A role of peripheral myelin protein 2 in lipid homeostasis of myelinating Schwann cells

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Zenker, J.; Stettner, M.; Ruskamo, S.; Domenech-Estevez, E.; Baloui, H.; Medard, J.J.; Verheijen, M.H.G.; Brouwers, J.F.; Kursula, P.; Kieseier, B.C.; Chrast, R.

2014-01-01

Peripheral myelin protein 2 (Pmp2, P2 or Fabp8), a member of the fatty acid binding protein family, was originally described together with myelin basic protein (Mbp or P1) and myelin protein zero (Mpz or P0) as one of the most abundant myelin proteins in the peripheral nervous system (PNS). Although

A role of peripheral myelin protein 2 in lipid homeostasis of myelinating Schwann cells.

NARCIS (Netherlands)

Zenker, Jennifer; ruskamo, salla; domenech-estevez, Enric; medard, jean-jacques; Verheijen, M.H.; Brouwers, Jos|info:eu-repo/dai/nl/173812694; Kursula, Petri; kieseier, bernd; Chrast, Roman

Peripheral myelin protein 2 (Pmp2, P2 or Fabp8), a member of the fatty acid binding protein family, was originally described together with myelin basic protein (Mbp or P1) and myelin protein zero (Mpz or P0) as one of the most abundant myelin proteins in the peripheral nervous system (PNS). Although

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

International Nuclear Information System (INIS)

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

1997-01-01

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

Bony fish myelin: evidence for common major structural glycoproteins in central and peripheral myelin of trout.

Science.gov (United States)

Jeserich, G; Waehneldt, T V

1986-02-01

Peripheral nervous system (PNS) myelin from the rainbow trout (Salmo gairdneri) banded at a density of 0.38 M sucrose. The main myelin proteins consisted of (1) two basic proteins, BPa and BPb (11,500 and 13,000 MW, similar to those of trout central nervous system (CNS) myelin proteins BP1 and BP2), and (2) two glycosylated components, IPb (24,400 MW) and IPc (26,200 MW). IPc comigrated with trout CNS myelin protein IP2 in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, whereas trout CNS myelin protein IP1 had a lower molecular weight (23,000). Following two-dimensional separation, however, both IPb and IPc from PNS showed two components; the more acidic component of IPc comigrated with IP2 from CNS. PNS tissue autolysis led to the formation of IPa (20,000 MW), consisting of two components in isoelectric focusing of which again the more acidic one comigrated with the CNS autolysis product IP0. Limited enzymatic digestion of isolated IP proteins from PNS and CNS led to closely similar degradation patterns, being most pronounced in the case of IP2 and IPc. Immunoblotting revealed that all IP components from trout PNS and CNS myelins reacted with antibodies to trout IP1 (CNS) and bovine P0 protein (PNS) whereas antibodies to rat PLP (CNS) were entirely unreactive. All BP components from trout PNS and CNS myelins bound to antibodies against human myelin basic protein. On the basis of these studies trout PNS and CNS myelins contain at least one common IP glycoprotein, whereas other members of the IP myelin protein family appear closely related. In the CNS myelin of trout the IP components appear to replace PLP.(ABSTRACT TRUNCATED AT 250 WORDS)

Schwann cell myelination requires Dynein function

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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.

Cholesterol in myelin biogenesis and hypomyelinating disorders.

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Saher, Gesine; Stumpf, Sina Kristin

2015-08-01

The largest pool of free cholesterol in mammals resides in myelin membranes. Myelin facilitates rapid saltatory impulse propagation by electrical insulation of axons. This function is achieved by ensheathing axons with a tightly compacted stack of membranes. Cholesterol influences myelination at many steps, from the differentiation of myelinating glial cells, over the process of myelin membrane biogenesis, to the functionality of mature myelin. Cholesterol emerged as the only integral myelin component that is essential and rate-limiting for the development of myelin in the central and peripheral nervous system. Moreover, disorders that interfere with sterol synthesis or intracellular trafficking of cholesterol and other lipids cause hypomyelination and neurodegeneration. This review summarizes recent results on the roles of cholesterol in CNS myelin biogenesis in normal development and under different pathological conditions. This article is part of a Special Issue entitled Brain Lipids. Copyright © 2015 Elsevier B.V. All rights reserved.

Networks of myelin covariance

Science.gov (United States)

Slater, David; Ruef, Anne; Sanabria‐Diaz, Gretel; Preisig, Martin; Kherif, Ferath; Draganski, Bogdan; Lutti, Antoine

2017-01-01

Abstract Networks of anatomical covariance have been widely used to study connectivity patterns in both normal and pathological brains based on the concurrent changes of morphometric measures (i.e., cortical thickness) between brain structures across subjects (Evans, 2013). However, the existence of networks of microstructural changes within brain tissue has been largely unexplored so far. In this article, we studied in vivo the concurrent myelination processes among brain anatomical structures that gathered together emerge to form nonrandom networks. We name these “networks of myelin covariance” (Myelin‐Nets). The Myelin‐Nets were built from quantitative Magnetization Transfer data—an in‐vivo magnetic resonance imaging (MRI) marker of myelin content. The synchronicity of the variations in myelin content between anatomical regions was measured by computing the Pearson's correlation coefficient. We were especially interested in elucidating the effect of age on the topological organization of the Myelin‐Nets. We therefore selected two age groups: Young‐Age (20–31 years old) and Old‐Age (60–71 years old) and a pool of participants from 48 to 87 years old for a Myelin‐Nets aging trajectory study. We found that the topological organization of the Myelin‐Nets is strongly shaped by aging processes. The global myelin correlation strength, between homologous regions and locally in different brain lobes, showed a significant dependence on age. Interestingly, we also showed that the aging process modulates the resilience of the Myelin‐Nets to damage of principal network structures. In summary, this work sheds light on the organizational principles driving myelination and myelin degeneration in brain gray matter and how such patterns are modulated by aging. PMID:29271053

Adaptive myelination from fish to man.

Science.gov (United States)

Baraban, Marion; Mensch, Sigrid; Lyons, David A

2016-06-15

Myelinated axons with nodes of Ranvier are an evolutionary elaboration common to essentially all jawed vertebrates. Myelin made by Schwann cells in our peripheral nervous system and oligodendrocytes in our central nervous system has been long known to facilitate rapid energy efficient nerve impulse propagation. However, it is now also clear, particularly in the central nervous system, that myelin is not a simple static insulator but that it is dynamically regulated throughout development and life. New myelin sheaths can be made by newly differentiating oligodendrocytes, and mature myelin sheaths can be stimulated to grow again in the adult. Furthermore, numerous studies in models from fish to man indicate that neuronal activity can affect distinct stages of oligodendrocyte development and the process of myelination itself. This begs questions as to how these effects of activity are mediated at a cellular and molecular level and whether activity-driven adaptive myelination is a feature common to all myelinated axons, or indeed all oligodendrocytes, or is specific to cells or circuits with particular functions. Here we review the recent literature on this topic, elaborate on the key outstanding questions in the field, and look forward to future studies that incorporate investigations in systems from fish to man that will provide further insight into this fundamental aspect of nervous system plasticity. This article is part of a Special Issue entitled SI: Myelin Evolution. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Magnetic resonance imaging and myelin

International Nuclear Information System (INIS)

Adamsbaum, C.; Andre, C.; Rolland, Y.

1995-01-01

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

Cholesterol: a novel regulatory role in myelin formation.

Science.gov (United States)

Saher, Gesine; Quintes, Susanne; Nave, Klaus-Armin

2011-02-01

Myelin consists of tightly compacted membranes that form an insulating sheath around axons. The function of myelin for rapid saltatory nerve conduction is dependent on its unique composition, highly enriched in glycosphingolipids and cholesterol. Cholesterol emerged as the only integral myelin component that is essential and rate limiting for the development of CNS and PNS myelin. Experiments with conditional mouse mutants that lack cholesterol biosynthesis in oligodendrocytes revealed that only minimal changes of the CNS myelin lipid composition are tolerated. In Schwann cells of the PNS, protein trafficking and myelin compaction depend on cholesterol. In this review, the authors summarize the role of cholesterol in myelin biogenesis and myelin disease.

Autophagy is involved in the reduction of myelinating Schwann cell cytoplasm during myelin maturation of the peripheral nerve.

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So Young Jang

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

Astrocytes promote myelination in response to electrical impulses.

Science.gov (United States)

Ishibashi, Tomoko; Dakin, Kelly A; Stevens, Beth; Lee, Philip R; Kozlov, Serguei V; Stewart, Colin L; Fields, R Douglas

2006-03-16

Myelin, the insulating layers of membrane wrapped around axons by oligodendrocytes, is essential for normal impulse conduction. It forms during late stages of fetal development but continues into early adult life. Myelination correlates with cognitive development and can be regulated by impulse activity through unknown molecular mechanisms. Astrocytes do not form myelin, but these nonneuronal cells can promote myelination in ways that are not understood. Here, we identify a link between myelination, astrocytes, and electrical impulse activity in axons that is mediated by the cytokine leukemia inhibitory factor (LIF). These findings show that LIF is released by astrocytes in response to ATP liberated from axons firing action potentials, and LIF promotes myelination by mature oligodendrocytes. This activity-dependent mechanism promoting myelination could regulate myelination according to functional activity or environmental experience and may offer new approaches to treating demyelinating diseases.

A Novel Approach for Studying the Physiology and Pathophysiology of Myelinated and Non-Myelinated Axons in the CNS White Matter.

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Lijun Li

Full Text Available Advances in brain connectomics set the need for detailed knowledge of functional properties of myelinated and non-myelinated (if present axons in specific white matter pathways. The corpus callosum (CC, a major white matter structure interconnecting brain hemispheres, is extensively used for studying CNS axonal function. Unlike another widely used CNS white matter preparation, the optic nerve where all axons are myelinated, the CC contains also a large population of non-myelinated axons, making it particularly useful for studying both types of axons. Electrophysiological studies of optic nerve use suction electrodes on nerve ends to stimulate and record compound action potentials (CAPs that adequately represent its axonal population, whereas CC studies use microelectrodes (MEs, recording from a limited area within the CC. Here we introduce a novel robust isolated "whole" CC preparation comparable to optic nerve. Unlike ME recordings where the CC CAP peaks representing myelinated and non-myelinated axons vary broadly in size, "whole" CC CAPs show stable reproducible ratios of these two main peaks, and also reveal a third peak, suggesting a distinct group of smaller caliber non-myelinated axons. We provide detailed characterization of "whole" CC CAPs and conduction velocities of myelinated and non-myelinated axons along the rostro-caudal axis of CC body and show advantages of this preparation for comparing axonal function in wild type and dysmyelinated shiverer mice, studying the effects of temperature dependence, bath-applied drugs and ischemia modeled by oxygen-glucose deprivation. Due to the isolation from gray matter, our approach allows for studying CC axonal function without possible "contamination" by reverberating signals from gray matter. Our analysis of "whole" CC CAPs revealed higher complexity of myelinated and non-myelinated axonal populations, not noticed earlier. This preparation may have a broad range of applications as a robust

Nonenzymatic glycosylation of bovine myelin basic protein

International Nuclear Information System (INIS)

Hitz, J.B.

1987-01-01

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

Axon-glia interaction and membrane traffic in myelin formation

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Robin eWhite

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.

MRI assessment of myelination: an age standardization

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Staudt, M. (Kinderklinik Dritter Orden, Passau (Germany)); Schropp, C. (Kinderklinik Dritter Orden, Passau (Germany)); Staudt, F. (Kinderklinik Dritter Orden, Passau (Germany)); Obletter, N. (Radiologische Praxis, Klinikum Ingolstadt (Germany)); Bise, K. (Neuropathologisches Inst., Muenchen Univ. (Germany)); Breit, A. (MR Tomographie, Klinikum Passau (Germany)); Weinmann, H.M. (Kinderklinik Schwabing, Muenchen (Germany))

1994-04-01

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.)

Peripheral myelin protein 22 alters membrane architecture

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Mittendorf, Kathleen F.; Marinko, Justin T.; Hampton, Cheri M.; Ke, Zunlong; Hadziselimovic, Arina; Schlebach, Jonathan P.; Law, Cheryl L.; Li, Jun; Wright, Elizabeth R.; Sanders, Charles R.; Ohi, Melanie D.

2017-01-01

Peripheral myelin protein 22 (PMP22) is highly expressed in myelinating Schwann cells of the peripheral nervous system. PMP22 genetic alterations cause the most common forms of Charcot-Marie-Tooth disease (CMTD), which is characterized by severe dysmyelination in the peripheral nerves. However, the functions of PMP22 in Schwann cell membranes remain unclear. We demonstrate that reconstitution of purified PMP22 into lipid vesicles results in the formation of compressed and cylindrically wrapped protein-lipid vesicles that share common organizational traits with compact myelin of peripheral nerves in vivo. The formation of these myelin-like assemblies depends on the lipid-to-PMP22 ratio, as well as on the PMP22 extracellular loops. Formation of the myelin-like assemblies is disrupted by a CMTD-causing mutation. This study provides both a biochemical assay for PMP22 function and evidence that PMP22 directly contributes to membrane organization in compact myelin. PMID:28695207

Localisation of N-acetylaspartate in oligodendrocytes/myelin.

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Nordengen, Kaja; Heuser, Christoph; Rinholm, Johanne Egge; Matalon, Reuben; Gundersen, Vidar

2015-03-01

The role of N-acetylaspartate in the brain is unclear. Here we used specific antibodies against N-acetylaspartate and immunocytochemistry of carbodiimide-fixed adult rodent brain to show that, besides staining of neuronal cell bodies in the grey matter, N-acetylaspartate labelling was present in oligodendrocytes/myelin in white matter tracts. Immunoelectron microscopy of the rat hippocampus showed that N-acetylaspartate was concentrated in the myelin. Also neuronal cell bodies and axons contained significant amounts of N-acetylaspartate, while synaptic elements and astrocytes were low in N-acetylaspartate. Mitochondria in axons and neuronal cell bodies contained higher levels of N-acetylaspartate compared to the cytosol, compatible with synthesis of N-acetylaspartate in mitochondria. In aspartoacylase knockout mice, in which catabolism of N-acetylaspartate is blocked, the levels of N-acetylaspartate were largely increased in oligodendrocytes/myelin. In these mice, the highest myelin concentration of N-acetylaspartate was found in the cerebellum, a region showing overt dysmyelination. In organotypic cortical slice cultures there was no evidence for N-acetylaspartate-induced myelin toxicity, supporting the notion that myelin damage is induced by the lack of N-acetylaspartate for lipid production. Our findings also implicate that N-acetylaspartate signals on magnetic resonance spectroscopy reflect not only vital neurons but also vital oligodendrocytes/myelin.

Myelin-associated proteins labelled by slow axonal transport

International Nuclear Information System (INIS)

Giorgi, P.P.; DuBois, H.

1981-01-01

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

High cholesterol level is essential for myelin membrane growth.

Science.gov (United States)

Saher, Gesine; Brügger, Britta; Lappe-Siefke, Corinna; Möbius, Wiebke; Tozawa, Ryu-ichi; Wehr, Michael C; Wieland, Felix; Ishibashi, Shun; Nave, Klaus-Armin

2005-04-01

Cholesterol in the mammalian brain is a risk factor for certain neurodegenerative diseases, raising the question of its normal function. In the mature brain, the highest cholesterol content is found in myelin. We therefore created mice that lack the ability to synthesize cholesterol in myelin-forming oligodendrocytes. Mutant oligodendrocytes survived, but CNS myelination was severely perturbed, and mutant mice showed ataxia and tremor. CNS myelination continued at a reduced rate for many months, and during this period, the cholesterol-deficient oligodendrocytes actively enriched cholesterol and assembled myelin with >70% of the cholesterol content of wild-type myelin. This shows that cholesterol is an indispensable component of myelin membranes and that cholesterol availability in oligodendrocytes is a rate-limiting factor for brain maturation.

Ephaptic coupling of myelinated nerve fibers

DEFF Research Database (Denmark)

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

2001-01-01

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...

Cross-population myelination covariance of human cerebral cortex.

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Ma, Zhiwei; Zhang, Nanyin

2017-09-01

Cross-population covariance of brain morphometric quantities provides a measure of interareal connectivity, as it is believed to be determined by the coordinated neurodevelopment of connected brain regions. Although useful, structural covariance analysis predominantly employed bulky morphological measures with mixed compartments, whereas studies of the structural covariance of any specific subdivisions such as myelin are rare. Characterizing myelination covariance is of interest, as it will reveal connectivity patterns determined by coordinated development of myeloarchitecture between brain regions. Using myelin content MRI maps from the Human Connectome Project, here we showed that the cortical myelination covariance was highly reproducible, and exhibited a brain organization similar to that previously revealed by other connectivity measures. Additionally, the myelination covariance network shared common topological features of human brain networks such as small-worldness. Furthermore, we found that the correlation between myelination covariance and resting-state functional connectivity (RSFC) was uniform within each resting-state network (RSN), but could considerably vary across RSNs. Interestingly, this myelination covariance-RSFC correlation was appreciably stronger in sensory and motor networks than cognitive and polymodal association networks, possibly due to their different circuitry structures. This study has established a new brain connectivity measure specifically related to axons, and this measure can be valuable to investigating coordinated myeloarchitecture development. Hum Brain Mapp 38:4730-4743, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Abundant extracellular myelin in the meninges of patients with multiple sclerosis.

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Kooi, E-J; van Horssen, J; Witte, M E; Amor, S; Bø, L; Dijkstra, C D; van der Valk, P; Geurts, J J G

2009-06-01

In multiple sclerosis (MS) myelin debris has been observed within MS lesions, in cerebrospinal fluid and cervical lymph nodes, but the route of myelin transport out of the brain is unknown. Drainage of interstitial fluid from the brain parenchyma involves the perivascular spaces and leptomeninges, but the presence of myelin debris in these compartments has not been described. To determine whether myelin products are present in the meninges and perivascular spaces of MS patients. Formalin-fixed brain tissue containing meninges from 29 MS patients, 9 non-neurological controls, 6 Alzheimer's disease, 5 stroke, 5 meningitis and 7 leucodystrophy patients was investigated, and immunohistochemically stained for several myelin proteins [proteolipid protein (PLP), myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase)]. On brain material from MS patients and (non)neurological controls, PLP immunostaining was used to systematically investigate the presence of myelin debris in the meninges, using a semiquantitative scale. Extensive extracellular presence of myelin particles, positive for PLP, MBP, MOG and CNPase in the leptomeninges of MS patients, was observed. Myelin particles were also observed in perivascular spaces of MS patients. Immunohistochemical double-labelling for macrophage and dendritic cell markers and PLP confirmed that the vast majority of myelin particles were located extracellularly. Extracellular myelin particles were virtually absent in meningeal tissue of non-neurological controls, Alzheimer's disease, stroke, meningitis and leucodystrophy cases. In MS leptomeninges and perivascular spaces, abundant extracellular myelin can be found, whereas this is not the case for controls and other neurological disease. This may be relevant for understanding sustained immunogenicity or, alternatively, tolerogenicity in MS.

Confocal mapping of myelin figures with micro-Raman spectroscopy

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Huang, Jung-Ren; Cheng, Yu-Che; Huang, Hung Ji; Chiang, Hai-Pang

2018-01-01

We employ confocal micro-Raman spectroscopy (CMRS) with submicron spatial resolution to study the myelin structures (cylindrical lamellae) composed of nested surfactant C12E3 or lipid DMPC bilayers. The CMRS mapping indicates that for a straight C12E3 myelin, the surfactant concentration increases with the myelin width and is higher in the center region than in the peripheral region. For a curved C12E3 myelin, the convex side has a higher surfactant concentration than the corresponding concave side. The spectrum of DMPC myelins undergoes a qualitative change as the temperature increases above 60 °C, suggesting that the surfactant molecules may be damaged. Our work demonstrates the utility of CMRS in bio-soft material research.

Subtle changes in myelination due to childhood experiences: label-free microscopy to infer nerve fibers morphology and myelination in brain (Conference Presentation)

Science.gov (United States)

Gasecka, Alicja; Tanti, Arnaud; Lutz, Pierre-Eric; Mechawar, Naguib; Cote, Daniel C.

2017-02-01

Adverse childhood experiences have lasting detrimental effects on mental health and are strongly associated with impaired cognition and increased risk of developing psychopathologies. Preclinical and neuroimaging studies have suggested that traumatic events during brain development can affect cerebral myelination particularly in areas and tracts implicated in mood and emotion. Although current neuroimaging techniques are quite powerful, they lack the resolution to infer myelin integrity at the cellular level. Recently demonstrated coherent Raman microscopy has accomplished cellular level imaging of myelin sheaths in the nervous system. However, a quantitative morphometric analysis of nerve fibers still remains a challenge. In particular, in brain, where fibres exhibit small diameters and varying local orientation. In this work, we developed an automated myelin identification and analysis method that is capable of providing a complete picture of axonal myelination and morphology in brain samples. This method performs three main procedures 1) detects molecular anisotropy of membrane phospholipids based on polarization resolved coherent Raman microscopy, 2) identifies regions of different molecular organization, 3) calculates morphometric features of myelinated axons (e.g. myelin thickness, g-ratio). We applied this method to monitor white matter areas from suicides adults that suffered from early live adversity and depression compared to depressed suicides adults and psychiatrically healthy controls. We demonstrate that our method allows for the rapid acquisition and automated analysis of neuronal networks morphology and myelination. This is especially useful for clinical and comparative studies, and may greatly enhance the understanding of processes underlying the neurobiological and psychopathological consequences of child abuse.

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

International Nuclear Information System (INIS)

Viquez, Olga M.; Lai, Barry; Ahn, Jae Hee; Does, Mark D.; Valentine, Holly L.; Valentine, William M.

2009-01-01

Dithiocarbamates are a commercially important class of compounds that can produce peripheral neuropathy in humans and experimental animals. Previous studies have supported a requirement for copper accumulation and enhanced lipid peroxidation in dithiocarbamate-mediated myelinopathy. The study presented here extends previous investigations in two areas. Firstly, although total copper levels have been shown to increase within the nerve it has not been determined whether copper is increased within the myelin compartment, the primary site of lesion development. Therefore, the distribution of copper in sciatic nerve was characterized using synchrotron X-ray fluorescence microscopy to determine whether the neurotoxic dithiocarbamate, N,N-diethyldithiocarbamate, increases copper levels in myelin. Secondly, because lipid peroxidation is an ongoing process in normal nerve and the levels of lipid peroxidation products produced by dithiocarbamate exposure demonstrated an unusual cumulative dose response in previous studies the biological impact of dithiocarbamate-mediated lipid peroxidation was evaluated. Experiments were performed to determine whether dithiocarbamate-mediated lipid peroxidation products elicit an antioxidant response through measuring the protein expression levels of three enzymes, superoxide dismutase 1, heme oxygenase 1, and glutathione transferase α, that are linked to the antioxidant response element promoter. To establish the potential of oxidative injury to contribute to myelin injury the temporal relationship of the antioxidant response to myelin injury was determined. Myelin structure in peripheral nerve was assessed using multi-exponential transverse relaxation measurements (MET 2 ) as a function of exposure duration, and the temporal relationship of protein expression changes relative to the onset of changes in myelin integrity were determined. Initial assessments were also performed to explore the potential contribution of dithiocarbamate

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

NARCIS (Netherlands)

M.E. Sheean (Maria); E. McShane (Erik); C. Cheret (Cyril); J. Walcher (Jan); T. Müller (Thomas); A. Wulf-Goldenberg (Annika); S. Hoelper (Soraya); A.N. Garratt (Alistair); M. Krüger (Markus); K. Rajewsky (Klaus); D.N. Meijer (Dies); W. Birchmeier (Walter); G.R. Lewin (Gary); M. Selbach (Matthias); C. Birchmeier (Carmen)

2014-01-01

textabstractMyelination depends on the synthesis of large amounts of myelin transcripts and proteins and is controlled by Nrg1/ErbB/Shp2 signaling. We developed a novel pulse labeling strategy based on stable isotope labeling with amino acids in cell culture (SILAC) to measure the dynamics of myelin

Formation of compact myelin is required for maturation of the axonal cytoskeleton

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Brady, S. T.; Witt, A. S.; Kirkpatrick, L. L.; de Waegh, S. M.; Readhead, C.; Tu, P. H.; Lee, V. M.

1999-01-01

Although traditional roles ascribed to myelinating glial cells are structural and supportive, the importance of compact myelin for proper functioning of the nervous system can be inferred from mutations in myelin proteins and neuropathologies associated with loss of myelin. Myelinating Schwann cells are known to affect local properties of peripheral axons (de Waegh et al., 1992), but little is known about effects of oligodendrocytes on CNS axons. The shiverer mutant mouse has a deletion in the myelin basic protein gene that eliminates compact myelin in the CNS. In shiverer mice, both local axonal features like phosphorylation of cytoskeletal proteins and neuronal perikaryon functions like cytoskeletal gene expression are altered. This leads to changes in the organization and composition of the axonal cytoskeleton in shiverer unmyelinated axons relative to age-matched wild-type myelinated fibers, although connectivity and patterns of neuronal activity are comparable. Remarkably, transgenic shiverer mice with thin myelin sheaths display an intermediate phenotype indicating that CNS neurons are sensitive to myelin sheath thickness. These results indicate that formation of a normal compact myelin sheath is required for normal maturation of the neuronal cytoskeleton in large CNS neurons.

Remarkable Stability of Myelinating Oligodendrocytes in Mice

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Richa B. Tripathi

2017-10-01

Full Text Available New myelin-forming oligodendrocytes (OLs are generated in the mouse central nervous system during adulthood. These adult-born OLs might augment the existing population, contributing to neural plasticity, or else replace OLs that die in use (turnover. To distinguish between these alternatives, we induced genetic labeling of mature myelinating OLs in young adult mice and tracked their subsequent survival. OL survival rates were region dependent, being higher in corpus callosum (∼90% survival over 20 months and motor cortex (∼70% survival than in corticospinal tract or optic nerve (50%–60% survival. Survival rates over the first 8 months were 90%–100% in all regions except the optic nerve. In the corpus callosum, new OLs accumulate during young adulthood and are therefore likely to participate in adaptive myelination. We also found that the number of myelin internodes maintained by individual cortical OLs is stable for at least 8 months but declines ∼12% in the following year.

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

DEFF Research Database (Denmark)

Drøjdahl, Nina; Nielsen, Helle Hvilsted; Gardi, Jonathan E

2010-01-01

Axons are linked to induction of myelination during development and to the maintenance of myelin and myelinated tracts in the adult CNS. Currently, it is unknown whether and how axonal plasticity in adult CNS impacts the myelinating cells and their precursors. In this article, we report that newly...... formed axonal sprouts are able to induce a protracted myelination response in adult CNS. We show that newly formed axonal sprouts, induced by lesion of the entorhino-hippocampal perforant pathway, have the ability to induce a myelination response in stratum radiatum and lucidum CA3. The lesion resulted...... in significant recruitment of newly formed myelinating cells, documented by incorporation of the proliferation marker bromodeoxyuridine into chondroitin sulphate NG2 expressing cells in stratum radiatum and lucidum CA3 early after lesion, and the occurrence of a 28% increase in the number of oligodendrocytes...

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

International Nuclear Information System (INIS)

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

2011-01-01

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

Promoting peripheral myelin repair.

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Zhou, Ye; Notterpek, Lucia

2016-09-01

Compared to the central nervous system (CNS), peripheral nerves have a remarkable ability to regenerate and remyelinate. This regenerative capacity to a large extent is dependent on and supported by Schwann cells, the myelin-forming glial cells of the peripheral nervous system (PNS). In a variety of paradigms, Schwann cells are critical in the removal of the degenerated tissue, which is followed by remyelination of newly-regenerated axons. This unique plasticity of Schwann cells has been the target of myelin repair strategies in acute injuries and chronic diseases, such as hereditary demyelinating neuropathies. In one approach, the endogenous regenerative capacity of Schwann cells is enhanced through interventions such as exercise, electrical stimulation or pharmacological means. Alternatively, Schwann cells derived from healthy nerves, or engineered from different tissue sources have been transplanted into the PNS to support remyelination. These transplant approaches can then be further enhanced by exercise and/or electrical stimulation, as well as by the inclusion of biomaterial engineered to support glial cell viability and neurite extension. Advances in our basic understanding of peripheral nerve biology, as well as biomaterial engineering, will further improve the functional repair of myelinated peripheral nerves. Copyright © 2016 Elsevier Inc. All rights reserved.

Myelin injury in the central nervous system and Alzheimer's diseases.

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Wang, Sha-Sha; Zhang, Zhao; Zhu, Tian-Bi; Chu, Shi-Feng; He, Wen-Bin; Chen, Nai-Hong

2018-05-03

Myelin is a membrane wrapped around the axon of the nerve cell, which is composed of the mature oligodendrocytes. The role of myelin is to insulate and prevent the nerve electrical impulses from the axon of the neurons to the axons of the other neurons, which is essential for the proper functioning of the nervous system. Minor changes in myelin thickness could lead to substantial changes in conduction speed and may thus alter neural circuit function. Demyelination is the myelin damage, which characterized by the loss of nerve sheath and the relative fatigue of the neuronal sheath and axon. Studies have shown that myelin injury may be closely related to neurodegenerative diseases and may be an early diagnostic criteria and therapeutic target. Thus this review summarizes the recent result of pathologic effect and signal pathways of myelin injury in neurodegenerative diseases, especially the Alzheimer's disease to provide new and effective therapeutic targets. Copyright © 2018. Published by Elsevier Inc.

Vesicular glutamate release from central axons contributes to myelin damage.

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Doyle, Sean; Hansen, Daniel Bloch; Vella, Jasmine; Bond, Peter; Harper, Glenn; Zammit, Christian; Valentino, Mario; Fern, Robert

2018-03-12

The axon myelin sheath is prone to injury associated with N-methyl-D-aspartate (NMDA)-type glutamate receptor activation but the source of glutamate in this context is unknown. Myelin damage results in permanent action potential loss and severe functional deficit in the white matter of the CNS, for example in ischemic stroke. Here, we show that in rats and mice, ischemic conditions trigger activation of myelinic NMDA receptors incorporating GluN2C/D subunits following release of axonal vesicular glutamate into the peri-axonal space under the myelin sheath. Glial sources of glutamate such as reverse transport did not contribute significantly to this phenomenon. We demonstrate selective myelin uptake and retention of a GluN2C/D NMDA receptor negative allosteric modulator that shields myelin from ischemic injury. The findings potentially support a rational approach toward a low-impact prophylactic therapy to protect patients at risk of stroke and other forms of excitotoxic injury.

Neuronal Regulation of Schwann Cell Mitochondrial Ca(2+) Signaling during Myelination.

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Ino, Daisuke; Sagara, Hiroshi; Suzuki, Junji; Kanemaru, Kazunori; Okubo, Yohei; Iino, Masamitsu

2015-09-29

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 Ca(2+) increases in the cytosol and the mitochondrial matrix of surrounding SCs via purinergic receptor activation. Chronic suppression of this pathway during active myelination suppressed the longitudinal and radial development of myelinating SCs and caused hypomyelination. These results demonstrate a neuron-to-SC mitochondria signaling, which is likely to have an important role in proper myelination. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Neuronal Regulation of Schwann Cell Mitochondrial Ca2+ Signaling during Myelination

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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 the longitudinal and radial development of myelinating SCs and caused hypomyelination. These results demonstrate a neuron-to-SC mitochondria signaling, which is likely to have an important role in proper myelination.

The structural and functional role of myelin fast-migrating cerebrosides

DEFF Research Database (Denmark)

Podbielska, Maria; Levery, Steven B; Hogan, Edward L

2011-01-01

A family of neutral glycosphingolipids containing a 3-O-acetyl-sphingosine galactosylceramide (3-SAG) has been characterized. Seven new derivatives of galactosylceramide (GalCer), designated as fast-migrating cerebrosides (FMCs) by TLC retention factor, have been identified. The simplest compounds...... myelin lipid biomarkers coappear with GalCer during myelinogenesis and disappear along with GalCer in de- or dys-myelinating disorders. Myelin lipid antigens, including FMCs, are keys to myelin biology, opening the possibility of new and novel immune modulatory tools for treatment of autoimmune diseases...

Evaluation of dermal myelinated nerve fibers in diabetes mellitus

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

2013-01-01

Skin biopsies have primarily been used to study the non-myelinated nerve fibers of the epidermis in a variety of neuropathies. In the present study, we have expanded the skin biopsy technique to glabrous, non-hairy skin to evaluate myelinated nerve fibers in the most highly prevalent peripheral nerve disease, diabetic polyneuropathy (DPN). Twenty patients with DPN (Type I, n=9; Type II, n=11) and sixteen age-matched healthy controls (ages 29–73) underwent skin biopsy of the index finger, nerve conduction studies, and composite neuropathy scoring. In patients with DPN, we found a statistically significant reduction of both mechanoreceptive Meissner corpuscles (MC) and their afferent myelinated nerve fibers (p=0.01). This myelinated nerve fiber loss was correlated with the decreased amplitudes of sensory/motor responses in nerve conduction studies. This study supports the utilization of skin biopsy to quantitatively evaluate axonal loss of myelinated nerve fibers in patients with DPN. PMID:23781963

DC-Evoked Modulation of Excitability of Myelinated Nerve Fibers and Their Terminal Branches; Differences in Sustained Effects of DC.

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Kaczmarek, Dominik; Jankowska, Elzbieta

2018-03-15

Direct current (DC) evokes long-lasting changes in neuronal networks both presynaptically and postsynaptically and different mechanisms were proposed to be involved in them. Different mechanisms were also suggested to account for the different dynamics of presynaptic DC actions on myelinated nerve fibers stimulated before they entered the spinal gray matter and on their terminal branches. The aim of the present study was to examine whether these different dynamics might be related to differences in the involvement of K + channels. To this end, we compared effects of the K + channel blocker 4-amino-pyridine (4-AP) on DC-evoked changes in the excitability of afferent fibers stimulated within the dorsal columns (epidurally) and within their projection areas in the dorsal horn and motor nuclei (intraspinally). 4-AP was applied systemically in deeply anesthetized rats. DC-evoked increases in the excitability of epidurally stimulated afferent nerve fibers, and increases in field potentials evoked by these fibers, were not affected by 4-AP. In contrast, sustained decreases rather than increases in the excitability of intraspinally stimulated terminal nerve branches were evoked by local application of DC in conjunction with 4-AP. The study leads to the conclusion that 4-AP-sensitive K + channels contribute to the sustained DC-evoked post-polarization increases in the excitability at the level of terminal branches of nerve fibers but not of the nodes of Ranvier nor within the juxta-paranodal regions where other mechanisms would be involved in inducing the sustained DC-evoked changes. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Staining Methods for Normal and Regenerative Myelin in the Nervous System.

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Carriel, Víctor; Campos, Antonio; Alaminos, Miguel; Raimondo, Stefania; Geuna, Stefano

2017-01-01

Histochemical techniques enable the specific identification of myelin by light microscopy. Here we describe three histochemical methods for the staining of myelin suitable for formalin-fixed and paraffin-embedded materials. The first method is conventional luxol fast blue (LFB) method which stains myelin in blue and Nissl bodies and mast cells in purple. The second method is a LBF-based method called MCOLL, which specifically stains the myelin as well the collagen fibers and cells, giving an integrated overview of the histology and myelin content of the tissue. Finally, we describe the osmium tetroxide method, which consist in the osmication of previously fixed tissues. Osmication is performed prior the embedding of tissues in paraffin giving a permanent positive reaction for myelin as well as other lipids present in the tissue.

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

International Nuclear Information System (INIS)

Schulz, P.; Moscarello, M.A.; Cruz, T.F.

1988-01-01

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 [ 32 P]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

Combining Quantitative Susceptibility Mapping with Automatic Zero Reference (QSM0) and Myelin Water Fraction Imaging to Quantify Iron-Related Myelin Damage in Chronic Active MS Lesions.

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Yao, Y; Nguyen, T D; Pandya, S; Zhang, Y; Hurtado Rúa, S; Kovanlikaya, I; Kuceyeski, A; Liu, Z; Wang, Y; Gauthier, S A

2018-02-01

A hyperintense rim on susceptibility in chronic MS lesions is consistent with iron deposition, and the purpose of this study was to quantify iron-related myelin damage within these lesions as compared with those without rim. Forty-six patients had 2 longitudinal quantitative susceptibility mapping with automatic zero reference scans with a mean interval of 28.9 ± 11.4 months. Myelin water fraction mapping by using fast acquisition with spiral trajectory and T2 prep was obtained at the second time point to measure myelin damage. Mixed-effects models were used to assess lesion quantitative susceptibility mapping and myelin water fraction values. Quantitative susceptibility mapping scans were on average 6.8 parts per billion higher in 116 rim-positive lesions compared with 441 rim-negative lesions ( P quantitative susceptibility mapping values of both the rim and core regions ( P Quantitative susceptibility mapping scans and myelin water fraction in rim-positive lesions decreased from rim to core, which is consistent with rim iron deposition. Whole lesion myelin water fractions for rim-positive and rim-negative lesions were 0.055 ± 0.07 and 0.066 ± 0.04, respectively. In the mixed-effects model, rim-positive lesions had on average 0.01 lower myelin water fraction compared with rim-negative lesions ( P quantitative susceptibility mapping scan was negatively associated with follow-up myelin water fraction ( P Quantitative susceptibility mapping rim-positive lesions maintained a hyperintense rim, increased in susceptibility, and had more myelin damage compared with rim-negative lesions. Our results are consistent with the identification of chronic active MS lesions and may provide a target for therapeutic interventions to reduce myelin damage. © 2018 by American Journal of Neuroradiology.

Nanoscale Correlated Disorder in Out-of-Equilibrium Myelin Ultrastructure.

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Campi, Gaetano; Di Gioacchino, Michael; Poccia, Nicola; Ricci, Alessandro; Burghammer, Manfred; Ciasca, Gabriele; Bianconi, Antonio

2018-01-23

Ultrastructural fluctuations at nanoscale are fundamental to assess properties and functionalities of advanced out-of-equilibrium materials. We have taken myelin as a model of supramolecular assembly in out-of-equilibrium living matter. Myelin sheath is a simple stable multilamellar structure of high relevance and impact in biomedicine. Although it is known that myelin has a quasi-crystalline ultrastructure, there is no information on its fluctuations at nanoscale in different states due to limitations of the available standard techniques. To overcome these limitations, we have used scanning micro X-ray diffraction, which is a unique non-invasive probe of both reciprocal and real space to visualize statistical fluctuations of myelin order of the sciatic nerve of Xenopus laevis. The results show that the ultrastructure period of the myelin is stabilized by large anticorrelated fluctuations at nanoscale, between hydrophobic and hydrophilic layers. The ratio between the total thickness of hydrophilic and hydrophobic layers defines the conformational parameter, which describes the different states of myelin. Our key result is that myelin in its out-of-equilibrium functional state fluctuates point-to-point between different conformations showing a correlated disorder described by a Levy distribution. As the system approaches the thermodynamic equilibrium in an aged state, the disorder loses its correlation degree and the structural fluctuation distribution changes to Gaussian. In a denatured state at low pH, it changes to a completely disordered stage. Our results aim to clarify the degradation mechanism in biological systems by associating these states with ultrastructural dynamic fluctuations at nanoscale.

Dynamics of myelin content decrease in the rat stroke model

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Kisel, A.; Khodanovich, M.; Atochin, D.; Mustafina, L.; Yarnykh, V.

2017-08-01

The majority of studies were usually focused on neuronal death after brain ischemia; however, stroke affects all cell types including oligodendrocytes that form myelin sheath in the CNS. Our study is focused on the changes of myelin content in the ischemic core and neighbor structures in early terms (1, 3 and 10 days) after stroke. Stroke was modeled with middle cerebral artery occlusion (MCAo) in 15 male rats that were divided into three groups by time points after operation. Brain sections were histologically stained with Luxol Fast Blue (LFB) for myelin quantification. The significant demyelination was found in the ischemic core, corpus callosum, anterior commissure, whereas myelin content was increased in caudoputamen, internal capsule and piriform cortex compared with the contralateral hemisphere. The motor cortex showed a significant increase of myelin content on the 1st day and a significant decrease on the 3rd and 10th days after MCAo. These results suggest that stroke influences myelination not only in the ischemic core but also in distant structures.

Neuronal Regulation of Schwann Cell Mitochondrial Ca2+ Signaling during Myelination

OpenAIRE

Daisuke Ino; Hiroshi Sagara; Junji Suzuki; Kazunori Kanemaru; Yohei Okubo; Masamitsu Iino

2015-01-01

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 stimulati...

Regulation of Central Nervous System Myelination in Higher Brain Functions

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Mara Nickel

2018-01-01

Full Text Available The hippocampus and the prefrontal cortex are interconnected brain regions, playing central roles in higher brain functions, including learning and memory, planning complex cognitive behavior, and moderating social behavior. The axons in these regions continue to be myelinated into adulthood in humans, which coincides with maturation of personality and decision-making. Myelin consists of dense layers of lipid membranes wrapping around the axons to provide electrical insulation and trophic support and can profoundly affect neural circuit computation. Recent studies have revealed that long-lasting changes of myelination can be induced in these brain regions by experience, such as social isolation, stress, and alcohol abuse, as well as by neurological and psychiatric abnormalities. However, the mechanism and function of these changes remain poorly understood. Myelin regulation represents a new form of neural plasticity. Some progress has been made to provide new mechanistic insights into activity-independent and activity-dependent regulations of myelination in different experimental systems. More extensive investigations are needed in this important but underexplored research field, in order to shed light on how higher brain functions and myelination interplay in the hippocampus and prefrontal cortex.

Enhanced uptake of multiple sclerosis-derived myelin by THP-1 macrophages and primary human microglia.

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Hendrickx, Debbie A E; Schuurman, Karianne G; van Draanen, Michael; Hamann, Jörg; Huitinga, Inge

2014-03-31

The pathological hallmark of multiple sclerosis (MS) is myelin phagocytosis. It remains unclear why microglia and macrophages demyelinate axons in MS, but previously found or yet-unknown changes in the myelin of MS patients could contribute to this process. We therefore studied whether myelin from normal-appearing white matter (NAWM) of MS donors is phagocytosed more efficiently than myelin from control donors. Myelin was isolated from 11 MS and 12 control brain donors and labeled with the pH-sensitive fluorescent dye pHrodo to quantify uptake in lysosomes. Phagocytosis by differentiated THP-1 macrophages and by primary human microglia was quantified with flow cytometry. Whereas myelin uptake by THP-1 macrophages reached a plateau after approximately 24 hours, uptake by primary human microglia showed an almost linear increase over a 72-hour period. Data were statistically analyzed with the Mann-Whitney U test. MS-derived myelin was phagocytosed more efficiently by THP-1 macrophages after 6-hour incubation (P = 0.001 for the percentage of myelin-phagocytosing cells and P = 0.0005 for total myelin uptake) and after 24-hour incubation (P = 0.0006 and P = 0.0001, respectively), and by microglia after 24-hour incubation (P = 0.0106 for total myelin uptake). This enhanced uptake was not due to differences in the oxidation status of the myelin. Interestingly, myelin phagocytosis correlated negatively with the age of myelin donors, whereas the age of microglia donors showed a positive trend with myelin phagocytosis. Myelin isolated from normal-appearing white matter of MS donors was phagocytosed more efficiently than was myelin isolated from control brain donors by both THP-1 macrophages and primary human microglia. These data indicate that changes in MS myelin might precede phagocyte activation and subsequent demyelination in MS. Identifying these myelin changes responsible for enhancing phagocytic ability could be an interesting therapeutic target to

Rapid myelin water content mapping on clinical MR systems

International Nuclear Information System (INIS)

Tonkova, Vyara; Arhelger, Volker; Schenk, Jochen; Neeb, Heiko; Koblenz Univ.

2012-01-01

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

Rac1 controls Schwann cell myelination through cAMP and NF2/merlin

Science.gov (United States)

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

2013-01-01

During peripheral nervous system development, Schwann cells (SCs) surrounding single large axons differentiate into myelinating SCs. Previous studies implicate RhoGTPases in SC myelination, but the mechanisms involved in RhoGTPase regulation of SC myelination are unknown. Here, we show that SC myelination is arrested in Rac1 conditional knockout (Rac1-CKO) mice. Rac1 knockout abrogated phosphorylation of the effector p21-activated kinase (PAK) and decreased NF2/merlin phosphorylation. Mutation of NF2/merlin rescued the myelin deficit in Rac1-CKO mice in vivo, and the shortened processes in cultured Rac1-CKO SCs in vitro. Mechanistically, cyclic adenosine monophosphate (cAMP) levels and E-cadherin expression were decreased in the absence of Rac1, and both were restored by mutation of NF2/merlin. Reduced cAMP is a cause of the myelin deficiency in Rac1-CKO mice, as elevation of cAMP by rolipram in Rac1-CKO mice in vivo allowed myelin formation. Thus NF2/merlin and cAMP function downstream of Rac1 signaling in SC myelination, and cAMP levels control Rac1-regulated SC myelination. PMID:23197717

Axo-Glia Interaction Preceding CNS Myelination Is Regulated by Bidirectional Eph-Ephrin Signaling

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Cecilie Linneberg

2015-09-01

Full Text Available In the central nervous system, myelination of axons is required to ensure fast saltatory conduction and for survival of neurons. However, not all axons are myelinated, and the molecular mechanisms involved in guiding the oligodendrocyte processes toward the axons to be myelinated are not well understood. Only a few negative or positive guidance clues that are involved in regulating axo-glia interaction prior to myelination have been identified. One example is laminin, known to be required for early axo-glia interaction, which functions through α6β1 integrin. Here, we identify the Eph-ephrin family of guidance receptors as novel regulators of the initial axo-glia interaction, preceding myelination. We demonstrate that so-called forward and reverse signaling, mediated by members of both Eph and ephrin subfamilies, has distinct and opposing effects on processes extension and myelin sheet formation. EphA forward signaling inhibits oligodendrocyte process extension and myelin sheet formation, and blocking of bidirectional signaling through this receptor enhances myelination. Similarly, EphB forward signaling also reduces myelin membrane formation, but in contrast to EphA forward signaling, this occurs in an integrin-dependent manner, which can be reversed by overexpression of a constitutive active β1-integrin. Furthermore, ephrin-B reverse signaling induced by EphA4 or EphB1 enhances myelin sheet formation. Combined, this suggests that the Eph-ephrin receptors are important mediators of bidirectional signaling between axons and oligodendrocytes. It further implies that balancing Eph-ephrin forward and reverse signaling is important in the selection process of axons to be myelinated.

Schwann Cell Glycogen Selectively Supports Myelinated Axon Function

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Brown, Angus M; Evans, Richard D; Black, Joel; Ransom, Bruce R

2012-01-01

Objectives Interruption of energy supply to peripheral axons is a cause of axon loss. We determined if glycogen was present in mammalian peripheral nerve, and if it supported axon conduction during aglycemia. Methods We used biochemical assay and electron microscopy to determine the presence of glycogen, and electrophysiology to monitor axon function. Results Glycogen was present in sciatic nerve, its concentration varying directly with ambient [glucose]. Electron microscopy detected glycogen granules primarily in myelinating Schwann cell cytoplasm and these diminished after exposure to aglycemia. During aglycemia, conduction failure in large myelinated axons (A fibers) mirrored the time-course of glycogen loss. Latency to CAP failure was directly related to nerve glycogen content at aglycemia onset. Glycogen did not benefit the function of slow-conducting, small diameter unmyelinated axons (C fibers) during aglycemia. Blocking glycogen breakdown pharmacologically accelerated CAP failure during aglycemia in A fibers, but not in C fibers. Lactate was as effective as glucose in supporting sciatic nerve function, and was continuously released into the extracellular space in the presence of glucose and fell rapidly during aglycemia. Interpretation Our findings indicated that glycogen is present in peripheral nerve, primarily in myelinating Schwann cells, and exclusively supports large diameter, myelinated axon conduction during aglycemia. Available evidence suggests that peripheral nerve glycogen breaks down during aglycemia and is passed, probably as lactate, to myelinated axons to support function. Unmyelinated axons are not protected by glycogen and are more vulnerable to dysfunction during periods of hypoglycemia. PMID:23034913

Rapid myelin water content mapping on clinical MR systems

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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.)

Lipid metabolism in myelinating glial cells: lessons from human inherited disorders and mouse models.

Science.gov (United States)

Chrast, Roman; Saher, Gesine; Nave, Klaus-Armin; Verheijen, Mark H G

2011-03-01

The integrity of central and peripheral nervous system myelin is affected in numerous lipid metabolism disorders. This vulnerability was so far mostly attributed to the extraordinarily high level of lipid synthesis that is required for the formation of myelin, and to the relative autonomy in lipid synthesis of myelinating glial cells because of blood barriers shielding the nervous system from circulating lipids. Recent insights from analysis of inherited lipid disorders, especially those with prevailing lipid depletion and from mouse models with glia-specific disruption of lipid metabolism, shed new light on this issue. The particular lipid composition of myelin, the transport of lipid-associated myelin proteins, and the necessity for timely assembly of the myelin sheath all contribute to the observed vulnerability of myelin to perturbed lipid metabolism. Furthermore, the uptake of external lipids may also play a role in the formation of myelin membranes. In addition to an improved understanding of basic myelin biology, these data provide a foundation for future therapeutic interventions aiming at preserving glial cell integrity in metabolic disorders.

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

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Philip R Lee

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.

Cthrc1 is a negative regulator of myelination in Schwann cells.

Science.gov (United States)

Apra, Caroline; Richard, Laurence; Coulpier, Fanny; Blugeon, Corinne; Gilardi-Hebenstreit, Pascale; Vallat, Jean-michel; Lindner, Volkhard; Charnay, Patrick; Decker, Laurence

2012-03-01

The analysis of the molecular mechanisms involved in the initial interaction between neurons and Schwann cells is a key issue in understanding the myelination process. We recently identified Cthrc1 (Collagen triple helix repeat containing 1) as a gene upregulated in Schwann cells upon interaction with the axon. Cthrc1 encodes a secreted protein previously shown to be involved in migration and proliferation in different cell types. We performed a functional analysis of Cthrc1 in Schwann cells by loss-of- and gain-of-function approaches using RNA interference knockdown in cell culture and a transgenic mouse line that overexpresses the gene. This work establishes that Cthrc1 enhances Schwann cell proliferation but prevents myelination. In particular, time-course analysis of myelin formation intransgenic animals reveals that overexpression of Cthrc1 in Schwann cells leads to a delay in myelin formation with cells maintaining a proliferative state. Our data, therefore, demonstrate that Cthrc1 plays a negative regulatory role, fine-tuning the onset of peripheral myelination.

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

International Nuclear Information System (INIS)

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

2004-01-01

The objective of this study was to measure myelination of frontal lobe changes in infants and young children. Twenty-four cases of infants and children (age range 12-121 months) were evaluated by a quantitative assessment of T2-weighted MR image features. Reliable quantitative changes between white and gray matter correlated with developmental age in a group of children with no neurological findings. Myelination appears to be an increasing exponential function with the greatest rate of 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.)

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

Energy Technology Data Exchange (ETDEWEB)

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

2004-09-01

The objective of this study was to measure myelination of frontal lobe changes in infants and young children. Twenty-four cases of infants and children (age range 12-121 months) were evaluated by a quantitative assessment of T2-weighted MR image features. Reliable quantitative changes between white and gray matter correlated with developmental age in a group of children with no neurological findings. Myelination appears to be an increasing exponential function with the greatest rate of change occurring over the first 3 years of life. The quantitative changes observed were in accordance with previous qualitative judgments of myelination development. Children with periventricular leukomalacia (PVL) showed delays in achieving levels of myelination when compared to normal children and adjusted for chronological age. The quantitative measure of myelination development may prove to be useful in assessing the stages of development and helpful in the quantitative descriptions of white matter disorders such as PVL. (orig.)

