema and myelin change within acute lesions, suggests that the extent of initial inflammation impacts final myelin recovery.

  6. Proposed Evolutionary Changes In The Role Of Myelin

    Directory of Open Access Journals (Sweden)

    JaySCoggan

    2013-11-01

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

  7. Proposed evolutionary changes in the role of myelin.

    Science.gov (United States)

    Stiefel, Klaus M; Torben-Nielsen, Benjamin; Coggan, Jay S

    2013-01-01

    Myelin is the multi-layered lipid sheet periodically wrapped around neuronal axons. It is most frequently found in vertebrates. Myelin allows for saltatory action potential (AP) conduction along axons. During this form of conduction, the AP travels passively along the myelin-covered part of the axon, and is recharged at the intermittent nodes of Ranvier. Thus, myelin can reduce the energy load needed and/or increase the speed of AP conduction. Myelin first evolved during the Ordovician period. We hypothesize that myelin's first role was mainly energy conservation. During the later "Mesozoic marine revolution," marine ecosystems changed toward an increase in marine predation pressure. We hypothesize that the main purpose of myelin changed from energy conservation to conduction speed increase during this Mesozoic marine revolution. To test this hypothesis, we optimized models of myelinated axons for a combination of AP conduction velocity and energy efficiency. We demonstrate that there is a trade-off between these objectives. We then compared the simulation results to empirical data and conclude that while the data are consistent with the theory, additional measurements are necessary for a complete evaluation of the proposed hypothesis. PMID:24265603

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

    Science.gov (United States)

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

    2014-01-01

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

  9. 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.

  10. Canonic Route Splitting

    OpenAIRE

    Knapen, Luk; Bellemans, Tom; Janssens, Davy; Wets, Geert

    2014-01-01

    There are multiple ways to split a path in a directed graph into largest sub-paths of minimal cost. All possible splits constitute path partitions of the same size. By calculating two specific path splittings, it is possible to identify subsets of the vertices (splitVer- texSets) that can be used to generate every possible path splitting by taking one vertex from each such subset and connecting the resulting vertices by a least cost path. This is interesting in transportation science when inv...

  11. Regulation of prefrontal cortex myelination by the microbiota.

    Science.gov (United States)

    Hoban, A E; Stilling, R M; Ryan, F J; Shanahan, F; Dinan, T G; Claesson, M J; Clarke, G; Cryan, J F

    2016-01-01

    The prefrontal cortex (PFC) is a key region implicated in a range of neuropsychiatric disorders such as depression, schizophrenia and autism. In parallel, the role of the gut microbiota in contributing to these disorders is emerging. Germ-free (GF) animals, microbiota-deficient throughout life, have been instrumental in elucidating the role of the microbiota in many aspects of physiology, especially the role of the microbiota in anxiety-related behaviours, impaired social cognition and stress responsivity. Here we aim to further elucidate the mechanisms of the microbial influence by investigating changes in the homeostatic regulation of neuronal transcription of GF mice within the PFC using a genome-wide transcriptome profiling approach. Our results reveal a marked, concerted upregulation of genes linked to myelination and myelin plasticity. This coincided with upregulation of neural activity-induced pathways, potentially driving myelin plasticity. Subsequent investigation at the ultrastructural level demonstrated the presence of hypermyelinated axons within the PFC of GF mice. Notably, these changes in myelin and activity-related gene expression could be reversed by colonization with a conventional microbiota following weaning. In summary, we believe we demonstrate for the first time that the microbiome is necessary for appropriate and dynamic regulation of myelin-related genes with clear implications for cortical myelination at an ultrastructural level. The microbiota is therefore a potential therapeutic target for psychiatric disorders involving dynamic myelination in the PFC. PMID:27045844

  12. Alterations in hippocampal myelin and oligodendrocyte precursor cells during epileptogenesis.

    Science.gov (United States)

    Luo, Yuanyuan; Hu, Qiao; Zhang, Qian; Hong, Siqi; Tang, Xiaoju; Cheng, Li; Jiang, Li

    2015-11-19

    Recent reports have described damage to myelinated fibers in the central nervous system (CNS) in patients with temporal lobe epilepsy (TLE) and animal models. However, only limited data are available on the dynamic changes that occur in myelinated fibers, oligodendrocytes (which are myelin-forming cells), and oligodendrocyte precursor cells (OPCs), which are a reservoir of new oligodendrocytes, in the hippocampus throughout epileptogenesis. The current study was designed to examine this issue using a rat model of lithium-pilocarpine-induced epilepsy. Electroencephalography (EEG), immunofluorescence, and Western blot analysis showed that the loss of myelin and oligodendrocytes in the rat hippocampus began during the acute stage of epileptogenesis, and the severity of this loss increased throughout epileptogenesis. Accompanying this loss of myelin and oligodendrocytes, OPCs in the rat hippocampus became activated and their populations increased during several phases of epileptogenesis (the acute, latent and chronic phases). The transcription factors olig1 and olig2, which play crucial roles in regulating OPC proliferation, differentiation and remyelination, were up-regulated during the early phases (the acute and latent phases) followed by a sharp decline in their expression during the chronic and late chronic phases. This study is the first to confirm the loss of myelin and oligodendrocytes during lithium-pilocarpine-induced epileptogenesis accompanied by a transient increase in the number of OPCs. Prevention of the loss of myelin and oligodendrocytes may provide a novel treatment strategy for epilepsy. PMID:26433043

  13. The mechanism of neuropathy in peripheral myelin protein 22 mice

    OpenAIRE

    Robertson, A.M.

    1999-01-01

    Mutations in the gene for peripheral myelin protein 22 (PMP22) are associated with peripheral neuropathy in mice and humans. PMP22 is produced mainly in Schwann cells in the peripheral nervous system where it is localised to compact myelin. The function of PMP22 is unclear but its low abundance makes it unlikely to be a structural myelin protein. I have studied the peripheral nerves of two different mouse models with alterations in the pmp22 gene. (1) The Trembler-J (Tr^J) mous...

  14. Dicer in Schwann cells is required for myelination and axonal integrity

    DEFF Research Database (Denmark)

    Pereira, Jorge A.; Baumann, Reto; Norrmén, Camilla; Somandin, Christian; Miehe, Michaela; Jacob, Claire; Lühmann, Tessa; Hall-Bozic, Heike; Mantei, Ned; Meijer, Dies; Suter, Ueli

    2010-01-01

    promyelinating stage and fail to start forming myelin. At the molecular level, the promyelinating transcription factor Krox20 and several myelin proteins [including myelin associated glycoprotein (MAG) and PMP22] were strongly reduced in mutant sciatic nerves. In contrast, the myelination inhibitors SOX2, Notch1......, and Hes1 were increased, providing an additional potential basis for impaired myelination. A minor fraction of SCs, with some peculiar differences between sensory and motor fibers, overcame the myelination block and formed unusually thin myelin, in line with observed impaired neuregulin and AKT...

  15. Peripheral neuropathies caused by mutations in the myelin protein zero.

    Science.gov (United States)

    Shy, Michael E

    2006-03-15

    Charcot-Marie-Tooth disease type 1B (CMT1B) is caused by mutations in the major PNS myelin protein myelin protein zero (MPZ). MPZ is a member of the immunoglobulin supergene family and functions as an adhesion molecule helping to mediate compaction of PNS myelin. Mutations in MPZ appear to either disrupt myelination during development, leading to severe early onset neuropathies, or to disrupt axo-glial interactions leading to late onset neuropathies in adulthood. Identifying molecular pathways involved in early and late onset CMT1B will be crucial to understand how MPZ mutations cause CMT1B so that rational therapies for both early and late onset neuropathies can be developed. PMID:16414078

  16. Mapping early stage of myelin degradation at nanoscale resolution

    CERN Document Server

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

    2013-01-01

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

  17. Hemimegalencephaly: signal changes suggesting abnormal myelination on MRI

    Energy Technology Data Exchange (ETDEWEB)

    Yagishita, A. [Dept. of Neuroradiology, Tokyo Metropolitan Neurological Hospital (Japan); Arai, N. [Dept. of Clinical Neuropathology, Tokyo Metropolitan Inst. for Neuroscience, Tokyo (Japan); Tamagawa, K. [Dept. of Neuropediatrics, Tokyo Metropolitan Neurological Hospital, Tokyo (Japan); Oda, M. [Dept. of Neuropathology, Tokyo Metropolitan Neurological Hospital, Tokyo (Japan)

    1998-11-01

    We reviewed the MRI of 17 patients with hemimegalencephaly to investigate abnormal myelination in this condition. On images of seven patients aged 18 months or less, the white matter on the affected side suggested advanced myelination for the age. On T1-weighted images of three patients aged 1 month, the anterior limb of the internal capsule in the affected hemisphere was myelinated, and T1 shortening was not clearly seen in the pre- and postcentral gyri. The cortical grey matter and subcortical white matter was isointense in two patients. Images of two patients aged 4 to 5 months and of five patients aged 8-18 months showed myelination that extended more peripherally in the white matter of the affected hemisphere. (orig.) With 3 figs., 1 tab., 8 refs.

  18. CNS Myelin Sheath Lengths Are an Intrinsic Property of Oligodendrocytes

    Science.gov (United States)

    Bechler, Marie E.; Byrne, Lauren; ffrench-Constant, Charles

    2015-01-01

    Summary Since Río-Hortega’s description of oligodendrocyte morphologies nearly a century ago, many studies have observed myelin sheath-length diversity between CNS regions [1–3]. Myelin sheath length directly impacts axonal conduction velocity by influencing the spacing between nodes of Ranvier. Such differences likely affect neural signal coordination and synchronization [4]. What accounts for regional differences in myelin sheath lengths is unknown; are myelin sheath lengths determined solely by axons or do intrinsic properties of different oligodendrocyte precursor cell populations affect length? The prevailing view is that axons provide molecular cues necessary for oligodendrocyte myelination and appropriate sheath lengths. This view is based upon the observation that axon diameters correlate with myelin sheath length [1, 5, 6], as well as reports that PNS axonal neuregulin-1 type III regulates the initiation and properties of Schwann cell myelin sheaths [7, 8]. However, in the CNS, no such instructive molecules have been shown to be required, and increasing in vitro evidence supports an oligodendrocyte-driven, neuron-independent ability to differentiate and form initial sheaths [9–12]. We test this alternative signal-independent hypothesis—that variation in internode lengths reflects regional oligodendrocyte-intrinsic properties. Using microfibers, we find that oligodendrocytes have a remarkable ability to self-regulate the formation of compact, multilamellar myelin and generate sheaths of physiological length. Our results show that oligodendrocytes respond to fiber diameters and that spinal cord oligodendrocytes generate longer sheaths than cortical oligodendrocytes on fibers, co-cultures, and explants, revealing that oligodendrocytes have regional identity and generate different sheath lengths that mirror internodes in vivo. PMID:26320951

  19. A novel PET marker for in vivo quantification of myelination.

    Science.gov (United States)

    Wu, Chunying; Wang, Changning; Popescu, Daniela C; Zhu, Wenxia; Somoza, Eduardo A; Zhu, Junqing; Condie, Allison G; Flask, Christopher A; Miller, Robert H; Macklin, Wendy; Wang, Yanming

    2010-12-15

    C-11-labeled N-methyl-4,4'-diaminostilbene ([(11)C]MeDAS) was synthesized and evaluated as a novel radiotracer for in vivo microPET imaging of myelination. [(11)C]MeDAS exhibits optimal lipophilicity for brain uptake with a logP(oct) value of 2.25. Both in vitro and ex vivo staining exhibited MeDAS accumulation in myelinated regions such as corpus callosum and striatum. The corpus callosum region visualized by MeDAS is much larger in the hypermyelinated Plp-Akt-DD mouse brain than in the wild-type mouse brain, a pattern that was also consistently observed in Black-Gold or MBP antibody staining. Ex vivo autoradiography demonstrated that [(11)C]MeDAS readily entered the mouse brain and selectively labeled myelinated regions with high specificity. Biodistribution studies showed abundant initial brain uptake of [(11)C]MeDAS with 2.56% injected dose/whole brain at 5 min post injection and prolonged retention in the brain with 1.37% injected dose/whole brain at 60 min post injection. An in vivo pharmacokinetic profile of [(11)C]MeDAS was quantitatively analyzed through a microPET study in an Plp-Akt-DD hypermyelinated mouse model. MicroPET studies showed that [(11)C]MeDAS exhibited a pharmacokinetic profile that readily correlates the radioactivity concentration to the level of myelination in the brain. These studies suggest that MeDAS is a sensitive myelin probe that provides a direct means to detect myelin changes in the brain. Thus, it can be used as a myelin-imaging marker to monitor myelin pathology in vivo. PMID:21071233

  20. Self-segregation of myelin membrane lipids in model membranes.

    Science.gov (United States)

    Yurlova, Larisa; Kahya, Nicoletta; Aggarwal, Shweta; Kaiser, Hermann-Josef; Chiantia, Salvatore; Bakhti, Mostafa; Pewzner-Jung, Yael; Ben-David, Oshrit; Futerman, Anthony H; Brgger, Britta; Simons, Mikael

    2011-12-01

    Rapid conduction of nerve impulses requires coating of axons by myelin sheaths, which are multilamellar, lipid-rich membranes produced by oligodendrocytes in the central nervous system. To act as an insulator, myelin has to form a stable and firm membrane structure. In this study, we have analyzed the biophysical properties of myelin membranes prepared from wild-type mice and from mouse mutants that are unable to form stable myelin. Using C-Laurdan and fluorescence correlation spectroscopy, we find that lipids are tightly organized and highly ordered in myelin isolated from wild-type mice, but not from shiverer and ceramide synthase 2 null mice. Furthermore, only myelin lipids from wild-type mice laterally segregate into physically distinct lipid phases in giant unilamellar vesicles in a process that requires very long chain glycosphingolipids. Taken together, our findings suggest that oligodendrocytes exploit the potential of lipids to self-segregate to generate a highly ordered membrane for electrical insulation of axons. PMID:22261060

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

    Directory of Open Access Journals (Sweden)

    Edward L. Hogan

    2013-08-01

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

  2. Coded Splitting Tree Protocols

    DEFF Research Database (Denmark)

    Sørensen, Jesper Hemming; Stefanovic, Cedomir; Popovski, Petar

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

  3. Accuracy of tablet splitting.

    Science.gov (United States)

    McDevitt, J T; Gurst, A H; Chen, Y

    1998-01-01

    We attempted to determine the accuracy of manually splitting hydrochlorothiazide tablets. Ninety-four healthy volunteers each split ten 25-mg hydrochlorothiazide tablets, which were then weighed using an analytical balance. Demographics, grip and pinch strength, digit circumference, and tablet-splitting experience were documented. Subjects were also surveyed regarding their willingness to pay a premium for commercially available, lower-dose tablets. Of 1752 manually split tablet portions, 41.3% deviated from ideal weight by more than 10% and 12.4% deviated by more than 20%. Gender, age, education, and tablet-splitting experience were not predictive of variability. Most subjects (96.8%) stated a preference for commercially produced, lower-dose tablets, and 77.2% were willing to pay more for them. For drugs with steep dose-response curves or narrow therapeutic windows, the differences we recorded could be clinically relevant. PMID:9469693

  4. Split Cord Malformations

    Directory of Open Access Journals (Sweden)

    Yurdal Gezercan

    2015-06-01

    Full Text Available Split cord malformations are rare form of occult spinal dysraphism in children. Split cord malformations are characterized by septum that cleaves the spinal canal in sagittal plane within the single or duplicated thecal sac. Although their precise incidence is unknown, split cord malformations are exceedingly rare and represent %3.8-5 of all congenital spinal anomalies. Characteristic neurological, urological, orthopedic clinical manifestations are variable and asymptomatic course is possible. Earlier diagnosis and surgical intervention for split cord malformations is associated with better long-term fuctional outcome. For this reason, diagnostic imaging is indicated for children with associated cutaneous and orthopedic signs. Additional congenital anomalies usually to accompany the split cord malformations. Earlier diagnosis, meticuolus surgical therapy and interdisciplinary careful evaluation and follow-up should be made for good prognosis. [Cukurova Med J 2015; 40(2.000: 199-207

  5. 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

  6. Myelin and oligodendrocyte development in the canine spinal cord.

    Science.gov (United States)

    Mayer, Joshua A; Figari, Carlos; Radcliff, Abigail B; Mckee, Camille; Duncan, Ian D

    2016-04-01

    We studied the developmental pattern of oligodendrocyte differentiation and myelin formation in the fetal canine spinal cord from E40 to P0. The pattern of development matches what has been described in the spinal cord of humans, rodents, and many other species. Oligodendrocytes were first found at E40, close to the central canal, with their spread in a tangential manner to the ventral and then lateral columns. Myelin development followed the same pattern but was not seen until E46. A clear subpial zone lacking glial cells and myelin was seen in the lateral column in early development, suggesting that there may also be a radial component of migration of oligodendrocyte progenitor cells (OPCs) from a ventral site. This spatial-temporal developmental pattern seen in wild type matches a delay in myelination of the superficial tracts of the spinal cord seen in a canine myelin mutant, suggesting that the mutation prevents the distribution and differentiation of OPCs at an early, but narrow, window of time during fetal development. J. Comp. Neurol. 524:930-939, 2016. 2015 Wiley Periodicals, Inc. PMID:26338416

  7. Selective and compartmentalized myelin expression of HspB5.

    Science.gov (United States)

    Quraishe, S; Wyttenbach, A; Matinyarare, N; Perry, V H; Fern, R; O'Connor, V

    2016-03-01

    In the present study, we reveal myelin-specific expression and targeting of mRNA and biochemical pools of HspB5 in the mouse CNS. Our observations are based on in situ hybridization, electron microscopy and co-localization with 2',3'-Cyclic-Nucleotide 3'-Phosphodiesterase (CNPase), reinforcing this myelin-selective expression. HspB5 mRNA might be targeted to these structures based on its presence in discrete clusters resembling RNA granules and the presence of a putative RNA transport signal. Further, sub-cellular fractionation of myelin membranes reveals a distinct sub-compartment-specific association and detergent solubility of HspB5. This is akin to other abundant myelin proteins and is consistent with HspB5's association with cytoskeletal/membrane assemblies. Oligodendrocytes have a pivotal role in supporting axonal function via generating and segregating the ensheathing myelin. This specialization places extreme structural and metabolic demands on this glial cell type. Our observations place HspB5 in oligodendrocytes which may require selective and specific chaperone capabilities to maintain normal function and neuronal support. PMID:26718604

  8. 48 echo T2 myelin imaging of white matter in first-episode schizophrenia: Evidence for aberrant myelination

    Directory of Open Access Journals (Sweden)

    Donna J.M. Lang

    2014-01-01

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

  9. 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.)

  10. A Novel PET Marker for In Vivo Quantification of Myelination

    OpenAIRE

    Wu, Chunying; Wang, Changing; Popescu, Daniela; Zhu, Wenxia; Somoza, Eduardo; Zhu, Junqing; Condie, Allison G.; Flask, Chris; Miller, Robert H.; Macklin, Wendy; Wang, Yanming

    2010-01-01

    C-11-Labeled N-methyl-4,4?-diaminostilbene ([11C]MeDAS) was synthesized and evaluated as a novel radiotracer for in vivo microPET imaging of myelination. [11C]MeDAS exhibits optimal lipophilicity for brain uptake with a logPoct value of 2.25. Both in vitro and ex vivo staining exhibited MeDAS accumulation in myelinated regions such as corpus callosum and striatum. The corpus callosum region visualized by MeDAS is much larger in the hypermyelinated Plp-Akt-DD mouse brain than in the wild-type ...

  11. Trends and Properties of Human Cerebral Cortex: Correlations with Cortical Myelin Content

    OpenAIRE

    Glasser, Matthew F.; Goyal, Manu S.; Preuss, Todd M; Raichle, Marcus E.; Van Essen, David C.

    2013-01-01

    “In vivo Brodmann mapping” or non-invasive cortical parcellation using MRI, especially by measuring cortical myelination, has recently become a popular research topic, though myeloarchitectonic cortical parcellation in humans previously languished in favor of cytoarchitecture. We review recent in vivo myelin mapping studies and discuss some of the different methods for estimating myelin content. We discuss some ways in which myelin maps may improve surface registration and be useful for cross...

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

    OpenAIRE

    Benson, M. Douglas; Mario I Romero; 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-...

  13. Classic and Golli Myelin Basic Protein have distinct developmental trajectories in human visual cortex

    OpenAIRE

    Siu, Caitlin R.; Balsor, Justin L.; Jones, David G.; Murphy, Kathryn M

    2015-01-01

    Traditionally, myelin is viewed as insulation around axons, however, more recent studies have shown it also plays an important role in plasticity, axonal metabolism, and neuroimmune signaling. Myelin is a complex multi-protein structure composed of hundreds of proteins, with Myelin Basic Protein (MBP) being the most studied. MBP has two families: Classic-MBP that is necessary for activity driven compaction of myelin around axons, and Golli-MBP that is found in neurons, oligodendrocytes, and T...

  14. Molecular anatomy and genetics of myelin proteins in the peripheral nervous system.

    OpenAIRE

    Snipes, G. J.; Suter, U.

    1995-01-01

    Myelin contains a number of proteins, the major examples of which are protein zero (Po), P2 protein, peripheral myelin protein 22 (PMP22), myelin basic proteins (MBPs), myelin-associated glycoprotein (MAG) and the recently described connexin 32 (Cx32). This list is probably still incomplete. The localisation and possible functions of these proteins are reviewed. In the past few years a number of inherited demyelinating neuropathies in mice and the human have been shown to be due to mutations ...

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

    OpenAIRE

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

    2009-01-01

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

  16. Aspect splits and parasitic marking

    OpenAIRE

    Woolford, Ellen

    2009-01-01

    Aspect splits can affect agreement, Case, and even preposition insertion. This paper discusses the functional why and the theoretical how of aspect splits. Aspect splits are an economical way to mark aspect by preserving or suppressing some independent element in one aspect. In formal terms, they are produced in the same way as coda conditions in phonology, with positional/contextual faithfulness.This approach captures the additive effects of cross-cutting splits. Aspect splits are analyz...

  17. (O)Mega Split

    CERN Document Server

    Benakli, Karim; Goodsell, Mark

    2015-01-01

    We study two realisations of the Fake Split Supersymmetry Model (FSSM), the simplest model that can easily reproduce the experimental value of the Higgs mass for an arbitrarily high supersymmetry scale, as a consequence of swapping higgsinos for equivalent states, fake higgsinos, with suppressed Yukawa couplings. If the LSP is identified as the main Dark matter component, then a standard thermal history of the Universe implies upper bounds on the supersymmetry scale, which we derive. On the other hand, we show that renormalisation group running of soft masses above the supersymmetry scale barely constrains the model - in stark contrast to Split Supersymmetry - and hence we can have a "Mega Split" spectrum even with all of these assumptions and constraints, which include the requirements of a correct relic abundance, a gluino life-time compatible with Big Bang Nucleosynthesis and absence of signals in present direct detection experiments of inelastic dark matter. In an appendix we describe a related scenario, ...

  18. Split spline screw

    Science.gov (United States)

    Vranish, John M. (Inventor)

    1993-01-01

    A split spline screw type payload fastener assembly, including three identical male and female type split spline sections, is discussed. The male spline sections are formed on the head of a male type spline driver. Each of the split male type spline sections has an outwardly projecting load baring segment including a convex upper surface which is adapted to engage a complementary concave surface of a female spline receptor in the form of a hollow bolt head. Additionally, the male spline section also includes a horizontal spline releasing segment and a spline tightening segment below each load bearing segment. The spline tightening segment consists of a vertical web of constant thickness. The web has at least one flat vertical wall surface which is designed to contact a generally flat vertically extending wall surface tab of the bolt head. Mutual interlocking and unlocking of the male and female splines results upon clockwise and counter clockwise turning of the driver element.

  19. Split Malcev Algebras

    Indian Academy of Sciences (India)

    Antonio J Calderón Martín; Manuel Forero Piulestán; José M Sánchez Delgado

    2012-05-01

    We study the structure of split Malcev algebras of arbitrary dimension over an algebraically closed field of characteristic zero. We show that any such algebras is of the form $M=\\mathcal{U}+\\sum_jI_j$ with $\\mathcal{U}$ a subspace of the abelian Malcev subalgebra and any $I_j$ a well described ideal of satisfying $[I_j, I_k]=0$ if ≠ . Under certain conditions, the simplicity of is characterized and it is shown that is the direct sum of a semisimple split Lie algebra and a direct sum of simple non-Lie Malcev algebras.

  20. Splitting Ward identity

    OpenAIRE

    Safari, Mahmoud

    2015-01-01

    Within the background-field framework we present a path integral derivation of the splitting Ward identity for the one-particle irreducible effective action in the presence of an infrared regulator, and make connection with earlier works on the subject. The approach is general in the sense that it does not rely on how the splitting is performed. This identity is then used to address the problem of background dependence of the effective action at an arbitrary energy scale. We next introduce th...

  1. Splitting Ward identity

    CERN Document Server

    Safari, Mahmoud

    2015-01-01

    Within the background field framework we present a path integral derivation of the splitting Ward identity for the one-particle irreducible effective action in the presence of an infrared regulator, and make connection with earlier works on the subject. The approach is general in the sense that it does not rely on how the splitting is performed. This identity is then used to address the problem of background dependence of the effective action at an arbitrary energy scale. We finally introduce the modified master equation and emphasize its role in constraining the effective action.

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

    Directory of Open Access Journals (Sweden)

    Johann Steiner

    2014-11-01

    Our findings support the superior impact of clozapine on white matter integrity in schizophrenia as previously observed, suggesting that this drug improves the energy supply and myelin lipid synthesis in oligodendrocytes. Characterizing the underlying signal transduction pathways may pave the way for novel oligodendrocyte-directed schizophrenia therapies.

  3. (O)Mega split

    Science.gov (United States)

    Benakli, Karim; Darmé, Luc; Goodsell, Mark D.

    2015-11-01

    We study two realisations of the Fake Split Supersymmetry Model (FSSM), the simplest model that can easily reproduce the experimental value of the Higgs mass for an arbitrarily high supersymmetry scale M S , as a consequence of swapping higgsinos for equivalent states, fake higgsinos, with suppressed Yukawa couplings. If the LSP is identified as the main Dark matter component, then a standard thermal history of the Universe implies upper bounds on M S , which we derive. On the other hand, we show that renormalisation group running of soft masses above M S barely constrains the model — in stark contrast to Split Supersymmetry — and hence we can have a "Mega Split" spectrum even with all of these assumptions and constraints, which include the requirements of a correct relic abundance, a gluino life-time compatible with Big Bang Nucleosynthesis and absence of signals in present direct detection experiments of inelastic dark matter. In an appendix we describe a related scenario, Fake Split Extended Supersymmetry, which enjoys similar properties.

  4. Plasmonic solar water splitting

    International Nuclear Information System (INIS)

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

  5. 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)

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

    DEFF Research Database (Denmark)

    Brazhe, Alexey; Maksimov, G. V.; Mosekilde, Erik; Sosnovtseva, O. V.

    2011-01-01

    . Uptake of potassium leads to Schwann cell swelling and myelin restructuring that impacts the electrical properties of the myelin. In order to further understand the dynamic interaction that takes place between the myelin and the axon, we have modelled submyelin potassium accumulation and related changes...... in myelin resistance during prolonged high-frequency stimulation. We predict that potassium-mediated decrease in myelin resistance leads to a functional excitation block with various patterns of altered spike trains. The patterns are found to depend on stimulation frequency and amplitude and to range...

  7. Astrocytic TIMP-1 Promotes Oligodendrocyte Differentiation and Enhances CNS Myelination

    Science.gov (United States)

    Moore, Craig S.; Milner, Richard; Nishiyama, Akiko; Frausto, Ricardo F.; Serwanski, David R.; Pagarigan, Roberto R.; Whitton, J. Lindsay; Miller, Robert H.; Crocker, Stephen J.

    2011-01-01

    Tissue inhibitor of metalloproteinase-1 (TIMP-1) is an extracellular protein and endogenous regulator of matrix metalloproteinases (MMPs) secreted by astrocytes in response to CNS myelin injury. We have previously reported that adult TIMP-1KO mice exhibit poor myelin repair following demyelinating injury. This observation led us to hypothesize a role for TIMP-1 in oligodendrogenesis and CNS myelination. Herein, we demonstrate that compact myelin formation is significantly delayed in TIMP-1KO mice which coincided with dramatically reduced numbers of white matter astrocytes in the developing CNS. Analysis of differentiation in CNS progenitor cells (neurosphere) cultures from TIMP-1KO mice revealed a specific deficit of NG2+ oligodendrocyte progenitor cells. Application of rmTIMP-1 to TIMP-1KO neurosphere cultures evoked a dose-dependent increase in NG2+ cell numbers, while treatment with GM6001, a potent broad spectrum MMP inhibitor did not. Similarly, administration of recombinant murine TIMP-1 (rmTIMP-1) to A2B5+ immunopanned oligodendrocyte progenitors significantly increased the number of differentiated O1+ oligodendrocytes, while antisera to TIMP-1 reduced oligodendrocyte numbers. We also determined that A2B5+ oligodendrocyte progenitors grown in conditioned media derived from TIMP-1KO primary glial cultures resulted in reduced differentiation of mature O1+ oligodendrocytes. Finally, we report that addition of rmTIMP-1 to primary glial cultures resulted in a dose-dependent proliferative response of astrocytes. Together, these findings describe a previously uncharacterized role for TIMP-1 in the regulation of oligodendrocytes and astrocytes during development and provide a novel function for TIMP-1 on myelination in the developing CNS. PMID:21508247

  8. Altered PLP1 splicing causes hypomyelination of early myelinating structures

    Science.gov (United States)

    Kevelam, Sietske H; Taube, Jennifer R; van Spaendonk, Rosalina M L; Bertini, Enrico; Sperle, Karen; Tarnopolsky, Mark; Tonduti, Davide; Valente, Enza Maria; Travaglini, Lorena; Sistermans, Erik A; Bernard, Geneviève; Catsman-Berrevoets, Coriene E; van Karnebeek, Clara D M; Østergaard, John R; Friederich, Richard L; Fawzi Elsaid, Mahmoud; Schieving, Jolanda H; Tarailo-Graovac, Maja; Orcesi, Simona; Steenweg, Marjan E; van Berkel, Carola G M; Waisfisz, Quinten; Abbink, Truus E M; van der Knaap, Marjo S; Hobson, Grace M; Wolf, Nicole I

    2015-01-01

    Objective The objective of this study was to investigate the genetic etiology of the X-linked disorder “Hypomyelination of Early Myelinating Structures” (HEMS). Methods We included 16 patients from 10 families diagnosed with HEMS by brain MRI criteria. Exome sequencing was used to search for causal mutations. In silico analysis of effects of the mutations on splicing and RNA folding was performed. In vitro gene splicing was examined in RNA from patients’ fibroblasts and an immortalized immature oligodendrocyte cell line after transfection with mutant minigene splicing constructs. Results All patients had unusual hemizygous mutations of PLP1 located in exon 3B (one deletion, one missense and two silent), which is spliced out in isoform DM20, or in intron 3 (five mutations). The deletion led to truncation of PLP1, but not DM20. Four mutations were predicted to affect PLP1/DM20 alternative splicing by creating exonic splicing silencer motifs or new splice donor sites or by affecting the local RNA structure of the PLP1 splice donor site. Four deep intronic mutations were predicted to destabilize a long-distance interaction structure in the secondary PLP1 RNA fragment involved in regulating PLP1/DM20 alternative splicing. Splicing studies in fibroblasts and transfected cells confirmed a decreased PLP1/DM20 ratio. Interpretation Brain structures that normally myelinate early are poorly myelinated in HEMS, while they are the best myelinated structures in Pelizaeus–Merzbacher disease, also caused by PLP1 alterations. Our data extend the phenotypic spectrum of PLP1-related disorders indicating that normal PLP1/DM20 alternative splicing is essential for early myelination and support the need to include intron 3 in diagnostic sequencing. PMID:26125040

  9. Neuronal Regulation of Schwann Cell Mitochondrial Ca2+ Signaling during Myelination

    Directory of Open Access Journals (Sweden)

    Daisuke Ino

    2015-09-01

    Full Text Available Schwann cells (SCs myelinate peripheral neurons to promote the rapid conduction of action potentials, and the process of myelination is known to be regulated by signals from axons to SCs. Given that SC mitochondria are one of the potential regulators of myelination, we investigated whether SC mitochondria are regulated by axonal signaling. Here, we show a purinergic mechanism that sends information from neurons to SC mitochondria during myelination. Our results show that electrical stimulation of rat sciatic nerve increases extracellular ATP levels enough to activate purinergic receptors. Indeed, electrical stimulation of sciatic nerves induces Ca2+ increases in the cytosol and the mitochondrial matrix of surrounding SCs via purinergic receptor activation. Chronic suppression of this pathway during active myelination suppressed thelongitudinal and radial development of myelinating SCs and caused hypomyelination. These resultsdemonstrate a neuron-to-SC mitochondria signaling, which is likely to have an important role in proper myelination.

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

    Directory of Open Access Journals (Sweden)

    Douglas Fields

    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.

