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Sample records for neurite length-dependent accumulation

  1. AMPK over-activation leads to accumulation of α-synuclein oligomers and decrease of neurites

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    Jiang, Peizhou; Gan, Ming; Ebrahim, Abdul Shukkur; Castanedes-Casey, Monica; Dickson, Dennis W.; Yen, Shu-Hui C.

    2012-01-01

    Neuronal inclusions of α-synuclein (α-syn), termed Lewy bodies, are a hallmark of Parkinson disease (PD). Increased α-syn levels can occur in brains of aging human and neurotoxin treated mice. Since previous studies have shown increased brain lactate levels in aging brains, in PD affected subjects when compared to age-matched controls, and in mice treated with MPTP, we tested the effects of lactate exposure on α-syn in a cell based-study. We demonstrated that (i) lactate treatment led to α-syn accumulation and oligomerization in a time- and concentration-dependent manner, (ii) such alterations were mediated via adenosine-monophosphate activated protein kinase (AMPK) and associated with increasing cytoplasmic phosphorylated AMPK levels, (iii) AMPK activation facilitated α-syn accumulation and phosphorylation, (iv) lactate treatment or overexpression of active form of AMPK decreased α-syn turnover and neurite outgrowth and (v) Lewy body-bearing neurons displayed abnormal cytoplasmic distribution of phosphorylated AMPK, which normally is located in nuclei. Together, our results suggest that chronic neuronal accumulation of α-syn induced by lactate-triggered AMPK activation in aging brains may be a novel mechanism underlying α-synucleionpathies in PD and related disorders. PMID:23200460

  2. Early long-term administration of the CSF1R inhibitor PLX3397 ablates microglia and reduces accumulation of intraneuronal amyloid, neuritic plaque deposition and pre-fibrillar oligomers in 5XFAD mouse model of Alzheimer's disease.

    Science.gov (United States)

    Sosna, Justyna; Philipp, Stephan; Albay, Ricardo; Reyes-Ruiz, Jorge Mauricio; Baglietto-Vargas, David; LaFerla, Frank M; Glabe, Charles G

    2018-03-01

    Besides the two main classical features of amyloid beta aggregation and tau-containing neurofibrillary tangle deposition, neuroinflammation plays an important yet unclear role in the pathophysiology of Alzheimer's disease (AD). Microglia are believed to be key mediators of neuroinflammation during AD and responsible for the regulation of brain homeostasis by balancing neurotoxicity and neuroprotective events. We have previously reported evidence that neuritic plaques are derived from dead neurons that have accumulated intraneuronal amyloid and further recruit Iba1-positive cells, which play a role in either neuronal demise or neuritic plaque maturation or both. To study the impact of microglia on neuritic plaque development, we treated two-month-old 5XFAD mice with a selective colony stimulation factor 1 receptor (CSF1R) inhibitor, PLX3397, for a period of 3 months, resulting in a significant ablation of microglia. Directly after this treatment, we analyzed the amount of intraneuronal amyloid and neuritic plaques and performed behavioral studies including Y-maze, fear conditioning and elevated plus maze. We found that early long-term PLX3397 administration results in a dramatic reduction of both intraneuronal amyloid as well as neuritic plaque deposition. PLX3397 treated young 5XFAD mice also displayed a significant decrease of soluble fibrillar amyloid oligomers in brain lysates, a depletion of soluble pre-fibrillar oligomers in plasma and an improvement in cognitive function measured by fear conditioning tests. Our findings demonstrate that CSF1R signaling, either directly on neurons or mediated by microglia, is crucial for the accumulation of intraneuronal amyloid and formation of neuritic plaques, suggesting that these two events are serially linked in a causal pathway leading to neurodegeneration and neuritic plaque formation. CSF1R inhibitors represent potential preventative or therapeutic approach that target the very earliest stages of the formation of

  3. Understanding the length dependence of molecular junction thermopower

    DEFF Research Database (Denmark)

    Karlström, Sven Olov Harald; Strange, Mikkel; Solomon, Gemma

    2014-01-01

    Thermopower of molecular junctions is sensitive to details in the junction and may increase, decrease, or saturate with increasing chain length, depending on the system. Using McConnell's theory for exponentially suppressed transport together with a simple and easily interpretable tight binding...... model, we show how these different behaviors depend on the molecular backbone and its binding to the contacts. We distinguish between resonances from binding groups or undercoordinated electrode atoms, and those from the periodic backbone. It is demonstrated that while the former gives a length......-independent contribution to the thermopower, possibly changing its sign, the latter determines its length dependence. This means that the question of which orbitals from the periodic chain that dominate the transport should not be inferred from the sign of the thermopower but from its length dependence. We find...

  4. Stalk-length-dependence of the contractility of Vorticella convallaria

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    Gul Chung, Eun; Ryu, Sangjin

    2017-12-01

    Vorticella convallaria is a sessile protozoan of which the spasmoneme contracts on a millisecond timescale. Because this contraction is induced and powered by the binding of calcium ions (Ca2+), the spasmoneme showcases Ca2+-powered cellular motility. Because the isometric tension of V. convallaria increases linearly with its stalk length, it is hypothesized that the contractility of V. convallaria during unhindered contraction depends on the stalk length. In this study, the contractile force and energetics of V. convallaria cells of different stalk lengths were evaluated using a fluid dynamic drag model which accounts for the unsteadiness and finite Reynolds number of the water flow caused by contracting V. convallaria and the wall effect of the no-slip substrate. It was found that the contraction displacement, peak contraction speed, peak contractile force, total mechanical work, and peak power depended on the stalk length. The observed stalk-length-dependencies were simulated using a damped spring model, and the model estimated that the average spring constant of the contracting stalk was 1.34 nN µm‑1. These observed length-dependencies of Vorticella’s key contractility parameters reflect the biophysical mechanism of the spasmonemal contraction, and thus they should be considered in developing a theoretical model of the Vorticella spasmoneme.

  5. Length-dependent thermal transport and ballistic thermal conduction

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    Bor-Woei Huang

    2015-05-01

    Full Text Available Probing length-dependent thermal conductivity of a given material has been considered as an important experimental method to determine the length of ballistic thermal conduction, or equivalently, the averaged phonon mean free path (l. However, many previous thermal transport measurements have focused on varying the lateral dimensions of samples, rendering the experimental interpretation indirect. Moreover, deducing l is model-dependent in many optical measurement techniques. In addition, finite contact thermal resistances and variations of sample qualities are very likely to obscure the effect in practice, leading to an overestimation of l. We point out that directly investigating one-dimensional length-dependent (normalized thermal resistance is a better experimental method to determine l. In this regard, we find that no clear experimental data strongly support ballistic thermal conduction of Si or Ge at room temperature. On the other hand, data of both homogeneously-alloyed SiGe nanowires and heterogeneously-interfaced Si-Ge core-shell nanowires provide undisputed evidence for ballistic thermal conduction over several micrometers at room temperature.

  6. The Deacetylase HDAC6 Mediates Endogenous Neuritic Tau Pathology

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    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.

  7. 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...... in PC12E2 cells and primary hippocampal neurons. BASP1 overexpression stimulated neurite outgrowth in both cell types. The effects of BASP1 and trans-homophilic NCAM interactions were additive, and BASP1-induced neurite outgrowth was not inhibited by ectopic expression of cytoplasmic NCAM domains...... on neurite outgrowth. Finally, coexpression experiments with dominant negative and wild-type versions of GAP-43 and BASP1 demonstrated that the two proteins could substitute for each other with respect to induction of NCAM-independent neurite outgrowth, whereas BASP1 was unable to replace the stimulatory...

  8. Boundary condition-selective length dependence of the flexural rigidity of microtubules

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    Zhang, Jin; Wang, Chengyuan

    2017-07-01

    Length-dependent flexural rigidity (FR) is observed experimentally for microtubules (MTs) subjected to certain boundary conditions. To shed some light on this unique feature, we have studied the FR of MTs with different boundary conditions. A molecular structural mechanics method is employed to accurately describe the real boundary conditions imposed on MTs in experiments. Some of component protofilaments of MTs are blocked at the ends while others are free. In addition, linked kinesin is treated as an elastic body rather than a rigid body. Our simulations show that for relatively long MTs having a length comparable to those measured in experiments the length-dependent rigidity is detected only for those with fixed-free and fixed-fixed ends, which is consistent with the experimental observation. To capture the physics leading to the above phenomenon, Timoshenko beam model is adopted accounting for both transverse shear effect (TSE) and imperfect boundary effect (IBE). Comparison between TSE and IBE indicates that the boundary condition-selective length-dependence achieved for the FR of relatively long MTs is primarily a result of the influence of IBE rather than TSE.

  9. Conversion Disorder Presenting As Neuritic Leprosy

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    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.

  10. Olfactory ensheathing cell-neurite alignment enhances neurite outgrowth in scar-like cultures

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    Khankan, Rana R.; Wanner, Ina B.; Phelps, Patricia E.

    2015-01-01

    The regenerative capacity of the adult CNS neurons after injury is strongly inhibited by the spinal cord lesion site environment that is composed primarily of the reactive astroglial scar and invading meningeal fibroblasts. Olfactory ensheathing cell (OEC) transplantation facilitates neuronal survival and functional recovery after a complete spinal cord transection, yet the mechanisms by which this recovery occurs remain unclear. We used a unique multicellular scar-like culture model to test if OECs promote neurite outgrowth in growth inhibitory areas. Astrocytes were mechanically injured and challenged by meningeal fibroblasts to produce key inhibitory elements of a spinal cord lesion. Neurite outgrowth of postnatal cerebral cortical neurons was assessed on three substrates: quiescent astrocyte control cultures, reactive astrocyte scar-like cultures, and scar-like cultures with OECs. Initial results showed that OECs enhanced total neurite outgrowth of cortical neurons in a scar-like environment by 60%. We then asked if the neurite growth-promoting properties of OECs depended on direct alignment between neuronal and OEC processes. Neurites that aligned with OECs were nearly three times longer when they grew on inhibitory meningeal fibroblast areas and twice as long on reactive astrocyte zones compared to neurites not associated with OECs. Our results show that OECs can independently enhance neurite elongation and that direct OEC-neurite cell contact can provide a permissive substrate that overcomes the inhibitory nature of the reactive astrocyte scar border and the fibroblast-rich spinal cord lesion core. PMID:25863021

  11. Smooth muscle length-dependent PI(4,5)P2 synthesis and paxillin tyrosine phosphorylation.

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    Sul, D; Baron, C B; Broome, R; Coburn, R F

    2001-07-01

    We studied effects of increasing the length of porcine trachealis muscle on 5.5 microM carbachol (CCh)-evoked phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] synthesis and other parameters of phosphatidylinositol (PI) turnover. PI(4,5)P2 resynthesis rates in muscle held at 1.0 optimal length (L(o)), measured over the first 6 min of CCh stimulation, were 140 +/- 12 and 227 +/- 14% of values found in muscle held at 0.5 L(o) and in free-floating muscle, respectively. Time-dependent changes in cellular masses of PI(4,5)P2, PI, and phosphatidic acid, and PI resynthesis rates, were also altered by the muscle length at which contraction occurred. In free-floating muscle, CCh did not evoke increases in tyrosine-phosphorylated paxillin (PTyr-paxillin), an index of beta1-integrin signaling; however, there were progressive increases in PTyr-paxillin in muscle held at 0.5 and 1.0 L(o) during contraction, which correlated with increases in PI(4,5)P2 synthesis rates. These data indicate that PI(4,5)P2 synthesis rates and other parameters of CCh-stimulated inositol phospholipid turnover are muscle length-dependent and provide evidence that supports the hypothesis that length-dependent beta1-integrin signals may exert control on CCh-activated PI(4,5)P2 synthesis.

  12. Chain length dependent alkane/β-cyclodextrin nonamphiphilic supramolecular building blocks.

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    Zhou, Chengcheng; Huang, Jianbin; Yan, Yun

    2016-02-07

    In this work we report the chain length dependent behavior of the nonamphiphilic supramolecular building blocks based on the host-guest inclusion complexes of alkanes and β-cyclodextrins (β-CD). (1)H NMR, ESI-MS, and SAXS measurements verified that upon increasing the chain length of alkanes, the building blocks for vesicle formation changed from channel type 2alkane@2β-CD via channel type alkane@2β-CD to non-channel type 2alkane@2β-CD. FT-IR and TGA experiments indicated that hydrogen bonding is the extensive driving force for vesicle formation. It revealed that water molecules are involved in vesicle formation in the form of structural water. Upon changing the chain length, the average number of water molecules associated with per building block is about 16-21, depending on the chain length.

  13. Telomerase inhibition targets clonogenic multiple myeloma cells through telomere length-dependent and independent mechanisms.

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    Sarah K Brennan

    2010-09-01

    Full Text Available Plasma cells constitute the majority of tumor cells in multiple myeloma (MM but lack the potential for sustained clonogenic growth. In contrast, clonotypic B cells can engraft and recapitulate disease in immunodeficient mice suggesting they serve as the MM cancer stem cell (CSC. These tumor initiating B cells also share functional features with normal stem cells such as drug resistance and self-renewal potential. Therefore, the cellular processes that regulate normal stem cells may serve as therapeutic targets in MM. Telomerase activity is required for the maintenance of normal adult stem cells, and we examined the activity of the telomerase inhibitor imetelstat against MM CSC. Moreover, we carried out both long and short-term inhibition studies to examine telomere length-dependent and independent activities.Human MM CSC were isolated from cell lines and primary clinical specimens and treated with imetelstat, a specific inhibitor of the reverse transcriptase activity of telomerase. Two weeks of exposure to imetelstat resulted in a significant reduction in telomere length and the inhibition of clonogenic MM growth both in vitro and in vivo. In addition to these relatively long-term effects, 72 hours of imetelstat treatment inhibited clonogenic growth that was associated with MM CSC differentiation based on expression of the plasma cell antigen CD138 and the stem cell marker aldehyde dehydrogenase. Short-term treatment of MM CSC also decreased the expression of genes typically expressed by stem cells (OCT3/4, SOX2, NANOG, and BMI1 as revealed by quantitative real-time PCR.Telomerase activity regulates the clonogenic growth of MM CSC. Moreover, reductions in MM growth following both long and short-term telomerase inhibition suggest that it impacts CSC through telomere length-dependent and independent mechanisms.

  14. Pure neuritic leprosy: Current status and relevance.

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    Rao, P Narasimha; Suneetha, Sujai

    2016-01-01

    Pure neuritic leprosy has always been an enigma due to its clinical and management ambiguities. Although only the Indian Association of Leprologist's classification recognizes 'pure neuritic leprosy' as a distinct sub group of leprosy, cases nonetheless are reported from various countries of Asia, Africa, South America and Europe, indicating its global relevance. It is important to maintain pure neuritic leprosy as a subgroup as it constitutes a good percentage of leprosy cases reported from India, which contributes to more than half of global leprosy numbers. Unfortunately, a high proportion of these patients present with Grade 2 disability at the time of initial reporting itself due to the early nerve involvement. Although skin lesions are absent by definition, when skin biopsies were performed from the skin along the distribution of the affected nerve, a proportion of patients demonstrated leprosy pathology, revealing sub-clinical skin involvement. In addition on follow-up, skin lesions are noted to develop in up to 20% of pure neuritic leprosy cases, indicating its progression to manifest cutaneous disease. Over the decades, the confirmation of diagnosis of pure neuritic leprosy has been subjective, however, with the arrival and use of high-resolution ultrasonography (HRUS) for nerve imaging, we have a tool not only to objectively measure and record the nerve thickening but also to assess the morphological alterations in the nerve including echo texture, fascicular pattern and vascularity. Management of pure neuritic leprosy requires multidrug therapy along with appropriate dose of systemic corticosteroids, for both acute and silent neuritis. Measures for pain relief, self-care of limbs and physiotherapy are important to prevent as well as manage disabilities in this group of patients.

  15. Pure neuritic leprosy: Current status and relevance

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    P Narasimha Rao

    2016-01-01

    Full Text Available Pure neuritic leprosy has always been an enigma due to its clinical and management ambiguities. Although only the Indian Association of Leprologist's classification recognizes 'pure neuritic leprosy' as a distinct sub group of leprosy, cases nonetheless are reported from various countries of Asia, Africa, South America and Europe, indicating its global relevance. It is important to maintain pure neuritic leprosy as a subgroup as it constitutes a good percentage of leprosy cases reported from India, which contributes to more than half of global leprosy numbers. Unfortunately, a high proportion of these patients present with Grade 2 disability at the time of initial reporting itself due to the early nerve involvement. Although skin lesions are absent by definition, when skin biopsies were performed from the skin along the distribution of the affected nerve, a proportion of patients demonstrated leprosy pathology, revealing sub-clinical skin involvement. In addition on follow-up, skin lesions are noted to develop in up to 20% of pure neuritic leprosy cases, indicating its progression to manifest cutaneous disease. Over the decades, the confirmation of diagnosis of pure neuritic leprosy has been subjective, however, with the arrival and use of high-resolution ultrasonography (HRUS for nerve imaging, we have a tool not only to objectively measure and record the nerve thickening but also to assess the morphological alterations in the nerve including echo texture, fascicular pattern and vascularity. Management of pure neuritic leprosy requires multidrug therapy along with appropriate dose of systemic corticosteroids, for both acute and silent neuritis. Measures for pain relief, self-care of limbs and physiotherapy are important to prevent as well as manage disabilities in this group of patients.

  16. Sarcomere length-dependence of activity-dependent twitch potentiation in mouse skeletal muscle

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    MacIntosh Brian R

    2002-12-01

    Full Text Available Abstract Background It has been reported that potentiation of a skeletal muscle twitch response is proportional to muscle length with a negative slope during staircase, and a positive slope during posttetanic potentiation. This study was done to directly compare staircase and posttetanic responses with measurement of sarcomere length to compare their length-dependence. Methods Mouse extensor digitorum longus (EDL muscles were dissected to small bundles of fibers, which permit measurement of sarcomere length (SL, by laser diffraction. In vitro fixed-end contractions of EDL fiber bundles were elicited at 22°C and 35°C at sarcomere lengths ranging from 2.35 μm to 3.85 μm. Twitch contractions were assessed before and after 1.5 s of 75 Hz stimulation at 22°C or during 10 s of 10 Hz stimulation at 22°C or 35°C. Results Staircase potentiation was greater at 35°C than 22°C, and the relative magnitude of the twitch contraction (Pt*/Pt was proportional to sarcomere length with a negative slope, over the range 2.3 μm – 3.7 μm. Linear regression yielded the following: Pt*/Pt = -0.59·SL+3.27 (r2 = 0.74; Pt*/Pt = -0.39·SL+2.34 (r2 = 0.48; and Pt*/Pt = -0.50·SL+2.45 (r2 = 0.80 for staircase at 35°C, and 22°C and posttetanic response respectively. Posttetanic depression rather than potentiation was present at long SL. This indicates that there may be two processes operating in these muscles to modulate the force: one that enhances and a second that depresses the force. Either or both of these processes may have a length-dependence of its mechanism. Conclusion There is no evidence that posttetanic potentiation is fundamentally different from staircase in these muscles.

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

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    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

  18. Anomalous length dependence of the conductance of graphene nanoribbons with zigzag edges

    KAUST Repository

    Bilić, Ante

    2013-01-01

    Charge transport through two sets of symmetric graphene nanoribbons with zigzag shaped edges in a two-terminal device has been investigated, using density functional theory combined with the non-equilibrium Green\\'s function method. The conductance has been explored as a function of nanoribbon length, bias voltage, and the strength of terminal coupling. The set of narrower nanoribbons, in the form of thiolated linear acenes, shows an anomalous length dependence of the conductance, which at first exhibits a drop and a minimum, followed by an evident rise. The length trend is shown to arise because of a gradual transformation in the transport mechanism, which changes from being governed by a continuum of out-of-plane π type and in-plane state channels to being fully controlled by a single, increasingly more resonant, occupied π state channel. For the set of nanoribbons with a wider profile, a steady increase is observed across the whole length range, owing to the absence of the former transport mechanism. The predicted trends are confirmed by the inclusion of self-interaction correction in the calculations. For both sets of nanoribbons the replacement of the strongly coupling thiol groups by weakly bonding phenathroline has been found to cause a strong attenuation with the length and a generally low conductance. © 2013 American Institute of Physics.

  19. Chain Length Dependence of the Dielectric Constant and Polarizability in Conjugated Organic Thin Films.

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    Van Dyck, Colin; Marks, Tobin J; Ratner, Mark A

    2017-06-27

    Dielectric materials are ubiquitous in optics, electronics, and materials science. Recently, there have been new efforts to characterize the dielectric performance of thin films composed of molecular assemblies. In this context, we investigate here the relationship between the polarizability of the constituent molecules and the film dielectric constant, using periodic density functional theory (DFT) calculations, for polyyne and saturated alkane chains. In particular, we explore the implication of the superlinear chain length dependence of the polarizability, a specific feature of conjugated molecules. We show and explain from DFT calculations and a simple depolarization model that this superlinearity is attenuated by the collective polarization. However, it is not completely suppressed. This confers a very high sensitivity of the dielectric constant to the thin film thickness. This latter can increase by a factor of 3-4 at reasonable coverages, by extending the molecular length. This significantly limits the decline of the thin film capacitance with the film thickness. Therefore, the conventional fit of the capacitance versus thickness is not appropriate to determine the dielectric constant of the film. Finally, we show that the failures of semilocal approximations of the exchange-correlation functional lead to a very significant overestimation of this effect.

  20. Length dependence of rectification in organic co-oligomer spin rectifiers

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    Gui-Chao, Hu; Zhao, Zhang; Ying, Li; Jun-Feng, Ren; Chuan-Kui, Wang

    2016-05-01

    The rectification ratio of organic magnetic co-oligomer diodes is investigated theoretically by changing the molecular length. The results reveal two distinct length dependences of the rectification ratio: for a short molecular diode, the charge-current rectification changes little with the increase of molecular length, while the spin-current rectification is weakened sharply by the length; for a long molecular diode, both the charge-current and spin-current rectification ratios increase quickly with the length. The two kinds of dependence switch at a specific length accompanied with an inversion of the rectifying direction. The molecular ortibals and spin-resolved transmission analysis indicate that the dominant mechanism of rectification suffers a change at this specific length, that is, from asymmetric shift of molecular eigenlevels to asymmetric spatial localization of wave functions upon the reversal of bias. This work demonstrates a feasible way to control the rectification in organic co-oligomer spin diodes by adjusting the molecular length. Project supported by the National Natural Science Foundation of China (Grant No. 11374195), the Natural Science Foundation of Shandong Province, China (Grant No. ZR2014AM017), the Taishan Scholar Project of Shandong Province, China, and the Excellent Young Scholars Research Fund of Shandong Normal University, China.

  1. Addressing the path-length-dependency confound in white matter tract segmentation.

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    Matthew G Liptrot

    Full Text Available We derive the Iterative Confidence Enhancement of Tractography (ICE-T framework to address the problem of path-length dependency (PLD, the streamline dispersivity confound inherent to probabilistic tractography methods. We show that PLD can arise as a non-linear effect, compounded by tissue complexity, and therefore cannot be handled using linear correction methods. ICE-T is an easy-to-implement framework that acts as a wrapper around most probabilistic streamline tractography methods, iteratively growing the tractography seed regions. Tract networks segmented with ICE-T can subsequently be delineated with a global threshold, even from a single-voxel seed. We investigated ICE-T performance using ex vivo pig-brain datasets where true positives were known via in vivo tracers, and applied the derived ICE-T parameters to a human in vivo dataset. We examined the parameter space of ICE-T: the number of streamlines emitted per voxel, and a threshold applied at each iteration. As few as 20 streamlines per seed-voxel, and a robust range of ICE-T thresholds, were shown to sufficiently segment the desired tract network. Outside this range, the tract network either approximated the complete white-matter compartment (too low threshold or failed to propagate through complex regions (too high threshold. The parameters were shown to be generalizable across seed regions. With ICE-T, the degree of both near-seed flare due to false positives, and of distal false negatives, are decreased when compared with thresholded probabilistic tractography without ICE-T. Since ICE-T only addresses PLD, the degree of remaining false-positives and false-negatives will consequently be mainly attributable to the particular tractography method employed. Given the benefits offered by ICE-T, we would suggest that future studies consider this or a similar approach when using tractography to provide tract segmentations for tract based analysis, or for brain network analysis.

  2. Neuritic Patient at Sanglah General Hospital Denpasar

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    Ni Putu Dita-Rinjani

    2012-05-01

    Full Text Available Objective: Treatment of optic neuritic as recommended by the Optic Neuritic Treatment Trial (ONTT was intravenous methylprednisolon followed by oral prednisone. This study aims to describe  characteristics and response to intravenous methylprednisolon followed by oral prednisone treatment of optic neuritic patient in Sanglah General Hospital Denpasar. Method: This report is an analytical cross sectional study. Data were collected retrospectively from medical report of optic neuritic patient who came to Sanglah General Hospital during a period of January 1st 2010 until December 31st 2011. Patient characteristics were analyzed with descriptive analyses and presented as frequency, percentage, mean and standar deviation. Visual acuity and contrast sensitivity improvement after intravenous methylprednisolon followed by oral prednisone treatment were statistically analyzed with Wilcoxon test Results:  Optic neuritic were found in twenty-three patients (33 eyes, majority was in age group of 15-40 years (56.5% with female predominance (65.2% and unilateral involvement was 56.3%. Mean onset patient presented to the hospital was 21.7±2.21 days and the most common symptom was decreasing vision (87.9%.  The majority of patient presented with papillitis (54.5%, totally color blindness found in 39.4% eyes, and the type of visual field defect at presentation was central scotoma (18.2%. All cases show lesion of optic nerve from visual evoked potential (VEP examination and magnetic resonance imaging (MRI shows normal results (39.1% patient. The mean of pretreatment logMAR visual acuity and contrast sensitivity were significant improve after treatment from 1.59±0.47 to 0.59±0.62 (p=0.0001 and 0.31±0.56 to 1.25±0.56 (p=0.0001, respectively. All cases in this study were idiopathic. Recurrences were seen in 2 eyes and none of patient had clinical features suggestive of multiple sclerosis. Conclusions: Visual acuity and contrast sensitivity improvement

  3. The combinatorics of neurite self-avoidance.

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    Forbes, Elizabeth M; Hunt, Jonathan J; Goodhill, Geoffrey J

    2011-11-01

    During neural development in Drosophila, the ability of neurite branches to recognize whether they are from the same or different neurons depends crucially on the molecule Dscam1. In particular, this recognition depends on the stochastic acquisition of a unique combination of Dscam1 isoforms out of a large set of possible isoforms. To properly interpret these findings, it is crucial to understand the combinatorics involved, which has previously been attempted only using stochastic simulations for some specific parameter combinations. Here we present closed-form solutions for the general case. These reveal the relationships among the key variables and how these constrain possible biological scenarios.

  4. Pea3 transcription factor promotes neurite outgrowth

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    BASAK eKANDEMIR

    2014-06-01

    Full Text Available Pea3 subfamily of ETS transcription factors consist of three major proteins, Pea3, ERM and ER81. Although important for many different tissues that exhibit branching morphogenesis, the function of Pea3 family in nervous system development and regeneration is only beginning to unfold. In this study, we provide evidence that Pea3 can directs neurite extension and axonal outgrowth in different model systems, and that Serine 90 is important for this function. We have also identified neurofilament-L and neurofilament-M as two putative novel targets for Pea3.

  5. Rab35 promotes the recruitment of Rab8, Rab13 and Rab36 to recycling endosomes through MICAL-L1 during neurite outgrowth

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    Hotaka Kobayashi

    2014-08-01

    Full Text Available Small GTPase Rab35 is an important molecular switch for endocytic recycling that regulates various cellular processes, including cytokinesis, cell migration, and neurite outgrowth. We previously showed that active Rab35 promotes nerve growth factor (NGF-induced neurite outgrowth of PC12 cells by recruiting MICAL-L1, a multiple Rab-binding protein, to Arf6-positive recycling endosomes. However, the physiological significance of the multiple Rab-binding ability of MICAL-L1 during neurite outgrowth remained completely unknown. Here we report that Rab35 and MICAL-L1 promote the recruitment of Rab8, Rab13, and Rab36 to Arf6-positive recycling endosomes during neurite outgrowth. We found that Rab35 functions as a master Rab that determines the intracellular localization of MICAL-L1, which in turn functions as a scaffold for Rab8, Rab13, and Rab36. We further showed by functional ablation experiments that each of these downstream Rabs regulates neurite outgrowth in a non-redundant manner downstream of Rab35 and MICAL-L1, e.g. by showing that knockdown of Rab36 inhibited recruitment of Rab36-specific effector JIP4 to Arf6-positive recycling endosomes, and caused inhibition of neurite outgrowth without affecting accumulation of Rab8 and Rab13 in the same Arf6-positive area. Our findings suggest the existence of a novel mechanism that recruits multiple Rab proteins at the Arf6-positive compartment by MICAL-L1.

  6. Transient analysis of a queue with queue-length dependent MAP and its application to SS7 network

    Directory of Open Access Journals (Sweden)

    Bong Dae Choi

    1999-01-01

    Full Text Available We analyze the transient behavior of a Markovian arrival queue with congestion control based on a double of thresholds, where the arrival process is a queue-length dependent Markovian arrival process. We consider Markov chain embedded at arrival epochs and derive the one-step transition probabilities. From these results, we obtain the mean delay and the loss probability of the nth arrival packet. Before we study this complex model, first we give a transient analysis of an MAP/M/1 queueing system without congestion control at arrival epochs. We apply our result to a signaling system No. 7 network with a congestion control based on thresholds.

  7. Mechanical stress activates neurites and somata of myenteric neurons

    Directory of Open Access Journals (Sweden)

    Eva Maria Kugler

    2015-09-01

    Full Text Available The particular location of myenteric neurons, sandwiched between the 2 muscle layers of the gut, implies that their somata and neurites undergo mechanical stress during gastrointestinal motility. Existence of mechanosensitive enteric neurons (MEN is undoubted but many of their basic features remain to be studied. In this study, we used ultra-fast neuroimaging to record activity of primary cultured myenteric neurons of guinea pig and human intestine after von Frey hair evoked deformation of neurites and somata. Independent component analysis was applied to reconstruct neuronal morphology and follow neuronal signals. Of the cultured neurons 45% (114 out of 256, 30 guinea pigs responded to neurite probing with a burst spike frequency of 13.4 Hz. Action potentials generated at the stimulation site invaded the soma and other neurites. Mechanosensitive sites were expressed across large areas of neurites. Many mechanosensitive neurites appeared to have afferent and efferent functions as those that responded to deformation also conducted spikes coming from the soma. Mechanosensitive neurites were also activated by nicotine application. This supported the concept of multifunctional MEN. 14% of the neurons (13 out of 96, 18 guinea pigs responded to soma deformation with burst spike discharge of 17.9 Hz. Firing of MEN adapted rapidly (RAMEN, slowly (SAMEN or ultra-slowly (USAMEN. The majority of MEN showed SAMEN behavior although significantly more RAMEN occurred after neurite probing. Cultured myenteric neurons from human intestine had similar properties. Compared to MEN, dorsal root ganglion neurons were activated by neurite but not by soma deformation with slow adaptation of firing. We demonstrated that MEN exhibit specific features very likely reflecting adaptation to their specialized functions in the gut.

