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Sample records for neurite outgrowth anisotropy

  1. Characterization of BASP1-mediated neurite outgrowth

    DEFF Research Database (Denmark)

    Korshunova, Irina; Caroni, Pico; Kolkova, Kateryna

    2008-01-01

    The brain acid-soluble protein BASP1 (CAP-23, NAP-22) belongs to the family of growth-associated proteins, which also includes GAP-43, a protein recently shown to regulate neural cell adhesion molecule (NCAM)-mediated neurite outgrowth. Here, the effects of BASP1 overexpression were investigated...

  2. Electric field-induced astrocyte alignment directs neurite outgrowth.

    Science.gov (United States)

    Alexander, John K; Fuss, Babette; Colello, Raymond J

    2006-05-01

    The extension and directionality of neurite outgrowth are key to achieving successful target connections during both CNS development and during the re-establishment of connections lost after neural trauma. The degree of axonal elongation depends, in large part, on the spatial arrangement of astrocytic processes rich in growth-promoting proteins. Because astrocytes in culture align their processes on exposure to an electrical field of physiological strength, we sought to determine the extent to which aligned astrocytes affect neurite outgrowth. To this end, dorsal root ganglia cells were seeded onto cultured rat astrocytes that were pre-aligned by exposure to an electric field of physiological strength (500 mV mm(-1)). Using confocal microscopy and digital image analysis, we found that neurite outgrowth at 24 hours and at 48 hours is enhanced significantly and directed consistently along the aligned astrocyte processes. Moreover, this directed neurite outgrowth is maintained when grown on fixed, aligned astrocytes. Collectively, these results indicate that endogenous electric fields present within the developing CNS might act to align astrocyte processes, which can promote and direct neurite growth. Furthermore, these results demonstrate a simple method to produce an aligned cellular substrate, which might be used to direct regenerating neurites.

  3. Glial membranes at the node of Ranvier prevent neurite outgrowth

    DEFF Research Database (Denmark)

    Huang, Jeffrey K; Phillips, Greg R; Roth, Alejandro D

    2005-01-01

    of neurite outgrowth, including the oligodendrocyte myelin glycoprotein (OMgp). In rat spinal cord, OMgp was not localized to compact myelin, as previously thought, but to oligodendroglia-like cells, whose processes converge to form a ring that completely encircles the nodes. In OMgp-null mice, CNS nodes......Nodes of Ranvier are regularly placed, nonmyelinated axon segments along myelinated nerves. Here we show that nodal membranes isolated from the central nervous system (CNS) of mammals restricted neurite outgrowth of cultured neurons. Proteomic analysis of these membranes revealed several inhibitors...

  4. Comparative sensitivity of human and rat neural cultures to chemical-induced inhibition of neurite outgrowth

    Energy Technology Data Exchange (ETDEWEB)

    Harrill, Joshua A.; Freudenrich, Theresa M.; Robinette, Brian L.; Mundy, William R., E-mail: mundy.william@epa.gov

    2011-11-15

    There is a need for rapid, efficient and cost-effective alternatives to traditional in vivo developmental neurotoxicity testing. In vitro cell culture models can recapitulate many of the key cellular processes of nervous system development, including neurite outgrowth, and may be used as screening tools to identify potential developmental neurotoxicants. The present study compared primary rat cortical cultures and human embryonic stem cell-derived neural cultures in terms of: 1) reproducibility of high content image analysis based neurite outgrowth measurements, 2) dynamic range of neurite outgrowth measurements and 3) sensitivity to chemicals which have been shown to inhibit neurite outgrowth. There was a large increase in neurite outgrowth between 2 and 24 h in both rat and human cultures. Image analysis data collected across multiple cultures demonstrated that neurite outgrowth measurements in rat cortical cultures were more reproducible and had higher dynamic range as compared to human neural cultures. Human neural cultures were more sensitive than rat cortical cultures to chemicals previously shown to inhibit neurite outgrowth. Parallel analysis of morphological (neurite count, neurite length) and cytotoxicity (neurons per field) measurements were used to detect selective effects on neurite outgrowth. All chemicals which inhibited neurite outgrowth in rat cortical cultures did so at concentrations which did not concurrently affect the number of neurons per field, indicating selective effects on neurite outgrowth. In contrast, more than half the chemicals which inhibited neurite outgrowth in human neural cultures did so at concentrations which concurrently decreased the number of neurons per field, indicating that effects on neurite outgrowth were secondary to cytotoxicity. Overall, these data demonstrate that the culture models performed differently in terms of reproducibility, dynamic range and sensitivity to neurite outgrowth inhibitors. While human neural

  5. Comparative sensitivity of human and rat neural cultures to chemical-induced inhibition of neurite outgrowth

    International Nuclear Information System (INIS)

    Harrill, Joshua A.; Freudenrich, Theresa M.; Robinette, Brian L.; Mundy, William R.

    2011-01-01

    There is a need for rapid, efficient and cost-effective alternatives to traditional in vivo developmental neurotoxicity testing. In vitro cell culture models can recapitulate many of the key cellular processes of nervous system development, including neurite outgrowth, and may be used as screening tools to identify potential developmental neurotoxicants. The present study compared primary rat cortical cultures and human embryonic stem cell-derived neural cultures in terms of: 1) reproducibility of high content image analysis based neurite outgrowth measurements, 2) dynamic range of neurite outgrowth measurements and 3) sensitivity to chemicals which have been shown to inhibit neurite outgrowth. There was a large increase in neurite outgrowth between 2 and 24 h in both rat and human cultures. Image analysis data collected across multiple cultures demonstrated that neurite outgrowth measurements in rat cortical cultures were more reproducible and had higher dynamic range as compared to human neural cultures. Human neural cultures were more sensitive than rat cortical cultures to chemicals previously shown to inhibit neurite outgrowth. Parallel analysis of morphological (neurite count, neurite length) and cytotoxicity (neurons per field) measurements were used to detect selective effects on neurite outgrowth. All chemicals which inhibited neurite outgrowth in rat cortical cultures did so at concentrations which did not concurrently affect the number of neurons per field, indicating selective effects on neurite outgrowth. In contrast, more than half the chemicals which inhibited neurite outgrowth in human neural cultures did so at concentrations which concurrently decreased the number of neurons per field, indicating that effects on neurite outgrowth were secondary to cytotoxicity. Overall, these data demonstrate that the culture models performed differently in terms of reproducibility, dynamic range and sensitivity to neurite outgrowth inhibitors. While human neural

  6. Discovery of pyrroloimidazoles as agents stimulating neurite outgrowth

    NARCIS (Netherlands)

    Beck, Barbara; Leppert, Christian A.; Mueller, Bernhard K.; Dömling, Alexander

    2006-01-01

    A diverse library of substituted pyrroloimidazoles was assembled by a multicomponent reaction (MCR) of tosylmethyl isocyanides (TOSMIC), indole carbaldehydes and primary amines in a van Leusen reaction. A library of this scaffold was screened in a phenotypic assay for neurite outgrowth. Several

  7. Shoc2/Sur8 protein regulates neurite outgrowth.

    Directory of Open Access Journals (Sweden)

    Gonzalo Leon

    Full Text Available The Shoc2 protein has been implicated in the positive regulation of the Ras-ERK pathway by increasing the functional binding interaction between Ras and Raf, leading to increased ERK activity. Here we found that Shoc2 overexpression induced sustained ERK phosphorylation, notably in the case of EGF stimulation, and Shoc2 knockdown inhibited ERK activation. We demonstrate that ectopic overexpression of human Shoc2 in PC12 cells significantly promotes neurite extension in the presence of EGF, a stimulus that induces proliferation rather than differentiation in these cells. Finally, Shoc2 depletion reduces both NGF-induced neurite outgrowth and ERK activation in PC12 cells. Our data indicate that Shoc2 is essential to modulate the Ras-ERK signaling outcome in cell differentiation processes involved in neurite outgrowth.

  8. Electrospun fiber surface nanotopography influences astrocyte-mediated neurite outgrowth.

    Science.gov (United States)

    Johnson, Christopher D; D'Amato, Anthony R; Puhl, Devan L; Wich, Douglas M; Vespermann, Amanda; Gilbert, Ryan J

    2018-05-15

    Aligned, electrospun fiber scaffolds provide topographical guidance for regenerating neurons and glia after central nervous system injury. To date, no study has explored how fiber surface nanotopography affects astrocyte response to fibrous scaffolds. Astrocytes play important roles in the glial scar, the blood brain barrier, and in maintaining homeostasis in the central nervous system. In this study, electrospun poly L-lactic acid fibers were engineered with smooth, pitted, or divoted surface nanotopography. Cortical or spinal cord primary rat astrocytes were cultured on the surfaces for either 1 or 3 days to examine the astrocyte response over time. The results showed that cortical astrocytes were significantly shorter and broader on the pitted and divoted fibers compared to those on smooth fibers. However, spinal cord astrocyte morphology was not significantly altered by the surface features. These findings indicate that astrocytes from unique anatomical locations respond differently to the presence of nanotopography. Western Blot results show that the differences in morphology were not associated with significant changes in GFAP or vinculin in either astrocyte population, suggesting that surface pits and divots do not induce a reactive phenotype in either cortical or spinal cord astrocytes. Finally, astrocytes were co-cultured with dorsal root ganglia to determine how the surfaces affected astrocyte-mediated neurite outgrowth. Astrocytes cultured on the fibers for shorter periods of time (1 day) generally supported longer neurite outgrowth. Pitted and divoted fibers restricted spinal cord astrocyte-mediated neurite outgrowth, while smooth fibers increased 3 day spinal cord astrocyte-mediated neurite outgrowth. In total, fiber surface nanotopography can influence astrocyte elongation and influence the capability of astrocytes to direct neurites. Therefore, fiber surface characteristics should be carefully controlled to optimize astrocyte-mediated axonal

  9. Hydrogel Design for Supporting Neurite Outgrowth and Promoting Gene Delivery to Maximize Neurite Extension

    Science.gov (United States)

    Shepard, Jaclyn A.; Stevans, Alyson C.; Holland, Samantha; Wang, Christine E.; Shikanov, Ariella; Shea, Lonnie D.

    2012-01-01

    Hydrogels capable of gene delivery provide a combinatorial approach for nerve regeneration, with the hydrogel supporting neurite outgrowth and gene delivery inducing the expression of inductive factors. This report investigates the design of hydrogels that balance the requirements for supporting neurite growth with those requirements for promoting gene delivery. Enzymatically-degradable PEG hydrogels encapsulating dorsal root ganglia explants, fibroblasts, and lipoplexes encoding nerve growth factor were gelled within channels that can physically guide neurite outgrowth. Transfection of fibroblasts increased with increasing concentration of Arg-Gly-Asp (RGD) cell adhesion sites and decreasing PEG content. The neurite length increased with increasing RGD concentration within 10% PEG hydrogels, yet was maximal within 7.5% PEG hydrogels at intermediate RGD levels. Delivering lipoplexes within the gel produced longer neurites than culture in NGF-supplemented media or co-culture with cells exposed to DNA prior to encapsulation. Hydrogels designed to support neurite outgrowth and deliver gene therapy vectors locally may ultimately be employed to address multiple barriers that limit regeneration. PMID:22038654

  10. Electric field-induced astrocyte alignment directs neurite outgrowth

    OpenAIRE

    ALEXANDER, JOHN K.; FUSS, BABETTE; COLELLO, RAYMOND J.

    2006-01-01

    The extension and directionality of neurite outgrowth are key to achieving successful target connections during both CNS development and during the re-establishment of connections lost after neural trauma. The degree of axonal elongation depends, in large part, on the spatial arrangement of astrocytic processes rich in growth-promoting proteins. Because astrocytes in culture align their processes on exposure to an electrical field of physiological strength, we sought to determine the extent t...

  11. Neurite outgrowth in human iPSC-derived neurons

    Science.gov (United States)

    Data on morphology of rat and human neurons in cell cultureThis dataset is associated with the following publication:Druwe, I., T. Freudenrich , K. Wallace , T. Shafer , and W. Mundy. Comparison of Human Induced PluripotentStem Cell-Derived Neurons and Rat Primary CorticalNeurons as In Vitro Models of Neurite Outgrowth. Applied In vitro Toxicology. Mary Ann Liebert, Inc., Larchmont, NY, USA, 2(1): 26-36, (2016).

  12. GIT1 enhances neurite outgrowth by stimulating microtubule assembly

    Directory of Open Access Journals (Sweden)

    Yi-sheng Li

    2016-01-01

    Full Text Available GIT1, a G-protein-coupled receptor kinase interacting protein, has been reported to be involved in neurite outgrowth. However, the neurobiological functions of the protein remain unclear. In this study, we found that GIT1 was highly expressed in the nervous system, and its expression was maintained throughout all stages of neuritogenesis in the brain. In primary cultured mouse hippocampal neurons from GIT1 knockout mice, there was a significant reduction in total neurite length per neuron, as well as in the average length of axon-like structures, which could not be prevented by nerve growth factor treatment. Overexpression of GIT1 significantly promoted axon growth and fully rescued the axon outgrowth defect in the primary hippocampal neuron cultures from GIT1 knockout mice. The GIT1 N terminal region, including the ADP ribosylation factor-GTPase activating protein domain, the ankyrin domains and the Spa2 homology domain, were sufficient to enhance axonal extension. Importantly, GIT1 bound to many tubulin proteins and microtubule-associated proteins, and it accelerated microtubule assembly in vitro. Collectively, our findings suggest that GIT1 promotes neurite outgrowth, at least partially by stimulating microtubule assembly. This study provides new insight into the cellular and molecular pathogenesis of GIT1-associated neurological diseases.

  13. Stimulation of neuronal neurite outgrowth using functionalized carbon nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, K; Sato, C; Shimizu, N [Graduate School of Life Sciences, Toyo University, 1-1-1 Izumino, Itakura-machi, Ora-gun, Gunma 374-0193 (Japan); Naka, Y [Bio-Nano Electronics Research Center, Toyo University, 2100 Kujirai, Kawagoe-shi, Saitama 350-8585 (Japan); Whitby, R, E-mail: shimizu@toyonet.toyo.ac.jp [School of Pharmacy and Biomolecular Sciences, University of Brighton, Cockroft Building, Lewes Road, Brighton BN2 4GJ (United Kingdom)

    2010-03-19

    Low concentrations (0.11-1.7 {mu}g ml{sup -1}) of functionalized carbon nanotubes (CNTs), which are multi-walled CNTs modified by amino groups, when added with nerve growth factor (NGF), promoted outgrowth of neuronal neurites in dorsal root ganglion (DRG) neurons and rat pheochromocytoma cell line PC12h cells in culture media. The quantity of active extracellular signal-regulated kinase (ERK) was higher after the addition of both 0.85 {mu}g ml{sup -1} CNTs and NGF than that with NGF alone. CNTs increased the number of cells with neurite outgrowth in DRG neurons and PC12h cells after the inhibition of the ERK signaling pathway using a mitogen-activated protein kinase (MAPK)/ERK kinase (MEK) inhibitor. Active ERK proteins were detected in MEK inhibitor-treated neurons after the addition of CNTs to the culture medium. These results demonstrate that CNTs may stimulate neurite outgrowth by activation of the ERK signaling pathway. Thus, CNTs are biocompatible and are promising candidates for biological applications and devices.

  14. Bifenthrin inhibits neurite outgrowth in differentiating PC12 cells.

    Science.gov (United States)

    Tran, Van; Hoffman, Natalie; Mofunanaya, Adaobi; Pryor, Stephen C; Ojugbele, Olutosin; McLaughlin, Ashlea; Gibson, Lydia; Bonventre, Josephine A; Flynn, Katherine; Weeks, Benjamin S

    2006-02-01

    Bifenthrin is a third generation member of the synthetic pyrethroid family of insecticides. As a new pesticide within a relatively new class of pesticides, bifenthrin is considered relatively safe. Here, we used the PC12 neuronal cell line to examine the effect of bifenthrin on the formation of neurites and the potential developmental neurotoxicity of this pesticide. PC12 cells were exposed to varying concentrations of technical grade bifenthrin or Ortho Home Defense. Cell viability was determined using the AlmarBlue Toxicity Assay. Nontoxic concentrations of these chemicals were concomitantly with nerve growth factor and neurite outgrowth was assessed. Ortho Home Defense preparation reduced PC12 cell viability by approximately 50% and 70% at dilutions that correlate to bifenthrin concentrations of 10(-5) M and 10(-4) M, respectively. In contrast, technical grade bifenthrin, was not toxic to PC12 cells at 10(-3) M, which was the highest concentration tested that was soluble. At "nontoxic" concentrations of 10(-7) M and 10(-6) M, the Ortho Home Defense inhibited nerve growth factor-mediated neurite outgrowth by 30% and 55% respectively. Furthermore the nontoxic concentrations of technical grade bifenthrin of 10(-6) M and 10(-3) M inhibited neurite outgrowth by approximately 35% and 75% respectively. These data suggest that the toxicity of the Ortho Home Defense preparation was due to the "inert" additives in the preparation and not the bifenthrin itself. Further, these data suggest that, even in the absence of overt toxicity, bifenthrin may have deleterious effects to developing nervous system.

  15. Chimeric ZHHH neuroglobin acts as a cell membrane-penetrating inducer of neurite outgrowth.

    Science.gov (United States)

    Takahashi, Nozomu; Onozuka, Wataru; Watanabe, Seiji; Wakasugi, Keisuke

    2017-09-01

    Neuroglobin (Ngb) is a heme protein expressed in the vertebrate brain. We previously engineered a chimeric Ngb protein, in which module M1 of human Ngb is replaced by that of zebrafish Ngb, and showed that the chimeric ZHHH Ngb has a cell membrane-penetrating activity similar to that of zebrafish Ngb and also rescues cells from death caused by hypoxia/reoxygenation as does human Ngb. Recently, it was reported that overexpression of mammalian Ngb in neuronal cells induces neurite outgrowth. In this study, we performed neurite outgrowth assays of chimeric Ngb using rat pheochromocytoma PC12 cells. Addition of chimeric Ngb, but not human or zebrafish Ngb, exogenously to the cell medium induces neurite outgrowth. On the other hand, the K7A/K9Q chimeric Ngb double mutant, which cannot translocate into cells, did not induce neurite outgrowth, suggesting that the cell membrane-penetrating activity of the chimeric Ngb is crucial for its neurite outgrowth-promoting activity. We also prepared several site-directed chimeric Ngb mutants and demonstrated that residues crucial for neurite outgrowth-inducing activity of the chimeric Ngb are not exactly the same as those for its neuroprotective activity.

  16. Neuronal adaptor FE65 stimulates Rac1-mediated neurite outgrowth by recruiting and activating ELMO1.

    Science.gov (United States)

    Li, Wen; Tam, Ka Ming Vincent; Chan, Wai Wan Ray; Koon, Alex Chun; Ngo, Jacky Chi Ki; Chan, Ho Yin Edwin; Lau, Kwok-Fai

    2018-04-03

    Neurite outgrowth is a crucial process in developing neurons for neural network formation. Understanding the regulatory mechanisms of neurite outgrowth is essential for developing strategies to stimulate neurite regeneration after nerve injury and in neurodegenerative disorders. FE65 is a brain-enriched adaptor that stimulates Rac1-mediated neurite elongation. However, the precise mechanism by which FE65 promotes the process remains elusive. Here, we show that ELMO1, a subunit of ELMO1-DOCK180 bipartite Rac1 GEF, interacts with the FE65 N-terminal region. Overexpression of FE65 and/or ELMO1 enhances whereas knockdown of FE65 or ELMO1 inhibits neurite outgrowth and Rac1 activation. The effect of FE65 alone or together with ELMO1 is attenuated by an FE65 double mutation that disrupts FE65-ELMO1 interaction. Notably, FE65 is found to activate ELMO1 by diminishing ELMO1 intramolecular autoinhibitory interaction and to promote the targeting of ELMO1 to the plasma membrane where Rac1 is activated. We also show that FE65, ELMO1 and DOCK180 form a tripartite complex. Knockdown of DOCK180 reduces the stimulatory effect of FE65-ELMO1 on Rac1 activation and neurite outgrowth. Thus, we identify a novel mechanism that FE65 stimulates Rac1-mediated neurite outgrowth by recruiting and activating of ELMO1. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Critical time window of neuronal cholesterol synthesis during neurite outgrowth.

    Science.gov (United States)

    Fünfschilling, Ursula; Jockusch, Wolf J; Sivakumar, Nandhini; Möbius, Wiebke; Corthals, Kristina; Li, Sai; Quintes, Susanne; Kim, Younghoon; Schaap, Iwan A T; Rhee, Jeong-Seop; Nave, Klaus-Armin; Saher, Gesine

    2012-05-30

    Cholesterol is an essential membrane component enriched in plasma membranes, growth cones, and synapses. The brain normally synthesizes all cholesterol locally, but the contribution of individual cell types to brain cholesterol metabolism is unknown. To investigate whether cortical projection neurons in vivo essentially require cholesterol biosynthesis and which cell types support neurons, we have conditionally ablated the cholesterol biosynthesis in these neurons in mice either embryonically or postnatally. We found that cortical projection neurons synthesize cholesterol during their entire lifetime. At all stages, they can also benefit from glial support. Adult neurons that lack cholesterol biosynthesis are mainly supported by astrocytes such that their functional integrity is preserved. In contrast, microglial cells support young neurons. However, compensatory efforts of microglia are only transient leading to layer-specific neuronal death and the reduction of cortical projections. Hence, during the phase of maximal membrane growth and maximal cholesterol demand, neuronal cholesterol biosynthesis is indispensable. Analysis of primary neurons revealed that neurons tolerate only slight alteration in the cholesterol content and plasma membrane tension. This quality control allows neurons to differentiate normally and adjusts the extent of neurite outgrowth, the number of functional growth cones and synapses to the available cholesterol. This study highlights both the flexibility and the limits of horizontal cholesterol transfer in vivo and may have implications for the understanding of neurodegenerative diseases.

  18. Berberine regulates neurite outgrowth through AMPK-dependent pathways by lowering energy status

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Jiaqi; Cao, Yuanzhao; Cheng, Kuoyuan; Xu, Bo; Wang, Tianchang; Yang, Qi; Yang, Qin [State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing (China); Feng, Xudong, E-mail: xudong.feng@childrens.harvard.edu [Department of Medicine, Children' s Hospital Boston, Harvard Medical School, 300 Longwood Ave, Boston, MA 02115 (United States); Xia, Qing, E-mail: xqing@hsc.pku.edu.cn [State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing (China)

    2015-06-10

    As a widely used anti-bacterial agent and a metabolic inhibitor as well as AMP-activated protein kinase (AMPK) activator, berberine (BBR) has been shown to cross the blood–brain barrier. Its efficacy has been investigated in various disease models of the central nervous system. Neurite outgrowth is critical for nervous system development and is a highly energy-dependent process regulated by AMPK-related pathways. In the present study, we aimed to investigate the effects of BBR on AMPK activation and neurite outgrowth in neurons. The neurite outgrowth of primary rat cortical neurons at different stages of polarization was monitored after exposure of BBR. Intracellular energy level, AMPK activation and polarity-related pathways were also inspected. The results showed that BBR suppressed neurite outgrowth and affected cytoskeleton stability in the early stages of neuronal polarization, which was mediated by lowered energy status and AMPK activation. Liver kinase B1 and PI3K–Akt–GSK3β signaling pathways were also involved. In addition, mitochondrial dysfunction and endoplasmic reticulum stress contributed to the lowered energy status induced by BBR. This study highlighted the knowledge of the complex activities of BBR in neurons and corroborated the significance of energy status during the neuronal polarization. - Highlights: • BBR inhibited neurite outgrowth in early stages of neuronal development. • Lowered neuronal energy status was induced by BBR treatment. • Neuronal energy stress induced by BBR activated AMPK-related pathways. • BBR induced mitochondrial dysfunction and endoplasmic reticulum stress.

  19. Berberine regulates neurite outgrowth through AMPK-dependent pathways by lowering energy status

    International Nuclear Information System (INIS)

    Lu, Jiaqi; Cao, Yuanzhao; Cheng, Kuoyuan; Xu, Bo; Wang, Tianchang; Yang, Qi; Yang, Qin; Feng, Xudong; Xia, Qing

    2015-01-01

    As a widely used anti-bacterial agent and a metabolic inhibitor as well as AMP-activated protein kinase (AMPK) activator, berberine (BBR) has been shown to cross the blood–brain barrier. Its efficacy has been investigated in various disease models of the central nervous system. Neurite outgrowth is critical for nervous system development and is a highly energy-dependent process regulated by AMPK-related pathways. In the present study, we aimed to investigate the effects of BBR on AMPK activation and neurite outgrowth in neurons. The neurite outgrowth of primary rat cortical neurons at different stages of polarization was monitored after exposure of BBR. Intracellular energy level, AMPK activation and polarity-related pathways were also inspected. The results showed that BBR suppressed neurite outgrowth and affected cytoskeleton stability in the early stages of neuronal polarization, which was mediated by lowered energy status and AMPK activation. Liver kinase B1 and PI3K–Akt–GSK3β signaling pathways were also involved. In addition, mitochondrial dysfunction and endoplasmic reticulum stress contributed to the lowered energy status induced by BBR. This study highlighted the knowledge of the complex activities of BBR in neurons and corroborated the significance of energy status during the neuronal polarization. - Highlights: • BBR inhibited neurite outgrowth in early stages of neuronal development. • Lowered neuronal energy status was induced by BBR treatment. • Neuronal energy stress induced by BBR activated AMPK-related pathways. • BBR induced mitochondrial dysfunction and endoplasmic reticulum stress

  20. Signaling mechanisms of neurite outgrowth induced by the cell adhesion molecules NCAM and N-cadherin

    DEFF Research Database (Denmark)

    Hansen, S M; Berezin, V; Bock, E

    2008-01-01

    Formation of appropriate neural circuits depends on a complex interplay between extracellular guiding cues and intracellular signaling events that result in alterations of cytoskeletal dynamics and a neurite growth response. Surface-expressed cell adhesion molecules (CAMs) interact with the surro......Formation of appropriate neural circuits depends on a complex interplay between extracellular guiding cues and intracellular signaling events that result in alterations of cytoskeletal dynamics and a neurite growth response. Surface-expressed cell adhesion molecules (CAMs) interact...... extracellular guidance cues to intracellular events and thereby regulating neurite outgrowth. In this review, we focus on two CAMs, the neural cell adhesion molecule (NCAM) and N-cadherin, and their ability to mediate signaling associated with a neurite outgrowth response. In particular, we will focus on direct...

  1. Diazinon and diazoxon impair the ability of astrocytes to foster neurite outgrowth in primary hippocampal neurons

    International Nuclear Information System (INIS)

    Pizzurro, Daniella M.; Dao, Khoi; Costa, Lucio G.

    2014-01-01

    Evidence from in vivo and epidemiological studies suggests that organophosphorus insecticides (OPs) are developmental neurotoxicants, but possible underlying mechanisms are still unclear. Astrocytes are increasingly recognized for their active role in normal neuronal development. This study sought to investigate whether the widely-used OP diazinon (DZ), and its oxygen metabolite diazoxon (DZO), would affect glial–neuronal interactions as a potential mechanism of developmental neurotoxicity. Specifically, we investigated the effects of DZ and DZO on the ability of astrocytes to foster neurite outgrowth in primary hippocampal neurons. The results show that both DZ and DZO adversely affect astrocyte function, resulting in inhibited neurite outgrowth in hippocampal neurons. This effect appears to be mediated by oxidative stress, as indicated by OP-induced increased reactive oxygen species production in astrocytes and prevention of neurite outgrowth inhibition by antioxidants. The concentrations of OPs were devoid of cytotoxicity, and cause limited acetylcholinesterase inhibition in astrocytes (18 and 25% for DZ and DZO, respectively). Among astrocytic neuritogenic factors, the most important one is the extracellular matrix protein fibronectin. DZ and DZO decreased levels of fibronectin in astrocytes, and this effect was also attenuated by antioxidants. Underscoring the importance of fibronectin in this context, adding exogenous fibronectin to the co-culture system successfully prevented inhibition of neurite outgrowth caused by DZ and DZO. These results indicate that DZ and DZO increase oxidative stress in astrocytes, and this in turn modulates astrocytic fibronectin, leading to impaired neurite outgrowth in hippocampal neurons. - Highlights: • DZ and DZO inhibit astrocyte-mediated neurite outgrowth in rat hippocampal neurons. • Oxidative stress is involved in inhibition of neuritogenesis by DZ and DZO. • DZ and DZO decrease expression of the neuritogenic

  2. Diazinon and diazoxon impair the ability of astrocytes to foster neurite outgrowth in primary hippocampal neurons

    Energy Technology Data Exchange (ETDEWEB)

    Pizzurro, Daniella M.; Dao, Khoi [Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA (United States); Costa, Lucio G. [Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA (United States); Department of Neuroscience, University of Parma, Parma (Italy)

    2014-02-01

    Evidence from in vivo and epidemiological studies suggests that organophosphorus insecticides (OPs) are developmental neurotoxicants, but possible underlying mechanisms are still unclear. Astrocytes are increasingly recognized for their active role in normal neuronal development. This study sought to investigate whether the widely-used OP diazinon (DZ), and its oxygen metabolite diazoxon (DZO), would affect glial–neuronal interactions as a potential mechanism of developmental neurotoxicity. Specifically, we investigated the effects of DZ and DZO on the ability of astrocytes to foster neurite outgrowth in primary hippocampal neurons. The results show that both DZ and DZO adversely affect astrocyte function, resulting in inhibited neurite outgrowth in hippocampal neurons. This effect appears to be mediated by oxidative stress, as indicated by OP-induced increased reactive oxygen species production in astrocytes and prevention of neurite outgrowth inhibition by antioxidants. The concentrations of OPs were devoid of cytotoxicity, and cause limited acetylcholinesterase inhibition in astrocytes (18 and 25% for DZ and DZO, respectively). Among astrocytic neuritogenic factors, the most important one is the extracellular matrix protein fibronectin. DZ and DZO decreased levels of fibronectin in astrocytes, and this effect was also attenuated by antioxidants. Underscoring the importance of fibronectin in this context, adding exogenous fibronectin to the co-culture system successfully prevented inhibition of neurite outgrowth caused by DZ and DZO. These results indicate that DZ and DZO increase oxidative stress in astrocytes, and this in turn modulates astrocytic fibronectin, leading to impaired neurite outgrowth in hippocampal neurons. - Highlights: • DZ and DZO inhibit astrocyte-mediated neurite outgrowth in rat hippocampal neurons. • Oxidative stress is involved in inhibition of neuritogenesis by DZ and DZO. • DZ and DZO decrease expression of the neuritogenic

  3. DA-9801 promotes neurite outgrowth via ERK1/2-CREB pathway in PC12 cells.

    Science.gov (United States)

    Won, Jong Hoon; Ahn, Kyong Hoon; Back, Moon Jung; Ha, Hae Chan; Jang, Ji Min; Kim, Ha Hyung; Choi, Sang-Zin; Son, Miwon; Kim, Dae Kyong

    2015-01-01

    In the present study, we examined the mechanisms underlying the effect of DA-9801 on neurite outgrowth. We found that DA-9801 elicits its effects via the mitogen-activated protein kinase (MEK) extracellular signal-regulated kinase (ERK)1/2-cAMP response element-binding protein (CREB) pathway. DA-9801, an extract from a mixture of Dioscorea japonica and Dioscorea nipponica, was reported to promote neurite outgrowth in PC12 cells. The effects of DA-9801 on cell viability and expression of neuronal markers were evaluated in PC12 cells. To investigate DA-9801 action, specific inhibitors targeting the ERK signaling cascade were used. No cytotoxicity was observed in PC12 cells at DA-9801 concentrations of less than 30 µg/mL. In the presence of nerve growth factor (NGF, 2 ng/mL), DA-9801 promoted neurite outgrowth and increased the relative mRNA levels of neurofilament-L (NF-L), a marker of neuronal differentiation. The Raf-1 inhibitor GW5074 and MEK inhibitor PD98059 significantly attenuated DA-9801-induced neurite outgrowth. Additionally, the MEK1 and MEK2 inhibitor SL327 significantly attenuated the increase in the percentage of neurite-bearing PC12 cells induced by DA-9801 treatment. Conversely, the selective p38 mitogen-activated protein kinase inhibitor SB203580 did not attenuate the DA-9801 treatment-induced increase in the percentage of neurite-bearing PC12 cells. DA-9801 enhanced the phosphorylation of ERK1/2 and CREB in PC12 cells incubated with and without NGF. Pretreatment with PD98059 blocked the DA-9801-induced phosphorylation of ERK1/2 and CREB. In conclusion, DA-9801 induces neurite outgrowth by affecting the ERK1/2-CREB signaling pathway. Insights into the mechanism underlying this effect of DA-9801 may suggest novel potential strategies for the treatment of peripheral neuropathy.

  4. Microelectrode array-induced neuronal alignment directs neurite outgrowth: analysis using a fast Fourier transform (FFT).

    Science.gov (United States)

    Radotić, Viktorija; Braeken, Dries; Kovačić, Damir

    2017-12-01

    Many studies have shown that the topography of the substrate on which neurons are cultured can promote neuronal adhesion and guide neurite outgrowth in the same direction as the underlying topography. To investigate this effect, isotropic substrate-complementary metal-oxide-semiconductor (CMOS) chips were used as one example of microelectrode arrays (MEAs) for directing neurite growth of spiral ganglion neurons. Neurons were isolated from 5 to 7-day-old rat pups, cultured 1 day in vitro (DIV) and 4 DIV, and then fixed with 4% paraformaldehyde. For analysis of neurite alignment and orientation, fast Fourier transformation (FFT) was used. Results revealed that on the micro-patterned surface of a CMOS chip, neurons orient their neurites along three directional axes at 30, 90, and 150° and that neurites aligned in straight lines between adjacent pillars and mostly followed a single direction while occasionally branching perpendicularly. We conclude that the CMOS substrate guides neurites towards electrodes by means of their structured pillar organization and can produce electrical stimulation of aligned neurons as well as monitoring their neural activities once neurites are in the vicinity of electrodes. These findings are of particular interest for neural tissue engineering with the ultimate goal of developing a new generation of MEA essential for improved electrical stimulation of auditory neurons.

  5. Prostaglandin E2 facilitates neurite outgrowth in a motor neuron-like cell line, NSC-34

    Directory of Open Access Journals (Sweden)

    Hiroshi Nango

    2017-10-01

    Full Text Available Prostaglandin E2 (PGE2 exerts various biological effects by binding to E-prostanoid receptors (EP1-4. Although recent studies have shown that PGE2 induces cell differentiation in some neuronal cells such as mouse DRG neurons and sensory neuron-like ND7/23 cells, it is unclear whether PGE2 plays a role in differentiation of motor neurons. In the present study, we investigated the mechanism of PGE2-induced differentiation of motor neurons using NSC-34, a mouse motor neuron-like cell line. Exposure of undifferentiated NSC-34 cells to PGE2 and butaprost, an EP2-selective agonist, resulted in a reduction of MTT reduction activity without increase the number of propidium iodide-positive cells and in an increase in the number of neurite-bearing cells. Sulprostone, an EP1/3 agonist, also significantly lowered MTT reduction activity by 20%; however, no increase in the number of neurite-bearing cells was observed within the concentration range tested. PGE2-induced neurite outgrowth was attenuated significantly in the presence of PF-0441848, an EP2-selective antagonist. Treatment of these cells with dibutyryl-cAMP increased the number of neurite-bearing cells with no effect on cell proliferation. These results suggest that PGE2 promotes neurite outgrowth and suppresses cell proliferation by activating the EP2 subtype, and that the cAMP-signaling pathway is involved in PGE2-induced differentiation of NSC-34 cells. Keywords: Prostaglandin E2, E-prostanoid receptors, Motor neuron, Neurite outgrowth, cAMP

  6. Quantitative assessment of neurite outgrowth in human embryonic stem-cell derived neurons using automated high-content image analysis

    Science.gov (United States)

    During development neurons undergo a number of morphological changes including neurite outgrowth from the cell body. Exposure to neurotoxicants that interfere with this process may cause in permanent deficits in nervous system function. While many studies have used rodent primary...

  7. Large enhancement in neurite outgrowth on a cell membrane-mimicking conducting polymer

    Science.gov (United States)

    Zhu, Bo; Luo, Shyh-Chyang; Zhao, Haichao; Lin, Hsing-An; Sekine, Jun; Nakao, Aiko; Chen, Chi; Yamashita, Yoshiro; Yu, Hsiao-Hua

    2014-07-01

    Although electrically stimulated neurite outgrowth on bioelectronic devices is a promising means of nerve regeneration, immunogenic scar formation can insulate electrodes from targeted cells and tissues, thereby reducing the lifetime of the device. Ideally, an electrode material capable of electrically interfacing with neurons selectively and efficiently would be integrated without being recognized by the immune system and minimize its response. Here we develop a cell membrane-mimicking conducting polymer possessing several attractive features. This polymer displays high resistance towards nonspecific enzyme/cell binding and recognizes targeted cells specifically to allow intimate electrical communication over long periods of time. Its low electrical impedance relays electrical signals efficiently. This material is capable to integrate biochemical and electrical stimulation to promote neural cellular behaviour. Neurite outgrowth is enhanced greatly on this new conducting polymer; in addition, electrically stimulated secretion of proteins from primary Schwann cells can also occur on it.

  8. Induction of neurite outgrowth in 3D hydrogel-based environments

    International Nuclear Information System (INIS)

    Assunção-Silva, Rita C; Oliveira, Cátia Costa; Gomes, Eduardo D; Sousa, Nuno; Silva, Nuno A; Salgado, António J; Ziv-Polat, Ofra; Sahar, Abraham

    2015-01-01

    The ability of peripheral nervous system (PNS) axons to regenerate and re-innervate their targets after an injury has been widely recognized. However, despite the considerable advances made in microsurgical techniques, complete functional recovery is rarely achieved, especially for severe peripheral nerve injuries (PNIs). Therefore, alternative therapies that can successfully repair peripheral nerves are still essential. In recent years the use of biodegradable hydrogels enriched with growth-supporting and guidance cues, cell transplantation, and biomolecular therapies have been explored for the treatment of PNIs. Bearing this in mind, the aim of this study was to assess whether Gly-Arg-Gly-Asp-Ser synthetic peptide (GRGDS)-modified gellan gum (GG) based hydrogels could foster an amenable environment for neurite/axonal growth. Additionally, strategies to further improve the rate of neurite outgrowth were also tested, namely the use of adipose tissue derived stem cells (ASCs), as well as the glial derived neurotrophic factor (GDNF). In order to increase its stability and enhance its bioactivity, the GDNF was conjugated covalently to iron oxide nanoparticles (IONPs). The impact of hydrogel modification as well as the effect of the GDNF-IONPs on ASC behavior was also screened. The results revealed that the GRGDS-GG hydrogel was able to support dorsal root ganglia (DRG)-based neurite outgrowth, which was not observed for non-modified hydrogels. Moreover, the modified hydrogels were also able to support ASCs attachment. In contrast, the presence of the GDNF-IONPs had no positive or negative impact on ASC behavior. Further experiments revealed that the presence of ASCs in the hydrogel improved axonal growth. On the other hand, GDNF-IONPs alone or combined with ASCs significantly increased neurite outgrowth from DRGs, suggesting a beneficial role of the proposed strategy for future applications in PNI regenerative medicine. (note)

  9. Actin Waves Do Not Boost Neurite Outgrowth in the Early Stages of Neuron Maturation

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    Simone Mortal

    2017-12-01

    Full Text Available During neurite development, Actin Waves (AWs emerge at the neurite base and move up to its tip, causing a transient retraction of the Growth Cone (GC. Many studies have shown that AWs are linked to outbursts of neurite growth and, therefore, contribute to the fast elongation of the nascent axon. Using long term live cell-imaging, we show that AWs do not boost neurite outgrowth and that neurites without AWs can elongate for several hundred microns. Inhibition of Myosin II abolishes the transient GC retraction and strongly modifies the AWs morphology. Super-resolution nanoscopy shows that Myosin IIB shapes the growth cone-like AWs structure and is differently distributed in AWs and GCs. Interestingly, depletion of membrane cholesterol and inhibition of Rho GTPases decrease AWs frequency and velocity. Our results indicate that Myosin IIB, membrane tension, and small Rho GTPases are important players in the regulation of the AW dynamics. Finally, we suggest a role for AWs in maintaining the GCs active during environmental exploration.

  10. Binding of Cdc42 to phospholipase D1 is important in neurite outgrowth of neural stem cells

    International Nuclear Information System (INIS)

    Yoon, Mee-Sup; Cho, Chan Ho; Lee, Ki Sung; Han, Joong-Soo

    2006-01-01

    We previously demonstrated that phospholipase D (PLD) expression and PLD activity are upregulated during neuronal differentiation. In the present study, employing neural stem cells from the brain cortex of E14 rat embryos, we investigated the role of Rho family GTPases in PLD activation and in neurite outgrowth of neural stem cells during differentiation. As neuronal differentiation progressed, the expression levels of Cdc42 and RhoA increased. Furthermore, Cdc42 and PLD1 were mainly localized in neurite, whereas RhoA was localized in cytosol. Co-immunoprecipitation revealed that Cdc42 was bound to PLD1 during differentiation, whereas RhoA was associated with PLD1 during both proliferation and differentiation. These results indicate that the association between Cdc42 and PLD1 is related to neuronal differentiation. To examine the effect of Cdc42 on PLD activation and neurite outgrowth, we transfected dominant negative Cdc42 (Cdc42N17) and constitutively active Cdc42 (Cdc42V12) into neural stem cells, respectively. Overexpression of Cdc42N17 decreased both PLD activity and neurite outgrowth, whereas co-transfection with Cdc42N17 and PLD1 restored them. On the other hand, Cdc42V12 increased both PLD activity and neurite outgrowth, suggesting that active state of Cdc42 is important in upregulation of PLD activity which is responsible for the increase of neurite outgrowth

  11. Resveratrol Enhances Neurite Outgrowth and Synaptogenesis Via Sonic Hedgehog Signaling Following Oxygen-Glucose Deprivation/Reoxygenation Injury

    Directory of Open Access Journals (Sweden)

    Fanren Tang

    2017-09-01

    Full Text Available Background/Aims: Neurite outgrowth and synaptogenesis are critical steps for functional recovery after stroke. Resveratrol promotes neurite outgrowth and synaptogenesis, but the underlying mechanism is not well understood, although the Sonic hedgehog (Shh signaling pathway may be involved. Given that resveratrol activates sirtuin (Sirt1, the present study examined whether this is mediated by Shh signaling. Methods: Primary cortical neuron cultures were pretreated with drugs before oxygen-glucose deprivation/reoxygenation (OGD/R. Cell viability and apoptosis were evaluated with Cell Counting Kit 8 and by terminal deoxynucleotidyl transferase dUTP nick end labeling, respectively. Neurite outgrowth and synaptogenesis were assessed by immunocytochemistry and western blotting, which was also used to examine the expression of Sirt1 and Shh signaling proteins. Results: Resveratrol and the Smoothened (Smo agonist purmophamine, which activates Shh signaling, increased viability, reduced apoptosis, and stimulated neurite outgrowth after OGD/R injury. Moreover, the expression of growth-associated protein(GAP-43, synaptophysin, Shh, Patched (Ptc-1, Smo, glioma-associated oncogene homolog (Gli-1, and Sirt1 were upregulated under these conditions. These effects were reversed by treatment with the Smo inhibitor cyclopamine, whereas the Sirt1 inhibitor sirtinol reduced the levels of Shh, Ptc-1, Smo, and Gli-1. Conclusions: Resveratrol reduces neuronal injury following OGD/R injury and enhances neurite outgrowth and synaptogenesis by activating Shh signaling, which in turn induces Sirt1.

  12. Enhanced Neural Cell Adhesion and Neurite Outgrowth on Graphene-Based Biomimetic Substrates

    Directory of Open Access Journals (Sweden)

    Suck Won Hong

    2014-01-01

    Full Text Available Neural cell adhesion and neurite outgrowth were examined on graphene-based biomimetic substrates. The biocompatibility of carbon nanomaterials such as graphene and carbon nanotubes (CNTs, that is, single-walled and multiwalled CNTs, against pheochromocytoma-derived PC-12 neural cells was also evaluated by quantifying metabolic activity (with WST-8 assay, intracellular oxidative stress (with ROS assay, and membrane integrity (with LDH assay. Graphene films were grown by using chemical vapor deposition and were then coated onto glass coverslips by using the scooping method. Graphene sheets were patterned on SiO2/Si substrates by using photolithography and were then covered with serum for a neural cell culture. Both types of CNTs induced significant dose-dependent decreases in the viability of PC-12 cells, whereas graphene exerted adverse effects on the neural cells just at over 62.5 ppm. This result implies that graphene and CNTs, even though they were the same carbon-based nanomaterials, show differential influences on neural cells. Furthermore, graphene-coated or graphene-patterned substrates were shown to substantially enhance the adhesion and neurite outgrowth of PC-12 cells. These results suggest that graphene-based substrates as biomimetic cues have good biocompatibility as well as a unique surface property that can enhance the neural cells, which would open up enormous opportunities in neural regeneration and nanomedicine.

  13. Enhancement of neurite outgrowth in neuron cancer stem cells by growth on 3-D collagen scaffolds

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Chih-Hao [Department of Electrical Engineering, I-Shou University, Taiwan, ROC (China); Neurosurgery, Department of Surgery, Kaohsiung Veterans General Hospital, Taiwan, ROC (China); Department of Biomedical Engineering, I-Shou University, Taiwan, ROC (China); Kuo, Shyh Ming [Department of Biomedical Engineering, I-Shou University, Taiwan, ROC (China); Liu, Guei-Sheung [Centre for Eye Research Australia, University of Melbourne (Australia); Chen, Wan-Nan U. [Department of Biological Science and Technology, I-Shou University, Taiwan, ROC (China); Chuang, Chin-Wen [Department of Electrical Engineering, I-Shou University, Taiwan, ROC (China); Liu, Li-Feng, E-mail: liulf@isu.edu.tw [Department of Biological Science and Technology, I-Shou University, Taiwan, ROC (China)

    2012-11-09

    Highlights: Black-Right-Pointing-Pointer Neuron cancer stem cells (NCSCs) behave high multiply of growth on collagen scaffold. Black-Right-Pointing-Pointer Enhancement of NCSCs neurite outgrowth on porous collagen scaffold. Black-Right-Pointing-Pointer 3-D collagen culture of NCSCs shows an advance differentiation than 2-D culture. -- Abstract: Collagen is one component of the extracellular matrix that has been widely used for constructive remodeling to facilitate cell growth and differentiation. The 3-D distribution and growth of cells within the porous scaffold suggest a clinical significance for nerve tissue engineering. In the current study, we investigated proliferation and differentiation of neuron cancer stem cells (NCSCs) on a 3-D porous collagen scaffold that mimics the natural extracellular matrix. We first generated green fluorescence protein (GFP) expressing NCSCs using a lentiviral system to instantly monitor the transitions of morphological changes during growth on the 3-D scaffold. We found that proliferation of GFP-NCSCs increased, and a single cell mass rapidly grew with unrestricted expansion between days 3 and 9 in culture. Moreover, immunostaining with neuronal nuclei (NeuN) revealed that NCSCs grown on the 3-D collagen scaffold significantly enhanced neurite outgrowth. Our findings confirmed that the 80 {mu}m porous collagen scaffold could enhance attachment, viability and differentiation of the cancer neural stem cells. This result could provide a new application for nerve tissue engineering and nerve regeneration.

  14. Enhancement of neurite outgrowth in neuron cancer stem cells by growth on 3-D collagen scaffolds

    International Nuclear Information System (INIS)

    Chen, Chih-Hao; Kuo, Shyh Ming; Liu, Guei-Sheung; Chen, Wan-Nan U.; Chuang, Chin-Wen; Liu, Li-Feng

    2012-01-01

    Highlights: ► Neuron cancer stem cells (NCSCs) behave high multiply of growth on collagen scaffold. ► Enhancement of NCSCs neurite outgrowth on porous collagen scaffold. ► 3-D collagen culture of NCSCs shows an advance differentiation than 2-D culture. -- Abstract: Collagen is one component of the extracellular matrix that has been widely used for constructive remodeling to facilitate cell growth and differentiation. The 3-D distribution and growth of cells within the porous scaffold suggest a clinical significance for nerve tissue engineering. In the current study, we investigated proliferation and differentiation of neuron cancer stem cells (NCSCs) on a 3-D porous collagen scaffold that mimics the natural extracellular matrix. We first generated green fluorescence protein (GFP) expressing NCSCs using a lentiviral system to instantly monitor the transitions of morphological changes during growth on the 3-D scaffold. We found that proliferation of GFP-NCSCs increased, and a single cell mass rapidly grew with unrestricted expansion between days 3 and 9 in culture. Moreover, immunostaining with neuronal nuclei (NeuN) revealed that NCSCs grown on the 3-D collagen scaffold significantly enhanced neurite outgrowth. Our findings confirmed that the 80 μm porous collagen scaffold could enhance attachment, viability and differentiation of the cancer neural stem cells. This result could provide a new application for nerve tissue engineering and nerve regeneration.

  15. Neurite outgrowth induced by a synthetic peptide ligand of neural cell adhesion molecule requires fibroblast growth factor receptor activation

    DEFF Research Database (Denmark)

    Rønn, L C; Doherty, P; Holm, A

    2000-01-01

    identified a neuritogenic ligand, termed the C3 peptide, of the first immunoglobulin (lg) module of NCAM using a combinatorial library of synthetic peptides. Here we investigate whether stimulation of neurite outgrowth by this synthetic ligand of NCAM involves FGFRs. In primary cultures of cerebellar neurons...... from wild-type mice, the C3 peptide stimulated neurite outgrowth. This response was virtually absent in cultures of cerebellar neurons from transgenic mice expressing a dominant-negative form of the FGFR1. Likewise, in PC12E2 cells transiently expressing a dominant-negative form of the mouse FGFR1...

  16. Berberine, a natural antidiabetes drug, attenuates glucose neurotoxicity and promotes Nrf2-related neurite outgrowth

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Ya-Yun [Department of Pharmacology, School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Tseng, Yu-Ting [Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Lo, Yi-Ching, E-mail: yichlo@kmu.edu.tw [Department of Pharmacology, School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China)

    2013-11-01

    Reactive oxygen intermediates production and apoptotic damage induced by high glucose are major causes of neuronal damage in diabetic neuropathy. Berberine (BBR), a natural antidiabetes drug with PI3K-activating activity, holds promise for diabetes because of its dual antioxidant and anti-apoptotic activities. We have previously reported that BBR attenuated H{sub 2}O{sub 2} neurotoxicity via activating the PI3K/Akt/Nrf2-dependent pathway. In this study, we further explored the novel protective mechanism of BBR on high glucose-induced apoptotic death and neurite damage of SH-SY5Y cells. Results indicated BBR (0.1–10 nM) significantly attenuated reactive oxygen species (ROS) production, nucleus condensation, and apoptotic death in high glucose-treated cells. However, AG1024, an inhibitor of insulin growth factor-1 (IGF-1) receptor, significantly abolished BBR protection against high glucose-induced neuronal death. BBR also increased Bcl-2 expression and decreased cytochrome c release. High glucose down-regulated IGF-1 receptor and phosphorylation of Akt and GSK-3β, the effects of which were attenuated by BBR treatment. BBR also activated nuclear erythroid 2-related factor 2 (Nrf2), the key antioxidative transcription factor, which is accompanied with up-regulation of hemeoxygenase-1 (HO-1). Furthermore, BBR markedly enhanced nerve growth factor (NGF) expression and promoted neurite outgrowth in high glucose-treated cells. To further determine the role of the Nrf2 in BBR neuroprotection, RNA interference directed against Nrf2 was used. Results indicated Nrf2 siRNA abolished BBR-induced HO-1, NGF, neurite outgrowth and ROS decrease. In conclusion, BBR attenuated high glucose-induced neurotoxicity, and we are the first to reveal this novel mechanism of BBR as an Nrf2 activator against glucose neurotoxicity, providing another potential therapeutic use of BBR on the treatment of diabetic complications. - Highlights: • BBR attenuates high glucose-induced ROS

  17. Berberine, a natural antidiabetes drug, attenuates glucose neurotoxicity and promotes Nrf2-related neurite outgrowth

    International Nuclear Information System (INIS)

    Hsu, Ya-Yun; Tseng, Yu-Ting; Lo, Yi-Ching

    2013-01-01

    Reactive oxygen intermediates production and apoptotic damage induced by high glucose are major causes of neuronal damage in diabetic neuropathy. Berberine (BBR), a natural antidiabetes drug with PI3K-activating activity, holds promise for diabetes because of its dual antioxidant and anti-apoptotic activities. We have previously reported that BBR attenuated H 2 O 2 neurotoxicity via activating the PI3K/Akt/Nrf2-dependent pathway. In this study, we further explored the novel protective mechanism of BBR on high glucose-induced apoptotic death and neurite damage of SH-SY5Y cells. Results indicated BBR (0.1–10 nM) significantly attenuated reactive oxygen species (ROS) production, nucleus condensation, and apoptotic death in high glucose-treated cells. However, AG1024, an inhibitor of insulin growth factor-1 (IGF-1) receptor, significantly abolished BBR protection against high glucose-induced neuronal death. BBR also increased Bcl-2 expression and decreased cytochrome c release. High glucose down-regulated IGF-1 receptor and phosphorylation of Akt and GSK-3β, the effects of which were attenuated by BBR treatment. BBR also activated nuclear erythroid 2-related factor 2 (Nrf2), the key antioxidative transcription factor, which is accompanied with up-regulation of hemeoxygenase-1 (HO-1). Furthermore, BBR markedly enhanced nerve growth factor (NGF) expression and promoted neurite outgrowth in high glucose-treated cells. To further determine the role of the Nrf2 in BBR neuroprotection, RNA interference directed against Nrf2 was used. Results indicated Nrf2 siRNA abolished BBR-induced HO-1, NGF, neurite outgrowth and ROS decrease. In conclusion, BBR attenuated high glucose-induced neurotoxicity, and we are the first to reveal this novel mechanism of BBR as an Nrf2 activator against glucose neurotoxicity, providing another potential therapeutic use of BBR on the treatment of diabetic complications. - Highlights: • BBR attenuates high glucose-induced ROS production and

  18. Potentiation of nerve growth factor-induced neurite outgrowth in PC12 cells by ifenprodil: the role of sigma-1 and IP3 receptors.

    Directory of Open Access Journals (Sweden)

    Tamaki Ishima

    Full Text Available In addition to both the α1 adrenergic receptor and N-methyl-D-aspartate (NMDA receptor antagonists, ifenprodil binds to the sigma receptor subtypes 1 and 2. In this study, we examined the effects of ifenprodil on nerve growth factor (NGF-induced neurite outgrowth in PC12 cells. Ifenprodil significantly potentiated NGF-induced neurite outgrowth, in a concentration-dependent manner. In contrast, the α1 adrenergic receptor antagonist, prazosin and the NMDA receptor NR2B antagonist, Ro 25-6981 did not alter NGF-induced neurite outgrowth. Potentiation of NGF-induced neurite outgrowth mediated by ifenprodil was significantly antagonized by co-administration of the selective sigma-1 receptor antagonist, NE-100, but not the sigma-2 receptor antagonist, SM-21. Similarly, ifenprodil enhanced NGF-induced neurite outgrowth was again significantly reduced by the inositol 1,4,5-triphosphate (IP(3 receptor antagonists, xestospongin C and 2-aminoethoxydiphenyl borate (2-APB treatment. Furthermore, BAPTA-AM, a chelator of intracellular Ca(2+, blocked the effects of ifenprodil on NGF-induced neurite outgrowth, indicating the role of intracellular Ca(2+ in the neurite outgrowth. These findings suggest that activation at sigma-1 receptors and subsequent interaction with IP(3 receptors may mediate the pharmacological effects of ifenprodil on neurite outgrowth.

  19. β-Hydroxy-β-Methylbutyrate (HMB) Promotes Neurite Outgrowth in Neuro2a Cells.

    Science.gov (United States)

    Salto, Rafael; Vílchez, Jose D; Girón, María D; Cabrera, Elena; Campos, Nefertiti; Manzano, Manuel; Rueda, Ricardo; López-Pedrosa, Jose M

    2015-01-01

    β-Hydroxy-β-methylbutyrate (HMB) has been shown to enhance cell survival, differentiation and protein turnover in muscle, mainly activating phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinases/ extracellular-signal-regulated kinases (MAPK/ERK) signaling pathways. Since these two pathways are related to neuronal survival and differentiation, in this study, we have investigated the neurotrophic effects of HMB in mouse neuroblastoma Neuro2a cells. In Neuro2a cells, HMB promotes differentiation to neurites independent from any effects on proliferation. These effects are mediated by activation of both the PI3K/Akt and the extracellular-signal-regulated kinases (ERK1/2) signaling as demonstrated by the use of specific inhibitors of these two pathways. As myocyte-enhancer factor 2 (MEF2) family of transcription factors are involved in neuronal survival and plasticity, the transcriptional activity and protein levels of MEF2 were also evaluated. HMB promoted MEF2-dependent transcriptional activity mediated by the activation of Akt and ERK1/2 pathways. Furthermore, HMB increases the expression of brain glucose transporters 1 (GLUT1) and 3 (GLUT3), and mTOR phosphorylation, which translates in a higher protein synthesis in Neuro2a cells. Furthermore, Torin1 and rapamycin effects on MEF2 transcriptional activity and HMB-dependent neurite outgrowth support that HMB acts through mTORC2. Together, these findings provide clear evidence to support an important role of HMB in neurite outgrowth.

  20. Slit2 inactivates GSK3β to signal neurite outgrowth inhibition.

    Directory of Open Access Journals (Sweden)

    Justin Byun

    Full Text Available Slit molecules comprise one of the four canonical families of axon guidance cues that steer the growth cone in the developing nervous system. Apart from their role in axon pathfinding, emerging lines of evidence suggest that a wide range of cellular processes are regulated by Slit, ranging from branch formation and fasciculation during neurite outgrowth to tumor progression and to angiogenesis. However, the molecular and cellular mechanisms downstream of Slit remain largely unknown, in part, because of a lack of a readily manipulatable system that produces easily identifiable traits in response to Slit. The present study demonstrates the feasibility of using the cell line CAD as an assay system to dissect the signaling pathways triggered by Slit. Here, we show that CAD cells express receptors for Slit (Robo1 and Robo2 and that CAD cells respond to nanomolar concentrations of Slit2 by markedly decelerating the rate of process extension. Using this system, we reveal that Slit2 inactivates GSK3β and that inhibition of GSK3β is required for Slit2 to inhibit process outgrowth. Furthermore, we show that Slit2 induces GSK3β phosphorylation and inhibits neurite outgrowth in adult dorsal root ganglion neurons, validating Slit2 signaling in primary neurons. Given that CAD cells can be conveniently manipulated using standard molecular biological methods and that the process extension phenotype regulated by Slit2 can be readily traced and quantified, the use of a cell line CAD will facilitate the identification of downstream effectors and elucidation of signaling cascade triggered by Slit.

  1. New function of the adaptor protein SH2B1 in brain-derived neurotrophic factor-induced neurite outgrowth.

    Directory of Open Access Journals (Sweden)

    Chien-Hung Shih

    Full Text Available Neurite outgrowth is an essential process for the establishment of the nervous system. Brain-derived neurotrophic factor (BDNF binds to its receptor TrkB and regulates axonal and dendritic morphology of neurons through signal transduction and gene expression. SH2B1 is a signaling adaptor protein that regulates cellular signaling in various physiological processes. The purpose of this study is to investigate the role of SH2B1 in the development of the central nervous system. In this study, we show that knocking down SH2B1 reduces neurite formation of cortical neurons whereas overexpression of SH2B1β promotes the development of hippocampal neurons. We further demonstrate that SH2B1β promotes BDNF-induced neurite outgrowth and signaling using the established PC12 cells stably expressing TrkB, SH2B1β or SH2B1β mutants. Our data indicate that overexpressing SH2B1β enhances BDNF-induced MEK-ERK1/2, and PI3K-AKT signaling pathways. Inhibition of MEK-ERK1/2 and PI3K-AKT pathways by specific inhibitors suggest that these two pathways are required for SH2B1β-promoted BDNF-induced neurite outgrowth. Moreover, SH2B1β enhances BDNF-stimulated phosphorylation of signal transducer and activator of transcription 3 at serine 727. Finally, our data indicate that the SH2 domain and tyrosine phosphorylation of SH2B1β contribute to BDNF-induced signaling pathways and neurite outgrowth. Taken together, these findings demonstrate that SH2B1β promotes BDNF-induced neurite outgrowth through enhancing pathways involved MEK-ERK1/2 and PI3K-AKT.

  2. Electrical stimulation of schwann cells promotes sustained increases in neurite outgrowth.

    Science.gov (United States)

    Koppes, Abigail N; Nordberg, Andrea L; Paolillo, Gina M; Goodsell, Nicole M; Darwish, Haley A; Zhang, Linxia; Thompson, Deanna M

    2014-02-01

    Endogenous electric fields are instructive during embryogenesis by acting to direct cell migration, and postnatally, they can promote axonal growth after injury (McCaig 1991, Al-Majed 2000). However, the mechanisms for these changes are not well understood. Application of an appropriate electrical stimulus may increase the rate and success of nerve repair by directly promoting axonal growth. Previously, DC electrical stimulation at 50 mV/mm (1 mA, 8 h duration) was shown to promote neurite outgrowth and a more pronounced effect was observed if both peripheral glia (Schwann cells) and neurons were co-stimulated. If electrical stimulation is delivered to an injury site, both the neurons and all resident non-neuronal cells [e.g., Schwann cells, endothelial cells, fibroblasts] will be treated and this biophysical stimuli can influence axonal growth directly or indirectly via changes to the resident, non-neuronal cells. In this work, non-neuronal cells were electrically stimulated, and changes in morphology and neuro-supportive cells were evaluated. Schwann cell response (morphology and orientation) was examined after an 8 h stimulation over a range of DC fields (0-200 mV/mm, DC 1 mA), and changes in orientation were observed. Electrically prestimulating Schwann cells (50 mV/mm) promoted 30% more neurite outgrowth relative to co-stimulating both Schwann cells with neurons, suggesting that electrical stimulation modifies Schwann cell phenotype. Conditioned medium from the electrically prestimulated Schwann cells promoted a 20% increase in total neurite outgrowth and was sustained for 72 h poststimulation. An 11-fold increase in nerve growth factor but not brain-derived neurotrophic factor or glial-derived growth factor was found in the electrically prestimulated Schwann cell-conditioned medium. No significant changes in fibroblast or endothelial morphology and neuro-supportive behavior were observed poststimulation. Electrical stimulation is widely used in

  3. Identification of NCAM-binding peptides promoting neurite outgrowth via a heterotrimeric G-protein-coupled pathway

    DEFF Research Database (Denmark)

    Hansen, Raino Kristian; Christensen, Claus; Korshunova, Irina

    2007-01-01

    the fibroblast growth factor receptor, the Src-related non-receptor tyrosine kinase Fyn, and heterotrimeric G-proteins. Interestingly, neurite outgrowth stimulated by ENFIN2 and ENFIN11 was independent of signaling through fibroblast growth factor receptor and Fyn, but could be inhibited with pertussis toxin...

  4. The functionalized amino acid (S-Lacosamide subverts CRMP2-mediated tubulin polymerization to prevent constitutive and activity-dependent increase in neurite outgrowth

    Directory of Open Access Journals (Sweden)

    Sarah M Wilson

    2014-07-01

    Full Text Available Activity-dependent neurite outgrowth is a highly complex, regulated process with important implications for neuronal circuit remodeling in development as well as in seizure-induced sprouting in epilepsy. Recent work has linked outgrowth to collapsin response mediator protein 2 (CRMP2, an intracellular phosphoprotein originally identified as axon guidance and growth cone collapse protein. The neurite outgrowth promoting function of CRMP2 is regulated by its phosphorylation state. In this study, depolarization (potassium chloride-driven activity increased the level of active CRMP2 by decreasing its phosphorylation by GSK3β via a reduction in priming by Cdk5. To determine the contribution of CRMP2 in activity-driven neurite outgrowth, we screened a limited set of compounds for their ability to reduce neurite outgrowth but not modify voltage-gated sodium channel (VGSC biophysical properties. This led to the identification of (S-lacosamide ((S-LCM, a stereoisomer of the clinically used antiepileptic drug (R-LCM (Vimpat®, as a novel tool for preferentially targeting CRMP2-mediated neurite outgrowth. Whereas (S-LCM was ineffective in targeting VGSCs, the presumptive pharmacological targets of (R-LCM, (S-LCM was more efficient than (R-LCM in subverting neurite outgrowth. Biomolecular interaction analyses revealed that (S-LCM bound to wildtype CRMP2 with low micromolar affinity, similar to (R-LCM. Through the use of this novel tool, the activity-dependent increase in neurite outgrowth observed following depolarization was characterized to be reliant on CRMP2 function. Knockdown of CRMP2 by siRNA in cortical neurons resulted in reduced CRMP2-dependent neurite outgrowth; incubation with (S-LCM phenocopied this effect. Other CRMP2-mediated processes were unaffected. (S-LCM subverted neurite outgrowth not by affecting the canonical CRMP2-tubulin association but rather by impairing the ability of CRMP2 to promote tubulin polymerization, events that are

  5. Neurite outgrowth mediated by translation elongation factor eEF1A1: a target for antiplatelet agent cilostazol.

    Directory of Open Access Journals (Sweden)

    Kenji Hashimoto

    Full Text Available Cilostazol, a type-3 phosphodiesterase (PDE3 inhibitor, has become widely used as an antiplatelet drug worldwide. A recent second Cilostazol Stroke Prevention Study demonstrated that cilostazol is superior to aspirin for prevention of stroke after an ischemic stroke. However, its precise mechanisms of action remain to be determined. Here, we report that cilostazol, but not the PDE3 inhibitors cilostamide and milrinone, significantly potentiated nerve growth factor (NGF-induced neurite outgrowth in PC12 cells. Furthermore, specific inhibitors for the endoplasmic reticulum protein inositol 1,4,5-triphosphate (IP(3 receptors and several common signaling pathways (PLC-γ, PI3K, Akt, p38 MAPK, and c-Jun N-terminal kinase (JNK, and the Ras/Raf/ERK/MAPK significantly blocked the potentiation of NGF-induced neurite outgrowth by cilostazol. Using a proteomics analysis, we identified that levels of eukaryotic translation elongation factor eEF1A1 protein were significantly increased by treatment with cilostazol, but not cilostamide, in PC12 cells. Moreover, the potentiating effects of cilostazol on NGF-induced neurite outgrowth were significantly antagonized by treatment with eEF1A1 RNAi, but not the negative control of eEF1A1. These findings suggest that eEF1A1 and several common cellular signaling pathways might play a role in the mechanism of cilostazol-induced neurite outgrowth. Therefore, agents that can increase the eEF1A1 protein may have therapeutic relevance in diverse conditions with altered neurite outgrowth.

  6. Chemoenzymatically prepared konjac ceramide inhibits NGF-induced neurite outgrowth by a semaphorin 3A-like action

    Directory of Open Access Journals (Sweden)

    Seigo Usuki

    2016-03-01

    Full Text Available Dietary sphingolipids such as glucosylceramide (GlcCer are potential nutritional factors associated with prevention of metabolic syndrome. Our current understanding is that dietary GlcCer is degraded to ceramide and further metabolized to sphingoid bases in the intestine. However, ceramide is only found in trace amounts in food plants and thus is frequently taken as GlcCer in a health supplement. In the present study, we successfully prepared konjac ceramide (kCer using endoglycoceramidase I (EGCase I. Konjac, a plant tuber, is an enriched source of GlcCer (kGlcCer, and has been commercialized as a dietary supplement to improve dry skin and itching that are caused by a deficiency of epidermal ceramide. Nerve growth factor (NGF produced by skin cells is one of the itch factors in the stratum corneum of the skin. Semaphorin 3A (Sema 3A has been known to inhibit NGF-induced neurite outgrowth of epidermal nerve fibers. It is well known that the itch sensation is regulated by the balance between NGF and Sema 3A. In the present study, while kGlcCer did not show an in vitro inhibitory effect on NGF-induced neurite outgrowth of PC12 cells, kCer was demonstrated to inhibit a remarkable neurite outgrowth. In addition, the effect of kCer was similar to that of Sema 3A in cell morphological changes and neurite retractions, but different from C2-Ceramide. kCer showed a Sema 3A-like action, causing CRMP2 phosphorylation, which results in a collapse of neurite growth cones. Thus, it is expected that kCer is an advanced konjac ceramide material that may have neurite outgrowth-specific action to relieve uncontrolled and serious itching, in particular, from atopic eczema.

  7. Electrically conductive biodegradable polymer composite for nerve regeneration: electricity-stimulated neurite outgrowth and axon regeneration.

    Science.gov (United States)

    Zhang, Ze; Rouabhia, Mahmoud; Wang, Zhaoxu; Roberge, Christophe; Shi, Guixin; Roche, Phillippe; Li, Jiangming; Dao, Lê H

    2007-01-01

    Normal and electrically stimulated PC12 cell cultures and the implantation of nerve guidance channels were performed to evaluate newly developed electrically conductive biodegradable polymer composites. Polypyrrole (PPy) doped by butane sulfonic acid showed a significantly higher number of viable cells compared with PPy doped by polystyrenesulfonate after a 6-day culture. The PC12 cells were left to proliferate for 6 days, and the PPy-coated membranes, showing less initial cell adherence, recorded the same proliferation rate as did the noncoated membranes. Direct current electricity at various intensities was applied to the PC12 cell-cultured conductive membranes. After 7 days, the greatest number of neurites appeared on the membranes with a current intensity approximating 1.7-8.4 microA/cm. Nerve guidance channels made of conductive biodegradable composite were implanted into rats to replace 8 mm of sciatic nerve. The implants were harvested after 2 months and analyzed with immunohistochemistry and transmission electron microscopy. The regenerated nerve tissue displayed myelinated axons and Schwann cells that were similar to those in the native nerve. Electrical stimulation applied through the electrically conductive biodegradable polymers therefore enhanced neurite outgrowth in a current-dependent fashion. The conductive polymers also supported sciatic nerve regeneration in rats.

  8. Neurotrophin Promotes Neurite Outgrowth by Inhibiting Rif GTPase Activation Downstream of MAPKs and PI3K Signaling.

    Science.gov (United States)

    Tian, Xiaoxia; Yan, Huijuan; Li, Jiayi; Wu, Shuang; Wang, Junyu; Fan, Lifei

    2017-01-13

    Members of the well-known semaphorin family of proteins can induce both repulsive and attractive signaling in neural network formation and their cytoskeletal effects are mediated in part by small guanosine 5'-triphosphatase (GTPases). The aim of this study was to investigate the cellular role of Rif GTPase in the neurotrophin-induced neurite outgrowth. By using PC12 cells which are known to cease dividing and begin to show neurite outgrowth responding to nerve growth factor (NGF), we found that semaphorin 6A was as effective as nerve growth factor at stimulating neurite outgrowth in PC12 cells, and that its neurotrophic effect was transmitted through signaling by mitogen-activated protein kinases (MAPKs) and phosphatidylinositol-3-kinase (PI3K). We further found that neurotrophin-induced neurite formation in PC12 cells could be partially mediated by inhibition of Rif GTPase activity downstream of MAPKs and PI3K signaling. In conclusion, we newly identified Rif as a regulator of the cytoskeletal rearrangement mediated by semaphorins.

  9. Moringa oleifera with promising neuronal survival and neurite outgrowth promoting potentials.

    Science.gov (United States)

    Hannan, Md Abdul; Kang, Ji-Young; Mohibbullah, Md; Hong, Yong-Ki; Lee, Hyunsook; Choi, Jae-Suk; Choi, In Soon; Moon, Il Soo

    2014-02-27

    Moringa oleifera Lam. (Moringaceae) by virtue of its high nutritional as well as ethnomedical values has been gaining profound interest both in nutrition and medicinal research. The leaf of this plant is used in ayurvedic medicine to treat paralysis, nervous debility and other nerve disorders. In addition, research evidence also suggests the nootropic as well as neuroprotective roles of Moringa oleifera leaf in animal models. The aim of the present study was to evaluate the effect of Moringa oleifera leaf in the primary hippocampal neurons regarding its neurotrophic and neuroprotective properties. The primary culture of embryonic hippocampal neurons was incubated with the ethanol extract of Moringa oleifera leaf (MOE). After an indicated time, cultures were either stained directly with a lipophilic dye, DiO, or fixed and immunolabeled to visualize the neuronal morphology. Morphometric analyses for neurite maturation and synaptogenesis were performed using Image J software. Neuronal viability was evaluated using trypan blue exclusion and lactate dehydrogenase assays. MOE promoted neurite outgrowth in a concentration-dependent manner with an optimal concentration of 30 μg/mL. As a very initial effect, MOE significantly promoted the earlier stages of neuronal differentiation. Subsequently, MOE significantly increased the number and length of dendrites, the length of axon, and the number and length of both dendrite and axonal branches, and eventually facilitated synaptogenesis. The β-carotene, one major compound of MOE, promoted neuritogensis, but the increase was not comparable with the effect of MOE. In addition, MOE supported neuronal survival by protecting neurons from naturally occurring cell death in vitro. Our findings indicate that MOE promotes axodendritic maturation as well as provides neuroprotection suggesting a promising pharmacological importance of this nutritionally and ethnomedically important plant for the well-being of nervous system. Copyright

  10. Neurite outgrowth stimulatory effects of culinary-medicinal mushrooms and their toxicity assessment using differentiating Neuro-2a and embryonic fibroblast BALB/3T3

    OpenAIRE

    Phan, Chia-Wei; David, Pamela; Naidu, Murali; Wong, Kah-Hui; Sabaratnam, Vikineswary

    2013-01-01

    Background Mushrooms are not only regarded as gourmet cuisine but also as therapeutic agent to promote cognition health. However, little toxicological information is available regarding their safety. Therefore, the aim of this study was to screen selected ethno-pharmacologically important mushrooms for stimulatory effects on neurite outgrowth and to test for any cytotoxicity. Methods The stimulatory effect of mushrooms on neurite outgrowth was assessed in differentiating mouse neuroblastoma (...

  11. Pleurotus giganteus (Berk.) Karunarathna & K.D. Hyde: Nutritional value and in vitro neurite outgrowth activity in rat pheochromocytoma cells.

    Science.gov (United States)

    Phan, Chia-Wei; Wong, Wei-Lun; David, Pamela; Naidu, Murali; Sabaratnam, Vikineswary

    2012-07-19

    Drugs dedicated to alleviate neurodegenerative diseases like Parkinson's and Alzheimer's have always been associated with debilitating side effects. Medicinal mushrooms which harness neuropharmacological compounds offer a potential possibility for protection against such diseases. Pleurotus giganteus (formerly known as Panus giganteus) has been consumed by the indigenous people in Peninsular Malaysia for many years. Domestication of this wild mushroom is gaining popularity but to our knowledge, medicinal properties reported for this culinary mushroom are minimal. The fruiting bodies P. giganteus were analysed for its nutritional values. Cytotoxicity of the mushroom's aqueous and ethanolic extracts towards PC12, a rat pheochromocytoma cell line was assessed by using 3-[4,5-dimethythiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Neurite outgrowth stimulation assay was carried out with nerve growth factor (NGF) as control. To elucidate signaling mechanisms involved by mushroom extract-induced neurite outgrowth, treatment of specific inhibitor for MEK/ERK and PI3K signalling pathway was carried out. The fruiting bodies of P. giganteus were found to have high carbohydrate, dietary fibre, potassium, phenolic compounds and triterpenoids. Both aqueous and ethanolic extracts induced neurite outgrowth of PC12 cells in a dose- and time-dependant manner with no detectable cytotoxic effect. At day 3, 25 μg/ml of aqueous extract and 15 μg/ml of ethanolic extract showed the highest percentage of neurite-bearing cells, i.e. 31.7 ± 1.1% and 33.3 ± 0.9%; respectively. Inhibition treatment results suggested that MEK/ERK and PI3K/Akt are responsible for neurite outgrowth of PC12 cells stimulated by P. giganteus extract. The high potassium content (1345.7 mg/100 g) may be responsible for promoting neurite extension, too. P. giganteus contains bioactive compounds that mimic NGF and are responsible for neurite stimulation. Hence, this mushroom may be

  12. Neurite outgrowth is significantly increased by the simultaneous presentation of Schwann cells and moderate exogenous electric fields

    Science.gov (United States)

    Koppes, Abigail N.; Seggio, Angela M.; Thompson, Deanna M.

    2011-08-01

    Axonal extension is influenced by a variety of external guidance cues; therefore, the development and optimization of a multi-faceted approach is probably necessary to address the intricacy of functional regeneration following nerve injury. In this study, primary dissociated neonatal rat dorsal root ganglia neurons and Schwann cells were examined in response to an 8 h dc electrical stimulation (0-100 mV mm-1). Stimulated samples were then fixed immediately, immunostained, imaged and analyzed to determine Schwann cell orientation and characterize neurite outgrowth relative to electric field strength and direction. Results indicate that Schwann cells are viable following electrical stimulation with 10-100 mV mm-1, and retain a normal morphology relative to unstimulated cells; however, no directional bias is observed. Neurite outgrowth was significantly enhanced by twofold following exposure to either a 50 mV mm-1 electric field (EF) or co-culture with unstimulated Schwann cells by comparison to neurons cultured alone. Neurite outgrowth was further increased in the presence of simultaneously applied cues (Schwann cells + 50 mV mm-1 dc EF), exhibiting a 3.2-fold increase over unstimulated control neurons, and a 1.2-fold increase over either neurons cultured with unstimulated Schwann cells or the electrical stimulus alone. These results indicate that dc electric stimulation in combination with Schwann cells may provide synergistic guidance cues for improved axonal growth relevant to nerve injuries in the peripheral nervous system.

  13. Enhanced differentiation of neural stem cells to neurons and promotion of neurite outgrowth by oxygen-glucose deprivation.