  11. Enhanced Action Potential Passage Through the Node of Ranvier of Myelinated Axons via Proton Hopping.

    Science.gov (United States)

    Kier, Lemont; Hall, Lowell; Tombes, Robert M

    2015-01-01

    Nerve impulses travel along myelinated axons as much as 300-fold faster than they do along unmyelinated axons. Myelination is essential for normal nervous system behavior in vertebrates as illustrated by leukodystrophies, such as amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS), where myelin is degenerated or damaged. The increased conduction velocity that occurs in myelinated axons is dependent on gaps in the myelin called Nodes of Ranvier that are enriched in ion channels. These Nodes are separated by long stretches of myelin insulation where no transmembrane ion conductance occurs. It is believed that the action potential jumps or skips between nodes, conserving its information content, while maintaining its speed. In this study, a model is presented that implicates Nodes of Ranvier as responsible for regenerating the proton hopping that is responsible for nerve impulse conductance in myelinated axons. PMID:26205832

  12. Specific inhibition of secreted NRG1 types I-II by heparin enhances Schwann Cell myelination.

    Science.gov (United States)

    Eshed-Eisenbach, Yael; Gordon, Aaron; Sukhanov, Natalya; Peles, Elior

    2016-07-01

    Primary cultures of mixed neuron and Schwann cells prepared from dorsal root ganglia (DRG) are extensively used as a model to study myelination. These dissociated DRG cultures have the particular advantage of bypassing the difficulty in purifying mouse Schwann cells, which is often required when using mutant mice. However, the drawback of this experimental system is that it yields low amounts of myelin. Here we report a simple and efficient method to enhance myelination in vitro. We show that the addition of heparin or low molecular weight heparin to mixed DRG cultures markedly increases Schwann cells myelination. The myelin promoting activity of heparin results from specific inhibition of the soluble immunoglobulin (Ig)-containing isoforms of neuregulin 1 (i.e., NRG1 types I and II) that negatively regulates myelination. Heparin supplement provides a robust and reproducible method to increase myelination in a simple and commonly used culture system. GLIA 2016;64:1227-1234. PMID:27143444

  13. Of mothers and myelin: Aberrant myelination phenotypes in mouse model of Angelman syndrome are dependent on maternal and dietary influences.

    Science.gov (United States)

    Grier, Mark D; Carson, Robert P; Lagrange, Andre H

    2015-09-15

    Angelman syndrome (AS) is a neurodevelopmental disorder characterized by a number of neurological problems, including developmental delay, movement disorders, and epilepsy. AS results from the loss of UBE3A (an imprinted gene) expressed from the maternal chromosome in neurons. Given the ubiquitous expression of Ube3a and the devastating nature of AS, the role of environmental and maternal effects has been largely ignored. Severe ataxia, anxiety-like behaviors and learning deficits are well-documented in patients and AS mice. More recently, clinical imaging studies of AS patients suggest myelination may be delayed or reduced. Utilizing a mouse model of AS, we found disrupted expression of cortical myelin proteins, the magnitude of which is influenced by maternal status, in that the aberrant myelination in the AS pups of AS affected mothers were more pronounced than those seen in AS pups raised by unaffected (Ube3a (m+/p-)) Carrier mothers. Furthermore, feeding the breeding mothers a higher fat (11% vs 5%) diet normalizes these myelin defects. These effects are not limited to myelin proteins. Since AS mice have abnormal stress responses, including altered glucocorticoid receptor (GR) expression, we measured GR expression in pups from Carrier and affected AS mothers. AS pups had higher GR expression than their WT littermates. However, we also found an effect of maternal status, with reduced GR levels in pups from affected mothers compared to genotypically identical pups raised by unaffected Carrier mothers. Taken together, our findings suggest that the phenotypes observed in AS mice may be modulated by factors independent of Ube3a genotype. PMID:26028516

  14. The Split sudmja

    Directory of Open Access Journals (Sweden)

    Petar imunovi?

    2015-10-01

    Full Text Available The name of the Split feast Sudamja!Sudajma ("festa sancti Domnii" has not yet been adequately explained. The author believes that the name originated from the Old Dalmatian adjective san(ctu + Domn?u. In the adjective santu the cluster /an/ in front ofa consonant gave in Croatian the back nasal /q/ pronounced until the end of the 10th century and giving /u/ after that. In this way the forms *Sudumja and similar originated. The short stressed /u/ in the closed syllable was percieved by the Croatian folk as their semivowel which later gave /a/ = Sudamja. The author connects this feature with that in the toponimes Makar (< *mt.k"br < *mukru < Muccurum, Bakar (< *btk"&r < *bukur < Buccuri, Skadar (< *skbdr < *skudr < Skutari, Skopje(< *sktp < Skupi etc. The metathesis /mj/ > /jm/ is well known in Croatian dialectology (sumja > sujma, and it resembles the metatheses which occurs in the Split toponimes: Sukojn > Sukojn ( < *santu Cassianu, Pojin/Pojiin (< *pasianu < Pansianu. The author finds the same feature in the toponime Dumja?a (: *Dumi- + -a?a. He considers these features as Croatian popular adaptations which have not occured in the personal name Dujam, the toponime Dujmova?a "terrae s. Domnii" and in the adjective sandujamski, because of the link with the saint's name Domnio!Duymo etc., which has been well liked and is frequent as name of Split Romas as well as Croats from the foundation of Split, has never been broken.

  15. Split Thickness Skin Grafting

    OpenAIRE

    Shoemaker, P. J.

    1982-01-01

    Primary care physicians often see wounds in which skin loss is a major factor. Although most of these wounds will heal with local care and with a reasonable functional result, split thickness skin grafting as a simple outpatient or bedside procedure can speed healing more comfortably for the patient and with greatly improved functional results. This article outlines the techniques of skin grafting as part of a minor surgical armamentarium.

  16. The control of central nervous system myelination and the phenotypic characterisation of a novel zebrafish mutant: akineto(u45).

    OpenAIRE

    Hawkins, T.

    2004-01-01

    Part 1 of this thesis addresses the control of myelination in the central nervous system (CNS). We have a sound knowledge of myelin structure, particularly the molecules and cells involved in its make-up. However, our understanding of the control of myelin formation is scanty. Myelination of CNS tracts during development follows a strictly ordered schedule suggesting local control by axons. Here I present evidence that CNS axons need to form synaptic connections before they can be myelinated....

  17. Tablet Splitting: A Risky Practice

    Science.gov (United States)

    ... helps to release the medicine slowly. Splitting these tablets destroys the coating, which means you might absorb the medicine too fast or not at all. What if You Still Want to Split a Tablet? FDA has approved drugs where tablet splitting is ...

  18. Altered Oligodendrocyte Maturation and Myelin Maintenance: The Role of Antiretrovirals in HIV-Associated Neurocognitive Disorders.

    Science.gov (United States)

    Jensen, Brigid K; Monnerie, Hubert; Mannell, Maggie V; Gannon, Patrick J; Espinoza, Cagla Akay; Erickson, Michelle A; Bruce-Keller, Annadora J; Gelman, Benjamin B; Briand, Lisa A; Pierce, R Christopher; Jordan-Sciutto, Kelly L; Grinspan, Judith B

    2015-11-01

    Despite effective viral suppression through combined antiretroviral therapy (cART), approximately half of HIV-positive individuals have HIV-associated neurocognitive disorders (HAND). Studies of antiretroviral-treated patients have revealed persistent white matter abnormalities including diffuse myelin pallor, diminished white matter tracts, and decreased myelin protein mRNAs. Loss of myelin can contribute to neurocognitive dysfunction because the myelin membrane generated by oligodendrocytes is essential for rapid signal transduction and axonal maintenance. We hypothesized that myelin changes in HAND are partly due to effects of antiretroviral drugs on oligodendrocyte survival and/or maturation. We showed that primary mouse oligodendrocyte precursor cell cultures treated with therapeutic concentrations of HIV protease inhibitors ritonavir or lopinavir displayed dose-dependent decreases in oligodendrocyte maturation; however, this effect was rapidly reversed after drug removal. Conversely, nucleoside reverse transcriptase inhibitor zidovudine had no effect. Furthermore, in vivo ritonavir administration to adult mice reduced frontal cortex myelin protein levels. Finally, prefrontal cortex tissue from HIV-positive individuals with HAND on cART showed a significant decrease in myelin basic protein compared with untreated HIV-positive individuals with HAND or HIV-negative controls. These findings demonstrate that antiretrovirals can impact myelin integrity and have implications for myelination in juvenile HIV patients and myelin maintenance in adults on lifelong therapy. PMID:26469251

  19. Physiological noise compensation in gradient-echo myelin water imaging.

    Science.gov (United States)

    Nam, Yoonho; Kim, Dong-Hyun; Lee, Jongho

    2015-10-15

    In MRI, physiological noise which originates from cardiac and respiratory functions can induce substantial errors in detecting small signals in the brain. In this work, we explored the effects of the physiological noise and their compensation methods in gradient-echo myelin water imaging (GRE-MWI). To reduce the cardiac function induced inflow noise, flow saturation RF pulses were applied to the inferior portion of the head, saturating inflow blood signals. For the respiratory function induced B0 fluctuation compensation, a navigator echo was acquired, and respiration induced phase errors were corrected during reconstruction. After the compensations, the resulting myelin water images show substantially improved image quality and reproducibility. These improvements confirm the importance and usefulness of the physiological noise compensations in GRE-MWI. PMID:26172308

  20. CHOP and the endoplasmic reticulum stress response in myelinating glia

    OpenAIRE

    Gow, Alexander; Wrabetz, Lawrence

    2009-01-01

    The unfolded protein response (UPR) comprises kinase signaling and transcription factor activation cascades delineated over the past 20 years. Most studies conclude that this stress response is adaptive but, nevertheless, includes maladaptive programs involving CHOP expression which drive cell-autonomous apoptosis. Herein, we highlight several studies of UPR diseases involving myelinating glia of the central and peripheral nervous systems that do not support a primary role for CHOP in apoptos...

  1. 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...

  2. MYELIN, COPPER, AND THE CUPRIZONE MODEL OF SCHIZOPHRENIA

    OpenAIRE

    Herring, Nicole R.; Konradi, Christine

    2011-01-01

    In recent years increasing evidence is pointing toward white matter abnormalities in schizophrenia and other psychiatric disorders. The present paper will provide an overview over the role of myelin in cognition and brain function, and its potential involvement in brain disorders. Furthermore, we will examine one particular experimental model for the study of dysmyelination, created by the administration of the toxin cuprizone. Cuprizone, a copper chelator, causes white matter abnormalities i...

  3. Effect of prenatal iron deficiency on myelination in rat pups.

    OpenAIRE

    Yu, G S; Steinkirchner, T. M.; Rao, G. A.; Larkin, E. C.

    1986-01-01

    In this study, a histopathologic examination of the brain from iron-deficient or iron-supplemented rat pups was carried out. Pups were obtained from female rats, which were fed an iron-deficient or iron-supplemented diet during both pregnancy and lactation. Immediately after anesthesia and the collection of blood, pups were fixed by intracardiac infusion of 2% glutaraldehyde. Brain and cervical spinal cord were fixed, embedded in paraffin, and cut at 6-mu thickness. Myelin was identified usin...

  4. Oligodendrocyte progenitor programming and reprogramming: Toward myelin regeneration.

    Science.gov (United States)

    Lopez Juarez, Alejandro; He, Danyang; Richard Lu, Q

    2016-05-01

    Demyelinating diseases such as multiple sclerosis (MS) are among the most disabling and cost-intensive neurological disorders. The loss of myelin in the central nervous system, produced by oligodendrocytes (OLs), impairs saltatory nerve conduction, leading to motor and cognitive deficits. Immunosuppression therapy has a limited efficacy in MS patients, arguing for a paradigm shift to strategies that target OL lineage cells to achieve myelin repair. The inhibitory microenvironment in MS lesions abrogates the expansion and differentiation of resident OL precursor cells (OPCs) into mature myelin-forming OLs. Recent studies indicate that OPCs display a highly plastic ability to differentiate into alternative cell lineages under certain circumstances. Thus, understanding the mechanisms that maintain and control OPC fate and differentiation into mature OLs in a hostile, non-permissive lesion environment may open new opportunities for regenerative therapies. In this review, we will focus on 1) the plasticity of OPCs in terms of their developmental origins, distribution, and differentiation potentials in the normal and injured brain; 2) recent discoveries of extrinsic and intrinsic factors and small molecule compounds that control OPC specification and differentiation; and 3) therapeutic potential for motivation of neural progenitor cells and reprogramming of differentiated cells into OPCs and their likely impacts on remyelination. OL-based therapies through activating regenerative potentials of OPCs or cell replacement offer exciting opportunities for innovative strategies to promote remyelination and neuroprotection in devastating demyelinating diseases like MS. This article is part of a Special Issue entitled SI:NG2-glia(Invited only). PMID:26546966

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

    International Nuclear Information System (INIS)

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

  6. 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)

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

    CERN Document Server

    Xue, Jiongwei

    2012-01-01

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

  8. In vivo assessment of myelination by phase imaging at high magnetic field

    OpenAIRE

    Lodygensky, Gregory A; Marques, Jose P.; Maddage, Rajika; Perroud, Elodie; Sizonenko, Stephane V.; Hueppi, Petra S.; Gruetter, Rolf

    2012-01-01

    The present study evaluated the potential of using the phase of T-2* weighted MR images to characterize myelination during brain development and pathology in rodents at 9.4 T. Phase contrast correlated with myelin content assessed by histology and suggests that most contrast between white and cortical gray matter is modulated by myelin. Ex vivo experiments showed that gray-white matter phase contrast remains unchanged after iron extraction. In dysmyelinated shiverer mice, phase imaging correl...

  9. Assessing white matter ischemic damage in dementia patients by measurement of myelin proteins

    OpenAIRE

    Barker, Rachel; Wellington, Dannielle; Esiri, Margaret M; Love, Seth

    2013-01-01

    White matter ischemia is difficult to quantify histologically. Myelin-associated glycoprotein (MAG) is highly susceptible to ischemia, being expressed only adaxonally, far from the oligodendrocyte cell body. Myelin-basic protein (MBP) and proteolipid protein (PLP) are expressed throughout the myelin sheath. We compared MAG, MBP, and PLP levels in parietal white matter homogenates from 17 vascular dementia (VaD), 49 Alzheimer's disease (AD), and 33 control brains, after assessing the post-mort...

  10. Exercise Decreases Myelin-Associated Glycoprotein Expression in the Spinal Cord and Positively Modulates Neuronal Growth

    OpenAIRE

    Ghiani, Cristina A.; Ying, Zhe; de Vellis, Jean; GOMEZ-PINILLA, FERNANDO

    2007-01-01

    To successfully grow, neurons need to overcome the effects of hostile environments, such as the inhibitory action of myelin. We have evaluated the potential of exercise to overcome the intrinsic limitation of the central nervous system for axonal growth. In line with the demonstrated ability of exercise to increase the regenerative potential of neurons, here we show that exercise reduces the inhibitory capacity of myelin. Cortical neurons grown on myelin from exercised rats showed a more pron...

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

    OpenAIRE

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

    2014-01-01

    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 anti-inflammatory 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 inflammator...

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

    International Nuclear Information System (INIS)

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

  13. Advances in myelin imaging with potential clinical application to pediatric imaging

    OpenAIRE

    Spader, Heather S.; Ellermeier, Anna; O’Muircheartaigh, Jonathan; Dean, Douglas C.; Dirks, Holly; BOXERMAN, JERROLD L.; Cosgrove, G. Rees; Deoni, Sean C.L.

    2013-01-01

    White matter development and myelination are critical processes in neurodevelopment. Myelinated white matter facilitates the rapid and coordinated brain messaging required for higher-order cognitive and behavioral processing. Whereas several neurological disorders such as multiple sclerosis are associated with gross white matter damage and demyelination, other disorders such as epilepsy may involve altered myelination in the efferent or afferent white matter pathways adjoining epileptic foci....

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    Fractions containing myelin of varying degrees of compaction were prepared from human white matter. Protein kinase activity in these fractions was measured by using both endogenous and exogenous myelin basic protein (MBP) as substrates. In both cases, less compact myelin fractions possessed higher levels of protein kinase activity than the compact myelin fraction. In addition, the specific activity of phosphorylated basic protein was greater in the loosely compacted fractions than in compact multilamellar myelin. When basic protein in compact myelin or the myelin fractions was phosphorylated by the endogenous kinase, approximately 70% of the [32P]phosphate was incorporated at a single site, identified as Ser-102. The remaining 30% was found in three other minor sites. Electron microscopy of less compact myelin showed it was composed of fewer lamellae which correlated with a relative decrease in the proportion of cationic charge isomers (microheteromers) when MBP was subjected to gel electrophoresis at alkaline pH. The shift in charge microheterogeneity of basic protein to the less cationic isomers in the less compact myelin fractions correlated with an increase in protein kinase activity and a greater specific activity of phosphorylated basic protein

  16. In vivo detection of Egr2 binding to target genes during peripheral nerve myelination.

    Science.gov (United States)

    Jang, Sung-Wook; LeBlanc, Scott E; Roopra, Avtar; Wrabetz, Lawrence; Svaren, John

    2006-09-01

    Egr2/Krox20 is a zinc finger transactivator that regulates a diverse array of genes required for peripheral nerve myelination. Although several studies have elucidated the Egr2-regulated gene network, it is not clear if Egr2 regulates its target genes directly or indirectly through induction of other transactivators. Moreover, very few Egr2 binding sites have been identified in regulatory elements of myelin genes. To address this issue, we have successfully adapted chromatin immunoprecipitation assays to test if Egr2 binds directly to target genes in myelinating rat sciatic nerve. These experiments demonstrate direct binding of Egr2 to previously described binding sites within the Schwann cell enhancer of the myelin basic protein gene. Furthermore, we show Egr2 binding to a conserved site within the myelin-associated glycoprotein gene. Finally, our experiments provide the first evidence that Egr2 directly regulates expression of desert hedgehog, which is critically involved in development, maintenance and regeneration of multiple nerve elements including myelinated fibers. Surprisingly, this analysis has identified an apparent preponderance of Egr2 binding sites within conserved intron sequences of several myelin genes. Application of chromatin immunoprecipitation analysis to myelination in vivo will prove to be a valuable asset in assaying transcription factor binding and chromatin modifications during activation of myelin genes. PMID:16923174

  17. Leptogenesis from split fermions

    International Nuclear Information System (INIS)

    We present a new type of leptogenesis mechanism based on a two-scalar split-fermions framework. At high temperatures the bulk scalar vacuum expectation values (VEVs) vanish and lepton number is strongly violated. Below some temperature, Tc, the scalars develop extra dimension dependent VEVs. This transition is assumed to proceed via a first order phase transition. In the broken phase the fermions are localized and lepton number violation is negligible. The lepton-bulk scalar Yukawa couplings contain sizable CP phases which induce lepton production near the interface between the two phases. We provide a qualitative estimation of the resultant baryon asymmetry which agrees with current observation. The neutrino flavor parameters are accounted for by the above model with an additional approximate U(1) symmetry

  18. Leptogenesis from split fermions

    Energy Technology Data Exchange (ETDEWEB)

    Nagatani, Yukinori; Perez, Gilad

    2004-01-11

    We present a new type of leptogenesis mechanism based on a two-scalar split-fermions framework. At high temperatures the bulk scalar vacuum expectation values (VEVs) vanish and lepton number is strongly violated. Below some temperature, T{sub c}, the scalars develop extra dimension dependent VEVs. This transition is assumed to proceed via a first order phase transition. In the broken phase the fermions are localized and lepton number violation is negligible. The lepton-bulk scalar Yukawa couplings contain sizable CP phases which induce lepton production near the interface between the two phases. We provide a qualitative estimation of the resultant baryon asymmetry which agrees with current observation. The neutrino flavor parameters are accounted for by the above model with an additional approximate U(1) symmetry.

  19. 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.)

  20. Myelin Biogenesis And Oligodendrocyte Development: Parsing Out The Roles Of Glycosphingolipids

    OpenAIRE

    Jackman, Nicole; Ishii, Akihiro; Bansal, Rashmi

    2009-01-01

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

  1. Myelin debris regulates inflammatory responses in an experimental demyelination animal model and multiple sclerosis lesions.

    Science.gov (United States)

    Clarner, Tim; Diederichs, Felix; Berger, Katharina; Denecke, Bernd; Gan, Lin; van der Valk, Paul; Beyer, Cordian; Amor, Sandra; Kipp, Markus

    2012-10-01

    In multiple sclerosis (MS), gray matter pathology is characterized by less pronounced inflammation when compared with white matter lesions. Although regional differences in the cytoarchitecture may account for these differences, the amount of myelin debris in the cortex during a demyelinating event might also be contributory. To analyze the association between myelin debris levels and inflammatory responses, cortical areas with distinct and sparse myelination were analyzed for micro- and astrogliosis before and after cuprizone-induced demyelination in mice. In postmortem tissue of MS patients, leucocortical lesions were assessed for the type and level of inflammation in the cortical and white matter regions of the lesion. Furthermore, mice were injected intracerebrally with myelin-enriched debris, and the inflammatory response analyzed in white and grey matter areas. Our studies show that the magnitude of myelin loss positively correlates with microgliosis in the cuprizone model. In MS, the number of MHC class II expressing cells is higher in the white compared with the grey matter part of leucocortical lesions. Finally, direct application of myelin debris into the corpus callosum or cortex of mice induces profound and comparable inflammation in both regions. Our data suggest that myelin debris is an important variable in the inflammatory response during demyelinating events. Whether myelin-driven inflammation affects neuronal integrity remains to be clarified. PMID:22689449

  2. Delayed myelination in children with developmental delay detected by volumetric MRI.

    Science.gov (United States)

    Pujol, Jesús; López-Sala, Anna; Sebastián-Gallés, Núria; Deus, Joan; Cardoner, Narcís; Soriano-Mas, Carles; Moreno, Angel; Sans, Anna

    2004-06-01

    Delayed acquisition of developmental motor and cognitive milestones is a common clinical expression of many etiological processes. Imaging exams of developmentally delayed children often show no structural brain alterations despite suspicion of brain maturation delay. MRI studies increasingly suggest that white matter myelination finely reflects the progression in functional brain maturation. In this volumetric MRI study, we sought to evaluate whether developmental delay in children with normal conventional MRI exams is associated with reduced myelinated white matter. A total of 100 children (mean age, 4.4 years) with developmental delay and 50 normally developing age-matched control children underwent 3-D MRI to measure the volume of myelinated white matter. Patients showed a significant reduction in the relative content of myelinated white matter (accounting for 19.8% of brain volume in patients and 21.4% in control subjects, P = 0.005). The observed difference was equivalent to a 3.2-year myelination delay. Although the whole hemispheres were invariably symmetrical, the volume of myelinated white matter was asymmetrical in 30% of patients and 10% of control subjects (P = 0.006). We conclude that volumetric assessment of white matter may reveal a reduction in brain myelination beyond early childhood in developmentally delayed children showing normal brain appearance. This finding further emphasizes the view of white matter myelination as an indicator of functional brain maturation. PMID:15193620

  3. Demyelination induces the decline of the myelinated fiber length in aged rat white matter

    DEFF Research Database (Denmark)

    Li, Chen; Yang, Shu; Zhang, Wei; Lu, Wei; Nyengaard, Jens R; Morrison, John H; Tang, Yong

    2009-01-01

    formed from the demyelination of the myelinated fibers could not replenish the age-related loss of the unmyelinated fibers in the white matter. In conclusion, this study suggested that demyelination of myelinated fibers with small diameters in aged white matter might be the key mechanism of the...

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

    Directory of Open Access Journals (Sweden)

    Alan Peters

    2009-07-01

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

  5. Preliminary Evidence of Increased Hippocampal Myelin Content in Veterans with Posttraumatic Stress Disorder

    Directory of Open Access Journals (Sweden)

    Linda L Chao

    2015-12-01

    Full Text Available Recent findings suggest the formation of myelin in the central nervous system by oligodendrocytes is a continuous process that can be modified with experience. For example, a recent study showed that immobilization stress increased oligodendrogensis in the dentate gyrus of adult rat hippocampus. Because changes in myelination represents an adaptive form of brain plasticity that has a greater reach in the adult brain than other forms of plasticity (e.g., neurogenesis, the objective of this proof of concept study was to examine whether there are differences in myelination in the hippocampi of humans with and without posttraumatic stress disorder (PTSD. We used the ratio of T1-weighted/T2-weighted magnetic resonance image (MRI intensity to estimate the degree of hippocampal myelination in 19 male veterans with PTSD and 19 matched trauma-exposed male veterans without PTSD (mean age: 43 +12 years. We found that veterans with PTSD had significantly more hippocampal myelin than trauma-exposed controls. There was also found a positive correlation between estimates of hippocampal myelination and PTSD and depressive symptom severity. To our knowledge, this is the first study to examine hippocampal myelination in humans with PTSD. These results provide preliminary evidence for stress-induced hippocampal myelin formation as a potential mechanism underlying the brain abnormalities associated with vulnerability to stress.

  6. Dipole Splitting Algorithm

    CERN Document Server

    Hasegawa, K

    2014-01-01

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

  7. Japanese neuropathy patients with peripheral myelin protein-22 gene aneuploidy

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-09-01

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

  8. Myelin-associated Glycoprotein gene and brain morphometry in schizophrenia

    Directory of Open Access Journals (Sweden)

    JamesKennedy

    2012-05-01

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

  9. In vivo assessment of myelination by phase imaging at high magnetic field.

    Science.gov (United States)

    Lodygensky, Gregory A; Marques, José P; Maddage, Rajika; Perroud, Elodie; Sizonenko, Stéphane V; Hüppi, Petra S; Gruetter, Rolf

    2012-02-01

    The present study evaluated the potential of using the phase of T2* weighted MR images to characterize myelination during brain development and pathology in rodents at 9.4 T. Phase contrast correlated with myelin content assessed by histology and suggests that most contrast between white and cortical gray matter is modulated by myelin. Ex vivo experiments showed that gray-white matter phase contrast remains unchanged after iron extraction. In dysmyelinated shiverer mice, phase imaging correlated strongly with myelin staining, showing reduced contrast between white and gray matter when compared to healthy controls. We conclude that high-resolution phase images, acquired at high field, allow assessment of myelination and dysmyelination. PMID:21985911

  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. 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.)

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

    OpenAIRE

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

    2012-01-01

    The elaboration of the myelinated white matter is essential for normal neurodevelopment, establishing and mediating rapid communication pathways throughout the brain. These pathways facilitate the synchronized communication required for higher order behavioral and cognitive functioning. Altered neural messaging (or ‘disconnectivity’) arising from abnormal white matter and myelin development may underlie a number of neurodevelopmental psychiatric disorders. Despite the vital role myelin plays,...

  13. 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.

  14. 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.

  15. Photocatalytic water splitting

    Science.gov (United States)

    Kuo, Yenting

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

  16. 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; ffrench-Constant, Charles

    2011-01-01

    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...

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    Yong Tang

    2011-05-01

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

  19. Claudin-11 Tight Junctions in Myelin Are a Barrier to Diffusion and Lack Strong Adhesive Properties.

    Science.gov (United States)

    Denninger, Andrew R; Breglio, Andrew; Maheras, Kathleen J; LeDuc, Geraldine; Cristiglio, Viviana; Dem, Bruno; Gow, Alexander; Kirschner, Daniel A

    2015-10-01

    The radial component is a network of interlamellar tight junctions (TJs) unique to central nervous system myelin. Ablation of claudin-11, a TJ protein, results in the absence of the radial component and compromises the passive electrical properties of myelin. Although TJs are known to regulate paracellular diffusion, this barrier function has not been directly demonstrated for the radial component, and some evidence suggests that the radial component may also mediate adhesion between myelin membranes. To investigate the physical properties of claudin-11 TJs, we compared fresh, unfixed Claudin 11-null and control nerves using x-ray and neutron diffraction. In Claudin 11-null tissue, we detected no changes in myelin structure, stability, or membrane interactions, which argues against the notion that myelin TJs exhibit significant adhesive properties. Moreover, our osmotic stressing and D2O-H2O exchange experiments demonstrate that myelin lacking claudin-11 is more permeable to water and small osmolytes. Thus, our data indicate that the radial component serves primarily as a diffusion barrier and elucidate the mechanism by which TJs govern myelin function. PMID:26445439

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

    Directory of Open Access Journals (Sweden)

    Murata Ken-ya

    2013-01-01

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

  2. Reduced Myelination and Increased Glia Reactivity Resulting from Severe Neonatal Hyperbilirubinemia.

    Science.gov (United States)

    Barateiro, Andreia; Chen, Shujuan; Yueh, Mei-Fei; Fernandes, Adelaide; Domingues, Helena Sofia; Relvas, Joo; Barbier, Olivier; Nguyen, Nghia; Tukey, Robert H; Brites, Dora

    2016-01-01

    Bilirubin-induced neurologic dysfunction (BIND) and kernicterus has been used to describe moderate to severe neurologic dysfunction observed in children exposed to excessive levels of total serum bilirubin (TSB) during the neonatal period. Here we use a new mouse model that targets deletion of the Ugt1 locus and the Ugt1a1 gene in liver to promote hyperbilirubinemia-induced seizures and central nervous system toxicity. The accumulation of TSB in these mice leads to diffuse yellow coloration of brain tissue and a marked cerebellar hypoplasia that we characterize as kernicterus. Histologic studies of brain tissue demonstrate that the onset of severe neonatal hyperbilirubinemia, characterized by seizures, leads to alterations in myelination and glia reactivity. Kernicterus presents as axonopathy with myelination deficits at different brain regions, including pons, medulla oblongata, and cerebellum. The excessive accumulation of TSB in the early neonatal period (5 days after birth) promotes activation of the myelin basic protein (Mbp) gene with an accelerated loss of MBP that correlates with a lack of myelin sheath formation. These changes were accompanied by increased astroglial and microglial reactivity, possibly as a response to myelination injury. Interestingly, cerebellum was the area most affected, with greater myelination impairment and glia burden, and showing a marked loss of Purkinje cells and reduced arborization of the remaining ones. Thus, kernicterus in this model displays not only axonal damage but also myelination deficits and glial activation in different brain regions that are usually related to the neurologic sequelae observed after severe hyperbilirubinemia. PMID:26480925

  3. Advances in myelin imaging with potential clinical application to pediatric imaging.

    Science.gov (United States)

    Spader, Heather S; Ellermeier, Anna; O'Muircheartaigh, Jonathan; Dean, Douglas C; Dirks, Holly; Boxerman, Jerrold L; Cosgrove, G Rees; Deoni, Sean C L

    2013-04-01

    White matter development and myelination are critical processes in neurodevelopment. Myelinated white matter facilitates the rapid and coordinated brain messaging required for higher-order cognitive and behavioral processing. Whereas several neurological disorders such as multiple sclerosis are associated with gross white matter damage and demyelination, other disorders such as epilepsy may involve altered myelination in the efferent or afferent white matter pathways adjoining epileptic foci. Current MRI techniques including T1 weighting, T2 weighting, FLAIR, diffusion tensor imaging, and MR spectroscopy permit visualization of gross white matter abnormalities and evaluation of underlying white matter fiber architecture and integrity, but they provide only qualitative information regarding myelin content. Quantification of these myelin changes could provide new insight into disease severity and prognosis, reveal information regarding spatial location of foci or lesions and the associated affected neural systems, and create a metric to evaluate treatment efficacy. Multicomponent analysis of T1 and T2 relaxation data, or multicomponent relaxometry (MCR), is a quantitative imaging technique that is sensitive and specific to myelin content alteration. In the past, MCR has been associated with lengthy imaging times, but a new, faster MCR technique (mcDESPOT) has made quantitative analysis of myelin content more accessible for clinical research applications. The authors briefly summarize traditional white matter imaging techniques, describe MCR and mcDESPOT, and discuss current and future clinical applications of MCR, with a particular focus on pediatric epilepsy. PMID:23544415

  4. Mapping an index of the myelin g-ratio in infants using magnetic resonance imaging

    Science.gov (United States)

    Dean, Douglas C.; O'Muircheartaigh, Jonathan; Dirks, Holly; Travers, Brittany G.; Adluru, Nagesh; Alexander, Andrew L.; Deoni, Sean C.L.

    2016-01-01

    Optimal myelination of neuronal axons is essential for effective brain and cognitive function. The ratio of the axon diameter to the outer fiber diameter, known as the g-ratio, is a reliable measure to assess axonal myelination and is an important index reflecting the efficiency and maximal conduction velocity of white matter pathways. Although advanced neuroimaging techniques including multicomponent relaxometry (MCR) and diffusion tensor imaging afford insight into the microstructural characteristics of brain tissue, by themselves they do not allow direct analysis of the myelin g-ratio. Here, we show that by combining myelin content information (obtained with mcDESPOT MCR) with neurite density information (obtained through NODDI diffusion imaging) an index of the myelin g-ratio may be estimated. Using this framework, we present the first quantitative study of myelin g-ratio index changes across childhood, examining 18 typically developing children 3 months to 7.5 years of age. We report a spatio-temporal pattern of maturation that is consistent with histological and developmental MRI studies, as well as theoretical studies of the myelin g-ratio. This work represents the first ever in vivo visualization of the evolution of white matter g-ratio indices throughout early childhood. PMID:26908314

  5. Heterogeneity of Multiple Sclerosis Lesions in Multislice Myelin Water Imaging

    Science.gov (United States)

    Faizy, Tobias Djamsched; Thaler, Christian; Kumar, Dushyant; Sedlacik, Jan; Broocks, Gabriel; Grosser, Malte; Stellmann, Jan-Patrick; Heesen, Christoph; Fiehler, Jens; Siemonsen, Susanne

    2016-01-01

    Purpose To assess neuroprotection and remyelination in Multiple Sclerosis (MS), we applied a more robust myelin water imaging (MWI) processing technique, including spatial priors into image reconstruction, which allows for lower SNR, less averages and shorter acquisition times. We sought to evaluate this technique in MS-patients and healthy controls (HC). Materials and Methods Seventeen MS-patients and 14 age-matched HCs received a 3T Magnetic Resonance Imaging (MRI) examination including MWI (8 slices, 12 minutes acquisition time), T2w and T1mprage pre and post gadolinium (GD) administration. Black holes (BH), contrast enhancing lesions (CEL) and T2 lesions were marked and registered to MWI. Additionally, regions of interest (ROI) were defined in the frontal, parietal and occipital normal appearing white matter (NAWM)/white matter (WM), the corticospinal tract (CST), the splenium (SCC) and genu (GCC) of the corpus callosum in patients and HCs. Mean values of myelin water fraction (MWF) were determined for each ROI. Results Significant differences (p≤0.05) of the MWF were found in all three different MS-lesion types (BH, CEL, T2 lesions), compared to the WM of HCs. The mean MWF values among the different lesion types were significantly differing from each other. Comparing MS-patients vs. HCs, we found a significant (p≤0.05) difference of the MWF in all measured ROIs except of GCC and SCC. The mean reduction of MWF in the NAWM of MS-patients compared to HCs was 37%. No age, sex, disability score and disease duration dependency was found for the NAWM MWF. Conclusion MWF measures were in line with previous studies and lesions were clearly visible in MWI. MWI allows for quantitative assessment of NAWM and lesions in MS, which could be used as an additional sensitive imaging endpoint for larger MS studies. Measurements of the MWF also differ between patients and healthy controls. PMID:26990645

  6. Mobilization of endogenous neural stem cells for myelin repair

    Directory of Open Access Journals (Sweden)

    Myriam Cayre

    2009-11-01

    Full Text Available In the adult brain, a pool of neural stem cells resides in the subventricular zone (SVZ, including oligodendrocyte progenitors. One strategy to enhance myelin repair properties of SVZ progenitors is to control their migration behaviour and to favour their exit from the rostral migratory stream (RMS leading them to the olfactory bulb (OB. We evidenced that SVZ progenitors grafted in white matter tracts of the intact adult forebrain can migrate along them and give rise efficiently to myelinating oligodendrocytes. Thus, one limiting step in the repair process seems to be the capacity of progenitors to exit the RMS, which we attempted to overcome by several approaches. We first demonstrated that environmental enrichment associated with physical exercise promotes SVZ cell mobilization in the context of demyelinating lesions. Among candidate neurotrophin mediators, we focused on EGF and showed that intranasal HB-EGF administration, which robustly stimulates neural progenitor cell proliferation, promotes SVZ cell recruitment towards demyelinated lesions as well, but commits SVZ-recruited cells toward an astroglial phenotype. Then we targeted molecules that modulate the migration of SVZ progenitor cells such as the intrinsic glycoprotein Reelin. Using grafts of SVZ progenitors engineered to produce Reelin, we showed that ectopic expression of Reelin in the corpus callosum increased migration of SVZ and RMS progenitors toward periventricular structures. In vitro, Reelin influences neuronal and astrocytic differentiation of cultured neural stem/progenitor cells. Finally, we used microarray analysis to decipher the mechanisms underlying the migration of SVZ progenitors to the subcortical white matter in experimental autoimmune encephalomyelitis mice.