  8. Merlin inhibits neurite outgrowth in the CNS.

    Science.gov (United States)

    Schulz, Alexander; Geissler, Katja J; Kumar, Sujeet; Leichsenring, Gregor; Morrison, Helen; Baader, Stephan L

    2010-07-28

    The neurofibromatosis type 2 gene product merlin is known to provoke gliogenic tumors as a result of its mutagenic loss. Merlin's physiological anti-mitogenic function makes it unique among its ezrin-radixin-moesin (ERM) family members. Although ERM proteins and merlin are known to be expressed in glial cells of the peripheral nervous system and CNS, the neuronal expression pattern and function of merlin have been less well investigated. We report here expression of merlin in developing and mature neurons of the murine CNS. Within cerebellar Purkinje cells (PCs), merlin was localized in the soma, sprouting dendrites and axons. Merlin expression in PCs was high during the period of initial dendrite regression and declined during later phases of dendrite elongation. Consistently, merlin expression in vivo was increased in Engrailed-2-overexpressing PCs, which are characterized by a reduced dendritic extension. Furthermore, overexpression of merlin in dissociated cerebellar cultures and in neurogenic P19 cells caused a significant decline in neurite outgrowth, while, conversely, inhibition of merlin expression increased process formation. This effect was dependent on phosphorylation of serine 518 and involved the inactivation of the growth-promoting GTPase Rac. We thus provide evidence that merlin plays a pivotal role in controlling the neuronal wiring in the developing CNS.

  9. 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

  10. High-content neurite development study using optically patterned substrates.

    Directory of Open Access Journals (Sweden)

    Jonathan M Bélisle

    Full Text Available The study of neurite guidance in vitro relies on the ability to reproduce the distribution of attractive and repulsive guidance molecules normally expressed in vivo. The identification of subtle variations in the neurite response to changes in the spatial distribution of extracellular molecules can be achieved by monitoring the behavior of cells on protein gradients. To do this, automated high-content screening assays are needed to quantify the morphological changes resulting from growth on gradients of guidance molecules. Here, we present the use of laser-assisted protein adsorption by photobleaching (LAPAP to allow the fabrication of large-scale substrate-bound laminin-1 gradients to study neurite extension. We produced thousands of gradients of different slopes and analyzed the variations in neurite attraction of neuron-like cells (RGC-5. An image analysis algorithm processed bright field microscopy images, detecting each cell and quantifying the soma centroid and the initiation, terminal and turning angles of the longest neurite.

  11. Antiaromatic bisindeno-[n]thienoacenes with small singlet biradical characters: Syntheses, structures and chain length dependent physical properties

    KAUST Repository

    Shi, Xueliang

    2014-01-01

    Recent studies demonstrated that aromaticity and biradical character play important roles in determining the ground-state structures and physical properties of quinoidal polycyclic hydrocarbons and oligothiophenes, a kind of molecular materials showing promising applications for organic electronics, photonics and spintronics. In this work, we designed and synthesized a new type of hybrid system, the so-called bisindeno-[n]thienoacenes (n = 1-4), by annulation of quinoidal fused α-oligothiophenes with two indene units. The obtained molecules can be regarded as antiaromatic systems containing 4n π electrons with small singlet biradical character (y0). Their ground-state geometry and electronic structures were studied by X-ray crystallographic analysis, NMR, ESR and Raman spectroscopy, assisted by density functional theory calculations. With extension of the chain length, the molecules showed a gradual increase of the singlet biradical character accompanied by decreased antiaromaticity, finally leading to a highly reactive bisindeno[4]thienoacene (S4-TIPS) which has a singlet biradical ground state (y0= 0.202). Their optical and electronic properties in the neutral and charged states were systematically investigated by one-photon absorption, two-photon absorption, transient absorption spectroscopy, cyclic voltammetry and spectroelectrochemistry, which could be correlated to the chain length dependent antiaromaticity and biradical character. Our detailed studies revealed a clear structure-aromaticity-biradical character-physical properties-reactivity relationship, which is of importance for tailored material design in the future. This journal is

  12. SP-PLP-EPR Investigations into the Chain-Length-Dependent Termination of Methyl Methacrylate Bulk Polymerization.

    Science.gov (United States)

    Barth, Johannes; Buback, Michael

    2009-11-02

    Termination kinetics of methyl methacrylate (MMA) bulk polymerization has been studied via the single pulsed laser polymerization-electron paramagnetic resonance method. MMA-d(8) has been investigated to enhance the signal-to-noise quality of microsecond time-resolved measurement of radical concentration. Chain-length-dependent termination rate coefficients of radicals of identical size, k ti,i, are reported for 5-70 °C and up to i = 100. k ti,i decreases according to the power-law expression $k_{\\rm t}^{i,i} = k_{\\rm t}^{{\\rm 1,1}} \\cdot i^{ - \\alpha }$. At 5 °C, k(t) for two MMA radicals of chain-length unity is k t1,1 = (5.8 ± 1.3) · 10(8)  L · mol(-1)  · s(-1) . The associated activation energy and power-law exponent are: E(A) (k t1,1) ≈ 9 ± 2 kJ · mol(-1) and α ≈ 0.63 ± 0.15, respectively. Copyright © 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. 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.

  14. Fine Needle Aspiration Cytology in Diagnosis of Pure Neuritic Leprosy

    Directory of Open Access Journals (Sweden)

    Bipin Kumar

    2011-01-01

    Full Text Available Leprosy is a chronic infection affecting mainly the skin and peripheral nerve. Pure neuritic form of this disease manifests by involvement of the nerve in the absence of skin lesions. Therefore, it can sometimes create a diagnostic problem. It often requires a nerve biopsy for diagnosis, which is an invasive procedure and may lead to neural deficit. Fine needle aspiration cytology (FNAC of an affected nerve can be a valuable and less invasive procedure for the diagnosis of such cases. We report five suspected cases of pure neuritic Hansen's disease involving the common and superficial peroneal, ulnar, and median nerve, who underwent FNAC. Smears revealed nerve fibers infiltrated by chronic inflammatory cells in all cases, presence of epithelioid cells granulomas, and Langhans giant cells in three cases, and acid fast bacilli in two cases. In conclusion, FNAC is a safe, less invasive, and time saving procedure for the diagnosis of pure neuritic leprosy.

  15. Fine Needle Aspiration Cytology in Diagnosis of Pure Neuritic Leprosy

    Science.gov (United States)

    Kumar, Bipin; Pradhan, Anju

    2011-01-01

    Leprosy is a chronic infection affecting mainly the skin and peripheral nerve. Pure neuritic form of this disease manifests by involvement of the nerve in the absence of skin lesions. Therefore, it can sometimes create a diagnostic problem. It often requires a nerve biopsy for diagnosis, which is an invasive procedure and may lead to neural deficit. Fine needle aspiration cytology (FNAC) of an affected nerve can be a valuable and less invasive procedure for the diagnosis of such cases. We report five suspected cases of pure neuritic Hansen's disease involving the common and superficial peroneal, ulnar, and median nerve, who underwent FNAC. Smears revealed nerve fibers infiltrated by chronic inflammatory cells in all cases, presence of epithelioid cells granulomas, and Langhans giant cells in three cases, and acid fast bacilli in two cases. In conclusion, FNAC is a safe, less invasive, and time saving procedure for the diagnosis of pure neuritic leprosy. PMID:21660285

  16. Genetic susceptibility for Alzheimer disease neuritic plaque pathology.

    Science.gov (United States)

    Shulman, Joshua M; Chen, Kewei; Keenan, Brendan T; Chibnik, Lori B; Fleisher, Adam; Thiyyagura, Pradeep; Roontiva, Auttawut; McCabe, Cristin; Patsopoulos, Nikolaos A; Corneveaux, Jason J; Yu, Lei; Huentelman, Matthew J; Evans, Denis A; Schneider, Julie A; Reiman, Eric M; De Jager, Philip L; Bennett, David A

    2013-09-01

    While numerous genetic susceptibility loci have been identified for clinical Alzheimer disease (AD), it is important to establish whether these variants are risk factors for the underlying disease pathology, including neuritic plaques. To investigate whether AD susceptibility loci from genome-wide association studies affect neuritic plaque pathology and to additionally identify novel risk loci for this trait. Candidate analysis of single-nucleotide polymorphisms and genome-wide association study in a joint clinicopathologic cohort, including 725 deceased subjects from the Religious Orders Study and the Rush Memory and Aging Project (2 prospective, community-based studies), followed by targeted validation in an independent neuroimaging cohort, including 114 subjects from multiple clinical and research centers. A quantitative measure of neuritic plaque pathologic burden, based on assessments of silver-stained tissue averaged from multiple brain regions. Validation based on β-amyloid load by immunocytochemistry, and replication with fibrillar β-amyloid positron emission tomographic imaging with Pittsburgh Compound B or florbetapir. Besides the previously reported APOE and CR1 loci, we found that the ABCA7 (rs3764650; P = .02) and CD2AP (rs9349407; P = .03) AD susceptibility loci are associated with neuritic plaque burden. In addition, among the top results of our genome-wide association study, we discovered a novel variant near the amyloid precursor protein gene (APP, rs2829887) that is associated with neuritic plaques (P = 3.3 × 10-6). This polymorphism was associated with postmortem β-amyloid load as well as fibrillar β-amyloid in 2 independent cohorts of adults with normal cognition. These findings enhance understanding of AD risk factors by relating validated susceptibility alleles to increased neuritic plaque pathology and implicate common genetic variation at the APP locus in the earliest, presymptomatic stages of AD.

  17. Neuroprotective copper bis(thiosemicarbazonato complexes promote neurite elongation.

    Directory of Open Access Journals (Sweden)

    Laura Bica

    Full Text Available Abnormal biometal homeostasis is a central feature of many neurodegenerative disorders including Alzheimer's disease (AD, Parkinson's disease (PD, and motor neuron disease. Recent studies have shown that metal complexing compounds behaving as ionophores such as clioquinol and PBT2 have robust therapeutic activity in animal models of neurodegenerative disease; however, the mechanism of neuroprotective action remains unclear. These neuroprotective or neurogenerative processes may be related to the delivery or redistribution of biometals, such as copper and zinc, by metal ionophores. To investigate this further, we examined the effect of the bis(thiosemicarbazonato-copper complex, Cu(II(gtsm on neuritogenesis and neurite elongation (neurogenerative outcomes in PC12 neuronal-related cultures. We found that Cu(II(gtsm induced robust neurite elongation in PC12 cells when delivered at concentrations of 25 or 50 nM overnight. Analogous effects were observed with an alternative copper bis(thiosemicarbazonato complex, Cu(II(atsm, but at a higher concentration. Induction of neurite elongation by Cu(II(gtsm was restricted to neurites within the length range of 75-99 µm with a 2.3-fold increase in numbers of neurites in this length range with 50 nM Cu(II(gtsm treatment. The mechanism of neurogenerative action was investigated and revealed that Cu(II(gtsm inhibited cellular phosphatase activity. Treatment of cultures with 5 nM FK506 (calcineurin phosphatase inhibitor resulted in analogous elongation of neurites compared to 50 nM Cu(II(gtsm, suggesting a potential link between Cu(II(gtsm-mediated phosphatase inhibition and neurogenerative outcomes.

  18. 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

    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...... 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...

  19. SU-E-I-16: Scan Length Dependency of the Radial Dose Distribution in a Long Polyethylene Cylinder

    Energy Technology Data Exchange (ETDEWEB)

    Bakalyar, D; McKenney, S [Henry Ford Health System, Detroit, MI (United States); Feng, W [New York Presbyterian Hospital, Tenafly, NJ (United States)

    2015-06-15

    Purpose: The area-averaged dose in the central plane of a long cylinder following a CT scan depends upon the radial dose distribution and the length of the scan. The ICRU/TG200 phantom, a polyethylene cylinder 30 cm in diameter and 60 cm long, was the subject of this study. The purpose was to develop an analytic function that could determine the dose for a scan length L at any point in the central plane of this phantom. Methods: Monte Carlo calculations were performed on a simulated ICRU/TG200 phantom under conditions of cylindrically symmetric conditions of irradiation. Thus, the radial dose distribution function must be an even function that accounts for two competing effects: The direct beam makes its weakest contribution at the center while the scatter begins abruptly at the outer radius and grows as the center is approached. The scatter contribution also increases with scan length with the increase approaching its limiting value at the periphery faster than along the central axis. An analytic function was developed that fit the data and possessed these features. Results: Symmetry and continuity dictate a local extremum at the center which is a minimum for the ICRU/TG200 phantom. The relative depth of the minimum decreases as the scan length grows and an absolute maximum can occur between the center and outer edge of the cylinders. As the scan length grows, the relative dip in the center decreases so that for very long scan lengths, the dose profile is relatively flat. Conclusion: An analytic function characterizes the radial and scan length dependency of dose for long cylindrical phantoms. The function can be integrated with the results expressed in closed form. One use for this is to help determine average dose distribution over the central cylinder plane for any scan length.

  20. The effects of hematopoietic growth factors on neurite outgrowth.

    Science.gov (United States)

    Su, Ye; Cui, Lili; Piao, Chunshu; Li, Bin; Zhao, Li-Ru

    2013-01-01

    Stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) are initially discovered as the essential hematopoietic growth factors regulating bone marrow stem cell proliferation and differentiation, and SCF in combination with G-CSF (SCF+G-CSF) has synergistic effects on bone marrow stem cell mobilization. In this study we have determined the effect of SCF and G-CSF on neurite outgrowth in rat cortical neurons. Using molecular and cellular biology and live cell imaging approaches, we have revealed that receptors for SCF and G-CSF are expressed on the growth core of cortical neurons, and that SCF+G-CSF synergistically enhances neurite extension through PI3K/AKT and NFκB signaling pathways. Moreover, SCF+G-CSF induces much greater NFκB activation, NFκB transcriptional binding and brain-derived neurotrophic factor (BDNF) production than SCF or G-CSF alone. In addition, we have also observed that BDNF, the target gene of NFκB, is required for SCF+G-CSF-induced neurite outgrowth. These data suggest that SCF+G-CSF has synergistic effects to promote neurite growth. This study provides new insights into the contribution of hematopoietic growth factors in neuronal plasticity.

  1. The effects of hematopoietic growth factors on neurite outgrowth.

    Directory of Open Access Journals (Sweden)

    Ye Su

    Full Text Available Stem cell factor (SCF and granulocyte colony-stimulating factor (G-CSF are initially discovered as the essential hematopoietic growth factors regulating bone marrow stem cell proliferation and differentiation, and SCF in combination with G-CSF (SCF+G-CSF has synergistic effects on bone marrow stem cell mobilization. In this study we have determined the effect of SCF and G-CSF on neurite outgrowth in rat cortical neurons. Using molecular and cellular biology and live cell imaging approaches, we have revealed that receptors for SCF and G-CSF are expressed on the growth core of cortical neurons, and that SCF+G-CSF synergistically enhances neurite extension through PI3K/AKT and NFκB signaling pathways. Moreover, SCF+G-CSF induces much greater NFκB activation, NFκB transcriptional binding and brain-derived neurotrophic factor (BDNF production than SCF or G-CSF alone. In addition, we have also observed that BDNF, the target gene of NFκB, is required for SCF+G-CSF-induced neurite outgrowth. These data suggest that SCF+G-CSF has synergistic effects to promote neurite growth. This study provides new insights into the contribution of hematopoietic growth factors in neuronal plasticity.

  2. 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

  3. TERAHERTZ RADIATION INFLUENCE ON THE GROWING OF NEURITES

    Directory of Open Access Journals (Sweden)

    M. V. Tsurkan

    2013-01-01

    Full Text Available Our research was devoted to the impact of broadband pulsed THz radiation in the frequency range of 0.05 to 2 THz on the neurite growth in the sensory ganglia of 10-12-day chicken embryos. Dependence of changes in functional responses of cells on the average output power has been found.

  4. 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).

  5. 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.

  6. Neurite outgrowth on fluorinated polyimide film micropatterned by ion irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Okuyama, Y.; Sato, M.; Nagaoka, S.; Kawakami, H. E-mail: kawakami-hiroyoshi@c.metro-u.ac.jp; Suzuki, Y.; Iwaki, M

    2003-05-01

    In this study, we investigated neurite outgrowth on a fluorinated polyimide film micropatterned by ion irradiation. We used the fluorinated polyimide because of its excellent thermal and mechanical properties and biocompatibility. Rattus norvegicus chromaphin (PC12) cells were used for in vitro studies. The polyimide films were irradiated with He{sup +}, Ne{sup +} or Kr{sup +} at 1 x 10{sup 14} ions/cm{sup 2} using an ion-beam mask. The lines in the mask were 120 and 160 {mu}m wide and 120-160 {mu}m apart. PC12 cells were selectively adhered on the polyimide film micropatterned by Kr{sup +}-irradiation. However, the neurite length on the film irradiated by Kr{sup +} was shorter than that determined in the film irradiated by He{sup +}. On the other hand, neurite outgrowth on the polyimide film micropatterned by He{sup +}-irradiation was at least 100 {mu}m in length. This initial study indicated the enhanced outgrowth of PC12 cells on the fluorinated polyimide film micropatterned by ion irradiation.

  7. Stimulation of neuronal neurite outgrowth using functionalized carbon nanotubes

    Science.gov (United States)

    Matsumoto, K.; Sato, C.; Naka, Y.; Whitby, R.; Shimizu, N.

    2010-03-01

    Low concentrations (0.11-1.7 µg ml - 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 µg ml - 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.

  8. Tangier′s disease: An uncommon cause of facial weakness and non-length dependent demyelinating neuropathy

    Directory of Open Access Journals (Sweden)

    Madhu Nagappa

    2016-01-01

    Full Text Available Tangier disease is an autosomal recessive disorder characterized by an abnormal accumulation of cholesterol esters in various organs secondary to adenotriphosphate binding cassette transporter A-1 (ABCA-1 transporter deficiency and disrupted reverse cholesterol transport. It causes neuropathy in half of the affected individuals. We present the clinical, electrophysiological, and histopathological findings in a middle aged gentleman of Tangier disease who was initially misdiagnosed leprosy and treated with antileprosy drugs. The presence of a demyelinating neuropathy on electrophysiology in a patient with predominant upper limb involvement and facial diplegia should raise the suspicion of Tangier disease. The characteristic lipid profile of Tangier disease was noted in this patient viz. extremely low high density lipoprotein (HDL, elevated triglyceride (TG, and reduced apolipoprotein A1. Estimation of serum lipids should form a part of routine evaluation in order to avoid misdiagnosis.

  9. Large-scale analysis of neurite growth dynamics on micropatterned substrates

    OpenAIRE

    Wissner-Gross, Zachary D.; Scott, Mark Andrew; Ku, David L.; Ramaswamy, Priya

    2010-01-01

    During both development and regeneration of the nervous system, neurons display complex growth dynamics, and several neurites compete to become the neuron's single axon. Numerous mathematical and biophysical models have been proposed to explain this competition, which remain experimentally unverified. Large-scale, precise, and repeatable measurements of neurite dynamics have been difficult to perform, since neurons have varying numbers of neurites, which themselves have complex morphologies. ...

  10. Stimulation of Neurite Outgrowth Using an Electrically Conducting Polymer

    Science.gov (United States)

    Schmidt, Christine E.; Shastri, Venkatram R.; Vacanti, Joseph P.; Langer, Robert

    1997-08-01

    Damage to peripheral nerves often cannot be repaired by the juxtaposition of the severed nerve ends. Surgeons have typically used autologous nerve grafts, which have several drawbacks including the need for multiple surgical procedures and loss of function at the donor site. As an alternative, the use of nerve guidance channels to bridge the gap between severed nerve ends is being explored. In this paper, the electrically conductive polymer--oxidized polypyrrole (PP)--has been evaluated for use as a substrate to enhance nerve cell interactions in culture as a first step toward potentially using such polymers to stimulate in vivo nerve regeneration. Image analysis demonstrates that PC-12 cells and primary chicken sciatic nerve explants attached and extended neurites equally well on both PP films and tissue culture polystyrene in the absence of electrical stimulation. In contrast, PC-12 cells interacted poorly with indium tin oxide (ITO), poly(L-lactic acid) (PLA), and poly(lactic acid-coglycolic acid) surfaces. However, PC-12 cells cultured on PP films and subjected to an electrical stimulus through the film showed a significant increase in neurite lengths compared with ones that were not subjected to electrical stimulation through the film and tissue culture polystyrene controls. The median neurite length for PC-12 cells grown on PP and subjected to an electrical stimulus was 18.14 μ m (n = 5643) compared with 9.5 μ m (n = 4440) for controls. Furthermore, animal implantation studies reveal that PP invokes little adverse tissue response compared with poly(lactic acid-coglycolic acid).

  11. ADF/cofilin-mediated actin retrograde flow directs neurite formation in the developing brain.

    Science.gov (United States)

    Flynn, Kevin C; Hellal, Farida; Neukirchen, Dorothee; Jacob, Sonja; Tahirovic, Sabina; Dupraz, Sebastian; Stern, Sina; Garvalov, Boyan K; Gurniak, Christine; Shaw, Alisa E; Meyn, Liane; Wedlich-Söldner, Roland; Bamburg, James R; Small, J Victor; Witke, Walter; Bradke, Frank

    2012-12-20

    Neurites are the characteristic structural element of neurons that will initiate brain connectivity and elaborate information. Early in development, neurons are spherical cells but this symmetry is broken through the initial formation of neurites. This fundamental step is thought to rely on actin and microtubule dynamics. However, it is unclear which aspects of the complex actin behavior control neuritogenesis and which molecular mechanisms are involved. Here, we demonstrate that augmented actin retrograde flow and protrusion dynamics facilitate neurite formation. Our data indicate that a single family of actin regulatory proteins, ADF/Cofilin, provides the required control of actin retrograde flow and dynamics to form neurites. In particular, the F-actin severing activity of ADF/Cofilin organizes space for the protrusion and bundling of microtubules, the backbone of neurites. Our data reveal how ADF/Cofilin organizes the cytoskeleton to drive actin retrograde flow and thus break the spherical shape of neurons. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Growth, collapse, and stalling in a mechanical model for neurite motility

    CERN Document Server

    Recho, Pierre; Goriely, Alain

    2015-01-01

    Neurites, the long cellular protrusions that form the routes of the neuronal network are capable to actively extend during early morphogenesis or to regenerate after trauma. To perform this task, they rely on their cytoskeleton for mechanical support. In this paper, we present a three-component active gel model that describes neurites in the three robust mechanical states observed experimentally: collapsed, static, and motile. These states arise from an interplay between the physical forces driven by growth of the microtubule-rich inner core of the neurite and the acto-myosin contractility of its surrounding cortical membrane. In particular, static states appear as a mechanical traction/compression balance of these two parallel structures. The model predicts how the response of a neurite to a towing force depends on the force magnitude and recovers the response of neurites to several drug treatments that modulate the cytoskeleton active and passive properties.

  13. Mapping dynamic branch displacements: A versatile method to quantify spatiotemporal neurite dynamics

    Directory of Open Access Journals (Sweden)

    Masaki eHiramoto

    2011-09-01

    Full Text Available AbstractQuantification of the movement of axons and dendrites is essential to study circuit formation. Several methods have been developed to quantify the movement of neurites in simplified systems, however these quantification methods are specialized for a limited type of predicted movements in the particular assay systems. The movement of neurites in vivo includes many unexpected rearrangements. Establishment of a method that can detect and quantify a variety of patterning events will reveal novel phenomena in circuit formation and make it possible to conduct deeper investigation of the molecular and cellular bases of these events. Here we present a versatile method that represents a quantitative analysis of the integrated movement of neurites on a spatial map. We show that the method is useful to analyze several types of neurite behaviors, such as changes in the directionality of neurite movements, fasciculation of axons or changes in territories of dendritic fields.

  14. Telomerase inhibitor imetelstat has preclinical activity across the spectrum of non-small cell lung cancer oncogenotypes in a telomere length dependent manner.

    Science.gov (United States)

    Frink, Robin E; Peyton, Michael; Schiller, Joan H; Gazdar, Adi F; Shay, Jerry W; Minna, John D

    2016-05-31

    Telomerase was evaluated as a therapeutic oncotarget by studying the efficacy of the telomerase inhibitor imetelstat in non-small cell lung cancer (NSCLC) cell lines to determine the range of response phenotypes and identify potential biomarkers of response. A panel of 63 NSCLC cell lines was studied for telomere length and imetelstat efficacy in inhibiting colony formation and no correlation was found with patient characteristics, tumor histology, and oncogenotypes. While there was no overall correlation between imetelstat efficacy with initial telomere length (ranging from 1.5 to 20 kb), the quartile of NSCLC lines with the shortest telomeres was more sensitive than the quartile with the longest telomeres. Continuous long-term treatment with imetelstat resulted in sustained telomerase inhibition, progressive telomere shortening and eventual growth inhibition in a telomere-length dependent manner. Cessation of imetelstat therapy before growth inhibition was followed by telomere regrowth. Likewise, in vivo imetelstat treatment caused tumor xenograft growth inhibition in a telomere-length dependent manner. We conclude from these preclinical studies of telomerase as an oncotarget tested by imetelstat response that imetelstat has efficacy across the entire oncogenotype spectrum of NSCLC, continuous therapy is necessary to prevent telomere regrowth, and short telomeres appears to be the best treatment biomarker.

  15. Length-dependent retention of carbon nanotubes in the pleural space of mice initiates sustained inflammation and progressive fibrosis on the parietal pleura.

    Science.gov (United States)

    Murphy, Fiona A; Poland, Craig A; Duffin, Rodger; Al-Jamal, Khuloud T; Ali-Boucetta, Hanene; Nunes, Antonio; Byrne, Fiona; Prina-Mello, Adriele; Volkov, Yuri; Li, Shouping; Mather, Stephen J; Bianco, Alberto; Prato, Maurizio; Macnee, William; Wallace, William A; Kostarelos, Kostas; Donaldson, Ken

    2011-06-01

    The fibrous shape of carbon nanotubes (CNTs) raises concern that they may pose an asbestos-like inhalation hazard, leading to the development of diseases, especially mesothelioma. Direct instillation of long and short CNTs into the pleural cavity, the site of mesothelioma development, produced asbestos-like length-dependent responses. The response to long CNTs and long asbestos was characterized by acute inflammation, leading to progressive fibrosis on the parietal pleura, where stomata of strictly defined size limit the egress of long, but not short, fibers. This was confirmed by demonstrating clearance of short, but not long, CNT and nickel nanowires and by visualizing the migration of short CNTs from the pleural space by single-photon emission computed tomographic imaging. Our data confirm the hypothesis that, although a proportion of all deposited particles passes through the pleura, the pathogenicity of long CNTs and other fibers arises as a result of length-dependent retention at the stomata on the parietal pleura. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  16. Abnormal Paraplegin Expression in Swollen Neurites, τ- and α-Synuclein Pathology in a Case of Hereditary Spastic Paraplegia SPG7 with an Ala510Val Mutation.

    Science.gov (United States)

    Thal, Dietmar R; Züchner, Stephan; Gierer, Stephan; Schulte, Claudia; Schöls, Ludger; Schüle, Rebecca; Synofzik, Matthis

    2015-10-21

    Mutations in the SPG7 gene are the most frequent cause of autosomal recessive hereditary spastic paraplegias and spastic ataxias. Ala510Val is the most common SPG7 mutation, with a frequency of up to 1% in the general population. Here we report the clinical, genetic, and neuropathological findings in a homozygous Ala510Val SPG7 case with spastic ataxia. Neuron loss with associated gliosis was found in the inferior olivary nucleus, the dentate nucleus of the cerebellum, the substantia nigra and the basal nucleus of Meynert. Neurofilament and/or paraplegin accumulation was observed in swollen neurites in the cerebellar and cerebral cortex. This case also showed subcortical τ-pathology in an unique distribution pattern largely restricted to the brainstem. α-synuclein containing Lewy bodies (LBs) were observed in the brainstem and the cortex, compatible with a limbic pattern of Braak LB-Disease stage 4. Taken together, this case shows that the spectrum of pathologies in SPG7 can include neuron loss of the dentate nucleus and the inferior olivary nucleus as well as neuritic pathology. The progressive supranuclear palsy-like brainstem predominant pattern of τ pathology and α-synuclein containing Lewy bodies in our SPG7 cases may be either coincidental or related to SPG7 in addition to neuron loss and neuritic pathology.

  17. Abnormal Paraplegin Expression in Swollen Neurites, τ- and α-Synuclein Pathology in a Case of Hereditary Spastic Paraplegia SPG7 with an Ala510Val Mutation

    Directory of Open Access Journals (Sweden)

    Dietmar R. Thal

    2015-10-01

    Full Text Available Mutations in the SPG7 gene are the most frequent cause of autosomal recessive hereditary spastic paraplegias and spastic ataxias. Ala510Val is the most common SPG7 mutation, with a frequency of up to 1% in the general population. Here we report the clinical, genetic, and neuropathological findings in a homozygous Ala510Val SPG7 case with spastic ataxia. Neuron loss with associated gliosis was found in the inferior olivary nucleus, the dentate nucleus of the cerebellum, the substantia nigra and the basal nucleus of Meynert. Neurofilament and/or paraplegin accumulation was observed in swollen neurites in the cerebellar and cerebral cortex. This case also showed subcortical τ-pathology in an unique distribution pattern largely restricted to the brainstem. α-synuclein containing Lewy bodies (LBs were observed in the brainstem and the cortex, compatible with a limbic pattern of Braak LB-Disease stage 4. Taken together, this case shows that the spectrum of pathologies in SPG7 can include neuron loss of the dentate nucleus and the inferior olivary nucleus as well as neuritic pathology. The progressive supranuclear palsy-like brainstem predominant pattern of τ pathology and α-synuclein containing Lewy bodies in our SPG7 cases may be either coincidental or related to SPG7 in addition to neuron loss and neuritic pathology.