Live-imaging in the CNS: New insights on oligodendrocytes, myelination, and their responses to inflammation.

Science.gov (United States)

Rassul, Sayed Muhammed; Neely, Robert K; Fulton, Daniel

2016-11-01

The formation and repair of myelin involves alterations in the molecular and physical properties of oligodendrocytes, and highly coordinated interactions with their target axons. Characterising the nature and timing of these events at the molecular and cellular levels illuminates the fundamental events underlying myelin formation, and provides opportunities for the development of therapies to replace myelin lost through traumatic injury and inflammation. The dynamic nature of these events requires that live-imaging methods be used to capture this information accurately and completely. Developments in imaging technologies, and model systems suitable for their application to myelination, have advanced the study of myelin formation, injury and repair. Similarly, new techniques for single molecule imaging, and novel imaging probes, are providing opportunities to resolve the dynamics of myelin proteins during myelination. Here, we explore these developments in the context of myelin formation and injury, identify unmet needs within the field where progress can be advanced through live-imaging approaches, identify technical challenges that are limiting this progress, and highlight practical applications for these approaches that could lead to therapies for the protection of oligodendrocytes and myelin from injury, and restore myelin lost through injury and disease. This article is part of the Special Issue entitled 'Oligodendrocytes in Health and Disease'. Copyright © 2015 Elsevier Ltd. All rights reserved.

Schwann cell autophagy, myelinophagy, initiates myelin clearance from injured nerves

NARCIS (Netherlands)

Gomez-Sanchez, Jose A.; Carty, Lucy; Iruarrizaga-Lejarreta, Marta; Palomo-Irigoyen, Marta; Varela-Rey, Marta; Griffith, Megan; Hantke, Janina; Macias-Camara, Nuria; Azkargorta, Mikel; Aurrekoetxea, Igor; de Juan, Virginia Gutiérrez; Jefferies, Harold B. J.; Aspichueta, Patricia; Elortza, Félix; Aransay, Ana M.; Martínez-Chantar, María L.; Baas, Frank; Mato, José M.; Mirsky, Rhona; Woodhoo, Ashwin; Jessen, Kristján R.

2015-01-01

Although Schwann cell myelin breakdown is the universal outcome of a remarkably wide range of conditions that cause disease or injury to peripheral nerves, the cellular and molecular mechanisms that make Schwann cell-mediated myelin digestion possible have not been established. We report that

Engineering Biomaterials to Influence Oligodendroglial Growth, Maturation, and Myelin Production.

Science.gov (United States)

Russell, Lauren N; Lampe, Kyle J

2016-01-01

Millions of people suffer from damage or disease to the nervous system that results in a loss of myelin, such as through a spinal cord injury or multiple sclerosis. Diminished myelin levels lead to further cell death in which unmyelinated neurons die. In the central nervous system, a loss of myelin is especially detrimental because of its poor ability to regenerate. Cell therapies such as stem or precursor cell injection have been investigated as stem cells are able to grow and differentiate into the damaged cells; however, stem cell injection alone has been unsuccessful in many areas of neural regeneration. Therefore, researchers have begun exploring combined therapies with biomaterials that promote cell growth and differentiation while localizing cells in the injured area. The regrowth of myelinating oligodendrocytes from neural stem cells through a biomaterials approach may prove to be a beneficial strategy following the onset of demyelination. This article reviews recent advancements in biomaterial strategies for the differentiation of neural stem cells into oligodendrocytes, and presents new data indicating appropriate properties for oligodendrocyte precursor cell growth. In some cases, an increase in oligodendrocyte differentiation alongside neurons is further highlighted for functional improvements where the biomaterial was then tested for increased myelination both in vitro and in vivo. © 2016 S. Karger AG, Basel.

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

Variation in myelin lipid composition induced by change in environmental temperature of goldfish (Carassius auratus L. )

Energy Technology Data Exchange (ETDEWEB)

Selivonchick, D.P.; Roots, B.I.

1976-04-01

Goldfish (Carassius auratus L.) were acclimated to 5, 15, and 30/sup 0/C, and the lipid and protein composition of brain and spinal cord myelin was determined. Goldfish myelin contains less galactolipid, but more protein and phospholipid than mammalian and bird myelin. Phosphatidyl choline was the predominant phospholipid in both brain and spinal cord myelin. Fish myelin also showed a greater plasmalogen content with an average ethanolamine plasmalogen/total phosphatidyl ethanolamine ratio of 0.84. Total brain and myelin lipids, with the exception of plasmalogens, showed a resistance to change with thermal acclimation. Differences between brain and spinal cord myelin protein and phospholipids were not observed. It is suggested that temperature acclimation in poikilotherms may be used as a tool in the study of membrane adaptability.

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

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 from...

Is There Evidence for Myelin Modeling by Astrocytes in the Normal Adult Brain?

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Alfredo Varela-Echevarría

2017-09-01

Full Text Available A set of astrocytic process associated with altered myelinated axons is described in the forebrain of normal adult rodents with confocal, electron microscopy, and 3D reconstructions. Each process consists of a protuberance that contains secretory organelles including numerous lysosomes which polarize and open next to disrupted myelinated axons. Because of the distinctive asymmetric organelle distribution and ubiquity throughout the forebrain neuropil, this enlargement is named paraxial process (PAP. The myelin envelope contiguous to the PAP displays focal disruption or disintegration. In routine electron microscopy clusters of large, confluent, lysosomes proved to be an effective landmark for PAP identification. In 3D assemblies lysosomes organize a series of interconnected saccules that open up to the plasmalemma next to the disrupted myelin envelope(s. Activity for acid hydrolases was visualized in lysosomes, and extracellularly at the PAP-myelin interface and/or between the glial and neuronal outer aspects. Organelles in astrocytic processes involved in digesting pyknotic cells and debris resemble those encountered in PAPs supporting a likewise lytic function of the later. Conversely, processes entangling tripartite synapses and glomeruli were devoid of lysosomes. Both oligodendrocytic and microglial processes were not associated with altered myelin envelopes. The possible roles of the PAP in myelin remodeling in the context of the oligodendrocyte-astrocyte interactions and in the astrocyte's secretory pathways are discussed.

Kif13b Regulates PNS and CNS Myelination through the Dlg1 Scaffold.

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Roberta Noseda

2016-04-01

Full Text Available Microtubule-based kinesin motors have many cellular functions, including the transport of a variety of cargos. However, unconventional roles have recently emerged, and kinesins have also been reported to act as scaffolding proteins and signaling molecules. In this work, we further extend the notion of unconventional functions for kinesin motor proteins, and we propose that Kif13b kinesin acts as a signaling molecule regulating peripheral nervous system (PNS and central nervous system (CNS myelination. In this process, positive and negative signals must be tightly coordinated in time and space to orchestrate myelin biogenesis. Here, we report that in Schwann cells Kif13b positively regulates myelination by promoting p38γ mitogen-activated protein kinase (MAPK-mediated phosphorylation and ubiquitination of Discs large 1 (Dlg1, a known brake on myelination, which downregulates the phosphatidylinositol 3-kinase (PI3K/v-AKT murine thymoma viral oncogene homolog (AKT pathway. Interestingly, Kif13b also negatively regulates Dlg1 stability in oligodendrocytes, in which Dlg1, in contrast to Schwann cells, enhances AKT activation and promotes myelination. Thus, our data indicate that Kif13b is a negative regulator of CNS myelination. In summary, we propose a novel function for the Kif13b kinesin in glial cells as a key component of the PI3K/AKT signaling pathway, which controls myelination in both PNS and CNS.

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

Science.gov (United States)

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

2011-02-06

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

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

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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.

Neuroimaging evidence of deficient axon myelination in Wolfram syndrome.

Science.gov (United States)

Lugar, Heather M; Koller, Jonathan M; Rutlin, Jerrel; Marshall, Bess A; Kanekura, Kohsuke; Urano, Fumihiko; Bischoff, Allison N; Shimony, Joshua S; Hershey, Tamara

2016-02-18

Wolfram syndrome is a rare autosomal recessive genetic disease characterized by insulin dependent diabetes and vision, hearing and brain abnormalities which generally emerge in childhood. Mutations in the WFS1 gene predispose cells to endoplasmic reticulum stress-mediated apoptosis and may induce myelin degradation in neuronal cell models. However, in vivo evidence of this phenomenon in humans is lacking. White matter microstructure and regional volumes were measured using magnetic resonance imaging in children and young adults with Wolfram syndrome (n = 21) and healthy and diabetic controls (n = 50). Wolfram patients had lower fractional anisotropy and higher radial diffusivity in major white matter tracts and lower volume in the basilar (ventral) pons, cerebellar white matter and visual cortex. Correlations were found between key brain findings and overall neurological symptoms. This pattern of findings suggests that reduction in myelin is a primary neuropathological feature of Wolfram syndrome. Endoplasmic reticulum stress-related dysfunction in Wolfram syndrome may interact with the development of myelin or promote degeneration of myelin during the progression of the disease. These measures may provide objective indices of Wolfram syndrome pathophysiology that will be useful in unraveling the underlying mechanisms and in testing the impact of treatments on the brain.

Molecular mechanisms of acrolein-mediated myelin destruction in CNS trauma and disease

Science.gov (United States)

Shi, Riyi; Page, Jessica; Tully, Melissa

2016-01-01

Myelin is a critical component of the nervous system facilitating efficient propagation of electrical signals and thus communication between the central and peripheral nervous systems and organ systems they innervate throughout the body. In instances of neurotrauma and neurodegenerative disease, injury to myelin is a prominent pathological feature responsible for conduction deficits and leaves axons vulnerable to damage from noxious compounds. Although the pathological mechanisms underlying myelin loss have yet to be fully characterized, oxidative stress appears to play a prominent role. Specifically, acrolein, a neurotoxic aldehyde that is both a product and instigator of oxidative stress, has been observed in studies to elicit demyelination through calcium-independent and -dependent mechanisms and also by affecting glutamate uptake and promoting excitotoxicity. Furthermore, pharmacological scavenging of acrolein has demonstrated a neuroprotective effect in animal disease models by conserving myelin structural integrity and alleviating functional deficits. This evidence is indicative that acrolein may be a key culprit of myelin damage while acrolein scavenging could potentially be a promising therapeutic approach for patients suffering from nervous system trauma and disease. PMID:25879847

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

International Nuclear Information System (INIS)

Boulias, C.; Moscarello, M.A.

1989-01-01

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

Fast-spiking Parvalbumin Interneurons are Frequently Myelinated in the Cerebral Cortex of Mice and Humans

NARCIS (Netherlands)

Stedehouder, J. (J.); J.J. Couey (Jonathan J); Brizee, D. (D.); B. Hosseini; J.A. Slotman (Johan A.); C.M.F. Dirven (Clemens); G. Shpak (Guy); A.B. Houtsmuller (Adriaan); S.A. Kushner (Steven)

2017-01-01

textabstractMyelination, the insulating ensheathment of axons by oligodendrocytes, is thought to both optimize signal propagation and provide metabolic support. Despite the well-established physiological importance of myelination to neuronal function, relatively little is known about the myelination

Myelination Is Associated with Processing Speed in Early Childhood: Preliminary Insights.

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Nicolas Chevalier

Full Text Available Processing speed is an important contributor to working memory performance and fluid intelligence in young children. Myelinated white matter plays a central role in brain messaging, and likely mediates processing speed, but little is known about the relationship between myelination and processing speed in young children. In the present study, processing speed was measured through inspection times, and myelin volume fraction (VFM was quantified using a multicomponent magnetic resonance imaging (MRI approach in 2- to 5-years of age. Both inspection times and VFM were found to increase with age. Greater VFM in the right and left occipital lobes, the body of the corpus callosum, and the right cerebellum was significantly associated with shorter inspection times, after controlling for age. A hierarchical regression showed that VFM in the left occipital lobe predicted inspection times over and beyond the effects of age and the VFM in the other brain regions. These findings are consistent with the hypothesis that myelin supports processing speed in early childhood.

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

Science.gov (United States)

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

2011-11-01

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

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

Science.gov (United States)

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

2011-11-01

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

Myelin activates FAK/Akt/NF-kappaB pathways and provokes CR3-dependent inflammatory response in murine system.

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Xin Sun

2010-02-01

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

A Laminin-2, Dystroglycan, Utrophin Axis is Required for Compartmentalization and Elongation of Myelin Segments

OpenAIRE

Court, Felipe A.; Hewitt, Jane E.; Davies, Kay; Patton, Bruce L.; Uncini, Antonino; Wrabetz, Lawrence; Feltri, M. Laura

2009-01-01

Animal and plant cells compartmentalize to perform morphogenetic functions. Compartmentalization of myelin-forming Schwann cells may favor elongation of myelin segments to the size required for efficient conduction of nerve impulses. Compartments in myelinated fibers were described by Ramon-y-Cajal and depend on periaxin, mutated in the hereditary neuropathy Charcot-Marie-Tooth 4F. Lack of periaxin in mice causes loss of compartments, formation of short myelin segments (internodes) and reduce...

Requirement of cAMP signaling for Schwann cell differentiation restricts the onset of myelination.

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Ketty Bacallao

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

Exploitation of detergent thermodynamics in the direct solubilization of myelin membrane proteins for two-dimensional gel electrophoresis for proteomic analysis.

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Nair, Sreepriya; Xavier, Tessy; Kumar, Madathiparambil Kumaran Satheesh; Saha, Sharmistha; Menon, Krishnakumar N

2011-12-01

Performing 2-DE of lipid-rich multilamellar membranes like myelin is a cumbersome task. However, for understanding its molecular organization and changes during diseases, identification of proteins of myelin is essential. Although the 2-D-proteomic approach of myelin has been employed to understand the myelin proteome, representation of myelin proteins in its entirety is still a challenge. 2-DE profiling of myelin proteins is very important for the detection of immuno-reactivity to myelin proteins from various biological fluids following Western blotting in diseases like multiple sclerosis. Here we developed a novel approach by exploiting the thermodynamic principles behind detergent-mediated solubilization of myelin membranes without any conventional processing of myelin involving precipitation of myelin proteins. We show that the addition of myelin to ASB-14-4 resulted in significant increase in protein representation of myelin in 2-DE compared with the addition of ASB-14-4 to myelin. Moreover, the number and resolution of spots are significantly higher in myelin to ASB-14-4 strategy than other strategies of myelin sample processing such as ASB-14-4 to myelin or ethanol or acetone or methanol-ammonium acetate precipitation of myelin proteins. In addition, the step involves no precipitation that selective removal of any proteins as a result of precipitation is nil and a qualitative representation of myelin proteins in a 2-D gel is achieved. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Myelination and isochronicity in neural networks

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Fumitaka Kimura

2009-07-01

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

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

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

2012-06-01

The pathogenesis of multiple sclerosis (MS), a disease characterized by demyelination and subsequent axonal degeneration, is as yet unknown. Also, the nature of the disease is as yet not established, since doubts have been cast on its autoimmune origin. Genetic and environmental factors have been implied in MS, leading to the idea of an overall multifactorial origin. An unexpected role in energizing the axon has been reported for myelin, supposed to be the site of consumption of most of oxygen in brain. Myelin would be able to perform oxidative phosphorylation to supply the axons with ATP, thanks to the expression therein of mitochondrial F(o)F(1)-ATP synthase, and respiratory chains. Interestingly, myelin expresses the pathway of heme synthesis, hence of cytochromes, that rely on heme group, in turn depending on Fe availability. Poisoning by these pollutants shares the common characteristic to bring about demyelination both in animal models and in man. Carbon monoxide (CO) and lead poisoning which cause functional imbalance of the heme group, as well as of heme synthesis, cause myelin damage. On the other hand, a lack of essential metals such as iron and copper, produces dramatic myelin decrease. Myelin is a primary target, of iron shortage, indicating that in myelin Fe-dependent processes are more active than in other tissues. The predominant spread of MS in industrialized countries where pollution by heavy metals, and CO poisoning is widespread, suggests a relationship among toxic action of metal pollutants and MS. According to the present hypothesis, MS can be primarily triggered by environmental factors acting on a genetic susceptibility, while the immune response may be a consequence of a primary oxidative damage due to reactive oxygen species produced consequently to an imbalance of cytochromes and respiratory chains in the sheath. Copyright © 2012 Elsevier Ltd. All rights reserved.

Direct visualization of membrane architecture of myelinating cells in transgenic mice expressing membrane-anchored EGFP.

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Deng, Yaqi; Kim, BongWoo; He, Xuelian; Kim, Sunja; Lu, Changqing; Wang, Haibo; Cho, Ssang-Goo; Hou, Yiping; Li, Jianrong; Zhao, Xianghui; Lu, Q Richard

2014-04-01

Myelinogenesis is a complex process that involves substantial and dynamic changes in plasma membrane architecture and myelin interaction with axons. Highly ramified processes of oligodendrocytes in the central nervous system (CNS) make axonal contact and then extrapolate to wrap around axons and form multilayer compact myelin sheathes. Currently, the mechanisms governing myelin sheath assembly and axon selection by myelinating cells are not fully understood. Here, we generated a transgenic mouse line expressing the membrane-anchored green fluorescent protein (mEGFP) in myelinating cells, which allow live imaging of details of myelinogenesis and cellular behaviors in the nervous systems. mEGFP expression is driven by the promoter of 2'-3'-cyclic nucleotide 3'-phosphodiesterase (CNP) that is expressed in the myelinating cell lineage. Robust mEGFP signals appear in the membrane processes of oligodendrocytes in the CNS and Schwann cells in the peripheral nervous system (PNS), wherein mEGFP expression defines the inner layers of myelin sheaths and Schmidt-Lanterman incisures in adult sciatic nerves. In addition, mEGFP expression can be used to track the extent of remyelination after demyelinating injury in a toxin-induced demyelination animal model. Taken together, the membrane-anchored mEGFP expression in the new transgenic line would facilitate direct visualization of dynamic myelin membrane formation and assembly during development and process remodeling during remyelination after various demyelinating injuries.

Myelin Basic Protein synthesis is regulated by small non-coding RNA 715

NARCIS (Netherlands)

Bauer, N.M.; Moos, C.; van Horssen, J.; Witte, M.E.; van der Valk, P.; Altenhein, B.; Luhmann, H.J.; White, R.

2012-01-01

Oligodendroglial Myelin Basic Protein (MBP) synthesis is essential for myelin formation in the central nervous system. During oligodendrocyte differentiation, MBP mRNA is kept in a translationally silenced state while intracellularly transported, until neuron-derived signals initiate localized MBP

Hypothyroidism coordinately and transiently affects myelin protein gene expression in most rat brain regions during postnatal development.

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Ibarrola, N; Rodríguez-Peña, A

1997-03-28

To assess the role of thyroid hormone on myelin gene expression, we have studied the effect of hypothyroidism on the mRNA steady state levels for the major myelin protein genes: myelin basic protein (MBP), proteolipid protein (PLP), myelin-associated glycoprotein (MAG) and 2':3'-cyclic nucleotide 3'-phosphodiesterase (CNP) in different rat brain regions, during the first postnatal month. We found that hypothyroidism reduces the levels of every myelin protein transcript, with striking differences between the different brain regions. Thus, in the more caudal regions, the effect of hypothyroidism was extremely modest, being only evident at the earlier stages of myelination. In contrast, in the striatum and the cerebral cortex the important decrease in the myelin protein transcripts is maintained beyond the first postnatal month. Therefore, thyroid hormone modulates in a synchronous fashion the expression of the myelin genes and the length of its effect depends on the brain region. On the other hand, hyperthyroidism leads to an increase of the major myelin protein transcripts above control values. Finally, lack of thyroid hormone does not change the expression of the oligodendrocyte progenitor-specific gene, the platelet derived growth factor receptor alpha.

Regulation of Central Nervous System Myelination in Higher Brain Functions

OpenAIRE

Nickel, Mara; Gu, Chen

2018-01-01

The hippocampus and the prefrontal cortex are interconnected brain regions, playing central roles in higher brain functions, including learning and memory, planning complex cognitive behavior, and moderating social behavior. The axons in these regions continue to be myelinated into adulthood in humans, which coincides with maturation of personality and decision-making. Myelin consists of dense layers of lipid membranes wrapping around the axons to provide electrical insulation and trophic sup...

The formation of lipid droplets favors intracellular Mycobacterium leprae survival in SW-10, non-myelinating Schwann cells.

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Jin, Song-Hyo; An, Sung-Kwan; Lee, Seong-Beom

2017-06-01

Leprosy is a chronic infectious disease that is caused by the obligate intracellular pathogen Mycobacterium leprae (M.leprae), which is the leading cause of all non-traumatic peripheral neuropathies worldwide. Although both myelinating and non-myelinating Schwann cells are infected by M.leprae in patients with lepromatous leprosy, M.leprae preferentially invades the non-myelinating Schwann cells. However, the effect of M.leprae infection on non-myelinating Schwann cells has not been elucidated. Lipid droplets (LDs) are found in M.leprae-infected Schwann cells in the nerve biopsies of lepromatous leprosy patients. M.leprae-induced LD formation favors intracellular M.leprae survival in primary Schwann cells and in a myelinating Schwann cell line referred to as ST88-14. In the current study, we initially characterized SW-10 cells and investigated the effects of LDs on M.leprae-infected SW-10 cells, which are non-myelinating Schwann cells. SW-10 cells express S100, a marker for cells from the neural crest, and NGFR p75, a marker for immature or non-myelinating Schwann cells. SW-10 cells, however, do not express myelin basic protein (MBP), a marker for myelinating Schwann cells, and myelin protein zero (MPZ), a marker for precursor, immature, or myelinating Schwann cells, all of which suggests that SW-10 cells are non-myelinating Schwann cells. In addition, SW-10 cells have phagocytic activity and can be infected with M. leprae. Infection with M. leprae induces the formation of LDs. Furthermore, inhibiting the formation of M. leprae-induced LD enhances the maturation of phagosomes containing live M.leprae and decreases the ATP content in the M. leprae found in SW-10 cells. These facts suggest that LD formation by M. leprae favors intracellular M. leprae survival in SW-10 cells, which leads to the logical conclusion that M.leprae-infected SW-10 cells can be a new model for investigating the interaction of M.leprae with non-myelinating Schwann cells.

Quantification of myelin in children using multiparametric quantitative MRI: a pilot study

International Nuclear Information System (INIS)

Kim, Hyun Gi; Choi, Jin Wook; Moon, Won-Jin; Han, JinJoo

2017-01-01

The purpose of this study was to evaluate the usefulness of multiparametric quantitative MRI for myelination quantification in children. We examined 22 children (age 0-14 years) with multiparametric quantitative MRI. The total volume of myelin partial volume (Msum), the percentage of Msum within the whole brain parenchyma (Mbpv), and the percentage of Msum within the intracranial volume (Micv) were obtained. Four developmental models of myelin maturation (the logarithmic, logistic, Gompertz, and modified Gompertz models) were examined to find the most representative model of the three parameters. We acquired myelin partial volume values in different brain regions and assessed the goodness of fit for the models. The ranges of Msum, Mbpv, and Micv were 0.8-160.9 ml, 0.2-13%, and 0.0-11.6%, respectively. The Gompertz model was the best fit for the three parameters. For developmental model analysis of myelin partial volume in each brain region, the Gompertz model was the best-fit model for pons (R"2 = 74.6%), middle cerebeller peduncle (R"2 = 76.4%), putamen (R"2 = 95.8%), and centrum semiovale (R"2 = 77.7%). The logistic model was the best-fit model for the genu and splenium of the corpus callosum (R"2 = 79.7-93.6%), thalamus (R"2 = 81.7%), and frontal, parietal, temporal, and occipital white matter (R"2 = 92.5-96.5%). Multiparametric quantitative MRI depicts the normal developmental pattern of myelination in children. It is a potential tool for research studies on pediatric brain development evaluation. (orig.)

Quantification of myelin in children using multiparametric quantitative MRI: a pilot study

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Kim, Hyun Gi; Choi, Jin Wook [Ajou University School of Medicine, Ajou University Medical Center, Department of Radiology, Suwon (Korea, Republic of); Moon, Won-Jin [Konkuk University Hospital, Konkuk University School of Medicine, Department of Radiology, Seoul (Korea, Republic of); Han, JinJoo [Ajou University School of Medicine, Office of Biostatistics, Department of Humanities and Social Medicine, Suwon (Korea, Republic of)

2017-10-15

The purpose of this study was to evaluate the usefulness of multiparametric quantitative MRI for myelination quantification in children. We examined 22 children (age 0-14 years) with multiparametric quantitative MRI. The total volume of myelin partial volume (Msum), the percentage of Msum within the whole brain parenchyma (Mbpv), and the percentage of Msum within the intracranial volume (Micv) were obtained. Four developmental models of myelin maturation (the logarithmic, logistic, Gompertz, and modified Gompertz models) were examined to find the most representative model of the three parameters. We acquired myelin partial volume values in different brain regions and assessed the goodness of fit for the models. The ranges of Msum, Mbpv, and Micv were 0.8-160.9 ml, 0.2-13%, and 0.0-11.6%, respectively. The Gompertz model was the best fit for the three parameters. For developmental model analysis of myelin partial volume in each brain region, the Gompertz model was the best-fit model for pons (R{sup 2} = 74.6%), middle cerebeller peduncle (R{sup 2} = 76.4%), putamen (R{sup 2} = 95.8%), and centrum semiovale (R{sup 2} = 77.7%). The logistic model was the best-fit model for the genu and splenium of the corpus callosum (R{sup 2} = 79.7-93.6%), thalamus (R{sup 2} = 81.7%), and frontal, parietal, temporal, and occipital white matter (R{sup 2} = 92.5-96.5%). Multiparametric quantitative MRI depicts the normal developmental pattern of myelination in children. It is a potential tool for research studies on pediatric brain development evaluation. (orig.)

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

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Saher, Gesine; Quintes, Susanne; Möbius, Wiebke; Wehr, Michael C; Krämer-Albers, Eva-Maria; Brügger, 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.

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

International Nuclear Information System (INIS)

Miyamachi, Keikichi; Miyasaka, Kazuo; Abe, Hiroshi

1990-01-01

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.)

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

International Nuclear Information System (INIS)

Knaap, M.S. van der; Valk, J.

1990-01-01

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.)

Mild myelin disruption elicits early alteration in behavior and proliferation in the subventricular zone.

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Gould, Elizabeth A; Busquet, Nicolas; Shepherd, Douglas; Dietz, Robert M; Herson, Paco S; Simoes de Souza, Fabio M; Li, Anan; George, Nicholas M; Restrepo, Diego; Macklin, Wendy B

2018-02-13

Myelin, the insulating sheath around axons, supports axon function. An important question is the impact of mild myelin disruption. In the absence of the myelin protein proteolipid protein (PLP1), myelin is generated but with age, axonal function/maintenance is disrupted. Axon disruption occurs in Plp1 -null mice as early as 2 months in cortical projection neurons. High-volume cellular quantification techniques revealed a region-specific increase in oligodendrocyte density in the olfactory bulb and rostral corpus callosum that increased during adulthood. A distinct proliferative response of progenitor cells was observed in the subventricular zone (SVZ), while the number and proliferation of parenchymal oligodendrocyte progenitor cells was unchanged. This SVZ proliferative response occurred prior to evidence of axonal disruption. Thus, a novel SVZ response contributes to the region-specific increase in oligodendrocytes in Plp1 -null mice. Young adult Plp1- null mice exhibited subtle but substantial behavioral alterations, indicative of an early impact of mild myelin disruption. © 2018, Gould et al.

Promoting peripheral myelin repair

OpenAIRE

Zhou, Ye; Notterpek, Lucia

2016-01-01

Compared to the central nervous system (CNS), peripheral nerves have a remarkable ability to regenerate and remyelinate. This regenerative capacity to a large extent is dependent on and supported by Schwann cells, the myelin-forming glial cells of the peripheral nervous system (PNS). In a variety of paradigms, Schwann cells are critical in the removal of the degenerated tissue, which is followed by remyelination of newly-regenerated axons. This unique plasticity of Schwann cells has been the ...

X-ray diffraction evidence for myelin disorder in brain from humans with Alzheimer's disease.

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Chia, L S; Thompson, J E; Moscarello, M A

1984-09-05

Wide-angle X-ray diffraction studies revealed that the lipid phase transition temperature of myelin from brain tissue of humans with Alzheimer's disease was about 12 degrees C lower than that of normal age-matched controls, indicating differences in the physical organization of the myelin lipid bilayer. Elevated levels of malondialdehyde and conjugated diene were found in brain tissue from humans with Alzheimer's disease, indicating an increased amount of lipid peroxidation over the controls. An increase in myelin disorder and in lipid peroxidation can both be correlated with aging in human brain, but the changes in myelin from humans with Alzheimer's disease are more pronounced than in normal aging. These changes might represent severe or accelerated aging.

The formation of lipid droplets favors intracellular Mycobacterium leprae survival in SW-10, non-myelinating Schwann cells

OpenAIRE

Jin, Song-Hyo; An, Sung-Kwan; Lee, Seong-Beom

2017-01-01

Leprosy is a chronic infectious disease that is caused by the obligate intracellular pathogen Mycobacterium leprae (M.leprae), which is the leading cause of all non-traumatic peripheral neuropathies worldwide. Although both myelinating and non-myelinating Schwann cells are infected by M.leprae in patients with lepromatous leprosy, M.leprae preferentially invades the non-myelinating Schwann cells. However, the effect of M.leprae infection on non-myelinating Schwann cells has not been elucidate...

On the biogenesis of the myelin sheath : Cognate polarized trafficking pathways in oligodendrocytes

NARCIS (Netherlands)

de Vries, H; Hoekstra, D

2000-01-01

Oligodendrocytes, the myelinating cells of the central nervous system, are capable of transporting vast quantities of proteins and of lipids, In particular galactosphingolipids, to the myelin sheath. The sheath is continuous with the plasma membrane of the oligodendrocyte, but the composition of

A critical role for the cholesterol-associated proteolipids PLP and M6B in myelination of the central nervous system.

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Werner, Hauke B; Krämer-Albers, Eva-Maria; Strenzke, Nicola; Saher, Gesine; Tenzer, Stefan; Ohno-Iwashita, Yoshiko; De Monasterio-Schrader, Patricia; Möbius, Wiebke; Moser, Tobias; Griffiths, Ian R; Nave, Klaus-Armin

2013-04-01

The formation of central nervous system myelin by oligodendrocytes requires sterol synthesis and is associated with a significant enrichment of cholesterol in the myelin membrane. However, it is unknown how oligodendrocytes concentrate cholesterol above the level found in nonmyelin membranes. Here, we demonstrate a critical role for proteolipids in cholesterol accumulation. Mice lacking the most abundant myelin protein, proteolipid protein (PLP), are fully myelinated, but PLP-deficient myelin exhibits a reduced cholesterol content. We therefore hypothesized that "high cholesterol" is not essential in the myelin sheath itself but is required for an earlier step of myelin biogenesis that is fully compensated for in the absence of PLP. We also found that a PLP-homolog, glycoprotein M6B, is a myelin component of low abundance. By targeting the Gpm6b-gene and crossbreeding, we found that single-mutant mice lacking either PLP or M6B are fully myelinated, while double mutants remain severely hypomyelinated, with enhanced neurodegeneration and premature death. As both PLP and M6B bind membrane cholesterol and associate with the same cholesterol-rich oligodendroglial membrane microdomains, we suggest a model in which proteolipids facilitate myelination by sequestering cholesterol. While either proteolipid can maintain a threshold level of cholesterol in the secretory pathway that allows myelin biogenesis, lack of both proteolipids results in a severe molecular imbalance of prospective myelin membrane. However, M6B is not efficiently sorted into mature myelin, in which it is 200-fold less abundant than PLP. Thus, only PLP contributes to the high cholesterol content of myelin by association and co-transport. Copyright © 2013 Wiley Periodicals, Inc.

Cytoskeletal Linker Protein Dystonin Is Not Critical to Terminal Oligodendrocyte Differentiation or CNS Myelination.

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Samantha F Kornfeld

Full Text Available Oligodendrocyte differentiation and central nervous system myelination require massive reorganization of the oligodendrocyte cytoskeleton. Loss of specific actin- and tubulin-organizing factors can lead to impaired morphological and/or molecular differentiation of oligodendrocytes, resulting in a subsequent loss of myelination. Dystonin is a cytoskeletal linker protein with both actin- and tubulin-binding domains. Loss of function of this protein results in a sensory neuropathy called Hereditary Sensory Autonomic Neuropathy VI in humans and dystonia musculorum in mice. This disease presents with severe ataxia, dystonic muscle and is ultimately fatal early in life. While loss of the neuronal isoforms of dystonin primarily leads to sensory neuron degeneration, it has also been shown that peripheral myelination is compromised due to intrinsic Schwann cell differentiation abnormalities. The role of this cytoskeletal linker in oligodendrocytes, however, remains unclear. We sought to determine the effects of the loss of neuronal dystonin on oligodendrocyte differentiation and central myelination. To address this, primary oligodendrocytes were isolated from a severe model of dystonia musculorum, Dstdt-27J, and assessed for morphological and molecular differentiation capacity. No defects could be discerned in the differentiation of Dstdt-27J oligodendrocytes relative to oligodendrocytes from wild-type littermates. Survival was also compared between Dstdt-27J and wild-type oligodendrocytes, revealing no significant difference. Using a recently developed migration assay, we further analysed the ability of primary oligodendrocyte progenitor cell motility, and found that Dstdt-27J oligodendrocyte progenitor cells were able to migrate normally. Finally, in vivo analysis of oligodendrocyte myelination was done in phenotype-stage optic nerve, cerebral cortex and spinal cord. The density of myelinated axons and g-ratios of Dstdt-27J optic nerves was normal, as

Evaluation of neonatal brain myelination using the T1- and T2-weighted MRI ratio.

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Soun, Jennifer E; Liu, Michael Z; Cauley, Keith A; Grinband, Jack

2017-09-01

To validate the T1- and T2-weighted (T1w/T2w) MRI ratio technique in evaluating myelin in the neonatal brain. T1w and T2w MR images of 10 term neonates with normal-appearing brain parenchyma were obtained from a single 1.5 Tesla MRI and retrospectively analyzed. T1w/T2w ratio images were created with a postprocessing pipeline and qualitatively compared with standard clinical sequences (T1w, T2w, and apparent diffusion coefficient [ADC]). Quantitative assessment was also performed to assess the ratio technique in detecting areas of known myelination (e.g., posterior limb of the internal capsule) and very low myelination (e.g., optic radiations) using linear regression analysis and the Michelson Contrast equation, a measure of luminance contrast intensity. The ratio image provided qualitative improvements in the ability to visualize regional variation in myelin content of neonates. Linear regression analysis demonstrated a significant inverse relationship between the ratio intensity values and ADC values in the posterior limb of the internal capsule and the optic radiations (R 2  = 0.96 and P ratio images were 1.6 times higher than T1w, 2.6 times higher than T2w, and 1.8 times higher than ADC (all P ratio improved visualization of the corticospinal tract, one of the earliest myelinated pathways. The T1w/T2w ratio accentuates contrast between myelinated and less myelinated structures and may enhance our diagnostic ability to detect myelination patterns in the neonatal brain. 2 Technical Efficacy: Stage2 J. MAGN. RESON. IMAGING 2017;46:690-696. © 2016 International Society for Magnetic Resonance in Medicine.

Myelin-induced inhibition in a spiral ganglion organ culture - Approaching a natural environment in vitro.

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Kramer, Benedikt; Tropitzsch, Anke; Müller, Marcus; Löwenheim, Hubert

2017-08-15

The performance of a cochlear implant depends on the defined interaction between afferent neurons of the spiral ganglion and the inserted electrode. Neurite outgrowth can be induced by neurotrophins such as brain-derived neurotrophic factor (BDNF) via tropomyosin kinase receptor B (TrkB). However, neurotrophin signaling through the p75 neurotrophin receptor (p75) inhibits neurite outgrowth in the presence of myelin. Organotypic cultures derived from postnatal (P3-5) mice were used to study myelin-induced inhibition in the cochlear spiral ganglion. Neurite outgrowth was analyzed and quantified utilizing an adapted Sholl analysis. Stimulation of neurite outgrowth was quantified after application of BDNF, the selective TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) and a selective inhibitor of the Rho-associated kinase (Y27632), which inhibits the p75 pathway. Myelin-induced inhibition was assessed by application of myelin-associated glycoprotein (MAG-Fc) to stimulate the inhibitory p75 pathway. Inhibition of neurite outgrowth was achieved by the selective TrkB inhibitor K252a. Stimulation of neurite outgrowth was observed after treatment with BDNF, 7,8 DHF and a combination of BDNF and Y27632. The 7,8-DHF-induced growth effects could be inhibited by K252a. Furthermore, inhibition of neurite outgrowth was observed after supplementation with MAG-Fc. Myelin-induced inhibition could be overcome by 7,8-DHF and the combination of BDNF and Y27632. In this study, myelin-induced inhibition of neurite outgrowth was established in a spiral ganglion model. We reveal that 7,8-DHF is a viable novel compound for the stimulation of neurite outgrowth in a myelin-induced inhibitory environment. The combination of TrkB stimulation and ROCK inhibition can be used to overcome myelin inhibition. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Ribosomal trafficking is reduced in Schwann cells following induction of myelination

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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

Myelination progression in language-correlated regions in brain of normal children determined by quantitative MRI assessment.

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Su, Peijen; Kuan, Chen-Chieh; Kaga, Kimitaka; Sano, Masaki; Mima, Kazuo

2008-12-01

To investigate the myelination progression course in language-correlated regions of children with normal brain development by quantitative magnetic resonance imaging (MRI) analysis compared with histological studies. The subjects were 241 neurologically intact neonates, infants and young children (128 boys and 113 girls) who underwent MRI between 2001 and 2007 at the University of Tokyo Hospital, ranging in age from 0 to 429 weeks corrected by postnatal age. To compare their data with adult values, 25 adolescents and adults (14 men and 11 women, aged from 14 to 83 years) were examined as controls. Axial T2-weighted images were obtained using spin-echo sequences at 1.5 T. Subjects with a history of prematurity, birth asphyxia, low Apgar score, seizures, active systemic disease, congenital anomaly, delayed development, infarcts, hemorrhages, brain lesions, or central nervous system malformation were excluded from the analysis. Seven regions of interest in language-correlated areas, namely Broca's area, Wernicke's area, the arcuate fasciculus, and the angular gyrus, as well as their right hemisphere homologous regions, and the auditory cortex, the motor cortex, and the visual cortex were examined. Signal intensity obtained by a region-of-interest methodology progresses from hyper- to hypointensity during myelination. We chose the inferior cerebellar peduncle as the internal standard of maturation. Myelination in all these seven language-correlated regions examined in this study shared the same curve pattern: no myelination was observed at birth, it reached maturation at about 1.5 years of age, and it continued to progress slowly thereafter into adult life. On the basis of scatter plot results, we put these areas into three groups: Group A, which included the motor cortex, the auditory cortex, and the visual cortex, myelinated faster than Group B, which included Broca's area, Wernicke's area, and the angular gyrus before 1.5 years old; Group C, consisting of the

Splanchnic preganglionic neurons in man. III. Morphometry of myelinated fibers of rami communicantes.

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Low, P A; Dyck, P J

1978-01-01

The myelinated fiber (MF) composition of T6-T8 Rami Communicantes were obtained in 9 healthy persons of various ages. The textbook picture that distal rami (DR) contain all of the myelinated fibers and therefore are white, while proximal rami (PR) contain none of them and therefore are grey must be modified. We found that DR usually contained abundant MFs and that PR concordance was found between segmental numbers of intermediolateral nuclei cytons, ventral root small myelinated fibers (SMFs), and rami total small MFs to suggest that both rami probably contain the distal myelinated axons of preganglionic autonomic fibers. Finally, there was an attrition of total MFs of rami with age, similar to what we had previously found for ILC cytons and for root SMFs. The decrease in number of pre-ganglionic autonomic neurons with age is thought to be of sufficient magnitude to account for the dysautonomia of the elderly.

Clozapine promotes glycolysis and myelin lipid synthesis in cultured oligodendrocytes

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Johann eSteiner

2014-11-01

Full Text Available Clozapine has stronger systemic metabolic side effects than haloperidol and it was hypothesized that therapeutic antipsychotic and adverse metabolic effects might be related. Considering that cerebral disconnectivity through oligodendrocyte dysfunction has been implicated in schizophrenia, it is important to determine the effect of these drugs on oligodendrocyte energy metabolism and myelin lipid production.Effects of clozapine and haloperidol on glucose and myelin lipid metabolism were evaluated and compared in cultured OLN-93 oligodendrocytes. First, glycolytic activity was assessed by measurement of extra- and intracellular glucose and lactate levels. Next, the expression of glucose (GLUT and monocarboxylate (MCT transporters was determined after 6h and 24h. And finally mitochondrial respiration, acetyl-CoA carboxylase, free fatty acids, and expression of the myelin lipid galactocerebroside were analyzed.Both drugs altered oligodendrocyte glucose metabolism, but in opposite directions. Clozapine improved the glucose uptake, production and release of lactate, without altering GLUT and MCT. In contrast, haloperidol led to higher extracellular levels of glucose and lower levels of lactate, suggesting reduced glycolysis. Antipsychotics did not alter significantly the number of functionally intact mitochondria, but clozapine enhanced the efficacy of oxidative phosphorylation and expression of galactocerebroside.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.

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

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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.

Myelination competent conditionally immortalized mouse Schwann cells

NARCIS (Netherlands)

Saavedra, José T.; Wolterman, Ruud A.; Baas, Frank; ten Asbroek, Anneloor L. M. A.

2008-01-01

Numerous mouse myelin mutants are available to analyze the biology of the peripheral nervous system related to health and disease in vivo. However, robust in vitro biochemical characterizations of players in peripheral nerve processes are still not possible due to the limited growth capacities of

MAL Is a Regulator of the Recruitment of Myelin Protein PLP to Membrane Microdomains

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Bijlard, Marjolein; de Jonge, Jenny C.; Klunder, Bert; Nomden, Anita; Hoekstra, Dick; Baron, Wia

2016-01-01

In oligodendrocytes (OLGs), an indirect, transcytotic pathway is mediating transport of de novo synthesized PLP, a major myelin specific protein, from the apical-like plasma membrane to the specialized basolateral-like myelin membrane to prevent its premature compaction. MAL is a well-known

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

International Nuclear Information System (INIS)

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

2008-01-01

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

Transcriptional Regulation of Brain-Derived Neurotrophic Factor (BDNF) by Methyl CpG Binding Protein 2 (MeCP2): a Novel Mechanism for Re-Myelination and/or Myelin Repair Involved in the Treatment of Multiple Sclerosis (MS).

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KhorshidAhmad, Tina; Acosta, Crystal; Cortes, Claudia; Lakowski, Ted M; Gangadaran, Surendiran; Namaka, Michael

2016-03-01

Multiple sclerosis (MS) is a chronic progressive, neurological disease characterized by the targeted immune system-mediated destruction of central nervous system (CNS) myelin. Autoreactive CD4+ T helper cells have a key role in orchestrating MS-induced myelin damage. Once activated, circulating Th1-cells secrete a variety of inflammatory cytokines that foster the breakdown of blood-brain barrier (BBB) eventually infiltrating into the CNS. Inside the CNS, they become reactivated upon exposure to the myelin structural proteins and continue to produce inflammatory cytokines such as tumor necrosis factor α (TNFα) that leads to direct activation of antibodies and macrophages that are involved in the phagocytosis of myelin. Proliferating oligodendrocyte precursors (OPs) migrating to the lesion sites are capable of acute remyelination but unable to completely repair or restore the immune system-mediated myelin damage. This results in various permanent clinical neurological disabilities such as cognitive dysfunction, fatigue, bowel/bladder abnormalities, and neuropathic pain. At present, there is no cure for MS. Recent remyelination and/or myelin repair strategies have focused on the role of the neurotrophin brain-derived neurotrophic factor (BDNF) and its upstream transcriptional repressor methyl CpG binding protein (MeCP2). Research in the field of epigenetic therapeutics involving histone deacetylase (HDAC) inhibitors and lysine acetyl transferase (KAT) inhibitors is being explored to repress the detrimental effects of MeCP2. This review will address the role of MeCP2 and BDNF in remyelination and/or myelin repair and the potential of HDAC and KAT inhibitors as novel therapeutic interventions for MS.

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

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Hadas Smadar

2012-07-01

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

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

2008-01-01

protein (MBP), a major autoantigen in MS, is a potent and specific ligand for the integrin αMβ2 (Mac-1, CD11b/CD18) expressed mainly on phagocytic cells. MBP undergoes a dramatic conformational change when liberated from the lipid-rich environment of the myelin sheath. The MS drug glatiramer acetate......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...

Type a niemann-pick disease. Description of three cases with delayed myelination.

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D'Amico, A; Sibilio, M; Caranci, F; Bartiromo, F; Taurisano, R; Balivo, F; Melis, D; Parenti, G; Cirillo, S; Elefante, R; Brunetti, A

2008-06-03

We describe three patients with type A Niemann-Pick disease (NPD-A). NPD-A is an autosomal recessive neuronal storage disease classified among the sphingolipidoses, characterized by accumulation of sphingomyelin in various tissues and in the brain. Magnetic Resonance imaging (MRI) of our three patients showed a marked delay of myelination with frontal atrophy. Few descriptions of this MRI pattern of delayed myelination have been published to date.

Lipid metabolism in myelinating glial cells: lessons from human inherited disorders and mouse models

NARCIS (Netherlands)

Chrast, R.; Saher, G.; Nave, K.A.; Verheijen, M.H.G.

2011-01-01

The integrity of central and peripheral nervous system myelin is affected in numerous lipid metabolism disorders. This vulnerability was so far mostly attributed to the extraordinarily high level of lipid synthesis that is required for the formation of myelin, and to the relative autonomy in lipid

Ultrastructural study of myelinating cells and sub-pial astrocytes in developing rat spinal cord.

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Nagashima, K

1979-12-01

The anterior funiculus of the spinal cervical cord of post-natal rats was examined ultrastructurally. The myelinating cells found one day after brith contained a large amount of evenly distributed ribosomes up to the outer tongue of mesaxons, representing the cytoplasmic density. These cells were separated by astrocytic processes from the pial basement membrane, even when they were located on the pial surface. Astrocytes contained glial fibrils from one day onwards and often attached their processes to the pial basement membrane. Although the cytoplasmic processes of astrocytes occasionally wrapped axons, they were never shown to form the initial layer of myelin sheaths. However, the tenuous processes of the sub-pial astrocytes were occasionally rolled in myelin lamellae, as if a part of the myelin sheaths was constructed by astrocytic processes. The interpretation for this finding is discussed in relation to function and potency of the astrocytes, and variations and anomalies of nervous ontogeny.

Could myelin damage from radiofrequency electromagnetic field exposure help explain the functional impairment electrohypersensitivity? A review of the evidence.

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Redmayne, Mary; Johansson, Olle

2014-01-01

Myelin provides the electrical insulation for the central and peripheral nervous system and develops rapidly in the first years of life, but continues into mid-life or later. Myelin integrity is vital to healthy nervous system development and functioning. This review outlines the development of myelin through life, and then considers the evidence for an association between myelin integrity and exposure to low-intensity radiofrequency electromagnetic fields (RF-EMFs) typical in the modern world. In RF-EMF peer-reviewed literature examining relevant impacts such as myelin sheath, multiple sclerosis, and other myelin-related diseases, cellular examination was included. There are surprisingly little data available in each area, but considered together a picture begins to emerge in RF-EMF-exposed cases: (1) significant morphological lesions in the myelin sheath of rats; (2) a greater risk of multiple sclerosis in a study subgroup; (3) effects in proteins related to myelin production; and (4) physical symptoms in individuals with functional impairment electrohypersensitivity, many of which are the same as if myelin were affected by RF-EMF exposure, giving rise to symptoms of demyelination. In the latter, there are exceptions; headache is common only in electrohypersensitivity, while ataxia is typical of demyelination but infrequently found in the former group. Overall, evidence from in vivo and in vitro and epidemiological studies suggests an association between RF-EMF exposure and either myelin deterioration or a direct impact on neuronal conduction, which may account for many electrohypersensitivity symptoms. The most vulnerable are likely to be those in utero through to at least mid-teen years, as well as ill and elderly individuals.

Neurotoxocarosis alters myelin protein gene transcription and expression.

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

2015-06-01

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

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

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

2007-08-01

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

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

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Laulumaa Saara

2015-01-01

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

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

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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.

Gemfibrozil, a lipid-lowering drug, increases myelin genes in human oligodendrocytes via peroxisome proliferator-activated receptor-β.

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Jana, Malabendu; Mondal, Susanta; Gonzalez, Frank J; Pahan, Kalipada

2012-10-05

An increase in CNS remyelination and a decrease in CNS inflammation are important steps to halt the progression of multiple sclerosis. Earlier studies have shown that gemfibrozil, a lipid-lowering drug, has anti-inflammatory properties. The current study identified another novel property of gemfibrozil in stimulating the expression of myelin-specific genes (myelin basic protein, myelin oligodendrocyte glycoprotein, 2',3'-cyclic-nucleotide 3'-phosphodiesterase, and proteolipid protein (PLP)) in primary human oligodendrocytes, mixed glial cells, and spinal cord organotypic cultures. Although gemfibrozil is a known activator of peroxisome proliferator-activated receptor-α (PPAR-α), we were unable to detect PPAR-α in either gemfibrozil-treated or untreated human oligodendrocytes, and gemfibrozil increased the expression of myelin genes in oligodendrocytes isolated from both wild type and PPAR-α(-/-) mice. On the other hand, gemfibrozil markedly increased the expression of PPAR-β but not PPAR-γ. Consistently, antisense knockdown of PPAR-β, but not PPAR-γ, abrogated the stimulatory effect of gemfibrozil on myelin genes in human oligodendrocytes. Gemfibrozil also did not up-regulate myelin genes in oligodendroglia isolated from PPAR-β(-/-) mice. Chromatin immunoprecipitation analysis showed that gemfibrozil induced the recruitment of PPAR-β to the promoter of PLP and myelin oligodendrocyte glycoprotein genes in human oligodendrocytes. Furthermore, gemfibrozil treatment also led to the recruitment of PPAR-β to the PLP promoter in vivo in the spinal cord of experimental autoimmune encephalomyelitis mice and suppression of experimental autoimmune encephalomyelitis symptoms in PLP-T cell receptor transgenic mice. These results suggest that gemfibrozil stimulates the expression of myelin genes via PPAR-β and that gemfibrozil, a prescribed drug for humans, may find further therapeutic use in demyelinating diseases.

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.

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

DEFF Research Database (Denmark)

Moldovan, Mihai; Alvarez Herrero, Susana; Pinchenko, Volodymyr

2011-01-01

Myelin protein zero mutations were found to produce Charcot-Marie-Tooth disease phenotypes with various degrees of myelin impairment and axonal loss, ranging from the mild 'demyelinating' adult form to severe and early onset forms. Protein zero deficient homozygous mice ( ) show a severe and prog......Myelin protein zero mutations were found to produce Charcot-Marie-Tooth disease phenotypes with various degrees of myelin impairment and axonal loss, ranging from the mild 'demyelinating' adult form to severe and early onset forms. Protein zero deficient homozygous mice ( ) show a severe...... and progressive dysmyelinating neuropathy from birth with compromised myelin compaction, hypomyelination and distal axonal degeneration. A previous study using immunofluorescence showed that motor nerves deficient of myelin protein zero upregulate the Na(V)1.8 voltage gated sodium channel isoform, which...... is normally present only in restricted populations of sensory axons. The aim of this study was to investigate the function of motor axons in protein zero-deficient mice with particular emphasis on ectopic Na(V)1.8 voltage gated sodium channel. We combined 'threshold tracking' excitability studies...