  7. 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.

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

    International Nuclear Information System (INIS)

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

  9. Entropy Splitting and Numerical Dissipation

    Science.gov (United States)

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

    2000-07-01

    A rigorous stability estimate for arbitrary order of accuracy of spatial central difference schemes for initial boundary value problems of nonlinear symmetrizable systems of hyperbolic conservation laws was established recently by Olsson and Oliger (1994, “Energy and Maximum Norm Estimates for Nonlinear Conservation Laws”, RIACS Report, NASA Ames Research Center) and Olsson (1995, Math. Comput.64, 212) and was applied to the two-dimensional compressible Euler equations for a perfect gas by Gerritsen and Olsson (1996, J. Comput. Phys.129, 245) and Gerritsen (1996, “Designing an Efficient Solution Strategy for Fluid Flows, Ph.D. Thesis, Stanford). The basic building block in developing the stability estimate is a generalized energy approach based on a special splitting of the flux derivative via a convex entropy function and certain homogeneous properties. Due to some of the unique properties of the compressible Euler equations for a perfect gas, the splitting resulted in the sum of a conservative portion and a non-conservative portion of the flux derivative, hereafter referred to as the “entropy splitting.” There are several potentially desirable attributes and side benefits of the entropy splitting for the compressible Euler equations that were not fully explored in Gerritsen and Olsson. This paper has several objectives. The first is to investigate the choice of the arbitrary parameter that determines the amount of splitting and its dependence on the type of physics of current interest to computational fluid dynamics. The second is to investigate in what manner the splitting affects the nonlinear stability of the central schemes for long time integrations of unsteady flows such as in nonlinear aeroacoustics and turbulence dynamics. If numerical dissipation indeed is needed to stabilize the central scheme, can the splitting help minimize the numerical dissipation compared to its un-split cousin? Extensive numerical study on the vortex preservation capab ility of the splitting in conjunction with central schemes for long time integrations will be presented. The third is to study the effect of the non-conservative proportion of splitting in obtaining the correct shock location for high speed complex shock-turbulence interactions. The fourth is to determine if this method can be extended to other physical equations of state and other evolutionary equation sets. If numerical dissipation is needed, the Yee, Sandham, and Djomehri (1999, J. Comput. Phys.150, 199) numerical dissipation is employed. The Yee et al. schemes fit in the Olsson and Oliger framework.

  10. Entropy Splitting and Numerical Dissipation

    Science.gov (United States)

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

    1999-01-01

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

  11. 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...

  12. Focally folded myelin in Charcot-Marie-Tooth neuropathy type 1B with Ser49Leu in the myelin protein zero.

    Science.gov (United States)

    Fabrizi, G M; Taioli, F; Cavallaro, T; Rigatelli, F; Simonati, A; Mariani, G; Perrone, P; Rizzuto, N

    2000-09-01

    Charcot-Marie-Tooth disease type 1 B (CMT1B) is a demyelinating neuropathy caused by mutations in the myelin protein zero (P0) gene (MPZ). A few cases of CMT1B were recently found to be characterized by focally folded myelin sheaths in nerve biopsy specimens; the significance of this association is unknown. Here, we describe two unrelated pedigrees harboring a heterozygous Ser49Leu substitution in P0ex. In both pedigrees, the mutation caused a late-onset, relatively mild CMT1B; in one pedigree, two patients had atrophy of peroneal muscles but hypertrophy of the gastrocnemius muscles. The sural nerve biopsy performed in the two index cases revealed an identical chronic demyelinating and remyelinating neuropathy dominated by focal foldings of the myelin sheath shaped either as tomacula or as out/infoldings. The report adds Ser49Leu to the mutations of P0ex associated with focally folded myelin and provides strong evidence that such a structural alteration of the myelin sheath reflects a distinct pathogenetic mechanism in a subgroup of CMT1B. PMID:10965800

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

    Science.gov (United States)

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

    2003-09-01

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

  14. Brain and cord myelin water imaging: a progressive multiple sclerosis biomarker

    Directory of Open Access Journals (Sweden)

    Shannon Kolind

    2015-01-01

    Interpretation: In this study we demonstrated that mcDESPOT can be used to measure myelin and atrophy in the brain and spinal cord. Results correlate well with clinical disability scores in PPMS representing cognitive, fine motor and ambulatory disability.

  15. Normal expression of myelin protein zero with frame-shift mutation correlates with mild phenotype.

    Science.gov (United States)

    Steck, Andreas J; Erne, Beat; Pareyson, Davide; Sghirlanzoni, Angelo; Taroni, Franco; Schaeren-Wiemers, Nicole

    2006-03-01

    Mutations in the gene encoding for myelin protein zero (MPZ) cause inherited demyelinating peripheral neuropathies of different severity. The molecular and cellular mechanisms by which the MPZ mutations cause neuropathy are incompletely understood. We investigated MPZ, myelin basic protein, and peripheral myelin protein 22 (PMP22) protein expression levels in a nerve biopsy of a Charcot-Marie-Tooth type 1B patient heterozygous for the Val 102 frame-shift mutation. We demonstrate by quantitative immunohistochemical as well as by Western blot analyses that MPZ expression levels were not reduced in myelin membranes, a finding that is in accordance with the mild phenotype of this patient. Our data show that heterozygous 'loss-of-function' of MPZ may not necessarily lead to reduced protein levels. In conclusion, we demonstrate that careful analysis of protein expression levels in peripheral nerve tissues provides important information with respect to the understanding of the molecular basis of these neuropathies. PMID:16519783

  16. Lesioned corticospinal tract axons regenerate in myelin-free rat spinal cord

    Energy Technology Data Exchange (ETDEWEB)

    Savio, T.; Schwab, M.E. (Univ. of Zurich (Switzerland))

    1990-06-01

    In the adult central nervous system (CNS) of higher vertebrates lesioned axons seemed unable to regenerate and reach their former target regions due to influences of the CNS microenvironment. Evidence from in vitro and biochemical experiments has demonstrated the presence of inhibitory substrate components in CNS tissue, in particular in white matter. These CNS components, which strongly inhibit neurite growth, were identified as minor membrane proteins of defined molecular mass (35 and 250 kDa) in oligodendrocyte membranes and CNS myelin. Oligodendrocyte development and myelin formation can be prevented by x-irradiation of newborn rats. Here we show that in myelin-free spinal cords cortico-spinal tract fibers transected at 2 weeks of age show reelongation of many millimeters within 2-3 weeks after the lesion. In normally myelinated controls, regenerative sprouts grew less than 1.7 mm caudal to the lesion.

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

    International Nuclear Information System (INIS)

    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. (authors)

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

    International Nuclear Information System (INIS)

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

  19. 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.

  20. On Split Lie Triple Systems

    Indian Academy of Sciences (India)

    Antonio J Calderón Martín

    2009-04-01

    We begin the study of arbitrary split Lie triple systems by focussing on those with a coherent 0-root space. We show that any such triple systems with a symmetric root system is of the form $T=\\mathcal{U}+\\sum_j I_j$ with $\\mathcal{U}$ a subspace of the 0-root space $T_0$ and any $I_j$ a well described ideal of , satisfying $[I_j,T,I_k]=0$ if $j≠ k$. Under certain conditions, it is shown that is the direct sum of the family of its minimal ideals, each one being a simple split Lie triple system, and the simplicity of is characterized. The key tool in this job is the notion of connection of roots in the framework of split Lie triple systems.

  1. Split liver transplantation: What's unique?

    Science.gov (United States)

    Dalal, Aparna R

    2015-09-24

    The intraoperative management of split liver transplantation (SLT) has some unique features as compared to routine whole liver transplantations. Only the liver has this special ability to regenerate that confers benefits in survival and quality of life for two instead of one by splitting livers. Primary graft dysfunction may result from small for size syndrome. Graft weight to recipient body weight ratio is significant for both trisegmental and hemiliver grafts. Intraoperative surgical techniques aim to reduce portal hyperperfusion and decrease venous portal pressure. Ischemic preconditioning can be instituted to protect against ischemic reperfusion injury which impacts graft regeneration. Advancement of the technique of SLT is essential as use of split cadaveric grafts expands the donor pool and potentially has an excellent future. PMID:26421261

  2. Solar water splitting: efficiency discussion

    CERN Document Server

    Juodkazyte, Jurga; Sebeka, Benjaminas; Savickaja, Irena; Malinauskas, Tadas; Badokas, Kazimieras; Juodkazis, Kestutis; Juodkazis, Saulius

    2016-01-01

    The current state of the art in direct water splitting in photo-electrochemical cells (PECs) is presented together with: (i) a case study of water splitting using a simple solar cell with the most efficient water splitting electrodes and (ii) a detailed mechanism analysis. Detailed analysis of the energy balance and efficiency of solar hydrogen production are presented. The role of hydrogen peroxide formation as an intermediate in oxygen evolution reaction is newly revealed and explains why an oxygen evolution is not taking place at the thermodynamically expected 1.23 V potential. Solar hydrogen production with electrical-to-hydrogen conversion efficiency of 52% is demonstrated using a simple ~0.7%-efficient n-Si/Ni Schottky solar cell connected to a water electrolysis cell. This case study shows that separation of the processes of solar harvesting and electrolysis avoids photo-electrode corrosion and utilizes optimal electrodes for hydrogen and oxygen evolution reactions and achieves ~10% efficiency in light...

  3. Morphometric analysis of pulpal myelinated nerve fibers in human teeth with chronic periodontitis and root sensitivity

    OpenAIRE

    Vaitkevičienė, Inga; Vaitkevičius, Raimundas; Paipalienė, Pajauta; žekonis, Gediminas

    2006-01-01

    Background. The reasons why root sensitivity occurs in some periodontally diseased teeth are still unknown. It is possible that root sensitivity may be related to changes of intradental myelinated nerve fibers, which are responsible for dentine sensitivity. Objective. The aim of this study was to define the pattern of myelinated nerve fiber changes in the pulps of teeth with and without root sensitivity in the presence of chronic periodontitis. Materials and methods. A total of 33 cros...

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

    OpenAIRE

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

    2012-01-01

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

  5. MerTK Is a Functional Regulator of Myelin Phagocytosis by Human Myeloid Cells.

    Science.gov (United States)

    Healy, Luke M; Perron, Gabrielle; Won, So-Yoon; Michell-Robinson, Mackenzie A; Rezk, Ayman; Ludwin, Samuel K; Moore, Craig S; Hall, Jeffery A; Bar-Or, Amit; Antel, Jack P

    2016-04-15

    Multifocal inflammatory lesions featuring destruction of lipid-rich myelin are pathologic hallmarks of multiple sclerosis. Lesion activity is assessed by the extent and composition of myelin uptake by myeloid cells present in such lesions. In the inflamed CNS, myeloid cells are comprised of brain-resident microglia, an endogenous cell population, and monocyte-derived macrophages, which infiltrate from the systemic compartment. Using microglia isolated from the adult human brain, we demonstrate that myelin phagocytosis is dependent on the polarization state of the cells. Myelin ingestion is significantly enhanced in cells exposed to TGF-β compared with resting basal conditions and markedly reduced in classically activated polarized cells. Transcriptional analysis indicated that TGF-β-treated microglia closely resembled M0 cells. The tyrosine kinase phagocytic receptor MerTK was one of the most upregulated among a select number of differentially expressed genes in TGF-β-treated microglia. In contrast, MerTK and its known ligands, growth arrest-specific 6 and Protein S, were downregulated in classically activated cells. MerTK expression and myelin phagocytosis were higher in CNS-derived microglia than observed in monocyte-derived macrophages, both basally and under all tested polarization conditions. Specific MerTK inhibitors reduced myelin phagocytosis and the resultant anti-inflammatory biased cytokine responses for both cell types. Defining and modulating the mechanisms that regulate myelin phagocytosis has the potential to impact lesion and disease evolution in multiple sclerosis. Relevant effects would include enhancing myelin clearance, increasing anti-inflammatory molecule production by myeloid cells, and thereby permitting subsequent tissue repair. PMID:26962228

  6. RA–RAR-β counteracts myelin-dependent inhibition of neurite outgrowth via Lingo-1 repression

    OpenAIRE

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

    2011-01-01

    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...

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

    OpenAIRE

    Bakhti, M.; Winter, C.; Simons, M.

    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...

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

    DEFF Research Database (Denmark)

    Hempel, Casper; Hyttel, Poul; Staals, Trine; Nyengaard, Jens Randel; Kurtzhals, Jrgen Al

    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...... 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...

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

    OpenAIRE

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

    2008-01-01

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

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

    OpenAIRE

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

    2001-01-01

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

  11. Peripheral Myelin Protein 22 is Regulated Post-Transcriptionally by miRNA-29a

    OpenAIRE

    Verrier, Jonathan D; Lau, Pierre; Hudson, Lynn; Murashov, Alexander K.; Renne, Rolf; Notterpek, Lucia

    2009-01-01

    Peripheral myelin protein 22 (PMP22) is a dose-sensitive, disease-associated protein primarily expressed in myelinating Schwann cells. Either reduction or overproduction of PMP22 can result in hereditary neuropathy, suggesting a requirement for correct protein expression for peripheral nerve biology. PMP22 is post-transcriptionally regulated and the 3?untranslated region (3?UTR) of the gene exerts a negative effect on translation. MicroRNAs (miRNAs) are small regulatory molecules that functio...

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

    OpenAIRE

    Tobler, Andreas R.; Ning LIU; 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...

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

    OpenAIRE

    White, Robin

    2007-01-01

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

  14. 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.)

  15. Geometrical Applications of Split Octonions

    CERN Document Server

    Gogberashvili, Merab

    2015-01-01

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

  16. Split ring containment attachment device

    International Nuclear Information System (INIS)

    A containment attachment device is described for operatively connecting a glovebag to plastic sheeting covering hazardous material. The device includes an inner split ring member connected on one end to a middle ring member wherein the free end of the split ring member is inserted through a slit in the plastic sheeting to captively engage a generally circular portion of the plastic sheeting. A collar potion having an outer ring portion is provided with fastening means for securing the device together wherein the glovebag is operatively connected to the collar portion. 5 figs

  17. Split supersymmetry in brane models

    Indian Academy of Sciences (India)

    Ignatios Antoniadis

    2006-11-01

    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. For weak magnetic fields, the correct Standard Model spectrum guarantees gauge coupling unification with sin2 W = 3/8 at the com-pactification scale of GUT ≃ 2 × 1016 GeV. I discuss mechanisms for generating gaugino and higgsino masses at the TeV scale, as well as generalizations to models with split extended supersymmetry in the gauge sector.

  18. 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

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

    Directory of Open Access Journals (Sweden)

    William L. Maxwell

    2013-09-01

    Full Text Available There is increasing evidence in the experimental and clinical traumatic brain injury (TBI literature that loss of central myelinated nerve fibers continues over the chronic post-traumatic phase after injury. However, the biomechanism(s of continued loss of axons is obscure. Stretch-injury to optic nerve fibers in adult guinea-pigs was used to test the hypothesis that damage to the myelin sheath and oligodendrocytes of the optic nerve fibers may contribute to, or facilitate, the continuance of axonal loss. Myelin dislocations occur within internodal myelin of larger axons within 12 h of TBI. The myelin dislocations contain elevated levels of free calcium. The volume of myelin dislocations increase with greater survival and are associated with disruption of the axonal cytoskeleton leading to secondary axotomy. Waves of Ca2+ depolarization or spreading depression extend from the initial locus injury for perhaps hundreds of microns after TBI. As astrocytes and oligodendrocytes are connected via gap junctions, it is hypothesized that spreading depression results in depolarization of central glia, disrupt axonal ionic homeostasis, injure axonal mitochondria and allow the onset of axonal degeneration throughout an increasing volume of brain tissue; and contribute toward post-traumatic continued loss of white matter.

  20. Polarization-dependent responses of fluorescent indicators partitioned into myelinated axons

    Science.gov (United States)

    Micu, Ileana; Brideau, Craig; Stys, Peter K.

    2012-02-01

    Myelination, i.e. the wrapping of axons in multiple layers of lipid-rich membrane, is a unique phenomenon in the nervous systems of both vertebrates and invertebrates, that greatly increases the speed and efficiency of signal transmission. In turn, disruption of axo-myelinic integrity underlies disability in numerous clinical disorders. The dependence of myelin physiology on nanometric organization of its lamellae makes it difficult to accurately study this structure in the living state. We expected that fluorescent probes might become highly oriented when partitioned into the myelin sheath, and in turn, this anisotropy could be interrogated by controlling the polarization state of the exciting laser field used for 2-photon excited fluorescence (TPEF). Live ex vivo myelinated rodent axons were labeled with a series of lipohilic and hydrophilic fluorescenct probes, and TPEF images acquired while laser polarization was varied at the sample over a broad range of ellipticities and orientations of the major angle [see Brideau, Micu & Stys, abstract this meeting]. We found that most probes exhibited strong dependence on both the major angle of polarization, and perhaps more surprisingly, on ellipticity as well. Lipophilic vs. hydrophilic probes exhibited distinctly different behavior. We propose that polarization-dependent TPEF microscopy represents a powerful tool for probing the nanostructural architecture of both myelin and axonal cytoskeleton in a domain far below the resolution limit of visible light microscopy. By selecting probes with different sizes and physicochemical properties, distinct aspects of cellular nanoarchitecture can be accurately interrogated in real-time in living tissue.

  1. Hypothyroxinemia induced by maternal mild iodine deficiency impairs hippocampal myelinated growth in lactational rats.

    Science.gov (United States)

    Wei, Wei; Wang, Yi; Dong, Jing; Wang, Yuan; Min, Hui; Song, Binbin; Shan, Zhongyan; Teng, Weiping; Xi, Qi; Chen, Jie

    2015-11-01

    Hypothyroxinemia induced by maternal mild iodine deficiency causes neurological deficits and impairments of brain function in offspring. Hypothyroxinemia is prevalent in developing and developed countries alike. However, the mechanism underlying these deficits remains less well known. Given that the myelin plays an important role in learning and memory function, we hypothesize that hippocampal myelinated growth may be impaired in rat offspring exposed to hypothyroxinemia induced by maternal mild iodine deficiency. To test this hypothesis, the female Wistar rats were used and four experimental groups were prepared: (1) control; (2) maternal mild iodine deficiency diet inducing hypothyroxinemia; (3) hypothyroidism induced by maternal severe iodine deficiency diet; (4) hypothyroidism induced by maternal methimazole water. The rats were fed the diet from 3 months before pregnancy to the end of lactation. Our results showed that the physiological changes occuring in the hippocampal myelin were altered in the mild iodine deficiency group as indicated by the results of immunofluorescence of myelin basic proteins on postnatal day 14 and postnatal day 21. Moreover, hypothyroxinemia reduced the expressions of oligodendrocyte lineage transcription factor 2 and myelin-related proteins in the treatments on postnatal day 14 and postnatal day 21. Our data suggested that hypothyroxinemia induced by maternal mild iodine deficiency may impair myelinated growth of the offspring. PMID:24753110

  2. Changes of magnetization transfer contrast of cerebral parenchyma during myelinating process in infants

    International Nuclear Information System (INIS)

    The myelinating processes are evaluated by spin echo MR images focused upon quantitative changes of myelin. The purpose of this study is to analyze a new method for the myelination using magnetization transfer ratios (MTRs) and calculated images. Thirty three newborns and infants (0 to 8 months) underwent MR study using gradient echo sequences with and without off-resonance pulse irradiation on a 1.5 T superconducting unit. The MTRs were measured in the internal capsula, genu and splenium of the corpus callosum, thalami, and putamina on the calculated images made out of two paired images. The MTRs in the white matter were lower than those of adult within 3 months and showed increase between 3 to 4 months followed by reaching the level of adult after 4 months. The gray matter represented similar MTR values as those of adult, however increased MTRs were also demonstrated between 3 to 4 months. As the white matter is composed of myelin which includes rich cholesterol, high MTRs in the white matter after 3 months suggested an increase of cholesterol and proportional changes between the lipid and cholesterol in the myelin. The gray matter also includes myelin components and it may reflect increasing of MTRs at the same period. (author)

  3. Understanding the Role of the Axon/glia Functional Unit in Myelination and Remyelination

    Directory of Open Access Journals (Sweden)

    Laura Montani

    2009-08-01

    Full Text Available Myelin loss is one of the major mechanisms underlying the pathology of several serious neurological disorders, e.g. multiple sclerosis. Remyelination is a process required to recover physiological activity and consists of a complex network of events thought to be regulated by multiple not yet understood pathways occurring in response to the unpredictable pathological process of demyelination in an adult system, therefore differing from the spatial and temporal organized process of developmental myelination. In the adult peripheral nervous system remyelination occurs spontaneously, allowing function restoration. In the central nervous system after few years of disease evolution ongoing CNS remyelination is often insufficient to preserve axon integrity and chronically demyelinated axons undergo degeneration causing irreversible clinical decline. In the past few years it has been realized that myelinating glial cells directly and extensively interacts with the axons through bidirectional communication. Recent data suggest an active role of the axon/glia functional unit in the maintenance of axon integrity, whose preservation could be the key to prevent chronic progressive disability. Despite of the importance of these processes, no comprehensive study has clarified the molecules involved in the establishment and maintenance of an efficient axon/glial functional unit in myelination/remyelination. We aim to address this question using a multidisciplinary systems biology approach integrating proteomics (iTRAQ, bioinformatics, cell and molecular biology. We plan to: - Elucidate which key molecules play a role in the establishment and maintenance of the CNS axon/glia functional unit during developmental myelination, by screening membrane proteins expressed on the nude axons just before myelination and on myelin; - compare the developmental axon/glia membrane proteome to that of the nude axon following demyelination and subsequently newly formed myelin, to identify differentially expressed proteins which could play a role in the establishment of an inefficient remyelination; - validate potential key players and test their role in myelination/remyelination in vitro by functional assays. Profiling the proteome could be the next fundamental step to understand myelination as well as the disregulation of the proteomic program which can cause defective CNS remyelination, and could permit the identification of new disease-related factors and therapeutical targets. Acknowledgements: L. Montani is EU founded under FP7 scheme: Marie Curie IEF 2008 - Intra European Fellowship - Project AXOGLIA, IBMC -

  4. Peripheral myelin of Xenopus laevis: role of electrostatic and hydrophobic interactions in membrane compaction.

    Science.gov (United States)

    Luo, XiaoYang; Cerullo, Jana; Dawli, Tamara; Priest, Christina; Haddadin, Zaid; Kim, Angela; Inouye, Hideyo; Suffoletto, Brian P; Avila, Robin L; Lees, Jonathan P B; Sharma, Deepak; Xie, Bo; Costello, Catherine E; Kirschner, Daniel A

    2008-04-01

    P0 glycoprotein is the major structural protein of peripheral nerve myelin where it is thought to modulate inter-membrane adhesion at both the extracellular apposition, which is labile upon changes in pH and ionic strength, and the cytoplasmic apposition, which is resistant to such changes. Most studies on P0 have focused on structure-function correlates in higher vertebrates. Here, we focused on its role in the structure and interactions of frog (Xenopus laevis) myelin, where it exists primarily in a dimeric form. As part of our study, we deduced the full sequence of X. laevis P0 (xP0) from its cDNA. The xP0 sequence was found to be similar to P0 sequences of higher vertebrates, suggesting that a common mechanism of PNS myelin compaction via P0 interaction might have emerged through evolution. As previously reported for mouse PNS myelin, a similar change of extracellular apposition in frog PNS myelin as a function of pH and ionic strength was observed, which can be explained by a conformational change of P0 due to protonation-deprotonation of His52 at P0's putative adhesive interface. On the other hand, the cytoplasmic apposition in frog PNS myelin, like that in the mouse, remained unchanged at different pH and ionic strength. The contribution of hydrophobic interactions to stabilizing the cytoplasmic apposition was tested by incubating sciatic nerves with detergents. Dramatic expansion at the cytoplasmic apposition was observed for both frog and mouse, indicating a common hydrophobic nature at this apposition. Urea also expanded the cytoplasmic apposition of frog myelin likely owing to denaturation of P0. Removal of the fatty acids that attached to the single Cys residue in the cytoplasmic domain of P0 did not change PNS myelin structure of either frog or mouse, suggesting that the P0-attached fatty acyl chain does not play a significant role in PNS myelin compaction and stability. These results help clarify the present understanding of P0's adhesion role and the role of its acylation in compact PNS myelin. PMID:18065238

  5. 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).

  6. Cool covered sky-splitting spectrum-splitting FK

    Science.gov (United States)

    Mohedano, Rubn; Miano, 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 Khler (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.

  7. Cool covered sky-splitting spectrum-splitting FK

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-09-26

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

  8. 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

  9. Mutation in the myelin proteolipid protein gene alters BK and SK channel function in the caudal medulla

    OpenAIRE

    Mayer, Catherine A; Macklin, Wendy B.; Avishai, Nanthawan; Balan, Kannan; Wilson, Christopher G.; Miller, Martha J.

    2009-01-01

    Proteolipid protein (Plp) gene mutation in rodents causes severe CNS dysmyelination, early death, and lethal hypoxic ventilatory depression (Miller et al. 2004). To determine if Plp mutation alters neuronal function critical for control of breathing, the nucleus tractus solitarii (nTS) of four rodent strains were studied: myelin deficient rats (MD), myelin synthesis deficient (Plpmsd), and Plpnull mice, as well as shiverer (Mbpshi) mice, a myelin basic protein mutant. Current-voltage relation...

  10. Neuroactive steroids influence peripheral myelination: A promising opportunity for preventing or treating age-dependent dysfunctions of peripheral nerves

    OpenAIRE

    R.C. Melcangi; Azcoitia, I.; M. Ballabio; Cavarretta, I.; Gonzalez, L.C.; Leonelli, E.; Magnaghi, V.; Veiga, S.; Garcia-Segura, Luis M

    2003-01-01

    The process of aging deeply influences morphological and functional parameters of peripheral nerves. The observations summarized here indicate that the deterioration of myelin occurring in the peripheral nerves during aging may be explained by the fall of the levels of the major peripheral myelin proteins [e.g., glycoprotein Po (Po) and peripheral myelin protein 22 (PMP22)]. Neuroactive steroids, such as progesterone (PROG), dihydroprogesterone (5?-DH PROG), and tetrahydroprogesterone (3?,5?-...

  11. Developmental abnormalities in the nerves of peripheral myelin protein 22-deficient mice.

    Science.gov (United States)

    Amici, Stephanie A; Dunn, William A; Notterpek, Lucia

    2007-02-01

    Peripheral myelin protein 22 (PMP22) is a tetraspan glycoprotein whose misexpression is associated with a family of hereditary peripheral neuropathies. In a recent report, we have characterized a novel PMP22-deficient mouse model in which the first two coding exons were replaced by the lacZ reporter. To investigate further the myelin abnormalities in the absence of PMP22, sciatic nerves and dorsal root ganglion (DRG) neuron explant cultures from PMP22-deficient mice were studied at various stages of myelination. Throughout the first 3 months of postnatal development, myelin protein and beta4 integrin levels are dramatically reduced, whereas p75 and beta1 integrin remain elevated. By immunostaining, the distributions of several glial proteins, including beta4 integrin, the voltage-gated potassium channel Kv1.1, and E-cadherin, are altered. Schwann cells from PMP22-deficient mice are able to produce limited amounts of myelin in DRG explant cultures, yet the internodal segments are dramatically fewer and shorter. The comparison of PMP22-deficient mice with other PMP22 mutant models reveals that the decrease in beta4 integrin is specific to an absence of PMP22. Furthermore, whereas lysosome-associated membrane protein 1 and ubiquitin are notably up-regulated in nerves of PMP22-deficient mice, heat shock protein 70 levels remain constant or decrease compared with wild-type or PMP22 mutant samples. Together these results support a role for PMP22 in the early events of peripheral nerve myelination. Additionally, although myelin abnormalities are a commonality among PMP22 neuropathic models, the underlying subcellular mechanisms are distinct and depend on the specific genetic abnormality. PMID:17131416

  12. Classic and Golli Myelin Basic Protein have distinct developmental trajectories in human visual cortex.

    Science.gov (United States)

    Siu, Caitlin R; Balsor, Justin L; Jones, David G; Murphy, Kathryn M

    2015-01-01

    Traditionally, myelin is viewed as insulation around axons, however, more recent studies have shown it also plays an important role in plasticity, axonal metabolism, and neuroimmune signaling. Myelin is a complex multi-protein structure composed of hundreds of proteins, with Myelin Basic Protein (MBP) being the most studied. MBP has two families: Classic-MBP that is necessary for activity driven compaction of myelin around axons, and Golli-MBP that is found in neurons, oligodendrocytes, and T-cells. Furthermore, Golli-MBP has been called a "molecular link" between the nervous and immune systems. In visual cortex specifically, myelin proteins interact with immune processes to affect experience-dependent plasticity. We studied myelin in human visual cortex using Western blotting to quantify Classic- and Golli-MBP expression in post-mortem tissue samples ranging in age from 20 days to 80 years. We found that Classic- and Golli-MBP have different patterns of change across the lifespan. Classic-MBP gradually increases to 42 years and then declines into aging. Golli-MBP has early developmental changes that are coincident with milestones in visual system sensitive period, and gradually increases into aging. There are three stages in the balance between Classic- and Golli-MBP expression, with Golli-MBP dominating early, then shifting to Classic-MBP, and back to Golli-MBP in aging. Also Golli-MBP has a wave of high inter-individual variability during childhood. These results about cortical MBP expression are timely because they compliment recent advances in MRI techniques that produce high resolution maps of cortical myelin in normal and diseased brain. In addition, the unique pattern of Golli-MBP expression across the lifespan suggests that it supports high levels of neuroimmune interaction in cortical development and in aging. PMID:25964736

  13. Cholesterol regulates the endoplasmic reticulum exit of the major membrane protein P0 required for peripheral myelin compaction.

    Science.gov (United States)

    Saher, Gesine; Quintes, Susanne; Mbius, Wiebke; Wehr, Michael C; Krmer-Albers, Eva-Maria; Brgger, Britta; Nave, Klaus-Armin

    2009-05-13

    Rapid impulse conduction requires electrical insulation of axons by myelin, a cholesterol-rich extension of the glial cell membrane with a characteristic composition of proteins and lipids. Mutations in several myelin protein genes cause endoplasmic reticulum (ER) retention and disease, presumably attributable to failure of misfolded proteins to pass the ER quality control. Because many myelin proteins partition into cholesterol-rich membrane rafts, their interaction with cholesterol could potentially be part of the ER quality control system. Here, we provide in vitro and in vivo evidence that the major peripheral myelin protein P0 requires cholesterol for exiting the ER and reaching the myelin compartment. Cholesterol dependency of P0 trafficking in heterologous cells is mediated by a cholesterol recognition/interaction amino acid consensus (CRAC) motif. Mutant mice lacking cholesterol biosynthesis in Schwann cells suffer from severe hypomyelination with numerous uncompacted myelin stretches. This demonstrates that high-level cholesterol coordinates P0 export with myelin membrane synthesis, which is required for the correct stoichiometry of myelin components and for myelin compaction. PMID:19439587

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

    International Nuclear Information System (INIS)

    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

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

    OpenAIRE

    Shin, Daesung; Howng, Shen Yi B.; Pt?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...

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

    Energy Technology Data Exchange (ETDEWEB)

    Knoll, W. [University Joseph Fourier, UFR PhiTEM, Grenoble (France); Institut Laue–Langevin, Grenoble (France); Peters, J. [University Joseph Fourier, UFR PhiTEM, Grenoble (France); Institut Laue–Langevin, Grenoble (France); Institut de Biologie Structurale, Grenoble (France); Kursula, P. [University of Oulu, Oulu (Finland); CSSB–HZI, DESY, Hamburg (Germany); Gerelli, Y. [Institut Laue–Langevin, Grenoble (France); Natali, F., E-mail: natali@ill.fr [Institut Laue–Langevin, Grenoble (France); CNR–IOM–OGG, c/o Institut Laue–Langevin, Grenoble (France)

    2014-11-28

    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.