  18. Dual pathways regulate neurite outgrowth in enteric ganglia.

    Science.gov (United States)

    Simeone, D M; Romanchuk, G; Mulholland, M W

    1994-10-01

    Primary cultures of guinea pig myenteric plexus ganglia were used to examine the ability of agents that activate adenylate cyclase or mimic intracellular adenosine 3',5'-cyclic monophosphate (cAMP) to stimulate morphological growth. Dose-dependent increases in neurite length and density were produced in enteric neuronal cultures by forskolin (212% of control), cholera toxin (356% of control), or the permeant cAMP analogues 8-bromoadenosine 3',5'-cyclic monophosphate and dibutyryl cAMP. (R)-p-adenosine 3',5'-cyclic monophosphorothioate, an inhibitor of cAMP-dependent kinases, blocked the growth-promoting effects of cAMP analogues but not of nerve growth factor (NGF). Activation of cAMP-dependent signaling pathways also increased production of mRNA for alpha-tubulin and microtubule-associated protein 2. Dual pathways, regulated by NGF and cAMP-dependent protein kinases, influence growth signaling in enteric ganglia.

  19. Insulin signaling regulates neurite growth during metamorphic neuronal remodeling

    Directory of Open Access Journals (Sweden)

    Tingting Gu

    2013-12-01

    Although the growth capacity of mature neurons is often limited, some neurons can shift through largely unknown mechanisms from stable maintenance growth to dynamic, organizational growth (e.g. to repair injury, or during development transitions. During insect metamorphosis, many terminally differentiated larval neurons undergo extensive remodeling, involving elimination of larval neurites and outgrowth and elaboration of adult-specific projections. Here, we show in the fruit fly, Drosophila melanogaster (Meigen, that a metamorphosis-specific increase in insulin signaling promotes neuronal growth and axon branching after prolonged stability during the larval stages. FOXO, a negative effector in the insulin signaling pathway, blocked metamorphic growth of peptidergic neurons that secrete the neuropeptides CCAP and bursicon. RNA interference and CCAP/bursicon cell-targeted expression of dominant-negative constructs for other components of the insulin signaling pathway (InR, Pi3K92E, Akt1, S6K also partially suppressed the growth of the CCAP/bursicon neuron somata and neurite arbor. In contrast, expression of wild-type or constitutively active forms of InR, Pi3K92E, Akt1, Rheb, and TOR, as well as RNA interference for negative regulators of insulin signaling (PTEN, FOXO, stimulated overgrowth. Interestingly, InR displayed little effect on larval CCAP/bursicon neuron growth, in contrast to its strong effects during metamorphosis. Manipulations of insulin signaling in many other peptidergic neurons revealed generalized growth stimulation during metamorphosis, but not during larval development. These findings reveal a fundamental shift in growth control mechanisms when mature, differentiated neurons enter a new phase of organizational growth. Moreover, they highlight strong evolutionarily conservation of insulin signaling in neuronal growth regulation.

  20. 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.

  1. CHLORHEXIDINE INHIBITS L1 CELL ADHESION MOLECULE MEDIATED NEURITE OUTGROWTH IN VITRO

    Science.gov (United States)

    Milstone, Aaron M.; Bamford, Penny; Aucott, Susan W.; Tang, Ningfeng; White, Kimberly R.; Bearer, Cynthia F.

    2013-01-01

    Background Chlorhexidine is a skin disinfectant that reduces skin and mucous membrane bacterial colonization and inhibits organism growth. Despite numerous studies assessing chlorhexidine safety in term infants, residual concerns have limited its use in hospitalized neonates, especially low birth weight preterm infants. The aim of this study was to assess the potential neurotoxicity of chlorhexidine on the developing central nervous system using a well-established in vitro model of neurite outgrowth that includes laminin and L1 cell adhesion molecule (L1) as neurite outgrowth promoting substrates. Methods Cerebellar granule neurons are plated on either poly L-lysine, L1 or laminin. Chlorhexidine, hexachlorophene or their excipients are added to the media. Neurons are grown for 24 h, then fixed and neurite length measured. Results Chlorhexidine significantly reduced the length of neurites grown on L1 but not laminin. Chlorhexidine concentrations as low as 125 ng/ml statistically significantly reduced neurite length on L1. Hexachlorophene did not affect neurite length. Conclusion Chlorhexidine at concentrations detected in the blood following topical applications in preterm infants specifically inhibited L1 mediated neurite outgrowth of cerebellar granule neurons. It is now vital to determine whether the blood brain barrier is permeable to chlorhexidine in preterm infants. PMID:24126818

  2. Computer vision profiling of neurite outgrowth dynamics reveals spatiotemporal modularity of Rho GTPase signaling.

    Science.gov (United States)

    Fusco, Ludovico; Lefort, Riwal; Smith, Kevin; Benmansour, Fethallah; Gonzalez, German; Barillari, Caterina; Rinn, Bernd; Fleuret, Francois; Fua, Pascal; Pertz, Olivier

    2016-01-04

    Rho guanosine triphosphatases (GTPases) control the cytoskeletal dynamics that power neurite outgrowth. This process consists of dynamic neurite initiation, elongation, retraction, and branching cycles that are likely to be regulated by specific spatiotemporal signaling networks, which cannot be resolved with static, steady-state assays. We present NeuriteTracker, a computer-vision approach to automatically segment and track neuronal morphodynamics in time-lapse datasets. Feature extraction then quantifies dynamic neurite outgrowth phenotypes. We identify a set of stereotypic neurite outgrowth morphodynamic behaviors in a cultured neuronal cell system. Systematic RNA interference perturbation of a Rho GTPase interactome consisting of 219 proteins reveals a limited set of morphodynamic phenotypes. As proof of concept, we show that loss of function of two distinct RhoA-specific GTPase-activating proteins (GAPs) leads to opposite neurite outgrowth phenotypes. Imaging of RhoA activation dynamics indicates that both GAPs regulate different spatiotemporal Rho GTPase pools, with distinct functions. Our results provide a starting point to dissect spatiotemporal Rho GTPase signaling networks that regulate neurite outgrowth. © 2016 Fusco et al.

  3. 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

    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......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...

  4. ANALYSIS OF THE STRUCTURE OF MAGNETIC FIELDS THAT INDUCED INHIBITION OF STIMULATED NEURITE OUTGROWTH

    Science.gov (United States)

    The important experiments showing nonlinear amplitude dependences of the neurite outgrowth in pheochromocytoma nerve cells due to ELF magnetic field exposure had been carried out in a nonuniform ac magnetic field. The nonuniformity entailed larger than expected variances in magne...

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

    Directory of Open Access Journals (Sweden)

    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

  6. Neurite outgrowth in cultured mouse pelvic ganglia - Effects of neurotrophins and bladder tissue.

    Science.gov (United States)

    Ekman, Mari; Zhu, Baoyi; Swärd, Karl; Uvelius, Bengt

    2017-07-01

    Neurotrophic factors regulate survival and growth of neurons. The urinary bladder is innervated via both sympathetic and parasympathetic neurons located in the major pelvic ganglion. The aim of the present study was to characterize the effects of the neurotrophins nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) on the sprouting rate of sympathetic and parasympathetic neurites from the female mouse ganglion. The pelvic ganglion was dissected out and attached to a petri dish and cultured in vitro. All three factors (BDNF, NT-3 and NGF) stimulated neurite outgrowth of both sympathetic and parasympathetic neurites although BDNF and NT-3 had a higher stimulatory effect on parasympathetic ganglion cells. The neurotrophin receptors TrkA, TrkB and TrkC were all expressed in neurons of the ganglia. Co-culture of ganglia with urinary bladder tissue, but not diaphragm tissue, increased the sprouting rate of neurites. Active forms of BDNF and NT-3 were detected in urinary bladder tissue using western blotting whereas tissue from the diaphragm expressed NGF. Neurite outgrowth from the pelvic ganglion was inhibited by a TrkB receptor antagonist. We therefore suggest that the urinary bladder releases trophic factors, including BDNF and NT-3, which regulate neurite outgrowth via activation of neuronal Trk-receptors. These findings could influence future strategies for developing pharmaceuticals to improve re-innervation due to bladder pathologies. Copyright © 2017. Published by Elsevier B.V.

  7. Analysis of Queue-Length Dependent Vacations and P-Limited Service in BMAP/G/1/N Systems: Stationary Distributions and Optimal Control

    Directory of Open Access Journals (Sweden)

    A. D. Banik

    2013-01-01

    Full Text Available We consider a finite-buffer single server queueing system with queue-length dependent vacations where arrivals occur according to a batch Markovian arrival process (BMAP. The service discipline is P-limited service, also called E-limited with limit variation (ELV where the server serves until either the system is emptied or a randomly chosen limit of L customers has been served. Depending on the number of customers present in the system, the server will monitor his vacation times. Queue-length distributions at various epochs such as before, arrival, arbitrary and after, departure have been obtained. Several other service disciplines like Bernoulli scheduling, nonexhaustive service, and E-limited service can be treated as special cases of the P-limited service. Finally, the total expected cost function per unit time is considered to determine locally optimal values N* of N or a maximum limit L^* of L^ as the number of customers served during a service period at a minimum cost.

  8. Quinoidal Oligo(9,10-anthryl)s with Chain-Length-Dependent Ground States: A Balance between Aromatic Stabilization and Steric Strain Release

    KAUST Repository

    Lim, Zhenglong

    2015-11-12

    Quinoidal π-conjugated polycyclic hydrocarbons have attracted intensive research interest due to their unique optical/electronic properties and possible magnetic activity, which arises from a thermally excited triplet state. However, there is still lack of fundamental understanding on the factors that determine the electronic ground states. Herein, by using quinoidal oligo(9,10-anthryl)s, it is demonstrated that both aromatic stabilisation and steric strain release play balanced roles in determining the ground states. Oligomers with up to four anthryl units were synthesised and their ground states were investigated by electronic absorption and electron spin resonance (ESR) spectroscopy, assisted by density functional theory (DFT) calculations. The quinoidal 9,10-anthryl dimer 1 has a closed-shell ground state, whereas the tri- (2) and tetramers (3) both have an open-shell diradical ground state with a small singlet-triplet gap. Such a difference results from competition between two driving forces: the large steric repulsion between the anthryl/phenyl units in the closed-shell quinoidal form that drives the molecule to a flexible open-shell diradical structure, and aromatic stabilisation due to the gain of more aromatic sextet rings in the closed-shell form, which drives the molecule towards a contorted quinoidal structure. The ground states of these oligomers thus depend on the overall balance between these two driving forces and show chain-length dependence. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Chain-length dependent growth dynamics of n-alkanes on silica investigated by energy-dispersive x-ray reflectivity in situ and in real-time.

    Science.gov (United States)

    Weber, C; Frank, C; Bommel, S; Rukat, T; Leitenberger, W; Schäfer, P; Schreiber, F; Kowarik, S

    2012-05-28

    We compare the growth dynamics of the three n-alkanes C(36)H(74), C(40)H(82), and C(44)H(90) on SiO(2) using real-time and in situ energy-dispersive x-ray reflectivity. All molecules investigated align in an upright-standing orientation on the substrate and exhibit a transition from layer-by-layer growth to island growth after about 4 monolayers under the conditions employed. Simultaneous fits of the reflected intensity at five distinct points in reciprocal space show that films formed by longer n-alkanes roughen faster during growth. This behavior can be explained by a chain-length dependent height of the Ehrlich-Schwoebel barrier. Further x-ray diffraction measurements after growth indicate that films consisting of longer n-alkanes also incorporate more lying-down molecules in the top region. While the results reveal behavior typical for chain-like molecules, the findings can also be useful for the optimization of organic field effect transistors where smooth interlayers of n-alkanes without coexistence of two or more molecular orientations are required.

  10. Abnormal accumulation of autophagic vesicles correlates with axonal and synaptic pathology in young Alzheimer's mice hippocampus.

    Science.gov (United States)

    Sanchez-Varo, Raquel; Trujillo-Estrada, Laura; Sanchez-Mejias, Elisabeth; Torres, Manuel; Baglietto-Vargas, David; Moreno-Gonzalez, Ines; De Castro, Vanessa; Jimenez, Sebastian; Ruano, Diego; Vizuete, Marisa; Davila, Jose Carlos; Garcia-Verdugo, Jose Manuel; Jimenez, Antonio Jesus; Vitorica, Javier; Gutierrez, Antonia

    2012-01-01

    Dystrophic neurites associated with amyloid plaques precede neuronal death and manifest early in Alzheimer's disease (AD). In this work we have characterized the plaque-associated neuritic pathology in the hippocampus of young (4- to 6-month-old) PS1(M146L)/APP(751SL) mice model, as the initial degenerative process underlying functional disturbance prior to neuronal loss. Neuritic plaques accounted for almost all fibrillar deposits and an axonal origin of the dystrophies was demonstrated. The early induction of autophagy pathology was evidenced by increased protein levels of the autophagosome marker LC3 that was localized in the axonal dystrophies, and by electron microscopic identification of numerous autophagic vesicles filling and causing the axonal swellings. Early neuritic cytoskeletal defects determined by the presence of phosphorylated tau (AT8-positive) and actin-cofilin rods along with decreased levels of kinesin-1 and dynein motor proteins could be responsible for this extensive vesicle accumulation within dystrophic neurites. Although microsomal Aβ oligomers were identified, the presence of A11-immunopositive Aβ plaques also suggested a direct role of plaque-associated Aβ oligomers in defective axonal transport and disease progression. Most importantly, presynaptic terminals morphologically disrupted by abnormal autophagic vesicle buildup were identified ultrastructurally and further supported by synaptosome isolation. Finally, these early abnormalities in axonal and presynaptic structures might represent the morphological substrate of hippocampal dysfunction preceding synaptic and neuronal loss and could significantly contribute to AD pathology in the preclinical stages.

  11. Revisiting Frank-Starling: regulatory light chain phosphorylation alters the rate of force redevelopment (ktr ) in a length-dependent fashion.

    Science.gov (United States)

    Toepfer, Christopher N; West, Timothy G; Ferenczi, Michael A

    2016-09-15

    Regulatory light chain (RLC) phosphorylation has been shown to alter the ability of muscle to produce force and power during shortening and to alter the rate of force redevelopment (ktr ) at submaximal [Ca(2+) ]. Increasing RLC phosphorylation ∼50% from the in vivo level in maximally [Ca(2+) ]-activated cardiac trabecula accelerates ktr . Decreasing RLC phosphorylation to ∼70% of the in vivo control level slows ktr and reduces force generation. ktr is dependent on sarcomere length in the physiological range 1.85-1.94 μm and RLC phosphorylation modulates this response. We demonstrate that Frank-Starling is evident at maximal [Ca(2+) ] activation and therefore does not necessarily require length-dependent change in [Ca(2+) ]-sensitivity of thin filament activation. The stretch response is modulated by changes in RLC phosphorylation, pinpointing RLC phosphorylation as a modulator of the Frank-Starling law in the heart. These data provide an explanation for slowed systolic function in the intact heart in response to RLC phosphorylation reduction. Force and power in cardiac muscle have a known dependence on phosphorylation of the myosin-associated regulatory light chain (RLC). We explore the effect of RLC phosphorylation on the ability of cardiac preparations to redevelop force (ktr ) in maximally activating [Ca(2+) ]. Activation was achieved by rapidly increasing the temperature (temperature-jump of 0.5-20ºC) of permeabilized trabeculae over a physiological range of sarcomere lengths (1.85-1.94 μm). The trabeculae were subjected to shortening ramps over a range of velocities and the extent of RLC phosphorylation was varied. The latter was achieved using an RLC-exchange technique, which avoids changes in the phosphorylation level of other proteins. The results show that increasing RLC phosphorylation by 50% accelerates ktr by ∼50%, irrespective of the sarcomere length, whereas decreasing phosphorylation by 30% slows ktr by ∼50%, relative to the ktr obtained

  12. Chain length-dependent effects of inulin-type fructan dietary fiber on human systemic immune responses against hepatitis-B.

    Science.gov (United States)

    Vogt, Leonie M; Elderman, Marlies E; Borghuis, Theo; de Haan, Bart J; Faas, Marijke M; de Vos, Paul

    2017-10-01

    In vivo studies demonstrating that only specific dietary-fibers contribute to immunity are still inconclusive, as measuring immune effects in healthy humans remains difficult. We applied a relatively inefficacious vaccination-challenge to study chain length-dependent effects of inulin-type fructan (ITF) dietary fibers on human immunity. ITFs with two different 'degree of polymerization-' (DP)-profiles were tested in vitro for effects on PBMC-cytokines and TLR2 activation. In a double-blind placebo-controlled trial, 40 healthy volunteers (18-29 years) were divided into three groups and supplemented from day 1 to day 14 with DP10-60 ITF, DP2-25 ITF (both n = 13), or fructose placebo (n = 14), 8 g/day. On day 7, all volunteers were vaccinated against hepatitis B. Anti-HbsAg-titer development and lymphocyte subsets were studied. In vitro, DP10-60 ITFs stimulated a Th1-like cytokine profile and stimulated TLR2 more strongly than DP2-25 ITFs. In vivo, DP10-60 increased anti-HBsAg titers, Th1-cells, and transitional B-cells. Both ITFs increased CD45ROhi CTLs at day 35, and CD161+ cytokine producing NK-cells at day 21 and 35. Support of immunity is determined by the chain length of ITFs. Only long-chain ITFs support immunity against pathogenic hepB-epitopes introduced by vaccination. Our findings demonstrate that specific dietary fibers need to be selected for immunity support. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Micropatterned coumarin polyester thin films direct neurite orientation.

    Science.gov (United States)

    McCormick, Aleesha M; Maddipatla, Murthy V S N; Shi, Shuojia; Chamsaz, Elaheh A; Yokoyama, Hiroshi; Joy, Abraham; Leipzig, Nic D

    2014-11-26

    Guidance and migration of cells in the nervous system is imperative for proper development, maturation, and regeneration. In the peripheral nervous system (PNS), it is challenging for axons to bridge critical-sized injury defects to achieve repair and the central nervous system (CNS) has a very limited ability to regenerate after injury because of its innate injury response. The photoreactivity of the coumarin polyester used in this study enables efficient micropatterning using a custom digital micromirror device (DMD) and has been previously shown to be biodegradable, making these thin films ideal for cell guidance substrates with potential for future in vivo applications. With DMD, we fabricated coumarin polyester thin films into 10×20 μm and 15×50 μm micropatterns with depths ranging from 15 to 20 nm to enhance nervous system cell alignment. Adult primary neurons, oligodendrocytes, and astrocytes were isolated from rat brain tissue and seeded onto the polymer surfaces. After 24 h, cell type and neurite alignment were analyzed using phase contrast and fluorescence imaging. There was a significant difference (pdistribution for both emergence angle (from the body of the cell) and orientation angle (at the tip of the growth cone) confirming alignment on patterned surfaces compared to control substrates (unpatterned polymer and glass surfaces). The expected frequency distribution for parallel alignment (≤15°) is 14% and the two micropatterned groups ranged from 42 to 49% alignment for emergence and orientation angle measurements, where the control groups range from 12 to 22% for parallel alignment. Despite depths being 15 to 20 nm, cell processes could sense these topographical changes and preferred to align to certain features of the micropatterns like the plateau/channel interface. As a result this initial study in utilizing these new DMD micropatterned coumarin polyester thin films has proven beneficial as an axon guidance platform for future nervous system

  14. Effects of organophosphates on cholinesterase activity and neurite regeneration in Aplysia.

    Science.gov (United States)

    Srivatsan, M

    1999-05-14

    In Aplysia, a marine mollusc, acetylcholinesterase (AChE) is present in cholinergic and non-cholinergic neurons and in hemolymph. Aplysia hemolymph has a very high level of AChE which promotes neurite growth in primary cultures of dopaminergic neurons via a non-catalytic mechanism. In contrast, AChE is known to facilitate neurite growth in cholinoceptive neurons by hydrolyzing ACh which inhibits neurite growth. In order to test whether AChE's site-specific neurotrophic action varies with the neuronal phenotype, we investigated the effects of active-site inhibited hemolymph AChE on neurite growth of cholinergic neurons of Aplysia in primary culture. Organophosphates being long-acting active site inhibitors of AChE were chosen for this study. The effects of active site inhibited hemolymph AChE was tested on large cholinergic neurons, R2 (abdominal ganglion) and LPL1 (left pleural ganglion) as well as small cholinergic neurons (buccal ganglion) of Aplysia, maintained in culture. Partially purified hemolymph AChE was inhibited by either 10 microM of echothiophate or 5 microM of paraoxon. Neurons were maintained in (1) L15 (defined medium) alone; (2) L15 + echothiophate; (3) L-15 + paraoxon; (4) L-15 + hemolymph AChE; (5) L15 + hemolymph AChE + echothiophate; and (6) L-15 + hemolymph AChE + paraoxon. Addition of uninhibited hemolymph AChE significantly increased neurite growth of cultured neurons compared to L15 alone. In the presence of echothiophate-inhibited or praoxon-inhibited AChE, neurite growth was significantly reduced when compared to L15 + uninhibited AChE. While the presence of echothiophate by itself did not reduce survival or neurite growth when compared to L-15 alone, the presence of paraoxon by itself markedly reduced survival and neurite growth of cultured neurons. The results show that AChE's catalytic action contributes to enhance neurite growth in cholinergic neurons and the effects of paraoxon appears to differ from that of echothiophate on

  15. 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.

  16. Lignosus rhinocerus (Cooke Ryvarden: A Medicinal Mushroom That Stimulates Neurite Outgrowth in PC-12 Cells

    Directory of Open Access Journals (Sweden)

    Lee-Fang Eik

    2012-01-01

    Full Text Available A national treasure mushroom, Lignosus rhinocerus, has been used to treat variety of ailments by local and indigenous communities in Malaysia. The aim of this study was to investigate the potential of the most valuable part of L. rhinocerus, the sclerotium, on neurite outgrowth activity by using PC-12Adh cell line. Differentiated cells with one thin extension at least double the length of the cell diameter were scored positive. Our results showed that aqueous sclerotium L. rhinocerus extract induced neurite outgrowths of 24.4% and 42.1% at 20 μg/mL (w/v of aqueous extract alone and a combination of 20 μg/mL (w/v aqueous extract and 30 ng/mL (w/v of NGF, respectively. Combination of NGF and sclerotium extract had additive effects and enhanced neurite outgrowth. Neuronal differentiation was demonstrated by indirect immunofluorescence of neurofilament protein. Aqueous sclerotium extract contained neuroactive compounds that stimulated neurite outgrowth in vitro. To our knowledge this is the first report on neurite-stimulating activities of L. rhinocerus.

  17. Inulin-Type Fructans Modulates Pancreatic-Gut Innate Immune Responses and Gut Barrier Integrity during Experimental Acute Pancreatitis in a Chain Length-Dependent Manner.

    Science.gov (United States)

    He, Yue; Wu, Chengfei; Li, Jiahong; Li, Hongli; Sun, Zhenghua; Zhang, Hao; de Vos, Paul; Pan, Li-Long; Sun, Jia

    2017-01-01

    -light-chain-enhancer of activated B cells (NF-κB) p65 (p-NF-κB p65) nuclear translocation and activation in the pancreas. Our findings demonstrate a clear chain length-dependent effect of inulin on AP. The attenuating effects are caused by modulating effects of long-chain inulin on the pancreatic-gut immunity via the pancreatic IRAK-4/p-JNK/p-NF-κBp65 signaling pathway and on prevention of disruption of the gut barrier.

  18. Inulin-Type Fructans Modulates Pancreatic–Gut Innate Immune Responses and Gut Barrier Integrity during Experimental Acute Pancreatitis in a Chain Length-Dependent Manner

    Science.gov (United States)

    He, Yue; Wu, Chengfei; Li, Jiahong; Li, Hongli; Sun, Zhenghua; Zhang, Hao; de Vos, Paul; Pan, Li-Long; Sun, Jia

    2017-01-01

    -light-chain-enhancer of activated B cells (NF-κB) p65 (p-NF-κB p65) nuclear translocation and activation in the pancreas. Our findings demonstrate a clear chain length-dependent effect of inulin on AP. The attenuating effects are caused by modulating effects of long-chain inulin on the pancreatic–gut immunity via the pancreatic IRAK-4/p-JNK/p-NF-κBp65 signaling pathway and on prevention of disruption of the gut barrier. PMID:29018453

  19. A novel life cycle modeling system for Ebola virus shows a genome length-dependent role of VP24 in virus infectivity.

    Science.gov (United States)

    Watt, Ari; Moukambi, Felicien; Banadyga, Logan; Groseth, Allison; Callison, Julie; Herwig, Astrid; Ebihara, Hideki; Feldmann, Heinz; Hoenen, Thomas

    2014-09-01

    Work with infectious Ebola viruses is restricted to biosafety level 4 (BSL4) laboratories, presenting a significant barrier for studying these viruses. Life cycle modeling systems, including minigenome systems and transcription- and replication-competent virus-like particle (trVLP) systems, allow modeling of the virus life cycle under BSL2 conditions; however, all current systems model only certain aspects of the virus life cycle, rely on plasmid-based viral protein expression, and have been used to model only single infectious cycles. We have developed a novel life cycle modeling system allowing continuous passaging of infectious trVLPs containing a tetracistronic minigenome that encodes a reporter and the viral proteins VP40, VP24, and GP1,2. This system is ideally suited for studying morphogenesis, budding, and entry, in addition to genome replication and transcription. Importantly, the specific infectivity of trVLPs in this system was ∼ 500-fold higher than that in previous systems. Using this system for functional studies of VP24, we showed that, contrary to previous reports, VP24 only very modestly inhibits genome replication and transcription when expressed in a regulated fashion, which we confirmed using infectious Ebola viruses. Interestingly, we also discovered a genome length-dependent effect of VP24 on particle infectivity, which was previously undetected due to the short length of monocistronic minigenomes and which is due at least partially to a previously unknown function of VP24 in RNA packaging. Based on our findings, we propose a model for the function of VP24 that reconciles all currently available data regarding the role of VP24 in nucleocapsid assembly as well as genome replication and transcription. Ebola viruses cause severe hemorrhagic fevers in humans, with no countermeasures currently being available, and must be studied in maximum-containment laboratories. Only a few of these laboratories exist worldwide, limiting our ability to study

  20. The role of the cytoskeleton in volume regulation and beading transitions in PC12 neurites

    CERN Document Server

    Fernandez, Pablo

    2010-01-01

    We present investigations on volume regulation and beading shape transitions in PC12 neurites conducted using a flow-chamber technique. By disrupting the cell cytoskeleton with specific drugs we investigate the role of its individual components in the volume regulation response. We find that microtubule disruption increases both swelling rate and maximum volume attained, but does not affect the ability of the neurite to recover its initial volume. In addition, investigation of axonal beading --also known as pearling instability-- provides additional clues on the mechanical state of the neurite. We conclude that the initial swelling phase is mechanically slowed down by microtubules, while the volume recovery is driven by passive diffusion of osmolites. Our experiments provide a framework to investigate the role of cytoskeletal mechanics in volume homeostasis.

  1. 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.

  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. Neurite outgrowth and branching of PC12 cells on very soft substrates sharply decreases below a threshold of substrate rigidity

    Science.gov (United States)

    Leach, Jennie B.; Brown, Xin Q.; Jacot, Jeffrey G.; Di Milla, Paul A.; Wong, Joyce Y.

    2007-06-01

    Rationally designed matrices for nerve tissue engineering and encapsulated cell therapies critically rely on a comprehensive understanding of neural response to biochemical as well as biophysical cues. Whereas biochemical cues are established mediators of neuronal behavior (e.g., outgrowth), physical cues such as substrate stiffness have only recently been recognized to influence cell behavior. In this work, we examine the response of PC12 neurites to substrate stiffness. We quantified and controlled fibronectin density on the substrates and measured multiple neurite behaviors (e.g., growth, branching, neurites per cell, per cent cells expressing neurites) in a large sample population. We found that PC12 neurons display a threshold response to substrate stiffness. On the softest substrates tested (shear modulus ~10 Pa), neurites were relatively few, short in length and unbranched. On stiffer substrates (shear modulus ~102-104 Pa), neurites were longer and more branched and a greater percentage of cells expressed neurites; significant differences in these measures were not found on substrates with a shear modulus >102 Pa. Based on these data and comparisons with published neurobiology and neuroengineering reports of neurite mechanotransduction, we hypothesize that results from studies of neuronal response to compliant substrates are cell-type dependent and sensitive to ligand density, sample size and the range of stiffness investigated.

  4. Autocrine fibronectin from differentiating mesenchymal stem cells induces the neurite elongation in vitro and promotes nerve fiber regeneration in transected spinal cord injury.

    Science.gov (United States)

    Zeng, Xiang; Ma, Yuan-Huan; Chen, Yuan-Feng; Qiu, Xue-Cheng; Wu, Jin-Lang; Ling, Eng-Ang; Zeng, Yuan-Shan

    2016-08-01

    Extracellular matrix (ECM) expression is temporally and spatially regulated during the development of stem cells. We reported previously that fibronectin (FN) secreted by bone marrow mesenchymal stem cells (MSCs) was deposited on the surface of gelatin sponge (GS) soon after culture. In this study, we aimed to assess the function of accumulated FN on neuronal differentiating MSCs as induced by Schwann cells (SCs) in three dimensional transwell co-culture system. The expression pattern and amount of FN of differentiating MSCs was examined by immunofluorescence, Western blot and immunoelectron microscopy. The results showed that FN accumulated inside GS scaffold, although its mRNA expression in MSCs was progressively decreased during neural induction. MSC-derived neuron-like cells showed spindle-shaped cell body and long extending processes on FN-decorated scaffold surface. However, after blocking of FN function by application of monoclonal antibodies, neuron-like cells showed flattened cell body with short and thick neurites, together with decreased expression of integrin β1. In vivo transplantation study revealed that autocrine FN significantly facilitated endogenous nerve fiber regeneration in spinal cord transection model. Taken together, the present results showed that FN secreted by MSCs in the early stage accumulated on the GS scaffold and promoted the neurite elongation of neuronal differentiating MSCs as well as nerve fiber regeneration after spinal cord injury. This suggests that autocrine FN has a dynamic influence on MSCs in a three dimensional culture system and its potential application for treatment of traumatic spinal cord injury. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1902-1911, 2016. © 2016 Wiley Periodicals, Inc.

  5. White matter microstructure pathology in classic galactosemia revealed by neurite orientation dispersion and density imaging.