    Science.gov (United States)

    Wang, Qin; Yang, Lin; Wang, Yaping

    2015-06-01

    Stroke has become the leading cause of mortality worldwide. Hypoxic or ischemic insults are crucial factors mediating the neural damage in the brain tissue of stroke patients. Neural stem cells (NSCs) have been recognized as a promising tool for the treatment of ischemic stroke and other neurodegenerative diseases due to their inducible pluripotency. In this study, we aim to mimick the cerebral hypoxic-ischemic injury in vitro using oxygen-glucose deprivation (OGD) strategy, and evaluate the effects of OGD on the NSC's neural differentiation, as well as the differentiated neurite outgrowth. Our data showed that NSCs under the short-term 2h OGD treatment are able to maintain cell viability and the capability to form neurospheres. Importantly, this moderate OGD treatment promotes NSC differentiation to neurons and enhances the performance of the mature neuronal networks, accompanying increased neurite outgrowth of differentiated neurons. However, long-term 6h and 8h OGD exposures in NSCs lead to decreased cell survival, reduced differentiation and diminished NSC-derived neurite outgrowth. The expressions of neuron-specific microtubule-associated protein 2 (MAP-2) and growth associated protein 43 (GAP-43) are increased by short-term OGD treatments but suppressed by long-term OGD. Overall, our results demonstrate that short-term OGD exposure in vitro induces differentiation of NSCs while maintaining their proliferation and survival, providing valuable insights of adopting NSC-based therapy for ischemic stroke and other neurodegenerative disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. NOGO-A induction and localization during chick brain development indicate a role disparate from neurite outgrowth inhibition

    Directory of Open Access Journals (Sweden)

    Liwnicz Boleslaw H

    2007-04-01

    Full Text Available Abstract Background Nogo-A, a myelin-associated protein, inhibits neurite outgrowth and abates regeneration in the adult vertebrate central nervous system (CNS and may play a role in maintaining neural pathways once established. However, the presence of Nogo-A during early CNS development is counterintuitive and hints at an additional role for Nogo-A beyond neurite inhibition. Results We isolated chicken NOGO-A and determined its sequence. A multiple alignment of the amino acid sequence across divergent species, identified five previously undescribed, Nogo-A specific conserved regions that may be relevant for development. NOGO gene transcripts (NOGO-A, NOGO-B and NOGO-C were differentially expressed in the CNS during development and a second NOGO-A splice variant was identified. We further localized NOGO-A expression during key phases of CNS development by in situ hybridization. CNS-associated NOGO-A was induced coincident with neural plate formation and up-regulated by FGF in the transformation of non-neural ectoderm into neural precursors. NOGO-A expression was diffuse in the neuroectoderm during the early proliferative phase of development, and migration, but localized to large projection neurons of the optic tectum and tectal-associated nuclei during architectural differentiation, lamination and network establishment. Conclusion These data suggest Nogo-A plays a functional role in the determination of neural identity and/or differentiation and also appears to play a later role in the networking of large projection neurons during neurite formation and synaptogenesis. These data indicate that Nogo-A is a multifunctional protein with additional roles during CNS development that are disparate from its later role of neurite outgrowth inhibition in the adult CNS.

  15. Activation of transglutaminase 2 by nerve growth factor in differentiating neuroblastoma cells: A role in cell survival and neurite outgrowth.

    Science.gov (United States)

    Algarni, Alanood S; Hargreaves, Alan J; Dickenson, John M

    2018-02-05

    NGF (nerve growth factor) and tissue transglutaminase (TG2) play important roles in neurite outgrowth and modulation of neuronal cell survival. In this study, we investigated the regulation of TG2 transamidase activity by NGF in retinoic acid-induced differentiating mouse N2a and human SH-SY5Y neuroblastoma cells. TG2 transamidase activity was determined using an amine incorporation and a peptide cross linking assay. In situ TG2 activity was assessed by visualising the incorporation of biotin-X-cadaverine using confocal microscopy. The role of TG2 in NGF-induced cytoprotection and neurite outgrowth was investigated by monitoring hypoxia-induced cell death and appearance of axonal-like processes, respectively. The amine incorporation and protein crosslinking activity of TG2 increased in a time and concentration-dependent manner following stimulation with NGF in N2a and SH-SY5Y cells. NGF mediated increases in TG2 activity were abolished by the TG2 inhibitors Z-DON (Z-ZON-Val-Pro-Leu-OMe; Benzyloxycarbonyl-(6-Diazo-5-oxonorleucinyl)-l-valinyl-l-prolinyl-l-leucinmethylester) and R283 (1,3,dimethyl-2[2-oxo-propyl]thio)imidazole chloride) and by pharmacological inhibition of extracellular signal-regulated kinases 1 and 2 (ERK1/2), protein kinase B (PKB) and protein kinase C (PKC), and removal of extracellular Ca 2+ . Fluorescence microscopy demonstrated NGF induced in situ TG2 activity. TG2 inhibition blocked NGF-induced attenuation of hypoxia-induced cell death and neurite outgrowth in both cell lines. Together, these results demonstrate that NGF stimulates TG2 transamidase activity via a ERK1/2, PKB and PKC-dependent pathway in differentiating mouse N2a and human SH-SY5Y neuroblastoma cells. Furthermore, NGF-induced cytoprotection and neurite outgrowth are dependent upon TG2. These results suggest a novel and important role of TG2 in the cellular functions of NGF. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Neto2 Assembles with Kainate Receptors in DRG Neurons during Development and Modulates Neurite Outgrowth in Adult Sensory Neurons.

    Science.gov (United States)

    Vernon, Claire G; Swanson, Geoffrey T

    2017-03-22

    Peripheral sensory neurons in the dorsal root ganglia (DRG) are the initial transducers of sensory stimuli, including painful stimuli, from the periphery to central sensory and pain-processing centers. Small- to medium-diameter non-peptidergic neurons in the neonatal DRG express functional kainate receptors (KARs), one of three subfamilies of ionotropic glutamate receptors, as well as the putative KAR auxiliary subunit Neuropilin- and tolloid-like 2 (Neto2). Neto2 alters recombinant KAR function markedly but has yet to be confirmed as an auxiliary subunit that assembles with and alters the function of endogenous KARs. KARs in neonatal DRG require the GluK1 subunit as a necessary constituent, but it is unclear to what extent other KAR subunits contribute to the function and proposed roles of KARs in sensory ganglia, which include promotion of neurite outgrowth and modulation of glutamate release at the DRG-dorsal horn synapse. In addition, KARs containing the GluK1 subunit are implicated in modes of persistent but not acute pain signaling. We show here that the Neto2 protein is highly expressed in neonatal DRG and modifies KAR gating in DRG neurons in a developmentally regulated fashion in mice. Although normally at very low levels in adult DRG neurons, Neto2 protein expression can be upregulated via MEK/ERK signaling and after sciatic nerve crush and Neto2 -/- neurons from adult mice have stunted neurite outgrowth. These data confirm that Neto2 is a bona fide KAR auxiliary subunit that is an important constituent of KARs early in sensory neuron development and suggest that Neto2 assembly is critical to KAR modulation of DRG neuron process outgrowth. SIGNIFICANCE STATEMENT Pain-transducing peripheral sensory neurons of the dorsal root ganglia (DRG) express kainate receptors (KARs), a subfamily of glutamate receptors that modulate neurite outgrowth and regulate glutamate release at the DRG-dorsal horn synapse. The putative KAR auxiliary subunit Neuropilin- and

  17. Low-Intensity Pulsed Ultrasound Enhances Nerve Growth Factor-Induced Neurite Outgrowth through Mechanotransduction-Mediated ERK1/2-CREB-Trx-1 Signaling.

    Science.gov (United States)

    Zhao, Lu; Feng, Yi; Hu, Hong; Shi, Aiwei; Zhang, Lei; Wan, Mingxi

    2016-12-01

    Enhancing the action of nerve growth factor (NGF) is a potential therapeutic approach to neural regeneration. To facilitate neural regeneration, we investigated whether combining low-intensity pulsed ultrasound (LIPUS) and NGF could promote neurite outgrowth, an essential process in neural regeneration. In the present study, PC12 cells were subjected to a combination of LIPUS (1 MHz, 30 or 50 mW/cm 2 , 20% duty cycle and 100-Hz pulse repetition frequency, 10 min every other day) and NGF (50 ng/mL) treatment, and then neurite outgrowth was compared. Our findings indicated that the combined treatment with LIPUS (50 mW/cm 2 ) and NGF (50 ng/mL) promotes neurite outgrowth that is comparable to that achieved by NGF (100 ng/mL) treatment alone. LIPUS significantly increased NGF-induced neurite length, but not neurite branching. These effects were attributed to the enhancing effects of LIPUS on NGF-induced phosphorylation of ERK1/2 and CREB and the expression of thioredoxin (Trx-1). Furthermore, blockage of stretch-activated ion channels with Gd 3+ suppressed the stimulating effects of LIPUS on NGF-induced neurite outgrowth and the downstream signaling activation. Taken together, our findings suggest that LIPUS enhances NGF-induced neurite outgrowth through mechanotransduction-mediated signaling of the ERK1/2-CREB-Trx-1 pathway. The combination of LIPUS and NGF could potentially be used for the treatment of nerve injury and neurodegenerative diseases. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  18. Salicin from Willow Bark can Modulate Neurite Outgrowth in Human Neuroblastoma SH-SY5Y Cells.

    Science.gov (United States)

    Wölfle, Ute; Haarhaus, Birgit; Kersten, Astrid; Fiebich, Bernd; Hug, Martin J; Schempp, Christoph M

    2015-10-01

    Salicin from willow bark has been used throughout centuries in China and Europe for the treatment of pain, headache, and inflammatory conditions. Recently, it could be demonstrated that salicin binds and activates the bitter taste receptor TAS2R16. Studies on rodent tissues showed the general expression of bitter taste receptors (TAS2Rs) in rodent brain. Here, we demonstrate the expression of hTAS2R16 in human neuronal tissues and the neuroblastoma cell line SH-SY5Y. The functionality was analyzed in the neuroblastoma cell line SH-SY5Y after stimulation with salicin, a known TAS2R16 agonist. In this setting salicin induced in SH-SY5Y cells phosphorylation of ERK and CREB, the key transcription factor of neuronal differentiation. PD98059, an inhibitor of the ERK pathway, as well as probenecid, a TAS2R16 antagonist, inhibited receptor phosphorylation as well as neurite outgrowth. These data show that salicin might modulate neurite outgrowth by bitter taste receptor activation. Copyright © 2015 John Wiley & Sons, Ltd.

  19. Sonic hedgehog promotes neurite outgrowth of cortical neurons under oxidative stress: Involving of mitochondria and energy metabolism.

    Science.gov (United States)

    He, Weiliang; Cui, Lili; Zhang, Cong; Zhang, Xiangjian; He, Junna; Xie, Yanzhao; Chen, Yanxia

    2017-01-01

    Oxidative stress has been demonstrated to be involved in the etiology of several neurobiological disorders. Sonic hedgehog (Shh), a secreted glycoprotein factor, has been implicated in promoting several aspects of brain remodeling process. Mitochondria may play an important role in controlling fundamental processes in neuroplasticity. However, little evidence is available about the effect and the potential mechanism of Shh on neurite outgrowth in primary cortical neurons under oxidative stress. Here, we revealed that Shh treatment significantly increased the viability of cortical neurons in a dose-dependent manner, which was damaged by hydrogen peroxide (H 2 O 2 ). Shh alleviated the apoptosis rate of H 2 O 2 -induced neurons. Shh also increased neuritogenesis injuried by H 2 O 2 in primary cortical neurons. Moreover, Shh reduced the generation of reactive oxygen species (ROS), increased the activities of SOD and and decreased the productions of MDA. In addition, Shh protected mitochondrial functions, elevated the cellular ATP levels and amelioratesd the impairment of mitochondrial complex II activities of cortical neurons induced by H 2 O 2 . In conclusion, all these results suggest that Shh acts as a prosurvival factor playing an essential role to neurite outgrowth of cortical neuron under H 2 O 2 -induced oxidative stress, possibly through counteracting ROS release and preventing mitochondrial dysfunction and ATP as well as mitochondrial complex II activities against oxidative stress. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Effect of 710 nm visible light irradiation on neurite outgrowth in primary rat cortical neurons following ischemic insult

    International Nuclear Information System (INIS)

    Choi, Dong-Hee; Lee, Kyoung-Hee; Kim, Ji-Hye; Kim, Moon Young; Lim, Jeong Hoon; Lee, Jongmin

    2012-01-01

    Highlights: ► 710 nm wavelength light (LED) has a protective effect in the stroke animal model. ► We determined the effects of LED irradiation in vitro stroke model. ► LED treatment promotes the neurite outgrowth through MAPK activation. ► The level of synaptic markers significantly increased with LED treatment. ► LED treatment protects cell death in the in vitro stroke model. -- Abstract: Objective: We previously reported that 710 nm Light-emitting Diode (LED) has a protective effect through cellular immunity activation in the stroke animal model. However, whether LED directly protects neurons suffering from neurodegeneration was entirely unknown. Therefore, we sought to determine the effects of 710 nm visible light irradiation on neuronal protection and neuronal outgrowth in an in vitro stroke model. Materials and methods: Primary cultured rat cortical neurons were exposed to oxygen-glucose deprivation (OGD) and reoxygenation and normal conditions. An LED array with a peak wavelength of 710 nm was placed beneath the covered culture dishes with the room light turned off and were irradiated accordingly. LED treatments (4 min at 4 J/cm 2 and 50 mW/cm 2 ) were given once to four times within 8 h at 2 h intervals for 7 days. Mean neurite density, mean neurite diameter, and total fiber length were also measured after microtubule associated protein 2 (MAP2) immunostaining using the Axio Vision program. Synaptic marker expression and MAPK activation were confirmed by Western blotting. Results: Images captured after MAP2 immunocytochemistry showed significant (p < 0.05) enhancement of post-ischemic neurite outgrowth with LED treatment once and twice a day. MAPK activation was enhanced by LED treatment in both OGD-exposed and normal cells. The levels of synaptic markers such as PSD 95, GAP 43, and synaptophysin significantly increased with LED treatment in both OGD-exposed and normal cells (p < 0.05). Conclusion: Our data suggest that LED treatment may promote

  1. Effect of 710 nm visible light irradiation on neurite outgrowth in primary rat cortical neurons following ischemic insult

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Dong-Hee [Center for Neuroscience Research, SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul (Korea, Republic of); Department of Medical Science, Konkuk University School of Medicine, Seoul (Korea, Republic of); Lee, Kyoung-Hee; Kim, Ji-Hye; Kim, Moon Young [Center for Neuroscience Research, SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul (Korea, Republic of); Lim, Jeong Hoon [Department of Rehabilitation Medicine, Konkuk University School of Medicine, Seoul (Korea, Republic of); Rehabilitation Medicine, Division of Neurology, Department of Medicine, National University Hospital, National University Health System (Singapore); Lee, Jongmin, E-mail: leej@kuh.ac.kr [Center for Neuroscience Research, SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul (Korea, Republic of); Department of Rehabilitation Medicine, Konkuk University School of Medicine, Seoul (Korea, Republic of)

    2012-06-01

    Highlights: Black-Right-Pointing-Pointer 710 nm wavelength light (LED) has a protective effect in the stroke animal model. Black-Right-Pointing-Pointer We determined the effects of LED irradiation in vitro stroke model. Black-Right-Pointing-Pointer LED treatment promotes the neurite outgrowth through MAPK activation. Black-Right-Pointing-Pointer The level of synaptic markers significantly increased with LED treatment. Black-Right-Pointing-Pointer LED treatment protects cell death in the in vitro stroke model. -- Abstract: Objective: We previously reported that 710 nm Light-emitting Diode (LED) has a protective effect through cellular immunity activation in the stroke animal model. However, whether LED directly protects neurons suffering from neurodegeneration was entirely unknown. Therefore, we sought to determine the effects of 710 nm visible light irradiation on neuronal protection and neuronal outgrowth in an in vitro stroke model. Materials and methods: Primary cultured rat cortical neurons were exposed to oxygen-glucose deprivation (OGD) and reoxygenation and normal conditions. An LED array with a peak wavelength of 710 nm was placed beneath the covered culture dishes with the room light turned off and were irradiated accordingly. LED treatments (4 min at 4 J/cm{sup 2} and 50 mW/cm{sup 2}) were given once to four times within 8 h at 2 h intervals for 7 days. Mean neurite density, mean neurite diameter, and total fiber length were also measured after microtubule associated protein 2 (MAP2) immunostaining using the Axio Vision program. Synaptic marker expression and MAPK activation were confirmed by Western blotting. Results: Images captured after MAP2 immunocytochemistry showed significant (p < 0.05) enhancement of post-ischemic neurite outgrowth with LED treatment once and twice a day. MAPK activation was enhanced by LED treatment in both OGD-exposed and normal cells. The levels of synaptic markers such as PSD 95, GAP 43, and synaptophysin significantly

  2. Co-effects of matrix low elasticity and aligned topography on stem cell neurogenic differentiation and rapid neurite outgrowth

    Science.gov (United States)

    Yao, Shenglian; Liu, Xi; Yu, Shukui; Wang, Xiumei; Zhang, Shuming; Wu, Qiong; Sun, Xiaodan; Mao, Haiquan

    2016-05-01

    The development of novel biomaterials that deliver precise regulatory signals to direct stem cell fate for nerve regeneration is the focus of current intensive research efforts. In this study, a hierarchically aligned fibrillar fibrin hydrogel (AFG) that was fabricated through electrospinning and the concurrent molecular self-assembly process mimics both the soft and oriented features of nerve tissue, thus providing hybrid biophysical cues to instruct cell behavior in vitro and in vivo. The electrospun hydrogels were examined by scanning electron microscopy (SEM), polarized light microscopy, small angle X-ray scattering assay and atomic force microscopy (AFM), showing a hierarchically linear-ordered structure from the nanoscale to the macroscale with a soft elastic character (elasticity ~1 kPa). We found that this low elasticity and aligned topography of AFG exhibit co-effects on promoting the neurogenic differentiation of human umbilical cord mesenchymal stem cells (hUMSCs) in comparison to random fibrin hydrogel (RFG) and tissue culture plate (TCP) control after two week cell culture in growth medium lacking supplementation with soluble neurogenic induction factors. In addition, AFG also induces dorsal root ganglion (DRG) neurons to rapidly project numerous long neurite outgrowths longitudinally along the AFG fibers for a total neurite extension distance of 1.96 mm in three days in the absence of neurotrophic factor supplementation. Moreover, the AFG implanted in a rat T9 dorsal hemisection spinal cord injury model was found to promote endogenous neural cell fast migration and axonal invasion along AFG fibers, resulting in aligned tissue cables in vivo. Our results suggest that matrix stiffness and aligned topography may instruct stem cell neurogenic differentiation and rapid neurite outgrowth, providing great promise for biomaterial design for applications in nerve regeneration.The development of novel biomaterials that deliver precise regulatory signals to

  3. Co-effects of matrix low elasticity and aligned topography on stem cell neurogenic differentiation and rapid neurite outgrowth.

    Science.gov (United States)

    Yao, Shenglian; Liu, Xi; Yu, Shukui; Wang, Xiumei; Zhang, Shuming; Wu, Qiong; Sun, Xiaodan; Mao, Haiquan

    2016-05-21

    The development of novel biomaterials that deliver precise regulatory signals to direct stem cell fate for nerve regeneration is the focus of current intensive research efforts. In this study, a hierarchically aligned fibrillar fibrin hydrogel (AFG) that was fabricated through electrospinning and the concurrent molecular self-assembly process mimics both the soft and oriented features of nerve tissue, thus providing hybrid biophysical cues to instruct cell behavior in vitro and in vivo. The electrospun hydrogels were examined by scanning electron microscopy (SEM), polarized light microscopy, small angle X-ray scattering assay and atomic force microscopy (AFM), showing a hierarchically linear-ordered structure from the nanoscale to the macroscale with a soft elastic character (elasticity ∼1 kPa). We found that this low elasticity and aligned topography of AFG exhibit co-effects on promoting the neurogenic differentiation of human umbilical cord mesenchymal stem cells (hUMSCs) in comparison to random fibrin hydrogel (RFG) and tissue culture plate (TCP) control after two week cell culture in growth medium lacking supplementation with soluble neurogenic induction factors. In addition, AFG also induces dorsal root ganglion (DRG) neurons to rapidly project numerous long neurite outgrowths longitudinally along the AFG fibers for a total neurite extension distance of 1.96 mm in three days in the absence of neurotrophic factor supplementation. Moreover, the AFG implanted in a rat T9 dorsal hemisection spinal cord injury model was found to promote endogenous neural cell fast migration and axonal invasion along AFG fibers, resulting in aligned tissue cables in vivo. Our results suggest that matrix stiffness and aligned topography may instruct stem cell neurogenic differentiation and rapid neurite outgrowth, providing great promise for biomaterial design for applications in nerve regeneration.

  4. IL-10 Promotes Neurite Outgrowth and Synapse Formation in Cultured Cortical Neurons after the Oxygen-Glucose Deprivation via JAK1/STAT3 Pathway.

    Science.gov (United States)

    Chen, Hongbin; Lin, Wei; Zhang, Yixian; Lin, Longzai; Chen, Jianhao; Zeng, Yongping; Zheng, Mouwei; Zhuang, Zezhong; Du, Houwei; Chen, Ronghua; Liu, Nan

    2016-07-26

    As a classic immunoregulatory and anti-inflammatory cytokine, interleukin-10 (IL-10) provides neuroprotection in cerebral ischemia in vivo or oxygen-glucose deprivation (OGD)-induced injury in vitro. However, it remains blurred whether IL-10 promotes neurite outgrowth and synapse formation in cultured primary cortical neurons after OGD injury. In order to evaluate its effect on neuronal apoptosis, neurite outgrowth and synapse formation, we administered IL-10 or IL-10 neutralizing antibody (IL-10NA) to cultured rat primary cortical neurons after OGD injury. We found that IL-10 treatment activated the Janus kinase 1 (JAK1)/signal transducers and activators of transcription 3 (STAT3) signaling pathway. Moreover, IL-10 attenuated OGD-induced neuronal apoptosis by down-regulating the Bax expression and up-regulating the Bcl-2 expression, facilitated neurite outgrowth by increasing the expression of Netrin-1, and promoted synapse formation in cultured primary cortical neurons after OGD injury. These effects were partly abolished by JAK1 inhibitor GLPG0634. Contrarily, IL-10NA produced opposite effects on the cultured cortical neurons after OGD injury. Taken together, our findings suggest that IL-10 not only attenuates neuronal apoptosis, but also promotes neurite outgrowth and synapse formation via the JAK1/STAT3 signaling pathway in cultured primary cortical neurons after OGD injury.

  5. 7, 8, 3′-Trihydroxyflavone Promotes Neurite Outgrowth and Protects Against Bupivacaine-Induced Neurotoxicity in Mouse Dorsal Root Ganglion Neurons

    Science.gov (United States)

    Shi, Haohong; Luo, Xingjing

    2016-01-01

    Background 7, 8, 3′-trihydroxyflavone (THF) is a novel pro-neuronal small molecule that acts as a TrkB agonist. In this study, we examined the effect of THF on promoting neuronal growth and protecting anesthetics-induced neurotoxicity in dorsal root ganglion (DRG) neurons in vitro. Material/Methods Neonatal mouse DRG neurons were cultured in vitro and treated with various concentrations of THF. The effect of THF on neuronal growth was investigated by neurite outgrowth assay and Western blot. In addition, the protective effects of THF on bupivacaine-induced neurotoxicity were investigated by apoptosis TUNEL assay, neurite outgrowth assay, and Western blot, respectively. Results THF promoted neurite outgrowth of DRG neurons in dose-dependent manner, with an EC50 concentration of 67.4 nM. Western blot analysis showed THF activated TrkB signaling pathway by inducing TrkB phosphorylation. THF also rescued bupivacaine-induced neurotoxicity by reducing apoptosis and protecting neurite retraction in DRG neurons. Furthermore, the protection of THF in bupivacaine-injured neurotoxicity was directly associated with TrkB phosphorylation in a concentration-dependent manner in DRG neurons. Conclusions THF has pro-neuronal effect on DRG neurons by promoting neurite growth and protecting against bupivacaine-induced neurotoxicity, likely through TrkB activation. PMID:27371503

  6. Neuroligin-1 induces neurite outgrowth through interaction with neurexin-1ß and activation of fibroblast growth factor receptor-1

    DEFF Research Database (Denmark)

    Gjørlund, Michelle D; Nielsen, Janne; Pankratova, Stanislava

    2012-01-01

    Neurexin-1 (NRXN1) and neuroligin-1 (NLGN1) are synaptic cell adhesion molecules that connect pre- and postsynaptic neurons at synapses and mediate signaling across the synapse, which modulates synaptic activity and determines the properties of neuronal networks. Defects in the genes encoding NLGN1...... have been linked to cognitive diseases such as autism. The roles of both NRXN1 and NLGN1 during synaptogenesis have been studied extensively, but little is known about the role of these molecules in neuritogenesis, which eventually results in neuronal circuitry formation. The present study investigated...... the neuritogenic effect of NLGN1 in cultures of hippocampal neurons. Our results show that NLGN1, both in soluble and membrane-bound forms, induces neurite outgrowth that depends on the interaction with NRXN1ß and on activation of fibroblast growth factor receptor-1. In addition, we demonstrate that a synthetic...

  7. A Loss-of-Function Screen for Phosphatases that Regulate Neurite Outgrowth Identifies PTPN12 as a Negative Regulator of TrkB Tyrosine Phosphorylation

    DEFF Research Database (Denmark)

    Ambjørn, Malene; Dubreuil, Véronique; Miozzo, Federico

    2013-01-01

    Alterations in function of the neurotrophin BDNF are associated with neurodegeneration, cognitive decline, and psychiatric disorders. BDNF promotes axonal outgrowth and branching, regulates dendritic tree morphology and is important for axonal regeneration after injury, responses that largely....... This approach identified phosphatases from diverse families, which either positively or negatively modulate BDNF-TrkB-mediated neurite outgrowth, and most of which have little or no previously established function related to NT signaling. "Classical" protein tyrosine phosphatases (PTPs) accounted for 13......% of the candidate regulatory phosphatases. The top classical PTP identified as a negative regulator of BDNF-TrkB-mediated neurite outgrowth was PTPN12 (also called PTP-PEST). Validation and follow-up studies showed that endogenous PTPN12 antagonizes tyrosine phosphorylation of TrkB itself, and the downstream...

  8. The metabolic enhancer piracetam ameliorates the impairment of mitochondrial function and neurite outgrowth induced by beta-amyloid peptide.

    Science.gov (United States)

    Kurz, C; Ungerer, I; Lipka, U; Kirr, S; Schütt, T; Eckert, A; Leuner, K; Müller, W E

    2010-05-01

    beta-Amyloid peptide (Abeta) is implicated in the pathogenesis of Alzheimer's disease by initiating a cascade of events from mitochondrial dysfunction to neuronal death. The metabolic enhancer piracetam has been shown to improve mitochondrial dysfunction following brain aging and experimentally induced oxidative stress. We used cell lines (PC12 and HEK cells) and murine dissociated brain cells. The protective effects of piracetam in vitro and ex vivo on Abeta-induced impairment of mitochondrial function (as mitochondrial membrane potential and ATP production), on secretion of soluble Abeta and on neurite outgrowth in PC12 cells were investigated. Piracetam improves mitochondrial function of PC12 cells and acutely dissociated brain cells from young NMRI mice following exposure to extracellular Abeta(1-42). Similar protective effects against Abeta(1-42) were observed in dissociated brain cells from aged NMRI mice, or mice transgenic for mutant human amyloid precursor protein (APP) treated with piracetam for 14 days. Soluble Abeta load was markedly diminished in the brain of those animals after treatment with piracetam. Abeta production by HEK cells stably transfected with mutant human APP was elevated by oxidative stress and this was reduced by piracetam. Impairment of neuritogenesis is an important consequence of Abeta-induced mitochondrial dysfunction and Abeta-induced reduction of neurite growth in PC12 cells was substantially improved by piracetam. Our findings strongly support the concept of improving mitochondrial function as an approach to ameliorate the detrimental effects of Abeta on brain function.

  9. Nanostructured Polyaniline Coating on ITO Glass Promotes the Neurite Outgrowth of PC 12 Cells by Electrical Stimulation.

    Science.gov (United States)

    Wang, Liping; Huang, Qianwei; Wang, Jin-Ye

    2015-11-10

    A conducting polymer polyaniline (PANI) with nanostructure was synthesized on indium tin oxide (ITO) glass. The effect of electrical stimulation on the proliferation and the length of neurites of PC 12 cells was investigated. The dynamic protein adsorption on PANI and ITO surfaces in a cell culture medium was also compared with and without electrical stimulation. The adsorbed proteins were characterized using SDS-PAGE. A PANI coating on ITO surface was shown with 30-50 nm spherical nanostructure. The number of PC 12 cells was significantly greater on the PANI/ITO surface than on ITO and plate surfaces after cell seeding for 24 and 36 h. This result confirmed that the PANI coating is nontoxic to PC 12 cells. The electrical stimulation for 1, 2, and 4 h significantly enhanced the cell numbers for both PANI and ITO conducting surfaces. Moreover, the application of electrical stimulation also improved the neurite outgrowth of PC 12 cells, and the number of PC 12 cells with longer neurite lengths increased obviously under electrical stimulation for the PANI surface. From the mechanism, the adsorption of DMEM proteins was found to be enhanced by electrical stimulation for both PANI/ITO and ITO surfaces. A new band 2 (around 37 kDa) was observed from the collected adsorbed proteins when PC 12 cells were cultured on these surfaces, and culturing PC 12 cells also seemed to increase the amount of band 1 (around 90 kDa). When immersing PANI/ITO and ITO surfaces in a DMEM medium without a cell culture, the number of band 3 (around 70 kDa) and band 4 (around 45 kDa) proteins decreased compared to that of PC 12 cell cultured surfaces. These results are valuable for the design and improvement of the material performance for neural regeneration.

  10. Non-cytotoxic Concentration of Cisplatin Decreases Neuroplasticity-Related Proteins and Neurite Outgrowth Without Affecting the Expression of NGF in PC12 Cells.

    Science.gov (United States)

    Ferreira, Rafaela Scalco; Dos Santos, Neife Aparecida Guinaim; Martins, Nádia Maria; Fernandes, Laís Silva; Dos Santos, Antonio Cardozo

    2016-11-01

    Cisplatin is the most effective and neurotoxic platinum chemotherapeutic agent. It induces a peripheral neuropathy characterized by distal axonal degeneration that might progress to degeneration of cell bodies and apoptosis. Most symptoms occur nearby distal axonal branches and axonal degeneration might induce peripheral neuropathy regardless neuronal apoptosis. The toxic mechanism of cisplatin has been mainly associated with DNA damage, but cisplatin might also affect neurite outgrowth. Nevertheless, the neurotoxic mechanism of cisplatin remains unclear. We investigated the early effects of cisplatin on axonal plasticity by using non-cytotoxic concentrations of cisplatin and PC12 cells as a model of neurite outgrowth and differentiation. PC12 cells express NGF-receptors (trkA) and respond to NGF by forming neurites, branches and synaptic vesicles. For comparison, we used a neuronal model (SH-SY5Y cells) that does not express trkA nor responds to NGF. Cisplatin did not change NGF expression in PC12 cells and decreased neurite outgrowth in both models, suggesting a NGF/trkA independent mechanism. It also reduced axonal growth (GAP-43) and synaptic (synapsin I and synaptophysin) proteins in PC12 cells, without inducing mitochondrial damage or apoptosis. Therefore, cisplatin might affect axonal plasticity before DNA damage, NGF/trkA down-regulation, mitochondrial damage or neuronal apoptosis. This is the first study to show that neuroplasticity-related proteins might be early targets of the neurotoxic action of cisplatin and their role on cisplatin-induced peripheral neuropathy should be investigated in vivo.

  11. Astrocytic αVβ3 integrin inhibits neurite outgrowth and promotes retraction of neuronal processes by clustering Thy-1.

    Directory of Open Access Journals (Sweden)

    Rodrigo Herrera-Molina

    Full Text Available Thy-1 is a membrane glycoprotein suggested to stabilize or inhibit growth of neuronal processes. However, its precise function has remained obscure, because its endogenous ligand is unknown. We previously showed that Thy-1 binds directly to α(Vβ(3 integrin in trans eliciting responses in astrocytes. Nonetheless, whether α(Vβ(3 integrin might also serve as a Thy-1-ligand triggering a neuronal response has not been explored. Thus, utilizing primary neurons and a neuron-derived cell line CAD, Thy-1-mediated effects of α(Vβ(3 integrin on growth and retraction of neuronal processes were tested. In astrocyte-neuron co-cultures, endogenous α(Vβ(3 integrin restricted neurite outgrowth. Likewise, α(Vβ(3-Fc was sufficient to suppress neurite extension in Thy-1(+, but not in Thy-1(- CAD cells. In differentiating primary neurons exposed to α(Vβ(3-Fc, fewer and shorter dendrites were detected. This effect was abolished by cleavage of Thy-1 from the neuronal surface using phosphoinositide-specific phospholipase C (PI-PLC. Moreover, α(Vβ(3-Fc also induced retraction of already extended Thy-1(+-axon-like neurites in differentiated CAD cells as well as of axonal terminals in differentiated primary neurons. Axonal retraction occurred when redistribution and clustering of Thy-1 molecules in the plasma membrane was induced by α(Vβ(3 integrin. Binding of α(Vβ(3-Fc was detected in Thy-1 clusters during axon retraction of primary neurons. Moreover, α(Vβ(3-Fc-induced Thy-1 clustering correlated in time and space with redistribution and inactivation of Src kinase. Thus, our data indicates that α(Vβ(3 integrin is a ligand for Thy-1 that upon binding not only restricts the growth of neurites, but also induces retraction of already existing processes by inducing Thy-1 clustering. We propose that these events participate in bi-directional astrocyte-neuron communication relevant to axonal repair after neuronal damage.

  12. Electrical Stimulation of Schwann Cells Promotes Sustained Increases in Neurite Outgrowth

    OpenAIRE

    Koppes, Abigail N.; Nordberg, Andrea L.; Paolillo, Gina M.; Goodsell, Nicole M.; Darwish, Haley A.; Zhang, Linxia; Thompson, Deanna M.

    2013-01-01

    Endogenous electric fields are instructive during embryogenesis by acting to direct cell migration, and postnatally, they can promote axonal growth after injury (McCaig 1991, Al-Majed 2000). However, the mechanisms for these changes are not well understood. Application of an appropriate electrical stimulus may increase the rate and success of nerve repair by directly promoting axonal growth. Previously, DC electrical stimulation at 50 mV/mm (1 mA, 8 h duration) was shown to promote neurite ou...

  13. miR-103 Promotes Neurite Outgrowth and Suppresses Cells Apoptosis by Targeting Prostaglandin-Endoperoxide Synthase 2 in Cellular Models of Alzheimer's Disease.

    Science.gov (United States)

    Yang, Hui; Wang, Hongcai; Shu, Yongwei; Li, Xuling

    2018-01-01

    miR-103 has been reported to be decreased in brain of transgenic mouse model of Alzheimer's disease (AD) and in cerebrospinal fluid (CSF) of AD patients, while the detailed mechanism of its effect on AD is obscure, thus this study aimed to investigate the effect of miR-103 expression on neurite outgrowth and cells apoptosis as well as its targets in cellular models of AD. Blank mimic (NC1-mimic), miR-103 mimic, blank inhibitor (NC2-mimic) and miR-103 inhibitor plasmids were transferred into PC12 cellular AD model and Cellular AD model of cerebral cortex neurons which were established by Aβ1-42 insult. Rescue experiment was subsequently performed by transferring Prostaglandin-endoperoxide synthase 2 (PTGS2) and miR-103 mimic plasmid. mRNA and protein expressions were detected by qPCR and Western Blot assays. Total neurite outgrowth was detected by microscope, cells apoptosis was determined by Hoechst/PI assay, and apoptotic markers Caspase 3 and p38 expressions were determined by Western Blot assay. In both PC12 and cerebral cortex neurons cellular AD models, miR-103 mimic increases the total neurite outgrowth compared with NC1-mimic, while miR-103 inhibitor decreases the total neurite outgrowth than NC2-inhibitor. The apoptosis rate was decreased in miR-103 mimic group than NC1-mimic group while increased in miR-103 inhibitor group than NC2-inhibitor group. PTGS2, Adisintegrin and metalloproteinase 10 (ADAM10) and neprilysin (NEP) were selected as target genes of miR-103 by bioinformatics analysis. And PTGS2 was found to be conversely regulated by miR-103 expression while ADAM10 and NEP were not affected. After transfection by PTGS2 and miR-103 mimic plasmid in PC12 cellular AD model, the total neurite growth was shortened compared with miR-103 mimic group, and cells apoptosis was enhanced which indicated PTGS2 mimic attenuated the influence of miR-103 mimic on progression of AD. In conclusion, miR-103 promotes total neurite outgrowth and inhibits cells apoptosis

  14. Neurite outgrowth in human induced pluripotent stem cell-derived neurons as a high-throughput screen for developmental neurotoxicity or neurotoxicity.

    Science.gov (United States)

    Ryan, Kristen R; Sirenko, Oksana; Parham, Fred; Hsieh, Jui-Hua; Cromwell, Evan F; Tice, Raymond R; Behl, Mamta

    2016-03-01

    Due to the increasing prevalence of neurological disorders and the large number of untested compounds in the environment, there is a need to develop reliable and efficient screening tools to identify environmental chemicals that could potentially affect neurological development. Herein, we report on a library of 80 compounds screened for their ability to inhibit neurite outgrowth, a process by which compounds may elicit developmental neurotoxicity, in a high-throughput, high-content assay using human neurons derived from induced pluripotent stem cells (iPSC). The library contains a diverse set of compounds including those that have been known to be associated with developmental neurotoxicity (DNT) and/or neurotoxicity (NT), environmental compounds with unknown neurotoxic potential (e.g., polycyclic aromatic hydrocarbons (PAHs) and flame retardants (FRs)), as well as compounds with no documented neurotoxic potential. Neurons were treated for 72h across a 6-point concentration range (∼0.3-100μM) in 384-well plates. Effects on neurite outgrowth were assessed by quantifying total outgrowth, branches, and processes. We also assessed the number ofviable cells per well. Concentration-response profiles were evaluated using a Hill model to derive benchmark concentration (BMC) values. Assay performance was evaluated using positive and negative controls and test replicates. Compounds were ranked by activity and selectivity (i.e., specific effects on neurite outgrowth in the absence of concomitant cytotoxicity) and repeat studies were conducted to confirm selectivity. Among the 80 compounds tested, 38 compounds were active, of which 16 selectively inhibited neurite outgrowth. Of these 16 compounds, 12 were known to cause DNT/NT and the remaining 4 compounds included 3 PAHs and 1 FR. In independent repeat studies, 14/16 selective compounds were reproducibly active in the assay, of which only 6 were selective for inhibition of neurite outgrowth. These 6 compounds were

  15. Zebrafish diras1 Promoted Neurite Outgrowth in Neuro-2a Cells and Maintained Trigeminal Ganglion Neurons In Vivo via Rac1-Dependent Pathway.

    Science.gov (United States)

    Yeh, Chi-Wei; Hsu, Li-Sung

    2016-12-01

    The small GTPase Ras superfamily regulates several neuronal functions including neurite outgrowth and neuron proliferation. In this study, zebrafish diras1a and diras1b were identified and were found to be mainly expressed in the central nervous system and dorsal neuron ganglion. Overexpression of green fluorescent protein (GFP)-diras1a or GFP-diras1b triggered neurite outgrowth of Neuro-2a cells. The wild types, but not the C terminus truncated forms, of diras1a and diras1b elevated the protein level of Ras-related C3 botulinum toxin substrate 1 (Rac1) and downregulated Ras homologous member A (RhoA) expression. Glutathione S-transferase (GST) pull-down assay also revealed that diras1a and diras1b enhanced Rac1 activity. Interfering with Rac1, Pak1, or cyclin-dependent kinase 5 (CDK5) activity or with the Arp2/3 inhibitor prevented diras1a and diras1b from mediating the neurite outgrowth effects. In the zebrafish model, knockdown of diras1a and/or diras1b by morpholino antisense oligonucleotides not only reduced axon guidance but also caused the loss of trigeminal ganglion without affecting the precursor markers, such as ngn1 and neuroD. Co-injection with messenger RNA (mRNA) derived from mouse diras1 or constitutively active human Rac1 restored the population of trigeminal ganglion. In conclusion, we provided preliminary evidence that diras1 is involved in neurite outgrowth and maintains the number of trigeminal ganglions through the Rac1-dependent pathway.

  16. Extracellular Nm23H1 stimulates neurite outgrowth from dorsal root ganglia neurons in vitro independently of nerve growth factor supplementation or its nucleoside diphosphate kinase activity

    International Nuclear Information System (INIS)

    Wright, K.T.; Seabright, R.; Logan, A.; Lilly, A.J.; Khanim, F.; Bunce, C.M.; Johnson, W.E.B.

    2010-01-01

    Research highlights: → Extracellular Nm23H1 stimulates nerve growth. → Extracellular Nm23H1 provides pathfinding cues to growth cones. → The neurotrophic activity of Nm23H1 is independent of NDP kinase activity. → The neurotrophic activity of Nm23H1 is independent of NGF. -- Abstract: The nucleoside diphosphate (NDP) kinase, Nm23H1, is a highly expressed during neuronal development, whilst induced over-expression in neuronal cells results in increased neurite outgrowth. Extracellular Nm23H1 affects the survival, proliferation and differentiation of non-neuronal cells. Therefore, this study has examined whether extracellular Nm23H1 regulates nerve growth. We have immobilised recombinant Nm23H1 proteins to defined locations of culture plates, which were then seeded with explants of embryonic chick dorsal root ganglia (DRG) or dissociated adult rat DRG neurons. The substratum-bound extracellular Nm23H1 was stimulatory for neurite outgrowth from chick DRG explants in a concentration-dependent manner. On high concentrations of Nm23H1, chick DRG neurite outgrowth was extensive and effectively limited to the location of the Nm23H1, i.e. neuronal growth cones turned away from adjacent collagen-coated substrata. Nm23H1-coated substrata also significantly enhanced rat DRG neuronal cell adhesion and neurite outgrowth in comparison to collagen-coated substrata. These effects were independent of NGF supplementation. Recombinant Nm23H1 (H118F), which does not possess NDP kinase activity, exhibited the same activity as the wild-type protein. Hence, a novel neuro-stimulatory activity for extracellular Nm23H1 has been identified in vitro, which may function in developing neuronal systems.

  17. Extremely Low-Frequency Electromagnetic Fields Promote In Vitro Neuronal Differentiation and Neurite Outgrowth of Embryonic Neural Stem Cells via Up-Regulating TRPC1

    Science.gov (United States)

    Ma, Qinlong; Chen, Chunhai; Deng, Ping; Zhu, Gang; Lin, Min; Zhang, Lei; Xu, Shangcheng; He, Mindi; Lu, Yonghui; Duan, Weixia; Pi, Huifeng; Cao, Zhengwang; Pei, Liping; Li, Min; Liu, Chuan; Zhang, Yanwen; Zhong, Min; Zhou, Zhou; Yu, Zhengping

    2016-01-01

    Exposure to extremely low-frequency electromagnetic fields (ELF-EMFs) can enhance hippocampal neurogenesis in adult mice. However, little is focused on the effects of ELF-EMFs on embryonic neurogenesis. Here, we studied the potential effects of ELF-EMFs on embryonic neural stem cells (eNSCs). We exposed eNSCs to ELF-EMF (50 Hz, 1 mT) for 1, 2, and 3 days with 4 hours per day. We found that eNSC proliferation and maintenance were significantly enhanced after ELF-EMF exposure in proliferation medium. ELF-EMF exposure increased the ratio of differentiated neurons and promoted the neurite outgrowth of eNSC-derived neurons without influencing astrocyes differentiation and the cell apoptosis. In addition, the expression of the proneural genes, NeuroD and Ngn1, which are crucial for neuronal differentiation and neurite outgrowth, was increased after ELF-EMF exposure. Moreover, the expression of transient receptor potential canonical 1 (TRPC1) was significantly up-regulated accompanied by increased the peak amplitude of intracellular calcium level induced by ELF-EMF. Furthermore, silencing TRPC1 expression eliminated the up-regulation of the proneural genes and the promotion of neuronal differentiation and neurite outgrowth induced by ELF-EMF. These results suggest that ELF-EMF exposure promotes the neuronal differentiation and neurite outgrowth of eNSCs via up-regulation the expression of TRPC1 and proneural genes (NeuroD and Ngn1). These findings also provide new insights in understanding the effects of ELF-EMF exposure on embryonic brain development. PMID:26950212

  18. Extracellular Nm23H1 stimulates neurite outgrowth from dorsal root ganglia neurons in vitro independently of nerve growth factor supplementation or its nucleoside diphosphate kinase activity

    Energy Technology Data Exchange (ETDEWEB)

    Wright, K.T. [Keele University at the RJAH Orthopaedic Hospital, Oswestry, Shropshire (United Kingdom); Seabright, R.; Logan, A. [Neuropharmacology and Neurobiology, School of Clinical and Experimental Medicine, Birmingham University, Birmingham (United Kingdom); Lilly, A.J.; Khanim, F.; Bunce, C.M. [Biosciences, Birmingham University, Birmingham (United Kingdom); Johnson, W.E.B., E-mail: w.e.johnson@aston.ac.uk [Life and Health Sciences, Aston University, Birmingham (United Kingdom)

    2010-07-16

    Research highlights: {yields} Extracellular Nm23H1 stimulates nerve growth. {yields} Extracellular Nm23H1 provides pathfinding cues to growth cones. {yields} The neurotrophic activity of Nm23H1 is independent of NDP kinase activity. {yields} The neurotrophic activity of Nm23H1 is independent of NGF. -- Abstract: The nucleoside diphosphate (NDP) kinase, Nm23H1, is a highly expressed during neuronal development, whilst induced over-expression in neuronal cells results in increased neurite outgrowth. Extracellular Nm23H1 affects the survival, proliferation and differentiation of non-neuronal cells. Therefore, this study has examined whether extracellular Nm23H1 regulates nerve growth. We have immobilised recombinant Nm23H1 proteins to defined locations of culture plates, which were then seeded with explants of embryonic chick dorsal root ganglia (DRG) or dissociated adult rat DRG neurons. The substratum-bound extracellular Nm23H1 was stimulatory for neurite outgrowth from chick DRG explants in a concentration-dependent manner. On high concentrations of Nm23H1, chick DRG neurite outgrowth was extensive and effectively limited to the location of the Nm23H1, i.e. neuronal growth cones turned away from adjacent collagen-coated substrata. Nm23H1-coated substrata also significantly enhanced rat DRG neuronal cell adhesion and neurite outgrowth in comparison to collagen-coated substrata. These effects were independent of NGF supplementation. Recombinant Nm23H1 (H118F), which does not possess NDP kinase activity, exhibited the same activity as the wild-type protein. Hence, a novel neuro-stimulatory activity for extracellular Nm23H1 has been identified in vitro, which may function in developing neuronal systems.

  19. The protection of acetylcholinesterase inhibitor on β-amyloid-induced injury of neurite outgrowth via regulating axon guidance related genes expression in neuronal cells

    OpenAIRE

    Shen, Jiao-Ning; Wang, Deng-Shun; Wang, Rui

    2012-01-01

    Cognitive deficits in AD correlate with progressive synaptic dysfunction and loss. The Rho family of small GTPases, including Rho, Rac, and Cdc42, has a central role in cellular motility and cytokinesis. Acetylcholinesterase inhibitor has been found to protect cells against a broad range of reagents-induced injuries. Present studies examined if the effect of HupA on neurite outgrowth in Aβ-treated neuronal cells executed via regulating Rho-GTPase mediated axon guidance relative gene expressio...

  20. The protection of acetylcholinesterase inhibitor on β-amyloid-induced injury of neurite outgrowth via regulating axon guidance related genes expression in neuronal cells

    Science.gov (United States)

    Shen, Jiao-Ning; Wang, Deng-Shun; Wang, Rui

    2012-01-01

    Cognitive deficits in AD correlate with progressive synaptic dysfunction and loss. The Rho family of small GTPases, including Rho, Rac, and Cdc42, has a central role in cellular motility and cytokinesis. Acetylcholinesterase inhibitor has been found to protect cells against a broad range of reagents-induced injuries. Present studies examined if the effect of HupA on neurite outgrowth in Aβ-treated neuronal cells executed via regulating Rho-GTPase mediated axon guidance relative gene expression. Affymetrix cDNA microarray assay followed by real-time RT-PCR and Western Blotting analysis were used to elucidate and analyze the signaling pathway involved in Aβ and HupA’s effects. The effects of Aβ and HupA on the neurite outgrowth were further confirmed via immunofluorescence staining. Aβ up-regulated the mRNA expressions of NFAT5, LIMK1, EPHA1, NTN4 and RAC2 markedly in SH-SY5Y cells. Co-incubation of Aβ and HupA reversed or decreased the changes of NFAT5, NTN4, RAC2, CDC42 and SEMA4F. HupA treated alone increased NFAT5, LIMK1, NTN4 significantly. Following qRT-PCR validation showed that the correlation of the gene expression ratio between microarray and qRT-PCR is significant. Western blot result showed that the change of CDC42 protein is consistent with the mRNA level while RAC2 is not. The morphological results confirmed that HupA improved, or partly reversed, the Aβ-induced damage of neurite outgrowth. The protective effect of HupA from Aβ induced morphological injury might be correlative to, at least partially, regulating the network of neurite outgrowth related genes. PMID:23119107

  1. The protection of acetylcholinesterase inhibitor on β-amyloid-induced the injury of neurite outgrowth via regulating axon guidance related genes expression in neuronal cells.

    Science.gov (United States)

    Shen, Jiao-Ning; Wang, Deng-Shun; Wang, Rui

    2012-01-01

    Cognitive deficits in AD correlate with progressive synaptic dysfunction and loss. The Rho family of small GTPases, including Rho, Rac, and Cdc42, has a central role in cellular motility and cytokinesis. Acetylcholinesterase inhibitor has been found to protect cells against a broad range of reagents-induced injuries. Present studies examined if the effect of HupA on neurite outgrowth in Aβ-treated neuronal cells executed via regulating Rho-GTPase mediated axon guidance relative gene expression. Affymetrix cDNA microarray assay followed by real-time RT-PCR and Western Blotting analysis were used to elucidate and analyze the signaling pathway involved in Aβ and HupA's effects. The effects of Aβ and HupA on the neurite outgrowth were further confirmed via immunofluorescence staining. Aβ up-regulated the mRNA expressions of NFAT5, LIMK1, EPHA1, NTN4 and RAC2 markedly in SH-SY5Y cells. Co-incubation of Aβ and HupA reversed or decreased the changes of NFAT5, NTN4, RAC2, CDC42 and SEMA4F. HupA treated alone increased NFAT5, LIMK1, NTN4 significantly. Following qRT-PCR validation showed that the correlation of the gene expression ratio between microarray and qRT-PCR is significant. Western blot result showed that the change of CDC42 protein is consistent with the mRNA level while RAC2 is not. The morphological results confirmed that HupA improved, or partly reversed, the Aβ-induced damage of neurite outgrowth. The protective effect of HupA from Aβ induced morphological injury might be correlative to, at least partially, regulating the network of neurite outgrowth related genes.

  2. Cocaine- and amphetamine-regulated transcript facilitates the neurite outgrowth in cortical neurons after oxygen and glucose deprivation through PTN-dependent pathway.

    Science.gov (United States)

    Wang, Y; Qiu, B; Liu, J; Zhu, Wei-Guo; Zhu, S

    2014-09-26

    Cocaine- and amphetamine-regulated transcript (CART) is a neuropeptide that plays neuroprotective roles in cerebral ischemia and reperfusion (I/R) injury in animal models or oxygen and glucose deprivation (OGD) in cultured neurons. Recent data suggest that intranasal CART treatment facilitates neuroregeneration in stroke brain. However, little is known about the effects of post-treatment with CART during the neuronal recovery after OGD and reoxygenation in cultured primary cortical neurons. The present study was to investigate the role of CART treated after OGD injury in neurons. Primary mouse cortical neurons were subjected to OGD and then treated with CART. Our data show that post-treatment with CART reduced the neuronal apoptosis caused by OGD injury. In addition, CART repaired OGD-impaired cortical neurons by increasing the expression of growth-associated protein 43 (GAP43), which promotes neurite outgrowth. This effect depends on pleiotrophin (PTN) as siRNA-mediated PTN knockdown totally abolished the increase in CART-stimulated GAP43 protein levels. In summary, our findings demonstrate that CART repairs the neuronal injury after OGD by facilitating neurite outgrowth through PTN-dependent pathway. The role for CART in neurite outgrowth makes it a new potential therapeutic agent for the treatment of neurodegenerative diseases. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. MiR-130a regulates neurite outgrowth and dendritic spine density by targeting MeCP2

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    Yunjia Zhang

    2016-06-01

    Full Text Available ABSTRACT MicroRNAs (miRNAs are critical for both development and function of the central nervous system. Significant evidence suggests that abnormal expression of miRNAs is associated with neurodevelopmental disorders. MeCP2 protein is an epigenetic regulator repressing or activating gene transcription by binding to methylated DNA. Both loss-of-function and gain-of-function mutations in the MECP2 gene lead to neurodevelopmental disorders such as Rett syndrome, autism and MECP2 duplication syndrome. In this study, we demonstrate that miR-130a inhibits neurite outgrowth and reduces dendritic spine density as well as dendritic complexity. Bioinformatics analyses, cell cultures and biochemical experiments indicate that miR-130a targets MECP2 and down-regulates MeCP2 protein expression. Furthermore, expression of the wild-type MeCP2, but not a loss-of-function mutant, rescues the miR-130a-induced phenotype. Our study uncovers the MECP2 gene as a previous unknown target for miR-130a, supporting that miR-130a may play a role in neurodevelopment by regulating MeCP2. Together with data from other groups, our work suggests that a feedback regulatory mechanism involving both miR-130a and MeCP2 may serve to ensure their appropriate expression and function in neural development.

  4. Disassembly of microtubules and inhibition of neurite outgrowth, neuroblastoma cell proliferation, and MAP kinase tyrosine dephosphorylation by dibenzyl trisulphide.

    Science.gov (United States)

    Rösner, H; Williams, L A; Jung, A; Kraus, W

    2001-08-22

    Dibenzyl trisulphide (DTS), a main lipophilic compound in Petiveria alliacea L. (Phytolaccaceae), was identified as one of the active immunomodulatory compounds in extracts of the plant. To learn more about its biological activities and molecular mechanisms, we conducted one-dimensional NMR interaction studies with bovine serum albumin (BSA) and tested DTS and related compounds in two well-established neuronal cell-and-tissue culture systems. We found that DTS preferentially binds to an aromatic region of BSA which is rich in tyrosyl residues. In SH-SY5Y neuroblastoma cells, DTS attenuates the dephosphorylation of tyrosyl residues of MAP kinase (erk1/erk2). In the same neuroblastoma cell line and in Wistar 38 human lung fibroblasts, DTS causes a reversible disassembly of microtubules, but it did not affect actin dynamics. Probably due to the disruption of the microtubule dynamics, DTS also inhibits neuroblastoma cell proliferation and neurite outgrowth from spinal cord explants. Related dibenzyl compounds with none, one, or two sulphur atoms were found to be significantly less effective. These data confirmed that the natural compound DTS has a diverse spectrum of biological properties, including cytostatic and neurotoxic actions in addition to immunomodulatory activities.

  5. Ubiquitination of MBNL1 Is Required for Its Cytoplasmic Localization and Function in Promoting Neurite Outgrowth

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    Pei-Ying Wang

    2018-02-01

    Full Text Available The Muscleblind-like protein family (MBNL plays an important role in regulating the transition between differentiation and pluripotency and in the pathogenesis of myotonic dystrophy type 1 (DM1, a CTG expansion disorder. How different MBNL isoforms contribute to the differentiation and are affected in DM1 has not been investigated. Here, we show that the MBNL1 cytoplasmic, but not nuclear, isoform promotes neurite morphogenesis and reverses the morphological defects caused by expanded CUG RNA. Cytoplasmic MBNL1 is polyubiquitinated by lysine 63 (K63. Reduced cytoplasmic MBNL1 in the DM1 mouse brain is consistent with the reduced extent of K63 ubiquitination. Expanded CUG RNA induced the deubiqutination of cytoplasmic MBNL1, which resulted in nuclear translocation and morphological impairment that could be ameliorated by inhibiting K63-linked polyubiquitin chain degradation. Our results suggest that K63-linked ubiquitination of MBNL1 is required for its cytoplasmic localization and that deubiquitination of cytoplasmic MBNL1 is pathogenic in the DM1 brain.

  6. Neurite outgrowth stimulatory effects of myco synthesized AuNPs from Hericium erinaceus (Bull.: Fr.) Pers. on pheochromocytoma (PC-12) cells.

    Science.gov (United States)

    Raman, Jegadeesh; Lakshmanan, Hariprasath; John, Priscilla A; Zhijian, Chan; Periasamy, Vengadesh; David, Pamela; Naidu, Murali; Sabaratnam, Vikineswary

    2015-01-01

    Hericium erinaceus has been reported to have a wide range of medicinal properties such as stimulation of neurite outgrowth, promotion of functional recovery of axonotmetic peroneal nerve injury, antioxidant, antihypertensive, and antidiabetic properties. In recent years, the green synthesis of gold nanoparticles (AuNPs) has attracted intense interest due to the potential use in biomedical applications. The aim of this study was to investigate the effects of AuNPs from aqueous extract of H. erinaceus on neurite outgrowth of rat pheochromocytoma (PC-12) cells. The formation of AuNPs was characterized by UV-visible spectrum, energy dispersive X-ray (EDX), field-emission scanning electron microscope (FESEM), transmission electron microscopy (TEM), particle size distribution, and Fourier transform-infrared spectroscopy (FTIR). Furthermore, the neurite extension study of synthesized AuNPs was evaluated by in vitro assay. The AuNPs exhibited maximum absorbance between 510 and 600 nm in UV-visible spectrum. FESEM and TEM images showed the existence of nanoparticles with sizes of 20-40 nm. FTIR measurements were carried out to identify the possible biomolecules responsible for capping and efficient stabilization of the nanoparticles. The purity and the crystalline properties were confirmed by EDX diffraction analysis, which showed strong signals with energy peaks in the range of 2-2.4 keV, indicating the existence of gold atoms. The synthesized AuNPs showed significant neurite extension on PC-12 cells. Nerve growth factor 50 ng/mL was used as a positive control. Treatment with different concentrations (nanograms) of AuNPs resulted in neuronal differentiation and neuronal elongation. AuNPs induced maximum neurite outgrowth of 13% at 600 ng/mL concentration. In this study, the AuNPs synthesis was achieved by a simple, low-cost, and rapid bioreduction approach. AuNPs were shown to have potential neuronal differentiation and stimulated neurite outgrowth. The water

  7. Effects of sub-lethal neurite outgrowth inhibitory concentrations of chlorpyrifos oxon on cytoskeletal proteins and acetylcholinesterase in differentiating N2a cells

    Energy Technology Data Exchange (ETDEWEB)

    Flaskos, J., E-mail: flaskos@vet.auth.gr [Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Nikolaidis, E. [Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Harris, W. [School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS (United Kingdom); Sachana, M. [Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Hargreaves, A.J., E-mail: alan.hargreaves@ntu.ac.uk [School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS (United Kingdom)

    2011-11-15

    Previous work in our laboratory has shown that sub-lethal concentrations (1-10 {mu}M) of chlorpyrifos (CPF), diazinon (DZ) and diazinon oxon (DZO) inhibit the outgrowth of axon-like neurites in differentiating mouse N2a neuroblastoma cells concomitant with altered levels and/or phosphorylation state of axonal cytoskeleton and growth-associated proteins. The aim of the present work was to determine whether chlorpyrifos oxon (CPO) was capable of inhibiting N2a cell differentiation in a similar manner. Using experimental conditions similar to our previous work, sub-lethal concentrations (1-10 {mu}M) of CPO were found to inhibit N2a cell differentiation. However, unlike previous studies with DZ and DZO, there was a high level of sustained inhibition of acetylcholinesterase (AChE) in CPO treated cells. Impairment of neurite outgrowth was also associated with reduced levels of growth associated protein-43 and neurofilament heavy chain (NFH), and the distribution of NFH in cells stained by indirect immunofluorescence was disrupted. However, in contrast to previous findings for DZO, the absolute level of phosphorylated NFH was unaffected by CPO exposure. Taken together, the findings suggest that sub-lethal concentrations of CPO inhibit axon outgrowth in differentiating N2a cells and that this effect involves reduced levels of two proteins that play key roles in axon outgrowth and maintenance. Although the inhibition of neurite outgrowth is unlikely to involve AChE inhibition directly, further work will help to determine whether the persistent inhibition of AChE by CPO can account for the different effects induced by CPO and DZO on the levels of total and phosphorylated NFH. -- Highlights: Black-Right-Pointing-Pointer Sub-lethal levels of chlorpyrifos oxon inhibit neurite outgrowth in N2a cells Black-Right-Pointing-Pointer Acetylcholinesterase exhibits sustained inhibition throughout exposure Black-Right-Pointing-Pointer The levels of neurofilament heavy chain and GAP-43

  8. Effects of sub-lethal neurite outgrowth inhibitory concentrations of chlorpyrifos oxon on cytoskeletal proteins and acetylcholinesterase in differentiating N2a cells

    International Nuclear Information System (INIS)

    Flaskos, J.; Nikolaidis, E.; Harris, W.; Sachana, M.; Hargreaves, A.J.

    2011-01-01

    Previous work in our laboratory has shown that sub-lethal concentrations (1–10 μM) of chlorpyrifos (CPF), diazinon (DZ) and diazinon oxon (DZO) inhibit the outgrowth of axon-like neurites in differentiating mouse N2a neuroblastoma cells concomitant with altered levels and/or phosphorylation state of axonal cytoskeleton and growth-associated proteins. The aim of the present work was to determine whether chlorpyrifos oxon (CPO) was capable of inhibiting N2a cell differentiation in a similar manner. Using experimental conditions similar to our previous work, sub-lethal concentrations (1–10 μM) of CPO were found to inhibit N2a cell differentiation. However, unlike previous studies with DZ and DZO, there was a high level of sustained inhibition of acetylcholinesterase (AChE) in CPO treated cells. Impairment of neurite outgrowth was also associated with reduced levels of growth associated protein-43 and neurofilament heavy chain (NFH), and the distribution of NFH in cells stained by indirect immunofluorescence was disrupted. However, in contrast to previous findings for DZO, the absolute level of phosphorylated NFH was unaffected by CPO exposure. Taken together, the findings suggest that sub-lethal concentrations of CPO inhibit axon outgrowth in differentiating N2a cells and that this effect involves reduced levels of two proteins that play key roles in axon outgrowth and maintenance. Although the inhibition of neurite outgrowth is unlikely to involve AChE inhibition directly, further work will help to determine whether the persistent inhibition of AChE by CPO can account for the different effects induced by CPO and DZO on the levels of total and phosphorylated NFH. -- Highlights: ► Sub-lethal levels of chlorpyrifos oxon inhibit neurite outgrowth in N2a cells ► Acetylcholinesterase exhibits sustained inhibition throughout exposure ► The levels of neurofilament heavy chain and GAP-43 protein are reduced ► Neurofilament heavy chain forms aggregates in cell

  9. Atorvastatin enhances neurite outgrowth in cortical neurons in vitro via up-regulating the Akt/mTOR and Akt/GSK-3β signaling pathways

    Science.gov (United States)

    Jin, Ying; Sui, Hai-juan; Dong, Yan; Ding, Qi; Qu, Wen-hui; Yu, Sheng-xue; Jin, Ying-xin

    2012-01-01

    Aim: To investigate whether atorvastatin can promote formation of neurites in cultured cortical neurons and the signaling mechanisms responsible for this effect. Methods: Cultured rat cerebral cortical neurons were incubated with atorvastatin (0.05–10 μmol/L) for various lengths of time. For pharmacological experiments, inhibitors were added 30 min prior to addition of atorvastatin. Control cultures received a similar amount of DMSO. Following the treatment period, phase-contrast digital images were taken. Digital images of neurons were analyzed for total neurite branch length (TNBL), neurite number, terminal branch number, and soma area by SPOT Advanced Imaging software. After incubation with atorvastatin for 48 h, the levels of phosphorylated 3-phosphoinoside-dependent protein kinase-1 (PDK1), phospho-Akt, phosphorylated mammalian target of rapamycin (mTOR), phosphorylated 4E-binding protein 1 (4E-BP1), p70S6 kinase (p70S6K), and glycogen synthase kinase-3β (GSK-3β) in the cortical neurons were evaluated using Western blotting analyses. Results: Atorvastatin (0.05–10 μmol/L) resulted in dose-dependent increase in neurite number and length in these neurons. Pretreatment of the cortical neurons with phosphatidylinositol 3-kinase (PI3K) inhibitors LY294002 (30 μmol/L) and wortmannin (5 μmol/L), Akt inhibitor tricribine (1 μmol/L) or mTOR inhibitor rapamycin (100 nmol/L) blocked the atorvastatin-induced increase in neurite outgrowth, suggesting that atorvastatin promoted neurite outgrowth via activating the PI3K/Akt/mTOR signaling pathway. Atorvastatin (10 μmol/L) significantly increased the levels of phosphorylated PDK1, Akt and mTOR in the cortical neurons, which were prevented by LY294002 (30 μmol/L). Moreover, atorvastatin (10 μmol/L) stimulated the phosphorylation of 4E-BP1 and p70S6K, the substrates of mTOR, in the cortical neurons. In addition, atorvastatin (10 μmol/L) significantly increased the phosphorylated GSK-3β level in the cortical

  10. Neurite outgrowth stimulatory effects of culinary-medicinal mushrooms and their toxicity assessment using differentiating Neuro-2a and embryonic fibroblast BALB/3T3

    Science.gov (United States)

    2013-01-01

    Background Mushrooms are not only regarded as gourmet cuisine but also as therapeutic agent to promote cognition health. However, little toxicological information is available regarding their safety. Therefore, the aim of this study was to screen selected ethno-pharmacologically important mushrooms for stimulatory effects on neurite outgrowth and to test for any cytotoxicity. Methods The stimulatory effect of mushrooms on neurite outgrowth was assessed in differentiating mouse neuroblastoma (N2a) cells. Neurite length was measured using Image-Pro Insight processor system. Neuritogenesis activity was further validated by fluorescence immunocytochemical staining of neurofilaments. In vitro cytotoxicity was investigated by using mouse embryonic fibroblast (BALB/3T3) and N2a cells for any embryo- and neuro-toxic effects; respectively. Results Aqueous extracts of Ganoderma lucidum, Lignosus rhinocerotis, Pleurotus giganteus and Grifola frondosa; as well as an ethanol extract of Cordyceps militaris significantly (p < 0.05) promoted the neurite outgrowth in N2a cells by 38.4 ± 4.2%, 38.1 ± 2.6%, 33.4 ± 4.6%, 33.7 ± 1.5%, and 35.8 ± 3.4%; respectively. The IC50 values obtained from tetrazolium (MTT), neutral red uptake (NRU) and lactate dehydrogenase (LDH) release assays showed no toxic effects following 24 h exposure of N2a and 3T3 cells to mushroom extracts. Conclusion Our results indicate that G. lucidum, L. rhinocerotis, P. giganteus, G. frondosa and C. militaris may be developed as safe and healthy dietary supplements for brain and cognitive health. PMID:24119256

  11. Role of transglutaminase 2 in PAC1 receptor mediated protection against hypoxia-induced cell death and neurite outgrowth in differentiating N2a neuroblastoma cells.

    Science.gov (United States)

    Algarni, Alanood S; Hargreaves, Alan J; Dickenson, John M

    2017-03-15

    The PAC 1 receptor and tissue transglutaminase (TG2) play important roles in neurite outgrowth and modulation of neuronal cell survival. In this study, we investigated the regulation of TG2 activity by the PAC 1 receptor in retinoic acid-induced differentiating N2a neuroblastoma cells. TG2 transamidase activity was determined using an amine incorporation and a peptide cross linking assay. In situ TG2 activity was assessed by visualising the incorporation of biotin-X-cadaverine using confocal microscopy. TG2 phosphorylation was monitored via immunoprecipitation and Western blotting. The role of TG2 in PAC 1 receptor-induced cytoprotection and neurite outgrowth was investigated by monitoring hypoxia-induced cell death and appearance of axonal-like processes, respectively. The amine incorporation and protein crosslinking activity of TG2 increased in a time and concentration-dependent manner following stimulation with pituitary adenylate cyclase-activating polypeptide-27 (PACAP-27). PACAP-27 mediated increases in TG2 activity were abolished by the TG2 inhibitors Z-DON and R283 and by pharmacological inhibition of protein kinase A (KT 5720 and Rp-cAMPs), protein kinase C (Ro 31-8220), MEK1/2 (PD 98059), and removal of extracellular Ca 2+ . Fluorescence microscopy demonstrated PACAP-27 induced in situ TG2 activity. TG2 inhibition blocked PACAP-27 induced attenuation of hypoxia-induced cell death and outgrowth of axon-like processes. TG2 activation and cytoprotection were also observed in human SH-SY5Y cells. Together, these results demonstrate that TG2 activity was stimulated downstream of the PAC 1 receptor via a multi protein kinase dependent pathway. Furthermore, PAC 1 receptor-induced cytoprotection and neurite outgrowth are dependent upon TG2. These results highlight the importance of TG2 in the cellular functions of the PAC 1 receptor. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. The metabolic enhancer piracetam ameliorates the impairment of mitochondrial function and neurite outgrowth induced by ß-amyloid peptide

    Science.gov (United States)

    Kurz, C; Ungerer, I; Lipka, U; Kirr, S; Schütt, T; Eckert, A; Leuner, K; Müller, WE

    2010-01-01

    Background and purpose: β-Amyloid peptide (Aβ) is implicated in the pathogenesis of Alzheimer's disease by initiating a cascade of events from mitochondrial dysfunction to neuronal death. The metabolic enhancer piracetam has been shown to improve mitochondrial dysfunction following brain aging and experimentally induced oxidative stress. Experimental approach: We used cell lines (PC12 and HEK cells) and murine dissociated brain cells. The protective effects of piracetam in vitro and ex vivo on Aβ-induced impairment of mitochondrial function (as mitochondrial membrane potential and ATP production), on secretion of soluble Aβ and on neurite outgrowth in PC12 cells were investigated. Key results: Piracetam improves mitochondrial function of PC12 cells and acutely dissociated brain cells from young NMRI mice following exposure to extracellular Aβ1-42. Similar protective effects against Aβ1-42 were observed in dissociated brain cells from aged NMRI mice, or mice transgenic for mutant human amyloid precursor protein (APP) treated with piracetam for 14 days. Soluble Aβ load was markedly diminished in the brain of those animals after treatment with piracetam. Aβ production by HEK cells stably transfected with mutant human APP was elevated by oxidative stress and this was reduced by piracetam. Impairment of neuritogenesis is an important consequence of Aβ-induced mitochondrial dysfunction and Aβ-induced reduction of neurite growth in PC12 cells was substantially improved by piracetam. Conclusion and implications: Our findings strongly support the concept of improving mitochondrial function as an approach to ameliorate the detrimental effects of Aβ on brain function. This article is commented on by Moncada, pp. 217–219 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2010.00706.x and to view related papers by Pravdic et al. and Puerta et al. visit http://dx.doi.org/10.1111/j.1476-5381.2010.00698.x and http://dx.doi.org/10.1111/j

  13. A low-cost microwell device for high-resolution imaging of neurite outgrowth in 3D

    Science.gov (United States)

    Ren, Yuan; Mlodzianoski, Michael J.; Cheun Lee, Aih; Huang, Fang; Suter, Daniel M.

    2018-06-01

    Objective. Current neuronal cell culture is mostly performed on two-dimensional (2D) surfaces, which lack many of the important features of the native environment of neurons, including topographical cues, deformable extracellular matrix, and spatial isotropy or anisotropy in three dimensions. Although three-dimensional (3D) cell culture systems provide a more physiologically relevant environment than 2D systems, their popularity is greatly hampered by the lack of easy-to-make-and-use devices. We aim to develop a widely applicable 3D culture procedure to facilitate the transition of neuronal cultures from 2D to 3D. Approach. We made a simple microwell device for 3D neuronal cell culture that is inexpensive, easy to assemble, and fully compatible with commonly used imaging techniques, including super-resolution microscopy. Main results. We developed a novel gel mixture to support 3D neurite regeneration of Aplysia bag cell neurons, a system that has been extensively used for quantitative analysis of growth cone dynamics in 2D. We found that the morphology and growth pattern of bag cell growth cones in 3D culture closely resemble the ones of growth cones observed in vivo. We demonstrated the capability of our device for high-resolution imaging of cytoskeletal and signaling proteins as well as organelles. Significance. Neuronal cell culture has been a valuable tool for neuroscientists to study the behavior of neurons in a controlled environment. Compared to 2D, neurons cultured in 3D retain the majority of their native characteristics, while offering higher accessibility, control, and repeatability. We expect that our microwell device will facilitate a wider adoption of 3D neuronal cultures to study the mechanisms of neurite regeneration.

  14. Neurite Outgrowth and Neuroprotective Effects of Quercetin from Caesalpinia mimosoides Lamk. on Cultured P19-Derived Neurons

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    Napat Tangsaengvit

    2013-01-01

    Full Text Available Quercetin has been isolated for the first time from ethyl acetate extract of Caesalpinia mimosoides Lamk. C. mimosoides Lamk. (Fabaceae or Cha rueat (Thai name is an indigenous plant found in mixed deciduous forest in northern and north-eastern parts of Thailand. Thai rural people consume its young shoots and leaves as a fresh vegetable, as well as it is used for medicinal purposes.The antioxidant capacity in terms of radical scavenging activity of quercetin was determined as IC50 of 3.18 ± 0.07 µg/mL, which was higher than that of Trolox and ascorbic acid (12.54 ± 0.89 and 10.52 ± 0.48 µg/mL, resp.. The suppressive effect of quercetin on both purified and cellular acetylcholinesterase (AChE enzymes was investigated as IC50 56.84 ± 2.64 and 36.60 ± 2.78 µg/mL, respectively. In order to further investigate the protective ability of quercetin on neuronal cells, P19-derived neurons were used as a neuronal model in this study. As a result, quercetin at a very low dose of 1 nM enhanced survival and induced neurite outgrowth of P19-derived neurons. Furthermore, this flavonoid also possessed significant protection against oxidative stress induced by serum deprivation. Altogether, these findings suggest that quercetin is a multifunctional compound and promising valuable drugs candidate for the treatment of neurodegenerative disease.

  15. Light-Mediated Kinetic Control Reveals the Temporal Effect of the Raf/MEK/ERK Pathway in PC12 Cell Neurite Outgrowth

    Science.gov (United States)

    Zhang, Kai; Duan, Liting; Ong, Qunxiang; Lin, Ziliang; Varman, Pooja Mahendra; Sung, Kijung; Cui, Bianxiao

    2014-01-01

    It has been proposed that differential activation kinetics allows cells to use a common set of signaling pathways to specify distinct cellular outcomes. For example, nerve growth factor (NGF) and epidermal growth factor (EGF) induce different activation kinetics of the Raf/MEK/ERK signaling pathway and result in differentiation and proliferation, respectively. However, a direct and quantitative linkage between the temporal profile of Raf/MEK/ERK activation and the cellular outputs has not been established due to a lack of means to precisely perturb its signaling kinetics. Here, we construct a light-gated protein-protein interaction system to regulate the activation pattern of the Raf/MEK/ERK signaling pathway. Light-induced activation of the Raf/MEK/ERK cascade leads to significant neurite outgrowth in rat PC12 pheochromocytoma cell lines in the absence of growth factors. Compared with NGF stimulation, light stimulation induces longer but fewer neurites. Intermittent on/off illumination reveals that cells achieve maximum neurite outgrowth if the off-time duration per cycle is shorter than 45 min. Overall, light-mediated kinetic control enables precise dissection of the temporal dimension within the intracellular signal transduction network. PMID:24667437

  16. Neurite outgrowth stimulatory effects of culinary-medicinal mushrooms and their toxicity assessment using differentiating Neuro-2a and embryonic fibroblast BALB/3T3.

    Science.gov (United States)

    Phan, Chia-Wei; David, Pamela; Naidu, Murali; Wong, Kah-Hui; Sabaratnam, Vikineswary

    2013-10-11

    Mushrooms are not only regarded as gourmet cuisine but also as therapeutic agent to promote cognition health. However, little toxicological information is available regarding their safety. Therefore, the aim of this study was to screen selected ethno-pharmacologically important mushrooms for stimulatory effects on neurite outgrowth and to test for any cytotoxicity. The stimulatory effect of mushrooms on neurite outgrowth was assessed in differentiating mouse neuroblastoma (N2a) cells. Neurite length was measured using Image-Pro Insight processor system. Neuritogenesis activity was further validated by fluorescence immunocytochemical staining of neurofilaments. In vitro cytotoxicity was investigated by using mouse embryonic fibroblast (BALB/3T3) and N2a cells for any embryo- and neuro-toxic effects; respectively. Aqueous extracts of Ganoderma lucidum, Lignosus rhinocerotis, Pleurotus giganteus and Grifola frondosa; as well as an ethanol extract of Cordyceps militaris significantly (p effects following 24 h exposure of N2a and 3T3 cells to mushroom extracts. Our results indicate that G. lucidum, L. rhinocerotis, P. giganteus, G. frondosa and C. militaris may be developed as safe and healthy dietary supplements for brain and cognitive health.