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

    Science.gov (United States)

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

    2004-03-01

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

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

    Science.gov (United States)

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

    2014-08-01

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

  19. Characterization of dodecylphosphocholine/myelin basic protein complexes

    International Nuclear Information System (INIS)

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

  20. Evaluation of Optimal Split-Plot Designs

    OpenAIRE

    Julian Mbegbu; Ogege Ikhata Francis

    2012-01-01

    The study introduced an algorithm for generating optimal split-plot designs. The designs were considered as optimal because they were capable and ecient in estimating the xed e ects of the statistical model that is appropriate given the split-plot design structure. Here, we introduced I-optimal design of split-plot experiments. The algorithm used in this research does not require the prior speci cation of a candidate set. Therefore, making the design of split-plot experiments computationally ...

  1. Splitting methods with complex coefficients

    CERN Document Server

    Blanes, Sergio; Murua, Ander

    2010-01-01

    Splitting methods for the numerical integration of differential equations of order greater than two involve necessarily negative coefficients. This order barrier can be overcome by considering complex coefficients with positive real part. In this work we review the composition technique used to construct methods of this class, propose new sixth-order integrators and analyze their main features on a pair of numerical examples, in particular how the errors are propagated along the evolution.

  2. Splitting methods with complex coefficients

    OpenAIRE

    Blanes, Sergio; Casas Pérez, Fernando; Murua, Ander

    2010-01-01

    Splitting methods for the numerical integration of differential equations of order greater than two involve necessarily negative coefficients. This order barrier can be overcome by considering complex coefficients with positive real part. In this work we review the composition technique used to construct methods of this class, propose new sixth- order integrators and analyze their main features on a pair of numerical examples, in particular how the errors are propagated along the evolution.

  3. Split Nonthreshold Laplacian Integral Graphs

    OpenAIRE

    Kirkland, Stephen; de Freitas, Maria Aguieiras Alvarez; Del Vecchio, Renata Raposo; de Abreu, Nair Maria Maia

    2010-01-01

    The aim of this article is to answer a question posed by Merris in European Journal of Combinatorics, 24(2003)413¡430, about the pos sibility of finding split nonthreshold graphs that are Laplacian integral, i.e., graphs for which the eigenvalues of the corresponding Laplacian matrix are integers. Using Kronecker products, balanced incomplete block designs, and solutions to certain Diophantine equations, we show how to build infinite families of these graphs.

  4. A strategic range split problem

    OpenAIRE

    Degraeve, Zeger; Jans, Raf

    2000-01-01

    This paper describes a real life case of a joint production-marketing decision problem at a large international manufacturer. The range of products considered in this study is split up into product families. All the models within each product family make use of some common basic components. The company wants to redesign the products. The goal of the redesign is to increase quality and reliability and boost benefits for the customers in addition to lowering production costs. The cost reduction...

  5. Matrix recovery using Split Bregman

    OpenAIRE

    Gogna, Anupriya; Shukla, Ankita; Majumdar, Angshul

    2013-01-01

    In this paper we address the problem of recovering a matrix, with inherent low rank structure, from its lower dimensional projections. This problem is frequently encountered in wide range of areas including pattern recognition, wireless sensor networks, control systems, recommender systems, image/video reconstruction etc. Both in theory and practice, the most optimal way to solve the low rank matrix recovery problem is via nuclear norm minimization. In this paper, we propose a Split Bregman a...

  6. Splitting Methods for Convex Clustering

    OpenAIRE

    Chi, Eric C.; Lange, Kenneth

    2013-01-01

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

  7. 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

  8. Split torque transmission load sharing

    Science.gov (United States)

    Krantz, T. L.; Rashidi, M.; Kish, J. G.

    1992-10-01

    Split torque transmissions are attractive alternatives to conventional planetary designs for helicopter transmissions. The split torque designs can offer lighter weight and fewer parts but have not been used extensively for lack of experience, especially with obtaining proper load sharing. Two split torque designs that use different load sharing methods have been studied. Precise indexing and alignment of the geartrain to produce acceptable load sharing has been demonstrated. An elastomeric torque splitter that has large torsional compliance and damping produces even better load sharing while reducing dynamic transmission error and noise. However, the elastomeric torque splitter as now configured is not capable over the full range of operating conditions of a fielded system. A thrust balancing load sharing device was evaluated. Friction forces that oppose the motion of the balance mechanism are significant. A static analysis suggests increasing the helix angle of the input pinion of the thrust balancing design. Also, dynamic analysis of this design predicts good load sharing and significant torsional response to accumulative pitch errors of the gears.

  9. Testing split supersymmetry with inflation

    Science.gov (United States)

    Craig, Nathaniel; Green, Daniel

    2014-07-01

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

  10. 7 CFR 51.2002 - Split shell.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Split shell. 51.2002 Section 51.2002 Agriculture... Standards for Grades of Filberts in the Shell 1 Definitions § 51.2002 Split shell. Split shell means a shell... of the shell, measured in the direction of the crack....

  11. Actin filament turnover drives leading edge growth during myelin sheath formation in the central nervous system

    Science.gov (United States)

    Schmitt, Sebastian; Snaidero, Nicolas; Mitkovski, Mio; Velte, Caroline; Brckner, Bastian R.; Alexopoulos, Ioannis; Czopka, Tim; Jung, Sang Y.; Rhee, Jeong S.; Janshoff, Andreas; Witke, Walter; Schaap, Iwan A.T.; Lyons, David A.; Simons, Mikael

    2016-01-01

    Summary During central nervous system development, oligodendrocytes wrap their plasma membrane around axons to generate multi-lamellar myelin sheaths. To drive growth at the leading edge of myelin at the interface with the axon, mechanical forces are necessary, but the underlying mechanisms are not known. Using an interdisciplinary approach that combines morphological, genetic and biophysical analyses, we identified a key role for actin filament network turnover in myelin growth. At the onset of myelin biogenesis, F-actin is redistributed to the leading edge, where its polymerization-based forces push out non-adhesive and motile protrusions. F-actin disassembly converts protrusions into sheets by reducing surface tension and in turn inducing membrane spreading and adhesion. We identified the actin depolymerizing factor ADF/Cofilin1, which mediates high F-actin turnover rates, as essential factor in this process. We propose that F-actin turnover is the driving force in myelin wrapping by regulating repetitive cycles of leading edge protrusion and spreading. PMID:26166299

  12. Insertion of Mutant Proteolipid Protein Results in Missorting of Myelin Proteins

    Science.gov (United States)

    Vaurs-Barriere, Catherine; Wong, Kondi; Weibel, Thais D.; Abu-Asab, Mones; Weiss, Michael D.; Kaneski, Christine R.; Mixon, Tong-Hui; Bonavita, Simona; Creveaux, Isabelle; Heiss, John D.; Tsokos, Maria; Goldin, Ehud; Quarles, Richard H.; Boespflug-Tanguy, Odile; Schiffmann, Raphael

    2014-01-01

    Two brothers with a leukodystrophy, progressive spastic diplegia, and peripheral neuropathy were found to have proteinaceous aggregates in the peripheral nerve myelin sheath. The patients mother had only subclinical peripheral neuropathy, but the maternal grandmother had adult-onset leukodystrophy. Sequencing of the proteolipid protein (PLP) gene showed a point mutation IVS4 + 1 G?A within the donor splice site of intron 4. We identified one transcript with a deletion of exon 4 (?ex4, 169bp) encoding for PLP and DM20 proteins and lacking two transmembrane domains, and a second transcript with exon 4 + 10bp encoding three transmembrane domains. Immunohistochemistry showed abnormal aggregation in the myelin sheath of MBP and P0. Myelin-associated glycoprotein was present in the SchmidtLanterman clefts but significantly reduced in the periaxonal region. Using immunogold electron microscopy, we demonstrated the presence of mutated PLP/DM20 and the absence of the intact protein in the patient peripheral myelin sheath. We conclude that insertion of mutant PLP/DM20 with resulting aberrant distribution of other myelin proteins in peripheral nerve may constitute an important mechanism of dysmyelination in disorders associated with PLP mutations. PMID:14681886

  13. Water translocation from the axial cylinder to myelin sheath structures of the nerve fiber.

    Science.gov (United States)

    Sotnikov, O S; Kokurina, T N; Kuznetsova, I N; Vasyagina, N Yu

    2011-10-01

    We studied isolated myelinated nerve fibers from frog sciatic nerve surviving in Ringer solution or in water-free liquid perfluorodecalin immiscible with water or mineral oil. Swelling of incisures and perikaryon, loosening of myelin in the node, and formation of the axial cylinder varicosities were found in the fibers surviving in Ringer solution after 5-7 h. The same process, swelling of Schmidt-Lantermann myelin incisures, Schwann cell perikaryon, and loosening of myelin lamellae in the Ranvier nodes was found in water-free perfluorodecalin medium. However, swelling of the perikaryon and incisures spread along the axial cylinder and the reaction of the fiber developed in perfluorodecalin much later and unfolded slower than in the control. These changes developed much sooner and progressed much more rapidly than in perfluorodecalin in fibers surviving in mineral oil. Swelling of the myelin sheath structures in water-free medium indicated an uncommon new form of the neuron-glia relationships: water translocation from the axial cylinder to Schwann cell under unfavorable conditions. PMID:22485225

  14. 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)

  15. CNS myelin structural modification induced in vitro by phospholipases A2.

    Science.gov (United States)

    Yunes Quartino, Pablo J; Pusterla, Julio M; Galván Josa, Victor M; Fidelio, Gerardo D; Oliveira, Rafael G

    2016-01-01

    Myelin is the self-stacked membrane surrounding axons; it is also the target of several pathological and/or neurodegenerative processes like multiple sclerosis. These processes involve, among others, the hydrolytic attack by phospholipases. In this work we describe the changes in isolated myelin structure after treatment with several secreted PLA2 (sPLA2), by using small angle x-ray scattering (SAXS) measurements. It was observed that myelin treated with all the tested sPLA2s (from cobra and bee venoms and from pig pancreas) preserved the lamellar structure but displayed an enlarged separation between membranes in certain zones. Additionally, the peak due to membrane asymmetry was clearly enhanced. The coherence length was also lower than the non-treated myelin, indicating increased disorder. These SAXS results were complemented by Langmuir film experiments to follow myelin monolayer hydrolysis at the air/water interface by a decrease in electric surface potential at different surface pressures. All enzymes produced hydrolysis with no major qualitative difference between the isoforms tested. PMID:26514604

  16. 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

  17. Movement and structure of mitochondria in oligodendrocytes and their myelin sheaths.

    Science.gov (United States)

    Rinholm, Johanne E; Vervaeke, Koen; Tadross, Michael R; Tkachuk, Ariana N; Kopek, Benjamin G; Brown, Timothy A; Bergersen, Linda H; Clayton, David A

    2016-05-01

    Mitochondria play several crucial roles in the life of oligodendrocytes. During development of the myelin sheath they are essential providers of carbon skeletons and energy for lipid synthesis. During normal brain function their consumption of pyruvate will be a key determinant of how much lactate is available for oligodendrocytes to export to power axonal function. Finally, during calcium-overload induced pathology, as occurs in ischemia, mitochondria may buffer calcium or induce apoptosis. Despite their important functions, very little is known of the properties of oligodendrocyte mitochondria, and mitochondria have never been observed in the myelin sheaths. We have now used targeted expression of fluorescent mitochondrial markers to characterize the location and movement of mitochondria within oligodendrocytes. We show for the first time that mitochondria are able to enter and move within the myelin sheath. Within the myelin sheath the highest number of mitochondria was in the cytoplasmic ridges along the sheath. Mitochondria moved more slowly than in neurons and, in contrast to their behavior in neurons and astrocytes, their movement was increased rather than inhibited by glutamate activating NMDA receptors. By electron microscopy we show that myelin sheath mitochondria have a low surface area of cristae, which suggests a low ATP production. These data specify fundamental properties of the oxidative phosphorylation system in oligodendrocytes, the glial cells that enhance cognition by speeding action potential propagation and provide metabolic support to axons. GLIA 2016;64:810-825. PMID:26775288

  18. 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.

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

    International Nuclear Information System (INIS)

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

  20. 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

  1. Innovative wedge axe in making split firewood

    International Nuclear Information System (INIS)

    Interteam Oy, a company located in Espoo, has developed a new method for making split firewood. The tools on which the patented System Logmatic are based are wedge axe and cylindrical splitting-carrying frame. The equipment costs about 495 FIM. The block of wood to be split is placed inside the upright carrying frame and split in a series of splitting actions using the innovative wedge axe. The finished split firewood remains in the carrying frame, which (as its name indicates) also serves as the means for carrying the firewood. This innovative wedge-axe method was compared with the conventional splitting of wood using an axe (Fiskars -handy 1400 splitting axe costing about 200 FIM) in a study conducted at TTS-Institute. There were eight test subjects involved in the study. In the case of the wedge-axe method, handling of the blocks to be split and of the finished firewood was a little quicker, but in actual splitting it was a little slower than the conventional axe method. The average productivity of splitting the wood and of the work stages related to it was about 0.4 m3 per effective hour in both methods. The methods were also equivalent of one another in terms of the load imposed by the work when measured in terms of the heart rate. As regards work safety, the wedge-axe method was superior to the conventional method, but the continuous striking action and jolting transmitted to the arms were unpleasant (orig.)

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Zaman, M.S.

    1989-01-01

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

  4. Chronic intermittent ethanol induced axon and myelin degeneration is attenuated by calpain inhibition.

    Science.gov (United States)

    Samantaray, Supriti; Knaryan, Varduhi H; Patel, Kaushal S; Mulholland, Patrick J; Becker, Howard C; Banik, Naren L

    2015-10-01

    Chronic alcohol consumption causes multifaceted damage to the central nervous system (CNS), underlying mechanisms of which are gradually being unraveled. In our previous studies, activation of calpain, a calcium-activated neutral protease has been found to cause detrimental alterations in spinal motor neurons following ethanol (EtOH) exposure in vitro. However, it is not known whether calpain plays a pivotal role in chronic EtOH exposure-induced structural damage to CNS in vivo. To test the possible involvement of calpain in EtOH-associated neurodegenerative mechanisms the present investigation was conducted in a well-established mouse model of alcohol dependence - chronic intermittent EtOH (CIE) exposure and withdrawal. Our studies indicated significant loss of axonal proteins (neurofilament light and heavy, 50-60%), myelin proteins (myelin basic protein, 20-40% proteolipid protein, 25%) and enzyme (2', 3'-cyclic-nucleotide 3'-phosphodiesterase, 21-55%) following CIE in multiple regions of brain including hippocampus, corpus callosum, cerebellum, and importantly in spinal cord. These CIE-induced deleterious effects escalated after withdrawal in each CNS region tested. Increased expression and activity of calpain along with enhanced ratio of active calpain to calpastatin (sole endogenous inhibitor) was observed after withdrawal compared to EtOH exposure. Pharmacological inhibition of calpain with calpeptin (25 ?g/kg) prior to each EtOH vapor inhalation significantly attenuated damage to axons and myelin as demonstrated by immuno-profiles of axonal and myelin proteins, and Luxol Fast Blue staining. Calpain inhibition significantly protected the ultrastructural integrity of axons and myelin compared to control as confirmed by electron microscopy. Together, these findings confirm CIE exposure and withdrawal induced structural alterations in axons and myelin, predominantly after withdrawal and corroborate calpain inhibition as a potential protective strategy against EtOH associated CNS degeneration. PMID:26100335

  5. Involvement of MeCP2 in Regulation of Myelin-Related Gene Expression in Cultured Rat Oligodendrocytes.

    Science.gov (United States)

    Sharma, Kedarlal; Singh, Juhi; Pillai, Prakash P; Frost, Emma E

    2015-10-01

    Methyl CpG binding protein 2 (MeCP2) is a multifunctional protein which binds to methylated CpG, mutation of which cause a neurodevelopmental disorder, Rett syndrome. MeCP2 can function as both transcriptional activator and repressor of target gene. MeCP2 regulate gene expression in both neuron and glial cells in central nervous system (CNS). Oligodendrocytes, the myelinating cells of CNS, are required for normal functioning of neurons and are regulated by several transcription factors during their differentiation. In current study, we focused on the role of MeCP2 as transcription regulator of myelin genes in cultured rat oligodendrocytes. We have observed expression of MeCP2 at all stages of oligodendrocyte development. MeCP2 knockdown in cultured oligodendrocytes by small interference RNA (siRNA) has shown increase in myelin genes (myelin basic protein (MBP), proteolipid protein (PLP), myelin oligodendrocyte glycoprotein (MOG), and myelin-associated oligodendrocyte basic protein (MOBP)), neurotrophin (brain-derived neurotrophic factor (BDNF)), and transcriptional regulator (YY1) transcripts level, which are involved in regulation of oligodendrocyte differentiation and myelination. Further, we also found that protein levels of MBP, PLP, DM-20, and BDNF also significantly upregulated in MeCP2 knockdown oligodendrocytes. Our study suggests that the MeCP2 acts as a negative regulator of myelin protein expression. PMID:26140854

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

    International Nuclear Information System (INIS)

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

  7. Mutations in the Myelin Protein Zero result in a spectrum of Charcot-Marie-Tooth phenotypes.

    Science.gov (United States)

    Kocha?ski, A

    2004-05-01

    Initially the Myelin Protein Zero gene was shown to be mutated in the demyelinating form of Charcot-Marie-Tooth disease (CMT1). The vast majority of the mutations in the Myelin Protein Zero gene have been detected in the Charcot-Marie-Tooth (1B) disease, however, some of them were found in patients suffering from congenital hypomyelinating neuropathy and axonal type Charcot-Marie-Tooth disease. In this study, a Charcot-Marie-Tooth disease phenotype diversity associated with different mutations in the MPZ gene, is described. PMID:15298082

  8. Gain of glycosylation: a new pathomechanism of myelin protein zero mutations.

    Science.gov (United States)

    Prada, Valeria; Passalacqua, Mario; Bono, Maria; Luzzi, Paola; Scazzola, Sara; Nobbio, Lucilla Alessandra; Capponi, Simona; Bellone, Emilia; Mandich, Paola; Mancardi, Gianluigi; Shy, Michael; Schenone, Angelo; Grandis, Marina

    2012-03-01

    We report the first case of a missense mutation in MPZ causing a gain of glycosylation in myelin protein zero, the main protein of peripheral nervous system myelin. The patient was affected by a severe demyelinating neuropathy caused by a missense mutation, D32N, that created a new glycosylation sequence. We confirmed that the mutant protein is hyperglycosylated, is partially retained into the Golgi apparatus in vitro, and disrupts intercellular adhesion. By sequential experiments, we demonstrated that hyperglycosylation is the main mechanism of this mutation. Gain of glycosylation is a new mechanism in Charcot-Marie-Tooth type 1B. PMID:22451207

  9. 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.)

  10. Peripheral myelin of Xenopus laevis: Role of electrostatic and hydrophobic interactions in membrane compaction

    OpenAIRE

    Luo, Xiaoyang; Cerullo, Jana; Dawli, Tamara; Priest, Christina; Haddadin, Zaid; Kim, Angela; Inouye, Hideyo; Suffoletto, Brian P; Avila, Robin L; Lees, Jonathan P. B.; Sharma, Deepak; Xie, Bo; Catherine E. Costello; Kirschner, Daniel A

    2007-01-01

    P0 glycoprotein is the major structural protein of peripheral nerve myelin where it is thought to modulate inter-membrane adhesion at both the extracellular apposition, which is labile upon changes in pH and ionic strength, and the cytoplasmic apposition, which is resistant to such changes. Most studies on P0 have focused on structure-function correlates in higher vertebrates. Here, we focused on its role in the structure and interactions of frog (Xenopus laevis) myelin, where it exists prima...

  11. Dominant-negative effect on adhesion by myelin Po protein truncated in its cytoplasmic domain

    OpenAIRE

    1996-01-01

    The myelin Po protein is believed to hold myelin together via interactions of both its extracellular and cytoplasmic domains. We have already shown that the extracellular domains of Po can interact in a homophilic manner (Filbin, M.T., F.S. Walsh, B.D. Trapp, J.A. Pizzey, and G.I. Tennekoon. 1990. Nature (Lond.). 344:871-872). In addition, we have shown that for this homophilic adhesion to take place, the cytoplasmic domain of Po must be intact and most likely interacting with the cytoskeleto...

  12. Expression of Transcripts for Myelin Related Genes in Postmortem Brain from Cocaine Abusers

    OpenAIRE

    Kristiansen, Lars V.; Meador-Woodruff, James H.; Bannon, Michael J.

    2008-01-01

    Chronic abuse of cocaine is known to cause neuroadaptive changes in the nucleus accumbens (NAc) and ventral tegmental area (VTA). In addition, altered expression of the myelin-related genes MBP, MOBP, PLP1 as well as of MAL2 in NAc was recently reported by gene array analysis in brains from cocaine abusers. In the present study we used in situ hybridization to quantify transcript expression of these four genes, as well as for the myelin-related transcripts encoding quaking, EDG2, claudin-11, ...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-07-01

    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).

  14. Rectangular split-ring resonators with single-split and two-splits under different excitations at microwave frequencies

    Directory of Open Access Journals (Sweden)

    S. Zahertar

    2015-11-01

    Full Text Available In this work, transmission characteristics of rectangular split-ring resonators with single-split and two-splits are analyzed at microwave frequencies. The resonators are coupled with monopole antennas for excitation. The scattering parameters of the devices are investigated under different polarizations of E and H fields. The magnetic resonances induced by E and H fields are identified and the differences in the behavior of the resonators due to orientations of the fields are explained based on simulation and experimental results. The addition of the second split of the device is investigated considering different configurations of the excitation vectors. It is demonstrated that the single-split and the two-splits resonators exhibit identical transmission characteristics for a certain excitation configuration as verified with simulations and experiments. The presented resonators can effectively function as frequency selective media for varying excitation conditions.

  15. Rectangular split-ring resonators with single-split and two-splits under different excitations at microwave frequencies

    Science.gov (United States)

    Zahertar, S.; Yalcinkaya, A. D.; Torun, H.

    2015-11-01

    In this work, transmission characteristics of rectangular split-ring resonators with single-split and two-splits are analyzed at microwave frequencies. The resonators are coupled with monopole antennas for excitation. The scattering parameters of the devices are investigated under different polarizations of E and H fields. The magnetic resonances induced by E and H fields are identified and the differences in the behavior of the resonators due to orientations of the fields are explained based on simulation and experimental results. The addition of the second split of the device is investigated considering different configurations of the excitation vectors. It is demonstrated that the single-split and the two-splits resonators exhibit identical transmission characteristics for a certain excitation configuration as verified with simulations and experiments. The presented resonators can effectively function as frequency selective media for varying excitation conditions.

  16. Structural insight into the function of myelin basic protein as a ligand for integrin αMβ2

    DEFF Research Database (Denmark)

    Stapulionis, Romualdas; Oliveira, Cristiano; Gjelstrup, Mikkel Carstensen; Pedersen, Jan Skov; Hokland, Marianne; Hoffmann, Søren Vrønning; Poulsen, Knud; Jacobsen, Christian; Vorup-Jensen, Thomas

    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...

  17. Spin resonance without spin splitting

    Science.gov (United States)

    Hell, M.; Sothmann, B.; Leijnse, M.; Wegewijs, M. R.; König, J.

    2015-05-01

    We predict that a single-level quantum dot without discernible splitting of its spin states develops a spin-precession resonance in charge transport when embedded into a spin valve. The resonance occurs in the generic situation of Coulomb blockaded transport with ferromagnetic leads whose polarizations deviate from perfect antiparallel alignment. The resonance appears when electrically tuning the interaction-induced exchange field perpendicular to one of the polarizations—a simple condition relying on vectors in contrast to usual resonance conditions associated with energy splittings. The spin resonance can be detected by stationary d I /d V spectroscopy and by oscillations in the time-averaged current using a gate-pulsing scheme. The generic noncollinearity of the ferromagnets and junction asymmetry allow for an all-electric determination of the spin-injection asymmetry, the anisotropy of spin relaxation, and the magnitude of the exchange field. We also investigate the impact of a nearby superconductor on the resonance position. Our simplistic model turns out to be generic for a broad class of coherent few-level quantum systems.

  18. Gluon splitting in a shockwave

    Science.gov (United States)

    Iancu, E.; Laidet, J.

    2013-10-01

    The study of azimuthal correlations in particle production at forward rapidities in proton-nucleus collisions provides direct information about high gluon density effects, like gluon saturation, in the nuclear wavefunction. In the kinematical conditions for proton-lead collisions at the LHC, the forward di-hadron production is dominated by partonic processes in which a gluon from the proton splits into a pair of gluons, while undergoing multiple scattering off the dense gluon system in the nucleus. We compute the corresponding cross-section using the Colour Glass Condensate effective theory, which enables us to include the effects of multiple scattering and gluon saturation in the leading logarithmic approximation at high energy. This opens the way towards systematic studies of angular correlations in two-gluon production, similar to previous studies for quark-gluon production in the literature. We consider in more detail two special kinematical limits: the "back-to-back correlation limit", where the transverse momenta of the produced gluons are much larger than the nuclear saturation momentum, and the "double parton scattering limit", where the two gluons are produced by a nearly collinear splitting occurring prior to the collision. We argue that saturation effects remain important even for relatively high transverse momenta (i.e. for nearly back-to-back configurations), leading to geometric scaling in the azimuthal distribution.

  19. Gluon splitting in a shockwave

    Energy Technology Data Exchange (ETDEWEB)

    Iancu, E., E-mail: edmond.iancu@cea.fr; Laidet, J., E-mail: julien.laidet@cea.fr

    2013-10-23

    The study of azimuthal correlations in particle production at forward rapidities in protonnucleus collisions provides direct information about high gluon density effects, like gluon saturation, in the nuclear wavefunction. In the kinematical conditions for protonlead collisions at the LHC, the forward di-hadron production is dominated by partonic processes in which a gluon from the proton splits into a pair of gluons, while undergoing multiple scattering off the dense gluon system in the nucleus. We compute the corresponding cross-section using the Colour Glass Condensate effective theory, which enables us to include the effects of multiple scattering and gluon saturation in the leading logarithmic approximation at high energy. This opens the way towards systematic studies of angular correlations in two-gluon production, similar to previous studies for quarkgluon production in the literature. We consider in more detail two special kinematical limits: the back-to-back correlation limit, where the transverse momenta of the produced gluons are much larger than the nuclear saturation momentum, and the double parton scattering limit, where the two gluons are produced by a nearly collinear splitting occurring prior to the collision. We argue that saturation effects remain important even for relatively high transverse momenta (i.e. for nearly back-to-back configurations), leading to geometric scaling in the azimuthal distribution.

  20. Signature splitting in 135Pr

    International Nuclear Information System (INIS)

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

  1. Algebraic techniques for diagonalization of a split quaternion matrix in split quaternionic mechanics

    International Nuclear Information System (INIS)

    In the study of the relation between complexified classical and non-Hermitian quantum mechanics, physicists found that there are links to quaternionic and split quaternionic mechanics, and this leads to the possibility of employing algebraic techniques of split quaternions to tackle some problems in complexified classical and quantum mechanics. This paper, by means of real representation of a split quaternion matrix, studies the problem of diagonalization of a split quaternion matrix and gives algebraic techniques for diagonalization of split quaternion matrices in split quaternionic mechanics

  2. Algebraic techniques for diagonalization of a split quaternion matrix in split quaternionic mechanics

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Tongsong, E-mail: jiangtongsong@sina.com [Department of Mathematics, Linyi University, Linyi, Shandong 276005 (China); Department of Mathematics, Heze University, Heze, Shandong 274015 (China); Jiang, Ziwu; Zhang, Zhaozhong [Department of Mathematics, Linyi University, Linyi, Shandong 276005 (China)

    2015-08-15

    In the study of the relation between complexified classical and non-Hermitian quantum mechanics, physicists found that there are links to quaternionic and split quaternionic mechanics, and this leads to the possibility of employing algebraic techniques of split quaternions to tackle some problems in complexified classical and quantum mechanics. This paper, by means of real representation of a split quaternion matrix, studies the problem of diagonalization of a split quaternion matrix and gives algebraic techniques for diagonalization of split quaternion matrices in split quaternionic mechanics.

  3. Algebraic techniques for diagonalization of a split quaternion matrix in split quaternionic mechanics

    Science.gov (United States)

    Jiang, Tongsong; Jiang, Ziwu; Zhang, Zhaozhong

    2015-08-01

    In the study of the relation between complexified classical and non-Hermitian quantum mechanics, physicists found that there are links to quaternionic and split quaternionic mechanics, and this leads to the possibility of employing algebraic techniques of split quaternions to tackle some problems in complexified classical and quantum mechanics. This paper, by means of real representation of a split quaternion matrix, studies the problem of diagonalization of a split quaternion matrix and gives algebraic techniques for diagonalization of split quaternion matrices in split quaternionic mechanics.

  4. 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.

  5. Enhanced microglial clearance of myelin debris in T cell-infiltrated central nervous system

    DEFF Research Database (Denmark)

    Nielsen, Helle Hvilsted; Ladeby, Rune; Fenger, Christina; Toft-Hansen, Henrik; Babcock, Alicia A; Owens, Trevor; Finsen, Bente

    2009-01-01

    Acute multiple sclerosis lesions are characterized by accumulation of T cells and macrophages, destruction of myelin and oligodendrocytes, and axonal damage. There is, however, limited information on neuroimmune interactions distal to sites of axonal damage in the T cell-infiltrated central nervous...... regeneration after a neural antigen-specific T cell-mediated immune response in multiple sclerosis....

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

    DEFF Research Database (Denmark)

    Lozeron, Pierre; Krarup, Christian; Schmalbruch, Henning

    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...

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

    Energy Technology Data Exchange (ETDEWEB)

    Natali, F. [OGG-INFM, Grenoble (France); Gliozzi, A.; Rolandi, R.; Relini, A. [Dipartimento di Fisica and Istituto Nazionale per la Fisica della Materia, Universita di Genova (Italy); Cavatorta, P.; Deriu, A. [Dipartimento di Fisica and Istituto Nazionale per la Fisica della Materia, Universita di Parma (Italy); Fasano, A. [Dipartimento di Biochimica e Biologia Molecolare, Universita di Bari (Italy); Riccio, P. [Dipartimento di Biologia D.B.A.F., Universita della Basilicata, Potenza (Italy)

    2002-07-01

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

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

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

  10. Autophagic myelin destruction by schwann cells during wallerian degeneration and segmental demyelination.

    Science.gov (United States)

    Jang, So Young; Shin, Yoon Kyung; Park, So Young; Park, Joo Youn; Lee, Hye Jeong; Yoo, Young Hyun; Kim, Jong Kuk; Park, Hwan Tae

    2016-05-01

    As lysosomal hydrolysis has long been suggested to be responsible for myelin clearance after peripheral nerve injury, in this study, we investigated the possible role of autophagolysosome formation in myelin phagocytosis by Schwann cells and its final contribution to nerve regeneration. We found that the canonical formation of autophagolysosomes was induced in demyelinating Schwann cells after injury, and the inhibition of autophagy via Schwann cell-specific knockout of the atg7 gene or pharmacological intervention of lysosomal function caused a significant delay in myelin clearance. However, Schwann cell dedifferentiation, as demonstrated by extracellular signal-regulated kinase activation and c-Jun induction, and redifferentiation were not significantly affected, and thus the entire repair program progressed normally in atg7 knockout mice. Finally, autophagic Schwann cells were also found during segmental demyelination in a mouse model of inflammatory peripheral neuropathy. Together, our findings suggest that autophagy is the self-myelin destruction mechanism of Schwann cells, but mechanistically, it is a process distinct from Schwann cell plasticity for nerve repair. GLIA 2016;64:730-742. PMID:26712109

  11. LINGO-1 antibody ameliorates myelin impairment and spatial memory deficits in experimental autoimmune encephalomyelitis mice.

    Science.gov (United States)

    Sun, Jun-Jun; Ren, Qing-Guo; Xu, Lin; Zhang, Zhi-Jun

    2015-01-01

    More than 50% of multiple sclerosis patients develop cognitive impairment. However, the underlying mechanisms are still unclear, and there is no effective treatment. LINGO-1 (LRR and Ig domain containing NOGO receptor interacting protein 1) has been identified as an inhibitor of oligodendrocyte differentiation and myelination. Using the experimental autoimmune encephalomyelitis (EAE) mouse model, we assessed cognitive function at early and late stages of EAE, determined brain expression of myelin basic protein (MBP) and investigated whether the LINGO-1 antibody could restore deficits in learning and memory and ameliorate any loss of MBP. We found that deficits in learning and memory occurred in late EAE and identified decreased expression of MBP in the parahippocampal cortex (PHC) and fimbria-fornix. Moreover, the LINGO-1 antibody significantly improved learning and memory in EAE and partially restored MBP in PHC. Furthermore, the LINGO-1 antibody activated the AKT/mTOR signaling pathway regulating myelin growth. Our results suggest that demyelination in the PHC and fimbria-fornix might contribute to cognitive deficits and the LINGO-1 antibody could ameliorate these deficits by promoting myelin growth in the PHC. Our research demonstrates that LINGO-1 antagonism may be an effective approach to the treatment of the cognitive impairment of multiple sclerosis patients. PMID:26383267

  12. 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

  13. Reoxygenation of anoxic peripheral nerve myelinated axons promotes re-establishment of normal elemental composition.

    Science.gov (United States)

    Lehning, E J; Stys, P K; LoPachin, R M

    1996-04-01

    Previously we have shown that in vitro anoxia of rat peripheral nerve myelinated axons causes sequential deregulation of axoplasmic Na, K and Ca; i.e., an initial influx of Na and loss of K is coupled to subsequent Ca accumulation [7]. In the present study, we examined the ability of PNS axons to recover normal elemental composition following oxygen deprivation. Thus, electron probe X-ray microanalysis was used to determine the effects of post-anoxia reoxygenation on the concentrations of elements (i.e., Na, K, Cl, Ca, Mg, P and S) in rat posterior tibial nerve myelinated axons and Schwann cells. Results indicate that following 180 min of anoxia, peripheral nerve reoxygenation (60 and 120 min) promoted progressive recovery of normal elemental composition in axoplasm and mitochondria of small, medium and large diameter tibial nerve fibers. Our observations also indicate that small axons recovered normal elemental concentrations more rapidly than larger counterparts. Schwann cells and myelin exhibited only modest elemental disruption during anoxia from which reoxygenation promoted full reparation. The ability of peripheral nerve axons to restore normal elemental composition during post-anoxia reoxygenation is in marked contrast to the exacerbation of elemental deregulation which ensued during in vitro reoxygenation of anoxic rat CNS fibers [14]. This differential response to reoxygenation represents a fundamental difference in the pathophysiology of myelinated axons in the CNS and PNS. PMID:8739638

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

    DEFF Research Database (Denmark)

    Drøjdahl, Nina; Nielsen, Helle Hvilsted; Gardi, Jonathan E; Wree, Andreas; Peterson, Alan C; Nyengaard, Jens Randel; Eyer, Joël; Finsen, Bente

    2010-01-01

    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...