    Science.gov (United States)

    Timmers, Inge; Zhang, Hui; Bastiani, Matteo; Jansma, Bernadette M; Roebroeck, Alard; Rubio-Gozalbo, M Estela

    2015-03-01

    White matter abnormalities have been observed in patients with classic galactosemia, an inborn error of galactose metabolism. However, magnetic resonance imaging (MRI) data collected in the past were generally qualitative in nature. Our objective was to investigate white matter microstructure pathology and examine correlations with outcome and behaviour in this disease, by using multi-shell diffusion weighted imaging. In addition to standard diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI) was used to estimate density and orientation dispersion of neurites in a group of eight patients (aged 16-21 years) and eight healthy controls (aged 15-20 years). Extensive white matter abnormalities were found: neurite density index (NDI) was lower in the patient group in bilateral anterior areas, and orientation dispersion index (ODI) was increased mainly in the left hemisphere. These specific regional profiles are in agreement with the cognitive profile observed in galactosemia, showing higher order cognitive impairments, and language and motor impairments, respectively. Less favourable white matter properties correlated positively with age and age at onset of diet, and negatively with behavioural outcome (e.g. visual working memory). To conclude, this study provides evidence of white matter pathology regarding density and dispersion of neurites in these patients. The results are discussed in light of suggested pathophysiological mechanisms.

  6. Adhesion and neurite development of cortical neurons on micropatterns of polyethylenimine and fluorcarbon

    NARCIS (Netherlands)

    Ruardij, T.G.; Goedbloed, M.H.; Rutten, Wim

    2000-01-01

    This study aims on the preparation of isolated islands of cortical neurons on modified glass surfaces. Isolated islands of cortical neurons were obtained with a combination of neuron-adhesive polyethylenimine (PEI) and neuron-repellent plasma-deposited fluorocarbon (FC). Neurite development and

  7. 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.

  8. Nerve growth factor promotes neurite outgrowth in guinea pig myenteric plexus ganglia.

    Science.gov (United States)

    Mulholland, M W; Romanchuk, G; Lally, K; Simeone, D M

    1994-10-01

    Nerve growth factor (NGF) has important developmental actions in both central and peripheral nervous systems. Primary cultures of neonatal guinea pig myenteric plexus ganglia were used to examine the ability of NGF to stimulate morphological development in enteric neurons. NGF, in the presence of a serum-free medium, produced dose-dependent increases in neurite density, significant at 1 ng/ml and maximal at 100 ng/ml (4.5-fold increase vs. control). Maximum neurite length was also significantly increased at 1 ng/ml, with maximal effects at 100 ng/ml. Coincubation of NGF (50 ng/ml) with monoclonal NGF antibodies abolished increases in both neurite density (128 +/- 19 processes/mm for control, 369 +/- 19 for NGF, 183 +/- 28 for NGF+monoclonal antibodies) and neurite length. Exposure of enteric neurons to low concentrations of NGF (1 ng/ml) was also associated with increased mRNA levels for cytoskeletal genes. alpha-Tubulin mRNA levels were increased 3.9 +/- 0.7 times basal at 48 h. mRNA levels for microtubule-associated protein 2 were increased threefold at 48 h of NGF incubation. NGF demonstrates activities in cultured enteric ganglia that stimulate morphological development.

  9. Stochastic continuous time neurite branching models with tree and segment dependent rates

    NARCIS (Netherlands)

    van Elburg, Ronald A. J.

    2011-01-01

    In this paper we introduce a continuous time stochastic neurite branching model closely related to the discrete time stochastic BES-model. The discrete time BES-model is underlying current attempts to simulate cortical development, but is difficult to analyze. The new continuous time formulation

  10. Luteolin induces microRNA-132 expression and modulates neurite outgrowth in PC12 cells.

    Directory of Open Access Journals (Sweden)

    Lian-Fang Lin

    Full Text Available Luteolin (3',4',5,7-tetrahydroxyflavone, a food-derived flavonoid, has been reported to exert neurotrophic properties that are associated with its capacity to promote neuronal survival and neurite outgrowth. In this study, we report for the first time that luteolin induces the persistent expression of microRNA-132 (miR-132 in PC12 cells. The correlation between miR-132 knockdown and a decrease in luteolin-mediated neurite outgrowth may indicate a mechanistic link by which miR-132 functions as a mediator for neuritogenesis. Furthermore, we find that luteolin led to the phosphorylation and activation of cAMP response element binding protein (CREB, which is associated with the up-regulation of miR-132 and neurite outgrowth. Moreover, luteolin-induced CREB activation, miR-132 expression and neurite outgrowth were inhibited by adenylate cyclase, protein kinase A (PKA and MAPK/ERK kinase 1/2 (MEK1/2 inhibitors but not by protein kinase C (PKC or calcium/calmodulin-dependent protein kinase II (CaMK II inhibitors. Consistently, we find that luteolin treatment increases ERK phosphorylation and PKA activity in PC12 cells. These results show that luteolin induces the up-regulation of miR-132, which serves as an important regulator for neurotrophic actions, mainly acting through the activation of cAMP/PKA- and ERK-dependent CREB signaling pathways in PC12 cells.

  11. Tiam1 as a signaling mediator of nerve growth factor-dependent neurite outgrowth.

    Directory of Open Access Journals (Sweden)

    Shahrzad Shirazi Fard

    Full Text Available Nerve Growth Factor (NGF-induced neuronal differentiation requires the activation of members of the Rho family of small GTPases. However, the molecular mechanisms through which NGF regulates cytoskeletal changes and neurite outgrowth are not totally understood. In this work, we identify the Rac1-specific guanine exchange factor (GEF Tiam1 as a novel mediator of NGF/TrkA-dependent neurite elongation. In particular, we report that knockdown of Tiam1 causes a significant reduction in Rac1 activity and neurite outgrowth induced by NGF. Physical interaction between Tiam1 and active Ras (Ras-GTP, but not tyrosine phosphorylation of Tiam1, plays a central role in Rac1 activation by NGF. In addition, our findings indicate that Ras is required to associate Tiam1 with Rac1 and promote Rac1 activation upon NGF stimulation. Taken together, these findings define a novel molecular mechanism through which Tiam1 mediates TrkA signaling and neurite outgrowth induced by NGF.

  12. Patterned and functionalized nanofiber scaffolds in three-dimensional hydrogel constructs enhance neurite outgrowth and directional control.

    Science.gov (United States)

    McMurtrey, Richard J

    2014-12-01

    Neural tissue engineering holds incredible potential to restore functional capabilities to damaged neural tissue. It was hypothesized that patterned and functionalized nanofiber scaffolds could control neurite direction and enhance neurite outgrowth. A method of creating aligned electrospun nanofibers was implemented and fiber characteristics were analyzed using environmental scanning electron microscopy. Nanofibers were composed of polycaprolactone (PCL) polymer, PCL mixed with gelatin, or PCL with a laminin coating. Three-dimensional hydrogels were then integrated with embedded aligned nanofibers to support neuronal cell cultures. Microscopic images were captured at high-resolution in single and multi-focal planes with eGFP-expressing neuronal SH-SY5Y cells in a fluorescent channel and nanofiber scaffolding in another channel. Neuronal morphology and neurite tracking of nanofibers were then analyzed in detail. Aligned nanofibers were shown to enable significant control over the direction of neurite outgrowth in both two-dimensional (2D) and three-dimensional (3D) neuronal cultures. Laminin-functionalized nanofibers in 3D hyaluronic acid (HA) hydrogels enabled significant alignment of neurites with nanofibers, enabled significant neurite tracking of nanofibers, and significantly increased the distance over which neurites could extend. Specifically, the average length of neurites per cell in 3D HA constructs with laminin-functionalized nanofibers increased by 66% compared to the same laminin fibers on 2D laminin surfaces, increased by 59% compared to 2D laminin-coated surface without fibers, and increased by 1052% compared to HA constructs without fibers. Laminin functionalization of fibers also doubled average neurite length over plain PCL fibers in the same 3D HA constructs. In addition, neurites also demonstrated tracking directly along the fibers, with 66% of neurite lengths directly tracking laminin-coated fibers in 3D HA constructs, which was a 65% relative

  13. The muscle protein dysferlin accumulates in the Alzheimer brain

    Science.gov (United States)

    Palamand, Divya; Strider, Jeff; Milone, Margherita; Pestronk, Alan

    2006-01-01

    Dysferlin is a transmembrane protein that is highly expressed in muscle. Dysferlin mutations cause limb-girdle dystrophy type 2B, Miyoshi myopathy and distal anterior compartment myopathy. Dysferlin has also been described in neural tissue. We studied dysferlin distribution in the brains of patients with Alzheimer disease (AD) and controls. Twelve brains, staged using the Clinical Dementia Rating were examined: 9 AD cases (mean age: 85.9 years and mean disease duration: 8.9 years), and 3 age-matched controls (mean age: 87.5 years). Dysferlin is a cytoplasmic protein in the pyramidal neurons of normal and AD brains. In addition, there were dysferlin-positive dystrophic neurites within Aβ plaques in the AD brain, distinct from tau-positive neurites. Western blots of total brain protein (RIPA) and sequential extraction buffers (high salt, high salt/Triton X-100, SDS and formic acid) of increasing protein extraction strength were performed to examine solubility state. In RIPA fractions, dysferlin was seen as 230–272 kDa bands in normal and AD brains. In serial extractions, there was a shift of dysferlin from soluble phase in high salt/Triton X-100 to the more insoluble SDS fraction in AD. Dysferlin is a new protein described in the AD brain that accumulates in association with neuritic plaques. In muscle, dysferlin plays a role in the repair of muscle membrane damage. The accumulation of dysferlin in the AD brain may be related to the inability of neurons to repair damage due to Aβ deposits accumulating in the AD brain. PMID:17024495

  14. Nimodipine enhances neurite outgrowth in dopaminergic brain slice co-cultures.

    Science.gov (United States)

    Sygnecka, Katja; Heine, Claudia; Scherf, Nico; Fasold, Mario; Binder, Hans; Scheller, Christian; Franke, Heike

    2015-02-01

    Calcium ions (Ca(2+)) play important roles in neuroplasticity and the regeneration of nerves. Intracellular Ca(2+) concentrations are regulated by Ca(2+) channels, among them L-type voltage-gated Ca(2+) channels, which are inhibited by dihydropyridines like nimodipine. The purpose of this study was to investigate the effect of nimodipine on neurite growth during development and regeneration. As an appropriate model to study neurite growth, we chose organotypic brain slice co-cultures of the mesocortical dopaminergic projection system, consisting of the ventral tegmental area/substantia nigra and the prefrontal cortex from neonatal rat brains. Quantification of the density of the newly built neurites in the border region (region between the two cultivated slices) of the co-cultures revealed a growth promoting effect of nimodipine at concentrations of 0.1μM and 1μM that was even more pronounced than the effect of the growth factor NGF. This beneficial effect was absent when 10μM nimodipine were applied. Toxicological tests revealed that the application of nimodipine at this higher concentration slightly induced caspase 3 activation in the cortical part of the co-cultures, but did neither affect the amount of lactate dehydrogenase release or propidium iodide uptake nor the ratio of bax/bcl-2. Furthermore, the expression levels of different genes were quantified after nimodipine treatment. The expression of Ca(2+) binding proteins, immediate early genes, glial fibrillary acidic protein, and myelin components did not change significantly after treatment, indicating that the regulation of their expression is not primarily involved in the observed nimodipine mediated neurite growth. In summary, this study revealed for the first time a neurite growth promoting effect of nimodipine in the mesocortical dopaminergic projection system that is highly dependent on the applied concentrations. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

  15. 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

  16. Waves of actin and microtubule polymerization drive microtubule-based transport and neurite growth before single axon formation

    Science.gov (United States)

    Winans, Amy M; Collins, Sean R; Meyer, Tobias

    2016-01-01

    Many developing neurons transition through a multi-polar state with many competing neurites before assuming a unipolar state with one axon and multiple dendrites. Hallmarks of the multi-polar state are large fluctuations in microtubule-based transport into and outgrowth of different neurites, although what drives these fluctuations remains elusive. We show that actin waves, which stochastically migrate from the cell body towards neurite tips, direct microtubule-based transport during the multi-polar state. Our data argue for a mechanical control system whereby actin waves transiently widen the neurite shaft to allow increased microtubule polymerization to direct Kinesin-based transport and create bursts of neurite extension. Actin waves also require microtubule polymerization, arguing that positive feedback links these two components. We propose that actin waves create large stochastic fluctuations in microtubule-based transport and neurite outgrowth, promoting competition between neurites as they explore the environment until sufficient external cues can direct one to become the axon. DOI: http://dx.doi.org/10.7554/eLife.12387.001 PMID:26836307

  17. Glial cell line-derived neurotrophic factor (GDNF) enhances sympathetic neurite growth in rat hearts at early developmental stages

    NARCIS (Netherlands)

    Miwa, Keiko; Lee, Jong-Kook; Takagishi, Yoshiko; Opthof, Tobias; Fu, Xianming; Kodama, Itsuo

    2010-01-01

    Molecular signaling of sympathetic innervation of myocardium is an unresolved issue. The purpose of this study was to investigate the effect of neurotrophic factors on sympathetic neurite growth towards cardiomyocytes. Cardiomyocytes (CMs) and sympathetic neurons (SNs) were isolated from neonatal

  18. Pituitary adenylate cyclase-activating peptide stimulates neurite growth in PC12 cells.

    Science.gov (United States)

    Hernandez, A; Kimball, B; Romanchuk, G; Mulholland, M W

    1995-01-01

    The ability of PACAP-38 to stimulate morphological development was studied using rat pheochromocytoma PC12 cells. PACAP-38 produced concentration-dependent increases in percentage of cells exhibiting neurite extension. Similar increases were produced by forskolin (28 +/- 2% at 96 h) and 8-bromo cAMP (30 +/- 2%). Vasoactive intestinal peptide and alpha-calcitonin gene-related peptide were without effect. PACAP-38 produced significant increases in PC12 cell cAMP content and inositol phosphate turnover. Intracellular [Ca2+] increased from 169 +/- 14 nM to 560 +/- 58 nM in response to 1 microM PACAP-38. PACAP-stimulated neurite outgrowth was abolished by RpcAMPS, an inhibitor of cAMP-dependent kinases but was unaffected by the protein kinase C antagonist H7.

  19. 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.

  20. Terpenoids with neurite outgrowth-promoting activity from the branches and leaves of Illicium merrillianum.

    Science.gov (United States)

    Tian, Xin-Hui; Yue, Rong-Cai; Fang, Xin; Zhang, Jian-Ping; Wang, Guo-Wei; Shan, Lei; Zhang, Wei-Dong; Shen, Yun-Heng

    2016-05-01

    Eighteen terpenoids (1-18) were isolated from Illicium merrillianum. Compound 1 was identified as new compound, and its structure was established by comprehensive spectroscopic analysis and single-crystal X-ray diffraction. All compounds were evaluated for nerve growth factor (NGF)-mediated neurite outgrowth activity using rat pheochromocytoma (PC12) cells as a model system of neuronal differentiation. Compounds 1, 3, 18 showed significant neurite outgrowth-promoting activity in the presence of 20 ng/ml NGF in a dose-dependent manner at concentrations of 1-100 μM after 24-h treatment. Subtle difference of functional groups at C-2 position in hopane-type triterpene resulted in enormous bioactivity difference, compound 1 was neurotrophic but 2 was cytotoxic.

  1. Mechanisms involved in the regulation of neuropeptide-mediated neurite outgrowth: a minireview

    Directory of Open Access Journals (Sweden)

    Lestanova Z.

    2016-04-01

    Full Text Available The present knowledge, regarding the neuronal growth and neurite extension, includes neuropeptide action in the central nervous system. Research reports have brought much information about the multiple intracellular signaling pathways of neuropeptides. However, regardless of the differences in the local responses elicited by neuropeptides, there exist certain functional similarities in the effects of neuropeptides, mediated by their receptors. In the present review, data of the relevant studies, focused on G protein-coupled receptors activated by neuropeptides, are summarized. Particularly, receptors that activate phosphatidylinositol-calcium system and protein kinase C pathways, resulting in the reorganization of the neuronal cytoskeleton and changes in the neuronal morphology, are discussed. Based on our data received, we are showing that oxytocin increases the gene expression of GTPase cell division cycle protein 42 (Cdc42, implicated in many aspects of the neuronal growth and morphology. We are also paying a special attention to neurite extension and retraction in the context of neuropeptide regulation.

  2. 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

  3. Rewiring Neuronal Circuits: A New Method for Fast Neurite Extension and Functional Neuronal Connection.

    Science.gov (United States)

    Magdesian, Margaret H; Anthonisen, Madeleine; Lopez-Ayon, G Monserratt; Chua, Xue Ying; Rigby, Matthew; Grütter, Peter

    2017-06-13

    Brain and spinal cord injury may lead to permanent disability and death because it is still not possible to regenerate neurons over long distances and accurately reconnect them with an appropriate target. Here a procedure is described to rapidly initiate, elongate, and precisely connect new functional neuronal circuits over long distances. The extension rates achieved reach over 1.2 mm/h, 30-60 times faster than the in vivo rates of the fastest growing axons from the peripheral nervous system (0.02 to 0.04 mm/h)(28) and 10 times faster than previously reported for the same neuronal type at an earlier stage of development(4). First, isolated populations of rat hippocampal neurons are grown for 2-3 weeks in microfluidic devices to precisely position the cells, enabling easy micromanipulation and experimental reproducibility. Next, beads coated with poly-D-lysine (PDL) are placed on neurites to form adhesive contacts and pipette micromanipulation is used to move the resulting bead-neurite complex. As the bead is moved, it pulls out a new neurite that can be extended over hundreds of micrometers and functionally connected to a target cell in less than 1 h. This process enables experimental reproducibility and ease of manipulation while bypassing slower chemical strategies to induce neurite growth. Preliminary measurements presented here demonstrate a neuronal growth rate far exceeding physiological ones. Combining these innovations allows for the precise establishment of neuronal networks in culture with an unprecedented degree of control. It is a novel method that opens the door to a plethora of information and insights into signal transmission and communication within the neuronal network as well as being a playground in which to explore the limits of neuronal growth. The potential applications and experiments are widespread with direct implications for therapies that aim to reconnect neuronal circuits after trauma or in neurodegenerative diseases.

  4. Influence of micro-patterned PLLA membranes on outgrowth and orientation of hippocampal neurites.

    Science.gov (United States)

    Morelli, Sabrina; Salerno, Simona; Piscioneri, Antonella; Papenburg, Bernke J; Di Vito, Anna; Giusi, Giuseppina; Canonaco, Marcello; Stamatialis, Dimitrios; Drioli, Enrico; De Bartolo, Loredana

    2010-09-01

    In neuronal tissue engineering many efforts are focused on creating biomaterials with physical and chemical pathways for controlling cellular proliferation and orientation. Neurons have the ability to respond to topographical features in their microenvironment causing among others, axons to proliferate along surface features such as substrate grooves in micro-and nanoscales. As a consequence these neuronal elements are able to correctly adhere, migrate and orient within their new environment during growth. Here we explored the polarization and orientation of hippocampal neuronal cells on nonpatterned and micro-patterned biodegradable poly(l-lactic acid) (PLLA) membranes with highly selective permeable properties. Dense and porous nonpatterned and micro-patterned membranes were prepared from PLLA by Phase Separation Micromolding. The micro-patterned membranes have a three-dimensional structure consisting of channels and ridges and of bricks of different widths. Nonpatterned and patterned membranes were used for hippocampal neuronal cultures isolated from postnatal days 1-3 hamsters and the neurite length, orientation and specific functions of cells were investigated up to 12 days of culture. Neurite outgrowth, length plus orientation tightly overlapped the pattern of the membrane surface. Cell distribution occurred only in correspondence to membrane grooves characterized by continuous channels whereas on membranes with interconnected channels, cells not only adhered to and elongated their cellular processes in the grooves but also in the breaking points. High orientation degrees of cells were determined particularly on the patterned porous membranes with channel width of 20 mum and ridges of 17 mum whereas on dense nonpatterned membranes as well as on polystyrene culture dish (PSCD) controls, a larger number of primary developed neurites were distributed. Based on these results, PLLA patterned membranes may directly improve the guidance of neurite extension and

  5. NIR-responsive upconversion nanoparticles stimulate neurite outgrowth in PC12 cells.

    Science.gov (United States)

    Guan, Yijia; Li, Meng; Dong, Kai; Ren, Jinsong; Qu, Xiaogang

    2014-09-24

    Nerve regeneration is of diagnostic importance in neuroscience in regards to the treatment of degenerative disease. Owing to the ability to release rare-earth ions and produce ROS during upconversion process, upconversion nanoparticles are first reported for promoting neurite outgrowth. Different charged coating materials which play a critical role in cell attachment, can further lead to different effects on cell differentiation. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Ethanol-induced disruption of Golgi apparatus morphology, primary neurite number and cellular orientation in developing cortical neurons.

    Science.gov (United States)

    Powrozek, Teresa A; Olson, Eric C

    2012-11-01

    Prenatal ethanol exposure disrupts cortical neurite initiation and outgrowth, but prior studies have reported both ethanol-dependent growth promotion and inhibition. To resolve this ambiguity and better approximate in vivo conditions, we quantitatively analyzed neuronal morphology using a new, whole hemisphere explant model. In this model, Layer 6 (L6) cortical neurons migrate, laminate and extend neurites in an organotypic fashion. To selectively label L6 neurons, we performed ex utero electroporation of a GFP expression construct at embryonic day 13 and allowed the explants to develop for 2 days in vitro. Explants were exposed to (400 mg/dL) ethanol for either 4 or 24 h prior to fixation. Complete 3-D reconstructions were made of >80 GFP-positive neurons in each experimental condition. Acute responses to ethanol exposure included compaction of the Golgi apparatus accompanied by elaboration of supernumerary primary apical neurites, as well as a modest (∼15%) increase in higher order apical neurite length. With longer exposure time, ethanol exposure leads to a consistent, significant disorientation of the cell (cell body, primary apical neurite, and Golgi) with respect to the pial surface. The effects on cellular orientation were accompanied by decreased expression of cytoskeletal elements, microtubule-associated protein 2 and F-actin. These findings indicate that upon exposure to ethanol, developing L6 neurons manifest disruptions in Golgi apparatus and cytoskeletal elements which may in turn trigger selective and significant perturbations to primary neurite formation and neuronal polarity. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Directional neurite growth using carbon nanotube patterned substrates as a biomimetic cue

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Min Jee; Nam, Yoonkey [Department of Bio and Brain Engineering, KAIST, Daejeon (Korea, Republic of); Namgung, Seon; Hong, Seunghun, E-mail: seunghun@snu.ac.kr, E-mail: ynam@kaist.ac.kr [Department of Physics and Astronomy, Seoul National University, Seoul (Korea, Republic of)

    2010-06-11

    Researchers have made extensive efforts to mimic or reverse-engineer in vivo neural circuits using micropatterning technology. Various surface chemical cues or topographical structures have been proposed to design neuronal networks in vitro. In this paper, we propose a carbon nanotube (CNT)-based network engineering method which naturally mimics the structure of extracellular matrix (ECM). On CNT patterned substrates, poly-L-lysine (PLL) was coated, and E18 rat hippocampal neurons were cultured. In the early developmental stage, soma adhesion and neurite extension occurred in disregard of the surface CNT patterns. However, later the majority of neurites selectively grew along CNT patterns and extended further than other neurites that originally did not follow the patterns. Long-term cultured neuronal networks had a strong resemblance to the in vivo neural circuit structures. The selective guidance is possibly attributed to higher PLL adsorption on CNT patterns and the nanomesh structure of the CNT patterns. The results showed that CNT patterned substrates can be used as novel neuronal patterning substrates for in vitro neural engineering.

  8. Visualization of neuritic plaques in Alzheimer’s disease by polarization-sensitive optical coherence microscopy

    Science.gov (United States)

    Baumann, Bernhard; Woehrer, Adelheid; Ricken, Gerda; Augustin, Marco; Mitter, Christian; Pircher, Michael; Kovacs, Gabor G.; Hitzenberger, Christoph K.

    2017-03-01

    One major hallmark of Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA) is the deposition of extracellular senile plaques and vessel wall deposits composed of amyloid-beta (Aβ). In AD, degeneration of neurons is preceded by the formation of Aβ plaques, which show different morphological forms. Most of them are birefringent owing to the parallel arrangement of amyloid fibrils. Here, we present polarization sensitive optical coherence microscopy (PS-OCM) for imaging mature neuritic Aβ plaques based on their birefringent properties. Formalin-fixed, post-mortem brain samples of advanced stage AD patients were investigated. In several cortical brain regions, neuritic Aβ plaques were successfully visualized in tomographic and three-dimensional (3D) images. Cortical grey matter appeared polarization preserving, whereas neuritic plaques caused increased phase retardation. Consistent with the results from PS-OCM imaging, the 3D structure of senile Aβ plaques was computationally modelled for different illumination settings and plaque sizes. Furthermore, the birefringent properties of cortical and meningeal vessel walls in CAA were investigated in selected samples. Significantly increased birefringence was found in smaller vessels. Overall, these results provide evidence that PS-OCM is able to assess amyloidosis based on intrinsic birefringent properties.

  9. Age-dependent differences in brain tissue microstructure assessed with neurite orientation dispersion and density imaging.

    Science.gov (United States)

    Merluzzi, Andrew P; Dean, Douglas C; Adluru, Nagesh; Suryawanshi, Gaurav S; Okonkwo, Ozioma C; Oh, Jennifer M; Hermann, Bruce P; Sager, Mark A; Asthana, Sanjay; Zhang, Hui; Johnson, Sterling C; Alexander, Andrew L; Bendlin, Barbara B

    2016-07-01

    Human aging is accompanied by progressive changes in executive function and memory, but the biological mechanisms underlying these phenomena are not fully understood. Using neurite orientation dispersion and density imaging, we sought to examine the relationship between age, cellular microstructure, and neuropsychological scores in 116 late middle-aged, cognitively asymptomatic participants. Results revealed widespread increases in the volume fraction of isotropic diffusion and localized decreases in neurite density in frontal white matter regions with increasing age. In addition, several of these microstructural alterations were associated with poorer performance on tests of memory and executive function. These results suggest that neurite orientation dispersion and density imaging is capable of measuring age-related brain changes and the neural correlates of poorer performance on tests of cognitive functioning, largely in accordance with published histological findings and brain-imaging studies of people of this age range. Ultimately, this study sheds light on the processes underlying normal brain development in adulthood, knowledge that is critical for differentiating healthy aging from changes associated with dementia. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. A Wnt-Frz/Ror-Dsh pathway regulates neurite outgrowth in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Song Song

    2010-08-01

    Full Text Available One of the challenges to understand the organization of the nervous system has been to determine how axon guidance molecules govern axon outgrowth. Through an unbiased genetic screen, we identified a conserved Wnt pathway which is crucial for anterior-posterior (A/P outgrowth of neurites from RME head motor neurons in Caenorhabditis elegans. The pathway is composed of the Wnt ligand CWN-2, the Frizzled receptors CFZ-2 and MIG-1, the co-receptor CAM-1/Ror, and the downstream component Dishevelled/DSH-1. Among these, CWN-2 acts as a local attractive cue for neurite outgrowth, and its activity can be partially substituted with other Wnts, suggesting that spatial distribution plays a role in the functional specificity of Wnts. As a co-receptor, CAM-1 functions cell-autonomously in neurons and, together with CFZ-2 and MIG-1, transmits the Wnt signal to downstream effectors. Yeast two-hybrid screening identified DSH-1 as a binding partner for CAM-1, indicating that CAM-1 could facilitate CWN-2/Wnt signaling by its physical association with DSH-1. Our study reveals an important role of a Wnt-Frz/Ror-Dsh pathway in regulating neurite A/P outgrowth.

  11. Non-Obese Diabetic Mice Rapidly Develop Dramatic Sympathetic Neuritic Dystrophy

    Science.gov (United States)

    Schmidt, Robert E.; Dorsey, Denise A.; Beaudet, Lucie N.; Frederick, Kathy E.; Parvin, Curtis A.; Plurad, Santiago B.; Levisetti, Matteo G.

    2003-01-01

    To address the pathogenesis of diabetic autonomic neuropathy, we have examined the sympathetic nervous system in non-obese diabetic (NOD) and streptozotocin (STZ)-induced diabetic mice, two models of type 1 diabetes, and the db/db mouse, a model of type 2 diabetes. After only 3 to 5 weeks of diabetes, NOD mice developed markedly swollen axons and dendrites (“neuritic dystrophy”) in the prevertebral superior mesenteric and celiac ganglia (SMG-CG), similar to the pathology described in diabetic STZ- and BBW-rat and man. Comparable changes failed to develop in the superior cervical ganglia of the NOD mouse or in the SMG-CG of non-diabetic NOD siblings. STZ-induced diabetic mice develop identical changes, although at a much slower pace and to a lesser degree than NOD mice. NOD-SCID mice, which are genetically identical to NOD mice except for the absence of T and B cells, do not develop diabetes or neuropathology comparable to diabetic NOD mice. However, STZ-treated NOD-SCID mice develop severe neuritic dystrophy, evidence against an exclusively autoimmune pathogenesis for autonomic neuropathy in this model. Chronically diabetic type 2 db/db mice fail to develop neuritic dystrophy, suggesting that hyperglycemia alone may not be the critical and sufficient element. The NOD mouse appears to be a valuable model of diabetic sympathetic autonomic neuropathy with unambiguous, rapidly developing neuropathology which corresponds closely to the characteristic pathology of other rodent models and man. PMID:14578206

  12. Target deletion of the cytoskeleton-associated protein palladin does not impair neurite outgrowth in mice.

    Directory of Open Access Journals (Sweden)

    Run-Zhe Shu

    Full Text Available Palladin is an actin cytoskeleton-associated protein which is crucial for cell morphogenesis and motility. Previous studies have shown that palladin is localized to the axonal growth cone in neurons and may play an important role in axonal extension. Previously, we have generated palladin knockout mice which display cranial neural tube closure defect and embryonic lethality before embryonic day 15.5 (E15.5. To further study the role of palladin in the developing nervous system, we examined the innervation of palladin-deficient mouse embryos since the 200 kd, 140 kd, 90-92 kd and 50 kd palladin isoforms were undetectable in the mutant mouse embryo brain. Contrary to the results of previous studies, we found no inhibition of the axonal extension in palladin-deficient mouse embryos. The cortical neurons derived from palladin-deficient mice also showed no significant difference in neurite outgrowth as compared with those from wild-type mice. Moreover, no difference was found in neurite outgrowth of neural stem cell derived-neurons between palladin-deficient mice and wild-type mice. In conclusion, these results suggest that palladin is dispensable for normal neurite outgrowth in mice.