  17. Neurite outgrowth stimulatory effects of myco­synthesized AuNPs from Hericium erinaceus (Bull.: Fr. Pers. on pheochromocytoma (PC-12 cells

    Directory of Open Access Journals (Sweden)

    Raman J

    2015-09-01

    Full Text Available Jegadeesh Raman,1 Hariprasath Lakshmanan,1 Priscilla A John,1,2 Chan Zhijian,3 Vengadesh Periasamy,3 Pamela David,1,4 Murali Naidu,1,4 Vikineswary Sabaratnam1,2 1Mushroom Research Centre, 2Institute of Biological Sciences, Faculty of Science, University of Malaya, 3Low Dimensional Materials Research Center (LDMRC, Department of Physics, Faculty of Science, 4Department of Anatomy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia Background: Hericium erinaceus has been reported to have a wide range of medicinal properties such as stimulation of neurite outgrowth, promotion of functional recovery of axonotmetic peroneal nerve injury, antioxidant, antihypertensive, and antidiabetic properties. In recent years, the green synthesis of gold nanoparticles (AuNPs has attracted intense interest due to the potential use in biomedical applications. The aim of this study was to investigate the effects of AuNPs from aqueous extract of H. erinaceus on neurite outgrowth of rat pheochromocytoma (PC-12 cells. Methods: The formation of AuNPs was characterized by UV–visible spectrum, energy dispersive X-ray (EDX, field-emission scanning electron microscope (FESEM, transmission electron microscopy (TEM, particle size distribution, and Fourier transform-infrared spectroscopy (FTIR. Furthermore, the neurite extension study of synthesized AuNPs was evaluated by in vitro assay. Results: The AuNPs exhibited maximum absorbance between 510 and 600 nm in UV–visible spectrum. FESEM and TEM images showed the existence of nanoparticles with sizes of 20–40 nm. FTIR measurements were carried out to identify the possible biomolecules responsible for capping and efficient stabilization of the nanoparticles. The purity and the crystalline properties were confirmed by EDX diffraction analysis, which showed strong signals with energy peaks in the range of 2–2.4 keV, indicating the existence of gold atoms. The synthesized AuNPs showed significant neurite

  18. The Traditional Japanese Herbal Medicine Hachimijiogan Elicits Neurite Outgrowth Effects in PC12 Cells and Improves Cognitive in AD Model Rats via Phosphorylation of CREB

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    Kaori Kubota

    2017-11-01

    Full Text Available Hachimijiogan (HJG is a traditional herbal medicine that improves anxiety disorders in patients with dementia. In this study, we tested the hypothesis that HJG exerts neurotrophic factor-like effects to ameliorate memory impairment in Alzheimer disease (AD model rats. First, we describe that HJG acts to induce neurite outgrowth in PC12 cells (a rat pheochromocytoma cell line like nerve growth factor (NGF in a concentration-dependent manner (3 μg/ml HJG, p < 0.05; 10–500 μg/ml HJG, p < 0.001. While six herbal constituents of HJG, Rehmannia root, Dioscorea rhizome, Rhizoma Alismatis, Poria sclerotium, Moutan bark, and Cinnamon bark, could induce neurite outgrowth effects, the effect was strongest with HJG (500 μg/ml. Second, we demonstrated that HJG-induced neurite outgrowth was blocked by an inhibitor of cAMP response element binding protein (CREB, KG-501 (10 μM, p < 0.001. Moreover, HJG was observed to induce CREB phosphorylation 20–90 min after treatment (20 min, 2.50 ± 0.58-fold and CRE-mediated transcription in cultured PC12 cells (500 μg/ml, p < 0.01; 1000 μg/ml, p < 0.001. These results suggest a CREB-dependent mechanism underlies the neurotrophic effects of HJG. Finally, we examined improvements of memory impairment following HJG treatment using a Morris water maze in AD model animals (CI + Aβ rats. Repeated oral administration of HJG improved memory impairment (300 mg/kg, p < 0.05; 1000 mg/kg, p < 0.001 and induced CREB phosphorylation within the hippocampus (1000 mg/kg, p < 0.01. Together, our results suggest that HJG possesses neurotrophic effects similar to those of NGF, and can ameliorate cognitive dysfunction in a rat dementia model via CREB activation. Thus, HJG could potentially be a substitute for neurotrophic factors as a treatment for dementia.

  19. Neurite density imaging versus imaging of microscopic anisotropy in diffusion MRI: A model comparison using spherical tensor encoding.

    Science.gov (United States)

    Lampinen, Björn; Szczepankiewicz, Filip; Mårtensson, Johan; van Westen, Danielle; Sundgren, Pia C; Nilsson, Markus

    2017-02-15

    In diffusion MRI (dMRI), microscopic diffusion anisotropy can be obscured by orientation dispersion. Separation of these properties is of high importance, since it could allow dMRI to non-invasively probe elongated structures such as neurites (axons and dendrites). However, conventional dMRI, based on single diffusion encoding (SDE), entangles microscopic anisotropy and orientation dispersion with intra-voxel variance in isotropic diffusivity. SDE-based methods for estimating microscopic anisotropy, such as the neurite orientation dispersion and density imaging (NODDI) method, must thus rely on model assumptions to disentangle these features. An alternative approach is to directly quantify microscopic anisotropy by the use of variable shape of the b-tensor. Along those lines, we here present the 'constrained diffusional variance decomposition' (CODIVIDE) method, which jointly analyzes data acquired with diffusion encoding applied in a single direction at a time (linear tensor encoding, LTE) and in all directions (spherical tensor encoding, STE). We then contrast the two approaches by comparing neurite density estimated using NODDI with microscopic anisotropy estimated using CODIVIDE. Data were acquired in healthy volunteers and in glioma patients. NODDI and CODIVIDE differed the most in gray matter and in gliomas, where NODDI detected a neurite fraction higher than expected from the level of microscopic diffusion anisotropy found with CODIVIDE. The discrepancies could be explained by the NODDI tortuosity assumption, which enforces a connection between the neurite density and the mean diffusivity of tissue. Our results suggest that this assumption is invalid, which leads to a NODDI neurite density that is inconsistent between LTE and STE data. Using simulations, we demonstrate that the NODDI assumptions result in parameter bias that precludes the use of NODDI to map neurite density. With CODIVIDE, we found high levels of microscopic anisotropy in white matter

  20. Lion's Mane, Hericium erinaceus and Tiger Milk, Lignosus rhinocerotis (Higher Basidiomycetes) Medicinal Mushrooms Stimulate Neurite Outgrowth in Dissociated Cells of Brain, Spinal Cord, and Retina: An In Vitro Study.

    Science.gov (United States)

    Samberkar, Snehlata; Gandhi, Sivasangkary; Naidu, Murali; Wong, Kah-Hui; Raman, Jegadeesh; Sabaratnam, Vikineswary

    2015-01-01

    Neurodegenerative disease is defined as a deterioration of the nervous system in the intellectual and cognitive capabilities. Statistics show that more than 80-90 million individuals age 65 and above in 2050 may be affected by neurodegenerative conditions like Alzheimer's and Parkinson's disease. Studies have shown that out of 2000 different types of edible and/or medicinal mushrooms, only a few countable mushrooms have been selected until now for neurohealth activity. Hericium erinaceus is one of the well-established medicinal mushrooms for neuronal health. It has been documented for its regenerative capability in peripheral nerve. Another mushroom used as traditional medicine is Lignosus rhinocerotis, which has been used for various illnesses. It has been documented for its neurite outgrowth potential in PC12 cells. Based on the regenerative capabilities of both the mushrooms, priority was given to select them for our study. The aim of this study was to investigate the potential of H. erinaceus and L. rhinocerotis to stimulate neurite outgrowth in dissociated cells of brain, spinal cord, and retina from chick embryo when compared to brain derived neurotrophic factor (BDNF). Neurite outgrowth activity was confirmed by the immu-nofluorescence method in all tissue samples. Treatment with different concentrations of extracts resulted in neuronal differentiation and neuronal elongation. H. erinaceus extract at 50 µg/mL triggered neurite outgrowth at 20.47%, 22.47%, and 21.70% in brain, spinal cord, and retinal cells. L. rhinocerotis sclerotium extract at 50 µg/mL induced maximum neurite outgrowth of 20.77% and 24.73% in brain and spinal cord, whereas 20.77% of neurite outgrowth was observed in retinal cells at 25 µg/mL, respectively.

  1. Chemical Constituents from Hericium erinaceus Promote Neuronal Survival and Potentiate Neurite Outgrowth via the TrkA/Erk1/2 Pathway.

    Science.gov (United States)

    Zhang, Cheng-Chen; Cao, Chen-Yu; Kubo, Miwa; Harada, Kenichi; Yan, Xi-Tao; Fukuyama, Yoshiyasu; Gao, Jin-Ming

    2017-07-30

    Hericium erinaceus is a culinary-medicinal mushroom used traditionally in Eastern Asia to improve memory. In this work, we investigated the neuroprotective and neuritogenic effects of the secondary metabolites isolated from the MeOH extract of cultured mycelium of H. erinaceus and the primary mechanisms involved. One new dihydropyridine compound ( 6 ) and one new natural product ( 2 ) together with five known compounds ( 1 , 3 - 5 , 7 ) were obtained and their structures were elucidated by spectroscopic analysis, including 2D NMR and HRMS. The cell-based screening for bioactivity showed that 4-chloro-3,5-dimethoxybenzoic methyl ester ( 1 ) and a cyathane diterpenoid, erincine A ( 3 ), not only potentiated NGF-induced neurite outgrowth but also protected neuronally-differentiated cells against deprivation of NGF in PC12 pheochromocytoma cells. Additionally, compound 3 induced neuritogenesis in primary rat cortex neurons. Furthermore, our results revealed that TrkA-mediated and Erk1/2-dependant pathways could be involved in 1 and 3 -promoted NGF-induced neurite outgrowth in PC12 cells.

  2. Chemical Constituents from Hericium erinaceus Promote Neuronal Survival and Potentiate Neurite Outgrowth via the TrkA/Erk1/2 Pathway

    Directory of Open Access Journals (Sweden)

    Cheng-Chen Zhang

    2017-07-01

    Full Text Available Hericium erinaceus is a culinary-medicinal mushroom used traditionally in Eastern Asia to improve memory. In this work, we investigated the neuroprotective and neuritogenic effects of the secondary metabolites isolated from the MeOH extract of cultured mycelium of H. erinaceus and the primary mechanisms involved. One new dihydropyridine compound (6 and one new natural product (2 together with five known compounds (1,3–5,7 were obtained and their structures were elucidated by spectroscopic analysis, including 2D NMR and HRMS. The cell-based screening for bioactivity showed that 4-chloro-3,5-dimethoxybenzoic methyl ester (1 and a cyathane diterpenoid, erincine A (3, not only potentiated NGF-induced neurite outgrowth but also protected neuronally-differentiated cells against deprivation of NGF in PC12 pheochromocytoma cells. Additionally, compound 3 induced neuritogenesis in primary rat cortex neurons. Furthermore, our results revealed that TrkA-mediated and Erk1/2-dependant pathways could be involved in 1 and 3-promoted NGF-induced neurite outgrowth in PC12 cells.

  3. Surface microstructures on planar substrates and textile fibers guide neurite outgrowth: a scaffold solution to push limits of critical nerve defect regeneration?

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    Stefan Weigel

    Full Text Available The treatment of critical size peripheral nerve defects represents one of the most serious problems in neurosurgery. If the gap size exceeds a certain limit, healing can't be achieved. Connection mismatching may further reduce the clinical success. The present study investigates how far specific surface structures support neurite outgrowth and by that may represent one possibility to push distance limits that can be bridged. For this purpose, growth cone displacement of fluorescent embryonic chicken spinal cord neurons was monitored using time-lapse video. In a first series of experiments, parallel patterns of polyimide ridges of different geometry were created on planar silicon oxide surfaces. These channel-like structures were evaluated with and without amorphous hydrogenated carbon (a-C:H coating. In a next step, structured and unstructured textile fibers were investigated. All planar surface materials (polyimide, silicon oxide and a-C:H proved to be biocompatible, i.e. had no adverse effect on nerve cultures and supported neurite outgrowth. Mean growth cone migration velocity measured on 5 minute base was marginally affected by surface structuring. However, surface structure variability, i.e. ridge height, width and inter-ridge spacing, significantly enhanced the resulting net velocity by guiding the growth cone movement. Ridge height and inter-ridge distance affected the frequency of neurites crossing over ridges. Of the evaluated dimensions ridge height, width, and inter-ridge distance of respectively 3, 10, and 10 µm maximally supported net axon growth. Comparable artificial grooves, fabricated onto the surface of PET fibers by using an excimer laser, showed similar positive effects. Our data may help to further optimize surface characteristics of artificial nerve conduits and bioelectronic interfaces.

  4. Effect of Exosomes from Rat Adipose-Derived Mesenchymal Stem Cells on Neurite Outgrowth and Sciatic Nerve Regeneration After Crush Injury.

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    Bucan, Vesna; Vaslaitis, Desiree; Peck, Claas-Tido; Strauß, Sarah; Vogt, Peter M; Radtke, Christine

    2018-06-21

    Peripheral nerve injury requires optimal conditions in both macro-environment and microenvironment for promotion of axonal regeneration. However, most repair strategies of traumatic peripheral nerve injury often lead to dissatisfying results in clinical outcome. Though various strategies have been carried out to improve the macro-environment, the underlying molecular mechanism of axon regeneration in the microenvironment provided by nerve conduit remains unclear. In this study, we evaluate the effects of from adipose-derived mesenchymal stem cells (adMSCs) originating exosomes with respect to sciatic nerve regeneration and neurite growth. Molecular and immunohistochemical techniques were used to investigate the presence of characteristic exosome markers. A co-culture system was established to determine the effect of exosomes on neurite elongation in vitro. The in vivo walking behaviour of rats was evaluated by footprint analysis, and the nerve regeneration was assessed by immunocytochemistry. adMSCs secrete nano-vesicles known as exosomes, which increase neurite outgrowth in vitro and enhance regeneration after sciatic nerve injury in vivo. Furthermore, we showed the presence of neural growth factors transcripts in adMSC exosomes for the first time. Our results demonstrate that exosomes, constitutively produced by adMSCs, are involved in peripheral nerve regeneration and have the potential to be utilised as a therapeutic tool for effective tissue-engineered nerves.

  5. Ectodomain shedding of Limbic System-Associated Membrane Protein (LSAMP) by ADAM Metallopeptidases promotes neurite outgrowth in DRG neurons.

    Science.gov (United States)

    Sanz, Ricardo L; Ferraro, Gino B; Girouard, Marie-Pier; Fournier, Alyson E

    2017-08-11

    IgLONs are members of the immunoglobulin superfamily of cell adhesion proteins implicated in the process of neuronal outgrowth, cell adhesion and subdomain target recognition. IgLONs form homophilic and heterophilic complexes on the cell surface that repress or promote growth depending on the neuronal population, the developmental stage and surface repertoire of IgLON family members. In the present study, we identified a metalloproteinase-dependent mechanism necessary to promote growth in embryonic dorsal root ganglion cells (DRGs). Treatment of embryonic DRG neurons with pan-metalloproteinase inhibitors, tissue inhibitor of metalloproteinase-3, or an inhibitor of ADAM Metallopeptidase Domain 10 (ADAM10) reduces outgrowth from DRG neurons indicating that metalloproteinase activity is important for outgrowth. The IgLON family members Neurotrimin (NTM) and Limbic System-Associated Membrane Protein (LSAMP) were identified as ADAM10 substrates that are shed from the cell surface of DRG neurons. Overexpression of LSAMP and NTM suppresses outgrowth from DRG neurons. Furthermore, LSAMP loss of function decreases the outgrowth sensitivity to an ADAM10 inhibitor. Together our findings support a role for ADAM-dependent shedding of cell surface LSAMP in promoting outgrowth from DRG neurons.

  6. The inverse F-BAR domain protein srGAP2 acts through srGAP3 to modulate neuronal differentiation and neurite outgrowth of mouse neuroblastoma cells.

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    Yue Ma

    Full Text Available The inverse F-BAR (IF-BAR domain proteins srGAP1, srGAP2 and srGAP3 are implicated in neuronal development and may be linked to mental retardation, schizophrenia and seizure. A partially overlapping expression pattern and highly similar protein structures indicate a functional redundancy of srGAPs in neuronal development. Our previous study suggests that srGAP3 negatively regulates neuronal differentiation in a Rac1-dependent manner in mouse Neuro2a cells. Here we show that exogenously expressed srGAP1 and srGAP2 are sufficient to inhibit valporic acid (VPA-induced neurite initiation and growth in the mouse Neuro2a cells. While ectopic- or over-expression of RhoGAP-defective mutants, srGAP1(R542A and srGAP2(R527A exert a visible inhibitory effect on neuronal differentiation. Unexpectedly, knockdown of endogenous srGAP2 fails to facilitate the neuronal differentiation induced by VPA, but promotes neurite outgrowth of differentiated cells. All three IF-BAR domains from srGAP1-3 can induce filopodia formation in Neuro2a, but the isolated IF-BAR domain from srGAP2, not from srGAP1 and srGAP3, can promote VPA-induced neurite initiation and neuronal differentiation. We identify biochemical and functional interactions of the three srGAPs family members. We propose that srGAP3-Rac1 signaling may be required for the effect of srGAP1 and srGAP2 on attenuating neuronal differentiation. Furthermore, inhibition of Slit-Robo interaction can phenocopy a loss-of-function of srGAP3, indicating that srGAP3 may be dedicated to the Slit-Robo pathway. Our results demonstrate the interplay between srGAP1, srGAP2 and srGAP3 regulates neuronal differentiation and neurite outgrowth. These findings may provide us new insights into the possible roles of srGAPs in neuronal development and a potential mechanism for neurodevelopmental diseases.

  7. Role of glial cell line-derived neurotrophic factor (GDNF)-neural cell adhesion molecule (NCAM) interactions in induction of neurite outgrowth and identification of a binding site for NCAM in the heel region of GDNF

    DEFF Research Database (Denmark)

    Nielsen, Janne; Gotfryd, Kamil; Li, Shizhong

    2009-01-01

    NCAM-induced neurite outgrowth by being independent of NCAM polysialylation. Additionally, we investigated the structural basis for GDNF-NCAM interactions and find that NCAM Ig3 is necessary for GDNF binding. Furthermore, we identify within the heel region of GDNF a binding site for NCAM...

  8. Neural cell adhesion molecule-stimulated neurite outgrowth depends on activation of protein kinase C and the Ras-mitogen-activated protein kinase pathway

    DEFF Research Database (Denmark)

    Kolkova, K; Novitskaya, V; Pedersen, N

    2000-01-01

    , inhibitors of the nonreceptor tyrosine kinase p59(fyn), PLC, PKC and MEK and an activator of PKC, phorbol-12-myristate-13-acetate (PMA). MEK2 transfection rescued cells treated with all inhibitors. The same was found for PMA treatment, except when cells concomitantly were treated with the MEK inhibitor....... Arachidonic acid rescued cells treated with antibodies to the FGF receptor or the PLC inhibitor, but not cells in which the activity of PKC, p59(fyn), FAK, Ras, or MEK was inhibited. Interaction of NCAM with a synthetic NCAM peptide ligand, known to induce neurite outgrowth, was shown to stimulate...... phosphorylation of the MAP kinases extracellular signal-regulated kinases ERK1 and ERK2. The MAP kinase activation was sustained, because ERK1 and ERK2 were phosphorylated in PC12-E2 cells and primary hippocampal neurons even after 24 hr of cultivation on NCAM-expressing fibroblasts. Based on these results, we...

  9. Reaching Out to Send a Message: Proteins Associated with Neurite Outgrowth and Neurotransmission are Altered with Age in the Long-Lived Naked Mole-Rat.

    Science.gov (United States)

    Triplett, Judy C; Swomley, Aaron M; Kirk, Jessime; Grimes, Kelly M; Lewis, Kaitilyn N; Orr, Miranda E; Rodriguez, Karl A; Cai, Jian; Klein, Jon B; Buffenstein, Rochelle; Butterfield, D Allan

    2016-07-01

    Aging is the greatest risk factor for developing neurodegenerative diseases, which are associated with diminished neurotransmission as well as neuronal structure and function. However, several traits seemingly evolved to avert or delay age-related deterioration in the brain of the longest-lived rodent, the naked mole-rat (NMR). The NMR remarkably also exhibits negligible senescence, maintaining an extended healthspan for ~75 % of its life span. Using a proteomic approach, statistically significant changes with age in expression and/or phosphorylation levels of proteins associated with neurite outgrowth and neurotransmission were identified in the brain of the NMR and include: cofilin-1; collapsin response mediator protein 2; actin depolymerizing factor; spectrin alpha chain; septin-7; syntaxin-binding protein 1; synapsin-2 isoform IIB; and dynamin 1. We hypothesize that such changes may contribute to the extended lifespan and healthspan of the NMR.

  10. Endothelin-2/Vasoactive Intestinal Contractor: Regulation of Expression via Reactive Oxygen Species Induced by CoCl22, and Biological Activities Including Neurite Outgrowth in PC12 Cells

    Directory of Open Access Journals (Sweden)

    Eiichi Kotake-Nara

    2006-01-01

    Full Text Available This paper reviews the local hormone endothelin-2 (ET-2, or vasoactive intestinal contractor (VIC, a member of the vasoconstrictor ET peptide family, where ET-2 is the human orthologous peptide of the murine VIC. While ET-2/VIC gene expression has been observed in some normal tissues, ET-2 recently has been reported to act as a tumor marker and as a hypoxia-induced autocrine survival factor in tumor cells. A recently published study reported that the hypoxic mimetic agent CoCl2 at 200 µM increased expression of the ET-2/VIC gene, decreased expression of the ET-1 gene, and induced intracellular reactive oxygen species (ROS increase and neurite outgrowth in neuronal model PC12 cells. The ROS was generated by addition of CoCl2 to the culture medium, and the CoCl2-induced effects were completely inhibited by the antioxidant N-acetyl cysteine. Furthermore, interleukin-6 (IL-6 gene expression was up-regulated upon the differentiation induced by CoCl2. These results suggest that expression of ET-2/VIC and ET-1 mediated by CoCl2-induced ROS may be associated with neuronal differentiation through the regulation of IL-6 expression. CoCl2 acts as a pro-oxidant, as do Fe(II, III and Cu(II. However, some biological activities have been reported for CoCl2 that have not been observed for other metal salts such as FeCl3, CuSO4, and NiCl2. The characteristic actions of CoCl2 may be associated with the differentiation of PC12 cells. Further elucidation of the mechanism of neurite outgrowth and regulation of ET-2/VIC expression by CoCl2 may lead to the development of treatments for neuronal disorders.

  11. TRPC6 channel-mediated neurite outgrowth in PC12 cells and hippocampal neurons involves activation of RAS/MEK/ERK, PI3K, and CAMKIV signaling.

    Science.gov (United States)

    Heiser, Jeanine H; Schuwald, Anita M; Sillani, Giacomo; Ye, Lian; Müller, Walter E; Leuner, Kristina

    2013-11-01

    The non-selective cationic transient receptor canonical 6 (TRPC6) channels are involved in synaptic plasticity changes ranging from dendritic growth, spine morphology changes and increase in excitatory synapses. We previously showed that the TRPC6 activator hyperforin, the active antidepressant component of St. John's wort, induces neuritic outgrowth and spine morphology changes in PC12 cells and hippocampal CA1 neurons. However, the signaling cascade that transmits the hyperforin-induced transient rise in intracellular calcium into neuritic outgrowth is not yet fully understood. Several signaling pathways are involved in calcium transient-mediated changes in synaptic plasticity, ranging from calmodulin-mediated Ras-induced signaling cascades comprising the mitogen-activated protein kinase, PI3K signal transduction pathways as well as Ca(2+) /calmodulin-dependent protein kinase II (CAMKII) and CAMKIV. We show that several mechanisms are involved in TRPC6-mediated synaptic plasticity changes in PC12 cells and primary hippocampal neurons. Influx of calcium via TRPC6 channels activates different pathways including Ras/mitogen-activated protein kinase/extracellular signal-regulated kinases, phosphatidylinositide 3-kinase/protein kinase B, and CAMKIV in both cell types, leading to cAMP-response element binding protein phosphorylation. These findings are interesting not only in terms of the downstream targets of TRPC6 channels but also because of their potential to facilitate further understanding of St. John's wort extract-mediated antidepressant activity. Alterations in synaptic plasticity are considered to play an important role in the pathogenesis of depression. Beside several other proteins, TRPC6 channels regulate synaptic plasticity. This study demonstrates that different pathways including Ras/MEK/ERK, PI3K/Akt, and CAMKIV are involved in the improvement of synaptic plasticity by the TRPC6 activator hyperforin, the antidepressant active constituent of St. John

  12. Human adipose tissue-derived multilineage progenitor cells exposed to oxidative stress induce neurite outgrowth in PC12 cells through p38 MAPK signaling

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    Moriyama Mariko

    2012-08-01

    Full Text Available Abstract Background Adipose tissues contain populations of pluripotent mesenchymal stem cells that also secrete various cytokines and growth factors to support repair of damaged tissues. In this study, we examined the role of oxidative stress on human adipose-derived multilineage progenitor cells (hADMPCs in neurite outgrowth in cells of the rat pheochromocytoma cell line (PC12. Results We found that glutathione depletion in hADMPCs, caused by treatment with buthionine sulfoximine (BSO, resulted in the promotion of neurite outgrowth in PC12 cells through upregulation of bone morphogenetic protein 2 (BMP2 and fibroblast growth factor 2 (FGF2 transcription in, and secretion from, hADMPCs. Addition of N-acetylcysteine, a precursor of the intracellular antioxidant glutathione, suppressed the BSO-mediated upregulation of BMP2 and FGF2. Moreover, BSO treatment caused phosphorylation of p38 MAPK in hADMPCs. Inhibition of p38 MAPK was sufficient to suppress BMP2 and FGF2 expression, while this expression was significantly upregulated by overexpression of a constitutively active form of MKK6, which is an upstream molecule from p38 MAPK. Conclusions Our results clearly suggest that glutathione depletion, followed by accumulation of reactive oxygen species, stimulates the activation of p38 MAPK and subsequent expression of BMP2 and FGF2 in hADMPCs. Thus, transplantation of hADMPCs into neurodegenerative lesions such as stroke and Parkinson’s disease, in which the transplanted hADMPCs are exposed to oxidative stress, can be the basis for simple and safe therapies.

  13. The Secretome of Bone Marrow and Wharton Jelly Derived Mesenchymal Stem Cells Induces Differentiation and Neurite Outgrowth in SH-SY5Y Cells

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    Ana O. Pires

    2014-01-01

    Full Text Available The goal of this study was to determine and compare the effects of the secretome of mesenchymal stem cells (MSCs isolated from human bone-marrow (BMSCs and the Wharton jelly surrounding the vein and arteries of the umbilical cord (human umbilical cord perivascular cells (HUCPVCs on the survival and differentiation of a human neuroblastoma cell line (SH-SY5Y. For this purpose, SH-SY5Y cells were differentiated with conditioned media (CM from the MSCs populations referred above. Retinoic acid cultured cells were used as control for neuronal differentiated SH-SY5Y cells. SH-SY5Y cells viability assessment revealed that the secretome of BMSCs and HUCPVCs, in the form of CM, was able to induce their survival. Moreover, immunocytochemical experiments showed that CM from both MSCs was capable of inducing neuronal differentiation of SH-SY5Y cells. Finally, neurite lengths assessment and quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR analysis demonstrated that CM from BMSCs and HUCPVCs differently induced neurite outgrowth and mRNA levels of neuronal markers exhibited by SH-SY5Y cells. Overall, our results show that the secretome of both BMSCs and HUCPVCs was capable of supporting SH-SY5Y cells survival and promoting their differentiation towards a neuronal phenotype.

  14. Effects of huperzine A on secretion of nerve growth factor in cultured rat cortical astrocytes and neurite outgrowth in rat PC12 cells.

    Science.gov (United States)

    Tang, Li-li; Wang, Rui; Tang, Xi-can

    2005-06-01

    To study the effects of huperzine A (HupA) on neuritogenic activity and the expression of nerve growth factor (NGF). After being treated with 10 micromol/L HupA, neurite outgrowth of PC12 cells was observed and counted under phase-contrast microscopy. Mitogenic activity was assayed by [3H]thymidine incorporation. Cell cytotoxicity was evaluated by lactate dehydrogenase (LDH) release. AChE activity, mRNA and protein expression were measured by the Ellman method, RT-PCR, and Western blot, respectively. NGF mRNA and protein levels were determined by RT-PCR and ELISA assays. Treatment of PC12 cells with 10 micromol/L HupA for 48 h markedly increased the number of neurite-bearing cells, but caused no significant alteration in cell viability or other signs of cytotoxicity. In addition to inhibiting AChE activity, 10 micromol/L HupA also increased the mRNA and protein levels of this enzyme. In addition, following 2 h exposure of the astrocytes to 10 micromol/L HupA, there was a significant up-regulation of mRNA for NGF and P75 low-affinity NGF receptor. The protein level of NGF was also increased after 24 h treatment with HupA. Our findings demonstrate for the first time that HupA has a direct or indirect neurotrophic activity, which might be beneficial in treatment of neurodegenerative disorders such as Alzheimer disease.

  15. The selective and inducible activation of endogenous PI 3-kinase in PC12 cells results in efficient NGF-mediated survival but defective neurite outgrowth.

    Science.gov (United States)

    Ashcroft, M; Stephens, R M; Hallberg, B; Downward, J; Kaplan, D R

    1999-08-12

    The Trk/Nerve Growth Factor receptor mediates the rapid activation of a number of intracellular signaling proteins, including phosphatidylinositol 3-kinase (PI 3-kinase). Here, we describe a novel, NGF-inducible system that we used to specifically address the signaling potential of endogenous PI 3-kinase in NGF-mediated neuronal survival and differentiation processes. This system utilizes a Trk receptor mutant (Trk(def)) lacking sequences Y490, Y785 and KFG important for the activation of the major Trk targets; SHC, PLC-gammal, Ras, PI 3-kinase and SNT. Trk(def) was kinase active but defective for NGF-induced responses when stably expressed in PC12nnr5 cells (which lack detectable levels of TrkA and are non-responsive to NGF). The PI 3-kinase consensus binding site, YxxM (YVPM), was introduced into the insert region within the kinase domain of Trk(def). NGF-stimulated tyrosine phosphorylation of the Trk(def)+PI 3-kinase addback receptor, resulted in the direct association and selective activation of PI 3-kinase in vitro and the production of PI(3,4)P2 and PI(3,4,5)P3 in vivo (comparable to wild-type). PC12nnr5 cells stably expressing Trk(def) + PI 3-kinase, initiated neurite outgrowth but failed to stably extend and maintain these neurites in response to NGF as compared to PC12 parental cells, or PC12nnr5 cells overexpressing wild-type Trk. However, Trk(def) + PI 3-kinase was fully competent in mediating NGF-induced survival processes. We propose that while endogenous PI 3-kinase can contribute in part to neurite initiation processes, its selective activation and subsequent signaling to downstream effectors such as Akt, functions mainly to promote cell survival in the PC12 system.

  16. AMP N1-Oxide, a Unique Compound of Royal Jelly, Induces Neurite Outgrowth from PC12 Vells via Signaling by Protein Kinase A Independent of that by Mitogen-Activated Protein Kinase

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    Noriko Hattori

    2010-01-01

    Full Text Available Earlier we identified adenosine monophosphate (AMP N1-oxide as a unique compound of royal jelly (RJ that induces neurite outgrowth (neuritegenesis from cultured rat pheochromocytoma PC12 cells via the adenosine A2A receptor. Now, we found that AMP N1-oxide stimulated the phosphorylation of not only mitogen-activated protein kinase (MAPK but also that of cAMP/calcium-response element-binding protein (CREB in a dose-dependent manner. Inhibition of MAPK activation by a MEK inhibitor, PD98059, did not influence the AMP N1-oxide-induced neuritegenesis, whereas that of protein kinase A (PKA by a selective inhibitor, KT5720, significantly reduced neurite outgrowth. AMP N1-oxide also had the activity of suppressing the growth of PC12 cells, which correlated well with the neurite outgrowth-promoting activity. KT5720 restored the growth of AMP N1-oxide-treated PC12 cells. It is well known that nerve growth factor suppresses proliferation of PC12 cells before causing stimulation of neuronal differentiation. Thus, AMP N1-oxide elicited neuronal differentiation of PC12 cells, as evidenced by generation of neurites, and inhibited cell growth through adenosine A2A receptor-mediated PKA signaling, which may be responsible for characteristic actions of RJ.

  17. Prenatal low-dose methylmercury exposure impairs neurite outgrowth and synaptic protein expression and suppresses TrkA pathway activity and eEF1A1 expression in the rat cerebellum

    Energy Technology Data Exchange (ETDEWEB)

    Fujimura, Masatake, E-mail: fujimura@nimd.go.jp [Department of Basic Medical Sciences, National Institute for Minamata Disease, Kumamoto (Japan); Usuki, Fusako [Department of Clinical Medicine, National Institute for Minamata Disease, Kumamoto (Japan); Cheng, Jinping; Zhao, Wenchang [School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240 (China)

    2016-05-01

    Methylmercury (MeHg) is a highly neurotoxic environmental chemical that can cause developmental impairments. Human fetuses and neonates are particularly susceptible to MeHg toxicity; however, the mechanisms governing its effects in the developing brain are unclear. In the present study, we investigated the effects of prenatal and lactational MeHg exposure on the developing cerebellum in rats. We demonstrated that exposure to 5 ppm MeHg decreased postnatal expression of pre- and postsynaptic proteins, suggesting an impairment in synaptic development. MeHg exposure also reduced neurite outgrowth, as shown by a decrease in the expression of the neurite marker neurofilament H. These changes were not observed in rats exposed to 1 ppm MeHg. In order to define the underlying mechanism, we investigated the effects of MeHg exposure on the tropomyosin receptor kinase (Trk) A pathway, which plays important roles in neuronal differentiation and synapse formation. We demonstrated suppression of the TrkA pathway on gestation day 20 in rats exposed to 5 ppm MeHg. In addition, down-regulation of eukaryotic elongation factor 1A1 (eEF1A1) was observed on postnatal day 1. eEF1A1 knockdown in differentiating PC12 cells impaired neurite outgrowth and synaptic protein expression, similar to the results of MeHg exposure in the cerebellum. These results suggest that suppression of the TrkA pathway and subsequent decreases in eEF1A1 expression induced by prenatal exposure to MeHg may lead to reduced neurite outgrowth and synaptic protein expression in the developing cerebellum. - Highlights: • Prenatal exposure to MeHg decreased postnatal expression of synaptic proteins. • MeHg exposure also reduced neurite outgrowth postnatally. • Suppression of the TrkA pathway and eEF1A1 expression was induced by MeHg exposure. • eEF1A1 knockdown impaired neurite outgrowth and synaptic protein expression.

  18. Prenatal low-dose methylmercury exposure impairs neurite outgrowth and synaptic protein expression and suppresses TrkA pathway activity and eEF1A1 expression in the rat cerebellum

    International Nuclear Information System (INIS)

    Fujimura, Masatake; Usuki, Fusako; Cheng, Jinping; Zhao, Wenchang

    2016-01-01

    Methylmercury (MeHg) is a highly neurotoxic environmental chemical that can cause developmental impairments. Human fetuses and neonates are particularly susceptible to MeHg toxicity; however, the mechanisms governing its effects in the developing brain are unclear. In the present study, we investigated the effects of prenatal and lactational MeHg exposure on the developing cerebellum in rats. We demonstrated that exposure to 5 ppm MeHg decreased postnatal expression of pre- and postsynaptic proteins, suggesting an impairment in synaptic development. MeHg exposure also reduced neurite outgrowth, as shown by a decrease in the expression of the neurite marker neurofilament H. These changes were not observed in rats exposed to 1 ppm MeHg. In order to define the underlying mechanism, we investigated the effects of MeHg exposure on the tropomyosin receptor kinase (Trk) A pathway, which plays important roles in neuronal differentiation and synapse formation. We demonstrated suppression of the TrkA pathway on gestation day 20 in rats exposed to 5 ppm MeHg. In addition, down-regulation of eukaryotic elongation factor 1A1 (eEF1A1) was observed on postnatal day 1. eEF1A1 knockdown in differentiating PC12 cells impaired neurite outgrowth and synaptic protein expression, similar to the results of MeHg exposure in the cerebellum. These results suggest that suppression of the TrkA pathway and subsequent decreases in eEF1A1 expression induced by prenatal exposure to MeHg may lead to reduced neurite outgrowth and synaptic protein expression in the developing cerebellum. - Highlights: • Prenatal exposure to MeHg decreased postnatal expression of synaptic proteins. • MeHg exposure also reduced neurite outgrowth postnatally. • Suppression of the TrkA pathway and eEF1A1 expression was induced by MeHg exposure. • eEF1A1 knockdown impaired neurite outgrowth and synaptic protein expression.

  19. cAMP-induced activation of protein kinase A and p190B RhoGAP mediates down-regulation of TC10 activity at the plasma membrane and neurite outgrowth.

    Science.gov (United States)

    Koinuma, Shingo; Takeuchi, Kohei; Wada, Naoyuki; Nakamura, Takeshi

    2017-11-01

    Cyclic AMP plays a pivotal role in neurite growth. During outgrowth, a trafficking system supplies membrane at growth cones. However, the cAMP-induced signaling leading to the regulation of membrane trafficking remains unknown. TC10 is a Rho family GTPase that is essential for specific types of vesicular trafficking. Recent studies have shown a role of TC10 in neurite growth in NGF-treated PC12 cells. Here, we investigated a mechanical linkage between cAMP and TC10 in neuritogenesis. Plasmalemmal TC10 activity decreased abruptly after cAMP addition in neuronal cells. TC10 was locally inactivated at extending neurite tips in cAMP-treated PC12 cells. TC10 depletion led to a decrease in cAMP-induced neurite outgrowth. Constitutively active TC10 could not rescue this growth reduction, supporting our model for a role of GTP hydrolysis of TC10 in neuritogenesis by accelerating vesicle fusion. The cAMP-induced TC10 inactivation was mediated by PKA. Considering cAMP-induced RhoA inactivation, we found that p190B, but not p190A, mediated inactivation of TC10 and RhoA. Upon cAMP treatment, p190B was recruited to the plasma membrane. STEF depletion and Rac1-N17 expression reduced cAMP-induced TC10 inactivation. Together, the PKA-STEF-Rac1-p190B pathway leading to inactivation of TC10 and RhoA at the plasma membrane plays an important role in cAMP-induced neurite outgrowth. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  20. Chemical constituents from Hericium erinaceus and their ability to stimulate NGF-mediated neurite outgrowth on PC12 cells.

    Science.gov (United States)

    Zhang, Cheng-Chen; Yin, Xia; Cao, Chen-Yu; Wei, Jing; Zhang, Qiang; Gao, Jin-Ming

    2015-11-15

    One new meroterpenoid, named hericenone K (11), along with 10 known compounds (1-10), ergosterol peroxide (1), cerevisterol (2), 3β,5α,9α-trihydroxy-ergosta-7,22-dien-6-one (3), inoterpene A (4), astradoric acid C (5), betulin (6), oleanolic acid (7), ursolic acid (8), hemisceramide (9), and 3,4-dihydro-5-methoxy-2-methyl-2-(4'-methyl-2'-oxo-3'-pentenyl)-9(7H)-oxo-2H-furo[3,4-h]benzopyran (10), was isolated from the fruiting bodies of the mushroom Hericium erinaceus. Their structures were characterized on the basis of spectroscopic methods, as well as through comparison with previously reported data. Compounds 3-6, 8, and 9 were isolated from Hericium species for the first time. Compounds 10 and 11 was suggested to be racemic by the CD spectrum data and specific rotations, which ware resolved by chiral HPLC into respective enantiomers. Compounds 1-3, (±)-10, (-)-10 and (+)-10 in the presence of NGF (20 ng/mL) exerted a significant increase in neurite-bearing cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. A characteristic chondroitin sulfate trisaccharide unit with a sulfated fucose branch exhibits neurite outgrowth-promoting activity: Novel biological roles of fucosylated chondroitin sulfates isolated from the sea cucumber Apostichopus japonicus.

    Science.gov (United States)

    Shida, Miharu; Mikami, Tadahisa; Tamura, Jun-Ichi; Kitagawa, Hiroshi

    2017-06-03

    Chondroitin sulfate (CS) is a class of sulfated glycosaminoglycan (GAG) chains that consist of repeating disaccharide unit composed of glucuronic acid (GlcA) and N-acetylgalactosamine (GalNAc). CS chains are found throughout the pericellular and extracellular spaces and contribute to the formation of functional microenvironments for numerous biological events. However, their structure-function relations remain to be fully characterized. Here, a fucosylated CS (FCS) was isolated from the body wall of the sea cucumber Apostichopus japonicus. Its promotional effects on neurite outgrowth were assessed by using isolated polysaccharides and the chemically synthesized FCS trisaccharide β-D-GalNAc(4,6-O-disulfate) (1-4)[α-l-fucose (2,4-O-disulfate) (1-3)]-β-D-GlcA. FCS polysaccharides contained the E-type disaccharide unit GlcA-GalNAc(4,6-O-disulfate) as a CS major backbone structure and carried distinct sulfated fucose branches. Despite their relatively lower abundance of E unit, FCS polysaccharides exhibited neurite outgrowth-promoting activity comparable to squid cartilage-derived CS-E polysaccharides, which are characterized by their predominant E units, suggesting potential roles of the fucose branch in neurite outgrowth. Indeed, the chemically synthesized FCS trisaccharide was as effective as CS-E tetrasaccharide in stimulating neurite elongation in vitro. In conclusion, FCS trisaccharide units with 2,4-O-disulfated fucose branches may provide new insights into understanding the structure-function relations of CS chains. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Downstream of tyrosine kinase/docking protein 6, as a novel substrate of tropomyosin-related kinase C receptor, is involved in neurotrophin 3-mediated neurite outgrowth in mouse cortex neurons

    Directory of Open Access Journals (Sweden)

    Yuan Jian

    2010-06-01

    Full Text Available Abstract Background The downstream of tyrosine kinase/docking protein (Dok adaptor protein family has seven members, Dok1 to Dok7, that act as substrates of multiple receptor tyrosine kinase and non-receptor tyrosine kinase. The tropomyosin-related kinase (Trk receptor family, which has three members (TrkA, TrkB and TrkC, are receptor tyrosine kinases that play pivotal roles in many stages of nervous system development, such as differentiation, migration, axon and dendrite projection and neuron patterning. Upon related neurotrophin growth factor stimulation, dimerisation and autophosphorylation of Trk receptors can occur, recruiting adaptor proteins to mediate signal transduction. Results In this report, by using yeast two-hybrid assays, glutathione S-transferase (GST precipitation assays and coimmunoprecipitation (Co-IP experiments, we demonstrate that Dok6 selectively binds to the NPQY motif of TrkC through its phosphotyrosine-binding (PTB domain in a kinase activity-dependent manner. We further confirmed their interaction by coimmunoprecipitation and colocalisation in E18.5 mouse cortex neurons, which provided more in vivo evidence. Next, we demonstrated that Dok6 is involved in neurite outgrowth in mouse cortex neurons via the RNAi method. Knockdown of Dok6 decreased neurite outgrowth in cortical neurons upon neurotrophin 3 (NT-3 stimulation. Conclusions We conclude that Dok6 interacts with the NPQY motif of the TrkC receptor through its PTB domain in a kinase activity-dependent manner, and works as a novel substrate of the TrkC receptor involved in NT-3-mediated neurite outgrowth in mouse cortex neurons.

  3. A three-dimensional image processing program for accurate, rapid, and semi-automated segmentation of neuronal somata with dense neurite outgrowth

    Science.gov (United States)

    Ross, James D.; Cullen, D. Kacy; Harris, James P.; LaPlaca, Michelle C.; DeWeerth, Stephen P.

    2015-01-01

    Three-dimensional (3-D) image analysis techniques provide a powerful means to rapidly and accurately assess complex morphological and functional interactions between neural cells. Current software-based identification methods of neural cells generally fall into two applications: (1) segmentation of cell nuclei in high-density constructs or (2) tracing of cell neurites in single cell investigations. We have developed novel methodologies to permit the systematic identification of populations of neuronal somata possessing rich morphological detail and dense neurite arborization throughout thick tissue or 3-D in vitro constructs. The image analysis incorporates several novel automated features for the discrimination of neurites and somata by initially classifying features in 2-D and merging these classifications into 3-D objects; the 3-D reconstructions automatically identify and adjust for over and under segmentation errors. Additionally, the platform provides for software-assisted error corrections to further minimize error. These features attain very accurate cell boundary identifications to handle a wide range of morphological complexities. We validated these tools using confocal z-stacks from thick 3-D neural constructs where neuronal somata had varying degrees of neurite arborization and complexity, achieving an accuracy of ≥95%. We demonstrated the robustness of these algorithms in a more complex arena through the automated segmentation of neural cells in ex vivo brain slices. These novel methods surpass previous techniques by improving the robustness and accuracy by: (1) the ability to process neurites and somata, (2) bidirectional segmentation correction, and (3) validation via software-assisted user input. This 3-D image analysis platform provides valuable tools for the unbiased analysis of neural tissue or tissue surrogates within a 3-D context, appropriate for the study of multi-dimensional cell-cell and cell-extracellular matrix interactions. PMID

  4. DNA topoisomerase IIβ stimulates neurite outgrowth in neural differentiated human mesenchymal stem cells through regulation of Rho-GTPases (RhoA/Rock2 pathway) and Nurr1 expression.

    Science.gov (United States)

    Zaim, Merve; Isik, Sevim

    2018-04-25

    DNA topoisomerase IIβ (topo IIβ) is known to regulate neural differentiation by inducing the neuronal genes responsible for critical neural differentiation events such as neurite outgrowth and axon guidance. However, the pathways of axon growth controlled by topo IIβ have not been clarified yet. Microarray results of our previous study have shown that topo IIβ silencing in neural differentiated primary human mesenchymal stem cells (hMSCs) significantly alters the expression pattern of genes involved in neural polarity, axonal growth, and guidance, including Rho-GTPases. This study aims to further analyze the regulatory role of topo IIβ on the process of axon growth via regulation of Rho-GTPases. For this purpose, topo IIβ was silenced in neurally differentiated hMSCs. Cells lost their morphology because of topo IIβ deficiency, becoming enlarged and flattened. Additionally, a reduction in both neural differentiation efficiency and neurite length, upregulation in RhoA and Rock2, downregulation in Cdc42 gene expression were detected. On the other hand, cells were transfected with topo IIβ gene to elucidate the possible neuroprotective effect of topo IIβ overexpression on neural-induced hMSCs. Topo IIβ overexpression prompted all the cells to exhibit neural cell morphology as characterized by longer neurites. RhoA and Rock2 expressions were downregulated, whereas Cdc42 expression was upregulated. Nurr1 expression level correlated with topo IIβ in both topo IIβ-overexpressed and -silenced cells. Furthermore, differential translocation of Rho-GTPases was detected by immunostaining in response to topo IIβ. Our results suggest that topo IIβ deficiency could give rise to neurodegeneration through dysregulation of Rho-GTPases. However, further in-vivo research is needed to demonstrate if re-regulation of Rho GTPases by topo IIβ overexpression could be a neuroprotective treatment in the case of neurodegenerative diseases.

  5. Toward the Development of an Artificial Brain on a Micropatterned and Material-Regulated Biochip by Guiding and Promoting the Differentiation and Neurite Outgrowth of Neural Stem/Progenitor Cells.

    Science.gov (United States)

    Liu, Yung-Chiang; Lee, I-Chi; Lei, Kin Fong

    2018-02-14

    An in vitro model mimicking the in vivo environment of the brain must be developed to study neural communication and regeneration and to obtain an understanding of cellular and molecular responses. In this work, a multilayered neural network was successfully constructed on a biochip by guiding and promoting neural stem/progenitor cell differentiation and network formation. The biochip consisted of 3 × 3 arrays of cultured wells connected with channels. Neurospheroids were cultured on polyelectrolyte multilayer (PEM) films in the culture wells. Neurite outgrowth and neural differentiation were guided and promoted by the micropatterns and the PEM films. After 5 days in culture, a 3 × 3 neural network was constructed on the biochip. The function and the connections of the network were evaluated by immunocytochemistry and impedance measurements. Neurons were generated and produced functional and recyclable synaptic vesicles. Moreover, the electrical connections of the neural network were confirmed by measuring the impedance across the neurospheroids. The current work facilitates the development of an artificial brain on a chip for investigations of electrical stimulations and recordings of multilayered neural communication and regeneration.

  6. Role of G protein-regulated inducer of neurite outgrowth 3 (GRIN3) in β-arrestin 2-Akt signaling and dopaminergic behaviors.

    Science.gov (United States)

    Mototani, Yasumasa; Okamura, Tadashi; Goto, Motohito; Shimizu, Yukiko; Yanobu-Takanashi, Rieko; Ito, Aiko; Kawamura, Naoya; Yagisawa, Yuka; Umeki, Daisuke; Nariyama, Megumi; Suita, Kenji; Ohnuki, Yoshiki; Shiozawa, Kouichi; Sahara, Yoshinori; Kozasa, Tohru; Saeki, Yasutake; Okumura, Satoshi

    2018-06-01

    The G protein-regulated inducer of neurite growth (GRIN) family has three isoforms (GRIN1-3), which bind to the Gαi/o subfamily of G protein that mediate signal processing via G protein-coupled receptors (GPCRs). Here, we show that GRIN3 is involved in regulation of dopamine-dependent behaviors and is essential for activation of the dopamine receptors (DAR)-β-arrestin signaling cascade. Analysis of functional regions of GRIN3 showed that a di-cysteine motif (Cys751/752) is required for plasma membrane localization. GRIN3 was co-immunoprecipitated with GPCR kinases 2/6 and β-arrestins 1/2. Among GRINs, only GRIN3, which is highly expressed in striatum, strongly interacted with β-arrestin 2. We also generated GRIN3-knockout mice (GRIN3KO). GRIN3KO exhibited reduced locomotor activity and increased anxiety-like behavior in the elevated maze test, as well as a reduced locomoter response to dopamine stimulation. We also examined the phosphorylation of Akt at threonine 308 (phospho308-Akt), which is dephosphorylated via a β-arrestin 2-mediated pathway. Dephosphorylation of phospho308-Akt via the D2R-β-arrestin 2 signaling pathway was completely abolished in striatum of GRIN3KO. Our results suggest that GRIN3 has a role in recruitment and assembly of proteins involved in β-arrestin-dependent, G protein-independent signaling.

  7. Progranulin regulates neuronal outgrowth independent of Sortilin

    Directory of Open Access Journals (Sweden)

    Gass Jennifer

    2012-07-01

    Full Text Available Abstract Background Progranulin (PGRN, a widely secreted growth factor, is involved in multiple biological functions, and mutations located within the PGRN gene (GRN are a major cause of frontotemporal lobar degeneration with TDP-43-positive inclusions (FLTD-TDP. In light of recent reports suggesting PGRN functions as a protective neurotrophic factor and that sortilin (SORT1 is a neuronal receptor for PGRN, we used a Sort1-deficient (Sort1−/− murine primary hippocampal neuron model to investigate whether PGRN’s neurotrophic effects are dependent on SORT1. We sought to elucidate this relationship to determine what role SORT1, as a regulator of PGRN levels, plays in modulating PGRN’s neurotrophic effects. Results As the first group to evaluate the effect of PGRN loss in Grn knockout primary neuronal cultures, we show neurite outgrowth and branching are significantly decreased in Grn−/− neurons compared to wild-type (WT neurons. More importantly, we also demonstrate that PGRN overexpression can rescue this phenotype. However, the recovery in outgrowth is not observed following treatment with recombinant PGRN harboring missense mutations p.C139R, p.P248L or p.R432C, indicating that these mutations adversely affect the neurotrophic properties of PGRN. In addition, we also present evidence that cleavage of full-length PGRN into granulin peptides is required for increased neuronal outgrowth, suggesting that the neurotrophic functions of PGRN are contained within certain granulins. To further characterize the mechanism by which PGRN impacts neuronal morphology, we assessed the involvement of SORT1. We demonstrate that PGRN induced-outgrowth occurs in the absence of SORT1 in Sort1−/− cultures. Conclusion We demonstrate that loss of PGRN impairs proper neurite outgrowth and branching, and that exogenous PGRN alleviates this impairment. Furthermore, we determined that exogenous PGRN induces outgrowth independent of SORT1, suggesting another

  8. The C1 domain-targeted isophthalate derivative HMI-1b11 promotes neurite outgrowth and GAP-43 expression through PKCα activation in SH-SY5Y cells.

    Science.gov (United States)

    Talman, Virpi; Amadio, Marialaura; Osera, Cecilia; Sorvari, Salla; Boije Af Gennäs, Gustav; Yli-Kauhaluoma, Jari; Rossi, Daniela; Govoni, Stefano; Collina, Simona; Ekokoski, Elina; Tuominen, Raimo K; Pascale, Alessia

    2013-07-01

    Protein kinase C (PKC) is a family of serine/threonine phosphotransferases ubiquitously expressed and involved in multiple cellular functions, such as proliferation, apoptosis and differentiation. The C1 domain of PKC represents an attractive drug target, especially for developing PKC activators. Dialkyl 5-(hydroxymethyl)isophthalates are a novel group of synthetic C1 domain ligands that exhibit antiproliferative effect in HeLa cervical carcinoma cells. Here we selected two isophthalates, HMI-1a3 and HMI-1b11, and characterized their effects in the human neuroblastoma cell line SH-SY5Y. Both of the active isophthalates exhibited significant antiproliferative and differentiation-inducing effects. Since HMI-1b11 did not impair cell survival even at the highest concentration tested (20μM), and supported neurite growth and differentiation of SH-SY5Y cells, we focused on studying its downstream signaling cascades and effects on gene expression. Consistently, genome-wide gene expression microarray and gene set enrichment analysis indicated that HMI-1b11 (10μM) induced changes in genes mainly related to cell differentiation. In particular, further studies revealed that HMI-1b11 exposure induced up-regulation of GAP-43, a marker for neurite sprouting and neuronal differentiation. These effects were induced by a 7-min HMI-1b11 treatment and specifically depended on PKCα activation, since pretreatment with the selective inhibitor Gö6976 abolished the up-regulation of GAP-43 protein observed at 12h. In parallel, we found that a 7-min exposure to HMI-1b11 induced PKCα accumulation to the cytoskeleton, an effect that was again prevented by pretreatment with Gö6976. Despite similar binding affinities to PKC, the isophthalates had different effects on PKC-dependent ERK1/2 signaling: HMI-1a3-induced ERK1/2 phosphorylation was transient, while HMI-1b11 induced a rapid but prolonged ERK1/2 phosphorylation. Overall our data are in accordance with previous studies showing that

  9. The molluscan RING-finger protein L-TRIM is essential for neuronal outgrowth

    NARCIS (Netherlands)

    van Diepen, M. T.; Spencer, G.E.; Minnen, J.; Gouwenberg, Y.; Bouwman, J.G.; Smit, A. B.; van Kesteren, R.E.

    2005-01-01

    The tripartite motif proteins TRIM-2 and TRIM-3 have been put forward as putative organizers of neuronal outgrowth and structural plasticity. Here, we identified a molluscan orthologue of TRIM-2/3, named L-TRIM, which is up-regulated during in vitro neurite outgrowth of central neurons. In adult

  10. Amine functionalized nanodiamond promotes cellular adhesion, proliferation and neurite outgrowth

    International Nuclear Information System (INIS)

    Hopper, A P; Dugan, J M; Gill, A A; Haycock, J W; Claeyssens, F; Fox, O J L; May, P W

    2014-01-01

    In this study, we report the production of amine functionalized nanodiamond. The amine functionalized nanodiamond forms a conformal monolayer on a negatively charged surface produced via plasma polymerization of acrylic acid. Nanodiamond terminated surfaces were studied as substrates for neuronal cell culture. NG108-15 neuroblastoma-glyoma hybrid cells were successfully cultured upon amine functionalized nanodiamond coated surfaces for between 1 and 7 d. Additionally, primary dorsal root ganglion (DRG) neurons and Schwann cells isolated from Wistar rats were also successfully cultured over a period of 21 d illustrating the potential of the coating for applications in the treatment of peripheral nerve injury. (paper)

  11. Neurite outgrowth in human iPSC-derived neurons

    Data.gov (United States)

    U.S. Environmental Protection Agency — Data on morphology of rat and human neurons in cell culture. This dataset is associated with the following publication: Druwe, I., T. Freudenrich , K. Wallace , T....

  12. Sigma-1 receptor enhances neurite elongation of cerebellar granule neurons via TrkB signaling.

    Science.gov (United States)

    Kimura, Yuriko; Fujita, Yuki; Shibata, Kumi; Mori, Megumi; Yamashita, Toshihide

    2013-01-01

    Sigma-1 receptor (Sig-1R) is an integral membrane protein predominantly expressed in the endoplasmic reticulum. Sig-1R demonstrates a high affinity to various synthetic compounds including well-known psychotherapeutic drugs in the central nervous system (CNS). For that, it is considered as an alternative target for psychotherapeutic drugs. On the cellular level, when Sig-1R is activated, it is known to play a role in neuroprotection and neurite elongation. These effects are suggested to be mediated by its ligand-operated molecular chaperone activity, and/or upregulation of various Ca(2+) signaling. In addition, recent studies show that Sig-1R activation induces neurite outgrowth via neurotrophin signaling. Here, we tested the hypothesis that Sig-1R activation promotes neurite elongation through activation of tropomyosin receptor kinase (Trk), a family of neurotrophin receptors. We found that 2-(4-morpholinethyl)1-phenylcyclohexanecarboxylate (PRE-084), a selective Sig-1R agonist, significantly promoted neurite outgrowth, and K252a, a Trk inhibitor, attenuated Sig-1R-mediated neurite elongation in cerebellar granule neurons (CGNs). Moreover, we revealed that Sig-1R interacts with TrkB, and PRE-084 treatment enhances phosphorylation of Y515, but not Y706. Thus, our results indicate that Sig-1R activation promotes neurite outgrowth in CGNs through Y515 phosphorylation of TrkB.

  13. Effect of chondroitin sulfate proteoglycans on neuronal cell adhesion, spreading and neurite growth in culture

    Directory of Open Access Journals (Sweden)

    Jingyu Jin

    2018-01-01

    Full Text Available As one major component of extracellular matrix (ECM in the central nervous system, chondroitin sulfate proteoglycans (CSPGs have long been known as inhibitors enriched in the glial scar that prevent axon regeneration after injury. Although many studies have shown that CSPGs inhibited neurite outgrowth in vitro using different types of neurons, the mechanism by which CSPGs inhibit axonal growth remains poorly understood. Using cerebellar granule neuron (CGN culture, in this study, we evaluated the effects of different concentrations of both immobilized and soluble CSPGs on neuronal growth, including cell adhesion, spreading and neurite growth. Neurite length decreased while CSPGs concentration arised, meanwhile, a decrease in cell density accompanied by an increase in cell aggregates formation was observed. Soluble CSPGs also showed an inhibition on neurite outgrowth, but it required a higher concentration to induce cell aggregates formation than coated CSPGs. We also found that growth cone size was significantly reduced on CSPGs and neuronal cell spreading was restrained by CSPGs, attributing to an inhibition on lamellipodial extension. The effect of CSPGs on neuron adhesion was further evidenced by interference reflection microscopy (IRM which directly demonstrated that both CGNs and cerebral cortical neurons were more loosely adherent to a CSPG substrate. These data demonstrate that CSPGs have an effect on cell adhesion and spreading in addition to neurite outgrowth.

  14. Mechanosensitivity of Embryonic Neurites Promotes Their Directional Extension and Schwann Cells Progenitors Migration

    Directory of Open Access Journals (Sweden)

    Gonzalo Rosso

    2017-11-01

    Full Text Available Background/Aims: Migration of Schwann cells (SCs progenitors and neurite outgrowth from embryonic dorsal root ganglions (DRGs are two central events during the development of the peripheral nervous system (PNS. How these two enthralling events preceding myelination are promoted is of great relevance from basic research and clinical aspects alike. Recent evidence demonstrates that biophysical cues (extracellular matrix stiffness and biochemical signaling act in concert to regulate PNS myelination. Microenvironment stiffness of SCs progenitors and embryonic neurites dynamically changes during development. Methods: DRG explants were isolated from day 12.5 to 13.5 mice embryos and plated on laminin-coated substrates with varied stiffness values. After 4 days in culture and immunostaining with specific markers, neurite outgrowth pattern, SCs progenitors migration, and growth cone shape and advance were analyzed with confocal fluorescence microscopy. Results: We found out that growing substrate stiffness promotes directional neurite outgrowth, SCs progenitors migration, growth cone advance and presumably axons fasciculation. Conclusions: DRG explants are in vitro models for the research of PNS development, myelination and regeneration. Consequently, we conclude the following: Our observations point out the importance of mechanosensitivity for the PNS. At the same time, they prompt the investigation of the important yet unclear links between PNS biomechanics and inherited neuropathies with myelination disorders such as Charcot-Marie-Tooth 1A and hereditary neuropathy with liability to pressure palsies. Finally, they encourage the consideration of mechanosensitivity in bioengineering of scaffolds to aid nerve regeneration after injury.

  15. Matrix metalloproteinase 2 and membrane type 1 matrix metalloproteinase co-regulate axonal outgrowth of mouse retinal ganglion cells

    DEFF Research Database (Denmark)

    Gaublomme, Djoere; Buyens, Tom; De Groef, Lies

    2014-01-01

    regenerative therapies, an improved understanding of axonal outgrowth and the various molecules influencing it, is highly needed. Matrix metalloproteinases (MMPs) constitute a family of zinc-dependent proteases that were sporadically reported to influence axon outgrowth. Using an ex vivo retinal explant model......, but not MMP-9, are involved in this process. Furthermore, administration of a novel antibody to MT1-MMP that selectively blocks pro-MMP-2 activation revealed a functional co-involvement of these proteinases in determining RGC axon outgrowth. Subsequent immunostainings showed expression of both MMP-2 and MT1...... nervous system is lacking in adult mammals, thereby impeding recovery from injury to the nervous system. Matrix metalloproteinases (MMPs) constitute a family of zinc-dependent proteases that were sporadically reported to influence axon outgrowth. Inhibition of specific MMPs reduced neurite outgrowth from...

  16. Differential regulation of axon outgrowth and reinnervation by neurotrophin-3 and neurotrophin-4 in the hippocampal formation.

    Science.gov (United States)

    Hechler, Daniel; Boato, Francesco; Nitsch, Robert; Hendrix, Sven

    2010-08-01

    In this study, we investigated the hypothesis whether neurotrophins have a differential influence on neurite growth from the entorhinal cortex depending on the presence or absence of hippocampal target tissue. We investigated organotypic brain slices derived from the entorhinal-hippocampal system to analyze the effects of endogenous and recombinant neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) on neurite outgrowth and reinnervation. In the reinnervation assay, entorhinal cortex explants of transgenic mice expressing enhanced green fluorescent protein (EGFP) were co-cultured with wild-type hippocampi under the influence of recombinant NT-3 and NT-4 (500 ng/ml). Both recombinant NT-3 and NT-4 significantly increased the growth of EGFP+ nerve fibers into the target tissue. Consistently, reinnervation of the hippocampi of NT-4(-/-) and NT-3(+/-)NT-4(-/-) mice was substantially reduced. In contrast, the outgrowth assay did not exhibit reduction in axon outgrowth of NT-4(-/-) or NT-3(+/-)NT-4(-/-) cortex explants, while the application of recombinant NT-3 (500 ng/ml) induced a significant increase in the neurite extension of cortex explants. Recombinant NT-4 had no effect. In summary, only recombinant NT-3 stimulates axon outgrowth from cortex explants, while both endogenous and recombinant NT-3 and NT-4 synergistically promote reinnervation of the denervated hippocampus. These results suggest that endogenous and exogenous NT-3 and NT-4 differentially influence neurite growth depending on the presence or absence of target tissue.

  17. Applied electric field enhances DRG neurite growth: influence of stimulation media, surface coating and growth supplements

    Science.gov (United States)

    Wood, Matthew D.; Willits, Rebecca Kuntz

    2009-08-01

    Electrical therapies have been found to aid repair of nerve injuries and have been shown to increase and direct neurite outgrowth during stimulation. This enhanced neural growth existed even after the electric field (EF) or stimulation was removed, but the factors that may influence the enhanced growth, such as stimulation media or surface coating, have not been fully investigated. This study characterized neurite outgrowth and branching under various conditions: EF magnitude and application time, ECM surface coating, medium during EF application and growth supplements. A uniform, low-magnitude EF (24 or 44 V m-1) was applied to dissociated chick embryo dorsal root ganglia seeded on collagen or laminin-coated surfaces. During the growth period, cells were either exposed to NGF or N2, and during stimulation cells were exposed to either unsupplemented media (Ca2+) or PBS (no Ca2+). Parallel controls for each experiment included cells exposed to the chamber with no stimulation and cells remaining outside the chamber. After brief electrical stimulation (10 min), neurite length significantly increased 24 h after application for all conditions studied. Of particular interest, increased stimulation time (10-100 min) further enhanced neurite length on laminin but not on collagen surfaces. Neurite branching was not affected by stimulation on any surface, and no preferential growth of neurites was noted after stimulation. Overall, the results of this report suggest that short-duration electric stimulation is sufficient to enhance neurite length under a variety of conditions. While further data are needed to fully elucidate a mechanism for this increased growth, these data suggest that one focus of those investigations should be the interaction between the growth cone and the substrata.

  18. Nanotechnology versus stem cell engineering: in vitro comparison of neurite inductive potentials.

    Science.gov (United States)

    Morano, Michela; Wrobel, Sandra; Fregnan, Federica; Ziv-Polat, Ofra; Shahar, Abraham; Ratzka, Andreas; Grothe, Claudia; Geuna, Stefano; Haastert-Talini, Kirsten

    2014-01-01

    Innovative nerve conduits for peripheral nerve reconstruction are needed in order to specifically support peripheral nerve regeneration (PNR) whenever nerve autotransplantation is not an option. Specific support of PNR could be achieved by neurotrophic factor delivery within the nerve conduits via nanotechnology or stem cell engineering and transplantation. Here, we comparatively investigated the bioactivity of selected neurotrophic factors conjugated to iron oxide nanoparticles (np-NTFs) and of bone marrow-derived stem cells genetically engineered to overexpress those neurotrophic factors (NTF-BMSCs). The neurite outgrowth inductive activity was monitored in culture systems of adult and neonatal rat sensory dorsal root ganglion neurons as well as in the cell line from rat pheochromocytoma (PC-12) cell sympathetic culture model system. We demonstrate that np-NTFs reliably support numeric neurite outgrowth in all utilized culture models. In some aspects, especially with regard to their long-term bioactivity, np-NTFs are even superior to free NTFs. Engineered NTF-BMSCs proved to be less effective in induction of sensory neurite outgrowth but demonstrated an increased bioactivity in the PC-12 cell culture system. In contrast, primary nontransfected BMSCs were as effective as np-NTFs in sensory neurite induction and demonstrated an impairment of neuronal differentiation in the PC-12 cell system. Our results evidence that nanotechnology as used in our setup is superior over stem cell engineering when it comes to in vitro models for PNR. Furthermore, np-NTFs can easily be suspended in regenerative hydrogel matrix and could be delivered that way to nerve conduits for future in vivo studies and medical application.

  19. Identification of neural outgrowth genes using genome-wide RNAi.

    Directory of Open Access Journals (Sweden)

    Katharine J Sepp

    2008-07-01

    Full Text Available While genetic screens have identified many genes essential for neurite outgrowth, they have been limited in their ability to identify neural genes that also have earlier critical roles in the gastrula, or neural genes for which maternally contributed RNA compensates for gene mutations in the zygote. To address this, we developed methods to screen the Drosophila genome using RNA-interference (RNAi on primary neural cells and present the results of the first full-genome RNAi screen in neurons. We used live-cell imaging and quantitative image analysis to characterize the morphological phenotypes of fluorescently labelled primary neurons and glia in response to RNAi-mediated gene knockdown. From the full genome screen, we focused our analysis on 104 evolutionarily conserved genes that when downregulated by RNAi, have morphological defects such as reduced axon extension, excessive branching, loss of fasciculation, and blebbing. To assist in the phenotypic analysis of the large data sets, we generated image analysis algorithms that could assess the statistical significance of the mutant phenotypes. The algorithms were essential for the analysis of the thousands of images generated by the screening process and will become a valuable tool for future genome-wide screens in primary neurons. Our analysis revealed unexpected, essential roles in neurite outgrowth for genes representing a wide range of functional categories including signalling molecules, enzymes, channels, receptors, and cytoskeletal proteins. We also found that genes known to be involved in protein and vesicle trafficking showed similar RNAi phenotypes. We confirmed phenotypes of the protein trafficking genes Sec61alpha and Ran GTPase using Drosophila embryo and mouse embryonic cerebral cortical neurons, respectively. Collectively, our results showed that RNAi phenotypes in primary neural culture can parallel in vivo phenotypes, and the screening technique can be used to identify many new

  20. Nanotechnology versus stem cell engineering: in vitro comparison of neurite inductive potentials

    Directory of Open Access Journals (Sweden)

    Morano M

    2014-11-01

    Full Text Available Michela Morano,1,* Sandra Wrobel,2,3,* Federica Fregnan,1 Ofra Ziv-Polat,4 Abraham Shahar,4 Andreas Ratzka,2 Claudia Grothe,2,3 Stefano Geuna,1 Kirsten Haastert-Talini2,3 1Department of Clinical and Biological Sciences, Università Degli Studi di Torino, Orbassano, Piemonte, Italy; 2Institute of Neuroanatomy, Hannover Medical School, Hannover, Lower-Saxony, Germany; 3Center for Systems Neuroscience (ZSN, Hannover, Lower-Saxony, Germany; 4NVR Research Ltd, Ness-Ziona, Israel *These authors contributed equally to this work and share first authorship Purpose: Innovative nerve conduits for peripheral nerve reconstruction are needed in order to specifically support peripheral nerve regeneration (PNR whenever nerve autotransplantation is not an option. Specific support of PNR could be achieved by neurotrophic factor delivery within the nerve conduits via nanotechnology or stem cell engineering and transplantation.Methods: Here, we comparatively investigated the bioactivity of selected neurotrophic factors conjugated to iron oxide nanoparticles (np-NTFs and of bone marrow-derived stem cells genetically engineered to overexpress those neurotrophic factors (NTF-BMSCs. The neurite outgrowth inductive activity was monitored in culture systems of adult and neonatal rat sensory dorsal root ganglion neurons as well as in the cell line from rat pheochromocytoma (PC-12 cell sympathetic culture model system.Results: We demonstrate that np-NTFs reliably support numeric neurite outgrowth in all utilized culture models. In some aspects, especially with regard to their long-term bioactivity, np-NTFs are even superior to free NTFs. Engineered NTF-BMSCs proved to be less effective in induction of sensory neurite outgrowth but demonstrated an increased bioactivity in the PC-12 cell culture system. In contrast, primary nontransfected BMSCs were as effective as np-NTFs in sensory neurite induction and demonstrated an impairment of neuronal differentiation in the PC-12

  1. Quantifying Spiral Ganglion Neurite and Schwann Behavior on Micropatterned Polymer Substrates.

    Science.gov (United States)

    Cheng, Elise L; Leigh, Braden; Guymon, C Allan; Hansen, Marlan R

    2016-01-01

    The first successful in vitro experiments on the cochlea were conducted in 1928 by Honor Fell (Fell, Arch Exp Zellforsch 7(1):69-81, 1928). Since then, techniques for culture of this tissue have been refined, and dissociated primary culture of the spiral ganglion has become a widely accepted in vitro model for studying nerve damage and regeneration in the cochlea. Additionally, patterned substrates have been developed that facilitate and direct neural outgrowth. A number of automated and semi-automated methods for quantifying this neurite outgrowth have been utilized in recent years (Zhang et al., J Neurosci Methods 160(1):149-162, 2007; Tapias et al., Neurobiol Dis 54:158-168, 2013). Here, we describe a method to study the effect of topographical cues on spiral ganglion neurite and Schwann cell alignment. We discuss our microfabrication process, characterization of pattern features, cell culture techniques for both spiral ganglion neurons and spiral ganglion Schwann cells. In addition, we describe protocols for reducing fibroblast count, immunocytochemistry, and methods for quantifying neurite and Schwann cell alignment.

  2. Effect of Testosterone on Neuronal Morphology and Neuritic Growth of Fetal Lamb Hypothalamus-Preoptic Area and Cerebral Cortex in Primary Culture.

    Directory of Open Access Journals (Sweden)

    Radhika C Reddy

    Full Text Available Testosterone plays an essential role in sexual differentiation of the male sheep brain. The ovine sexually dimorphic nucleus (oSDN, is 2 to 3 times larger in males than in females, and this sex difference is under the control of testosterone. The effect of testosterone on oSDN volume may result from enhanced expansion of soma areas and/or dendritic fields. To test this hypothesis, cells derived from the hypothalamus-preoptic area (HPOA and cerebral cortex (CTX of lamb fetuses were grown in primary culture to examine the direct morphological effects of testosterone on these cellular components. We found that within two days of plating, neurons derived from both the HPOA and CTX extend neuritic processes and express androgen receptors and aromatase immunoreactivity. Both treated and control neurites continue to grow and branch with increasing time in culture. Treatment with testosterone (10 nM for 3 days significantly (P < 0.05 increased both total neurite outgrowth (35% and soma size (8% in the HPOA and outgrowth (21% and number of branch points (33% in the CTX. These findings indicate that testosterone-induced somal enlargement and neurite outgrowth in fetal lamb neurons may contribute to the development of a fully masculine sheep brain.

  3. Comparison of neurite density measured by MRI and histology after TBI.

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    Shiyang Wang

    Full Text Available Functional recovery after brain injury in animals is improved by marrow stromal cells (MSC which stimulate neurite reorganization. However, MRI measurement of neurite density changes after injury has not been performed. In this study, we investigate the feasibility of MRI measurement of neurite density in an animal model of traumatic brain injury (TBI with and without MSC treatment.Fifteen male Wistar rats, were treated with saline (n = 6 or MSCs (n = 9 and were sacrificed at 6 weeks after controlled cortical impact (CCI. Healthy non-CCI rats (n = 5, were also employed. Ex-vivo MRI scans were performed two days after the rats were sacrificed. Multiple-shell hybrid diffusion imaging encoding scheme and spherical harmonic expansion of a two-compartment water diffusion displacement model were used to extract neurite related parameters. Bielshowski and Luxol Fast blue was used for staining axons and myelin, respectively. Modified Morris water maze and neurological severity score (mNSS test were performed for functional evaluation. The treatment effects, the correlations between neurite densities measured by MRI and histology, and the correlations between MRI and functional variables were calculated by repeated measures analysis of variance, the regression correlation analysis tests, and spearman correlation coefficients.Neurite densities exhibited a significant correlation (R(2>0.80, p<1E-20 between MRI and immuno-histochemistry measurements with 95% lower bound of the intra-correlation coefficient (ICC as 0.86. The conventional fractional anisotropy (FA correlated moderately with histological neurite density (R(2 = 0.59, P<1E-5 with 95% lower bound of ICC as 0.76. MRI data revealed increased neurite reorganization with MSC treatment compared with saline treatment, confirmed by histological data from the same animals. mNSS were significantly correlated with MRI neurite density in the hippocampus region.The present studies

  4. Progranulin functions as a neurotrophic factor to regulate neurite outgrowth and enhance neuronal survival

    NARCIS (Netherlands)

    P. van Damme (Damme); A. van Hoecke (Annelies); D. Lambrechts (Diether); P. Vanacker (Peter); E. Bogaert (Elke); J.C. van Swieten (John); P. Carmeliet (Peter); L. van den Bosch (Ludo); W. Robberecht (Wim)

    2008-01-01

    textabstractRecently, mutations in the progranulin (PGRN) gene were found to cause familial and apparently sporadic frontotemporal lobe dementia (FTLD). Moreover, missense changes in PGRN were identified in patients with motor neuron degeneration, a condition that is related to FTLD. Most mutations

  5. Transcallosal Projections Require Glycoprotein M6-Dependent Neurite Growth and Guidance.

    Science.gov (United States)

    Mita, Sakura; de Monasterio-Schrader, Patricia; Fünfschilling, Ursula; Kawasaki, Takahiko; Mizuno, Hidenobu; Iwasato, Takuji; Nave, Klaus-Armin; Werner, Hauke B; Hirata, Tatsumi

    2015-11-01

    The function of mature neurons critically relies on the developmental outgrowth and projection of their cellular processes. It has long been postulated that the neuronal glycoproteins M6a and M6b are involved in axon growth because these four-transmembrane domain-proteins of the proteolipid protein family are highly enriched on growth cones, but in vivo evidence has been lacking. Here, we report that the function of M6 proteins is required for normal axonal extension and guidance in vivo. In mice lacking both M6a and M6b, a severe hypoplasia of axon tracts was manifested. Most strikingly, the corpus callosum was reduced in thickness despite normal densities of cortical projection neurons. In single neuron tracing, many axons appeared shorter and disorganized in the double-mutant cortex, and some of them were even misdirected laterally toward the subcortex. Probst bundles were not observed. Upon culturing, double-mutant cortical and cerebellar neurons displayed impaired neurite outgrowth, indicating a cell-intrinsic function of M6 proteins. A rescue experiment showed that the intracellular loop of M6a is essential for the support of neurite extension. We propose that M6 proteins are required for proper extension and guidance of callosal axons that follow one of the most complex trajectories in the mammalian nervous system. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Conversion Disorder Presenting As Neuritic Leprosy

    Directory of Open Access Journals (Sweden)

    Sayal SK

    2000-01-01

    Full Text Available Conversion disorder is not normally listed amongst the conditions in differential diagnosis of leprosy neuropathy. A case conversion reaction who was initially diagnosed as neuritic leprosy is reported. Patient responded to narcosuggestion and psychotherapy.

  7. Deficits in Neurite Density Underlie White Matter Structure Abnormalities in First-Episode Psychosis.

    Science.gov (United States)

    Rae, Charlotte L; Davies, Geoff; Garfinkel, Sarah N; Gabel, Matt C; Dowell, Nicholas G; Cercignani, Mara; Seth, Anil K; Greenwood, Kathryn E; Medford, Nick; Critchley, Hugo D

    2017-11-15

    Structural abnormalities across multiple white matter tracts are recognized in people with early psychosis, consistent with dysconnectivity as a neuropathological account of symptom expression. We applied advanced neuroimaging techniques to characterize microstructural white matter abnormalities for a deeper understanding of the developmental etiology of psychosis. Thirty-five first-episode psychosis patients, and 19 healthy controls, participated in a quantitative neuroimaging study using neurite orientation dispersion and density imaging, a multishell diffusion-weighted magnetic resonance imaging technique that distinguishes white matter fiber arrangement and geometry from changes in neurite density. Fractional anisotropy (FA) and mean diffusivity images were also derived. Tract-based spatial statistics compared white matter structure between patients and control subjects and tested associations with age, symptom severity, and medication. Patients with first-episode psychosis had lower regional FA in multiple commissural, corticospinal, and association tracts. These abnormalities predominantly colocalized with regions of reduced neurite density, rather than aberrant fiber bundle arrangement (orientation dispersion index). There was no direct relationship with active symptoms. FA decreased and orientation dispersion index increased with age in patients, but not control subjects, suggesting accelerated effects of white matter geometry change. Deficits in neurite density appear fundamental to abnormalities in white matter integrity in early psychosis. In the first application of neurite orientation dispersion and density imaging in psychosis, we found that processes compromising axonal fiber number, density, and myelination, rather than processes leading to spatial disruption of fiber organization, are implicated in the etiology of psychosis. This accords with a neurodevelopmental origin of aberrant brain-wide structural connectivity predisposing individuals to

  8. BIG1, a brefeldin A-inhibited guanine nucleotide-exchange protein regulates neurite development via PI3K-AKT and ERK signaling pathways.