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

    Science.gov (United States)

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

    2014-10-01

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

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

    Science.gov (United States)

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

  17. 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.

  18. On the Linear Stability of Splitting Methods

    OpenAIRE

    Blanes, Sergio; Casas Pérez, Fernando; Murua, Ander

    2008-01-01

    A comprehensive linear stability analysis of splitting methods is carried out by means of a 2 × 2 matrix K(x) with polynomial entries (the stability matrix) and the stability polynomial p(x) (the trace of K(x) divided by two). An algorithm is provided for determining the coefficients of all possible time- reversible splitting schemes for a prescribed stability polynomial. It is shown that p(x) carries essentially all the information needed to construct processed splitting methods ...

  19. Wave splitting and lattice dynamics

    International Nuclear Information System (INIS)

    A wave-splitting approach used elsewhere to solve a black-hole scattering problem is adapted to the formal solution of arbitrary self-adjoint wave equations in 1+1 dimensions and yields potentially useful results in this more general case. It is then shown that the self-adjoint wave equation being solved, and the non-self-adjoint linear wave equations satisfied by the one-way component waves, are naturally related to a pair of motions of the (1+1)-dimensional Toda lattice that together comprise a motion of the Kac-van Moerbeke lattice. This provides a partial explanation for the peculiar fact that every motion of the Kac-van Moerbeke lattice can be viewed as two interpolated motions of the Toda lattice. (author)

  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. Gluon splitting in a shockwave

    CERN Document Server

    Iancu, Edmond

    2013-01-01

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

  2. Gauge Mediated Mini-Split

    CERN Document Server

    Cohen, Timothy; Knapen, Simon

    2015-01-01

    We propose a simple model of split supersymmetry from gauge mediation. This model features gauginos that are parametrically a loop factor lighter than scalars, accommodates a Higgs boson mass of 125 GeV, and incorporates a simple solution to the $\\mu-b_\\mu$ problem. The gaugino mass suppression can be understood as resulting from collective symmetry breaking. Imposing collider bounds on $\\mu$ and requiring viable electroweak symmetry breaking implies small $a$-terms and small $\\tan \\beta$ -- the stop mass ranges from $10^5$ to $10^8 \\mbox{ GeV}$. In contrast with models with anomaly + gravity mediation (which also predict a one-loop loop suppression for gaugino masses), our gauge mediated scenario predicts aligned squark masses and a gravitino LSP. Gluinos, electroweakinos and Higgsinos can be accessible at the LHC and/or future colliders for a wide region of the allowed parameter space.

  3. Salt splitting using ceramic membranes

    International Nuclear Information System (INIS)

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

  4. 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.

  5. Ribosomal trafficking is reduced in Schwann cells following induction of myelination

    Directory of Open Access Journals (Sweden)

    James M. Love

    2015-08-01

    Full Text Available Local synthesis of proteins within the Schwann cell periphery is extremely important for efficient process extension and myelination, when cells undergo dramatic changes in polarity and geometry. Still, it is unclear how ribosomal distributions are developed and maintained within Schwann cell projections to sustain local translation. In this multi-disciplinary study, we expressed a plasmid encoding a fluorescently labeled ribosomal subunit (L4-GFP in cultured primary rat Schwann cells. This enabled the generation of high-resolution, quantitative data on ribosomal distributions and trafficking dynamics within Schwann cells during early stages of myelination, induced by ascorbic acid treatment. Ribosomes were distributed throughout Schwann cell projections, with ~2-3 bright clusters along each projection. Clusters emerged within 1 day of culture and were maintained throughout early stages of myelination. Three days after induction of myelination, net ribosomal movement remained anterograde (directed away from the Schwann cell body, but ribosomal velocity decreased to about half the levels of the untreated group. Statistical and modeling analysis provided additional insight into key factors underlying ribosomal trafficking. Multiple regression analysis indicated that net transport at early time points was dependent on anterograde velocity, but shifted to dependence on anterograde duration at later time points. A simple, data-driven rate kinetics model suggested that the observed decrease in net ribosomal movement was primarily dictated by an increased conversion of anterograde particles to stationary particles, rather than changes in other directional parameters. These results reveal the strength of a combined experimental and theoretical approach in examining protein localization and transport, and provide evidence of an early establishment of ribosomal populations within Schwann cell projections with a reduction in trafficking following initiation of myelination.

  6. Astrocytic tissue inhibitor of metalloproteinase-1 (TIMP-1) promotes oligodendrocyte differentiation and enhances CNS myelination.

    Science.gov (United States)

    Moore, Craig S; Milner, Richard; Nishiyama, Akiko; Frausto, Ricardo F; Serwanski, David R; Pagarigan, Roberto R; Whitton, J Lindsay; Miller, Robert H; Crocker, Stephen J

    2011-04-20

    Tissue inhibitor of metalloproteinase-1 (TIMP-1) is an extracellular protein and endogenous regulator of matrix metalloproteinases (MMPs) secreted by astrocytes in response to CNS myelin injury. We have previously reported that adult TIMP-1 knock-out (KO) mice exhibit poor myelin repair following demyelinating injury. This observation led us to hypothesize a role for TIMP-1 in oligodendrogenesis and CNS myelination. Herein, we demonstrate that compact myelin formation is significantly delayed in TIMP-1 KO mice, a situation that coincided with dramatically reduced numbers of white matter astrocytes in the developing CNS. Analysis of differentiation in CNS progenitor cells (neurosphere) cultures from TIMP-1 KO mice revealed a specific deficit of NG2(+) oligodendrocyte progenitor cells. Application of recombinant murine TIMP-1 (rmTIMP-1) to TIMP-1 KO neurosphere cultures evoked a dose-dependent increase in NG2(+) cell numbers, while treatment with GM6001, a potent broad-spectrum MMP inhibitor did not. Similarly, administration of rmTIMP-1 to A2B5(+) immunopanned oligodendrocyte progenitors significantly increased the number of differentiated O1(+) oligodendrocytes, while antisera to TIMP-1 reduced oligodendrocyte numbers. We also determined that A2B5(+) oligodendrocyte progenitors grown in conditioned media derived from TIMP-1 KO primary glial cultures resulted in reduced differentiation of mature O1(+) oligodendrocytes. Finally, we report that addition of rmTIMP-1 to primary glial cultures resulted in a dose-dependent proliferative response of astrocytes. Together, these findings describe a previously uncharacterized role for TIMP-1 in the regulation of oligodendrocytes and astrocytes during development and provide a novel function for TIMP-1 on myelination in the developing CNS. PMID:21508247

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

    Science.gov (United States)

    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

    2011-11-01

    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 microglia. Although galectin-1 was abundant in immature but not in differentiated OLGs, galectin-3 was upregulated during OLG differentiation. Biochemical analysis revealed increased activity of metalloproteinases responsible for cleaving galectin-3 during OLG differentiation and modulating its biological activity. Exposure to galectin-3 promoted OLG differentiation in a dose- and carbohydrate-dependent fashion consistent with the 'glycosylation signature' of immature versus differentiated OLG. Accordingly, conditioned media from galectin-3-expressing, but not galectin-3-deficient (Lgals3(-/-)) microglia, successfully promoted OLG differentiation. Supporting these findings, morphometric analysis showed a significant decrease in the frequency of myelinated axons, myelin turns (lamellae) and g-ratio in the corpus callosum and striatum of Lgals3(-/-) compared with wild-type (WT) mice. Moreover, the myelin structure was loosely wrapped around the axons and less smooth in Lgals3(-/-) mice versus WT mice. Behavior analysis revealed decreased anxiety in Lgals3(-/-) mice similar to that observed during early demyelination induced by cuprizone intoxication. Finally, commitment toward the oligodendroglial fate was favored in neurospheres isolated from WT but not Lgals3(-/-) mice. Hence, glial-derived galectin-3, but not galectin-1, promotes OLG differentiation, thus contributing to myelin integrity and function with critical implications in the recovery of inflammatory demyelinating disorders. PMID:21566659

  8. 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

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

    Directory of Open Access Journals (Sweden)

    Nicole Wenderoth

    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.

  10. Quantitative analysis of the myelin g-ratio from electron microscopy images of the macaque corpus callosum

    Directory of Open Access Journals (Sweden)

    Nikola Stikov

    2015-09-01

    Full Text Available We provide a detailed morphometric analysis of eight transmission electron micrographs (TEMs obtained from the corpus callosum of one cynomolgus macaque. The raw TEM images are included in the article, along with the distributions of the axon caliber and the myelin g-ratio in each image. The distributions are analyzed to determine the relationship between axon caliber and g-ratio, and compared against the aggregate metrics (myelin volume fraction, fiber volume fraction, and the aggregate g-ratio, as defined in the accompanying research article entitled ‘In vivo histology of the myelin g-ratio with magnetic resonance imaging’ (Stikov et al., NeuroImage, 2015.

  11. Tracking Water Absorption in Split Susceptible Blueberries

    Science.gov (United States)

    Rain related fruit splitting in blueberries has been a problem for commercial blueberry growers in the Southeastern US. The presence of split berries can cause an entire batch of berries to be rejected. Rejection of batches can be devastating to the growers and their income. Previous studies ha...

  12. 2-Photon tandem device for water splitting

    DEFF Research Database (Denmark)

    Seger, Brian; Castelli, Ivano Eligio; Vesborg, Peter Christian Kjærgaard; Jacobsen, Karsten Wedel; Hansen, Ole; Chorkendorff, Ib

    2014-01-01

    Within the field Of photocatalytic water splitting there are several strategies to achieve the goal of efficient and cheap photocatalytic water splitting. This work examines one particular strategy by focusing on monolithically stacked, two-photon photoelectrochemical cells. The overall aim of the...

  13. Standard Model Particles from Split Octonions

    CERN Document Server

    Gogberashvili, Merab

    2016-01-01

    We model physical signals using elements of the algebra of split octonions over the field of real numbers. Elementary particles are corresponded to the special elements of the algebra that nullify octonionic norms (zero divisors). It is shown that the standard model particle spectrum naturally follows from the classification of the independent primitive zero divisors of split octonions.

  14. 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.

  15. Line splitting in the Schumann resonance oscillations

    Science.gov (United States)

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

    2007-04-01

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

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

    International Nuclear Information System (INIS)

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

  17. 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.

  18. 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.

  19. Role of endogenous pituitary adenylate cyclase activating polypeptide (PACAP) in myelination of the rodent brain: lessons from PACAP-deficient mice.

    Science.gov (United States)

    Vincze, András; Reglodi, Dóra; Helyes, Zsuzsanna; Hashimoto, Hitoshi; Shintani, Norihito; Abrahám, Hajnalka

    2011-12-01

    Pituitary adenylate-cyclase activator polypeptide (PACAP), as a consequence of its effect on the elevation of intracellular cAMP level, strongly influences brain development including myelination. While proliferation of oligodendroglial progenitors is stimulated by PACAP applied in vitro, their differentiation is inhibited. However, the in vivo role of PACAP on myelination has never been examined. In the present study the role of endogenous PACAP in myelination was examined in PACAP-deficient mice, in several areas of the brain with a special attention to the cerebral cortex. In young postnatal and adult mice myelination was studied with immunohistochemistry detecting a protein present in the myelin sheath, the myelin basic protein, with Luxol Fast Blue staining and with electron microscopy. Results obtained in PACAP-deficient mice were compared to age-matched wild type controls. We found that the sequence of myelination in the PACAP-deficient animals was similar to that observed in controls. According to this, in both PACAP-deficient and wild type mice, the somatosensory cortex was myelinated before motor areas that preceded the myelination of associational cortical areas. Archicortical associational areas such as the cingulate cortex were myelinated before neocortical areas. Myelination in the corpus callosum followed the known rostro-caudal direction in both PACAP-deficient and wild type animals, and the ventrolateral part of the corpus callosum was myelinated earlier than the dorsomedial part in both groups. In contrast to the similarity in its sequence, striking difference was found in the onset of myelination that started earlier in PACAP-deficient mice than in wild type controls in all of the examined brain regions, including cerebral archi- and neocortex. The first myelinated axons in each of the examined brain regions were observed earlier in the PACAP-deficient mice than in controls. When age-matched animals of the two groups were compared, density of myelinated fibers in the PACAP-deficient mice was higher than in controls in all of the examined areas. We propose that endogenous PACAP exerts an inhibitory role on myelination in vivo. Since myelin sheath of the central nervous system contains several factors blocking neurite outgrowth, inhibition of myelination by PACAP gives time for axonal development and synapse formation, and therefore, strengthens neuronal plasticity. PMID:21726625

  20. Split-course versus continuous radiotherapy

    International Nuclear Information System (INIS)

    A randomized clinical trial was performed from 1964 to 1967 to compare the therapeutic results of split-course external beam radiotherapy with those of continuously fractionated treatment. Altogether 439 consecutive patients with carcinoma of larynx, nasopharynx, hypopharynx, oropharynx, oral cavity, oesophagus and urinary bladder were included in the series. 227 patients received split-course treatment and 212 were treated by the continuous-course method. In the split-course treatment there was a 2-3 weeks' interruption after 25-30 Gy. This break was compensated by a 10% increase in the total dose. For each tumour site local control and failure rates for the 2 treatment techniques were similar. No significant differences in 5- and 10-year survival were noted. Acute side effects were milder in all patients treated with split-course. The occurrence of late reactions was similar in both treatment groups. However, severe late reactions in the urinary bladder were somewhat more in patients treated with split-course technique; the difference was not statistically significant. We conclude that there were no significant differences in local control, long-term survival and late normal tissue reactions between the treatment groups. The acute normal tissue reactions were milder in the split-course treated groups. We still regard split-course as a useful treatment modality provided the interruption is compensated with about 10% increase in total dose. However, more studies are needed to show which tumours proliferate during prolonged radiotherapy. (orig.)

  1. Modeling the Presence of Myelin and Edema in the Brain Based on Multi-Parametric Quantitative MRI

    OpenAIRE

    Warntjes, Marcel; Engström, Maria; Tisell, Anders; Lundberg, Peter

    2016-01-01

    The aim of this study was to present a model that uses multi-parametric quantitative MRI to estimate the presence of myelin and edema in the brain. The model relates simultaneous measurement of R1 and R2 relaxation rates and proton density to four partial volume compartments, consisting of myelin partial volume, cellular partial volume, free water partial volume, and excess parenchymal water partial volume. The model parameters were obtained using spatially normalized brain images of a group ...

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

    OpenAIRE

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

    2015-01-01

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

  3. The effect of buffer molarity on the size, shape and sheath thickness of peripheral myelinated nerve fibres.

    OpenAIRE

    Holland, G R

    1982-01-01

    Nineteen rats were perfused intracardially with a 2% glutaraldehyde solution in cacodylate buffers adjusted in molarity from 0 to 0.4 M. Ultrathin sections of the inferior alveolar nerve were photographed in the electron microscope. The circumference, a shape factor, small diameter and myelin sheath thickness of each myelinated nerve fibre were measured using a semi-automatic image analysis system. Statistical analysis of the data revealed that the nerve profiles increasingly deviate from a t...

  4. Myelin Formation during Development of the CNS Is Delayed in Matrix Metalloproteinase-9 and -12 Null Mice

    DEFF Research Database (Denmark)

    Larsen, Peter Hjørringgaard; DaSilva, Angelika G.; Conant, Kathrine; Young, V. Wee

    2006-01-01

    around a demyelinating lesion of the spinal cord of adult mice facilitated remyelination. In the current study, we have addressed whether and how MMPs might be required for myelin formation in normal ontogeny. Using a probe for multiple MMPs and the developing mouse optic nerve, we found two members, MMP...... to remain high in MMP-deficient mice. These results reveal a novel function for MMP-9 and -12 in developmental myelination likely through regulating IGF-1 bioavailability....

  5. Modulation of Epithelial Morphology, Monolayer Permeability, and Cell Migration by Growth Arrest Specific 3/Peripheral Myelin Protein 22

    OpenAIRE

    Roux, Kyle J.; Amici, Stephanie A.; Fletcher, Bradley S.; Notterpek, Lucia

    2005-01-01

    Peripheral myelin protein 22 (PMP22) is associated with a subset of hereditary peripheral neuropathies. Although predominantly recognized as a transmembrane constituent of peripheral nerve myelin, PMP22 is localized to epithelial and endothelial cell-cell junctions, where its function remains unknown. In this report, we investigated the role of PMP22 in epithelial biology. Expression of human PMP22 (hPMP22) slows cell growth and induces a flattened morphology in Madin-Darby canine kidney (MDC...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1993-09-01

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

  7. Small Angle X-Ray Scattering from Lipid-Bound Myelin Basic Protein in Solution

    Science.gov (United States)

    Haas, H.; Oliveira, C. L. P.; Torriani, I. L.; Polverini, E.; Fasano, A.; Carlone, G.; Cavatorta, P.; Riccio, P.

    2004-01-01

    The structure of myelin basic protein (MBP), purified from the myelin sheath in both lipid-free (LF-MBP) and lipid-bound (LB-MBP) forms, was investigated in solution by small angle x-ray scattering. The water-soluble LF-MBP, extracted at pH 7.0. Under all conditions, the scattering from the two protein forms was different, indicating different molecular shapes. For the LB-MBP, well-defined scattering curves were obtained, suggesting that the protein had a unique, compact (but not globular) structure. Furthermore, these data were compatible with earlier results from molecular modeling calculations on the MBP structure which have been refined by us. In contrast, the LF-MBP data were in accordance with the expected open-coil conformation. The results represent the first direct structural information from x-ray scattering measurements on MBP in its native lipidic environment in solution. PMID:14695288

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

    DEFF Research Database (Denmark)

    Lozeron, Pierre; Krarup, Christian; Schmalbruch, Henning

    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...... 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....

  9. Selective excitation of myelin water using inversion-recovery-based preparations.

    Science.gov (United States)

    Travis, Adam R; Does, Mark D

    2005-09-01

    T1 and T2 relaxation of excised frog sciatic nerve water was characterized at 7 T. Based on these findings, optimal timings for multiple inversion-recovery magnetization preparations were determined to selectively excite the so-called myelin-water T2 component. Subsequent double inversion-recovery and triple inversion-recovery preparations were used in combination with CPMG acquisitions to experimentally determine optimal timings and effect of the preparation. Using double inversion-recovery, optimal timings were found to excite magnetization that is predominantly (approximately 93%) derived from the myelin-water component. Greater selectivity (approximately 96%) was found by extending the preparation to triple inversion-recovery, at the price of decreasing SNR by a factor of approximately 2. PMID:16088884

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

    Science.gov (United States)

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

    2014-01-01

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

  11. Split-coil-system SULTAN

    International Nuclear Information System (INIS)

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

  12. 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 nerve fibres, increase degenerated mitochondria, and decreased microtubules. (author)

  13. Anomalous Kondo Spin Splitting in Quantum Dots

    OpenAIRE

    Hualde, J. M. Aguiar; Chiappe, G.; 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...

  14. Muonic hydrogen ground state hyperfine splitting

    CERN Document Server

    Faustov, R N

    2003-01-01

    Corrections of order alpha^5, alpha^6 are calculated in the hyperfine splitting of muonic hydrogen ground state. Nuclear structure effects are taken into account in one- and two-loop Feynman amplitudes by means of the proton electromagnetic form factors. The modification of the hyperfine splitting part of the Breit potential due to electron vacuum polarization is considered. Total numerical value of the 1S state hyperfine splitting 182.725 meV in (mu p) can play the role of proper estimation for the corresponding experiment with the accuracy 30 ppm.

  15. Insertion of Mutant Proteolipid Protein Results in Missorting of Myelin Proteins

    OpenAIRE

    Vaurs-Barriere, Catherine; Wong, Kondi; Weibel, Thais D.; ABU-ASAB, Mones; Weiss, Michael D.; Kaneski, Christine R.; Mixon, Tong-Hui; Bonavita, Simona; Creveaux, Isabelle; Heiss, John D; Tsokos, Maria; Goldin, Ehud; Quarles, Richard H.; Boespflug-Tanguy, Odile; Schiffmann, Raphael

    2003-01-01

    Two brothers with a leukodystrophy, progressive spastic diplegia, and peripheral neuropathy were found to have proteinaceous aggregates in the peripheral nerve myelin sheath. The patients mother had only subclinical peripheral neuropathy, but the maternal grandmother had adult-onset leukodystrophy. Sequencing of the proteolipid protein (PLP) gene showed a point mutation IVS4 + 1 G?A within the donor splice site of intron 4. We identified one transcript with a deletion of exon 4 (?ex4, 169bp)...

  16. 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; G.A. Rabinovich; 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 microgli...

  17. 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 LongEvans 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 o...

  18. LINGO-1 antibody ameliorates myelin impairment and spatial memory deficits in experimental autoimmune encephalomyelitis mice

    OpenAIRE

    Jun-Jun Sun; Qing-Guo Ren; Lin Xu; Zhi-Jun Zhang

    2015-01-01

    More than 50% of multiple sclerosis patients develop cognitive impairment. However, the underlying mechanisms are still unclear, and there is no effective treatment. LINGO-1 (LRR and Ig domain containing NOGO receptor interacting protein 1) has been identified as an inhibitor of oligodendrocyte differentiation and myelination. Using the experimental autoimmune encephalomyelitis (EAE) mouse model, we assessed cognitive function at early and late stages of EAE, determined brain expression of my...

  19. 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)

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

    OpenAIRE

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

    2010-01-01

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

  1. Reversible Folding of Human Peripheral Myelin Protein 22, a Tetraspan Membrane Protein

    OpenAIRE

    Schlebach, Jonathan P.; Peng, Dungeng; Kroncke, Brett M.; Mittendorf, Kathleen F.; Narayan, Malathi; Carter, Bruce D.; Sanders, Charles R

    2013-01-01

    Misfolding of the ?-helical membrane protein peripheral myelin protein 22 (PMP22) has been implicated in the pathogenesis of the common neurodegenerative disease known as Charcot-Marie-Tooth disease (CMTD) and also several other related peripheral neuropathies. Emerging evidence suggests that the propensity of PMP22 to misfold in the cell may be due to an intrinsic lack of conformational stability. Therefore, quantitative studies of the conformational equilibrium of PMP22 are needed to gain i...

  2. Pharmacological induction of the heat shock response improves myelination in a neuropathic model

    OpenAIRE

    Rangaraju, Sunitha; Madorsky, Irina; Pileggi, Jocelyn Go; Kamal, Adeela; Notterpek, Lucia

    2008-01-01

    Misexpression and intracellular retention of peripheral myelin protein 22 (PMP22) is associated with hereditary neuropathies in humans, including Charcot-Marie-Tooth disease type 1A (CMT1A). Mice expressing extra copies of the human PMP22, termed C22, display morphologic and behavioral characteristics of CMT1A. In neuropathic Schwann cells, the turnover of the newly-synthesized PMP22 is decreased, leading to the formation of cytosolic protein aggregates. To aid the processing of PMP22 and all...

  3. Skin-derived neural precursors competitively generate functional myelin in adult demyelinated mice

    OpenAIRE

    Mozafari, Sabah; Laterza, Cecilia; Roussel, Delphine; Bachelin, Corinne; Marteyn, Antoine; Deboux, Cyrille; Martino, Gianvito; Evercooren, Anne Baron-Van

    2015-01-01

    Induced pluripotent stem cell–derived (iPS-derived) neural precursor cells may represent the ideal autologous cell source for cell-based therapy to promote remyelination and neuroprotection in myelin diseases. So far, the therapeutic potential of reprogrammed cells has been evaluated in neonatal demyelinating models. However, the repair efficacy and safety of these cells has not been well addressed in the demyelinated adult CNS, which has decreased cell plasticity and scarring. Moreover, it i...

  4. 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.

  5. Intracellular Protein Shuttling: A Mechanism Relevant for Myelin Repair in Multiple Sclerosis?

    Directory of Open Access Journals (Sweden)

    Peter Göttle

    2015-07-01

    Full Text Available A prominent feature of demyelinating diseases such as multiple sclerosis (MS is the degeneration and loss of previously established functional myelin sheaths, which results in impaired signal propagation and axonal damage. However, at least in early disease stages, partial replacement of lost oligodendrocytes and thus remyelination occur as a result of resident oligodendroglial precursor cell (OPC activation. These cells represent a widespread cell population within the adult central nervous system (CNS that can differentiate into functional myelinating glial cells to restore axonal functions. Nevertheless, the spontaneous remyelination capacity in the adult CNS is inefficient because OPCs often fail to generate new oligodendrocytes due to the lack of stimulatory cues and the presence of inhibitory factors. Recent studies have provided evidence that regulated intracellular protein shuttling is functionally involved in oligodendroglial differentiation and remyelination activities. In this review we shed light on the role of the subcellular localization of differentiation-associated factors within oligodendroglial cells and show that regulation of intracellular localization of regulatory factors represents a crucial process to modulate oligodendroglial maturation and myelin repair in the CNS.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1993-11-15

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

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

    Science.gov (United States)

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

    2013-04-01

    P0 glycoprotein is an abundant product of terminal differentiation in myelinating Schwann cells. The mutant P0S63del causes Charcot-Marie-Tooth 1B neuropathy in humans, and a very similar demyelinating neuropathy in transgenic mice. P0S63del is retained in the endoplasmic reticulum of Schwann cells, where it promotes unfolded protein stress and elicits an unfolded protein response (UPR) associated with translational attenuation. Ablation of Chop, a UPR mediator, from S63del mice completely rescues their motor deficit and reduces active demyelination by half. Here, we show that Gadd34 is a detrimental effector of CHOP that reactivates translation too aggressively in myelinating Schwann cells. Genetic or pharmacological limitation of Gadd34 function moderates translational reactivation, improves myelination in S63del nerves, and reduces accumulation of P0S63del in the ER. Resetting translational homeostasis may provide a therapeutic strategy in tissues impaired by misfolded proteins that are synthesized during terminal differentiation. PMID:23547100

  8. Attractin/Mahogany/Zitter plays a critical role in myelination of the central nervous system

    Science.gov (United States)

    Kuramoto, Takashi; Kitada, Kazuhiro; Inui, Toshihide; Sasaki, Yoshifumi; Ito, Kazumi; Hase, Takao; Kawagachi, Saburo; Ogawa, Yoshihiro; Nakao, Kazuwa; Barsh, Gregory S.; Nagao, Minako; Ushijima, Toshikazu; Serikawa, Tadao

    2001-01-01

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

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

    Science.gov (United States)

    Montava, Marion; Garcia, Stphane; Mancini, Julien; Jammes, Yves; Courageot, Jol; Lavieille, Jean-Pierre; Feron, Franois

    2015-10-01

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

  10. Examining the relationships between cortical maturation and white matter myelination throughout early childhood.

    Science.gov (United States)

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

    2016-01-15

    Cortical development and white matter myelination are hallmark processes of infant and child neurodevelopment, and play a central role in the evolution of cognitive and behavioral functioning. Non-invasive magnetic resonance imaging (MRI) has been used to independently track these microstructural and morphological changes in vivo, however few studies have investigated the relationship between them despite their concurrency in the developing brain. Further, because measures of cortical morphology rely on underlying gray-white matter tissue contrast, which itself is a function of white matter myelination, it is unclear if contrast-based measures of cortical development accurately reflect cortical architecture, or if they merely represent adjacent white matter maturation. This may be particularly true in young children, in whom brain structure is rapidly maturing. Here for the first time, we investigate the dynamic relationship between cortical and white matter development across early childhood, from 1 to 6years. We present measurements of cortical thickness with respect to cortical and adjacent myelin water fraction (MWF) in 33 bilateral cortical regions. Significant results in only 14 of 66 (21%) cortical regions suggest that cortical thickness measures are not heavily driven by changes in adjacent white matter, and that brain imaging studies of cortical and white matter maturation reflect distinct, but complimentary, neurodevelopmental processes. PMID:26499814

  11. Impaired myelination and reduced brain ferric iron in the mouse model of mucolipidosis IV.

    Science.gov (United States)

    Grishchuk, Yulia; Peña, Karina A; Coblentz, Jessica; King, Victoria E; Humphrey, Daniel M; Wang, Shirley L; Kiselyov, Kirill I; Slaugenhaupt, Susan A

    2015-12-01

    Mucolipidosis type IV (MLIV) is a lysosomal storage disease caused by mutations in the MCOLN1 gene, which encodes the lysosomal transient receptor potential ion channel mucolipin-1 (TRPML1). MLIV causes impaired motor and cognitive development, progressive loss of vision and gastric achlorhydria. How loss of TRPML1 leads to severe psychomotor retardation is currently unknown, and there is no therapy for MLIV. White matter abnormalities and a hypoplastic corpus callosum are the major hallmarks of MLIV brain pathology. Here, we report that loss of TRPML1 in mice results in developmental aberrations of brain myelination as a result of deficient maturation and loss of oligodendrocytes. Defective myelination is evident in Mcoln1(-/-) mice at postnatal day 10, an active stage of postnatal myelination in the mouse brain. Expression of mature oligodendrocyte markers is reduced in Mcoln1(-/-) mice at postnatal day 10 and remains lower throughout the course of the disease. We observed reduced Perls' staining in Mcoln1(-/-) brain, indicating lower levels of ferric iron. Total iron content in unperfused brain is not significantly different between Mcoln1(-/-) and wild-type littermate mice, suggesting that the observed maturation delay or loss of oligodendrocytes might be caused by impaired iron handling, rather than by global iron deficiency. Overall, these data emphasize a developmental rather than a degenerative disease course in MLIV, and suggest that there should be a stronger focus on oligodendrocyte maturation and survival to better understand MLIV pathogenesis and aid treatment development. PMID:26398942

  12. RA-RAR-β 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 β (RAR-β), 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-β 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-β. Our findings identify a novel link between RA-RAR-β-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

  13. Rubidium uptake and accumulation in peripheral myelinated internodal axons and Schwann cells.

    Science.gov (United States)

    Lehning, E J; Gaughan, C L; Eichberg, J; LoPachin, R M

    1997-09-01

    To study mechanisms of K+ transport in peripheral nerve, uptake of rubidium (Rb+), a K+ tracer, was characterized in rat tibial nerve myelinated axons and glia. Isolated nerve segments were perfused with zero-K+ Ringer's solutions containing Rb+ (1-20 mM) and x-ray microanalysis was used to measure water content and concentrations of Rb, Na, K, and Cl in internodal axoplasm, mitochondria, and Schwann cell cytoplasm and myelin. Both axons and Schwann cells were capable of removing extracellular Rb+ (Rb+(o)) and exchanging it for internal K+. Uptake into axoplasm, Schwann cytoplasm, and myelin was a saturable process over the 1-10 mM Rb+(o) concentration range, although corresponding axoplasmic uptake rates were higher than respective glial velocities. Mitochondrial accumulation was a linear function of axoplasmic Rb+ concentrations, which suggests involvement of a nonenzymatic process. At 20 mM Rb+(o), a differential stimulatory response was observed; i.e., axoplasmic Rb+ uptake velocities increased more than fivefold relative to the 10 mM rate, and glial cytoplasmic uptake rose almost threefold. Finally, Rb+(o) uptake rate into axons and glia was completely inhibited by ouabain (2-4 mM) exposure or incubation at 4 degrees C. These results suggest that Rb+ uptake into peripheral nerve internodal axons and Schwann cells is mediated by Na+,K+-ATPase activity and implicate the presence of axonal- and glial-specific Na+ pump isozymes. PMID:9282918

  14. 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)

  15. Spacetime Splitting, Admissible Coordinates and Causality

    CERN Document Server

    Bini, D; Mashhoon, B

    2012-01-01

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

  16. Split rank of triangle and quadrilateral inequalities

    CERN Document Server

    Dey, Santanu

    2009-01-01

    A simple relaxation of two rows of a simplex tableau is a mixed integer set consisting of two equations with two free integer variables and non-negative continuous variables. Recently Andersen, Louveaux, Weismantel and Wolsey (2007) and Cornuejols and Margot (2008) showed that the facet-defining inequalities of this set are either split cuts or intersection cuts obtained from lattice-free triangles and quadrilaterals. Through a result by Cook, Kannan and Schrijver (1990), it is known that one particular class of facet-defining triangle inequality does not have a finite split rank. In this paper, we show that all other facet-defining triangle and quadrilateral inequalities have a finite split-rank. The proof is constructive and given a facet-defining triangle or quadrilateral inequality we present an explicit sequence of split inequalities that can be used to generate it.

  17. Split as an In-migration Centre

    OpenAIRE

    Klempi?, Sanja

    2004-01-01

    This paper deals with problems of demographic development in Split with an emphasis on in-migration. The analysis covers the central urban zone of Split (central city). Industrialisation after the Second World War had a decisive impact on the economic and demographic development of the city. This process attracted a large number of in-migrants from the neighbouring islands, from Zagora (i.e. the Dalmatian Hinterland) and from other parts of Dalmatia. This paper presents the results of researc...