Myelin Breakdown Mediates Age-Related Slowing in Cognitive Processing Speed in Healthy Elderly Men

Science.gov (United States)

Lu, Po H.; Lee, Grace J.; Tishler, Todd A.; Meghpara, Michael; Thompson, Paul M.; Bartzokis, George

2013-01-01

Background: To assess the hypothesis that in a sample of very healthy elderly men selected to minimize risk for Alzheimer's disease (AD) and cerebrovascular disease, myelin breakdown in late-myelinating regions mediates age-related slowing in cognitive processing speed (CPS). Materials and methods: The prefrontal lobe white matter and the genu of…

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).

Gemfibrozil, a Lipid-lowering Drug, Increases Myelin Genes in Human Oligodendrocytes via Peroxisome Proliferator-activated Receptor-β*

Science.gov (United States)

Jana, Malabendu; Mondal, Susanta; Gonzalez, Frank J.; Pahan, Kalipada

2012-01-01

An increase in CNS remyelination and a decrease in CNS inflammation are important steps to halt the progression of multiple sclerosis. Earlier studies have shown that gemfibrozil, a lipid-lowering drug, has anti-inflammatory properties. The current study identified another novel property of gemfibrozil in stimulating the expression of myelin-specific genes (myelin basic protein, myelin oligodendrocyte glycoprotein, 2′,3′-cyclic-nucleotide 3′-phosphodiesterase, and proteolipid protein (PLP)) in primary human oligodendrocytes, mixed glial cells, and spinal cord organotypic cultures. Although gemfibrozil is a known activator of peroxisome proliferator-activated receptor-α (PPAR-α), we were unable to detect PPAR-α in either gemfibrozil-treated or untreated human oligodendrocytes, and gemfibrozil increased the expression of myelin genes in oligodendrocytes isolated from both wild type and PPAR-α(−/−) mice. On the other hand, gemfibrozil markedly increased the expression of PPAR-β but not PPAR-γ. Consistently, antisense knockdown of PPAR-β, but not PPAR-γ, abrogated the stimulatory effect of gemfibrozil on myelin genes in human oligodendrocytes. Gemfibrozil also did not up-regulate myelin genes in oligodendroglia isolated from PPAR-β(−/−) mice. Chromatin immunoprecipitation analysis showed that gemfibrozil induced the recruitment of PPAR-β to the promoter of PLP and myelin oligodendrocyte glycoprotein genes in human oligodendrocytes. Furthermore, gemfibrozil treatment also led to the recruitment of PPAR-β to the PLP promoter in vivo in the spinal cord of experimental autoimmune encephalomyelitis mice and suppression of experimental autoimmune encephalomyelitis symptoms in PLP-T cell receptor transgenic mice. These results suggest that gemfibrozil stimulates the expression of myelin genes via PPAR-β and that gemfibrozil, a prescribed drug for humans, may find further therapeutic use in demyelinating diseases. PMID:22879602

Embryo splitting

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Karl Illmensee

2010-04-01

Full Text Available Mammalian embryo splitting has successfully been established in farm animals. Embryo splitting is safely and efficiently used for assisted reproduction in several livestock species. In the mouse, efficient embryo splitting as well as single blastomere cloning have been developed in this animal system. In nonhuman primates embryo splitting has resulted in several pregnancies. Human embryo splitting has been reported recently. Microsurgical embryo splitting under Institutional Review Board approval has been carried out to determine its efficiency for blastocyst development. Embryo splitting at the 6–8 cell stage provided a much higher developmental efficiency compared to splitting at the 2–5 cell stage. Embryo splitting may be advantageous for providing additional embryos to be cryopreserved and for patients with low response to hormonal stimulation in assisted reproduction programs. Social and ethical issues concerning embryo splitting are included regarding ethics committee guidelines. Prognostic perspectives are presented for human embryo splitting in reproductive medicine.

Combinatorial actions of Tgfβ and Activin ligands promote oligodendrocyte development and CNS myelination.

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Dutta, Dipankar J; Zameer, Andleeb; Mariani, John N; Zhang, Jingya; Asp, Linnea; Huynh, Jimmy; Mahase, Sean; Laitman, Benjamin M; Argaw, Azeb Tadesse; Mitiku, Nesanet; Urbanski, Mateusz; Melendez-Vasquez, Carmen V; Casaccia, Patrizia; Hayot, Fernand; Bottinger, Erwin P; Brown, Chester W; John, Gareth R

2014-06-01

In the embryonic CNS, development of myelin-forming oligodendrocytes is limited by bone morphogenetic proteins, which constitute one arm of the transforming growth factor-β (Tgfβ) family and signal canonically via Smads 1/5/8. Tgfβ ligands and Activins comprise the other arm and signal via Smads 2/3, but their roles in oligodendrocyte development are incompletely characterized. Here, we report that Tgfβ ligands and activin B (ActB) act in concert in the mammalian spinal cord to promote oligodendrocyte generation and myelination. In mouse neural tube, newly specified oligodendrocyte progenitors (OLPs) are first exposed to Tgfβ ligands in isolation, then later in combination with ActB during maturation. In primary OLP cultures, Tgfβ1 and ActB differentially activate canonical Smad3 and non-canonical MAP kinase signaling. Both ligands enhance viability, and Tgfβ1 promotes proliferation while ActB supports maturation. Importantly, co-treatment strongly activates both signaling pathways, producing an additive effect on viability and enhancing both proliferation and differentiation such that mature oligodendrocyte numbers are substantially increased. Co-treatment promotes myelination in OLP-neuron co-cultures, and maturing oligodendrocytes in spinal cord white matter display strong Smad3 and MAP kinase activation. In spinal cords of ActB-deficient Inhbb(-/-) embryos, apoptosis in the oligodendrocyte lineage is increased and OLP numbers transiently reduced, but numbers, maturation and myelination recover during the first postnatal week. Smad3(-/-) mice display a more severe phenotype, including diminished viability and proliferation, persistently reduced mature and immature cell numbers, and delayed myelination. Collectively, these findings suggest that, in mammalian spinal cord, Tgfβ ligands and ActB together support oligodendrocyte development and myelin formation. © 2014. Published by The Company of Biologists Ltd.

Combinatorial actions of Tgfβ and Activin ligands promote oligodendrocyte development and CNS myelination

Science.gov (United States)

Dutta, Dipankar J.; Zameer, Andleeb; Mariani, John N.; Zhang, Jingya; Asp, Linnea; Huynh, Jimmy; Mahase, Sean; Laitman, Benjamin M.; Argaw, Azeb Tadesse; Mitiku, Nesanet; Urbanski, Mateusz; Melendez-Vasquez, Carmen V.; Casaccia, Patrizia; Hayot, Fernand; Bottinger, Erwin P.; Brown, Chester W.; John, Gareth R.

2014-01-01

In the embryonic CNS, development of myelin-forming oligodendrocytes is limited by bone morphogenetic proteins, which constitute one arm of the transforming growth factor-β (Tgfβ) family and signal canonically via Smads 1/5/8. Tgfβ ligands and Activins comprise the other arm and signal via Smads 2/3, but their roles in oligodendrocyte development are incompletely characterized. Here, we report that Tgfβ ligands and activin B (ActB) act in concert in the mammalian spinal cord to promote oligodendrocyte generation and myelination. In mouse neural tube, newly specified oligodendrocyte progenitors (OLPs) are first exposed to Tgfβ ligands in isolation, then later in combination with ActB during maturation. In primary OLP cultures, Tgfβ1 and ActB differentially activate canonical Smad3 and non-canonical MAP kinase signaling. Both ligands enhance viability, and Tgfβ1 promotes proliferation while ActB supports maturation. Importantly, co-treatment strongly activates both signaling pathways, producing an additive effect on viability and enhancing both proliferation and differentiation such that mature oligodendrocyte numbers are substantially increased. Co-treatment promotes myelination in OLP-neuron co-cultures, and maturing oligodendrocytes in spinal cord white matter display strong Smad3 and MAP kinase activation. In spinal cords of ActB-deficient Inhbb−/− embryos, apoptosis in the oligodendrocyte lineage is increased and OLP numbers transiently reduced, but numbers, maturation and myelination recover during the first postnatal week. Smad3−/− mice display a more severe phenotype, including diminished viability and proliferation, persistently reduced mature and immature cell numbers, and delayed myelination. Collectively, these findings suggest that, in mammalian spinal cord, Tgfβ ligands and ActB together support oligodendrocyte development and myelin formation. PMID:24917498

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

International Nuclear Information System (INIS)

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

Evidence of demyelination in mild cognitive impairment and dementia using a direct and specific magnetic resonance imaging measure of myelin content.

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Bouhrara, Mustapha; Reiter, David A; Bergeron, Christopher M; Zukley, Linda M; Ferrucci, Luigi; Resnick, Susan M; Spencer, Richard G

2018-04-18

We investigated brain demyelination in aging, mild cognitive impairment (MCI), and dementia using magnetic resonance imaging of myelin. Brains of young and old controls and old subjects with MCI, Alzheimer's disease, or vascular dementia were scanned using our recently developed myelin water fraction (MWF) mapping technique, which provides greatly improved accuracy over previous comparable methods. Maps of MWF, a direct and specific myelin measure, and relaxation times and magnetization transfer ratio, indirect and nonspecific measures, were constructed. MCI subjects showed decreased MWF compared with old controls. Demyelination was greater in Alzheimer's disease or vascular dementia. As expected, decreased MWF was accompanied by decreased magnetization transfer ratio and increased relaxation times. The young subjects showed greater myelin content than the old subjects. We believe this to be the first demonstration of myelin loss in MCI, Alzheimer's disease, and vascular dementia using a method that provides a quantitative magnetic resonance imaging-based measure of myelin. Our findings add to the emerging evidence that myelination may represent an important biomarker for the pathology of MCI and dementia. This study supports the investigation of the role of myelination in MCI and dementia through use of this quantitative magnetic resonance imaging approach in clinical studies of disease progression, relationship of functional status to myelination status, and therapeutics. Furthermore, mapping MWF may permit myelin to serve as a therapeutic target in clinical trials. Copyright © 2018. Published by Elsevier Inc.

Ex vivo and in vivo coherent Raman imaging of the peripheral and central nervous system

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Huff, Terry Brandon

A hallmark of nervous system disorders is damage or degradation of the myelin sheath. Unraveling the mechanisms underlying myelin degeneration and repair represent one of the great challenges in medicine. This thesis work details the development and utilization of advanced optical imaging methods to gain insight into the structure and function of myelin in both healthy and diseased states in the in vivo environment. This first part of this thesis discusses ex vivo studies of the effects of high-frequency stimulation of spinal tissues on the structure of the node of Ranvier as investigated by coherent anti-Stokes Raman scattering (CARS) imaging (manuscript submitted to Journal of Neurosciece). Reversible paranodal myelin retraction at the nodes of Ranvier was observed during 200 Hz electrical stimulation, beginning minutes after the onset and continuing for up to 10 min after stimulation was ceased. A mechanistic study revealed a Ca2+ dependent pathway: high-frequency stimulation induced paranodal myelin retraction via pathologic calcium influx into axons, calpain activation, and cytoskeleton degradation through spectrin break-down. Also, the construction of dual-scanning CARS microscope for large area mapping of CNS tissues is detailed (Optics Express, 2008, 16:19396-193409). A confocal scanning head equipped with a rotating polygon mirror provides high speed, high resolution imaging and is coupled with a motorized sample stage to generate high-resolution large-area images of mouse brain coronal section and guinea pig spinal cord cross section. The polygon mirror decreases the mosaic acquisition time significantly without reducing the resolution of individual images. The ex vivo studies are then extended to in vivo imaging of mouse sciatic nerve tissue by CARS and second harmonic generation (SHG) imaging (Journal of Microscopy, 2007, 225: 175-182). Following a minimally invasive surgery to open the skin, CARS imaging of myelinated axons and SHG imaging of the

The deterioration seen in myelin related morphophysiology in ...

African Journals Online (AJOL)

Oligodendrocyte development and myelination occurs vigorously during the early post natal period which coincides with the period of peak mobilization of iron. Oligodendrocyte progenitor cells (OPCs) are easily disturbed by any agent that affects iron homeostasis and its assimilation into these cells. Environmental ...

Activation of Sterol Regulatory Element Binding Factors by Fenofibrate and Gemfibrozil Stimulate Myelination in Zebrafish

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Yuhei Nishimura

2016-07-01

Full Text Available Oligodendrocytes are major myelin-producing cells and play essential roles in the function of a healthy nervous system. However, they are also one of the most vulnerable neural cell types in the central nervous system (CNS, and myelin abnormalities in the CNS are found in a wide variety of neurological disorders, including multiple sclerosis, adrenoleukodystrophy, and schizophrenia. There is an urgent need to identify small molecular weight compounds that can stimulate myelination. In this study, we performed comparative transcriptome analysis to identify pharmacodynamic effects common to miconazole and clobetasol, which have been shown to stimulate myelination by mouse oligodendrocyte progenitor cells (OPCs. Of the genes differentially expressed in both miconazole- and clobetasol-treated mouse OPCs compared with untreated cells, we identified differentially expressed genes (DEGs common to both drug treatments. Gene ontology analysis revealed that these DEGs are significantly associated with the sterol biosynthetic pathway, and further bioinformatics analysis suggested that sterol regulatory element binding factors (SREBFs might be key upstream regulators of the DEGs. In silico screening of a public database for chemicals associated with SREBF activation identified fenofibrate, a peroxisome proliferator-activated receptor α (PPARα agonist, as a drug that increases the expression of known SREBF targets, raising the possibility that fenofibrate may also stimulate myelination. To test this, we performed in vivo imaging of zebrafish expressing a fluorescent reporter protein under the control of the myelin basic protein (mbp promoter. Treatment of zebrafish with fenofibrate significantly increased expression of the fluorescent reporter compared with untreated zebrafish. This increase was attenuated by co-treatment with fatostatin, a specific inhibitor of SREBFs, confirming that the fenofibrate effect was mediated via SREBFs. Furthermore, incubation

Prolonged Sox4 Expression in Oligodendrocytes Interferes with Normal Myelination in the Central Nervous System▿ †

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

2007-01-01

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

Study of the Peripheral Nerve Fibers Myelin Structure Changes during Activation of Schwann Cell Acetylcholine Receptors.

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Ekaterina E Verdiyan

Full Text Available In the present paper we consider a new type of mechanism by which neurotransmitter acetylcholine (ACh regulates the properties of peripheral nerve fibers myelin. Our data show the importance of the relationship between the changes in the number of Schwann cell (SC acetylcholine receptors (AChRs and the axon excitation (different intervals between action potentials (APs. Using Raman spectroscopy, an effect of activation of SC AChRs on the myelin membrane fluidity was investigated. It was found, that ACh stimulates an increase in lipid ordering degree of the myelin lipids, thus providing evidence for specific role of the "axon-SC" interactions at the axon excitation. It was proposed, that during the axon excitation, the SC membrane K+- depolarization and the Ca2+-influx led to phospholipase activation or exocytosis of intracellular membrane vesicles and myelin structure reorganization.

Stimulation of adult oligodendrogenesis by myelin-specific T cells

DEFF Research Database (Denmark)

Hvilsted Nielsen, Helle; Toft-Hansen, Henrik; Lambertsen, Kate Lykke

2011-01-01

of calretinergic associational/commissural fibers within the dentate gyrus. These results have implications for the perception of MS pathogenesis because they show that infiltrating myelin-specific T cells can stimulate oligodendrogenesis in the adult central nervous system....

Rapid myelin water imaging in human cervical spinal cord.

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Ljungberg, Emil; Vavasour, Irene; Tam, Roger; Yoo, Youngjin; Rauscher, Alexander; Li, David K B; Traboulsee, Anthony; MacKay, Alex; Kolind, Shannon

2017-10-01

Myelin water imaging (MWI) using multi-echo T 2 relaxation is a quantitative MRI technique that can be used as an in vivo biomarker for myelin in the central nervous system. MWI using a multi-echo spin echo sequence currently takes more than 20 min to acquire eight axial slices (5 mm thickness) in the cervical spinal cord, making spinal cord MWI impractical for implementation in clinical studies. In this study, an accelerated gradient and spin echo sequence (GRASE), previously validated for brain MWI, was adapted for spinal cord MWI. Ten healthy volunteers were scanned with the GRASE sequence (acquisition time 8.5 min) and compared with the multi-echo spin echo sequence (acquisition time 23.5 min). Using region of interest analysis, myelin estimates obtained from the two sequences were found to be in good agreement (mean difference = -0.0092, 95% confidence interval =  - 0.0092 ± 0.061; regression slope = 1.01, ρ = 0.9). MWI using GRASE was shown to be highly reproducible with an average coefficient of variation of 6.1%. The results from this study show that MWI can be performed in the cervical spinal cord in less than 10 min, allowing for practical implementation in multimodal clinical studies. Magn Reson Med 78:1482-1487, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

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

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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

A novel approach to 32-channel peripheral nervous system myelin imaging in vivo, with single axon resolution.

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Grochmal, Joey; Teo, Wulin; Gambhir, Hardeep; Kumar, Ranjan; Stratton, Jo Anne; Dhaliwal, Raveena; Brideau, Craig; Biernaskie, Jeff; Stys, Peter K; Midha, Rajiv

2018-01-19

OBJECTIVE Intravital spectral imaging of the large, deeply situated nerves in the rat peripheral nervous system (PNS) has not been well described. Here, the authors have developed a highly stable platform for performing imaging of the tibial nerve in live rodents, thus allowing the capture of high-resolution, high-magnification spectral images requiring long acquisition times. By further exploiting the qualities of the topically applied myelin dye Nile red, this technique is capable of visualizing the detailed microenvironment of peripheral nerve demyelination injury and recovery, while allowing us to obtain images of exogenous Schwann cell myelination in a living animal. METHODS The authors caused doxorubicin-induced focal demyelination in the tibial nerves of 25 Thy-1 GFP rats, of which 2 subsets (n = 10 each) received either BFP-labeled SKP-SCs or SCs to the zone of injury. Prior to acquiring images of myelin recovery in these nerves, a tibial nerve window was constructed using a silicone hemitube, a fast drying silicone polymer, and a small coverslip. This construct was then affixed to a 3D-printed nerve stage, which in turn was affixed to an external fixation/microscope stage device. Myelin visualization was facilitated by the topical application of Nile red. RESULTS The authors reliably demonstrated intravital peripheral nerve myelin imaging with micron-level resolution and magnification, and minimal movement artifact. The detailed microenvironment of nerve remyelination can be vividly observed, while exogenously applied Schwann cells and skin-derived precursor Schwann cells can be seen myelinating axons. CONCLUSIONS Topically applied Nile red enables intravital study of myelin in the living rat PNS. Furthermore, the use of a tibial nerve window facilitates stable intravital peripheral nerve imaging, making possible high-definition spectral imaging with long acquisition times.

Salvianolic acid B protects the myelin sheath around injured spinal cord axons

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Zhe Zhu

2016-01-01

Full Text Available Salvianolic acid B, an active pharmaceutical compound present in Salvia miltiorrhiza, exerts a neuroprotective effect in animal models of brain and spinal cord injury. Salvianolic acid B can promote recovery of neurological function; however, its protective effect on the myelin sheath after spinal cord injury remains poorly understood. Thus, in this study, in vitro tests showed that salvianolic acid B contributed to oligodendrocyte precursor cell differentiation, and the most effective dose was 20 μg/mL. For in vivo investigation, rats with spinal cord injury were intraperitoneally injected with 20 mg/kg salvianolic acid B for 8 weeks. The amount of myelin sheath and the number of regenerating axons increased, neurological function recovered, and caspase-3 expression was decreased in the spinal cord of salvianolic acid B-treated animals compared with untreated control rats. These results indicate that salvianolic acid B can protect axons and the myelin sheath, and can promote the recovery of neurological function. Its mechanism of action is likely to be associated with inhibiting apoptosis and promoting the differentiation and maturation of oligodendrocyte precursor cells.

Myelin basic protein in brains of rats with low dose lead encephalopathy

Energy Technology Data Exchange (ETDEWEB)

Sundstroem, R; Karlsson, B

1987-02-01

In the present study control rats and lead exposed rats which did not have any retardation of growth were examined by radioimmunological assay of myelin basic protein (MBP) of homogenates of cerebrum and cerebellum at 30, 60 and 120 days of age. Lead was administered on postnatal days 1-15 by daily intraperitoneal injections of 10 mg lead nitrate/kg body weight. This lead dose results in light microscopically discernible hemorrhagic encephalopathy in the cerebellum of 15-day old rats, but does not induce growth retardation. The controls were injected with vehicle only. The amount of lead in the blood and brain homogenates of lead-exposed and control rats 15-200 days old was estimated by atomic absorption spectrophotometry. Significant differences between the lead-exposed and control rats were not found in the cerebral or cerebellar content of MBP. Considering the results of previous investigations, the findings do not exclude a hypo-myelinating effect of lead, but they suggest that exposure to lead without concomitant malnutrition does not cause hypo-myelination in the cerebrum and cerebellum of the developing rat.

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. �

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

International Nuclear Information System (INIS)

Rai, Nagendra Kumar; Ashok, Anushruti; Rai, Asit; Tripathi, Sachin; Nagar, Geet Kumar; Mitra, Kalyan; Bandyopadhyay, Sanghamitra

2013-01-01

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. �

Proliferation of Schwann cells induced by axolemmal and myelin membranes

International Nuclear Information System (INIS)

Dinneen, M.

1985-01-01

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 3 H-thymidine uptake. The axolemmal mitogen was sensitive to heat (80 0 C for 10 minutes), trypsin digestion (0.05% x 30 mins) or to treatment with endoglycosidase D, suggesting that it could be a glycoprotein. Fifty percent of the axolemmal mitogenic activity was solubilized in 1% octyl-glucoside. The solubilized material, however, was very unstable and further purification was not possible. The myelin associated mitogenic activity was markedly different. It was resistant to freeze thaw cycles, trypsin digestion of endoglycosidase treatment and the activity was actually enhanced by heating at 100 0 C for two hours. It is proposed that the axolemmal activity is responsible for Schwann cell proliferation during development and that the myelin associated activity promotes Schwann cell proliferation during Wallerian degeneration

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cholecalciferol (vitamin D₃ improves myelination and recovery after nerve injury.

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Jean-Francois Chabas

Full Text Available Previously, we demonstrated i that ergocalciferol (vitamin D2 increases axon diameter and potentiates nerve regeneration in a rat model of transected peripheral nerve and ii that cholecalciferol (vitamin D3 improves breathing and hyper-reflexia in a rat model of paraplegia. However, before bringing this molecule to the clinic, it was of prime importance i to assess which form - ergocalciferol versus cholecalciferol - and which dose were the most efficient and ii to identify the molecular pathways activated by this pleiotropic molecule. The rat left peroneal nerve was cut out on a length of 10 mm and autografted in an inverted position. Animals were treated with either cholecalciferol or ergocalciferol, at the dose of 100 or 500 IU/kg/day, or excipient (Vehicle, and compared to unlesioned rats (Control. Functional recovery of hindlimb was measured weekly, during 12 weeks, using the peroneal functional index. Ventilatory, motor and sensitive responses of the regenerated axons were recorded and histological analysis was performed. In parallel, to identify the genes regulated by vitamin D in dorsal root ganglia and/or Schwann cells, we performed an in vitro transcriptome study. We observed that cholecalciferol is more efficient than ergocalciferol and, when delivered at a high dose (500 IU/kg/day, cholecalciferol induces a significant locomotor and electrophysiological recovery. We also demonstrated that cholecalciferol increases i the number of preserved or newly formed axons in the proximal end, ii the mean axon diameter in the distal end, and iii neurite myelination in both distal and proximal ends. Finally, we found a modified expression of several genes involved in axogenesis and myelination, after 24 hours of vitamin supplementation. Our study is the first to demonstrate that vitamin D acts on myelination via the activation of several myelin-associated genes. It paves the way for future randomised controlled clinical trials for peripheral

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

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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.

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

DEFF Research Database (Denmark)

Lozeron, Pierre; Krarup, Christian; Schmalbruch, Henning

2004-01-01

cells that had been labelled, i.e., that had regenerated axons towards or beyond the injection site, were counted in serial sections. Large and small neurons with presumably myelinated and unmyelinated axons, respectively, were classified by immunostaining for neurofilaments. The axonal growth rate......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...

Multiple sclerosis : Mechanisms of myelin phagocytosis and lesion expansion

NARCIS (Netherlands)

Hendrickx, D.A.E.

2018-01-01

Multiple sclerosis (MS) is characterized by immune activation and focal demyelination in the central nervous system. The aim of this thesis was to gain more insight into the mechanisms of myelin phagocytosis by resident microglia and infiltrating macrophages. We first evaluated the expression of the

Local delivery of thyroid hormone enhances oligodendrogenesis and myelination after spinal cord injury

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Shultz, Robert B.; Wang, Zhicheng; Nong, Jia; Zhang, Zhiling; Zhong, Yinghui

2017-06-01

Objective. Traumatic spinal cord injury (SCI) causes apoptosis of myelin-forming oligodendrocytes (OLs) and demyelination of surviving axons, resulting in conduction failure. Remyelination of surviving denuded axons provides a promising therapeutic target for spinal cord repair. While cell transplantation has demonstrated efficacy in promoting remyelination and functional recovery, the lack of ideal cell sources presents a major obstacle to clinical application. The adult spinal cord contains oligodendrocyte precursor cells and multipotent neural stem/progenitor cells that have the capacity to differentiate into mature, myelinating OLs. However, endogenous oligodendrogenesis and remyelination processes are limited by the upregulation of remyelination-inhibitory molecules in the post-injury microenvironment. Multiple growth factors/molecules have been shown to promote OL differentiation and myelination. Approach. In this study we screened these therapeutics and found that 3, 3‧, 5-triiodothyronine (T3) is the most effective in promoting oligodendrogenesis and OL maturation in vitro. However, systemic administration of T3 to achieve therapeutic doses in the injured spinal cord is likely to induce hyperthyroidism, resulting in serious side effects. Main results. In this study we developed a novel hydrogel-based drug delivery system for local delivery of T3 to the injury site without eliciting systemic toxicity. Significance. Using a clinically relevant cervical contusion injury model, we demonstrate that local delivery of T3 at doses comparable to safe human doses promoted new mature OL formation and myelination after SCI.

Long-term consequences of chronic fluoxetine exposure on the expression of myelination-related genes in the rat hippocampus

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Kroeze, Y; Peeters, D; Boulle, F; van den Hove, D L A; van Bokhoven, H; Zhou, H; Homberg, J R

2015-01-01

The selective serotonin reuptake inhibitor (SSRI) fluoxetine is widely prescribed for the treatment of symptoms related to a variety of psychiatric disorders. After chronic SSRI treatment, some symptoms remediate on the long term, but the underlying mechanisms are not yet well understood. Here we studied the long-term consequences (40 days after treatment) of chronic fluoxetine exposure on genome-wide gene expression. During the treatment period, we measured body weight; and 1 week after treatment, cessation behavior in an SSRI-sensitive anxiety test was assessed. Gene expression was assessed in hippocampal tissue of adult rats using transcriptome analysis and several differentially expressed genes were validated in independent samples. Gene ontology analysis showed that upregulated genes induced by chronic fluoxetine exposure were significantly enriched for genes involved in myelination. We also investigated the expression of myelination-related genes in adult rats exposed to fluoxetine at early life and found two myelination-related genes (Transferrin (Tf) and Ciliary neurotrophic factor (Cntf)) that were downregulated by chronic fluoxetine exposure. Cntf, a neurotrophic factor involved in myelination, showed regulation in opposite direction in the adult versus neonatally fluoxetine-exposed groups. Expression of myelination-related genes correlated negatively with anxiety-like behavior in both adult and neonatally fluoxetine-exposed rats. In conclusion, our data reveal that chronic fluoxetine exposure causes on the long-term changes in expression of genes involved in myelination, a process that shapes brain connectivity and contributes to symptoms of psychiatric disorders. PMID:26393488

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

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

2013-01-01

Protective properties of moderate wine consumption against cancers, cardiovascular, metabolic and degenerative diseases have been reported in various clinical studies. Here, we analysed the effect of red wine (RW) and white wine (WW) on myelination using an in vitro embryonic co-culture mouse model. The total amount of myelin was found to be significantly increased after RW and WW treatment, while only RW significantly increased the number of internodes. Both types of wine increased rat Schwann cell- (rSC) expression of the NAD+-dependent deacetylase sirtuin-two-homolog 2 (Sirt2), a protein known to be involved in myelination. Detailed chemical analysis of RW revealed a broad spectrum of anthocyanins, piceids, and phenolics, including resveratrol (RSV). In our assay system RSV in low concentrations induced myelination. Furthermore RSV raised intracellular glutathione concentrations in rSCs and in co-cultures and therefore augmented antioxidant capacity. We conclude that wine promotes myelination in a rodent in vitro model by controlling intracellular metabolism and SC plasticity. During this process, RSV exhibits protective properties; however, the fostering effect on myelinaton during exposure to wine appears to be a complex interaction of various compounds. PMID:23762469

Transverse Magnetic Waves in Myelinated Nerves

Science.gov (United States)

2001-10-25

IN MYELINATED NERVES M. Mª Villapecellín-Cid1, L. Mª Roa2, and J. Reina-Tosina1 1Área de Teoría de la Señal y Comunicaciones , E.S. de Ingeniería...Element Number Author(s) Project Number Task Number Work Unit Number Performing Organization Name(s) and Address(es) Área de Teoría de la Señal...y Comunicaciones , E.S. de Ingeniería, University of Seville, Seville, Spain Performing Organization Report Number Sponsoring/Monitoring Agency Name(s

SplitDist—Calculating Split-Distances for Sets of Trees

DEFF Research Database (Denmark)

Mailund, T

2004-01-01

We present a tool for comparing a set of input trees, calculating for each pair of trees the split-distances, i.e., the number of splits in one tree not present in the other.......We present a tool for comparing a set of input trees, calculating for each pair of trees the split-distances, i.e., the number of splits in one tree not present in the other....

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

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

2013-04-08

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.

Demyelinating polyneuropathy with focally folded myelin sheaths in a family of Miniature Schnauzer dogs.

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Vanhaesebrouck, An E; Couturier, Jérôme; Cauzinille, Laurent; Mizisin, Andrew P; Shelton, G Diane; Granger, Nicolas

2008-12-15

A spontaneous demyelinating polyneuropathy in two young Miniature Schnauzer dogs was characterized clinically, electrophysiologically and histopathologically. Both dogs were related and a third dog, belonging to the same family, had similar clinical signs. On presentation, clinical signs were restricted to respiratory dysfunction. Electrophysiological tests showed a dramatic decrease in both motor and sensory nerve conduction velocities. Microscopic examination of peripheral nerve biopsies (light and electron microscopy, teased nerve fibers), showed that this neuropathy was characterized by segmental demyelination and focally folded myelin sheaths. Various clinical syndromes associated with tomacula or focal thickening of the myelin sheath of the peripheral nerves have been described in humans and shown to be caused by gene mutations affecting the myelin proteins, such as the hereditary neuropathy with liability to pressure palsies or the demyelinating forms of Charcot-Marie-Tooth disease. In animals, a tomaculous neuropathy has been reported in cattle and chickens but not in carnivores. Here we report a demyelinating peripheral neuropathy with tomacula in two Miniature Schnauzer dogs.

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

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

2005-10-01

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

Flavonoids inhibit myelin phagocytosis by macrophages; a structure-activity relationship study

NARCIS (Netherlands)

Hendriks, Jerome J. A.; de Vries, Helga E.; van der Pol, Susanne M. A.; van den Berg, Timo K.; van Tol, Eric A. F.; Dijkstra, Christine D.

2003-01-01

Demyelination is a characteristic hallmark of the neuro-inflammatory disease multiple sclerosis. During demyelination, macrophages phagocytose myelin and secrete inflammatory mediators that worsen the disease. Here, we investigated whether flavonoids, naturally occurring immunomodulating compounds,

Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric features.

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Heidari, M; Johnstone, D M; Bassett, B; Graham, R M; Chua, A C G; House, M J; Collingwood, J F; Bettencourt, C; Houlden, H; Ryten, M; Olynyk, J K; Trinder, D; Milward, E A

2016-11-01

The 'neurodegeneration with brain iron accumulation' (NBIA) disease family entails movement or cognitive impairment, often with psychiatric features. To understand how iron loading affects the brain, we studied mice with disruption of two iron regulatory genes, hemochromatosis (Hfe) and transferrin receptor 2 (Tfr2). Inductively coupled plasma atomic emission spectroscopy demonstrated increased iron in the Hfe -/- × Tfr2 mut brain (P=0.002, n ≥5/group), primarily localized by Perls' staining to myelinated structures. Western immunoblotting showed increases of the iron storage protein ferritin light polypeptide and microarray and real-time reverse transcription-PCR revealed decreased transcript levels (Pgross myelin structure and integrity appear unaffected (P>0.05). Overlap (P0.05). These results implicate myelin-related systems involved in NBIA neuropathogenesis in early responses to iron loading. This may contribute to behavioral symptoms in NBIA and hemochromatosis and is relevant to patients with abnormal iron status and psychiatric disorders involving myelin abnormalities or resistant to conventional treatments.

Long-lasting masculinizing effects of postnatal androgens on myelin governed by the brain androgen receptor

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Abi Ghanem, Charly; Degerny, Cindy; Hussain, Rashad; Liere, Philippe; Pianos, Antoine; Tourpin, Sophie; Habert, René; Schumacher, Michael

2017-01-01

The oligodendrocyte density is greater and myelin sheaths are thicker in the adult male mouse brain when compared with females. Here, we show that these sex differences emerge during the first 10 postnatal days, precisely at a stage when a late wave of oligodendrocyte progenitor cells arises and starts differentiating. Androgen levels, analyzed by gas chromatography/tandem-mass spectrometry, were higher in males than in females during this period. Treating male pups with flutamide, an androgen receptor (AR) antagonist, or female pups with 5α-dihydrotestosterone (5α-DHT), revealed the importance of postnatal androgens in masculinizing myelin and their persistent effect into adulthood. A key role of the brain AR in establishing the sexual phenotype of myelin was demonstrated by its conditional deletion. Our results uncover a new persistent effect of postnatal AR signaling, with implications for neurodevelopmental disorders and sex differences in multiple sclerosis. PMID:29107990

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)

ElBarrany, Wagih G.; Hamdy, Raid M.; AlHayani, Abdulmonem A.; Jalalah, Sawsan M.

2009-01-01

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)

Schwann cell-derived Apolipoprotein D controls the dynamics of post-injury myelin recognition and degradation

Directory of Open Access Journals (Sweden)

Nadia eGarcía-Mateo

2014-11-01

Full Text Available Management of lipids, particularly signaling lipids that control neuroinflammation, is crucial for the regeneration capability of a damaged nervous system. Knowledge of pro- and anti-inflammatory signals after nervous system injury is extensive, most of them being proteins acting through well-known receptors and intracellular cascades. However, the role of lipid binding extracellular proteins able to modify the fate of lipids released after injury is not well understood.Apolipoprotein D (ApoD is an extracellular lipid binding protein of the Lipocalin family induced upon nervous system injury. Our previous study shows that axon regeneration is delayed without ApoD, and suggests its participation in early events during Wallerian degeneration. Here we demonstrate that ApoD is expressed by myelinating and non-myelinating Schwann cells and is induced early upon nerve injury. We show that ApoD, known to bind arachidonic acid (AA, also interacts with lysophosphatidylcholine (LPC in vitro. We use an in vivo model of nerve crush injury, a nerve explant injury model, and cultured macrophages exposed to purified myelin, to uncover that: (i ApoD regulates denervated Schwann cell-macrophage signaling, dampening MCP1- and Tnf-dependent macrophage recruitment and activation upon injury; (ii ApoD controls the over-expression of the phagocytosis activator Galectin-3 by infiltrated macrophages; (iii ApoD controls the basal and injury-triggered levels of LPC and AA; (iv ApoD modifies the dynamics of myelin-macrophage interaction, favoring the initiation of phagocytosis and promoting myelin degradation.Regulation of macrophage behaviour by Schwann-derived ApoD is therefore a key mechanism conditioning nerve injury resolution. These results place ApoD as a lipid binding protein controlling the signals exchanged between glia, neurons and blood-borne cells during nerve recovery after injury, and open the possibility for a therapeutic use of ApoD as a regeneration

Sustained neonatal hyperthyroidism in the rat affects myelination in the central nervous system.

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Marta, C B; Adamo, A M; Soto, E F; Pasquini, J M

1998-07-15

We have carried out a study of the effects of sustained neonatal hyperthyroidism on myelin and on the oligodendroglial cells, in an effort to obtain further insight into the molecular mechanisms underlying the action of thyroid hormones on the central nervous system (CNS). Expression of the mRNAs of myelin basic protein (MBP) myelin proteolipid protein (PLP), 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), transferrin, and c-Jun was investigated in 10- and 17-day-old normal and hyperthyroid rats, using Northern blot analysis. At 10 days of age, the levels of all the explored mRNAs were markedly higher in the experimental animals. The mRNA of transferrin showed a ninefold increase over control values, suggesting the possibility that this putative trophic factor might act as one of the mediators in the action of thyroid hormones. At 17 days of age on the other hand, the levels of all the mRNAs decreased markedly, reaching values below control, except for c-Jun, which remained higher than in normals. At 70 days of age, hyperthyroid rats showed clear evidence of myelin deficit, in agreement with previous results of our laboratories (Pasquini et al.: J Neurochem 57: Suppl S124, 1991). Immunocytochemistry of 70-day-old rat brain tissue sections showed a substantial reduction in the amount of MBP-reacting structures and a marked decrease in the number of oligodendroglial cells. Although the above-mentioned results could be the consequence, as proposed by Barres et al. (Development 120:1097-1108, 1994) and Baas et al. (Glia 19:324-332, 1997) of a premature arrest in oligodendroglial cell proliferation followed by early differentiation, the persistent high levels of expression of c-Jun, together with the dramatic decrease in the number of oligodendrocytes, suggested the possibility that prolonged hyperthyroidism could activate apoptotic mechanisms in the myelin forming cells. Using propidium iodide-labeled isolated oligodendroglial cells, we found, by flow cytometry

The effect of DDT and dieldrin on myelinated nerve fibres

NARCIS (Netherlands)

Bercken, J. van den

1972-01-01

The effects of the chlorinated hydrocarbon insecticides, DDT and dieldrin, on myelinated nerve fibres of the clawed toad, Xenopus laevis, were studied by recording compound action nerve fibres, and membrane potentials of single nodes of Ranvier. The effect of DDT (5 × 10−4 M) was found to be

Histological methods for assessing myelin sheaths and axons in human nerve trunks.

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Miko, T L; Gschmeissner, S E

1994-03-01

Although there are many histological techniques for assessing myelin sheaths and axons in paraffin embedded or frozen sections of the peripheral nervous system, modern approaches usually use plastic embedded material. Although plastic embedding is superior for small cutaneous branches, this method has limited value for histological assessment of nerve trunks. We report three methods which together yield a comprehensive approach for thorough and detailed investigation of human nerve trunks. The rapid osmication method permitted assessment of myelinated nerve fibers from frozen sections at operation, thus providing the surgeon with guidance on the extent of nerve resection. The modification presented here resulted in permanent slides, allowing comparison of results with those of the other two procedures. The new osmium-hematoxylin technique could be performed on paraffin embedded nerves. Paraffin, unlike plastic, permitted the study of the whole cross sectional area of the nerve in single sections. Moreover, the sharp image of the myelin permitted computerized morphometry. The significantly modified axonal silver impregnation technique was performed on frozen sections mounted on glass slides, as opposed to the time-consuming impregnation of free-floating sections. The latter technique had a high success rate and permitted semiquantitative assessment of axons in nerve trunks. These methods can be performed in any routine histology laboratory and resulted in greater accuracy compared to conventional methods.

Modelling the presence of myelin and oedema in the brain based on multi-parametric quantitative MRI

Directory of Open Access Journals (Sweden)

Marcel eWarntjes

2016-02-01

Full Text Available The aim of this study was to present a model that uses multi-parametric quantitative MRI to estimate the presence of myelin and oedema 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 normalised brain images of a group of 20 healthy controls. The pathological brain was modelled in terms of the reduction of myelin content and presence of excess parenchymal water, which indicates the degree of oedema. The method was tested on spatially normalised brain images of a group of 20 age-matched multiple sclerosis (MS patients. Clear differences were observed with respect to the healthy controls: the MS group had a 79 mL smaller brain volume (1069 vs. 1148 mL, a 38 mL smaller myelin volume (119 vs. 157 mL and a 21 mL larger excess parenchymal water volume (78 vs. 57 mL. Template regions of interest of various brain structures indicated that the myelin partial volume in the MS group was 1.6±1.5% lower for grey matter (GM structures and 2.8±1.0% lower for white matter (WM structures. The excess parenchymal water partial volume was 9±10% larger for GM and 5±2% larger for WM. Manually placed ROIs indicated that the results using the template ROIs may have suffered from loss of anatomical detail due to the spatial normalization process. Examples of the application of the method on high-resolution images are provided for three individual subjects, a 45-year-old healthy subject, a 72-year-old healthy subject and a 45-year-old MS patient. The observed results agreed with the expected behaviour considering both age and disease. In conclusion, the proposed model may provide clinically important parameters such as the total brain volume, degree of myelination and degree of oedema, based on

Introducing axonal myelination in connectomics: A preliminary analysis of g-ratio distribution in healthy subjects.

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Mancini, Matteo; Giulietti, Giovanni; Dowell, Nicholas; Spanò, Barbara; Harrison, Neil; Bozzali, Marco; Cercignani, Mara

2017-09-14

Microstructural imaging and connectomics are two research areas that hold great potential for investigating brain structure and function. Combining these two approaches can lead to a better and more complete characterization of the brain as a network. The aim of this work is characterizing the connectome from a novel perspective using the myelination measure given by the g-ratio. The g-ratio is the ratio of the inner to the outer diameters of a myelinated axon, whose aggregated value can now be estimated in vivo using MRI. In two different datasets of healthy subjects, we reconstructed the structural connectome and then used the g-ratio estimated from diffusion and magnetization transfer data to characterize the network structure. Significant characteristics of g-ratio weighted graphs emerged. First, the g-ratio distribution across the edges of the graph did not show the power-law distribution observed using the number of streamlines as a weight. Second, connections involving regions related to motor and sensory functions were the highest in myelin content. We also observed significant differences in terms of the hub structure and the rich-club organization suggesting that connections involving hub regions present higher myelination than peripheral connections. Taken together, these findings offer a characterization of g-ratio distribution across the connectome in healthy subjects and lay the foundations for further investigating plasticity and pathology using a similar approach. Copyright © 2017. Published by Elsevier Inc.

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

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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.

Automated brain tissue and myelin volumetry based on quantitative MR imaging with various in-plane resolutions.

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Andica, C; Hagiwara, A; Hori, M; Nakazawa, M; Goto, M; Koshino, S; Kamagata, K; Kumamaru, K K; Aoki, S

2018-05-01

Segmented brain tissue and myelin volumes can now be automatically calculated using dedicated software (SyMRI), which is based on quantification of R 1 and R 2 relaxation rates and proton density. The aim of this study was to determine the validity of SyMRI brain tissue and myelin volumetry using various in-plane resolutions. We scanned 10 healthy subjects on a 1.5T MR scanner with in-plane resolutions of 0.8, 2.0 and 3.0mm. Two scans were performed for each resolution. The acquisition time was 7-min and 24-sec for 0.8mm, 3-min and 9-sec for 2.0mm and 1-min and 56-sec for 3.0mm resolutions. The volumes of white matter (WM), gray matter (GM), cerebrospinal fluid (CSF), non-WM/GM/CSF (NoN), brain parenchymal volume (BPV), intracranial volume (ICV) and myelin were compared between in-plane resolutions. Repeatability for each resolution was then analyzed. No significant differences in volumes measured were found between the different in-plane resolutions, except for NoN between 0.8mm and 2.0mm and between 2.0mm and 3.0mm. The repeatability error value for the WM, GM, CSF, NoN, BPV and myelin volumes relative to ICV was 0.97%, 1.01%, 0.65%, 0.86%, 1.06% and 0.25% in 0.8mm; 1.22%, 1.36%, 0.73%, 0.37%, 1.18% and 0.35% in 2.0mm and 1.18%, 1.02%, 0.96%, 0.45%, 1.36%, and 0.28% in 3.0mm resolutions. SyMRI brain tissue and myelin volumetry with low in-plane resolution and short acquisition times is robust and has a good repeatability so could be useful for follow-up studies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Quantifying visual pathway axonal and myelin loss in multiple sclerosis and neuromyelitis optica.

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Manogaran, Praveena; Vavasour, Irene M; Lange, Alex P; Zhao, Yinshan; McMullen, Katrina; Rauscher, Alexander; Carruthers, Robert; Li, David K B; Traboulsee, Anthony L; Kolind, Shannon H

2016-01-01

The optic nerve is frequently injured in multiple sclerosis and neuromyelitis optica, resulting in visual dysfunction, which may be reflected by measures distant from the site of injury. To determine how retinal nerve fiber layer as a measure of axonal health, and macular volume as a measure of neuronal health are related to changes in myelin water fraction in the optic radiations of multiple sclerosis and neuromyelitis optica participants with and without optic neuritis and compared to healthy controls. 12 healthy controls, 42 multiple sclerosis (16 with optic neuritis), and 10 neuromyelitis optica participants (8 with optic neuritis) were included in this study. Optical coherence tomography assessment involved measurements of the segmented macular layers (total macular, ganglion cell layer, inner plexiform layer, and inner nuclear layer volume) and paripapillary retinal nerve fiber layer thickness. The MRI protocol included a 32-echo T2-relaxation GRASE sequence. Average myelin water fraction values were calculated within the optic radiations as a measure of myelin density. Multiple sclerosis and neuromyelitis optica eyes with optic neuritis history had lower retinal nerve fiber layer thickness, total macular, ganglion cell and inner plexiform layer volumes compared to eyes without optic neuritis history and controls. Inner nuclear layer volume increased in multiple sclerosis with optic neuritis history (mean = 0.99 mm(3), SD = 0.06) compared to those without (mean = 0.97 mm(3), SD = 0.06; p = 0.003). Mean myelin water fraction in the optic radiations was significantly lower in demyelinating diseases (neuromyelitis optica: mean = 0.098, SD = 0.01, multiple sclerosis with optic neuritis history: mean = 0.096, SD = 0.01, multiple sclerosis without optic neuritis history: mean = 0.098, SD = 0.02; F3,55 = 3.35, p = 0.03) compared to controls. Positive correlations between MRI and optical coherence tomography measures were also apparent

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

International Nuclear Information System (INIS)

Jiang, Tongsong; Jiang, Ziwu; Zhang, Zhaozhong

2015-01-01

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

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

Science.gov (United States)

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-mortem stability of these proteins. Small vessel disease (SVD) and cerebral amyloid angiopathy (CAA) severity had been assessed in paraffin sections. The concentration of MAG remained stable post-mortem, declined with increasing SVD, and was significantly lower in VaD than controls. The concentration of MBP fell progressively post-mortem, limiting its diagnostic utility in this context. Proteolipid protein was stable post-mortem and increased significantly with SVD severity. The MAG/PLP ratio declined significantly with SVD and CAA severity. The MAG and PLP levels and MAG/PLP did not differ significantly between AD and control brains. We validated the utility of MAG and MAG/PLP measurements on analysis of 74 frontal white matter samples from an Oxford cohort in which SVD had previously been scored. MAG concentration and the MAG/PLP ratio are useful post-mortem measures of ante-mortem white matter ischemia. PMID:23532085

Exposure to the Epstein–Barr Viral Antigen Latent Membrane Protein 1 Induces Myelin-Reactive Antibodies In Vivo

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Yakov Lomakin

2017-07-01

Full Text Available Multiple sclerosis (MS is an autoimmune chronic inflammatory disease of the central nervous system (CNS. Cross-reactivity of neuronal proteins with exogenous antigens is considered one of the possible mechanisms of MS triggering. Previously, we showed that monoclonal myelin basic protein (MBP-specific antibodies from MS patients cross-react with Epstein–Barr virus (EBV latent membrane protein 1 (LMP1. In this study, we report that exposure of mice to LMP1 results in induction of myelin-reactive autoantibodies in vivo. We posit that chronic exposure or multiple acute exposures to viral antigen may redirect B cells from production of antiviral antibodies to antibodies, specific to myelin antigen. However, even in inbred animals, which are almost identical in terms of their genomes, such an effect is only observed in 20–50% of animals, indicating that this change occurs by chance, rather than systematically. Cross-immunoprecipitation analysis showed that only part of anti-MBP antibodies from LMP1-immunized mice might simultaneously bind LMP1. In contrast, the majority of anti-LMP1 antibodies from MBP-immunized mice bind MBP. De novo sequencing of anti-LMP1 and anti-MBP antibodies by mass spectrometry demonstrated enhanced clonal diversity in LMP1-immunized mice in comparison with MBP-immunized mice. We suggest that induction of MBP-reactive antibodies in LMP1-immunized mice may be caused by either Follicular dendritic cells (FDCs or by T cells that are primed by myelin antigens directly in CNS. Our findings help to elucidate the still enigmatic link between EBV infection and MS development, suggesting that myelin-reactive antibodies raised as a response toward EBV protein LMP1 are not truly cross-reactive but are primarily caused by epitope spreading.

Exposure to the Epstein–Barr Viral Antigen Latent Membrane Protein 1 Induces Myelin-Reactive Antibodies In Vivo

Science.gov (United States)

Lomakin, Yakov; Arapidi, Georgii Pavlovich; Chernov, Alexander; Ziganshin, Rustam; Tcyganov, Evgenii; Lyadova, Irina; Butenko, Ivan Olegovich; Osetrova, Maria; Ponomarenko, Natalia; Telegin, Georgy; Govorun, Vadim Markovich; Gabibov, Alexander; Belogurov, Alexey

2017-01-01

Multiple sclerosis (MS) is an autoimmune chronic inflammatory disease of the central nervous system (CNS). Cross-reactivity of neuronal proteins with exogenous antigens is considered one of the possible mechanisms of MS triggering. Previously, we showed that monoclonal myelin basic protein (MBP)-specific antibodies from MS patients cross-react with Epstein–Barr virus (EBV) latent membrane protein 1 (LMP1). In this study, we report that exposure of mice to LMP1 results in induction of myelin-reactive autoantibodies in vivo. We posit that chronic exposure or multiple acute exposures to viral antigen may redirect B cells from production of antiviral antibodies to antibodies, specific to myelin antigen. However, even in inbred animals, which are almost identical in terms of their genomes, such an effect is only observed in 20–50% of animals, indicating that this change occurs by chance, rather than systematically. Cross-immunoprecipitation analysis showed that only part of anti-MBP antibodies from LMP1-immunized mice might simultaneously bind LMP1. In contrast, the majority of anti-LMP1 antibodies from MBP-immunized mice bind MBP. De novo sequencing of anti-LMP1 and anti-MBP antibodies by mass spectrometry demonstrated enhanced clonal diversity in LMP1-immunized mice in comparison with MBP-immunized mice. We suggest that induction of MBP-reactive antibodies in LMP1-immunized mice may be caused by either Follicular dendritic cells (FDCs) or by T cells that are primed by myelin antigens directly in CNS. Our findings help to elucidate the still enigmatic link between EBV infection and MS development, suggesting that myelin-reactive antibodies raised as a response toward EBV protein LMP1 are not truly cross-reactive but are primarily caused by epitope spreading. PMID:28729867

Exposure to the Epstein-Barr Viral Antigen Latent Membrane Protein 1 Induces Myelin-Reactive Antibodies In Vivo.