  13. LINGO-1 Interacts with WNK1 to Regulate Nogo-induced Inhibition of Neurite Extension*

    Science.gov (United States)

    Zhang, Zhaohuan; Xu, Xiaohui; Zhang, Yong; Zhou, Jianfeng; Yu, Zhongwang; He, Cheng

    2009-01-01

    LINGO-1 is a component of the tripartite receptor complexes, which act as a convergent mediator of the intracellular signaling in response to myelin-associated inhibitors and lead to collapse of growth cone and inhibition of neurite extension. Although the function of LINGO-1 has been intensively studied, its downstream signaling remains elusive. In the present study, a novel interaction between LINGO-1 and a serine-threonine kinase WNK1 was identified by yeast two-hybrid screen. The interaction was further validated by fluorescence resonance energy transfer and co-immunoprecipitation, and this interaction was intensified by Nogo66 treatment. Morphological evidences showed that WNK1 and LINGO-1 were co-localized in cortical neurons. Furthermore, either suppressing WNK1 expression by RNA interference or overexpression of WNK1-(123–510) attenuated Nogo66-induced inhibition of neurite extension and inhibited the activation of RhoA. Moreover, WNK1 was identified to interact with Rho-GDI1, and this interaction was attenuated by Nogo66 treatment, further indicating its regulatory effect on RhoA activation. Taken together, our results suggest that WNK1 is a novel signaling molecule involved in regulation of LINGO-1 mediated inhibition of neurite extension. PMID:19363035

  14. LINGO-1 interacts with WNK1 to regulate nogo-induced inhibition of neurite extension.

    Science.gov (United States)

    Zhang, Zhaohuan; Xu, Xiaohui; Zhang, Yong; Zhou, Jianfeng; Yu, Zhongwang; He, Cheng

    2009-06-05

    LINGO-1 is a component of the tripartite receptor complexes, which act as a convergent mediator of the intracellular signaling in response to myelin-associated inhibitors and lead to collapse of growth cone and inhibition of neurite extension. Although the function of LINGO-1 has been intensively studied, its downstream signaling remains elusive. In the present study, a novel interaction between LINGO-1 and a serine-threonine kinase WNK1 was identified by yeast two-hybrid screen. The interaction was further validated by fluorescence resonance energy transfer and co-immunoprecipitation, and this interaction was intensified by Nogo66 treatment. Morphological evidences showed that WNK1 and LINGO-1 were co-localized in cortical neurons. Furthermore, either suppressing WNK1 expression by RNA interference or overexpression of WNK1-(123-510) attenuated Nogo66-induced inhibition of neurite extension and inhibited the activation of RhoA. Moreover, WNK1 was identified to interact with Rho-GDI1, and this interaction was attenuated by Nogo66 treatment, further indicating its regulatory effect on RhoA activation. Taken together, our results suggest that WNK1 is a novel signaling molecule involved in regulation of LINGO-1 mediated inhibition of neurite extension.

  15. Robust neurite extension following exogenous electrical stimulation within single walled carbon nanotube-composite hydrogels.

    Science.gov (United States)

    Koppes, A N; Keating, K W; McGregor, A L; Koppes, R A; Kearns, K R; Ziemba, A M; McKay, C A; Zuidema, J M; Rivet, C J; Gilbert, R J; Thompson, D M

    2016-07-15

    The use of exogenous electrical stimulation to promote nerve regeneration has achieved only limited success. Conditions impeding optimized outgrowth may arise from inadequate stimulus presentation due to differences in injury geometry or signal attenuation. Implantation of an electrically-conductive biomaterial may mitigate this attenuation and provide a more reproducible signal. In this study, a conductive nanofiller (single-walled carbon nanotubes [SWCNT]) was selected as one possible material to manipulate the bulk electrical properties of a collagen type I-10% Matrigel™ composite hydrogel. Neurite outgrowth within hydrogels (SWCNT or nanofiller-free controls) was characterized to determine if: (1) nanofillers influence neurite extension and (2) electrical stimulation of the nanofiller composite hydrogel enhances neurite outgrowth. Increased SWCNT loading (10-100-μg/mL) resulted in greater bulk conductivity (up to 1.7-fold) with no significant changes to elastic modulus. Neurite outgrowth increased 3.3-fold in 20-μg/mL SWCNT loaded biomaterials relative to the nanofiller-free control. Electrical stimulation promoted greater outgrowth (2.9-fold) within SWCNT-free control. The concurrent presentation of electrical stimulation and SWCNT-loaded biomaterials resulted in a 7.0-fold increase in outgrowth relative to the unstimulated, nanofiller-free controls. Local glia residing within the DRG likely contribute, in part, to the observed increases in outgrowth; but it is unknown which specific nanofiller properties influence neurite extension. Characterization of neuronal behavior in model systems, such as those described here, will aid the rational development of biomaterials as well as the appropriate delivery of electrical stimuli to support nerve repair. Novel biomedical devices delivering electrical stimulation are being developed to mitigate symptoms of Parkinson's, treat drug-resistant depression, control movement or enhance verve regeneration. Carbon

  16. 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

  17. Enhanced neurite outgrowth of human model (NT2) neurons by small-molecule inhibitors of Rho/ROCK signaling.

    Science.gov (United States)

    Roloff, Frank; Scheiblich, Hannah; Dewitz, Carola; Dempewolf, Silke; Stern, Michael; Bicker, Gerd

    2015-01-01

    Axonal injury in the adult human central nervous system often results in loss of sensation and motor functions. Promoting regeneration of severed axons requires the inactivation of growth inhibitory influences from the tissue environment and stimulation of the neuron intrinsic growth potential. Especially glial cell derived factors, such as chondroitin sulfate proteoglycans, Nogo-A, myelin-associated glycoprotein, and myelin in general, prevent axon regeneration. Most of the glial growth inhibiting factors converge onto the Rho/ROCK signaling pathway in neurons. Although conditions in the injured nervous system are clearly different from those during neurite outgrowth in vitro, here we use a chemical approach to manipulate Rho/ROCK signalling with small-molecule agents to encourage neurite outgrowth in cell culture. The development of therapeutic treatments requires drug testing not only on neurons of experimental animals, but also on human neurons. Using human NT2 model neurons, we demonstrate that the pain reliever Ibuprofen decreases RhoA (Ras homolog gene family, member A GTPase) activation and promotes neurite growth. Inhibition of the downstream effector Rho kinase by the drug Y-27632 results in a strong increase in neurite outgrowth. Conversely, activation of the Rho pathway by lysophosphatidic acid results in growth cone collapse and eventually to neurite retraction. Finally, we show that blocking of Rho kinase, but not RhoA results in an increase in neurons bearing neurites. Due to its anti-inflammatory and neurite growth promoting action, the use of a pharmacological treatment of damaged neural tissue with Ibuprofen should be explored.

  18. Enhanced neurite outgrowth of human model (NT2 neurons by small-molecule inhibitors of Rho/ROCK signaling.

    Directory of Open Access Journals (Sweden)

    Frank Roloff

    Full Text Available Axonal injury in the adult human central nervous system often results in loss of sensation and motor functions. Promoting regeneration of severed axons requires the inactivation of growth inhibitory influences from the tissue environment and stimulation of the neuron intrinsic growth potential. Especially glial cell derived factors, such as chondroitin sulfate proteoglycans, Nogo-A, myelin-associated glycoprotein, and myelin in general, prevent axon regeneration. Most of the glial growth inhibiting factors converge onto the Rho/ROCK signaling pathway in neurons. Although conditions in the injured nervous system are clearly different from those during neurite outgrowth in vitro, here we use a chemical approach to manipulate Rho/ROCK signalling with small-molecule agents to encourage neurite outgrowth in cell culture. The development of therapeutic treatments requires drug testing not only on neurons of experimental animals, but also on human neurons. Using human NT2 model neurons, we demonstrate that the pain reliever Ibuprofen decreases RhoA (Ras homolog gene family, member A GTPase activation and promotes neurite growth. Inhibition of the downstream effector Rho kinase by the drug Y-27632 results in a strong increase in neurite outgrowth. Conversely, activation of the Rho pathway by lysophosphatidic acid results in growth cone collapse and eventually to neurite retraction. Finally, we show that blocking of Rho kinase, but not RhoA results in an increase in neurons bearing neurites. Due to its anti-inflammatory and neurite growth promoting action, the use of a pharmacological treatment of damaged neural tissue with Ibuprofen should be explored.

  19. Ginsenoside-Rd Promotes Neurite Outgrowth of PC12 Cells through MAPK/ERK- and PI3K/AKT-Dependent Pathways.

    Science.gov (United States)

    Wu, Song-Di; Xia, Feng; Lin, Xue-Mei; Duan, Kang-Li; Wang, Fang; Lu, Qing-Li; Cao, Huan; Qian, Yi-Hua; Shi, Ming

    2016-01-29

    Panax ginseng is a famous herbal medicine widely used in Asia. Ginsenosides have been identified as the principle active ingredients for Panax ginseng's biological activity, among which ginsenoside Rd (Rd) attracts extensive attention for its obvious neuroprotective activities. Here we investigated the effect of Rd on neurite outgrowth, a crucial process associated with neuronal repair. PC12 cells, which respond to nerve growth factor (NGF) and serve as a model for neuronal cells, were treated with different concentrations of Rd, and then their neurite outgrowth was evaluated. Our results showed that 10 μM Rd significantly increased the percentages of long neurite- and branching neurite-bearing cells, compared with respective controls. The length of the longest neurites and the total length of neurites in Rd-treated PC12 cells were much longer than that of respective controls. We also showed that Rd activated ERK1/2 and AKT but not PKC signalings, and inhibition of ERK1/2 by PD98059 or/and AKT by LY294002 effectively attenuated Rd-induced neurite outgrowth. Moreover, Rd upregulated the expression of GAP-43, a neuron-specific protein involved in neurite outgrowth, while PD98059 or/and LY294002 decreased Rd-induced increased GAP-43 expression. Taken together, our results provided the first evidence that Rd may promote the neurite outgrowth of PC12 cells by upregulating GAP-43 expression via ERK- and ARK-dependent signaling pathways.

  20. Sialylation of neurites inhibits complement-mediated macrophage removal in a human macrophage-neuron co-culture system

    Science.gov (United States)

    Linnartz-Gerlach, Bettina; Schuy, Christine; Shahraz, Anahita; Tenner, Andrea J.; Neumann, Harald

    2015-01-01

    The complement system has been implicated in the removal of dysfunctional synapses and neurites during development and in disease processes in the mouse, but it is unclear how far the mouse data can be transferred to humans. Here, we co-cultured macrophages derived from human THP1 monocytes and neurons derived from human induced pluripotent stem cells, to study the role of the complement system in a human model. Components of the complement system were expressed by the human macrophages and human neuronal culture, while receptors of the complement cascade were expressed by human macrophages as shown via gene transcript analysis and flow cytometry. We mimicked pathological conditions leading to an altered glycocalyx by treatment of human neurons with sialidases. Desialylated human neurites were opsonized by the complement component C1q. Furthermore, human neurites with an intact sialic acid cap remained untouched, while desialylated human neurites were removed and ingested by human macrophages. While blockage of the complement receptor 1 (CD35) had no effect, blockage of CD11b as part of the complement receptor 3 (CR3) reversed the effect on macrophage phagocytosis of desialylated human neurites. Data demonstrate that in the human system sialylation of the neuronal glycocalyx serves as an inhibitory flag for complement binding and CR3 mediated phagocytosis by macrophages. PMID:26257016

  1. μ2-Dependent endocytosis of N-cadherin is regulated by β-catenin to facilitate neurite outgrowth.

    Science.gov (United States)

    Chen, Yi-Ting; Tai, Chin-Yin

    2017-05-01

    Circuit formation in the brain requires neurite outgrowth throughout development to establish synaptic contacts with target cells. Active endocytosis of several adhesion molecules facilitates the dynamic exchange of these molecules at the surface and promotes neurite outgrowth in developing neurons. The endocytosis of N-cadherin, a calcium-dependent adhesion molecule, has been implicated in the regulation of neurite outgrowth, but the mechanism remains unclear. Here, we identified that a fraction of N-cadherin internalizes through clathrin-mediated endocytosis (CME). Two tyrosine-based motifs in the cytoplasmic domain of N-cadherin recognized by the μ2 subunit of the AP-2 adaptor complex are responsible for CME of N-cadherin. Moreover, β-catenin, a core component of the N-cadherin adhesion complex, inhibits N-cadherin endocytosis by masking the 2 tyrosine-based motifs. Removal of β-catenin facilitates μ2 binding to N-cadherin, thereby increasing clathrin-mediated N-cadherin endocytosis and neurite outgrowth without affecting the steady-state level of surface N-cadherin. These results identify and characterize the mechanism controlling N-cadherin endocytosis through β-catenin-regulated μ2 binding to modulate neurite outgrowth. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. White Matter Changes of Neurite Density and Fiber Orientation Dispersion during Human Brain Maturation.

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    Yi Shin Chang

    Full Text Available Diffusion tensor imaging (DTI studies of human brain development have consistently shown widespread, but nonlinear increases in white matter anisotropy through childhood, adolescence, and into adulthood. However, despite its sensitivity to changes in tissue microstructure, DTI lacks the specificity to disentangle distinct microstructural features of white and gray matter. Neurite orientation dispersion and density imaging (NODDI is a recently proposed multi-compartment biophysical model of brain microstructure that can estimate non-collinear properties of white matter, such as neurite orientation dispersion index (ODI and neurite density index (NDI. In this study, we apply NODDI to 66 healthy controls aged 7-63 years to investigate changes of ODI and NDI with brain maturation, with comparison to standard DTI metrics. Using both region-of-interest and voxel-wise analyses, we find that NDI exhibits striking increases over the studied age range following a logarithmic growth pattern, while ODI rises following an exponential growth pattern. This novel finding is consistent with well-established age-related changes of FA over the lifespan that show growth during childhood and adolescence, plateau during early adulthood, and accelerating decay after the fourth decade of life. Our results suggest that the rise of FA during the first two decades of life is dominated by increasing NDI, while the fall in FA after the fourth decade is driven by the exponential rise of ODI that overcomes the slower increases of NDI. Using partial least squares regression, we further demonstrate that NODDI better predicts chronological age than DTI. Finally, we show excellent test-retest reliability of NODDI metrics, with coefficients of variation below 5% in all measured regions of interest. Our results support the conclusion that NODDI reveals biologically specific characteristics of brain development that are more closely linked to the microstructural features of white

  3. Low-frequency dielectric dispersion of brain tissue due to electrically long neurites

    Science.gov (United States)

    Monai, Hiromu; Inoue, Masashi; Miyakawa, Hiroyoshi; Aonishi, Toru

    2012-12-01

    The dielectric properties of brain tissue are important for understanding how neural activity is related to local field potentials and electroencephalograms. It is known that the permittivity of brain tissue exhibits strong frequency dependence (dispersion) and that the permittivity is very large in the low-frequency region. However, little is known with regard to the cause of the large permittivity in the low-frequency region. Here, we postulate that the dielectric properties of brain tissue can be partially accounted for by assuming that neurites are of sufficient length to be “electrically long.” To test this idea, we consider a model in which a neurite is treated as a long, narrow body, and it is subjected to a stimulus created by electrodes situated in the region external to it. With regard to this electric stimulus, the neurite can be treated as a passive cable. Assuming adequate symmetry so that the tissue packed with multiple cables is equivalent to an isolated system consisting of a single cable and a surrounding extracellular resistive medium, we analytically calculate the extracellular potential of the tissue in response to such an externally created alternating-current electric field using a Green's function that we obtained previously. Our results show that brain tissue modeled by such a cable existing within a purely resistive extracellular medium exhibits a large effective permittivity in the low-frequency region. Moreover, we obtain results suggesting that an extremely large low-frequency permittivity can coexist with weak low-pass filter characteristics in brain tissue.

  4. Exposure to 1800 MHz radiofrequency radiation impairs neurite outgrowth of embryonic neural stem cells

    Science.gov (United States)

    Chen, Chunhai; Ma, Qinlong; Liu, Chuan; Deng, Ping; Zhu, Gang; Zhang, Lei; He, Mindi; Lu, Yonghui; Duan, Weixia; Pei, Liping; Li, Min; Yu, Zhengping; Zhou, Zhou

    2014-01-01

    A radiofrequency electromagnetic field (RF-EMF) of 1800 MHz is widely used in mobile communications. However, the effects of RF-EMFs on cell biology are unclear. Embryonic neural stem cells (eNSCs) play a critical role in brain development. Thus, detecting the effects of RF-EMF on eNSCs is important for exploring the effects of RF-EMF on brain development. Here, we exposed eNSCs to 1800 MHz RF-EMF at specific absorption rate (SAR) values of 1, 2, and 4 W/kg for 1, 2, and 3 days. We found that 1800 MHz RF-EMF exposure did not influence eNSC apoptosis, proliferation, cell cycle or the mRNA expressions of related genes. RF-EMF exposure also did not alter the ratio of eNSC differentiated neurons and astrocytes. However, neurite outgrowth of eNSC differentiated neurons was inhibited after 4 W/kg RF-EMF exposure for 3 days. Additionally, the mRNA and protein expression of the proneural genes Ngn1 and NeuroD, which are crucial for neurite outgrowth, were decreased after RF-EMF exposure. The expression of their inhibitor Hes1 was upregulated by RF-EMF exposure. These results together suggested that 1800 MHz RF-EMF exposure impairs neurite outgrowth of eNSCs. More attention should be given to the potential adverse effects of RF-EMF exposure on brain development. PMID:24869783

  5. Exposure to 1800 MHz radiofrequency radiation impairs neurite outgrowth of embryonic neural stem cells.

    Science.gov (United States)

    Chen, Chunhai; Ma, Qinlong; Liu, Chuan; Deng, Ping; Zhu, Gang; Zhang, Lei; He, Mindi; Lu, Yonghui; Duan, Weixia; Pei, Liping; Li, Min; Yu, Zhengping; Zhou, Zhou

    2014-05-29

    A radiofrequency electromagnetic field (RF-EMF) of 1800 MHz is widely used in mobile communications. However, the effects of RF-EMFs on cell biology are unclear. Embryonic neural stem cells (eNSCs) play a critical role in brain development. Thus, detecting the effects of RF-EMF on eNSCs is important for exploring the effects of RF-EMF on brain development. Here, we exposed eNSCs to 1800 MHz RF-EMF at specific absorption rate (SAR) values of 1, 2, and 4 W/kg for 1, 2, and 3 days. We found that 1800 MHz RF-EMF exposure did not influence eNSC apoptosis, proliferation, cell cycle or the mRNA expressions of related genes. RF-EMF exposure also did not alter the ratio of eNSC differentiated neurons and astrocytes. However, neurite outgrowth of eNSC differentiated neurons was inhibited after 4 W/kg RF-EMF exposure for 3 days. Additionally, the mRNA and protein expression of the proneural genes Ngn1 and NeuroD, which are crucial for neurite outgrowth, were decreased after RF-EMF exposure. The expression of their inhibitor Hes1 was upregulated by RF-EMF exposure. These results together suggested that 1800 MHz RF-EMF exposure impairs neurite outgrowth of eNSCs. More attention should be given to the potential adverse effects of RF-EMF exposure on brain development.

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

    Directory of Open Access Journals (Sweden)

    Rafael Salto

    Full Text Available 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.

  7. Two new dendrocandins with neurite outgrowth-promoting activity from Dendrobium officinale.

    Science.gov (United States)

    Yang, Liu; Liu, Shou-Jin; Luo, Huai-Rong; Cui, Juan; Zhou, Jun; Wang, Xuan-Jun; Sheng, Jun; Hu, Jiang-Miao

    2015-01-01

    Two new bibenzyl derivatives, dendrocandin T (1) and dendrocandin U (2), together with eight known bibenzyls, were isolated from the stems of Dendrobium officinale. Those compounds were sent for the first time for central nervous system-related bioassay and the results indicated that compounds 3, 4, and 5 have a certain degree of neurite outgrowth-promoting activity, and compounds 1, 2, 6, and 7 also have weak activity. The results indicated that D. officinale used as health food and traditional Chinese medicine "Tiepi Shihu" has a health function of neurotrophic effects.

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

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    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

  9. Inhibition of lysophosphatidic acid-induced neurite retraction and cell rounding by SR 57746A.

    Science.gov (United States)

    Magazin, M; Schiltz, P; Zachayus, J L; Cavrois, E; Caput, D; Ferrara, P

    1998-01-01

    Rapid neurite retraction and transient rounding of serum-starved NG108-15 and PC12 cells by lysophosphatidic acid (LPA) is retarded and reduced by pre-incubation of the cells with the small non-peptidic molecule, SR 57746A, which exhibits neurotrophic properties. The compound also antagonizes the redistribution of filamentous actin by LPA in both cell types. We hypothesize that the SR 57746A attenuation of LPA-induced effects may account for at least some of the neuroprotective properties of this molecule.

  10. Wave length dependence of photomorphogenesis in plants

    NARCIS (Netherlands)

    Stolwijk, J.A.J.

    1954-01-01

    Light of various spectral regions (at low or high intensities) supplemented a short day (SD) in white light, or was used alone at high intensity. Two types of relation of wave length to photoperiodic reaction were found: Crucifers were sensitive to blue and infrared (even SD exposure promoted

  11. Stimulation of myenteric plexus neurite outgrowth by insulin and insulin-like growth factors I and II.

    Science.gov (United States)

    Mulholland, M W; Romanchuk, G; Simeone, D M; Flowe, K

    1992-01-01

    A defined culture medium containing insulin, insulin-like growth factor I (IGF-I) or insulin-like growth factor II (IGF-II) supported morphological development of myenteric plexus neurons derived from neonatal guinea pigs. Insulin increased neurite outgrowth 3-fold at concentrations as low as 0.2 nM. Similar significant and dose-dependent increases in neurite outgrowth were noted with IGF-I and IGF-II. Stimulation of neurite outgrowth was abolished by exposure to cytosine arabinofuranoside, an agent toxic to non-neuronal cells, implying that trophic effects of insulin or insulin-like growth factors require the presence of non-neuronal elements in culture.

  12. Phosphatidylinositol 4-phosphate 5-kinase α negatively regulates nerve growth factor-induced neurite outgrowth in PC12 cells.

    Science.gov (United States)

    Liu, Tian; Lee, Sang Yoon

    2013-03-29

    Neurite outgrowth, a cell differentiation process involving membrane morphological changes, is critical for neuronal network and development. The membrane lipid, phosphatidylinositol (PI) 4,5-bisphosphate (PIP2), is a key regulator of many important cell surface events of membrane signaling, trafficking and dynamics. This lipid is produced mainly by the type I PI 4-phosphate 5-kinase (PIP5K) family members. In this study, we addressed whether PIP5Kα, an isoform of PIP5K, could have a role in neurite outgrowth induced by nerve growth factor (NGF). For this purpose, we knocked down PIP5Kα in PC12 rat pheochromocytoma cells by stable expression of PIP5Kα microRNA that significantly reduced PIP5Kα expression and PIP2 level. Interestingly, NGF-induced neurite outgrowth was more prominent in PIP5Kα-knockdown (KD) cells than in control cells. Conversely, add-back of PIP5Kα into PIP5Kα KD cells abrogated the effect of NGF on neurite outgrowth. NGF treatment activated PI 3-kinase (PI3K)/Akt pathway, which seemed to be associated with reactive oxygen species generation. Similar to the changes in neurite outgrowth, the PI3K/Akt activation by NGF was potentiated by PIP5Kα KD, but was attenuated by the reintroduction of PIP5Kα. Moreover, exogenously applied PIP2 to PIP5Kα KD cells also suppressed Akt activation by NGF. Together, our results suggest that PIP5Kα acts as a negative regulator of NGF-induced neurite outgrowth by inhibiting PI3K/Akt signaling pathway in PC12 cells.

  13. 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.

  14. Orexin A Inhibits Propofol-Induced Neurite Retraction by a Phospholipase D/Protein Kinase Cε-Dependent Mechanism in Neurons

    Science.gov (United States)

    Björnström, Karin; Turina, Dean; Strid, Tobias; Sundqvist, Tommy; Eintrei, Christina

    2014-01-01

    Background The intravenous anaesthetic propofol retracts neurites and reverses the transport of vesicles in rat cortical neurons. Orexin A (OA) is an endogenous neuropeptide regulating wakefulness and may counterbalance anaesthesia. We aim to investigate if OA interacts with anaesthetics by inhibition of the propofol-induced neurite retraction. Methods In primary cortical cell cultures from newborn rats’ brains, live cell light microscopy was used to measure neurite retraction after propofol (2 µM) treatment with or without OA (10 nM) application. The intracellular signalling involved was tested using a protein kinase C (PKC) activator [phorbol 12-myristate 13-acetate (PMA)] and inhibitors of Rho-kinase (HA-1077), phospholipase D (PLD) [5-fluoro-2-indolyl des-chlorohalopemide (FIPI)], PKC (staurosporine), and a PKCε translocation inhibitor peptide. Changes in PKCε Ser729 phosphorylation were detected with Western blot. Results The neurite retraction induced by propofol is blocked by Rho-kinase and PMA. OA blocks neurite retraction induced by propofol, and this inhibitory effect could be prevented by FIPI, staurosporine and PKCε translocation inhibitor peptide. OA increases via PLD and propofol decreases PKCε Ser729 phosphorylation, a crucial step in the activation of PKCε. Conclusions Rho-kinase is essential for propofol-induced neurite retraction in cortical neuronal cells. Activation of PKC inhibits neurite retraction caused by propofol. OA blocks propofol-induced neurite retraction by a PLD/PKCε-mediated pathway, and PKCε maybe the key enzyme where the wakefulness and anaesthesia signal pathways converge. PMID:24828410

  15. Oligomerization of ZFYVE27 (Protrudin is necessary to promote neurite extension.

    Directory of Open Access Journals (Sweden)

    D V Krishna Pantakani

    Full Text Available ZFYVE27 (Protrudin was originally identified as an interacting partner of spastin, which is most frequently mutated in hereditary spastic paraplegia. ZFYVE27 is a novel member of FYVE family, which is implicated in the formation of neurite extensions by promoting directional membrane trafficking in neurons. Now, through a yeast two-hybrid screen, we have identified that ZFYVE27 interacts with itself and the core interaction region resides within the third hydrophobic region (HR3 of the protein. We confirmed the ZFYVE27's self-interaction in the mammalian cells by co-immunoprecipitation and co-localization studies. To decipher the oligomeric nature of ZFYVE27, we performed sucrose gradient centrifugation and showed that ZFYVE27 oligomerizes into dimer/tetramer forms. Sub-cellular fractionation and Triton X-114 membrane phase separation analysis indicated that ZFYVE27 is a peripheral membrane protein. Furthermore, ZFYVE27 also binds to phosphatidylinositol 3-phosphate lipid moiety. Interestingly, cells expressing ZFYVE27(ΔHR3 failed to produce protrusions instead caused swelling of cell soma. When ZFYVE27(ΔHR3 was co-expressed with wild-type ZFYVE27 (ZFYVE27(WT, it exerted a dominant negative effect on ZFYVE27(WT as the cells co-expressing both proteins were also unable to induce protrusions and showed cytoplasmic swelling. Altogether, it is evident that a functionally active form of oligomer is crucial for ZFYVE27 ability to promote neurite extensions.

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

    Science.gov (United States)

    Lee, Jong Ho; Kang, Seok Hee; Hwang, Eun Young; Hwang, Yu-Shik; Lee, Mi Hee; Park, Jong-Chul

    2014-01-01

    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. PMID:24592382

  17. Neuroprotective and neuroregenerative effects of nimodipine in a model system of neuronal differentiation and neurite outgrowth.

    Science.gov (United States)

    Bork, Kaya; Wurm, Franziska; Haller, Hannes; Strauss, Christian; Scheller, Christian; Gnanapragassam, Vinayaga S; Horstkorte, Rüdiger

    2015-01-09

    Nimodipine is a Ca2+-channel antagonist mainly used for the management of aneurysmal subarachnoid hemorrhage (aSAH) to prevent cerebral vasospasms. However, it is not clear if the better outcome of nimodipine-treated patients is mainly due to vasodilatation or whether other cellular neuroprotective or neuregenerative effects of nimodipine are involved. We analysed PC12 cells after different stress stimuli with or without nimodipine pretreatment. Cytotoxicity of 200 mM EtOH and osmotic stress (450 mosmol/L) was significantly reduced with nimodipine pretreatment, while nimodipine has no influence on the hypoxia-induced cytotoxicity in PC12 cells. The presence of nimodipine also increased the NGF-induced neurite outgrowth in PC12 cells. However, nimodipine alone was not able to induce neurite outgrowth in PC12 cells. These results support the idea that nimodipine has general neuroprotective or neuregenerative effect beside its role in vasodilatation and is maybe useful also in other clinical applications beside aSAH.

  18. Neuroprotective and Neuroregenerative Effects of Nimodipine in a Model System of Neuronal Differentiation and Neurite Outgrowth

    Directory of Open Access Journals (Sweden)

    Kaya Bork

    2015-01-01

    Full Text Available Nimodipine is a Ca2+-channel antagonist mainly used for the management of aneurysmal subarachnoid hemorrhage (aSAH to prevent cerebral vasospasms. However, it is not clear if the better outcome of nimodipine-treated patients is mainly due to vasodilatation or whether other cellular neuroprotective or neuregenerative effects of nimodipine are involved. We analysed PC12 cells after different stress stimuli with or without nimodipine pretreatment. Cytotoxicity of 200 mM EtOH and osmotic stress (450 mosmol/L was significantly reduced with nimodipine pretreatment, while nimodipine has no influence on the hypoxia-induced cytotoxicity in PC12 cells. The presence of nimodipine also increased the NGF-induced neurite outgrowth in PC12 cells. However, nimodipine alone was not able to induce neurite outgrowth in PC12 cells. These results support the idea that nimodipine has general neuroprotective or neuregenerative effect beside its role in vasodilatation and is maybe useful also in other clinical applications beside aSAH.