  18. 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...

  19. Observers and Splitting Structures in Relativistic Electrodynamics

    OpenAIRE

    Auchmann, Bernhard; Kurz, Stefan

    2014-01-01

    We introduce a relativistic splitting structure as a means to map fields and equations of electromagnetism from curved four-dimensional space-time to three-dimensional observer's space. We focus on a minimal set of mathematical structures that are directly motivated by the language of the physical theory. Space-time, world-lines, time translation, space platforms, and time synchronization all find their mathematical counterparts. The splitting structure is defined without recourse to coordina...

  20. Ray splitting in paraxial optical cavities

    OpenAIRE

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

    2003-01-01

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

  1. Localization in splitting of matter waves

    OpenAIRE

    Jääskeläinen, Markku; Stenholm, Stig

    2003-01-01

    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 ...

  2. Application of Operator Splitting Methods in Finance

    OpenAIRE

    Hout, Karel in 't; Jari Toivanen

    2015-01-01

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

  3. Antenna Splitting Functions for Massive Particles

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-06-22

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

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

    Science.gov (United States)

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

    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 evaluate PMP22 over-expression in patients with CMT1A and determine whether levels of PMP22 are molecular markers of disease severity. PMP22 expression was measured by taking skin biopsies from patients with CMT1A (n = 20) and both healthy controls (n = 7) and patients with Hereditary Neuropathy with liability to Pressure Palsies (HNPP) (n = 6), in which patients have only a single copy of PMP22. Immunological electron microscopy was performed on the skin biopsies to quantify PMP22 expression in compact myelin. Similar biopsies were analysed by real time PCR to measure PMP22 mRNA levels. Results were also correlated with impairment in CMT1A, as measured by the validated CMT Neuropathy Score. Most, but not all patients with CMT1A, had elevated PMP22 levels in myelin compared with the controls. The levels of PMP22 in CMT1A were highly variable, but not in HNPP or the controls. However, there was no correlation between neurological disabilities and the level of over-expression of PMP22 protein or mRNA in patients with CMT1A. The extra copy of PMP22 in CMT1A results in disruption of the tightly regulated expression of PMP22. Thus, variability of PMP22 levels, rather than absolute level of PMP22, may play an important role in the pathogenesis of CMT1A. PMID:19447823

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

    International Nuclear Information System (INIS)

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

  6. Quintessence and phantom emerging from the split-complex field and the split-quaternion field

    Science.gov (United States)

    Gao, Changjun; Chen, Xuelei; Shen, You-Gen

    2016-01-01

    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.

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

    OpenAIRE

    Saadat, Laleh; DUPREE, JEFFREY L.; Kilkus, John; Han, Xianlin; Traka, Maria; Proia, Richard L; Dawson, Glyn; POPKO, BRIAN

    2010-01-01

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

  8. Downregulation of the microtubule associated protein tau impairs process outgrowth and myelin basic protein mRNA transport in oligodendrocytes.

    Science.gov (United States)

    Seiberlich, Veronika; Bauer, Nina G; Schwarz, Lisa; Ffrench-Constant, Charles; Goldbaum, Olaf; Richter-Landsberg, Christiane

    2015-09-01

    Oligodendrocytes, the myelin forming cells of the CNS, are characterized by their numerous membranous extensions, which enwrap neuronal axons and form myelin sheaths. During differentiation oligodendrocytes pass different morphological stages, downregulate the expression of the proteoglycan NG2, and acquire major myelin specific proteins, such as myelin basic proteins (MBP) and proteolipid protein. MBP mRNA is transported in RNA granules along the microtubules (MTs) to the periphery and translated locally. MTs participate in the elaboration and stabilization of the myelin forming extensions and are essential for cellular sorting processes. Their dynamic properties are regulated by microtubule associated proteins (MAPs). The MAP tau is present in oligodendrocytes and involved in the regulation and stabilization of the MT network. To further elucidate the functional significance of tau in oligodendrocytes, we have downregulated tau by siRNA technology and studied the effects on cell differentiation and neuron-glia contact formation. The data show that tau knockdown impairs process outgrowth and leads to a decrease in MBP expression. Furthermore, MBP mRNA transport to distant cellular extensions is impaired and cells remain in the NG2 stage. In myelinating cocultures with dorsal root ganglion neurons, oligodendrocyte precursor cells after tau miR RNA lentiviral knockdown develop into NG2 positive cells with very long and thin processes, contacting axons loosely, but fail to form internodes. This demonstrates that tau is important for MBP mRNA transport and involved in process formation. The disturbance of the balance of tau leads to abnormalities in oligodendrocyte differentiation, neuron-glia contact formation and the early myelination process. PMID:25847153

  9. Quetiapine inhibits microglial activation by neutralizing abnormal STIM1 mediated intercellular calcium homeostasis and promotes myelin repair in a cuprizone -induced mouse model of de-myelination

    Directory of Open Access Journals (Sweden)

    Jiming Kong

    2015-12-01

    Full Text Available Microglial activation has been considered as a crucial process in the pathogenesis of neuro-inflammation and psychiatric disorders. Several antipsychotic drugs have been shown to display inhibitory effects on microglial activation in vitro, possibly through the suppression of elevated intracellular calcium (Ca2+ concentration. However the exact underlying mechanisms still remain elusive. In this study, we aimed to investigate the inhibitory effects of quetiapine (Que, an atypical antipsychotic drug, on microglial activation. We utilize a chronic cuprizone (CPZ-induced de-myelination mouse model to determine the direct effect of Que on microglial activation. Our results show that treatment with Que significantly reduced recruitment and activation of microglia/macrophage in the lesion of corpus callosum and promoted re-myelination after CPZ withdraw. Our in vitro studies also confirm the direct effect of Que on lipopolysaccharide (LPS-induced activation of microglial N9 cells whereby Que significantly inhibited the release of nitric oxide (NO and tumor necrosis factor α (TNF-α. Moreover, we demonstrated that pre-treatment with Que, neutralized the up-regulation of STIM1 induced by LPS and declined both LPS and thapsigargin (Tg-induced store operated Ca2+ entry (SOCE. Finally we found that pre-treatment with Que significantly reduced the translocation of nuclear factor kappa B (NF-κB p65 subunit from cytoplasm to nuclei in LPS-activated primary microglial cells. Overall, our data suggested that Que may inhibit microglial activation by neutralization of the LPS-induced abnormal STIM1 mediated intercellular calcium homeostasis.

  10. 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

  11. 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.

  12. Compressive Split-Step Fourier Method

    CERN Document Server

    Bayindir, Cihan

    2015-01-01

    In this paper an approach for decreasing the computational effort required for the split-step Fourier method (SSFM) is introduced. It is shown that using the sparsity property of the simulated signals, the compressive sampling algorithm can be used as a very efficient tool for the split-step spectral simulations of various phenomena which can be modeled by using differential equations. The proposed method depends on the idea of using a smaller number of spectral components compared to the classical split-step Fourier method with a high number of components. After performing the time integration with a smaller number of spectral components and using the compressive sampling technique with l1 minimization, it is shown that the sparse signal can be reconstructed with a significantly better efficiency compared to the classical split-step Fourier method. Proposed method can be named as compressive split-step Fourier method (CSSFM). For testing of the proposed method the Nonlinear Schrodinger Equation and its one-s...

  13. Splinting the penis for split skin grafting: Use of longitudinally split plastic syringe

    OpenAIRE

    Sharma Ramesh; Cyriac Chacko

    2006-01-01

    We describe a new method of splinting the penile shaft following split skin grafting for avulsion injuries of the penis. A 10 ml syringe is split longitudinally and one half is applied either dorsally or ventrally after placing absorbent dressing on the grafted area. This is then held in place with either tape or bandage.

  14. Splinting the penis for split skin grafting: Use of longitudinally split plastic syringe

    Directory of Open Access Journals (Sweden)

    Sharma Ramesh

    2006-01-01

    Full Text Available We describe a new method of splinting the penile shaft following split skin grafting for avulsion injuries of the penis. A 10 ml syringe is split longitudinally and one half is applied either dorsally or ventrally after placing absorbent dressing on the grafted area. This is then held in place with either tape or bandage.

  15. Urban pattern: Layout design by hierarchical domain splitting

    KAUST Repository

    Yang, Yongliang

    2013-11-01

    We present a framework for generating street networks and parcel layouts. Our goal is the generation of high-quality layouts that can be used for urban planning and virtual environments. We propose a solution based on hierarchical domain splitting using two splitting types: streamline-based splitting, which splits a region along one or multiple streamlines of a cross field, and template-based splitting, which warps pre-designed templates to a region and uses the interior geometry of the template as the splitting lines. We combine these two splitting approaches into a hierarchical framework, providing automatic and interactive tools to explore the design space.

  16. Development and applications of a solid-phase radioimmunoassay for the P0 protein of peripheral myelin

    International Nuclear Information System (INIS)

    The assay uses antigen-coated plastic microwells, with antibody binding detected by 125I-labelled protein A. Either peripheral myelin proteins or purified P0 may be used as the antigen. This method allows the detection of 0.8 ng of P0 (20 ng/ml). Results showed little or no immunoreactivity in extracts of brain, central myelin, liver, purified myelin basic proteins, cultured, purified secondary Schwann cells, or membrane preparations from these cells. P0 was clearly detectable in Schwann cell cultures from 3- 4-day-old rats at 12-18 h after dissociation (4% of the level in adult sciatic nerve) and in extracts of one-day-old rat sciatic nerve (2% of the level in adult nerve). Myelin basic protein radioimmunoassays showed that the ratio of P0 to myelin basic protein is essentially constant in extracts of sciatic nerve from one-day-old, four-day-old, and young adult rats. Another results was that P0 levels are reduced in the trembler mouse sciatic nerve. (author)

  17. The Wlds mutation delays robust loss of motor and sensory axons in a genetic model for myelin-related axonopathy.

    Science.gov (United States)

    Samsam, Mohtashem; Mi, Weiqian; Wessig, Carsten; Zielasek, Jürgen; Toyka, Klaus V; Coleman, Michael P; Martini, Rudolf

    2003-04-01

    Mice deficient in the peripheral myelin component P0 mimic severe forms of inherited peripheral neuropathies in humans, with defective myelin formation and consequent axonal loss. We cross-bred these mice with the spontaneous mutant C57BL/Wld(s) typically showing protection from Wallerian degeneration because of fusion of the ubiquitination factor E4B (Ube4b) and nicotinamide mononucleotide adenylyltransferase (Nmnat) genes. We found that in the double mutants, the robust myelin-related axonal loss is reduced at 6 weeks and 3 months of age. Moreover, retrograde labeling from plantar nerves revealed an increased survival of motor axons. These motor axons appeared functionally active because both the amplitude of compound muscle action potentials and muscle strength were less reduced in the double mutants. At 6 months of age, reduction of axonal loss was no longer detectable in the double mutants when compared with littermates carrying the P0 null mutation only, although the Wld(s) gene was not reduced in its expression at this age. We conclude that myelin-related axonal loss is a process having some features in common with Wallerian degeneration. Introducing the Wld(s) gene would be a promising approach to delaying detrimental axonal loss in myelin disorders. PMID:12684470

  18. Electroactive biodegradable polyurethane significantly enhanced Schwann cells myelin gene expression and neurotrophin secretion for peripheral nerve tissue engineering.

    Science.gov (United States)

    Wu, Yaobin; Wang, Ling; Guo, Baolin; Shao, Yongpin; Ma, Peter X

    2016-05-01

    Myelination of Schwann cells (SCs) is critical for the success of peripheral nerve regeneration, and biomaterials that can promote SCs' neurotrophin secretion as scaffolds are beneficial for nerve repair. Here we present a biomaterials-approach, specifically, a highly tunable conductive biodegradable flexible polyurethane by polycondensation of poly(glycerol sebacate) and aniline pentamer, to significantly enhance SCs' myelin gene expression and neurotrophin secretion for peripheral nerve tissue engineering. SCs are cultured on these conductive polymer films, and the biocompatibility of these films and their ability to enhance myelin gene expressions and sustained neurotrophin secretion are successfully demonstrated. The mechanism of SCs' neurotrophin secretion on conductive films is demonstrated by investigating the relationship between intracellular Ca(2+) level and SCs' myelination. Furthermore, the neurite growth and elongation of PC12 cells are induced by adding the neurotrophin medium suspension produced from SCs-laden conductive films. These data suggest that these conductive degradable polyurethanes that enhance SCs' myelin gene expressions and sustained neurotrophin secretion perform great potential for nerve regeneration applications. PMID:26897537

  19. 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

  20. Tissue transglutaminase activity is involved in the differentiation of oligodendrocyte precursor cells into myelin-forming oligodendrocytes during CNS remyelination.

    Science.gov (United States)

    Van Strien, Miriam E; Baron, Wia; Bakker, Erik N T P; Bauer, Jan; Bol, John G J M; Brev, John J P; Binnekade, Rob; Van Der Laarse, Willem J; Drukarch, Benjamin; Van Dam, Anne-Marie

    2011-11-01

    During normal brain development, axons are myelinated by mature oligodendrocytes (OLGs). Under pathological, demyelinating conditions within the central nervous system (CNS), axonal remyelination is only partially successful because oligodendrocyte precursor cells (OPCs) largely remain in an undifferentiated state resulting in a failure to generate myelinating OLGs. Tissue Transglutaminase (TG2) is a multifunctional enzyme, which amongst other functions, is involved in cell differentiation. Therefore, we hypothesized that TG2 contributes to differentiation of OPCs into OLGs and thereby stimulates remyelination. In vivo studies, using the cuprizone model for de- and remyelination in TG2(-/-) and wild-type mice, showed that during remyelination expression of proteolipid protein mRNA, as a marker for remyelination, in the corpus callosum lags behind in TG2(-/-) mice resulting in less myelin formation and, moreover, impaired recovery of motor behavior. Subsequent in vitro studies showed that rat OPCs express TG2 protein and activity which reduces when the cells have matured into OLGs. Furthermore, when TG2 activity is pharmacologically inhibited, the differentiation of OPCs into myelin-forming OLGs is dramatically reduced. We conclude that TG2 plays a prominent role in remyelination of the CNS, probably through stimulating OPC differentiation into myelin-forming OLGs. Therefore, manipulating TG2 activity may represent an interesting new target for remyelination in demyelinating diseases. PMID:21818782

  1. Myelin protein zero: mutations in the cytoplasmic domain interfere with its cellular trafficking.

    Science.gov (United States)

    Konde, Viren; Eichberg, Joseph

    2006-05-01

    The cytoplasmic domain of myelin protein zero (MPZ), the principal protein of peripheral myelin, undergoes phosphorylation on several serine residues and a tyrosine group that is maximal during peak nerve myelination. Mutations that could affect MPZ phosphorylation cause the inherited neuropathy, Charcot-Marie-Tooth disease Type 1B. To investigate a possible role for phosphorylation in regulation of MPZ trafficking within the cell, we expressed wild-type and mutated MPZ-enhanced green fluorescent protein (GFP) fusion proteins in cultured Schwann-like cells. Whereas wild-type protein is present almost entirely at the cell surface, mutation of serine 204 to alanine or at a nearby presumed PKC substrate motif (198RSTK201) causes 40-60% of protein to be retained in the cytoplasm. Mutation of S204 to aspartate, which introduces a permanent negative charge, also impairs MPZ movement to the plasma membrane. In contrast, tyrosine 191 mutation has no effect on MPZ cellular distribution. Simultaneous alteration of S204 and Y191 produces much less perturbation of MPZ trafficking than mutation of S204 alone. Colocalization studies showed that mutated MPZ-EGFP trapped in the cytoplasm associates with all organelles in the secretory pathway. Previous studies have shown that cytoplasmic mutations at serine, but not tyrosine phosphorylation sites, abolish MPZ adhesive properties. Our results suggest that this loss of adhesion may be due, at least in part, to a failure of sufficient MPZ to reach the cell surface and that this impaired trafficking is associated with deficient serine phosphorylation in the cytoplasmic domain. PMID:16493674

  2. 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.

  3. Metabotropic GABA-B receptors in the PNS: role in nociception and myelination

    Directory of Open Access Journals (Sweden)

    B. Bettler

    2009-11-01

    Full Text Available Metabotropic GABA-B receptors are present in the CNS where they play important roles in the modulation of nociceptive transmission and pain. Many preclinical studies reported that the GABA-B specific agonist baclofen is antinociceptive in different models of acute and chronic pain. The study of GABA-B1 knockout mice further supports the contribution of GABA-B receptors to central nociceptive processing. These mice are hyperalgesic, showing a reduced latency to thermal and mechanical stimuli. A tonic GABA-B receptor activation therefore appears to contribute to the establishment of the nociceptive threshold. Interestingly, GABA-B receptors are expressed in the peripheral nervous system (PNS, mainly in the Schwann cells where they control cell proliferation and myelination. Emerging evidence obtained in GABA-B1 knockout mice indicates that these mice exhibit gait alterations and reduced allodynic sensitivity too. Furthermore, GABA-B1-deficient mice show morphological and molecular changes in peripheral nerves, including an increase in the number of small myelinated fibers, as well as in small neurons of the lumbar dorsal root ganglia. These fibers are supposed to be A_ nociceptive fibers. Consequently, it has been suggested that GABA-B receptors are implicated in the PNS myelination process. The possibility that PNS alterations contribute to the sensory phenotypes observed in GABAB1- deficient mice has been also hypothesized. The study in conditional mice that specifically lack the GABA-B1 receptor in the Schwann cells or in motoneurons will aim to clarify the role of GABA-B receptors in peripheral pain sensitivity.

  4. A Split Sprint mission to Mars

    Science.gov (United States)

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

    1992-01-01

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

  5. Observers and splitting structures in relativistic electrodynamics

    Science.gov (United States)

    Auchmann, B.; Kurz, S.

    2014-10-01

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

  6. Observers and splitting structures in relativistic electrodynamics

    International Nuclear Information System (INIS)

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

  7. Hyperfine interaction and zero-field splitting

    International Nuclear Information System (INIS)

    Unpaired electrons and nuclei with magnetic moments produce hyperfine and zero-field splittings in the spectra of molecules. From the former one learns about the character of the wavefunction and obtains some structural and spin-density information. Zero-field splittings are indicative of magnetic anisotropy which is also related to the electronic properties. Examples taken from electron-spin-resonance and far-infrared spectra of matrix-isolated molecules will be considered. Recent examples that may be discussed are a gallium arsenide cluster (Ga2As3), transition-metal dioxides and dihydrides (RhH2), transition-metal diatomic ions (Nb2+) and the zero-field splitting in nickelocene. In some of these cases, comparison can be made with an initio theoretical calculations of the properties of their ground electronic states

  8. Symmetric splitting of very light systems

    International Nuclear Information System (INIS)

    Fission reactions that produce fragments close to one half the mass of the composite system are traditionally observed in heavy nuclei. In light systems, symmetric splitting is rarely observed and poorly understood. It would be interesting to verify the existence of the symmetric splitting of compound nuclei with A 12C + 40Ca, 141 MeV 9Be + 40Ca and 153 MeV 6Li + 40Ca. The out-of-plane correlation of symmetric products was also measured for the reaction 186 MeV 12C + 40Ca. The coincidence measurements of the 12C + 40Ca system demonstrated that essentially all of the inclusive yield of symmetric products around 400 results from a binary decay. To characterize the dependence of the symmetric splitting process on the excitation energy of the 12C + 40C system, inclusive measurements were made at bombarding energies of 74, 132, 162, and 185 MeV

  9. Heterogeneous photocatalyst materials for water splitting.

    Science.gov (United States)

    Kudo, Akihiko; Miseki, Yugo

    2009-01-01

    This critical review shows the basis of photocatalytic water splitting and experimental points, and surveys heterogeneous photocatalyst materials for water splitting into H2 and O2, and H2 or O2 evolution from an aqueous solution containing a sacrificial reagent. Many oxides consisting of metal cations with d0 and d10 configurations, metal (oxy)sulfide and metal (oxy)nitride photocatalysts have been reported, especially during the latest decade. The fruitful photocatalyst library gives important information on factors affecting photocatalytic performances and design of new materials. Photocatalytic water splitting and H2 evolution using abundant compounds as electron donors are expected to contribute to construction of a clean and simple system for solar hydrogen production, and a solution of global energy and environmental issues in the future (361 references). PMID:19088977

  10. Myelin Abnormalities in the Optic and Sciatic Nerves in Mice With GM1-Gangliosidosis

    OpenAIRE

    Heinecke, Karie A.; Luoma, Adrienne; dAzzo, Alessandra; Kirschner, Daniel A; Seyfried, Thomas N

    2015-01-01

    GM1-gangliosidosis is a glycosphingolipid lysosomal storage disease involving accumulation of GM1 and its asialo form (GA1) primarily in the brain. Thin-layer chromatography and X-ray diffraction were used to analyze the lipid content/composition and the myelin structure of the optic and sciatic nerves from 7- and 10-month old ?-galactosidase (?-gal) +/? and ?-gal ?/? mice, a model of GM1gangliosidosis. Optic nerve weight was lower in the ?-gal ?/? mice than in unaffected ?-gal +/? mice, but ...

  11. Analysis of Chemokines and Receptors Expression Profile in the Myelin Mutant Taiep Rat

    OpenAIRE

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

    2015-01-01

    Taiep rat has a failure in myelination and remyelination processes leading to a state of hypomyelination throughout its life. Chemokines, which are known to play a role in inflammation, are also involved in the remyelination process. We aimed to demonstrate that remyelination-stimulating factors are altered in the brainstem of 1- and 6-month-old taiep rats. We used a Rat RT2 Profiler PCR Array to assess mRNA expression of 84 genes coding for cytokines, chemokines, and their receptors. We also...

  12. Myelin basic protein reduces molecular motions in DMPA, an elastic neutron scattering study

    Science.gov (United States)

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

    2001-07-01

    We have studied the effect of physiological amounts of myelin basic protein (MBP) on pure dimyristoyl L- ?-phosphatidic acid (DMPA) vesicles using the elastic neutron scattering technique. Elastic scans have been performed in a wide temperature range (20-300 K). In the lower temperature region the behaviour of the integrated elastic intensity was the typical one of harmonic systems. The analysis of the Q and T dependence performed in terms of an asymmetric double well potential clearly showed that the effect of the protein consisted in a significant reduction of the conformational mobility of the DMPA bilayers and in the stabilisation of the membrane.

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

    OpenAIRE

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

    2014-01-01

    Charcot-Marie-Tooth disease type 1A (CMT1A) is a hereditary peripheral neuropathy characterized by progressive demyelination and distal muscle weakness. Abnormal expression of peripheral myelin protein 22 (PMP22) has been linked to CMT1A and is modeled by Trembler J (TrJ) mice, which carry the same leucine to proline substitution in PMP22 as affected pedigrees. Pharmacologic modulation of autophagy by rapamycin in neuron-Schwann cell explant cultures from neuropathic mice reduced PMP22 aggreg...

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

    Directory of Open Access Journals (Sweden)

    Liu Huaqing

    2012-06-01

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

  15. Recognition of Unipolar and Generalised Split Graphs

    Directory of Open Access Journals (Sweden)

    Colin McDiarmid

    2015-02-01

    Full Text Available A graph is unipolar if it can be partitioned into a clique and a disjoint union of cliques, and a graph is a generalised split graph if it or its complement is unipolar. A unipolar partition of a graph can be used to find efficiently the clique number, the stability number, the chromatic number, and to solve other problems that are hard for general graphs. We present an O(n2-time algorithm for recognition of n-vertex generalised split graphs, improving on previous O(n3-time algorithms.

  16. Smooth globally hyperbolic splittings and temporal functions

    CERN Document Server

    Bernal, A N; Bernal, Antonio N.; S\\'anchez, Miguel

    2004-01-01

    Geroch's theorem about the splitting of globally hyperbolic spacetimes is a central result in global Lorentzian Geometry. Nevertheless, this result was obtained at a topological level, and the possibility to obtain a metric (or, at least, smooth) version has been controversial since its publication in 1970. In fact, this problem has remained open until a definitive proof, recently provided by the authors. Our purpose is to summarize the history of the problem, explain the smooth and metric splitting results (including smoothability of time functions in stably causal spacetimes), and sketch the ideas of the solution.

  17. 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.

  18. Spin splitting in open quantum dots

    OpenAIRE

    Evaldsson, M.; Zozoulenko, I. V.; Ciorga, M.; Zawadzki, P.; Sachrajda, A. S.

    2003-01-01

    We present results from a theoretical and experimental study of spin-splitting in small open lateral quantum dots (i.e. in the regime when the dot is connected to the reservoirs via leads that support one or more propagating modes). We demonstrate that the magnetoconductance shows a pronounced splitting of the conductance peaks (or dips) which persists over a wide range of magnetic fields (from zero field to the edge-state regime) and is virtually independent of magnetic field. A numerical an...

  19. 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...

  20. Myelinated fibers in Charcot-Marie-Tooth disease type 1B with Arg98His mutation of Po protein.

    Science.gov (United States)

    Ohnishi, A; Yamamoto, T; Yamamori, S; Sudo, K; Fukushima, Y; Ikeda, M

    1999-12-15

    This study was undertaken to characterize the clinical, electrophysiologic, and histopathologic features of five presumably unrelated Japanese patients with Charcot-Marie-Tooth (CMT) disease type 1B and Arg98His substitution of Po protein and, in particular, to correlate Arg98His substitution to the ultrastructural abnormalities of the myelin sheath. Systematic morphometric studies of the sural nerve, where the CMT type 1B gene abnormality is expressed, have not been performed, especially on the basis of the type of mutation causing CMT type 1B. Electrophysiologic evaluation of limb nerves and morphometric analysis of sural nerves obtained at biopsy were performed. Ultrastructural myelin abnormalities were precisely examined. Clinical symptoms appeared from the second to the fifth decade. All probands presented with gait disturbance. Motor and sensory conduction velocities in the median and ulnar nerves ranged from 10 to 30 m/s. Segmental demyelination and remyelination and marked loss of myelinated fibers were the main findings. On electron microscopy, widening between major dense lines was found between the paired intraperiod lines, where the extramembranous portion of the Po protein resides. This widening is probably directly related to Arg98His substitution. Focal uncompaction of major dense lines coexisted with this widening. This uncompaction, which directly decreases the number of myelin lamellae, may be a secondary effect of Arg98His substitution on the intramembranous domain of Po protein. In conclusion, myelin changes at both extracellular and cytoplasmic appositions of Schwann cell membranes were found in association with Arg98His substitution of Po protein. This study contributes to a better understanding of myelin abnormalities in patients with CMT type 1B and Arg98His or other similar extramembranous amino acid substitutions of Po protein. PMID:10581375

  1. In vivo expression of the Arf6 Guanine-nucleotide exchange factor cytohesin-1 in mice exhibits enhanced myelin thickness in nerves.

    Science.gov (United States)

    Torii, Tomohiro; Miyamoto, Yuki; Onami, Naoko; Tsumura, Hideki; Nemoto, Noriko; Kawahara, Katsumasa; Kato, Minoru; Kotera, Jun; Nakamura, Kazuaki; Tanoue, Akito; Yamauchi, Junji

    2013-10-01

    The myelin sheath consists of a unique multiple layer structure that acts as an insulator between neuronal axons to enhance the propagation of the action potential. In neuropathies such as demyelinating or dismyelinating diseases, chronic demyelination and defective remyelination occur repeatedly, leading to more severe neuropathy. As yet, little is known about the possibility of drug target-specific medicine for such diseases. In the developing peripheral nervous system (PNS), myelin sheaths form as Schwann cells wrap individual axons. It is thought that the development of a drug promoting myelination by Schwann cells would provide effective therapy against peripheral nerve disorders: to test such treatment, genetically modified mice overexpressing the drug target molecules are needed. We previously identified an Arf6 activator, the guanine-nucleotide exchange factor cytohesin-1, as the signaling molecule controlling myelination of peripheral axons by Schwann cells; yet, the important issue of whether cytohesin-1 itself promotes myelin thickness in vivo has remained unclear. Herein, we show that, in mouse PNS nerves, Schwann cell-specific expression of wild-type cytohesin-1 exhibits enhanced myelin thickness. Downstream activation of Arf6 is also seen in these transgenic mice, revealing the involvement of the cytohesin-1 and Arf6 signaling unit in promoting myelination. These results suggest that cytohesin-1 may be a candidate for the basis of a therapy for peripheral neuropathies through its enhancement of myelin thickness. PMID:23636892

  2. 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; Lehrmann, E; Diemer, Nils Henrik; Finsen, B

    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...

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    Mice with a heterozygous knock-out of the myelin protein P0 gene (P0+/-) develop a neuropathy similar to human Charcot-Marie-Tooth disease. They are indistinguishable from wild-types (WT) at birth and develop a slowly progressing demyelinating neuropathy. The aim of this study was to investigate...... 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....

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

    International Nuclear Information System (INIS)

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

  5. Retroviral-mediated gene transfer of the peripheral myelin protein PMP22 in Schwann cells: modulation of cell growth.

    OpenAIRE

    Zoidl, G.; Blass-Kampmann, S; D'Urso, D; Schmalenbach, C; Mller, H. W.

    1995-01-01

    The peripheral myelin gene PMP22 is the rat and human homologue of the murine growth arrest-specific gene gas3. Besides a putative role of PMP22 in myelination, a regulatory function in cell growth has been suspected. Here we have investigated both the expression of PMP22 during cell cycle progression of cultured rat Schwann cells and the influence of altered levels of PMP22 on Schwann cell growth. When resting cells were stimulated to begin the cell cycle, the regulation of PMP22 mRNA resemb...

  6. 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

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

    Science.gov (United States)

    Falzon, G.; Pearson, S.; Murison, R.; Hall, C.; Siu, K.; Round, A.; Schültke, E.; Kaye, A. H.; Lewis, R.

    2007-11-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-11-07

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

  9. Helioseismic Solar Cycle Changes and Splitting Coefficients

    Indian Academy of Sciences (India)

    S. C. Tripathy; Kiran Jain; A. Bhatnagar

    2000-09-01

    Using the GONG data for a period over four years, we have studied the variation of frequencies and splitting coefficients with solar cycle. Frequencies and even-order coefficients are found to change significantly with rising phase of the solar cycle. We also find temporal variations in the rotation rate near the solar surface.

  10. On Split Lie Triple Systems II

    Indian Academy of Sciences (India)

    Antonio J Calderón Martín; M Forero Piulestán

    2010-04-01

    In [4] it is studied that the structure of split Lie triple systems with a coherent 0-root space, that is, satisfying $[T_0,T_0,T]=0$ and $[T_0,T_,T_0]≠ 0$ for any nonzero root and where $T_0$ denotes the 0-root space and $T_$ the -root space, by showing that any of such triple systems with a symmetric root system is of the form $T=\\mathcal{U}+\\sum_j I_j$ with $\\mathcal{U}$ a subspace of the 0-root space $T_0$ and any $I_j$ a well described ideal of , satisfying $[I_j,T,I_k]=0$ if $j≠ k$. It is also shown in [4] that under certain conditions, a split Lie triple system with a coherent 0-root space is the direct sum of the family of its minimal ideals, each one being a simple split Lie triple system, and the simplicity of is characterized. In the present paper we extend these results to arbitrary split Lie triple systems with no restrictions on their 0-root spaces.

  11. 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 Λ 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|Λ in the form ul (x) = ∫Λ 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

  12. Conversion efficiency in a solar splitting system

    International Nuclear Information System (INIS)

    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

  13. Geometrical splitting and reduction of Feynman diagrams

    CERN Document Server

    Davydychev, Andrei I

    2016-01-01

    A geometrical approach to the calculation of N-point Feynman diagrams is reviewed. It is shown that the geometrical splitting yields useful connections between Feynman integrals with different momenta and masses. It is demonstrated how these results can be used to reduce the number of variables in the occurring functions.

  14. 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).

  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. Hydrogen production from thermochemical splitting of water

    International Nuclear Information System (INIS)

    The thermochemical cycles able to split water to oxygen and hydrogen by means of the high temperature reactor heat are compiled. On the basis of the available themodynamical data the potentiality of realization of the cycles are judged. Pipe-transport of hydrogen and methane is also compared. (author)

  17. Marked phenotypic variation in a family with a new myelin protein zero mutation.

    Science.gov (United States)

    Szabo, A; Zchner, S; Siska, E; Mechler, F; Molnar, M J

    2005-11-01

    Myelin protein zero (MPZ) is a member of the immunoglobulin gene superfamily, which has a role in myelin compaction. MPZ gene mutations cause mostly demyelinating neuropathies of the Charcot-Marie-Tooth 1B type (CMT1B), but axonal CMT have been described as well. There is a broad spectrum of phenotypic manifestation of neuropathies caused by MPZ mutations. Some mutations of MPZ cause severe early-onset neuropathies such as Dejerine-Sottas disease, while others cause the classical CMT phenotype with normal early milestones but development of disability during the first two decades of life. We describe a family in which five members of three consecutive generations had a heterozygous mutation in nucleotide position 143 with a T-C transition in exon 2 of the MPZ gene. The resulting substitution of Leu48 with proline has not been previously described. The age of onset of symptoms varied from 8 months to 41 years. The marked variation of the age of disease onset and clinical phenotype in this one family, related to the same MPZ mutation, suggests that in addition to the type and intragenic location of the mutation, other putative modifying gene(s) are regulating MPZ gene expression, mRNA stability and posttranslational protein modification and may have an important effect on the ultimate clinical phenotype. PMID:16198109

  18. Screening of the myelin protein zero gene in patients with Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Nowakowski, Adam; Kocha?ski, Andrzej

    2004-01-01

    The myelin protein zero gene (MPZ) coding for the most abundant protein of the peripheral myelin was shown to be mutated in Charcot-Marie-Tooth type 1B disease (CMT1B). Later on MPZ mutations have been shown in axonal type of CMT (CMT2). Recently three novel MPZ gene mutations were reported in congenital hypomyelinating neuropathy (CHN). In contrast to the previously reported studies, focused on CMT1B disease, we aimed to analyze the coding and promoter sequences of the MPZ gene in a group of patients with three CMT phenotypes i.e.: CMT1, CMT2 and CHN. Over 500 PCR products were screened by single strand conformation polymorphism analysis (SSCP) and heteroduplex analysis (HA). In one CMT2 family we founded the E56K mutation in the MPZ gene and in one CHN patient the T124K substitution was detected. In agreement with previously reported studies we conclude that MPZ gene screening should be performed for wide phenotype spectrum of CMT. PMID:15094849

  19. 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.