Science.gov (United States)

Lomakin, Yakov; Arapidi, Georgii Pavlovich; Chernov, Alexander; Ziganshin, Rustam; Tcyganov, Evgenii; Lyadova, Irina; Butenko, Ivan Olegovich; Osetrova, Maria; Ponomarenko, Natalia; Telegin, Georgy; Govorun, Vadim Markovich; Gabibov, Alexander; Belogurov, Alexey

2017-01-01

Multiple sclerosis (MS) is an autoimmune chronic inflammatory disease of the central nervous system (CNS). Cross-reactivity of neuronal proteins with exogenous antigens is considered one of the possible mechanisms of MS triggering. Previously, we showed that monoclonal myelin basic protein (MBP)-specific antibodies from MS patients cross-react with Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1). In this study, we report that exposure of mice to LMP1 results in induction of myelin-reactive autoantibodies in vivo . We posit that chronic exposure or multiple acute exposures to viral antigen may redirect B cells from production of antiviral antibodies to antibodies, specific to myelin antigen. However, even in inbred animals, which are almost identical in terms of their genomes, such an effect is only observed in 20-50% of animals, indicating that this change occurs by chance, rather than systematically. Cross-immunoprecipitation analysis showed that only part of anti-MBP antibodies from LMP1-immunized mice might simultaneously bind LMP1. In contrast, the majority of anti-LMP1 antibodies from MBP-immunized mice bind MBP. De novo sequencing of anti-LMP1 and anti-MBP antibodies by mass spectrometry demonstrated enhanced clonal diversity in LMP1-immunized mice in comparison with MBP-immunized mice. We suggest that induction of MBP-reactive antibodies in LMP1-immunized mice may be caused by either Follicular dendritic cells (FDCs) or by T cells that are primed by myelin antigens directly in CNS. Our findings help to elucidate the still enigmatic link between EBV infection and MS development, suggesting that myelin-reactive antibodies raised as a response toward EBV protein LMP1 are not truly cross-reactive but are primarily caused by epitope spreading.

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

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Liu Huaqing

2012-06-01

Full Text Available Abstract Background The myelin sheath provides electrical insulation of mechanosensory Aβ-afferent fibers. Myelin-degrading matrix metalloproteinases (MMPs damage the myelin sheath. The resulting electrical instability of Aβ-fibers is believed to activate the nociceptive circuitry in Aβ-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-α and IL-17A expression in nerves. MMP-9 proteolysis of myelin basic protein (MBP generated the MBP84-104 and MBP68-86 digest peptides, which are prominent immunogenic epitopes. In agreement, the endogenous MBP69-86 epitope co-localized with MHCII and MMP-9 in Schwann cells and along the nodes of Ranvier. Administration of either the MBP84-104 or MBP68-86 peptides into the naïve nerve rapidly produced robust mechanical allodynia with a concomitant increase in T cells and MHCII-reactive cell populations at the injection site. As shown by the genome-wide expression profiling, a single intraneural MBP84-104 injection stimulated the inflammatory, immune cell trafficking, and antigen presentation pathways in the injected naïve nerves and the associated spinal cords. Both MBP84-104-induced mechanical allodynia and characteristic pathway activation were remarkably less prominent in the T cell-deficient athymic nude rats. Conclusions These data implicate MBP as a novel mediator of pain. Furthermore, the action of MMPs expressed within 1�

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

Science.gov (United States)

Liu, Huaqing; Shiryaev, Sergey A; Chernov, Andrei V; Kim, Youngsoon; Shubayev, Igor; Remacle, Albert G; Baranovskaya, Svetlana; Golubkov, Vladislav S; Strongin, Alex Y; Shubayev, Veronica I

2012-06-07

The myelin sheath provides electrical insulation of mechanosensory Aβ-afferent fibers. Myelin-degrading matrix metalloproteinases (MMPs) damage the myelin sheath. The resulting electrical instability of Aβ-fibers is believed to activate the nociceptive circuitry in Aβ-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. 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-α and IL-17A expression in nerves. MMP-9 proteolysis of myelin basic protein (MBP) generated the MBP84-104 and MBP68-86 digest peptides, which are prominent immunogenic epitopes. In agreement, the endogenous MBP69-86 epitope co-localized with MHCII and MMP-9 in Schwann cells and along the nodes of Ranvier. Administration of either the MBP84-104 or MBP68-86 peptides into the naïve nerve rapidly produced robust mechanical allodynia with a concomitant increase in T cells and MHCII-reactive cell populations at the injection site. As shown by the genome-wide expression profiling, a single intraneural MBP84-104 injection stimulated the inflammatory, immune cell trafficking, and antigen presentation pathways in the injected naïve nerves and the associated spinal cords. Both MBP84-104-induced mechanical allodynia and characteristic pathway activation were remarkably less prominent in the T cell-deficient athymic nude rats. 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, myelin and behavior: Temporal patterns following mild traumatic brain injury in mice.

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Toufik Taib

Full Text Available Traumatic brain injury (TBI results in white matter injury (WMI that is associated with neurological deficits. Neuroinflammation originating from microglial activation may participate in WMI and associated disorders. To date, there is little information on the time courses of these events after mild TBI. Therefore we investigated (i neuroinflammation, (ii WMI and (iii behavioral disorders between 6 hours and 3 months after mild TBI. For that purpose, we used experimental mild TBI in mice induced by a controlled cortical impact. (i For neuroinflammation, IL-1b protein as well as microglial phenotypes, by gene expression for 12 microglial activation markers on isolated CD11b+ cells from brains, were studied after TBI. IL-1b protein was increased at 6 hours and 1 day. TBI induced a mixed population of microglial phenotypes with both pro-inflammatory, anti-inflammatory and immunomodulatory markers from 6 hours to 3 days post-injury. At 7 days, microglial activation was completely resolved. (ii Three myelin proteins were assessed after TBI on ipsi- and contralateral corpus callosum, as this structure is enriched in white matter. TBI led to an increase in 2',3'-cyclic-nucleotide 3'-phosphodiesterase, a marker of immature and mature oligodendrocyte, at 2 days post-injury; a bilateral demyelination, evaluated by myelin basic protein, from 7 days to 3 months post-injury; and an increase in myelin oligodendrocyte glycoprotein at 6 hours and 3 days post-injury. Transmission electron microscopy study revealed various myelin sheath abnormalities within the corpus callosum at 3 months post-TBI. (iii TBI led to sensorimotor deficits at 3 days post-TBI, and late cognitive flexibility disorder evidenced by the reversal learning task of the Barnes maze 3 months after injury. These data give an overall invaluable overview of time course of neuroinflammation that could be involved in demyelination and late cognitive disorder over a time-scale of 3 months in a model

Polarization Insensitivity in Double-Split Ring and Triple-Split Ring Terahertz Resonators

International Nuclear Information System (INIS)

Wu Qian-Nan; Lan Feng; Tang Xiao-Pin; Yang Zi-Qiang

2015-01-01

A modified double-split ring resonator and a modified triple-split ring resonator, which offer polarization-insensitive performance, are investigated, designed and fabricated. By displacing the two gaps of the conventional double-split ring resonator away from the center, the second resonant frequency for the 0° polarized wave and the resonant frequency for the 90° polarized wave become increasingly close to each other until they are finally identical. Theoretical and experimental results show that the modified double-split ring resonator and the modified triple-split ring resonator are insensitive to different polarized waves and show strong resonant frequency dips near 433 and 444 GHz, respectively. The results of this work suggest new opportunities for the investigation and design of polarization-dependent terahertz devices based on split ring resonators. (paper)

Sustained Expression of Negative Regulators of Myelination Protects Schwann Cells from Dysmyelination in a Charcot-Marie-Tooth 1B Mouse Model.

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Florio, Francesca; Ferri, Cinzia; Scapin, Cristina; Feltri, M Laura; Wrabetz, Lawrence; D'Antonio, Maurizio

2018-05-02

Schwann cell differentiation and myelination in the PNS are the result of fine-tuning of positive and negative transcriptional regulators. As myelination starts, negative regulators are downregulated, whereas positive ones are upregulated. Fully differentiated Schwann cells maintain an extraordinary plasticity and can transdifferentiate into "repair" Schwann cells after nerve injury. Reactivation of negative regulators of myelination is essential to generate repair Schwann cells. Negative regulators have also been implicated in demyelinating neuropathies, although their role in disease remains elusive. Here, we used a mouse model of Charcot-Marie-Tooth neuropathy type 1B (CMT1B), the P0S63del mouse characterized by ER stress and the activation of the unfolded protein response, to show that adult Schwann cells are in a partial differentiation state because they overexpress transcription factors that are normally expressed only before myelination. We provide evidence that two of these factors, Sox2 and Id2, act as negative regulators of myelination in vivo However, their sustained expression in neuropathy is protective because ablation of Sox2 or/and Id2 from S63del mice of both sexes results in worsening of the dysmyelinating phenotype. This is accompanied by increased levels of mutant P0 expression and exacerbation of ER stress, suggesting that limited differentiation may represent a novel adaptive mechanism through which Schwann cells counter the toxic effect of a mutant terminal differentiation protein. SIGNIFICANCE STATEMENT In many neuropathies, Schwann cells express high levels of early differentiation genes, but the significance of these altered expression remained unclear. Because many of these factors may act as negative regulators of myelination, it was suggested that their misexpression could contribute to dysmyelination. Here, we show that the transcription factors Sox2 and Id2 act as negative regulators of myelination in vivo , but that their sustained

Bad splits in bilateral sagittal split osteotomy: systematic review of fracture patterns.

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Steenen, S A; Becking, A G

2016-07-01

An unfavourable and unanticipated pattern of the mandibular sagittal split osteotomy is generally referred to as a 'bad split'. Few restorative techniques to manage the situation have been described. In this article, a classification of reported bad split pattern types is proposed and appropriate salvage procedures to manage the different types of undesired fracture are presented. A systematic review was undertaken, yielding a total of 33 studies published between 1971 and 2015. These reported a total of 458 cases of bad splits among 19,527 sagittal ramus osteotomies in 10,271 patients. The total reported incidence of bad split was 2.3% of sagittal splits. The most frequently encountered were buccal plate fractures of the proximal segment (types 1A-F) and lingual fractures of the distal segment (types 2A and 2B). Coronoid fractures (type 3) and condylar neck fractures (type 4) have seldom been reported. The various types of bad split may require different salvage approaches. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Boric acid reduces axonal and myelin damage in experimental sciatic nerve injury

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Zahir Kizilay

2016-01-01

Full Text Available The aim of this study was to investigate the effects of boric acid in experimental acute sciatic nerve injury. Twenty-eight adult male rats were randomly divided into four equal groups (n = 7: control (C, boric acid (BA, sciatic nerve injury (I , and sciatic nerve injury + boric acid treatment (BAI. Sciatic nerve injury was generated using a Yasargil aneurysm clip in the groups I and BAI. Boric acid was given four times at 100 mg/kg to rats in the groups BA and BAI after injury (by gavage at 0, 24, 48 and 72 hours but no injury was made in the group BA. In vivo electrophysiological tests were performed at the end of the day 4 and sciatic nerve tissue samples were taken for histopathological examination. The amplitude of compound action potential, the nerve conduction velocity and the number of axons were significantly lower and the myelin structure was found to be broken in group I compared with those in groups C and BA. However, the amplitude of the compound action potential, the nerve conduction velocity and the number of axons were significantly greater in group BAI than in group I. Moreover, myelin injury was significantly milder and the intensity of nuclear factor kappa B immunostaining was significantly weaker in group BAI than in group I. The results of this study show that administration of boric acid at 100 mg/kg after sciatic nerve injury in rats markedly reduces myelin and axonal injury and improves the electrophysiological function of injured sciatic nerve possibly through alleviating oxidative stress reactions.

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

International Nuclear Information System (INIS)

Vargas, V.; Vargas, R.; Marquez, G.; Vonasek, E.; Mateu, L.; Luzzati, V.; Borges, J.

2000-01-01

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.)

After Nerve Injury, Lineage Tracing Shows That Myelin and Remak Schwann Cells Elongate Extensively and Branch to Form Repair Schwann Cells, Which Shorten Radically on Remyelination.

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Gomez-Sanchez, Jose A; Pilch, Kjara S; van der Lans, Milou; Fazal, Shaline V; Benito, Cristina; Wagstaff, Laura J; Mirsky, Rhona; Jessen, Kristjan R

2017-09-13

There is consensus that, distal to peripheral nerve injury, myelin and Remak cells reorganize to form cellular columns, Bungner's bands, which are indispensable for regeneration. However, knowledge of the structure of these regeneration tracks has not advanced for decades and the structure of the cells that form them, denervated or repair Schwann cells, remains obscure. Furthermore, the origin of these cells from myelin and Remak cells and their ability to give rise to myelin cells after regeneration has not been demonstrated directly, although these conversions are believed to be central to nerve repair. Using genetic lineage-tracing and scanning-block face electron microscopy, we show that injury of sciatic nerves from mice of either sex triggers extensive and unexpected Schwann cell elongation and branching to form long, parallel processes. Repair cells are 2- to 3-fold longer than myelin and Remak cells and 7- to 10-fold longer than immature Schwann cells. Remarkably, when repair cells transit back to myelinating cells, they shorten ∼7-fold to generate the typically short internodes of regenerated nerves. The present experiments define novel morphological transitions in injured nerves and show that repair Schwann cells have a cell-type-specific structure that differentiates them from other cells in the Schwann cell lineage. They also provide the first direct evidence using genetic lineage tracing for two basic assumptions in Schwann cell biology: that myelin and Remak cells generate the elongated cells that build Bungner bands in injured nerves and that such cells can transform to myelin cells after regeneration. SIGNIFICANCE STATEMENT After injury to peripheral nerves, the myelin and Remak Schwann cells distal to the injury site reorganize and modify their properties to form cells that support the survival of injured neurons, promote axon growth, remove myelin-associated growth inhibitors, and guide regenerating axons to their targets. We show that the

Market Structure and Stock Splits

OpenAIRE

David Michayluk; Paul Kofman

2001-01-01

Enhanced liquidity is one possible motivation for stock splits but empirical research frequently documents declines in liquidity following stock splits. Despite almost thirty years of inquiry, little is known about all the changes in a stock's trading activity following a stock split. We examine how liquidity measures change around more than 2,500 stock splits and find a pervasive decline in most measures. Large stock splits exhibit a more severe liquidity decline than small stock splits, esp...

Impact of morphometry, myelinization and synaptic current strength on spike conduction in human and cat spiral ganglion neurons.

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Frank Rattay

Full Text Available Our knowledge about the neural code in the auditory nerve is based to a large extent on experiments on cats. Several anatomical differences between auditory neurons in human and cat are expected to lead to functional differences in speed and safety of spike conduction.Confocal microscopy was used to systematically evaluate peripheral and central process diameters, commonness of myelination and morphology of spiral ganglion neurons (SGNs along the cochlea of three human and three cats. Based on these morphometric data, model analysis reveales that spike conduction in SGNs is characterized by four phases: a postsynaptic delay, constant velocity in the peripheral process, a presomatic delay and constant velocity in the central process. The majority of SGNs are type I, connecting the inner hair cells with the brainstem. In contrast to those of humans, type I neurons of the cat are entirely myelinated. Biophysical model evaluation showed delayed and weak spikes in the human soma region as a consequence of a lack of myelin. The simulated spike conduction times are in accordance with normal interwave latencies from auditory brainstem response recordings from man and cat. Simulated 400 pA postsynaptic currents from inner hair cell ribbon synapses were 15 times above threshold. They enforced quick and synchronous spiking. Both of these properties were not present in type II cells as they receive fewer and much weaker (∼26 pA synaptic stimuli.Wasting synaptic energy boosts spike initiation, which guarantees the rapid transmission of temporal fine structure of auditory signals. However, a lack of myelin in the soma regions of human type I neurons causes a large delay in spike conduction in comparison with cat neurons. The absent myelin, in combination with a longer peripheral process, causes quantitative differences of temporal parameters in the electrically stimulated human cochlea compared to the cat cochlea.

Impact of Morphometry, Myelinization and Synaptic Current Strength on Spike Conduction in Human and Cat Spiral Ganglion Neurons

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Rattay, Frank; Potrusil, Thomas; Wenger, Cornelia; Wise, Andrew K.; Glueckert, Rudolf; Schrott-Fischer, Anneliese

2013-01-01

Background Our knowledge about the neural code in the auditory nerve is based to a large extent on experiments on cats. Several anatomical differences between auditory neurons in human and cat are expected to lead to functional differences in speed and safety of spike conduction. Methodology/Principal Findings Confocal microscopy was used to systematically evaluate peripheral and central process diameters, commonness of myelination and morphology of spiral ganglion neurons (SGNs) along the cochlea of three human and three cats. Based on these morphometric data, model analysis reveales that spike conduction in SGNs is characterized by four phases: a postsynaptic delay, constant velocity in the peripheral process, a presomatic delay and constant velocity in the central process. The majority of SGNs are type I, connecting the inner hair cells with the brainstem. In contrast to those of humans, type I neurons of the cat are entirely myelinated. Biophysical model evaluation showed delayed and weak spikes in the human soma region as a consequence of a lack of myelin. The simulated spike conduction times are in accordance with normal interwave latencies from auditory brainstem response recordings from man and cat. Simulated 400 pA postsynaptic currents from inner hair cell ribbon synapses were 15 times above threshold. They enforced quick and synchronous spiking. Both of these properties were not present in type II cells as they receive fewer and much weaker (∼26 pA) synaptic stimuli. Conclusions/Significance Wasting synaptic energy boosts spike initiation, which guarantees the rapid transmission of temporal fine structure of auditory signals. However, a lack of myelin in the soma regions of human type I neurons causes a large delay in spike conduction in comparison with cat neurons. The absent myelin, in combination with a longer peripheral process, causes quantitative differences of temporal parameters in the electrically stimulated human cochlea compared to the cat

Differential distribution of voltage-gated ion channels in cortical neurons: implications for epilepsy.

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Child, Nicholas D; Benarroch, Eduardo E

2014-03-18

Neurons contain different functional somatodendritic and axonal domains, each with a characteristic distribution of voltage-gated ion channels, synaptic inputs, and function. The dendritic tree of a cortical pyramidal neuron has 2 distinct domains, the basal and the apical dendrites, both containing dendritic spines; the different domains of the axon are the axonal initial segment (AIS), axon proper (which in myelinated axons includes the node of Ranvier, paranodes, juxtaparanodes, and internodes), and the axon terminals. In the cerebral cortex, the dendritic spines of the pyramidal neurons receive most of the excitatory synapses; distinct populations of γ-aminobutyric acid (GABA)ergic interneurons target specific cellular domains and thus exert different influences on pyramidal neurons. The multiple synaptic inputs reaching the somatodendritic region and generating excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) sum and elicit changes in membrane potential at the AIS, the site of initiation of the action potential.

Morphometric analysis of the diameter and g-ratio of the myelinated nerve fibers of the human sciatic nerve during the aging process.

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Ugrenović, Sladjana; Jovanović, Ivan; Vasović, Ljiljana; Kundalić, Braca; Čukuranović, Rade; Stefanović, Vladisav

2016-06-01

Myelinated nerve fibers suffer from different degrees of atrophy with age. The success of subsequent regeneration varies. The aim of this research was to analyze myelinated fibers of the human sciatic nerve during the aging process. Morphometric analysis was performed on 17 cases with an age range from 9 to 93 years. The outer and inner diameter of 100 randomly selected nerve fibers was measured in each of the cases evaluated, and the g-ratio (axonal diameter/outer diameter of the whole nerve fiber) of each was calculated. Scatter plots of the diameters and g-ratios of the analyzed fibers were then analyzed. Nerve fibers of each case were classified into three groups according to the g-ratio values: group I (g-ratio lower than 0.6), group II (g-ratio from 0.6 to 0.7) and group III (g-ratio higher than 0.7). Afterwards, nerve fibers of group II were further classified into small and large subgroups. The percentages of each group of nerve fibers were computed for each case and these values were used for correlational and bivariate linear regression analysis. The percentage of myelinated nerve fibers with large diameter and optimal g-ratio of the sciatic nerve declines significantly with age. This is accompanied by a simultaneous significant increase in the percentage of small myelinated fibers with g-ratio values close to 1 that occupy the upper left quadrant of the scatter plot. It can be concluded that aging of the sciatic nerve is associated with significant atrophy of large myelinated fibers. Additionally, a significant increase in regenerated nerve fibers with thinner myelin sheath is observed with age, which, together with the large myelinated fiber atrophy, might be the cause of the age-related decline in conduction velocity. A better understanding of the changes in aging peripheral nerves might improve interpretation of their pathological changes, as well as comprehension of their regeneration in individuals of different age.

What is the optimal value of the g-ratio for myelinated fibers in the rat CNS? A theoretical approach.

Directory of Open Access Journals (Sweden)

Taylor Chomiak

2009-11-01

Full Text Available The biological process underlying axonal myelination is complex and often prone to injury and disease. The ratio of the inner axonal diameter to the total outer diameter or g-ratio is widely utilized as a functional and structural index of optimal axonal myelination. Based on the speed of fiber conduction, Rushton was the first to derive a theoretical estimate of the optimal g-ratio of 0.6 [1]. This theoretical limit nicely explains the experimental data for myelinated axons obtained for some peripheral fibers but appears significantly lower than that found for CNS fibers. This is, however, hardly surprising given that in the CNS, axonal myelination must achieve multiple goals including reducing conduction delays, promoting conduction fidelity, lowering energy costs, and saving space.In this study we explore the notion that a balanced set-point can be achieved at a functional level as the micro-structure of individual axons becomes optimized, particularly for the central system where axons tend to be smaller and their myelin sheath thinner. We used an intuitive yet novel theoretical approach based on the fundamental biophysical properties describing axonal structure and function to show that an optimal g-ratio can be defined for the central nervous system (approximately 0.77. Furthermore, by reducing the influence of volume constraints on structural design by about 40%, this approach can also predict the g-ratio observed in some peripheral fibers (approximately 0.6.These results support the notion of optimization theory in nervous system design and construction and may also help explain why the central and peripheral systems have evolved different g-ratios as a result of volume constraints.

What is the optimal value of the g-ratio for myelinated fibers in the rat CNS? A theoretical approach.

Science.gov (United States)

Chomiak, Taylor; Hu, Bin

2009-11-13

The biological process underlying axonal myelination is complex and often prone to injury and disease. The ratio of the inner axonal diameter to the total outer diameter or g-ratio is widely utilized as a functional and structural index of optimal axonal myelination. Based on the speed of fiber conduction, Rushton was the first to derive a theoretical estimate of the optimal g-ratio of 0.6 [1]. This theoretical limit nicely explains the experimental data for myelinated axons obtained for some peripheral fibers but appears significantly lower than that found for CNS fibers. This is, however, hardly surprising given that in the CNS, axonal myelination must achieve multiple goals including reducing conduction delays, promoting conduction fidelity, lowering energy costs, and saving space. In this study we explore the notion that a balanced set-point can be achieved at a functional level as the micro-structure of individual axons becomes optimized, particularly for the central system where axons tend to be smaller and their myelin sheath thinner. We used an intuitive yet novel theoretical approach based on the fundamental biophysical properties describing axonal structure and function to show that an optimal g-ratio can be defined for the central nervous system (approximately 0.77). Furthermore, by reducing the influence of volume constraints on structural design by about 40%, this approach can also predict the g-ratio observed in some peripheral fibers (approximately 0.6). These results support the notion of optimization theory in nervous system design and construction and may also help explain why the central and peripheral systems have evolved different g-ratios as a result of volume constraints.

'Leukodystrophy-like' phenotype in children with myelin oligodendrocyte glycoprotein antibody-associated disease.

Science.gov (United States)

Hacohen, Yael; Rossor, Thomas; Mankad, Kshitij; Chong, Wk 'Kling'; Lux, Andrew; Wassmer, Evangeline; Lim, Ming; Barkhof, Frederik; Ciccarelli, Olga; Hemingway, Cheryl

2018-04-01

To review the demographics and clinical and paraclinical parameters of children with myelin oligodendrocyte glycoprotein (MOG) antibody-associated relapsing disease. In this UK-based, multicentre study, 31 children with MOG antibody-associated relapsing disease were studied retrospectively. Of the 31 children studied, 14 presented with acute disseminated encephalomyelitis (ADEM); they were younger (mean 4.1y) than the remainder (mean 8.5y) who presented with optic neuritis and/or transverse myelitis (p<0.001). Similarly, children who had an abnormal brain magnetic resonance imaging (MRI) at onset (n=20) were younger than patients with normal MRI at onset (p=0.001) or at follow-up (p<0.001). 'Leukodystrophy-like' MRI patterns of confluent largely symmetrical lesions was seen during the course of the disease in 7 out of 14 children with a diagnosis of ADEM, and was only seen in children younger than 7 years of age. Their disability after a 3-year follow-up was mild to moderate, and most patients continued to relapse, despite disease-modifying treatments. MOG antibody should be tested in children presenting with relapsing neurological disorders associated with confluent, bilateral white matter changes, and distinct enhancement pattern. Children with MOG antibody-associated disease present with age-related differences in phenotypes, with a severe leukoencephalopathy phenotype in the very young and normal intracranial MRI in the older children. This finding suggests a susceptibility of the very young and myelinating brain to MOG antibody-mediated mechanisms of damage. Myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination manifest with an age-related phenotype. Children with MOG antibody and 'leukodystrophy-like' imaging patterns tend to have poor response to second-line immunotherapy. © 2017 Mac Keith Press.

Analysis of the induction of the myelin basic protein binding to the plasma membrane phospholipid monolayer

International Nuclear Information System (INIS)

Zhang Lei; Hao Changchun; Feng Ying; Gao Feng; Lu Xiaolong; Li Junhua; Sun Runguang

2016-01-01

Myelin basic protein (MBP) is an essential structure involved in the generation of central nervous system (CNS) myelin. Myelin shape has been described as liquid crystal structure of biological membrane. The interactions of MBP with monolayers of different lipid compositions are responsible for the multi-lamellar structure and stability of myelin. In this paper, we have designed MBP-incorporated model lipid monolayers and studied the phase behavior of MBP adsorbed on the plasma membrane at the air/water interface by thermodynamic method and atomic force microscopy (AFM). By analyzing the pressure–area ( π – A ) and pressure–time ( π – T ) isotherms, univariate linear regression equation was obtained. In addition, the elastic modulus, surface pressure increase, maximal insertion pressure, and synergy factor of monolayers were detected. These parameters can be used to modulate the monolayers binding of protein, and the results show that MBP has the strongest affinity for 1,2-dipalmitoyl-sn-glycero-3- phosphoserine (DPPS) monolayer, followed by DPPC/DPPS mixed and 1,2-dipalmitoyl-sn-glycero-3-phospho-choline (DPPC) monolayers via electrostatic and hydrophobic interactions. AFM images of DPPS and DPPC/DPPS mixed monolayers in the presence of MBP (5 nM) show a phase separation texture at the surface pressure of 20 mN/m and the incorporation of MBP put into the DPPC monolayers has exerted a significant effect on the domain structure. MBP is not an integral membrane protein but, due to its positive charge, interacts with the lipid head groups and stabilizes the membranes. The interaction between MBP and phospholipid membrane to determine the nervous system of the disease has a good biophysical significance and medical value. (special topic)

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

DEFF Research Database (Denmark)

Nielsen, Helle Hvilsted; Ladeby, Rune; Fenger, Christina

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 nervo...

Splitting methods for split feasibility problems with application to Dantzig selectors

International Nuclear Information System (INIS)

He, Hongjin; Xu, Hong-Kun

2017-01-01

The split feasibility problem (SFP), which refers to the task of finding a point that belongs to a given nonempty, closed and convex set, and whose image under a bounded linear operator belongs to another given nonempty, closed and convex set, has promising applicability in modeling a wide range of inverse problems. Motivated by the increasingly data-driven regularization in the areas of signal/image processing and statistical learning, in this paper, we study the regularized split feasibility problem (RSFP), which provides a unified model for treating many real-world problems. By exploiting the split nature of the RSFP, we shall gainfully employ several efficient splitting methods to solve the model under consideration. A remarkable advantage of our methods lies in their easier subproblems in the sense that the resulting subproblems have closed-form representations or can be efficiently solved up to a high precision. As an interesting application, we apply the proposed algorithms for finding Dantzig selectors, in addition to demonstrating the effectiveness of the splitting methods through some computational results on synthetic and real medical data sets. (paper)

Coded Splitting Tree Protocols

DEFF Research Database (Denmark)

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

2013-01-01

This paper presents a novel approach to multiple access control called coded splitting tree protocol. The approach builds on the known tree splitting protocols, code structure and successive interference cancellation (SIC). Several instances of the tree splitting protocol are initiated, each...... instance is terminated prematurely and subsequently iterated. The combined set of leaves from all the tree instances can then be viewed as a graph code, which is decodable using belief propagation. The main design problem is determining the order of splitting, which enables successful decoding as early...

Functional organization of an Mbp enhancer exposes striking transcriptional regulatory diversity within myelinating glia

DEFF Research Database (Denmark)

Dionne, Nancy; Dib, Samar; Finsen, Bente

2016-01-01

regulatory element combinations were found to drive expression in oligodendrocytes and Schwann cells with a minimal 129 bp sequence conferring expression in oligodendrocytes throughout myelin elaboration, maintenance and repair. Unexpectedly, M3 derivatives conferred markedly different spatial and temporal...

Evaluation of Mandibular Anatomy Associated With Bad Splits in Sagittal Split Ramus Osteotomy of Mandible.

Science.gov (United States)

Wang, Tongyue; Han, Jeong Joon; Oh, Hee-Kyun; Park, Hong-Ju; Jung, Seunggon; Park, Yeong-Joon; Kook, Min-Suk

2016-07-01

This study aimed to identify risk factors associated with bad splits during sagittal split ramus osteotomy by using three-dimensional computed tomography. This study included 8 bad splits and 47 normal patients without bad splits. Mandibular anatomic parameters related to osteotomy line were measured. These included anteroposterior width of the ramus at level of lingula, distance between external oblique ridge and lingula, distance between sigmoid notch and inferior border of mandible, mandibular angle, distance between inferior outer surface of mandibular canal and inferior border of mandible under distal root of second molar (MCEM), buccolingual thickness of the ramus at level of lingula, and buccolingual thickness of the area just distal to first molar (BTM1) and second molar (BTM2). The incidence of bad splits in 625 sagittal split osteotomies was 1.28%. Compared with normal group, bad split group exhibited significantly thinner BTM2 and shorter sigmoid notch and inferior border of mandible (P bad splits. These anatomic data may help surgeons to choose the safest surgical techniques and best osteotomy sites.

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. Copyright © 2015 Elsevier B.V. All rights reserved.

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

International Nuclear Information System (INIS)

Biggins, J.A.; Taylor, A.; Caspary, E.A.

1978-01-01

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)

Lewis-Sumner syndrome and Tangier disease.

Science.gov (United States)

Théaudin, Marie; Couvert, Philippe; Fournier, Emmanuel; Bouige, Daniel; Bruckert, Eric; Perrotte, Paul; Vaschalde, Yvan; Maisonobe, Thierry; Bonnefont-Rousselot, Dominique; Carrié, Alain; Le Forestier, Nadine

2008-07-01

To report unusual electrophysiologic data in a patient with Tangier disease in an effort to better understand the pathophysiologic features of the peripheral nerve lesions in this disease. Case report. A 15-year-old girl had subacute onset of asymmetric neuropathy with persistent conduction block, resembling Lewis-Sumner syndrome. Electrophysiologic data in Tangier disease. After initially unsuccessful treatment with intravenously administered immunoglobulins, the finding of an abnormal lipid profile led to the diagnosis of Tangier disease due to the R587W mutation in the adenotriphosphate-binding cassette transporter-1 gene (ABCA1) (OMIM 9q22-q31). Conduction block, which is the electrophysiologic hallmark of focal demyelination, can be present in Tangier disease. It could be induced by focal nerve ischemia or by preferential lipid deposition in the paranodal regions of myelinated Schwann cells. The presence of a conduction block in Tangier disease may lead to a misdiagnosis of dysimmune neuropathy.

The Split-Brain Phenomenon Revisited: A Single Conscious Agent with Split Perception.

Science.gov (United States)

Pinto, Yair; de Haan, Edward H F; Lamme, Victor A F

2017-11-01

The split-brain phenomenon is caused by the surgical severing of the corpus callosum, the main route of communication between the cerebral hemispheres. The classical view of this syndrome asserts that conscious unity is abolished. The left hemisphere consciously experiences and functions independently of the right hemisphere. This view is a cornerstone of current consciousness research. In this review, we first discuss the evidence for the classical view. We then propose an alternative, the 'conscious unity, split perception' model. This model asserts that a split brain produces one conscious agent who experiences two parallel, unintegrated streams of information. In addition to changing our view of the split-brain phenomenon, this new model also poses a serious challenge for current dominant theories of consciousness. Copyright © 2017 Elsevier Ltd. All rights reserved.

Triadic split-merge sampler

Science.gov (United States)

van Rossum, Anne C.; Lin, Hai Xiang; Dubbeldam, Johan; van der Herik, H. Jaap

2018-04-01

In machine vision typical heuristic methods to extract parameterized objects out of raw data points are the Hough transform and RANSAC. Bayesian models carry the promise to optimally extract such parameterized objects given a correct definition of the model and the type of noise at hand. A category of solvers for Bayesian models are Markov chain Monte Carlo methods. Naive implementations of MCMC methods suffer from slow convergence in machine vision due to the complexity of the parameter space. Towards this blocked Gibbs and split-merge samplers have been developed that assign multiple data points to clusters at once. In this paper we introduce a new split-merge sampler, the triadic split-merge sampler, that perform steps between two and three randomly chosen clusters. This has two advantages. First, it reduces the asymmetry between the split and merge steps. Second, it is able to propose a new cluster that is composed out of data points from two different clusters. Both advantages speed up convergence which we demonstrate on a line extraction problem. We show that the triadic split-merge sampler outperforms the conventional split-merge sampler. Although this new MCMC sampler is demonstrated in this machine vision context, its application extend to the very general domain of statistical inference.

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-06-20

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

Splitting: The Development of a Measure.

Science.gov (United States)

Gerson, Mary-Joan

1984-01-01

Described the development of a scale that measures splitting as a psychological structure. The construct validity of the splitting scale is suggested by the positive relationship between splitting scores and a diagnostic measure of the narcissistic personality disorder, as well as a negative relationship between splitting scores and levels of…

Association of a History of Child Abuse With Impaired Myelination in the Anterior Cingulate Cortex: Convergent Epigenetic, Transcriptional, and Morphological Evidence.

Science.gov (United States)

Lutz, Pierre-Eric; Tanti, Arnaud; Gasecka, Alicja; Barnett-Burns, Sarah; Kim, John J; Zhou, Yi; Chen, Gang G; Wakid, Marina; Shaw, Meghan; Almeida, Daniel; Chay, Marc-Aurele; Yang, Jennie; Larivière, Vanessa; M'Boutchou, Marie-Noël; van Kempen, Léon C; Yerko, Volodymyr; Prud'homme, Josée; Davoli, Maria Antonietta; Vaillancourt, Kathryn; Théroux, Jean-François; Bramoullé, Alexandre; Zhang, Tie-Yuan; Meaney, Michael J; Ernst, Carl; Côté, Daniel; Mechawar, Naguib; Turecki, Gustavo

2017-12-01

Child abuse has devastating and long-lasting consequences, considerably increasing the lifetime risk of negative mental health outcomes such as depression and suicide. Yet the neurobiological processes underlying this heightened vulnerability remain poorly understood. The authors investigated the hypothesis that epigenetic, transcriptomic, and cellular adaptations may occur in the anterior cingulate cortex as a function of child abuse. Postmortem brain samples from human subjects (N=78) and from a rodent model of the impact of early-life environment (N=24) were analyzed. The human samples were from depressed individuals who died by suicide, with (N=27) or without (N=25) a history of severe child abuse, as well as from psychiatrically healthy control subjects (N=26). Genome-wide DNA methylation and gene expression were investigated using reduced representation bisulfite sequencing and RNA sequencing, respectively. Cell type-specific validation of differentially methylated loci was performed after fluorescence-activated cell sorting of oligodendrocyte and neuronal nuclei. Differential gene expression was validated using NanoString technology. Finally, oligodendrocytes and myelinated axons were analyzed using stereology and coherent anti-Stokes Raman scattering microscopy. A history of child abuse was associated with cell type-specific changes in DNA methylation of oligodendrocyte genes and a global impairment of the myelin-related transcriptional program. These effects were absent in the depressed suicide completers with no history of child abuse, and they were strongly correlated with myelin gene expression changes observed in the animal model. Furthermore, a selective and significant reduction in the thickness of myelin sheaths around small-diameter axons was observed in individuals with history of child abuse. The results suggest that child abuse, in part through epigenetic reprogramming of oligodendrocytes, may lastingly disrupt cortical myelination, a

Analysis of the induction of the myelin basic protein binding to the plasma membrane phospholipid monolayer

Science.gov (United States)

Zhang, Lei; Hao, Changchun; Feng, Ying; Gao, Feng; Lu, Xiaolong; Li, Junhua; Sun, Runguang

2016-09-01

Myelin basic protein (MBP) is an essential structure involved in the generation of central nervous system (CNS) myelin. Myelin shape has been described as liquid crystal structure of biological membrane. The interactions of MBP with monolayers of different lipid compositions are responsible for the multi-lamellar structure and stability of myelin. In this paper, we have designed MBP-incorporated model lipid monolayers and studied the phase behavior of MBP adsorbed on the plasma membrane at the air/water interface by thermodynamic method and atomic force microscopy (AFM). By analyzing the pressure-area (π-A) and pressure-time (π-T) isotherms, univariate linear regression equation was obtained. In addition, the elastic modulus, surface pressure increase, maximal insertion pressure, and synergy factor of monolayers were detected. These parameters can be used to modulate the monolayers binding of protein, and the results show that MBP has the strongest affinity for 1,2-dipalmitoyl-sn-glycero-3- phosphoserine (DPPS) monolayer, followed by DPPC/DPPS mixed and 1,2-dipalmitoyl-sn-glycero-3-phospho-choline (DPPC) monolayers via electrostatic and hydrophobic interactions. AFM images of DPPS and DPPC/DPPS mixed monolayers in the presence of MBP (5 nM) show a phase separation texture at the surface pressure of 20 mN/m and the incorporation of MBP put into the DPPC monolayers has exerted a significant effect on the domain structure. MBP is not an integral membrane protein but, due to its positive charge, interacts with the lipid head groups and stabilizes the membranes. The interaction between MBP and phospholipid membrane to determine the nervous system of the disease has a good biophysical significance and medical value. Project supported by the National Natural Science Foundation of China (Grant Nos. 21402114 and 11544009), the Natural Science Basic Research Plan in Shaanxi Province of China (Grant No. 2016JM2010), the Fundamental Research Funds for the Central

Bad splits in bilateral sagittal split osteotomy: systematic review and meta-analysis of reported risk factors.

Science.gov (United States)

Steenen, S A; van Wijk, A J; Becking, A G

2016-08-01

An unfavourable and unanticipated pattern of the bilateral sagittal split osteotomy (BSSO) is generally referred to as a 'bad split'. Patient factors predictive of a bad split reported in the literature are controversial. Suggested risk factors are reviewed in this article. A systematic review was undertaken, yielding a total of 30 studies published between 1971 and 2015 reporting the incidence of bad split and patient age, and/or surgical technique employed, and/or the presence of third molars. These included 22 retrospective cohort studies, six prospective cohort studies, one matched-pair analysis, and one case series. Spearman's rank correlation showed a statistically significant but weak correlation between increasing average age and increasing occurrence of bad splits in 18 studies (ρ=0.229; Pbad split among the different splitting techniques. A meta-analysis pooling the effect sizes of seven cohort studies showed no significant difference in the incidence of bad split between cohorts of patients with third molars present and concomitantly removed during surgery, and patients in whom third molars were removed at least 6 months preoperatively (odds ratio 1.16, 95% confidence interval 0.73-1.85, Z=0.64, P=0.52). In summary, there is no robust evidence to date to show that any risk factor influences the incidence of bad split. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

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

International Nuclear Information System (INIS)

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

2007-01-01

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

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

DEFF Research Database (Denmark)

Lozeron, Pierre; Krarup, Christian; Schmalbruch, Henning

2004-01-01

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...

Differential distribution of voltage-gated channels in myelinated and unmyelinated baroreceptor afferents.

Science.gov (United States)

Schild, John H; Kunze, Diana L

2012-12-24

Voltage gated ion channels (VGC) make possible the frequency coding of arterial pressure and the neurotransmission of this information along myelinated and unmyelinated fiber pathways. Although many of the same VGC isoforms are expressed in both fiber types, it is the relative expression of each that defines the unique discharge properties of myelinated A-type and unmyelinated C-type baroreceptors. For example, the fast inward Na⁺ current is a major determinant of the action potential threshold and the regenerative transmembrane current needed to sustain repetitive discharge. In A-type baroreceptors the TTX-sensitive Na(v)1.7 VGC contributes to the whole cell Na⁺ current. Na(v)1.7 is expressed at a lower density in C-type neurons and in conjunction with TTX-insensitive Na(v)1.8 and Na(v)1.9 VGC. As a result, action potentials of A-type neurons have firing thresholds that are 15-20 mV more negative and upstroke velocities that are 5-10 times faster than unmyelinated C-type neurons. A more depolarized threshold in conjunction with a broader complement of non-inactivating K(V) VGC subtypes produces C-type action potentials that are 3-4 times longer in duration than A-type neurons and at markedly lower levels of cell excitability. Unmyelinated baroreceptors also express KCa1.1 which provides approximately 25% of the total outward K⁺ current. KCa1.1 plays a critically important role in shaping the action potential profile of C-type neurons and strongly impacts neuronal excitability. A-type neurons do not functionally express the KCa1.1 channel despite having a whole cell Ca(V) current quite similar to that of C-type neurons. As a result, A-type neurons do not have the frequency-dependent braking forces of KCa1.1. Lack of a KCa current and only a limited complement of non-inactivating K(V) VGC in addition to a hyperpolarization activated HCN1 current that is nearly 10 times larger than in C-type neurons leads to elevated levels of discharge in A-type neurons, a

Split Malcev algebras

Indian Academy of Sciences (India)

project of the Spanish Ministerio de Educación y Ciencia MTM2007-60333. References. [1] Calderón A J, On split Lie algebras with symmetric root systems, Proc. Indian. Acad. Sci (Math. Sci.) 118(2008) 351–356. [2] Calderón A J, On split Lie triple systems, Proc. Indian. Acad. Sci (Math. Sci.) 119(2009). 165–177.

Two-Loop Splitting Amplitudes

International Nuclear Information System (INIS)

Bern, Z.

2004-01-01

Splitting amplitudes govern the behavior of scattering amplitudes at the momenta of external legs become collinear. In this talk we outline the calculation of two-loop splitting amplitudes via the unitarity sewing method. This method retains the simple factorization properties of light-cone gauge, but avoids the need for prescriptions such as the principal value or Mandelstam-Leibbrandt ones. The encountered loop momentum integrals are then evaluated using integration-by-parts and Lorentz invariance identities. We outline a variety of applications for these splitting amplitudes

Two-loop splitting amplitudes

International Nuclear Information System (INIS)

Bern, Z.; Dixon, L.J.; Kosower, D.A.

2004-01-01

Splitting amplitudes govern the behavior of scattering amplitudes at the momenta of external legs become collinear. In this talk we outline the calculation of two-loop splitting amplitudes via the unitarity sewing method. This method retains the simple factorization properties of light-cone gauge, but avoids the need for prescriptions such as the principal value or Mandelstam-Leibbrandt ones. The encountered loop momentum integrals are then evaluated using integration-by-parts and Lorentz invariance identities. We outline a variety of applications for these splitting amplitudes

p25alpha relocalizes in oligodendroglia from myelin to cytoplasmic inclusions in multiple system atrophy

DEFF Research Database (Denmark)

Song, Yun Ju C; Lundvig, Ditte M S; Huang, Yue

2007-01-01

cytoplasmic inclusions. Overall, the data indicate that changes in the cellular interactions between MBP and p25alpha occur early in MSA and contribute to abnormalities in myelin and subsequent alpha-synuclein aggregation and the ensuing neuronal degeneration that characterizes this disease....

Epitope diversity of N-glycans from bovine peripheral myelin glycoprotein P0 revealed by mass spectrometry and nano probe magic angle spinning 1H NMR spectroscopy

NARCIS (Netherlands)

Vliegenthart, J.F.G.; Gutiérrez Gallego, R.; Jiménez Blanco, J.L.; Thijssen-van Zuylen, C.W.E.M.; Gotfredsen, C.H.; Voshol, H.; Duus, J.Ø.; Schachner, M.

2001-01-01

The carbohydrate structures present on the glycoproteins in the central and peripheral nerve systems are essential in many cell adhesion processes. The P0 glycoprotein, expressed by myelinating Schwann cells, plays an important role during the formation and maintenance of myelin, and it is the most

Concentric Split Flow Filter

Science.gov (United States)

Stapleton, Thomas J. (Inventor)

2015-01-01

A concentric split flow filter may be configured to remove odor and/or bacteria from pumped air used to collect urine and fecal waste products. For instance, filter may be designed to effectively fill the volume that was previously considered wasted surrounding the transport tube of a waste management system. The concentric split flow filter may be configured to split the air flow, with substantially half of the air flow to be treated traveling through a first bed of filter media and substantially the other half of the air flow to be treated traveling through the second bed of filter media. This split flow design reduces the air velocity by 50%. In this way, the pressure drop of filter may be reduced by as much as a factor of 4 as compare to the conventional design.

Investigation of sequential growth factor delivery during cuprizone challenge in mice aimed to enhance oligodendrogliogenesis and myelin repair.

Directory of Open Access Journals (Sweden)

Jennifer K Sabo

Full Text Available Repair in multiple sclerosis involves remyelination, a process in which axons are provided with a new myelin sheath by new oligodendrocytes. Bone morphogenic proteins (BMPs are a family of growth factors that have been shown to influence the response of oligodendrocyte progenitor cells (OPCs in vivo during demyelination and remyelination in the adult brain. We have previously shown that BMP4 infusion increases numbers of OPCs during cuprizone-induced demyelination, while infusion of Noggin, an endogenous antagonist of BMP4 increases numbers of mature oligodendrocytes and remyelinated axons following recovery. Additional studies have shown that insulin-like growth factor-1 (IGF-1 promotes the survival of OPCs during cuprizone-induced demyelination. Based on these data, we investigated whether myelin repair could be further enhanced by sequential infusion of these agents firstly, BMP4 to increase OPC numbers, followed by either Noggin or IGF-1 to increase the differentiation and survival of the newly generated OPCs. We identified that sequential delivery of BMP4 and IGF-1 during cuprizone challenge increased the number of mature oligodendrocytes and decreased astrocyte numbers following recovery compared with vehicle infused mice, but did not alter remyelination. However, sequential delivery of BMP4 and Noggin during cuprizone challenge did not alter numbers of oligodendrocytes or astrocytes in the corpus callosum compared with vehicle infused mice. Furthermore, electron microscopy analysis revealed no change in average myelin thickness in the corpus callosum between vehicle infused and BMP4-Noggin infused mice. Our results suggest that while single delivery of Noggin or IGF-1 increased the production of mature oligodendrocytes in vivo in the context of demyelination, only Noggin infusion promoted remyelination. Thus, sequential delivery of BMP4 and Noggin or IGF-1 does not further enhance myelin repair above what occurs with delivery of Noggin

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.)

The effect of beta-interferon therapy on myelin basic protein-elicited CD4+ T cell proliferation and cytokine production in multiple sclerosis

DEFF Research Database (Denmark)

Hedegaard, Chris J; Krakauer, Martin; Bendtzen, Klaus

2008-01-01

Interferon (IFN)-beta therapy has well-established clinical benefits in multiple sclerosis (MS), but the underlying modulation of cytokine responses to myelin self-antigens remains poorly understood. We analysed the CD4+ T cell proliferation and cytokine responses elicited by myelin basic protein...... (MBP) and a foreign recall antigen, tetanus toxoid (TT), in mononuclear cell cultures from fourteen MS patients undergoing IFN-beta therapy. The MBP-elicited IFN-gamma-, TNF-alpha- and IL-10 production decreased during therapy (p...

Effects of the mode of re-socialization after juvenile social isolation on medial prefrontal cortex myelination and function.

Science.gov (United States)

Makinodan, Manabu; Ikawa, Daisuke; Yamamuro, Kazuhiko; Yamashita, Yasunori; Toritsuka, Michihiro; Kimoto, Sohei; Yamauchi, Takahira; Okumura, Kazuki; Komori, Takashi; Fukami, Shin-Ichi; Yoshino, Hiroki; Kanba, Shigenobu; Wanaka, Akio; Kishimoto, Toshifumi

2017-07-14

Social isolation is an important factor in the development of psychiatric disorders. It is necessary to develop an effective psychological treatment, such as cognitive rehabilitation, for children who have already suffered from social isolation, such as neglect and social rejection. We used socially isolated mice to validate whether elaborate re-socialization after juvenile social isolation can restore hypomyelination in the medial prefrontal cortex (mPFC) and the attendant functions manifested in socially isolated mice. While mice who underwent re-socialization with socially isolated mice after juvenile social isolation (Re-IS mice) demonstrated less mPFC activity during exposure to a strange mouse, as well as thinner myelin in the mPFC than controls, mice who underwent re-socialization with socially housed mice after juvenile social isolation (Re-SH mice) caught up with the controls in terms of most mPFC functions, as well as myelination. Moreover, social interaction of Re-IS mice was reduced as compared to controls, but Re-SH mice showed an amount of social interaction comparable to that of controls. These results suggest that the mode of re-socialization after juvenile social isolation has significant effects on myelination in the mPFC and the attendant functions in mice, indicating the importance of appropriate psychosocial intervention after social isolation.

Split-illumination electron holography

Energy Technology Data Exchange (ETDEWEB)

Tanigaki, Toshiaki; Aizawa, Shinji; Suzuki, Takahiro; Park, Hyun Soon [Advanced Science Institute, RIKEN, Hirosawa 2-1, Wako, Saitama 351-0198 (Japan); Inada, Yoshikatsu [Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Katahira 2-1-1, Sendai 980-8577 (Japan); Matsuda, Tsuyoshi [Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Taniyama, Akira [Corporate Research and Development Laboratories, Sumitomo Metal Industries, Ltd., Amagasaki, Hyogo 660-0891 (Japan); Shindo, Daisuke [Advanced Science Institute, RIKEN, Hirosawa 2-1, Wako, Saitama 351-0198 (Japan); Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Katahira 2-1-1, Sendai 980-8577 (Japan); Tonomura, Akira [Advanced Science Institute, RIKEN, Hirosawa 2-1, Wako, Saitama 351-0198 (Japan); Okinawa Institute of Science and Technology, Graduate University, Onna-son, Okinawa 904-0495 (Japan); Central Research Laboratory, Hitachi, Ltd., Hatoyama, Saitama 350-0395 (Japan)

2012-07-23

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.

Split-illumination electron holography

International Nuclear Information System (INIS)

Tanigaki, Toshiaki; Aizawa, Shinji; Suzuki, Takahiro; Park, Hyun Soon; Inada, Yoshikatsu; Matsuda, Tsuyoshi; Taniyama, Akira; Shindo, Daisuke; Tonomura, Akira

2012-01-01

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.

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

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....

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.

Bad split during bilateral sagittal split osteotomy of the mandible with separators: a retrospective study of 427 patients.