  19. Study of laser uncaging induced morphological alteration of rat cortical neurites using atomic force microscopy.

    Science.gov (United States)

    Tian, Jian; Tu, Chunlong; Liang, Yitao; Zhou, Jian; Ye, Xuesong

    2015-09-30

    Activity-dependent structural remodeling is an important aspect of neuronal plasticity. In the previous researches, neuronal structure variations resulting from external interventions were detected by the imaging instruments such as the fluorescence microscopy, the scanning/transmission electron microscopy (SEM/TEM) and the laser confocal microscopy. In this article, a new platform which combined the photochemical stimulation with atomic force microscopy (AFM) was set up to detect the activity-dependent structural remodeling. In the experiments, the cortical neurites on the glass coverslips were stimulated by locally uncaged glutamate under the ultraviolet (UV) laser pulses, and a calcium-related structural collapse of neurites (about 250 nm height decrease) was observed by an AFM. This was the first attempt to combine the laser uncaging with AFM in living cell researches. With the advantages of highly localized stimulation (<5 μm), super resolution imaging (<3.8 nm), and convenient platform building, this system was suitable for the quantitative observation of the neuron mechanical property variations and morphological alterations modified by neural activities under different photochemical stimulations, which would be helpful for studying physiological and pathological mechanisms of structural and functional changes induced by the biomolecule acting. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. 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.

  1. Atlastin regulates store-operated calcium entry for nerve growth factor-induced neurite outgrowth.

    Science.gov (United States)

    Li, Jing; Yan, Bing; Si, Hongjiang; Peng, Xu; Zhang, Shenyuan L; Hu, Junjie

    2017-02-27

    Homotypic membrane fusion of the endoplasmic reticulum (ER) is mediated by a class of dynamin-like GTPases known as atlastin (ATL). Depletion of or mutations in ATL cause an unbranched ER morphology and hereditary spastic paraplegia (HSP), a neurodegenerative disease characterized by axon shortening in corticospinal motor neurons and progressive spasticity of the lower limbs. How ER shaping is linked to neuronal defects is poorly understood. Here, we show that dominant-negative mutants of ATL1 in PC-12 cells inhibit nerve growth factor (NGF)-induced neurite outgrowth. Overexpression of wild-type or mutant ATL1 or depletion of ATLs alters ER morphology and affects store-operated calcium entry (SOCE) by decreasing STIM1 puncta formation near the plasma membrane upon calcium depletion of the ER. In addition, blockage of the STIM1-Orai pathway effectively abolishes neurite outgrowth of PC-12 cells stimulated by NGF. These results suggest that SOCE plays an important role in neuronal regeneration, and mutations in ATL1 may cause HSP, partly by undermining SOCE.

  2. Nerve growth factor-immobilized polypyrrole: Bioactive electrically conducting polymer for enhanced neurite extension

    Science.gov (United States)

    Gomez, Natalia; Schmidt, Christine E.

    2010-01-01

    Biomaterials that present multiple stimuli are attractive for a number of biomedical applications. In particular, electrical and biological cues are important factors to include in interfaces with neurons for applications such as nerve conduits and neural probes. Here, we report the combination of these two stimuli, by immobilizing nerve growth factor (NGF) on the surface of the electrically conducting polymer polypyrrole (PPy). NGF was immobilized using an intermediate linker provided by a layer of polyallylamine conjugated to an arylazido functional group. Upon exposure to UV light and activation of the azido groups, NGF was fixed to the substrate. Three different surface concentrations were obtained (0.21–0.98 ng/mm2) and similar levels of neurite extension were observed on immobilized NGF as with soluble NGF. Additionally, electrical stimulation experiments were conducted with the modified polymer and revealed a 50% increase in neurite outgrowth in PC12 cells compared to experiments without electrical stimulation. This novel modification of PPy provides both electrical and biological stimulation, by presenting tethered growth factors and only producing a small decrease in the material's properties (conductivity ~10 S cm−1) when compared to other modification techniques (conductivity ~10−3–10−6 S cm−1. PMID:17111407

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

    Science.gov (United States)

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

    2011-06-27

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

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

    Science.gov (United States)

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

    2011-01-01

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

  5. A Wnt-planar polarity pathway instructs neurite branching by restricting F-actin assembly through endosomal signaling

    Science.gov (United States)

    Chen, Chun-Hao; Liao, Chien-Po

    2017-01-01

    Spatial arrangement of neurite branching is instructed by both attractive and repulsive cues. Here we show that in C. elegans, the Wnt family of secreted glycoproteins specify neurite branching sites in the PLM mechanosensory neurons. Wnts function through MIG-1/Frizzled and the planar cell polarity protein (PCP) VANG-1/Strabismus/Vangl2 to restrict the formation of F-actin patches, which mark branching sites in nascent neurites. We find that VANG-1 promotes Wnt signaling by facilitating Frizzled endocytosis and genetically acts in a common pathway with arr-1/β-arrestin, whose mutation results in defective PLM branching and F-actin patterns similar to those in the Wnt, mig-1 or vang-1 mutants. On the other hand, the UNC-6/Netrin pathway intersects orthogonally with Wnt-PCP signaling to guide PLM branch growth along the dorsal-ventral axis. Our study provides insights for how attractive and repulsive signals coordinate to sculpt neurite branching patterns, which are critical for circuit connectivity. PMID:28384160

  6. MAGNETIC FIELD INFLUENCE ON NGF-STIMULATED NEURITE OUTGROWTH IN PC-12 CELLS: EFFECT OF PAINT FUMES

    Science.gov (United States)

    MAGNETIC FIELD INFLUENCE ON NGF-STIMULATED NEURITE OUTGROWTH IN PC-12 CELLS: EFFECT OF PAINT FUMES. C. F. Blackman1, D. E. House2*, S. G. Benane3*, A. Ubeda4, M.A. TrilIo4. 1 National Health and Environmental Effects Research Laboratory, EPA,Research Triangle Park, North Caro...

  7. Ultrafast optical recording reveals distinct capsaicin-induced ion dynamics along single nociceptive neurite terminals in vitro

    Science.gov (United States)

    Goldstein, Robert H.; Katz, Ben; Lev, Shaya; Binshtok, Alexander M.

    2017-07-01

    Pain signals are detected by terminals of nociceptive peripheral fibers situated among the keratinocytes and epithelial cells. Despite being key structures for pain-related stimuli detection and transmission, little is known about the functional organization of terminals. This is mainly due to their minute size, rendering them largely inaccessible by conventional experimental approaches. Here, we report the implementation of an ultrafast optical recording approach for studying cultured neurite terminals, which are readily accessible for assay manipulations. Using this approach, we were able to study capsaicin-induced calcium and sodium dynamics in the nociceptive processes, at a near-action potential time resolution. The approach was sensitive enough to detect differences in latency, time-to-peak, and amplitude of capsaicin-induced ion transients along the terminal neurites. Using this approach, we found that capsaicin evokes distinctive calcium signals along the neurite. At the terminal, the signal was insensitive to voltage-gated sodium channel blockers, and showed slower kinetics and smaller signal amplitudes, compared with signals that were measured further up the neurite. These latter signals were mainly abolished by sodium channel blockers. We propose this ultrafast optical recording approach as a model for studying peripheral terminal signaling, forming a basis for studying pain mechanisms in normal and pathological states.

  8. 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

    The neural cell adhesion molecule NCAM is involved in axonal outgrowth and target recognition in the developing nervous system. In vitro, NCAM-NCAM binding has been shown to induce neurite outgrowth, presumably through an activation of fibroblast growth factor receptors (FGFRs). We have recently...

  9. Neurite Mistargeting and Inverse Order of Intraretinal Vascular Plexus Formation Precede Subretinal Vascularization in Vldlr Mutant Mice.

    Directory of Open Access Journals (Sweden)

    Verity Johnson

    Full Text Available In the retina blood vessels are required to support a high metabolic rate, however, uncontrolled vascular growth can lead to impaired vision and blindness. Subretinal vascularization (SRV, one type of pathological vessel growth, occurs in retinal angiomatous proliferation and proliferative macular telangiectasia. In these diseases SRV originates from blood vessels within the retina. We use mice with a targeted disruption in the Vldl-receptor (Vldlr gene as a model to study SRV with retinal origin. We find that Vldlr mRNA is strongly expressed in the neuroretina, and we observe both vascular and neuronal phenotypes in Vldlr-/- mice. Unexpectedly, horizontal cell (HC neurites are mistargeted prior to SRV in this model, and the majority of vascular lesions are associated with mistargeted neurites. In Foxn4-/- mice, which lack HCs and display reduced amacrine cell (AC numbers, we find severe defects in intraretinal capillary development. However, SRV is not suppressed in Foxn4-/-;Vldlr-/- mice, which reveals that mistargeted HC neurites are not required for vascular lesion formation. In the absence of VLDLR, the intraretinal capillary plexuses form in an inverse order compared to normal development, and subsequent to this early defect, vascular proliferation is increased. We conclude that SRV in the Vldlr-/- model is associated with mistargeted neurites and that SRV is preceded by altered retinal vascular development.

  10. Manipulation of gene expression in the mammalian nervous system: application in the study of neurite outgrowth and neuroregeneration related proteins

    NARCIS (Netherlands)

    Gispen, W.H.; Holtmaat, A.J.G.D.; Oestreicher, A.B.; Verhaagen, J.

    1998-01-01

    A fundamental issue in neurobiology entails the study of the formation of neuronal connections and their potential to regenerate following injury. In recent years, an expanding number of gene families has been identified involved in different aspects of neurite outgrowth and regeneration. These

  11. Atopic keratinocytes induce increased neurite outgrowth in a coculture model of porcine dorsal root ganglia neurons and human skin cells.

    Science.gov (United States)

    Roggenkamp, Dennis; Falkner, Susanne; Stäb, Franz; Petersen, Marlen; Schmelz, Martin; Neufang, Gitta

    2012-07-01

    Skin of patients suffering from atopic eczema displays a higher epidermal nerve fiber density, associated with neurogenic inflammation and pruritus. Using an in vitro coculture system, allowing a spatially compartmented culture of somata from porcine dorsal root ganglion neurons and human primary skin cells, we investigated the influence of dermal fibroblasts and keratinocytes on neurite outgrowth. In comparison with dermal fibroblasts, keratinocytes induced more branched and less calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibers. By adding neutralizing antibodies, we showed that nerve growth factor (NGF) and glial cell-line-derived neurotrophic factor (GDNF) are pivotal neurotrophic factors of skin cell-induced neurite outgrowth. Keratinocytes and dermal fibroblasts secreted different ratios of neurotrophic factors, influencing morphology and CGRP immunoreactivity of neurites. To investigate changes of the peripheral nervous system in the pathogenesis of atopic eczema in vitro, we analyzed neurite outgrowth mediated by atopic skin cells. Atopic keratinocytes produced elevated levels of NGF and mediated an increased outgrowth of CGRP-positive sensory fibers. Our results demonstrate the impact of dermal fibroblasts and keratinocytes on skin innervation and emphasize the role of keratinocytes as key players of hyperinnervation in atopic eczema.

  12. Turning Death to Growth: Hematopoietic Growth Factors Promote Neurite Outgrowth through MEK/ERK/p53 Pathway.

    Science.gov (United States)

    Gao, Mei; Zhao, Li-Ru

    2017-11-08

    Stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) are the essential hematopoietic growth factors to control hematopoiesis. However, the role of SCF and G-CSF in the central nervous system remains poorly understood. Here, we have demonstrated the involvement of MEK/ERK/p53 signaling in SCF + G-CSF-enhanced neurite extension. Cortical neurons dissected from embryonic rat brains were seeded onto the membranes of transwell inserts, and neurite outgrowth was determined by using both the neurite outgrowth quantification assay kit and immunostaining of β III tubulin. Quantitative RT-PCR and western blotting were used for determining gene and protein expression of ERK and p53, respectively. p53 small interfering RNA (siRNAs) were introduced into neurons for examining the involvement of p53 in SCF + G-CSF-mediated neurite outgrowth. We observed that both SCF and G-CSF alone increased activation of MEK/ERK and gene expression of p53, while SCF + G-CSF synergistically activated the MEK/ERK signaling and upregulated p53 expression. MEK specific inhibitors (PD98059 and U0126) blocked the SCF + G-CSF-increased ERK phosphorylation and p53 gene and protein expression, and the MEK specific inhibitors also eliminated the SCF + G-CSF-promoted neurite outgrowth. p53 siRNAs knocked down the SCF + G-CSF-elevated p53 protein and prevented the SCF + G-CSF-enhanced neurite outgrowth. These findings suggest that activation of MEK/ERK/p53 signaling is required for SCF + G-CSF-promoted neurite outgrowth. Through the pro-apoptotic pathway of the MEK/ERK/p53, SCF + G-CSF turns neuronal fate from apoptotic commitment toward neural network generation. This observation provides novel insights into the putative role of SCF + G-CSF in supporting generation of neural connectivity during CNS development and in brain repair under pathological or neurodegenerative conditions.

  13. 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

  14. Interaction of new antidepressants with sigma-1 receptor chaperones and their potentiation of neurite outgrowth in PC12 cells.

    Science.gov (United States)

    Ishima, Tamaki; Fujita, Yuko; Hashimoto, Kenji

    2014-03-15

    The sigma-1 receptor chaperone located in the endoplasmic reticulum (ER) may be implicated in the mechanistic action of some antidepressants. The present study was undertaken to examine whether new antidepressant drugs interact with the sigma-1 receptor chaperone. First, we examined the effects of selective serotonin reuptake inhibitors (SSRIs) (fluvoxamine, paroxetine, sertraline, citalopram and escitalopram), serotonin and noradrenaline reuptake inhibitors (SNRIs) (duloxetine, venlafaxine, milnacipran), and mirtazapine, a noradrenaline and specific serotonergic antidepressant (NaSSA), on [(3)H](+)-pentazocine binding to rat brain membranes. Then, we examined the effects of these drugs on nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. The order of potency for drugs at the sigma-1 receptor chaperone was as follows: fluvoxamine>sertraline>fluoxetine>escitalopram>citalopram>paroxetine>duoxetine. Venlafaxine, milnacipran, and mirtazapine showed very weak affinity for this chaperone. Furthermore, fluvoxamine, fluoxetine, escitalopram, and mirtazapine significantly potentiated NGF-induced neurite outgrowth in cell assays, and the effects of all these drugs, excluding mirtazapine, were antagonized by NE-100, a selective antagonist of the sigma-1 receptor chaperone. Moreover, the effects of fluvoxamine and fluoxetine on neurite outgrowth were also antagonized by sertraline, indicating that sertraline may be an antagonist at the sigma-1 receptor chaperone. The effect of mirtazapine on neurite outgrowth was antagonized by the selective 5-hydroxytryptamine1A receptor antagonist WAY-100635. These findings suggest that activation at the sigma-1 receptor chaperone may be involved in the action of some SSRIs, such as fluvoxamine, fluoxetine and escitalopram. In contrast, mirtazapine independently potentiated neurite outgrowth in PC12 cells, indicating that this beneficial effect may mediate its pharmacological effect. Copyright © 2014 Elsevier B.V. All

  15. Lysophosphatidylinositol causes neurite retraction via GPR55, G13 and RhoA in PC12 cells.

    Directory of Open Access Journals (Sweden)

    Yutaro Obara

    Full Text Available GPR55 was recently identified as a putative receptor for certain cannabinoids, and lysophosphatidylinositol (LPI. Recently, the role of cannabinoids as GPR55 agonists has been disputed by a number of reports, in part, because studies investigating GPR55 often utilized overexpression systems, such as the GPR55-overexpressing HEK293 cells, which make it difficult to deduce the physiological role of endogenous GPR55. In the present study, we found that PC12 cells, a neural model cell line, express endogenous GPR55, and by using these cells, we were able to examine the role of endogenous GPR55. Although GPR55 mRNA and protein were expressed in PC12 cells, neither CB(1 nor CB(2 mRNA was expressed in these cells. GPR55 was predominantly localized on the plasma membrane in undifferentiated PC12 cells. However, GPR55 was also localized in the growth cones or the ruffled border in differentiated PC12 cells, suggesting a potential role for GPR55 in the regulation of neurite elongation. LPI increased intracellular Ca(2+ concentration and RhoA activity, and induced ERK1/2 phosphorylation, whereas endogenous and synthetic cannabinoids did not, thereby suggesting that cannabinoids are not GPR55 agonists. LPI also caused neurite retraction in a time-dependent manner accompanied by the loss of neurofilament light chain and redistribution of actin in PC12 cells differentiated by NGF. This LPI-induced neurite retraction was found to be G(q-independent and G(13-dependent. Furthermore, inactivation of RhoA function via C3 toxin and GPR55 siRNA knockdown prevented LPI-induced neurite retraction. These results suggest that LPI, and not cannabinoids, causes neurite retraction in differentiated PC12 cells via a GPR55, G(13 and RhoA signaling pathway.

  16. 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.

  17. Functional role of a specific ganglioside in neuronal migration and neurite outgrowth

    Directory of Open Access Journals (Sweden)

    Mendez-Otero R.

    2003-01-01

    Full Text Available Cell migration occurs extensively during mammalian brain development and persists in a few regions in the adult brain. Defective migratory behavior of neurons is thought to be the underlying cause of several congenital disorders. Knowledge of the dynamics and molecular mechanisms of neuronal movement could expand our understanding of the normal development of the nervous system as well as help decipher the pathogenesis of neurological developmental disorders. In our studies we have identified and characterized a specific ganglioside (9-O-acetyl GD3 localized to the membrane of neurons and glial cells that is expressed in regions of cell migration and neurite outgrowth in the developing and adult rat nervous system. In the present article we review our findings that demonstrate the functional role of this molecule in neuronal motility.

  18. Fundamental Elements in Autism: From Neurogenesis and Neurite Growth to Synaptic Plasticity

    Science.gov (United States)

    Gilbert, James; Man, Heng-Ye

    2017-01-01

    Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders with a high prevalence and impact on society. ASDs are characterized by deficits in both social behavior and cognitive function. There is a strong genetic basis underlying ASDs that is highly heterogeneous; however, multiple studies have highlighted the involvement of key processes, including neurogenesis, neurite growth, synaptogenesis and synaptic plasticity in the pathophysiology of neurodevelopmental disorders. In this review article, we focus on the major genes and signaling pathways implicated in ASD and discuss the cellular, molecular and functional studies that have shed light on common dysregulated pathways using in vitro, in vivo and human evidence. Highlights Autism spectrum disorder (ASD) has a prevalence of 1 in 68 children in the United States.ASDs are highly heterogeneous in their genetic basis.ASDs share common features at the cellular and molecular levels in the brain.Most ASD genes are implicated in neurogenesis, structural maturation, synaptogenesis and function. PMID:29209173

  19. Rit contributes to neurite outgrowth triggered by the alpha subunit of Go.

    Science.gov (United States)

    Kim, Seung Hyun; Kim, Soyeon; Ghil, Sung Ho

    2008-03-26

    Heterotrimeric GTP-binding protein transduce signals initiated by a variety of hormones and neurotransmitters. Go, a member of the Go/Gi family, is the most abundant heterotrimeric GTP-binding protein in nervous tissues and has been implicated in neuronal differentiation. The mechanism by which Go modulates neuronal differentiation has not been, however, fully elucidated. Here, we identified small GTPase Rit as an interacting partner of the alpha-subunit of Go (Goalpha). The biochemical characterizations of Goalpha::Rit interaction revealed that Rit is a candidate downstream effector for Goalpha. Furthermore, dominant negative Rit inhibited Goalpha-induced neurite outgrowth and Erk phosphorylation in Neuro2a cells. These results suggest that Rit may be involved in the signaling pathway for Goalpha-mediated neuronal differentiation.

  20. 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

  1. The effects of microenvironment on the redifferentiation of regenerating neurones: neurite architecture, acetylcholine receptors and Ca2+ channel distribution.

    Science.gov (United States)

    Spira, M E; Zeldes, D; Hochner, B; Dormann, A

    1987-09-01

    Severed adult neurones, which are capable of regrowth, encounter different microenvironments from those encountered during development. Moreover, adult neurones may respond in a different manner from developing neurones to the same environmental cues. Thus, the recovery of the integrative and transmission capabilities (which depend on the neuronal architecture, passive and active membrane properties, and synaptic receptor distribution) by a regenerating adult neurone may not be complete. In the present review, we examine several aspects of the outcome of the interaction between the microenvironment and regrowing neurones using the cockroach giant interneurones (GINs) as a model system. We demonstrate that whereas extrinsic cues govern the morphological redifferentiation and distribution of synaptic receptors, the distribution of voltage-dependent Ca2+ channels is to a large extent determined by intrinsic factors. The pathway of regrowth and the architecture of regenerating GINs were studied by examination of intracellularly stained fibres. The environments provided by the connectives and ganglia are different. The elongating sprouts in the connective appeared as smooth cylinders. Within the ganglionic domain, the main longitudinal sprouts emitted neurites which extended and branched into the neuropile. The local cues for branching of neurites were eliminated by freezing and thawing of the ganglia prior to the arrival of the growing tips. The failure to extend neurites under these conditions is attributed to the elimination of extrinsic signals for morphological redifferentiation of the fibres, since the same fibres emit neurites in anterior ganglia which have not been subjected to freezing and thawing. The distribution of acetylcholine receptors (AChRs) on the GINs was mapped by ionophoretic application of ACh. In both the intact and regenerating GINs receptors were located only on the neurites. Freezing and thawing of a ganglion eliminated the local signals for

  2. Icariin improves memory impairment in Alzheimer's disease model mice (5xFAD) and attenuates amyloid β-induced neurite atrophy.

    Science.gov (United States)

    Urano, Takuya; Tohda, Chihiro

    2010-11-01

    Essential therapeutic drugs for Alzheimer's disease (AD) have not been developed. Since the neuritic atrophy leading to synaptic losses is one of the critical causes of memory impairment in AD, the effects of several constituents in tonic herbal medicines on neuritic atrophy and memory deficits have been studied. The present study investigated the effects of icariin, a main constituent in Epimedii Herba, a well known tonic crude drug, in an in vitro AD model and transgenic mouse AD model (5xFAD). Amyloid β(1-42)-induced atrophies of axons and dendrites were restored by post-treatment with icariin in rat cortical neurons. Administration of icariin for 8 days (p.o.) improved spatial memory impairment in 5xFAD mice. These novel findings suggest that icariin may improve memory dysfunction in AD and have a potential to extend neurites even when amyloid β-induced neurite atrophy has already occurred. Copyright © 2010 John Wiley & Sons, Ltd.

  3. Myelin-associated Glycoprotein Interacts with Neurons via a Sialic Acid Binding Site at ARG118 and a Distinct Neurite Inhibition Site

    OpenAIRE

    Tang, Song; Shen, Ying Jing; DeBellard, Maria Elena; Mukhopadhyay, Gitali; Salzer, James L.; Crocker, Paul R.; Filbin, Marie T.

    1997-01-01

    Inhibitory components in myelin are largely responsible for the lack of regeneration in the mammalian CNS. Myelin-associated glycoprotein (MAG), a sialic acid binding protein and a component of myelin, is a potent inhibitor of neurite outgrowth from a variety of neurons both in vitro and in vivo. Here, we show that MAG's sialic acid binding site is distinct from its neurite inhibitory activity. Alone, sialic acid–dependent binding of MAG to neurons is insufficient to effect inhibition of axon...

  4. 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 (...

  5. 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

    and ENFIN11) were confirmed to bind to F3I-F3II of NCAM by surface plasmon resonance. The peptides induced neurite outgrowth in primary cerebellar neurons and PC12E2 cells, but had no apparent neuroprotective properties. NCAM is known to activate different intracellular pathways, including signaling through......A combinatorial library of undecapeptides was produced and utilized for the isolation of peptide binding to the fibronectin type 3 modules (F3I-F3II) of the neural cell adhesion molecule (NCAM). The isolated peptides were sequenced and produced as dendrimers. Two of the peptides (denoted ENFIN2...... 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...

  6. Morphine enhances HIV-1SF162-mediated neuron death and delays recovery of injured neurites.

    Science.gov (United States)

    Masvekar, Ruturaj R; El-Hage, Nazira; Hauser, Kurt F; Knapp, Pamela E

    2014-01-01

    HIV-1 enters the CNS soon after initial systemic infection; within the CNS parenchyma infected and/or activated perivascular macrophages, microglia and astrocytes release viral and cellular toxins that drive secondary toxicity in neurons and other cell types. Our previous work has largely modeled HIV-neuropathology using the individual viral proteins Tat or gp120, with murine striatal neurons as targets. To model disease processes more closely, the current study uses supernatant from HIV-1-infected cells. Supernatant from HIV-1SF162-infected differentiated-U937 cells (HIV+sup) was collected and p24 level was measured by ELISA to assess the infection. Injection drug abuse is a significant risk factor for HIV-infection, and opiate drug abusers show increased HIV-neuropathology, even with anti-retroviral treatments. We therefore assessed HIV+sup effects on neuronal survival and neurite growth/pruning with or without concurrent exposure to morphine, an opiate that preferentially acts through µ-opioid receptors. Effects of HIV+sup ± morphine were assessed on neuronal populations, and also by time-lapse imaging of individual cells. HIV+sup caused dose-dependent toxicity over a range of p24 levels (10-500 pg/ml). Significant interactions occurred with morphine at lower p24 levels (10 and 25 pg/ml), and GSK3β was implicated as a point of convergence. In the presence of glia, selective neurotoxic measures were significantly enhanced and interactions with morphine were also augmented, perhaps related to a decreased level of BDNF. Importantly, the arrest of neurite growth that occurred with exposure to HIV+sup was reversible unless neurons were continuously exposed to morphine. Thus, while reducing HIV-infection levels may be protective, ongoing exposure to opiates may limit recovery. Opiate interactions observed in this HIV-infective environment were similar, though not entirely concordant, with Tat/gp120 interactions reported previously, suggesting unique interactions

  7. Morphine enhances HIV-1SF162-mediated neuron death and delays recovery of injured neurites.

    Directory of Open Access Journals (Sweden)

    Ruturaj R Masvekar

    Full Text Available HIV-1 enters the CNS soon after initial systemic infection; within the CNS parenchyma infected and/or activated perivascular macrophages, microglia and astrocytes release viral and cellular toxins that drive secondary toxicity in neurons and other cell types. Our previous work has largely modeled HIV-neuropathology using the individual viral proteins Tat or gp120, with murine striatal neurons as targets. To model disease processes more closely, the current study uses supernatant from HIV-1-infected cells. Supernatant from HIV-1SF162-infected differentiated-U937 cells (HIV+sup was collected and p24 level was measured by ELISA to assess the infection. Injection drug abuse is a significant risk factor for HIV-infection, and opiate drug abusers show increased HIV-neuropathology, even with anti-retroviral treatments. We therefore assessed HIV+sup effects on neuronal survival and neurite growth/pruning with or without concurrent exposure to morphine, an opiate that preferentially acts through µ-opioid receptors. Effects of HIV+sup ± morphine were assessed on neuronal populations, and also by time-lapse imaging of individual cells. HIV+sup caused dose-dependent toxicity over a range of p24 levels (10-500 pg/ml. Significant interactions occurred with morphine at lower p24 levels (10 and 25 pg/ml, and GSK3β was implicated as a point of convergence. In the presence of glia, selective neurotoxic measures were significantly enhanced and interactions with morphine were also augmented, perhaps related to a decreased level of BDNF. Importantly, the arrest of neurite growth that occurred with exposure to HIV+sup was reversible unless neurons were continuously exposed to morphine. Thus, while reducing HIV-infection levels may be protective, ongoing exposure to opiates may limit recovery. Opiate interactions observed in this HIV-infective environment were similar, though not entirely concordant, with Tat/gp120 interactions reported previously, suggesting

  8. The effect of gallium nitride on long-term culture induced aging of neuritic function in cerebellar granule cells.

    Science.gov (United States)

    Chen, Chi-Ruei; Young, Tai-Horng

    2008-04-01

    Gallium nitride (GaN) has been developed for a variety of microelectronic and optical applications due to its unique electric property and chemical stability. In the present study, n-type and p-type GaN were used as substrates to culture cerebellar granule neurons to examine the effect of GaN on cell response for a long-term culture period. It was found that GaN could rapidly induce cultured neurons to exhibit a high phosphorylated Akt level after 20h of incubation. It was assumed that the anti-apoptotic effect of Akt phosphorylation could be correlated with cell survival, neurite growth and neuronal function for up to 35 days of incubation. Morphological studies showed GaN induced larger neuronal aggregates and neurite fasciculation to exhibit a dense fiber network after 8 days of incubation. Western blot analysis and immunocytochemical characterization showed that GaN still exhibited the expression of neurite growth and function, such as high levels of GAP-43, synapsin I and synaptophysin even after 35 days of incubation. In addition, survival of cerebellar granule neurons on GaN was improved by the analysis of lactate dehydrogenase (LDH) release from damaged cells. These results indicated that neuronal connections were formed on GaN by a gradual process from Akt activation and cell aggregation to develop neurite growth, fasciculation and function. Therefore, GaN offers a good model system to identify a well-characterized pattern of neuronal behavior for a long-term culture period, consistent with the development of a neurochip requiring the integration of biological system and semiconductor material.

  9. 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.

  10. Non-obese diabetic mice rapidly develop dramatic sympathetic neuritic dystrophy: a new experimental model of diabetic autonomic neuropathy.

    Science.gov (United States)

    Schmidt, Robert E; Dorsey, Denise A; Beaudet, Lucie N; Frederick, Kathy E; Parvin, Curtis A; Plurad, Santiago B; Levisetti, Matteo G

    2003-11-01

    To address the pathogenesis of diabetic autonomic neuropathy, we have examined the sympathetic nervous system in non-obese diabetic (NOD) and streptozotocin (STZ)-induced diabetic mice, two models of type 1 diabetes, and the db/db mouse, a model of type 2 diabetes. After only 3 to 5 weeks of diabetes, NOD mice developed markedly swollen axons and dendrites ("neuritic dystrophy") in the prevertebral superior mesenteric and celiac ganglia (SMG-CG), similar to the pathology described in diabetic STZ- and BBW-rat and man. Comparable changes failed to develop in the superior cervical ganglia of the NOD mouse or in the SMG-CG of non-diabetic NOD siblings. STZ-induced diabetic mice develop identical changes, although at a much slower pace and to a lesser degree than NOD mice. NOD-SCID mice, which are genetically identical to NOD mice except for the absence of T and B cells, do not develop diabetes or neuropathology comparable to diabetic NOD mice. However, STZ-treated NOD-SCID mice develop severe neuritic dystrophy, evidence against an exclusively autoimmune pathogenesis for autonomic neuropathy in this model. Chronically diabetic type 2 db/db mice fail to develop neuritic dystrophy, suggesting that hyperglycemia alone may not be the critical and sufficient element. The NOD mouse appears to be a valuable model of diabetic sympathetic autonomic neuropathy with unambiguous, rapidly developing neuropathology which corresponds closely to the characteristic pathology of other rodent models and man.