  20. Subtelomeric deletions of 1q43q44 and severe brain impairment associated with delayed myelination.

    Science.gov (United States)

    Shimojima, Keiko; Okamoto, Nobuhiko; Suzuki, Yume; Saito, Mari; Mori, Masato; Yamagata, Tatanori; Momoi, Mariko Y; Hattori, Hideji; Okano, Yoshiyuki; Hisata, Ken; Okumura, Akihisa; Yamamoto, Toshiyuki

    2012-09-01

    Subtelomeric deletions of 1q44 cause mental retardation, developmental delay and brain anomalies, including abnormalities of the corpus callosum (ACC) and microcephaly in most patients. We report the cases of six patients with 1q44 deletions; two patients with interstitial deletions of 1q44; and four patients with terminal deletions of 1q. One of the patients showed an unbalanced translocation between chromosome 5. All the deletion regions overlapped with previously reported critical regions for ACC, microcephaly and seizures, indicating the recurrent nature of the core phenotypic features of 1q44 deletions. The four patients with terminal deletions of 1q exhibited severe volume loss in the brain as compared with patients who harbored interstitial deletions of 1q44. This indicated that telomeric regions have a role in severe volume loss of the brain. In addition, two patients with terminal deletions of 1q43, beyond the critical region for 1q44 deletion syndrome exhibited delayed myelination. As the deletion regions identified in these patients extended toward centromere, we conclude that the genes responsible for delayed myelination may be located in the neighboring region of 1q43. PMID:22718018

  1. Production, crystallization and neutron diffraction of fully deuterated human myelin peripheral membrane protein P2.

    Science.gov (United States)

    Laulumaa, Saara; Blakeley, Matthew P; Raasakka, Arne; Moulin, Martine; Hrtlein, Michael; Kursula, Petri

    2015-11-01

    The molecular details of the formation of the myelin sheath, a multilayered membrane in the nervous system, are to a large extent unknown. P2 is a peripheral membrane protein from peripheral nervous system myelin, which is believed to play a role in this process. X-ray crystallographic studies and complementary experiments have provided information on the structure-function relationships in P2. In this study, a fully deuterated sample of human P2 was produced. Crystals that were large enough for neutron diffraction were grown by a ten-month procedure of feeding, and neutron diffraction data were collected to a resolution of 2.4 from a crystal of 0.09 mm(3) in volume. The neutron crystal structure will allow the positions of H atoms in P2 and its fatty-acid ligand to be visualized, as well as shedding light on the fine details of the hydrogen-bonding networks within the P2 ligand-binding cavity. PMID:26527266

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

    Directory of Open Access Journals (Sweden)

    Francisco J Rivera

    2012-01-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

  4. Microinjection of l-arginine into corpus callosum cause reduction in myelin concentration and neuroinflammation.

    Science.gov (United States)

    Kouhsar, Samaneh Sheikhi; Karami, Manizheh; Tafreshi, Azita Parvaneh; Roghani, Mehrdad; Nadoushan, Mohammad-Reza Jalali

    2011-05-25

    Role of nitric oxide (NO) in inflammationary diseases such as multiple sclerosis (MS) has been proposed previously. We sought to examine if NO plays centrally a key role in MS related phenomena; demyelination or neuroinflammation. Female Wistar rats (weighing 200-250 g) were mounted in a stereotaxic apparatus and received injections of l-arginine aimed at corpus callosum (AP: 1.2, L: ±1.8, V: 3.2). The drug (50-200 μg/rat) was microinjected intra-corpus callosum repeatedly (3-5 times/each per day). Control groups solely received saline (1 μg/rat) into the corpus callosum. The animals were tested for the novelty seeking behavior using the conditioning task. Memory impairment was examined using the shuttle box and Y-maze. l-NAME was pre-injected to l-arginine to involve the NO. All animals' brains were also processed for histological evaluation. l-arginine produced significant changes in the novelty seeking behavior but not in the memory formation, evidenced by passive avoidance and alternation behaviors. Pre-injection of l-NAME reversed the response to l-arginine. Present study further revealed a prominent inflammation as well as myelin elimination in the l-arginine treated rats' brains. These data suggest that the NO infusion in the myelin rich areas such as corpus callosum may lead to MS signs centrally. PMID:21447326

  5. 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

  6. Regulatory effect of triiodothyronine on brain myelination and astrogliosis after cuprizone-induced demyelination in mice.

    Science.gov (United States)

    Zendedel, Adib; Kashani, Iraj Ragerdi; Azimzadeh, Maryam; Pasbakhsh, Parichehr; Omidi, Negar; Golestani, Abolfazl; Beyer, Cordian; Clarner, Tim

    2016-04-01

    Chronic demyelination and plaque formation in multiple sclerosis is accompanied by persisting astrogliosis, negatively influencing central nervous system recovery and remyelination. Triiodothyronin (T3) is thought to enhance remyelination in the adult brain by the induction of oligodendrocyte maturation. We investigated additional astrocyte-mediated mechanisms by which T3 might promote remyelination in chronically demyelinated lesions using the cuprizone mouse model. C57BL/6 mice were fed cuprizone for 12 weeks to induce lesions with an impaired remyelination capacity. While the expression of oligodenrocyte progenitor markers, i.e., platelet derived growth factor-α receptor was not affected by T3 administration, myelination status, myelin protein expression as well as total and adult oligodendrocyte numbers were markedly increased compared to cuprizone treated controls. In addition to these effects on oligodendrocyte numbers and function, astrogliosis but not microgliosis was ameliorated by T3 administration. Intermediate filament proteins vimentin and nestin as well as the extracellular matrix component tenascin C were significantly reduced after T3 exposure, indicating additional effects of T3 on astrocytes and astrogliosis. Our data clearly indicate that T3 promotes remyelination in chronic lesions by both enhancing oligodendrocyte maturation and attenuating astrogliosis. PMID:26725831

  7. Gabapentin attenuates neuropathic pain and improves nerve myelination after chronic sciatic constriction in rats.

    Science.gov (United States)

    Cmara, Carlos C; Arajo, Celina V; de Sousa, Kalina Kelma Oliveira; Brito, Gerly A C; Vale, Mariana L; Raposo, Ramon da Silva; Mendona, Fabiana Evaristo; Mietto, Bruno S; Martinez, Ana Maria B; Ori, Reinaldo B

    2015-10-21

    Gabapentin (GBP) is an anti-convulsive drug often used as analgesic to control neuropathic pain. This study aimed at evaluating oral GBP treatment (30, 60, 120mg/kg, 60min prior to chronic constriction of the sciatic nerve (CCSN) along 15-day treatment post-injury, 12h/12h) by monitoring spontaneous and induced-pain behaviors in Wistar rats on 5th and 15th days post-injury during early neuropathic events. CCSN animals receiving saline were used as controls. Another aim of this study was to evaluate GBP effects on myelin basic protein (MBP) on the 5th and 15th days post-injury and nerve morphology by transmission electron microscopy to address nerve regeneration. On the 5th and 15th days, GBP (60mg/kg) reduced neuropathic pain behaviors (scratching and biting) in the ipsilateral paw and alleviated mechanical allodynia in comparison with the neuropathic saline group. GBP significantly increased climbing and rearing behaviors in CCSN and CCSN-free animals suggesting increased motor activity rather than sedation. We found three-fold significant increase in MBP expression by western blots on the 15th day when compared to controls. In addition, GPB (60mg/kg) improved nerve axonal, fiber and myelin area 15 days post-surgery. In conclusion, GBP alleviated mechanical and thermal allodynia and spontaneous pain-related behaviors and improved later nerve morphology. Our findings suggest that GBP improve nerve remyelination after chronic constriction of the sciatic nerve. PMID:26391746

  8. SncRNA715 Inhibits Schwann Cell Myelin Basic Protein Synthesis.

    Science.gov (United States)

    Müller, Christina; Hochhaus, Nina M; Fontana, Xavier; Luhmann, Heiko J; White, Robin

    2015-01-01

    Myelin basic proteins (MBP) are major constituents of the myelin sheath in the central nervous system (CNS) and the peripheral nervous system (PNS). In the CNS Mbp translation occurs locally at the axon-glial contact site in a neuronal activity-dependent manner. Recently we identified the small non-coding RNA 715 (sncRNA715) as a key inhibitor of Mbp translation during transport in oligodendrocytes. Mbp mRNA localization in Schwann cells has been observed, but has not been investigated in much detail. Here we could confirm translational repression of Mbp mRNA in Schwann cells. We show that sncRNA715 is expressed and its levels correlate inversely with MBP in cultured Schwann cells and in the sciatic nerve in vivo. Furthermore we could reduce MBP protein levels in cultured Schwann cells by increasing the levels of the inhibitory sncRNA715. Our findings suggest similarities in sncRNA715-mediated translational repression of Mbp mRNA in oligodendrocytes and Schwann cells. PMID:26317513

  9. On the additive splitting procedures and their computer realization

    DEFF Research Database (Denmark)

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

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Hayashi Nobuhiro

    2008-02-01

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

  11. [Interdependent changes of the axon and Schwann cell in the process of reactive remodeling of a myelinated nerve fiber].

    Science.gov (United States)

    Kokurina, T N; Sotnikov, O S; Novakovskaia, S A; Egorov, A S; Kozhevets, R V; Solnushkin, S D; Chikhman, V N

    2013-01-01

    Using the inverted phase-contrast microscope, the living undamaged frog sciatic nerve fibers and the fibers mechanically injured to varying degrees, were studied. It was found that the swelling of myelin incisures (MI) (of Schmidt-Lanterman) occured according to the principles similar to those controlling the changes of the myelin gap (node of Ranvier) and depended on the swelling of a Schwann cell (SC) perikaryon. It was detected that this was a single process, which which could be united in a complex of nonspecific changes of a myelinated nerve fiber. It was also demonstrated that under the action of mechanical injury and hypotonic solution, swelling of MI, nodes of Ranvier and SC perikaryon occurred without modifications of outer fiber diameter, due to the pronounced local axon thinning. Electron microscopic study of the cytoskeletal axonal structures showed that there was not a simple local contraction of an axon, but a significant local increase in the density of cytoskeletal components of the axoplasm (by 200-275%). Reactive reversible remodeling of a myelinated fiber suggests a new type of interaction between the axon and SC, the mechanism of reversible translocation of liquid axoplasmic fraction to the glial cell cytoplasm. PMID:23898720

  12. Local Control of Neurofilament Accumulation during Radial Growth of Myelinating Axons in Vivo: Selective Role of Site-Specific Phosphorylation

    OpenAIRE

    Snchez, Ivelisse; HASSINGER, LINDA; Sihag, Ram K; Cleveland, Don W; Mohan, Panaiyur; Nixon, Ralph A

    2000-01-01

    The accumulation of neurofilaments required for postnatal radial growth of myelinated axons is controlled regionally along axons by oligodendroglia. Developmentally regulated processes previously suspected of modulating neurofilament number, including heavy neurofilament subunit (NFH) expression, attainment of mature neurofilament subunit stoichiometry, and expansion of interneurofilament spacing cannot be primary determinants of regional accumulation as we show each of these factors precede ...

  13. Chronic stress regulates NG2(+) cell maturation and myelination in the prefrontal cortex through induction of death receptor 6.

    Science.gov (United States)

    Yang, Youjun; Zhang, Yini; Luo, Fei; Li, Baoming

    2016-03-01

    Chronic stress significantly affects neuron morphometry and function in the prefrontal cortex, a brain region controlling cognition and emotion. However, whether and how chronic stress regulates the maturation of NG2-expressing oligodendrocyte precursor cell (NG2(+) cell) and the importance of these changes remained unknown. Here, we report that exposing adult mice to chronic stress results in NG2(+) cell atrophy and myelination arrested in the medial prefrontal cortex (mPFC), and impaired mPFC-dependent functions. These alterations, are phenocopied by overexpression of death receptor 6 (DR6) in NG2(+) cell. Conversely, selectively silencing of DR6 in the NG2(+) cell can partly rescue NG2(+) cell atrophy and cognitive deficiency caused by chronic stress. We further demonstrate that myelination appears necessary for mPFC-dependent cognitive processes, as lysolecithin (LPC)-induced demyelination specifically in the mPFC is sufficient to cause these behavioral and cognitive impairments. Our results indicate that chronic stress impairs cognitive functions, at least in part, through modulation of NG2(+) cell maturation and myelination, and suggest that myelination is require for normal cognitive functions. PMID:26772637

  14. Myelin staining of deep white matter in the dorsolateral prefrontal cortex in schizophrenia, bipolar disorder, and unipolar major depression.

    Science.gov (United States)

    Regenold, William T; Phatak, Pornima; Marano, Christopher M; Gearhart, Lorie; Viens, Claudia H; Hisley, K Calvin

    2007-06-30

    Neuroimaging and postmortem studies suggest the involvement of white matter disease in schizophrenia, bipolar disorder, and unipolar major depression. To date there is no published, collective study of myelin staining in these three psychiatric disorders. Deep white matter lesions, potentially affecting corticolimbic circuits, have been particularly implicated in late life depression and poor outcome bipolar disorder. We hypothesized that individuals with these disorders would manifest reduced deep white matter myelin staining compared to normal controls. Sixty transverse sections of fixed dorsolateral prefrontal cortex - 15 from individuals with each psychiatric disorder and 15 from normal controls - were stained according to the method of Kluver and Barrera. Myelin staining intensity was quantified by digital image analysis and expressed as a percent of grey matter staining for a given section. Mean deep (but not gyral) white matter myelin staining was less intense in all three psychiatric groups compared to control. This difference was statistically significant for the bipolar and unipolar groups, with a strong trend toward attenuated staining in the schizophrenic group. Our findings are consistent with postmortem and neuroimaging studies of affective disorders that indicate an increased prevalence of deep white matter lesions in unipolar and bipolar affective disorders. PMID:17433451

  15. 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.)

  16. Concept Development of a Split Air Conditioner

    OpenAIRE

    Lundén, Hanna

    2014-01-01

    Detta examensarbete är en konceptutveckling utförd för Home Comfort avdelningen på Electrolux och Kungliga Tekniska Högskolan under vårterminen 2014. Författaren Hanna Lundén samarbetar med Industridesignstudenten Luis R. Velazquez från Lunds Universitet. Målet är att omdefiniera vad en Split airconditioner är idag och utveckla ett koncept i linje med vad användaren vill ha, önskar och åtrår. Projektet är begränsat till att använda den teknik som finns i dagens Split enheter samt att endast u...

  17. Evolution of Advection Upstream Splitting Method Schemes

    Science.gov (United States)

    Liou, Meng-Sing

    2010-01-01

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

  18. Splitting Technique Initialization in Local PCA

    Directory of Open Access Journals (Sweden)

    Alok Sharma

    2006-01-01

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

  19. Spin polarization of the split Kondo state.

    Science.gov (United States)

    von Bergmann, Kirsten; Ternes, Markus; Loth, Sebastian; Lutz, Christopher P; Heinrich, Andreas J

    2015-02-20

    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. PMID:25763966

  20. 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.

  1. 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.

  2. Oblique split technique in septal reconstruction.

    Science.gov (United States)

    Tastan, Eren; Sozen, Tevfik

    2013-12-01

    The septum is considered to be the most important anatomical structure in providing nasal support. Because of a variety of potential etiologies nasal septum could be severely deformed or even diminished. Autogenous cartilage has generally been considered the gold standard grafting material in reconstructive septal surgery for creating the infrastructure of the nose. In the restructuring of the nasal skeleton autogenous cartilage can be harvested from the auricle or the rib. For the major septal problems requiring a large volume of tissues with severe structural defects costal cartilage is considered the best graft material. Apart from its advantages, warping has been the main problem with costal cartilage grafting. Oblique split method, provides straight costal cartilage grafts of varying thicknesses without the risk of warping. Segmental reconstruction of the L-strut with oblique split method, composed of dorsal and caudal struts, enables fine adjustment of height of the reconstructed septum. PMID:24327247

  3. Solar Water Splitting Using Semiconductor Photocatalyst Powders.

    Science.gov (United States)

    Takanabe, Kazuhiro

    2016-01-01

    Solar energy conversion is essential to address the gap between energy production and increasing demand. Large scale energy generation from solar energy can only be achieved through equally large scale collection of the solar spectrum. Overall water splitting using heterogeneous photocatalysts with a single semiconductor enables the direct generation of H2 from photoreactors and is one of the most economical technologies for large-scale production of solar fuels. Efficient photocatalyst materials are essential to make this process feasible for future technologies. To achieve efficient photocatalysis for overall water splitting, all of the parameters involved at different time scales should be improved because the overall efficiency is obtained by the multiplication of all these fundamental efficiencies. Accumulation of knowledge ranging from solid-state physics to electrochemistry and a multidisciplinary approach to conduct various measurements are inevitable to be able to understand photocatalysis fully and to improve its efficiency. PMID:26134367

  4. Large Bandgap Semiconductors for Solar Water Splitting

    DEFF Research Database (Denmark)

    Malizia, Mauro

    Photoelectrochemical water splitting represents an eco-friendly technology that could enable the production of hydrogen using water as reactant and solar energy as primary energy source. The exploitation of solar energy for the production of hydrogen would help modern society to reduce the reliance...... Solar-to-Hydrogen efficiency lower than 0.5%. In addition, BiVO4 was synthesized on the back-side of a Si back-illuminated photocathode to produce a preliminary monolithic solar water splitting device.The Faradaic efficiency of different types of catalysts for the electrochemical production of hydrogen...... on fossil fuels as primary feedstock for hydrogen production and diminish the emission of greenhouse gases in the atmosphere, weakening the global warming phenomenon.The dissertation reports the development of GaP (gallium phosphide) photocathodes as a large bandgap semiconductor for...

  5. 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.

  6. A thermodynamically compatible splitting procedure in hyperelasticity

    International Nuclear Information System (INIS)

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

  7. Splitting of inviscid fluxes for real gases

    Science.gov (United States)

    Liou, Meng-Sing; Van Leer, Bram; Shuen, Jian-Shun

    1990-01-01

    Flux-vector and flux-difference splittings for the inviscid terms of the compressible flow equations are derived under the assumption of a general equation of state for a real gas in equilibrium. No necessary assumptions, approximations for auxiliary quantities are introduced. The formulas derived include several particular cases known for ideal gases and readily apply to curvilinear coordinates. Applications of the formulas in a TVD algorithm to one-dimensional shock-tube and nozzle problems show their quality and robustness.

  8. Splitting and focusing of neutrino collective states

    OpenAIRE

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

    2003-01-01

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

  9. Height in Splittings of Hyperbolic Groups

    Indian Academy of Sciences (India)

    Mahan Mitra

    2004-02-01

    Suppose is a hyperbolic subgroup of a hyperbolic group . Assume there exists > 0 such that the intersection of essentially distinct conjugates of is always finite. Further assume splits over with hyperbolic vertex and edge groups and the two inclusions of are quasi-isometric embeddings. Then is quasiconvex in . This answers a question of Swarup and provides a partial converse to the main theorem of [23].

  10. Universal exchange-driven phonon splitting

    Science.gov (United States)

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

    2012-02-01

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

  11. Dynamics of a split torque helicopter transmission

    Science.gov (United States)

    Rashidi, Majid; Krantz, Timothy

    1992-01-01

    A high reduction ratio split torque gear train has been proposed as an alternative to a planetary configuration for the final stage of a helicopter transmission. A split torque design allows a high ratio of power-to-weight for the transmission. The design studied in this work includes a pivoting beam that acts to balance thrust loads produced by the helical gear meshes in each of two parallel power paths. When the thrust loads are balanced, the torque is split evenly. A mathematical model was developed to study the dynamics of the system. The effects of time varying gear mesh stiffness, static transmission errors, and flexible bearing supports are included in the model. The model was demonstrated with a test case. Results show that although the gearbox has a symmetric configuration, the simulated dynamic behavior of the first and second compound gears are not the same. Also, results show that shaft location and mesh stiffness tuning are significant design parameters that influence the motions of the system.

  12. Dynamics of a split torque helicopter transmission

    Science.gov (United States)

    Rashidi, Majid; Krantz, Timothy

    A high reduction ratio split torque gear train has been proposed as an alternative to a planetary configuration for the final stage of a helicopter transmission. A split torque design allows a high ratio of power-to-weight for the transmission. The design studied in this work includes a pivoting beam that acts to balance thrust loads produced by the helical gear meshes in each of two parallel power paths. When the thrust loads are balanced, the torque is split evenly. A mathematical model was developed to study the dynamics of the system. The effects of time varying gear mesh stiffness, static transmission errors, and flexible bearing supports are included in the model. The model was demonstrated with a test case. Results show that although the gearbox has a symmetric configuration, the simulated dynamic behavior of the first and second compound gears are not the same. Also, results show that shaft location and mesh stiffness tuning are significant design parameters that influence the motions of the system.

  13. P-wave Cooper pair splitting

    Directory of Open Access Journals (Sweden)

    Henning Soller

    2012-07-01

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

  14. 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.

  15. 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

    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 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

  16. Clobetasol and Halcinonide Act as Smoothened Agonists to Promote Myelin Gene Expression and RxR? Receptor Activation.

    Science.gov (United States)

    Porcu, Giampiero; Serone, Eliseo; De Nardis, Velia; Di Giandomenico, Daniele; Lucisano, Giuseppe; Scardapane, Marco; Poma, Anna; Ragnini-Wilson, Antonella

    2015-01-01

    One of the causes of permanent disability in chronic multiple sclerosis patients is the inability of oligodendrocyte progenitor cells (OPCs) to terminate their maturation program at lesions. To identify key regulators of myelin gene expression acting at the last stages of OPC maturation we developed a drug repositioning strategy based on the mouse immortalized oligodendrocyte (OL) cell line Oli-neu brought to the premyelination stage by stably expressing a key factor regulating the last stages of OL maturation. The Prestwick Chemical Library of 1,200 FDA-approved compound(s) was repositioned at three dosages based on the induction of Myelin Basic Protein (MBP) expression. Drug hits were further validated using dosage-dependent reproducibility tests and biochemical assays. The glucocorticoid class of compounds was the most highly represented and we found that they can be divided in three groups according to their efficacy on MBP up-regulation. Since target identification is crucial before bringing compounds to the clinic, we searched for common targets of the primary screen hits based on their known chemical-target interactomes, and the pathways predicted by top ranking compounds were validated using specific inhibitors. Two of the top ranking compounds, Halcinonide and Clobetasol, act as Smoothened (Smo) agonists to up-regulate myelin gene expression in the Oli-neuM cell line. Further, RxR? activation is required for MBP expression upon Halcinonide and Clobetasol treatment. These data indicate Clobetasol and Halcinonide as potential promyelinating drugs and also provide a mechanistic understanding of their mode of action in the pathway leading to myelination in OPCs. Furthermore, our classification of glucocorticoids with respect to MBP expression provides important novel insights into their effects in the CNS and a rational criteria for their choice in combinatorial therapies in de-myelinating diseases. PMID:26658258

  17. 7 CFR 51.2731 - U.S. Spanish Splits.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false U.S. Spanish Splits. 51.2731 Section 51.2731... STANDARDS) United States Standards for Grades of Shelled Spanish Type Peanuts Grades § 51.2731 U.S. Spanish Splits. “U.S. Spanish Splits” consists of shelled Spanish type peanut kernels which are split or...

  18. $F$ tests for the strip-split plot design

    OpenAIRE

    Díaz-Pachón, Daniel Andrés; Francisco J.P. Zimmermann; López, Luis Alberto

    2015-01-01

    In this article we present the structure of the $F$ tests, the variance components and the approximate degrees of freedom for each of the eight possible mixed models of the strip-split plot design. We present an example to illustrate the model and compare it to more traditional settings like a three-way factorial design and a split-split plot model.

  19. 26 CFR 1.7872-15 - Split-dollar loans.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Split-dollar loans. 1.7872-15 Section 1.7872-15...) INCOME TAXES General Actuarial Valuations § 1.7872-15 Split-dollar loans. (a) General rules—(1) Introduction. This section applies to split-dollar loans as defined in paragraph (b)(1) of this section. If...

  20. De- Moivre's and Euler Formulas for Matrices of Split Quaternions

    OpenAIRE

    Erdogdu, Melek; Ozdemir, Mustafa

    2015-01-01

    In this paper, real matrix representations of split quaternions are examined in terms of the casual character of quaternion. Then, we give De-Moivre' s formula for real matrices of timelike and spacelike split quaternions, separately. Finally, we state the Euler theorem for real matrices of pure split quaternions.

  1. Paving the way for adequate myelination: The contribution of galectin-3, transferrin and iron.

    Science.gov (United States)

    Franco, Paula G; Pasquini, Laura A; Pérez, María J; Rosato-Siri, María V; Silvestroff, Lucas; Pasquini, Juana M

    2015-11-14

    Considering the worldwide incidence of well characterized demyelinating disorders such as Multiple Sclerosis (MS) and the increasing number of pathologies recently found to involve hypomyelinating factors such as micronutrient deficits, elucidating the molecular basis of central nervous system (CNS) demyelination, remyelination and hypomyelination becomes essential to the development of future neuroregenerative therapies. In this context, this review discusses novel findings on the contribution of galectin-3 (Gal-3), transferrin (Tf) and iron to the processes of myelination and remyelination and their potentially positive regulation of oligodendroglial precursor cell (OPC) differentiation. Studies were conducted in cuprizone (CPZ)-induced demyelination and iron deficiency (ID)-induced hypomyelination, and the participation of glial and neural stem cells (NSC) in the remyelination process was evaluated by means of both in vivo and in vitro assays on primary cell cultures. PMID:26296311

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

    Science.gov (United States)

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

    2009-12-01

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

  3. 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-α-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

    Energy Technology Data Exchange (ETDEWEB)

    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-{alpha}-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. 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.

  6. Palmitoylethanolamide restores myelinated-fibre function in patients with chemotherapy-induced painful neuropathy.

    Science.gov (United States)

    Truini, A; Biasiotta, A; Di Stefano, G; La Cesa, S; Leone, C; Cartoni, C; Federico, V; Petrucci, M T; Cruccu, G

    2011-12-01

    We assessed the effect of palmitoylethanolamide (PEA) on pain and nerve function in patients with chemotherapy-induced painful neuropathy, in 20 patients undergoing thalidomide and bortezomib treatment for multiple myeloma. All patients were evaluated before and after a two-month treatment with PEA 300 mg BID using pain and warmth thresholds; blinded examiners measured motor and sensory nerve fibre function and laser-evoked potentials. Although no variables returned to normal values, pain and all neurophysiological measures ? assessing A?, A?, and A? fibres ? significantly improved (P 0.50). Although a placebo effect might play a role in the reported pain relief, the changes in neurophysiological measures indicate that PEA exerted a positive action on myelinated fibre groups. PEA, possibly by moderating mast cell hyperactivity, relieved conduction blocks secondary to endoneural edema. In a severe condition such as painful neuropathy associated with multiple myeloma and chemotherapy, a safe substance such as PEA provides significant restoration of nerve function. PMID:22229320

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

    Science.gov (United States)

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

    2012-05-30

    Mitochondrial remodeling (replication, fission/fusion) is a dynamically regulated process with diverse functions in neurons. A myelinated axon is an extension from the cell soma of a fully differentiated neuron. Mitochondria, once synthesized in the cell body, enter the axon displaying robust trafficking and accumulation at nodes of Ranvier to match metabolic needs. This long-distance deployment of mitochondria to axons raises the issue of whether myelinated axons can function independently of the cell body to execute mitochondrial remodeling to match local demands. Mitochondrial fusion has been suggested to occur in axons in simple neuronal cultures in vitro. However, whether such events occur in vivo in an intact nervous system remains unanswered. Here we describe a novel technique which allows monitoring of mitochondrial fusion in intact sciatic nerve of frog (Xenopus laevis). Mitochondrial population was labeled by injecting two different MitoTracker dyes (Red and Green), spatially apart along sciatic nerves surgically and then allow to "meet"in vivo. At 24h post-surgery, the sciatic nerves were taken out for mitochondrial imaging at the half-way point. During the post-injection periods, the anterograde-directed Green mitochondria meet with the retrograde-directed Red mitochondria. If fusion occurs, the merged of Green and Red fluorophores in the same mitochondrion will produce a Yellow color in merged images. The labeled mitochondria were observed with a Nikon A1 confocal microscope. Our new mitochondrial imaging method opens an avenue to separately assess the role of local axonal mitochondrial fusion, independent of the cell body of nerve fibers. PMID:22484559

  8. Membrane proteins in reverse micelles: myelin basic protein in a membrane-mimetic environment.

    Science.gov (United States)

    Nicot, C; Vacher, M; Vincent, M; Gallay, J; Waks, M

    1985-11-19

    The solubility, reactivity, and conformational dynamics of myelin basic protein (MBP) from bovine brain were studied in reverse micelles of sodium bis(2-ethylhexyl) sulfosuccinate (AOT)-isooctane and water. Such a membrane-mimetic system resembles the aqueous spaces of native myelin sheath in terms of physicochemical properties as reflected in the high affinity of MBP for interfacial bound water. This is marked by the unusual profile of the solubility curve of the protein in reverse micelles, which shows optimal solubility at a much lower molar ratio of water to surfactant ([ H2O]/[AOT] = w0) than that reported for other water-soluble proteins. The role of counterions and/or charged polar head groups in the solubilization process is revealed by comparison of the solubility of MBP in nonionic surfactant micellar solutions. Whereas MBP is unfolded in aqueous solutions, insertion into reverse micelles generates a more folded structure, characterized by the presence of 20% alpha-helix. This conformation is unaffected by variations in the water content of the system (in the 2.0-22.4 w0 range). The reactivity of epsilon-amino groups of lysine residues with aqueous solutions of o-phthalaldehyde demonstrates that segments of the peptide chain are accessible to water. Similar results were obtained with the sequence involved in heme binding. In contrast, the sole tryptophan residue, Trp-117, is shielded from the aqueous solvent, as indicated by lack of reaction with N-bromosuccinimide. The invariance of the wavelength maximum emission in the fluorescence spectra as a function of w0 is consistent with this result.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2416347

  9. 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)

  10. Nonuniform molecular features of myelinating Schwann cells in models for CMT1: distinct disease patterns are associated with NCAM and c-Jun upregulation.

    Science.gov (United States)

    Klein, Dennis; Groh, Janos; Wettmarshausen, Jennifer; Martini, Rudolf

    2014-05-01

    We investigated three models for Charcot-Marie-Tooth type 1 (CMT1) neuropathy, comprising mice lacking connexin 32 (Cx32def), mice with reduced myelin protein zero (P0) expression (P0het) and transgenic mouse mutants overexpressing peripheral myelin protein 22 (PMP22tg), with regard of the expression of the developmentally regulated molecules NCAM, L1, the low-affinity NGF-receptor p75 (p75(NTR) ) and the transcription factor component c-Jun. We found that all molecules were uniformly expressed by myelin deficient and supernumerary Schwann cells. The mutant myelinating Schwann cells of PMP22tg mice showed a robust NCAM-immunoreactivity in Schmidt-Lanterman incisures (SLI) that accompanies other early onset abnormalities, such as the presence of supernumerary Schwann cells and impaired myelin formation in some fibers. In line with this, Cx32def and P0het mice, which represent demyelinating models, only rarely express NCAM in SLI. Surprisingly, c-Jun immunoreactivity displayed a mosaic-like pattern with mostly negative and some weakly or moderately positive nuclei both in myelinating Schwann cells and Remak cells of wildtype (wt), P0het and PMP22tg mice. However, c-Jun expression was substantially upregulated in myelinating Schwann cells of Cx32def mice and spatially associated with axon perturbation, a typical predemyelinating feature of Cx32 deficiency. Additionally, c-Jun upregulation was correlated with an elevated level of GDNF, possibly causally linked to the typical compensatory sprouting of axons in Cx32def mice and CMT1X patients. Our findings suggest that in myelinating Schwann cells of distinct models of CMT1, c-Jun upregulation is a marker for predemyelinating axonal perturbation while myelin-related NCAM expression is indicative for early Schwann cell abnormalities. PMID:24526449

  11. Semiconductor Nanowires for Photoelectrochemical Water Splitting

    Science.gov (United States)

    Hwang, Yun Jeong

    Photolysis of water with semiconductor materials has been investigated intensely as a clean and renewable energy resource by storing solar energy in chemical bonds such as hydrogen. One-dimensional (1D) nanostructures such as nanowires can provide several advantages for photoelectrochemical (PEC) water splitting due to their high surface areas and excellent charge transport and collection efficiency. This dissertation discusses various nanowire photoelectrodes for single or dual semiconductor systems, and their linked PEC cells for self-driven water splitting. After an introduction of solar water splitting in the first chapter, the second chapter demonstrates water oxidative activities of hydrothermally grown TiO2 nanowire arrays depending on their length and surface properties. The photocurrents with TiO2 nanowire arrays approach saturation due to their poor charge collection efficiency with longer nanowires despite increased photon absorption efficiency. Epitaxial grains of rutile atomic layer deposition (ALD) shell on TiO2 nanowire increase the photocurrent density by 1.5 times due to improved charge collection efficiency especially in the short wavelength region. Chapter three compares the photocurrent density of the planar Si and Si nanowire arrays coated by anatase ALD TiO 2 thin film as a model system of a dual bandgap system. The electroless etched Si nanowire coated by ALD TiO2 (Si EENW/TiO2) shows 2.5 times higher photocurrent density due to lower reflectance and higher surface area. Also, this chapter illustrates that n-Si/n-TiO2 heterojunction is a promising structure for the photoanode application of a dual semiconductor system, since it can enhance the photocurrent density compared to p-Si/n-TiO 2 junction with the assistance of bend banding at the interface. Chapter four demonstrates the charge separation and transport of photogenerated electrons and holes within a single asymmetric Si/TiO2 nanowire. Kelvin probe force microscopy measurements show the higher surface potential on the n-TiO 2 (photoanode) side relative to the p-Si (photocathode) side under UV illumination as the result of hole accumulation on the TiO2 side and electron accumulation on the Si side which are desirable charge separation for solar water splitting. In chapter five, TiO2 is replaced with single phase InGaN nanowire in a dual bandgap photoanode to show the potential for solar water splitting with high surface area Si/InGaN hierarchical nanowire arrays and InGaN as a possible candidate for visible light absorber. An enhancement of 5 times in photocurrent was observed when the surface area increased from InGaN nanowires on planar Si to InGaN nanowires on Si wires. Chapter six demonstrates a self-driven water splitting device with the p/n PEC cell which consists of a photocathode and a photoanode. The operating photocurrent (Iop) with the p/n PEC cell is enhanced when n-Si/p-Si photovoltage cell was embedded under an n-TiO2 photoanode by utilizing the photovoltage generated by a Si PV cell. Also, the Si nanowire photocathode surface is modified with Pt and TiO2 to increase hydrogen reducing activity and stability which enhances Iop of the p/n PEC cell as well. When Si/TiO 2 nanowire photocathode is linked with n-Si/p-Si photovoltage cell embedded TiO2 nanowire photoanode, the p/n PEC cell shows water splitting without bias voltage confirmed with 2:1 ratio of hydrogen:oxygen gas evolution and a 92 % Faradic efficiency. These studies represent a significant step towards realizing the benefit of the advanced 1D nanowire configuration for efficient solar to energy conversion.