Science.gov (United States)

Mensink, Gertjan; Verweij, Jop P; Frank, Michael D; Eelco Bergsma, J; Richard van Merkesteyn, J P

2013-09-01

An unfavourable fracture, known as a bad split, is a common operative complication in bilateral sagittal split osteotomy (BSSO). The reported incidence ranges from 0.5 to 5.5%/site. Since 1994 we have used sagittal splitters and separators instead of chisels for BSSO in our clinic in an attempt to prevent postoperative hypoaesthesia. Theoretically an increased percentage of bad splits could be expected with this technique. In this retrospective study we aimed to find out the incidence of bad splits associated with BSSO done with splitters and separators. We also assessed the risk factors for bad splits. The study group comprised 427 consecutive patients among whom the incidence of bad splits was 2.0%/site, which is well within the reported range. The only predictive factor for a bad split was the removal of third molars at the same time as BSSO. There was no significant association between bad splits and age, sex, class of occlusion, or the experience of the surgeon. We think that doing a BSSO with splitters and separators instead of chisels does not increase the risk of a bad split, and is therefore safe with predictable results. Copyright © 2012 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Differentially Severe Cognitive Effects of Compromised Cerebral Blood Flow in Aged Mice: Association with Myelin Degradation and Microglia Activation

Directory of Open Access Journals (Sweden)

Gilly Wolf

2017-06-01

Full Text Available Bilateral common carotid artery stenosis (BCAS models the effects of compromised cerebral blood flow on brain structure and function in mice. We compared the effects of BCAS in aged (21 month and young adult (3 month female mice, anticipating a differentially more severe effect in the older mice. Four weeks after surgery there was a significant age by time by treatment interaction on the radial-arm water maze (RAWM; p = 0.014: on the first day of the test, latencies of old mice were longer compared to the latencies of young adult mice, independent of BCAS. However, on the second day of the test, latencies of old BCAS mice were significantly longer than old control mice (p = 0.049, while latencies of old controls were similar to those of the young adult mice, indicating more severe impairment of hippocampal dependent learning and working memory by BCAS in the older mice. Fluorescence staining of myelin basic protein (MBP showed that old age and BCAS both induced a significant decrease in fluorescence intensity. Evaluation of the number oligodendrocyte precursor cells demonstrated augmented myelin replacement in old BCAS mice (p < 0.05 compared with young adult BCAS and old control mice. While microglia morphology was assessed as normal in young adult control and young adult BCAS mice, microglia of old BCAS mice exhibited striking activation in the area of degraded myelin compared to young adult BCAS (p < 0.01 and old control mice (p < 0.05. These findings show a differentially more severe effect of cerebral hypoperfusion on cognitive function, myelin integrity and inflammatory processes in aged mice. Hypoperfusion may exacerbate degradation initiated by aging, which may induce more severe neuronal and cognitive phenotypes.

Geometrical splitting in Monte Carlo

International Nuclear Information System (INIS)

Dubi, A.; Elperin, T.; Dudziak, D.J.

1982-01-01

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

Innovative wedge axe in making split firewood

International Nuclear Information System (INIS)

Mutikainen, A.

1998-01-01

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 m 3 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.)

Analysis of White Matter Damage in Patients with Multiple Sclerosis via a Novel In Vivo MR Method for Measuring Myelin, Axons, and G-Ratio.

Science.gov (United States)

Hagiwara, A; Hori, M; Yokoyama, K; Nakazawa, M; Ueda, R; Horita, M; Andica, C; Abe, O; Aoki, S

2017-10-01

Myelin and axon volume fractions can now be estimated via MR imaging in vivo, as can the g-ratio, which equals the ratio of the inner to the outer diameter of a nerve fiber. The purpose of this study was to evaluate WM damage in patients with MS via this novel MR imaging technique. Twenty patients with relapsing-remitting MS with a combined total of 149 chronic plaques were analyzed. Myelin volume fraction was calculated based on simultaneous tissue relaxometry. Intracellular and CSF compartment volume fractions were quantified via neurite orientation dispersion and density imaging. Axon volume fraction and g-ratio were calculated by combining these measurements. Myelin and axon volume fractions and g-ratio were measured in plaques, periplaque WM, and normal-appearing WM. All metrics differed significantly across the 3 groups ( P ratio between periplaque WM and normal-appearing WM). Those in plaques differed most from those in normal-appearing WM. The percentage changes in plaque and periplaque WM metrics relative to normal-appearing WM were significantly larger in absolute value for myelin volume fraction than for axon volume fraction and g-ratio ( P ratio may potentially be useful for evaluating WM damage in patients with MS. © 2017 by American Journal of Neuroradiology.

TMD splitting functions in kT factorization. The real contribution to the gluon-to-gluon splitting

International Nuclear Information System (INIS)

Hentschinski, M.; Kusina, A.; Kutak, K.; Serino, M.

2018-01-01

We calculate the transverse momentum dependent gluon-to-gluon splitting function within k T -factorization, generalizing the framework employed in the calculation of the quark splitting functions in Hautmann et al. (Nucl Phys B 865:54-66, arXiv:1205.1759, 2012), Gituliar et al. (JHEP 01:181, arXiv:1511.08439, 2016), Hentschinski et al. (Phys Rev D 94(11):114013, arXiv:1607.01507, 2016) and demonstrate at the same time the consistency of the extended formalism with previous results. While existing versions of k T factorized evolution equations contain already a gluon-to-gluon splitting function i.e. the leading order Balitsky-Fadin-Kuraev-Lipatov (BFKL) kernel or the Ciafaloni-Catani-Fiorani-Marchesini (CCFM) kernel, the obtained splitting function has the important property that it reduces both to the leading order BFKL kernel in the high energy limit, to the Dokshitzer-Gribov-Lipatov-Altarelli-Parisi (DGLAP) gluon-to-gluon splitting function in the collinear limit as well as to the CCFM kernel in the soft limit. At the same time we demonstrate that this splitting kernel can be obtained from a direct calculation of the QCD Feynman diagrams, based on a combined implementation of the Curci-Furmanski-Petronzio formalism for the calculation of the collinear splitting functions and the framework of high energy factorization. (orig.)

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-04-15

Commissural white matter fibers comprising the callosal splenium are diverse. Subsections of the splenium myelinate at different times, in a centrolineal manner. The aims of this study are to depict the normal callosal splenium myelination pattern and to distinguish the transient age-related mid splenium hypointensity from pathology. We reviewed 131 consecutive brain MRIs in patients between ages 3 and 6 months from a single academic children's hospital. Patients that were preterm, hydrocephalic, and/or had volume loss were excluded. Fifty total MR exams that included T1-weighted MR imaging (T1WI), T2-weighted MR imaging (T2WI), and diffusion tensor imaging (DTI) were reviewed. Regions of callosal splenium myelination manifested by T1 and T2 shortening were evaluated. Tractography was performed with seeds placed over the posterior, mid, and anterior splenium to define the origin, destination, and course of traversing fibers. Splenium signal varied significantly from 3 to 6 months, with distinct age-related trends. On T1WI, the splenium was hypointense at 3 months (12/13), centrally hypointense/peripherally hyperintense at 4 months (15/16), and hyperintense at 6 months (10/11). Tractography revealed three distinct white matter tract populations: medial occipital (posterior); precuneus, posterior cingulate, and medial temporal (middle); and postcentral gyri (anterior). Specific commissural fiber components of the splenium myelinate at different times. The transient developmental mid splenium hypointensity on T1WI corresponds to tracts from the associative cortex, principally the precuneus. Heterogeneous splenium signal alteration in patients ages 3-6 months is a normal developmental phenomenon that should not be confused with pathologic lesions. (orig.)

Urban pattern: Layout design by hierarchical domain splitting

KAUST Repository

Yang, Yongliang; Wang, Jun; Vouga, Etienne; Wonka, Peter

2013-01-01

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.

Urban pattern: Layout design by hierarchical domain splitting

KAUST Repository

Yang, Yongliang

2013-11-06

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.

Relationship between mandibular anatomy and the occurrence of a bad split upon sagittal split osteotomy.

Science.gov (United States)

Aarabi, Mohammadali; Tabrizi, Reza; Hekmat, Mina; Shahidi, Shoaleh; Puzesh, Ayatollah

2014-12-01

A bad split is a troublesome complication of the sagittal split osteotomy (SSO). The aim of this study was to evaluate the relation between the occurrence of a bad split and mandibular anatomy in SSO using cone-beam computed tomography. The authors designed a cohort retrospective study. Forty-eight patients (96 SSO sites) were studied. The buccolingual thickness of the retromandibular area (BLR), the buccolingual thickness of the ramus at the level of the lingula (BLTR), the height of the mandible from the alveolar crest to the inferior border of the mandible, (ACIB), the distance between the sigmoid notch and the inferior border of the mandible (SIBM), and the anteroposterior width of the ramus (APWR) were measured. The independent t test was applied to compare anatomic measurements between the group with and the group without bad splits. The receiver operating characteristic (ROC) test was used to find a cutoff point in anatomic size for various parts of the mandible related to the occurrence of bad splits. The mean SIBM was 47.05±6.33 mm in group 1 (with bad splits) versus 40.66±2.44 mm in group 2 (without bad splits; P=.01). The mean BLTR was 5.74±1.11 mm in group 1 versus 3.19±0.55 mm in group 2 (P=.04). The mean BLR was 14.98±2.78 mm in group 1 versus 11.21±1.29 mm in group 2 (P=.001). No statistically significant difference was found for APWR and ACIB between the 2 groups. The ROC test showed cutoff points of 10.17 mm for BLR, 36.69 mm for SIBM, and 4.06 mm for BLTR. This study showed that certain mandibular anatomic differences can increase the risk of a bad split during SSO surgery. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

SplitRacer - a new Semi-Automatic Tool to Quantify And Interpret Teleseismic Shear-Wave Splitting

Science.gov (United States)

Reiss, M. C.; Rumpker, G.

2017-12-01

We have developed a semi-automatic, MATLAB-based GUI to combine standard seismological tasks such as the analysis and interpretation of teleseismic shear-wave splitting. Shear-wave splitting analysis is widely used to infer seismic anisotropy, which can be interpreted in terms of lattice-preferred orientation of mantle minerals, shape-preferred orientation caused by fluid-filled cracks or alternating layers. Seismic anisotropy provides a unique link between directly observable surface structures and the more elusive dynamic processes in the mantle below. Thus, resolving the seismic anisotropy of the lithosphere/asthenosphere is of particular importance for geodynamic modeling and interpretations. The increasing number of seismic stations from temporary experiments and permanent installations creates a new basis for comprehensive studies of seismic anisotropy world-wide. However, the increasingly large data sets pose new challenges for the rapid and reliably analysis of teleseismic waveforms and for the interpretation of the measurements. Well-established routines and programs are available but are often impractical for analyzing large data sets from hundreds of stations. Additionally, shear wave splitting results are seldom evaluated using the same well-defined quality criteria which may complicate comparison with results from different studies. SplitRacer has been designed to overcome these challenges by incorporation of the following processing steps: i) downloading of waveform data from multiple stations in mseed-format using FDSNWS tools; ii) automated initial screening and categorizing of XKS-waveforms using a pre-set SNR-threshold; iii) particle-motion analysis of selected phases at longer periods to detect and correct for sensor misalignment; iv) splitting analysis of selected phases based on transverse-energy minimization for multiple, randomly-selected, relevant time windows; v) one and two-layer joint-splitting analysis for all phases at one station by

Structure and function of the contactin-associated protein family in myelinated axons and their relationship with nerve diseases

Institute of Scientific and Technical Information of China (English)

Yan Zou; De-en Xu; Wei-feng Zhang; Hai-ying Liu; Xia Li; Xing Zhang; Xiao-fang Ma; Yang Sun; Shi-yi Jiang; Quan-hong Ma

2017-01-01

The contactin-associated protein (Caspr) family participates in nerve excitation and conduction, and neurotransmitter release in myelinated axons. We analyzed the structures and functions of the Caspr family–CNTNAP1 (Caspr1), CNTNAP2 (Caspr2), CNTNAP3 (Caspr3), CNTNAP4 (Caspr4) and CNTNAP5 (Caspr5), Caspr1–5 is not only involved in the formation of myelinated axons, but also participates in maintaining the stability of adjacent connections. Caspr1 participates in the formation, differentiation, and proliferation of neurons and astrocytes, and in motor control and cognitive function. We also analyzed the relationship between the Caspr family and neurodegenerative diseases, multiple sclerosis, and autoimmune encephalitis. However, the effects of Caspr on disease course and prognosis remain poorly understood. The effects of Caspr on disease diagnosis and treatment need further investigation.

Maternal exposure to hexachlorophene targets intermediate-stage progenitor cells of the hippocampal neurogenesis in rat offspring via dysfunction of cholinergic inputs by myelin vacuolation

International Nuclear Information System (INIS)

Itahashi, Megu; Abe, Hajime; Tanaka, Takeshi; Mizukami, Sayaka; Kimura, Masayuki; Yoshida, Toshinori; Shibutani, Makoto

2015-01-01

Highlights: • The effect of maternal exposure to HCP on rat hippocampal neurogenesis was examined. • HCP induces myelin vacuolation of nerve tracts in the septal–hippocampal pathway. • Myelin changes suppress Chrnb2-mediated cholinergic inputs to the dentate gyrus. • SGZ apoptosis occurs via the mitochondrial pathway and targets type-2b cells. • Dysfunction of cholinergic inputs is related to type-2b SGZ cell apoptosis. - Abstract: Hexachlorophene (HCP) is known to induce myelin vacuolation corresponding to intramyelinic edema of nerve fibers in the central and peripheral nervous system in animals. This study investigated the effect of maternal exposure to HCP on hippocampal neurogenesis in rat offspring using pregnant rats supplemented with 0 (controls), 100, or 300 ppm HCP in the diet from gestational day 6 to day 21 after delivery. On postnatal day (PND) 21, the numbers of T box brain 2 + progenitor cells and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling + apoptotic cells in the hippocampal subgranular zone (SGZ) decreased in female offspring at 300 ppm, which was accompanied by myelin vacuolation and punctate tubulin beta-3 chain staining of nerve fibers in the hippocampal fimbria. In addition, transcript levels of the cholinergic receptor, nicotinic beta 2 (Chrnb2) and B-cell CLL/lymphoma 2 (Bcl2) decreased in the dentate gyrus. HCP-exposure did not alter the numbers of SGZ proliferating cells and reelin- or calcium-binding protein-expressing γ-aminobutyric acid (GABA)-ergic interneuron subpopulations in the dentate hilus on PND 21 and PND 77. Although some myelin vacuolation remained, all other changes observed in HCP-exposed offspring on PND 21 disappeared on PND 77. These results suggest that maternal HCP exposure reversibly decreases type-2b intermediate-stage progenitor cells via the mitochondrial apoptotic pathway in offspring hippocampal neurogenesis at 300 ppm HCP. Neurogenesis may be affected by dysfunction

The neuronal metabolite NAA regulates histone H3 methylation in oligodendrocytes and myelin lipid composition.

Science.gov (United States)

Singhal, N K; Huang, H; Li, S; Clements, R; Gadd, J; Daniels, A; Kooijman, E E; Bannerman, P; Burns, T; Guo, F; Pleasure, D; Freeman, E; Shriver, L; McDonough, J

2017-01-01

The neuronal mitochondrial metabolite N-acetylaspartate (NAA) is decreased in the multiple sclerosis (MS) brain. NAA is synthesized in neurons by the enzyme N-acetyltransferase-8-like (NAT8L) and broken down in oligodendrocytes by aspartoacylase (ASPA) into acetate and aspartate. We have hypothesized that NAA links the metabolism of axons with oligodendrocytes to support myelination. To test this hypothesis, we performed lipidomic analyses using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and high-performance thin-layer chromatography (HPTLC) to identify changes in myelin lipid composition in postmortem MS brains and in NAT8L knockout (NAT8L -/- ) mice which do not synthesize NAA. We found reduced levels of sphingomyelin in MS normal appearing white matter that mirrored decreased levels of NAA. We also discovered decreases in the amounts of sphingomyelin and sulfatide lipids in the brains of NAT8L -/- mice compared to controls. Metabolomic analysis of primary cultures of oligodendrocytes treated with NAA revealed increased levels of α-ketoglutarate, which has been reported to regulate histone demethylase activity. Consistent with this, NAA treatment resulted in alterations in the levels of histone H3 methylation, including H3K4me3, H3K9me2, and H3K9me3. The H3K4me3 histone mark regulates cellular energetics, metabolism, and growth, while H3K9me3 has been linked to alterations in transcriptional repression in developing oligodendrocytes. We also noted the NAA treatment was associated with increases in the expression of genes involved in sulfatide and sphingomyelin synthesis in cultured oligodendrocytes. This is the first report demonstrating that neuronal-derived NAA can signal to the oligodendrocyte nucleus. These data suggest that neuronal-derived NAA signals through epigenetic mechanisms in oligodendrocytes to support or maintain myelination.

Curcumin-loaded nanoparticles ameliorate glial activation and improve myelin repair in lyolecithin-induced focal demyelination model of rat corpus callosum.

Science.gov (United States)

Naeimi, Reza; Safarpour, Fatemeh; Hashemian, Mona; Tashakorian, Hamed; Ahmadian, Seyed Raheleh; Ashrafpour, Manouchehr; Ghasemi-Kasman, Maryam

2018-05-01

Curcumin has been introduced as effective anti-inflammatory agent in treatment of several inflammatory disorders. Despite the wide range pharmacological activities, clinical application of curcumin is restricted mainly due to the low water solubility of this substance. More recently, we could remarkably improve the aqueous solubility of curcumin by its encapsulation in chitosan-alginate-sodium tripolyphosphate nanoparticles (CS-ALG-STPP NPs). In this study, the anti-inflammatory and myelin protective effects of curcumin-loaded NPs were evaluated in lysolecithin (LPC)-induced focal demyelination model. Pharmacokinetic of curcumin was assessed using high performance liquid chromatography (HPLC). Local demyelination was induced by injection of LPC into corpus callosum of rats. Animals were pre-treated with intraperitoneal (i.p.) injections of curcumin or curcumin-loaded NPs at dose of 12.5 mg/kg, 10 days prior to LPC injection and the injections were continued for 7 or 14 days post lesion. Hematoxylin and eosin (H&E) staining and immunostaining against activated glial cells including astrocytes and microglia were carried out for assessment of inflammation level in lesion site. Myelin specific staining was performed to evaluate the effect of curcumin-loaded NPs on myelination of LPC receiving animals. HPLC results showed the higher plasma concentration of curcumin after administration of NPs. Histological evaluation demonstrated that, the extent of demyelination areas was reduced in animals under treatment of curcumin-loaded NPs. Furthermore, treatment with curcumin-loaded NPs effectively attenuated glial activation and inflammation in LPC-induced demyelination model compared to curcumin receiving animals. Overall; these findings indicate that treatment with curcumin-loaded NPs preserve myelinated axons through amelioration of glial activation and inflammation in demyelination context. Copyright © 2018 Elsevier B.V. All rights reserved.

Are Ducted Mini-Splits Worth It?

Energy Technology Data Exchange (ETDEWEB)

Winkler, Jonathan M [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Maguire, Jeffrey B [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Metzger, Cheryn E. [Pacific Northwest National Laboratory; Zhang, Jason [Pacific Northwest National Laboratory

2018-02-01

Ducted mini-split heat pumps are gaining popularity in some regions of the country due to their energy-efficient specifications and their ability to be hidden from sight. Although product and install costs are typically higher than the ductless mini-split heat pumps, this technology is well worth the premium for some homeowners who do not like to see an indoor unit in their living area. Due to the interest in this technology by local utilities and homeowners, the Bonneville Power Administration (BPA) has funded the Pacific Northwest National Laboratory (PNNL) and the National Renewable Energy Laboratory (NREL) to develop capabilities within the Building Energy Optimization (BEopt) tool to model ducted mini-split heat pumps. After the fundamental capabilities were added, energy-use results could be compared to other technologies that were already in BEopt, such as zonal electric resistance heat, central air source heat pumps, and ductless mini-split heat pumps. Each of these technologies was then compared using five prototype configurations in three different BPA heating zones to determine how the ducted mini-split technology would perform under different scenarios. The result of this project was a set of EnergyPlus models representing the various prototype configurations in each climate zone. Overall, the ducted mini-split heat pumps saved about 33-60% compared to zonal electric resistance heat (with window AC systems modeled in the summer). The results also showed that the ducted mini-split systems used about 4% more energy than the ductless mini-split systems, which saved about 37-64% compared to electric zonal heat (depending on the prototype and climate).

Particulate photocatalysts for overall water splitting

Science.gov (United States)

Chen, Shanshan; Takata, Tsuyoshi; Domen, Kazunari

2017-10-01

The conversion of solar energy to chemical energy is a promising way of generating renewable energy. Hydrogen production by means of water splitting over semiconductor photocatalysts is a simple, cost-effective approach to large-scale solar hydrogen synthesis. Since the discovery of the Honda-Fujishima effect, considerable progress has been made in this field, and numerous photocatalytic materials and water-splitting systems have been developed. In this Review, we summarize existing water-splitting systems based on particulate photocatalysts, focusing on the main components: light-harvesting semiconductors and co-catalysts. The essential design principles of the materials employed for overall water-splitting systems based on one-step and two-step photoexcitation are also discussed, concentrating on three elementary processes: photoabsorption, charge transfer and surface catalytic reactions. Finally, we outline challenges and potential advances associated with solar water splitting by particulate photocatalysts for future commercial applications.

(O)Mega split

Energy Technology Data Exchange (ETDEWEB)

Benakli, Karim; Darmé, Luc; Goodsell, Mark D. [Sorbonne Universités, UPMC Univ Paris 06, UMR 7589,LPTHE, F-75005, Paris (France); CNRS, UMR 7589,LPTHE, F-75005, Paris (France)

2015-11-16

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{sub 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{sub S}, which we derive. On the other hand, we show that renormalisation group running of soft masses aboveM{sub 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.

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-01-01

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

An algorithm for the split-feasibility problems with application to the split-equality problem.

Science.gov (United States)

Chuang, Chih-Sheng; Chen, Chi-Ming

2017-01-01

In this paper, we study the split-feasibility problem in Hilbert spaces by using the projected reflected gradient algorithm. As applications, we study the convex linear inverse problem and the split-equality problem in Hilbert spaces, and we give new algorithms for these problems. Finally, numerical results are given for our main results.

Heterogeneity of Multiple Sclerosis Lesions in Multislice Myelin Water Imaging.

Directory of Open Access Journals (Sweden)

Tobias Djamsched Faizy

Full Text Available 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.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.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.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.

Structure and function of the contactin-associated protein family in myelinated axons and their relationship with nerve diseases

Directory of Open Access Journals (Sweden)

Yan Zou

2017-01-01

Full Text Available The contactin-associated protein (Caspr family participates in nerve excitation and conduction, and neurotransmitter release in myelinated axons. We analyzed the structures and functions of the Caspr family–CNTNAP1 (Caspr1, CNTNAP2 (Caspr2, CNTNAP3 (Caspr3, CNTNAP4 (Caspr4 and CNTNAP5 (Caspr5, Caspr1–5 is not only involved in the formation of myelinated axons, but also participates in maintaining the stability of adjacent connections. Caspr1 participates in the formation, differentiation, and proliferation of neurons and astrocytes, and in motor control and cognitive function. We also analyzed the relationship between the Caspr family and neurodegenerative diseases, multiple sclerosis, and autoimmune encephalitis. However, the effects of Caspr on disease course and prognosis remain poorly understood. The effects of Caspr on disease diagnosis and treatment need further investigation.

Stochastic split determinant algorithms

International Nuclear Information System (INIS)

Horvatha, Ivan

2000-01-01

I propose a large class of stochastic Markov processes associated with probability distributions analogous to that of lattice gauge theory with dynamical fermions. The construction incorporates the idea of approximate spectral split of the determinant through local loop action, and the idea of treating the infrared part of the split through explicit diagonalizations. I suggest that exact algorithms of practical relevance might be based on Markov processes so constructed

M-Split: A Graphical User Interface to Analyze Multilayered Anisotropy from Shear Wave Splitting

Science.gov (United States)

Abgarmi, Bizhan; Ozacar, A. Arda

2017-04-01

Shear wave splitting analysis are commonly used to infer deep anisotropic structure. For simple cases, obtained delay times and fast-axis orientations are averaged from reliable results to define anisotropy beneath recording seismic stations. However, splitting parameters show systematic variations with back azimuth in the presence of complex anisotropy and cannot be represented by average time delay and fast axis orientation. Previous researchers had identified anisotropic complexities at different tectonic settings and applied various approaches to model them. Most commonly, such complexities are modeled by using multiple anisotropic layers with priori constraints from geologic data. In this study, a graphical user interface called M-Split is developed to easily process and model multilayered anisotropy with capabilities to properly address the inherited non-uniqueness. M-Split program runs user defined grid searches through the model parameter space for two-layer anisotropy using formulation of Silver and Savage (1994) and creates sensitivity contour plots to locate local maximas and analyze all possible models with parameter tradeoffs. In order to minimize model ambiguity and identify the robust model parameters, various misfit calculation procedures are also developed and embedded to M-Split which can be used depending on the quality of the observations and their back-azimuthal coverage. Case studies carried out to evaluate the reliability of the program using real noisy data and for this purpose stations from two different networks are utilized. First seismic network is the Kandilli Observatory and Earthquake research institute (KOERI) which includes long term running permanent stations and second network comprises seismic stations deployed temporary as part of the "Continental Dynamics-Central Anatolian Tectonics (CD-CAT)" project funded by NSF. It is also worth to note that M-Split is designed as open source program which can be modified by users for

Plasma myelin basic protein assay using Gilford enzyme immunoassay cuvettes.

Science.gov (United States)

Groome, N P

1981-10-01

The assay of myelin basic protein in body fluids has potential clinical importance as a routine indicator of demyelination. Preliminary details of a competitive enzyme immunoassay for this protein have previously been published by the author (Groome, N. P. (1980) J. Neurochem. 35, 1409-1417). The present paper now describes the adaptation of this assay for use on human plasma and various aspects of routine data processing. A commercially available cuvette system was found to have advantages over microtitre plates but required a permuted arrangement of sample replicates for consistent results. For dose interpolation, the standard curve could be fitted to a three parameter non-linear equation by regression analysis or linearised by the logit/log transformation.

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

2006-01-01

was correlated with fewer mature oligodendrocytes, but similar precursor cell numbers, in MMP null animals compared with wild type. Because an important growth factor for oligodendrocyte maturation is insulin-like growth factor-1 (IGF-1), we addressed whether this was involved in the deficient myelination in MMP...

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.

Additive operator-difference schemes splitting schemes

CERN Document Server

Vabishchevich, Petr N

2013-01-01

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

Alteration of split renal function during Captopril treatment

International Nuclear Information System (INIS)

Aburano, Tamio; Takayama, Teruhiko; Nakajima, Kenichi; Tonami, Norihisa; Hisada, Kinichi; Yasuhara, Shuichirou; Miyamori, Isamu; Takeda, Ryoyu

1987-01-01

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)

Schwann Cell Precursors from Human Pluripotent Stem Cells as a Potential Therapeutic Target for Myelin Repair.

Science.gov (United States)

Kim, Han-Seop; Lee, Jungwoon; Lee, Da Yong; Kim, Young-Dae; Kim, Jae Yun; Lim, Hyung Jin; Lim, Sungmin; Cho, Yee Sook

2017-06-06

Schwann cells play a crucial role in successful nerve repair and regeneration by supporting both axonal growth and myelination. However, the sources of human Schwann cells are limited both for studies of Schwann cell development and biology and for the development of treatments for Schwann cell-associated diseases. Here, we provide a rapid and scalable method to produce self-renewing Schwann cell precursors (SCPs) from human pluripotent stem cells (hPSCs), using combined sequential treatment with inhibitors of the TGF-β and GSK-3 signaling pathways, and with neuregulin-1 for 18 days under chemically defined conditions. Within 1 week, hPSC-derived SCPs could be differentiated into immature Schwann cells that were functionally confirmed by their secretion of neurotrophic factors and their myelination capacity in vitro and in vivo. We propose that hPSC-derived SCPs are a promising, unlimited source of functional Schwann cells for treating demyelination disorders and injuries to the peripheral nervous system. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Spin Splitting in Different Semiconductor Quantum Wells

International Nuclear Information System (INIS)

Hao Yafei

2012-01-01

We theoretically investigate the spin splitting in four undoped asymmetric quantum wells in the absence of external electric field and magnetic field. The quantum well geometry dependence of spin splitting is studied with the Rashba and the Dresselhaus spin-orbit coupling included. The results show that the structure of quantum well plays an important role in spin splitting. The Rashba and the Dresselhaus spin splitting in four asymmetric quantum wells are quite different. The origin of the distinction is discussed in this work. (condensed matter: electronic structure, electrical, magnetic, and optical properties)

Splitting Ward identity

Energy Technology Data Exchange (ETDEWEB)

Safari, Mahmoud [Institute for Research in Fundamental Sciences (IPM), School of Particles and Accelerators, P.O. Box 19395-5531, Tehran (Iran, Islamic Republic of)

2016-04-15

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 the modified master equation and emphasize its role in constraining the effective action. Finally, application to general gauge theories within the geometric approach is discussed. (orig.)

Splitting Ward identity

International Nuclear Information System (INIS)

Safari, Mahmoud

2016-01-01

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 the modified master equation and emphasize its role in constraining the effective action. Finally, application to general gauge theories within the geometric approach is discussed. (orig.)

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.

Heteromeric Kv7.2/7.3 channels differentially regulate action potential initiation and conduction in neocortical myelinated axons

NARCIS (Netherlands)

Battefeld, A.; Tran, B.T.; Gavrilis, J.; Cooper, E.C.; Kole, Maarten|info:eu-repo/dai/nl/256257574

2014-01-01

Rapid energy-efficient signaling along vertebrate axons is achieved through intricate subcellular arrangements of voltage-gated ion channels and myelination. One recently appreciated example is the tight colocalization of Kv7 potassium channels and voltage-gated sodium (Nav ) channels in the axonal

Heteromeric Kv7.2/7.3 channels differentially regulate action potential initiation and conduction in neocortical myelinated axons

NARCIS (Netherlands)

Battefeld, A.; Tran, Baouyen T; Gavrilis, Jason; Cooper, Edward C; Kole, Maarten H P

2014-01-01

Rapid energy-efficient signaling along vertebrate axons is achieved through intricate subcellular arrangements of voltage-gated ion channels and myelination. One recently appreciated example is the tight colocalization of K(v)7 potassium channels and voltage-gated sodium (Na(v)) channels in the

Pharmaceutical counselling about different types of tablet-splitting methods based on the results of weighing tests and mechanical development of splitting devices.

Science.gov (United States)

Somogyi, O; Meskó, A; Csorba, L; Szabó, P; Zelkó, R

2017-08-30

The division of tablets and adequate methods of splitting them are a complex problem in all sectors of health care. Although tablet-splitting is often required, this procedure can be difficult for patients. Four tablets were investigated with different external features (shape, score-line, film-coat and size). The influencing effect of these features and the splitting methods was investigated according to the precision and "weight loss" of splitting techniques. All four types of tablets were halved by four methods: by hand, with a kitchen knife, with an original manufactured splitting device and with a modified tablet splitter based on a self-developed mechanical model. The mechanical parameters (harness and friability) of the products were measured during the study. The "weight loss" and precision of splitting methods were determined and compared by statistical analysis. On the basis of the results, the external features (geometry), the mechanical parameters of tablets and the mechanical structure of splitting devices can influence the "weight loss" and precision of tablet-splitting. Accordingly, a new decision-making scheme was developed for the selection of splitting methods. In addition, the skills of patients and the specialties of therapy should be considered so that pharmaceutical counselling can be more effective regarding tablet-splitting. Copyright © 2017 Elsevier B.V. All rights reserved.

Iterative Splitting Methods for Differential Equations

CERN Document Server

Geiser, Juergen

2011-01-01

Iterative Splitting Methods for Differential Equations explains how to solve evolution equations via novel iterative-based splitting methods that efficiently use computational and memory resources. It focuses on systems of parabolic and hyperbolic equations, including convection-diffusion-reaction equations, heat equations, and wave equations. In the theoretical part of the book, the author discusses the main theorems and results of the stability and consistency analysis for ordinary differential equations. He then presents extensions of the iterative splitting methods to partial differential

Global gene expression profiles in brain regions reflecting abnormal neuronal and glial functions targeting myelin sheaths after 28-day exposure to cuprizone in rats

Energy Technology Data Exchange (ETDEWEB)

Abe, Hajime [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193 (Japan); Saito, Fumiyo [Chemicals Evaluation and Research Institute, Japan, 1-4-25 Koraku, Bunkyo-ku, Tokyo 112-0004 (Japan); Tanaka, Takeshi; Mizukami, Sayaka; Watanabe, Yousuke [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193 (Japan); Imatanaka, Nobuya; Akahori, Yumi [Chemicals Evaluation and Research Institute, Japan, 1-4-25 Koraku, Bunkyo-ku, Tokyo 112-0004 (Japan); Yoshida, Toshinori [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Shibutani, Makoto, E-mail: mshibuta@cc.tuat.ac.jp [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan)

2016-11-01

Both developmental and postpubertal cuprizone (CPZ) exposure impairs hippocampal neurogenesis in rats. We previously found that developmental CPZ exposure alters the expression of genes related to neurogenesis, myelination, and synaptic transmission in specific brain regions of offspring. Here, we examined neuronal and glial toxicity profiles in response to postpubertal CPZ exposure by using expression microarray analysis in the hippocampal dentate gyrus, corpus callosum, cerebral cortex, and cerebellar vermis of 5-week-old male rats exposed to 0, 120, and 600 mg/kg CPZ for 28 days. Genes showing transcript upregulation were subjected to immunohistochemical analysis. We found transcript expression alterations at 600 mg/kg for genes related to synaptic transmission, Ache and Prima1, and cell cycle regulation, Tfap4 and Cdkn1a, in the dentate gyrus, which showed aberrant neurogenesis in the subgranular zone. This dose downregulated myelination-related genes in multiple brain regions, whereas KLOTHO{sup +} oligodendrocyte density was decreased only in the corpus callosum. The corpus callosum showed an increase in transcript levels for inflammatory response-related genes and in the number of CD68{sup +} microglia, MT{sup +} astrocytes, and TUNEL{sup +} apoptotic cells. These results suggest that postpubertal CPZ exposure targets synaptic transmission and cell cycle regulation to affect neurogenesis in the dentate gyrus. CPZ suppressed myelination in multiple brain regions and KLOTHO-mediated oligodendrocyte maturation only in the corpus callosum. The increased number of CD68{sup +} microglia, MT{sup +} astrocytes, and TUNEL{sup +} apoptotic cells in the corpus callosum may be involved in the induction of KLOTHO{sup +} oligodendrocyte death and be a protective mechanism against myelin damage following CPZ exposure. - Highlights: • Target gene expression profiles were examined in rats after 28-day CPZ exposure. • Multiple brain region-specific global gene expression

Global gene expression profiles in brain regions reflecting abnormal neuronal and glial functions targeting myelin sheaths after 28-day exposure to cuprizone in rats

International Nuclear Information System (INIS)

Abe, Hajime; Saito, Fumiyo; Tanaka, Takeshi; Mizukami, Sayaka; Watanabe, Yousuke; Imatanaka, Nobuya; Akahori, Yumi; Yoshida, Toshinori; Shibutani, Makoto

2016-01-01

Both developmental and postpubertal cuprizone (CPZ) exposure impairs hippocampal neurogenesis in rats. We previously found that developmental CPZ exposure alters the expression of genes related to neurogenesis, myelination, and synaptic transmission in specific brain regions of offspring. Here, we examined neuronal and glial toxicity profiles in response to postpubertal CPZ exposure by using expression microarray analysis in the hippocampal dentate gyrus, corpus callosum, cerebral cortex, and cerebellar vermis of 5-week-old male rats exposed to 0, 120, and 600 mg/kg CPZ for 28 days. Genes showing transcript upregulation were subjected to immunohistochemical analysis. We found transcript expression alterations at 600 mg/kg for genes related to synaptic transmission, Ache and Prima1, and cell cycle regulation, Tfap4 and Cdkn1a, in the dentate gyrus, which showed aberrant neurogenesis in the subgranular zone. This dose downregulated myelination-related genes in multiple brain regions, whereas KLOTHO + oligodendrocyte density was decreased only in the corpus callosum. The corpus callosum showed an increase in transcript levels for inflammatory response-related genes and in the number of CD68 + microglia, MT + astrocytes, and TUNEL + apoptotic cells. These results suggest that postpubertal CPZ exposure targets synaptic transmission and cell cycle regulation to affect neurogenesis in the dentate gyrus. CPZ suppressed myelination in multiple brain regions and KLOTHO-mediated oligodendrocyte maturation only in the corpus callosum. The increased number of CD68 + microglia, MT + astrocytes, and TUNEL + apoptotic cells in the corpus callosum may be involved in the induction of KLOTHO + oligodendrocyte death and be a protective mechanism against myelin damage following CPZ exposure. - Highlights: • Target gene expression profiles were examined in rats after 28-day CPZ exposure. • Multiple brain region-specific global gene expression profiling was performed. • CPZ

2-Photon tandem device for water splitting

DEFF Research Database (Denmark)

Seger, Brian; Castelli, Ivano Eligio; Vesborg, Peter Christian Kjærgaard

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...... for photocatalytic water splitting by using a large bandgap photocathode and a low bandgap photoanode with attached protection layers....

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

2013-01-01

Mice with a heterozygous knock-out of the myelin protein P0 gene (P0+/-) develop a neuropathy similar to human Charcot-Marie-Tooth disease. They are indistinguishable from wild-types (WT) at birth and develop a slowly progressing demyelinating neuropathy. The aim of this study was to investigate...... whether the regeneration capacity of early symptomatic P0+/- is impaired as compared to age matched WT. Right sciatic nerves were lesioned at the thigh in 7-8 months old mice. Tibial motor axons at ankle were investigated by conventional motor conduction studies and axon excitability studies using...... threshold tracking. To evaluate regeneration we monitored the recovery of motor function after crush, and then compared the fiber distribution by histology. The overall motor performance was investigated using Rotor-Rod. P0+/- had reduced compound motor action potential amplitudes and thinner myelinated...

Semi-strong split domination in graphs

Directory of Open Access Journals (Sweden)

Anwar Alwardi

2014-06-01

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

Improved determination of the myelin water fraction in human brain using magnetic resonance imaging through Bayesian analysis of mcDESPOT.

Science.gov (United States)

Bouhrara, Mustapha; Spencer, Richard G

2016-02-15

Myelin water fraction (MWF) mapping with magnetic resonance imaging has led to the ability to directly observe myelination and demyelination in both the developing brain and in disease. Multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) has been proposed as a rapid approach for multicomponent relaxometry and has been applied to map MWF in the human brain. However, even for the simplest two-pool signal model consisting of myelin-associated and non-myelin-associated water, the dimensionality of the parameter space for obtaining MWF estimates remains high. This renders parameter estimation difficult, especially at low-to-moderate signal-to-noise ratios (SNRs), due to the presence of local minima and the flatness of the fit residual energy surface used for parameter determination using conventional nonlinear least squares (NLLS)-based algorithms. In this study, we introduce three Bayesian approaches for analysis of the mcDESPOT signal model to determine MWF. Given the high-dimensional nature of the mcDESPOT signal model, and, therefore the high-dimensional marginalizations over nuisance parameters needed to derive the posterior probability distribution of the MWF, the Bayesian analyses introduced here use different approaches to reduce the dimensionality of the parameter space. The first approach uses normalization by average signal amplitude, and assumes that noise can be accurately estimated from signal-free regions of the image. The second approach likewise uses average amplitude normalization, but incorporates a full treatment of noise as an unknown variable through marginalization. The third approach does not use amplitude normalization and incorporates marginalization over both noise and signal amplitude. Through extensive Monte Carlo numerical simulations and analysis of in vivo human brain datasets exhibiting a range of SNR and spatial resolution, we demonstrated markedly improved accuracy and precision in the estimation of MWF

Postnatal Sonic hedgehog (Shh) responsive cells give rise to oligodendrocyte lineage cells during myelination and in adulthood contribute to remyelination.

Science.gov (United States)

Sanchez, Maria A; Armstrong, Regina C

2018-01-01

Sonic hedgehog (Shh) regulates a wave of oligodendrocyte production for extensive myelination during postnatal development. During this postnatal period of oligodendrogenesis, we fate-labeled cells exhibiting active Shh signaling to examine their contribution to the regenerative response during remyelination. Bitransgenic mouse lines were generated for induced genetic fate-labeling of cells actively transcribing Shh or Gli1. Gli1 transcription is an effective readout for canonical Shh signaling. Shh CreERT2 mice and Gli1 CreERT2 mice were crossed to either R26 tdTomato mice to label cells with red fluorescence, or, R26 IAP mice to label membranes with alkaline phosphatase. When tamoxifen (TMX) was given on postnatal days 6-9 (P6-9), Shh ligand synthesis was prevalent in neurons of Shh CreERT2 ; R26 tdTomato mice and Shh CreERT2 ;R26 IAP mice. In Gli1 CreERT2 crosses, TMX from P6-9 detected Gli1 transcription in cells that populated the corpus callosum (CC) during postnatal myelination. Delaying TMX to P14-17, after the peak of oligodendrogenesis, significantly reduced labeling of Shh synthesizing neurons and Gli1 expressing cells in the CC. Importantly, Gli1 CreERT2 ;R26 tdTomato mice given TMX from P6-9 showed Gli1 fate-labeled cells in the adult (P56) CC, including cycling progenitor cells identified by EdU incorporation and NG2 immunolabeling. Furthermore, after cuprizone demyelination of the adult CC, Gli1 fate-labeled cells incorporated EdU and were immunolabeled by NG2 early during remyelination while forming myelin-like membranes after longer periods for remyelination to progress. These studies reveal a postnatal cell population with transient Shh signaling that contributes to oligodendrogenesis during CC myelination, and gives rise to cells that continue to proliferate in adulthood and contribute to CC remyelination. Published by Elsevier Inc.

Numerical investigation of a dual-loop EGR split strategy using a split index and multi-objective Pareto optimization

International Nuclear Information System (INIS)

Park, Jungsoo; Song, Soonho; Lee, Kyo Seung

2015-01-01

Highlights: • Model-based control of dual-loop EGR system is performed. • EGR split index is developed to provide non-dimensional index for optimization. • EGR rates are calibrated using EGR split index at specific operating conditions. • Multi-objective Pareto optimization is performed to minimize NO X and BSFC. • Optimum split strategies are suggested with LP-rich dual-loop EGR at high load. - Abstract: A proposed dual-loop exhaust-gas recirculation (EGR) system that combines the features of high-pressure (HP) and low-pressure (LP) systems is considered a key technology for improving the combustion behavior of diesel engines. The fraction of HP and LP flows, known as the EGR split, for a given dual-loop EGR rate play an important role in determining the engine performance and emission characteristics. Therefore, identifying the proper EGR split is important for the engine optimization and calibration processes, which affect the EGR response and deNO X efficiencies. The objective of this research was to develop a dual-loop EGR split strategy using numerical analysis and one-dimensional (1D) cycle simulation. A control system was modeled by coupling the 1D cycle simulation and the control logic. An EGR split index was developed to investigate the HP/LP split effects on the engine performance and emissions. Using the model-based control system, a multi-objective Pareto (MOP) analysis was used to minimize the NO X formation and fuel consumption through optimized engine operating parameters. The MOP analysis was performed using a response surface model extracted from Latin hypercube sampling as a fractional factorial design of experiment. By using an LP rich dual-loop EGR, a high EGR rate was attained at low, medium, and high engine speeds, increasing the applicable load ranges compared to base conditions

Splitting Functions at High Transverse Momentum

CERN Document Server

Moutafis, Rhea Penelope; CERN. Geneva. TH Department

2017-01-01

Among the production channels of the Higgs boson one contribution could become significant at high transverse momentum which is the radiation of a Higgs boson from another particle. This note focuses on the calculation of splitting functions and cross sections of such processes. The calculation is first carried out on the example $e\\rightarrow e\\gamma$ to illustrate the way splitting functions are calculated. Then the splitting function of $e\\rightarrow eh$ is calculated in similar fashion. This procedure can easily be generalized to processes such as $q\\rightarrow qh$ or $g\\rightarrow gh$.

SplitRacer - a semi-automatic tool for the analysis and interpretation of teleseismic shear-wave splitting

Science.gov (United States)

Reiss, Miriam Christina; Rümpker, Georg

2017-04-01

We present a semi-automatic, graphical user interface tool for the analysis and interpretation of teleseismic shear-wave splitting in MATLAB. Shear wave splitting analysis is a standard tool to infer seismic anisotropy, which is often interpreted as due to lattice-preferred orientation of e.g. mantle minerals or shape-preferred orientation caused by cracks or alternating layers in the lithosphere and hence provides a direct link to the earth's kinematic processes. The increasing number of permanent stations and temporary experiments result in comprehensive studies of seismic anisotropy world-wide. Their successive comparison with a growing number of global models of mantle flow further advances our understanding the earth's interior. However, increasingly large data sets pose the inevitable question as to how to process them. Well-established routines and programs are accurate but often slow and impractical for analyzing a large amount of data. Additionally, shear wave splitting results are seldom evaluated using the same quality criteria which complicates a straight-forward comparison. SplitRacer consists of several processing steps: i) download of data per FDSNWS, ii) direct reading of miniSEED-files and an initial screening and categorizing of XKS-waveforms using a pre-set SNR-threshold. iii) an analysis of the particle motion of selected phases and successive correction of the sensor miss-alignment based on the long-axis of the particle motion. iv) splitting analysis of selected events: seismograms are first rotated into radial and transverse components, then the energy-minimization method is applied, which provides the polarization and delay time of the phase. To estimate errors, the analysis is done for different randomly-chosen time windows. v) joint-splitting analysis for all events for one station, where the energy content of all phases is inverted simultaneously. This allows to decrease the influence of noise and to increase robustness of the measurement

Cranial nerve vascular compression syndromes of the trigeminal, facial and vago-glossopharyngeal nerves: comparative anatomical study of the central myelin portion and transitional zone; correlations with incidences of corresponding hyperactive dysfunctional syndromes.

Science.gov (United States)

Guclu, Bulent; Sindou, Marc; Meyronet, David; Streichenberger, Nathalie; Simon, Emile; Mertens, Patrick

2011-12-01

The aim of this study was to evaluate the anatomy of the central myelin portion and the central myelin-peripheral myelin transitional zone of the trigeminal, facial, glossopharyngeal and vagus nerves from fresh cadavers. The aim was also to investigate the relationship between the length and volume of the central myelin portion of these nerves with the incidences of the corresponding cranial dysfunctional syndromes caused by their compression to provide some more insights for a better understanding of mechanisms. The trigeminal, facial, glossopharyngeal and vagus nerves from six fresh cadavers were examined. The length of these nerves from the brainstem to the foramen that they exit were measured. Longitudinal sections were stained and photographed to make measurements. The diameters of the nerves where they exit/enter from/to brainstem, the diameters where the transitional zone begins, the distances to the most distal part of transitional zone from brainstem and depths of the transitional zones were measured. Most importantly, the volume of the central myelin portion of the nerves was calculated. Correlation between length and volume of the central myelin portion of these nerves and the incidences of the corresponding hyperactive dysfunctional syndromes as reported in the literature were studied. The distance of the most distal part of the transitional zone from the brainstem was 4.19  ±  0.81 mm for the trigeminal nerve, 2.86  ±  1.19 mm for the facial nerve, 1.51  ±  0.39 mm for the glossopharyngeal nerve, and 1.63  ±  1.15 mm for the vagus nerve. The volume of central myelin portion was 24.54  ±  9.82 mm(3) in trigeminal nerve; 4.43  ±  2.55 mm(3) in facial nerve; 1.55  ±  1.08 mm(3) in glossopharyngeal nerve; 2.56  ±  1.32 mm(3) in vagus nerve. Correlations (p  nerves and incidences of the corresponding diseases. At present it is rather well-established that primary trigeminal neuralgia, hemifacial spasm and vago

Generalized field-splitting algorithms for optimal IMRT delivery efficiency

Energy Technology Data Exchange (ETDEWEB)

Kamath, Srijit [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States); Sahni, Sartaj [Department of Computer and Information Science and Engineering, University of Florida, Gainesville, FL (United States); Li, Jonathan [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States); Ranka, Sanjay [Department of Computer and Information Science and Engineering, University of Florida, Gainesville, FL (United States); Palta, Jatinder [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States)

2007-09-21

Intensity-modulated radiation therapy (IMRT) uses radiation beams of varying intensities to deliver varying doses of radiation to different areas of the tissue. The use of IMRT has allowed the delivery of higher doses of radiation to the tumor and lower doses to the surrounding healthy tissue. It is not uncommon for head and neck tumors, for example, to have large treatment widths that are not deliverable using a single field. In such cases, the intensity matrix generated by the optimizer needs to be split into two or three matrices, each of which may be delivered using a single field. Existing field-splitting algorithms used the pre-specified arbitrary split line or region where the intensity matrix is split along a column, i.e., all rows of the matrix are split along the same column (with or without the overlapping of split fields, i.e., feathering). If three fields result, then the two splits are along the same two columns for all rows. In this paper we study the problem of splitting a large field into two or three subfields with the field width as the only constraint, allowing for an arbitrary overlap of the split fields, so that the total MU efficiency of delivering the split fields is maximized. Proof of optimality is provided for the proposed algorithm. An average decrease of 18.8% is found in the total MUs when compared to the split generated by a commercial treatment planning system and that of 10% is found in the total MUs when compared to the split generated by our previously published algorithm. For more information on this article, see medicalphysicsweb.org.

Split-plot fractional designs: Is minimum aberration enough?

DEFF Research Database (Denmark)

Kulahci, Murat; Ramirez, Jose; Tobias, Randy

2006-01-01

Split-plot experiments are commonly used in industry for product and process improvement. Recent articles on designing split-plot experiments concentrate on minimum aberration as the design criterion. Minimum aberration has been criticized as a design criterion for completely randomized fractional...... factorial design and alternative criteria, such as the maximum number of clear two-factor interactions, are suggested (Wu and Hamada (2000)). The need for alternatives to minimum aberration is even more acute for split-plot designs. In a standard split-plot design, there are several types of two...... for completely randomized designs. Consequently, we provide a modified version of the maximum number of clear two-factor interactions design criterion to be used for split-plot designs....

Heteromeric K(v)7.2/7.3 Channels Differentially Regulate Action Potential Initiation and Conduction in Neocortical Myelinated Axons

NARCIS (Netherlands)

Battefeld, Arne; Tran, Baouyen T.; Gavrilis, Jason; Cooper, Edward C.; Kole, Maarten H. P.

2014-01-01

Rapid energy-efficient signaling along vertebrate axons is achieved through intricate subcellular arrangements of voltage-gated ion channels and myelination. One recently appreciated example is the tight colocalization of K(v)7 potassium channels and voltage-gated sodium (Na-v) channels in the

Antibodies to myelin oligodendrocyte glycoprotein in idiopathic optic neuritis.

Science.gov (United States)

Nakajima, Hideki; Motomura, Masakatsu; Tanaka, Keiko; Fujikawa, Azusa; Nakata, Ruka; Maeda, Yasuhiro; Shima, Tomoaki; Mukaino, Akihiro; Yoshimura, Shunsuke; Miyazaki, Teiichiro; Shiraishi, Hirokazu; Kawakami, Atsushi; Tsujino, Akira

2015-04-02

To investigate the differences of clinical features, cerebrospinal fluid (CSF), MRI findings and response to steroid therapies between patients with optic neuritis (ON) who have myelin oligodendrocyte glycoprotein (MOG) antibodies and those who have seronegative ON. We recruited participants in the department of neurology and ophthalmology in our hospital in Japan. We retrospectively evaluated the clinical features and response to steroid therapies of patients with ON. Sera from patients were tested for antibodies to MOG and aquaporin-4 (AQP4) with a cell-based assay. Between April 2009 and March 2014, we enrolled serial 57 patients with ON (27 males, 30 females; age range 16-84 years) who ophthalmologists had diagnosed as having or suspected to have ON with acute visual impairment and declined critical flicker frequency, abnormal findings of brain MRI, optical coherence tomography and fluorescein fundus angiography at their onset or recurrence. We excluded those patients who fulfilled the diagnostic criteria of neuromyelitis optica (NMO)/NMO spectrum disorders (NMOSD), MS McDonald's criteria, and so on. Finally we defined 29 patients with idiopathic ON (14 males, 15 females, age range 16-84 years). 27.6% (8/29) were positive for MOG antibodies and 3.4% (1/29) were positive for AQP4. Among the eight patients with MOG antibodies, five had optic pain (p=0.001) and three had prodromal infection (p=0.179). Three of the eight MOG-positive patients showed significantly high CSF levels of myelin basic protein (p=0.021) and none were positive for oligoclonal band in CSF. On MRIs, seven MOG-positive patients showed high signal intensity on optic nerve, three had a cerebral lesion and one had a spinal cord lesion. Seven of the eight MOG-positive patients had a good response to steroid therapy. Although not proving primary pathogenicity of anti-MOG antibodies, the present results indicate that the measurement of MOG antibodies is useful in diagnosing and treating ON

Reduced myelin basic protein and actin-related gene expression in visual cortex in schizophrenia.