    Science.gov (United States)

    Zhou, C; Li, C; Li, D; Wang, Y; Shao, W; You, Y; Peng, J; Zhang, X; Lu, L; Shen, X

    2013-12-19

    The elongation of neuron is highly dependent on membrane trafficking. Brefeldin A (BFA)-inhibited guanine nucleotide-exchange protein 1 (BIG1) functions in the membrane trafficking between the Golgi apparatus and the plasma membrane. BFA, an uncompetitive inhibitor of BIG1 can inhibit neurite outgrowth and polarity development. In this study, we aimed to define the possible role of BIG1 in neurite development and to further investigate the potential mechanism. By immunostaining, we found that BIG1 was extensively colocalized with synaptophysin, a marker for synaptic vesicles in soma and partly in neurites. The amount of both protein and mRNA of BIG1 were up-regulated during rat brain development. BIG1 depletion significantly decreased the neurite length and inhibited the phosphorylation of phosphatidylinositide 3-kinase (PI3K) and protein kinase B (AKT). Inhibition of BIG1 guanine nucleotide-exchange factor (GEF) activity by BFA or overexpression of the dominant-negative BIG1 reduced PI3K and AKT phosphorylation, indicating regulatory effects of BIG1 on PI3K-AKT signaling pathway is dependent on its GEF activity. BIG1 siRNA or BFA treatment also significantly reduced extracellular signal-regulated kinase (ERK) phosphorylation. Overexpression of wild-type BIG1 significantly increased ERK phosphorylation, but the dominant-negative BIG1 had no effect on ERK phosphorylation, indicating the involvement of BIG1 in ERK signaling regulation may not be dependent on its GEF activity. Our result identified a novel function of BIG1 in neurite development. The newly recognized function integrates the function of BIG1 in membrane trafficking with the activation of PI3K-AKT and ERK signaling pathways which are critical in neurite development. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. A role for complexes of survival of motor neurons (SMN) protein with gemins and profilin in neurite-like cytoplasmic extensions of cultured nerve cells

    International Nuclear Information System (INIS)

    Sharma, Aarti; Lambrechts, Anja; Le thi Hao; Le, Thanh T.; Sewry, Caroline A.; Ampe, Christophe; Burghes, Arthur H.M.; Morris, Glenn E.

    2005-01-01

    Spinal muscular atrophy (SMA) is caused by reduced levels of SMN (survival of motor neurons protein) and consequent loss of motor neurons. SMN is involved in snRNP transport and nuclear RNA splicing, but axonal transport of SMN has also been shown to occur in motor neurons. SMN also binds to the small actin-binding protein, profilin. We now show that SMN and profilin II co-localise in the cytoplasm of differentiating rat PC12 cells and in neurite-like extensions, especially at their growth cones. Many components of known SMN complexes were also found in these extensions, including gemin2 (SIP-1), gemin6, gemin7 and unrip (unr-interacting protein). Coilin p80 and Sm core protein immunoreactivity, however, were seen only in the nucleus. SMN is known to associate with β-actin mRNA and specific hnRNPs in axons and in neurite extensions of cultured nerve cells, and SMN also stimulates neurite outgrowth in cultures. Our results are therefore consistent with SMN complexes, rather than SMN alone, being involved in the transport of actin mRNPs along the axon as in the transport of snRNPs into the nucleus by similar SMN complexes. Antisense knockdown of profilin I and II isoforms inhibited neurite outgrowth of PC12 cells and caused accumulation of SMN and its associated proteins in cytoplasmic aggregates. BIAcore studies demonstrated a high affinity interaction of SMN with profilin IIa, the isoform present in developing neurons. Pathogenic missense mutations in SMN, or deletion of exons 5 and 7, prevented this interaction. The interaction is functional in that SMN can modulate actin polymerisation in vitro by reducing the inhibitory effect of profilin IIa. This suggests that reduced SMN in SMA might cause axonal pathfinding defects by disturbing the normal regulation of microfilament growth by profilins

  10. Electrospun silk fibroin scaffolds coated with reduced graphene promote neurite outgrowth of PC-12 cells under electrical stimulation.

    Science.gov (United States)

    Aznar-Cervantes, Salvador; Pagán, Ana; Martínez, Jose G; Bernabeu-Esclapez, Antonia; Otero, Toribio F; Meseguer-Olmo, Luis; Paredes, Juan I; Cenis, Jose L

    2017-10-01

    Novel approaches to neural research require biocompatible materials capable to act as electrode structures or scaffolds for tissue engineering in order to stimulate or restore the functionality of damaged tissues. This work offers promising results that indicate the potential use of electrospun silk fibroin (SF) scaffolds coated with reduced graphene oxide (rGO) in this sense. The coated material becomes conductor and electroactive. A complete characterisation of SF/rGO scaffolds is provided in terms of electrochemistry, mechanical behaviour and chemical conformation of fibroin. The excellent biocompatibility of this novel material is proved with cultures of PC-12 cells. The coating with rGO improved the adhesion of cells in comparison with cells growing onto the surface of pure SF scaffolds. Also, the use of SF/rGO scaffolds combined with electrical stimulation promoted the differentiation into neural phenotypes reaching comparable or even superior levels to those obtained by means of the traditional treatment with neural growth factor (NGF). Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Peptides modeled after the alpha-domain of metallothionein induce neurite outgrowth and promote survival of cerebellar granule neurons

    DEFF Research Database (Denmark)

    Asmussen, Johanne Wirenfeldt; Ambjørn, Malene; Bock, Elisabeth

    2009-01-01

    amino acids, as potent stimulators of neuronal differentiation and survival of primary neurons. In addition, we show that a peptide derived from the N-terminus of the MT beta-domain, EmtinBn, promotes neuronal survival. The neuritogenic and survival promoting effects of EmtinAc, similar to MT and Emtin...

  12. ASSESSMENT OF CHEMICAL EFFECTS ON NEURITE OUTGROWTH, NEURONAL POLARIZATION AND SYNAPTOGENESIS IN RAT CORTICAL NEURONS USING HIGH CONTENT IMAGE ANALYSIS

    Science.gov (United States)

    There is a need for efficient, cost-effective methods for screening and prioritization of potential developmental neurotoxicants. One approach uses in vitro cell culture models that can recapitulate the critical processes of nervous system development. In vitro, primary cultures ...

  13. Neuron cell positioning on polystyrene in culture by silver-negative ion implantation and region control of neural outgrowth

    International Nuclear Information System (INIS)

    Tsuji, Hiroshi; Sato, Hiroko; Baba, Takahiro; Ikemura, Shin'ichi; Gotoh, Yasuhito; Ishikawa, Junzo

    2000-01-01

    A new method to control the position of neuron cell attachment and extension region of neural outgrowth has been developed by using a pattering ion implantation with silver-negative ions into polystyrene dishes. This technique offers a promising method to form an artificially designed neural network in cell culture in vitro. Silver-negative ions were implanted into non-treated polystyrene dishes (NTPS) at conditions of 20 keV and 3x10 15 ions/cm 2 through a pattering mask, which had as many as 67 slits of 60 μm in width and 4 mm in length with a spacing of 60 μm. For cell culture in vitro, nerve cells of PC-12h (rat adrenal phechromocytoma) were used because they respond to a nerve growth factor (NGF). In the first 2 days in culture without NGF, we observed a selective cell attachment only to the ion-implanted region in patterning Ag - implanted polystyrene sample (p-Ag/NTPS). In another 2 days in culture with NGF, the nerve cells expanded neurites only over the ion-implanted region. For collagen-coated p-Ag/NTPS sample of which collagen was coated after the ion implantation (Collagen/p-Ag/NTPS), most nerve cells were also attached on the ion-implanted region. However, neurites expanded in both ion-implanted and unimplanted regions. The contact angle of NTPS decreased after the ion implantation from 86 deg. to 74 deg. . The region selectivity of neuron attachment and neurite extension is considered to be due to contact angle lowering by the ion implantation as radiation effect on the surface

  14. Constitutive Overexpression of the Basic Helix-Loop-Helix Nex1/MATH-2 Transcription Factor Promotes Neuronal Differentiation of PC12 Cells and Neurite Regeneration

    Science.gov (United States)

    Uittenbogaard, Martine; Chiaramello, Anne

    2009-01-01

    Elucidation of the intricate transcriptional pathways leading to neural differentiation and the establishment of neuronal identity is critical to the understanding and design of therapeutic approaches. Among the important players, the basic helix-loop-helix (bHLH) transcription factors have been found to be pivotal regulators of neurogenesis. In this study, we investigate the role of the bHLH differentiation factor Nex1/MATH-2 in conjunction with the nerve growth factor (NGF) signaling pathway using the rat phenochromocytoma PC12 cell line. We report that the expression of Nex1 protein is induced after 5 hr of NGF treatment and reaches maximal levels at 24 hr, when very few PC12 cells have begun extending neurites and ceased cell division. Furthermore, our study demonstrates that Nex1 has the ability to trigger neuronal differentiation of PC12 cells in the absence of neurotrophic factor. We show that Nex1 plays an important role in neurite outgrowth and has the capacity to regenerate neurite outgrowth in the absence of NGF. These results are corroborated by the fact that Nex1 targets a repertoire of distinct types of genes associated with neuronal differentiation, such as GAP-43, βIII-tubulin, and NeuroD. In addition, our findings show that Nex1 up-regulates the expression of the mitotic inhibitor p21WAF1, thus linking neuronal differentiation to cell cycle withdrawal. Finally, our studies show that overexpression of a Nex1 mutant has the ability to block the execution of NGF-induced differentiation program, suggesting that Nex1 may be an important effector of the NGF signaling pathway. PMID:11782967

  15. Neurite, a finite difference large scale parallel program for the simulation of electrical signal propagation in neurites under mechanical loading.

    Directory of Open Access Journals (Sweden)

    Julián A García-Grajales

    Full Text Available With the growing body of research on traumatic brain injury and spinal cord injury, computational neuroscience has recently focused its modeling efforts on neuronal functional deficits following mechanical loading. However, in most of these efforts, cell damage is generally only characterized by purely mechanistic criteria, functions of quantities such as stress, strain or their corresponding rates. The modeling of functional deficits in neurites as a consequence of macroscopic mechanical insults has been rarely explored. In particular, a quantitative mechanically based model of electrophysiological impairment in neuronal cells, Neurite, has only very recently been proposed. In this paper, we present the implementation details of this model: a finite difference parallel program for simulating electrical signal propagation along neurites under mechanical loading. Following the application of a macroscopic strain at a given strain rate produced by a mechanical insult, Neurite is able to simulate the resulting neuronal electrical signal propagation, and thus the corresponding functional deficits. The simulation of the coupled mechanical and electrophysiological behaviors requires computational expensive calculations that increase in complexity as the network of the simulated cells grows. The solvers implemented in Neurite--explicit and implicit--were therefore parallelized using graphics processing units in order to reduce the burden of the simulation costs of large scale scenarios. Cable Theory and Hodgkin-Huxley models were implemented to account for the electrophysiological passive and active regions of a neurite, respectively, whereas a coupled mechanical model accounting for the neurite mechanical behavior within its surrounding medium was adopted as a link between electrophysiology and mechanics. This paper provides the details of the parallel implementation of Neurite, along with three different application examples: a long myelinated axon

  16. Elastic anisotropy of crystals

    Directory of Open Access Journals (Sweden)

    Christopher M. Kube

    2016-09-01

    Full Text Available An anisotropy index seeks to quantify how directionally dependent the properties of a system are. In this article, the focus is on quantifying the elastic anisotropy of crystalline materials. Previous elastic anisotropy indices are reviewed and their shortcomings discussed. A new scalar log-Euclidean anisotropy measure AL is proposed, which overcomes these deficiencies. It is based on a distance measure in a log-Euclidean space applied to fourth-rank elastic tensors. AL is an absolute measure of anisotropy where the limiting case of perfect isotropy yields zero. It is a universal measure of anisotropy applicable to all crystalline materials. Specific examples of strong anisotropy are highlighted. A supplementary material provides an anisotropy table giving the values of AL for 2,176 crystallite compounds.

  17. Morphological identification and development of neurite in Drosophila ventral nerve cord neuropil.

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    Guangming Gan

    Full Text Available In Drosophila, ventral nerve cord (VNC occupies most of the larval central nervous system (CNS. However, there is little literature elaborating upon the specific types and growth of neurites as defined by their structural appearance in Drosophila larval VNC neuropil. Here we report the ultrastructural development of different types VNC neurites in ten selected time points in embryonic and larval stages utilizing transmission electron microscopy. There are four types of axonal neurites as classified by the type of vesicular content: clear vesicle (CV neurites have clear vesicles and some T-bar structures; Dense-core vesicle (DV neurites have dense-core vesicles and without T-bar structures; Mixed vesicle (MV neurites have mixed vesicles and some T-bar structures; Large vesicle (LV neurites are dominated by large, translucent spherical vesicles but rarely display T-bar structures. We found dramatic remodeling in CV neurites which can be divided into five developmental phases. The neurite is vacuolated in primary (P phase, they have mitochondria, microtubules or big dark vesicles in the second (S phase, and they contain immature synaptic features in the third (T phase. The subsequent bifurcate (B phase appears to undergo major remodeling with the appearance of the bifurcation or dendritic growth. In the final mature (M phase, high density of commensurate synaptic vesicles are distributed around T-bar structures. There are four kinds of morphological elaboration of the CVI neurite sub-types. First, new neurite produces at the end of axon. Second, new neurite bubbles along the axon. Third, the preexisting neurite buds and develops into several neurites. The last, the bundled axons form irregularly shape neurites. Most CVI neurites in M phase have about 1.5-3 µm diameter, they could be suitable to analyze their morphology and subcellular localization of specific proteins by light microscopy, and they could serve as a potential model in CNS in vivo

  18. Morphological identification and development of neurite in Drosophila ventral nerve cord neuropil.

    Science.gov (United States)

    Gan, Guangming; Lv, Huihui; Xie, Wei

    2014-01-01

    In Drosophila, ventral nerve cord (VNC) occupies most of the larval central nervous system (CNS). However, there is little literature elaborating upon the specific types and growth of neurites as defined by their structural appearance in Drosophila larval VNC neuropil. Here we report the ultrastructural development of different types VNC neurites in ten selected time points in embryonic and larval stages utilizing transmission electron microscopy. There are four types of axonal neurites as classified by the type of vesicular content: clear vesicle (CV) neurites have clear vesicles and some T-bar structures; Dense-core vesicle (DV) neurites have dense-core vesicles and without T-bar structures; Mixed vesicle (MV) neurites have mixed vesicles and some T-bar structures; Large vesicle (LV) neurites are dominated by large, translucent spherical vesicles but rarely display T-bar structures. We found dramatic remodeling in CV neurites which can be divided into five developmental phases. The neurite is vacuolated in primary (P) phase, they have mitochondria, microtubules or big dark vesicles in the second (S) phase, and they contain immature synaptic features in the third (T) phase. The subsequent bifurcate (B) phase appears to undergo major remodeling with the appearance of the bifurcation or dendritic growth. In the final mature (M) phase, high density of commensurate synaptic vesicles are distributed around T-bar structures. There are four kinds of morphological elaboration of the CVI neurite sub-types. First, new neurite produces at the end of axon. Second, new neurite bubbles along the axon. Third, the preexisting neurite buds and develops into several neurites. The last, the bundled axons form irregularly shape neurites. Most CVI neurites in M phase have about 1.5-3 µm diameter, they could be suitable to analyze their morphology and subcellular localization of specific proteins by light microscopy, and they could serve as a potential model in CNS in vivo development.

  19. Conditioned medium of dental pulp cells stimulated by Chinese propolis show neuroprotection and neurite extension in vitro.

    Science.gov (United States)

    Kudo, Daichi; Inden, Masatoshi; Sekine, Shin-Ichiro; Tamaoki, Naritaka; Iida, Kazuki; Naito, Eiji; Watanabe, Kazuhiro; Kamishina, Hiroaki; Shibata, Toshiyuki; Hozumi, Isao

    2015-03-04

    The purpose of this study was to clarify the effect of Chinese propolis on the expression level of neurotrophic factors in dental pulp cells (DPCs). We also investigated that the effects of the conditioned medium (CM) of DPCs stimulated by the propolis against oxidative and endoplasmic reticulum (ER) stresses in human neuroblastoma SH-SY5Y cells, and on neurite extensions in rat adrenal pheochromocytoma PC12 cells. To investigate the effect of the propolis on the levels of neurotrophic factors in DPCs, we performed a qRT-PCR experiment. As results, NGF, but not BDNF and NT-3, in DPCs was significantly elevated by the propolis in a concentration-dependent manner. H2O2-induced cell death was significantly inhibited by the treatment with the CM of DPCs. In addition, the treatment with the propolis-stimulated CM of DPCs had a more protective effect than that with the CM of DPCs. We also examine the effect of the propolis-stimulated CM of DPCs against a tunicamycin-induced ER stress. The treatment with the propolis-stimulated CM as well as the CM of DPCs significantly inhibited tunicamycin-induced cell death. Moreover, the treatment with the propolis-stimulated CM of DPCs significantly induced neurite outgrowth from PC12 cells than that with the CM of DPCs. These results suggest that the CM of DPCs as well as DPCs will be an efficient source of new treatments for neurodegenerative diseases and that the propolis promote the advantage of the CM of DPCs via producing neurotrophic factors. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. The Deacetylase HDAC6 Mediates Endogenous Neuritic Tau Pathology

    Directory of Open Access Journals (Sweden)

    Jui-Heng Tseng

    2017-08-01

    Full Text Available The initiating events that promote tau mislocalization and pathology in Alzheimer’s disease (AD are not well defined, partly because of the lack of endogenous models that recapitulate tau dysfunction. We exposed wild-type neurons to a neuroinflammatory trigger and examined the effect on endogenous tau. We found that tau re-localized and accumulated within pathological neuritic foci, or beads, comprised of mostly hypo-phosphorylated, acetylated, and oligomeric tau. These structures were detected in aged wild-type mice and were enhanced in response to neuroinflammation in vivo, highlighting a previously undescribed endogenous age-related tau pathology. Strikingly, deletion or inhibition of the cytoplasmic shuttling factor HDAC6 suppressed neuritic tau bead formation in neurons and mice. Using mass spectrometry-based profiling, we identified a single neuroinflammatory factor, the metalloproteinase MMP-9, as a mediator of neuritic tau beading. Thus, our study uncovers a link between neuroinflammation and neuritic tau beading as a potential early-stage pathogenic mechanism in AD.

  1. Shape anisotropy: tensor distance to anisotropy measure

    Science.gov (United States)

    Weldeselassie, Yonas T.; El-Hilo, Saba; Atkins, M. S.

    2011-03-01

    Fractional anisotropy, defined as the distance of a diffusion tensor from its closest isotropic tensor, has been extensively studied as quantitative anisotropy measure for diffusion tensor magnetic resonance images (DT-MRI). It has been used to reveal the white matter profile of brain images, as guiding feature for seeding and stopping in fiber tractography and for the diagnosis and assessment of degenerative brain diseases. Despite its extensive use in DT-MRI community, however, not much attention has been given to the mathematical correctness of its derivation from diffusion tensors which is achieved using Euclidean dot product in 9D space. But, recent progress in DT-MRI has shown that the space of diffusion tensors does not form a Euclidean vector space and thus Euclidean dot product is not appropriate for tensors. In this paper, we propose a novel and robust rotationally invariant diffusion anisotropy measure derived using the recently proposed Log-Euclidean and J-divergence tensor distance measures. An interesting finding of our work is that given a diffusion tensor, its closest isotropic tensor is different for different tensor distance metrics used. We demonstrate qualitatively that our new anisotropy measure reveals superior white matter profile of DT-MR brain images and analytically show that it has a higher signal to noise ratio than fractional anisotropy.

  2. Live-imaging of Bacillus subtilis spore germination and outgrowth

    NARCIS (Netherlands)

    Pandey, R.

    2014-01-01

    Spores of Gram-positive bacteria such as Bacillus and Clostridium cause huge economic losses to the food industry. In food products, spores survive under food preservation conditions and subsequent germination and outgrowth eventually causes food spoilage. Therefore efforts are being made to

  3. Characterisation of bovine epiblast-derived outgrowth colonies

    DEFF Research Database (Denmark)

    Østrup, Esben; Gjørret, Jakob; Schauser, Kirsten Hallundbæk

    2010-01-01

    The aim of the present study was to characterise bovine epiblast-derived outgrowth colonies (OCs) with respect to the embryonic origin of their cellular components. Epiblasts were isolated mechanically from bovine Day 12 embryos. Epiblasts were cultured on feeder layers of SNL cells (neomycin...

  4. Expression of Rac1 alternative 3' UTRs is a cell specific mechanism with a function in dendrite outgrowth in cortical neurons.

    Science.gov (United States)

    Braz, Sandra Oliveira; Cruz, Andrea; Lobo, Andrea; Bravo, Joana; Moreira-Ribeiro, Joana; Pereira-Castro, Isabel; Freitas, Jaime; Relvas, Joao B; Summavielle, Teresa; Moreira, Alexandra

    2017-06-01

    The differential expression of mRNAs containing tandem alternative 3' UTRs, achieved by mechanisms of alternative polyadenylation and post-transcriptional regulation, has been correlated with a variety of cellular states. In differentiated cells and brain tissues there is a general use of distal polyadenylation signals, originating mRNAs with longer 3' UTRs, in contrast with proliferating cells and other tissues such as testis, where most mRNAs contain shorter 3' UTRs. Although cell type and state are relevant in many biological processes, how these mechanisms occur in specific brain cell types is still poorly understood. Rac1 is a member of the Rho family of small GTPases with essential roles in multiple cellular processes, including cell differentiation and axonal growth. Here we used different brain cell types and tissues, including oligodendrocytes, microglia, astrocytes, cortical and hippocampal neurons, and optical nerve, to show that classical Rho GTPases express mRNAs with alternative 3' UTRs differently, by gene- and cell- specific mechanisms. In particular, we show that Rac1 originate mRNA isoforms with longer 3' UTRs specifically during neurite growth of cortical, but not hippocampal neurons. Furthermore, we demonstrate that the longest Rac1 3' UTR is necessary for driving the mRNA to the neurites, and also for neurite outgrowth in cortical neurons. Our results indicate that the expression of Rac1 longer 3' UTR is a gene and cell-type specific mechanism in the brain, with a new physiological function in cortical neuron differentiation. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Application of neurite orientation dispersion and density imaging (NODDI) to a tau pathology model of Alzheimer's disease.

    LENUS (Irish Health Repository)

    Colgan, N

    2015-10-23

    Increased hyperphosphorylated tau and the formation of intracellular neurofibrillary tangles are associated with the loss of neurons and cognitive decline in Alzheimer\\'s disease, and related neurodegenerative conditions. We applied two diffusion models, diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI), to in vivo diffusion magnetic resonance images (dMRI) of a mouse model of human tauopathy (rTg4510) at 8.5months of age. In grey matter regions with the highest degree of tau burden, microstructural indices provided by both NODDI and DTI discriminated the rTg4510 (TG) animals from wild type (WT) controls; however only the neurite density index (NDI) (the volume fraction that comprises axons or dendrites) from the NODDI model correlated with the histological measurements of the levels of hyperphosphorylated tau protein. Reductions in diffusion directionality were observed when implementing both models in the white matter region of the corpus callosum, with lower fractional anisotropy (DTI) and higher orientation dispersion (NODDI) observed in the TG animals. In comparison to DTI, histological measures of tau pathology were more closely correlated with NODDI parameters in this region. This in vivo dMRI study demonstrates that NODDI identifies potential tissue sources contributing to DTI indices and NODDI may provide greater specificity to pathology in Alzheimer\\'s disease.

  6. Light Signaling in Bud Outgrowth and Branching in Plants

    Directory of Open Access Journals (Sweden)

    Nathalie Leduc

    2014-04-01

    Full Text Available Branching determines the final shape of plants, which influences adaptation, survival and the visual quality of many species. It is an intricate process that includes bud outgrowth and shoot extension, and these in turn respond to environmental cues and light conditions. Light is a powerful environmental factor that impacts multiple processes throughout plant life. The molecular basis of the perception and transduction of the light signal within buds is poorly understood and undoubtedly requires to be further unravelled. This review is based on current knowledge on bud outgrowth-related mechanisms and light-mediated regulation of many physiological processes. It provides an extensive, though not exhaustive, overview of the findings related to this field. In parallel, it points to issues to be addressed in the near future.

  7. Chlorpyrifos- and chlorpyrifos oxon-induced neurite retraction in pre-differentiated N2a cells is associated with transient hyperphosphorylation of neurofilament heavy chain and ERK 1/2

    Energy Technology Data Exchange (ETDEWEB)

    Sindi, Ramya A., E-mail: ramya.sindi2010@my.ntu.ac.uk [Interdisciplinary Biomedical Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS (United Kingdom); School of Applied Medical Sciences, Umm Al-Qura University, Makkah (Saudi Arabia); Harris, Wayne [Interdisciplinary Biomedical Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS (United Kingdom); Arnott, Gordon [School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS (United Kingdom); Flaskos, John [Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Lloyd Mills, Chris [School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS (United Kingdom); Hargreaves, Alan J., E-mail: alan.hargreaves@ntu.ac.uk [Interdisciplinary Biomedical Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS (United Kingdom)

    2016-10-01

    Chlorpyrifos (CPF) and CPF-oxon (CPO) are known to inhibit neurite outgrowth but little is known about their ability to induce neurite retraction in differentiating neuronal cells. The aims of this study were to determine the ability of these compounds to destabilize neurites and to identify the key molecular events involved. N2a cells were induced to differentiate for 20 h before exposure to CPF or CPO for 2–8 h. Fixed cell monolayers labeled with carboxyfluorescein succinimidyl ester or immunofluorescently stained with antibodies to tubulin (B512) or phosphorylated neurofilament heavy chain (Ta51) showed time- and concentration-dependent reductions in numbers and length of axon-like processes compared to the control, respectively, retraction of neurites being observed within 2 h of exposure by live cell imaging. Neurofilament disruption was also observed in treated cells stained by indirect immunofluorescence with anti-phosphorylated neurofilament heavy chain (NFH) monoclonal antibody SMI34, while the microtubule network was unaffected. Western blotting analysis revealed transiently increased levels of reactivity of Ta51 after 2 h exposure and reduced levels of reactivity of the same antibody following 8 h treatment with both compounds, whereas reactivity with antibodies to anti-total NFH or anti-tubulin was not affected. The alteration in NFH phosphorylation at 2 h exposure was associated with increased activation of extracellular signal-regulated protein kinase ERK 1/2. However, increased levels of phosphatase activity were observed following 8 h exposure. These findings suggest for the first time that organophosphorothionate pesticide-induced neurite retraction in N2a cells is associated with transient increases in NFH phosphorylation and ERK1/2 activation. - Highlights: • Chlorpyrifos and chlorpyrifos oxon induced rapid neurite retraction in N2a cells. • This occurred following transient hyperphosphorylation of ERK 1/2. • It was concomitant with

  8. Chlorpyrifos- and chlorpyrifos oxon-induced neurite retraction in pre-differentiated N2a cells is associated with transient hyperphosphorylation of neurofilament heavy chain and ERK 1/2

    International Nuclear Information System (INIS)

    Sindi, Ramya A.; Harris, Wayne; Arnott, Gordon; Flaskos, John; Lloyd Mills, Chris; Hargreaves, Alan J.

    2016-01-01

    Chlorpyrifos (CPF) and CPF-oxon (CPO) are known to inhibit neurite outgrowth but little is known about their ability to induce neurite retraction in differentiating neuronal cells. The aims of this study were to determine the ability of these compounds to destabilize neurites and to identify the key molecular events involved. N2a cells were induced to differentiate for 20 h before exposure to CPF or CPO for 2–8 h. Fixed cell monolayers labeled with carboxyfluorescein succinimidyl ester or immunofluorescently stained with antibodies to tubulin (B512) or phosphorylated neurofilament heavy chain (Ta51) showed time- and concentration-dependent reductions in numbers and length of axon-like processes compared to the control, respectively, retraction of neurites being observed within 2 h of exposure by live cell imaging. Neurofilament disruption was also observed in treated cells stained by indirect immunofluorescence with anti-phosphorylated neurofilament heavy chain (NFH) monoclonal antibody SMI34, while the microtubule network was unaffected. Western blotting analysis revealed transiently increased levels of reactivity of Ta51 after 2 h exposure and reduced levels of reactivity of the same antibody following 8 h treatment with both compounds, whereas reactivity with antibodies to anti-total NFH or anti-tubulin was not affected. The alteration in NFH phosphorylation at 2 h exposure was associated with increased activation of extracellular signal-regulated protein kinase ERK 1/2. However, increased levels of phosphatase activity were observed following 8 h exposure. These findings suggest for the first time that organophosphorothionate pesticide-induced neurite retraction in N2a cells is associated with transient increases in NFH phosphorylation and ERK1/2 activation. - Highlights: • Chlorpyrifos and chlorpyrifos oxon induced rapid neurite retraction in N2a cells. • This occurred following transient hyperphosphorylation of ERK 1/2. • It was concomitant with

  9. Expression profiling of prospero in the Drosophila larval chemosensory organ: Between growth and outgrowth

    Directory of Open Access Journals (Sweden)

    Raharijaona Mahatsangy

    2010-01-01

    Full Text Available Abstract Background The antenno-maxilary complex (AMC forms the chemosensory system of the Drosophila larva and is involved in gustatory and olfactory perception. We have previously shown that a mutant allele of the homeodomain transcription factor Prospero (prosVoila1, V1, presents several developmental defects including abnormal growth and altered taste responses. In addition, many neural tracts connecting the AMC to the central nervous system (CNS were affected. Our earlier reports on larval AMC did not argue in favour of a role of pros in cell fate decision, but strongly suggested that pros could be involved in the control of other aspect of neuronal development. In order to identify these functions, we used microarray analysis of larval AMC and CNS tissue isolated from the wild type, and three other previously characterised prospero alleles, including the V1 mutant, considered as a null allele for the AMC. Results A total of 17 samples were first analysed with hierarchical clustering. To determine those genes affected by loss of pros function, we calculated a discriminating score reflecting the differential expression between V1 mutant and other pros alleles. We identified a total of 64 genes in the AMC. Additional manual annotation using all the computed information on the attributed role of these genes in the Drosophila larvae nervous system, enabled us to identify one functional category of potential Prospero target genes known to be involved in neurite outgrowth, synaptic transmission and more specifically in neuronal connectivity remodelling. The second category of genes found to be differentially expressed between the null mutant AMC and the other alleles concerned the development of the sensory organs and more particularly the larval olfactory system. Surprisingly, a third category emerged from our analyses and suggests an association of pros with the genes that regulate autophagy, growth and insulin pathways. Interestingly, EGFR and

  10. Neovascularization Potential of Blood Outgrowth Endothelial Cells From Patients With Stable Ischemic Heart Failure Is Preserved

    OpenAIRE

    Dauwe, Dieter; Pelacho, Beatriz; Wibowo, Arief; Walravens, Ann-Sophie; Verdonck, Kristoff; Gillijns, Hilde; Caluwe, Ellen; Pokreisz, Peter; van Gastel, Nick; Carmeliet, Geert; Depypere, Maarten; Maes, Frederik; Vanden Driessche, Nina; Droogne, Walter; Van Cleemput, Johan

    2016-01-01

    Background Blood outgrowth endothelial cells (BOECs) mediate therapeutic neovascularization in experimental models, but outgrowth characteristics and functionality of BOECs from patients with ischemic cardiomyopathy (ICMP) are unknown. We compared outgrowth efficiency and in?vitro and in?vivo functionality of BOECs derived from ICMP with BOECs from age?matched (ACON) and healthy young (CON) controls. Methods and Results We isolated 3.6?0.6 BOEC colonies/100?106 mononuclear cells (MNCs) from 6...

  11. NGF-Dependent neurite outgrowth in PC12 cells overexpressing the Src homology 2-domain protein shb requires activation of the Rap1 pathway

    NARCIS (Netherlands)

    Lu, L.; Annerén, C.; Reedquist, K. A.; Bos, J. L.; Welsh, M.

    2000-01-01

    The Src homology 2 (SH2) domain adaptor protein Shb has been shown to transmit NGF- and FGF-2-dependent differentiation signals in PC12 cells. To study if this involves signaling through the small GTPase Rap1, Rap1 activity was assessed in Shb-overexpressing PC12 cells. We demonstrate that NGF and

  12. Loss of function of KIAA2022 causes mild to severe intellectual disability with an autism spectrum disorder and impairs neurite outgrowth

    NARCIS (Netherlands)

    Maldergem, L. van; Hou, Q.; Kalscheuer, V.M.M.; Rio, M. del; Doco-Fenzy, M.; Medeira, A.; Brouwer, A.P.M. de; Cabrol, C.; Haas, S.A.; Cacciagli, P.; Moutton, S.; Landais, E.; Motte, J.; Colleaux, L.; Bonnet, C.; Villard, L.; Dupont, J.; Man, H.Y.

    2013-01-01

    Existence of a discrete new X-linked intellectual disability (XLID) syndrome due to KIAA2022 deficiency was questioned by disruption of KIAA2022 by an X-chromosome pericentric inversion in a XLID family we reported in 2004. Three additional families with likely pathogenic KIAA2022 mutations were

  13. Comparison of Human Induced Pluripotent Stem Cell-Derived Neurons and Rat Primary CorticalNeurons as In Vitro Models of Neurite Outgrowth

    Science.gov (United States)

    High-throughput assays that can quantify chemical-induced changes at the cellular and molecular level have been recommended for use in chemical safety assessment. High-throughput, high content imaging assays for the key cellular events of neurodevelopment have been proposed to ra...

  14. Peptides derived from the solvent-exposed loops 3 and 4 of BDNF bind TrkB and p75(NTR) receptors and stimulate neurite outgrowth and survival

    DEFF Research Database (Denmark)

    Fobian, Kristina; Owczarek, Sylwia; Budtz, Christian

    2010-01-01

    Brain-derived neurotrophic factor (BDNF) is critically involved in modeling the developing nervous system and is an important regulator of a variety of crucial functions in the mature CNS. BDNF exerts its action through interactions with two transmembrane receptors, either separately or in concert....... BDNF has been implicated in several neurological disorders, and irregularities in BDNF function may have severe consequences. Administration of BDNF as a drug has thus far yielded few practicable results, and the potential side effects when using a multifunctional protein are substantial. In an effort...... to produce more specific compounds without side effects, small peptides mimicking protein function have been developed. The present study characterized two mimetic peptides, Betrofin 3 and Betrofin 4, derived from the BDNF sequence. Both Betrofins bound the cognate BDNF receptors, TrkB and p75(NTR...

  15. The Secretome of Bone Marrow and Wharton Jelly Derived Mesenchymal Stem Cells Induces Differentiation and Neurite Outgrowth in SH-SY5Y Cells

    OpenAIRE

    Ana O. Pires; Andreia Neves-Carvalho; Nuno Sousa; António J. Salgado

    2014-01-01

    The goal of this study was to determine and compare the effects of the secretome of mesenchymal stem cells (MSCs) isolated from human bone-marrow (BMSCs) and the Wharton jelly surrounding the vein and arteries of the umbilical cord (human umbilical cord perivascular cells (HUCPVCs)) on the survival and differentiation of a human neuroblastoma cell line (SH-SY5Y). For this purpose, SH-SY5Y cells were differentiated with conditioned media (CM) from the MSCs populations referred above. Retinoic ...

  16. c-SRC mediates neurite outgrowth through recruitment of Crk to the scaffolding protein Sin/Efs without altering the kinetics of ERK activation

    DEFF Research Database (Denmark)

    Yang, Liang-Tung; Alexandropoulos, Konstantina; Sap, Jan

    2002-01-01

    moderate activation of endogenous SRC by receptor-protein-tyrosine phosphatase alpha (a physiological SRC activator). We show that such a qualitative change in the response to EGF is not accompanied by changes in the extent or kinetics of ERK induction in response to this factor. Instead, the pathway...

  17. Neural cell adhesion molecule-180-mediated homophilic binding induces epidermal growth factor receptor (EGFR) down-regulation and uncouples the inhibitory function of EGFR in neurite outgrowth

    DEFF Research Database (Denmark)

    Povlsen, Gro Klitgaard; Berezin, Vladimir; Bock, Elisabeth

    2008-01-01

    The neural cell adhesion molecule (NCAM) plays important roles in neuronal development, regeneration, and synaptic plasticity. NCAM homophilic binding mediates cell adhesion and induces intracellular signals, in which the fibroblast growth factor receptor plays a prominent role. Recent studies...... this NCAM-180-induced EGFR down-regulation involves increased EGFR ubiquitination and lysosomal EGFR degradation. Furthermore, NCAM-180-mediated EGFR down-regulation requires NCAM homophilic binding and interactions of the cytoplasmic domain of NCAM-180 with intracellular interaction partners, but does...

  18. A peptide antagonist of ErbB receptors, Inherbin3, induces neurite outgrowth from rat cerebellar granule neurons through ErbB1 inhibition

    DEFF Research Database (Denmark)

    Xu, Ruodan; Pankratova, Stanislava; Christiansen, Søren Hofman

    2013-01-01

    ErbB receptors not only function in cancer, but are also key developmental regulators in the nervous system. We previously identified an ErbB1 peptide antagonist, Inherbin3, that is capable of inhibiting tumor growth in vitro and in vivo. In this study, we found that inhibition of ErbB1 kinase ac...

  19. A peptide derived from a trans-homophilic binding site in neural cell adhesion molecule induces neurite outgrowth and neuronal survival

    DEFF Research Database (Denmark)

    Køhler, Lene B; Soroka, Vladislav; Korshunova, Irina

    2010-01-01

    The neural cell adhesion molecule (NCAM) plays a key role in neural development, regeneration, and synaptic plasticity. The crystal structure of a fragment of NCAM comprising the three N-terminal immunoglobulin (Ig)-like modules indicates that the first and second Ig modules bind to each other, t...

  20. Cometin is a novel neurotrophic factor that promotes neurite outgrowth and neuroblast migration in vitro and supports survival of spiral ganglion neurons in vivo

    DEFF Research Database (Denmark)

    Jørgensen, Jesper Roland; Fransson, Anette; Fjord-Larsen, Lone

    2012-01-01

    properties in vitro, combined with the restricted inner ear expression during development, we further investigated Cometin in relation to deafness. In neomycin deafened guinea pigs, two weeks intracochlear infusion of recombinant Cometin supports spiral ganglion neuron survival and function. In contrast...... to the control group receiving artificial perilymph, Cometin treated animals retain normal electrically-evoked brainstem response which is maintained several weeks after treatment cessation. Neuroprotection is also evident from stereological analysis of the spiral ganglion. Altogether, these studies show...

  1. The astrocyte/meningeal cell interface is a barrier to neurite outgrowth which can be overcome by manipulation of inhibitory molecules or axonal signalling pathways

    NARCIS (Netherlands)

    Shearer, Morven C; Niclou, Simone P; Brown, David; Asher, Richard A; Holtmaat, Anthony J D G; Levine, Joel M; Verhaagen, J.; Fawcett, James W

    2003-01-01

    Invading meningeal cells form a barrier to axon regeneration after damage to the spinal cord and other parts of the CNS, axons stopping at the interface between meningeal cells and astrocytes. Axon behavior was examined using an in vitro model of astrocyte/meningeal cell interfaces, created by

  2. Spontaneous Age-Related Neurite Branching in C. elegans

    Science.gov (United States)

    Tank, Elizabeth M. H.; Rodgers, Kasey E.; Kenyon, Cynthia

    2011-01-01

    The analysis of morphological changes that occur in the nervous system during normal aging could provide insight into cognitive decline and neurodegenerative disease. Previous studies have suggested that the nervous system of C. elegans maintains its structural integrity with age despite the deterioration of surrounding tissues. Unexpectedly, we observed that neurons in aging animals frequently displayed ectopic branches, and that the prevalence of these branches increased with time. Within age-matched populations, the branching of mechnosensory neurons correlated with decreased response to light touch and decreased mobility. The incidence of branching was influenced by two pathways that can affect the rate of aging, the Jun kinase pathway and the insulin/IGF-1 pathway. Loss of Jun kinase signaling, which slightly shortens lifespan, dramatically increased and accelerated the frequency of neurite branching. Conversely, inhibition of the daf-2 insulin/IGF-1-like signaling pathway, which extends lifespan, delayed and suppressed branching, and this delay required DAF-16/FOXO activity. Both JNK-1 and DAF-16 appeared to act within neurons in a cell-autonomous manner to influence branching, and, through their tissue-specific expression, it was possible to disconnect the rate at which branching occurred from the overall rate of aging of the animal. Old age has generally been associated with the decline and deterioration of different tissues, except in the case of tumor cell growth. To our knowledge, this is the first indication that aging can potentiate another form of growth, the growth of neurite branches, in normal animals. PMID:21697377

  3. Plasma sheet pressure anisotropies

    International Nuclear Information System (INIS)

    Stiles, G.S.; Hones, E.W. Jr; Bame, S.J.; Asbridge, J.R.

    1978-01-01

    The ecliptic plane components of the pressure tensors for low-energy ( or =1.2 approximately 25% of the time. Due to the low energy density of the electrons, however, this anisotropy is not itself sufficient to balance the tension of the magnetic field

  4. CMB anisotropies interpolation

    NARCIS (Netherlands)

    Zinger, S.; Delabrouille, Jacques; Roux, Michel; Maitre, Henri

    2010-01-01

    We consider the problem of the interpolation of irregularly spaced spatial data, applied to observation of Cosmic Microwave Background (CMB) anisotropies. The well-known interpolation methods and kriging are compared to the binning method which serves as a reference approach. We analyse kriging

  5. A case study of occipital outgrowth: a rare suboccipital abnormality.

    Science.gov (United States)

    Mushkin, A Y; Gubin, A V; Ulrich, E V; Snischuk, V P

    2016-05-01

    To describe the clinical and radiological characteristics of uncommon upper cervical spine abnormality in children. Clinical and diagnostic characteristics of three patients aged 6-12 years with a similar uncommon type of occipital anomaly are described. The patients were admitted in 2007, 2009, and 2014, respectively. All patients were clinically and radiologically examined. In each case the massive, additional unilateral outgrowth of the occipital bone (os occipitale) was visualized. The signs and symptoms included torticollis, acute brain ischemia, and limited head motion. Two of the three patients underwent surgical treatment: an occipital-cervical fusion was performed in the first patient, and the outgrowth was removed in the second patient. After 1 year of follow-up the results were estimated as good for both patients, with better functional outcome for the second patient. The parents of the third patient did not consent for the surgical treatment. The unique features of this abnormality distinguish it from previous descriptions of the manifestation of pro-atlas, atlas, or atlanto-occipital synostosis. The presented abnormality had different manifestation of various severity in each case, from torticollis to acute vascular disorder. Clinical case series. IV.

  6. Giant Atretic Occipital Lipoencephalocele in an Adult with Bony Outgrowth.

    Science.gov (United States)

    Nimkar, Kshama; Sood, Dinesh; Soni, Pawan; Chauhan, Narvir; Surya, Mukesh

    2016-01-01

    We present unique case of a giant extracranial atretic occipital lipoencephalocele in an adult patient with new bone formation within it which was not associated with any developmental malformation of brain. Resection of the lipoencephalocele was performed for esthetic reasons. 18 year old female patient presented to the surgery OPD with complains of a large mass in the occipital region present since birth. It was of size of a betel nut at the time of birth and gradually increased in size over a long period of time. It was painless and not associated with any other constitutional symptoms. On examination the rounded fluctuant mass was present in the midline in occipital region covered with alopecic skin with dimpling in the overlying skin. On MRI there was mass showing both T1 and T2 hyperintense signal area suggestive of fat component. Herniation of meninges and atretic brain parenchyma was also seen through a defect in the occipital bone in the midline. There was a Y shaped bony outgrowth seen arising from occipital bone into the mass which was quite unusual in association with an atretic lipoencephalocele. A large lipoencephalocele with bony outgrowth in an adult patient is a rare presentation of atreic occipital encephalocele.

  7. Accelerated axon outgrowth, guidance, and target reinnervation across nerve transection gaps following a brief electrical stimulation paradigm.

    Science.gov (United States)

    Singh, Bhagat; Xu, Qing-Gui; Franz, Colin K; Zhang, Rumi; Dalton, Colin; Gordon, Tessa; Verge, Valerie M K; Midha, Rajiv; Zochodne, Douglas W

    2012-03-01

    Regeneration of peripheral nerves is remarkably restrained across transection injuries, limiting recovery of function. Strategies to reverse this common and unfortunate outcome are limited. Remarkably, however, new evidence suggests that a brief extracellular electrical stimulation (ES), delivered at the time of injury, improves the regrowth of motor and sensory axons. In this work, the authors explored and tested this ES paradigm, which was applied proximal to transected sciatic nerves in mice, and identified several novel and compelling impacts of the approach. Using thy-1 yellow fluorescent protein mice with fluorescent axons that allow serial in vivo tracking of regeneration, the morphological, electrophysiological, and behavioral indices of nerve regrowth were measured. The authors show that ES is associated with a 30%-50% improvement in several indices of regeneration: regrowth of axons and their partnered Schwann cells across transection sites, maturation of regenerated fibers in gaps spanning transection zones, and entry of axons into their muscle and cutaneous target zones. In parallel studies, the authors analyzed adult sensory neurons and their response to extracellular ES while plated on a novel microelectrode array construct designed to deliver the identical ES paradigm used in vivo. The ES accelerated neurite outgrowth, supporting the concept of a neuron-autonomous mechanism of action. Taken together, these results support a robust role for brief ES following peripheral nerve injuries in promoting regeneration. Electrical stimulation has a wider repertoire of impact than previously recognized, and its impact in vitro supports the hypothesis that a neuron-specific reprogrammed injury response is recruited by the ES protocol.

  8. Elastic Anisotropy of Basalt

    Science.gov (United States)

    Becker, K.; Shapiro, S.; Stanchits, S.; Dresen, G.; Kaselow, A.; Vinciguerra, S.

    2005-12-01

    Elastic properties of rocks are sensitive to changes of the in-situ stress and damage state. In particular, seismic velocities are strongly affected by stress-induced formation and deformation of cracks or shear-enhanced pore collapse. The effect of stress on seismic velocities as a result of pore space deformation in isotropic rock at isostatic compression may be expressed by the equation: A+K*P-B*exp (-D*P) (1), where P=Pc-Pp is the effective pressure, the pure difference between confining pressure and pore pressure. The parameter A, K, B and D describe material constants determined using experimental data. The physical meaning of the parameters is given by Shapiro (2003, in Geophysics Vol.68(Nr.2)). Parameter D is related to the stress sensitivity of the rock. A similar relation was derived by Shapiro and Kaselow (2005, in Geophysics in press) for weak anisotropic rocks under arbitrary load. They describe the stress dependent anisotropy in terms of Thomson's (1986, in Geophysics, Vol. 51(Nr.10)) anisotropy parameters ɛ and γ as a function of stress in the case of an initially isotropic rock: ɛ ∝ E2-E3, γ ∝ E3-E2 (2) with Ei=exp (D*Pi). The exponential terms Ei are controlled by the effective stress components Pi. To test this relation, we have conducted a series of triaxial compression tests on dry samples of initially isotropic Etnean Basalt in a servo-controlled MTS loading frame equipped with a pressure cell. Confining pressure was 60, 40 and 20 MPa. Samples were 5 cm in diameter and 10 cm in length. Elastic anisotropy was induced by axial compression of the samples through opening and growth of microcracks predominantly oriented parallel to the sample axis. Ultrasonic P- and S- wave velocities were monitored parallel and normal to the sample axis by an array of 20 piezoceramic transducers glued to the surface. Preamplified full waveform signals were stored in two 12 channel transient recorders. According to equation 2 the anisotropy parameters are

  9. Quarkonium dissociation by anisotropy

    Science.gov (United States)

    Chernicoff, Mariano; Fernández, Daniel; Mateos, David; Trancanelli, Diego

    2013-01-01

    We compute the screening length for quarkonium mesons moving through an anisotropic, strongly coupled mathcal{N} = 4 super Yang-Mills plasma by means of its gravity dual. We present the results for arbitrary velocities and orientations of the mesons, as well as for arbitrary values of the anisotropy. The anisotropic screening length can be larger or smaller than the isotropic one, and this depends on whether the comparison is made at equal temperatures or at equal entropy densities. For generic motion we find that: (i) mesons dissociate above a certain critical value of the anisotropy, even at zero temperature; (ii) there is a limiting velocity for mesons in the plasma, even at zero temperature; (iii) in the ultra-relativistic limit the screening length scales as (1 - v 2)ɛ with ɛ = 1 /2, in contrast with the isotropic result ɛ = 1 /4.

  10. Supernovae anisotropy power spectrum

    Energy Technology Data Exchange (ETDEWEB)

    Ghodsi, Hoda; Baghram, Shant [Department of Physics, Sharif University of Technology, P.O. Box 11155-9161, Tehran (Iran, Islamic Republic of); Habibi, Farhang, E-mail: h.ghodsi@mehr.sharif.ir, E-mail: baghram@sharif.edu, E-mail: habibi@lal.in2p3.fr [LAL-IN2P3/CNRS, BP 34, 91898 Orsay Cedex (France)

    2017-10-01

    We contribute another anisotropy study to this field of research using Type Ia supernovae (SNe Ia). In this work, we utilise the power spectrum calculation method and apply it to both the current SNe Ia data and simulation. Using the Union2.1 data set at all redshifts, we compare the spectrum of the residuals of the observed distance moduli to that expected from an isotropic universe affected by the Union2.1 observational uncertainties at low multipoles. Through this comparison we find a dipolar anisotropy with tension of less that 2σ towards l = 171° ± 21° and b = −26° ± 28° which is mainly induced by anisotropic spatial distribution of the SNe with z > 0.2 rather than being a cosmic effect. Furthermore, we find a tension of ∼ 4σ at ℓ = 4 between the two spectra. Our simulations are constructed with the characteristics of the upcoming surveys like the Large Synoptic Survey Telescope (LSST), which shall bring us the largest SNe Ia collection to date. We make predictions for the amplitude of a possible dipolar anisotropy that would be detectable by future SNe Ia surveys.

  11. Charge-balanced biphasic electrical stimulation inhibits neurite extension of spiral ganglion neurons.

    Science.gov (United States)

    Shen, Na; Liang, Qiong; Liu, Yuehong; Lai, Bin; Li, Wen; Wang, Zhengmin; Li, Shufeng

    2016-06-15

    Intracochlear application of exogenous or transgenic neurotrophins, such as neurotrophin-3 (NT-3) and brain derived neurotrophic factor (BDNF), could promote the resprouting of spiral ganglion neuron (SGN) neurites in deafened animals. These resprouting neurites might reduce the gap between cochlear implant electrodes and their targeting SGNs, allowing for an improvement of spatial resolution of electrical stimulation. This study is to investigate the impact of electrical stimulation employed in CI on the extension of resprouting SGN neurites. We established an in vitro model including the devices delivering charge-balanced biphasic electrical stimulation, and spiral ganglion (SG) dissociated culture treated with BDNF and NT-3. After electrical stimulation with varying durations and intensities, we quantified neurite lengths and Schwann cell densities in SG cultures. Stimulations that were greater than 50μA or longer than 8h significantly decreased SG neurite length. Schwann cell density under 100μA electrical stimulation for 48h was significantly lower compared to that in non-stimulated group. These electrical stimulation-induced decreases of neurite extension and Schwann cell density were attenuated by various types of voltage-dependent calcium channel (VDCC) blockers, or completely prevented by their combination, cadmium or calcium-free medium. Our study suggested that charge-balanced biphasic electrical stimulation inhibited the extension of resprouting SGN neurites and decreased Schwann cell density in vitro. Calcium influx through multiple types of VDCCs was involved in the electrical stimulation-induced inhibition. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Naftidrofuryl affects neurite regeneration by injured adult auditory neurons.

    Science.gov (United States)

    Lefebvre, P P; Staecker, H; Moonen, G; van de Water, T R

    1993-07-01

    Afferent auditory neurons are essential for the transmission of auditory information from Corti's organ to the central auditory pathway. Auditory neurons are very sensitive to acute insult and have a limited ability to regenerate injured neuronal processes. Therefore, these neurons appear to be a limiting factor in restoration of hearing function following an injury to the peripheral auditory receptor. In a previous study nerve growth factor (NGF) was shown to stimulate neurite repair but not survival of injured auditory neurons. In this study, we have demonstrated a neuritogenesis promoting effect of naftidrofuryl in an vitro model for injury to adult auditory neurons, i.e. dissociated cell cultures of adult rat spiral ganglia. Conversely, naftidrofuryl did not have any demonstrable survival promoting effect on these in vitro preparations of injured auditory neurons. The potential uses of this drug as a therapeutic agent in acute diseases of the inner ear are discussed in the light of these observations.

  13. Neurotrophins differentially stimulate the growth of cochlear neurites on collagen surfaces and in gels☆

    Science.gov (United States)

    Xie, Joanna; Pak, Kwang; Evans, Amaretta; Kamgar-Parsi, Andy; Fausti, Stephen; Mullen, Lina; Ryan, Allen Frederic

    2013-01-01

    The electrodes of a cochlear implant are located far from the surviving neurons of the spiral ganglion, which results in decreased precision of neural activation compared to the normal ear. If the neurons could be induced to extend neurites toward the implant, it might be possible to stimulate more discrete subpopulations of neurons, and to increase the resolution of the device. However, a major barrier to neurite growth toward a cochlear implant is the fluid filling the scala tympani, which separates the neurons from the electrodes. The goal of this study was to evaluate the growth of cochlear neurites in three-dimensional extracellular matrix molecule gels, and to increase biocompatibility by using fibroblasts stably transfected to produce neurotrophin-3 and brain-derived neurotrophic factor. Spiral ganglion explants from neonatal rats were evaluated in cultures. They were exposed to soluble neurotrophins, cells transfected to secrete neurotrophins, and/or collagen gels. We found that cochlear neurites grew readily on collagen surfaces and in three-dimensional collagen gels. Co-culture with cells producing neurotrophin-3 resulted in increased numbers of neurites, and neurites that were longer than when explants were cultured with control fibroblasts stably transfected with green fluorescent protein. Brain-derived neurotrophic factor-producing cells resulted in a more dramatic increase in the number of neurites, but there was no significant effect on neurite length. It is suggested that extracellular matrix molecule gels and cells transfected to produce neurotrophins offer an opportunity to attract spiral ganglion neurites toward a cochlear implant. PMID:24459465

  14. Tendon cell outgrowth rates and morphology associated with kevlar-49.

    Science.gov (United States)

    Zimmerman, M; Gordon, K E

    1988-12-01

    A rat tendon cell model was used to evaluate the in vitro biocompatibility of kevlar-49. The cell response to kevlar was compared to carbon AS-4 and nylon sutures. Three trials were run and cell growth rates were statistically similar for all the materials tested. A separate experiment was conducted in which the same fiber materials were placed in the same Petri dish. Again, the rates were similar for each material. Finally, the cells were observed with a scanning electron microscope, and the three classic cell morphologies associated with this tendon cell model were observed. Also, cellular attachment to the fiber and cellular encapsulation of the fiber were identical for the three materials tested. Kevlar-49 proved to be comparable to carbon AS4 and nylon sutures in terms of cellular response and cell outgrowth rates.

  15. Flow stress anisotropy

    DEFF Research Database (Denmark)

    Winther, G.

    1996-01-01

    stress Variation in the rolling plane, which may be as high as 20%, are presented. The traditional Taylor model is applied to the data to account for the effect of texture. However, texture effects alone are not enough to explain all of the observed anisotropy. New models which take the combined effects...... of texture and deformation microstructure into account are presented. The models are based on the Taylor and Sachs models but modified with an anisotropic critical shear stress to account for the effect of the microstructure. The agreement between experimental data and model predictions is definitely better...

  16. Proteomic analysis of differentiating neuroblastoma cells treated with sub-lethal neurite inhibitory concentrations of diazinon: Identification of novel biomarkers of effect

    International Nuclear Information System (INIS)

    Harris, W.; Sachana, M.; Flaskos, J.; Hargreaves, A.J.

    2009-01-01

    In previous work we showed that sub-lethal levels of diazinon inhibited neurite outgrowth in differentiating N2a neuroblastoma cells. Western blotting analysis targeted at proteins involved in axon growth and stress responses, revealed that such exposure led to a reduction in the levels of neurofilament heavy chain, microtubule associated protein 1 B (MAP 1B) and HSP-70. The aim of this study was to apply the approach of 2 dimensional polyacrylamide gel electrophoresis and mass spectrometry to identify novel biomarkers of effect. A number of proteins were found to be up-regulated compared to the control on silver-stained gels. These were classified in to 3 main groups of proteins: cytosolic factors, chaperones and the actin-binding protein cofilin, all of which are involved in cell differentiation, survival or metabolism. The changes observed for cofilin were further confirmed by quantitative Western blotting analysis with anti-actin and anti-cofilin antibodies. Indirect immunofluorescence staining with the same antibodies indicated that the microfilament network was disrupted in diazinon-treated cells. Our data suggest that microfilament organisation is disrupted by diazinon exposure, which may be related to increased cofilin expression.

  17. Bifenthrin causes neurite retraction in the absence of cell death: a model for pesticide associated neurodegeneration.

    Science.gov (United States)

    Nandi, Avishek; Chandil, Daljit; Lechesal, Rethabile; Pryor, Stephen C; McLaughlin, Ashlea; Bonventre, Josephine A; Flynnx, Katherine; Weeks, Benjamin S

    2006-05-01

    Bifenthrin is a synthetic pyrethroid insecticide derivative of naturally occurring pyrethrins from chrysanthemum flowers. Bifenthrin is considered relatively safe and therefore incorporated as the active ingredient in preparations sold over the counter for household use. Recent studies have raised concern that chronic exposure to pesticides in the home setting may increase the risk for neurodegenerative diseases. To address this concer, in the present study, bifenthrin is added to pre-differentiated PC12 and effect of bifenthrin on the retraction of existing neurites is observed a model for neurodegeneration. PC12 cells were differentiated with nerve growth factor for twenty-four hours and then treated with what was determined to be a sublethal dose of bifenthrin for up to an additional 48 hours. The percent of cells with neurites was assessed at various times before and after nerve growth factor treatment. Bifenthrin toxicity was determined using trypan blue exclusion. Bifenthrin was not toxic to PC12 cells at concentrations ranging from 1 x 10(-10) M to 1 x 10(-4) M. Twenty-four hours after nerve growth factor treatment, a maximum percent of cells had formed neurites and with a treatment of 1 x 10(-5) M bifenthrin, approximately 80% of these neurites retracted in within 12 additional hours and almost all neurites had retracted within 48 hours. Trypan exclusion showed that these cells were viable. These data show that bifenthrin can stimulate the retraction of neurites in the absence of frank toxicity.

  18. Progenitor outgrowth from the niche in Drosophila trachea is guided by FGF from decaying branches.

    Science.gov (United States)

    Chen, Feng; Krasnow, Mark A

    2014-01-10

    Although there has been progress identifying adult stem and progenitor cells and the signals that control their proliferation and differentiation, little is known about the substrates and signals that guide them out of their niche. By examining Drosophila tracheal outgrowth during metamorphosis, we show that progenitors follow a stereotyped path out of the niche, tracking along a subset of tracheal branches destined for destruction. The embryonic tracheal inducer branchless FGF (fibroblast growth factor) is expressed dynamically just ahead of progenitor outgrowth in decaying branches. Knockdown of branchless abrogates progenitor outgrowth, whereas misexpression redirects it. Thus, reactivation of an embryonic tracheal inducer in decaying branches directs outgrowth of progenitors that replace them. This explains how the structure of a newly generated tissue is coordinated with that of the old.

  19. Hepassocin is required for hepatic outgrowth during zebrafish hepatogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Ming [Tianjin University, Department of Pharmaceutical Engineering, Tianjin 300072 (China); Beijing Institute of Radiation Medicine, Beijing 100850 (China); Yan, Hui [Beijing Institute of Pharmacology and Toxicology, Beijing 100850 (China); Yin, Rong-Hua [Beijing Institute of Radiation Medicine, Beijing 100850 (China); State Key Laboratory of Proteomics, Beijing 100850 (China); Wang, Qiang [Institute of Zoology, Chinese Academy of Sciences, Beijing 100101 (China); Zhan, Yi-Qun; Yu, Miao; Ge, Chang-Hui; Li, Chang-Yan; Wang, Xiao-Hui [Beijing Institute of Radiation Medicine, Beijing 100850 (China); State Key Laboratory of Proteomics, Beijing 100850 (China); Ge, Zhi-Qiang [Tianjin University, Department of Pharmaceutical Engineering, Tianjin 300072 (China); Yang, Xiao-Ming, E-mail: xiaomingyang@sina.com [Tianjin University, Department of Pharmaceutical Engineering, Tianjin 300072 (China); Beijing Institute of Radiation Medicine, Beijing 100850 (China); State Key Laboratory of Proteomics, Beijing 100850 (China)

    2015-07-31

    Background & aims: Hepassocin (HPS) is a hepatotrophic growth factor that specifically stimulates hepatocyte proliferation and promotes liver regeneration after liver damage. In this paper, zebrafish were used to investigate the role of HPS in liver development. Methods and results: During zebrafish development, HPS expression is enriched in liver throughout hepatogenesis. Knockdown of HPS using its specific morpholino leads to a smaller liver phenotype. Further results showed that the HPS knockdown has no effect on the expression of the early endoderm marker gata6 and early hepatic marker hhex. In addition, results showed that the smaller-liver phenotype in HPS morphants was caused by suppression of cell proliferation, not induction of cell apoptosis. Conclusions: Current findings indicated that HPS is essential to the later stages of development in vertebrate liver organogenesis. - Highlights: • HPS is enriched in zebrafish liver and has strong similarities with other species. • Knocking down HPS with MOs results in small liver phenotype. • HPS depletion regulates liver outgrowth but not liver specification and budding. • HPS depletion causes hepatocyte proliferation arrest but not apoptosis induction.

  20. Hepassocin is required for hepatic outgrowth during zebrafish hepatogenesis

    International Nuclear Information System (INIS)

    Gao, Ming; Yan, Hui; Yin, Rong-Hua; Wang, Qiang; Zhan, Yi-Qun; Yu, Miao; Ge, Chang-Hui; Li, Chang-Yan; Wang, Xiao-Hui; Ge, Zhi-Qiang; Yang, Xiao-Ming

    2015-01-01

    Background & aims: Hepassocin (HPS) is a hepatotrophic growth factor that specifically stimulates hepatocyte proliferation and promotes liver regeneration after liver damage. In this paper, zebrafish were used to investigate the role of HPS in liver development. Methods and results: During zebrafish development, HPS expression is enriched in liver throughout hepatogenesis. Knockdown of HPS using its specific morpholino leads to a smaller liver phenotype. Further results showed that the HPS knockdown has no effect on the expression of the early endoderm marker gata6 and early hepatic marker hhex. In addition, results showed that the smaller-liver phenotype in HPS morphants was caused by suppression of cell proliferation, not induction of cell apoptosis. Conclusions: Current findings indicated that HPS is essential to the later stages of development in vertebrate liver organogenesis. - Highlights: • HPS is enriched in zebrafish liver and has strong similarities with other species. • Knocking down HPS with MOs results in small liver phenotype. • HPS depletion regulates liver outgrowth but not liver specification and budding. • HPS depletion causes hepatocyte proliferation arrest but not apoptosis induction

  1. Dcc regulates asymmetric outgrowth of forebrain neurons in zebrafish.

    Directory of Open Access Journals (Sweden)

    Jingxia Gao

    Full Text Available The guidance receptor DCC (deleted in colorectal cancer ortholog UNC-40 regulates neuronal asymmetry development in Caenorhabditis elegans, but it is not known whether DCC plays a role in the specification of neuronal polarity in vertebrates. To examine the roles of DCC in neuronal asymmetry regulation in vertebrates, we studied zebrafish anterior dorsal telencephalon (ADt neuronal axons. We generated transgenic zebrafish animals expressing the photo-convertible fluorescent protein Kaede in ADt neurons and then photo-converted Kaede to label specifically the ADt neuron axons. We found that ADt axons normally project ventrally. Knock down of Dcc function by injecting antisense morpholino oligonucleotides caused the ADt neurons to project axons dorsally. To examine the axon projection pattern of individual ADt neurons, we labeled single ADt neurons using a forebrain-specific promoter to drive fluorescent protein expression. We found that individual ADt neurons projected axons dorsally or formed multiple processes after morpholino knock down of Dcc function. We further found that knock down of the Dcc ligand, Netrin1, also caused ADt neurons to project axons dorsally. Knockdown of Neogenin1, a guidance receptor closely related to Dcc, enhanced the formation of aberrant dorsal axons in embryos injected with Dcc morpholino. These experiments provide the first evidence that Dcc regulates polarized axon initiation and asymmetric outgrowth of forebrain neurons in vertebrates.

  2. ALS/FTLD-linked TDP-43 regulates neurite morphology and cell survival in differentiated neurons

    Energy Technology Data Exchange (ETDEWEB)

    Han, Jeong-Ho; Yu, Tae-Hoon; Ryu, Hyun-Hee; Jun, Mi-Hee; Ban, Byung-Kwan [Department of Biotechnology, College of Life Science and Nanotechnology, Hannam University, Dajeon 305-811 (Korea, Republic of); Jang, Deok-Jin [Department of Applied Biology, College of Ecology and Environment, Kyungpook National University, 386, Gajang-dong, Sangju-si, Kyungbuk 742-711 (Korea, Republic of); Lee, Jin-A, E-mail: leeja@hnu.kr [Department of Biotechnology, College of Life Science and Nanotechnology, Hannam University, Dajeon 305-811 (Korea, Republic of)

    2013-08-01

    Tar-DNA binding protein of 43 kDa (TDP-43) has been characterized as a major component of protein aggregates in brains with neurodegenerative diseases such as frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). However, physiological roles of TDP-43 and early cellular pathogenic effects caused by disease associated mutations in differentiated neurons are still largely unknown. Here, we investigated the physiological roles of TDP-43 and the effects of missense mutations associated with diseases in differentiated cortical neurons. The reduction of TDP-43 by siRNA increased abnormal neurites and decreased cell viability. ALS/FTLD-associated missense mutant proteins (A315T, Q331K, and M337V) were partially mislocalized to the cytosol and neurites when compared to wild-type and showed abnormal neurites similar to those observed in cases of loss of TDP-43. Interestingly, cytosolic expression of wild-type TDP-43 with mutated nuclear localization signals also induced abnormal neurtie morphology and reduction of cell viability. However, there was no significant difference in the effects of cytosolic expression in neuronal morphology and cell toxicity between wild-type and missense mutant proteins. Thus, our results suggest that mislocalization of missense mutant TDP-43 may contribute to loss of TDP-43 function and affect neuronal morphology, probably via dominant negative action before severe neurodegeneration in differentiated cortical neurons. Highlights: • The function of nuclear TDP-43 in neurite morphology in mature neurons. • Partial mislocalization of TDP-43 missense mutants into cytosol from nucleus. • Abnormal neurite morphology caused by missense mutants of TDP-43. • The effect of cytosolic expression of TDP-43 in neurite morphology and in cell survival.

  3. ALS/FTLD-linked TDP-43 regulates neurite morphology and cell survival in differentiated neurons

    International Nuclear Information System (INIS)

    Han, Jeong-Ho; Yu, Tae-Hoon; Ryu, Hyun-Hee; Jun, Mi-Hee; Ban, Byung-Kwan; Jang, Deok-Jin; Lee, Jin-A

    2013-01-01

    Tar-DNA binding protein of 43 kDa (TDP-43) has been characterized as a major component of protein aggregates in brains with neurodegenerative diseases such as frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). However, physiological roles of TDP-43 and early cellular pathogenic effects caused by disease associated mutations in differentiated neurons are still largely unknown. Here, we investigated the physiological roles of TDP-43 and the effects of missense mutations associated with diseases in differentiated cortical neurons. The reduction of TDP-43 by siRNA increased abnormal neurites and decreased cell viability. ALS/FTLD-associated missense mutant proteins (A315T, Q331K, and M337V) were partially mislocalized to the cytosol and neurites when compared to wild-type and showed abnormal neurites similar to those observed in cases of loss of TDP-43. Interestingly, cytosolic expression of wild-type TDP-43 with mutated nuclear localization signals also induced abnormal neurtie morphology and reduction of cell viability. However, there was no significant difference in the effects of cytosolic expression in neuronal morphology and cell toxicity between wild-type and missense mutant proteins. Thus, our results suggest that mislocalization of missense mutant TDP-43 may contribute to loss of TDP-43 function and affect neuronal morphology, probably via dominant negative action before severe neurodegeneration in differentiated cortical neurons. Highlights: • The function of nuclear TDP-43 in neurite morphology in mature neurons. • Partial mislocalization of TDP-43 missense mutants into cytosol from nucleus. • Abnormal neurite morphology caused by missense mutants of TDP-43. • The effect of cytosolic expression of TDP-43 in neurite morphology and in cell survival

  4. Two-dimensional patterning of thin coatings for the control of tissue outgrowth

    DEFF Research Database (Denmark)

    Thissen, H.; Johnson, G.; Hartley, P.G.

    2006-01-01

    were used to provide evidence of successful surface modifications. Adsorption of the extracellular matrix protein collagen I followed by tissue outgrowth experiments with bovine corneal epithelial tissue for up to 21 days showed that two-dimensional control over tissue outgrowth is achievable with our......Control of the precise location and extent of cellular attachment and proliferation, and of tissue outgrowth is important in a number of biomedical applications, including biomaterials and tissue engineered medical devices. Here we describe a method to control and direct the location and define...... boundaries of tissue growth on surfaces in two dimensions. The method relies on the generation of a spatially defined surface chemistry comprising protein adsorbing and non-adsorbing areas that allow control over the adsorption of cell-adhesive glycoproteins. Surface modification was carried out...

  5. Pain Now or Later: An Outgrowth Account of Pain-Minimization

    Science.gov (United States)

    Chen, Shuai; Zhao, Dan; Rao, Li-Lin; Liang, Zhu-Yuan; Li, Shu

    2015-01-01

    The preference for immediate negative events contradicts the minimizing loss principle given that the value of a delayed negative event is discounted by the amount of time it is delayed. However, this preference is understandable if we assume that the value of a future outcome is not restricted to the discounted utility of the outcome per se but is complemented by an anticipated negative utility assigned to an unoffered dimension, which we termed the “outgrowth.” We conducted three studies to establish the existence of the outgrowth and empirically investigated the mechanism underlying the preference for immediate negative outcomes. Study 1 used a content analysis method to examine whether the outgrowth was generated in accompaniment with the delayed negative events. The results revealed that the investigated outgrowth was composed of two elements. The first component is the anticipated negative emotions elicited by the delayed negative event, and the other is the anticipated rumination during the waiting process, in which one cannot stop thinking about the negative event. Study 2 used a follow-up investigation to examine whether people actually experienced the negative emotions they anticipated in a real situation of waiting for a delayed negative event. The results showed that the participants actually experienced a number of negative emotions when waiting for a negative event. Study 3 examined whether the existence of the outgrowth could make the minimizing loss principle work. The results showed that the difference in pain anticipation between the immediate event and the delayed event could significantly predict the timing preference of the negative event. Our findings suggest that people’s preference for experiencing negative events sooner serves to minimize the overall negative utility, which is divided into two parts: the discounted utility of the outcome itself and an anticipated negative utility assigned to the outgrowth. PMID:25747461

  6. Anisotropy in the deep Earth

    Science.gov (United States)

    Romanowicz, Barbara; Wenk, Hans-Rudolf

    2017-08-01

    Seismic anisotropy has been found in many regions of the Earth's interior. Its presence in the Earth's crust has been known since the 19th century, and is due in part to the alignment of anisotropic crystals in rocks, and in part to patterns in the distribution of fractures and pores. In the upper mantle, seismic anisotropy was discovered 50 years ago, and can be attributed for the most part, to the alignment of intrinsically anisotropic olivine crystals during large scale deformation associated with convection. There is some indication for anisotropy in the transition zone, particularly in the vicinity of subducted slabs. Here we focus on the deep Earth - the lower mantle and core, where anisotropy is not yet mapped in detail, nor is there consensus on its origin. Most of the lower mantle appears largely isotropic, except in the last 200-300 km, in the D″ region, where evidence for seismic anisotropy has been accumulating since the late 1980s, mostly from shear wave splitting measurements. Recently, a picture has been emerging, where strong anisotropy is associated with high shear velocities at the edges of the large low shear velocity provinces (LLSVPs) in the central Pacific and under Africa. These observations are consistent with being due to the presence of highly anisotropic MgSiO3 post-perovskite crystals, aligned during the deformation of slabs impinging on the core-mantle boundary, and upwelling flow within the LLSVPs. We also discuss mineral physics aspects such as ultrahigh pressure deformation experiments, first principles calculations to obtain information about elastic properties, and derivation of dislocation activity based on bonding characteristics. Polycrystal plasticity simulations can predict anisotropy but models are still highly idealized and neglect the complex microstructure of polyphase aggregates with strong and weak components. A promising direction for future progress in understanding the origin of seismic anisotropy in the deep mantle

  7. Surface energy anisotropy of tungsten

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, R; Grenga, H E [Georgia Inst. of Tech., Atlanta (USA). School of Chemical Engineering

    1976-10-01

    Field-ion microscopy was used to study the faceting behavior and/or surface energy anisotropy of tungsten in vacuum and in hydrogen. In vacuum below 1700 K the activation energy for (110) facet growth agreed with values previously reported for surface diffusion on tungsten. The observed anisotropy values at 0.5 Tsub(m), where Tsub(m) is the absolute melting temperature of tungsten (approximately 3680 K), were different from those previously reported at higher temperatures and more nearly agreed with broken bond calculations based on Mie potential using m=5, n=8, and a 1.5% lattice expansion. Hydrogen appeared to have a negligible effect on surface energy anisotropy, but did preferentially increase surface diffusion rates on (310) regions.

  8. Momentum anisotropy at freeze out

    International Nuclear Information System (INIS)

    Feld, S.; Borghini, N.; Lang, C.

    2017-01-01

    The transition from a hydrodynamical modeling to a particle-based approach is a crucial element of the description of high-energy heavy-ion collisions. Assuming this “freeze out” happens instantaneously at each point of the expanding medium, we show that the local phase-space distribution of the emitted particles is asymmetric in momentum space. This suggests the use of anisotropic hydrodynamics for the last stages of the fluid evolution. We discuss how observables depend on the amount of momentum-space anisotropy at freeze out and how smaller or larger anisotropies allow for different values of the freeze-out temperature. (paper)

  9. Visualisation of plastid outgrowths in potato (Solanum tuberosum L.) tubers by carboxyfluorescein diacetate staining.

    Science.gov (United States)

    Borucki, Wojciech; Bederska, Magdalena; Sujkowska-Rybkowska, Marzena

    2015-05-01

    We describe two types of plastid outgrowths visualised in potato tubers after carboxyfluorescein diacetate staining. Probable esterase activity of the outgrowths has been demonstrated for the first time ever. Plastid outgrowths were observed in the phelloderm and storage parenchyma cells of red potato (S. tuberosum L. cv. Rosalinde) tubers after administration of carboxyfluorescein diacetate stain. Endogenous esterases cleaved off acetic groups to release membrane-unpermeable green fluorescing carboxyfluorescein which accumulated differentially in particular cell compartments. The intensive green fluorescence of carboxyfluorescein exhibited highly branched stromules (stroma-filled plastid tubular projections of the plastid envelope) and allowed distinguishing them within cytoplasmic strands of the phelloderm cells. Stromules (1) were directed towards the nucleus or (2) penetrated the whole cells through the cytoplasmic bands of highly vacuolated phelloderm cells. Those directed towards the nucleus were flattened and adhered to the nuclear envelope. Stromule-like interconnections between two parts of the same plastids (isthmuses) were also observed. We also documented the formation of another type of the stroma-filled plastid outgrowths, referred to here as protrusions, which differed from previously defined stromules in both morphology and esterase activity. Unlike stromules, the protrusions were found to be associated with developmental processes leading to starch accumulation in the storage parenchyma cells. These results strongly suggest that stromules and protrusions exhibit esterase activity. This has been demonstrated for the first time. Morphological and biochemical features as well as possible functions of stromules and protrusions are discussed below.

  10. Flow stress anisotropy in aluminium

    DEFF Research Database (Denmark)

    Juul Jensen, D.; Hansen, N.

    1990-01-01

    The plastic anisotropy of cold-rolled high purity aluminum (99.996%) and commercially pure aluminum (99.6%) has been investigated. Sample parameters were the initial grain size and the degree of plastic strain (ϵ < 3.00). Flow stresses (0.2% offset) were measured at room temperature by uniaxial t...

  11. The Cosmic Microwave Background Anisotropy

    Science.gov (United States)

    Bennett, C. L.

    1994-12-01

    The properties of the cosmic microwave background radiation provide unique constraints on the history and evolution of the universe. The first detection of anisotropy of the microwave radiation was reported by the COBE Team in 1992, based on the first year of flight data. The latest analyses of the first two years of COBE data are reviewed in this talk, including the amplitude of the microwave anisotropy as a function of angular scale and the statistical nature of the fluctuations. The two-year results are generally consistent with the earlier first year results, but the additional data allow for a better determination of the key cosmological parameters. In this talk the COBE results are compared with other observational anisotropy results and directions for future cosmic microwave anisotropy observations will be discussed. The National Aeronautics and Space Administration/Goddard Space Flight Center (NASA/GSFC) is responsible for the design, development, and operation of the Cosmic Background Explorer (COBE). Scientific guidance is provided by the COBE Science Working Group.

  12. MiR-145 mediates zebrafish hepatic outgrowth through progranulin A signaling.

    Directory of Open Access Journals (Sweden)

    Ya-Wen Li

    Full Text Available MicroRNAs (miRs are mRNA-regulatory molecules that fine-tune gene expression and modulate both processes of development and tumorigenesis. Our previous studies identified progranulin A (GrnA as a growth factor which induces zebrafish hepatic outgrowth through MET signaling. We also found that miR-145 is one of potential fine-tuning regulators of GrnA involved in embryonic hepatic outgrowth. The low level of miR-145 seen in hepatocarinogenesis has been shown to promote pathological liver growth. However, little is known about the regulatory mechanism of miR-145 in embryonic liver development. In this study, we demonstrate a significant decrease in miR-145 expression during hepatogenesis. We modulate miR-145 expression in zebrafish embryos by injection with a miR-145 mimic or a miR-145 hairpin inhibitor. Altered embryonic liver outgrowth is observed in response to miR-145 expression modulation. We also confirm a critical role of miR-145 in hepatic outgrowth by using whole-mount in situ hybridization. Loss of miR-145 expression in embryos results in hepatic cell proliferation, and vice versa. Furthermore, we demonstrate that GrnA is a target of miR-145 and GrnA-induced MET signaling is also regulated by miR-145 as determined by luciferase reporter assay and gene expression analysis, respectively. In addition, co-injection of GrnA mRNA with miR-145 mimic or MO-GrnA with miR-145 inhibitor restores the liver defects caused by dysregulation of miR-145 expression. In conclusion, our findings suggest an important role of miR-145 in regulating GrnA-dependent hepatic outgrowth in zebrafish embryonic development.

  13. Anisotropy of acoustic properties in paratellurite

    International Nuclear Information System (INIS)

    Parygin, Vladimir N.

    1996-01-01

    One of the peculiarities of the TeO 2 crystal consists of its strong acoustic anisotropy. This anisotropy demonstrates itself by acoustic energy walk-off and anisotropic distortion of an acoustic beam. Four constants completely characterise the acoustic anisotropy of the medium. In this paper these constants are calculated for various directions of the acoustic beam in crystal. (authors)

  14. Magnetic anisotropy of lecithin membranes. A new anisotropy susceptometer

    OpenAIRE

    Scholz, F.; Boroske, E.; Helfrich, W.