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

    OpenAIRE

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

    1992-01-01

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

  13. THE MARKET REACTION TO STOCK SPLITS — EVIDENCE FROM INDIA

    OpenAIRE

    Mishra, A. K.

    2007-01-01

    Stock splits are a relatively new phenomenon in the Indian context. This paper examines the market effect of stock splits on stock price, return, volatility, and trading volume around the split ex-dates for a sample of stock splits undertaken in the Indian stock market over the period 1999–2005.The traditional view of stock splits as cosmetic transactions that simply divide the same pie into more slices is inconsistent with the significant wealth effect associated with the announcement of a s...

  14. Splitting in dual-phase 590 high strength steel plates

    International Nuclear Information System (INIS)

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

  15. SplitRFLab: A MATLAB GUI toolbox for receiver function analysis based on SplitLab

    Science.gov (United States)

    Xu, Mijian; Huang, Hui; Huang, Zhouchuan; Wang, Liangshu

    2016-02-01

    We add new modules for receiver function (RF) analysis in SplitLab toolbox, which includes the manual RF analysis module, automatic RF analysis and related quality control modules, and H- k stacking module. The updated toolbox (named SplitRFLab toolbox), especially its automatic RF analysis module, could calculate the RFs quickly and efficiently, which is very useful in RF analysis with huge amount of seismic data. China is now conducting the ChinArray project that plans to deploy thousands of portable stations across Chinese mainland. Our SplitRFLab toolbox may obtain reliable RF results quickly at the first time, which provide essentially new constraint to the crustal and mantle structures.

  16. The Splitting Index: construction of a scale measuring the defense mechanism of splitting.

    Science.gov (United States)

    Gould, J R; Prentice, N M; Ainslie, R C

    1996-04-01

    The Splitting Index (SI), a self-report scale based on the writings of Kernberg (e.g., 1976) on self and object representations and the defense mechanism of splitting, was constructed. After development over the course of 6 pilot studies, the SI was validated through 2 further studies. Factor analyses revealed a 24-item scale with three 8-item subscales, measuring the splitting of self, family, and others' images. The SI and its subscales were demonstrated to be internally consistent and stable over a 4-week period. Convergent validity was supported by significant correlations with measures of borderline and narcissistic personality disorders, self-image stability, self-esteem, depression, and negative affectivity. Discriminant validity was demonstrated by near-zero correlations with two measures of cognitive complexity. Contrary to predictions, the SI was significantly correlated with the Dogmatism Scale (Rokeach, 1960), a third measure of cognitive complexity. Research and clinical applications of the SI are discussed. PMID:8869581

  17. Numerical modelling of SHPB splitting tests

    Science.gov (United States)

    Galvez, F.; Sanchez Galvez, V.

    2003-09-01

    The Splitting or Brazi1ian test of disks is a useful method to measure tensile strength on brittle materials. When the tensile stress reaches the tensile strength, the disk fails on the loading plane. Nevertheless, the stress state is not uniaxial and the material undergoes compressive stresses, normal to the tensile ones. On materials with a high compressive/tensile strength ratio as ceramics or concrete, the failure of the material is produced by the tensile stress, whereas no damage is caused by compressive stresses. This is the reason why splitting tests of disks have been proved to be an excellent solution to measure tensile strength on brittle materials like ceramics or concrete. This technique bas been used for years to test brittle materials on static conditions, and more recently, it has been brought into use on dynamic tests, as Hopkinson bar experiments. The results obtained on these experiments have been useful and fully accepted by the materials researchers. The loading process has been modelled by different authors and tests results have been justified when loading conditions remain static or in a low strain rate. In this paper, a numerical modelling of the splitting test is extended to high strain rates in 3D. Numerical results are compared with actual tests carried out in a Hopkinson bar published in previous papers. Results show that the specimen is under equilibrium only if the initial slope of the incident pulse is not very abrupt. A 3D effect has been noticed showing that tensile stress levels are higher on the specimen surfaces than inside the material, and it bas a direct influence on the tensile strength measured by means of the maximum load achieved and has to be taken into account. Finally, the crack patterns of the failure on the specimen are compared with actual tests showing a good agreement.

  18. Modular Grammars and Splitting of Catamorphisms

    OpenAIRE

    Badouel, Eric; Djeumen, Rodrigue,

    2007-01-01

    An abstract context-free grammar can be viewed as a system of polynomial functors. The initial algebra of this functor coincides with its least fixed-point; and this fixed-point can be computed by a method of substitution using Bek\\`{\\i}c theorem. By doing so the system of polynomial functors is transformed into a related system of regular functors. We introduce a splitting operation on algebras producing an algebra for the resulting system of regular functors from an algebra of the original ...

  19. Basic dynamics of split Stirling refrigerators

    Science.gov (United States)

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

    2008-09-01

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

  20. The second order pole over split quaternions

    Science.gov (United States)

    Libine, Matvei

    2015-04-01

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

  1. Dominated Splitting and Pesin's Entropy Formula

    CERN Document Server

    Sun, Wenxiang

    2010-01-01

    Let $M$ be a compact manifold and $f:\\,M\\to M$ be a $C^1$ diffeomorphism on $M$. If $\\mu$ is an $f$-invariant probability measure which is absolutely continuous relative to Lebesgue measure and for $\\mu$ $a.\\,\\,e.\\,\\,x\\in M,$ there is a dominated splitting $T_{orb(x)}M=E\\oplus F$ on its orbit $orb(x)$, then we give an estimation through Lyapunov characteristic exponents from below in Pesin's entropy formula, i.e., the metric entropy $h_\\mu(f)$ satisfies

  2. Multibreed analysis by splitting the breeding values

    Directory of Open Access Journals (Sweden)

    García-Cortés Luis

    2006-11-01

    Full Text Available Abstract An equivalent model for multibreed variance covariance estimation is presented. It considers the additive case including or not the segregation variances. The model is based on splitting the additive genetic values in several independent parts depending on their genetic origin. For each part, it expresses the covariance between relatives as a partial numerator relationship matrix times the corresponding variance component. Estimation of fixed effects, random effects or variance components provided by the model are as simple as any model including several random factors. We present a small example describing the mixed model equations for genetic evaluations and two simulated examples to illustrate the Bayesian variance component estimation.

  3. Dark Matter Generation and Split Supersymmetry

    OpenAIRE

    Kaplan, Jared

    2006-01-01

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

  4. On split graphs with four distinct eigenvalues

    OpenAIRE

    Goldberg, Felix; Kirkland, Steve; Varghese, Anu; Vijayakumar, Ambat

    2014-01-01

    It is a well-known fact that a graph of diameter $d$ has at least $d+1$ eigenvalues. Let us call a graph \\emph{$d$-extremal} if it has diameter $d$ and exactly $d+1$ eigenvalues. Such graphs have been intensively studied by various authors. %Much attention has been devoted to the study of graphs that are extremal with respect to this relation: \\emph{i.e} have diameter $d$ and exactly $d+1$ distinct eigenvalues. A graph is \\emph{split} if its vertex set can be partitioned into a clique and a s...

  5. Comparing Electrochemical and Biological Water Splitting

    DEFF Research Database (Denmark)

    Rossmeisl, Jan; Dimitrievski, Kristian; Siegbahn, P.; Nørskov, Jens Kehlet

    2007-01-01

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

  6. Split Hubbard bands at low densities

    Science.gov (United States)

    Hansen, Daniel; Perepelitsky, Edward; Shastry, B. Sriram

    2011-05-01

    We present a numerical scheme for the Hubbard model that throws light on the rather esoteric nature of the upper and lower Hubbard bands, which have been invoked often in literature. We present a self-consistent solution of the ladder-diagram equations for the Hubbard model, and show that these provide, at least in the limit of low densities of particles, a vivid picture of the Hubbard split bands. We also address the currently topical problem of decay of the doublon states that are measured in optical trap studies, using both the ladder scheme and also an exact two-particle calculation of a relevant Green’s function.

  7. 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 Cornuéjols 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 triang...

  8. Split rank of two-row cuts

    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 Cornuéjols 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 et al. it is known that one particular class of facet-defining triangle inequality d...

  9. Alteration of split renal function during Captopril treatment

    International Nuclear Information System (INIS)

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

  10. Design of a Cocoa Pod Splitting Machine

    Directory of Open Access Journals (Sweden)

    Adetunde, I.A

    2010-10-01

    Full Text Available This study outlines the design of a very efficient, highly productive, cost- effective, ergonomic and environmentally friendly cocoa splitting machine that will be used by cocoa Farmers world - wide to increase and boost productivity and enhance the quality of coca products to the highest possible level devoid of any hazards, dangers or perils. This machine can be manufactured from locally available scraps and assembled and maintained at a relatively low cost. The knives which do the splitting are actuated by simple hydraulic mechanisms devoid any major stresses, forces or moments acting on them. These mechanisms are powered by simple low - powered lobe positive displacement or hydrostatic hydraulic pumps of power rating of 87.5 kW (65.625 Hp. The machine can be assembled and/or disassembled easily and quickly, and, therefore can be owned patronized by a group of cocoa farmers who can easily bear the low cost of maintenance of the already relative cheap machine.

  11. SKS Splitting offshore California from ALBACORE

    Science.gov (United States)

    Ramsay, J.; Davis, P. M.; Kohler, M. D.

    2012-12-01

    The development and evolution of the Pacific-North America plate boundary offshore Southern California is of great geodynamical interest. For better understanding, the Asthenospheric and Lithospheric Broadband Architecture from the California Offshore Region Experiment (ALBACORE) was initiated. ALBACORE is a network of 24 broadband and 10 short-period ocean bottom seismometers (OBSs) deployed across the southwestern region of the Pacific-North American plate boundary. Other than at scattered island stations present seismic array data ends at the coastline due to the difficulty of measurements further to sea. The experiment is intended to study many aspects of the Pacific-North American plate boundary. In this study we calculate SKS splitting parameters in an effort to measure the anisotropy of the region. The first step involved determining the orientations of each seismometer due to twisting during deployment. P wave arrivals are used and waveforms of each OBS are compared to nearby island stations of the California Seismic Network. The horizontal waveforms from the OBS's are rotated until the rotated components achieved maximum correlation with North and East components at a nearby station. The rotation angle is further constrained by particle motion. Once orientations are established, we calculate SKS splitting parameters by minimizing energy in the transverse component.

  12. Cdc42 and Rac1 signaling are both required for and act synergistically in the correct formation of myelin sheaths in the CNS

    DEFF Research Database (Denmark)

    Thurnherr, Tina; Benninger, Yves; Wu, Xunwei; Chrostek, Anna; Krause, Sven M; Nave, Klaus-Armin; Franklin, Robin J M; Brakebusch, Cord; Suter, Ueli; Relvas, João B

    2006-01-01

    . This was characterized by the extraordinary enlargement of the inner tongue of the oligodendrocyte process and concomitant formation of a myelin outfolding as a result of abnormal accumulation of cytoplasm in this region. Ablation of Rac1 also resulted in the abnormal accumulation of cytoplasm in the...... inner tongue of the oligodendrocyte process, and we provide genetic evidence that rac1 synergizes with cdc42 in a gene dosage-dependent way to regulate myelination....

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

    OpenAIRE

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

    2005-01-01

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

  14. T cell reactivity to P0, P2, PMP-22, and myelin basic protein in patients with Guillain-Barr 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-Barr 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).

  15. Myelin/oligodendrocyte glycoproteindeficient (MOG-deficient) mice reveal lack of immune tolerance to MOG in wild-type mice

    OpenAIRE

    Delarasse, Ccile; Daubas, Philippe; Mars, Lennart T.; Vizler, Csaba; Litzenburger, Tobias; Iglesias, Antonio; Bauer, Jan; Della Gaspera, Bruno; Schubart, Anna; Decker, Laurence; Dimitri, Dalia; Roussel, Guy; Dierich, Andre; Amor, Sandra; Dautigny, Andr

    2003-01-01

    We studied the immunological basis for the very potent encephalitogenicity of myelin/oligodendrocyte glycoprotein (MOG), a minor component of myelin in the CNS that is widely used to induce experimental autoimmune encephalomyelitis (EAE). For this purpose, we generated a mutant mouse lacking a functional mog gene. This MOG-deficient mouse presents no clinical or histological abnormalities, permitting us to directly assess the role of MOG as a target autoantigen in EAE. In contrast to WT mice,...

  16. Non-split and split deformations of AdS_5

    CERN Document Server

    Hoare, Ben

    2016-01-01

    The eta-deformation of the AdS_5 x S^5 superstring depends on a non-split r matrix for the superalgebra psu(2,2|4). Much of the investigation into this model has considered one particular choice, however there are a number of inequivalent alternatives. This is also true for the bosonic sector of the theory with su(2,2), the isometry algebra of AdS_5, admitting one split and three non-split r matrices. In this article we explore these r matrices and the corresponding geometries. We investigate their contraction limits, comment on supergravity backgrounds and demonstrate their relation to gauged-WZW deformations. We then extend the three non-split cases to AdS_5 x S^5 and compute four separate bosonic two-particle tree-level S-matrices based on inequivalent BMN-type light-cone gauges. The resulting S-matrices, while different, are related by momentum-dependent one-particle changes of basis.

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

    Science.gov (United States)

    Speevak, Marsha D; Farrell, Sandra A

    2013-10-01

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

  18. Absence of oligodendroglial glucosylceramide synthesis does not result in CNS myelin abnormalities or alter the dysmyelinating phenotype of CGT-deficient mice.

    Science.gov (United States)

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

    2010-03-01

    To examine the function of glycosphingolipids (GSLs) in oligodendrocytes, the myelinating cells of the central nervous system (CNS), mice were generated that lack oligodendroglial expression of UDP-glucose ceramide glucosyltransferase (encoded by Ugcg). These mice (Ugcg(flox/flox);Cnp/Cre) did not show any apparent clinical phenotype, their total brain and myelin extracts had normal GSL content, including ganglioside composition, and myelin abnormalities were not detected in their CNS. These data indicate that the elimination of gangliosides from oligodendrocytes is not detrimental to myelination. These mice were also used to asses the potential compensatory effect of hydroxyl fatty acid glucosylceramide (HFA-GlcCer) accumulation in UDP-galactose:ceramide galactosyltransferase (encoded by Cgt, also known as Ugt8a) deficient mice. At postnatal day 18, the phenotypic characteristics of the Ugcg(flox/flox);Cnp/Cre;Cgt(-/-) mutants, including the degree of hypomyelination, were surprisingly similar to that of Cgt(-/-) mice, suggesting that the accumulation of HFA-GlcCer in Cgt(-/-) mice does not modify their phenotype. These studies demonstrate that abundant, structurally intact myelin can form in the absence of glycolipids, which normally represent over 20% of the dry weight of myelin. PMID:19705459

  19. Amplified Mechanically Gated Currents in Distinct Subsets of Myelinated Sensory Neurons following In Vivo Inflammation of Skin and Muscle

    OpenAIRE

    Weyer, Andy D.; O'Hara, Crystal L.; Stucky, Cheryl L

    2015-01-01

    Primary afferents are sensitized to mechanical stimuli following in vivo inflammation, but whether sensitization of mechanically gated ion channels contributes to this phenomenon is unknown. Here we identified two populations of murine A fiber-type sensory neurons that display markedly different responses to focal mechanical stimuli of the membrane based on their expression of calcitonin gene-related peptide (CGRP). Following inflammation of the hindpaw, myelinated, CGRP-positive neurons proj...

  20. Diffusion of myelin oligodendrocyte glycoprotein in living OLN-93 cells investigated by raster-scanning image correlation spectroscopy (RICS)

    OpenAIRE

    Gielen, Ellen; SMISDOM, Nick; De Clercq, Ben; Van De Ven, Martin; Gijsbers, Rik; Debyser, Zeger; Rigo, Jean-Michel; Hofkens, Johan; Engelborghs, Yves; Ameloot, Marcel

    2008-01-01

    Many membrane proteins and lipids are partially confined in substructures ranging from tens of nanometers to micrometers in size. Evidence for heterogeneities in the membrane of oligodendrocytes, i.e. the myelin-producing cells of the central nervous system, is almost exclusively based on detergent methods. However, as application of detergents can alter the membrane phase behaviour, it is important to investigate membrane heterogeneities in living cells. Here, we report on the first investig...

  1. Early postnatal myelin content estimate of white matter via T1w/T2w ratio

    Science.gov (United States)

    Lee, Kevin; Cherel, Marie; Budin, Francois; Gilmore, John; Zaldarriaga Consing, Kirsten; Rasmussen, Jerod; Wadhwa, Pathik D.; Entringer, Sonja; Glasser, Matthew F.; Van Essen, David C.; Buss, Claudia; Styner, Martin

    2015-03-01

    To develop and evaluate a novel processing framework for the relative quantification of myelin content in cerebral white matter (WM) regions from brain MRI data via a computed ratio of T1 to T2 weighted intensity values. We employed high resolution (1mm3 isotropic) T1 and T2 weighted MRI from 46 (28 male, 18 female) neonate subjects (typically developing controls) scanned on a Siemens Tim Trio 3T at UC Irvine. We developed a novel, yet relatively straightforward image processing framework for WM myelin content estimation based on earlier work by Glasser, et al. We first co-register the structural MRI data to correct for motion. Then, background areas are masked out via a joint T1w and T2 foreground mask computed. Raw T1w/T2w-ratios images are computed next. For purpose of calibration across subjects, we first coarsely segment the fat-rich facial regions via an atlas co-registration. Linear intensity rescaling based on median T1w/T2w-ratio values in those facial regions yields calibrated T1w/T2wratio images. Mean values in lobar regions are evaluated using standard statistical analysis to investigate their interaction with age at scan. Several lobes have strongly positive significant interactions of age at scan with the computed T1w/T2w-ratio. Most regions do not show sex effects. A few regions show no measurable effects of change in myelin content change within the first few weeks of postnatal development, such as cingulate and CC areas, which we attribute to sample size and measurement variability. We developed and evaluated a novel way to estimate white matter myelin content for use in studies of brain white matter development.

  2. Are PrP(C)s involved in some human myelin diseases? Relating experimental studies to human pathology.

    Science.gov (United States)

    Veber, Daniela; Scalabrino, Giuseppe

    2015-12-15

    We have experimentally demonstrated that cobalamin (Cbl) deficiency increases normal cellular prion (PrP(C)) levels in rat spinal cord (SC) and cerebrospinal fluid (CSF), and decreases PrP(C)-mRNA levels in rat SC. Repeated intracerebroventricular administrations of anti-octapeptide repeat-PrP(C)-region antibodies to Cbl-deficient (Cbl-D) rats prevent SC myelin lesions, and the administrations of PrP(C)s to otherwise normal rats cause SC white matter lesions similar to those induced by Cbl deficiency. Cbl positively regulates SC PrP(C) synthesis in rat by stimulating the local synthesis of epidermal growth factor (EGF), which also induces the local synthesis of PrP(C)-mRNAs, and downregulating the local synthesis of tumor necrosis factor(TNF)-α, thus preventing local PrP(C) overproduction. We have clinically demonstrated that PrP(C) levels are increased in the CSF of patients with subacute combined degeneration (SCD), unchanged in the CSF of patients with Alzheimer's disease and amyotrophic lateral sclerosis, and decreased in the CSF and SC of patients with multiple sclerosis (MS), regardless of its clinical course. We conclude that SCD (human and experimental) is a neurological disease due to excess PrP(C) without conformational change and aggregation, that the increase in PrP(C) levels in SCD and Cbl-D polyneuropathy and their decrease in MS CNS make them antipodian myelin diseases in terms of quantitative PrP(C) abnormalities, and that these abnormalities are related to myelin damage in the former, and impede myelin repair in the latter. PMID:26478128

  3. 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 ...

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

    International Nuclear Information System (INIS)

    Commissural white matter fibers comprising the callosal splenium are diverse. Subsections of the splenium myelinate at different times, in a centrolineal manner. The aims of this study are to depict the normal callosal splenium myelination pattern and to distinguish the transient age-related mid splenium hypointensity from pathology. We reviewed 131 consecutive brain MRIs in patients between ages 3 and 6 months from a single academic children's hospital. Patients that were preterm, hydrocephalic, and/or had volume loss were excluded. Fifty total MR exams that included T1-weighted MR imaging (T1WI), T2-weighted MR imaging (T2WI), and diffusion tensor imaging (DTI) were reviewed. Regions of callosal splenium myelination manifested by T1 and T2 shortening were evaluated. Tractography was performed with seeds placed over the posterior, mid, and anterior splenium to define the origin, destination, and course of traversing fibers. Splenium signal varied significantly from 3 to 6 months, with distinct age-related trends. On T1WI, the splenium was hypointense at 3 months (12/13), centrally hypointense/peripherally hyperintense at 4 months (15/16), and hyperintense at 6 months (10/11). Tractography revealed three distinct white matter tract populations: medial occipital (posterior); precuneus, posterior cingulate, and medial temporal (middle); and postcentral gyri (anterior). Specific commissural fiber components of the splenium myelinate at different times. The transient developmental mid splenium hypointensity on T1WI corresponds to tracts from the associative cortex, principally the precuneus. Heterogeneous splenium signal alteration in patients ages 3-6 months is a normal developmental phenomenon that should not be confused with pathologic lesions. (orig.)

  5. Association of calnexin with mutant peripheral myelin protein-22 ex vivo: A basis for gain-of-function ER diseases

    OpenAIRE

    Dickson, K. M.; Bergeron, J. J. M.; Shames, I.; Colby, J; Nguyen, D. T.; Chevet, E.; Thomas, D Y; Snipes, G. J.

    2002-01-01

    Schwann cell-derived peripheral myelin protein-22 (PMP-22) when mutated or overexpressed causes heritable neuropathies with a previously unexplained gain-of-function endoplasmic reticulum (ER) retention phenotype. In wild-type sciatic nerves, PMP-22 associates in a specific, transient (t1/2 ? 11 min), and oligosaccharide processing-dependent manner with the lectin chaperone calnexin (CNX), but not calreticulin nor BiP. In Trembler-J (Tr-J) sciatic nerves, prolonged association of mutant PMP...

  6. The formation of peripheral myelin protein 22 aggregates is hindered by the enhancement of autophagy and expression of cytoplasmic chaperones

    OpenAIRE

    Fortun, Jenny; Verrier, Jonathan D; Go, Jocelyn C.; Madorsky, Irina; Dunn, William A; Notterpek, Lucia

    2006-01-01

    The accumulation of misfolded proteins is associated with various neurodegenerative conditions. Peripheral myelin protein 22 (PMP22) is a hereditary neuropathy-linked, short-lived molecule that forms aggresomes when the proteasome is inhibited or the protein is mutated. We previously showed that the removal of pre-existing PMP22 aggregates is assisted by autophagy. Here we examined whether the accumulation of such aggregates could be suppressed by experimental induction of autophagy and/or ch...

  7. Unravelling crucial biomechanical resilience of myelinated peripheral nerve fibres provided by the Schwann cell basal lamina and PMP22

    OpenAIRE

    Gonzalo Rosso; Ivan Liashkovich; Burkhard Gess; Peter Young; Alejandra Kun; Victor Shahin

    2014-01-01

    There is an urgent need for the research of the close and enigmatic relationship between nerve biomechanics and the development of neuropathies. Here we present a research strategy based on the application atomic force and confocal microscopy for simultaneous nerve biomechanics and integrity investigations. Using wild-type and hereditary neuropathy mouse models, we reveal surprising mechanical protection of peripheral nerves. Myelinated peripheral wild-type fibres promptly and fully recover f...

  8. 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; Ltzelschwab, 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...

  9. Mechanisms of injury-induced calcium entry into peripheral nerve myelinated axons: in vitro anoxia and ouabain exposure.

    Science.gov (United States)

    Lehning, E J; Doshi, R; Stys, P K; LoPachin, R M

    1995-10-01

    In the present investigation, electron probe X-ray microanalysis was used to characterize the effects of in vitro ouabain (2 mM) or anoxia on elemental composition (e.g. Na, K, Ca) and water content of rat peripheral (tibial) nerve myelinated axons and Schwann cells. Results showed that independent of axon size, both ouabain and anoxia markedly increased axoplasmic Na and decreased K concentrations. However, only anoxia was associated with significant elevation of axonal Ca content. Mitochondrial areas from ouabain- or anoxia-exposed fibers exhibited changes in element and water contents that were similar to axoplasmic alterations. Schwann cells and myelin displayed small increases in Na and substantial losses of K in response to ouabain exposure. In contrast, these glial compartments were relatively resistant to anoxia as indicated by the modest and delayed nature of the elemental changes. Nonetheless, neither treatment significantly affected glial Ca concentrations. Our results suggest that Ca2+ accumulation in peripheral nerve axons is complex and involves not only deregulation of Na+ and K+ but other fundamental pathogenic changes as well. In addition to providing baseline information, we have identified an in vitro model (anoxia) which features Ca2+ build-up in PNS myelinated axons. Thus, the present study offers a foundation for investigation into mechanisms of Ca2+ entry following peripheral nerve injury. PMID:8974640

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

    Science.gov (United States)

    Budel, Stphane; Padukkavidana, Thihan; Liu, Betty P; Feng, Zeny; Hu, Fenghua; Johnson, Sam; Lauren, Juha; Park, James H; McGee, Aaron W; Liao, Ji; Stillman, Althea; Kim, Ji-Eun; Yang, Bao-Zhu; Sodi, Stefano; Gelernter, Joel; Zhao, Hongyu; Hisama, Fuki; Arnsten, Amy F T; Strittmatter, Stephen M

    2008-12-01

    In schizophrenia, genetic predisposition has been linked to chromosome 22q11 and myelin-specific genes are misexpressed in schizophrenia. Nogo-66 receptor 1 (NGR or RTN4R) has been considered to be a 22q11 candidate gene for schizophrenia susceptibility because it encodes an axonal protein that mediates myelin inhibition of axonal sprouting. Confirming previous studies, we found that variation at the NGR locus is associated with schizophrenia in a Caucasian case-control analysis, and this association is not attributed to population stratification. Within a limited set of schizophrenia-derived DNA samples, we identified several rare NGR nonconservative coding sequence variants. Neuronal cultures demonstrate that four different schizophrenia-derived NgR1 variants fail to transduce myelin signals into axon inhibition, and function as dominant negatives to disrupt endogenous NgR1. This provides the first evidence that certain disease-derived human NgR1 variants are dysfunctional proteins in vitro. Mice lacking NgR1 protein exhibit reduced working memory function, consistent with a potential endophenotype of schizophrenia. For a restricted subset of individuals diagnosed with schizophrenia, the expression of dysfunctional NGR variants may contribute to increased disease risk. PMID:19052207

  11. Unravelling crucial biomechanical resilience of myelinated peripheral nerve fibres provided by the Schwann cell basal lamina and PMP22.

    Science.gov (United States)

    Rosso, Gonzalo; Liashkovich, Ivan; Gess, Burkhard; Young, Peter; Kun, Alejandra; Shahin, Victor

    2014-01-01

    There is an urgent need for the research of the close and enigmatic relationship between nerve biomechanics and the development of neuropathies. Here we present a research strategy based on the application atomic force and confocal microscopy for simultaneous nerve biomechanics and integrity investigations. Using wild-type and hereditary neuropathy mouse models, we reveal surprising mechanical protection of peripheral nerves. Myelinated peripheral wild-type fibres promptly and fully recover from acute enormous local mechanical compression while maintaining functional and structural integrity. The basal lamina which enwraps each myelinated fibre separately is identified as the major contributor to the striking fibre's resilience and integrity. In contrast, neuropathic fibres lacking the peripheral myelin protein 22 (PMP22), which is closely connected with several hereditary human neuropathies, fail to recover from light compression. Interestingly, the structural arrangement of the basal lamina of Pmp22(-/-) fibres is significantly altered compared to wild-type fibres. In conclusion, the basal lamina and PMP22 act in concert to contribute to a resilience and integrity of peripheral nerves at the single fibre level. Our findings and the presented technology set the stage for a comprehensive research of the links between nerve biomechanics and neuropathies. PMID:25446378

  12. Meson mass splittings in unquenched quark models (EEF70)

    CERN Document Server

    Burns, T J

    2014-01-01

    General results are obtained for meson mass splittings and mixings in unquenched (coupled-channel) quark models. Theorems derived previously in perturbation theory are generalised to the full coupled-channel system. A new formula is obtained for the mass splittings of physical states in terms of the splittings of the valence states. The S-wave hyperfine splitting decreases due to unquenching, but its relation to the vector $e^+e^-$ width is unchanged; this yields a prediction for the missing $\\eta_b(3S)$. The ordinary (quenched) quark model result that the P-wave hyperfine splitting vanishes also survives unquenching. A ratio of mass splittings used to discriminate quarkonium potential models is scarcely affected by unquenching.

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

    Directory of Open Access Journals (Sweden)

    Phoocharoensil, Supakorn

    2013-01-01

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

  14. A Separated Splitting Technique for Disconnected Rare Event Sets

    OpenAIRE

    Wadman, Wander J.; Crommelin, D.T.; Frank, Jason

    2015-01-01

    A key challenge for an efficient splitting technique is defining the importance function. If the rare event set consists of multiple separated subsets this challenge becomes bigger since the most likely path to the rare event set may be very different from the most likely path to an intermediate level. We propose to mitigate this problem of path deviation by estimating the subset probabilities separately using a modified splitting technique. We compare the proposed separated splitting techniq...

  15. Quantitative analysis on electric dipole energy in Rashba band splitting

    OpenAIRE

    Jisook Hong; Jun-Won Rhim; Changyoung Kim; Seung Ryong Park; Ji Hoon Shim

    2015-01-01

    We report on quantitative comparison between the electric dipole energy and the Rashba band splitting in model systems of Bi and Sb triangular monolayers under a perpendicular electric field. We used both first-principles and tight binding calculations on p-orbitals with spin-orbit coupling. First-principles calculation shows Rashba band splitting in both systems. It also shows asymmetric charge distributions in the Rashba split bands which are induced by the orbital angular momentum. We calc...

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

    OpenAIRE

    Phoocharoensil, Supakorn

    2013-01-01

    The split infinitive in English has been controversial for over a century. Whilst a prescriptive grammar rule forbids infinitive splitting, it seems that modern grammar academics, as well as users, accept and allow for its occurrence. The approval of split-infinitive structure has also been clearly substantiated by plenty of convincing linguistic evidence: real data from native-speaker corpora confirms its existence in different varieties of English. The present study, using the data collecte...

  17. Unequal-Split Strip-Line Power Divider

    Science.gov (United States)

    Bailey, M. C.

    1982-01-01

    Simple technique for designing strip-line or microstrip power dividers can be used for unequal, but inphase power split. Technique allows power splits ranging from equal to as large as required, with advantage of using same line impedances and line spacings for all splits. Output power ratio is determined by selecting location of input port in manner analogous to tap point for electric-power transformer.

  18. Conditional beam splitting attack on quantum key distribution

    CERN Document Server

    Calsamiglia, J; Ltkenhaus, N; Calsamiglia, John; Barnett, Stephen M.

    2002-01-01

    We present a novel attack on quantum key distribution based on the idea of \\emph{adaptive absorption}\\cite{calsam01}. The conditional beam splitting attack is shown to be much more efficient than the conventional beam spitting attack, achieving a performance similar to the, powerful but currently unfeasible, photon number splitting attack. The implementation of the conditional beam splitting attack, based solely on linear optical elements, is well within reach of current technology.

  19. Splitting Magnetoelastic Shifting Waves in Screening Magnetic Field

    Directory of Open Access Journals (Sweden)

    Martirosyan E. V.

    2007-06-01

    Full Text Available We consider a system of elastic perfectly conducting semi – space and straightforward layer which separated by vacuum split. There is external constant magnetic field acting in a plane that perpendicular to the boundary of semi – space. It shown that the interaction between indignant electromagnetic field and fields of elastic displacements of semi – space and split becomes to existence of splitting surface shifting wave.

  20. Vertical lid split approach for optic nerve sheath decompression

    OpenAIRE

    Prabhakaran Venkatesh; Selva Dinesh

    2009-01-01

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