Science.gov (United States)

Matthews, Paul R; Eastwood, Sharon L; Harrison, Paul J

2012-01-01

Most brain gene expression studies of schizophrenia have been conducted in the frontal cortex or hippocampus. The extent to which alterations occur in other cortical regions is not well established. We investigated primary visual cortex (Brodmann area 17) from the Stanley Neuropathology Consortium collection of tissue from 60 subjects with schizophrenia, bipolar disorder, major depression, or controls. We first carried out a preliminary array screen of pooled RNA, and then used RT-PCR to quantify five mRNAs which the array identified as differentially expressed in schizophrenia (myelin basic protein [MBP], myelin-oligodendrocyte glycoprotein [MOG], β-actin [ACTB], thymosin β-10 [TB10], and superior cervical ganglion-10 [SCG10]). Reduced mRNA levels were confirmed by RT-PCR for MBP, ACTB and TB10. The MBP reduction was limited to transcripts containing exon 2. ACTB and TB10 mRNAs were also decreased in bipolar disorder. None of the transcripts were altered in subjects with major depression. Reduced MBP mRNA in schizophrenia replicates findings in other brain regions and is consistent with oligodendrocyte involvement in the disorder. The decreases in expression of ACTB, and the actin-binding protein gene TB10, suggest changes in cytoskeletal organisation. The findings confirm that the primary visual cortex shows molecular alterations in schizophrenia and extend the evidence for a widespread, rather than focal, cortical pathophysiology.

26 CFR 1.7872-15 - Split-dollar loans.

Science.gov (United States)

2010-04-01

...'s death benefit proceeds, the policy's cash surrender value, or both. (ii) Payments that are only... regarding certain split-dollar term loans payable on the death of an individual, certain split-dollar term... insurance arrangement make a representation—(i) Requirement. An otherwise noncontingent payment on a split...

Rapid whole brain myelin water content mapping without an external water standard at 1.5T.

Science.gov (United States)

Nguyen, Thanh D; Spincemaille, Pascal; Gauthier, Susan A; Wang, Yi

2017-06-01

The objective of this study is to develop rapid whole brain mapping of myelin water content (MWC) at 1.5T. The Fast Acquisition with Spiral Trajectory and T2prep (FAST-T2) pulse sequence originally developed for myelin water fraction (MWF) mapping was modified to obtain fast mapping of T1 and receiver coil sensitivity needed for MWC computation. The accuracy of the proposed T1 mapping was evaluated by comparing with the standard IR-FSE method. Numerical simulations were performed to assess the accuracy and reliability of the proposed MWC mapping. We also compared MWC values obtained with either cerebrospinal fluid (CSF) or an external water tube attached to the subject's head as the water reference. Our results from healthy volunteers show that whole brain MWC mapping is feasible in 7min and provides accurate brain T1 values. Regional brain WC and MWC measurements obtained with the internal CSF-based water standard showed excellent correlation (R>0.99) and negligible bias within narrow limits of agreement compared to those obtained with an external water standard. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Directory of Open Access Journals (Sweden)

Debra A. Mayes

2013-09-01

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

A guiding oblique osteotomy cut to prevent bad split in sagittal split ramus osteotomy: a technical note

Directory of Open Access Journals (Sweden)

Gururaj Arakeri

2015-06-01

Full Text Available Aim: To present a simple technical modification of a medial osteotomy cut which prevents its misdirection and overcomes various anatomical variations as well as technical problems. Methods: The medial osteotomy cut is modified in the posterior half at an angle of 15°-20° following novel landmarks. Results: The proposed cut exclusively directs the splitting forces downwards to create a favorable lingual fracture, preventing the possibility of an upwards split which would cause a coronoid or condylar fracture. Conclusion: This modification has proven to be successful to date without encountering the complications of a bad split or nerve damage.

Splitting and non splitting are pollution models photochemical reactions in the urban areas of greater Tehran area

International Nuclear Information System (INIS)

Heidarinasab, A.; Dabir, B.; Sahimi, M.; Badii, Kh.

2003-01-01

During the past years, one of the most important problems has been air pollution in urban areas. In this regards, ozone, as one of the major products of photochemical reactions, has great importance. The term 'photochemical' is applied to a number of secondary pollutants that appear as a result of sun-related reactions, ozone being the most important one. So far various models have been suggested to predict these pollutants. In this paper, we developed the model that has been introduced by Dabir, et al. [4]. In this model more than 48 chemical species and 114 chemical reactions are involved. The result of this development, showed good to excellent agreement across the region for compounds such as O 3 , NO, NO 2 , CO, and SO 2 with regard to VOC and NMHC. The results of the simulation were compared with previous work [4] and the effects of increasing the number of components and reactions were evaluated. The results of the operator splitting method were compared with non splitting solving method. The result showed that splitting method with one-tenth time step collapsed with non splitting method (Crank-Nicolson, under-relaxation iteration method without splitting of the equation terms). Then we developed one dimensional model to 3-D and were compared with experimental data

Tune splitting in the presence of linear coupling

International Nuclear Information System (INIS)

Parzen, G.

1991-01-01

The presence of random skew quadrupole field errors will couple the x and y motions. The x and y motions are then each given by the sum of 2 normal modes with the tunes v 1 and v 2 , which may differ appreciably from v x and v y , the unperturbed tunes. This is often called tune splitting since |v 1 - v 2 | is usually larger than |v x - v y |. This tune splitting may be large in proton accelerators using superconducting magnets, because of the relatively large random skew quadrupole field errors that are expected in these magnets. This effect is also increased by the required insertions in proton colliders which generate large β-functions in the insertion region. This tune splitting has been studied in the RHIC accelerator. For RHIC, a tune splitting as large as 0.2 was found in one worse case. A correction system has been developed for correcting this large tune splitting which uses two families of skew quadrupole correctors. It has been found that this correction system corrects most of the large tune splitting, but a residual tune splitting remains that is still appreciable. This paper discusses the corrections to this residual time

Split-plot designs for robotic serial dilution assays.

Science.gov (United States)

Buzas, Jeffrey S; Wager, Carrie G; Lansky, David M

2011-12-01

This article explores effective implementation of split-plot designs in serial dilution bioassay using robots. We show that the shortest path for a robot to fill plate wells for a split-plot design is equivalent to the shortest common supersequence problem in combinatorics. We develop an algorithm for finding the shortest common supersequence, provide an R implementation, and explore the distribution of the number of steps required to implement split-plot designs for bioassay through simulation. We also show how to construct collections of split plots that can be filled in a minimal number of steps, thereby demonstrating that split-plot designs can be implemented with nearly the same effort as strip-plot designs. Finally, we provide guidelines for modeling data that result from these designs. © 2011, The International Biometric Society.

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 broken...

Split scheduling with uniform setup times.

NARCIS (Netherlands)

F. Schalekamp; R.A. Sitters (René); S.L. van der Ster; L. Stougie (Leen); V. Verdugo; A. van Zuylen

2015-01-01

htmlabstractWe study a scheduling problem in which jobs may be split into parts, where the parts of a split job may be processed simultaneously on more than one machine. Each part of a job requires a setup time, however, on the machine where the job part is processed. During setup, a

Numerical simulation and experiment on multilayer stagger-split die.

Science.gov (United States)

Liu, Zhiwei; Li, Mingzhe; Han, Qigang; Yang, Yunfei; Wang, Bolong; Sui, Zhou

2013-05-01

A novel ultra-high pressure device, multilayer stagger-split die, has been constructed based on the principle of "dividing dies before cracking." Multilayer stagger-split die includes an encircling ring and multilayer assemblages, and the mating surfaces of the multilayer assemblages are mutually staggered between adjacent layers. In this paper, we investigated the stressing features of this structure through finite element techniques, and the results were compared with those of the belt type die and single split die. The contrast experiments were also carried out to test the bearing pressure performance of multilayer stagger-split die. It is concluded that the stress distributions are reasonable and the materials are utilized effectively for multilayer stagger-split die. And experiments indicate that the multilayer stagger-split die can bear the greatest pressure.

Tensor products of higher almost split sequences

OpenAIRE

Pasquali, Andrea

2015-01-01

We investigate how the higher almost split sequences over a tensor product of algebras are related to those over each factor. Herschend and Iyama gave a precise criterion for when the tensor product of an $n$-representation finite algebra and an $m$-representation finite algebra is $(n+m)$-representation finite. In this case we give a complete description of the higher almost split sequences over the tensor product by expressing every higher almost split sequence as the mapping cone of a suit...

Conditional Toxin Splicing Using a Split Intein System.

Science.gov (United States)

Alford, Spencer C; O'Sullivan, Connor; Howard, Perry L

2017-01-01

Protein toxin splicing mediated by split inteins can be used as a strategy for conditional cell ablation. The approach requires artificial fragmentation of a potent protein toxin and tethering each toxin fragment to a split intein fragment. The toxin-intein fragments are, in turn, fused to dimerization domains, such that addition of a dimerizing agent reconstitutes the split intein. These chimeric toxin-intein fusions remain nontoxic until the dimerizer is added, resulting in activation of intein splicing and ligation of toxin fragments to form an active toxin. Considerations for the engineering and implementation of conditional toxin splicing (CTS) systems include: choice of toxin split site, split site (extein) chemistry, and temperature sensitivity. The following method outlines design criteria and implementation notes for CTS using a previously engineered system for splicing a toxin called sarcin, as well as for developing alternative CTS systems.

Split Scheduling with Uniform Setup Times

NARCIS (Netherlands)

Schalekamp, F.; Sitters, R.A.; van der Ster, S.L.; Stougie, L.; Verdugo, V.; van Zuylen, A.

2015-01-01

We study a scheduling problem in which jobs may be split into parts, where the parts of a split job may be processed simultaneously on more than one machine. Each part of a job requires a setup time, however, on the machine where the job part is processed. During setup, a machine cannot process or

NNLO time-like splitting functions in QCD

International Nuclear Information System (INIS)

Moch, S.; Vogt, A.

2008-07-01

We review the status of the calculation of the time-like splitting functions for the evolution of fragmentation functions to the next-to-next-to-leading order in perturbative QCD. By employing relations between space-like and time-like deep-inelastic processes, all quark-quark and the gluon-gluon time-like splitting functions have been obtained to three loops. The corresponding quantities for the quark-gluon and gluon-quark splitting at this order are presently still unknown except for their second Mellin moments. (orig.)

Recent Progress in Energy-Driven Water Splitting.

Science.gov (United States)

Tee, Si Yin; Win, Khin Yin; Teo, Wee Siang; Koh, Leng-Duei; Liu, Shuhua; Teng, Choon Peng; Han, Ming-Yong

2017-05-01

Hydrogen is readily obtained from renewable and non-renewable resources via water splitting by using thermal, electrical, photonic and biochemical energy. The major hydrogen production is generated from thermal energy through steam reforming/gasification of fossil fuel. As the commonly used non-renewable resources will be depleted in the long run, there is great demand to utilize renewable energy resources for hydrogen production. Most of the renewable resources may be used to produce electricity for driving water splitting while challenges remain to improve cost-effectiveness. As the most abundant energy resource, the direct conversion of solar energy to hydrogen is considered the most sustainable energy production method without causing pollutions to the environment. In overall, this review briefly summarizes thermolytic, electrolytic, photolytic and biolytic water splitting. It highlights photonic and electrical driven water splitting together with photovoltaic-integrated solar-driven water electrolysis.

Mini-Split Heat Pumps Multifamily Retrofit Feasibility Study

Energy Technology Data Exchange (ETDEWEB)

Dentz, Jordan [ARIES Collaborative, New York, NY (United States); Podorson, David [ARIES Collaborative, New York, NY (United States); Varshney, Kapil [ARIES Collaborative, New York, NY (United States)

2014-05-01

Mini-split heat pumps can provide space heating and cooling in many climates and are relatively affordable. These and other features make them potentially suitable for retrofitting into multifamily buildings in cold climates to replace electric resistance heating or other outmoded heating systems. This report investigates the suitability of mini-split heat pumps for multifamily retrofits. Various technical and regulatory barriers are discussed and modeling was performed to compare long-term costs of substituting mini-splits for a variety of other heating and cooling options. A number of utility programs have retrofit mini-splits in both single family and multifamily residences. Two such multifamily programs are discussed in detail.

Communication: Tunnelling splitting in the phosphine molecule

Science.gov (United States)

Sousa-Silva, Clara; Tennyson, Jonathan; Yurchenko, Sergey N.

2016-09-01

Splitting due to tunnelling via the potential energy barrier has played a significant role in the study of molecular spectra since the early days of spectroscopy. The observation of the ammonia doublet led to attempts to find a phosphine analogous, but these have so far failed due to its considerably higher barrier. Full dimensional, variational nuclear motion calculations are used to predict splittings as a function of excitation energy. Simulated spectra suggest that such splittings should be observable in the near infrared via overtones of the ν2 bending mode starting with 4ν2.

[Ultrastructural changes of myelinated fibers in the brain in continuous and attack-like paranoid schizophrenia].

Science.gov (United States)

Uranova, N A; Kolomeets, N S; Vikhreva, O V; Zimina, I S; Rakhmanova, V I; Orlovskaya, D D

Previously the authors have reported the ultrastructural pathology of myelinated fibers (MF) in the brain in schizophrenia. The aim of the present study was to compare the effect of disease course on ultrastructural changes of MF. Postmortem electron microscopic morphometric study of MF was performed in the prefrontal cortex, caudate nucleus and hippocampus in 19 cases of paranoid schizophrenia. Fourteen cases of continuous schizophrenia, 5 cases of attack-like schizophrenia and 25 normal matched control cases were studied. The proportion (percentage) of pathological MF was estimated in the prefrontal cortex, layer 5, CA3 area of hippocampus, pyramidal layer, and in the head of the caudate nucleus. The percentage of MF having axonal atrophy and swelling of periaxonal oligodendrocyte process was significantly higher in both continuous and attack-like schizophrenia in all brain structures studied as compared to the control group. In the hippocampus and caudate nucleus, this parameter was increased significantly in attack-like schizophrenia as compared to continuous schizophrenia. In the prefrontal cortex. The percentage of the pathological MF having signs of deformation and destruction of myelin sheaths increased significantly only in continuous schizophrenia as compared to the control group. MF pathology is similar in attack-like and continuous paranoid schizophrenia but differ by the degree of severity of pathological MF. Abnormalities in MF contribute to the disconnectivity between the prefrontal cortex, caudate nucleus and hippocampus.

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 methods in communication, imaging, science, and engineering

CERN Document Server

Osher, Stanley; Yin, Wotao

2016-01-01

This book is about computational methods based on operator splitting. It consists of twenty-three chapters written by recognized splitting method contributors and practitioners, and covers a vast spectrum of topics and application areas, including computational mechanics, computational physics, image processing, wireless communication, nonlinear optics, and finance. Therefore, the book presents very versatile aspects of splitting methods and their applications, motivating the cross-fertilization of ideas. .

Irradiation-induced amorphization in split-dislocation cores

International Nuclear Information System (INIS)

Ovid'ko, I.A.; Rejzis, A.B.

1999-01-01

The model describing special splitting of lattice and grain-boundary dislocations as one of the micromechanisms of solid-phase amorphization in irradiated crystals is proposed. Calculation of energy characteristics of the process of dislocations special splitting is carried out [ru

Standard Model Particles from Split Octonions

Directory of Open Access Journals (Sweden)

Gogberashvili M.

2016-01-01

Full Text Available 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.

The Splitting Loope

Science.gov (United States)

Wilkins, Jesse L. M.; Norton, Anderson

2011-01-01

Teaching experiments have generated several hypotheses concerning the construction of fraction schemes and operations and relationships among them. In particular, researchers have hypothesized that children's construction of splitting operations is crucial to their construction of more advanced fractions concepts (Steffe, 2002). The authors…

A New Method for Automated Identification and Morphometry of Myelinated Fibers Through Light Microscopy Image Analysis

OpenAIRE

Novas, Romulo Bourget; Fazan, Valeria Paula Sassoli; Felipe, Joaquim Cezar

2015-01-01

Nerve morphometry is known to produce relevant information for the evaluation of several phenomena, such as nerve repair, regeneration, implant, transplant, aging, and different human neuropathies. Manual morphometry is laborious, tedious, time consuming, and subject to many sources of error. Therefore, in this paper, we propose a new method for the automated morphometry of myelinated fibers in cross-section light microscopy images. Images from the recurrent laryngeal nerve of adult rats and ...

Splitting Strip Detector Clusters in Dense Environments

CERN Document Server

Nachman, Benjamin Philip; The ATLAS collaboration

2018-01-01

Tracking in high density environments, particularly in high energy jets, plays an important role in many physics analyses at the LHC. In such environments, there is significant degradation of track reconstruction performance. Between runs 1 and 2, ATLAS implemented an algorithm that splits pixel clusters originating from multiple charged particles, using charge information, resulting in the recovery of much of the lost efficiency. However, no attempt was made in prior work to split merged clusters in the Semi Conductor Tracker (SCT), which does not measure charge information. In spite of the lack of charge information in SCT, a cluster-splitting algorithm has been developed in this work. It is based primarily on the difference between the observed cluster width and the expected cluster width, which is derived from track incidence angle. The performance of this algorithm is found to be competitive with the existing pixel cluster splitting based on track information.

Fee Splitting among General Practitioners: A Cross-Sectional Study in Iran.

Science.gov (United States)

Parsa, Mojtaba; Larijani, Bagher; Aramesh, Kiarash; Nedjat, Saharnaz; Fotouhi, Akbar; Yekaninejad, Mir Saeed; Ebrahimian, Nejatollah; Kandi, Mohamad Jafar

2016-12-01

Fee splitting is a process whereby a physician refers a patient to another physician or a healthcare facility and receives a portion of the charge in return. This survey was conducted to study general practitioners' (GPs) attitudes toward fee splitting as well as the prevalence, causes, and consequences of this process. This is a cross-sectional study on 223 general practitioners in 2013. Concerning the causes and consequences of fee splitting, an unpublished qualitative study was conducted by interviewing a number of GPs and specialists and the questionnaire options were the results of the information obtained from this study. Of the total 320 GPs, 247 returned the questionnaires. The response rate was 77.18%. Of the 247 returned questionnaires, 223 fulfilled the inclusion criteria. Among the participants, 69.1% considered fee splitting completely wrong and 23.2% (frequently or rarely) practiced fee splitting. The present study showed that the prevalence of fee splitting among physicians who had positive attitudes toward fee splitting was 4.63 times higher than those who had negative attitudes. In addition, this study showed that, compared to private hospitals, fee splitting is less practiced in public hospitals. The major cause of fee splitting was found to be unrealistic/unfair tariffs and the main consequence of fee splitting was thought to be an increase in the number of unnecessary patient referrals. Fee splitting is an unethical act, contradicts the goals of the medical profession, and undermines patient's best interest. In Iran, there is no code of ethics on fee splitting, but in this study, it was found that the majority of GPs considered it unethical. However, among those who had negative attitudes toward fee splitting, there were physicians who did practice fee splitting. The results of the study showed that physicians who had a positive attitude toward fee splitting practiced it more than others. Therefore, if physicians consider fee splitting unethical

The human amygdaloid complex: a cytologic and histochemical atlas using Nissl, myelin, acetylcholinesterase and nicotinamide adenine dinucleotide phosphate diaphorase staining.

Science.gov (United States)

Sims, K S; Williams, R S

1990-01-01

We examined the distribution of acetylcholinesterase and nicotinamide adenine dinucleotide phosphate diaphorase enzyme activity in the human amygdala using histochemical techniques. Both methods revealed compartments of higher or lower enzyme activity, in cells or neuropil, which corresponded to the nuclear subdivisions of the amygdala as defined with classical Nissl and myelin methods. The boundaries between the histochemical compartments were usually so sharp that the identification of these nuclear subdivisions was enhanced. There was also variation of staining intensity within many of the nuclear subdivisions, such as the lateral and central nuclei, anterior amygdaloid area and the intercalated groups. This histochemical difference corresponded to more subtle differences in Nissl and myelin staining patterns, and suggests further structural subdivisions of potential functional significance. We present a revised scheme of anatomical parcellation of the human amygdala based upon serial analysis with all four techniques. Our expectation is that this will allow the delineation of a clearer homology between the cytoarchitectonic subdivisions of the human amygdala and those of experimental animals.

The Split sudâmja

Directory of Open Access Journals (Sweden)

Petar Šimunović

1991-12-01

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 + Domnĭu. In the adjective santu the cluster /an/ in front of·a 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 ( /jm/ is well known in Croatian dialectology (sumja > sujma, and it resembles the metatheses which occurs in the Split toponimes: Sukošjân > Sukojšãn ( < *santu Cassianu, Pojišân/Pojšiin (< *pasianu < Pansianu. The author finds the same feature in the toponime Dumjača (: *Dumi- + -ača. He considers these features as Croatian popular adaptations which have not occured in the personal name Dujam, the toponime Dujmovača "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.

Communication: Tunnelling splitting in the phosphine molecule

Energy Technology Data Exchange (ETDEWEB)

Sousa-Silva, Clara; Tennyson, Jonathan; Yurchenko, Sergey N. [Department of Physics and Astronomy, University College London, London WC1E 6BT (United Kingdom)

2016-09-07

Splitting due to tunnelling via the potential energy barrier has played a significant role in the study of molecular spectra since the early days of spectroscopy. The observation of the ammonia doublet led to attempts to find a phosphine analogous, but these have so far failed due to its considerably higher barrier. Full dimensional, variational nuclear motion calculations are used to predict splittings as a function of excitation energy. Simulated spectra suggest that such splittings should be observable in the near infrared via overtones of the ν{sub 2} bending mode starting with 4ν{sub 2}.

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?...

The Splitting Group

Science.gov (United States)

Norton, Anderson; Wilkins, Jesse L. M.

2012-01-01

Piagetian theory describes mathematical development as the construction and organization of mental operations within psychological structures. Research on student learning has identified the vital roles of two particular operations--splitting and units coordination--play in students' development of advanced fractions knowledge. Whereas Steffe and…

Experimental Autoimmune Encephalomyelitis (EAE-Induced Elevated Expression of the E1 Isoform of Methyl CpG Binding Protein 2 (MeCP2E1: Implications in Multiple Sclerosis (MS-Induced Neurological Disability and Associated Myelin Damage

Directory of Open Access Journals (Sweden)

Tina Khorshid Ahmad

2017-06-01

Full Text Available Multiple sclerosis (MS is a chronic neurological disease characterized by the destruction of central nervous system (CNS myelin. At present, there is no cure for MS due to the inability to repair damaged myelin. Although the neurotrophin brain derived neurotrophic factor (BDNF has a beneficial role in myelin repair, these effects may be hampered by the over-expression of a transcriptional repressor isoform of methyl CpG binding protein 2 (MeCP2 called MeCP2E1. We hypothesize that following experimental autoimmune encephalomyelitis (EAE-induced myelin damage, the immune system induction of the pathogenic MeCP2E1 isoform hampers the myelin repair process by repressing BDNF expression. Using an EAE model of MS, we identify the temporal gene and protein expression changes of MeCP2E1, MeCP2E2 and BDNF. The expression changes of these key biological targets were then correlated with the temporal changes in neurological disability scores (NDS over the entire disease course. Our results indicate that MeCP2E1 mRNA levels are elevated in EAE animals relative to naïve control (NC and active control (AC animals during all time points of disease progression. Our results suggest that the EAE-induced elevations in MeCP2E1 expression contribute to the repressed BDNF production in the spinal cord (SC. The sub-optimal levels of BDNF result in sustained NDS and associated myelin damage throughout the entire disease course. Conversely, we observed no significant differences in the expression patterns displayed for the MeCP2E2 isoform amongst our experimental groups. However, our results demonstrate that baseline protein expression ratios between the MeCP2E1 versus MeCP2E2 isoforms in the SC are higher than those identified within the dorsal root ganglia (DRG. Thus, the DRG represents a more conducive environment than that of the SC for BDNF production and transport to the CNS to assist in myelin repair. Henceforth, the sub-optimal BDNF levels we report in the SC

Experimental Autoimmune Encephalomyelitis (EAE)-Induced Elevated Expression of the E1 Isoform of Methyl CpG Binding Protein 2 (MeCP2E1): Implications in Multiple Sclerosis (MS)-Induced Neurological Disability and Associated Myelin Damage.

Science.gov (United States)

Khorshid Ahmad, Tina; Zhou, Ting; AlTaweel, Khaled; Cortes, Claudia; Lillico, Ryan; Lakowski, Ted Martin; Gozda, Kiana; Namaka, Michael Peter

2017-06-12

Multiple sclerosis (MS) is a chronic neurological disease characterized by the destruction of central nervous system (CNS) myelin. At present, there is no cure for MS due to the inability to repair damaged myelin. Although the neurotrophin brain derived neurotrophic factor (BDNF) has a beneficial role in myelin repair, these effects may be hampered by the over-expression of a transcriptional repressor isoform of methyl CpG binding protein 2 (MeCP2) called MeCP2E1. We hypothesize that following experimental autoimmune encephalomyelitis (EAE)-induced myelin damage, the immune system induction of the pathogenic MeCP2E1 isoform hampers the myelin repair process by repressing BDNF expression. Using an EAE model of MS, we identify the temporal gene and protein expression changes of MeCP2E1, MeCP2E2 and BDNF. The expression changes of these key biological targets were then correlated with the temporal changes in neurological disability scores (NDS) over the entire disease course. Our results indicate that MeCP2E1 mRNA levels are elevated in EAE animals relative to naïve control (NC) and active control (AC) animals during all time points of disease progression. Our results suggest that the EAE-induced elevations in MeCP2E1 expression contribute to the repressed BDNF production in the spinal cord (SC). The sub-optimal levels of BDNF result in sustained NDS and associated myelin damage throughout the entire disease course. Conversely, we observed no significant differences in the expression patterns displayed for the MeCP2E2 isoform amongst our experimental groups. However, our results demonstrate that baseline protein expression ratios between the MeCP2E1 versus MeCP2E2 isoforms in the SC are higher than those identified within the dorsal root ganglia (DRG). Thus, the DRG represents a more conducive environment than that of the SC for BDNF production and transport to the CNS to assist in myelin repair. Henceforth, the sub-optimal BDNF levels we report in the SC may arise

One-loop triple collinear splitting amplitudes in QCD

Energy Technology Data Exchange (ETDEWEB)

Badger, Simon; Buciuni, Francesco; Peraro, Tiziano [Higgs Centre for Theoretical Physics, School of Physics and Astronomy, University of Edinburgh,Edinburgh EH9 3JZ, Scotland (United Kingdom)

2015-09-28

We study the factorisation properties of one-loop scattering amplitudes in the triple collinear limit and extract the universal splitting amplitudes for processes initiated by a gluon. The splitting amplitudes are derived from the analytic Higgs plus four partons amplitudes. We present compact results for primitive helicity splitting amplitudes making use of super-symmetric decompositions. The universality of the collinear factorisation is checked numerically against the full colour six parton squared matrix elements.

Splitting in Dual-Phase 590 high strength steel plates

International Nuclear Information System (INIS)

Yang Min; Chao, Yuh J.; Li Xiaodong; Tan Jinzhu

2008-01-01

Charpy V-notch impact tests on 5.5 mm thick, hot-rolled Dual-Phase 590 (DP590) steel plate were evaluated at temperatures ranging from 90 deg. C to -120 deg. C. Similar tests on 2.0 mm thick DP590 HDGI steel plate were also conducted at room temperature. Splitting or secondary cracks was observed on the fractured surfaces. The mechanisms of the splitting were then investigated. Fracture surfaces were analyzed by optical microscope (OM) and scanning electron microscope (SEM). Composition of the steel plates was determined by electron probe microanalysis (EPMA). Micro Vickers hardness of the steel plates was also surveyed. Results show that splitting occurred on the main fractured surfaces of hot-rolled steel specimens at various testing temperatures. At temperatures above the ductile-brittle-transition-temperature (DBTT), -95 deg. C, where the fracture is predominantly ductile, the length and amount of splitting decreased with increasing temperature. At temperatures lower than the DBTT, where the fracture is predominantly brittle, both the length and width of the splitting are insignificant. Splitting in HDGI steel plates only appeared in specimens of T-L direction. The analysis revealed that splitting in hot-rolled plate is caused by silicate and carbide inclusions while splitting in HDGI plate results from strip microstructure due to its high content of manganese and low content of silicon. The micro Vickers hardness of either the inclusions or the strip microstructures is higher than that of the respective base steel

Split ring containment attachment device

International Nuclear Information System (INIS)

Sammel, A.G.

1996-01-01

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

Split NMSSM with electroweak baryogenesis

Energy Technology Data Exchange (ETDEWEB)

Demidov, S.V.; Gorbunov, D.S. [Institute for Nuclear Research of the Russian Academy of Sciences, 60th October Anniversary prospect 7a, Moscow 117312 (Russian Federation); Moscow Institute of Physics and Technology,Institutsky per. 9, Dolgoprudny 141700 (Russian Federation); Kirpichnikov, D.V. [Institute for Nuclear Research of the Russian Academy of Sciences, 60th October Anniversary prospect 7a, Moscow 117312 (Russian Federation)

2016-11-24

In light of the Higgs boson discovery and other results of the LHC we reconsider generation of the baryon asymmetry in the split Supersymmetry model with an additional singlet superfield in the Higgs sector (non-minimal split SUSY). We find that successful baryogenesis during the first order electroweak phase transition is possible within a phenomenologically viable part of the model parameter space. We discuss several phenomenological consequences of this scenario, namely, predictions for the electric dipole moments of electron and neutron and collider signatures of light charginos and neutralinos.

Mass splitting induced by gravitation

International Nuclear Information System (INIS)

Maia, M.D.

1982-08-01

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

Splitting of turbulent spot in transitional pipe flow

Science.gov (United States)

Wu, Xiaohua; Moin, Parviz; Adrian, Ronald J.

2017-11-01

Recent study (Wu et al., PNAS, 1509451112, 2015) demonstrated the feasibility and accuracy of direct computation of the Osborne Reynolds' pipe transition problem without the unphysical, axially periodic boundary condition. Here we use this approach to study the splitting of turbulent spot in transitional pipe flow, a feature first discovered by E.R. Lindgren (Arkiv Fysik 15, 1959). It has been widely believed that spot splitting is a mysterious stochastic process that has general implications on the lifetime and sustainability of wall turbulence. We address the following two questions: (1) What is the dynamics of turbulent spot splitting in pipe transition? Specifically, we look into any possible connection between the instantaneous strain rate field and the spot splitting. (2) How does the passive scalar field behave during the process of pipe spot splitting. In this study, the turbulent spot is introduced at the inlet plane through a sixty degree wide numerical wedge within which fully-developed turbulent profiles are assigned over a short time interval; and the simulation Reynolds numbers are 2400 for a 500 radii long pipe, and 2300 for a 1000 radii long pipe, respectively. Numerical dye is tagged on the imposed turbulent spot at the inlet. Splitting of the imposed turbulent spot is detected very easily. Preliminary analysis of the DNS results seems to suggest that turbulent spot slitting can be easily understood based on instantaneous strain rate field, and such spot splitting may not be relevant in external flows such as the flat-plate boundary layer.

Specific interaction of central nervous system myelin basic protein with lipids effects of basic protein on glucose leakage from liposomes

NARCIS (Netherlands)

Gould, R.M.; London, Y.

1972-01-01

The leakage from liposomes preloaded with glucose was continuously monitored in a Perkin-Elmer Model 356 dual beam spectrophotometer using an enzyme-linked assay system. The central nervous system myelin basic protein (A1 protein) caused a 3–4-fold increase in the rate of leakage from liposomes

Myelin-specific T cells induce interleukin-1beta expression in lesion-reactive microglial-like cells in zones of axonal degeneration

DEFF Research Database (Denmark)

Grebing, Manuela; Nielsen, Helle H; Fenger, Christina D

2016-01-01

lesion-reactive CD11b(+) ramified microglia. These results suggest that myelin-specific T cells stimulate lesion-reactive microglial-like cells to produce IL-1β. These findings are relevant to understand the consequences of T-cell infiltration in white and gray matter lesions in patients with MS. GLIA...

Guidelines to Develop Efficient Photocatalysts for Water Splitting

KAUST Repository

Garcia Esparza, Angel T.

2016-01-01

Photocatalytic overall water splitting is the only viable solar-to-fuel conversion technology. The research discloses an investigation process wherein by dissecting the photocatalytic water splitting device, electrocatalysts, and semiconductor

Exposing the QCD Splitting Function with CMS Open Data.

Science.gov (United States)

Larkoski, Andrew; Marzani, Simone; Thaler, Jesse; Tripathee, Aashish; Xue, Wei

2017-09-29

The splitting function is a universal property of quantum chromodynamics (QCD) which describes how energy is shared between partons. Despite its ubiquitous appearance in many QCD calculations, the splitting function cannot be measured directly, since it always appears multiplied by a collinear singularity factor. Recently, however, a new jet substructure observable was introduced which asymptotes to the splitting function for sufficiently high jet energies. This provides a way to expose the splitting function through jet substructure measurements at the Large Hadron Collider. In this Letter, we use public data released by the CMS experiment to study the two-prong substructure of jets and test the 1→2 splitting function of QCD. To our knowledge, this is the first ever physics analysis based on the CMS Open Data.

Split-plot designs for multistage experimentation

DEFF Research Database (Denmark)

Kulahci, Murat; Tyssedal, John

2016-01-01

at the same time will be more efficient. However, there have been only a few attempts in the literature to provide an adequate and easy-to-use approach for this problem. In this paper, we present a novel methodology for constructing two-level split-plot and multistage experiments. The methodology is based...... be accommodated in each stage. Furthermore, split-plot designs for multistage experiments with good projective properties are also provided....

Hydrogen Production from Semiconductor-based Photocatalysis via Water Splitting

Directory of Open Access Journals (Sweden)

Jeffrey C. S. Wu

2012-10-01

Full Text Available Hydrogen is the ideal fuel for the future because it is clean, energy efficient, and abundant in nature. While various technologies can be used to generate hydrogen, only some of them can be considered environmentally friendly. Recently, solar hydrogen generated via photocatalytic water splitting has attracted tremendous attention and has been extensively studied because of its great potential for low-cost and clean hydrogen production. This paper gives a comprehensive review of the development of photocatalytic water splitting for generating hydrogen, particularly under visible-light irradiation. The topics covered include an introduction of hydrogen production technologies, a review of photocatalytic water splitting over titania and non-titania based photocatalysts, a discussion of the types of photocatalytic water-splitting approaches, and a conclusion for the current challenges and future prospects of photocatalytic water splitting. Based on the literatures reported here, the development of highly stable visible–light-active photocatalytic materials, and the design of efficient, low-cost photoreactor systems are the key for the advancement of solar-hydrogen production via photocatalytic water splitting in the future.

Optimal field splitting for large intensity-modulated fields

International Nuclear Information System (INIS)

Kamath, Srijit; Sahni, Sartaj; Ranka, Sanjay; Li, Jonathan; Palta, Jatinder

2004-01-01

The multileaf travel range limitations on some linear accelerators require the splitting of a large intensity-modulated field into two or more adjacent abutting intensity-modulated subfields. The abutting subfields are then delivered as separate treatment fields. This workaround not only increases the treatment delivery time but it also increases the total monitor units (MU) delivered to the patient for a given prescribed dose. It is imperative that the cumulative intensity map of the subfields is exactly the same as the intensity map of the large field generated by the dose optimization algorithm, while satisfying hardware constraints of the delivery system. In this work, we describe field splitting algorithms that split a large intensity-modulated field into two or more intensity-modulated subfields with and without feathering, with optimal MU efficiency while satisfying the hardware constraints. Compared to a field splitting technique (without feathering) used in a commercial planning system, our field splitting algorithm (without feathering) shows a decrease in total MU of up to 26% on clinical cases and up to 63% on synthetic cases

Iterative group splitting algorithm for opportunistic scheduling systems

KAUST Repository

Nam, Haewoon; Alouini, Mohamed-Slim

2014-01-01

An efficient feedback algorithm for opportunistic scheduling systems based on iterative group splitting is proposed in this paper. Similar to the opportunistic splitting algorithm, the proposed algorithm adjusts (or lowers) the feedback threshold

Normal myelination of the child brain on MRI - a meta-analysis; Die normale Myelinisierung des kindlichen Gehirns in der MRT - eine Metaanalyse

Energy Technology Data Exchange (ETDEWEB)

Staudt, M.; Grodd, W. [Tuebingen Univ. (Germany). Abt. fuer Neuroradiologie; Kraegeloh-Mann, I. [Tuebingen Univ. (Germany). Abt. Entwicklungsneurologie und Neuropaediatrie

2000-10-01

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

Point-splitting regularization of composite operators and anomalies

International Nuclear Information System (INIS)

Novotny, J.; Schnabl, M.

2000-01-01

The point-splitting regularization technique for composite operators is discussed in connection with anomaly calculation. We present a pedagogical and self-contained review of the topic with an emphasis on the technical details. We also develop simple algebraic tools to handle the path ordered exponential insertions used within the covariant and non-covariant version of the point-splitting method. The method is then applied to the calculation of the chiral, vector, trace, translation and Lorentz anomalies within diverse versions of the point-splitting regularization and a connection between the results is described. As an alternative to the standard approach we use the idea of deformed point-split transformation and corresponding Ward-Takahashi identities rather than an application of the equation of motion, which seems to reduce the complexity of the calculations. (orig.)

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.)

Axonal sprouting regulates myelin basic protein gene expression in denervated mouse hippocampus

DEFF Research Database (Denmark)

Jensen, M B; Poulsen, F R; Finsen, B

2000-01-01

to 35 days after transection of the entorhino-hippocampal perforant path axonal projection. In situ hybridization analysis showed that anterograde axonal and terminal degeneration lead to upregulated oligodendrocyte MBP mRNA expression starting between day 2 and day 4, in (1) the deep part of stratum...... axonal and terminal degeneration, myelin degenerative changes, microglial activation and axotomi-induced axonal sprouting. Oligodendrocyte MBP mRNA expression reached maximum in both these areas at day 7. MBP gene transcription remained constant in stratum radiatum, stratum pyramidale and stratum oriens...... of CA1, areas that were unaffected by perforant path transection. These results provide strong evidence that oligodendrocyte MBP gene expression can be regulated by axonal sprouting independently of microglial activation in the injured adult CNS....

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

Directory of Open Access Journals (Sweden)

Riyi Shi

2013-10-01

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

Identification of a novel SPLIT-HULL (SPH) gene associated with hull splitting in rice (Oryza sativa L.).

Science.gov (United States)

Lee, Gileung; Lee, Kang-Ie; Lee, Yunjoo; Kim, Backki; Lee, Dongryung; Seo, Jeonghwan; Jang, Su; Chin, Joong Hyoun; Koh, Hee-Jong

2018-07-01

The split-hull phenotype caused by reduced lemma width and low lignin content is under control of SPH encoding a type-2 13-lipoxygenase and contributes to high dehulling efficiency. Rice hulls consist of two bract-like structures, the lemma and palea. The hull is an important organ that helps to protect seeds from environmental stress, determines seed shape, and ensures grain filling. Achieving optimal hull size and morphology is beneficial for seed development. We characterized the split-hull (sph) mutant in rice, which exhibits hull splitting in the interlocking part between lemma and palea and/or the folded part of the lemma during the grain filling stage. Morphological and chemical analysis revealed that reduction in the width of the lemma and lignin content of the hull in the sph mutant might be the cause of hull splitting. Genetic analysis indicated that the mutant phenotype was controlled by a single recessive gene, sph (Os04g0447100), which encodes a type-2 13-lipoxygenase. SPH knockout and knockdown transgenic plants displayed the same split-hull phenotype as in the mutant. The sph mutant showed significantly higher linoleic and linolenic acid (substrates of lipoxygenase) contents in spikelets compared to the wild type. It is probably due to the genetic defect of SPH and subsequent decrease in lipoxygenase activity. In dehulling experiment, the sph mutant showed high dehulling efficiency even by a weak tearing force in a dehulling machine. Collectively, the results provide a basis for understanding of the functional role of lipoxygenase in structure and maintenance of hulls, and would facilitate breeding of easy-dehulling rice.

15 CFR 30.28 - “Split shipments” by air.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false âSplit shipmentsâ by air. 30.28... Transactions § 30.28 “Split shipments” by air. When a shipment by air covered by a single EEI submission is... showing the portion of the split shipment carried on that flight, a notation will be made showing the air...

Electroweak splitting functions and high energy showering

Science.gov (United States)

Chen, Junmou; Han, Tao; Tweedie, Brock

2017-11-01

We derive the electroweak (EW) collinear splitting functions for the Standard Model, including the massive fermions, gauge bosons and the Higgs boson. We first present the splitting functions in the limit of unbroken SU(2) L × U(1) Y and discuss their general features in the collinear and soft-collinear regimes. These are the leading contributions at a splitting scale ( k T ) far above the EW scale ( v). We then systematically incorporate EW symmetry breaking (EWSB), which leads to the emergence of additional "ultra-collinear" splitting phenomena and naive violations of the Goldstone-boson Equivalence Theorem. We suggest a particularly convenient choice of non-covariant gauge (dubbed "Goldstone Equivalence Gauge") that disentangles the effects of Goldstone bosons and gauge fields in the presence of EWSB, and allows trivial book-keeping of leading power corrections in v/ k T . We implement a comprehensive, practical EW showering scheme based on these splitting functions using a Sudakov evolution formalism. Novel features in the implementation include a complete accounting of ultra-collinear effects, matching between shower and decay, kinematic back-reaction corrections in multi-stage showers, and mixed-state evolution of neutral bosons ( γ/ Z/ h) using density-matrices. We employ the EW showering formalism to study a number of important physical processes at O (1-10 TeV) energies. They include (a) electroweak partons in the initial state as the basis for vector-boson-fusion; (b) the emergence of "weak jets" such as those initiated by transverse gauge bosons, with individual splitting probabilities as large as O (35%); (c) EW showers initiated by top quarks, including Higgs bosons in the final state; (d) the occurrence of O (1) interference effects within EW showers involving the neutral bosons; and (e) EW corrections to new physics processes, as illustrated by production of a heavy vector boson ( W ') and the subsequent showering of its decay products.

Tantalum-based semiconductors for solar water splitting.

Science.gov (United States)

Zhang, Peng; Zhang, Jijie; Gong, Jinlong

2014-07-07

Solar energy utilization is one of the most promising solutions for the energy crises. Among all the possible means to make use of solar energy, solar water splitting is remarkable since it can accomplish the conversion of solar energy into chemical energy. The produced hydrogen is clean and sustainable which could be used in various areas. For the past decades, numerous efforts have been put into this research area with many important achievements. Improving the overall efficiency and stability of semiconductor photocatalysts are the research focuses for the solar water splitting. Tantalum-based semiconductors, including tantalum oxide, tantalate and tantalum (oxy)nitride, are among the most important photocatalysts. Tantalum oxide has the band gap energy that is suitable for the overall solar water splitting. The more negative conduction band minimum of tantalum oxide provides photogenerated electrons with higher potential for the hydrogen generation reaction. Tantalates, with tunable compositions, show high activities owning to their layered perovskite structure. (Oxy)nitrides, especially TaON and Ta3N5, have small band gaps to respond to visible-light, whereas they can still realize overall solar water splitting with the proper positions of conduction band minimum and valence band maximum. This review describes recent progress regarding the improvement of photocatalytic activities of tantalum-based semiconductors. Basic concepts and principles of solar water splitting will be discussed in the introduction section, followed by the three main categories regarding to the different types of tantalum-based semiconductors. In each category, synthetic methodologies, influencing factors on the photocatalytic activities, strategies to enhance the efficiencies of photocatalysts and morphology control of tantalum-based materials will be discussed in detail. Future directions to further explore the research area of tantalum-based semiconductors for solar water splitting

Specific Depletion of Myelin-Reactive B Cells via BCR-Targeting.

Science.gov (United States)

Stepanov, A V; Belogurov, A A; Kothapalli, P; Shamborant, O G; Knorre, V D; Telegin, G B; Ovsepyan, A A; Ponomarenko, N A; Deyev, S M; Kaveri, S V; Gabibov, A G

2015-01-01

B cells play a crucial role in the development and pathogenesis of systemic and organ-specific autoimmune diseases. Autoreactive B cells not only produce antibodies, but also secrete pro-inflammatory cytokines and present specific autoantigens to T cells. The treatment of autoimmune diseases via the elimination of the majority of B cells using the monoclonal anti-CD19/20 antibody (Rituximab) causes systemic side effects and, thus, requires a major revision. Therapeutic intervention directed towards selective elimination of pathogenic autoreactive B cells has the potential to become a universal approach to the treatment of various autoimmune abnormalities. Here, we developed a recombinant immunotoxin based on the immunodominant peptide of the myelin basic protein (MBP), fused to the antibody Fc domain. We showed that the obtained immunotoxin provides selective in vivo elimination of autoreactive B cells in mice with experimental autoimmune encephalomyelitis. The proposed conception may be further used for the development of new therapeutics for a targeted treatment of multiple sclerosis and other autoimmune disorders.

High efficiency beam splitting for H- accelerators

International Nuclear Information System (INIS)

Kramer, S.L.; Stipp, V.; Krieger, C.; Madsen, J.

1985-01-01

Beam splitting for high energy accelerators has typically involved a significant loss of beam and radiation. This paper reports on a new method of splitting beams for H - accelerators. This technique uses a high intensity flash of light to strip a fraction of the H - beam to H 0 which are then easily separated by a small bending magnet. A system using a 900-watt (average electrical power) flashlamp and a highly efficient collector will provide 10 -3 to 10 -2 splitting of a 50 MeV H - beam. Results on the operation and comparisons with stripping cross sections are presented. Also discussed is the possibility for developing this system to yield a higher stripping fraction

Optimal space-energy splitting in MCNP with the DSA

International Nuclear Information System (INIS)

Dubi, A.; Gurvitz, N.

1990-01-01

The Direct Statistical Approach (DSA) particle transport theory is based on the possibility of obtaining exact explicit expressions for the dependence of the second moment and calculation time on the splitting parameters. This allows the automatic optimization of the splitting parameters by ''learning'' the bulk parameters from which the problem dependent coefficients of the quality function (second moment time) are constructed. The above procedure was exploited to implement an automatic optimization of the splitting parameters in the Monte Carlo Neutron Photon (MCNP) code. This was done in a number of steps. In the first instance, only spatial surface splitting was considered. In this step, the major obstacle has been the truncation of an infinite series of ''products'' of ''surface path's'' leading from the source to the detector. Encouraging results from the first phase led to the inclusion of full space/energy phase space splitting. (author)

Splitting automorphisms of free Burnside groups

International Nuclear Information System (INIS)

Atabekyan, Varuzhan S

2013-01-01

It is proved that, if the order of a splitting automorphism of odd period n≥1003 of a free Burnside group B(m,n) is a prime, then the automorphism is inner. This implies, for every prime n≥1009, an affirmative answer to the question on the coincidence of the splitting automorphisms of period n of the group B(m,n) with the inner automorphisms (this question was posed in the 'Kourovka Notebook' in 1990). Bibliography: 17 titles.

Photoelectrochemical water splitting: optimizing interfaces and light absorption

NARCIS (Netherlands)

Park, Sun-Young

2015-01-01

In this thesis several photoelectrochemical water splitting devices based on semiconductor materials were investigated. The aim was the design, characterization, and fabrication of solar-to-fuel devices which can absorb solar light and split water to produce hydrogen.

7 CFR 51.2543 - U.S. Non-Split.

Science.gov (United States)

2010-01-01

... Standards for Grades of Pistachio Nuts in the Shell § 51.2543 U.S. Non-Split. “U.S. Non-Split” consists of non-split pistachio nuts in the shell which meet the following requirements: (a) Basic requirements...

Cheating More when the Spoils Are Split

Science.gov (United States)

Wiltermuth, Scott S.

2011-01-01

Four experiments demonstrated that people are more likely to cheat when the benefits of doing so are split with another person, even an anonymous stranger, than when the actor alone captures all of the benefits. In three of the studies, splitting the benefits of over-reporting one's performance on a task made such over-reporting seem less…

ISR split-field magnet

CERN Multimedia

CERN PhotoLab

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.

A splitting algorithm for directional regularization and sparsification

DEFF Research Database (Denmark)

Rakêt, Lars Lau; Nielsen, Mads

2012-01-01

We present a new split-type algorithm for the minimization of a p-harmonic energy with added data fidelity term. The half-quadratic splitting reduces the original problem to two straightforward problems, that can be minimized efficiently. The minimizers to the two sub-problems can typically...... be computed pointwise and are easily implemented on massively parallel processors. Furthermore the splitting method allows for the computation of solutions to a large number of more advanced directional regularization problems. In particular we are able to handle robust, non-convex data terms, and to define...

GABA and its B-receptor are present at the node of Ranvier in a small population of sensory fibers, implicating a role in myelination

DEFF Research Database (Denmark)

Corell, Mikael; Wicher, Grzegorz; Radomska, Katarzyna J

2015-01-01

throughout development and after injury. A small population of myelinated sensory fibers displayed all of these molecules at the node of Ranvier, indicating a role in axon-glia communication. Functional studies using GABAB receptor agonists and antagonists were performed in fetal DRG primary cultures...... to study the function of this receptor during development. The results show that GABA, via its B receptor, is involved in the myelination process but not in Schwann cell proliferation. The data from adult nerves suggest additional roles in axon-glia communication after injury.......The γ-aminobutyric acid (GABA) type B receptor has been implicated in glial cell development in the peripheral nervous system (PNS), although the exact function of GABA signaling is not known. To investigate GABA and its B receptor in PNS development and degeneration, we studied the expression...

Geometrical Applications of Split Octonions

Directory of Open Access Journals (Sweden)

Merab Gogberashvili

2015-01-01

Full Text Available It is shown that physical signals and space-time intervals modeled on split-octonion geometry naturally exhibit properties from conventional (3 + 1-theory (e.g., number of dimensions, existence of maximal velocities, Heisenberg uncertainty, and particle generations. This paper demonstrates these properties using an explicit representation of the automorphisms on split-octonions, the noncompact form of the exceptional Lie group G2. This group generates specific rotations of (3 + 4-vector parts of split octonions with three extra time-like coordinates and in infinitesimal limit imitates standard Poincare transformations. In this picture translations are represented by noncompact Lorentz-type rotations towards the extra time-like coordinates. It is shown how the G2 algebra’s chirality yields an intrinsic left-right asymmetry of a certain 3-vector (spin, as well as a parity violating effect on light emitted by a moving quantum system. Elementary particles are connected with the special elements of the algebra which nullify octonionic intervals. Then the zero-norm conditions lead to free particle Lagrangians, which allow virtual trajectories also and exhibit the appearance of spatial horizons governing by mass parameters.

Can the ''doublet-triplet splitting'' problem be solved without doublet-triplet splitting?

International Nuclear Information System (INIS)

Dvali, G.R.