    1984-01-01

    Cylindrical giant vesicles prepared from egg lecithin and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) are oriented in an external magnetic field and observed by phase contrast microscopy. The anisotropic part of the diamagnetic susceptibility of the lecithin membrane is determined from the distribution of angles between the magnetic field and the long cylinder axis due to thermal fluctuations. The anisotropy of DMPC is found to be larger by a factor of 2 than that of egg lecithin. This...

  15. Effects of a synthetic bioactive peptide on neurite growth and nerve growth factor release in chondroitin sulfate hydrogels

    OpenAIRE

    Conovaloff, Aaron W.; Beier, Brooke L.; Irazoqui, Pedro P.; Panitch, Alyssa

    2011-01-01

    Previous work has revealed robust dorsal root ganglia neurite growth in hydrogels of chondroitin sulfate. In the current work, it was determined whether addition of a synthetic bioactive peptide could augment neurite growth in these matrices via enhanced binding and sequestering of growth factors. Fluorescence recovery after photobleaching studies revealed that addition of peptide slowed nerve growth factor diffusivity in chondroitin sulfate gels, but not in control gels of hyaluronic acid. F...

  16. Anisotropy of domain wall resistance

    Science.gov (United States)

    Viret; Samson; Warin; Marty; Ott; Sondergard; Klein; Fermon

    2000-10-30

    The resistive effect of domain walls in FePd films with perpendicular anisotropy was studied experimentally as a function of field and temperature. The films were grown directly on MgO substrates, which induces an unusual virgin magnetic configuration composed of 60 nm wide parallel stripe domains. This allowed us to carry out the first measurements of the anisotropy of domain wall resistivity in the two configurations of current perpendicular and parallel to the walls. At 18 K, we find 8.2% and 1.3% for the domain wall magnetoresistance normalized to the wall width (8 nm) in these two respective configurations. These values are consistent with the predictions of Levy and Zhang.

  17. Active Achilles tendon kinesitherapy accelerates Achilles tendon repair by promoting neurite regeneration.

    Science.gov (United States)

    Jielile, Jiasharete; Aibai, Minawa; Sabirhazi, Gulnur; Shawutali, Nuerai; Tangkejie, Wulanbai; Badelhan, Aynaz; Nuerduola, Yeermike; Satewalede, Turde; Buranbai, Darehan; Hunapia, Beicen; Jialihasi, Ayidaer; Bai, Jingping; Kizaibek, Murat

    2012-12-15

    Active Achilles tendon kinesitherapy facilitates the functional recovery of a ruptured Achilles tendon. However, protein expression during the healing process remains a controversial issue. New Zealand rabbits, aged 14 weeks, underwent tenotomy followed immediately by Achilles tendon microsurgery to repair the Achilles tendon rupture. The tendon was then immobilized or subjected to postoperative early motion treatment (kinesitherapy). Mass spectrography results showed that after 14 days of motion treatment, 18 protein spots were differentially expressed, among which, 12 were up-regulated, consisting of gelsolin isoform b and neurite growth-related protein collapsing response mediator protein 2. Western blot analysis showed that gelsolin isoform b was up-regulated at days 7-21 of motion treatment. These findings suggest that active Achilles tendon kinesitherapy promotes the neurite regeneration of a ruptured Achilles tendon and gelsolin isoform b can be used as a biomarker for Achilles tendon healing after kinesitherapy.

  18. Active Achilles tendon kinesitherapy accelerates Achilles tendon repair by promoting neurite regeneration☆

    Science.gov (United States)

    Jielile, Jiasharete; Aibai, Minawa; Sabirhazi, Gulnur; Shawutali, Nuerai; Tangkejie, Wulanbai; Badelhan, Aynaz; Nuerduola, Yeermike; Satewalede, Turde; Buranbai, Darehan; Hunapia, Beicen; Jialihasi, Ayidaer; Bai, Jingping; Kizaibek, Murat

    2012-01-01

    Active Achilles tendon kinesitherapy facilitates the functional recovery of a ruptured Achilles tendon. However, protein expression during the healing process remains a controversial issue. New Zealand rabbits, aged 14 weeks, underwent tenotomy followed immediately by Achilles tendon microsurgery to repair the Achilles tendon rupture. The tendon was then immobilized or subjected to postoperative early motion treatment (kinesitherapy). Mass spectrography results showed that after 14 days of motion treatment, 18 protein spots were differentially expressed, among which, 12 were up-regulated, consisting of gelsolin isoform b and neurite growth-related protein collapsing response mediator protein 2. Western blot analysis showed that gelsolin isoform b was up-regulated at days 7–21 of motion treatment. These findings suggest that active Achilles tendon kinesitherapy promotes the neurite regeneration of a ruptured Achilles tendon and gelsolin isoform b can be used as a biomarker for Achilles tendon healing after kinesitherapy. PMID:25317130

  19. Influence of food matrix on outgrowth heterogeneity of heat damaged Bacillus cereus spores.

    Science.gov (United States)

    Warda, Alicja K; den Besten, Heidy M W; Sha, Na; Abee, Tjakko; Nierop Groot, Masja N

    2015-05-18

    Spoilage of heat treated foods can be caused by the presence of surviving spore-formers. It is virtually impossible to prevent contamination at the primary production level as spores are ubiquitous present in the environment and can contaminate raw products. As a result spore inactivation treatments are widely used by food producing industries to reduce the microbial spore loads. However consumers prefer mildly processed products that have less impact on its quality and this trend steers industry towards milder preservation treatments. Such treatments may result in damaged instead of inactivated spores, and these spores may germinate, repair, and grow out, possibly leading to quality and safety issues. The ability to repair and grow out is influenced by the properties of the food matrix. In the current communication we studied the outgrowth from heat damaged Bacillus cereus ATCC 14579 spores on Anopore membrane, which allowed following outgrowth heterogeneity of individual spores on broccoli and rice-based media as well as standard and mildly acidified (pH 5.5) meat-based BHI. Rice, broccoli and BHI pH 5.5 media resulted in delayed outgrowth from untreated spores, and increased heterogeneity compared to BHI pH 7.4, with the most pronounced effect in rice media. Exposure to wet heat for 1 min at 95 °C caused 2 log inactivation and approximately 95% of the spores in the surviving fraction were damaged resulting in substantial delay in outgrowth based on the time required to reach a maximum microcolony size of 256 cells. The delay was most pronounced for heat-treated spores on broccoli medium followed by spores on rice media (both untreated and treated). Interestingly, the increase in outgrowth heterogeneity of heat treated spores on BHI pH 7.4 was more pronounced than on rice, broccoli and BHI pH 5.5 conceivably reflecting that conditions in BHI pH 7.4 better support spore damage repair. This study compares the effects of three main factors, namely heat treatment, p

  20. Navigating neurites utilize cellular topography of Schwann cell somas and processes for optimal guidance

    Science.gov (United States)

    Lopez-Fagundo, Cristina; Mitchel, Jennifer A.; Ramchal, Talisha D.; Dingle, Yu-Ting L.; Hoffman-Kim, Diane

    2013-01-01

    The path created by aligned Schwann cells (SCs) after nerve injury underlies peripheral nerve regeneration. We developed geometric bioinspired substrates to extract key information needed for axon guidance by deconstructing the topographical cues presented by SCs. We have previously reported materials that directly replicate SC topography with micro- and nanoscale resolution, but a detailed explanation of the means of directed axon extension on SC topography has not yet been described. Here, using neurite tracing and time-lapse microscopy, we analyzed the SC features that influence axon guidance. Novel poly(dimethylsiloxane) materials, fabricated via photolithography, incorporated bioinspired topographical components with the shapes and sizes of aligned SCs, namely somas and processes, where the length of the processes were varied but the soma geometry and dimensions were kept constant. Rat dorsal root ganglia neurites aligned to all materials presenting bioinspired topography after a 5 days in culture and to bioinspired materials presenting soma and process features after only 17 hours in culture. Key findings of this study were: Neurite response to underlying bioinspired topographical features was time dependent, where at 5 days, neurites aligned most strongly to materials presenting combinations of soma and process features, with higher than average density of either process or soma features; but at 17 hours they aligned more strongly to materials presenting average densities of soma and process features and to materials presenting process features only. These studies elucidate the influence of SC topography on axon guidance in a time-dependent setting and have implications for the optimization of nerve regeneration strategies. PMID:23557939

  1. Active learning of neuron morphology for accurate automated tracing of neurites

    Science.gov (United States)

    Gala, Rohan; Chapeton, Julio; Jitesh, Jayant; Bhavsar, Chintan; Stepanyants, Armen

    2014-01-01

    Automating the process of neurite tracing from light microscopy stacks of images is essential for large-scale or high-throughput quantitative studies of neural circuits. While the general layout of labeled neurites can be captured by many automated tracing algorithms, it is often not possible to differentiate reliably between the processes belonging to different cells. The reason is that some neurites in the stack may appear broken due to imperfect labeling, while others may appear fused due to the limited resolution of optical microscopy. Trained neuroanatomists routinely resolve such topological ambiguities during manual tracing tasks by combining information about distances between branches, branch orientations, intensities, calibers, tortuosities, colors, as well as the presence of spines or boutons. Likewise, to evaluate different topological scenarios automatically, we developed a machine learning approach that combines many of the above mentioned features. A specifically designed confidence measure was used to actively train the algorithm during user-assisted tracing procedure. Active learning significantly reduces the training time and makes it possible to obtain less than 1% generalization error rates by providing few training examples. To evaluate the overall performance of the algorithm a number of image stacks were reconstructed automatically, as well as manually by several trained users, making it possible to compare the automated traces to the baseline inter-user variability. Several geometrical and topological features of the traces were selected for the comparisons. These features include the total trace length, the total numbers of branch and terminal points, the affinity of corresponding traces, and the distances between corresponding branch and terminal points. Our results show that when the density of labeled neurites is sufficiently low, automated traces are not significantly different from manual reconstructions obtained by trained users. PMID

  2. Active learning of neuron morphology for accurate automated tracing of neurites

    Directory of Open Access Journals (Sweden)

    Rohan eGala

    2014-05-01

    Full Text Available Automating the process of neurite tracing from light microscopy stacks of images is essential for large-scale or high-throughput quantitative studies of neural circuits. While the general layout of labeled neurites can be captured by many automated tracing algorithms, it is often not possible to differentiate reliably between the processes belonging to different cells. The reason is that some neurites in the stack may appear broken due to imperfect labeling, while others may appear fused due to the limited resolution of optical microscopy. Trained neuroanatomists routinely resolve such topological ambiguities during manual tracing tasks by combining information about distances between branches, branch orientations, intensities, calibers, tortuosities, colors, as well as the presence of spines or boutons. Likewise, to evaluate different topological scenarios automatically, we developed a machine learning approach that combines many of the above mentioned features. A specifically designed confidence measure was used to actively train the algorithm during user-assisted tracing procedure. Active learning significantly reduces the training time and makes it possible to obtain less than 1% generalization error rates by providing few training examples. To evaluate the overall performance of the algorithm a number of image stacks were reconstructed automatically, as well as manually by several trained users, making it possible to compare the automated traces to the baseline inter-user variability. Several geometrical and topological features of the traces were selected for the comparisons. These features include the total trace length, the total numbers of branch and terminal points, the affinity of corresponding traces, and the distances between corresponding branch and terminal points. Our results show that when the density of labeled neurites is sufficiently low, automated traces are not significantly different from manual reconstructions obtained by

  3. [Cosmic Microwave Background (CMB) Anisotropies

    Science.gov (United States)

    Silk, Joseph

    1998-01-01

    One of the main areas of research is the theory of cosmic microwave background (CMB) anisotropies and analysis of CMB data. Using the four year COBE data we were able to improve existing constraints on global shear and vorticity. We found that, in the flat case (which allows for greatest anisotropy), (omega/H)0 less than 10(exp -7), where omega is the vorticity and H is the Hubble constant. This is two orders of magnitude lower than the tightest, previous constraint. We have defined a new set of statistics which quantify the amount of non-Gaussianity in small field cosmic microwave background maps. By looking at the distribution of power around rings in Fourier space, and at the correlations between adjacent rings, one can identify non-Gaussian features which are masked by large scale Gaussian fluctuations. This may be particularly useful for identifying unresolved localized sources and line-like discontinuities. Levin and collaborators devised a method to determine the global geometry of the universe through observations of patterns in the hot and cold spots of the CMB. We have derived properties of the peaks (maxima) of the CMB anisotropies expected in flat and open CDM models. We represent results for angular resolutions ranging from 5 arcmin to 20 arcmin (antenna FWHM), scales that are relevant for the MAP and COBRA/SAMBA space missions and the ground-based interferometer. Results related to galaxy formation and evolution are also discussed.

  4. Neurite orientation dispersion and density imaging in the substantia nigra in idiopathic Parkinson disease.

    Science.gov (United States)

    Kamagata, Koji; Hatano, Taku; Okuzumi, Ayami; Motoi, Yumiko; Abe, Osamu; Shimoji, Keigo; Kamiya, Kouhei; Suzuki, Michimasa; Hori, Masaaki; Kumamaru, Kanako K; Hattori, Nobutaka; Aoki, Shigeki

    2016-08-01

    We used neurite orientation dispersion and density imaging (NODDI) to quantify changes in the substantia nigra pars compacta (SNpc) and striatum in Parkinson disease (PD). Diffusion-weighted magnetic resonance images were acquired from 58 PD patients and 36 age- and sex-matched controls. The intracellular volume fraction (Vic), orientation dispersion index (OD), and isotropic volume fraction (Viso) of the basal ganglia were compared between groups. Multivariate logistic regression analysis determined which diffusion parameters were independent predictors of PD. Receiver operating characteristic (ROC) analysis compared the diagnostic accuracies of the evaluated indices. Pearson coefficient analysis correlated each diffusional parameter with disease severity. Vic in the contralateral SNpc and putamen were significantly lower in PD patients than in healthy controls (P disease severity. Multivariate logistic analysis revealed that Vic (P = 0.0000046) and mean diffusivity (P = 0.019) in the contralateral SNpc were the independent predictors of PD. In the ROC analysis, Vic in the contralateral SNpc showed the best diagnostic performance (mean cutoff, 0.62; sensitivity, 0.88; specificity, 0.83). NODDI is likely to be useful for diagnosing PD and assessing its progression. • Neurite orientation dispersion and density imaging (NODDI) is a new diffusion MRI technique • NODDI estimates neurite microstructure more specifically than diffusion tensor imaging • By using NODDI, nigrostriatal alterations in PD can be evaluated in vivo • NOODI is useful for diagnosing PD and assessing its disease progression.

  5. Modeling extracellular electrical stimulation: I. Derivation and interpretation of neurite equations.

    Science.gov (United States)

    Meffin, Hamish; Tahayori, Bahman; Grayden, David B; Burkitt, Anthony N

    2012-12-01

    Neuroprosthetic devices, such as cochlear and retinal implants, work by directly stimulating neurons with extracellular electrodes. This is commonly modeled using the cable equation with an applied extracellular voltage. In this paper a framework for modeling extracellular electrical stimulation is presented. To this end, a cylindrical neurite with confined extracellular space in the subthreshold regime is modeled in three-dimensional space. Through cylindrical harmonic expansion of Laplace's equation, we derive the spatio-temporal equations governing different modes of stimulation, referred to as longitudinal and transverse modes, under types of boundary conditions. The longitudinal mode is described by the well-known cable equation, however, the transverse modes are described by a novel ordinary differential equation. For the longitudinal mode, we find that different electrotonic length constants apply under the two different boundary conditions. Equations connecting current density to voltage boundary conditions are derived that are used to calculate the trans-impedance of the neurite-plus-thin-extracellular-sheath. A detailed explanation on depolarization mechanisms and the dominant current pathway under different modes of stimulation is provided. The analytic results derived here enable the estimation of a neurite's membrane potential under extracellular stimulation, hence bypassing the heavy computational cost of using numerical methods.

  6. Osseous outgrowth on the buccal maxilla associated with piezosurgery-assisted en-masse retraction: A case series.

    Science.gov (United States)

    Tunçer, Nilüfer İrem; Arman-Özçırpıcı, Ayça; Oduncuoğlu, Bahar Füsun; Kantarcı, Alpdoğan

    2018-01-01

    Piezoelectric surgery is a novel surgical approach used in orthodontic treatment for rapid tooth movement. This paper presents a case series wherein osseous outgrowths were observed in response to piezosurgery-assisted en-masse retraction. Sixteen patients requiring upper premolar extractions were treated with miniscrew-supported en-masse retraction and received minimally invasive decortication via piezosurgery. Computed tomography (CT) of the maxillary anterior region was performed to investigate the nature of the outgrowths. In 8 of the 16 patients, hemispheric or disc-shaped osseous outgrowths were observed on the sites where piezosurgery was performed during retraction. CT images revealed that these outgrowths were alveolar bone. This case series presents a previously unreported osseous response to piezosurgery-assisted tooth movement during orthodontic treatment. The response is mostly transient and is observed in 50% of the treated patients, suggesting a bone turnover that can be assessed clinically and radiographically.

  7. ADAM28 localizes to HLA-G+ trophoblasts and promotes column cell outgrowth.

    Science.gov (United States)

    De Luca, L C; Le, H T; Mara, D L; Beristain, A G

    2017-07-01

    Trophoblast progenitor cell differentiation towards the extravillous trophoblast (EVT) lineage initiates within proximal regions of anchoring columns of first trimester placental villi. While molecular processes controlling the initial stages of progenitor cell differentiation along the EVT pathway have been described, much remains unknown about factors important in distal column cell differentiation into invasive EVTs. ADAMs are proteases that regulate growth factor signaling, cell-matrix adhesion, and matrix proteolysis, and thus impact many processes relevant in placentation. Global gene expression studies identified the ADAM subtype, ADAM28, to be highly expressed in EVT-like trophoblasts, suggesting that it may play a role in EVT function. This study aims to test the functional importance of ADAM28 in column cell outgrowth and maintenance. ADAM28 mRNA levels and protein localization were determined by qPCR and immunofluorescence microscopy analyses in purified placental villi cell populations and tissues. ADAM28 function in trophoblast column outgrowth was examined using ADAM28-targetting siRNAs in Matrigel-imbedded placental explant cultures. Within placental villi, ADAM28 mRNA levels were highest in HLA-G + column trophoblasts, and consistent with this, ADAM28 was preferentially localized to HLA-G + trophoblasts within distal anchoring columns and decidual tissue. siRNA-directed loss of ADAM28 impaired trophoblast column outgrowth and resulted in increased apoptosis in matrix-invading trophoblasts. Our findings suggest that ADAM28 promotes column outgrowth by providing survival cues within anchoring column cells. This study also provides insight into a possible role for ADAM28 in driving differentiation of column trophoblasts into invasive HLA-G + EVT subsets. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Metabolic activity in dormant conidia of Aspergillus niger and developmental changes during conidial outgrowth

    OpenAIRE

    Novodvorska, Michaela; Stratford, Malcolm; Blythe, Martin J.; Wilson, Raymond; Beniston, Richard G.; Archer, David B.

    2016-01-01

    The early stages of development of Aspergillus niger conidia during outgrowth were explored by combining genome-wide gene expression analysis (RNAseq), proteomics, Warburg manometry and uptake studies. Resting conidia suspended in water were demonstrated for the first time to be metabolically active as low levels of oxygen uptake and the generation of carbon dioxide were detected, suggesting that low-level respiratory metabolism occurs in conidia for maintenance. Upon triggering of spore germ...

  9. Metabolic activity in dormant conidia of Aspergillus niger and developmental changes during conidial outgrowth.

    Science.gov (United States)

    Novodvorska, Michaela; Stratford, Malcolm; Blythe, Martin J; Wilson, Raymond; Beniston, Richard G; Archer, David B

    2016-09-01

    The early stages of development of Aspergillus niger conidia during outgrowth were explored by combining genome-wide gene expression analysis (RNAseq), proteomics, Warburg manometry and uptake studies. Resting conidia suspended in water were demonstrated for the first time to be metabolically active as low levels of oxygen uptake and the generation of carbon dioxide were detected, suggesting that low-level respiratory metabolism occurs in conidia for maintenance. Upon triggering of spore germination, generation of CO2 increased dramatically. For a short period, which coincided with mobilisation of the intracellular polyol, trehalose, there was no increase in uptake of O2 indicating that trehalose was metabolised by fermentation. Data from genome-wide mRNA profiling showed the presence of transcripts associated with fermentative and respiratory metabolism in resting conidia. Following triggering of conidial outgrowth, there was a clear switch to respiration after 25min, confirmed by cyanide inhibition. No effect of SHAM, salicylhydroxamic acid, on respiration suggests electron flow via cytochrome c oxidase. Glucose entry into spores was not detectable before 1h after triggering germination. The impact of sorbic acid on germination was examined and we showed that it inhibits glucose uptake. O2 uptake was also inhibited, delaying the onset of respiration and extending the period of fermentation. In conclusion, we show that conidia suspended in water are not completely dormant and that conidial outgrowth involves fermentative metabolism that precedes respiration. Copyright © 2016. Published by Elsevier Inc.

  10. MicroRNA-338 Attenuates Cortical Neuronal Outgrowth by Modulating the Expression of Axon Guidance Genes.

    Science.gov (United States)

    Kos, Aron; Klein-Gunnewiek, Teun; Meinhardt, Julia; Loohuis, Nikkie F M Olde; van Bokhoven, Hans; Kaplan, Barry B; Martens, Gerard J; Kolk, Sharon M; Aschrafi, Armaz

    2017-07-01

    MicroRNAs (miRs) are small non-coding RNAs that confer robustness to gene networks through post-transcriptional gene regulation. Previously, we identified miR-338 as a modulator of axonal outgrowth in sympathetic neurons. In the current study, we examined the role of miR-338 in the development of cortical neurons and uncovered its downstream mRNA targets. Long-term inhibition of miR-338 during neuronal differentiation resulted in reduced dendritic complexity and altered dendritic spine morphology. Furthermore, monitoring axon outgrowth in cortical cells revealed that miR-338 overexpression decreased, whereas inhibition of miR-338 increased axonal length. To identify gene targets mediating the observed phenotype, we inhibited miR-338 in cortical neurons and performed whole-transcriptome analysis. Pathway analysis revealed that miR-338 modulates a subset of transcripts involved in the axonal guidance machinery by means of direct and indirect gene targeting. Collectively, our results implicate miR-338 as a novel regulator of cortical neuronal maturation by fine-tuning the expression of gene networks governing cortical outgrowth.

  11. Inhibitory effects of brain-derived neurotrophic factor precursor on viability and neurite growth of murine hippocampal neurons

    Directory of Open Access Journals (Sweden)

    Jia CHEN

    2014-10-01

    Full Text Available Objective To explore the mediation effect of p75 neurotrophin receptor (p75NTR in the effect of brainderived neurotrophic factor precursor (proBDNF on viability and neurite growth of murine hippocampal neurons. Methods  Hippocampal neurons were obtained from p75NTR+/+ and p75NTR-/- 18-day mice and primarily cultured. For p75NTR+/+ neurons, three experimental groups were set, i.e. control, proBDNF (30ng/ml, and proBDNF (30ng/ml+p75/Fc (30µg/ml groups. For p75NTR-/- neurons, two experimental groups were set, i.e. control and proBDNF (30ng/ml groups. MTT assays were performed after 24h to examine the viability of neonatal primary neurons. Immunofluorescent staining was conducted after 72h to investigate the neurite length. Results With MAP2 and DAPI double fluorescent staining it was identified that the neonatal hippocampal neurons were successfully cultured in vitro with high purity. For viability assay of p75NTR+/+ neurons, it was found that the absorbance value at 570nm (A570 in proBDNF group was significantly lower than that in control group (P0.05. With neurite growth assay of p75NTR+/+ neurons, it was found that the neurite length in proBDNF group was significantly shorter than that in control group (P0.05. With neurite growth assay of p75NTR-/- neurons, no difference in neurite length was observed between proBDNF group and control group. Conclusion proBDNF may inhibit the neuronal viability and neurite growth via p75NTR. DOI: 10.11855/j.issn.0577-7402.2014.09.03

  12. Anisotropy of the cosmic background radiation

    International Nuclear Information System (INIS)

    Silk, J.

    1988-01-01

    The characteristics of the cosmic microwave background radiation (CBR) are reviewed, focusing on intrinsic anisotropies caused by primordial matter fluctuations. The basic elements of the CBR are outlined and the contributions to anisotropy at different angular scales are discussed. Possible fluctuation spectra that can generate the observed large-scale structure of the universe through gravitational instability and nonlinear evolution are examined and compared with observational searches for cosmic microwave anisotropies. 21 refs

  13. Magnetic anisotropy of Ni/Cr multilayers

    International Nuclear Information System (INIS)

    Kang, S.; Xia, H.

    1997-01-01

    The magnetic anisotropy of Ni/Cr multilayers has been investigated by using vibrating sample magnetometer (VSM) and ferromagnetic resonance techniques (FMR). The FMR spectra are obtained as a function of the orientation of the applied magnetic field from in-plane to out-of-plane. The results are fitted theoretically to determine the magnetic anisotropy. From VSM and FMR, a positive value for Ni/Cr interface anisotropy is obtained, which favours a perpendicular easy axis. The possible mechanism for the perpendicular anisotropy has been discussed and it may be attributed to the magnetostriction, caused by intrinsic stress due to lattice mismatch. (orig.). With 005 figs., 001 tabs

  14. Azimuthal anisotropy measurements by STAR

    Science.gov (United States)

    Yi, Li

    2014-06-01

    The recent study of centrality and transverse momentum (pT) dependence of inclusive charged hardron elliptic anisotropy (v2) at midrapidity (|η|<1.0) in Au+Au collision at √{sNN}=7.7,11.5,19.6,27, and 39 GeV in STAR Beam Energy Scan program is presented. We show that the observed increase of inclusive v2 is mainly due to the average pT increase with energy. In Au+Au 200 GeV collisions, the triangular anisotropy (v3) measurements highly depend on measurement methods; v3 is strongly dependent on Δη. The difference between two- and four-particle cumulants v2{2} and v2{4} for Au+Au and Cu+Cu collision at √{sNN}=62.4 and 200 GeV is used to explore flow fluctuations. Furthermore, by exploiting the symmetry of average flow in pseudorapidity η about midrapidity, the Δη-dependent and independent components are separated using v2{2} and v2{4}.

  15. Azimuthal anisotropy measurements by STAR

    Energy Technology Data Exchange (ETDEWEB)

    Yi, Li

    2014-06-15

    The recent study of centrality and transverse momentum (p{sub T}) dependence of inclusive charged hardron elliptic anisotropy (v{sub 2}) at midrapidity (|η|<1.0) in Au+Au collision at √(s{sub NN})=7.7,11.5,19.6,27, and39 GeV in STAR Beam Energy Scan program is presented. We show that the observed increase of inclusive v{sub 2} is mainly due to the average p{sub T} increase with energy. In Au+Au 200 GeV collisions, the triangular anisotropy (v{sub 3}) measurements highly depend on measurement methods; v{sub 3} is strongly dependent on Δη. The difference between two- and four-particle cumulants v{sub 2}{2} and v{sub 2}{4} for Au+Au and Cu+Cu collision at √(s{sub NN})=62.4 and 200 GeV is used to explore flow fluctuations. Furthermore, by exploiting the symmetry of average flow in pseudorapidity η about midrapidity, the Δη-dependent and independent components are separated using v{sub 2}{2} and v{sub 2}{4}.

  16. Azimuthal anisotropy measurements by STAR

    International Nuclear Information System (INIS)

    Yi, Li

    2014-01-01

    The recent study of centrality and transverse momentum (p T ) dependence of inclusive charged hardron elliptic anisotropy (v 2 ) at midrapidity (|η|<1.0) in Au+Au collision at √(s NN )=7.7,11.5,19.6,27, and39 GeV in STAR Beam Energy Scan program is presented. We show that the observed increase of inclusive v 2 is mainly due to the average p T increase with energy. In Au+Au 200 GeV collisions, the triangular anisotropy (v 3 ) measurements highly depend on measurement methods; v 3 is strongly dependent on Δη. The difference between two- and four-particle cumulants v 2 {2} and v 2 {4} for Au+Au and Cu+Cu collision at √(s NN )=62.4 and 200 GeV is used to explore flow fluctuations. Furthermore, by exploiting the symmetry of average flow in pseudorapidity η about midrapidity, the Δη-dependent and independent components are separated using v 2 {2} and v 2 {4}

  17. The neurite growth inhibitory effects of soluble TNFα on developing sympathetic neurons are dependent on developmental age.

    Science.gov (United States)

    Nolan, Aoife M; Collins, Louise M; Wyatt, Sean L; Gutierrez, Humberto; O'Keeffe, Gerard W

    2014-01-01

    During development, the growth of neural processes is regulated by an array of cellular and molecular mechanisms which influence growth rate, direction and branching. Recently, many members of the TNF superfamily have been shown to be key regulators of neurite growth during development. The founder member of this family, TNFα can both promote and inhibit neurite growth depending on the cellular context. Specifically, transmembrane TNFα promotes neurite growth, while soluble TNFα inhibits it. While the growth promoting effects of TNFα are restricted to a defined developmental window of early postnatal development, whether the growth inhibitory effects of soluble TNFα occur throughout development is unknown. In this study we used the extensively studied, well characterised neurons of the superior cervical ganglion to show that the growth inhibitory effects of soluble TNFα are restricted to a specific period of late embryonic and early postnatal development. Furthermore, we show that this growth inhibitory effect of soluble TNFα requires NF-κB signalling at all developmental stages at which soluble TNFα inhibits neurite growth. These findings raise the possibility that increases in the amount of soluble TNFα in vivo, for example as a result of maternal inflammation, could negatively affect neurite growth in developing neurons at specific stages of development. Copyright © 2015 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  18. A neurite quality index and machine vision software for improved quantification of neurodegeneration.

    Science.gov (United States)

    Romero, Peggy; Miller, Ted; Garakani, Arman

    2009-12-01

    Current methods to assess neurodegradation in dorsal root ganglion cultures as a model for neurodegenerative diseases are imprecise and time-consuming. Here we describe two new methods to quantify neuroprotection in these cultures. The neurite quality index (NQI) builds upon earlier manual methods, incorporating additional morphological events to increase detection sensitivity for the detection of early degeneration events. Neurosight is a machine vision-based method that recapitulates many of the strengths of NQI while enabling high-throughput screening applications with decreased costs.

  19. Higher-order anisotropies in the blast-wave model: Disentangling flow and density field anisotropies

    Energy Technology Data Exchange (ETDEWEB)

    Cimerman, Jakub [Czech Technical University in Prague, FNSPE, Prague (Czech Republic); Comenius University, FMPI, Bratislava (Slovakia); Tomasik, Boris [Czech Technical University in Prague, FNSPE, Prague (Czech Republic); Univerzita Mateja Bela, FPV, Banska Bystrica (Slovakia); Csanad, Mate; Loekoes, Sandor [Eoetvoes Lorand University, Budapest (Hungary)

    2017-08-15

    We formulate a generalisation of the blast-wave model which is suitable for the description of higher-order azimuthal anisotropies of the hadron production. The model includes anisotropy in the density profile as well as an anisotropy in the transverse expansion velocity field. We then study how these two kinds of anisotropies influence the single-particle distributions and the correlation radii of two-particle correlation functions. Particularly we focus on the third-order anisotropy and consideration is given averaging over different orientations of the event plane. (orig.)

  20. Frazzled/DCC facilitates cardiac cell outgrowth and attachment during Drosophila dorsal vessel formation.

    Science.gov (United States)

    Macabenta, Frank D; Jensen, Amber G; Cheng, Yi-Shan; Kramer, Joseph J; Kramer, Sunita G

    2013-08-15

    Drosophila embryonic dorsal vessel (DV) morphogenesis is a highly stereotyped process that involves the migration and morphogenesis of 52 pairs of cardioblasts (CBs) in order to form a linear tube. This process requires spatiotemporally-regulated localization of signaling and adhesive proteins in order to coordinate the formation of a central lumen while maintaining simultaneous adhesion between CBs. Previous studies have shown that the Slit/Roundabout and Netrin/Unc5 repulsive signaling pathways facilitate site-specific loss of adhesion between contralateral CBs in order to form a luminal space. However, the concomitant mechanism by which attraction initiates CB outgrowth and discrete localization of adhesive proteins remains poorly understood. Here we provide genetic evidence that Netrin signals through DCC (Deleted in Colorectal Carcinoma)/UNC-40/Frazzled (Fra) to mediate CB outgrowth and attachment and that this function occurs prior to and independently of Netrin/UNC-5 signaling. fra mRNA is expressed in the CBs prior to and during DV morphogenesis. Loss-of-fra-function results in significant defects in cell shape and alignment between contralateral CB rows. In addition, CB outgrowth and attachment is impaired in both fra loss- and gain-of-function mutants. Deletion of both Netrin genes (NetA and NetB) results in CB attachment phenotypes similar to fra mutants. Similar defects are also seen when both fra and unc5 are deleted. Finally we show that Fra accumulates at dorsal and ventral leading edges of paired CBs, and this localization is dependent upon Netrin. We propose that while repulsive guidance mechanisms contribute to lumen formation by preventing luminal domains from coming together, site-specific Netrin/Frazzled signaling mediates CB attachment. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. In vitro formation of the Merkel cell-neurite complex in embryonic mouse whiskers using organotypic co-cultures.

    Science.gov (United States)

    Ishida, Kentaro; Saito, Tetsuichiro; Mitsui, Toshiyuki

    2018-06-01

    A Merkel cell-neurite complex is a touch receptor composed of specialized epithelial cells named Merkel cells and peripheral sensory nerves in the skin. Merkel cells are found in touch-sensitive skin components including whisker follicles. The nerve fibers that innervate Merkel cells of a whisker follicle extend from the maxillary branch of the trigeminal ganglion. Whiskers as a sensory organ attribute to the complicated architecture of the Merkel cell-neurite complex, and therefore it is intriguing how the structure is formed. However, observing the dynamic process of the formation of a Merkel cell-neurite complex in whiskers during embryonic development is still difficult. In this study, we tried to develop an organotypic co-culture method of a whisker pad and a trigeminal ganglion explant to form the Merkel cell-neurite complex in vitro. We initially developed two distinct culture methods of a single whisker row and a trigeminal ganglion explant, and then combined them. By dissecting and cultivating a single row from a whisker pad, the morphogenesis of whisker follicles could be observed under a microscope. After the co-cultivation of the whisker row with a trigeminal ganglion explant, a Merkel cell-neurite complex composed of Merkel cells, which were positive for both cytokeratin 8 and SOX2, Neurofilament-H-positive trigeminal nerve fibers and Schwann cells expressing Nestin, SOX2 and SOX10 was observed via immunohistochemical analyses. These results suggest that the process for the formation of a Merkel cell-neurite complex can be observed under a microscope using our organotypic co-culture method. © 2018 Japanese Society of Developmental Biologists.

  2. Evaluation of electrical resistivity anisotropy in geological mapping ...

    African Journals Online (AJOL)

    user

    Key words: Electrical resistivity anisotropy, radial vertical electrical sounding, anisotropy polygons. INTRODUCTION ... electrical resistivity survey in the geological interpretation ... resistivity and other electrical or electromagnetic based.

  3. Effects of 4-aminopyridine on organelle movement in cultured mouse dorsal root ganglion neurites.

    Science.gov (United States)

    Hiruma, Hiromi; Kawakami, Tadashi

    2010-03-01

    Aminopyridines, widely used as a K(+) channel blocker, are membrane-permeable weak bases and have the ability to form vacuoles in the cytoplasm. The vacuoles originate from acidic organelles such as lysosomes. Here, we investigated the effects of 4-aminopyridine (4-AP) on organelle movement in neurites of cultured mouse dorsal root ganglion (DRG) neurons by using video-enhanced microscopy. Some experiments were carried out using fluorescent dyes for lysosomes and mitochondria and confocal microscopy. Treatment of DRG neurons with 4 mM 4-AP caused Brownian movement of some lysosomes within 5 min. The Brownian movement gradually became rapid and vacuoles were formed around individual lysosomes 10-20 min after the start of treatment. Axonal transport of organelles was inhibited by 4-AP. Lysosomes showing Brownian movement were not transported in longitudinal direction of the neurite and the transport of mitochondria was interrupted by vacuoles. The 4-AP-induced Brownian movement of lysosomes with vacuole formation and inhibition of axonal transport were prevented by the simultaneous treatment with vacuolar H(+) ATPase inhibitor bafilomycin A1 or in Cl(-)-free SO(4)(2-) medium. These results indicate that changes in organelle movement by 4-AP are related to vacuole formation and the vacuolar H(+) ATPase and Cl(-) are required for the effects of 4-AP.

  4. Primordial anisotropies in gauged hybrid inflation

    Science.gov (United States)

    Akbar Abolhasani, Ali; Emami, Razieh; Firouzjahi, Hassan

    2014-05-01

    We study primordial anisotropies generated in the model of gauged hybrid inflation in which the complex waterfall field is charged under a U(1)gauge field. Primordial anisotropies are generated either actively during inflation or from inhomogeneities modulating the surface of end of inflation during waterfall transition. We present a consistent δN mechanism to calculate the anisotropic power spectrum and bispectrum. We show that the primordial anisotropies generated at the surface of end of inflation do not depend on the number of e-folds and therefore do not produce dangerously large anisotropies associated with the IR modes. Furthermore, one can find the parameter space that the anisotropies generated from the surface of end of inflation cancel the anisotropies generated during inflation, therefore relaxing the constrains on model parameters imposed from IR anisotropies. We also show that the gauge field fluctuations induce a red-tilted power spectrum so the averaged power spectrum from the gauge field can change the total power spectrum from blue to red. Therefore, hybrid inflation, once gauged under a U(1) field, can be consistent with the cosmological observations.

  5. Primordial anisotropies in gauged hybrid inflation

    International Nuclear Information System (INIS)

    Abolhasani, Ali Akbar; Emami, Razieh; Firouzjahi, Hassan

    2014-01-01

    We study primordial anisotropies generated in the model of gauged hybrid inflation in which the complex waterfall field is charged under a U(1)gauge field. Primordial anisotropies are generated either actively during inflation or from inhomogeneities modulating the surface of end of inflation during waterfall transition. We present a consistent δN mechanism to calculate the anisotropic power spectrum and bispectrum. We show that the primordial anisotropies generated at the surface of end of inflation do not depend on the number of e-folds and therefore do not produce dangerously large anisotropies associated with the IR modes. Furthermore, one can find the parameter space that the anisotropies generated from the surface of end of inflation cancel the anisotropies generated during inflation, therefore relaxing the constrains on model parameters imposed from IR anisotropies. We also show that the gauge field fluctuations induce a red-tilted power spectrum so the averaged power spectrum from the gauge field can change the total power spectrum from blue to red. Therefore, hybrid inflation, once gauged under a U(1) field, can be consistent with the cosmological observations

  6. Layer 6 cortical neurons require Reelin-Dab1 signaling for cellular orientation, Golgi deployment, and directed neurite growth into the marginal zone.

    Science.gov (United States)

    O'Dell, Ryan S; Ustine, Candida J M; Cameron, David A; Lawless, Sean M; Williams, Rebecca M; Zipfel, Warren R; Olson, Eric C

    2012-07-07

    The secreted ligand Reelin is believed to regulate the translocation of prospective layer 6 (L6) neocortical neurons into the preplate, a loose layer of pioneer neurons that overlies the ventricular zone. Recent studies have also suggested that Reelin controls neuronal orientation and polarized dendritic growth during this period of early cortical development. To explicitly characterize and quantify how Reelin controls this critical aspect of neurite initiation and growth we used a new ex utero explant model of early cortical development to selectively label a subset of L6 cortical neurons for complete 3-D reconstruction. The total neurite arbor sizes of neurons in Reelin-deficient (reeler mutant) and Dab1-deficient (Reelin-non-responsive scrambler mutant) cortices were quantified and unexpectedly were not different than control arbor lengths (p = 0.51). For each mutant, however, arbor organization was markedly different: mutant neurons manifested more primary processes (neurites emitted directly from the soma) than wild type, and these neurites were longer and displayed less branching. Reeler and scrambler mutant neurites extended tangentially rather than radially, and the Golgi apparatus that normally invests the apical neurite was compact in both reeler and scrambler mutants. Mutant cortices also exhibited a neurite "exclusion zone" which was relatively devoid of L6 neuron neurites and extended at least 15 μm beneath the pial surface, an area corresponding to the marginal zone (MZ) in the wild type explants. The presence of an exclusion zone was also indicated in the orientation of mutant primary neurite and neuronal somata, which failed to adopt angles within ~20˚ of the radial line to the pial surface. Injection of recombinant Reelin to reeler, but not scrambler, mutant cortices fully rescued soma orientation, Golgi organization, and dendritic projection defects within four hrs. These findings indicate Reelin promotes directional dendritic growth into

  7. Diacylglycerol kinase β promotes dendritic outgrowth and spine maturation in developing hippocampal neurons

    Directory of Open Access Journals (Sweden)

    Otani Koichi

    2009-08-01

    Full Text Available Abstract Background Diacylglycerol kinase (DGK is an enzyme that phosphorylates diacylglycerol to phosphatidic acid and comprises multiple isozymes of distinct properties. Of DGKs, mRNA signal for DGKβ is strongly detected in the striatum, and one of the transcripts derived from the human DGKβ locus is annotated in GenBank as being differentially expressed in bipolar disorder patients. Recently, we have reported that DGKβ is expressed in medium spiny neurons of the striatum and is highly concentrated at the perisynapse of dendritic spines. However, it remains elusive how DGKβ is implicated in pathophysiological role in neurons at the cellular level. Results In the present study, we investigated the expression and subcellular localization of DGKβ in the hippocampus, together with its functional implication using transfected hippocampal neurons. DGKβ is expressed not only in projection neurons but also in interneurons and is concentrated at perisynaptic sites of asymmetrical synapses. Overexpression of wild-type DGKβ promotes dendrite outgrowth at 7 d in vitro (DIV and spine maturation at 14 DIV in transfected hippocampal neurons, although its kinase-dead mutant has no effect. Conclusion In the hippocampus, DGKβ is expressed in both projection neurons and interneurons and is accumulated at the perisynapse of dendritic spines in asymmetrical synapses. Transfection experiments suggest that DGKβ may be involved in the molecular machineries of dendrite outgrowth and spinogenesis through its kinase activity.

  8. The influence of electrospun fibre size on Schwann cell behaviour and axonal outgrowth

    Energy Technology Data Exchange (ETDEWEB)

    Gnavi, S., E-mail: sara.gnavi@unito.it [Department of Clinical and Biological Sciences, University of Torino, Orbassano 10043 (Italy); Neuroscience Institute of the Cavalieri-Ottolenghi Foundation, University of Torino, Orbassano 10043 (Italy); Fornasari, B.E., E-mail: benedettaelena.fornasari@unito.it [Department of Clinical and Biological Sciences, University of Torino, Orbassano 10043 (Italy); Neuroscience Institute of the Cavalieri-Ottolenghi Foundation, University of Torino, Orbassano 10043 (Italy); Tonda-Turo, C., E-mail: chiara.tondaturo@polito.it [Politecnico di Torino, Department of Mechanical and Aerospace Engineering, Politecnico of Torino, Torino 10100 (Italy); Ciardelli, G., E-mail: gianluca.ciardelli@polito.it [Politecnico di Torino, Department of Mechanical and Aerospace Engineering, Politecnico of Torino, Torino 10100 (Italy); CNR-IPCF UOS, Pisa 56124 (Italy); Zanetti, M., E-mail: marco.zanetti@unito.it [Nanostructured Interfaces and Surfaces, Department of Chemistry, University of Torino, Torino 10100 (Italy); Geuna, S., E-mail: stefano.geuna@unito.it [Department of Clinical and Biological Sciences, University of Torino, Orbassano 10043 (Italy); Neuroscience Institute of the Cavalieri-Ottolenghi Foundation, University of Torino, Orbassano 10043 (Italy); Perroteau, I., E-mail: isabelle.perroteau@unito.it [Department of Clinical and Biological Sciences, University of Torino, Orbassano 10043 (Italy)

    2015-03-01

    Fibrous substrates functioning as temporary extracellular matrices can be prepared easily by electrospinning, yielding fibrous matrices suitable as internal fillers for nerve guidance channels. In this study, gelatin micro- or nano-fibres were prepared by electrospinning by tuning the gelatin concentration and solution flow rate. The effect of gelatin fibre diameter on cell adhesion and proliferation was tested in vitro using explant cultures of Schwann cells (SC) and dorsal root ganglia (DRG). Cell adhesion was assessed by quantifying the cell spreading area, actin cytoskeleton organization and focal adhesion complex formation. Nano-fibres promoted cell spreading and actin cytoskeleton organization, increasing cellular adhesion and the proliferation rate. However, both migration rate and motility, quantified by transwell and time lapse assays respectively, were greater in cells cultured on micro-fibres. Finally, there was more DRG axon outgrowth on micro-fibres. These data suggest that the topography of electrospun gelatin fibres can be adjusted to modulate SC and axon organization and that both nano- and micro-fibres are promising fillers for the design of devices for peripheral nerve repair. - Highlights: • Electrospinning used to produce gelatin nano- and micro-fibre matrices. • Nano-fibre matrices promote Schwann cell organization and increase proliferation rate. • Micro-fibre matrices promote Schwann cell migration. • Micro-fibre matrices promote axonal outgrowth.

  9. Prostaglandin E2 Regulates Liver versus Pancreas Cell Fate Decisions and Endodermal Outgrowth

    Science.gov (United States)

    Nissim, Sahar; Sherwood, Richard I.; Wucherpfennig, Julia; Saunders, Diane; Harris, James M.; Esain, Virginie; Carroll, Kelli J.; Frechette, Gregory M.; Kim, Andrew J.; Hwang, Katie L.; Cutting, Claire C.; Elledge, Susanna; North, Trista E.; Goessling, Wolfram

    2014-01-01

    SUMMARY The liver and pancreas arise from common endodermal progenitors. How these distinct cell fates are specified is poorly understood. Here, we describe prostaglandin E2 (PGE2) as a regulator of endodermal fate specification during development. Modulating PGE2 activity has opposing effects on liver-versus-pancreas specification in zebrafish embryos as well as mouse endodermal progenitors. The PGE2 synthetic enzyme cox2a and receptor ep2a are patterned such that cells closest to PGE2 synthesis acquire a liver fate whereas more distant cells acquire a pancreas fate. PGE2 interacts with the bmp2b pathway to regulate fate specification. At later stages of development, PGE2 acting via the ep4a receptor promotes outgrowth of both the liver and pancreas. PGE2 remains important for adult organ growth, as it modulates liver regeneration. This work provides in vivo evidence that PGE2 may act as a morphogen to regulate cell fate decisions and outgrowth of the embryonic endodermal anlagen. PMID:24530296

  10. A perturbative DFT approach for magnetic anisotropy

    Energy Technology Data Exchange (ETDEWEB)

    Khoo, Khoong Hong; Laskowski, Robert, E-mail: rolask@ihpc.a-star.edu.sg

    2017-04-15

    We develop a perturbative formalism for computing magnetocrystalline anisotropy within density functional theory and the magnetic force theorem. Instead of computing eigenvalues of the spin–orbit Hamiltonian for selected spin polarizations, as in the conventional “force theorem” approach, we show that the effect can be cast into a redefined form of the spin–orbit operator. This allows to separate the large eigenvalue shift due to spin-orbit interaction common for both polarizations from the much smaller magnetic anisotropy splitting. As a consequence the anisotropy splitting may by considered as a perturbation.

  11. Solvent induced supramolecular anisotropy in molecular gels

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, Michael A., E-mail: mroger09@uoguelph.ca [Department of Food Science, University of Guelph, Guelph, Ontario, N3C3X9 (Canada); Corradini, Maria G. [Department of Food Science, University of Massachusetts Amherst, Amherst, MA, 01003 (United States); Emge, Thomas [Department of Chemistry and Biochemistry, Rutgers University, New Brunswick, NJ, 08901 (United States)

    2017-06-15

    Herein is the first report of solvent induced anisotropy in 12-hydroxystearic acid self-assembled fibrillar networks. Increasing the chain length of polar solvent, such as nitriles and ketones, tailored the anisotropy of the fibrillar aggregates. 12HSA molecular gels, comprised of alkanes, exhibited an isotropic fibrillar network irrespective of the alkane chain length. In polar solvents, anisotropy, observed using 2D powder x-ray diffraction profiles, is correlated to a fibrillar supramolecular morphologies in long chain nitriles and ketones while sphereulitic crystals are correlated to x-ray diffraction patterns with an isotropic scatter intensity in short chain ketones and nitriles. These changes directly modify the final physical properties of the gels. - Highlights: • 12-HSA self-assembles into crystalline supramolecular morphologies depending on the solvent. • Alkanes, short chain nitriles and ketones led to 12-HSA displaying supramolecular isotropy. • In long chain nitriles and ketones, 12-HSA displays supramolecular anisotropy.

  12. Solvent induced supramolecular anisotropy in molecular gels

    International Nuclear Information System (INIS)

    Rogers, Michael A.; Corradini, Maria G.; Emge, Thomas

    2017-01-01

    Herein is the first report of solvent induced anisotropy in 12-hydroxystearic acid self-assembled fibrillar networks. Increasing the chain length of polar solvent, such as nitriles and ketones, tailored the anisotropy of the fibrillar aggregates. 12HSA molecular gels, comprised of alkanes, exhibited an isotropic fibrillar network irrespective of the alkane chain length. In polar solvents, anisotropy, observed using 2D powder x-ray diffraction profiles, is correlated to a fibrillar supramolecular morphologies in long chain nitriles and ketones while sphereulitic crystals are correlated to x-ray diffraction patterns with an isotropic scatter intensity in short chain ketones and nitriles. These changes directly modify the final physical properties of the gels. - Highlights: • 12-HSA self-assembles into crystalline supramolecular morphologies depending on the solvent. • Alkanes, short chain nitriles and ketones led to 12-HSA displaying supramolecular isotropy. • In long chain nitriles and ketones, 12-HSA displays supramolecular anisotropy.

  13. Texture and anisotropy analysis of Qusaiba shales

    KAUST Repository

    Kanitpanyacharoen, Waruntorn; Wenk, Hans-Rudolf; Kets, Frans; Lehr, Christian; Wirth, Richard

    2011-01-01

    Scanning and transmission electron microscopy, synchrotron X-ray diffraction, microtomography and ultrasonic velocity measurements were used to characterize microstructures and anisotropy of three deeply buried Qusaiba shales from the Rub

  14. Cellulose and the Control of Growth Anisotropy

    Energy Technology Data Exchange (ETDEWEB)

    Tobias I. Baskin

    2004-04-01

    The authors research aims to understand morphogenesis, focusing on growth anisotropy, a process that is crucial to make organs with specific and heritable shapes. For the award, the specific aims were to test hypotheses concerning how growth anisotropy is controlled by cell wall structure, particularly by the synthesis and alignment of cellulose microfibrils, the predominant mechanical element in the cell wall. This research has involved characterizing the basic physiology of anisotropic expansion, including measuring it at high resolution; and second, characterizing the relationship between growth anisotropy, and cellulose microfibrils. Important in this relationship and also to the control of anisotropic expansion are structures just inside the plasma membrane called cortical microtubules, and the research has also investigated their contribution to controlling anisotropy and microfibril alignment. In addition to primary experimental papers, I have also developed improved methods relating to these objectives as well as written relevant reviews. Major accomplishments in each area will now be described.

  15. Higher-order anisotropies in the Buda-Lund model: Disentangling flow and density field anisotropies

    Energy Technology Data Exchange (ETDEWEB)

    Loekoes, Sandor [Eoetvoes Lorand University, Budapest (Hungary); Csanad, Mate [Eoetvoes Lorand University, Budapest (Hungary); Stony Brook University, Stony Brook, NY (United States); Tomasik, Boris [Univerzita Mateja Bela, Banska Bystrica (Slovakia); Czech Technical University in Prague, FNSPE, Prague (Czech Republic); Csoergo, Tamas [Wigner RCP, Budapest (Hungary); KRF, Gyoengyoes (Hungary)

    2016-10-15

    The Buda-Lund hydro model describes an expanding ellipsoidal fireball, and fits the observed elliptic flow and oscillating HBT radii successfully. Due to fluctuations in energy depositions, the fireball shape however fluctuates on an event-by-event basis. The transverse plane asymmetry can be translated into a series of multipole anisotropy coefficients. These anisotropies then result in measurable momentum-space anisotropies, to be measured with respect to their respective symmetry planes. In this paper we detail an extension of the Buda-Lund model to multipole anisotropies and investigate the resulting flow coefficients and oscillations of HBT radii. (orig.)

  16. Slow electron contribution to inelastic reflection anisotropy

    International Nuclear Information System (INIS)

    Podsvirov, O.A.; Kuznetsov, Yu.A.

    1980-01-01

    Investigated is electron contribution with low energy (up to 1 keV) to the anisotropy of electron inelastic reflection (IRE) from silicon monocrystal (111) within 12-50 keV energy range of primary electrons. Experimental data on IRE anisotropy are presented: delay curves for silicon monocrystal, permitting to separate electrons with the energy up to 1 keV, dependences of IRE anisotropy on the energy of primary electrons for the systems - monocrystalline silicon-amorphous silicon film and delay curves for such systems (film thickness varies from 20 to 2000 A). Suggested is a phenomenologic model, permitting to take into account the contribution of slow electrons to IRE anisotropy: it is supposed, that three groups of electrons take part in the formation of the latter: elastic and inelastic reflected electrons, slow electrons, excited by primary electrons and slow electrons, generated by the reverse flow of the scattered electrons. Contribution of electrons, different by origin, to IRE anisotropy is evaluated in accordance with the experimental data on the basis of this model. It is stated, that slow electrons constitute approximately one half of the IRE anisotropy value, the contribution of both groups of slow electrons being approximately equal

  17. Neurite regeneration in adult rat retinas exposed to advanced glycation end-products and regenerative effects of neurotrophin-4.

    Science.gov (United States)

    Bikbova, Guzel; Oshitari, Toshiyuki; Yamamoto, Shuichi

    2013-10-09

    The purpose of this study was to determine the effect of low concentrations of advanced glycation end-products on neurite regeneration in isolated rat retinas, and to determine the effects of neurotrophin-4 on regeneration in advanced glycation end-products exposed retinas. Retinal explants of 4 adult Sprague-Dawley rats were cultured on collagen gel and were incubated in; (1) serum-free control culture media, (2) glucose-advanced glycation end-products-bovine serum albumin media, (3) glycolaldehyde-advanced glycation end-products-bovine serum albumin media, (4) glyceraldehyde-advanced glycation end-products-bovine serum albumin media, (5) glucose-advanced glycation end-products+neurotrophin-4 media, (6) glycolaldehyde-advanced glycation end-products+neurotrophin-4 media, or (7) glyceraldehyde-advanced glycation end-products+neurotrophin-4 supplemented culture media. After 7 days, the number of regenerating neurites from the explants was counted. Then, explants were fixed, cryosectioned, and stained for TUNEL. The ratio of TUNEL-positive cells to all cells in the ganglion cell layer was determined. Immunohistochemical examinations for the active-form of caspase-9 and apoptosis-inducing factor were performed. In retinas incubated with advanced glycation end-products containing media, the number of regenerating neurites were fewer than in retinas without advanced glycation end-products, and the number of TUNEL-positive cells and caspase-9- and apoptosis-inducing factor-immunopositive cells was significantly higher than in control media. Neurotrophin-4 supplementation increased the numbers of regenerating neuritis, and the number of TUNEL-positives, caspase-9-, and apoptosis-inducing factor-immunopositive cells were significantly fewer than that in advanced glycation end-products without neurotrophin-4 media. Low doses of advanced glycation end-products impede neurite regeneration in the rat retinas. Neurotrophin-4 significantly enhances neurite regeneration in

  18. Friction anisotropy in boronated graphite

    International Nuclear Information System (INIS)

    Kumar, N.; Radhika, R.; Kozakov, A.T.; Pandian, R.; Chakravarty, S.; Ravindran, T.R.; Dash, S.; Tyagi, A.K.

    2015-01-01

    Graphical abstract: - Highlights: • Friction anisotropy in boronated graphite is observed in macroscopic sliding condition. • Low friction coefficient is observed in basal plane and becomes high in prismatic direction. • 3D phase of boronated graphite transformed into 2D structure after friction test. • Chemical activity is high in prismatic plane forming strong bonds between the sliding interfaces. - Abstract: Anisotropic friction behavior in macroscopic scale was observed in boronated graphite. Depending upon sliding speed and normal loads, this value was found to be in the range 0.1–0.35 in the direction of basal plane and becomes high 0.2–0.8 in prismatic face. Grazing-incidence X-ray diffraction analysis shows prominent reflection of (0 0 2) plane at basal and prismatic directions of boronated graphite. However, in both the wear tracks (1 1 0) plane become prominent and this transformation is induced by frictional energy. The structural transformation in wear tracks is supported by micro-Raman analysis which revealed that 3D phase of boronated graphite converted into a disordered 2D lattice structure. Thus, the structural aspect of disorder is similar in both the wear tracks and graphite transfer layers. Therefore, the crystallographic aspect is not adequate to explain anisotropic friction behavior. Results of X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy shows weak signature of oxygen complexes and functional groups in wear track of basal plane while these species dominate in prismatic direction. Abundance of these functional groups in prismatic plane indicates availability of chemically active sites tends to forming strong bonds between the sliding interfaces which eventually increases friction coefficient

  19. Friction anisotropy in boronated graphite

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, N., E-mail: niranjan@igcar.gov.in [Materials Science Group, Indira Gandhi Centre for Atomic Research, Kalpakkam (India); Radhika, R. [Crystal Growth Centre, Anna University, Chennai (India); Kozakov, A.T. [Research Institute of Physics, Southern Federal University, Rostov-on-Don (Russian Federation); Pandian, R. [Materials Science Group, Indira Gandhi Centre for Atomic Research, Kalpakkam (India); Chakravarty, S. [UGC-DAE CSR, Kalpakkam (India); Ravindran, T.R.; Dash, S.; Tyagi, A.K. [Materials Science Group, Indira Gandhi Centre for Atomic Research, Kalpakkam (India)

    2015-01-01

    Graphical abstract: - Highlights: • Friction anisotropy in boronated graphite is observed in macroscopic sliding condition. • Low friction coefficient is observed in basal plane and becomes high in prismatic direction. • 3D phase of boronated graphite transformed into 2D structure after friction test. • Chemical activity is high in prismatic plane forming strong bonds between the sliding interfaces. - Abstract: Anisotropic friction behavior in macroscopic scale was observed in boronated graphite. Depending upon sliding speed and normal loads, this value was found to be in the range 0.1–0.35 in the direction of basal plane and becomes high 0.2–0.8 in prismatic face. Grazing-incidence X-ray diffraction analysis shows prominent reflection of (0 0 2) plane at basal and prismatic directions of boronated graphite. However, in both the wear tracks (1 1 0) plane become prominent and this transformation is induced by frictional energy. The structural transformation in wear tracks is supported by micro-Raman analysis which revealed that 3D phase of boronated graphite converted into a disordered 2D lattice structure. Thus, the structural aspect of disorder is similar in both the wear tracks and graphite transfer layers. Therefore, the crystallographic aspect is not adequate to explain anisotropic friction behavior. Results of X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy shows weak signature of oxygen complexes and functional groups in wear track of basal plane while these species dominate in prismatic direction. Abundance of these functional groups in prismatic plane indicates availability of chemically active sites tends to forming strong bonds between the sliding interfaces which eventually increases friction coefficient.

  20. C. elegans fmi-1/flamingo and Wnt pathway components interact genetically to control the anteroposterior neurite growth of the VD GABAergic neurons.

    Science.gov (United States)

    Huarcaya Najarro, Elvis; Ackley, Brian D

    2013-05-01

    Directed axonal growth is essential to establish neuronal networks. During the early development of the VD neurons, an anterior neurite that will become the VD axon extends along the anteroposterior (A/P) axis in the ventral nerve cord (VNC) in Caenorhabditis elegans. Little is known about the cellular and molecular mechanisms that are important for correct neurite growth in the VNC. In fmi-1/flamingo mutant animals, we observed that some postembryonically born VD neurons had a posterior neurite instead of a normal anterior neurite, which caused aberrant VD commissure patterning along the A/P axis. In addition, VD anterior neurites had underextension defects in the VNC in fmi-1 animals, whereas VD commissure growth along the dorsoventral (D/V) axis occurred normally in these animals, suggesting that fmi-1 is important for neurite growth along the A/P axis but not the D/V axis. We also uncovered unknown details of the early development of the VD neurons, indicating that the neurite defects arose during their early development. Interestingly, though fmi-1 is present at this time in the VNC, we did not observe FMI-1 in the VD neurons themselves, suggesting that fmi-1 might be working in a cell non-autonomous fashion. Furthermore, fmi-1 appears to be working in a novel pathway, independently from the planar cell polarity pathway and in parallel to lin-17/frizzled and dsh-1/dishevelled, to determine the direction of neurite growth. Our findings indicate that redundant developmental pathways regulate neurite growth in the VNC in C. elegans. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Anisoft - Advanced Treatment of Magnetic Anisotropy Data

    Science.gov (United States)

    Chadima, M.

    2017-12-01

    Since its first release, Anisoft (Anisotropy Data Browser) has gained a wide popularity in magnetic fabric community mainly due to its simple and user-friendly interface enabling very fast visualization of magnetic anisotropy tensors. Here, a major Anisoft update is presented transforming a rather simple data viewer into a platform offering an advanced treatment of magnetic anisotropy data. The updated software introduces new enlarged binary data format which stores both in-phase and out-of-phase (if measured) susceptibility tensors (AMS) or tensors of anisotropy of magnetic remanence (AMR) together with their respective confidence ellipses and values of F-tests for anisotropy. In addition to the tensor data, a whole array of specimen orientation angles, orientation of mesoscopic foliation(s) and lineation(s) is stored for each record enabling later editing or corrections. The input data may be directly acquired by AGICO Kappabridges (AMS) or Spinner Magnetometers (AMR); imported from various data formats, including the long-time standard binary ran-format; or manually created. Multiple anisotropy files can be combined together or split into several files by manual data selection or data filtering according to their values. Anisotropy tensors are conventionally visualized as principal directions (eigenvectors) in equal-area projection (stereoplot) together with a wide array of quantitative anisotropy parameters presented in histograms or in color-coded scatter plots showing mutual relationship of up to three quantitative parameters. When dealing with AMS in variable low fields, field-independent and field-dependent components of anisotropy can be determined (Hrouda 2009). For a group of specimens, individual principal directions can be contoured, or a mean tensor and respective confidence ellipses of its principal directions can be calculated using either the Hext-Jelinek (Jelinek 1978) statistics or the Bootstrap method (Constable & Tauxe 1990). Each graphical

  2. Transforming growth factor-beta 1, 2, and 3 can inhibit epithelial tissue outgrowth on smooth and microgrooved substrates.

    NARCIS (Netherlands)

    Walboomers, X.F.; Dalton, B.A.; Evans, M.D.; Steele, J.G.; Jansen, J.A.

    2002-01-01

    In this study, we describe the influence of parallel surface microgrooves, and of TGF-beta, on the outgrowth of corneal epithelial tissue. Microgrooves (depth 1 microm, width 1-10 microm) were made in polystyrene culturing surfaces. These surfaces were left untreated, or loaded with TGF-beta 1, 2,

  3. The chemokine receptor CXCR4 is required for outgrowth of colon carcinoma micrometastases.

    Science.gov (United States)

    Zeelenberg, Ingrid S; Ruuls-Van Stalle, Lisette; Roos, Ed

    2003-07-01

    CXCR4, the receptor for the chemokine stromal cell-derived factor (SDF)-1 (CXCL12), is involved in lymphocyte trafficking. We have demonstrated previously that it is required for invasion of lymphoma cells into tissues and therefore essential for lymphoma metastasis. CXCR4 is also expressed by carcinoma cells, and CXCR4 antibodies were recently shown to reduce metastasis of a mammary carcinoma cell line. This was also ascribed to impaired invasion. We have blocked CXCR4 function in CT-26 colon carcinoma cells by transfection of SDF-1, extended with a KDEL sequence. The SDF-KDEL protein is retained in the endoplasmic reticulum by the KDEL-receptor and binds CXCR4, which is thus prevented from reaching the cell surface. We found that metastasis of these cells to liver and lungs was greatly reduced and often completely blocked. Surprisingly, however, our observations indicate that this was not attributable to inhibition of invasion but rather to impairment of outgrowth of micrometastases: (a) in contrast to the lymphoma cells, metastasis was not affected by the transfected S1 subunit of pertussis toxin. S1 completely inhibited Gi protein signaling, which is required for SDF-1-induced invasion; (b) CXCR4 levels were very low in CT-26 cells grown in vitro but strongly up-regulated in vivo. Strong up-regulation was not seen in the lungs until 7 days after tail vein injection. CXCR4 can thus have no role in initial invasion in the lungs; and (c) CXCR4-deficient cells did colonize the lungs to the same extent as control cells and survived. However, they did not expand, whereas control cells proliferated rapidly after a lag period of > or = 7 days. We conclude that CXCR4 is up-regulated by the microenvironment and that isolated metastatic cells are likely to require CXCR4 signals to initiate proliferation. Our results suggest that CXCR4 inhibitors have potential as anticancer agents to suppress outgrowth of micrometastases.

  4. Ultra-Sensitive HIV-1 Latency Viral Outgrowth Assays Using Humanized Mice.

    Science.gov (United States)

    Schmitt, Kimberly; Akkina, Ramesh

    2018-01-01

    In the current quest for a complete cure for HIV/AIDS, highly sensitive HIV-1 latency detection methods are critical to verify full viral eradication. Until now, the in vitro quantitative viral outgrowth assays (qVOA) have been the gold standard for assessing latent HIV-1 viral burden. However, these assays have been inadequate in detecting the presence of ultralow levels of latent virus in a number of patients who were initially thought to have been cured, but eventually showed viral rebound. In this context, new approaches utilizing in vivo mouse-based VOAs are promising. In the murine VOA (mVOA), large numbers of CD4 + T cells or PBMC from aviremic subjects are xenografted into immunodeficient NSG mice, whereas in the humanized mouse-based VOA (hmVOA) patient CD4 + T cell samples are injected into BLT or hu-hematopoetic stem cells (hu-HSC) humanized mice. While latent virus could be recovered in both of these systems, the hmVOA provides higher sensitivity than the mVOA using a fewer number of input cells. In contrast to the mVOA, the hmVOA provides a broader spectrum of highly susceptible HIV-1 target cells and enables newly engrafted cells to home into preformed human lymphoid organs where they can infect cells in situ after viral activation. Hu-mice also allow for both xenograft- and allograft-driven cell expansions with less severe GvH providing a longer time frame for potential viral outgrowth from cells with a delayed latent viral activation. Based on these advantages, the hmVOA has great potential in playing an important role in HIV-1 latency and cure research.

  5. Mechanism and site of inhibition of Bacillus cereus spore outgrowth by nitrosothiols

    International Nuclear Information System (INIS)

    Morris, S.L.

    1982-01-01

    Structure vs. activity studies demonstrate that nitrosothiols inhibit outgrowth of B. cereus spores by reversible covalent bond formation with sensitive spore components. Kinetic studies of the binding of nitrosothiols and iodoacetate, a known sulfhydryl reagent, show that they complete for the same spore sites. Since two other nitrite derivatives, the Perigo factor and the transferrin inhibitor, interfere with iodoacetate label uptake in a kinetically similar fashion, all of these compounds may inhibit spore outgrowth by interacting with the same spore thiol groups. Disruption of spores which have been inhibited by radioactive iodoacetate demonstrates that much of the label is incorporated into a membrane-rich fraction that sediments as a single peak on a sucrose density gradient. SDS gel electrophoresis and autofluorography allows the identification of four intensely labelled proteins with molecular weights of 13,000, 28,000, 29,000, and 30,000. If the iodoacetate labelling is carried out in the presence of nitrosothiol, incorporation is greatly reduced into all components. When germinating spores are labelled with succinate or the lactose analog, o-nitrophenylgalactopyranoside, a significant reduction in the amount of label bound is also observed suggesting that two iodoacetate-reactive sites may be the succinate and lactose permease systems. Severe decreases in the transport of succinate and lactose into iodoacetate and nitrosothiol inhibited spores further implicates a nitrosothiol (iodoacetate) permease interaction. Iodoacetate and nitrosothiols therefore may exert their inhibitory effects by interfering with critical membrane protein sulfhydryl groups, possibly by a a covalent modification mechanism. Some of these sensitive thiols may be involved in active transport processes

  6. Modeling elastic anisotropy in strained heteroepitaxy.

    Science.gov (United States)

    Dixit, Gopal Krishna; Ranganathan, Madhav

    2017-09-20

    Using a continuum evolution equation, we model the growth and evolution of quantum dots in the heteroepitaxial Ge on Si(0 0 1) system in a molecular beam epitaxy unit. We formulate our model in terms of evolution due to deposition, and due to surface diffusion which is governed by a free energy. This free energy has contributions from surface energy, curvature, wetting effects and elastic energy due to lattice mismatch between the film and the substrate. In addition to anisotropy due to surface energy which favors facet formation, we also incorporate elastic anisotropy due to an underlying crystal lattice. The complicated elastic problem of the film-substrate system subjected to boundary conditions at the free surface, interface and the bulk substrate is solved by perturbation analysis using a small slope approximation. This permits an analysis of effects at different orders in the slope and sheds new light on the observed behavior. Linear stability analysis shows the early evolution of the instability towards dot formation. The elastic anisotropy causes a change in the alignment of dots in the linear regime, whereas the surface energy anisotropy changes the dot shapes at the nonlinear regime. Numerical simulation of the full nonlinear equations shows the evolution of the surface morphology. In particular, we show, for parameters of the [Formula: see text] [Formula: see text] on Si(0 0 1), the surface energy anisotropy dominates the shapes of the quantum dots, whereas their alignment is influenced by the elastic energy anisotropy. The anisotropy in elasticity causes a further elongation of the islands whose coarsening is interrupted due to [Formula: see text] facets on the surface.

  7. Modeling elastic anisotropy in strained heteroepitaxy

    Science.gov (United States)

    Krishna Dixit, Gopal; Ranganathan, Madhav

    2017-09-01

    Using a continuum evolution equation, we model the growth and evolution of quantum dots in the heteroepitaxial Ge on Si(0 0 1) system in a molecular beam epitaxy unit. We formulate our model in terms of evolution due to deposition, and due to surface diffusion which is governed by a free energy. This free energy has contributions from surface energy, curvature, wetting effects and elastic energy due to lattice mismatch between the film and the substrate. In addition to anisotropy due to surface energy which favors facet formation, we also incorporate elastic anisotropy due to an underlying crystal lattice. The complicated elastic problem of the film-substrate system subjected to boundary conditions at the free surface, interface and the bulk substrate is solved by perturbation analysis using a small slope approximation. This permits an analysis of effects at different orders in the slope and sheds new light on the observed behavior. Linear stability analysis shows the early evolution of the instability towards dot formation. The elastic anisotropy causes a change in the alignment of dots in the linear regime, whereas the surface energy anisotropy changes the dot shapes at the nonlinear regime. Numerical simulation of the full nonlinear equations shows the evolution of the surface morphology. In particular, we show, for parameters of the Ge0.25 Si0.75 on Si(0 0 1), the surface energy anisotropy dominates the shapes of the quantum dots, whereas their alignment is influenced by the elastic energy anisotropy. The anisotropy in elasticity causes a further elongation of the islands whose coarsening is interrupted due to facets on the surface.

  8. Anisotropies in the cosmic neutrino background after Wilkinson Microwave Anisotropy Probe five-year data

    International Nuclear Information System (INIS)

    De Bernardis, Francesco; Pagano, Luca; Melchiorri, Alessandro; Serra, Paolo; Cooray, Asantha

    2008-01-01

    We search for the presence of cosmological neutrino background (CNB) anisotropies in recent Wilkinson Microwave Anisotropy Probe (WMAP) five-year data using their signature imprinted on modifications to the cosmic microwave background (CMB) anisotropy power spectrum. By parameterizing the neutrino background anisotropies with the speed viscosity parameter c vis , we find that the WMAP five-year data alone provide only a weak indication for CNB anisotropies with c vis 2 >0.06 at the 95% confidence level. When we combine CMB anisotropy data with measurements of galaxy clustering, the SN-Ia Hubble diagram, and other cosmological information, the detection increases to c vis 2 >0.16 at the same 95% confidence level. Future data from Planck, combined with a weak lensing survey such as the one expected with DUNE from space, will be able to measure the CNB anisotropy parameter at about 10% accuracy. We discuss the degeneracy between neutrino background anisotropies and other cosmological parameters such as the number of effective neutrinos species and the dark energy equation of state

  9. Neurite sprouting and synapse deterioration in the aging Caenorhabditis elegans nervous system.

    Science.gov (United States)

    Toth, Marton Lorant; Melentijevic, Ilija; Shah, Leena; Bhatia, Aatish; Lu, Kevin; Talwar, Amish; Naji, Haaris; Ibanez-Ventoso, Carolina; Ghose, Piya; Jevince, Angela; Xue, Jian; Herndon, Laura A; Bhanot, Gyan; Rongo, Chris; Hall, David H; Driscoll, Monica

    2012-06-27

    Caenorhabditis elegans is a powerful model for analysis of the conserved mechanisms that modulate healthy aging. In the aging nematode nervous system, neuronal death and/or detectable loss of processes are not readily apparent, but because dendrite restructuring and loss of synaptic integrity are hypothesized to contribute to human brain decline and dysfunction, we combined fluorescence microscopy and electron microscopy (EM) to screen at high resolution for nervous system changes. We report two major components of morphological change in the aging C. elegans nervous system: (1) accumulation of novel outgrowths from specific neurons, and (2) physical decline in synaptic integrity. Novel outgrowth phenotypes, including branching from the main dendrite or new growth from somata, appear at a high frequency in some aging neurons, but not all. Mitochondria are often associated with age-associated branch sites. Lowered insulin signaling confers some maintenance of ALM and PLM neuron structural integrity into old age, and both DAF-16/FOXO and heat shock factor transcription factor HSF-1 exert neuroprotective functions. hsf-1 can act cell autonomously in this capacity. EM evaluation in synapse-rich regions reveals a striking decline in synaptic vesicle numbers and a diminution of presynaptic density size. Interestingly, old animals that maintain locomotory prowess exhibit less synaptic decline than same-age decrepit animals, suggesting that synaptic integrity correlates with locomotory healthspan. Our data reveal similarities between the aging C. elegans nervous system and mammalian brain, suggesting conserved neuronal responses to age. Dissection of neuronal aging mechanisms in C. elegans may thus influence the development of brain healthspan-extending therapies.

  10. Shape-induced anisotropy in antiferromagnetic nanoparticles

    International Nuclear Information System (INIS)

    Gomonay, O.; Kondovych, S.; Loktev, V.

    2014-01-01

    High fraction of the surface atoms considerably enhances the influence of size and shape on the magnetic and electronic properties of nanoparticles. Shape effects in ferromagnetic nanoparticles are well understood and allow us to set and control the parameters of a sample that affect its magnetic anisotropy during production. In the present paper we study the shape effects in the other widely used magnetic materials – antiferromagnets, – which possess vanishingly small or zero macroscopic magnetization. We take into account the difference between the surface and bulk magnetic anisotropy of a nanoparticle and show that the effective magnetic anisotropy depends on the particle shape and crystallographic orientation of its faces. The corresponding shape-induced contribution to the magnetic anisotropy energy is proportional to the particle volume, depends on magnetostriction, and can cause formation of equilibrium domain structure. Crystallographic orientation of the nanoparticle surface determines the type of domain structure. The proposed model allows us to predict the magnetic properties of antiferromagnetic nanoparticles depending on their shape and treatment. - Highlights: • We demonstrate that the shape effects in antiferromagnetic nanoparticles stem from the difference of surface and bulk magnetic properties combined with strong magnetoelastic coupling. • We predict shape-induced anisotropy in antiferromagnetic particles with large aspect ratio. • We predict different types of domain structures depending on the orientation of the particle faces

  11. Dermal matrix proteins initiate re-epithelialization but are not sufficient for coordinated epidermal outgrowth in a new fish skin culture model.

    Science.gov (United States)

    Matsumoto, Reiko; Sugimoto, Masazumi

    2007-02-01

    We have established a new culture system to study re-epithelialization during fish epidermal wound healing. In this culture system, fetal bovine serum (FBS) stimulates the epidermal outgrowth of multi-cellular layers from scale skin mounted on a coverslip, even when cell proliferation is blocked. The rate of outgrowth is about 0.4 mm/h, and at 3 h after incubation, the area occupied by the epidermal sheet is nine times larger than the area of the original scale skin. Cells at the bottom of the outgrowth show a migratory phenotype with lamellipodia, and "purse string"-like actin bundles have been found over the leading-edge cells with polarized lamellipodia. In the superficial cells, re-development of adherens junctions and microridges has been detected, together with the appearance and translocation of phosphorylated p38 MAPK into nuclear areas. Thus, this culture system provides an excellent model to study the mechanisms of epidermal outgrowth accompanied by migration and re-differentiation. We have also examined the role of extracellular matrix proteins in the outgrowth. Type I collagen or fibronectin stimulates moderate outgrowth in the absence of FBS, but development of microridges and the distribution of phosphorylated p38 MAPK are attenuated in the superficial cells. In addition, the leading-edge cells do not have apparent "purse string"-like actin bundles. The outgrowth stimulated by FBS is inhibited by laminin. These results suggest that dermal substrates such as type I collagen and fibronectin are able to initiate epidermal outgrowth but require other factors to enhance such outgrowth, together with coordinated alterations in cellular phenotype.

  12. Large Friction Anisotropy of a Polydiacetylene Monolayer

    International Nuclear Information System (INIS)

    Burns, A.R.; Carpick, R.W.; Sasaki, D.Y.

    1999-01-01

    Friction force microscopy measurements of a polydiacetylene monolayer film reveal a 300% friction anisotropy that is correlated with the film structure. The film consists of a monolayer of the red form of N-(2-ethanol)- 10,12 pentacosadiynamide, prepared on a Langmuir trough and deposited on a mica substrate. As confirmed by atomic force microscopy and fluorescence microscopy, the monolayer consists of domains of linearly oriented conjugated backbones with pendant hydrocarbon side chains above and below the backbones. Maximum friction occurs when the sliding direction is perpendicular to the backbone. We propose that the backbones impose anisotropic packing of the hydrocarbon side chains which leads to the observed friction anisotropy. Friction anisotropy is therefore a sensitive, optically-independent indicator of polymer backbone direction and monolayer structural properties

  13. Measurements of magnetic anisotropy in sickle cells

    International Nuclear Information System (INIS)

    Salvo Souza, L.H. de.