  11. Protective Effects of Rosa damascena and Its Active Constituent on Aβ(25–35-Induced Neuritic Atrophy

    Directory of Open Access Journals (Sweden)

    Suresh Awale

    2011-01-01

    Full Text Available Dementia is a clinical syndrome characterized by multiple cognitive deficits and causes progressive neurodegeneration leading eventually to death. The incidence of dementia is increasing worldwide with the increase in ageing population. However, no effective treatment is available yet. It has been hypothesized that drugs activating neurite outgrowth might induce neuronal reconstruction and help in the recovery of brain function. Working on this hypothesis, we recently observed that the chloroform extract of the Rosa damascena significantly induced the neurite outgrowth activity and inhibited the Aβ(25–35-induced atrophy and cell death. Further workup led the isolation of a very long polyunsaturated fatty acid having molecular formula C37H64O2 as an active constituent. The structure of this compound was established by extensive analysis of fragmentations observed in EI-MS mode. The isolated compound protected Aβ(25–35-induced atrophy and displayed strong neurite outgrowth activity. The length of dendrite in the cells treated with this compound were comparable to those of nerve growth factor (NGF treated cells.

  12. Protective Effects of Rosa damascena and Its Active Constituent on Aβ(25-35)-Induced Neuritic Atrophy.

    Science.gov (United States)

    Awale, Suresh; Tohda, Chihiro; Tezuka, Yasuhiro; Miyazaki, Makoto; Kadota, Shigetoshi

    2011-01-01

    Dementia is a clinical syndrome characterized by multiple cognitive deficits and causes progressive neurodegeneration leading eventually to death. The incidence of dementia is increasing worldwide with the increase in ageing population. However, no effective treatment is available yet. It has been hypothesized that drugs activating neurite outgrowth might induce neuronal reconstruction and help in the recovery of brain function. Working on this hypothesis, we recently observed that the chloroform extract of the Rosa damascena significantly induced the neurite outgrowth activity and inhibited the Aβ(25-35)-induced atrophy and cell death. Further workup led the isolation of a very long polyunsaturated fatty acid having molecular formula C(37)H(64)O(2) as an active constituent. The structure of this compound was established by extensive analysis of fragmentations observed in EI-MS mode. The isolated compound protected Aβ(25-35)-induced atrophy and displayed strong neurite outgrowth activity. The length of dendrite in the cells treated with this compound were comparable to those of nerve growth factor (NGF) treated cells.

  13. Coseeded Schwann cells myelinate neurites from differentiated neural stem cells in neurotrophin-3-loaded PLGA carriers

    Science.gov (United States)

    Xiong, Yi; Zhu, Ji-Xiang; Fang, Zheng-Yu; Zeng, Cheng-Guang; Zhang, Chao; Qi, Guo-Long; Li, Man-Hui; Zhang, Wei; Quan, Da-Ping; Wan, Jun

    2012-01-01

    Biomaterials and neurotrophic factors represent promising guidance for neural repair. In this study, we combined poly-(lactic acid-co-glycolic acid) (PLGA) conduits and neurotrophin-3 (NT-3) to generate NT-3-loaded PLGA carriers in vitro. Bioactive NT-3 was released stably and constantly from PLGA conduits for up to 4 weeks. Neural stem cells (NSCs) and Schwann cells (SCs) were coseeded into an NT-releasing scaffold system and cultured for 14 days. Immunoreactivity against Map2 showed that most of the grafted cells (>80%) were differentiated toward neurons. Double-immunostaining for synaptogenesis and myelination revealed the formation of synaptic structures and myelin sheaths in the coculture, which was also observed under electron microscope. Furthermore, under depolarizing conditions, these synapses were excitable and capable of releasing synaptic vesicles labeled with FM1-43 or FM4-64. Taken together, coseeding NSCs and SCs into NT-3-loaded PLGA carriers increased the differentiation of NSCs into neurons, developed synaptic connections, exhibited synaptic activities, and myelination of neurites by the accompanying SCs. These results provide an experimental basis that supports transplantation of functional neural construction in spinal cord injury. PMID:22619535

  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. Synaptic profiles during neurite extension, refinement and retraction in the developing cochlea

    Directory of Open Access Journals (Sweden)

    Huang Lin-Chien

    2012-12-01

    Full Text Available Abstract Background During development, excess synapses form between the central and peripheral nervous systems that are then eliminated to achieve correct connectivity. In the peripheral auditory system, the developing type I spiral ganglion afferent fibres undergo a dramatic re-organisation, initially forming connections with both sensory inner hair cells (IHCs and outer hair cells (OHCs. The OHC connections are then selectively eliminated, leaving sparse innervation by type II afferent fibres, whilst the type I afferent synapses with IHCs are consolidated. Results We examined the molecular makeup of the synaptic contacts formed onto the IHCs and OHCs during this period of afferent fibre remodelling. We observed that presynaptic ribbons initially form at all the afferent neurite contacts, i.e. not only at the expected developing IHC-type I fibre synapses but also at OHCs where type I fibres temporarily contact. Moreover, the transient contacts forming onto OHCs possess a broad set of pre- and postsynaptic proteins, suggesting that functional synaptic connections are formed prior to the removal of type I fibre innervation. AMPA-type glutamate receptor subunits were transiently observed at the base of the OHCs, with their downregulation occurring in parallel with the withdrawal of type I fibres, dispersal of presynaptic ribbons, and downregulation of the anchoring proteins Bassoon and Shank. Conversely, at developing type I afferent IHC synapses, the presence of pre- and postsynaptic scaffold proteins was maintained, with differential plasticity in AMPA receptor subunits observed and AMPA receptor subunit composition changing around hearing onset. Conclusions Overall our data show a differential balance in the patterns of synaptic proteins at developing afferent IHC versus OHC synapses that likely reflect their stable versus transient fates.

  16. Restriction spectrum imaging reveals decreased neurite density in patients with temporal lobe epilepsy.

    Science.gov (United States)

    Loi, Richard Q; Leyden, Kelly M; Balachandra, Akshara; Uttarwar, Vedang; Hagler, Donald J; Paul, Brianna M; Dale, Anders M; White, Nathan S; McDonald, Carrie R

    2016-11-01

    Diffusion tensor imaging (DTI) has become a popular tool for delineating the location and extent of white matter injury in temporal lobe epilepsy (TLE). However, DTI yields nonspecific measures that are confounded by changes occurring within both the intracellular and extracellular environments. This study investigated whether an advanced diffusion method, restriction spectrum imaging (RSI) could provide a more robust measure of white matter injury in TLE relative to DTI due to RSI's ability to separate intraaxonal diffusion (i.e., neurite density; ND) from diffusion associated with extraaxonal factors (e.g., inflammation; crossing fibers). RSI and DTI scans were obtained on 21 patients with TLE and 11 age-matched controls. RSI-derived maps of ND, isotropic-hindered (IH) and isotropic-free (IF) water, and crossing fibers (CFs) were compared to DTI-derived fractional anisotropy (FA) maps. Voxelwise and tract-based analyses were performed comparing patients with TLE to controls on each diffusion metric. Reductions in FA were seen primarily in frontotemporal white matter in TLE, and they were most pronounced proximal to the seizure focus. Reductions in ND corresponded to those seen in the FA maps; however, ND reductions were greater in magnitude, more lateralized to the epileptogenic hemisphere, and showed a broader pattern. Increases in IF/IH and effects from CFs also contributed to reduced FA in the ipsilateral parahippocampal cingulum and fornix, with decreases in IH extending into extratemporal regions. Reduced ND of the uncinate fasciculus was associated with longer disease duration, whereas FA was not associated with any clinical variables. RSI may provide a more specific measure of white matter pathology in TLE, distinguishing regions primarily affected by axonal/myelin loss from those where CFs and increases in extracellular water also play a role. By providing a more specific measure of axonal/myelin loss, RSI-derived ND may better reflect overall white

  17. Nerve Growth Factor Regulates Transient Receptor Potential Vanilloid 2 via Extracellular Signal-Regulated Kinase Signaling To Enhance Neurite Outgrowth in Developing Neurons.

    Science.gov (United States)

    Cohen, Matthew R; Johnson, William M; Pilat, Jennifer M; Kiselar, Janna; DeFrancesco-Lisowitz, Alicia; Zigmond, Richard E; Moiseenkova-Bell, Vera Y

    2015-12-01

    Neurite outgrowth is key to the formation of functional circuits during neuronal development. Neurotrophins, including nerve growth factor (NGF), increase neurite outgrowth in part by altering the function and expression of Ca(2+)-permeable cation channels. Here we report that transient receptor potential vanilloid 2 (TRPV2) is an intracellular Ca(2+)-permeable TRPV channel upregulated by NGF via the mitogen-activated protein kinase (MAPK) signaling pathway to augment neurite outgrowth. TRPV2 colocalized with Rab7, a late endosome protein, in addition to TrkA and activated extracellular signal-regulated kinase (ERK) in neurites, indicating that the channel is closely associated with signaling endosomes. In line with these results, we showed that TRPV2 acts as an ERK substrate and identified the motifs necessary for phosphorylation of TRPV2 by ERK. Furthermore, neurite length, TRPV2 expression, and TRPV2-mediated Ca(2+) signals were reduced by mutagenesis of these key ERK phosphorylation sites. Based on these findings, we identified a previously uncharacterized mechanism by which ERK controls TRPV2-mediated Ca(2+) signals in developing neurons and further establish TRPV2 as a critical intracellular ion channel in neuronal function. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  18. cAMP response element-binding protein and Yes-associated protein form a feedback loop that promotes neurite outgrowth.

    Science.gov (United States)

    Chen, Lei; Feng, Peimin; Peng, Anjiao; Qiu, Xiangmiao; Zhu, Xi; He, Shixu; Zhou, Dong

    2017-08-31

    The cAMP response element-binding (CREB) protein is a member of the CREB/activating transcription factor family that is activated by various extracellular stimuli. It has been shown that CREB-dependent transcription stimulation plays a key role in neuronal differentiation and plasticity, but the underlying mechanisms remain largely elusive. Here, we show that Yes-associated protein (YAP) is a direct target induced by CREB upon retinoic acid (RA)-induced neurite outgrowth stimuli in N2a cells. Interestingly, YAP knockout using the CRISPR/Cas9 system inhibits neuronal differentiation and reduced neurite length. We further show that YAP could directly bind to CREB via its N-terminal region, and loss of YAP results in instability of phosphorylated CREB upon neurite outgrowth stimuli. Transient expression of YAP could largely restore CREB expression and neurite outgrowth in YAP knockout cells. Together, our results suggest that CREB and YAP form a positive feedback loop that is critical to maintain the stability of phosphorylated CREB and promote neurite outgrowth. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  19. Maternal obesity and IL-6 lead to aberrant developmental gene expression and deregulated neurite growth in the fetal arcuate nucleus.

    Science.gov (United States)

    Sanders, Tessa R; Kim, Dong Won; Glendining, Kelly A; Jasoni, Christine L

    2014-07-01

    Maternal obesity during pregnancy increases the risk of obesity in the offspring. Several observations have pointed to a causative role for the proinflammatory cytokine IL-6, but whether it is present in the fetal circulation and how it acts on the developing fetus are unclear. We first observed that postnatal day 0 offspring from obese mothers had significantly reduced neuropeptide Y (NPY) innervation of the paraventricular nucleus (PVN) compared with that for offspring of normal-weight controls. Thus, the growth of NPY neurites from the arcuate nucleus (ARC) was impaired in the fetal brain by maternal obesity. The neurite growth regulator, Netrin-1, was expressed in the ARC and PVN and along the pathway between the two at gestational day (GD) 17.5 in normal animals, making it likely to be involved in the development of NPY ARC-PVN projections. In addition, the expression of Dcc and Unc5d, receptors for Netrin-1, were altered in the GD17.5 ARC in obese but not normal weight pregnancies. Thus, this important developmental pathway is perturbed by maternal obesity and may explain the defect in NPY innervation of the PVN that occurs in fetuses developing in obese mothers. To investigate whether IL-6 may play a role in these developmental changes, we found first that IL-6 was significantly elevated in the fetal and maternal circulation in pregnancies of obese mice compared with those of normal-weight mice. In addition, treatment of GD17.5 ARC tissue with IL-6 in vitro significantly reduced ARC neurite outgrowth and altered developmental gene expression similar to maternal obesity in vivo. These findings demonstrate that maternal obesity may alter the way in which fetal ARC NPY neurons respond to key developmental signals that regulate normal prenatal neural connectivity and suggest a causative role for elevated IL-6 in these changes.

  20. Involvement of gecko SNAP25b in spinal cord regeneration by promoting outgrowth and elongation of neurites.

    Science.gov (United States)

    Wang, Yingjie; Dong, Yingying; Song, Honghua; Liu, Yan; Liu, Mei; Yuan, Ying; Ding, Fei; Gu, Xiaosong; Wang, Yongjun

    2012-12-01

    SNARE complex mediates cellular membrane fusion events essential for neurotransmitter release and synaptogenesis. SNAP25, a member of the SNARE proteins, plays critical roles during the development of the central nervous system via regulation by alternative splicing and protein kinase phosphorylation. To date, little information is available regarding the protein in the spinal cord regeneration, especially for the postnatal highly expressed isoform SNAP25b. In the present study, we characterized gecko SNAP25b, which shared high identity with those of other vertebrates. Expression of gecko SNAP25b was temporally upregulated in both neurons of spinal cord and forming ependymal tube following tail amputation, coinciding with the occurrence of regenerate re-innervation. Overexpression of gecko wild type SNAP25b in the SH-SY5Y and undifferentiated PC12 cells promoted the elongation and outgrowth of neurites, while mutant constructs at Serine(187) resulted in differential effects for which S187A had a promoting role. Knockdown of endogenous SNAP25b affected the formation of neurites, which could be rescued by overexpression of SNAP25b. FM1-43 staining revealed that transfection of S187E mutant construct reduced the recruitment of vesicles. In addition, transfection of gecko SNAP25b in the astrocyte, which is absent from neuronal specific VAMP2, was capable of enhancing process elongation, indicating a potential for various alternative protein combinations. Taken together, our data suggest that gecko SNAP25b is involved in spinal cord regeneration by promoting outgrowth and elongation of neurites in a more extensive protein binding manner. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. 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

  2. TSP-1 secreted by bone marrow stromal cells contributes to retinal ganglion cell neurite outgrowth and survival.

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    Keming Yu

    Full Text Available BACKGROUND: Bone marrow stromal cells (BMSCs are pluripotent and thereby a potential candidate for cell replacement therapy for central nervous system degenerative disorders and traumatic injury. However, the mechanism of their differentiation and effect on neural tissues has not been fully elucidated. This study evaluates the effect of BMSCs on neural cell growth and survival in a retinal ganglion cell (RGCs model by assessing the effect of changes in the expression of a BMSC-secreted protein, thrombospondin-1 (TSP-1, as a putative mechanistic agent acting on RGCs. METHODS AND FINDINGS: The effect of co-culturing BMSCs and RGCs in vitro was evaluated by measuring the following parameters: neurite outgrowth, RGC survival, BMSC neural-like differentiation, and the effect of TSP-1 on both cell lines under basal secretion conditions and when TSP-1 expression was inhibited. Our data show that BMSCs improved RGC survival and neurite outgrowth. Synaptophysin, MAP-2, and TGF-beta expression are up-regulated in RGCs co-cultured with BMSCs. Interestingly, the BMSCs progressively displayed neural-like morphology over the seven-day study period. Restriction display polymerase chain reaction (RD-PCR was performed to screen for differentially expressed genes in BMSCs cultured alone or co-cultured with RGCs. TSP-1, a multifactorial extracellular matrix protein, is critically important in the formation of neural connections during development, so its function in our co-culture model was investigated by small interfering RNA (siRNA transfection. When TSP-1 expression was decreased with siRNA silencing, BMSCs had no impact on RGC survival, but reduced neurite outgrowth and decreased expression of synaptophysin, MAP-2 and TGF-beta in RGCs. Furthermore, the number of BMSCs with neural-like characteristics was significantly decreased by more than two-fold using siRNA silencing. CONCLUSIONS: Our data suggest that the TSP-1 signaling pathway might have an important

  3. 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

  4. Accumulation by Conservation

    NARCIS (Netherlands)

    Büscher, Bram; Fletcher, Robert

    2015-01-01

    Following the financial crisis and its aftermath, it is clear that the inherent contradictions of capitalist accumulation have become even more intense and plunged the global economy into unprecedented turmoil and urgency. Governments, business leaders and other elite agents are frantically

  5. Accumulation by Conservation

    NARCIS (Netherlands)

    Büscher, Bram; Fletcher, Robert

    2014-01-01

    Following the financial crisis and its aftermath, it is clear that the inherent contradictions of capitalist accumulation have become even more intense and plunged the global economy into unprecedented turmoil and urgency. Governments, business leaders and other elite agents are frantically

  6. Optimized Culture System to Induce Neurite Outgrowth From Retinal Ganglion Cells in Three-Dimensional Retinal Aggregates Differentiated From Mouse and Human Embryonic Stem Cells.

    Science.gov (United States)

    Maekawa, Yuki; Onishi, Akishi; Matsushita, Keizo; Koide, Naoshi; Mandai, Michiko; Suzuma, Kiyoshi; Kitaoka, Takashi; Kuwahara, Atsushi; Ozone, Chikafumi; Nakano, Tokushige; Eiraku, Mototsugu; Takahashi, Masayo

    2016-04-01

    To establish a practical research tool for studying the pathogenesis of retinal ganglion cell (RGC) diseases, we optimized culture procedures to induce neurite outgrowth from three-dimensional self-organizing optic vesicles (3D-retinas) differentiated in vitro from mouse and human embryonic stem cells (ESCs). The developing 3D-retinas isolated at various time points were placed on Matrigel-coated plates and cultured in media on the basis of the 3D-retinal culture or the retinal organotypic culture protocol. The number, length, and morphology of the neurites in each culture condition were compared. First, we confirmed that Venus-positive cells were double-labeled with a RGC marker, Brn3a, in the 3D-retina differentiated from Fstl4::Venus mouse ESCs, indicating specific RGC-subtype differentiation. Second, Venus-positive neurites grown from these RGC subsets were positive for beta-III tubulin and SMI312 by immunohistochemistry. Enhanced neurite outgrowth was observed in the B27-supplemented Neurobasal-A medium on Matrigel-coated plates from the optic vesicles isolated after 14 days of differentiation from mouse ESCs. For the differentiated RGCs from human ESCs, we obtained neurite extension of >4 mm by modifying Matrigel coating and the culture medium from the mouse RGC culture. We successfully optimized the culture conditions to enhance lengthy and high-frequency neurite outgrowth in mouse and human models. The procedure would be useful for not only developmental studies of RGCs, including maintenance and projection, but also clinical, pathological, and pharmacological studies of human RGC diseases.

  7. ShcA regulates neurite outgrowth stimulated by neural cell adhesion molecule but not by fibroblast growth factor 2: evidence for a distinct fibroblast growth factor receptor response to neural cell adhesion molecule activation

    DEFF Research Database (Denmark)

    Hinsby, Anders M; Lundfald, Line; Ditlevsen, Dorte K

    2004-01-01

    Homophilic binding in trans of the neural cell adhesion molecule (NCAM) mediates adhesion between cells and leads, via activation of intracellular signaling cascades, to neurite outgrowth in primary neurons as well as in the neuronal cell line PC12. NCAM mediates neurite extension in PC12 cells...

  8. Kihi-to, a herbal traditional medicine, improves Abeta(25–35-induced memory impairment and losses of neurites and synapses

    Directory of Open Access Journals (Sweden)

    Joyashiki Eri

    2008-08-01

    Full Text Available Abstract Background We previously hypothesized that achievement of recovery of brain function after the injury requires the reconstruction of neuronal networks, including neurite regeneration and synapse reformation. Kihi-to is composed of twelve crude drugs, some of which have already been shown to possess neurite extension properties in our previous studies. The effect of Kihi-to on memory deficit has not been examined. Thus, the goal of the present study is to determine the in vivo and in vitro effects of Kihi-to on memory, neurite growth and synapse reconstruction. Methods Effects of Kihi-to, a traditional Japanese-Chinese traditional medicine, on memory deficits and losses of neurites and synapses were examined using Alzheimer's disease model mice. Improvements of Aβ(25–35-induced neuritic atrophy by Kihi-to and the mechanism were investigated in cultured cortical neurons. Results Administration of Kihi-to for consecutive 3 days resulted in marked improvements of Aβ(25–35-induced impairments in memory acquisition, memory retention, and object recognition memory in mice. Immunohistochemical comparisons suggested that Kihi-to attenuated neuritic, synaptic and myelin losses in the cerebral cortex, hippocampus and striatum. Kihi-to also attenuated the calpain increase in the cerebral cortex and hippocampus. When Kihi-to was added to cells 4 days after Aβ(25–35 treatment, axonal and dendritic outgrowths in cultured cortical neurons were restored as demonstrated by extended lengths of phosphorylated neurofilament-H (P-NF-H and microtubule-associated protein (MAP2-positive neurites. Aβ(25–35-induced cell death in cortical culture was also markedly inhibited by Kihi-to. Since NF-H, MAP2 and myelin basic protein (MBP are substrates of calpain, and calpain is known to be involved in Aβ-induced axonal atrophy, expression levels of calpain and calpastatin were measured. Treatment with Kihi-to inhibited the Aβ(25–35-evoked increase in

  9. Kihi-to, a herbal traditional medicine, improves Abeta(25-35)-induced memory impairment and losses of neurites and synapses.

    Science.gov (United States)

    Tohda, Chihiro; Naito, Rie; Joyashiki, Eri

    2008-08-16

    We previously hypothesized that achievement of recovery of brain function after the injury requires the reconstruction of neuronal networks, including neurite regeneration and synapse reformation. Kihi-to is composed of twelve crude drugs, some of which have already been shown to possess neurite extension properties in our previous studies. The effect of Kihi-to on memory deficit has not been examined. Thus, the goal of the present study is to determine the in vivo and in vitro effects of Kihi-to on memory, neurite growth and synapse reconstruction. Effects of Kihi-to, a traditional Japanese-Chinese traditional medicine, on memory deficits and losses of neurites and synapses were examined using Alzheimer's disease model mice. Improvements of Abeta(25-35)-induced neuritic atrophy by Kihi-to and the mechanism were investigated in cultured cortical neurons. Administration of Kihi-to for consecutive 3 days resulted in marked improvements of Abeta(25-35)-induced impairments in memory acquisition, memory retention, and object recognition memory in mice. Immunohistochemical comparisons suggested that Kihi-to attenuated neuritic, synaptic and myelin losses in the cerebral cortex, hippocampus and striatum. Kihi-to also attenuated the calpain increase in the cerebral cortex and hippocampus. When Kihi-to was added to cells 4 days after Abeta(25-35) treatment, axonal and dendritic outgrowths in cultured cortical neurons were restored as demonstrated by extended lengths of phosphorylated neurofilament-H (P-NF-H) and microtubule-associated protein (MAP)2-positive neurites. Abeta(25-35)-induced cell death in cortical culture was also markedly inhibited by Kihi-to. Since NF-H, MAP2 and myelin basic protein (MBP) are substrates of calpain, and calpain is known to be involved in Abeta-induced axonal atrophy, expression levels of calpain and calpastatin were measured. Treatment with Kihi-to inhibited the Abeta(25-35)-evoked increase in the calpain level and decrease in the

  10. 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.

  11. Involvement of vimentin in neurite outgrowth damage induced by fipronil in SH-SY5Y cells.

    Science.gov (United States)

    Ruangjaroon, Theetat; Chokchaichamnankit, Daranee; Srisomsap, Chantragan; Svasti, Jisnuson; Paricharttanakul, N Monique

    2017-05-06

    Fipronil, a phenylpyrazole insecticide, is more selective in its potency towards insects than humans and is thus commonly used. In this study, we demonstrated that exposure to fipronil may pose a human health risk. We observed in vitro the shortening of neurite outgrowths of SH-SY5Y neuroblastoma cells upon treatment with fipronil, even at a non-cytotoxic concentration. Fipronil induced apoptosis involving caspase-6, which is an apoptotic effector highly implicated in neurodegenerative diseases. Moreover, at a concentration that did not induce apoptosis, mitochondrial dysfunction and autophagic vacuole formation were detected. Interestingly using proteomics, we identified vimentin to be dramatically expressed by SH-SY5Y cells as a response to fipronil treatment. Not only did the expression of total vimentin increase, different isoforms were observed, indicating alterations in post-translational modifications. Vimentin was localized at the neurite outgrowth, possibly to repair the damage in cellular structure. However at high concentrations of fipronil, vimentin was found in less defined fibrils, in bridge-like formation, and dense surrounding vacuoles. In all, our results indicate that vimentin plays an important role in fipronil-induced neurotoxicity in SH-SY5Y cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Controlled release of 6-aminonicotinamide from aligned, electrospun fibers alters astrocyte metabolism and dorsal root ganglia neurite outgrowth

    Science.gov (United States)

    Schaub, Nicholas J.; Gilbert, Ryan J.

    2011-08-01

    Following central nervous system (CNS) injury, activated astrocytes form a glial scar that inhibits the migration of axons ultimately leading to regeneration failure. Biomaterials developed for CNS repair can provide local delivery of therapeutics and/or guidance mechanisms to encourage cell migration into damaged regions of the brain or spinal cord. Electrospun fibers are a promising type of biomaterial for CNS injury since these fibers can direct cellular and axonal migration while slowly delivering therapy to the injury site. In this study, it was hypothesized that inclusion of an anti-metabolite, 6-aminonicotinamide (6AN), within poly-l-lactic acid electrospun fibers could attenuate astrocyte metabolic activity while still directing axonal outgrowth. Electrospinning parameters were varied to produce highly aligned electrospun fibers that contained 10% or 20% (w/w) 6AN. 6AN release from the fiber substrates occurred continuously over 2 weeks. Astrocytes placed onto drug-releasing fibers were less active than those cultured on scaffolds without 6AN. Dorsal root ganglia placed onto control and drug-releasing scaffolds were able to direct neurites along the aligned fibers. However, neurite outgrowth was stunted by fibers that contained 20% 6AN. These results show that 6AN release from aligned, electrospun fibers can decrease astrocyte activity while still directing axonal outgrowth.

  13. 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.

  14. Major vault protein is expressed along the nucleus-neurite axis and associates with mRNAs in cortical neurons.

    Science.gov (United States)

    Paspalas, Constantinos D; Perley, Casey C; Venkitaramani, Deepa V; Goebel-Goody, Susan M; Zhang, YongFang; Kurup, Pradeep; Mattis, Joanna H; Lombroso, Paul J

    2009-07-01

    Major Vault Protein (MVP), the main constituent of the vault ribonucleoprotein particle, is highly conserved in eukaryotic cells and upregulated in a variety of tumors. Vaults have been speculated to function as cargo transporters in several cell lines, yet no work to date has characterized the protein in neurons. Here we first describe the cellular and subcellular expression of MVP in primate and rodent cerebral cortex, and in cortical neurons in vitro. In prefrontal, somatosensory and hippocampal cortices, MVP was predominantly expressed in pyramidal neurons. Immunogold labeled free and attached ribosomes, and structures reminiscent of vaults on the rough endoplasmic reticulum and the nuclear envelope. The nucleus was immunoreactive in association with nucleopores. Axons and particularly principal dendrites expressed MVP along individual microtubules, and in pre- and postsynaptic structures. Synapses were not labeled. Colocalization with microtubule-associated protein-2, tubulin, tau, and phalloidin was observed in neurites and growth cones in culture. Immunoprecipitation coupled with reverse transcription PCR showed that MVP associates with mRNAs that are known to be translated in response to synaptic activity. Taken together, our findings provide the first characterization of neuronal MVP along the nucleus-neurite axis and may offer new insights into its possible function(s) in the brain.

  15. Antiproton Accumulator (AA)

    CERN Multimedia

    Photographic Service

    1980-01-01

    The AA in its final stage of construction, before it disappeared from view under concrete shielding. Antiprotons were first injected, stochastically cooled and accumulated in July 1980. From 1981 on, the AA provided antiprotons for collisions with protons, first in the ISR, then in the SPS Collider. From 1983 on, it also sent antiprotons, via the PS, to the Low-Energy Antiproton Ring (LEAR). The AA was dismantled in 1997 and shipped to Japan.

  16. Selenium accumulation by plants.

    Science.gov (United States)

    White, Philip J

    2016-02-01

    Selenium (Se) is an essential mineral element for animals and humans, which they acquire largely from plants. The Se concentration in edible plants is determined by the Se phytoavailability in soils. Selenium is not an essential element for plants, but excessive Se can be toxic. Thus, soil Se phytoavailability determines the ecology of plants. Most plants cannot grow on seleniferous soils. Most plants that grow on seleniferous soils accumulate plant species have evolved tolerance to Se, and commonly accumulate tissue Se concentrations >100 mg Se kg(-1) dry matter. These plants are considered to be Se accumulators. Some species can even accumulate Se concentrations of 1000-15 000 mg Se kg(-1 )dry matter and are called Se hyperaccumulators. This article provides an overview of Se uptake, translocation and metabolism in plants and highlights the possible genetic basis of differences in these between and within plant species. The review focuses initially on adaptations allowing plants to tolerate large Se concentrations in their tissues and the evolutionary origin of species that hyperaccumulate Se. It then describes the variation in tissue Se concentrations between and within angiosperm species and identifies genes encoding enzymes limiting the rates of incorporation of Se into organic compounds and chromosomal loci that might enable the development of crops with greater Se concentrations in their edible portions. Finally, it discusses transgenic approaches enabling plants to tolerate greater Se concentrations in the rhizosphere and in their tissues. The trait of Se hyperaccumulation has evolved several times in separate angiosperm clades. The ability to tolerate large tissue Se concentrations is primarily related to the ability to divert Se away from the accumulation of selenocysteine and selenomethionine, which might be incorporated into non-functional proteins, through the synthesis of less toxic Se metabilites. There is potential to breed or select crops

  17. Two-Phase Accumulator

    Science.gov (United States)

    Kalb, Charles E.; Kosson, Robert L.; Alario, Joseph P.; Brown, Richard F.; Edlestein, Fred

    1990-01-01

    Two-phase accumulator maintains pressure and temperature in thermal-bus system within predetermined range during variations in heat load on system. Stores liquid and vapor ammonia. Exchanges liquid ammonia with condenser to adjust level of liquid in condenser. Prototype has capacity of 13 gallons (49 liters). Simple and highly reliable. Responds quickly, restoring pressure and temperature to proper values within minutes. Low in cost and requires little further development. Used to dispose of waste heat, such as that from electronic equipment or power-plant.