1992-03-01

We consider a new possible mechanism for the natural solution of the doublet-triplet splitting problem in SUSY GUTs. In contrast to the usually discussed scenarios, in our case the GUT symmetry breaking does not provide any splitting between the Higgs doublet and the triplet masses. The weak doublet and its colour triplet partner both remain light, but the triplet automatically occurs decoupled from the quark and lepton superfields and cannot induce proton decay. The advantage of the above scenarios is the absence at the GUT scale of the baryon number violating the tree level d = 5 and d = 6 operators via the colour-triple exchange. It is shown that in flipped SU(5) GUT they do not appear at any scale. In the SO(10) model, such operators can be induced after SUSY breaking but are strongly suppressed. (author). 22 refs, 2 figs

Quantitative analysis on electric dipole energy in Rashba band splitting.

Science.gov (United States)

Hong, Jisook; Rhim, Jun-Won; Kim, Changyoung; Ryong Park, Seung; Hoon Shim, Ji

2015-09-01

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 calculated the electric dipole energies from coupling of the asymmetric charge distribution and external electric field, and compared it to the Rashba splitting. Remarkably, the total split energy is found to come mostly from the difference in the electric dipole energy for both Bi and Sb systems. A perturbative approach for long wave length limit starting from tight binding calculation also supports that the Rashba band splitting originates mostly from the electric dipole energy difference in the strong atomic spin-orbit coupling regime.

Optimizing TCP Performance over UMTS with Split TCP Proxy

DEFF Research Database (Denmark)

Hu, Liang; Dittmann, Lars

2009-01-01

. To cope with large delay bandwidth product, we propose a novel concept of split TCP proxy which is placed at GGSN between UNITS network and Internet. The split proxy divides the bandwidth delay product into two parts, resulting in two TCP connections with smaller bandwidth delay products which can...... be pipelined and thus operating at higher speeds. Simulation results show, the split TCP proxy can significantly improve the TCP performance in terms of RLC throughput under high bit rate DCH channel scenario (e.g.256 kbps). On the other hand, it only brings small performance improvement under low bit rate DCH...... scenario (e.g.64 kbps). Besides, the split TCP proxy brings more performance gain for downloading large files than downloading small ones. To the end, for the configuration of the split proxy, an aggressive initial TCP congestion window size (e.g. 10 MSS) at proxy is particularly useful for radio links...

Electrokinetic control of sample splitting at a channel bifurcation using isotachophoresis

International Nuclear Information System (INIS)

Persat, Alexandre; Santiago, Juan G

2009-01-01

We present a novel method for accurately splitting ionic samples at microchannel bifurcations. We leverage isotachophoresis (ITP) to focus and transport sample through a one-inlet, two-outlet microchannel bifurcation. We actively control the proportion of splitting by controlling potentials at end-channel reservoirs (and thereby controlling the current ratio). We explore the effect of buffer chemistry and local electric field on splitting dynamics and propose and validate a simple Kirchoff-type rule controlling the split ratio. We explore the effects of large applied electric fields on sample splitting and attribute a loss of splitting accuracy to electrohydrodynamic instabilities. We propose a scaling analysis to characterize the onset of this instability. This scaling is potentially useful for other electrokinetic flow problems with self-sharpening interfaces.

Symmetric splitting of very light systems

International Nuclear Information System (INIS)

Grotowski, K.; Majka, Z.; Planeta, R.

1985-01-01

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 12 C + 40 Ca, 141 MeV 9 Be + 40 Ca and 153 MeV 6 Li + 40 Ca. The out-of-plane correlation of symmetric products was also measured for the reaction 186 MeV 12 C + 40 Ca. The coincidence measurements of the 12 C + 40 Ca system demonstrated that essentially all of the inclusive yield of symmetric products around 40 0 results from a binary decay. To characterize the dependence of the symmetric splitting process on the excitation energy of the 12 C + 40 C system, inclusive measurements were made at bombarding energies of 74, 132, 162, and 185 MeV

Introducing inducible fluorescent split cholesterol oxidase to mammalian cells.

Science.gov (United States)

Chernov, Konstantin G; Neuvonen, Maarit; Brock, Ivonne; Ikonen, Elina; Verkhusha, Vladislav V

2017-05-26

Cholesterol oxidase (COase) is a bacterial enzyme catalyzing the first step in the biodegradation of cholesterol. COase is an important biotechnological tool for clinical diagnostics and production of steroid drugs and insecticides. It is also used for tracking intracellular cholesterol; however, its utility is limited by the lack of an efficient temporal control of its activity. To overcome this we have developed a regulatable fragment complementation system for COase cloned from Chromobacterium sp. The enzyme was split into two moieties that were fused to FKBP (FK506-binding protein) and FRB (rapamycin-binding domain) pair and split GFP fragments. The addition of rapamycin reconstituted a fluorescent enzyme, termed split GFP-COase, the fluorescence level of which correlated with its oxidation activity. A rapid decrease of cellular cholesterol induced by intracellular expression of the split GFP-COase promoted the dissociation of a cholesterol biosensor D4H from the plasma membrane. The process was reversible as upon rapamycin removal, the split GFP-COase fluorescence was lost, and cellular cholesterol levels returned to normal. These data demonstrate that the split GFP-COase provides a novel tool to manipulate cholesterol in mammalian cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Assessment of the Maximal Split-Half Coefficient to Estimate Reliability

Science.gov (United States)

Thompson, Barry L.; Green, Samuel B.; Yang, Yanyun

2010-01-01

The maximal split-half coefficient is computed by calculating all possible split-half reliability estimates for a scale and then choosing the maximal value as the reliability estimate. Osburn compared the maximal split-half coefficient with 10 other internal consistency estimates of reliability and concluded that it yielded the most consistently…

Evaluation of Certain Pharmaceutical Quality Attributes of Lisinopril Split Tablets

Directory of Open Access Journals (Sweden)

Khairi M. S. Fahelelbom

2016-10-01

Full Text Available Tablet splitting is an accepted practice for the administration of drugs for a variety of reasons, including dose adjustment, ease of swallowing and cost savings. The purpose of this study was to evaluate the physical properties of lisinopril tablets as a result of splitting the tablets either by hand or with a splitting device. The impact of the splitting technique of lisinopril (Zestril® tablets, 20 mg on certain physical parameters such as weight variation, friability, disintegration, dissolution and drug content were studied. Splitting the tablets either by hand or with a splitter resulted in a minute but statistically significant average weight loss of <0.25% of the tablet to the surrounding environment. The variability in the weight of the hand-split tablet halves was more pronounced (37 out of 40 tablet halves varied by more than 10% from the mean weight than when using the tablet splitter (3 out of 40 tablet halves. The dissolution and drug content of the hand-split tablets were therefore affected because of weight differences. However, the pharmacopoeia requirements for friability and disintegration time were met. Hand splitting of tablets can result in an inaccurate dose and may present clinical safety issues, especially for drugs with a narrow therapeutic window in which large fluctuations in drug concentrations are undesirable. It is recommended to use tablets with the exact desired dose, but if this is not an option, then a tablet splitter could be used.

77 FR 8184 - Foreign Tax Credit Splitting Events

Science.gov (United States)

2012-02-14

... Foreign Tax Credit Splitting Events AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of... these proposed regulations. The regulations affect taxpayers claiming foreign tax credits. Special... of the Federal Register.] Sec. 1.909-6 Pre-2011 foreign tax credit splitting events. [The text of...

Analysis of operator splitting errors for near-limit flame simulations

Energy Technology Data Exchange (ETDEWEB)

Lu, Zhen; Zhou, Hua [Center for Combustion Energy, Tsinghua University, Beijing 100084 (China); Li, Shan [Center for Combustion Energy, Tsinghua University, Beijing 100084 (China); School of Aerospace Engineering, Tsinghua University, Beijing 100084 (China); Ren, Zhuyin, E-mail: zhuyinren@tsinghua.edu.cn [Center for Combustion Energy, Tsinghua University, Beijing 100084 (China); School of Aerospace Engineering, Tsinghua University, Beijing 100084 (China); Lu, Tianfeng [Department of Mechanical Engineering, University of Connecticut, Storrs, CT 06269-3139 (United States); Law, Chung K. [Center for Combustion Energy, Tsinghua University, Beijing 100084 (China); Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ 08544 (United States)

2017-04-15

High-fidelity simulations of ignition, extinction and oscillatory combustion processes are of practical interest in a broad range of combustion applications. Splitting schemes, widely employed in reactive flow simulations, could fail for stiff reaction–diffusion systems exhibiting near-limit flame phenomena. The present work first employs a model perfectly stirred reactor (PSR) problem with an Arrhenius reaction term and a linear mixing term to study the effects of splitting errors on the near-limit combustion phenomena. Analysis shows that the errors induced by decoupling of the fractional steps may result in unphysical extinction or ignition. The analysis is then extended to the prediction of ignition, extinction and oscillatory combustion in unsteady PSRs of various fuel/air mixtures with a 9-species detailed mechanism for hydrogen oxidation and an 88-species skeletal mechanism for n-heptane oxidation, together with a Jacobian-based analysis for the time scales. The tested schemes include the Strang splitting, the balanced splitting, and a newly developed semi-implicit midpoint method. Results show that the semi-implicit midpoint method can accurately reproduce the dynamics of the near-limit flame phenomena and it is second-order accurate over a wide range of time step size. For the extinction and ignition processes, both the balanced splitting and midpoint method can yield accurate predictions, whereas the Strang splitting can lead to significant shifts on the ignition/extinction processes or even unphysical results. With an enriched H radical source in the inflow stream, a delay of the ignition process and the deviation on the equilibrium temperature are observed for the Strang splitting. On the contrary, the midpoint method that solves reaction and diffusion together matches the fully implicit accurate solution. The balanced splitting predicts the temperature rise correctly but with an over-predicted peak. For the sustainable and decaying oscillatory

A Regularized Algorithm for the Proximal Split Feasibility Problem

Directory of Open Access Journals (Sweden)

Zhangsong Yao

2014-01-01

Full Text Available The proximal split feasibility problem has been studied. A regularized method has been presented for solving the proximal split feasibility problem. Strong convergence theorem is given.

Study on Mechanical Features of Brazilian Splitting Fatigue Tests of Salt Rock

Directory of Open Access Journals (Sweden)

Weichao Wang

2016-01-01

Full Text Available The microtest, SEM, was carried out to study the fracture surface of salt rock after the Brazilian splitting test and splitting fatigue test were carried out with a servo-controlled test machine RMT-150B. The results indicate that the deviation of using the tablet splitting method is larger than that of using steel wire splitting method, in Brazilian splitting test of salt rock, when the conventional data processing method is adopted. There are similar deformation features in both the conventional splitting tests and uniaxial compression tests. The stress-strain curves include compaction, elasticity, yielding, and failure stage. Both the vertical deformation and horizontal deformation of splitting fatigue tests under constant average loading can be divided into three stages of “loosening-tightness-loosening.” The failure modes of splitting fatigue tests under the variational average loading are not controlled by the fracturing process curve of the conventional splitting tests. The deformation extent of fatigue tests under variational average loading is even greater than that of conventional splitting test. The tensile strength of salt rock has a relationship with crystallization conditions. Tensile strength of thick crystal salt rock is lower than the bonded strength of fine-grain crystals.

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

International Nuclear Information System (INIS)

Park, Jong Oag; Woo, Je Ho; Ki, Tae Sung; Lee, Jong Hwa; Chung, Jin Woo; Lee, Don Young

1994-01-01

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

Heat split imbalance study for annular fuel rod

International Nuclear Information System (INIS)

He Xiaojun; Ji Songtao; Zhang Yingchao

2014-01-01

Annular fuel rod has two gaps at inner and outer side. Under irradiation condition, the dimensional change of pellets is always larger than claddings' due to thermal expansion, swelling and densification, and this tends to enlarge the inner gap and reduce the outer gap. The gap size asymmetry must induce heat split imbalance problem that the heat flux will be larger at outer side of the rod. In this work, computer code AFPAC l.0 is used to simulate this heat split imbalance phenomena. The effect of initial gap size, rod inner pressure, roughness of pellets and cladding is studied, the results reveal that: l) Adjusting initial size of both gaps, reducing inner gap and enlarging outer gap could effectively alleviate heat split imbalance problem; 2) Adjusting the initial roughness of pellets and cladding is another effective approach to reducing heat split imbalance; 3) It seems that changing the rod inner pressure has a little effect on solving the heat flux asymmetry problem. (authors)

Higgs, Binos and Gluinos: Split Susy within Reach

Energy Technology Data Exchange (ETDEWEB)

Alves, Daniele S.M.; Izaguirre, Eder; /SLAC /Stanford U., Phys. Dept.; Wacker, Jay G.; /SLAC /Stanford U., ITP

2012-09-14

Recent results from the LHC for the Higgs boson with mass between 142 GeV {approx}< m{sub h{sup 0}} {approx}< 147 GeV points to PeV-scale Split Supersymmetry. This article explores the consequences of a Higgs mass in this range and possible discovery modes for Split Susy. Moderate lifetime gluinos, with decay lengths in the 25 {micro}m to 10 yr range, are its imminent smoking gun signature. The 7TeV LHC will be sensitive to the moderately lived gluinos and trilepton signatures from direct electroweakino production. Moreover, the dark matter abundance may be obtained from annihilation through an s-channel Higgs resonance, with the LSP almost purely bino and mass m{sub {chi}{sub 1}{sup 0}} {approx_equal} 70 GeV. The Higgs resonance region of Split Susy has visible signatures in dark matter direct and indirect detection and electric dipole moment experiments. If the anomalies go away, the majority of Split Susy parameter space will be excluded.

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.

Influence of the large-small split effect on strategy choice in complex subtraction.

Science.gov (United States)

Xiang, Yan Hui; Wu, Hao; Shang, Rui Hong; Chao, Xiaomei; Ren, Ting Ting; Zheng, Li Ling; Mo, Lei

2018-04-01

Two main theories have been used to explain the arithmetic split effect: decision-making process theory and strategy choice theory. Using the inequality paradigm, previous studies have confirmed that individuals tend to adopt a plausibility-checking strategy and a whole-calculation strategy to solve large and small split problems in complex addition arithmetic, respectively. This supports strategy choice theory, but it is unknown whether this theory also explains performance in solving different split problems in complex subtraction arithmetic. This study used small, intermediate and large split sizes, with each split condition being further divided into problems requiring and not requiring borrowing. The reaction times (RTs) for large and intermediate splits were significantly shorter than those for small splits, while accuracy was significantly higher for large and middle splits than for small splits, reflecting no speed-accuracy trade-off. Further, RTs and accuracy differed significantly between the borrow and no-borrow conditions only for small splits. This study indicates that strategy choice theory is suitable to explain the split effect in complex subtraction arithmetic. That is, individuals tend to choose the plausibility-checking strategy or the whole-calculation strategy according to the split size. © 2016 International Union of Psychological Science.

The lactate receptor HCAR1 promotes neuronal development and protects axons and myelin during hypoglycemia

DEFF Research Database (Denmark)

Kennedy, L. H.; Andersson, K. A.; Haugen, O. P.

2017-01-01

Lactate plays a significant role as an energy supply for neurons and has a neuroprotective effect in hypoglycemia and ischemia (1±5). Further, oligodendrocytes can use lactate for myelination when glucose levels are low. New studies suggest that lactate is not only a metabolic fuel but also...... in the development and survival of neurons and oligodendrocytes in normal conditions and hypoglycemia. We show that young HCAR1 KO mice have a reduced number of neural progenitor cells in the hippocampus and the cerebral cortex, and the average size of cortical axons is smaller in KO compared with WT mice...

Effects of myelin or cell body brainstem lesions on 3-channel Lissajous' trajectories of feline auditory brainstem evoked potentials.

Science.gov (United States)

Pratt, H; Zaaroor, M; Bleich, N; Starr, A

1991-06-01

Auditory brainstem evoked potentials (ABEP) were recorded from 16 awake cats to obtain 3-Channel Lissajous' Trajectories (3CLTs) using three orthogonal differential electrode configurations (nasion-midline nuchal ridge, left-right mastoids, vertex-midline under the mandible). Potentials, evoked by monaural 80 dBnHL (re, human threshold) clicks, were studied before, and up to 7 weeks after inducing neuronal lesions localized to the cochlear nucleus (CN) or the superior olivary complex (SOC), or myelin lesions localized to the fibers of the trapezoid body connecting these two structures. Neuronal lesions were induced by injection of kainic acid (KA), while myelin lesions were induced by injection of L-alpha-lysophosphatidylcholine (LPC). With CN neuronal lesions the major changes in 3CLT were in the time domain of 'b', 'c' and 'd' (components P2, P3 and P4 of single-channel ABEP). With SOC neuronal lesions the major changes were in 'c' and 'd' of 3CLT (P3 and P4 of ABEP). With trapezoid body lesions the major change was in 'c' (P3 of ABEP). The results are compatible with the peripheral generation of the first ABEP components (P1a and P1b). The second component (P2) is generated by ipsilateral CN neurones and their outputs. The third component (P3) is generated primarily by ipsilateral SOC neurones and their outputs, with the ipsilateral CN providing input. The The fourth component (P4) is generated bilaterally by the SOC neurones and their outputs, receiving their inputs from ipsilateral CN. The fifth ABEP component (P5) is generated by structures central to the SOCs and their immediate outputs. Neither focal neuronal nor myelin lesions were sufficient to produce obliteration of any component, consistent with a set of generators for each of the ABEP components, consisting of both cell bodies and their output fibers, that is distributed spatially in the brainstem.

Towards Highly Efficient Bias-Free Solar Water Splitting

NARCIS (Netherlands)

Abdi, F.F.

2013-01-01

Solar water splitting has attracted significant attention due to its potential of converting solar to chemical energy. It uses semiconductor to convert sunlight into electron-hole pairs, which then split water into hydrogen and oxygen. The hydrogen can be used as a renewable fuel, or it can serve as

77 FR 8127 - Foreign Tax Credit Splitting Events

Science.gov (United States)

2012-02-14

... Tax Credit Splitting Events AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Final and... affect taxpayers claiming foreign tax credits. The text of the temporary regulations also serves as the... that if there is a foreign tax credit splitting event with respect to a foreign income tax paid or...

Comparison of split double and triple twists in pair figure skating.

Science.gov (United States)

King, Deborah L; Smith, Sarah L; Brown, Michele R; McCrory, Jean L; Munkasy, Barry A; Scheirman, Gary I

2008-05-01

In this study, we compared the kinematic variables of the split triple twist with those of the split double twist to help coaches and scientists understand these landmark pair skating skills. High-speed video was taken during the pair short and free programmes at the 2002 Salt Lake City Winter Olympics and the 2003 International Skating Union Grand Prix Finals. Three-dimensional analyses of 14 split double twists and 15 split triple twists from eleven pairs were completed. In spite of considerable variability in the performance variables among the pairs, the main difference between the split double twists and split triple twists was an increase in rotational rate. While eight of the eleven pairs relied primarily on an increased rotational rate to complete the split triple twist, three pairs employed a combined strategy of increased rotational rate and increased flight time due predominantly to delayed or lower catches. These results were similar to observations of jumps in singles skating for which the extra rotation is typically due to an increase in rotational velocity; increases in flight time come primarily from delayed landings as opposed to additional height during flight. Combining an increase in flight time and rotational rate may be a good strategy for completing the split triple twist in pair skating.

Split warhead simultaneous impact

Directory of Open Access Journals (Sweden)

Rahul Singh Dhari

2017-12-01

Full Text Available A projectile system is proposed to improve efficiency and effectiveness of damage done by anti-tank weapon system on its target by designing a ballistic projectile that can split into multiple warheads and engage a target at the same time. This idea has been developed in interest of saving time consumed from the process of reloading and additional number of rounds wasted on target during an attack. The proposed system is achieved in three steps: Firstly, a mathematical model is prepared using the basic equations of motion. Second, An Ejection Mechanism of proposed warhead is explained with the help of schematics. Third, a part of numerical simulation which is done using the MATLAB software. The final result shows various ranges and times when split can be effectively achieved. With the new system, impact points are increased and hence it has a better probability of hitting a target.

Photoelectrochemical solar water splitting: From basic principles to advanced devices

Directory of Open Access Journals (Sweden)

Bandar Y.Alfaifi

2018-02-01

Full Text Available Photoelectrochemical water splitting (PEC offers a promising path for sustainable generation of hydrogen fuel. However, improving solar fuel water splitting efficiency facing tremendous challenges, due to the energy loss related to fast recombination of the photogenerated charge carriers, electrode degradation, as well as limited light harvesting. This review focuses on the brief introduction of basic fundamental of PEC water splitting and the concept of various types of water splitting approaches. Numerous engineering strategies for the investgating of the higher efficiency of the PEC, including charge separation, light harvesting, and co-catalysts doping, have been discussed. Moreover, recent remarkable progress and developments for PEC water splitting with some promising materials are discussed. Recent advanced applications of PEC are also reviewed. Finally, the review concludes with a summary and future outlook of this hot field.

Point splitting in a curved space-time background

International Nuclear Information System (INIS)

Liggatt, P.A.J.; Macfarlane, A.J.

1979-01-01

A prescription is given for point splitting in a curved space-time background which is a natural generalization of that familiar in quantum electrodynamics and Yang-Mills theory. It is applied (to establish its validity) to the verification of the gravitational anomaly in the divergence of a fermion axial current. Notable features of the prescription are that it defines a point-split current that can be differentiated straightforwardly, and that it involves a natural way of averaging (four-dimensionally) over the directions of point splitting. The method can extend directly from the spin-1/2 fermion case treated to other cases, e.g., to spin-3/2 Rarita-Schwinger fermions. (author)

Opportunistic splitting for scheduling using a score-based approach

KAUST Repository

Rashid, Faraan

2012-06-01

We consider the problem of scheduling a user in a multi-user wireless environment in a distributed manner. The opportunistic splitting algorithm is applied to find the best group of users without reporting the channel state information to the centralized scheduler. The users find the best among themselves while requiring just a ternary feedback from the common receiver at the end of each mini-slot. The original splitting algorithm is modified to handle users with asymmetric channel conditions. We use a score-based approach with the splitting algorithm to introduce time and throughput fairness while exploiting the multi-user diversity of the network. Analytical and simulation results are given to show that the modified score-based splitting algorithm works well as a fair scheduling scheme with good spectral efficiency and reduced feedback. © 2012 IEEE.

Loss-of-Function Mutations in LGI4, a Secreted Ligand Involved in Schwann Cell Myelination, Are Responsible for Arthrogryposis Multiplex Congenita.

Science.gov (United States)

Xue, Shifeng; Maluenda, Jérôme; Marguet, Florent; Shboul, Mohammad; Quevarec, Loïc; Bonnard, Carine; Ng, Alvin Yu Jin; Tohari, Sumanty; Tan, Thong Teck; Kong, Mung Kei; Monaghan, Kristin G; Cho, Megan T; Siskind, Carly E; Sampson, Jacinda B; Rocha, Carolina Tesi; Alkazaleh, Fawaz; Gonzales, Marie; Rigonnot, Luc; Whalen, Sandra; Gut, Marta; Gut, Ivo; Bucourt, Martine; Venkatesh, Byrappa; Laquerrière, Annie; Reversade, Bruno; Melki, Judith

2017-04-06

Arthrogryposis multiplex congenita (AMC) is a developmental condition characterized by multiple joint contractures resulting from reduced or absent fetal movements. Through genetic mapping of disease loci and whole-exome sequencing in four unrelated multiplex families presenting with severe AMC, we identified biallelic loss-of-function mutations in LGI4 (leucine-rich glioma-inactivated 4). LGI4 is a ligand secreted by Schwann cells that regulates peripheral nerve myelination via its cognate receptor ADAM22 expressed by neurons. Immunolabeling experiments and transmission electron microscopy of the sciatic nerve from one of the affected individuals revealed a lack of myelin. Functional tests using affected individual-derived iPSCs showed that these germline mutations caused aberrant splicing of the endogenous LGI4 transcript and in a cell-based assay impaired the secretion of truncated LGI4 protein. This is consistent with previous studies reporting arthrogryposis in Lgi4-deficient mice due to peripheral hypomyelination. This study adds to the recent reports implicating defective axoglial function as a key cause of AMC. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Split-Framework in Mandibular Implant-Supported Prosthesis

Directory of Open Access Journals (Sweden)

Danny Omar Mendoza Marin

2015-01-01

Full Text Available During oral rehabilitation of an edentulous patient with an implant-supported prosthesis, mandibular flexure must be considered an important biomechanical factor when planning the metal framework design, especially if implants are installed posterior to the interforaminal region. When an edentulous mandible is restored with a fixed implant-supported prosthesis connected by a fixed full-arch framework, mandibular flexure may cause needless stress in the overall restorative system and lead to screw loosening, poor fit of prosthesis, loss of the posterior implant, and patient’s discomfort due to deformation properties of the mandible during functional movements. The use of a split-framework could decrease the stress with a precise and passive fit on the implants and restore a more natural functional condition of the mandible, helping in the longevity of the prosthesis. Therefore, the present clinical report describes the oral rehabilitation of an edentulous patient by a mandibular fixed implant-supported prosthesis with a split-framework to compensate for mandibular flexure. Clinical Significance. The present clinical report shows that the use of a split-framework reduced the risk of loss of the posterior implants or screws loosening with acceptable patient comfort over the period of a year. The split-framework might have compensated for the mandibular flexure during functional activities.

Split brain: divided perception but undivided consciousness.

Science.gov (United States)

Pinto, Yair; Neville, David A; Otten, Marte; Corballis, Paul M; Lamme, Victor A F; de Haan, Edward H F; Foschi, Nicoletta; Fabri, Mara

2017-05-01

In extensive studies with two split-brain patients we replicate the standard finding that stimuli cannot be compared across visual half-fields, indicating that each hemisphere processes information independently of the other. Yet, crucially, we show that the canonical textbook findings that a split-brain patient can only respond to stimuli in the left visual half-field with the left hand, and to stimuli in the right visual half-field with the right hand and verbally, are not universally true. Across a wide variety of tasks, split-brain patients with a complete and radiologically confirmed transection of the corpus callosum showed full awareness of presence, and well above chance-level recognition of location, orientation and identity of stimuli throughout the entire visual field, irrespective of response type (left hand, right hand, or verbally). Crucially, we used confidence ratings to assess conscious awareness. This revealed that also on high confidence trials, indicative of conscious perception, response type did not affect performance. These findings suggest that severing the cortical connections between hemispheres splits visual perception, but does not create two independent conscious perceivers within one brain. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Nav1.7 expression is increased in painful human dental pulp

Directory of Open Access Journals (Sweden)

Levinson S Rock

2008-04-01

Full Text Available Abstract Background Animal studies and a few human studies have shown a change in sodium channel (NaCh expression after inflammatory lesions, and this change is implicated in the generation of pain states. We are using the extracted human tooth as a model system to study peripheral pain mechanisms and here examine the expression of the Nav1.7 NaCh isoform in normal and painful samples. Pulpal sections were labeled with antibodies against: 1 Nav1.7, N52 and PGP9.5, and 2 Nav1.7, caspr (a paranodal protein used to identify nodes of Ranvier, and myelin basic protein (MBP, and a z-series of optically-sectioned images were obtained with the confocal microscope. Nav1.7-immunofluorescence was quantified in N52/PGP9.5-identified nerve fibers with NIH ImageJ software, while Nav1.7 expression in myelinated fibers at caspr-identified nodal sites was evaluated and further characterized as either typical or atypical as based on caspr-relationships. Results Results show a significant increase in nerve area with Nav1.7 expression within coronal and radicular fiber bundles and increased expression at typical and atypical caspr-identified nodal sites in painful samples. Painful samples also showed an augmentation of Nav1.7 within localized areas that lacked MBP, including those associated with atypical caspr-identified sites, thus identifying NaCh remodeling within demyelinating axons as the basis for a possible pulpal pain mechanism. Conclusion This study identifies the increased axonal expression and augmentation of Nav1.7 at intact and remodeling/demyelinating nodes within the painful human dental pulp where these changes may contribute to constant, increased evoked and spontaneous pain responses that characterize the pain associated with toothache.

Kondo peak splitting and Kondo dip in single molecular magnet junctions

Energy Technology Data Exchange (ETDEWEB)

Niu, Pengbin, E-mail: 120233951@qq.com [Institute of Solid State Physics, Shanxi Datong University, Datong 037009 (China); Shi, Yunlong; Sun, Zhu [Institute of Solid State Physics, Shanxi Datong University, Datong 037009 (China); Nie, Yi-Hang [Institute of Theoretical Physics, Shanxi University, Taiyuan 030006 (China); Luo, Hong-Gang [Center for Interdisciplinary Studies & Key Laboratory for Magnetism and Magnetic Materials of the MoE, Lanzhou University, Lanzhou 730000 (China); Beijing Computational Science Research Center, Beijing 100084 (China)

2016-01-15

Many factors containing bias, spin–orbit coupling, magnetic fields applied, and so on can strongly influence the Kondo effect, and one of the consequences is Kondo peak splitting (KPS). It is natural that KPS should also appear when another spin degree of freedom is involved. In this work we study the KPS effects of single molecular magnets (SMM) coupled with two metallic leads in low-temperature regime. It is found that the Kondo transport properties are strongly influenced by the exchange coupling and anisotropy of the magnetic core. By employing Green's function method in Hubbard operator representation, we give an analytical expression for local retarded Green's function of SMM and discussed its low-temperature transport properties. We find that the anisotropy term behaves as a magnetic field and the splitting behavior of exchange coupling is quite similar to the spin–orbit coupling. These splitting behaviors are explained by introducing inter-level or intra-level transitions, which account for the seven-peak splitting structure. Moreover, we find a Kondo dip at Fermi level under proper parameters. These Kondo peak splitting behaviors in SMM deepen our understanding to Kondo physics and should be observed in the future experiments. - Highlights: • We study Kondo peak splitting in single molecular magnets. • We study Kondo effect by Hubbard operator Green's function method. • We find Kondo peak splitting structures and a Kondo dip at Fermi level. • The exchange coupling and magnetic anisotropy induce fine splitting structure. • The splitting structures are explained by inter-level or intra-level transitions.

Highly Efficient Photocatalytic Water Splitting over Edge-Modified Phosphorene Nanoribbons.

Science.gov (United States)

Hu, Wei; Lin, Lin; Zhang, Ruiqi; Yang, Chao; Yang, Jinlong

2017-11-01

Two-dimensional phosphorene with desirable optoelectronic properties (ideal band gap, high carrier mobility, and strong visible light absorption) is a promising metal-free photocatalyst for water splitting. However, the band edge positions of the valence band maximum (VBM) and conduction band maximum (CBM) of phosphorene are higher than the redox potentials in photocatalytic water splitting reactions. Thus, phosphorene can only be used as the photocathode for hydrogen evolution reaction as a low-efficiency visible-light-driven photocatalyst for hydrogen production in solar water splitting cells. Here, we propose a new mechanism to improve the photocatalytic efficiency of phosphorene nanoribbons (PNRs) by modifying their edges for full reactions in photocatalytic water splitting. By employing first-principles density functional theory calculations, we find that pseudohalogen (CN and OCN) passivated PNRs not only show desired VBM and CBM band edge positions induced by edge electric dipole layer, but also possess intrinsic optoelectronic properties of phosphorene, for both water oxidation and hydrogen reduction in photocatalytic water splitting without using extra energy. Furthermore, our calculations also predict that the maximum energy conversion efficiency of heterojunction solar cells consisting of different edge-modified PNRs can be as high as 20% for photocatalytic water splitting.

Divergent Immunomodulation Capacity of Individual Myelin Peptides—Components of Liposomal Therapeutic against Multiple Sclerosis

Directory of Open Access Journals (Sweden)

Vilena V. Ivanova

2017-10-01

Full Text Available Multiple sclerosis (MS is an autoimmune disease characterized by demyelination and consequent neuron injury. Although the pathogenesis of MS is largely unknown, a breach in immune self-tolerance to myelin followed by development of autoreactive encephalitogenic T cells is suggested to play the central role. The myelin basic protein (MBP is believed to be one of the main targets for autoreactive lymphocytes. Recently, immunodominant MBP peptides encapsulated into the mannosylated liposomes, referred as Xemys, were shown to suppress development of experimental autoimmune encephalomyelitis, a rodent model of MS, and furthermore passed the initial stage of clinical trials. Here, we investigated the role of individual polypeptide components [MBP peptides 46–62 (GH17, 124–139 (GK16, and 147–170 (QR24] of this liposomal peptide therapeutic in cytokine release and activation of immune cells from MS patients and healthy donors. The overall effects were assessed using peripheral blood mononuclear cells (PBMCs, whereas alterations in antigen-presenting capacities were studied utilizing plasmacytoid dendritic cells (pDCs. Among three MBP-immunodominant peptides, QR24 and GK16 activated leukocytes, while GH17 was characterized by an immunosuppressive effect. Peptides QR24 and GK16 upregulated CD4 over CD8 T cells and induced proliferation of CD25+ cells, whereas GH17 decreased the CD4/CD8 T cell ratio and had limited effects on CD25+ T cells. Accordingly, components of liposomal peptide therapeutic differed in upregulation of cytokines upon addition to PBMCs and pDCs. Peptide QR24 was evidently more effective in upregulation of pro-inflammatory cytokines, whereas GH17 significantly increased production of IL-10 through treated cells. Altogether, these data suggest a complexity of action of the liposomal peptide therapeutic that does not seem to involve simple helper T cells (Th-shift but rather the rebalancing of the immune system.

Atomic oxygen fine-structure splittings with tunable far-infrared spectroscopy

Science.gov (United States)

Zink, Lyndon R.; Evenson, Kenneth M.; Matsushima, Fusakazu; Nelis, Thomas; Robinson, Ruth L.

1991-01-01

Fine-structure splittings of atomic oxygen (O-16) in the ground state have been accurately measured using a tunable far-infrared spectrometer. The 3P0-3pl splitting is 2,060,069.09 (10) MHz, and the 3Pl-3P2 splitting is 4,744,777.49 (16) MHz. These frequencies are important for measuring atomic oxygen concentration in earth's atmosphere and the interstellar medium.

Iterative group splitting algorithm for opportunistic scheduling systems

KAUST Repository

Nam, Haewoon

2014-05-01

An efficient feedback algorithm for opportunistic scheduling systems based on iterative group splitting is proposed in this paper. Similar to the opportunistic splitting algorithm, the proposed algorithm adjusts (or lowers) the feedback threshold during a guard period if no user sends a feedback. However, when a feedback collision occurs at any point of time, the proposed algorithm no longer updates the threshold but narrows down the user search space by dividing the users into multiple groups iteratively, whereas the opportunistic splitting algorithm keeps adjusting the threshold until a single user is found. Since the threshold is only updated when no user sends a feedback, it is shown that the proposed algorithm significantly alleviates the signaling overhead for the threshold distribution to the users by the scheduler. More importantly, the proposed algorithm requires a less number of mini-slots than the opportunistic splitting algorithm to make a user selection with a given level of scheduling outage probability or provides a higher ergodic capacity given a certain number of mini-slots. © 2013 IEEE.

Interactions of myelin basic protein with mixed dodecylphosphocholine/palmitoyllysophosphatidic acid micelles

International Nuclear Information System (INIS)

Mendz, G.L.; Brown, L.R.; Martenson, R.E.

1990-01-01

The interactions of myelin basic protein and peptides derived from it with detergent micelles of lysophosphatidylglycerol, lysophosphatidylserine, palmitoyllysophosphatidic acid, and sodium lauryl sulfate, and with mixed micelles of the neutral detergent dodecylphosphocholine and the negatively charged detergent palmitoyllysophosphatidic acid, were investigated by 1 H NMR spectroscopy and circular dichroic spectropolarimetry. The results with single detergents suggested that there are discrete interaction sites in the protein molecule for neutral and anionic detergent micelles and that at least some of these sites are different for each type of detergent. The data on the binding of the protein and peptides to mixed detergent micelles suggested that intramolecular interactions in the intact protein and in one of the longer peptides limited the formation of helices and also that a balance between hydrophobic and ionic forces is achieved in the interactions of the peptides with the detergents. At high detergent/protein molar ratios, hydrophobic interactions appeared to be favored

Analysis of main dynamic parameters of split power transmission

Directory of Open Access Journals (Sweden)

A. Janulevičius

2008-06-01

Full Text Available The review carried out had shown one basic approach of split power transmission to the organization of drive which is applied to stepless transmissions of tractors and parallel hybrid cars. In the split power transmission the power split device uses a planetary gear. Tractor engine power in the split power transmission is transmitted to the drive shaft via a mechanical and hydraulic path. The theoretical analysis of main parameters of the split power transmission of the tractor is presented. The angular velocity of sun and coronary gears of the differential set is estimated by solution of the system of equations in which one equation is made for planetary differential gear, and another – for hydrostatic drive. The analysis of the transmission gear-ratio dependencies on the ratio of hydraulic machines capacities is carried out. Dependence of the variation of angular velocity of the coronary and the sun gears on the ground speed of the tractor is presented. Dependence of sum shaft torque and its constituents, carried by mechanical and hydraulic lines, on sum shaft angular velocity and ground speed of tractor and engine speed is also presented.

Identifying Patient-Specific Epstein-Barr Nuclear Antigen-1 Genetic Variation and Potential Autoreactive Targets Relevant to Multiple Sclerosis Pathogenesis.

Directory of Open Access Journals (Sweden)

Monika Tschochner

Full Text Available Epstein-Barr virus (EBV infection represents a major environmental risk factor for multiple sclerosis (MS, with evidence of selective expansion of Epstein-Barr Nuclear Antigen-1 (EBNA1-specific CD4+ T cells that cross-recognize MS-associated myelin antigens in MS patients. HLA-DRB1*15-restricted antigen presentation also appears to determine susceptibility given its role as a dominant risk allele. In this study, we have utilised standard and next-generation sequencing techniques to investigate EBNA-1 sequence variation and its relationship to HLA-DR15 binding affinity, as well as examining potential cross-reactive immune targets within the central nervous system proteome.Sanger sequencing was performed on DNA isolated from peripheral blood samples from 73 Western Australian MS cases, without requirement for primary culture, with additional FLX 454 Roche sequencing in 23 samples to identify low-frequency variants. Patient-derived viral sequences were used to predict HLA-DRB1*1501 epitopes (NetMHCII, NetMHCIIpan and candidates were evaluated for cross recognition with human brain proteins.EBNA-1 sequence variation was limited, with no evidence of multiple viral strains and only low levels of variation identified by FLX technology (8.3% nucleotide positions at a 1% cut-off. In silico epitope mapping revealed two known HLA-DRB1*1501-restricted epitopes ('AEG': aa 481-496 and 'MVF': aa 562-577, and two putative epitopes between positions 502-543. We identified potential cross-reactive targets involving a number of major myelin antigens including experimentally confirmed HLA-DRB1*15-restricted epitopes as well as novel candidate antigens within myelin and paranodal assembly proteins that may be relevant to MS pathogenesis.This study demonstrates the feasibility of obtaining autologous EBNA-1 sequences directly from buffy coat samples, and confirms divergence of these sequences from standard laboratory strains. This approach has identified a number of

Rabi splitting in an acoustic cavity embedded plate

International Nuclear Information System (INIS)

Ni, Xu; Liu, Xiao-Ping; Chen, Ze-Guo; Zheng, Li-Yang; Xu, Ye-Long; Lu, Ming-Hui; Chen, Yan-Feng

2014-01-01

We design a structure to realize Rabi splitting and Rabi oscillation in acoustics. We develop rigorous analytical models to analyze the splitting effect from the aspect of phase matching, and from the aspect of mode coupling using a coupled mode model. In this model, we discover that the splitting effect is caused by the coupling of the Fabry–Perot fundamental mode with the resonant mode of an artificial acoustic ‘atom’. We then extract the coupling strength and analyze the impact of structural parameters on it. In addition, we demonstrate Rabi oscillation in the time domain. Such quantum phenomena in the classical regime may have potential applications in the design of novel ultrasonic devices.

Reversible perspective and splitting in time.

Science.gov (United States)

Hart, Helen Schoenhals

2012-01-01

The element of time--the experience of it and the defensive use of it--is explored in conjunction with the use of reversible perspective as a psychotic defense. Clinical material from a long analysis illustrates how a psychotic patient used the reversible perspective, with its static splitting, to abolish the experience of time. When he improved and the reversible perspective became less effective for him, he replaced it with a more dynamic splitting mechanism using time gaps. With further improvement, the patient began to experience the passage of time, and along with it the excruciating pain of separation, envy, and loss.

Small-bubble transport and splitting dynamics in a symmetric bifurcation

KAUST Repository

Qamar, Adnan

2017-06-28

Simulations of small bubbles traveling through symmetric bifurcations are conducted to garner information pertinent to gas embolotherapy, a potential cancer treatment. Gas embolotherapy procedures use intra-arterial bubbles to occlude tumor blood supply. As bubbles pass through bifurcations in the blood stream nonhomogeneous splitting and undesirable bioeffects may occur. To aid development of gas embolotherapy techniques, a volume of fluid method is used to model the splitting process of gas bubbles passing through artery and arteriole bifurcations. The model reproduces the variety of splitting behaviors observed experimentally, including the bubble reversal phenomenon. Splitting homogeneity and maximum shear stress along the vessel walls is predicted over a variety of physical parameters. Small bubbles, having initial length less than twice the vessel diameter, were found unlikely to split in the presence of gravitational asymmetry. Maximum shear stresses were found to decrease exponentially with increasing Reynolds number. Vortex-induced shearing near the bifurcation is identified as a possible mechanism for endothelial cell damage.

Small-bubble transport and splitting dynamics in a symmetric bifurcation.

Science.gov (United States)

Qamar, Adnan; Warnez, Matthew; Valassis, Doug T; Guetzko, Megan E; Bull, Joseph L

2017-08-01

Simulations of small bubbles traveling through symmetric bifurcations are conducted to garner information pertinent to gas embolotherapy, a potential cancer treatment. Gas embolotherapy procedures use intra-arterial bubbles to occlude tumor blood supply. As bubbles pass through bifurcations in the blood stream nonhomogeneous splitting and undesirable bioeffects may occur. To aid development of gas embolotherapy techniques, a volume of fluid method is used to model the splitting process of gas bubbles passing through artery and arteriole bifurcations. The model reproduces the variety of splitting behaviors observed experimentally, including the bubble reversal phenomenon. Splitting homogeneity and maximum shear stress along the vessel walls is predicted over a variety of physical parameters. Small bubbles, having initial length less than twice the vessel diameter, were found unlikely to split in the presence of gravitational asymmetry. Maximum shear stresses were found to decrease exponentially with increasing Reynolds number. Vortex-induced shearing near the bifurcation is identified as a possible mechanism for endothelial cell damage.

Small-bubble transport and splitting dynamics in a symmetric bifurcation

KAUST Repository

Qamar, Adnan; Warnez, Matthew; Valassis, Doug T.; Guetzko, Megan E.; Bull, Joseph L.

2017-01-01

Simulations of small bubbles traveling through symmetric bifurcations are conducted to garner information pertinent to gas embolotherapy, a potential cancer treatment. Gas embolotherapy procedures use intra-arterial bubbles to occlude tumor blood supply. As bubbles pass through bifurcations in the blood stream nonhomogeneous splitting and undesirable bioeffects may occur. To aid development of gas embolotherapy techniques, a volume of fluid method is used to model the splitting process of gas bubbles passing through artery and arteriole bifurcations. The model reproduces the variety of splitting behaviors observed experimentally, including the bubble reversal phenomenon. Splitting homogeneity and maximum shear stress along the vessel walls is predicted over a variety of physical parameters. Small bubbles, having initial length less than twice the vessel diameter, were found unlikely to split in the presence of gravitational asymmetry. Maximum shear stresses were found to decrease exponentially with increasing Reynolds number. Vortex-induced shearing near the bifurcation is identified as a possible mechanism for endothelial cell damage.

Split-liver transplantation : An underused resource in liver transplantation

NARCIS (Netherlands)

Rogiers, Xavier; Sieders, Egbert

2008-01-01

Split-liver transplantation is an efficient tool to increase the number of liver grafts available for transplantation. More than 15 years after its introduction only the classical splitting technique has reached broad application. Consequently children are benefiting most from this possibility.

Mort Rainey's Split Personality in Secret Window

OpenAIRE

Sandjaya, Cynthya; Limanta, Liem Satya

2013-01-01

Psychological issue is the main issue discussed in David Koepp's Secret Window through its main character, Mort Rainey. Rainey's psychological struggle will be the main theme in this research. This thesis examines Rainey's split personality. Furthermore, in this study, we want to analyze the process of how Mort Rainey's personality splits into two different personalities. To meet the answer of this study, we will use the theory of Dissociative Identity Disorder with a support from Sigmund Fre...

Modeling habitat split: landscape and life history traits determine amphibian extinction thresholds.

Directory of Open Access Journals (Sweden)

Carlos Roberto Fonseca

Full Text Available Habitat split is a major force behind the worldwide decline of amphibian populations, causing community change in richness and species composition. In fragmented landscapes, natural remnants, the terrestrial habitat of the adults, are frequently separated from streams, the aquatic habitat of the larvae. An important question is how this landscape configuration affects population levels and if it can drive species to extinction locally. Here, we put forward the first theoretical model on habitat split which is particularly concerned on how split distance - the distance between the two required habitats - affects population size and persistence in isolated fragments. Our diffusive model shows that habitat split alone is able to generate extinction thresholds. Fragments occurring between the aquatic habitat and a given critical split distance are expected to hold viable populations, while fragments located farther away are expected to be unoccupied. Species with higher reproductive success and higher diffusion rate of post-metamorphic youngs are expected to have farther critical split distances. Furthermore, the model indicates that negative effects of habitat split are poorly compensated by positive effects of fragment size. The habitat split model improves our understanding about spatially structured populations and has relevant implications for landscape design for conservation. It puts on a firm theoretical basis the relation between habitat split and the decline of amphibian populations.

Modeling habitat split: landscape and life history traits determine amphibian extinction thresholds.

Science.gov (United States)

Fonseca, Carlos Roberto; Coutinho, Renato M; Azevedo, Franciane; Berbert, Juliana M; Corso, Gilberto; Kraenkel, Roberto A

2013-01-01

Habitat split is a major force behind the worldwide decline of amphibian populations, causing community change in richness and species composition. In fragmented landscapes, natural remnants, the terrestrial habitat of the adults, are frequently separated from streams, the aquatic habitat of the larvae. An important question is how this landscape configuration affects population levels and if it can drive species to extinction locally. Here, we put forward the first theoretical model on habitat split which is particularly concerned on how split distance - the distance between the two required habitats - affects population size and persistence in isolated fragments. Our diffusive model shows that habitat split alone is able to generate extinction thresholds. Fragments occurring between the aquatic habitat and a given critical split distance are expected to hold viable populations, while fragments located farther away are expected to be unoccupied. Species with higher reproductive success and higher diffusion rate of post-metamorphic youngs are expected to have farther critical split distances. Furthermore, the model indicates that negative effects of habitat split are poorly compensated by positive effects of fragment size. The habitat split model improves our understanding about spatially structured populations and has relevant implications for landscape design for conservation. It puts on a firm theoretical basis the relation between habitat split and the decline of amphibian populations.

Choice of Sample Split in Out-of-Sample Forecast Evaluation

DEFF Research Database (Denmark)

Hansen, Peter Reinhard; Timmermann, Allan

, while conversely the power of forecast evaluation tests is strongest with long out-of-sample periods. To deal with size distortions, we propose a test statistic that is robust to the effect of considering multiple sample split points. Empirical applications to predictabil- ity of stock returns......Out-of-sample tests of forecast performance depend on how a given data set is split into estimation and evaluation periods, yet no guidance exists on how to choose the split point. Empirical forecast evaluation results can therefore be difficult to interpret, particularly when several values...... and inflation demonstrate that out-of-sample forecast evaluation results can critically depend on how the sample split is determined....

Tablet splitting of narrow therapeutic index drugs: a nationwide survey in Taiwan.

Science.gov (United States)

Chou, Chia-Lin; Hsu, Chia-Chen; Chou, Chia-Yu; Chen, Tzeng-Ji; Chou, Li-Fang; Chou, Yueh-Ching

2015-12-01

Tablet splitting or pill splitting frequently occurs in daily medical practice. For drugs with special pharmacokinetic characters, such as drugs with narrow therapeutic index (NTI), unequal split tablets might lead to erroneous dose titration and it even cause toxicity. The aim of this study was to investigate the frequency of prescribing split NTI drugs at ambulatory setting in Taiwan. A population-based retrospective study was conducted using the National Health Insurance Research Database in Taiwan. All ambulatory visits were analyzed from the longitudinal cohort datasets of the National Health Insurance Research Database. The details of ambulatory prescriptions containing NTI drugs were extracted by using the claims datasets of one million beneficiaries from National Healthcare Insurance Research Database in 2010 in Taiwan. The analyses were stratified by dosage form, patient age and the number of prescribed tablets in a single dose for each NTI drugs. Main outcome measures Number and distinct dosage forms of available NTI drug items in Taiwan, number of prescriptions involved split NTI drugs, and number of patients received split NTI drugs. A total of 148,548 patients had received 512,398 prescriptions of NTI drugs and 41.8 % (n = 62,121) of patients had received 36.3 % (n = 185,936) of NTI drug prescriptions in form of split tablets. The percentage of splitting was highest in digoxin prescriptions (81.0 %), followed by warfarin (72.0 %). In the elderly patients, split tablets were very prevalent with digoxin (82.4 %) and warfarin (84.5 %). NTI drugs were frequently prescribed to be taken in split forms in Taiwan. Interventions may be needed to provide effective and convenient NTI drug use. Further studies are needed to evaluate the clinical outcome of inappropriate split NTI drugs.

T helper cell type 1 (Th1), Th2 and Th17 responses to myelin basic protein and disease activity in multiple sclerosis

DEFF Research Database (Denmark)

Hedegaard, Chris J; Krakauer, Martin; Bendtzen, Klaus

2008-01-01

Autoreactive T cells are thought to play an essential role in the pathogenesis of multiple sclerosis (MS). We examined the stimulatory effect of human myelin basic protein (MBP) on mononuclear cell (MNC) cultures from 22 patients with MS and 22 sex-matched and age-matched healthy individuals, and...

Polarized triple-collinear splitting functions at NLO for processes with photons

International Nuclear Information System (INIS)

Sborlini, Germán F.R.; Florian, Daniel de; Rodrigo, Germán

2015-01-01

We compute the polarized splitting functions in the triple collinear limit at next-to-leading order accuracy (NLO) in the strong coupling α_S, for the splitting processes γ→qq-barγ, γ→qq-barg and g→qq-barγ. The divergent structure of each splitting function was compared to the predicted behaviour according to Catani’s formula. The results obtained in this paper are compatible with the unpolarized splitting functions computed in a previous article. Explicit results for NLO corrections are presented in the context of conventional dimensional regularization (CDR).

Polarized triple-collinear splitting functions at NLO for processes with photons

Energy Technology Data Exchange (ETDEWEB)

Sborlini, Germán F.R. [Departamento de Física and IFIBA, FCEyN, Universidad de Buenos Aires (1428) Pabellón 1 Ciudad Universitaria, Capital Federal (Argentina); Instituto de Física Corpuscular, Universitat de València,Consejo Superior de Investigaciones Científicas,Parc Científic, E-46980 Paterna, Valencia (Spain); Florian, Daniel de [Departamento de Física and IFIBA, FCEyN, Universidad de Buenos Aires (1428) Pabellón 1 Ciudad Universitaria, Capital Federal (Argentina); Rodrigo, Germán [Instituto de Física Corpuscular, Universitat de València,Consejo Superior de Investigaciones Científicas,Parc Científic, E-46980 Paterna, Valencia (Spain)

2015-03-04

We compute the polarized splitting functions in the triple collinear limit at next-to-leading order accuracy (NLO) in the strong coupling α{sub S}, for the splitting processes γ→qq-barγ, γ→qq-barg and g→qq-barγ. The divergent structure of each splitting function was compared to the predicted behaviour according to Catani’s formula. The results obtained in this paper are compatible with the unpolarized splitting functions computed in a previous article. Explicit results for NLO corrections are presented in the context of conventional dimensional regularization (CDR).