    1982-03-01

    Room temperature magnetic measurements in deoxigenated sickle cells showed the existence of magnetic anisotropy, Δchi=1,29 x 10 -3 . This effect was supposed paramagnetic and considered to be due to the iron atoms of the hemoglobin molecules which are one over the other, forming ordered chains inside the erythrocytes. Low temperature (liquid He - 4,2K) measurements of the magnetic anisotropy of sickle cells and normal red blood cells diluted in a cryoprotector was made to confirm the paramagnetic origin of the fenomena. For that purpose it was used a superconductor magnetometer coupled to a SQUID, developed in the 'Laboratorio do Estado Solido do Departamento de Fisica da PUC-RJ'. The results obtained seem to confirm the expected paramagnetic anisotropy and, furthermore, suggest the presence of magnetic interactions among the iron atoms in the sickle cells samples. (Author) [pt

  14. COSMIC-RAY TRANSPORT AND ANISOTROPIES

    Energy Technology Data Exchange (ETDEWEB)

    Biermann, Peter L. [MPI for Radioastronomy, Auf dem Huegel 69, D-53121 Bonn (Germany); Becker Tjus, Julia; Mandelartz, Matthias [Ruhr-Universitaet Bochum, Fakultaet fuer Physik and Astronomie, Theoretische Physik I, D-44780 Bochum (Germany); Seo, Eun-Suk [Department of Physics, University of Maryland, College Park, MD 20742 (United States)

    2013-05-10

    We show that the large-scale cosmic-ray anisotropy at {approx}10 TeV can be explained by a modified Compton-Getting effect in the magnetized flow field of old supernova remnants. Cosmic rays arrive isotropically to the flow field and are then carried along with the flow to produce a large-scale anisotropy in the arrival direction. This approach suggests an optimum energy scale for detecting the anisotropy. Two key assumptions are that propagation is based on turbulence following a Kolmogorov law and that cosmic-ray interactions are dominated by transport via cosmic-ray-excited magnetic irregularities through the stellar wind of an exploding star and its shock shell. A prediction is that the amplitude is smaller at lower energies due to incomplete sampling of the velocity field and also smaller at larger energies due to smearing.

  15. Anisotropy of dilepton emission from nuclear collisions

    International Nuclear Information System (INIS)

    Bratkovskaya, E.L.; Teryaev, O.V.; Toneev, V.D.; Joint Inst. for Nuclear Research, Dubna

    1994-01-01

    Attention is paid to studying the angular characteristics of e + e - pairs created in collisions with nuclear targets at intermediate and relativistic energies. Arising due to general spin and angular momentum constraints, the dilepton anisotropy seems to be quite sensitive to the contribution of different sources and may be used for disentangling these sources (or models) as well as an additional signature of a possible chiral symmetry restoration and phase transition of hadrons into the quark-gluon plasma. An anisotropy estimate for some dilepton sources is given and its relevance to the problems mentioned is discussed

  16. Anisotropy of dilepton emission from nuclear collisions

    Energy Technology Data Exchange (ETDEWEB)

    Bratkovskaya, E.L.; Teryaev, O.V. [Joint Inst. for Nuclear Research, Dubna (Russian Federation). Bogolubov Lab. of Theoretical Physics; Toneev, V.D. [Washington Univ., Seattle, WA (United States). Inst. for Nuclear Theory]|[Joint Inst. for Nuclear Research, Dubna (Russian Federation). Bogolubov Lab. of Theoretical Physics

    1994-11-07

    Attention is paid to studying the angular characteristics of e{sup +}e{sup {minus}} pairs created in collisions with nuclear targets at intermediate and relativistic energies. Arising due to general spin and angular momentum constraints, the dilepton anisotropy seems to be quite sensitive to the contribution of different sources and may be used for disentangling these sources (or models) as well as an additional signature of a possible chiral symmetry restoration and phase transition of hadrons into the quark-gluon plasma. An anisotropy estimate for some dilepton sources is given and its relevance to the problems mentioned is discussed.

  17. Anisotropy of the Topopah Spring Member Tuff

    International Nuclear Information System (INIS)

    Martin, R.J. III; Boyd, P.J.; Haupt, R.W.; Price, R.H.

    1992-07-01

    Mechanical properties of the tuffaceous rocks within Yucca Mountain are needed for near and far-field modeling of the potential nuclear waste repository. If the mechanical properties are significantly anisotropic (i.e., direction-dependent), a more complex model is required. Relevant data from tuffs tested in earlier studies indicate that elastic and strength properties are anisotropic. This scoping study confirms the elastic anisotropy and concludes some tuffs are transversely isotropic. An approach for sampling and testing the rock to determine the magnitude of the anisotropy is proposed

  18. Magnetocrystalline and configurational anisotropies in Fe nanostructures

    International Nuclear Information System (INIS)

    Vavassori, P.; Bisero, D.; Carace, F.; Liberati, M.; Di Bona, A.; Gazzadi, G.C.; Valeri, S.

    2005-01-01

    Arrays of single-crystal Fe micron and submicron squares and disks, have been fabricated using a focused ion beam apparatus from a film epitaxially grown on MgO. The hysteresis loops of the patterned areas differ from those of the continuous film as a consequence of the different reversal determined by the lateral confinement of the Fe film. By means of modulated field magneto-optical anisometry measurements we studied the symmetry and the strength of the overall anisotropy. For the smaller square elements we observed a higher-order term in the overall anisotropy with eightfold symmetry arising from the configurational contribution

  19. The prescriptions from Shenghui soup enhanced neurite growth and GAP-43 expression level in PC12 cells.

    Science.gov (United States)

    Zhang, Qi; Zhang, Zi-Jian; Wang, Xing-Hua; Ma, Jie; Song, Yue-Han; Liang, Mi; Lin, Sen-Xiang; Zhao, Jie; Zhang, Ao-Zhe; Li, Feng; Hua, Qian

    2016-09-20

    Shenghui soup is a traditional Chinese herbal medicine used in clinic for the treatment of forgetfulness. In order to understanding the prescription principle, the effects of "tonifying qi and strengthening spleen" group (TQSS) including Poria cocos (Schw.) Wolf. and Panax ginseng C.A.Mey and "eliminating phlegm and strengthening intelligence" group (EPSI) composed of Polygala tenuifolia Willd., Acorus calamus L. and Sinapis alba L from the herb complex on neurite growth in PC12 cells, two disassembled prescriptions derived from Shenghui soup and their molecular mechanisms were investigated. Firstly, CCK-8 kit was used to detect the impact of the two prescriptions on PC12 cell viability; and Flow cytometry was performed to measure the cell apoptosis when PC12 cells were treated with these drugs. Secondly, the effect of the two prescriptions on the differentiation of PC12 cells was observed. Finally, the mRNA and protein expression levels of GAP-43 were analyzed by RT-PCR and western blot, respectively. "Tonifying qi and strengthening spleen" prescription decreased cell viability in a dose-dependent manner, but had no significant effect on cell apoptosis. Meanwhile, it could improve neurite growth and elevate the mRNA and protein expression level of GAP-43. "Eliminating phlegm and strengthening intelligence" prescription also exerted the similar effects on cell viability and apoptosis. Furthermore, it could also enhance cell neurite growth, with a higher expression level of GAP-43 mRNA and protein. "Tonifying qi and strengthening spleen" and "eliminating phlegm and strengthening intelligence" prescriptions from Shenghui soup have a positive effect on neurite growth. Their effects are related to the up-regulating expression of GAP-43.

  20. Vital role of protein kinase C-related kinase (PRK1) in the formation and stability of neurites during hypoxia

    OpenAIRE

    Thauerer, Bettina; zur Nedden, Stephanie; Baier-Bitterlich, Gabriele

    2010-01-01

    Exposure of pheochromocytoma (PC12) cells to hypoxia (1% O2) favors differentiation at the expense of cell viability. Additional incubation with nerve growth factor (NGF) and guanosine, a purine nucleoside with neurotrophin characteristics, rescued cell viability and further enhanced the extension of neurites. In parallel, an increase in the activity of protein kinase C-related kinase (PRK1), which is known to be involved in regulation of the actin cytoskeleton, was observed in hypoxic cells....

  1. Inhibitory Activity of Yokukansankachimpihange against Nerve Growth Factor-Induced Neurite Growth in Cultured Rat Dorsal Root Ganglion Neurons

    Directory of Open Access Journals (Sweden)

    Chiaki Murayama

    2015-08-01

    Full Text Available Chronic pruritus is a major and distressing symptom of many cutaneous diseases, however, the treatment remains a challenge in the clinic. The traditional Chinese-Japanese medicine (Kampo medicine is a conservative and increasingly popular approach to treat chronic pruritus for both patients and medical providers. Yokukansankachimpihange (YKH, a Kampo formula has been demonstrated to be effective in the treatment of itching of atopic dermatitis in Japan although its pharmacological mechanism is unknown clearly. In an attempt to clarify its pharmacological actions, in this study, we focused on the inhibitory activity of YKH against neurite growth induced with nerve growth factor (NGF in cultured rat dorsal root ganglion (DRG neurons because epidermal hyperinnervation is deeply related to itch sensitization. YKH showed approximately 200-fold inhibitory activity against NGF-induced neurite growth than that of neurotropin (positive control, a drug used clinically for treatment of chronic pruritus. Moreover, it also found that Uncaria hook, Bupleurum root and their chemical constituents rhynchophylline, hirsutine, and saikosaponin a, d showed inhibitory activities against NGF-induced neurite growth, suggesting they should mainly contribute to the inhibitory activity of YKH. Further study on the effects of YKH against epidermal nerve density in “itch-scratch” animal models is under investigation.

  2. [Inhibitory proteins of neuritic regeneration in the extracellular matrix: structure, molecular interactions and their functions. Mechanisms of extracellular balance].

    Science.gov (United States)

    Vargas, Javier; Uribe-Escamilla, Rebeca; Alfaro-Rodríguez, Alfonso

    2013-01-01

    After injury of the central nervous system (CNS) in higher vertebrates, neurons neither grow nor reconnect with their targets because their axons or dendrites cannot regenerate within the injured site. In the CNS, the signal from the environment regulating neurite regeneration is not exclusively generated by one molecular group. This signal is generated by the interaction of various types of molecules such as extracellular matrix proteins, soluble factors and surface membrane molecules; all these elements interact with one another generating the matrix's biological state: the extracellular balance. Proteins in the balanced extracellular matrix, support and promote cellular physiological states, including neuritic regeneration. We have reviewed three types of proteins of the extracellular matrix possessing an inhibitory effect and that are determinant of neuritic regeneration failure in the CNS: chondroitin sulfate proteoglycans, keratan sulfate proteoglycans and tenascin. We also review some of the mechanisms involved in the balance of extracellular proteins such as isomerization, epimerization, sulfation and glycosylation as well as the assemblage of the extracellular matrix, the interaction between the matrix and soluble factors and its proteolytic degradation. In the final section, we have presented some examples of the matrix's role in development and in tumor propagation.

  3. Integrated and Total HIV-1 DNA Predict Ex Vivo Viral Outgrowth.

    Directory of Open Access Journals (Sweden)

    Maja Kiselinova

    2016-03-01

    Full Text Available The persistence of a reservoir of latently infected CD4 T cells remains one of the major obstacles to cure HIV. Numerous strategies are being explored to eliminate this reservoir. To translate these efforts into clinical trials, there is a strong need for validated biomarkers that can monitor the reservoir over time in vivo. A comprehensive study was designed to evaluate and compare potential HIV-1 reservoir biomarkers. A cohort of 25 patients, treated with suppressive antiretroviral therapy was sampled at three time points, with median of 2.5 years (IQR: 2.4-2.6 between time point 1 and 2; and median of 31 days (IQR: 28-36 between time point 2 and 3. Patients were median of 6 years (IQR: 3-12 on ART, and plasma viral load (<50 copies/ml was suppressed for median of 4 years (IQR: 2-8. Total HIV-1 DNA, unspliced (us and multiply spliced HIV-1 RNA, and 2LTR circles were quantified by digital PCR in peripheral blood, at 3 time points. At the second time point, a viral outgrowth assay (VOA was performed, and integrated HIV-1 DNA and relative mRNA expression levels of HIV-1 restriction factors were quantified. No significant change was found for long- and short-term dynamics of all HIV-1 markers tested in peripheral blood. Integrated HIV-1 DNA was associated with total HIV-1 DNA (p<0.001, R² = 0.85, us HIV-1 RNA (p = 0.029, R² = 0.40, and VOA (p = 0.041, R2 = 0.44. Replication-competent virus was detected in 80% of patients by the VOA and it correlated with total HIV-1 DNA (p = 0.039, R² = 0.54. The mean quantification difference between Alu-PCR and VOA was 2.88 log10, and 2.23 log10 between total HIV-1 DNA and VOA. The levels of usHIV-1 RNA were inversely correlated with mRNA levels of several HIV-1 restriction factors (TRIM5α, SAMHD1, MX2, SLFN11, pSIP1. Our study reveals important correlations between the viral outgrowth and total and integrated HIV-1 DNA measures, suggesting that the total pool of HIV-1 DNA may predict the size of the

  4. Acoustic axes in weak triclinic anisotropy

    Czech Academy of Sciences Publication Activity Database

    Vavryčuk, Václav

    2005-01-01

    Roč. 163, č. 2 (2005), s. 629-638 ISSN 0956-540X R&D Projects: GA AV ČR IAA3012309 Institutional research plan: CEZ:AV0Z30120515 Keywords : elastic-wave theory * perturbation methods * seismic anisotropy Subject RIV: DC - Siesmology, Volcanology, Earth Structure Impact factor: 1.826, year: 2005

  5. Empirical evidence for inertial mass anisotropy

    International Nuclear Information System (INIS)

    Heller, M.; Siemieniec, G.

    1985-01-01

    A several attempts at measuring the possible deviations from inertial mass isotropy caused by a non-uniform distribution of matter are reviewed. A simple model of the inertial mass anisotropy and the results of the currently performed measurements concerning this effect are presented. 34 refs. (author)

  6. Anisotropy of Wood in the Microwave Region

    Science.gov (United States)

    Ziherl, Sasa; Bajc, Jurij; Urankar, Bernarda; Cepic, Mojca

    2010-01-01

    Wood is transparent for microwaves and due to its anisotropic structure has anisotropic dielectric properties. A laboratory experiment that allows for the qualitative demonstration and quantitative measurements of linear dichroism and birefringence in the microwave region is presented. As the proposed experiments are based on the anisotropy (of…

  7. What we learn from CMB Anisotropies

    CERN Multimedia

    CERN. Geneva

    2007-01-01

    George Smoot shared the 2006 Nobel Prize with John Mathere for the discovery of the fluctuations of the cosmic microwave background. In this talk (which will not be the same as the Nobel lecture), he will discuss what we have learned about the universe in the recent past from these anisotropies.

  8. Pseudospin anisotropy classification of quantum Hall ferromagnets

    Czech Academy of Sciences Publication Activity Database

    Jungwirth, Tomáš; MacDonald, A. H.

    2000-01-01

    Roč. 63, č. 3 (2000), s. 035305-1 - 035305-9 ISSN 0163-1829 R&D Projects: GA ČR GA202/98/0085 Institutional research plan: CEZ:AV0Z1010914 Keywords : quantum Hall ferromagnets * anisotropy Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 3.065, year: 2000

  9. Cosmology with cosmic microwave background anisotropy

    Indian Academy of Sciences (India)

    Measurements of CMB anisotropy and, more recently, polarization have played a very important role in allowing precise determination of various parameters of the `standard' cosmological model. The expectation of the paradigm of inflation and the generic prediction of the simplest realization of inflationary scenario in the ...

  10. Magnetic anisotropy in rare-earth metals

    DEFF Research Database (Denmark)

    Nielsen, Mourits; Bjerrum Møller, Hans; Lindgård, Per-Anker

    1970-01-01

    The magnetic field dependence of the energy of long- wavelength magnons in Tb-10%Ho has been studied by inelastic neutron scattering. The results agree with the `frozen-lattice' model, provided that the second-order magnetoelastic effect is taken into account. The planar anisotropy is almost...

  11. Azimuthal anisotropy of jet quenching at LHC

    Indian Academy of Sciences (India)

    Abstract. We analyze the azimuthal anisotropy of jet spectra due to energy loss of hard partons in quark–gluon plasma, created initially in nuclear overlap zone in collisions with non-zero impact parameter. The calculations are performed for semi-central Pb–Pb collisions at LHC energy.

  12. Relative sensitivity of formability to anisotropy

    International Nuclear Information System (INIS)

    Logan, R.W.; Maker, B.N.

    1997-01-01

    This work compares the relative importance of material anisotropy in sheet forming as compared to other material and process variables. The comparison is made quantitative by the use of normalized dependencies of depth to failure (forming limit is reached) on various measures of anisotropy, as well as strain and rate sensitivity, friction, and tooling. Comparisons are made for a variety of forming processes examined previously in the literature as well as two examples of complex stampings in this work. 7 The examples rover a range from nearly pure draw to nearly pure stretch situations, and show that for materials following a quadratic yield criterion, anisotropy is among the most sensitive parameters influencing formability. For materials following higher-exponent yield criteria, the dependency is milder but is still of the order of most other process parameters. However, depending on the particular forming operation, it is shown that in some cases anisotropy may be ignored, whereas in others its consideration is crucial to a good quality analysis

  13. Effective anisotropy through traveltime and amplitude matching

    KAUST Repository

    Wang, Hui

    2014-08-05

    Introducing anisotropy to seismic wave propagation reveals more realistic physics of our Earth\\'s subsurface as compared to the isotropic assumption. However wavefield modeling, the engine of seismic inverse problems, in anisotropic media still suffers from computational burdens, in particular with complex anisotropy such as transversely isotropic (TI) and Orthorhombic anisotropy. We develop effective isotropic velocity and density models to package the effects of anisotropy such that the wave propagation behavior using these effective models approximate those of the original anisotropic model. We build these effective models through the high frequency asymptotic approximation based on the eikonal and transport equations. We match the geometrical behavior of the wave-fields, given by traveltimes, from the anisotropic and isotropic eikonal equations. This matching yields the effective isotropic velocity that approximates the kinematics of the anisotropic wavefield. Equivalently, we calculate the effective densities by equating the anisotropic and isotropic transport equations. The effective velocities and densities are then fed into the isotropic acoustic variable density wave equation to obtain cheaper anisotropic wavefields. We justify our approach by testing it on an elliptical anisotropic model. The numerical results demonstrate a good matching of both traveltime and amplitude between anisotropic and effective isotropic wavefields.

  14. Diffusion Tensor Imaging Tractography in Pure Neuritic Leprosy: First Experience Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Michele R. Colonna

    2016-01-01

    Full Text Available Five years after both right ulnar and median nerve decompression for paraesthesias and palsy, a patient, coming from Nigeria but living in Italy, came to our unit claiming to have persistent pain and combined median and ulnar palsy. Under suspicion of leprosy, skin and left sural nerve biopsy were performed. Skin tests were negative, but Schwann cells resulted as positive for acid-fast bacilli (AFB, leading to the diagnosis of Pure Neuritic Leprosy (PNL. The patient was given PB multidrug therapy and recovered from pain in two months. After nine months both High Resolution Ultrasonography (HRUS and Magnetic Resonance Imaging (MRI were performed, revealing thickening of the nerves. Since demyelination is common in PNL, the Authors started to use Diffusion Tensor Imaging Tractography (DTIT to get better morphological and functional data about myelination than does the traditional imaging. DTIT proved successful in showing myelin discontinuity, reorganization, and myelination, and the Authors suggest that it can give more information about the evolution of the disease, as well as further indications for surgery (nerve decompression, nerve transfers, and babysitting for distal effector protection, and should be added to traditional imaging tools in leprosy.

  15. Neurite orientation dispersion and density imaging in the substantia nigra in idiopathic Parkinson disease

    International Nuclear Information System (INIS)

    Kamagata, Koji; Suzuki, Michimasa; Hori, Masaaki; Kumamaru, Kanako K.; Aoki, Shigeki; Hatano, Taku; Okuzumi, Ayami; Motoi, Yumiko; Hattori, Nobutaka; Abe, Osamu; Shimoji, Keigo; Kamiya, Kouhei

    2016-01-01

    We used neurite orientation dispersion and density imaging (NODDI) to quantify changes in the substantia nigra pars compacta (SNpc) and striatum in Parkinson disease (PD). Diffusion-weighted magnetic resonance images were acquired from 58 PD patients and 36 age- and sex-matched controls. The intracellular volume fraction (Vic), orientation dispersion index (OD), and isotropic volume fraction (Viso) of the basal ganglia were compared between groups. Multivariate logistic regression analysis determined which diffusion parameters were independent predictors of PD. Receiver operating characteristic (ROC) analysis compared the diagnostic accuracies of the evaluated indices. Pearson coefficient analysis correlated each diffusional parameter with disease severity. Vic in the contralateral SNpc and putamen were significantly lower in PD patients than in healthy controls (P < 0.00058). Vic and OD in the SNpc and putamen showed significant negative correlations (P < 0.05) with disease severity. Multivariate logistic analysis revealed that Vic (P = 0.0000046) and mean diffusivity (P = 0.019) in the contralateral SNpc were the independent predictors of PD. In the ROC analysis, Vic in the contralateral SNpc showed the best diagnostic performance (mean cutoff, 0.62; sensitivity, 0.88; specificity, 0.83). NODDI is likely to be useful for diagnosing PD and assessing its progression. (orig.)

  16. Ecdysone signaling regulates specification of neurons with a male-specific neurite in Drosophila

    Directory of Open Access Journals (Sweden)

    Binglong Zhang

    2018-02-01

    Full Text Available Some mAL neurons in the male brain form the ipsilateral neurite (ILN[+] in a manner dependent on FruBM, a male-specific transcription factor. FruBM represses robo1 transcription, allowing the ILN to form. We found that the proportion of ILN[+]-mALs in all observed single cell clones dropped from ∼90% to ∼30% by changing the heat-shock timing for clone induction from 4-5 days after egg laying (AEL to 6-7 days AEL, suggesting that the ILN[+]-mALs are produced predominantly by young neuroblasts. Upon EcR-A knockdown, ILN[+]-mALs were produced at a high rate (∼60%, even when heat shocked at 6-7 days AEL, yet EcR-B1 knockdown reduced the proportion of ILN[+]-mALs to ∼30%. Immunoprecipitation assays in S2 cells demonstrated that EcR-A and EcR-B1 form a complex with FruBM. robo1 reporter transcription was repressed by FruBM and ecdysone counteracted FruBM. We suggest that ecdysone signaling modulates the FruBM action to produce an appropriate number of male-type neurons.

  17. Sigma-1 receptor agonist increases axon outgrowth of hippocampal neurons via voltage-gated calcium ions channels.

    Science.gov (United States)

    Li, Dong; Zhang, Shu-Zhuo; Yao, Yu-Hong; Xiang, Yun; Ma, Xiao-Yun; Wei, Xiao-Li; Yan, Hai-Tao; Liu, Xiao-Yan

    2017-12-01

    Sigma-1 receptors (Sig-1Rs) are unique endoplasmic reticulum proteins that have been implicated in both neurodegenerative and ischemic diseases, such as Alzheimer's disease and stroke. Accumulating evidence has suggested that Sig-1R plays a role in neuroprotection and axon outgrowth. The underlying mechanisms of Sig-1R-mediated neuroprotection have been well elucidated. However, the mechanisms underlying the effects of Sig-1R on axon outgrowth are not fully understood. To clarify this issue, we utilized immunofluorescence to compare the axon lengths of cultured naïve hippocampal neurons before and after the application of the Sig-1R agonist, SA4503. Then, electrophysiology and immunofluorescence were used to examine voltage-gated calcium ion channel (VGCCs) currents in the cell membranes and growth cones. We found that Sig-1R activation dramatically enhanced the axonal length of the naïve hippocampal neurons. Application of the Sig-1R antagonist NE100 and gene knockdown techniques both demonstrated the effects of Sig-1R. The growth-promoting effect of SA4503 was accompanied by the inhibition of voltage-gated Ca 2+ influx and was recapitulated by incubating the neurons with the L-type, N-type, and P/Q-type VGCC blockers, nimodipine, MVIIA and ω-agatoxin IVA, respectively. This effect was unrelated to glial cells. The application of SA4503 transformed the growth cone morphologies from complicated to simple, which favored axon outgrowth. Sig-1R activation can enhance axon outgrowth and may have a substantial influence on neurogenesis and neurodegenerative diseases. © 2017 John Wiley & Sons Ltd.

  18. In vivo bio-distribution and homing of endothelial outgrowth cells in a tumour model

    International Nuclear Information System (INIS)

    Bertelsen, Lotte B.; Hagensen, Mette; Busk, Morten; Zhang, Rui; Knudsen, Anne S.; Nielsen, Nathalie; Falborg, Lise; Møller, Bjarne K.; Horsman, Michael R.; Stødkilde-Jørgensen, Hans

    2014-01-01

    Introduction: Endothelial progenitor cells (EPCs) has been reported to have the potential for advancing revascularization of ischemic tissue. However, the heterogeneous nature of these cells calls for specification of the angiogenic potential of each subtype. The purpose of this study was to gain additional insight on the homing capacity of the EPC subtype, endothelial outgrowth cells (EOCs) in tumours using a well-established tumour model. Methods: 111 Indium ( 111 In) – and 5-(and-6)-carboxyfluorescein diacetate succinimidyl ester (CFSE) labelled EOCs derived from human umbilical cord blood were injected into mice with a C3H mammary carcinoma foot tumour. The subsequent capture of the EOCs was traced by estimation of activity in individual organs, autoradiography and fluorescence microscopy. Results: 111 In activity was found in tumour and other organs. However, varying parts of the activity originated from free 111 In lost from EOCs. Autoradiography demonstrated accumulation of 111 In activity in the tumour rim. Microscopy proved that a least part of this radioactivity originated from the presence of human derived EOCs and that those EOCs were not located in the endothelial lining of vessels, in the tumour. Conclusion: The results demonstrated the presence of xenotransplanted EOCs in the rim of a C3H mammary carcinoma. They were, however, not located in the endothelial lining of the vessels, thus indicating that their effect in vasculogenesis might be mediated via paracrine mechanisms rather than differentiating into endothelial cells (ECs) in tumour vessels

  19. A developmental timing switch promotes axon outgrowth independent of known guidance receptors.

    Directory of Open Access Journals (Sweden)

    Katherine Olsson-Carter

    2010-08-01

    Full Text Available To form functional neuronal connections, axon outgrowth and guidance must be tightly regulated across space as well as time. While a number of genes and pathways have been shown to control spatial features of axon development, very little is known about the in vivo mechanisms that direct the timing of axon initiation and elongation. The Caenorhabditis elegans hermaphrodite specific motor neurons (HSNs extend a single axon ventrally and then anteriorly during the L4 larval stage. Here we show the lin-4 microRNA promotes HSN axon initiation after cell cycle withdrawal. Axons fail to form in lin-4 mutants, while they grow prematurely in lin-4-overexpressing animals. lin-4 is required to down-regulate two inhibitors of HSN differentiation--the transcriptional regulator LIN-14 and the "stemness" factor LIN-28--and it likely does so through a cell-autonomous mechanism. This developmental switch depends neither on the UNC-40/DCC and SAX-3/Robo receptors nor on the direction of axon growth, demonstrating that it acts independently of ventral guidance signals to control the timing of HSN axon elongation.

  20. What does anisotropy measure? Insights from increased and decreased anisotropy in selective fiber tracts in schizophrenia.

    Directory of Open Access Journals (Sweden)

    Gabriel A De Erausquin

    2013-03-01

    Full Text Available Schizophrenia is a common, severe and chronically disabling mental illness of unknown cause. Recent MRI studies have focused attention on white matter abnormalities in schizophrenia using diffusion tensor imaging (DTI. Indices commonly derived from DTI include (a mean diffusivity, independent of direction, (b fractional anisotropy (FA or relative anisotropy (RA, (c axial diffusivity, and (d radial diffusivity. In cerebral white matter, contributions to these indices come from fiber arrangements, degree of myelination, and axonal integrity. Relatively pure deficits in myelin result in a modest increase in radial diffusivity, without affecting axial diffusivity and with preservation of anisotropy. Although schizophrenia is not characterized by gross abnormalities of white matter, it does involve a profound dysregulation of myelin-associated gene expression, reductions in oligodendrocyte numbers, and marked abnormalities in the ultrastructure of myelin sheaths. Since each oligodendrocyte myelinates as many as 40 axon segments, changes in the number of oligodendrocytes, and/or in the integrity of myelin sheaths, and/or axoglial contacts can have a profound impact on signal propagation and the integrity of neuronal circuits. Whereas a number of studies have revealed inconsistent decreases in anisotropy in schizophrenia, we and others have found increased fractional anisotropy in key subcortical tracts associated with the circuits underlying symptom generation in schizophrenia. We review data revealing increased anisotropy in dopaminergic tracts in the mesencephalon of schizophrenics and their unaffected relatives, and discuss the possible biological underpinnings and physiological significance of this finding.

  1. Friction Anisotropy with Respect to Topographic Orientation

    Science.gov (United States)

    Yu, Chengjiao; Wang, Q. Jane

    2012-01-01

    Friction characteristics with respect to surface topographic orientation were investigated using surfaces of different materials and fabricated with grooves of different scales. Scratching friction tests were conducted using a nano-indentation-scratching system with the tip motion parallel or perpendicular to the groove orientation. Similar friction anisotropy trends were observed for all the surfaces studied, which are (1) under a light load and for surfaces with narrow grooves, the tip motion parallel to the grooves offers higher friction coefficients than does that perpendicular to them, (2) otherwise, equal or lower friction coefficients are found under this motion. The influences of groove size relative to the diameter of the mating tip (as a representative asperity), surface contact stiffness, contact area, and the characteristic stiction length are discussed. The appearance of this friction anisotropy is independent of material; however, the boundary and the point of trend transition depend on material properties. PMID:23248751

  2. Destabilization of TAE modes by particle anisotropy

    International Nuclear Information System (INIS)

    Wong, H.V.; Berk, H.L.

    1998-01-01

    Plasmas heated by ICRF produce energetic particle distribution functions which are sharply peaked in pitch-angle, and the authors show that at moderate toroidal mode numbers, this anisotropy is a competitive and even dominant instability drive when compared with the universal instability drive due to spatial gradient. The universal drive, acting along, destabilizes only co-propagating waves (i.e., waves propagating in the same toroidal direction as the diamagnetic flow of the energetic particles), but stabilizes counter-propagating waves (i.e., waves propagating in the opposite toroidal direction as the diamagnetic flow of the energetic particles). Nonetheless, the authors show that in a tokamak, it is possible that particle anisotropy can produce a larger linear growth rate for counter-propagating waves, and provide a mechanism for preferred destabilization of the counter-propagating TAE modes that are sometimes experimentally observed

  3. Anisotropies in the cosmic microwave background: Theory

    International Nuclear Information System (INIS)

    Dodelson, S.

    1998-02-01

    Anisotropies in the Cosmic Microwave Background (CMB) contain a wealth of information about the past history of the universe and the present values of cosmological parameters. I online some of the theoretical advances of the last few years. In particular, I emphasize that for a wide class of cosmological models, theorists can accurately calculate the spectrum to better than a percent. The spectrum of anisotropies today is directly related to the pattern of inhomogeneities present at the time of recombination. This recognition leads to a powerful argument that will enable us to distinguish inflationary models from other models of structure formation. If the inflationary models turn out to be correct, the free parameters in these models will be determined to unprecedented accuracy by the upcoming satellite missions

  4. Microwave background anisotropies in quasiopen inflation

    Science.gov (United States)

    García-Bellido, Juan; Garriga, Jaume; Montes, Xavier

    1999-10-01

    Quasiopenness seems to be generic to multifield models of single-bubble open inflation. Instead of producing infinite open universes, these models actually produce an ensemble of very large but finite inflating islands. In this paper we study the possible constraints from CMB anisotropies on existing models of open inflation. The effect of supercurvature anisotropies combined with the quasiopenness of the inflating regions make some models incompatible with observations, and severely reduces the parameter space of others. Supernatural open inflation and the uncoupled two-field model seem to be ruled out due to these constraints for values of Ω0<~0.98. Others, such as the open hybrid inflation model with suitable parameters for the slow roll potential can be made compatible with observations.

  5. General quadrupolar statistical anisotropy: Planck limits

    Energy Technology Data Exchange (ETDEWEB)

    Ramazanov, S. [Gran Sasso Science Institute (INFN), Viale Francesco Crispi 7, I-67100 L' Aquila (Italy); Rubtsov, G. [Institute for Nuclear Research of the Russian Academy of Sciences, Prospect of the 60th Anniversary of October 7a, 117312 Moscow (Russian Federation); Thorsrud, M. [Faculty of Engineering, Østfold University College, P.O. Box 700, 1757 Halden (Norway); Urban, F.R., E-mail: sabir.ramazanov@gssi.infn.it, E-mail: grisha@ms2.inr.ac.ru, E-mail: mikjel.thorsrud@hiof.no, E-mail: federico.urban@kbfi.ee [National Institute of Chemical Physics and Biophysics, Rävala 10, 10143 Tallinn (Estonia)

    2017-03-01

    Several early Universe scenarios predict a direction-dependent spectrum of primordial curvature perturbations. This translates into the violation of the statistical isotropy of cosmic microwave background radiation. Previous searches for statistical anisotropy mainly focussed on a quadrupolar direction-dependence characterised by a single multipole vector and an overall amplitude g {sub *}. Generically, however, the quadrupole has a more complicated geometry described by two multipole vectors and g {sub *}. This is the subject of the present work. In particular, we limit the amplitude g {sub *} for different shapes of the quadrupole by making use of Planck 2015 maps. We also constrain certain inflationary scenarios which predict this kind of more general quadrupolar statistical anisotropy.

  6. Seismic anisotropy in deforming salt bodies

    Science.gov (United States)

    Prasse, P.; Wookey, J. M.; Kendall, J. M.; Dutko, M.

    2017-12-01

    Salt is often involved in forming hydrocarbon traps. Studying salt dynamics and the deformation processes is important for the exploration industry. We have performed numerical texture simulations of single halite crystals deformed by simple shear and axial extension using the visco-plastic self consistent approach (VPSC). A methodology from subduction studies to estimate strain in a geodynamic simulation is applied to a complex high-resolution salt diapir model. The salt diapir deformation is modelled with the ELFEN software by our industrial partner Rockfield, which is based on a finite-element code. High strain areas at the bottom of the head-like strctures of the salt diapir show high amount of seismic anisotropy due to LPO development of halite crystals. The results demonstrate that a significant degree of seismic anisotropy can be generated, validating the view that this should be accounted for in the treatment of seismic data in, for example, salt diapir settings.

  7. Experimental investigation of ultrasonic velocity anisotropy in ...

    Indian Academy of Sciences (India)

    Permanent link: https://www.ias.ac.in/article/fulltext/pram/077/02/0345-0355. Keywords. Magnetic fluids; ultrasonic wave; sound velocity; anisotropy. Abstract. Magnetic field-induced dispersion of ultrasonic velocity in a Mn0.7Zn0.3Fe2O4 fluid (applied magnetic field is perpendicular to the ultrasonic propagation vector) is ...

  8. Transfer anisotropy effect in a turbulent plasma

    International Nuclear Information System (INIS)

    Bychenkov, V.Yu.; Gradov, O.M.; Silin, V.P.

    1982-01-01

    A theory is developed of transfer phenomena with pronounced ion-sound turbulence. A transfer anisotropy effect is observed which is due to the temperature gradient. The corresponding fluxes across the effective force vector generating the turbulence are found to be considerably greater than the longitudinal fluxes in a plasma with a comparatively low degree of nonisothermality. In a strongly nonisothermal plasma the suppression of transverse fluxes occurs, corresponding to the growth of thermal insulation of the current-carrying plasma filaments

  9. Ultrasonic evaluation of local human skin anisotropy

    Czech Academy of Sciences Publication Activity Database

    Tokar, Daniel; Převorovský, Zdeněk; Hradilová, Jana

    2014-01-01

    Roč. 19, č. 12 (2014) ISSN 1435-4934. [European Conference on Non-Destructive Testing (ECNDT 2014) /11./. Praha, 06.10.2014-10.10.2014] Institutional support: RVO:61388998 Keywords : anisotropy * ultrasonic testing * human skin in-vivo * fabric-fiber composite * signal processing Subject RIV: BI - Acoustics http://www.ndt.net/events/ECNDT2014/app/content/Paper/324_Tokar.pdf

  10. Anisotropy of dark matter velocity distribution

    OpenAIRE

    Nagao, Keiko I.

    2018-01-01

    Direct detection of dark matter with directional sensitivity has the potential to discriminate the dark matter velocity distribution. Especially, it will be suitable to discriminate isotropic distribution from anisotropic one. Analyzing data produced with Monte-Carlo simulation, required conditions for the discrimination is estimated. If energy threshold of detector is optimized, $O(10^3-10^4)$ event number is required to discriminate the anisotropy.

  11. Assessment of velocity anisotropy in rocks

    Czech Academy of Sciences Publication Activity Database

    Lokajíček, Tomáš; Goel, R. K.; Rudajev, Vladimír; Dwivedi, R.D.

    2013-01-01

    Roč. 57, January (2013), s. 142-152 ISSN 1365-1609 R&D Projects: GA ČR(CZ) GA205/08/0676; GA AV ČR IAA300130906; GA ČR(CZ) GAP104/12/0915 Institutional research plan: CEZ:AV0Z30130516 Keywords : elastic anisotropy * acoustic emission * uniaxial loading * hydrostatic loading Subject RIV: DB - Geology ; Mineralogy Impact factor: 1.424, year: 2013

  12. [Prevalence and clinical characteristics of oral bony outgrowth in a Moroccan population].

    Science.gov (United States)

    Oualalou, Y; Azaroual, M F; Zaoui, F; Chbicheb, S; Berrada, S

    2014-11-01

    Oral bony outgrowths (OBOs) are localized bony protuberances that arise from the cortical plate. Various types of OBOs have been described, the precise designation of which depends on anatomic location such as torus palatinus, torus mandibularis, buccal exostosis, or palatal exostosis. We had for aim to determine the prevalence and clinical characteristics of OBOs in a Moroccan population. This cross-sectional study was conducted between March 15 and June 30, 2011 at the Rabat-Salé teaching hospital dental consultation and treatment center, in Morocco. Three hundred and fifty-three patients (160 female and 193 male patients), 11 to 82 years of age, were examined clinically and radiologically to determine the presence of OBO. Twenty-four patients (6.8%) presented with OBOs. The prevalence for exostosis, torus mandibularis, torus palatinus, and associated OBOs was 3.1%, 2%, 0.8%, and 0.9% respectively. There was a significant difference (P=0,01) between the average age for patients presenting with OBO (43.2±12 years of age) and the average age for patients without any OBO (36.5±16 years of age). The prevalence of OBOs in female patients (7.3%) was higher than in male patients (6.3%) but the difference was not significant (P=0.439). Patients with occlusal parafunctional activity presented with significantly more OBO (P=0.016). The reported prevalence of OBO is extremely variable, according to age, gender, and ethnic group. The occurrence of OBO could be triggered by genetic factors associated with environmental factors. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  13. Rapid quantification of the latent reservoir for HIV-1 using a viral outgrowth assay.

    Directory of Open Access Journals (Sweden)

    Gregory M Laird

    Full Text Available HIV-1 persists in infected individuals in a stable pool of resting CD4(+ T cells as a latent but replication-competent provirus. This latent reservoir is the major barrier to the eradication of HIV-1. Clinical trials are currently underway investigating the effects of latency-disrupting compounds on the persistence of the latent reservoir in infected individuals. To accurately assess the effects of such compounds, accurate assays to measure the frequency of latently infected cells are essential. The development of a simpler assay for the latent reservoir has been identified as a major AIDS research priority. We report here the development and validation of a rapid viral outgrowth assay that quantifies the frequency of cells that can release replication-competent virus following cellular activation. This new assay utilizes bead and column-based purification of resting CD4(+ T cells from the peripheral blood of HIV-1 infected patients rather than cell sorting to obtain comparable resting CD4(+ T cell purity. This new assay also utilizes the MOLT-4/CCR5 cell line for viral expansion, producing statistically comparable measurements of the frequency of latent HIV-1 infection. Finally, this new assay employs a novel quantitative RT-PCR specific for polyadenylated HIV-1 RNA for virus detection, which we demonstrate is a more sensitive and cost-effective method to detect HIV-1 replication than expensive commercial ELISA detection methods. The reductions in both labor and cost make this assay suitable for quantifying the frequency of latently infected cells in clinical trials of HIV-1 eradication strategies.

  14. Engineering functional anisotropy in fibrocartilage neotissues.

    Science.gov (United States)

    MacBarb, Regina F; Chen, Alison L; Hu, Jerry C; Athanasiou, Kyriacos A

    2013-12-01

    The knee meniscus, intervertebral disc, and temporomandibular joint (TMJ) disc all possess complex geometric shapes and anisotropic matrix organization. While these characteristics are imperative for proper tissue function, they are seldom recapitulated following injury or disease. Thus, this study's objective was to engineer fibrocartilages that capture both gross and molecular structural features of native tissues. Self-assembled TMJ discs were selected as the model system, as the disc exhibits a unique biconcave shape and functional anisotropy. To drive anisotropy, 50:50 co-cultures of meniscus cells and articular chondrocytes were grown in biconcave, TMJ-shaped molds and treated with two exogenous stimuli: biomechanical (BM) stimulation via passive axial compression and bioactive agent (BA) stimulation via chondroitinase-ABC and transforming growth factor-β1. BM + BA synergistically increased Col/WW, Young's modulus, and ultimate tensile strength 5.8-fold, 14.7-fold, and 13.8-fold that of controls, respectively; it also promoted collagen fibril alignment akin to native tissue. Finite element analysis found BM stimulation to create direction-dependent strains within the neotissue, suggesting shape plays an essential role toward driving in vitro anisotropic neotissue development. Methods used in this study offer insight on the ability to achieve physiologic anisotropy in biomaterials through the strategic application of spatial, biomechanical, and biochemical cues. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. What does anisotropy measure? Insights from increased and decreased anisotropy in selective fiber tracts in schizophrenia.

    Science.gov (United States)

    Alba-Ferrara, L M; de Erausquin, Gabriel A

    2013-01-01

    Schizophrenia is a common, severe, and chronically disabling mental illness of unknown cause. Recent MRI studies have focused attention on white matter abnormalities in schizophrenia using diffusion tensor imaging (DTI). Indices commonly derived from DTI include (1) mean diffusivity, independent of direction, (2) fractional anisotropy (FA) or relative anisotropy (RA), (3) axial diffusivity, and (4) radial diffusivity. In cerebral white matter, contributions to these indices come from fiber arrangements, degree of myelination, and axonal integrity. Relatively pure deficits in myelin result in a modest increase in radial diffusivity, without affecting axial diffusivity and with preservation of anisotropy. Although schizophrenia is not characterized by gross abnormalities of white matter, it does involve a profound dysregulation of myelin-associated gene expression, reductions in oligodendrocyte numbers, and marked abnormalities in the ultrastructure of myelin sheaths. Since each oligodendrocyte myelinates as many as 40 axon segments, changes in the number of oligodendrocytes (OLG), and/or in the integrity of myelin sheaths, and/or axoglial contacts can have a profound impact on signal propagation and the integrity of neuronal circuits. Whereas a number of studies have revealed inconsistent decreases in anisotropy in schizophrenia, we and others have found increased FA in key subcortical tracts associated with the circuits underlying symptom generation in schizophrenia. We review data revealing increased anisotropy in dopaminergic tracts in the mesencephalon of schizophrenics and their unaffected relatives, and discuss the possible biological underpinnings and physiological significance of this finding.

  16. Pure neuritic leprosy presenting as ulnar nerve neuropathy: a case report of electrodiagnostic, radiographic, and histopathological findings.

    Science.gov (United States)

    Payne, Russell; Baccon, Jennifer; Dossett, John; Scollard, David; Byler, Debra; Patel, Akshal; Harbaugh, Kimberly

    2015-11-01

    Hansen's disease, or leprosy, is a chronic infectious disease with many manifestations. Though still a major health concern and leading cause of peripheral neuropathy in the developing world, it is rare in the United States, with only about 150 cases reported each year. Nevertheless, it is imperative that neurosurgeons consider it in the differential diagnosis of neuropathy. The causative organism is Mycobacterium leprae, which infects and damages Schwann cells in the peripheral nervous system, leading first to sensory and then to motor deficits. A rare presentation of Hansen's disease is pure neuritic leprosy. It is characterized by nerve involvement without the characteristic cutaneous stigmata. The authors of this report describe a case of pure neuritic leprosy presenting as ulnar nerve neuropathy with corresponding radiographic, electrodiagnostic, and histopathological data. This 11-year-old, otherwise healthy male presented with progressive right-hand weakness and numbness with no cutaneous abnormalities. Physical examination and electrodiagnostic testing revealed findings consistent with a severe ulnar neuropathy at the elbow. Magnetic resonance imaging revealed diffuse thickening and enhancement of the ulnar nerve and narrowing at the cubital tunnel. The patient underwent ulnar nerve decompression with biopsy. Pathology revealed acid-fast organisms within the nerve, which was pathognomonic for Hansen's disease. He was started on antibiotic therapy, and on follow-up he had improved strength and sensation in the ulnar nerve distribution. Pure neuritic leprosy, though rare in the United States, should be considered in the differential diagnosis of those presenting with peripheral neuropathy and a history of travel to leprosy-endemic areas. The long incubation period of M. leprae, the ability of leprosy to mimic other conditions, and the low sensitivity of serological tests make clinical, electrodiagnostic, and radiographic evaluation necessary for diagnosis

  17. Identification and expression analysis of the IPT and CKX gene families during axillary bud outgrowth in apple (Malus domestica Borkh.).

    Science.gov (United States)

    Tan, Ming; Li, Guofang; Qi, Siyan; Liu, Xiaojie; Chen, Xilong; Ma, Juanjuan; Zhang, Dong; Han, Mingyu

    2018-04-20

    Cytokinins (CKs) play a crucial role in promoting axillary bud outgrowth and targeting the control of CK metabolism can be used to enhance branching in plants. CK levels are maintained mainly by CK biosynthesis (isopentenyl transferase, IPT) and degradation (dehydrogenase, CKX) genes in plants. A systematic study of the IPT and CKX gene families in apple, however, has not been conducted. In the present study, 12 MdIPTs and 12 MdCKXs were identified in the apple genome. Systematic phylogenetic, structural, and synteny analyses were performed. Expression analysis of these genes in different tissues was also assessed. MdIPT and MdCKX genes exhibit distinct expression patterns in different tissues. The response of MdIPT, MdCKX, and MdPIN1 genes to various treatments (6-BA, decapitation and Lovastatin, an inhibitor of CKs synthesis) that impact branching were also investigated. Results indicated that most of the MdIPT and MdCKX, and MdPIN1 genes were upregulated by 6-BA and decapitation treatment, but inhibited by Lovastatin, a compound that effectively suppresses axillary bud outgrowth induced by decapitation. These findings suggest that cytokinin biosynthesis is required for the activation of bud break and the export of auxin from buds in apple tree with intact primary shoot apex or decapitated apple tree. MdCKX8 and MdCKX10, however, exhibited little response to decapitation, but were significantly up-regulated by 6-BA and Lovastatin, a finding that warrants further investigation in order to understand their function in bud-outgrowth. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Nerve growth factor stimulates axon outgrowth through negative regulation of growth cone actomyosin restraint of microtubule advance.

    Science.gov (United States)

    Turney, Stephen G; Ahmed, Mostafa; Chandrasekar, Indra; Wysolmerski, Robert B; Goeckeler, Zoe M; Rioux, Robert M; Whitesides, George M; Bridgman, Paul C

    2016-02-01

    Nerve growth factor (NGF) promotes growth, differentiation, and survival of sensory neurons in the mammalian nervous system. Little is known about how NGF elicits faster axon outgrowth or how growth cones integrate and transform signal input to motor output. Using cultured mouse dorsal root ganglion neurons, we found that myosin II (MII) is required for NGF to stimulate faster axon outgrowth. From experiments inducing loss or gain of function of MII, specific MII isoforms, and vinculin-dependent adhesion-cytoskeletal coupling, we determined that NGF causes decreased vinculin-dependent actomyosin restraint of microtubule advance. Inhibition of MII blocked NGF stimulation, indicating the central role of restraint in directed outgrowth. The restraint consists of myosin IIB- and IIA-dependent processes: retrograde actin network flow and transverse actin bundling, respectively. The processes differentially contribute on laminin-1 and fibronectin due to selective actin tethering to adhesions. On laminin-1, NGF induced greater vinculin-dependent adhesion-cytoskeletal coupling, which slowed retrograde actin network flow (i.e., it regulated the molecular clutch). On fibronectin, NGF caused inactivation of myosin IIA, which negatively regulated actin bundling. On both substrates, the result was the same: NGF-induced weakening of MII-dependent restraint led to dynamic microtubules entering the actin-rich periphery more frequently, giving rise to faster elongation. © 2016 Turney et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  19. Role of Tulipa gesneriana TEOSINTE BRANCHED1 (TgTB1) in the control of axillary bud outgrowth in bulbs.

    Science.gov (United States)

    Moreno-Pachon, Natalia M; Mutimawurugo, Marie-Chantal; Heynen, Eveline; Sergeeva, Lidiya; Benders, Anne; Blilou, Ikram; Hilhorst, Henk W M; Immink, Richard G H

    2018-06-01

    Tulip vegetative reproduction. Tulips reproduce asexually by the outgrowth of their axillary meristems located in the axil of each bulb scale. The number of axillary meristems in one bulb is low, and not all of them grow out during the yearly growth cycle of the bulb. Since the degree of axillary bud outgrowth in tulip determines the success of their vegetative propagation, this study aimed at understanding the mechanism controlling the differential axillary bud activity. We used a combined physiological and "bottom-up" molecular approach to shed light on this process and found that first two inner located buds do not seem to experience dormancy during the growth cycle, while mid-located buds enter dormancy by the end of the growing season. Dormancy was assessed by weight increase and TgTB1 expression levels, a conserved TCP transcription factor and well-known master integrator of environmental and endogenous signals influencing axillary meristem outgrowth in plants. We showed that TgTB1 expression in tulip bulbs can be modulated by sucrose, cytokinin and strigolactone, just as it has been reported for other species. However, the limited growth of mid-located buds, even when their TgTB1 expression is downregulated, points at other factors, probably physical, inhibiting their growth. We conclude that the time of axillary bud initiation determines the degree of dormancy and the sink strength of the bud. Thus, development, apical dominance, sink strength, hormonal cross-talk, expression of TgTB1 and other possibly physical but unidentified players, all converge to determine the growth capacity of tulip axillary buds.

  20. Blood Outgrowth Endothelial Cells Increase Tumor Growth Rates and Modify Tumor Physiology: Relevance for Therapeutic Targeting

    Energy Technology Data Exchange (ETDEWEB)

    Pagan, Jonathan, E-mail: jdpagan@uams.edu; Przybyla, Beata; Jamshidi-Parsian, Azemat [Department of Radiation Oncology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States); Gupta, Kalpna [Vascular Biology Center and Division of Hematology-Oncology Transplantation, Department of Medicine, University of Minnesota Medical School, MN 72223 (United States); Griffin, Robert J. [Department of Radiation Oncology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States)

    2013-02-18

    Endothelial cell precursors from human peripheral blood have been shown to home to areas of neovascularization and may assist tumor growth by increasing or fortifying blood vessel growth. In the present study, the influence of these cells on tumor growth and physiology was investigated and the role of these cells as a therapeutic target or in determining treatment sensitivity was tested. After isolation from human blood and expansion in vitro, actively growing cells with verified endothelial phenotype (Blood Outgrowth Endothelial Cell, BOEC) were injected i.v. into tumor bearing mice for three consecutive days. The growth rate was significantly enhanced in relatively small RERF human lung tumors (i.e., less than 150 mm{sup 3}) grown in immunocompromised mice by an average of 1.5-fold while it had no effect when injections were given to animals bearing larger tumors. There were no signs of toxicity or unwanted systemic effects. We also observed evidence of increased perfusion, vessel number, response to 15 Gy radiation and oxygenation in RERF tumors of animals injected with BOECs compared to control tumors. In addition, FSaII murine fibrosarcoma tumors were found to grow faster upon injection of BOECs. When FSaII tumors were subjected to a partial thermal ablation treatment using high intensity focused ultrasound (HIFU) there was consistently elevated detection of fluorescently labeled and i.v. injected endothelial precursors in the tumor when analyzed with optical imaging and/or histological preparations. Importantly, we also observed that BOECs treated with the novel anti-angiogenic peptide anginex in-vitro, show decreased proliferation and increased sensitivity to radiation. In vivo, the normal increase in FSaII tumor growth induced by injected BOECs was blunted by the addition of anginex treatment. It appears that endothelial precursors may significantly contribute to tumor vessel growth, tumor progression and/or repair of tumor damage and may improve the

  1. Blood Outgrowth Endothelial Cells Increase Tumor Growth Rates and Modify Tumor Physiology: Relevance for Therapeutic Targeting

    International Nuclear Information System (INIS)

    Pagan, Jonathan; Przybyla, Beata; Jamshidi-Parsian, Azemat; Gupta, Kalpna; Griffin, Robert J.

    2013-01-01

    Endothelial cell precursors from human peripheral blood have been shown to home to areas of neovascularization and may assist tumor growth by increasing or fortifying blood vessel growth. In the present study, the influence of these cells on tumor growth and physiology was investigated and the role of these cells as a therapeutic target or in determining treatment sensitivity was tested. After isolation from human blood and expansion in vitro, actively growing cells with verified endothelial phenotype (Blood Outgrowth Endothelial Cell, BOEC) were injected i.v. into tumor bearing mice for three consecutive days. The growth rate was significantly enhanced in relatively small RERF human lung tumors (i.e., less than 150 mm 3 ) grown in immunocompromised mice by an average of 1.5-fold while it had no effect when injections were given to animals bearing larger tumors. There were no signs of toxicity or unwanted systemic effects. We also observed evidence of increased perfusion, vessel number, response to 15 Gy radiation and oxygenation in RERF tumors of animals injected with BOECs compared to control tumors. In addition, FSaII murine fibrosarcoma tumors were found to grow faster upon injection of BOECs. When FSaII tumors were subjected to a partial thermal ablation treatment using high intensity focused ultrasound (HIFU) there was consistently elevated detection of fluorescently labeled and i.v. injected endothelial precursors in the tumor when analyzed with optical imaging and/or histological preparations. Importantly, we also observed that BOECs treated with the novel anti-angiogenic peptide anginex in-vitro, show decreased proliferation and increased sensitivity to radiation. In vivo, the normal increase in FSaII tumor growth induced by injected BOECs was blunted by the addition of anginex treatment. It appears that endothelial precursors may significantly contribute to tumor vessel growth, tumor progression and/or repair of tumor damage and may improve the

  2. Anisotropy effect on strengths of metamorphic rocks

    Directory of Open Access Journals (Sweden)

    Ahmet Özbek

    2018-02-01

    Full Text Available This paper aims to study the effect of anisotropy on strengths of several metamorphic rocks of southern (Çine submassif of Menderes metamorphic massif in southwest Turkey. Four different metamorphic rocks including foliated phyllite, schist, gneiss and marble (calcschist were selected and examined. Discontinuity surveys were made along lines for each rock and evaluated with DIPS program. L-type Schmidt hammer was applied in the directions parallel and perpendicular to foliation during the field study. Several hand samples and rock blocks were collected during the field study for measurements of dry and saturated densities, dry and saturated unit weights and porosity, and for petrographic analysis and strength determination in laboratory. L- and N-type Schmidt hammers were applied in the directions perpendicular (anisotropy angle of 0° and parallel (anisotropy angle of 90° to the foliation on selected blocks of phyllite, schist, gneiss and marble (calcschist. The phyllite and schist have higher porosity and lower density values than the other rocks. However, coarse crystalline gneiss and marble (calcschist have higher rebound values and strengths, and they are classified as strong–very strong rocks. Generally, the rebound values in the direction perpendicular to the foliation are slightly higher than that in the direction parallel to foliation. Rebound values of N-type Schmidt hammer are higher than the L-type values except for phyllite. Sometimes, the rebound values of laboratory and field applications gave different results. This may result from variable local conditions such as minerals differentiation, discontinuities, water content, weathering degree and thickness of foliated structure.

  3. Mathematical Relationships between Neuron Morphology and Neurite Growth Dynamics in Drosophila melanogaster Larva Class IV Sensory Neurons

    Science.gov (United States)

    Ganguly, Sujoy; Liang, Xin; Grace, Michael; Lee, Daniel; Howard, Jonathon

    The morphology of neurons is diverse and reflects the diversity of neuronal functions, yet the principles that govern neuronal morphogenesis are unclear. In an effort to better understand neuronal morphogenesis we will be focusing on the development of the dendrites of class IV sensory neuron in Drosophila melanogaster. In particular we attempt to determine how the the total length, and the number of branches of dendrites are mathematically related to the dynamics of neurite growth and branching. By imaging class IV neurons during early embryogenesis we are able to measure the change in neurite length l (t) as a function of time v (t) = dl / dt . We found that the distribution of v (t) is well characterized by a hyperbolic secant distribution, and that the addition of new branches per unit time is well described by a Poisson process. Combining these measurements with the assumption that branching occurs with equal probability anywhere along the dendrite we were able to construct a mathematical model that provides reasonable agreement with the observed number of branches, and total length of the dendrites of the class IV sensory neuron.

  4. Anisotropy in cohesive, frictional granular media

    International Nuclear Information System (INIS)

    Luding, Stefan

    2005-01-01

    The modelling of cohesive, frictional granular materials with a discrete particle molecular dynamics is reviewed. From the structure of the quasi-static granular solid, the fabric, stress, and stiffness tensors are determined, including both normal and tangential forces. The influence of the material properties on the flow behaviour is also reported, including relations between the microscopic attractive force and the macroscopic cohesion as well as the dependence of the macroscopic friction on the microscopic contact friction coefficient. Related to the dynamics, the anisotropy of both structure and stress are exponentially approaching the maximum

  5. Influence of spin on fission fragments anisotropy

    Directory of Open Access Journals (Sweden)

    Ghodsi Omid N.

    2005-01-01

    Full Text Available An analysis of selected fission fragment angular distribution when at least one of the spins of the projectile or target is appreciable in induced fission was made by using the statistical scission model. The results of this model predicate that the spins of the projectile or target are affected on the nuclear level density of the compound nucleus. The experimental data was analyzed by means of the couple channel spin effect formalism. This formalism suggests that the projectile spin is more effective on angular anisotropies within the limits of energy near the fusion barrier.

  6. Transfer anisotropy in a turbulent plasma

    International Nuclear Information System (INIS)

    Bychenkov, V.Y.; Gradov, O.M.; Silin, V.P.

    1982-01-01

    We formulate a theory for transfer phenomena in a plasma with developed ion-sound turbulence. A transfer anisotropy effect caused by a temperature gradient is revealed. The corresponding fluxes transverse to the effective force vector (1) which generates the turbulence turn out to be considerably larger than the longitudinal fluxes in a plasma with a relatively small degree of nonisothermality. For a strongly nonisothermal plasma a suppression of the transverse fluxes takes place and corresponds to a growth of the thermal insulation of the current-carrying plasma filaments

  7. Asymmetric beams and CMB statistical anisotropy

    International Nuclear Information System (INIS)

    Hanson, Duncan; Lewis, Antony; Challinor, Anthony

    2010-01-01

    Beam asymmetries result in statistically anisotropic cosmic microwave background (CMB) maps. Typically, they are studied for their effects on the CMB power spectrum, however they more closely mimic anisotropic effects such as gravitational lensing and primordial power asymmetry. We discuss tools for studying the effects of beam asymmetry on general quadratic estimators of anisotropy, analytically for full-sky observations as well as in the analysis of realistic data. We demonstrate this methodology in application to a recently detected 9σ quadrupolar modulation effect in the WMAP data, showing that beams provide a complete and sufficient explanation for the anomaly.

  8. Fusion barrier distributions and fission anisotropies

    International Nuclear Information System (INIS)

    Hinde, D.J.; Morton, C.R.; Dasgupta, M.; Leigh, J.R.; Lestone, J.P.; Lemmon, R.C.; Mein, J.C.; Newton, J.O.; Timmers, H.; Rowley, N.; Kruppa, A.T.

    1995-01-01

    Fusion excitation functions for 16,17 O+ 144 Sm have been measured to high precision. The extracted fusion barrier distributions show a double-peaked structure interpreted in terms of coupling to inelastic collective excitations of the target. The effect of the positive Q-value neutron stripping channel is evident in the reaction with 17 O. Fission and evaporation residue cross-sections and excitation functions have been measured for the reaction of 16 O+ 208 Pb and the fusion barrier distribution and fission anisotropies determined. It is found that the moments of the fusion l-distribution determined from the fusion and fission measurements are in good agreement. ((orig.))

  9. Cosmic anisotropy with reduced relativistic gas

    Energy Technology Data Exchange (ETDEWEB)

    Castardelli dos Reis, Simpliciano [Universidade Federal de Juiz de Fora, Departamento de Fisica, ICE, Juiz de Fora, MG (Brazil); Shapiro, Ilya L. [Universidade Federal de Juiz de Fora, Departamento de Fisica, ICE, Juiz de Fora, MG (Brazil); Tomsk State Pedagogical University, Tomsk (Russian Federation); Tomsk State University, Tomsk (Russian Federation)

    2018-02-15

    The dynamics of cosmological anisotropies is investigated for Bianchi type I universe filled by a relativistic matter represented by the reduced relativistic gas model (RRG), with equation of state interpolating between radiation and matter. Previously it was shown that the interpolation is observed in the background cosmological solutions for homogeneous and isotropic universe and also for the linear cosmological perturbations. We extend the application of RRG to the Bianchi type I anisotropic model and find that the solutions evolve to the isotropic universe with the pressureless matter contents. (orig.)

  10. Absorption anisotropy studies of polymethine dyes

    International Nuclear Information System (INIS)

    Lepkowicz, Richard S.; Cirloganu, Claudiu M.; Przhonska, Olga V.; Hagan, David J.; Van Stryland, Eric W.; Bondar, Mikhail V.; Slominsky, Yuriy L.; Kachkovski, Alexei D.; Mayboroda, Elena I.

    2004-01-01

    The determination of the spectral position of the excited states and orientation of the transition dipole moments of polymethine molecules is experimentally measured using two methods: the steady-state fluorescence anisotropy method, and a two-color polarization-resolved pump-probe method. This novel use of the pump-probe method is described in detail and a comparison to the fluorescence method is given. Quantum-chemical modeling on the effects of the bridge structure in the polymethine chromophore on the linear absorption spectrum is also discussed

  11. Molecular anisotropy effects in carbon K-edge scattering: depolarized diffuse scattering and optical anisotropy

    Energy Technology Data Exchange (ETDEWEB)

    Stone, Kevin H.

    2014-07-14

    Some polymer properties, such as conductivity, are very sensitive to short- and intermediate-range orientational and positional ordering of anisotropic molecular functional groups, and yet means to characterize orientational order in disordered systems are very limited. We demonstrate that resonant scattering at the carbon K-edge is uniquely sensitive to short-range orientation correlations in polymers through depolarized scattering at high momentum transfers, using atactic polystyrene as a well-characterized test system. Depolarized scattering is found to coexist with unpolarized fluorescence, and to exhibit pronounced anisotropy. We also quantify the spatially averaged optical anisotropy from low-angle reflectivity measurements, finding anisotropy consistent with prior visible, x-ray absorption, and theoretical studies. The average anisotropy is much smaller than that in the depolarized scattering and the two have different character. Both measurements exhibit clear spectral signatures from the phenyl rings and the polyethylene-like backbone. Discussion focuses on analysis considerations and prospects for using this depolarized scattering for studies of disorder in soft condensed matter.

  12. Electrical resistivity characterization of anisotropy in the Biscayne Aquifer.

    Science.gov (United States)

    Yeboah-Forson, Albert; Whitman, Dean

    2014-01-01

    Electrical anisotropy occurs when electric current flow varies with azimuth. In porous media, this may correspond to anisotropy in the hydraulic conductivity resulting from sedimentary fabric, fractures, or dissolution. In this study, a 28-electrode resistivity imaging system was used to investigate electrical anisotropy at 13 sites in the Biscayne Aquifer of SE Florida using the rotated square array method. The measured coefficient of electrical anisotropy generally ranged from 1.01 to 1.12 with values as high as 1.36 found at one site. The observed electrical anisotropy was used to estimate hydraulic anisotropy (ratio of maximum to minimum hydraulic conductivity) which ranged from 1.18 to 2.83. The largest values generally were located on the Atlantic Coastal Ridge while the lowest values were in low elevation areas on the margin of the Everglades to the west. The higher values of anisotropy found on the ridge may be due to increased dissolution rates of the oolitic facies of the Miami formation limestone compared with the bryozoan facies to the west. The predominate trend of minimum resistivity and maximum hydraulic conductivity was E-W/SE-NW beneath the ridge and E-W/SW-NE farther west. The anisotropy directions are similar to the predevelopment groundwater flow direction as indicated in published studies. This suggests that the observed anisotropy is related to the paleo-groundwater flow in the Biscayne Aquifer. © 2013, National Ground Water Association.

  13. Origin of perpendicular magnetic anisotropy in Co/Ni multilayers

    Science.gov (United States)

    Arora, M.; Hübner, R.; Suess, D.; Heinrich, B.; Girt, E.

    2017-07-01

    We studied the variation in perpendicular magnetic anisotropy of (111) textured Au /N ×[Co /Ni ]/Au films as a function of the number of bilayer repeats N . The ferromagnetic resonance and superconducting quantum interference device magnetometer measurements show that the perpendicular magnetic anisotropy of Co/Ni multilayers first increases with N for N ≤10 and then moderately decreases for N >10 . The model we propose reveals that the decrease of the anisotropy for N reduction in the magnetoelastic and magnetocrystalline anisotropies. A moderate decrease in the perpendicular magnetic anisotropy for N >10 is due to the reduction in the magnetocrystalline and the surface anisotropies. To calculate the contribution of magnetoelastic anisotropy in the Co/Ni multilayers, in-plane and out-of-plane x-ray diffraction measurements are performed to determine the spacing between Co/Ni (111) and (220) planes. The magnetocrystalline bulk anisotropy is estimated from the difference in the perpendicular and parallel g factors of Co/Ni multilayers that are measured using the in-plane and out-of-plane ferromagnetic resonance measurements. Transmission electron microscopy has been used to estimate the multilayer film roughness. These values are used to calculate the roughness-induced surface and magnetocrystalline anisotropy coefficients as a function of N .

  14. Middle-energy electron anisotropies in the auroral region

    Directory of Open Access Journals (Sweden)

    P. Janhunen

    2004-01-01

    Full Text Available Field-aligned anisotropic electron distribution functions of T > T type are observed on auroral field lines at both low and high altitudes. We show that typically the anisotropy is limited to a certain range of energies, often below 1keV, although sometimes extending to slightly higher energies as well. Almost always there is simultaneously an isotropic electron distribution at higher energies. Often the anisotropies are up/down symmetrical, although cases with net upward or downward electron flow also occur. For a statistical analysis of the anisotropies we divide the energy range into low (below 100eV, middle (100eV–1keV and high (above 1keV energies and develop a measure of anisotropy expressed in density units. The statistical magnetic local time and invariant latitude distribution of the middle-energy anisotropies obeys that of the average auroral oval, whereas the distributions of the low and high energy anisotropies are more irregular. This suggests that it is specifically the middle-energy anisotropies that have something to do with auroral processes. The anisotropy magnitude decreases monotonically with altitude, as one would expect, because electrons have high mobility along the magnetic field and thus, the anisotropy properties spread rapidly to different altitudes.

    Key words. Magnetospheric physics (auroral phenomena. Space plasma physics (wave-particle interactions; changed particle motion and acceleration

  15. Submicron scale tissue multifractal anisotropy in polarized laser light scattering

    Science.gov (United States)

    Das, Nandan Kumar; Dey, Rajib; Chakraborty, Semanti; Panigrahi, Prasanta K.; Meglinski, Igor; Ghosh, Nirmalya

    2018-03-01

    The spatial fluctuations of the refractive index within biological tissues exhibit multifractal anisotropy, leaving its signature as a spectral linear diattenuation of scattered polarized light. The multifractal anisotropy has been quantitatively assessed by the processing of relevant Mueller matrix elements in the Fourier domain, utilizing the Born approximation and subsequent multifractal analysis. The differential scaling exponent and width of the singularity spectrum appear to be highly sensitive to the structural multifractal anisotropy at the micron/sub-micron length scales. An immediate practical use of these multifractal anisotropy parameters was explored for non-invasive screening of cervical precancerous alterations ex vivo, with the indication of a strong potential for clinical diagnostic purposes.

  16. A Cardiac Cell Outgrowth Assay for Evaluating Drug Compounds Using a Cardiac Spheroid-on-a-Chip Device

    Directory of Open Access Journals (Sweden)

    Jonas Christoffersson

    2018-05-01

    Full Text Available Three-dimensional (3D models with cells arranged in clusters or spheroids have emerged as valuable tools to improve physiological relevance in drug screening. One of the challenges with cells cultured in 3D, especially for high-throughput applications, is to quickly and non-invasively assess the cellular state in vitro. In this article, we show that the number of cells growing out from human induced pluripotent stem cell (hiPSC-derived cardiac spheroids can be quantified to serve as an indicator of a drug’s effect on spheroids captured in a microfluidic device. Combining this spheroid-on-a-chip with confocal high content imaging reveals easily accessible, quantitative outgrowth data. We found that effects on outgrowing cell numbers correlate to the concentrations of relevant pharmacological compounds and could thus serve as a practical readout to monitor drug effects. Here, we demonstrate the potential of this semi-high-throughput “cardiac cell outgrowth assay” with six compounds at three concentrations applied to spheroids for 48 h. The image-based readout complements end-point assays or may be used as a non-invasive assay for quality control during long-term culture.

  17. Texture and Elastic Anisotropy of Mantle Olivine

    Science.gov (United States)

    Nikitin, A. N.; Ivankina, T. I.; Bourilitchev, D. E.; Klima, K.; Locajicek, T.; Pros, Z.

    Eight olivine rock samples from different European regions were collected for neu- tron texture analyses and for P-wave velocity measurements by means of ultrasonic sounding at various confining pressures. The orientation distribution functions (ODFs) of olivine were determined and pole figures of the main crystallographic planes were calculated. The spatial P-wave velocity distributions were determined at confining pressures from 0.1 to 400 MPa and modelled from the olivine textures. In dependence upon the type of rock (xenolith or dunite) different behavior of both the P-wave veloc- ity distributions and the anisotropy coefficients with various confining pressures was observed. In order to explain the interdependence of elastic anisotropy and hydrostatic pressure, a model for polycrystalline olivine rocks was suggested, which considers the influence of the crystallographic and the mechanical textures on the elastic behaviour of the polycrystal. Since the olivine texture depends upon the active slip systems and the deformation temperature, neutron texture analyses enable us to estimate depth and thermodynamical conditions during texture formation.

  18. Texture and anisotropy analysis of Qusaiba shales

    KAUST Repository

    Kanitpanyacharoen, Waruntorn

    2011-02-17

    Scanning and transmission electron microscopy, synchrotron X-ray diffraction, microtomography and ultrasonic velocity measurements were used to characterize microstructures and anisotropy of three deeply buried Qusaiba shales from the Rub\\'al-Khali basin, Saudi Arabia. Kaolinite, illite-smectite, illite-mica and chlorite show strong preferred orientation with (001) pole figure maxima perpendicular to the bedding plane ranging from 2.4-6.8 multiples of a random distribution (m.r.d.). Quartz, feldspars and pyrite crystals have a random orientation distribution. Elastic properties of the polyphase aggregate are calculated by averaging the single crystal elastic properties over the orientation distribution, assuming a nonporous material. The average calculated bulk P-wave velocities are 6.2 km/s (maximum) and 5.5 km/s (minimum), resulting in a P-wave anisotropy of 12%. The calculated velocities are compared with those determined from ultrasonic velocity measurements on a similar sample. In the ultrasonic experiment, which measures the effects of the shale matrix as well as the effects of porosity, velocities are smaller (P-wave maximum 5.3 km/s and minimum 4.1 km/s). The difference between calculated and measured velocities is attributed to the effects of anisotropic pore structure and to microfractures present in the sample, which have not been taken into account in the matrix averaging. © 2011 European Association of Geoscientists & Engineers.

  19. The Anisotropy of Replicated Aluminum Foams

    Directory of Open Access Journals (Sweden)

    Eugeny L. Furman

    2014-01-01

    Full Text Available The replication casting process gives the open-cell aluminum foams that can be used in many industrial applications as well as in filtering technology. The essential requirement for filters is the uniformity of filtering degree which is defined by the minimal pore size. However the structure of replication castings is often inhomogeneous and the minimal pore radius is decreasing in the direction of melt infiltration. The objective of this investigation is to study the dynamics of melt impregnation of the porous medium by vacuum suction to identify the possibility of reducing the anisotropy. Theoretical data illustrate the processes at the boundary between melt and gas medium. The experiments were carried out using the replication aluminum samples produced according to commercial technology. It was found that the permeability coefficient varies throughout the height of castings. A method for estimation of pressure on the line of melt movement was proposed. The resistance of NaCl layer and circular vents of the mold causes the inhomogeneity of castings. Finally the ways of minimizing the anisotropy were offered.

  20. Effects of pressure anisotropy on plasma transport

    International Nuclear Information System (INIS)

    Zawaideh, E.; Najmabadi, F.; Conn, R.W.

    1986-03-01

    In a recent paper a new set of generalized two-field equations is derived which describes plasma transport along the field lines of a space and time dependent magnetic field. These equations are valid for collisional to weakly collisional plasmas; they reduce to the conventional fluid equations of Braginskii for highly collisional plasmas. An important feature of these equations is that the anisotropy in the ion pressure is explicitly included. In this paper, these generalized transport equations are applied to a model problem of plasma flow through a magnetic mirror field. The profiles of the plasma parameters (density, flow speed, and pressures) are numerically calculated for plasma in different collisionality regimes. These profiles are explained by examining the competing terms in the transport equation. The pressure anisotropy is found to profoundly impact the plasma flow behavior. As a result, the new generalized equations predict flow behavior more accurately than the conventional transport equations. A large density and pressure drop is predicted as the flow passes through a magnetic mirror. Further, the new equations uniquely predict oscillations in the density profile, an effect missing in results from the conventional equations

  1. Cosmic ray anisotropy along with interplanetary transients

    Science.gov (United States)

    Mishra, Rajesh Kumar

    The present work deals with the study of first three harmonics of low amplitude anisotropic wave trains of cosmic ray intensity over the period 1991-1994 for Deep River neutron monitoring station. It is observed that the diurnal time of maximum remains in the corotational direction; whereas, the time of maximum for both diurnal and semi-diurnal anisotropy has significantly shifted towards later hours as compared to the quiet day annual average for majority of the LAE events. It is noticed that these events are not caused either by the high-speed solar wind streams or by the sources on the Sun responsible for producing these streams; such as, polar coronal holes. The direction of the tri-diurnal anisotropy shows a good negative correlation with Bz component of interplanetary magnetic field. The occurrence of low amplitude events is dominant for positive polarity of Bz. The Disturbance Storm Time index i.e. Dst remains consistently negative only throughout the entire low amplitude wave train event.

  2. Scanning anisotropy parameters in complex media

    KAUST Repository

    Alkhalifah, Tariq Ali

    2011-03-21

    Parameter estimation in an inhomogeneous anisotropic medium offers many challenges; chief among them is the trade-off between inhomogeneity and anisotropy. It is especially hard to estimate the anisotropy anellipticity parameter η in complex media. Using perturbation theory and Taylor’s series, I have expanded the solutions of the anisotropic eikonal equation for transversely isotropic (TI) media with a vertical symmetry axis (VTI) in terms of the independent parameter η from a generally inhomogeneous elliptically anisotropic medium background. This new VTI traveltime solution is based on a set of precomputed perturbations extracted from solving linear partial differential equations. The traveltimes obtained from these equations serve as the coefficients of a Taylor-type expansion of the total traveltime in terms of η. Shanks transform is used to predict the transient behavior of the expansion and improve its accuracy using fewer terms. A homogeneous medium simplification of the expansion provides classical nonhyperbolic moveout descriptions of the traveltime that are more accurate than other recently derived approximations. In addition, this formulation provides a tool to scan for anisotropic parameters in a generally inhomogeneous medium background. A Marmousi test demonstrates the accuracy of this approximation. For a tilted axis of symmetry, the equations are still applicable with a slightly more complicated framework because the vertical velocity and δ are not readily available from the data.

  3. Scanning anisotropy parameters in complex media

    KAUST Repository

    Alkhalifah, Tariq Ali

    2011-01-01

    Parameter estimation in an inhomogeneous anisotropic medium offers many challenges; chief among them is the trade-off between inhomogeneity and anisotropy. It is especially hard to estimate the anisotropy anellipticity parameter η in complex media. Using perturbation theory and Taylor’s series, I have expanded the solutions of the anisotropic eikonal equation for transversely isotropic (TI) media with a vertical symmetry axis (VTI) in terms of the independent parameter η from a generally inhomogeneous elliptically anisotropic medium background. This new VTI traveltime solution is based on a set of precomputed perturbations extracted from solving linear partial differential equations. The traveltimes obtained from these equations serve as the coefficients of a Taylor-type expansion of the total traveltime in terms of η. Shanks transform is used to predict the transient behavior of the expansion and improve its accuracy using fewer terms. A homogeneous medium simplification of the expansion provides classical nonhyperbolic moveout descriptions of the traveltime that are more accurate than other recently derived approximations. In addition, this formulation provides a tool to scan for anisotropic parameters in a generally inhomogeneous medium background. A Marmousi test demonstrates the accuracy of this approximation. For a tilted axis of symmetry, the equations are still applicable with a slightly more complicated framework because the vertical velocity and δ are not readily available from the data.

  4. Magnetic anisotropies in SmCo thin films

    International Nuclear Information System (INIS)

    Chen, K.