"Split Cast Mounting: Review and New Technique".

Science.gov (United States)

Gundawar, S M; Pande, Neelam A; Jaiswal, Priti; Radke, U M

2014-12-01

For the fabrication of a prosthesis, the Prosthodontist meticulously performs all the steps. The laboratory technician then make every effort/strives to perform the remaining lab procedures. However when the processed dentures are remounted on the articulator, some changes are seen. These changes may be divided into two categories: Pre-insertion and post-insertion changes, which deal with the physical properties of the materials involved (Parker, J Prosthet Dent 31:335-342, 1974). Split cast mounting is the method of mounting casts on the articulator. It is essentially a maxillary cast constructed in two parts with a horizontal division. The procedure allows for the verification of the accuracy of the initial mounting and the ease of removal and replacement of the cast. This provides a precise means of correcting the changes in occlusion occurring as a result of the processing technique (Nogueira et al., J Prosthet Dent 91:386-388, 2004). Instability of the split mounting has always been a problem to the Prosthodontist thereby limiting its use. There are various materials mentioned in the literature. The new technique by using Dowel pins and twill thread is very easy, cheaper and simple way to stabilize the split mounting. It is useful and easy in day to day laboratory procedures. The article presents different methods of split cast mounting and the new procedure using easily available materials in prosthetic laboratory.

The occurrence of IgM and complement factors along myelin sheaths of peripheral nerves An immunohistochemical study of the Guillain-Barre syndrome : Preliminary communication

NARCIS (Netherlands)

Luijten, J.A.F.M.; Baart de la Faille-Kuyper, E.H.

In nerve biopsies from 4 of 6 patients with the Guillain-Barré syndrome (GBS), IgM and complement factors were found, probably localized along myelin sheaths. The possible significance of this phenomenon has been discussed. No such findings were obtained in control subjects.

Dye-sensitized photocatalyst for effective water splitting catalyst

Science.gov (United States)

Watanabe, Motonori

2017-12-01

Renewable hydrogen production is a sustainable method for the development of next-generation energy technologies. Utilising solar energy and photocatalysts to split water is an ideal method to produce hydrogen. In this review, the fundamental principles and recent progress of hydrogen production by artificial photosynthesis are reviewed, focusing on hydrogen production from photocatalytic water splitting using organic-inorganic composite-based photocatalysts.

Advanced split-illumination electron holography without Fresnel fringes

International Nuclear Information System (INIS)

Tanigaki, Toshiaki; Aizawa, Shinji; Park, Hyun Soon; Matsuda, Tsuyoshi; Harada, Ken; Shindo, Daisuke

2014-01-01

Advanced split-illumination electron holography was developed by employing two biprisms in the illuminating system to split an electron wave into two coherent waves and two biprisms in the imaging system to overlap them. A focused image of an upper condenser-biprism filament was formed on the sample plane, and all other filaments were placed in its shadow. This developed system makes it possible to obtain precise reconstructed object waves without modulations due to Fresnel fringes, in addition to holograms of distant objects from reference waves. - Highlights: • Advanced split-illumination electron holography without Fresnel fringes is developed. • Two biprisms are installed in illuminating system of microscope. • High-precision holographic observations of an area locating far from the sample edge become possible

Advanced split-illumination electron holography without Fresnel fringes

Energy Technology Data Exchange (ETDEWEB)

Tanigaki, Toshiaki, E-mail: tanigaki-toshiaki@riken.jp [Center for Emergent Matter Science (CEMS), RIKEN, Hirosawa 2-1, Wako, Saitama 351-0198 (Japan); Aizawa, Shinji; Park, Hyun Soon [Center for Emergent Matter Science (CEMS), RIKEN, Hirosawa 2-1, Wako, Saitama 351-0198 (Japan); Matsuda, Tsuyoshi [Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Harada, Ken [Central Research Laboratory, Hitachi, Ltd., Hatoyama, Saitama 350-0395 (Japan); Shindo, Daisuke [Center for Emergent Matter Science (CEMS), RIKEN, Hirosawa 2-1, Wako, Saitama 351-0198 (Japan); Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Katahira 2-1-1, Sendai 980-8577 (Japan)

2014-02-01

Advanced split-illumination electron holography was developed by employing two biprisms in the illuminating system to split an electron wave into two coherent waves and two biprisms in the imaging system to overlap them. A focused image of an upper condenser-biprism filament was formed on the sample plane, and all other filaments were placed in its shadow. This developed system makes it possible to obtain precise reconstructed object waves without modulations due to Fresnel fringes, in addition to holograms of distant objects from reference waves. - Highlights: • Advanced split-illumination electron holography without Fresnel fringes is developed. • Two biprisms are installed in illuminating system of microscope. • High-precision holographic observations of an area locating far from the sample edge become possible.

The Differences Between Stock Splits and Stock Dividends

DEFF Research Database (Denmark)

Bechmann, Ken L.; Raaballe, Johannes

It is often asserted that stock splits and stock dividends are purely cosmetic events. However, many studies have documented several stock market effects associated with stock splits and stock dividends. This paper examines the effects of these two types of events for the Danish stock market...... different. Second, the positive stock market reaction is closely related to associated changes in a firm's payout policy, but the relationship varies for the two types of events. Finally, there is only very weak evidence for a change in the liquidity of the stock. On the whole, after controlling...... for the firm's payout policy, the results suggest that a stock split is a cosmetic event and that a stock dividend on its own is considered negative news....

Split School of High Energy Physics 2015

CERN Document Server

2015-01-01

Split School of High Energy Physics 2015 (SSHEP 2015) was held at the Faculty of Electrical Engineering, Mechanical Engineering and Naval Architecture (FESB), University of Split, from September 14 to September 18, 2015. SSHEP 2015 aimed at master and PhD students who were interested in topics pertaining to High Energy Physics. SSHEP 2015 is the sixth edition of the High Energy Physics School. Previous five editions were held at the Department of Physics, University of Sarajevo, Bosnia and Herzegovina.

Protein trans-splicing of multiple atypical split inteins engineered from natural inteins.

Directory of Open Access Journals (Sweden)

Ying Lin

Full Text Available Protein trans-splicing by split inteins has many uses in protein production and research. Splicing proteins with synthetic peptides, which employs atypical split inteins, is particularly useful for site-specific protein modifications and labeling, because the synthetic peptide can be made to contain a variety of unnatural amino acids and chemical modifications. For this purpose, atypical split inteins need to be engineered to have a small N-intein or C-intein fragment that can be more easily included in a synthetic peptide that also contains a small extein to be trans-spliced onto target proteins. Here we have successfully engineered multiple atypical split inteins capable of protein trans-splicing, by modifying and testing more than a dozen natural inteins. These included both S1 split inteins having a very small (11-12 aa N-intein fragment and S11 split inteins having a very small (6 aa C-intein fragment. Four of the new S1 and S11 split inteins showed high efficiencies (85-100% of protein trans-splicing both in E. coli cells and in vitro. Under in vitro conditions, they exhibited reaction rate constants ranging from ~1.7 × 10(-4 s(-1 to ~3.8 × 10(-4 s(-1, which are comparable to or higher than those of previously reported atypical split inteins. These findings should facilitate a more general use of trans-splicing between proteins and synthetic peptides, by expanding the availability of different atypical split inteins. They also have implications on understanding the structure-function relationship of atypical split inteins, particularly in terms of intein fragment complementation.

Isoniazid, pyrazinamide and rifampicin content variation in split fixed-dose combination tablets.

Science.gov (United States)

Pouplin, Thomas; Phuong, Pham Nguyen; Toi, Pham Van; Nguyen Pouplin, Julie; Farrar, Jeremy

2014-01-01

In most developing countries, paediatric tuberculosis is treated with split tablets leading to potential inaccuracy in the dose delivery and drug exposure. There is no data on the quality of first-line drugs content in split fixed-dose combination tablets. To determine Isoniazid, Pyrazinamide and Rifampicin content uniformity in split FDC tablets used in the treatment of childhood tuberculosis. Drug contents of 15 whole tablets, 30 half tablets and 36 third tablets were analysed by high performance liquid chromatography. The content uniformity was assessed by comparing drug content measured in split portions with their expected amounts and the quality of split portions was assessed applying qualitative specifications for whole tablets. All whole tablets measurements fell into the USP proxy for the three drugs. But a significant number of half and third portions was found outside the tolerated variation range and the split formulation failed the requirements for content uniformity. To correct for the inaccuracy of splitting the tablets into equal portions, a weight-adjustment strategy was used but this did not improve the findings. In split tablets the content of the three drugs is non-uniform and exceeded the USP recommendations. There is an absolute need to make child-friendly formulations available for the treatment of childhood tuberculosis.

Two-loop QED corrections to the Altarelli-Parisi splitting functions

Energy Technology Data Exchange (ETDEWEB)

Florian, Daniel de [International Center for Advanced Studies (ICAS), UNSAM,Campus Miguelete, 25 de Mayo y Francia (1650) Buenos Aires (Argentina); Sborlini, Germán F.R.; Rodrigo, Germán [Instituto de Física Corpuscular, Universitat de València,Consejo Superior de Investigaciones Científicas,Parc Científic, E-46980 Paterna, Valencia (Spain)

2016-10-11

We compute the two-loop QED corrections to the Altarelli-Parisi (AP) splitting functions by using a deconstructive algorithmic Abelianization of the well-known NLO QCD corrections. We present explicit results for the full set of splitting kernels in a basis that includes the leptonic distribution functions that, starting from this order in the QED coupling, couple to the partonic densities. Finally, we perform a phenomenological analysis of the impact of these corrections in the splitting functions.

An Examination Of Fracture Splitting Parameters Of Crackable Connecting Rods

Directory of Open Access Journals (Sweden)

Zafer Özdemir

2000-06-01

Full Text Available Fracture splitting method is an innovative processing technique in the field of automobile engine connecting rod (con/rod manufacturing. Compared with traditional method, this technique has remarkable advantages. Manufacturing procedures, equipment and tools investment can be decreased and energy consumption reduced remarkably. Furthermore, product quality and bearing capability can also be improved. It provides a high quality, high accuracy and low cost route for producing connecting rods (con/rods. With the many advantages mentioned above, this method has attracted manufacturers attention and has been utilized in many types of con/rod manufacturing. In this article, the method and the advantages it provides, such as materials, notches for fracture splitting, fracture splitting conditions and fracture splitting equipment are discussed in detail. The paper describes an analysis of examination of fracture splitting parameters and optik-SEM fractography of C70S6 crackable connectıng rod. Force and velocity parameters are investigated. That uniform impact force distrubition starting from the starting notch causes brittle and cleavage failure mode is obtained as a result. This induces to decrease the toughness.

Novel Split Chest Tube Improves Post-Surgical Thoracic Drainage

Science.gov (United States)

Olivencia-Yurvati, Albert H; Cherry, Brandon H; Gurji, Hunaid A; White, Daniel W; Newton, J Tyler; Scott, Gary F; Hoxha, Besim; Gourlay, Terence; Mallet, Robert T

2014-01-01

Objective Conventional, separate mediastinal and pleural tubes are often inefficient at draining thoracic effusions. Description We developed a Y-shaped chest tube with split ends that divide within the thoracic cavity, permitting separate intrathoracic placement and requiring a single exit port. In this study, thoracic drainage by the split drain vs. that of separate drains was tested. Methods After sternotomy, pericardiotomy, and left pleurotomy, pigs were fitted with separate chest drains (n=10) or a split tube prototype (n=9) with internal openings positioned in the mediastinum and in the costo-diaphragmatic recess. Separate series of experiments were conducted to test drainage of D5W or 0.58 M sucrose, an aqueous solution with viscosity approximating that of plasma. One litre of fluid was infused into the thorax, and suction was applied at −20 cm H2O for 30 min. Results When D5W was infused, the split drain left a residual volume of 53 ± 99 ml (mean value ± SD) vs. 148 ± 120 for the separate drain (P=0.007), representing a drainage efficiency (i.e. drained vol/[drained + residual vol]) of 95 ± 10% vs. 86 ± 12% for the separate drains (P = 0.011). In the second series, the split drain evacuated more 0.58 M sucrose in the first minute (967 ± 129 ml) than the separate drains (680 ± 192 ml, Pdrain evacuated a similar volume of sucrose vs. the conventional drain (1089 ± 72 vs. 1056 ± 78 ml; P = 0.5). Residual volume tended to be lower (25 ± 10 vs. 62 ± 72 ml; P = 0.128) and drainage efficiency tended to be higher (98 ± 1 vs. 95 ± 6%; P = 0.111) with the split drain vs. conventional separate drains. Conclusion The split chest tube drained the thoracic cavity at least as effectively as conventional separate tubes. This new device could potentially alleviate postoperative complications. PMID:25478289

Novel Split Chest Tube Improves Post-Surgical Thoracic Drainage.

Science.gov (United States)

Olivencia-Yurvati, Albert H; Cherry, Brandon H; Gurji, Hunaid A; White, Daniel W; Newton, J Tyler; Scott, Gary F; Hoxha, Besim; Gourlay, Terence; Mallet, Robert T

2014-01-01

Conventional, separate mediastinal and pleural tubes are often inefficient at draining thoracic effusions. We developed a Y-shaped chest tube with split ends that divide within the thoracic cavity, permitting separate intrathoracic placement and requiring a single exit port. In this study, thoracic drainage by the split drain vs. that of separate drains was tested. After sternotomy, pericardiotomy, and left pleurotomy, pigs were fitted with separate chest drains (n=10) or a split tube prototype (n=9) with internal openings positioned in the mediastinum and in the costo-diaphragmatic recess. Separate series of experiments were conducted to test drainage of D5W or 0.58 M sucrose, an aqueous solution with viscosity approximating that of plasma. One litre of fluid was infused into the thorax, and suction was applied at -20 cm H2O for 30 min. When D5W was infused, the split drain left a residual volume of 53 ± 99 ml (mean value ± SD) vs. 148 ± 120 for the separate drain (P=0.007), representing a drainage efficiency (i.e. drained vol/[drained + residual vol]) of 95 ± 10% vs. 86 ± 12% for the separate drains (P = 0.011). In the second series, the split drain evacuated more 0.58 M sucrose in the first minute (967 ± 129 ml) than the separate drains (680 ± 192 ml, Pdrain evacuated a similar volume of sucrose vs. the conventional drain (1089 ± 72 vs. 1056 ± 78 ml; P = 0.5). Residual volume tended to be lower (25 ± 10 vs. 62 ± 72 ml; P = 0.128) and drainage efficiency tended to be higher (98 ± 1 vs. 95 ± 6%; P = 0.111) with the split drain vs. conventional separate drains. The split chest tube drained the thoracic cavity at least as effectively as conventional separate tubes. This new device could potentially alleviate postoperative complications.

Gauge invariant frequency splitting of the continuum Yang-Mills field

International Nuclear Information System (INIS)

Mitter, P.K.; Valent, G.

1977-01-01

Frequency splitting plays an important role in Wilson's theory of critical phenomena. Here the authors give a theory of gauge invariant frequency splitting of the Yang-Mills field in 4 dimensions. (Auth.)

Two-Loop Gluon to Gluon-Gluon Splitting Amplitudes in QCD

International Nuclear Information System (INIS)

Bern, Z.

2004-01-01

Splitting amplitudes are universal functions governing the collinear behavior of scattering amplitudes for massless particles. We compute the two-loop g → gg splitting amplitudes in QCD, N = 1, and N = 4 super-Yang-Mills theories, which describe the limits of two-loop n-point amplitudes where two gluon momenta become parallel. They also represent an ingredient in a direct x-space computation of DGLAP evolution kernels at next-to-next-to-leading order. To obtain the splitting amplitudes, we use the unitarity sewing method. In contrast to the usual light-cone gauge treatment, our calculation does not rely on the principal-value or Mandelstam-Leibbrandt prescriptions, even though the loop integrals contain some of the denominators typically encountered in light-cone gauge. We reduce the integrals to a set of 13 master integrals using integration-by-parts and Lorentz invariance identities. The master integrals are computed with the aid of differential equations in the splitting momentum fraction z. The ε-poles of the splitting amplitudes are consistent with a formula due to Catani for the infrared singularities of two-loop scattering amplitudes. This consistency essentially provides an inductive proof of Catani's formula, as well as an ansatz for previously-unknown 1/ε pole terms having non-trivial color structure. Finite terms in the splitting amplitudes determine the collinear behavior of finite remainders in this formula

Cortical splitting of the mandible after irradiation. Special reference to osteoradionecrosis

International Nuclear Information System (INIS)

Katsura, Kouji; Ito, Jusuke; Hayashi, Takafumi; Taira, Shuhzou; Nakajima, Syunichi

2001-01-01

The purpose of this study was to discuss the relationship between radiation bone injuries and a splitting of the cortical bone in the radiation field. Between January 1993 and September 1998, 53 patients with head and neck cancer received radiotherapy. The study cohort consisted of 23 patients who were followed with computed tomographic scans more than one year after radiotherapy. We evaluated clinical and computed tomographic features. Computed tomographic scanning was performed with a section thickness of 3 or 4 mm. Bone images were obtained with identical window width (4000 Haunsfield units) and window level (1000 Haunsfield units). Splitting of the cortical bone was defined as disappearance of bone density in the cortical bone, showing a linear shape running parallel to the surface of the cortex. Splitting appeared in 9 sites in 8 patients. All patients fulfilled UICC criteria for classifying oral cancer. Most of the patients received external irradiation with a total radiation dose of 50 or 60 Gy. In all cases, splitting was found in the mandibular cortex at the site of muscle attachment, that was included in the radiation field. Appearance of bone changes in chronological order were periosteal reaction, splitting and bone necrosis. We speculate that splitting results from injuries to bone structure cells caused by blood flow disturbance after surgery and radiotherapy. It is suggested that such splitting can be a predictor of osteoradionecrosis. (author)

Nonlocal Cooper pair splitting in a pSn-junction

NARCIS (Netherlands)

Veldhorst, M.; Brinkman, Alexander

2010-01-01

Perfect Cooper pair splitting is proposed, based on crossed Andreev reflection (CAR) in a p-type semiconductor-superconductor-n-type semiconductor (pSn) junction. The ideal splitting is caused by the energy filtering that is enforced by the band structure of the electrodes. The pSn junction is

Split Labor Markets and Black-White Relations, 1865-1920.

Science.gov (United States)

Marks, Carole

1981-01-01

This paper modifies Edna Bonacich's theory of class conflict which cites the split labor market during the period of 1920-30 as the cause of racial antagonisms. The author states that Bonacich neglected the role of employers and technological advance in the creation of the split labor market. (ML)

The toughness of split graphs

NARCIS (Netherlands)

Woeginger, G.J.

1998-01-01

In this short note we argue that the toughness of split graphs can be computed in polynomial time. This solves an open problem from a recent paper by Kratsch et al. (Discrete Math. 150 (1996) 231–245).

Effect of superconducting electrons on the energy splitting of tunneling systems

International Nuclear Information System (INIS)

Yu, C.C.; Granato, A.V.

1985-01-01

We consider the effect of superconducting electrons on the magnitude of the energy splitting of a tunneling system. A specific example is a hydrogen atom tunneling in niobium. We find that in this case the splitting is roughly 20% smaller in the normal state than in the superconducting state. This difference in the splitting should be observable in neutron scattering and ultrasonic measurements

Threshold Multi Split-Row algorithm for decoding irregular LDPC codes

Directory of Open Access Journals (Sweden)

Chakir Aqil

2017-12-01

Full Text Available In this work, we propose a new threshold multi split-row algorithm in order to improve the multi split-row algorithm for LDPC irregular codes decoding. We give a complete description of our algorithm as well as its advantages for the LDPC codes. The simulation results over an additive white gaussian channel show that an improvement in code error performance between 0.4 dB and 0.6 dB compared to the multi split-row algorithm.

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.

Alterations of p75 neurotrophin receptor and Myelin transcription factor 1 in the hippocampus of perinatal phencyclidine treated rats.

Science.gov (United States)

Andrews, Jessica L; Newell, Kelly A; Matosin, Natalie; Huang, Xu-Feng; Fernandez-Enright, Francesca

2015-12-03

Postnatal administration of phencyclidine (PCP) in rodents causes major disturbances to neurological processes resulting in severe modifications to normal behavioral traits into adulthood. It is routinely used to model psychiatric disorders such as schizophrenia, producing many of the dysfunctional processes in the brain that are present in this devastating disorder, including elevated levels of apoptosis during neurodevelopment and disruptions to myelin and plasticity processes. Lingo-1 (or Leucine-rich repeat and immunoglobulin domain-containing protein) is responsible for negatively regulating neurite outgrowth and the myelination of axons. Recent findings using a postmortem human brain cohort showed that Lingo-1 signaling partners in the Nogo receptor (NgR)/p75/TNF receptor orphan Y (TROY) signaling complex, and downstream signaling partners With No Lysine (K) (WNK1) and Myelin transcription factor 1 (Myt1), play a significant part in schizophrenia pathophysiology. Here we have examined the implication of Lingo-1 and its signaling partners in a neurodevelopmental model of schizophrenia using PCP to determine if these pathways are altered in the hippocampus throughout different stages of neurodevelopment. Male Sprague-Dawley rats were injected subcutaneously with PCP (10mg/kg) or saline solution on postnatal days (PN) 7, 9, and 11. Rats (n=6/group) were sacrificed at PN12, 5weeks, or 14weeks. Relative expression levels of Lingo-1 signaling proteins were examined in the hippocampus of the treated rats. p75 and Myt1 were decreased (0.001≤p≤0.011) in the PCP treated rats at PN12. There were no significant changes in any of the tested proteins at 5weeks (p>0.05). At 14weeks, p75, TROY, and Myt1 were increased in the PCP treated rats (0.014≤p≤0.022). This is the first report of an alteration in Lingo-1 signaling proteins in the rat hippocampus, both directly after PCP treatment in early development and in adulthood. Based on our results, we propose that

Stability of split Stirling refrigerators

NARCIS (Netherlands)

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

2009-01-01

In many thermal systems spontaneous mechanical oscillations are generated under the influence of large temperature gradients. Well-known examples are Taconis oscillations in liquid-helium cryostats and oscillations in thermoacoustic systems. In split Stirling refrigerators the compressor and the

Time series evaluation of an intervention to increase statin tablet splitting by general practitioners.

Science.gov (United States)

Polinski, Jennifer M; Schneeweiss, Sebastian; Maclure, Malcolm; Marshall, Blair; Ramsden, Samuel; Dormuth, Colin

2011-02-01

Tablet splitting, in which a higher-dose tablet is split to get 2 doses, reduces patients' drug costs. Statins can be split safely. General practitioners (GPs) may not direct their patients to split statins because of safety concerns or unawareness of costs. Medical chart inserts provide cost-effective education to physicians. The aim of this study was to assess whether providing GPs with statin-splitting chart inserts would increase splitting rates, and to identify predictors of splitting. In 2005 and 2006, we faxed a statin chart insert to British Columbia GPs with a request for a telephone interview. Consenting GPs were mailed 3 statin chart inserts and interviewed by phone (the intervention). In an interrupted time series, we compared monthly rates of statin-splitting prescriptions among intervention and nonintervention GPs before, during, and after the intervention. In multivariate logistic regressions accounting for patient clustering, predictors of splitting included physician and patient demographics and the specific statin prescribed. Of 5051 GPs reached, 282 (6%) agreed to the intervention. Before the intervention, GPs' splitting rate was 2.6%; after intervention, GPs' splitting rate was 7.5%. The rate for the nonintervention GPs was 4.4%. Intervention GPs were 1.68 (95% CI, 1.12-2.53) times more likely to prescribe splitting after the intervention than were nonintervention GPs. Other predictors were a patient's female sex (odds ratio [OR] = 1.26; 95% CI, 1.18-1.34), lower patient income (OR = 1.33; 95% CI, 1.18-1.34), and a lack of drug insurance (OR = 1.89; 95% CI, 1.69-2.04). An inexpensive intervention was effective in producing a sustained increase in GPs' splitting rate during 22 months of observed follow-up. Expanding statin-splitting education to all GPs might reduce prescription costs for many patients and payors. Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.

Dynamics of the Peripheral Membrane Protein P2 from Human Myelin Measured by Neutron Scattering--A Comparison between Wild-Type Protein and a Hinge Mutant.

Directory of Open Access Journals (Sweden)

Saara Laulumaa

Full Text Available Myelin protein P2 is a fatty acid-binding structural component of the myelin sheath in the peripheral nervous system, and its function is related to its membrane binding capacity. Here, the link between P2 protein dynamics and structure and function was studied using elastic incoherent neutron scattering (EINS. The P38G mutation, at the hinge between the β barrel and the α-helical lid, increased the lipid stacking capacity of human P2 in vitro, and the mutated protein was also functional in cultured cells. The P38G mutation did not change the overall structure of the protein. For a deeper insight into P2 structure-function relationships, information on protein dynamics in the 10 ps to 1 ns time scale was obtained using EINS. Values of mean square displacements mainly from protein H atoms were extracted for wild-type P2 and the P38G mutant and compared. Our results show that at physiological temperatures, the P38G mutant is more dynamic than the wild-type P2 protein, especially on a slow 1-ns time scale. Molecular dynamics simulations confirmed the enhanced dynamics of the mutant variant, especially within the portal region in the presence of bound fatty acid. The increased softness of the hinge mutant of human myelin P2 protein is likely related to an enhanced flexibility of the portal region of this fatty acid-binding protein, as well as to its interactions with the lipid bilayer surface requiring conformational adaptations.

Use of computed tomography assessed kidney length to predict split renal GFR in living kidney donors

Energy Technology Data Exchange (ETDEWEB)

Gaillard, Francois; Fournier, Catherine; Leon, Carine; Legendre, Christophe [Paris Descartes University, AP-HP, Hopital Necker-Enfants Malades, Renal Transplantation Department, Paris (France); Pavlov, Patrik [Linkoeping University, Linkoeping (Sweden); Tissier, Anne-Marie; Correas, Jean-Michel [Paris Descartes University, AP-HP, Hopital Necker-Enfants Malades, Radiology Department, Paris (France); Harache, Benoit; Hignette, Chantal; Weinmann, Pierre [Paris Descartes University, AP-HP, Hopital Europeen Georges Pompidou, Nuclear Medicine Department, Paris (France); Eladari, Dominique [Paris Descartes University, and INSERM, Unit 970, AP-HP, Hopital Europeen Georges Pompidou, Physiology Department, Paris (France); Timsit, Marc-Olivier; Mejean, Arnaud [Paris Descartes University, AP-HP, Hopital Europeen Georges Pompidou, Urology Department, Paris (France); Friedlander, Gerard; Courbebaisse, Marie [Paris Descartes University, and INSERM, Unit 1151, AP-HP, Hopital Europeen Georges Pompidou, Physiology Department, Paris (France); Houillier, Pascal [Paris Descartes University, INSERM, Unit umrs1138, and CNRS Unit erl8228, AP-HP, Hopital Europeen Georges Pompidou, Physiology Department, Paris (France)

2017-02-15

Screening of living kidney donors may require scintigraphy to split glomerular filtration rate (GFR). To determine the usefulness of computed tomography (CT) to split GFR, we compared scintigraphy-split GFR to CT-split GFR. We evaluated CT-split GFR as a screening test to detect scintigraphy-split GFR lower than 40 mL/min/1.73 m{sup 2}/kidney. This was a monocentric retrospective study on 346 potential living donors who had GFR measurement, renal scintigraphy, and CT. We predicted GFR for each kidney by splitting GFR using the following formula: Volume-split GFR for a given kidney = measured GFR*[volume of this kidney/(volume of this kidney + volume of the opposite kidney)]. The same formula was used for length-split GFR. We compared length- and volume-split GFR to scintigraphy-split GFR at donation and with a 4-year follow-up. A better correlation was observed between length-split GFR and scintigraphy-split GFR (r = 0.92) than between volume-split GFR and scintigraphy-split GFR (r = 0.89). A length-split GFR threshold of 45 mL/min/1.73 m{sup 2}/kidney had a sensitivity of 100 % and a specificity of 75 % to detect scintigraphy-split GFR less than 40 mL/min/1.73 m{sup 2}/kidney. Both techniques with their respective thresholds detected living donors with similar eGFR evolution during follow-up. Length-split GFR can be used to detect patients requiring scintigraphy. (orig.)

Use of computed tomography assessed kidney length to predict split renal GFR in living kidney donors

International Nuclear Information System (INIS)

Gaillard, Francois; Fournier, Catherine; Leon, Carine; Legendre, Christophe; Pavlov, Patrik; Tissier, Anne-Marie; Correas, Jean-Michel; Harache, Benoit; Hignette, Chantal; Weinmann, Pierre; Eladari, Dominique; Timsit, Marc-Olivier; Mejean, Arnaud; Friedlander, Gerard; Courbebaisse, Marie; Houillier, Pascal

2017-01-01

Screening of living kidney donors may require scintigraphy to split glomerular filtration rate (GFR). To determine the usefulness of computed tomography (CT) to split GFR, we compared scintigraphy-split GFR to CT-split GFR. We evaluated CT-split GFR as a screening test to detect scintigraphy-split GFR lower than 40 mL/min/1.73 m"2/kidney. This was a monocentric retrospective study on 346 potential living donors who had GFR measurement, renal scintigraphy, and CT. We predicted GFR for each kidney by splitting GFR using the following formula: Volume-split GFR for a given kidney = measured GFR*[volume of this kidney/(volume of this kidney + volume of the opposite kidney)]. The same formula was used for length-split GFR. We compared length- and volume-split GFR to scintigraphy-split GFR at donation and with a 4-year follow-up. A better correlation was observed between length-split GFR and scintigraphy-split GFR (r = 0.92) than between volume-split GFR and scintigraphy-split GFR (r = 0.89). A length-split GFR threshold of 45 mL/min/1.73 m"2/kidney had a sensitivity of 100 % and a specificity of 75 % to detect scintigraphy-split GFR less than 40 mL/min/1.73 m"2/kidney. Both techniques with their respective thresholds detected living donors with similar eGFR evolution during follow-up. Length-split GFR can be used to detect patients requiring scintigraphy. (orig.)

Stock Splits and Liquidity for Two Major Capital Markets from Central–Eastern Europe

Directory of Open Access Journals (Sweden)

Józef Rudnicki

2012-12-01

Full Text Available In the stock market there occur some events that contradict the efficient market hypothesis therefore they are called anomalies. One of the mysterious corporate events which has attracted the attention of numerous researchers is a stock split. I perform the review of implications of splitting the stock for market liquidity of companies listed on the Warsaw Stock Exchange and the Vienna Stock Exchange. I use event study, in particular Market model method and Market adjusted return method, to inspect the behavior of abnormal changes in daily trading volume for stock splits performed between 2000 through 2011 over a short run and assuming a longer time interval. Moreover, I juxtapose the results for both stock exchanges to examine whether the stock split phenomenon for two major capital markets from this part of Europe can be better explained by means of existing theories on stock splits. The research is aimed at analyzing the implications of the split for market liquidity, i.e. whether there occurs an immediate effect following the split as well as whether this corporate event improves the level of market liquidity over long run. Furthermore, the goal of the paper is to investigate whether the investors can cash in on the stock split, more specifically, whether they can profit from lower transaction costs. I document a significant growth in the market liquidity of stock splitting firms over 36 months following the split for both capital markets what is indicative of lower transaction costs for investors. The 1–percent significant results are consistent with the liquidity hypothesis on stock splits.

Splitting Strategy for Simulating Genetic Regulatory Networks

Directory of Open Access Journals (Sweden)

Xiong You

2014-01-01

Full Text Available The splitting approach is developed for the numerical simulation of genetic regulatory networks with a stable steady-state structure. The numerical results of the simulation of a one-gene network, a two-gene network, and a p53-mdm2 network show that the new splitting methods constructed in this paper are remarkably more effective and more suitable for long-term computation with large steps than the traditional general-purpose Runge-Kutta methods. The new methods have no restriction on the choice of stepsize due to their infinitely large stability regions.

The 2-group of symmetries of a split chain complex

OpenAIRE

Elgueta, Josep

2010-01-01

We explicitly compute the 2-group of self-equivalences and (homotopy classes of) chain homotopies between them for any {\\it split} chain complex $A_{\\bullet}$ in an arbitrary $\\kb$-linear abelian category ($\\kb$ any commutative ring with unit). In particular, it is shown that it is a {\\it split} 2-group whose equivalence class depends only on the homology of $A_{\\bullet}$, and that it is equivalent to the trivial 2-group when $A_\\bullet$ is a split exact sequence. This provides a description ...

The Effectiveness of Managing Split Attention among Autistic Children

Science.gov (United States)

Aliee, Zeinab Shams; Jomhari, Nazean; Rezaei, Reza; Alias, Norlidah

2013-01-01

One of the most common problems in autistic children is split attention. Split attention prevents autism children from being able to focus attention on their learning, and tasks. As a result, it is important to identify how to make autistic individuals focus attention on learning. Considering autistic individuals have higher visual abilities in…

April / May 2006. 108 Harvesting split thickness skin in

African Journals Online (AJOL)

user

Background: In the third world countries like Ethiopia the majority of Hospitals have difficulties in harvesting split thickness skin ... The grafts were well taken by the recipient areas and technically there was no danger of deep bite. Conclusion: Split ... to meet the hospital needs. Thus we need to improvise and use appropriate.

Aligning workload control theory and practice : lot splitting and operation overlapping issues

NARCIS (Netherlands)

Fernandes, Nuno O.; Land, Martin J.; Carmo-Silva, S.

2016-01-01

This paper addresses the problem of lot splitting in the context of workload control (WLC). Past studies on WLC assumed that jobs released to the shop floor proceed through the different stages of processing without being split. However, in practice, large jobs are often split into smaller transfer

Alveolar Ridge Split Technique Using Piezosurgery with Specially Designed Tips

Directory of Open Access Journals (Sweden)

Alessandro Moro

2017-01-01

Full Text Available The treatment of patients with atrophic ridge who need prosthetic rehabilitation is a common problem in oral and maxillofacial surgery. Among the various techniques introduced for the expansion of alveolar ridges with a horizontal bone deficit is the alveolar ridge split technique. The aim of this article is to give a description of some new tips that have been specifically designed for the treatment of atrophic ridges with transversal bone deficit. A two-step piezosurgical split technique is also described, based on specific osteotomies of the vestibular cortex and the use of a mandibular ramus graft as interpositional graft. A total of 15 patients were treated with the proposed new tips by our department. All the expanded areas were successful in providing an adequate width and height to insert implants according to the prosthetic plan and the proposed tips allowed obtaining the most from the alveolar ridge split technique and piezosurgery. These tips have made alveolar ridge split technique simple, safe, and effective for the treatment of horizontal and vertical bone defects. Furthermore the proposed piezosurgical split technique allows obtaining horizontal and vertical bone augmentation.

Alveolar Ridge Split Technique Using Piezosurgery with Specially Designed Tips.

Science.gov (United States)

Moro, Alessandro; Gasparini, Giulio; Foresta, Enrico; Saponaro, Gianmarco; Falchi, Marco; Cardarelli, Lorenzo; De Angelis, Paolo; Forcione, Mario; Garagiola, Umberto; D'Amato, Giuseppe; Pelo, Sandro

2017-01-01

The treatment of patients with atrophic ridge who need prosthetic rehabilitation is a common problem in oral and maxillofacial surgery. Among the various techniques introduced for the expansion of alveolar ridges with a horizontal bone deficit is the alveolar ridge split technique. The aim of this article is to give a description of some new tips that have been specifically designed for the treatment of atrophic ridges with transversal bone deficit. A two-step piezosurgical split technique is also described, based on specific osteotomies of the vestibular cortex and the use of a mandibular ramus graft as interpositional graft. A total of 15 patients were treated with the proposed new tips by our department. All the expanded areas were successful in providing an adequate width and height to insert implants according to the prosthetic plan and the proposed tips allowed obtaining the most from the alveolar ridge split technique and piezosurgery. These tips have made alveolar ridge split technique simple, safe, and effective for the treatment of horizontal and vertical bone defects. Furthermore the proposed piezosurgical split technique allows obtaining horizontal and vertical bone augmentation.

Grand unification in higher dimensions with split supersymmetry

International Nuclear Information System (INIS)

Schuster, Philip C.

2006-01-01

We investigate gauge coupling unification in higher dimensional GUT models with split supersymmetry. We focus on 5d and 6d orbifold GUTs, which permit a simple solution to several problems of 4D GUTs as well as control over GUT scale threshold corrections. In orbifold GUTs, calculable threshold corrections can raise or lower the prediction for α s (M Z ) in a way that depends on the location of Higgs fields. On the other hand, split supersymmetry lowers the prediction for α s (M Z ). Consequently, split supersymmetry changes the preferred location of the Higgs fields in orbifold GUTs. In the simplest models, we find that gauge coupling unification favors higgs doublets that live on the orbifold fixed points instead of in the bulk. In addition, relatively high scales of supersymmetry breaking of 10 10±2 GeV are generically favored

Traffic dispersion through a series of signals with irregular split

Science.gov (United States)

Nagatani, Takashi

2016-01-01

We study the traffic behavior of a group of vehicles moving through a sequence of signals with irregular splits on a roadway. We present the stochastic model of vehicular traffic controlled by signals. The dynamic behavior of vehicular traffic is clarified by analyzing traffic pattern and travel time numerically. The group of vehicles breaks up more and more by the irregularity of signal's split. The traffic dispersion is induced by the irregular split. We show that the traffic dispersion depends highly on the cycle time and the strength of split's irregularity. Also, we study the traffic behavior through the series of signals at the green-wave strategy. The dependence of the travel time on offset time is derived for various values of cycle time. The region map of the traffic dispersion is shown in (cycle time, offset time)-space.

Split supersymmetry in brane models

Indian Academy of Sciences (India)

Type-I string theory in the presence of internal magnetic fields provides a concrete realization of split ... quantum picture of the Universe. It was then ... where the integers m, n correspond to the respective magnetic and electric charges; m is the ...

Temperature-dependent fine structure splitting in InGaN quantum dots

Science.gov (United States)

Wang, Tong; Puchtler, Tim J.; Zhu, Tongtong; Jarman, John C.; Kocher, Claudius C.; Oliver, Rachel A.; Taylor, Robert A.

2017-07-01

We report the experimental observation of temperature-dependent fine structure splitting in semiconductor quantum dots using a non-polar (11-20) a-plane InGaN system, up to the on-chip Peltier cooling threshold of 200 K. At 5 K, a statistical average splitting of 443 ± 132 μeV has been found based on 81 quantum dots. The degree of fine structure splitting stays relatively constant for temperatures less than 100 K and only increases above that temperature. At 200 K, we find that the fine structure splitting ranges between 2 and 12 meV, which is an order of magnitude higher than that at low temperatures. Our investigations also show that phonon interactions at high temperatures might have a correlation with the degree of exchange interactions. The large fine structure splitting at 200 K makes it easier to isolate the individual components of the polarized emission spectrally, increasing the effective degree of polarization for potential on-chip applications of polarized single-photon sources.

Checking the Adequacy of Fit of Models from Split-Plot Designs

DEFF Research Database (Denmark)

Almini, A. A.; Kulahci, Murat; Montgomery, D. C.

2009-01-01

models. In this article, we propose the computation of two R-2, R-2-adjusted, prediction error sums of squares (PRESS), and R-2-prediction statistics to measure the adequacy of fit for the WP and the SP submodels in a split-plot design. This is complemented with the graphical analysis of the two types......One of the main features that distinguish split-plot experiments from other experiments is that they involve two types of experimental errors: the whole-plot (WP) error and the subplot (SP) error. Taking this into consideration is very important when computing measures of adequacy of fit for split-plot...... of errors to check for any violation of the underlying assumptions and the adequacy of fit of split-plot models. Using examples, we show how computing two measures of model adequacy of fit for each split-plot design model is appropriate and useful as they reveal whether the correct WP and SP effects have...

Mode splitting effect in FEMs with oversized Bragg resonators

Energy Technology Data Exchange (ETDEWEB)

Peskov, N. Yu.; Sergeev, A. S. [Institute of Applied Physics Russian Academy of Sciences, Nizhny Novgorod (Russian Federation); Kaminsky, A. K.; Perelstein, E. A.; Sedykh, S. N. [Joint Institute for Nuclear Research, Dubna (Russian Federation); Kuzikov, S. V. [Institute of Applied Physics Russian Academy of Sciences, Nizhny Novgorod (Russian Federation); Nizhegorodsky State University, Nizhny Novgorod (Russian Federation)

2016-07-15

Splitting of the fundamental mode in an oversized Bragg resonator with a step of the corrugation phase, which operates over the feedback loop involving the waveguide waves of different transverse structures, was found to be the result of mutual influence of the neighboring zones of the Bragg scattering. Theoretical description of this effect was developed within the framework of the advanced (four-wave) coupled-wave approach. It is shown that mode splitting reduces the selective properties, restricts the output power, and decreases the stability of the narrow-band operating regime in the free-electron maser (FEM) oscillators based on such resonators. The results of the theoretical analysis were confirmed by 3D simulations and “cold” microwave tests. Experimental data on Bragg resonators with different parameters in a 30-GHz FEM are presented. The possibility of reducing the mode splitting by profiling the corrugation parameters is shown. The use of the mode splitting effect for the output power enhancement by passive compression of the double-frequency pulse generated in the FEM with such a resonator is discussed.

QED corrections to the Altarelli-Parisi splitting functions

Energy Technology Data Exchange (ETDEWEB)

Florian, Daniel de [Universidad de Buenos Aires, Departamento de Fisica and IFIBA, FCEyN, Capital Federal (Argentina); UNSAM, International Center for Advanced Studies (ICAS), Buenos Aires (Argentina); Sborlini, German F.R.; Rodrigo, German [Universitat de Valencia - Consejo Superior de Investigaciones Cientificas, Instituto de Fisica Corpuscular, Paterna, Valencia (Spain)

2016-05-15

We discuss the combined effect of QED and QCD corrections to the evolution of parton distributions. We extend the available knowledge of the Altarelli-Parisi splitting functions to one order higher in QED, and we provide explicit expressions for the splitting kernels up to O(α α{sub S}). The results presented in this article allow one to perform a parton distribution function analysis reaching full NLO QCD-QED combined precision. (orig.)

Split Octonion electrodynamics and unified fields of dyons

International Nuclear Information System (INIS)

Bisht, P.S.

2004-01-01

Split octonion electrodynamics has been developed in terms of Zorn's vector matrix realization by reformulating electromagnetic potential, current, field tensor and other dynamical quantities. Corresponding field equation (Unified Maxwell's equations) and equation of motion have been reformulated by means of split octonion and its Zorn vector realization in unique, simpler and consistent manner. It has been shown that this theory reproduces the dyon field equations in the absence of gravito-dyons and vice versa

26 CFR 1.61-22 - Taxation of split-dollar life insurance arrangements.

Science.gov (United States)

2010-04-01

... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Taxation of split-dollar life insurance..., and Taxable Income § 1.61-22 Taxation of split-dollar life insurance arrangements. (a) Scope—(1) In general. This section provides rules for the taxation of a split-dollar life insurance arrangement for...

The splitting of giant multipole states of deformed nuclei

International Nuclear Information System (INIS)

Suzuki, T.; Rowe, D.J.

1977-01-01

A vibrating potential model is applied to deformed nuclei with a deformed harmonic oscillator potential in order to discuss the splitting of isoscalar giant quadrupole states. Eigenfrequencies of the collective states are estimated to be √2ω(1 - delta/3), √2ω(1 - delta/6) and √2ω(1 + delta/3) for K = 0 + ,1 + and 2 + modes, respectively. The splitting of isovector dipole and isovector quadrupole states is also studied according to a schematic model as proposed by Bohr and Mottelson. It is shown that isovector dipole states are split, as in a hydrodynamic model, while isovector quadrupole states with the same scaling factors as those of isocalar quadrupole modes. (Auth.)

PENGARUH STOCK SPLIT TERHADAP LIKUIDITAS DAN RETURN SAHAM DI BURSA EFEK JAKARTA

Directory of Open Access Journals (Sweden)

Wang Sutrisno

2000-01-01

Full Text Available Research on stock splits has frequently been undertaken. The results vary, but fundamentally can be classified into two groups. First, the stock split is purely "cosmetic". Second, the stock split has a real effect on stocks. The difference between these opinions raises controversy. The purpose of this study is to examine whether stock splits influence stock liquidity and return of an individual stock as well as in a group of stocks as a portfolio. Overall, the results of this study show that stock splits did influence stock price, trading volume and bid-ask spread but did not influence stock risk and abnormal return from the point of view of an individual stock as well as in a group of stocks as a portfolio. The test of a relationship between bid-ask spread and stock price, trading volume and stock risk for each stock shows that all three variable did not significantly affect the bid-ask spread. On the other hand, the test of a relationship in a portfolio reveals that only stock prices significantly affect the bid-ask spread. Abstract in Bahasa Indonesia : Penelitian mengenai stock split sudah sering dilakukan. Hasil dari penelitian- penelitian tersebut bermacam - macam, tetapi pada dasarnya dapat dibedakan menjadi dua kelompok. Pertama, stock split dinyatakan murni hanya sebagai "kosmetik". Kedua, stock split dinyatakan mempunyai efek yang nyata terhadap saham. Perbedaan pendapat ini sering menimbulkan kontroversi. Tujuan dari penelitian ini adalah untuk menguji kembali apakah betul stock split dapat mempengaruhi likuiditas dan return saham baik ditinjau secara individual untuk masing - masing saham maupun seluruh saham sebagai sebuah portofolio. Secara keseluruhan, hasil dari penelitian ini menunjukkan bahwa stock split hanya mempengaruhi harga, volume perdagangan dan persentase spread, tetapi tidak mempengaruhi varians dan abnormal return baik ditinjau secara individual maupun sebagai sebuah portofolio. Sedangkan pengujian hubungan antara

Electric arc apparatus for severing split-pin assemblies of guide tubes of nuclear reactors

International Nuclear Information System (INIS)

Burns, D.C.; Kauric, C.E.; Persang, J.C.

1987-01-01

This patent describes an apparatus for use in the replacement of an old split-pin assembly of a guide tube of a nuclear reactor by a new split-pin assembly, the old split-pin assembly including an old split pin and an old nut securing the old split pin to the guide tube, the old split-pin assembly and the guide tube being radioactive. The apparatus includes a metal disintegration machining tool, the tool having an electrode, means for mounting the tool submerged in a pool of water in engagement with the guide tube and with the old split-pin assembly secured to the guide tube, the tool being so mounted with the electrode in position to coact electrically with the last-named old split-pin assembly but not with the guide tube, and means, connected to the tool, for firing a disintegrating arc between the electrode and the assembly to disintegrate the assembly into readily removable fragments

Improved Fast Centralized Retransmission Scheme for High-Layer Functional Split in 5G Network

Science.gov (United States)

Xu, Sen; Hou, Meng; Fu, Yu; Bian, Honglian; Gao, Cheng

2018-01-01

In order to satisfy the varied 5G critical requirements and the virtualization of the RAN hardware, a two-level architecture for 5G RAN has been studied in 3GPP 5G SI stage. The performance of the PDCP-RLC split option and intra-RLC split option, two mainly concerned options for high layer functional split, exist an ongoing debate. This paper firstly gives an overview of CU-DU split study work in 3GPP. By the comparison of implementation complexity, the standardization impact and system performance, our evaluation result shows the PDCP-RLC split Option outperforms the intra-RLC split option. Aiming to how to reduce the retransmission delay during the intra-CU inter-DU handover, the mainly drawback of PDCP-RLC split option, this paper proposes an improved fast centralized retransmission solution with a low implementation complexity. Finally, system level simulations show that the PDCP-RLC split option with the proposed scheme can significantly improve the UE’s experience.

Photocatalytic Water-Splitting Reaction from Catalytic and Kinetic Perspectives

KAUST Repository

Hisatomi, Takashi

2014-10-16

Abstract: Some particulate semiconductors loaded with nanoparticulate catalysts exhibit photocatalytic activity for the water-splitting reaction. The photocatalysis is distinct from the thermal catalysis because photocatalysis involves photophysical processes in particulate semiconductors. This review article presents a brief introduction to photocatalysis, followed by kinetic aspects of the photocatalytic water-splitting reaction.Graphical Abstract: [Figure not available: see fulltext.

Source splitting via the point source method

International Nuclear Information System (INIS)

Potthast, Roland; Fazi, Filippo M; Nelson, Philip A

2010-01-01

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 u j , j = 1, ..., n of n element of N sound sources supported in different bounded domains G 1 , ..., G n in R 3 from measurements of the field on some microphone array—mathematically speaking from the knowledge of the sum of the fields u = u 1 + ... + u n on some open subset Λ of a plane. The main idea of the scheme is to calculate filter functions g 1 ,…, g n , n element of N, to construct u l for l = 1, ..., n from u| Λ in the form u l (x) = ∫ Λ g l,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

Splitting up Beta’s change

OpenAIRE

Suarez, Ronny

2014-01-01

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

Giant Rashba spin splitting in Bi2Se3: Tl

KAUST Repository

Singh, Nirpendra; Saeed, Yasir; Schwingenschlö gl, Udo

2014-01-01

First-principles calculations are employed to demonstrate a giant Rashba spin splitting in Bi2Se3:Tl. Biaxial tensile and compressive strain is used to tune the splitting by modifying the potential gradient. The band gap is found to increase under

The Renewables Influence on Market Splitting: the Iberian Spot Electricity Market

OpenAIRE

Nuno Carvalho Figueiredo; Patrícia Pereira da Silva; Pedro Cerqueira

2014-01-01

This paper aims to assess the influence of wind power generation on the market splitting behaviour of the Iberian electricity spot markets. We use logit models to express the probability response for market splitting of day-ahead spot electricity prices together with explanatory variables like, wind speed, available transmission capacity and electricity demand. The results show that the probability of market splitting increases with the increase of wind power generation. The European intercon...

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.)

Effect of Repeated Food Morsel Splitting on Jaw Muscle Control

DEFF Research Database (Denmark)

A, Kumar; Svensson, Krister G; Baad-Hansen, Lene

2014-01-01

Mastication is a complex motor task often initiated by splitting of the food morsel between the anterior teeth. Training of complex motor tasks has consistently been shown to trigger neuroplastic changes in corticomotor control and optimization of muscle function. It is not known if training...... and repeated food morsel splitting lead to changes in jaw muscle function. Objective: To investigate if repeated splitting of food morsels in participants with natural dentition changes the force and jaw muscle electromyographic (EMG) activity. Methods: Twenty healthy volunteers (mean age = 26.2 ± 3.9 years......) participated in a single one-hour session divided into six series. Each series consisted of ten trials of a standardized behavioral task (total of 60 trials). The behavioral task was to hold and split a food morsel (8 mm, 180 mg placebo tablet) placed on a bite force transducer with the anterior teeth...

A Matrix Splitting Method for Composite Function Minimization

KAUST Repository

Yuan, Ganzhao

2016-12-07

Composite function minimization captures a wide spectrum of applications in both computer vision and machine learning. It includes bound constrained optimization and cardinality regularized optimization as special cases. This paper proposes and analyzes a new Matrix Splitting Method (MSM) for minimizing composite functions. It can be viewed as a generalization of the classical Gauss-Seidel method and the Successive Over-Relaxation method for solving linear systems in the literature. Incorporating a new Gaussian elimination procedure, the matrix splitting method achieves state-of-the-art performance. For convex problems, we establish the global convergence, convergence rate, and iteration complexity of MSM, while for non-convex problems, we prove its global convergence. Finally, we validate the performance of our matrix splitting method on two particular applications: nonnegative matrix factorization and cardinality regularized sparse coding. Extensive experiments show that our method outperforms existing composite function minimization techniques in term of both efficiency and efficacy.