    1993-01-01

    A systemic study of the deposition processes and magnetic properties for the Sm-Co film system has been carried out. Films of Sm-Co system with various magnetic anisotropies have been synthesized through sputter deposition in both crystalline and amorphous phases. The origins of various anisotropies have been studied. Thermalized sputter deposition process control was used to synthesize Fe enriched Sm-Co films with rhombohedral Th 2 Zn 17 type structure. The film exhibited unusually strong textures with the crystallographic c axes of the crystallites aligned in the film plane. A large anisotropy was resulted with easy axis in the film plane. A well defined and large in-the-film-plane anisotropy of exceptionally high value of 3.3 x 10 6 erg/cm 3 has been obtained in the amorphous SmCo films by applying a magnetic field in the film plane during deposition. It was found that the in-the-film-plane anisotropy depended essentially on the applied field and Sm concentration. For films not synthesized through thermallized sputtering, the easy axis of the film could reoriented. A perpendicular anisotropy was also presented in the film synthesized through thermallized sputtering deposition. A large in-plane anisotropy was obtained in films deposited above ambient temperatures. It was concluded that the surface induced short range ordering was the origin of the in-the-film-phase anisotropy observed in amorphous film deposited in the presence of a magnetic field. The formation mechanism was different from that of the short range ordering induced by field annealing. The perpendicular anisotropy was shown to be growth induced. Large in-plane anisotropy in amorphous films was resulted form partial crystallization in the film. Both the formation of growth induced structure and partial crystallization in the film prevented the formation of the pair ordering and decreased in-the-film-plane anisotropy

  5. The Adhesion Molecule KAL-1/anosmin-1 Regulates Neurite Branching through a SAX-7/L1CAM–EGL-15/FGFR Receptor Complex

    Directory of Open Access Journals (Sweden)

    Carlos A. Díaz-Balzac

    2015-06-01

    Full Text Available Neurite branching is essential for correct assembly of neural circuits, yet it remains a poorly understood process. For example, the neural cell adhesion molecule KAL-1/anosmin-1, which is mutated in Kallmann syndrome, regulates neurite branching through mechanisms largely unknown. Here, we show that KAL-1/anosmin-1 mediates neurite branching as an autocrine co-factor with EGL-17/FGF through a receptor complex consisting of the conserved cell adhesion molecule SAX-7/L1CAM and the fibroblast growth factor receptor EGL-15/FGFR. This protein complex, which appears conserved in humans, requires the immunoglobulin (Ig domains of SAX-7/L1CAM and the FN(III domains of KAL-1/anosmin-1 for formation in vitro as well as function in vivo. The kinase domain of the EGL-15/FGFR is required for branching, and genetic evidence suggests that ras-mediated signaling downstream of EGL-15/FGFR is necessary to effect branching. Our studies establish a molecular pathway that regulates neurite branching during development of the nervous system.

  6. The output of neuronotrophic and neurite-promoting agents from rat brain astroglial cells: a microculture method for screening potential regulatory molecules.

    Science.gov (United States)

    Rudge, J S; Manthorpe, M; Varon, S

    1985-04-01

    Throughout embryonic development, as well as in response to injury of the central nervous system, astroglial cells may present neurons with a critical supply of neuronotrophic and neurite-promoting factors which control, respectively, neuronal survival and axonal growth. The identification of such astroglial cell-derived factors, as well as of specific extrinsic agents regulating their production, will require the use of in vitro techniques. We define here a new microculture system in which added agents can be screened for their ability to enhance or inhibit the output of trophic and neurite-promoting factors from purified neonatal rat brain astroglial cells. With such a procedure, thousands of replicate secondary astroglial cultures can be set-up and maintained in chemically defined medium, on a defined substratum and in a viable, low proliferative stable state. These cultured astroglial cells release into their medium at least three distinct and separable types of agents addressing nerve cells in vitro: (i) high molecular weight trophic factors (Mr greater than 10,000) which support the survival of embryonic peripheral neurons; (ii) low molecular weight trophic agents (Mr less than 10,000) supporting embryonic central neurons; and (iii) polyornithine-binding neurite-promoting factors which enhance neuritic regeneration for both peripheral and central neurons. The temporal release patterns of these three agents from astroglial cultures are quite distinct suggesting that their output is independently regulated.

  7. CMB statistical anisotropy from noncommutative gravitational waves

    Energy Technology Data Exchange (ETDEWEB)

    Shiraishi, Maresuke; Ricciardone, Angelo [Dipartimento di Fisica e Astronomia ' ' G. Galilei' ' , Università degli Studi di Padova, via Marzolo 8, I-35131, Padova (Italy); Mota, David F. [Institute of Theoretical Astrophysics, University of Oslo, P.O. Box 1029 Blindern, N-0315 Oslo (Norway); Arroja, Frederico, E-mail: maresuke.shiraishi@pd.infn.it, E-mail: d.f.mota@astro.uio.no, E-mail: angelo.ricciardone@pd.infn.it, E-mail: arroja@pd.infn.it [INFN, Sezione di Padova, via Marzolo 8, I-35131, Padova (Italy)

    2014-07-01

    Primordial statistical anisotropy is a key indicator to investigate early Universe models and has been probed by the cosmic microwave background (CMB) anisotropies. In this paper, we examine tensor-mode CMB fluctuations generated from anisotropic gravitational waves, parametrised by P{sub h}(k) = P{sub h}{sup (0)}(k) [ 1 + ∑{sub LM} f{sub L}(k) g{sub LM} Y{sub LM} ( k-circumflex )], where P{sub h}{sup (0)}(k) is the usual scale-invariant power spectrum. Such anisotropic tensor fluctuations may arise from an inflationary model with noncommutativity of fields. It is verified that in this model, an isotropic component and a quadrupole asymmetry with f{sub 0}(k) = f{sub 2}(k) ∝ k{sup -2} are created and hence highly red-tilted off-diagonal components arise in the CMB power spectra, namely ℓ{sub 2} = ℓ{sub 1} ± 2 in TT, TE, EE and BB, and ℓ{sub 2} = ℓ{sub 1} ± 1 in TB and EB. We find that B-mode polarisation is more sensitive to such signals than temperature and E-mode polarisation due to the smallness of large-scale cosmic variance and we can potentially measure g{sub 00} = 30 and g{sub 2M} = 58 at 68% CL in a cosmic-variance-limited experiment. Such a level of signal may be measured in a PRISM like experiment, while the instrumental noise contaminates it in the Planck experiment. These results imply that it is impossible to measure the noncommutative parameter if it is small enough for the perturbative treatment to be valid. Our formalism and methodology for dealing with the CMB tensor statistical anisotropy are general and straightforwardly applicable to other early Universe models.

  8. Transference of Fermi Contour Anisotropy to Composite Fermions.

    Science.gov (United States)

    Jo, Insun; Rosales, K A Villegas; Mueed, M A; Pfeiffer, L N; West, K W; Baldwin, K W; Winkler, R; Padmanabhan, Medini; Shayegan, M

    2017-07-07

    There has been a surge of recent interest in the role of anisotropy in interaction-induced phenomena in two-dimensional (2D) charged carrier systems. A fundamental question is how an anisotropy in the energy-band structure of the carriers at zero magnetic field affects the properties of the interacting particles at high fields, in particular of the composite fermions (CFs) and the fractional quantum Hall states (FQHSs). We demonstrate here tunable anisotropy for holes and hole-flux CFs confined to GaAs quantum wells, via applying in situ in-plane strain and measuring their Fermi wave vector anisotropy through commensurability oscillations. For strains on the order of 10^{-4} we observe significant deformations of the shapes of the Fermi contours for both holes and CFs. The measured Fermi contour anisotropy for CFs at high magnetic field (α_{CF}) is less than the anisotropy of their low-field hole (fermion) counterparts (α_{F}), and closely follows the relation α_{CF}=sqrt[α_{F}]. The energy gap measured for the ν=2/3 FQHS, on the other hand, is nearly unaffected by the Fermi contour anisotropy up to α_{F}∼3.3, the highest anisotropy achieved in our experiments.

  9. George Smoot, Blackbody, and Anisotropy of the Cosmic Microwave Background

    Science.gov (United States)

    the Cosmic Microwave Background Radiation Resources with Additional Information * Videos 'George Smoot anisotropy of the cosmic microwave background radiation." '1 Smoot previously won the Ernest Orlando . Smoot, blackbody, and anisotropy of the Cosmic Microwave Background (CMB) radiation is available in full

  10. The role of layer-induced anisotropy in seismic exploration

    NARCIS (Netherlands)

    Hake, J.H.

    1993-01-01

    In this thesis we focus on anisotropy caused by fine layering. We analyse the conditions that must be satisfied so that fine layering is equivalent to anisotropy. In the long-wavelength (or quasi-static) approximation an interval of thickness H, consisting of a sequence of layers, is effectively

  11. The role of layer-induced anisotropy in seismic exploration

    NARCIS (Netherlands)

    Hake, J.H.

    1992-01-01

    184In this thesis we focus on anisotropy caused by fine layering. We analyse the conditions that must be satisfied so that fine layering is equivalent to anisotropy. In the long-wavelength (or quasi-static) approximation an interval of thickness H, consisting of a sequence of layers, is

  12. Tuning the Magnetic Anisotropy at a Molecule-Metal Interface

    DEFF Research Database (Denmark)

    Bairagi, K.; Bellec, A.; Repain, V.

    2015-01-01

    We demonstrate that a C60 overlayer enhances the perpendicular magnetic anisotropy of a Co thin film, inducing an inverse spin reorientation transition from in plane to out of plane. The driving force is the C60/Co interfacial magnetic anisotropy that we have measured quantitatively in situ...

  13. Magnetic anisotropy of YFe.sub.3./sub. compound

    Czech Academy of Sciences Publication Activity Database

    Bolyachkin, A.S.; Neznakhin, D.S.; Garaeva, T.V.; Andreev, Alexander V.; Bartashevich, M. I.

    2017-01-01

    Roč. 426, Mar (2017), s. 740-743 ISSN 0304-8853 R&D Projects: GA ČR GA16-03593S Institutional support: RVO:68378271 Keywords : magnetic anisotropy * magnetization anisotropy * single crystal Subject RIV: BM - Solid Matter Physics ; Magnetism OBOR OECD: Condensed matter physics (including formerly solid state physics, supercond.) Impact factor: 2.630, year: 2016

  14. Primordial statistical anisotropy generated at the end of inflation

    International Nuclear Information System (INIS)

    Yokoyama, Shuichiro; Soda, Jiro

    2008-01-01

    We present a new mechanism for generating primordial statistical anisotropy of curvature perturbations. We introduce a vector field which has a non-minimal kinetic term and couples with a waterfall field in a hybrid inflation model. In such a system, the vector field gives fluctuations of the end of inflation and hence induces a subcomponent of curvature perturbations. Since the vector has a preferred direction, the statistical anisotropy could appear in the fluctuations. We present the explicit formula for the statistical anisotropy in the primordial power spectrum and the bispectrum of curvature perturbations. Interestingly, there is the possibility that the statistical anisotropy does not appear in the power spectrum but does appear in the bispectrum. We also find that the statistical anisotropy provides the shape dependence to the bispectrum

  15. Primordial statistical anisotropy generated at the end of inflation

    Energy Technology Data Exchange (ETDEWEB)

    Yokoyama, Shuichiro [Department of Physics and Astrophysics, Nagoya University, Aichi 464-8602 (Japan); Soda, Jiro, E-mail: shu@a.phys.nagoya-u.ac.jp, E-mail: jiro@tap.scphys.kyoto-u.ac.jp [Department of Physics, Kyoto University, Kyoto 606-8501 (Japan)

    2008-08-15

    We present a new mechanism for generating primordial statistical anisotropy of curvature perturbations. We introduce a vector field which has a non-minimal kinetic term and couples with a waterfall field in a hybrid inflation model. In such a system, the vector field gives fluctuations of the end of inflation and hence induces a subcomponent of curvature perturbations. Since the vector has a preferred direction, the statistical anisotropy could appear in the fluctuations. We present the explicit formula for the statistical anisotropy in the primordial power spectrum and the bispectrum of curvature perturbations. Interestingly, there is the possibility that the statistical anisotropy does not appear in the power spectrum but does appear in the bispectrum. We also find that the statistical anisotropy provides the shape dependence to the bispectrum.

  16. Non-Gaussianity and the Cosmic Microwave Background Anisotropies

    CERN Document Server

    Bartolo, N; Riotto, A

    2010-01-01

    We review in a pedagogical way the present status of the impact of non-Gaussianity (NG) on the Cosmic Microwave Background (CMB) anisotropies. We first show how to set the initial conditions at second-order for the (gauge invariant) CMB anisotropies when some primordial NG is present. However, there are many sources of NG in CMB anisotropies, beyond the primordial one, which can contaminate the primordial signal. We mainly focus on the NG generated from the post-inflationary evolution of the CMB anisotropies at second-order in perturbation theory at large and small angular scales, such as the ones generated at the recombination epoch. We show how to derive the equations to study the second-order CMB anisotropies and provide analytical computations to evaluate their contamination to primordial NG (complemented with numerical examples). We also offer a brief summary of other secondary effects. This review requires basic knowledge of the theory of cosmological perturbations at the linear level.

  17. Non-Gaussianity and the Cosmic Microwave Background Anisotropies

    Directory of Open Access Journals (Sweden)

    N. Bartolo

    2010-01-01

    microwave background (CMB anisotropies. We first show how to set the initial conditions at second order for the CMB anisotropies when some primordial NG is present. However, there are many sources of NG in CMB anisotropies, beyond the primordial one, which can contaminate the primordial signal. We mainly focus on the NG generated from the post inflationary evolution of the CMB anisotropies at second order in perturbation theory at large and small angular scales, such as the ones generated at the recombination epoch. We show how to derive the equations to study the second-order CMB anisotropies and provide analytical computations to evaluate their contamination to primordial NG (complemented with numerical examples. We also offer a brief summary of other secondary effects. This paper requires basic knowledge of the theory of cosmological perturbations at the linear level.

  18. Modeling, analysis, and visualization of anisotropy

    CERN Document Server

    Özarslan, Evren; Hotz, Ingrid

    2017-01-01

    This book focuses on the modeling, processing and visualization of anisotropy, irrespective of the context in which it emerges, using state-of-the-art mathematical tools. As such, it differs substantially from conventional reference works, which are centered on a particular application. It covers the following topics: (i) the geometric structure of tensors, (ii) statistical methods for tensor field processing, (iii) challenges in mapping neural connectivity and structural mechanics, (iv) processing of uncertainty, and (v) visualizing higher-order representations. In addition to original research contributions, it provides insightful reviews. This multidisciplinary book is the sixth in a series that aims to foster scientific exchange between communities employing tensors and other higher-order representations of directionally dependent data. A significant number of the chapters were co-authored by the participants of the workshop titled Multidisciplinary Approaches to Multivalued Data: Modeling, Visualization,...

  19. Signatures of Beam - and Anisotropy Driven Oscillitons

    Science.gov (United States)

    Sauer, K.; Dubinin, E.; McKenzie, J. F.

    Oscillitons represent a new class of stationary nonlinear waves, first found in bi-ion plasmas (Sauer et al., 1991) where mode splitting of the `individual' wave modes leads to conditions for phase- and group-standing waves near the `crossing points'. The corresponding structures have signatures of the usual solitons, superimposed by spatial oscillations. Oscillitons may also occur in single-ion plasmas, e.g. in the elec- tron whistler branch. The characteristic features of different types of oscillitons under realistic conditions in space plasmas including damping, beams and anisotropies are analyzed. Relevant mechanisms of coherent waves observed in different frequency ranges (Lion Roars at Earth, ion cyclotron waves near Io and Mars) are discussed.

  20. Cosmic ray anisotropies at high energies

    Science.gov (United States)

    Martinic, N. J.; Alarcon, A.; Teran, F.

    1986-01-01

    The directional anisotropies of the energetic cosmic ray gas due to the relative motion between the observers frame and the one where the relativistic gas can be assumed isotropic is analyzed. The radiation fluxes formula in the former frame must follow as the Lorentz invariance of dp/E, where p, E are the 4-vector momentum-energy components; dp is the 3-volume element in the momentum space. The anisotropic flux shows in such a case an amplitude, in a rotating earth, smaller than the experimental measurements from say, EAS-arrays for primary particle energies larger than 1.E(14) eV. Further, it is shown that two consecutive Lorentz transformations among three inertial frames exhibit the violation of dp/E invariance between the first and the third systems of reference, due to the Wigner rotation. A discussion of this result in the context of the experimental anisotropic fluxes and its current interpretation is given.

  1. Classical anisotropies in models of open inflation

    International Nuclear Information System (INIS)

    Garriga, J.; Mukhanov, V.F.

    1997-01-01

    In the simplest model of open inflation there are two inflaton fields decoupled from each other. One of them, the tunneling field, produces a first stage of inflation which prepares the ground for the nucleation of a highly symmetric bubble. The other, a free field, drives a second period of slow-roll inflation inside the bubble. However, the second field also evolves during the first stage of inflation, which to some extent breaks the needed symmetry. We show that this generates large supercurvature anisotropies which, together with the results of Tanaka and Sasaki, rule out this class of simple models (unless, of course, Ω 0 is sufficiently close to 1). The problem does not arise in modified models where the second field does not evolve in the first stage of inflation. copyright 1997 The American Physical Society

  2. Nanomagnets with high shape anisotropy and strong crystalline anisotropy: perspectives on magnetic force microscopy

    International Nuclear Information System (INIS)

    Campanella, H; Llobet, J; Esteve, J; Plaza, J A; Jaafar, M; Vázquez, M; Asenjo, A; Del Real, R P

    2011-01-01

    We report on a new approach for magnetic imaging, highly sensitive even in the presence of external, strong magnetic fields. Based on FIB-assisted fabricated high-aspect-ratio rare-earth nanomagnets, we produce groundbreaking magnetic force tips with hard magnetic character where we combine a high aspect ratio (shape anisotropy) together with strong crystalline anisotropy (rare-earth-based alloys). Rare-earth hard nanomagnets are then FIB-integrated to silicon microcantilevers as highly sharpened tips for high-field magnetic imaging applications. Force resolution and domain reversing and recovery capabilities are at least one order of magnitude better than for conventional magnetic tips. This work opens new, pioneering research fields on the surface magnetization process of nanostructures based either on relatively hard magnetic materials—used in magnetic storage media—or on materials like superparamagnetic particles, ferro/antiferromagnetic structures or paramagnetic materials.

  3. Induction of neuronal axon outgrowth by Shati/Nat8l by energy metabolism in mice cultured neurons.

    Science.gov (United States)

    Sumi, Kazuyuki; Uno, Kyosuke; Matsumura, Shohei; Miyamoto, Yoshiaki; Furukawa-Hibi, Yoko; Muramatsu, Shin-Ichi; Nabeshima, Toshitaka; Nitta, Atsumi

    2015-09-09

    A novel N-acetyltransferase, Shati/Nat8l, was identified in the nucleus accumbens of mice repeatedly treated with methamphetamine (METH). Shati/Nat8l has been reported to inhibit the pharmacological action induced by METH. Shati/Nat8l produces N-acetylaspartate from aspartate and acetyl-CoA. Previously, we reported that overexpression of Shati/Nat8l in nucleus accumbens attenuates the response to METH by N-acetylaspartylglutamate (which is derived from N-acetylaspartate)-mGluR3 signaling in the mice brain. In the present study, to clarify the type of cells that produce Shati/Nat8l, we carried out in-situ hybridization for the detection of Shati/Nat8l mRNA along with immunohistochemical studies using serial sections of mice brain. Shati/Nat8l mRNA was detected in neuronal cells, but not in astrocytes or microglia cells. Next, we investigated the function of Shati/Nat8l in the neuronal cells in mice brain; then, we used an adeno-associated virus vector containing Shati/Nat8l for transfection and overexpression of Shati/Nat8l protein into the primary cultured neurons to investigate the contribution toward the neuronal activity of Shati/Nat8l. Overexpression of Shati/Nat8l in the mice primary cultured neurons induced axonal growth, but not dendrite elongation at day 1.5 (DIV). This finding indicated that Shati/Nat8l contributes toward neuronal development. LY341495, a selective group II mGluRs antagonist, did not abolish this axonal growth, and N-acetylaspartylglutamate itself did not abolish axon outgrowth in the same cultured system. The cultured neurons overexpressing Shati/Nat8l contained high ATP, suggesting that axon outgrowth is dependent on energy metabolism. This study shows that Shati/Nat8l in the neuron may induce axon outgrowth by ATP synthesis and not through mGluR3 signaling.

  4. Flow-induced elastic anisotropy of metallic glasses

    International Nuclear Information System (INIS)

    Sun, Y.H.; Concustell, A.; Carpenter, M.A.; Qiao, J.C.; Rayment, A.W.; Greer, A.L.

    2016-01-01

    As-cast bulk metallic glasses are isotropic, but anisotropy can be induced by thermomechanical treatments. For example, the diffraction halo in the structure function S(Q) observed in transmission becomes elliptical (rather than circular) after creep in uniaxial tension or compression. Published studies associate this with frozen-in anelastic strain and bond-orientational anisotropy. Results so far are inconsistent on whether viscoplastic flow of metallic glasses can induce anisotropy. Preliminary diffraction data suggest that the anisotropy, if any, is very low, while measurements of the elastic properties suggest that there is induced anisotropy, opposite in sign to that due to anelastic strain. We study three bulk metallic glasses, Ce 65 Al 10 Cu 20 Co 5 , La 55 Ni 10 Al 35 , and Pd 40 Ni 30 Cu 10 P 20 . By using resonant ultrasound spectroscopy to determine the full elasticity tensor, the effects of relaxation and rejuvenation can be reliably separated from uniaxial anisotropy (of either sign). The effects of viscoplastic flow in tension are reported for the first time. We find that viscoplastic flow of bulk metallic glasses, particularly in tension, can induce significant anisotropy that is distinct from that associated with frozen-in anelastic strain. The conditions for inducing such anisotropy are explored in terms of the Weissenberg number (ratio of relaxation times for primary relaxation and for shear strain rate). There is a clear need for further work to characterize the structural origins of flow-induced anisotropy and to explore the prospects for improved mechanical and other properties through induced anisotropy.

  5. Solo/Trio8, a membrane-associated short isoform of Trio, modulates endosome dynamics and neurite elongation.

    Science.gov (United States)

    Sun, Ying-Jie; Nishikawa, Kaori; Yuda, Hideki; Wang, Yu-Lai; Osaka, Hitoshi; Fukazawa, Nobuna; Naito, Akira; Kudo, Yoshihisa; Wada, Keiji; Aoki, Shunsuke

    2006-09-01

    With DNA microarrays, we identified a gene, termed Solo, that is downregulated in the cerebellum of Purkinje cell degeneration mutant mice. Solo is a mouse homologue of rat Trio8-one of multiple Trio isoforms recently identified in rat brain. Solo/Trio8 contains N-terminal sec14-like and spectrin-like repeat domains followed by a single guanine nucleotide exchange factor 1 (GEF1) domain, but it lacks the C-terminal GEF2, immunoglobulin-like, and kinase domains that are typical of Trio. Solo/Trio8 is predominantly expressed in Purkinje neurons of the mouse brain, and expression begins following birth and increases during Purkinje neuron maturation. We identified a novel C-terminal membrane-anchoring domain in Solo/Trio8 that is required for enhanced green fluorescent protein-Solo/Trio8 localization to early endosomes (positive for both early-endosome antigen 1 [EEA1] and Rab5) in COS-7 cells and primary cultured neurons. Solo/Trio8 overexpression in COS-7 cells augmented the EEA1-positive early-endosome pool, and this effect was abolished via mutation and inactivation of the GEF domain or deletion of the C-terminal membrane-anchoring domain. Moreover, primary cultured neurons transfected with Solo/Trio8 showed increased neurite elongation that was dependent on these domains. These results suggest that Solo/Trio8 acts as an early-endosome-specific upstream activator of Rho family GTPases for neurite elongation of developing Purkinje neurons.

  6. Control of bacillus cereus spore germination and outgrowth in cooked rice during chilling by nonorganic and organic appled, orange, and potato peel powders

    Science.gov (United States)

    The inhibition of Bacillus cereus spore germination and outgrowth in cooked rice by nine fruit and vegetable peel powders prepared from store-bought conventional (nonorganic) and organic apples, oranges, and potatoes was investigated. The powders were mixed into rice at 10% (wt/wt) along with heat ...

  7. Daytime Thermal Anisotropy of Urban Neighbourhoods: Morphological Causation

    Directory of Open Access Journals (Sweden)

    E. Scott Krayenhoff

    2016-01-01

    Full Text Available Surface temperature is a key variable in boundary-layer meteorology and is typically acquired by remote observation of emitted thermal radiation. However, the three-dimensional structure of cities complicates matters: uneven solar heating of urban facets produces an “effective anisotropy” of surface thermal emission at the neighbourhood scale. Remotely-sensed urban surface temperature varies with sensor view angle as a consequence. The authors combine a microscale urban surface temperature model with a thermal remote sensing model to predict the effective anisotropy of simplified neighbourhood configurations. The former model provides detailed surface temperature distributions for a range of “urban” forms, and the remote sensing model computes aggregate temperatures for multiple view angles. The combined model’s ability to reproduce observed anisotropy is evaluated against measurements from a neighbourhood in Vancouver, Canada. As in previous modeling studies, anisotropy is underestimated. Addition of moderate coverages of small (sub-facet scale structure can account for much of the missing anisotropy. Subsequently, over 1900 sensitivity simulations are performed with the model combination, and the dependence of daytime effective thermal anisotropy on diurnal solar path (i.e., latitude and time of day and blunt neighbourhood form is assessed. The range of effective anisotropy, as well as the maximum difference from nadir-observed brightness temperature, peak for moderate building-height-to-spacing ratios (H/W, and scale with canyon (between-building area; dispersed high-rise urban forms generate maximum anisotropy. Maximum anisotropy increases with solar elevation and scales with shortwave irradiance. Moreover, it depends linearly on H/W for H/W < 1.25, with a slope that depends on maximum off-nadir sensor angle. Decreasing minimum brightness temperature is primarily responsible for this linear growth of maximum anisotropy. These

  8. Magnetic anisotropy of ultrafine 316L stainless steel fibers

    Energy Technology Data Exchange (ETDEWEB)

    Shyr, Tien-Wei, E-mail: twshyr@fcu.edu.tw [Department of Fiber and Composite Materials, Feng Chia University, No. 100, Wenhwa Road, Seatwen, Taichung 40724, Taiwan, ROC (China); Huang, Shih-Ju [Department of Fiber and Composite Materials, Feng Chia University, No. 100, Wenhwa Road, Seatwen, Taichung 40724, Taiwan, ROC (China); Wur, Ching-Shuei [Department of Physics, National Cheng Kung University, No. 1, University Road, Tainan 70101, Taiwan, ROC (China)

    2016-12-01

    An as-received 316L stainless steel fiber with a diameter of 20 μm was drawn using a bundle drawing process at room temperature to form ultrafine stainless steel fibers with diameters of 12, 8, and 6 μm. The crystalline phases of the fibers were analyzed using the X-ray diffraction (XRD) profile fitting technique. The grain sizes of γ-austenite and α′-martensite were reduced to nanoscale sizes after the drawing process. XRD analysis and focused ion beam-scanning electron microscope observations showed that the newly formed α′-martensitic grains were closely arrayed in the drawing direction. The magnetic property was measured using a superconducting quantum interference device vibrating sample magnetometer. The magnetic anisotropy of the fibers was observed by applying a magnetic field parallel and perpendicular to the fiber axis. The results showed that the microstructure anisotropy including the shape anisotropy, magnetocrystalline anisotropy, and the orientation of the crystalline phases strongly contributed to the magnetic anisotropy. - Highlights: • The martensitic transformation of the 316L SS fiber occurred during the cold drawn. • The grain sizes of γ-austenite and α′-martensite were reduced to the nanoscale. • The newly formed martensitic grains were closely arrayed in the drawing direction. • The drawing process caused the magnetic easy axis to be aligned with the fiber axis. • The microstructure anisotropy strongly contributed to the magnetic anisotropy.

  9. Geomechanical Anisotropy and Rock Fabric in Shales

    Science.gov (United States)

    Huffman, K. A.; Connolly, P.; Thornton, D. A.

    2017-12-01

    Digital rock physics (DRP) is an emerging area of qualitative and quantitative scientific analysis that has been employed on a variety of rock types at various scales to characterize petrophysical, mechanical, and hydraulic rock properties. This contribution presents a generic geomechanically focused DRP workflow involving image segmentation by geomechanical constituents, generation of finite element (FE) meshes, and application of various boundary conditions (i.e. at the edge of the domain and at boundaries of various components such as edges of individual grains). The generic workflow enables use of constituent geological objects and relationships in a computational based approach to address specific questions in a variety of rock types at various scales. Two examples are 1) modeling stress dependent permeability, where it occurs and why it occurs at the grain scale; 2) simulating the path and complexity of primary fractures and matrix damage in materials with minerals or intervals of different mechanical behavior. Geomechanical properties and fabric characterization obtained from 100 micron shale SEM images using the generic DRP workflow are presented. Image segmentation and development of FE simulation composed of relatively simple components (elastic materials, frictional contacts) and boundary conditions enable the determination of bulk static elastic properties. The procedure is repeated for co-located images at pertinent orientations to determine mechanical anisotropy. The static moduli obtained are benchmarked against lab derived measurements since material properties (esp. frictional ones) are poorly constrained at the scale of investigation. Once confidence in the input material parameters is gained, the procedure can be used to characterize more samples (i.e. images) than is possible from rock samples alone. Integration of static elastic properties with grain statistics and geologic (facies) conceptual models derived from core and geophysical logs

  10. Switching the uniaxial magnetic anisotropy by ion irradiation induced compensation

    Science.gov (United States)

    Yuan, Ye; Amarouche, Teyri; Xu, Chi; Rushforth, Andrew; Böttger, Roman; Edmonds, Kevin; Campion, Richard; Gallagher, Bryan; Helm, Manfred; Jürgen von Bardeleben, Hans; Zhou, Shengqiang

    2018-04-01

    In the present work, the uniaxial magnetic anisotropy of GaMnAsP is modified by helium ion irradiation. According to the micro-magnetic parameters, e.g. resonance fields and anisotropy constants deduced from ferromagnetic resonance measurements, a rotation of the magnetic easy axis from out-of-plane [0 0 1] to in-plane [1 0 0] direction is achieved. From the application point of view, our work presents a novel avenue in modifying the uniaxial magnetic anisotropy in GaMnAsP with the possibility of lateral patterning by using lithography or focused ion beam.

  11. Magnetic transitions and phases in random-anisotropy magnets

    International Nuclear Information System (INIS)

    Sellmyer, D.J.; Nafis, S.; O'Shea, M.J.

    1988-01-01

    The generality and universality of the Ising spin-glass-like phase transitions observed in several rare-earth, random-anisotropy magnets are discussed. Some uncertainties and practical problems in determining critical exponents are considered, and a comparison is made to insulating spin glasses and crystalline spin glasses where an apparent anisotropy-induced crossover from Heisenberg to Ising-like behavior is seen. The observation of a reentrant transition in a weak anisotropy system and its correlation with the theory of Chudnovsky, Saslow, and Serota [Phys. Rev. B 33, 251 (1986)] for the correlated spin glass is discussed

  12. Magnetic transitions and phases in random-anisotropy magnets

    Science.gov (United States)

    Sellmyer, D. J.; Nafis, S.; O'Shea, M. J.

    1988-04-01

    The generality and universality of the Ising spin-glass-like phase transitions observed in several rare-earth, random-anisotropy magnets are discussed. Some uncertainties and practical problems in determining critical exponents are considered, and a comparison is made to insulating spin glasses and crystalline spin glasses where an apparent anisotropy-induced crossover from Heisenberg to Ising-like behavior is seen. The observation of a reentrant transition in a weak anisotropy system and its correlation with the theory of Chudnovsky, Saslow, and Serota [Phys. Rev. B 33, 251 (1986)] for the correlated spin glass is discussed.

  13. Canonical Transform Method for Treating Strongly Anisotropy Magnets

    DEFF Research Database (Denmark)

    Cooke, J. F.; Lindgård, Per-Anker

    1977-01-01

    An infinite-order perturbation approach to the theory of magnetism in magnets with strong single-ion anisotropy is given. This approach is based on a canonical transformation of the system into one with a diagonal crystal field, an effective two-ion anisotropy, and reduced ground-state corrections....... A matrix-element matching procedure is used to obtain an explicit expression for the spin-wave energy to second order. The consequences of this theory are illustrated by an application to a simple example with planar anisotropy and an external magnetic field. A detailed comparison between the results...

  14. Helically symmetric equilibria with pressure anisotropy and incompressible plasma flow

    Science.gov (United States)

    Evangelias, A.; Kuiroukidis, A.; Throumoulopoulos, G. N.

    2018-02-01

    We derive a generalized Grad-Shafranov equation governing helically symmetric equilibria with pressure anisotropy and incompressible flow of arbitrary direction. Through the most general linearizing ansatz for the various free surface functions involved therein, we construct equilibrium solutions and study their properties. It turns out that pressure anisotropy can act either paramegnetically or diamagnetically, the parallel flow has a paramagnetic effect, while the non-parallel component of the flow associated with the electric field has a diamagnetic one. Also, pressure anisotropy and flow affect noticeably the helical current density.

  15. Bianchi-V string cosmological model with dark energy anisotropy

    Science.gov (United States)

    Mishra, B.; Tripathy, S. K.; Ray, Pratik P.

    2018-05-01

    The role of anisotropic components on the dark energy and the dynamics of the universe is investigated. An anisotropic dark energy fluid with different pressures along different spatial directions is assumed to incorporate the effect of anisotropy. One dimensional cosmic strings aligned along x-direction supplement some kind of anisotropy. Anisotropy in the dark energy pressure is found to evolve with cosmic expansion at least at late times. At an early phase, the anisotropic effect due to the cosmic strings substantially affect the dynamics of the accelerating universe.

  16. Electron temperature anisotropy modeling and its effect on anisotropy-magnetic field coupling in an underdense laser heated plasma

    Energy Technology Data Exchange (ETDEWEB)

    Morreeuw, J.P.; Dubroca, B. [CEA Centre d' Etudes Scientifiques et Techniques d' Aquitaine, 33 - Le Barp (France); Sangam, A.; Dubroca, B.; Charrier, P.; Tikhonchuk, V.T. [Bordeaux-1 Univ., CELIA, 33 - Talence (France); Sangam, A.; Dubroca, B.; Charrier, P. [Bordeaux-1 Univ., MAB, 33 - Talence (France)

    2006-06-15

    The laser interaction with an underdense plasma leads to an anisotropic laser heating of electrons. This temperature anisotropy gradient in turn is the source of an early magnetic field, which has an important effect on the plasma evolution, due to the thermal flux reduction. We describe the temperature anisotropy by an evolution equation including the anisotropy-magnetic field coupling and observe a rather efficient magnetic field generation. However at high anisotropy levels, a small-scale instability emerges, leading to a serious problem in numerical calculations. We introduce the kinetics effects, which fix the problem by the anisotropy diffusion through the heat flux tensor. A constant-coefficient Fokker-Planck model in the 2-dimensional geometry allows us to derive an anisotropy diffusion term. The diffusion coefficient is fitted from the kinetic theory of the collisional anisotropic (Weibel) instability growth rate. Such an anisotropy diffusion term wipes out the unphysical instability without any undesirable smoothing. This diffusion along with the viscosity term leads also to a quite good restitution of the Weibel instability growth rate and to the short wavelength cutoff, even in a weakly collisional situation. This allows us to use such a model to predict the emergence of the Weibel instability as well as its saturation. (authors)

  17. Relationship between electrical conductivity anisotropy and fabric anisotropy in granular materials during drained triaxial compressive tests: a numerical approach

    Science.gov (United States)

    Niu, Qifei; Revil, André; Li, Zhaofeng; Wang, Yu-Hsing

    2017-07-01

    The anisotropy of granular media and its evolution during shearing are important aspects required in developing physics-based constitutive models in Earth sciences. The development of relationships between geoelectrical properties and the deformation of porous media has applications to the monitoring of faulting and landslides. However, such relationships are still poorly understood. In this study, we first investigate the definition of the electrical conductivity anisotropy tensor of granular materials in presence of surface conductivity of the grains. Fabric anisotropy is related to the components of the fabric tensor. We define an electrical anisotropy factor based on the Archie's exponent second-order symmetric tensor m of granular materials. We use numerical simulations to confirm a relationship between the evolution of electrical and fabric anisotropy factors during shearing. To realize the simulations, we build a virtual laboratory in which we can easily perform synthetic experiments. We first simulate drained compressive triaxial tests of loose and dense granular materials (porosity 0.45 and 0.38, respectively) using the discrete element method. Then, the electrical conductivity tensor of a set of deformed synthetic samples is computed using the finite-difference method. The numerical results show that shear strains are responsible for a measurable anisotropy in the bulk conductivity of granular media. The observed electrical anisotropy response, during shearing, is distinct for dense and loose synthetic samples. Electrical and fabric anisotropy factors exhibit however a unique linear correlation, regardless of the shear strain and the initial state (porosity) of the synthetic samples. The practical implication of this finding confirms the usefulness of the electrical conductivity method in studying the fabric tensor of granular media. This result opens the door in using time-lapse electrical resistivity to study non-intrusively the evolution of anisotropy

  18. Twinning anisotropy of tantalum during nanoindentation

    Energy Technology Data Exchange (ETDEWEB)

    Goel, Saurav, E-mail: S.GOEL@qub.ac.uk [School of Mechanical and Aerospace Engineering, Queen' s University, Belfast, BT9 5AH (United Kingdom); Beake, Ben [Micro Materials Limited, Willow House, Yale Business Village, Ellice Way, Wrexham LL13 7YL (United Kingdom); Dalton Research Institute, Manchester Metropolitan University, Manchester, M15GD (United Kingdom); Chan, Chi-Wai [School of Mechanical and Aerospace Engineering, Queen' s University, Belfast, BT9 5AH (United Kingdom); Haque Faisal, Nadimul [School of Engineering, Robert Gordon University, Garthdee Road, Aberdeen AB10 7GJ (United Kingdom); Dunne, Nicholas [School of Mechanical and Aerospace Engineering, Queen' s University, Belfast, BT9 5AH (United Kingdom)

    2015-03-11

    Unlike other BCC metals, the plastic deformation of nanocrystalline Tantalum (Ta) during compression is regulated by deformation twinning. Whether or not this twinning exhibits anisotropy was investigated through simulation of displacement-controlled nanoindentation test using molecular dynamics (MD) simulation. MD data was found to correlate well with the experimental data in terms of surface topography and hardness measurements. The mechanism of the transport of material was identified due to the formation and motion of prismatic dislocations loops (edge dislocations) belonging to the 1/2〈111〉 type and 〈100〉 type Burgers vector family. Further analysis of crystal defects using a fully automated dislocation extraction algorithm (DXA) illuminated formation and migration of twin boundaries on the (110) and (111) orientation but not on the (010) orientation and most importantly after retraction all the dislocations disappeared on the (110) orientation suggesting twinning to dominate dislocation nucleation in driving plasticity in tantalum. A significant finding was that the maximum shear stress (critical Tresca stress) in the deformation zone exceeded the theoretical shear strength of Ta (Shear modulus/2π~10.03 GPa) on the (010) orientation but was lower than it on the (110) and the (111) orientations. In light of this, the conventional lore of assuming the maximum shear stress being 0.465 times the mean contact pressure was found to break down at atomic scale.

  19. Cosmic ray anisotropy searches with AMS-02

    Energy Technology Data Exchange (ETDEWEB)

    Zeissler, Stefan; Gebauer, Iris; Trumpf, Ricarda [Karlsruher Institut fuer Technologie (KIT) (Germany)

    2016-07-01

    The Alpha Magnetic Spectrometer (AMS-02) is a state-of-the-art particle detector designed to operate as an external module on the International Space Station (ISS). In this unique space environment cosmic particles can be measured with high precision over an energy range from GeV up to TeV. The AMS collaboration provided precise measurements of the electron and positron fluxes, which indicate an additional source of positrons among the various cosmic particles. Possible candidates for this source are local pulsars, a local source of positrons produced in proton-gas interactions or dark matter annihilation. In the first two cases a possible anisotropy in the electrons and positrons incoming direction at Earth might be detectable. To determine the level of isotropy the measured data is compared to reference maps, which simulate the measurement of an isotropic sky. A common choice of reference maps are proton count maps or shuffled maps, which redistribute measured incoming directions over the whole measuring time. Both choices lead to difficulties in the reconstruction of a marginal signal with a big expansion over the galactic sky as it would be the case for charged cosmic particles. We developed a method to construct reference maps based on fundamental detector characteristics such as the lifetime and the geometric acceptance. Using this we are able to reconstruct the isotropic sky as it would be seen by the detector. We demonstrate the performance of the method using AMS-02 data.

  20. Studies of anisotropy of iron based superconductors

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, Jason A. [Iowa State Univ., Ames, IA (United States)

    2013-01-01

    To study the electronic anisotropy in iron based superconductors, the temperature dependent London penetration depth, Δλ(T), have been measured in several compounds, along with the angular dependent upper critical field, Hc2(T). Study was undertaken on single crystals of Ba(Fe1-xCox)2As2 with x=0.108 and x=0.127, in the overdoped range of the doping phase diagram, characterized by notable modulation of the superconducting gap. Heavy ion irradiation with matching field doses of 6 T and 6.5 T respectively, were used to create columnar defects and to study their effect on the temperature Δλ(T). The variation of the low-temperature penetration depth in both pristine and irradiated samples was fitted with a power-law function Δλ(T) = ATn. Irradiation increases the magnitude of the pre-factor A and decreases the exponent n, similar to the effect on the optimally doped samples. This finding supports the universal s ± scenario for the whole doping range.

  1. Nanoscale magnetic ratchets based on shape anisotropy

    Science.gov (United States)

    Cui, Jizhai; Keller, Scott M.; Liang, Cheng-Yen; Carman, Gregory P.; Lynch, Christopher S.

    2017-02-01

    Controlling magnetization using piezoelectric strain through the magnetoelectric effect offers several orders of magnitude reduction in energy consumption for spintronic applications. However strain is a uniaxial effect and, unlike directional magnetic field or spin-polarized current, cannot induce a full 180° reorientation of the magnetization vector when acting alone. We have engineered novel ‘peanut’ and ‘cat-eye’ shaped nanomagnets on piezoelectric substrates that undergo repeated deterministic 180° magnetization rotations in response to individual electric-field-induced strain pulses by breaking the uniaxial symmetry using shape anisotropy. This behavior can be likened to a magnetic ratchet, advancing magnetization clockwise with each piezostrain trigger. The results were validated using micromagnetics implemented in a multiphysics finite elements code to simulate the engineered spatial and temporal magnetic behavior. The engineering principles start from a target device function and proceed to the identification of shapes that produce the desired function. This approach opens a broad design space for next generation magnetoelectric spintronic devices.

  2. Wave anisotropy of shear viscosity and elasticity

    Science.gov (United States)

    Rudenko, O. V.; Sarvazyan, A. P.

    2014-11-01

    The paper presents the theory of shear wave propagation in a "soft solid" material possessing anisotropy of elastic and dissipative properties. The theory is developed mainly for understanding the nature of the low-frequency acoustic characteristics of skeletal muscles, which carry important diagnostic information on the functional state of muscles and their pathologies. It is shown that the shear elasticity of muscles is determined by two independent moduli. The dissipative properties are determined by the fourth-rank viscosity tensor, which also has two independent components. The propagation velocity and attenuation of shear waves in muscle depend on the relative orientation of three vectors: the wave vector, the polarization vector, and the direction of muscle fiber. For one of the many experiments where attention was distinctly focused on the vector character of the wave process, it was possible to make a comparison with the theory, estimate the elasticity moduli, and obtain agreement with the angular dependence of the wave propagation velocity predicted by the theory.

  3. Tailoring of magnetic anisotropy of Fe-rich microwires by stress induced anisotropy

    International Nuclear Information System (INIS)

    Zhukov, A.; Zhukova, V.; Larin, V.; Gonzalez, J.

    2006-01-01

    We report on tailoring of magnetic properties and GMI of Fe 69 B 12 Si 14 C 5 glass-coated microwires by stress annealing. The induced magnetic anisotropy field depend on temperature and time of annealing and applied stress. At certain conditions considerable GMI effect (up to 65%) has been achieved. Application of the tensile stress drastically affects the shape of the hysteresis loop of stress-annealed sample and its GMI effect. In this way the shape of the hysteresis loop and GMI effect can by tailored by controllable way

  4. Issues on generating primordial anisotropies at the end of inflation

    Energy Technology Data Exchange (ETDEWEB)

    Emami, Razieh; Firouzjahi, Hassan, E-mail: emami@mail.ipm.ir, E-mail: firouz@mail.ipm.ir [School of Physics, Institute for Research in Fundamental Sciences (IPM), P.O. Box 19395-5531, Tehran (Iran, Islamic Republic of)

    2012-01-01

    We revisit the idea of generating primordial anisotropies at the end of inflation in models of inflation with gauge fields. To be specific we consider the charged hybrid inflation model where the waterfall field is charged under a U(1) gauge field so the surface of end of inflation is controlled both by inflaton and the gauge fields. Using δN formalism properly we find that the anisotropies generated at the end of inflation from the gauge field fluctuations are exponentially suppressed on cosmological scales. This is because the gauge field evolves exponentially during inflation while in order to generate appreciable anisotropies at the end of inflation the spectator gauge field has to be frozen. We argue that this is a generic feature, that is, one can not generate observable anisotropies at the end of inflation within an FRW background.

  5. Issues on generating primordial anisotropies at the end of inflation

    International Nuclear Information System (INIS)

    Emami, Razieh; Firouzjahi, Hassan

    2012-01-01

    We revisit the idea of generating primordial anisotropies at the end of inflation in models of inflation with gauge fields. To be specific we consider the charged hybrid inflation model where the waterfall field is charged under a U(1) gauge field so the surface of end of inflation is controlled both by inflaton and the gauge fields. Using δN formalism properly we find that the anisotropies generated at the end of inflation from the gauge field fluctuations are exponentially suppressed on cosmological scales. This is because the gauge field evolves exponentially during inflation while in order to generate appreciable anisotropies at the end of inflation the spectator gauge field has to be frozen. We argue that this is a generic feature, that is, one can not generate observable anisotropies at the end of inflation within an FRW background

  6. Current sheets and pressure anisotropy in the reconnection exhaust

    International Nuclear Information System (INIS)

    Le, A.; Karimabadi, H.; Roytershteyn, V.; Egedal, J.; Ng, J.; Scudder, J.; Daughton, W.; Liu, Y.-H.

    2014-01-01

    A particle-in-cell simulation shows that the exhaust during anti-parallel reconnection in the collisionless regime contains a current sheet extending 100 inertial lengths from the X line. The current sheet is supported by electron pressure anisotropy near the X line and ion anisotropy farther downstream. Field-aligned electron currents flowing outside the magnetic separatrices feed the exhaust current sheet and generate the out-of-plane, or Hall, magnetic field. Existing models based on different mechanisms for each particle species provide good estimates for the levels of pressure anisotropy. The ion anisotropy, which is strong enough to reach the firehose instability threshold, is also important for overall force balance. It reduces the outflow speed of the plasma

  7. Current sheets and pressure anisotropy in the reconnection exhaust

    Energy Technology Data Exchange (ETDEWEB)

    Le, A.; Karimabadi, H.; Roytershteyn, V. [SciberQuest, Inc., Del Mar, California 92014 (United States); Egedal, J. [University of Wisconsin–Madison, Madison, Wisconsin 53706 (United States); Ng, J. [PPPL, Princeton University, Princeton, New Jersey 08543 (United States); Scudder, J. [University of Iowa, Iowa City, Iowa 52242 (United States); Daughton, W.; Liu, Y.-H. [Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States)

    2014-01-15

    A particle-in-cell simulation shows that the exhaust during anti-parallel reconnection in the collisionless regime contains a current sheet extending 100 inertial lengths from the X line. The current sheet is supported by electron pressure anisotropy near the X line and ion anisotropy farther downstream. Field-aligned electron currents flowing outside the magnetic separatrices feed the exhaust current sheet and generate the out-of-plane, or Hall, magnetic field. Existing models based on different mechanisms for each particle species provide good estimates for the levels of pressure anisotropy. The ion anisotropy, which is strong enough to reach the firehose instability threshold, is also important for overall force balance. It reduces the outflow speed of the plasma.

  8. Anisotropies of in-phase, out-of-phase,\

    Czech Academy of Sciences Publication Activity Database

    Hrouda, F.; Chadima, Martin; Ježek, J.; Kadlec, Jaroslav

    2018-01-01

    Roč. 62 (2018) ISSN 0039-3169 Institutional support: RVO:67985530 ; RVO:67985831 Keywords : anisotropy * out-of-phase susceptibility * frequency-dependent susceptibility Subject RIV: DB - Geology ; Mineralogy Impact factor: 0.764, year: 2016

  9. Dark matter electron anisotropy. A universal upper limit

    International Nuclear Information System (INIS)

    Borriello, Enrico; Maccione, Luca; Cuoco, Alessandro

    2010-12-01

    Indirect searches of particle Dark Matter (DM) with high energy Cosmic Rays (CR) are affected by large uncertainties, coming both from the DM side, and from poor understanding of the astrophysical backgrounds. We show that, on the contrary, the DM intrinsic degree of anisotropy in the arrival directions of high energy CR electrons and positrons does not suffer from these unknowns. Furthermore, if contributions from possible local sources are neglected, the intrinsic DM anisotropy sets the maximum degree of total anisotropy. As a consequence, if some anisotropy larger than the DM upper bound is detected, its origin could not be ascribed to DM, and would constitute an unambiguous evidence for the presence of astrophysical local discrete sources of high energy electrons and positrons. The Fermi-LAT will be able to probe such scenarios in the next years. (orig.)

  10. Anisotropy of magnetic susceptibility (AMS) studies of Campanian ...

    Indian Academy of Sciences (India)

    trial, paralic and shallow marine strata. It com- prises of lower ... Sillakkudi sandstone was deposited under shallow ..... Jelinek V 1978 Statistical processing of anisotropy of mag- ... reorientation of magnetic fabrics in deep-sea sediments at.

  11. Searches for Anisotropy of Cosmic Rays with the Telescope Array

    Science.gov (United States)

    Cady, Robert; Telescope Array Collaboration

    2016-03-01

    With over seven years of data from the TA surface detector array, we will present the results of various searches for anisotropies in the arrival direction of cosmic rays, including an update of the hotspot above 57 EeV.

  12. Computing magnetic anisotropy constants of single molecule magnets

    Indian Academy of Sciences (India)

    Administrator

    Treating the anisotropy Hamiltonian as perturbation, we compute ... The dependence of DM on the energy gap between the ground and the excited states in both the systems has also been studied by using different sets of exchange constants.

  13. Quantifying seismic anisotropy induced by small-scale chemical heterogeneities

    Science.gov (United States)

    Alder, C.; Bodin, T.; Ricard, Y.; Capdeville, Y.; Debayle, E.; Montagner, J. P.

    2017-12-01

    Observations of seismic anisotropy are usually used as a proxy for lattice-preferred orientation (LPO) of anisotropic minerals in the Earth's mantle. In this way, seismic anisotropy observed in tomographic models provides important constraints on the geometry of mantle deformation associated with thermal convection and plate tectonics. However, in addition to LPO, small-scale heterogeneities that cannot be resolved by long-period seismic waves may also produce anisotropy. The observed (i.e. apparent) anisotropy is then a combination of an intrinsic and an extrinsic component. Assuming the Earth's mantle exhibits petrological inhomogeneities at all scales, tomographic models built from long-period seismic waves may thus display extrinsic anisotropy. In this paper, we investigate the relation between the amplitude of seismic heterogeneities and the level of induced S-wave radial anisotropy as seen by long-period seismic waves. We generate some simple 1-D and 2-D isotropic models that exhibit a power spectrum of heterogeneities as what is expected for the Earth's mantle, that is, varying as 1/k, with k the wavenumber of these heterogeneities. The 1-D toy models correspond to simple layered media. In the 2-D case, our models depict marble-cake patterns in which an anomaly in shear wave velocity has been advected within convective cells. The long-wavelength equivalents of these models are computed using upscaling relations that link properties of a rapidly varying elastic medium to properties of the effective, that is, apparent, medium as seen by long-period waves. The resulting homogenized media exhibit extrinsic anisotropy and represent what would be observed in tomography. In the 1-D case, we analytically show that the level of anisotropy increases with the square of the amplitude of heterogeneities. This relation is numerically verified for both 1-D and 2-D media. In addition, we predict that 10 per cent of chemical heterogeneities in 2-D marble-cake models can

  14. Anisotropy of phase transformations in crystallization of polar compounds

    Energy Technology Data Exchange (ETDEWEB)

    Orlov, A M; Belashchenko, D K; Derikova, S A [Krasnoyarskij Inst. Tsvetnykh Metallov (USSR)

    1977-03-01

    Migration of molten inclusions in polar compounds of the type of A/sup 3/B/sup 5/ in the range of 750-950 deg C is characterized by clearly defined anisotropy. The values of the melting-crystallization rate constant for n-type InAs and GaAs conductivity are estimated. The anisotropy of the properties leaves its imprint not only on the drift velocity, but also on the form of the displaced inclusions.

  15. Stress-induced magnetic anisotropy in nanocrystalline alloys

    International Nuclear Information System (INIS)

    Varga, L.K.; Gercsi, Zs.; Kovacs, Gy.; Kakay, A.; Mazaleyrat, F.

    2003-01-01

    Stress-annealing experiments were extended to both nanocrystalline alloy families, Finemet and Nanoperm (Hitperm), and, for comparison, to amorphous Fe 62 Nb 8 B 30 alloy. For both Finemet and bulk amorphous, stress-annealing results in a strong induced transversal anisotropy (flattening of hysteresis loop) but yields longitudinal induced anisotropy (square hysteresis loop) in Nanoperm and Hitperm. These results are interpreted in terms of back-stress theory

  16. Anisotropy signature in extended images from reverse-time migration

    KAUST Repository

    Sava, Paul

    2012-11-04

    Reverse-time migration can accurately image complex geologic structures in anisotropic media. Extended images at selected locations in the earth, i.e. at common-image-point gathers (CIPs), carry enough information to characterize the angle-dependent illumination and to provide measurements for migration velocity analysis. Furthermore, inaccurate anisotropy leaves a distinctive signature in CIPs, which can be used to evaluate anisotropy through techniques similar to the ones used in conventional wavefield tomography.

  17. Anisotropy signature in extended images from reverse-time migration

    KAUST Repository

    Sava, Paul; Alkhalifah, Tariq Ali

    2012-01-01

    Reverse-time migration can accurately image complex geologic structures in anisotropic media. Extended images at selected locations in the earth, i.e. at common-image-point gathers (CIPs), carry enough information to characterize the angle-dependent illumination and to provide measurements for migration velocity analysis. Furthermore, inaccurate anisotropy leaves a distinctive signature in CIPs, which can be used to evaluate anisotropy through techniques similar to the ones used in conventional wavefield tomography.

  18. Geodynamic Constraints on the Sources of Seismic Anisotropy Beneath Madagascar

    Science.gov (United States)

    Rajaonarison, T. A.; Stamps, D. S.; Fishwick, S.

    2017-12-01

    The rheological structure of the lithosphere-asthenosphere system controls the degree in which the mantle drives surface motions. Seismic anisotropy is a proxy to infer information about previous tectonic events imprinted in lithospheric structures and/or asthenospheric flow pattern in regions absent of active volcanism, however, distinguishing between the shallow and deeper sources, respectively, remains ambiguous. Madagascar is an ideal natural laboratory to study the sources of anisotropy and the rheological implications for lithosphere-asthenosphere system because 1) active volcanism is minimal or absent, 2) there are well-exposed tectonic fabrics for comparison, and 3) numerous geological and geophysical observations provides evidence of present-day tectonic activities. Recent studies suggest new seismic anisotropy observations in southern Madagascar are sourced from both fossilized lithospheric structure and asthenospheric flow driven by rigid lithospheric plate motion. In this work we compare geodynamic simulations of the lithosphere-asthenosphere system with seismic anisotropy data set that includes all of Madagascar. We use the numerical code Advanced Solver for Problems in Earth's ConvecTion (ASPECT) to calculate instantaneous deformation in the lithosphere and edge-driven convective flow in the asthenosphere accounting for variations in buoyancy forces and temperature dependent viscosity. The initial temperature conditions are based on interpretations from high resolution regional surface wave tomography. We assume visco-plastic rheology for a uniform crust, dislocation creep for a laterally varying mantle lithospheric structure, and diffusion creep for the asthenosphere. To test for the source of anisotropy we compare our velocity solution azimuths with azimuths of anisotropy at 25 km depth intervals. Calculated asthenospheric flow aligns with measured seismic anisotropy with a 15° WRMS at 175 km depth and possibly down to 250 km suggesting the

  19. Deuterium Lamb shift via quenching-radiation anisotropy measurements

    International Nuclear Information System (INIS)

    van Wijngaarden, A.; Drake, G.W.F.

    1978-01-01

    The Lamb shift of a hydrogenic ion can be deduced from the anisotropy in the angular distribution of the 2s/sub 1/2/-1s/sub 1/2/ electric field quenching radiation. The accuracy of our previous anisotropy measurement for deuterium is improved to about +- 150 ppm. The derived Lamb shift is (1059.36 +- 0.16) MHz. The sources of error are carefully analyzed and the prospects for further improvements in the accuracy are discussed

  20. Large Magnetic Anisotropy in HfMnP

    Science.gov (United States)

    Parker, David; Lamichhane, Tej; Taufour, Valentin; Masters, Morgan; Thimmaiah, Srinivasa; Bud'Ko, Ser'gey; Canfield, Paul

    We present a theoretical and experimental study of two little-studied manganese phosphide ferromagnets, HfMnP and ZrMnP, with Curie temperatures above room temperature. We find an anisotropy field in HfMnP approaching 10 T - larger than that of the permanent magnet workhorse NdFeB magnets. From theory we determine the source of this anisotropy. Our results show the potential of 3d-element-based magnetic materials for magnetic applications.

  1. Electronic, magnetic, and magnetocrystalline anisotropy properties of light lanthanides

    Science.gov (United States)

    Hackett, Timothy A.; Baldwin, D. J.; Paudyal, D.

    2017-11-01

    Theoretical understanding of interactions between localized and mobile electrons and the crystal environment in light lanthanides is important because of their key role in much needed magnetic anisotropy in permanent magnet materials that have a great impact in automobile and wind turbine applications. We report electronic, magnetic, and magnetocrystalline properties of these basic light lanthanide elements studied from advanced density functional theory (DFT) calculations. We find that the inclusion of onsite 4f electron correlation and spin orbit coupling within the full-potential band structure is needed to understand the unique magnetocrystalline properties of these light lanthanides. The onsite electron correlation, spin orbit coupling, and full potential for the asphericity of charge densities must be taken into account for the proper treatment of 4f states. We find the variation of total energy as a function of lattice constants that indicate multiple structural phases in Ce contrasting to a single stable structure obtained in other light lanthanides. The 4f orbital magnetic moments are partially quenched as a result of crystalline electric field splitting that leads to magnetocrystalline anisotropy. The charge density plots have similar asphericity and environment in Pr and Nd indicating similar magnetic anisotropy. However, Ce and Sm show completely different asphericity and environment as both orbital moments are significantly quenched. In addition, the Fermi surface structures exemplified in Nd indicate structural stability and unravel a cause of anisotropy. The calculated magnetocrystalline anisotropy energy (MAE) reveals competing c-axis and in-plane anisotropies, and also predicts possibilities of unusual structural deformations in light lanthanides. The uniaxial magnetic anisotropy is obtained in the double hexagonal closed pack structures of the most of the light lanthanides, however, the anisotropy is reduced or turned to planar in the low symmetry

  2. Microstructure, Slip Systems and Yield Stress Anisotropy in Plastic Deformation

    DEFF Research Database (Denmark)

    Winther, Grethe; You, Ze Sheng; Lu, Lei

    The highly anisotropic microstructures in nanotwinned copper produced by electrodeposition provide an excellent opportunity to evaluate models for microstructurally induced mechanical anisotropy. A crystal plasticity model originally developed for the integration of deformation induced dislocatio...... boundaries with texture is applied to account for the effects of texture as well as twin and grain boundaries, providing good qualitative agreement with experimental yield stress and yield stress anisotropy data....

  3. The influence of anisotropy on capture zone analysis

    International Nuclear Information System (INIS)

    Hansen, K.

    1995-01-01

    Approximately 50,000 gallons of various grades of gasoline and aviation fuel were leaked into silty clay overburden overlying phyllite of the Wissahickon Formation. Pumping tests and measurements of water table recovery from recovery and production wells suggested that elliptical cones of depression were caused by anisotropic groundwater flow in steeply dipping fractures trending between N60 degree E and N75 degree E which were formed by weathered metamorphic foliation. Fracture trace analysis, outcrop measurements, borehole camera surveys, straddle packer testing, and test excavations supported this conceptual model for hydraulic conductivity. Using both quantitative and semi-quantitative methods, the magnitude of anisotropy was calculated from both pumping tests and water table recovery data. Calculated anisotropies showed variations related to the particular method of analysis. Simulations of capture zones using numerical techniques indicated that anisotropic conditions had produced actual capture zones influenced by groundwater flow not orthogonal to equipotential lines. Capture zone shapes were significantly distorted along the primary axis of anisotropy within the range of variation in anisotropy (n) measured by the different analysis methods. Using the mean value of anisotropy from this site (n = 14), actual recovery well capture areas were subsequently corrected for anisotropic effects. The use of capture areas corrected for the mean value of anisotropy enabled more effective placement of subsequent recovery wells. The relatively consistent foliation of rocks in the Wissahickon Formation suggested that capture zone correction should be considered when developing recovery strategies in aquifer systems where anisotropic conditions are likely

  4. Magnetic anisotropies of (Ga,Mn)As films and nanostructures

    Energy Technology Data Exchange (ETDEWEB)

    Hoffmann, Frank

    2011-02-02

    In this work the magnetic anisotropies of the diluted magnetic semiconductor (Ga,Mn)As were investigated experimentally. (Ga,Mn)As films show a superposition of various magnetic anisotropies which depend sensitively on various parameters such as temperature, carrier concentration or lattice strain. However, the anisotropies of lithographically prepared (Ga,Mn)As elements differ significantly from an unpatterned (Ga,Mn)As film. In stripe-shaped structures this behaviour is caused by anisotropic relaxation of the compressive lattice strain. In order to determine the magnetic anisotropies of individual (Ga,Mn)As nanostructures a combination of ferromagnetic resonance and time-resolved scanning Kerr microscopy was employed in this thesis. In addition, local changes of the magnetic anisotropy in circular and rectangular structures were visualized by making use of spatially resolved measurements. Finally, also the influence of the laterally inhomogeneous magnetic anisotropies on the static magnetic properties, such as coercive fields, was investigated employing spatially resolved static MOKE measurements on individual (Ga,Mn)As elements. (orig.)

  5. Limits on the ions temperature anisotropy in turbulent intracluster medium

    Energy Technology Data Exchange (ETDEWEB)

    Santos-Lima, R. [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); Potsdam Univ. (Germany). Inst. fuer Physik und Astronomie; Univ. de Sao Paulo (Brazil). Inst. de Astronomia, Geofisica e Ciencias Atmosfericas; Yan, H. [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); Potsdam Univ. (Germany). Inst. fuer Physik und Astronomie; Gouveia Dal Pino, E.M. de [Univ. de Sao Paulo (Brazil). Inst. de Astronomia, Geofisica e Ciencias Atmosfericas; Lazarian, A. [Wisconsin Univ., Madison, WI (United States). Dept. of Astronomy

    2016-05-15

    Turbulence in the weakly collisional intracluster medium of galaxies (ICM) is able to generate strong thermal velocity anisotropies in the ions (with respect to the local magnetic field direction), if the magnetic moment of the particles is conserved in the absence of Coulomb collisions. In this scenario, the anisotropic pressure magnetohydrodynamic (AMHD) turbulence shows a very different statistical behaviour from the standard MHD one and is unable to amplify seed magnetic fields, in disagreement with previous cosmological MHD simulations which are successful to explain the observed magnetic fields in the ICM. On the other hand, temperature anisotropies can also drive plasma instabilities which can relax the anisotropy. This work aims to compare the relaxation rate with the growth rate of the anisotropies driven by the turbulence. We employ quasilinear theory to estimate the ions scattering rate due to the parallel firehose, mirror, and ion-cyclotron instabilities, for a set of plasma parameters resulting from AMHD simulations of the turbulent ICM. We show that the ICM turbulence can sustain only anisotropy levels very close to the instabilities thresholds. We argue that the AMHD model which bounds the anisotropies at the marginal stability levels can describe the Alfvenic turbulence cascade in the ICM.

  6. Thermodynamics of strong coupling superconductors including the effect of anisotropy

    Science.gov (United States)

    Daams, J. M.; Carbotte, J. P.

    1981-05-01

    The thermodynamics of several elemental superconductors is computed from isotropic Eliashberg theory formulated on the imaginary frequency axis. A symmary of the available experimental literature is presented and a comparison with theory is given. The small disagreements that are found are all in the direction expected from anisotropy effects. We calculate the effect of a small amount of model anisotropy on the critical temperature, critical field, and high-temperature specific heat from an exact solution of the anisotropic Eliashberg equations. These are the first such results below the critical temperature; unlike previous analytical work, we include retardation, anisotropy in the mass enhancement, and the effect of the Coulomb repulsion in enhancing anisotropy, all of which are significant. We derive a new formula independent of any model anisotropy for the rate of decrease with impurity lifetime of the critical temperature. Finally we demonstrate how the commonly used formulas of Markowitz and Kadanoff and of Clem may give entirely misleading estimates of the gap anisotropy when used to interpret certain experiments.

  7. Characterization of optical anisotropy in quantum wells under compressive anisotropic in-plane strain

    Energy Technology Data Exchange (ETDEWEB)

    Biermann, Mark L [Physics Department, 566 Brownson Rd., U.S. Naval Academy, Annapolis, MD 21402 (United States); Walters, Matthew [Physics Department, 566 Brownson Rd., U.S. Naval Academy, Annapolis, MD 21402 (United States); Diaz-Barriga, James [Physics Department, 566 Brownson Rd., U.S. Naval Academy, Annapolis, MD 21402 (United States); Rabinovich, W S [Naval Research Laboratory, Code 5652, 4555 Overlook Ave. SW, Washington, DC 20375-5320 (United States)

    2003-10-21

    Anisotropic in-plane strain in quantum wells leads to an optical polarization anisotropy that can be exploited for device applications. We have determined that for many anisotropic compressive strain cases, the dependence of the optical anisotropy is linear in the strain anisotropy. This result holds for a variety of well and barrier materials and widths and for various overall strain conditions. Further, the polarization anisotropy per strain anisotropy varies as the reciprocal of the energy separation of the relevant hole sub-bands. Hence, a general result for the polarization anisotropy per strain anisotropy is available for cases of compressive anisotropic in-plane strain.

  8. Characterization of optical anisotropy in quantum wells under compressive anisotropic in-plane strain

    International Nuclear Information System (INIS)

    Biermann, Mark L; Walters, Matthew; Diaz-Barriga, James; Rabinovich, W S

    2003-01-01

    Anisotropic in-plane strain in quantum wells leads to an optical polarization anisotropy that can be exploited for device applications. We have determined that for many anisotropic compressive strain cases, the dependence of the optical anisotropy is linear in the strain anisotropy. This result holds for a variety of well and barrier materials and widths and for various overall strain conditions. Further, the polarization anisotropy per strain anisotropy varies as the reciprocal of the energy separation of the relevant hole sub-bands. Hence, a general result for the polarization anisotropy per strain anisotropy is available for cases of compressive anisotropic in-plane strain

  9. Anisotropy in electron-atom collisions

    International Nuclear Information System (INIS)

    Linden van den Heuvel, H.B. van.

    1982-01-01

    Most of the work described in this thesis deals with studies using coincidence experiments, particularly for investigating the electron impact excitation of the 2 1 P and 3 1 D states in helium. A peculiarity is that in the 3 1 D studies the directly emitted 3 1 D → 2 1 P photons are not observed but the 2 1 P → 1 1 S photons resulting from the 3 1 D → 2 1 P → 1 1 S cascade instead. Another interesting point is the choice of the quantisation axis. The author demonstrates that it is of great advantage to take the quantisation axis perpendicular to the scattering plane rather than in the direction of the incident beam, as was done (on historical grounds) in previously reported electron-photon coincidence experiments. Contrary to the incident beam direction the axis perpendicular to the scattering plane really represents an axis of symmetry in the coincidence experiment. In Chapter II the so-called 'parity unfavoured' excitation of the (2p 2 ) 3 P state of helium by electrons is studied. In chapter III the anisotropy parameters for the electron impact excitation of the 2 1 P state of helium in the energy range from 26.6 to 40 eV and in the angular range from 30 0 to 110 0 are determined. Chapter IV contains a description of a scattered electron cascaded-photon coincidence experiment on the electron impact excitation of helium's 3 1 D state. The measurement of complex scattering amplitudes for electron impact excitation of the 3 1 D and 3 1 P states of helium is discussed in Chapter V. (Auth./C.F.)

  10. Texture and anisotropy in ferroelectric lead metaniobate

    Science.gov (United States)

    Iverson, Benjamin John

    Ferroelectric lead metaniobate, PbNb2O6, is a piezoelectric ceramic typically used because of its elevated Curie temperature and anisotropic properties. However, the piezoelectric constant, d33, is relatively low in randomly oriented ceramics when compared to other ferroelectrics. Crystallographic texturing is often employed to increase the piezoelectric constant because the spontaneous polarization axes of grains are better aligned. In this research, crystallographic textures induced through tape casting are distinguished from textures induced through electrical poling. Texture is described using multiple quantitative approaches utilizing X-ray and neutron time-of-flight diffraction. Tape casting lead metaniobate with an inclusion of acicular template particles induces an orthotropic texture distribution. Templated grain growth from seed particles oriented during casting results in anisotropic grain structures. The degree of preferred orientation is directly linked to the shear behavior of the tape cast slurry. Increases in template concentration, slurry viscosity, and casting velocity lead to larger textures by inducing more particle orientation in the tape casting plane. The maximum 010 texture distributions were two and a half multiples of a random distribution. Ferroelectric texture was induced by electrical poling. Electric poling increases the volume of material oriented with the spontaneous polarization direction in the material. Samples with an initial paraelectric texture exhibit a greater change in the domain volume fraction during electrical poling than randomly oriented ceramics. In tape cast samples, the resulting piezoelectric response is proportional to the 010 texture present prior to poling. This results in property anisotropy dependent on initial texture. Piezoelectric properties measured on the most textured ceramics were similar to those obtained with a commercial standard.

  11. Polar plate theory for orthogonal anisotropy

    Science.gov (United States)

    Bailey, Michelle D.

    1998-11-01

    The following paper discusses the derivation and evaluation of the plate equations for a circular composite disk with orthogonal anisotropy. The work will be on a macromechanical level and include buckling, static and dynamic load applications. Necessary to a complete examination of the circular disk is the conversion of the stiffness matrix to cylindrical coordinates. In the transformed state, these coefficients are no longer constant, adding to the complexity of the proposed differential equations. Laminated fiber-reinforced (or filamentary) composites are used today for their high strength-to weight and stiffness-to-weight ratios. However, because of the typical anisotropic behavior of composites, determining the material properties on a microscopic level and the mechanics on a macroscopic level is much more difficult. This difficulty manifests itself particularly well in the evaluation of material properties and governing differential equations of a circular disk with the fibers of the lamina oriented orthogonally. One could encounter such a situation in space structures that require a circular geometry. For example, determining fastener pull through in a circular composite plate would best be performed in a polar coordinate system. In order to calculate the strain (which is a function of the angle, θ) from the displacements, the stiffness matrix and boundary conditions would need to be expressed in cylindrical coordinates. Naturally the composite would be constructed with fibers in orthogonal directions, then the necessary geometry would be cut out, thus the required lengthy transformation of coordinate systems. To bypass this derivation, numerical methods have been used and finite element models have been attempted. FEM over predicts plate stiffness by 20% and underpredicts failure by 70%. Obviously there is a need to transform classical plate theory to a cylindrical coordinate system.

  12. Neurite extension and neuronal differentiation of human induced pluripotent stem cell derived neural stem cells on polyethylene glycol hydrogels containing a continuous Young's Modulus gradient.

    Science.gov (United States)

    Mosley, Matthew C; Lim, Hyun Ju; Chen, Jing; Yang, Yueh-Hsun; Li, Shenglan; Liu, Ying; Smith Callahan, Laura A

    2017-03-01

    Mechanotransduction in neural cells involves multiple signaling pathways that are not fully understood. Differences in lineage and maturation state are suggested causes for conflicting reports on neural cell mechanosensitivity. To optimize matrices for use in stem cell therapy treatments transplanting human induced pluripotent stem cell derived neural stem cells (hNSC) into lesions after spinal cord injury, the effects of Young's Modulus changes on hNSC behavior must be understood. The present study utilizes polyethylene glycol hydrogels containing a continuous gradient in Young's modulus to examine changes in the Young's Modulus of the culture substrate on hNSC neurite extension and neural differentiation. Changes in the Young's Modulus of the polyethylene glycol hydrogels was found to affect neurite extension and cellular organization on the matrices. hNSC cultured on 907 Pa hydrogels were found to extend longer neurites than hNSC cultured on other tested Young's Moduli hydrogels. The gene expression of β tubulin III and microtubule-associated protein 2 in hNSC was affected by changes in the Young's Modulus of the hydrogel. The combinatory method approach used in the present study demonstrates that hNSC are mechanosensitive and the matrix Young's Modulus should be a design consideration for hNSC transplant applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 824-833, 2017. © 2016 Wiley Periodicals, Inc.

  13. Dopaminergic neuronal loss, reduced neurite complexity and autophagic abnormalities in transgenic mice expressing G2019S mutant LRRK2.

    Directory of Open Access Journals (Sweden)

    David Ramonet

    2011-04-01

    Full Text Available Mutations in the leucine-rich repeat kinase 2 (LRRK2 gene cause late-onset, autosomal dominant familial Parkinson's disease (PD and also contribute to idiopathic PD. LRRK2 mutations represent the most common cause of PD with clinical and neurochemical features that are largely indistinguishable from idiopathic disease. Currently, transgenic mice expressing wild-type or disease-causing mutants of LRRK2 have failed to produce overt neurodegeneration, although abnormalities in nigrostriatal dopaminergic neurotransmission have been observed. Here, we describe the development and characterization of transgenic mice expressing human LRRK2 bearing the familial PD mutations, R1441C and G2019S. Our study demonstrates that expression of G2019S mutant LRRK2 induces the degeneration of nigrostriatal pathway dopaminergic neurons in an age-dependent manner. In addition, we observe autophagic and mitochondrial abnormalities in the brains of aged G2019S LRRK2 mice and markedly reduced neurite complexity of cultured dopaminergic neurons. These new LRRK2 transgenic mice will provide important tools for understanding the mechanism(s through which familial mutations precipitate neuronal degeneration and PD.

  14. Distribution of precursor amyloid-β-protein messenger RNA in human cerebral cortex: relationship to neurofibrillary tangles and neuritic plaques

    International Nuclear Information System (INIS)

    Lewis, D.A.; Higgins, G.A.; Young, W.G.; Goldgaber, D.; Gajdusek, D.C.; Wilson, M.C.; Morrison, J.H.

    1988-01-01

    Neurofibrillary tangles (NFT) and neuritic plaques (NP), two neuropathological markers of Alzheimer disease, may both contain peptide fragments derived from the human amyloid β protein. However, the nature of the relationship between NFT and NP and the source of the amyloid β proteins found in each have remained unclear. The authors used in situ hybridization techniques to map the anatomical distribution of precursor amyloid-β-protein mRNA in the neocortex of brains from three subjects with no known neurologic disease and from five patients with Alzheimer disease. In brains from control subjects, positively hybridizing neurons were present in cortical regions and layers that contain a high density of neuropathological markers in Alzheimer disease, as well as in those loci that contain NP but few NFT. Quantitative analyses of in situ hybridization patterns within layers III and V of the superior frontal cortex revealed that the presence of high numbers of NFT in Alzheimer-diseased brains was associated with a decrease in the number of positively hybridizing neurons compared to controls and Alzheimer-diseased brains with few NFT. These findings suggest that the expression of precursor amyloid-β-protein mRNA may be a necessary but is clearly not a sufficient prerequisite for NFT formation. In addition, these results may indicate that the amyloid β protein, present in NP in a given region or layer of cortex, is not derived from the resident neuronal cell bodies that express the mRNA for the precursor protein

  15. Seismic Anisotropy of Soft Sands, Offshore Western AUstralia

    Science.gov (United States)

    Urosevic, M.; Gurevich, B.

    2007-05-01

    Seismic anisotropy is commonly measured in sand shale environment. Intrinsic polar anisotropy of the shale and its effect on seismic data processing and analysis is well established and reasonably well understood. In sandstone, azimuthal anisotropy is often detected and is typically connected to an in situ stress regime and the brittleness of the rock. This type of anisotropy, commonly referred to as fractured induced anisotropy, has been widely and extensively studied as it directly affects both permeability and the strength of the rock. Hence fracture induced anisotropy is not only important for hydrocarbon exploration but also for geotechnical studies, underground mining, etc. Interestingly, in the last few years azimuthal anisotropy has also been detected in soft, poorly consolidated clean sands, mainly by cross-dipole sonic log measurements. This is somewhat surprising as in such soft, typically highly porous and permeable rocks stress induced fractures are unlikely to be abundant. In this study we analyse the anisotropy in such sand class using well-log measurements, three-component VSP data, as well as 2D and 3D surface seismic (reflection) data. High-quality cross-dipole sonic log measurements showed significant shear wave splitting over unconsolidated, highly porous and permeable sand interval. The shear wave anisotropy was computed to be around 10-15%. This is commonly seen as an indication that the rock is fractured and that the fractures are likely to be open. However, image log data over the same sand section suggested dilute most likely non-conductive fractures. Analysis of the shear wave splitting in VSP data also suggested low fracture density. The frequency content of the direct fast and slow shear waves on the VSP data was very similar, not supporting the presence of open fluid saturated fractures. Unfortunately, the evidence from the VSP data is not very compelling because the reservoir is thin compared to the wavelength and sampling interval of

  16. Mycolactone-mediated neurite degeneration and functional effects in cultured human and rat DRG neurons: Mechanisms underlying hypoalgesia in Buruli ulcer.

    Science.gov (United States)

    Anand, U; Sinisi, M; Fox, M; MacQuillan, A; Quick, T; Korchev, Y; Bountra, C; McCarthy, T; Anand, P

    2016-01-01

    Mycolactone is a polyketide toxin secreted by the mycobacterium Mycobacterium ulcerans, responsible for the extensive hypoalgesic skin lesions characteristic of patients with Buruli ulcer. A recent pre-clinical study proposed that mycolactone may produce analgesia via activation of the angiotensin II type 2 receptor (AT2R). In contrast, AT2R antagonist EMA401 has shown analgesic efficacy in animal models and clinical trials for neuropathic pain. We therefore investigated the morphological and functional effects of mycolactone in cultured human and rat dorsal root ganglia (DRG) neurons and the role of AT2R using EMA401. Primary sensory neurons were prepared from avulsed cervical human DRG and rat DRG; 24 h after plating, neurons were incubated for 24 to 96 h with synthetic mycolactone A/B, followed by immunostaining with antibodies to PGP9.5, Gap43, β tubulin, or Mitotracker dye staining. Acute functional effects were examined by measuring capsaicin responses with calcium imaging in DRG neuronal cultures treated with mycolactone. Morphological effects: Mycolactone-treated cultures showed dramatically reduced numbers of surviving neurons and non-neuronal cells, reduced Gap43 and β tubulin expression, degenerating neurites and reduced cell body diameter, compared with controls. Dose-related reduction of neurite length was observed in mycolactone-treated cultures. Mitochondria were distributed throughout the length of neurites and soma of control neurons, but clustered in the neurites and soma of mycolactone-treated neurons. Functional effects: Mycolactone-treated human and rat DRG neurons showed dose-related inhibition of capsaicin responses, which were reversed by calcineurin inhibitor cyclosporine and phosphodiesterase inhibitor 3-isobutyl-1-Methylxanthine, indicating involvement of cAMP/ATP reduction. The morphological and functional effects of mycolactone were not altered by Angiotensin II or AT2R antagonist EMA401. Mycolactone induces toxic effects in DRG

  17. The ENU-3 protein family members function in the Wnt pathway parallel to UNC-6/Netrin to promote motor neuron axon outgrowth in C. elegans.

    Science.gov (United States)

    Florica, Roxana Oriana; Hipolito, Victoria; Bautista, Stephen; Anvari, Homa; Rapp, Chloe; El-Rass, Suzan; Asgharian, Alimohammad; Antonescu, Costin N; Killeen, Marie T

    2017-10-01

    The axons of the DA and DB classes of motor neurons fail to reach the dorsal cord in the absence of the guidance cue UNC-6/Netrin or its receptor UNC-5 in C. elegans. However, the axonal processes usually exit their cell bodies in the ventral cord in the absence of both molecules. Strains lacking functional versions of UNC-6 or UNC-5 have a low level of DA and DB motor neuron axon outgrowth defects. We found that mutations in the genes for all six of the ENU-3 proteins function to enhance the outgrowth defects of the DA and DB axons in strains lacking either UNC-6 or UNC-5. A mutation in the gene for the MIG-14/Wntless protein also enhances defects in a strain lacking either UNC-5 or UNC-6, suggesting that the ENU-3 and Wnt pathways function parallel to the Netrin pathway in directing motor neuron axon outgrowth. Our evidence suggests that the ENU-3 proteins are novel members of the Wnt pathway in nematodes. Five of the six members of the ENU-3 family are predicted to be single-pass trans-membrane proteins. The expression pattern of ENU-3.1 was consistent with plasma membrane localization. One family member, ENU-3.6, lacks the predicted signal peptide and the membrane-spanning domain. In HeLa cells ENU-3.6 had a cytoplasmic localization and caused actin dependent processes to appear. We conclude that the ENU-3 family proteins function in a pathway parallel to the UNC-6/Netrin pathway for motor neuron axon outgrowth, most likely in the Wnt pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Angiogenic dysfunction in bone marrow-derived early outgrowth cells from diabetic animals is attenuated by SIRT1 activation.

    Science.gov (United States)

    Yuen, Darren A; Zhang, Yanling; Thai, Kerri; Spring, Christopher; Chan, Lauren; Guo, Xiaoxin; Advani, Andrew; Sivak, Jeremy M; Gilbert, Richard E

    2012-12-01

    Impaired endothelial repair is a key contributor to microvascular rarefaction and consequent end-organ dysfunction in diabetes. Recent studies suggest an important role for bone marrow-derived early outgrowth cells (EOCs) in mediating endothelial repair, but the function of these cells is impaired in diabetes, as in advanced age. We sought to determine whether diabetes-associated EOC dysfunction might be attenuated by pharmacological activation of silent information regulator protein 1 (SIRT1), a lysine deacetylase implicated in nutrient-dependent life span extension in mammals. Despite being cultured in normal (5.5 mM) glucose for 7 days, EOCs from diabetic rats expressed less SIRT1 mRNA, induced less endothelial tube formation in vitro and neovascularization in vivo, and secreted less of the proangiogenic ELR(+) CXC chemokines CXCL1, CXCL3, and CXCL5. Ex vivo SIRT1 activation restored EOC chemokine secretion and increased the in vitro and in vivo angiogenic activity of EOC conditioned medium derived from diabetic animals to levels similar to that derived from control animals. These findings suggest a pivotal role for SIRT1 in diabetes-induced EOC dysfunction and that its pharmacologic activation may provide a new strategy for the restoration of EOC-mediated repair mechanisms.

  19. The influence of type-I collagen-coated PLLA aligned nanofibers on growth of blood outgrowth endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Feng Zhangqi; Huang Ningping; Wang Yichun; Gu Zhongze [State Key Laboratory of Bioelectronics, Southeast University, Nanjing 210096 (China); Lu Huijun [Department of Vascular Surgery, Wuxi People' s Hospital, Wuxi 214023 (China); Leach, Michelle K [Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109 (United States); Liu Changjian, E-mail: gu@seu.edu.c [Department of Vascular Surgery, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008 (China)

    2010-12-15

    Nanofibrous scaffolds have been applied widely in tissue engineering to simulate the nanostructure of natural extracellular matrix (ECM) and promote cell bioactivity. The aim of this study was to design a biocompatible nanofibrous scaffold for blood outgrowth endothelial cells (BOECs) and investigate the interaction between the topography of the nanofibrous scaffold and cell growth. Poly(l-lactic acid) (PLLA) random and aligned nanofibers with a uniform diameter distribution were fabricated by electrospinning. NH{sub 3} plasma etching was used to create a hydrophilic surface on the nanofibers to improve type-I collagen adsorption; the conditions of the NH{sub 3} plasma etching were optimized by XPS and water contact angle analysis. Cell attachment, proliferation, viability, phenotype and morphology of BOECs cultured on type-I collagen-coated PLLA film (col-Film), random fibers (col-RFs) and aligned fibers (col-AFs) were detected over a 7 day culture period. The results showed that collagen-coated PLLA nanofibers improved cell attachment and proliferation; col-AFs induced the directional growth of cells along the aligned nanofibers and enhanced endothelialization. We suggest that col-AFs may be a potential implantable scaffold for vascular tissue engineering.

  20. Consequences of elastic anisotropy in patterned substrate heteroepitaxy.

    Science.gov (United States)

    Dixit, Gopal Krishna; Ranganathan, Madhav

    2018-06-13

    The role of elastic anisotropy on quantum dot formation and evolution on a pre-patterned substrate is evaluated within the framework of a continuum model. We first extend the formulation for surface evolution to take elastic anisotropy into account. Using a small slope approximation, we derive the evolution equation and show how it can be numerically implemented up to linear and second order for stripe and egg-carton patterned substrates using an accurate and efficient procedure. The semi--infinite nature of the substrate is used to solve the elasticity problem subject to other boundary conditions at the free surface and at the film--substrate interface. The positioning of the quantum dots with respect to the peaks and valleys of the pattern is explained by a competition between the length scale of the pattern and the wavelength of the Asaro--Tiller--Grinfeld instability, which is also affected by the elastic anisotropy. The alignment of dots is affected by a competition between the elastic anisotropy of the film and the pattern orientation. A domain of pattern inversion, wherein the quantum dots form exclusively in the valleys of the patterns is identified as a function of the average film thickness and the elastic anisotropy, and the time--scale for this inversion as function of height is analyzed. © 2018 IOP Publishing Ltd.

  1. An estimator for statistical anisotropy from the CMB bispectrum

    International Nuclear Information System (INIS)

    Bartolo, N.; Dimastrogiovanni, E.; Matarrese, S.; Liguori, M.; Riotto, A.

    2012-01-01

    Various data analyses of the Cosmic Microwave Background (CMB) provide observational hints of statistical isotropy breaking. Some of these features can be studied within the framework of primordial vector fields in inflationary theories which generally display some level of statistical anisotropy both in the power spectrum and in higher-order correlation functions. Motivated by these observations and the recent theoretical developments in the study of primordial vector fields, we develop the formalism necessary to extract statistical anisotropy information from the three-point function of the CMB temperature anisotropy. We employ a simplified vector field model and parametrize the bispectrum of curvature fluctuations in such a way that all the information about statistical anisotropy is encoded in some parameters λ LM (which measure the anisotropic to the isotropic bispectrum amplitudes). For such a template bispectrum, we compute an optimal estimator for λ LM and the expected signal-to-noise ratio. We estimate that, for f NL ≅ 30, an experiment like Planck can be sensitive to a ratio of the anisotropic to the isotropic amplitudes of the bispectrum as small as 10%. Our results are complementary to the information coming from a power spectrum analysis and particularly relevant for those models where statistical anisotropy turns out to be suppressed in the power spectrum but not negligible in the bispectrum

  2. Phenomenological description of anisotropy effects in some ferromagnetic superconductors

    Energy Technology Data Exchange (ETDEWEB)

    Shopova, Diana V., E-mail: sho@issp.bas.bg [TCCM Research Group, Institute of Solid State Physics, Bulgarian Academy of Sciences, BG-1784 Sofia (Bulgaria); Todorov, Michail D. [Department of Applied Mathematics and Computer Science, Technical University of Sofia, 1000 Sofia (Bulgaria)

    2015-07-03

    We study phenomenologically the role of anisotropy in ferromagnetic superconductors UGe{sub 2}, URhGe, and UCoGe for the description of their phase diagrams. We use the Ginzburg–Landau free energy in its uniform form as we will consider only spatially independent solutions. This is an expansion of previously derived results where the effect of Cooper-pair and crystal anisotropies is not taken into account. The three compounds are separately discussed with the special stress on UGe{sub 2}. The main effect comes from the strong uniaxial anisotropy of magnetization while the anisotropy of Cooper pairs and crystal anisotropy only slightly change the phase diagram in the vicinity of Curie temperature. The limitations of this approach are also discussed. - Highlights: • Anisotropic Landau energy for description of ferromagnetic superconductors is proposed. • Meissner phases are described with their existence and stability conditions. • The application of the model to UGe{sub 2} is discussed. • The limitations to apply the model for description of experimental data are explained.

  3. Scaling of coercivity in a 3d random anisotropy model

    Energy Technology Data Exchange (ETDEWEB)

    Proctor, T.C., E-mail: proctortc@gmail.com; Chudnovsky, E.M., E-mail: EUGENE.CHUDNOVSKY@lehman.cuny.edu; Garanin, D.A.

    2015-06-15

    The random-anisotropy Heisenberg model is numerically studied on lattices containing over ten million spins. The study is focused on hysteresis and metastability due to topological defects, and is relevant to magnetic properties of amorphous and sintered magnets. We are interested in the limit when ferromagnetic correlations extend beyond the size of the grain inside which the magnetic anisotropy axes are correlated. In that limit the coercive field computed numerically roughly scales as the fourth power of the random anisotropy strength and as the sixth power of the grain size. Theoretical arguments are presented that provide an explanation of numerical results. Our findings should be helpful for designing amorphous and nanosintered materials with desired magnetic properties. - Highlights: • We study the random-anisotropy model on lattices containing up to ten million spins. • Irreversible behavior due to topological defects (hedgehogs) is elucidated. • Hysteresis loop area scales as the fourth power of the random anisotropy strength. • In nanosintered magnets the coercivity scales as the six power of the grain size.

  4. Cosmic-ray anisotropy studies with IceCube

    Science.gov (United States)

    McNally, Frank

    2014-03-01

    The IceCube neutrino observatory detects tens of billions of energetic muons per year produced by cosmic-ray interactions with the atmosphere. The size of this sample has allowed IceCube to observe a significant anisotropy in arrival direction for cosmic rays with median energies between 20 and 400 TeV. This anisotropy is characterized by a large scale structure of per-mille amplitude accompanied by structures with smaller amplitudes and with typical angular sizes between 10° and 20°. IceTop, the surface component of IceCube, has observed a similar anisotropy in the arrival direction distribution of cosmic rays, extending the study to PeV energies. The better energy resolution of IceTop allows for additional studies of the anisotropy, for example a comparison of the energy spectrum in regions of a cosmic-ray excess or deficit to the rest of the sky. We present an update on the cosmic-ray anisotropy observed with IceCube and IceTop and the results of first studies of the energy spectrum at locations of cosmic-ray excess or deficit.

  5. 3D Anisotropy of Solar Wind Turbulence, Tubes, or Ribbons?

    Science.gov (United States)

    Verdini, Andrea; Grappin, Roland; Alexandrova, Olga; Lion, Sonny

    2018-01-01

    We study the anisotropy with respect to the local magnetic field of turbulent magnetic fluctuations at magnetofluid scales in the solar wind. Previous measurements in the fast solar wind obtained axisymmetric anisotropy, despite that the analysis method allows nonaxisymmetric structures. These results are probably contaminated by the wind expansion that introduces another symmetry axis, namely, the radial direction, as indicated by recent numerical simulations. These simulations also show that while the expansion is strong, the principal fluctuations are in the plane perpendicular to the radial direction. Using this property, we separate 11 yr of Wind spacecraft data into two subsets characterized by strong and weak expansion and determine the corresponding turbulence anisotropy. Under strong expansion, the small-scale anisotropy is consistent with the Goldreich & Sridhar critical balance. As in previous works, when the radial symmetry axis is not eliminated, the turbulent structures are field-aligned tubes. Under weak expansion, we find 3D anisotropy predicted by the Boldyrev model, that is, turbulent structures are ribbons and not tubes. However, the very basis of the Boldyrev phenomenology, namely, a cross-helicity increasing at small scales, is not observed in the solar wind: the origin of the ribbon formation is unknown.

  6. Anisotropy of magnetoviscous effect in structure-forming ferrofluids

    Science.gov (United States)

    Sreekumari, Aparna; Ilg, Patrick

    2015-07-01

    The magnetoviscous effect, change in viscosity with change in magnetic field strength, and the anisotropy of the magnetoviscous effect, change in viscosity with orientation of magnetic field, have been a focus of interest for four decades. A satisfactory understanding of the microscopic origin of anisotropy of the magnetoviscous effect in magnetic fluids is still a matter of debate and a field of intense research. Here, we present an extensive simulation study to understand the relation between the anisotropy of the magnetoviscous effect and the underlying change in microstructures of ferrofluids. Our results indicate that field-induced chainlike structures respond very differently depending on their orientation relative to the direction of an externally applied shear flow, which leads to a pronounced anisotropy of viscosity. In this work, we focus on three exemplary values of dipolar interaction strengths which correspond to weak, intermediate, and strong interactions between dipolar colloidal particles. We compare our simulation results with an experimental study on cobalt-based ferrofluids as well as with an existing theoretical model called the chain model. A nonmonotonic behavior in the anisotropy of the magnetoviscous effect is observed with increasing dipolar interaction strength and is explained in terms of microstructure formation.

  7. Laser-induced nuclear orientation and gamma anisotropy in sodium

    International Nuclear Information System (INIS)

    Pappas, P.G.

    1980-12-01

    The use of laser optical pumping to induce nuclear orientation in several isotopes and one isomer of atomic sodium vapor is described. Essentially complete nuclear polarization, P > 90%, has been achieved in stable 23 Na when pumping with modest laser intensities (I approx. = 10 mW/cm 2 ). The volume of the sample cell was approximately 10 cc, and was filled with a sodium density of about 10'' atoms/cc. Complete coverage of the Doppler distribution was accomplished with the use of trace amounts (less than or equal to 1 torr) of argon buffer gas to induce velocity changing collisions. A theoretical model which accurately predicts the amount of polarization is developed. The orientation of nuclei which are unstable to gamma decay can manifest itself in anisotropic gamma ray emission. This anisotropy can be used to measure isotope and isomer shifts, from which nuclear properties can be derived. Gamma anisotropy was observed in two systems, 22 Na and /sup 24m/Na. From the observed anisotropy in /sup 24m/Na, a negative sign for the g factor is determined. Values are derived for the magnetic moment, μ = 2.56 +- 0.64 nm, and the isomer shift, deltaν/sub 24m/ = 288 +- 191 MHz (D1 line). A model is described which relates various laser and fubber gas parameters to the observed gamma anisotropy lineshape. This model facilitates the extraction of physical parameters from knowledge of the laser frequency at which the anisotropy is a maximum

  8. Procedure for measurement of anisotropy factor for neutron sources

    International Nuclear Information System (INIS)

    Creazolla, Prycylla Gomes

    2017-01-01

    Radioisotope neutron sources allow the production of reference fields for calibration of neutron detectors for radiation protection and analysis purposes. When the emission rate of these sources is isotropic, no correction is necessary. However, variations in source encapsulation and in the radioactive material concentration produce differences in its neutron emission rate, relative to the source axis, this effect is called anisotropy. In this study, is describe a procedure for measuring the anisotropy factor of neutron sources performed in the Laboratório de Metrologia de Neutrons (LN) using a Precision Long Counter (PLC) detector. A measurement procedure that takes into account the anisotropy factor of neutron sources contributes to solve some issues, particularly with respect to the high uncertainties associated with neutron dosimetry. Thus, a bibliographical review was carried out based on international standards and technical regulations specific to the area of neutron fields, and were later reproduced in practice by means of the procedure for measuring the anisotropy factor in neutron sources of the LN. The anisotropy factor is determined as a function of the angle of 90° in relation to the cylindrical axis of the source. This angle is more important due to its high use in measurements and also of its higher neutron emission rate if compared with other angles. (author)

  9. Role of the magnetic anisotropy in organic spin valves

    Directory of Open Access Journals (Sweden)

    V. Kalappattil

    2017-09-01

    Full Text Available Magnetic anisotropy plays an important role in determining the magnetic functionality of thin film based electronic devices. We present here, the first systematic study of the correlation between magnetoresistance (MR response in organic spin valves (OSVs and magnetic anisotropy of the bottom ferromagnetic electrode over a wide temperature range (10 K–350 K. The magnetic anisotropy of a La0.67Sr0.33MnO3 (LSMO film epitaxially grown on a SrTiO3 (STO substrate was manipulated by reducing film thickness from 200 nm to 20 nm. Substrate-induced compressive strain was shown to drastically increase the bulk in-plane magnetic anisotropy when the LSMO became thinner. In contrast, the MR response of LSMO/OSC/Co OSVs for many organic semiconductors (OSCs does not depend on either the in-plane magnetic anisotropy of the LSMO electrodes or their bulk magnetization. All the studied OSV devices show a similar temperature dependence of MR, indicating a similar temperature-dependent spinterface effect irrespective of LSMO thickness, resulting from the orbital hybridization of carriers at the OSC/LSMO interface.

  10. Accuracy and sensitivity analysis on seismic anisotropy parameter estimation

    Science.gov (United States)

    Yan, Fuyong; Han, De-Hua

    2018-04-01

    There is significant uncertainty in measuring the Thomsen’s parameter δ in laboratory even though the dimensions and orientations of the rock samples are known. It is expected that more challenges will be encountered in the estimating of the seismic anisotropy parameters from field seismic data. Based on Monte Carlo simulation of vertical transversely isotropic layer cake model using the database of laboratory anisotropy measurement from the literature, we apply the commonly used quartic non-hyperbolic reflection moveout equation to estimate the seismic anisotropy parameters and test its accuracy and sensitivities to the source-receive offset, vertical interval velocity error and time picking error. The testing results show that the methodology works perfectly for noise-free synthetic data with short spread length. However, this method is extremely sensitive to the time picking error caused by mild random noises, and it requires the spread length to be greater than the depth of the reflection event. The uncertainties increase rapidly for the deeper layers and the estimated anisotropy parameters can be very unreliable for a layer with more than five overlain layers. It is possible that an isotropic formation can be misinterpreted as a strong anisotropic formation. The sensitivity analysis should provide useful guidance on how to group the reflection events and build a suitable geological model for anisotropy parameter inversion.

  11. Strength and strain anisotropy of olkiluoto mica gneiss

    International Nuclear Information System (INIS)

    Hakala, M.; Kuula, H.; Hudson, J.

    2006-10-01

    An anisotropy in the elastic moduli values of intact rock with a ratio of more than 1.3∼1.5 has been reported to have an effect on the calculated magnitudes and orientations of the in situ principal stress components as measured by the overcoring method. Work related to the on-going site investigation for a deep radioactive waste repository at the Olkiluoto site in Western Finland has shown that the migmatic mica gneiss is anisotropic which could therefore affect the interpretation of overcoring stress measurement results. This paper includes a summary of the theory of anisotropy concerning the intact rock moduli via the strain compliance matrix, a description of the core sample testing methods, and interpretation of results for the migmatic mica gneiss from two site investigation boreholes. In this case study, 19 specimens were tested and the results showed a modulus anisotropy of about 1.4. Because such anisotropy is high enough to produce significant errors in the estimation of the in situ principal stresses, it is recommended to take this into account in the interpretation of the stress measurement results, both in the context of the current work in Finland and in other projects where similar anisotropy is encountered. (orig.)

  12. Ca2+ toxicity due to reverse Na+/Ca2+ exchange contributes to degeneration of neurites of DRG neurons induced by a neuropathy-associated Nav1.7 mutation

    Science.gov (United States)

    Estacion, M.; Vohra, B. P. S; Liu, S.; Hoeijmakers, J.; Faber, C. G.; Merkies, I. S. J.; Lauria, G.; Black, J. A.

    2015-01-01

    Gain-of-function missense mutations in voltage-gated sodium channel Nav1.7 have been linked to small-fiber neuropathy, which is characterized by burning pain, dysautonomia and a loss of intraepidermal nerve fibers. However, the mechanistic cascades linking Nav1.7 mutations to axonal degeneration are incompletely understood. The G856D mutation in Nav1.7 produces robust changes in channel biophysical properties, including hyperpolarized activation, depolarized inactivation, and enhanced ramp and persistent currents, which contribute to the hyperexcitability exhibited by neurons containing Nav1.8. We report here that cell bodies and neurites of dorsal root ganglion (DRG) neurons transfected with G856D display increased levels of intracellular Na+ concentration ([Na+]) and intracellular [Ca2+] following stimulation with high [K+] compared with wild-type (WT) Nav1.7-expressing neurons. Blockade of reverse mode of the sodium/calcium exchanger (NCX) or of sodium channels attenuates [Ca2+] transients evoked by high [K+] in G856D-expressing DRG cell bodies and neurites. We also show that treatment of WT or G856D-expressing neurites with high [K+] or 2-deoxyglucose (2-DG) does not elicit degeneration of these neurites, but that high [K+] and 2-DG in combination evokes degeneration of G856D neurites but not WT neurites. Our results also demonstrate that 0 Ca2+ or blockade of reverse mode of NCX protects G856D-expressing neurites from degeneration when exposed to high [K+] and 2-DG. These results point to [Na+] overload in DRG neurons expressing mutant G856D Nav1.7, which triggers reverse mode of NCX and contributes to Ca2+ toxicity, and suggest subtype-specific blockade of Nav1.7 or inhibition of reverse NCX as strategies that might slow or prevent axon degeneration in small-fiber neuropathy. PMID:26156380

  13. Studies of anisotropy of iron based superconductors

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, Jason [Iowa State Univ., Ames, IA (United States)

    2013-01-01

    To study the electronic anisotropy in iron based superconductors, the temperature dependent London penetration depth, Δλ (T), have been measured in several compounds, along with the angular dependent upper critical field, Hc2(T). Study was undertaken on single crystals of Ba(Fe1-xCox)2As2 with x=0.108 and x=0.127, in the overdoped range of the doping phase diagram, characterized by notable modulation of the superconducting gap. Heavy ion irradiation with matching field doses of 6 T and 6.5 T respectively, were used to create columnar defects and to study their effect on the temperature Δλ (T). The variation of the low-temperature penetration depth in both pristine and irradiated samples was fitted with a power-law function Δλ (T) = ATn. Irradiation increases the magnitude of the pre-factor A and decreases the exponent n, similar to the effect on the optimally doped samples. This finding supports the universal s± scenario for the whole doping range. Knowing that the s± gap symmetry exists across the superconducting dome for the electron doped systems, we next looked at λ (T), in optimally - doped, SrFe2(As1-xPx)2, x =0.35. Both, as-grown (Tc ~ 25 K) and annealed (Tc ~ 35 K) single crystals of SrFe2(As1-xPx)2 were measured. Annealing decreases the absolute value of the London penetration depth from λ(0) = 300 ± 10 nm in as-grown samples to λ (0) = 275±10 nm. At low temperatures, λ (T) ~ T indicates a superconducting gap with line nodes. Analysis of the full-temperature range superfluid density is consistent with the line nodes, but differs from the simple single-gap d-wave. The observed behavior is very similar to that of BaFe2(As1-xPx)2, showing that isovalently substituted pnictides are inherently different from

  14. Irradiation creep induced anisotropy in a/2 dislocation populations

    International Nuclear Information System (INIS)

    Gelles, D.S.

    1984-05-01

    The contribution of anisotropy in Burgers vector distribution to irradiation creep behavior has been largely ignored in irradiation creep models. However, findings on Frank loops suggest that it may be very important. Procedures are defined to identify the orientations of a/2 Burgers vectors for dislocations in face-centered cubic crystals. By means of these procedures the anisotropy in Burgers vector populations was determined for three Nimonic PE16 pressurized tube specimens irradiated under stress. Considerable anisotropy in Burgers vector population develops during irradiation creep. It is inferred that dislocation motion during irradiation creep is restricted primarily to a climb of a/2 dislocations on 100 planes. Effect of these results on irradiation creep modeling and deformation induced irradiation growth is considered

  15. Understanding the magnetic anisotropy in Fe-Si amorphous alloys

    Energy Technology Data Exchange (ETDEWEB)

    Diaz, J.; Hamdan, N.M.; Jalil, P.; Hussain, Z.; Valvidares, S.M.; Alameda, J.M.

    2002-08-01

    The origin of the magnetic anisotropy in a very disordered Fe-Si alloy has been investigated. The alloy containing 40 percent at. Si was prepared in the form of a thin film in a DC magnetron sputtering chamber. Structural disorder was obtained from Extended X-ray Absorption Fine Structure spectroscopy. The uniformity and lack of inhomogeneities at a microscopic level was checked by measuring their transverse magnetic susceptibility and hysteresis loops. The orbital component of the magnetic moment was measured by X-ray Magnetic Circular Dichroism spectroscopy. The orbital moment was extraordinary high, 0.4mB. Such a high value contrasted with the relatively small uniaxial anisotropy energy of the thin film (2kJ/m3). This suggests that the cause of the magnetic anisotropy in this alloy was a small degree of correlation in the orientation of the local orbital moments along a preferential direction.

  16. Understanding the magnetic anisotropy in Fe-Si amorphous alloys

    International Nuclear Information System (INIS)

    Diaz, J.; Hamdan, N.M.; Jalil, P.; Hussain, Z.; Valvidares, S.M.; Alameda, J.M.

    2002-01-01

    The origin of the magnetic anisotropy in a very disordered Fe-Si alloy has been investigated. The alloy containing 40 percent at. Si was prepared in the form of a thin film in a DC magnetron sputtering chamber. Structural disorder was obtained from Extended X-ray Absorption Fine Structure spectroscopy. The uniformity and lack of inhomogeneities at a microscopic level was checked by measuring their transverse magnetic susceptibility and hysteresis loops. The orbital component of the magnetic moment was measured by X-ray Magnetic Circular Dichroism spectroscopy. The orbital moment was extraordinary high, 0.4mB. Such a high value contrasted with the relatively small uniaxial anisotropy energy of the thin film (2kJ/m3). This suggests that the cause of the magnetic anisotropy in this alloy was a small degree of correlation in the orientation of the local orbital moments along a preferential direction

  17. Linking strain anisotropy and plasticity in copper metallization

    International Nuclear Information System (INIS)

    Murray, Conal E.; Jordan-Sweet, Jean; Priyadarshini, Deepika; Nguyen, Son

    2015-01-01

    The elastic anisotropy of copper leads to significant variation in the x-ray elastic constants (XEC), which link diffraction-based strain measurements to stress. An accurate depiction of the mechanical response in copper thin films requires a determination of an appropriate grain interaction model that lies between Voigt and Reuss limits. It is shown that the associated XEC weighting fraction, x*, between these limits provides a metric by which strain anisotropy can be quantified. Experimental values of x*, as determined by a linear regression scheme of diffraction data collected from multiple reflections, reveal the degree of strain anisotropy and its dependence on plastic deformation induced during in-situ and ex-situ thermal treatments

  18. Effects of electrons on the solar wind proton temperature anisotropy

    International Nuclear Information System (INIS)

    Michno, M. J.; Lazar, M.; Schlickeiser, R.; Yoon, P. H.

    2014-01-01

    Among the kinetic microinstabilities, the firehose instability is one of the most efficient mechanisms to restrict the unlimited increase of temperature anisotropy in the direction of an ambient magnetic field as predicted by adiabatic expansion of collision-poor solar wind. Indeed, the solar wind proton temperature anisotropy detected near 1 AU shows that it is constrained by the marginal firehose condition. Of the two types of firehose instabilities, namely, parallel and oblique, the literature suggests that the solar wind data conform more closely to the marginal oblique firehose condition. In the present work, however, it is shown that the parallel firehose instability threshold is markedly influenced by the presence of anisotropic electrons, such that under some circumstances, the cumulative effects of both electron and proton anisotropies could describe the observation without considering the oblique firehose mode.

  19. Magnetic Alignment of Block Copolymer Microdomains by Intrinsic Chain Anisotropy.

    Science.gov (United States)

    Rokhlenko, Yekaterina; Gopinadhan, Manesh; Osuji, Chinedum O; Zhang, Kai; O'Hern, Corey S; Larson, Steven R; Gopalan, Padma; Majewski, Paweł W; Yager, Kevin G

    2015-12-18

    We examine the role of intrinsic chain susceptibility anisotropy in magnetic field directed self-assembly of a block copolymer using in situ x-ray scattering. Alignment of a lamellar mesophase is observed on cooling across the disorder-order transition with the resulting orientational order inversely proportional to the cooling rate. We discuss the origin of the susceptibility anisotropy, Δχ, that drives alignment and calculate its magnitude using coarse-grained molecular dynamics to sample conformations of surface-tethered chains, finding Δχ≈2×10^{-8}. From field-dependent scattering data, we estimate that grains of ≈1.2  μm are present during alignment. These results demonstrate that intrinsic anisotropy is sufficient to support strong field-induced mesophase alignment and suggest a versatile strategy for field control of orientational order in block copolymers.

  20. Search for positron anisotropies in cosmic rays with AMS

    Energy Technology Data Exchange (ETDEWEB)

    Machate, Fabian [1. Physikalisches Institut B, RWTH Aachen University (Germany)

    2016-07-01

    The Alpha Magnetic Spectrometer (AMS-02) on the International Space Station has observed a significant excess of cosmic ray positrons over the background expected from secondary production at energies above 10 GeV. Nearby pulsars and annihilating dark matter particles as a primary source of electrons and positrons have been discussed as an explanation. A possible way of distinguishing between pulsar and dark matter origin is the measurement of dipole anisotropies in the positron flux or the positron to electron ratio. Any anisotropy will be reduced by diffusion in galactic magnetic fields to below the percent level. AMS-02 is the leading space-based experiment for cosmic ray detection and well suited for this search. A new analysis procedure for anisotropies using an event sample with large acceptance is presented. It relies on the ability of the Transition Radiation Detector (TRD) to separate positrons from the proton background.

  1. Fluorescense Anisotropy Studies of Molecularly Imprinted Polymer Sensors

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yin-Chu; Wang, Zheming; Yan, Mingdi; Prahl, Scott A.

    2005-08-03

    Molecularly imprinted polymers (MIPs) are used as recognition elements in biochemical sensors. In a fluorescence-based MIP sensor system, it is difficult to distinguish the analyte fluorescence from the background fluorescence of the polymer itself. We studied steady-state fluorescence anisotropy of anthracene imprinted in a polymer (polyurethane) matrix. Vertically polarized excitation light was incident on MIP films coated on silicon wafers; vertically and horizontally polarized emission was measured. We compared the fluorescence anisotropy of MIPs with imprinted molecules, MIPs with the imprinted molecules extracted, MIPs with rebound molecules, and nonimprinted control polymers (without binding cavities). It is shown that differences in fluorescence anisotropy between the polymers and imprinted fluorescent molecules may provide a means to discriminate the fluorescence of analyte from that of the background polymer.

  2. Magnetic anisotropy of (Sm, Y)2Fe17Ny compounds

    International Nuclear Information System (INIS)

    Lu, Y.; Tegus, O.; Li, Q.A.; Tang, N.; Yu, M.J.; Zhao, R.W.; Kuang, J.P.; Yang, F.M.; Zhou, G.F.; Li, X.; Boer, F.R. de

    1992-01-01

    A study of the crystal structure and the magnetic properties, especially the magnetocrystalline anisotropy of (Sm 1-x Y x ) 2 Fe 17 N y compounds (x = 0, 0.2, 0.4, 0.6, 0.8, and 1.0, 2 2 Zn 17 - or Th 2 Ni 17 -type structure as the original compounds. The Curie temperatures decrease from 750 to 700 K as x increases from 0 to 1. The anisotropy field decreases linearly with increasing yttrium content. The spin reorientation has been investigated by means of high field magnetization measurements, AC-susceptibility measurements and thermomagnetic analysis, combined with X-ray diffraction. The anisotropy constants K 1 , K 2 and K 3 were derived by a phenomenological analysis, using magnetization curves measured in high fields, applied perpendicular to the alignment direction of the powder samples. A tentative spin phase diagram of the series is presented. (orig.)

  3. Ion temperature anisotropy limitation in high beta plasmas

    International Nuclear Information System (INIS)

    Scime, Earl E.; Keiter, Paul A.; Balkey, Matthew M.; Boivin, Robert F.; Kline, John L.; Blackburn, Melanie; Gary, S. Peter

    2000-01-01

    Measurements of parallel and perpendicular ion temperatures in the Large Experiment on Instabilities and Anisotropies (LEIA) space simulation chamber display an inverse correlation between the upper bound on the ion temperature anisotropy and the parallel ion beta (β=8πnkT/B 2 ). Fluctuation measurements indicate the presence of low frequency, transverse, electromagnetic waves with wave numbers and frequencies that are consistent with predictions for Alfven Ion Cyclotron instabilities. These observations are also consistent with in situ spacecraft measurements in the Earth's magnetosheath and with a theoretical/computational model that predicts that such an upper bound on the ion temperature anisotropy is imposed by scattering from enhanced fluctuations due to growth of the Alfven ion cyclotron instability. (c) 2000 American Institute of Physics

  4. Simultaneous determination of glycols based on fluorescence anisotropy

    International Nuclear Information System (INIS)

    Garcia Sanchez, F.; Navas Diaz, A.; Lopez Guerrero, M.M.

    2007-01-01

    Simultaneous determination of non-fluorescent glycols in mixtures without separation or chemical transformation steps is described. Two methods based in the measure of fluorescence anisotropy of a probe such as fluorescein dissolved in the analyte or analyte mixtures are described. In the first method, the anisotropy spectra of pure and mixtures of analytes are used to quantitative determination (if the fluorophor concentration is in a range where fluorescence intensity is proportional to concentration). In the second method, a calibration curve anisotropy-concentration based on the application of the Perrin equation is established. The methods presented here are capable of directly resolving binary mixtures of non-fluorescent glycols on the basis of differences on the fluorescence anisotropy of a fluorescence tracer. Best analytical performances were obtained by application of the method based on Perrin equation. This method is simple, rapid and allows the determination of mixtures of glycols with reasonable accuracy and precision. Detection limits are limited by the quantum yield and anisotropy values of the tracer in the solvents. Recovery values are related to the differences in anisotropy values of the tracer in the pure solvents. Mixtures of glycerine/ethylene glycol (GL/EG), ethylene glycol/1,2-propane diol (EG/1,2-PPD) and polyethylene glycol 400/1,2-propane diol (PEG 400/1,2-PPD) were analysed and recovery values are within 95-120% in the Perrin method. Relative standard deviation are in the range 1.3-2.9% and detection limits in the range 3.9-8.9%

  5. Shear-wave splitting observations of mantle anisotropy beneath Alaska

    Science.gov (United States)

    Bellesiles, A. K.; Christensen, D. H.; Entwistle, E.; Litherland, M.; Abers, G. A.; Song, X.

    2009-12-01

    Observations of seismic anisotropy were obtained from three different PASSCAL broadband experiments throughout Alaska, using shear-wave splitting from teleseismic SKS phases. The MOOS (Multidisciplinary Observations Of Subduction), BEAAR (Broadband Experiment Across the Alaska Range), and ARCTIC (Alaska Receiving Cross-Transects for the Inner Core) networks were used along with selected permanent broadband stations operated by AEIC (Alaska Earthquake Information Center) to produce seismic anisotropy results for the state of Alaska along a north south transect from the active subduction zone in the south, through continental Alaska, to the passive margin in the north. The BEAAR network is in-between the ARCTIC and MOOS networks above the subducting Pacific Plate and mantle wedge and shows a tight ~90 degree rotation of anisotropy above the 70km contour of the subducting plate. The southern stations in BEAAR yield anisotropy results that are subparallel to the Pacific Plate motion as it subducts under North America. These stations have an average fast direction of -45 degrees and 1.03 seconds of delay on average. The MOOS network in south central Alaska yielded similar results with an average fast direction of -30 degrees and delay times of .9 seconds. In the north portion of the BEAAR network the anisotropy is along strike of the subduction zone and has an average fast direction of 27 degrees with an average delay time of 1.4 seconds, although the delay times above the mantle wedge range from 1 to 2.5 seconds and are directly correlated to the length of ray path in the mantle wedge. This general trend NE/SW is seen in the ARCTIC stations to the north although the furthest north stations are oriented more NNE compared to those in BEAAR. The average fast direction for the ARCTIC network is 40 degrees with an average delay time of 1.05 seconds. These results show two distinct orientations of anisotropy in Alaska separated by the subducting Pacific Plate.

  6. Characteristics of trapped proton anisotropy at Space Station Freedom altitudes

    Science.gov (United States)

    Armstrong, T. W.; Colborn, B. L.; Watts, J. W.

    1990-01-01

    The ionizing radiation dose for spacecraft in low-Earth orbit (LEO) is produced mainly by protons trapped in the Earth's magnetic field. Current data bases describing this trapped radiation environment assume the protons to have an isotropic angular distribution, although the fluxes are actually highly anisotropic in LEO. The general nature of this directionality is understood theoretically and has been observed by several satellites. The anisotropy of the trapped proton exposure has not been an important practical consideration for most previous LEO missions because the random spacecraft orientation during passage through the radiation belt 'averages out' the anisotropy. Thus, in spite of the actual exposure anisotropy, cumulative radiation effects over many orbits can be predicted as if the environment were isotropic when the spacecraft orientation is variable during exposure. However, Space Station Freedom will be gravity gradient stabilized to reduce drag, and, due to this fixed orientation, the cumulative incident proton flux will remain anisotropic. The anisotropy could potentially influence several aspects of Space Station design and operation, such as the appropriate location for radiation sensitive components and experiments, location of workstations and sleeping quarters, and the design and placement of radiation monitors. Also, on-board mass could possible be utilized to counteract the anisotropy effects and reduce the dose exposure. Until recently only omnidirectional data bases for the trapped proton environment were available. However, a method to predict orbit-average, angular dependent ('vector') trapped proton flux spectra has been developed from the standard omnidirectional trapped proton data bases. This method was used to characterize the trapped proton anisotropy for the Space Station orbit (28.5 degree inclination, circular) in terms of its dependence on altitude, solar cycle modulation (solar minimum vs. solar maximum), shielding thickness

  7. Colour-coded fractional anisotropy images: differential visualisation of white-matter tracts - preliminary experience

    International Nuclear Information System (INIS)

    Murata, T.; Higano, S.; Tamura, H.; Mugikura, S.; Takahashi, S.

    2002-01-01

    Diffusion-tensor analysis allows quantitative assessment of diffusion anisotropy. Fractional anisotropy (FA) is commonly used to quantify anisotropy. One of the limitations of FA imaging is, however, that it does not contain information about the directionality of anisotropy and it is therefore difficult to identify white-matter tracts on FA images. Our purpose was to describe a simple method of making composite images containing information about both magnitude and direction of diffusion anisotropy. The composite colour-coded FA images enabled us to identify different adjacent fibre bundles of similar degrees of diffusion anisotropy, and might be helpful in assessment of these fasciculi. (orig.)

  8. Topographical Anisotropy and Wetting of Ground Stainless Steel Surfaces

    Directory of Open Access Journals (Sweden)

    Cornelia Bellmann

    2012-12-01

    Full Text Available Microscopic and physico-chemical methods were used for a comprehensive surface characterization of different mechanically modified stainless steel surfaces. The surfaces were analyzed using high-resolution confocal microscopy, resulting in detailed information about the topographic properties. In addition, static water contact angle measurements were carried out to characterize the surface heterogeneity of the samples. The effect of morphological anisotropy on water contact angle anisotropy was investigated. The correlation between topography and wetting was studied by means of a model of wetting proposed in the present work, that allows quantifying the air volume of the interface water drop-stainless steel surface.

  9. Influence of Elastic Anisotropy on Extended Dislocation Nodes

    Energy Technology Data Exchange (ETDEWEB)

    Pettersson, B

    1971-09-15

    The interaction forces between the partial dislocations forming an extended dislocation node are calculated using elasticity theory for anisotropic media.s are carried out for nodes of screw, edge and mixed character in Ag, which has an anisotropy ratio A equal to 3, and in a hypothetic material with A = 1 and the same shear modulus as Ag. The results are compared with three previous theories using isotropic elasticity theory. As expected, in Ag the influence of anisotropy is of the same order as the uncertainty due to the dislocation core energy

  10. Anisotropy Spectra for Enantiomeric Differentiation of Biomolecular Building Blocks

    DEFF Research Database (Denmark)

    Evans, Amanda C.; Meinert, Cornelia; Bredehoft, Jan H.

    2013-01-01

    All biopolymers are composed of homochiral building blocks, and both D-sugars and L-amino acids uniquely constitute life on Earth. These monomers were originally enantiomerically differentiated under prebiotic conditions. Particular progress has recently been made in support of the photochemical...... light. This chapter will: (1) present the theory and configuration of anisotropy spectroscopy; (2) explain experimentally recorded anisotropy spectra of selected chiral biomolecules such as amino acids; and (3) discuss the relevance of these spectra for the investigation of the origin of the molecular...

  11. Friction anisotropy-driven domain imaging on exfoliated monolayer graphene.

    Science.gov (United States)

    Choi, Jin Sik; Kim, Jin-Soo; Byun, Ik-Su; Lee, Duk Hyun; Lee, Mi Jung; Park, Bae Ho; Lee, Changgu; Yoon, Duhee; Cheong, Hyeonsik; Lee, Ki Ho; Son, Young-Woo; Park, Jeong Young; Salmeron, Miquel

    2011-07-29

    Graphene produced by exfoliation has not been able to provide an ideal graphene with performance comparable to that predicted by theory, and structural and/or electronic defects have been proposed as one cause of reduced performance. We report the observation of domains on exfoliated monolayer graphene that differ by their friction characteristics, as measured by friction force microscopy. Angle-dependent scanning revealed friction anisotropy with a periodicity of 180° on each friction domain. The friction anisotropy decreased as the applied load increased. We propose that the domains arise from ripple distortions that give rise to anisotropic friction in each domain as a result of the anisotropic puckering of the graphene.

  12. Effects of scattering anisotropy approximation in multigroup radiation shielding calculations

    International Nuclear Information System (INIS)

    Altiparmakov, D.

    1983-01-01

    Expansion of the scattering cross sections into Legendre series is the usual way of solving neutron transport problems. Because of the large space gradients of the neutron flux, the effects of that approximation become especially remarkable in the radiation shielding calculations. In this paper, a method taking into account the scattering anisotropy is presented. From the point od view of the accuracy and computing rate, the optimal approximation of the scattering anisotropy is established for the basic protective materials on the basis of simple problem calculations. (author)

  13. Measuring the cosmological lepton asymmetry through the CMB anisotropy

    CERN Document Server

    Kinney, W H; Kinney, William H.; Riotto, Antonio

    1999-01-01

    A large lepton asymmetry in the Universe is still a viable possibility and leads to many interesting phenomena such as gauge symmetry nonrestoration at high temperature. We show that a large lepton asymmetry changes the predicted cosmic microwave background (CMB) anisotropy and that any degeneracy in the relic neutrino sea will be measured to a precision of 1% or better when the CMB anisotropy is measured at the accuracy expected to result from the planned satellite missions MAP and Planck. In fact, the current measurements already put an upper limit on the lepton asymmetry of the Universe which is stronger than the one coming from considerations of primordial nucleosynthesis and structure formation.

  14. Energy-based ferromagnetic material model with magnetic anisotropy

    Energy Technology Data Exchange (ETDEWEB)

    Steentjes, Simon, E-mail: simon.steentjes@iem.rwth-aachen.de [Institute of Electrical Machines - RWTH Aachen University, Schinkelstr. 4, D-52056 Aachen (Germany); Henrotte, François, E-mail: francois.henrotte@uclouvain.be [Institute of Mechanics Materials and Civil Engineering - UCL, Av. G. Lemaître 4-6, B-1348 Louvain-la-Neuve (Belgium); Hameyer, Kay [Institute of Electrical Machines - RWTH Aachen University, Schinkelstr. 4, D-52056 Aachen (Germany)

    2017-03-01

    Non-oriented soft magnetic materials are commonly assumed to be magnetically isotropic. However, due to the rolling process a preferred direction exists along the rolling direction. This uniaxial magnetic anisotropy, and the related magnetostriction effect, are critical to the accurate calculation of iron losses and magnetic forces in rotating electrical machines. This paper proposes an extension of an isotropic energy-based vector hysteresis model to account for these two effects. - Highlights: • Energy-based vector hysteresis model with magnetic anisotropy. • Two-scale model to account for pinning field distribution. • Pinning force and reluctivity are extended to anisotropic case.

  15. Magnetic anisotropy of nonmodulated Ni-Mn-Ga martensite revisited

    Czech Academy of Sciences Publication Activity Database

    Heczko, Oleg; Straka, L.; Novák, Václav; Fähler, S.

    2010-01-01

    Roč. 107, č. 9 (2010), 09A914/1-09A914/3 ISSN 0021-8979 Grant - others:AV ČR(CZ) M100100913 Institutional research plan: CEZ:AV0Z10100520 Keywords : magnetic anisotropy of non-modulated martensite * temperature dependence of anisotropy * Ni-Mn-Ga * adaptive martensite Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 2.064, year: 2010 http://jap.aip.org/resource/1/japiau/v107/i9/p09A914_s1

  16. Procedures for measurement of anisotropy factor of neutron sources

    International Nuclear Information System (INIS)

    Creazolla, P.G.; Camargo, A.; Astuto, A.; Silva, F.; Pereira, W.W.

    2017-01-01

    Radioisotope sources of neutrons allow the production of reference fields for calibration of neutron measurement devices for radioprotection and analysis purposes. When the emission rate of these sources is isotropic, no correction is necessary. However, variations in the source capsule material and variations in the concentration of the emitting material may produce differences in its neutron emission rate relative to the source axis, this effect is called anisotropy. A proposed procedure for measuring the anisotropy factor of the sources belonging to the IRD/LNMRI/LN Neutron Metrology Laboratory using a Precision Long Counter (PLC) detector will be presented

  17. Banana regime pressure anisotropy in a bumpy cylinder magnetic field

    International Nuclear Information System (INIS)

    Garcia-Perciante, A.L.; Callen, J.D.; Shaing, K.C.; Hegna, C.C.

    2006-01-01

    The pressure anisotropy is calculated for a plasma in a bumpy cylindrical magnetic field in the low collisionality (banana) regime for small magnetic-field modulations (ε≡ΔB/2B parallel is then calculated and is shown to exceed the flux-surface-averaged parallel viscous force parallel > by a factor of O(1/ε). A high-frequency limit (ω>>ν) for the pressure anisotropy is also determined and the calculation is then extended to include the full frequency dependence by using an expansion in Cordey eigenfunctions

  18. Determination of plastic anisotropy of zirconium alloys cladding

    International Nuclear Information System (INIS)

    Yamshchikov, N.V.; Prasolov, P.F.; Shestak, V.E.

    1991-01-01

    Method for determining plastic anisotropy of zurconium alloy cladding is described. It is based on consideration of material as a combination of transversal crystallites with known distribution over orientations. Such approach enables to describe cladding resistance to plastic deformation at arbitrary stressed state, using the results of texture investigations and uniaxial tests of samples, cut out of claddings along three directions. Plastic anisotropy of fuel element claddings 9.15 and 13.6 mm in diameter up to several percents of plastic deformation is shown

  19. Anisotropy of mechanical properties of zirconium and zirconium alloys

    International Nuclear Information System (INIS)

    Medrano, R.E.

    1975-01-01

    In studies of technological applications of zirconium to fuel elements of nuclear reactor, it was found that the use of plasticity equations for isotropic materials is not in agreement with experimental results, because of the strong anisotropy of zirconium. The present review describes recent progress on the knowledge of the influence of anisotropy on mechanical properties, after Douglass' review in 1971. The review was written to be selfconsistent, changing drastically the presentation of some of the referenced papers. It is also suggested some particular experiments to improve developments in this area

  20. Influence of temperature on the Zircaloy-4 plastic anisotropy

    International Nuclear Information System (INIS)

    Limon, R.; Bechade, J.L.; Lehmann, S.; Maury, R.; Soniak, A.

    1995-01-01

    In order to improve the comportment modelling of PWR fuel pin, and more precisely their canning tubes, Framatome and the CEA have undertake an important study program of Zircaloy-4 mechanical properties. It includes in particular the study of the plasticity between 20 and 400 degree Celsius. This material being not isotropic because of the zirconium hexagonal crystal network and the texture presented by the canning tubes, its plastic anisotropy has been measured. The obtained results for the canning in *slack* and recrystallized before irradiation Zircaloy-4 are presented and the deformation systems able to explain the observed anisotropy is researched. (O.L.). 6 refs., 4 figs., 1 tab

  1. Sidereal anisotropy of small air showers observed at Mt. Norikura

    International Nuclear Information System (INIS)

    Nagashima, K.; Sakakibara, S.; Fujimoto, K.; Fujii, Z.; Ueno, H.; Kondo, I.

    1977-01-01

    Observation of small air showers has been continued from August 1970, using a part of the multidirectional cosmic ray telescope at Mt. Norikura. Most significant result obtained from this observation was a sidereal diurnal anisotropy of amplitude 0.051 +- 0.004% with maximum at 1.0 +- 0.5 h, which showed a persistent trend over six years. Based on the results of the observation together with those obtained by Gombosi et al. and Fenton et al., a tentative model of sidereal anisotropies is presented. (author)

  2. Magnetic anisotropy in GaMnAs; Magnetische Anisotropie in GaMnAs

    Energy Technology Data Exchange (ETDEWEB)

    Daeubler, Joachim

    2009-07-02

    The goal of the present work was the detailed investigation of the impact of parameters like vertical strain, hole concentration, substrate orientation and patterning on the MA in GaMnAs. At first a method is introduced enabling us to determine the MA from angle-dependent magnetotransport measurements. This method was used to analyze the impact of vertical strain {epsilon}{sub zz} on the MA in a series of GaMnAs layers with a Mn content of 5% grown on relaxed InGaAs-templates. While hole concentration and Curie temperature were found to be unaffected by vertical strain, a significant dependence of the MA on {epsilon}{sub zz} was found. The most pronounced dependence was observed for the anisotropy parameter B{sub 2} {sub perpendicular} {sub to}, representing the intrinsic contribution to the MA perpendicular to the layer plane. For this parameter a linear dependence on {epsilon}{sub zz} was found, resulting in a strain-induced transition of the magnetic easy axis with increasing strain from in-plane to out-of-plane at {epsilon}{sub zz} {approx} -0.13%. Post-growth annealing of the samples leads to an outdiffusion and/or regrouping of the highly mobile Mn interstitial donor defects, resulting in an increase in both p and T{sub C}. For the annealed samples, the transition from in-plane to out-of-plane easy axis takes place at {epsilon}{sub zz} {approx} -0.07%. From a comparison of as-grown and annealed samples, B{sub 2} {sub perpendicular} {sub to} was found to be proportional to both p and {epsilon}{sub zz}, B{sub 2} {sub perpendicular} {sub to} {proportional_to} p .{epsilon}{sub zz}. To study the influence of substrate orientation on the magnetic properties of GaMnAs, a series of GaMnAs layers with Mn contents up to 5% was grown on (001)- and (113)A-oriented GaAs substrates. The hole densities and Curie temperatures, determined from magnetotransport measurements, are drastically reduced in the (113)A layers. The differences in the magnetic properties of (113)A- and

  3. miR-21 modulates tumor outgrowth induced by human adipose tissue-derived mesenchymal stem cells in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Keun Koo; Lee, Ae Lim; Kim, Jee Young [Department of Physiology, School of Medicine, Pusan National University, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Medical Research Center for Ischemic Tissue Engineering, Pusan National University, Yangsan, Gyeongnam 626-870 (Korea, Republic of); BK21 Medical Science Education Center, School of Medicine, Pusan National University, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Lee, Sun Young [Department of Physiology, School of Medicine, Pusan National University, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Medical Research Center for Ischemic Tissue Engineering, Pusan National University, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Bae, Yong Chan [Department of Plastic Surgery, School of Medicine, Pusan National University, Pusan 602-739 (Korea, Republic of); Jung, Jin Sup, E-mail: jsjung@pusan.ac.kr [Department of Physiology, School of Medicine, Pusan National University, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Medical Research Center for Ischemic Tissue Engineering, Pusan National University, Yangsan, Gyeongnam 626-870 (Korea, Republic of); BK21 Medical Science Education Center, School of Medicine, Pusan National University, Yangsan, Gyeongnam 626-870 (Korea, Republic of); Medical Research Institute, Pusan National University, Pusan 602-739 (Korea, Republic of)

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer miR-21 modulates hADSC-induced increase of tumor growth. Black-Right-Pointing-Pointer The action is mostly mediated by the modulation of TGF-{beta} signaling. Black-Right-Pointing-Pointer Inhibition of miR-21 enhances the blood flow recovery in hindlimb ischemia. -- Abstract: Mesenchymal stem cells (MSCs) have generated a great deal of interest in clinical situations, due principally to their potential use in regenerative medicine and tissue engineering applications. However, the therapeutic application of MSCs remains limited, unless the favorable effects of MSCs on tumor growth in vivo, and the long-term safety of the clinical applications of MSCs, can be more thoroughly understood. In this study, we determined whether microRNAs can modulate MSC-induced tumor outgrowth in BALB/c nude mice. Overexpression of miR-21 in human adipose-derived stem cells (hADSCs) inhibited hADSC-induced tumor growth, and inhibition of miR-21 increased it. Downregulation of transforming growth factor beta receptor II (TGFBR2), but not of signal transducer and activator of transcription 3, in hADSCs showed effects similar to those of miR-21 overexpression. Downregulation of TGFBR2 and overexpression of miR21 decreased tumor vascularity. Inhibition of miR-21 and the addition of TGF-{beta} increased the levels of vascular endothelial growth factor and interleukin-6 in hADSCs. Transplantation of miR-21 inhibitor-transfected hADSCs increased blood flow recovery in a hind limb ischemia model of nude mice, compared with transplantation of control oligo-transfected cells. These findings indicate that MSCs might favor tumor growth in vivo. Thus, it is necessary to study the long-term safety of this technique before MSCs can be used as therapeutic tools in regenerative medicine and tissue engineering.

  4. Motor cortex and spinal cord neuromodulation promote corticospinal tract axonal outgrowth and motor recovery after cervical contusion spinal cord injury.

    Science.gov (United States)

    Zareen, N; Shinozaki, M; Ryan, D; Alexander, H; Amer, A; Truong, D Q; Khadka, N; Sarkar, A; Naeem, S; Bikson, M; Martin, J H

    2017-11-01

    Cervical injuries are the most common form of SCI. In this study, we used a neuromodulatory approach to promote skilled movement recovery and repair of the corticospinal tract (CST) after a moderately severe C4 midline contusion in adult rats. We used bilateral epidural intermittent theta burst (iTBS) electrical stimulation of motor cortex to promote CST axonal sprouting and cathodal trans-spinal direct current stimulation (tsDCS) to enhance spinal cord activation to motor cortex stimulation after injury. We used Finite Element Method (FEM) modeling to direct tsDCS to the cervical enlargement. Combined iTBS-tsDCS was delivered for 30min daily for 10days. We compared the effect of stimulation on performance in the horizontal ladder and the Irvine Beattie and Bresnahan forepaw manipulation tasks and CST axonal sprouting in injury-only and injury+stimulation animals. The contusion eliminated the dorsal CST in all animals. tsDCS significantly enhanced motor cortex evoked responses after C4 injury. Using this combined spinal-M1 neuromodulatory approach, we found significant recovery of skilled locomotion and forepaw manipulation skills compared with injury-only controls. The spared CST axons caudal to the lesion in both animal groups derived mostly from lateral CST axons that populated the contralateral intermediate zone. Stimulation enhanced injury-dependent CST axonal outgrowth below and above the level of the injury. This dual neuromodulatory approach produced partial recovery of skilled motor behaviors that normally require integration of posture, upper limb sensory information, and intent for performance. We propose that the motor systems use these new CST projections to control movements better after injury. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Nerve growth factor alters microtubule targeting agent-induced neurotransmitter release but not MTA-induced neurite retraction in sensory neurons.

    Science.gov (United States)

    Pittman, Sherry K; Gracias, Neilia G; Fehrenbacher, Jill C

    2016-05-01

    Peripheral neuropathy is a dose-limiting side effect of anticancer treatment with the microtubule-targeted agents (MTAs), paclitaxel and epothilone B (EpoB); however, the mechanisms by which the MTAs alter neuronal function and morphology are unknown. We previously demonstrated that paclitaxel alters neuronal sensitivity, in vitro, in the presence of nerve growth factor (NGF). Evidence in the literature suggests that NGF may modulate the neurotoxic effects of paclitaxel. Here, we examine whether NGF modulates changes in neuronal sensitivity and morphology induced by paclitaxel and EpoB. Neuronal sensitivity was assessed using the stimulated release of calcitonin gene-related peptide (CGRP), whereas morphology of established neurites was evaluated using a high content screening system. Dorsal root ganglion cultures, maintained in the absence or presence of NGF, were treated from day 7 to day 12 in culture with paclitaxel (300nM) or EpoB (30nM). Following treatment, the release of CGRP was stimulated using capsaicin or high extracellular potassium. In the presence of NGF, EpoB mimicked the effects of paclitaxel: capsaicin-stimulated release was attenuated, potassium-stimulated release was slightly enhanced and the total peptide content was unchanged. In the absence of NGF, both paclitaxel and EpoB decreased capsaicin- and potassium-stimulated release and the total peptide content, suggesting that NGF may reverse MTA-induced hyposensitivity. Paclitaxel and EpoB both decreased neurite length and branching, and this attenuation was unaffected by NGF in the growth media. These differential effects of NGF on neuronal sensitivity and morphology suggest that neurite retraction is not a causative factor to alter neuronal sensitivity. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Loss of Aβ-nerve endings associated with the Merkel cell-neurite complex in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis.

    Science.gov (United States)

    Carrión, Daniela Calderón; Korkmaz, Yüksel; Cho, Britta; Kopp, Marion; Bloch, Wilhelm; Addicks, Klaus; Niedermeier, Wilhelm

    2016-03-30

    The Merkel cell-neurite complex initiates the perception of touch and mediates Aβ slowly adapting type I responses. Lichen planus is a chronic inflammatory autoimmune disease with T-cell-mediated inflammation, whereas hyperkeratosis is characterized with or without epithelial dysplasia in the oral mucosa. To determine the effects of lichen planus and hyperkeratosis on the Merkel cell-neurite complex, healthy oral mucosal epithelium and lesional oral mucosal epithelium of lichen planus and hyperkeratosis patients were stained by immunohistochemistry (the avidin-biotin-peroxidase complex and double immunofluorescence methods) using pan cytokeratin, cytokeratin 20 (K20, a Merkel cell marker), and neurofilament 200 (NF200, a myelinated Aβ- and Aδ-nerve fibre marker) antibodies. NF200-immunoreactive (ir) nerve fibres in healthy tissues and in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis were counted and statistically analysed. In the healthy oral mucosa, K20-positive Merkel cells with and without close association to the intraepithelial NF200-ir nerve fibres were detected. In the lesional oral mucosa of lichen planus and hyperkeratosis patients, extremely rare NF200-ir nerve fibres were detected only in the lamina propria. Compared with healthy tissues, lichen planus and hyperkeratosis tissues had significantly decreased numbers of NF200-ir nerve fibres in the oral mucosal epithelium. Lichen planus and hyperkeratosis were associated with the absence of Aβ-nerve endings in the oral mucosal epithelium. Thus, we conclude that mechanosensation mediated by the Merkel cell-neurite complex in the oral mucosal epithelium is impaired in lichen planus and hyperkeratosis.

  7. Anisotropy in elastic properties of lithium sodium sulphate ...

    Indian Academy of Sciences (India)

    Anisotropy in elastic properties of lithium sodium sulphate hexahydrate single crystal—An ultrasonic study. GEORGE VARUGHESE. ,∗. , A S KUMAR†, J PHILIP†† and GODFREY LOUIS#. Department of Physics, Catholicate College, Pathanamthitta 689 648, India. †SPAP, M.G. University, Kottayam 686 560, India. ††STIC ...

  8. Diffusion tensor MR microscopy of tissues with low diffusional anisotropy.

    Science.gov (United States)

    Bajd, Franci; Mattea, Carlos; Stapf, Siegfried; Sersa, Igor

    2016-06-01

    Diffusion tensor imaging exploits preferential diffusional motion of water molecules residing within tissue compartments for assessment of tissue structural anisotropy. However, instrumentation and post-processing errors play an important role in determination of diffusion tensor elements. In the study, several experimental factors affecting accuracy of diffusion tensor determination were analyzed. Effects of signal-to-noise ratio and configuration of the applied diffusion-sensitizing gradients on fractional anisotropy bias were analyzed by means of numerical simulations. In addition, diffusion tensor magnetic resonance microscopy experiments were performed on a tap water phantom and bovine articular cartilage-on-bone samples to verify the simulation results. In both, the simulations and the experiments, the multivariate linear regression of the diffusion-tensor analysis yielded overestimated fractional anisotropy with low SNRs and with low numbers of applied diffusion-sensitizing gradients. An increase of the apparent fractional anisotropy due to unfavorable experimental conditions can be overcome by applying a larger number of diffusion sensitizing gradients with small values of the condition number of the transformation matrix. This is in particular relevant in magnetic resonance microscopy, where imaging gradients are high and the signal-to-noise ratio is low.

  9. Seismic anisotropy of serpentinite from Val Malenco, Italy

    Czech Academy of Sciences Publication Activity Database

    Kern, H.; Lokajíček, Tomáš; Svitek, Tomáš; Wenk, H.-R.

    2015-01-01

    Roč. 120, č. 6 (2015), s. 4113-4129 ISSN 2169-9313 R&D Projects: GA MŠk LH13102 Institutional support: RVO:67985831 Keywords : serpentinite * anisotropy Subject RIV: DE - Earth Magnetism, Geodesy, Geography Impact factor: 3.318, year: 2015

  10. Magnetocrystalline anisotropy of FePt: a detailed view

    Czech Academy of Sciences Publication Activity Database

    Khan, S.A.; Blaha, P.; Ebert, H.; Minár, J.; Šipr, Ondřej

    2016-01-01

    Roč. 94, č. 14 (2016), 1-10, č. článku 144436. ISSN 2469-9950 Institutional support: RVO:68378271 Keywords : magnetocrystalline anisotropy * FePt * LDA Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 3.836, year: 2016

  11. Photoinduced Circular Anisotropy in Side-Chain Azobenzene Polyesters

    DEFF Research Database (Denmark)

    Nikolova, L.; Todorov, T.; Ivanov, M.

    1997-01-01

    We report for the first time the inducing of large circular anisotropy in previously unoriented films of side-chain azobenzene polyesters on illumination with circularly polarized light at a wavelength of 488 nm. The circular dichroism and optical activity are measured simultaneously in real time...

  12. Solar energetic particle anisotropies and insights into particle transport

    Energy Technology Data Exchange (ETDEWEB)

    Leske, R. A., E-mail: ral@srl.caltech.edu; Cummings, A. C.; Cohen, C. M. S.; Mewaldt, R. A.; Labrador, A. W.; Stone, E. C. [California Institute of Technology, Pasadena, CA 91125 (United States); Wiedenbeck, M. E. [Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109 (United States); Christian, E. R.; Rosenvinge, T. T. von [NASA/Goddard Space Flight Center, Greenbelt, MD 20771 (United States)

    2016-03-25

    As solar energetic particles (SEPs) travel through interplanetary space, their pitch-angle distributions are shaped by the competing effects of magnetic focusing and scattering. Measurements of SEP anisotropies can therefore reveal information about interplanetary conditions such as magnetic field strength, topology, and turbulence levels at remote locations from the observer. Onboard each of the two STEREO spacecraft, the Low Energy Telescope (LET) measures pitch-angle distributions for protons and heavier ions up to iron at energies of about 2-12 MeV/nucleon. Anisotropies observed using LET include bidirectional flows within interplanetary coronal mass ejections, sunward-flowing particles when STEREO was magnetically connected to the back side of a shock, and loss-cone distributions in which particles with large pitch angles underwent magnetic mirroring at an interplanetary field enhancement that was too weak to reflect particles with the smallest pitch angles. Unusual oscillations in the width of a beamed distribution at the onset of the 23 July 2012 SEP event were also observed and remain puzzling. We report LET anisotropy observations at both STEREO spacecraft and discuss their implications for SEP transport, focusing exclusively on the extreme event of 23 July 2012 in which a large variety of anisotropies were present at various times during the event.

  13. Computing magnetic anisotropy constants of single molecule magnets

    Indian Academy of Sciences (India)

    We present here a theoretical approach to compute the molecular magnetic anisotropy parameters, and for single molecule magnets in any given spin eigenstate of exchange spin Hamiltonian. We first describe a hybrid constant -valence bond (VB) technique of solving spin Hamiltonians employing full spatial ...

  14. Anisotropy of the magnetocaloric effect in DyNiAl

    Czech Academy of Sciences Publication Activity Database

    Kaštil, J.; Javorský, P.; Andreev, Alexander V.

    2009-01-01

    Roč. 321, č. 15 (2009), s. 2318-2321 ISSN 0304-8853 Institutional research plan: CEZ:AV0Z10100520 Keywords : magnetocaloric effec * DyNiAl * magnetism * anisotropy Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 1.204, year: 2009

  15. Solar diurnal anisotropy measured using muons in GRAPES-3 ...

    Indian Academy of Sciences (India)

    The mean energy of muons at sea level is ∼4 GeV with a rel- .... of decays of mesons and muons work against each other resulting in temperature coef- ..... The mean muon rate of 16 modules measured every 15 min for one week interval from .... 4. 8. 12. 16. 20. 24. Hours. Figure 12. Solar diurnal anisotropy measured in ...

  16. Anisotropy function for pion-proton elastic scattering

    Energy Technology Data Exchange (ETDEWEB)

    Saleem, Mohammad; Fazal-e-Aleem; Rashid, Haris

    1988-09-01

    By using the generalised Chou-Yang model and the experimental data on ..pi../sup -/p elastic scattering at 200 GeV/c, the anisotropy function which reflects the non-isotropic nature of elastic scattering is computed for the reaction ..pi../sup -/p -> ..pi../sup -/p.

  17. Anisotropy function for proton-proton elastic scattering

    Energy Technology Data Exchange (ETDEWEB)

    Saleem, Mohammad; Fazal-e-Aleem; Azhar, I.A. (Punjab Univ., Lahore (Pakistan). Centre for High Energy Physics)

    1990-07-01

    By using the generalized Chou-Yang model and the experimental data on pp elastic scattering at 53 GeV, the anisotropy function which reflects the non-isotropic nature of elastic scattering is computed for the reaction pp{yields}pp. (author).

  18. Anisotropy function for proton-proton elastic scattering

    International Nuclear Information System (INIS)

    Saleem, Mohammad; Fazal-e-Aleem; Azhar, I.A.

    1990-01-01

    By using the generalized Chou-Yang model and the experimental data on pp elastic scattering at 53 GeV, the anisotropy function which reflects the non-isotropic nature of elastic scattering is computed for the reaction pp→pp. (author)

  19. Anisotropy function for pion-proton elastic scattering

    International Nuclear Information System (INIS)

    Saleem, Mohammad; Fazal-e-Aleem; Rashid, Haris

    1988-01-01

    By using the generalised Chou-Yang model and the experimental data on π - p elastic scattering at 200 GeV/c, the anisotropy function which reflects the non-isotropic nature of elastic scattering is computed for the reaction π - p → π - p. (author)

  20. Illustrative view on the magnetocrystalline anisotropy of adatoms and monolayers

    Czech Academy of Sciences Publication Activity Database

    Šipr, Ondřej; Mankovsky, S.; Polesya, S.; Bornemann, S.; Minár, J.; Ebert, H.

    2016-01-01

    Roč. 93, č. 17 (2016), s. 1-13, č. článku 174409. ISSN 2469-9950 R&D Projects: GA ČR(CZ) GAP108/11/0853 Institutional support: RVO:68378271 Keywords : magnetic anisotropy * adatom * monolayer * spin-orbit coupling Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 3.836, year: 2016

  1. Angular anisotropy of the cosmic microwave background radiation

    International Nuclear Information System (INIS)

    Silk, J.

    1982-01-01

    The theory of fluctuations in the cosmic microwave background radiation is reviewed. Anisotropy on large-scale (dipole and quadrupole) and on small scales is discussed. The smoothing effects of secondary ionization (fractional ionization x) are found to be unimportant over an angular scale greater than approx.= 5(OMEGAx)sup(1/3) degrees. (author)

  2. Induced anisotropy in amorphous Sm-Co sputtered films

    International Nuclear Information System (INIS)

    Chen, K.; Hegde, H.; Cadieu, F.J.

    1992-01-01

    The variation of the in-the-film-plane anisotropy constant, K u , with composition and the magnitude of the field, H s , applied in plane during the sputter deposition of amorphous Sm x Co 1-x , 0.08≤x≤0.40, thin films has been studied. We demonstrate here that with a large H s , 5.0 kOe, a well defined and large in-the-film-plane anisotropy can be obtained. An exceptionally high value of K u =3.3x10 6 erg/cm 3 has been obtained. For the loop measured along the in-plane hard direction, the opening of the loop was undetectable, and the loop along the easy axis was a perfect rectangle. For certain conditions, the anisotropy field measured perpendicular to the film plane when corrected for demagnetization (N d =4π) was the same as that for the in-plane measurements. It is concluded that surface induced short range ordering was the origin of the anisotropy observed in amorphous films deposited in a magnetic field. The formation mechanism is different from that of the short range ordering induced by field annealing

  3. Anisotropy signature in reverse-time migration extended images

    KAUST Repository

    Sava, Paul C.; Alkhalifah, Tariq Ali

    2014-01-01

    Reverse-time migration can accurately image complex geologic structures in anisotropic media. Extended images at selected locations in the Earth, i.e., at common-image-point gathers, carry rich information to characterize the angle-dependent illumination and to provide measurements for migration velocity analysis. However, characterizing the anisotropy influence on such extended images is a challenge. Extended common-image-point gathers are cheap to evaluate since they sample the image at sparse locations indicated by the presence of strong reflectors. Such gathers are also sensitive to velocity error that manifests itself through moveout as a function of space and time lags. Furthermore, inaccurate anisotropy leaves a distinctive signature in common-image-point gathers, which can be used to evaluate anisotropy through techniques similar to the ones used in conventional wavefield tomography. It specifically admits a V-shaped residual moveout with the slope of the "V" flanks depending on the anisotropic parameter η regardless of the complexity of the velocity model. It reflects the fourth-order nature of the anisotropy influence on moveout as it manifests itself in this distinct signature in extended images after handling the velocity properly in the imaging process. Synthetic and real data observations support this assertion.

  4. Solar energetic particle anisotropies and insights into particle transport

    Science.gov (United States)

    Leske, R. A.; Cummings, A. C.; Cohen, C. M. S.; Mewaldt, R. A.; Labrador, A. W.; Stone, E. C.; Wiedenbeck, M. E.; Christian, E. R.; Rosenvinge, T. T. von

    2016-03-01

    As solar energetic particles (SEPs) travel through interplanetary space, their pitch-angle distributions are shaped by the competing effects of magnetic focusing and scattering. Measurements of SEP anisotropies can therefore reveal information about interplanetary conditions such as magnetic field strength, topology, and turbulence levels at remote locations from the observer. Onboard each of the two STEREO spacecraft, the Low Energy Telescope (LET) measures pitch-angle distributions for protons and heavier ions up to iron at energies of about 2-12 MeV/nucleon. Anisotropies observed using LET include bidirectional flows within interplanetary coronal mass ejections, sunward-flowing particles when STEREO was magnetically connected to the back side of a shock, and loss-cone distributions in which particles with large pitch angles underwent magnetic mirroring at an interplanetary field enhancement that was too weak to reflect particles with the smallest pitch angles. Unusual oscillations in the width of a beamed distribution at the onset of the 23 July 2012 SEP event were also observed and remain puzzling. We report LET anisotropy observations at both STEREO spacecraft and discuss their implications for SEP transport, focusing exclusively on the extreme event of 23 July 2012 in which a large variety of anisotropies were present at various times during the event.

  5. The large scale microwave background anisotropy in decaying particle cosmology

    International Nuclear Information System (INIS)

    Panek, M.

    1987-06-01

    We investigate the large-scale anisotropy of the microwave background radiation in cosmological models with decaying particles. The observed value of the quadrupole moment combined with other constraints gives an upper limit on the redshift of the decay z/sub d/ < 3-5. 12 refs., 2 figs

  6. Influence of magnetic anisotropy on the superferromagnetic ordering in nanocomposites

    DEFF Research Database (Denmark)

    Mørup, Steen; Christiansen, Gunnar Dan

    1993-01-01

    Magnetic interaction between ultrafine particles may result in superferromagnetism, i.e., ordering of the magnetic moments of particles which would be superparamagnetic if they were noninteracting. In this article we discuss the influence of the magnetic anisotropy on the temperature dependence o...

  7. Interfaces anisotropy in single crystal V/Fe/V trilayer

    Energy Technology Data Exchange (ETDEWEB)

    Louis, D. [Institut Jean Lamour, UMR CNRS 7198, Université de Lorraine, 54506 Vandoeuvre-lès-Nancy (France); Lytvynenko, Ia. [Sumy State University, 2, Rymskogo-Korsakova Street, 40007 Sumy (Ukraine); Hauet, T., E-mail: thomas.hauet@univ-lorraine.fr [Institut Jean Lamour, UMR CNRS 7198, Université de Lorraine, 54506 Vandoeuvre-lès-Nancy (France); Lacour, D.; Hehn, M.; Andrieu, S.; Montaigne, F. [Institut Jean Lamour, UMR CNRS 7198, Université de Lorraine, 54506 Vandoeuvre-lès-Nancy (France)

    2014-12-15

    The value and sign of V/Fe interface anisotropy are investigated. Epitaxial V/Fe/V/Au layers with different iron thicknesses were grown on single-crystalline (001) MgO substrate by ultra-high vacuum molecular beam epitaxy. Magnetometry was used to measure magnetization and out-of-plane anisotropy field. From these values, we quantify the number of dead layers due to V/Fe or Fe/V interfaces, and compare it with the literature. We deduce that dead layers occur mostly at the bottom V/Fe interface. An average value for V/Fe and Fe/V interface anisotropy around 0±0.1 erg/cm{sup 2} (mJ/m{sup 2}) was thus deduced. - Highlights: • In a V/Fe/V stack, dead layers (i.e. overall magnetization reduction) originate mostly from the bottom V/Fe interface. • The average value for V/Fe and Fe/V interface anisotropy in V/Fe/V stack has been quantified as 0±0.1 erg/cm{sup 2} (mJ/m{sup 2})

  8. Modification of magnetic anisotropy in metallic glasses using high ...

    Indian Academy of Sciences (India)

    The data gives a straight line as a best fit as shown in figure 4. It can be safely inferred that the residual stresses produced in the glassy metals could be the main cause of the reduction in in-plane magnetic anisotropy. This phe- nomenon is in conformity with the magnetostriction effect in which mechanical stresses. 1098.

  9. Anisotropy signature in reverse-time migration extended images

    KAUST Repository

    Sava, Paul C.

    2014-11-04

    Reverse-time migration can accurately image complex geologic structures in anisotropic media. Extended images at selected locations in the Earth, i.e., at common-image-point gathers, carry rich information to characterize the angle-dependent illumination and to provide measurements for migration velocity analysis. However, characterizing the anisotropy influence on such extended images is a challenge. Extended common-image-point gathers are cheap to evaluate since they sample the image at sparse locations indicated by the presence of strong reflectors. Such gathers are also sensitive to velocity error that manifests itself through moveout as a function of space and time lags. Furthermore, inaccurate anisotropy leaves a distinctive signature in common-image-point gathers, which can be used to evaluate anisotropy through techniques similar to the ones used in conventional wavefield tomography. It specifically admits a V-shaped residual moveout with the slope of the "V" flanks depending on the anisotropic parameter η regardless of the complexity of the velocity model. It reflects the fourth-order nature of the anisotropy influence on moveout as it manifests itself in this distinct signature in extended images after handling the velocity properly in the imaging process. Synthetic and real data observations support this assertion.

  10. Resolution of reservoir scale electrical anisotropy from marine CSEM data

    Energy Technology Data Exchange (ETDEWEB)

    Brown, V.; Hoversten, G.M.; Key, K.; Chen, J.

    2011-10-01

    A combination of 1D and 3D forward and inverse solutions is used to quantify the sensitivity and resolution of conventional controlled source electromagnetic (CSEM) data collected using a horizontal electric dipole source to transverse electrical anisotropy located in a deep-water exploration reservoir target. Since strongly anisotropic shale layers have a vertical resistivity that can be comparable to many reservoirs, we examine how CSEM can discriminate confounding shale layers through their characteristically lower horizontal resistivity. Forward modeling demonstrates that the sensitivity to reservoir level anisotropy is very low compared to the sensitivity to isotropic reservoirs, especially when the reservoir is deeper than about 2 km below the seabed. However, for 1D models where the number of inversion parameters can be fixed to be only a few layers, both vertical and horizontal resistivity of the reservoir can be well resolved using a stochastic inversion. We find that the resolution of horizontal resistivity increases as the horizontal resistivity decreases. We show that this effect is explained by the presence of strong horizontal current density in anisotropic layers with low horizontal resistivity. Conversely, when the reservoir has a vertical to horizontal resistivity ratio of about 10 or less, the current density is vertically polarized and hence has little sensitivity to the horizontal resistivity. Resistivity anisotropy estimates from 3D inversion for 3D targets suggest that resolution of reservoir level anisotropy for 3D targets will require good a priori knowledge of the background sediment conductivity and structural boundaries.

  11. Type I supernovae and angular anisotropy of the Hubble constant

    International Nuclear Information System (INIS)

    Le Denmat, Gerard; Vigier, J.-P.

    1975-01-01

    The observation of type I supernovae in distant galaxies yields an homogeneous sample of sources to evaluate their true distance. An