  18. Active components from Siberian ginseng (Eleutherococcus senticosus) for protection of amyloid β(25-35)-induced neuritic atrophy in cultured rat cortical neurons.

    Science.gov (United States)

    Bai, Yanjing; Tohda, Chihiro; Zhu, Shu; Hattori, Masao; Komatsu, Katsuko

    2011-07-01

    Not only neuronal death but also neuritic atrophy and synaptic loss underlie the pathogenesis of Alzheimer's disease as direct causes of the memory deficit. Extracts of Siberian ginseng (the rhizome of Eleutherococcus senticosus) were shown to have protective effects on the regeneration of neurites and the reconstruction of synapses in rat cultured cortical neurons damaged by amyloid β (Aβ)(25-35), and eleutheroside B was one of the active constituents. In this study, a comprehensive evaluation of constituents was conducted to explore active components from Siberian ginseng which can protect against neuritic atrophy induced by Aβ(25-35) in cultured rat cortical neurons. The ethyl acetate, n-butanol and water fractions from the methanol extract of Siberian ginseng showed protective effects against Aβ-induced neuritic atrophy. Twelve compounds were isolated from the active fractions and identified. Among them, eleutheroside B, eleutheroside E and isofraxidin showed obvious protective effects against Aβ(25-35)-induced atrophies of axons and dendrites at 1 and 10 μM.

  19. 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.

  20. Inhibition of mTOR by Rapamycin Results in Auditory Hair Cell Damage and Decreased Spiral Ganglion Neuron Outgrowth and Neurite Formation In Vitro

    Directory of Open Access Journals (Sweden)

    Katharina Leitmeyer

    2015-01-01

    Full Text Available Rapamycin is an antifungal agent with immunosuppressive properties. Rapamycin inhibits the mammalian target of rapamycin (mTOR by blocking the mTOR complex 1 (mTORC1. mTOR is an atypical serine/threonine protein kinase, which controls cell growth, cell proliferation, and cell metabolism. However, less is known about the mTOR pathway in the inner ear. First, we evaluated whether or not the two mTOR complexes (mTORC1 and mTORC2, resp. are present in the mammalian cochlea. Next, tissue explants of 5-day-old rats were treated with increasing concentrations of rapamycin to explore the effects of rapamycin on auditory hair cells and spiral ganglion neurons. Auditory hair cell survival, spiral ganglion neuron number, length of neurites, and neuronal survival were analyzed in vitro. Our data indicates that both mTOR complexes are expressed in the mammalian cochlea. We observed that inhibition of mTOR by rapamycin results in a dose dependent damage of auditory hair cells. Moreover, spiral ganglion neurite number and length of neurites were significantly decreased in all concentrations used compared to control in a dose dependent manner. Our data indicate that the mTOR may play a role in the survival of hair cells and modulates spiral ganglion neuronal outgrowth and neurite formation.

  1. Neural cell adhesion molecule 2 promotes the formation of filopodia and neurite branching by inducing submembrane increases in Ca2+ levels.

    Science.gov (United States)

    Sheng, Lifu; Leshchyns'ka, Iryna; Sytnyk, Vladimir

    2015-01-28

    Changes in expression of the neural cell adhesion molecule 2 (NCAM2) have been proposed to contribute to neurodevelopmental disorders in humans. The role of NCAM2 in neuronal differentiation remains, however, poorly understood. Using genetically encoded Ca(2+) reporters, we show that clustering of NCAM2 at the cell surface of mouse cortical neurons induces submembrane [Ca(2+)] spikes, which depend on the L-type voltage-dependent Ca(2+) channels (VDCCs) and require activation of the protein tyrosine kinase c-Src. We also demonstrate that clustering of NCAM2 induces L-type VDCC- and c-Src-dependent activation of CaMKII. NCAM2-dependent submembrane [Ca(2+)] spikes colocalize with the bases of filopodia. NCAM2 activation increases the density of filopodia along neurites and neurite branching and outgrowth in an L-type VDCC-, c-Src-, and CaMKII-dependent manner. Our results therefore indicate that NCAM2 promotes the formation of filopodia and neurite branching by inducing Ca(2+) influx and CaMKII activation. Changes in NCAM2 expression in Down syndrome and autistic patients may therefore contribute to abnormal neurite branching observed in these disorders. Copyright © 2015 the authors 0270-6474/15/351739-14$15.00/0.

  2. Optimisation of a 96-well electroporation assay for postnatal rat CNS neurons suitable for cost-effective medium-throughput screening of genes that promote neurite outgrowth

    Directory of Open Access Journals (Sweden)

    Thomas eHutson

    2011-12-01

    Full Text Available Following an injury, central nervous system (CNS neurons show a very limited regenerative response which results in their failure to successfully form functional connections with their original target. This is due in part to the reduced intrinsic growth state of CNS neurons, which is characterised by their failure to express key regeneration-associated genes (RAGs and by the presence of growth inhibitory molecules in CNS environment that form a molecular and physical barrier to regeneration. Here we have optimised a 96-well electroporation and neurite outgrowth assay for postnatal rat cerebellar granule neurons cultured upon an inhibitory cellular substrate expressing myelin-associated glycoprotein or a mixture of growth-inhibitory chondroitin sulphate proteoglycans. Optimal electroporation parameters resulted in 25% transfection efficiency and 50% viability for postnatal rat cerebellar granule neurons (CGNs. The neurite outgrowth of transduced neurons was quantitatively measured using a semi-automated image capture and analysis system. The neurite outgrowth was significantly reduced by the inhibitory substrates which we demonstrated could be partially reversed using a Rho Kinase inhibitor. We are now using this assay to screen large sets of RAGs for their ability to increase neurite outgrowth on a variety of growth inhibitory and permissive substrates.

  3. Recreational drugs, 3,4-Methylenedioxymethamphetamine(MDMA), 3,4-methylenedioxyamphetamine (MDA) and diphenylprolinol, inhibit neurite outgrowth in PC12 cells.

    Science.gov (United States)

    Kaizaki, Asuka; Tanaka, Sachiko; Tsujikawa, Kenji; Numazawa, Satoshi; Yoshida, Takemi

    2010-06-01

    3,4-Methylenedioxymethamphetamine (MDMA) is widely abused as a psychoactive recreational drug. It is well known that MDMA induces neurotoxic damage of serotonergic nerve endings. Although drug abuse is increasing among youths, it is unclear whether recreational drugs affect the development of nerve growth. Thus, the present study examined the effect of recreational drugs, such as MDMA, 3,4-methylenedioxyamphetamine (MDA) and diphenylprolinol, a novel recreational drug with a similar chemical structure as that of psychoactive agent pipradrol, on nerve growth factor (NGF)-induced neurite outgrowth. These recreational drugs induced a dose-dependent cell death in PC12 cells. The IC(50) values of MDMA, MDA, R-diphenylprolinol and S-diphenylprolinol were 4.11 mM, 2.75 mM, 1.00 mM and 0.77 mM, respectively, at 24 hr. To examine the effects of these recreational drugs on NGF-induced neurite outgrowth, PC12 cells were treated with NGF together with MDMA, MDA, S-diphenylprolinol or R-diphenylprolinol at low toxic concentrations. The recreational drugs significantly suppressed neurite outgrowth of PC12 cells induced by NGF. The results suggest that these psychoactive recreational drugs may inhibit neurite growth and thus be implicated in their elicited neurotoxicity.

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

    Science.gov (United States)

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

    2010-07-16

    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. Copyright 2010 Elsevier Inc. All rights reserved.

  5. Minocycline Promotes Neurite Outgrowth of PC12 Cells Exposed to Oxygen-Glucose Deprivation and Reoxygenation Through Regulation of MLCP/MLC Signaling Pathways.

    Science.gov (United States)

    Tao, Tao; Feng, Jin-Zhou; Xu, Guang-Hui; Fu, Jie; Li, Xiao-Gang; Qin, Xin-Yue

    2017-04-01

    Minocycline, a semi-synthetic second-generation derivative of tetracycline, has been reported to exert neuroprotective effects both in animal models and in clinic trials of neurological diseases. In the present study, we first investigated the protective effects of minocycline on oxygen-glucose deprivation and reoxygenation-induced impairment of neurite outgrowth and its potential mechanism in the neuronal cell line, PC12 cells. We found that minocycline significantly increased cell viability, promoted neurite outgrowth and enhanced the expression of growth-associated protein-43 (GAP-43) in PC12 cells exposed to oxygen-glucose deprivation/reoxygenation injury. In addition, immunoblots revealed that minocycline reversed the overexpression of phosphorylated myosin light chain (MLC) and the suppression of activated extracellular signal-regulated kinase 1/2 (ERK1/2) caused by oxygen-glucose deprivation/reoxygenation injury. Moreover, the minocycline-induced neurite outgrowth was significantly blocked by Calyculin A (1 nM), an inhibitor of myosin light chain phosphatase (MLCP), but not by an ERK1/2 inhibitor (U0126; 10 μM). These findings suggested that minocycline activated the MLCP/MLC signaling pathway in PC12 cells after oxygen-glucose deprivation/reoxygenation injury, which resulted in the promotion of neurite outgrowth.

  6. Potentiation of nerve growth factor-induced neurite outgrowth by fluvoxamine: role of sigma-1 receptors, IP3 receptors and cellular signaling pathways.

    Directory of Open Access Journals (Sweden)

    Tomoko Nishimura

    Full Text Available BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs have been widely used and are a major therapeutic advance in psychopharmacology. However, their pharmacology is quite heterogeneous. The SSRI fluvoxamine, with sigma-1 receptor agonism, is shown to potentiate nerve-growth factor (NGF-induced neurite outgrowth in PC 12 cells. However, the precise cellular and molecular mechanisms underlying potentiation by fluvoxamine are not fully understood. In this study, we examined the roles of cellular signaling pathways in the potentiation of NGF-induced neurite outgrowth by fluvoxamine and sigma-1 receptor agonists. METHODS AND FINDINGS: The effects of three SSRIs (fluvoxamine, sertraline, paroxetine and three sigma-1 receptor agonists (SA4503, 4-phenyl-1-(4-phenylbutyl piperidine (PPBP, and dehydroepiandrosterone (DHEA-sulfate on NGF-induced neurite outgrowth in PC12 cells were examined. Also examined were the effects of the sigma-1 receptor antagonist NE-100, inositol 1,4,5-triphosphate (IP(3 receptor antagonist, and specific inhibitors of signaling pathways in the potentiation of NGF-induced neurite outgrowth by selective sigma-1 receptor agonist SA4503. Fluvoxamine (but not sertraline or paroxetine and the sigma-1 receptor agonists SA4503, PPBP, and DHEA-sulfate significantly potentiated NGF-induced neurite outgrowth in PC12 cells in a concentration-dependent manner. The potentiation by fluvoxamine and the three sigma-1 receptor agonists was blocked by co-administration of the selective sigma-1 receptor antagonist NE-100, suggesting that sigma-1 receptors play a role in blocking the enhancement of NGF-induced neurite outgrowth. Moreover, the potentiation by SA4503 was blocked by co-administration of the IP(3 receptor antagonist xestospongin C. In addition, the specific inhibitors of phospholipase C (PLC-gamma, phosphatidylinositol 3-kinase (PI3K, p38MAPK, c-Jun N-terminal kinase (JNK, and the Ras/Raf/mitogen-activated protein kinase (MAPK

  7. Peripheral nerve regeneration and NGF-dependent neurite outgrowth of adult sensory neurons converge on STAT3 phosphorylation downstream of neuropoietic cytokine receptor gp130.

    Science.gov (United States)

    Quarta, Serena; Baeumer, Bastian E; Scherbakov, Nadja; Andratsch, Manfred; Rose-John, Stefan; Dechant, Georg; Bandtlow, Christine E; Kress, Michaela

    2014-09-24

    After nerve injury, adult sensory neurons can regenerate peripheral axons and reconnect with their target tissue. Initiation of outgrowth, as well as elongation of neurites over long distances, depends on the signaling of receptors for neurotrophic growth factors. Here, we investigated the importance of gp130, the signaling subunit of neuropoietic cytokine receptors in peripheral nerve regeneration. After sciatic nerve crush, functional recovery in vivo was retarded in SNS-gp130(-/-) mice, which specifically lack gp130 in sensory neurons. Correspondingly, a significantly reduced number of free nerve endings was detected in glabrous skin from SNS-gp130(-/-) compared with control mice after nerve crush. Neurite outgrowth and STAT3 activation in vitro were severely reduced in cultures in gp130-deficient cultured neurons. Surprisingly, in neurons obtained from SNS-gp130(-/-) mice the increase in neurite length was reduced not only in response to neuropoietic cytokine ligands of gp130 but also to nerve growth factor (NGF), which does not bind to gp130-containing receptors. Neurite outgrowth in the absence of neurotrophic factors was partially rescued in gp130-deficient neurons by leptin, which activates STAT3 downstream of leptic receptor and independent of gp130. The neurite outgrowth response of gp130-deficient neurons to NGF was fully restored in the presence of leptin. Based on these findings, gp130 signaling via STAT3 activation is suggested not only to be an important regulator of peripheral nerve regeneration in vitro and in vivo, but as determining factor for the growth promoting action of NGF in adult sensory neurons. Copyright © 2014 the authors 0270-6474/14/3413222-12$15.00/0.

  8. Co-administration of ciliary neurotrophic factor with its soluble receptor protects against neuronal death and enhances neurite outgrowth.

    Science.gov (United States)

    Ozog, Mark A; Modha, Geetanjalee; Church, John; Reilly, Rayne; Naus, Christian C

    2008-03-07

    Attempts to promote neuronal survival and repair with ciliary neurotrophic factor (CNTF) have met with limited success. The variability of results obtained with CNTF may, in part, reflect the fact that some of the biological actions of the cytokine are mediated by a complex formed between CNTF and its specific receptor, CNTFRalpha, which exists in both membrane-bound and soluble forms. In this study, we compared the actions of CNTF alone and CNTF complexed with soluble CNTFRalpha (hereafter termed "Complex") on neuronal survival and growth. Although CNTF alone produced limited effects, Complex protected against glutamate-mediated excitotoxicity via gap junction-dependent and -independent mechanisms. Further examination revealed that only Complex promoted neurite outgrowth. Differential gene expression analysis revealed that, compared with CNTF alone, Complex differentially regulates several neuroprotective and neurotrophic genes. Collectively, these findings indicate that CNTF exerts more robust effects on neuronal survival and growth when applied in combination with its soluble receptor.

  9. 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

    Metallothionein (MT) is a metal-binding protein capable of preventing oxidative stress and apoptotic cell death in the central nervous system of mammals, and hence is of putative therapeutic value in the treatment of neurodegenerative disorders. Recently, we demonstrated that a peptide modeled...... after the beta-domain of MT, EmtinB, induced neurite outgrowth and increased neuronal survival through binding to receptors of the low-density lipoprotein receptor family (LDLR). The present study identified two MT alpha-domain-derived peptide sequences termed EmtinAn and EmtinAc, each consisting of 14...... 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...

  10. The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C.

    Science.gov (United States)

    Loers, Gabriele; Astafiev, Steven; Hapiak, Yuliya; Saini, Vedangana; Mishra, Bibhudatta; Gul, Sheraz; Kaur, Gurcharan; Schachner, Melitta; Theis, Thomas

    2017-08-01

    Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues. It is generated by two polysialyltransferases and attached to N- and/or O-linked glycans, and its main carrier is the neural cell adhesion molecule (NCAM). PSA controls the development and regeneration of the nervous system by enhancing cell migration, axon pathfinding, synaptic targeting, synaptic plasticity, by regulating the differentiation of progenitor cells and by modulating cell-cell and cell-matrix adhesions. In the adult, PSA plays a role in the immune system, and PSA mimetics promote functional recovery after nervous system injury. In search for novel small molecule mimetics of PSA that are applicable for therapy, we identified idarubicin, an antineoplastic anthracycline, and irinotecan, an antineoplastic agent of the topoisomerase I inhibitor class, as PSA mimetics using a competition enzyme-linked immunosorbent assay. Idarubicin and irinotecan compete with the PSA-mimicking peptide and colominic acid, the bacterial analog of PSA, for binding to the PSA-specific monoclonal antibody 735. Idarubicin and irinotecan stimulate neurite outgrowth and survival of cultured cerebellar neurons after oxidative stress via protein kinase C and Erk1/2 in a similar manner as colominic acid, whereas Fyn, casein kinase II and the phosphatase and tensin homolog are only involved in idarubicin and irinotecan-stimulated neurite outgrowth. These novel results show that the structure and function of PSA can be mimicked by the small organic compounds irinotecan and idarubicin which trigger the same signaling cascades as PSA, thus introducing the possibility of retargeting these drugs to treat nervous system injuries. © 2017 International Society for Neurochemistry.

  11. Sialidase NEU4 hydrolyzes polysialic acids of neural cell adhesion molecules and negatively regulates neurite formation by hippocampal neurons.

    Science.gov (United States)

    Takahashi, Kohta; Mitoma, Junya; Hosono, Masahiro; Shiozaki, Kazuhiro; Sato, Chihiro; Yamaguchi, Kazunori; Kitajima, Ken; Higashi, Hideyoshi; Nitta, Kazuo; Shima, Hiroshi; Miyagi, Taeko

    2012-04-27

    Modulation of levels of polysialic acid (polySia), a sialic acid polymer, predominantly associated with the neural cell adhesion molecule (NCAM), influences neural functions, including synaptic plasticity, neurite growth, and cell migration. Biosynthesis of polySia depends on two polysialyltransferases ST8SiaII and ST8SiaIV in vertebrate. However, the enzyme involved in degradation of polySia in its physiological turnover remains uncertain. In the present study, we identified and characterized a murine sialidase NEU4 that catalytically degrades polySia. Murine NEU4, dominantly expressed in the brain, was found to efficiently hydrolyze oligoSia and polySia chains as substrates in sialidase in vitro assays, and also NCAM-Fc chimera as well as endogenous NCAM in tissue homogenates of postnatal mouse brain as assessed by immunoblotting with anti-polySia antibodies. Degradation of polySia by NEU4 was also evident in neuroblastoma Neuro2a cells that were co-transfected with Neu4 and ST8SiaIV genes. Furthermore, in mouse embryonic hippocampal primary neurons, the endogenously expressed NEU4 was found to decrease during the neuronal differentiation. Interestingly, GFP- or FLAG-tagged NEU4 was partially co-localized with polySia in neurites and significantly suppressed their outgrowth, whereas silencing of NEU4 showed the acceleration together with an increase in polySia expression. These results suggest that NEU4 is involved in regulation of neuronal function by polySia degradation in mammals.

  12. The adaptor protein SH2B3 (Lnk negatively regulates neurite outgrowth of PC12 cells and cortical neurons.

    Directory of Open Access Journals (Sweden)

    Tien-Cheng Wang

    Full Text Available SH2B adaptor protein family members (SH2B1-3 regulate various physiological responses through affecting signaling, gene expression, and cell adhesion. SH2B1 and SH2B2 were reported to enhance nerve growth factor (NGF-induced neuronal differentiation in PC12 cells, a well-established neuronal model system. In contrast, SH2B3 was reported to inhibit cell proliferation during the development of immune system. No study so far addresses the role of SH2B3 in the nervous system. In this study, we provide evidence suggesting that SH2B3 is expressed in the cortex of embryonic rat brain. Overexpression of SH2B3 not only inhibits NGF-induced differentiation of PC12 cells but also reduces neurite outgrowth of primary cortical neurons. SH2B3 does so by repressing NGF-induced activation of PLCγ, MEK-ERK1/2 and PI3K-AKT pathways and the expression of Egr-1. SH2B3 is capable of binding to phosphorylated NGF receptor, TrkA, as well as SH2B1β. Our data further demonstrate that overexpression of SH2B3 reduces the interaction between SH2B1β and TrkA. Consistent with this finding, overexpressing the SH2 domain of SH2B3 is sufficient to inhibit NGF-induced neurite outgrowth. Together, our data demonstrate that SH2B3, unlike the other two family members, inhibits neuronal differentiation of PC12 cells and primary cortical neurons. Its inhibitory mechanism is likely through the competition of TrkA binding with the positive-acting SH2B1 and SH2B2.

  13. The aeolian dust accumulation curve

    NARCIS (Netherlands)

    Goossens, D.

    2001-01-01

    This article presents a simple physical concept of aeolian dust accumulation, based on the behaviour of the subprocesses of dust deposition and dust erosion. The concept is tested in an aeolian dust wind tunnel. The agreement between the accumulation curve predicted by the model and the accumulation

  14. The Antiproton Accumulator (AA)

    CERN Multimedia

    1980-01-01

    Section 06 - 08*) of the AA where the dispersion (and hence the horizontal beam size) is large. One can distinguish (left to right): A vacuum-tank, two bending magnets (BST06 and BST07 in blue) with a quadrupole (QDN07, in red) in between, another vacuum-tank, a wide quadrupole (QFW08) and a further tank . The tanks are covered with heating tape for bake-out. The tank left of BST06 contained the stack core pickup for stochastic cooling (see 7906193, 7906190, 8005051), the two other tanks served mainly as vacuum chambers in the region where the beam was large. Peter Zettwoch works on BST06. *) see: H. Koziol, Antiproton Accumulator Parameter List, PS/AA/Note 84-2 (1984)

  15. Solids Accumulation Scouting Studies

    Energy Technology Data Exchange (ETDEWEB)

    Duignan, M. R.; Steeper, T. J.; Steimke, J. L.

    2012-09-26

    The objective of Solids Accumulation activities was to perform scaled testing to understand the behavior of remaining solids in a Double Shell Tank (DST), specifically AW-105, at Hanford during multiple fill, mix, and transfer operations. It is important to know if fissionable materials can concentrate when waste is transferred from staging tanks prior to feeding waste treatment plants. Specifically, there is a concern that large, dense particles containing plutonium could accumulate in poorly mixed regions of a blend tank heel for tanks that employ mixing jet pumps. At the request of the DOE Hanford Tank Operations Contractor, Washington River Protection Solutions, the Engineering Development Laboratory of the Savannah River National Laboratory performed a scouting study in a 1/22-scale model of a waste staging tank to investigate this concern and to develop measurement techniques that could be applied in a more extensive study at a larger scale. Simulated waste tank solids: Gibbsite, Zirconia, Sand, and Stainless Steel, with stainless steel particles representing the heavier particles, e.g., plutonium, and supernatant were charged to the test tank and rotating liquid jets were used to mix most of the solids while the simulant was pumped out. Subsequently, the volume and shape of the mounds of residual solids and the spatial concentration profiles for the surrogate for heavier particles were measured. Several techniques were developed and equipment designed to accomplish the measurements needed and they included: 1. Magnetic particle separator to remove simulant stainless steel solids. A device was designed and built to capture these solids, which represent the heavier solids during a waste transfer from a staging tank. 2. Photographic equipment to determine the volume of the solids mounds. The mounds were photographed as they were exposed at different tank waste levels to develop a composite of topographical areas. 3. Laser rangefinders to determine the volume of

  16. Chronic, low-dose rotenone reproduces Lewy neurites found in early stages of Parkinson's disease, reduces mitochondrial movement and slowly kills differentiated SH-SY5Y neural cells

    Directory of Open Access Journals (Sweden)

    Liu Lei

    2008-12-01

    Full Text Available Abstract Background Parkinson's disease, the most common adult neurodegenerative movement disorder, demonstrates a brain-wide pathology that begins pre-clinically with alpha-synuclein aggregates ("Lewy neurites" in processes of gut enteric and vagal motor neurons. Rostral progression into substantia nigra with death of dopamine neurons produces the motor impairment phenotype that yields a clinical diagnosis. The vast majority of Parkinson's disease occurs sporadically, and current models of sporadic Parkinson's disease (sPD can utilize directly infused or systemic neurotoxins. Results We developed a differentiation protocol for human SH-SY5Y neuroblastoma that yielded non-dividing dopaminergic neural cells with long processes that we then exposed to 50 nM rotenone, a complex I inhibitor used in Parkinson's disease models. After 21 days of rotenone, ~60% of cells died. Their processes retracted and accumulated ASYN-(+ and UB-(+ aggregates that blocked organelle transport. Mitochondrial movement velocities were reduced by 8 days of rotenone and continued to decline over time. No cytoplasmic inclusions resembling Lewy bodies were observed. Gene microarray analyses showed that the majority of genes were under-expressed. qPCR analyses of 11 mtDNA-encoded and 10 nDNA-encoded mitochondrial electron transport chain RNAs' relative expressions revealed small increases in mtDNA-encoded genes and lesser regulation of nDNA-encoded ETC genes. Conclusion Subacute rotenone treatment of differentiated SH-SY5Y neuroblastoma cells causes process retraction and partial death over several weeks, slowed mitochondrial movement in processes and appears to reproduce the Lewy neuritic changes of early Parkinson's disease pathology but does not cause Lewy body inclusions. The overall pattern of transcriptional regulation is gene under-expression with minimal regulation of ETC genes in spite of rotenone's being a complex I toxin. This rotenone-SH-SY5Y model in a

  17. 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

  18. The Antiproton Accumulator (AA)

    CERN Multimedia

    1980-01-01

    A section of the AA where the dispersion (and hence the horizontal beam size) is large. One can distinguish (left to right): A large vacuum-tank, a quadrupole (QDN09*), a bending magnet (BST08), another vacuum-tank, a wide quadrupole (QFW08) and (in the background) a further bending magnet (BST08). The tanks are covered with heating tape for bake-out. The tank left of QDN09 contained the kickers for stochastic pre-cooling (see 790621, 8002234, 8002637X), the other one served mainly as vacuum chamber in the region where the beam was large. Peter Zettwoch works on QFW08. * see: H. Koziol, Antiproton Accumulator Parameter List, PS/AA/Note 84-2 (1984) See under 7911303, 7911597X, 8004261 and 8202324. For photos of the AA in different phases of completion (between 1979 and 1982) see: 7911303, 7911597X, 8004261, 8004608X, 8005563X, 8005565X, 8006716X, 8006722X, 8010939X, 8010941X, 8202324, 8202658X, 8203628X .

  19. Botanical Drug Puerarin Coordinates with Nerve Growth Factor in the Regulation of Neuronal Survival and Neuritogenesis via Activating ERK1/2 and PI3K/Akt Signaling Pathways in the Neurite Extension Process

    National Research Council Canada - National Science Library

    Zhao, Jia; Cheng, Yuan‐Yuan; Fan, Wen; Yang, Chuan‐Bin; Ye, Shui‐Fen; Cui, Wei; Wei, Wei; Lao, Li‐Xing; Cai, Jing; Han, Yi‐Fan; Rong, Jian‐Hui

    2015-01-01

    .... This study was designed to investigate whether botanical drug C-glucosylated isoflavone puerarin coordinates with NGF to regulate neuritogenesis via activating ERK1/2 and PI3K/Akt in neurite extension process...

  20. 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

    SRC family kinases have been consistently and recurrently implicated in neurite extension events, yet the mechanism underlying their neuritogenic role has remained elusive. We report that epidermal growth factor (EGF) can be converted from a non-neuritogenic into a neuritogenic factor through...... 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...... of a dominant negative version of Sin interfered with receptor-protein-tyrosine phosphatase alpha/EGF- as well as fibroblast growth factor-induced neurite outgrowth. These observations uncouple neuritogenic signaling in PC12 cells from sustained activation of ERK kinases and for the first time identify...

  1. 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

    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......), and induced neurite outgrowth and enhanced neuronal survival, probably by inducing signaling through tha Akt and MAPK pathways. Distinct, charged residues within the Betrofin sequences were identified as important for generating the neuritogenic response, which was also inhibited when BDNF was added together...... with either Betrofin, indicating partial agonistic effects of the peptides. Thus, two peptides derived from BDNF induced neurite outgrowth and enhanced neuronal survival, probably through binding to BDNF receptors....

  2. 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...... that phosphatases belong to multiple independently evolved families, which are rarely studied together. We undertook a loss-of-function RNA-interference-based screen of virtually all known (254) human phosphatases to understand their function in BDNF/TrkB-mediated neurite outgrowth in differentiated SH-SY5Y cells....... 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...

  3. 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

    The signal transduction pathways associated with neural cell adhesion molecule (NCAM)-induced neuritogenesis are only partially characterized. We here demonstrate that NCAM-induced neurite outgrowth depends on activation of p59(fyn), focal adhesion kinase (FAK), phospholipase Cgamma (PLCgamma......), protein kinase C (PKC), and the Ras-mitogen-activated protein (MAP) kinase pathway. This was done using a coculture system consisting of PC12-E2 cells grown on fibroblasts, with or without NCAM expression, allowing NCAM-NCAM interactions resulting in neurite outgrowth. PC12-E2 cells were transiently...... propose a model of NCAM signaling involving two pathways: NCAM-Ras-MAP kinase and NCAM-FGF receptor-PLCgamma-PKC, and we propose that PKC serves as the link between the two pathways activating Raf and thereby creating the sustained activity of the MAP kinases necessary for neuronal differentiation....

  4. NF-κB activation via tyrosine phosphorylation of IκB-α is crucial for CNTF-promoted neurite growth from developing neurons

    OpenAIRE

    Gallagher, Denis; Gutierrez, Humberto; O'Keeffe, Gerard; Gavalda, Nuria; Hay, Ron; Davies, Alun M.

    2007-01-01

    The cytokine CNTF (ciliary neurotrophic factor) promotes the growth of neural processes from many kinds of neurons in the developing and regenerating adult nervous system, but the intracellular signalling mechanisms mediating this important function of CNTF are poorly understood. Here we show that CNTF activates the NF-κB transcriptional system in neonatal sensory neurons and that blocking NF-κB-dependent transcription inhibits CNTF-promoted neurite growth. Selectively blocking NF-κB activati...

  5. A beta-lactone related to lactacystin induces neurite outgrowth in a neuroblastoma cell line and inhibits cell cycle progression in an osteosarcoma cell line.

    OpenAIRE

    Fenteany, G; Standaert, R F; Reichard, G A; Corey, E J; Schreiber, S L

    1994-01-01

    Lactacystin, a microbial natural product, induces neurite outgrowth in Neuro 2A mouse neuroblastoma cells and inhibits progression of synchronized Neuro 2A cells and MG-63 human osteosarcoma cells beyond the G1 phase of the cell cycle. A related beta-lactone, clasto-lactacystin beta-lactone, formally the product of elimination of N-acetylcysteine from lactacystin, is also active, whereas the corresponding clastolactacystin dihydroxy acid is completely inactive. Structural analogs of lactacyst...

  6. Existing plaques and neuritic abnormalities in APP:PS1 mice are not affected by administration of the gamma-secretase inhibitor LY-411575

    Directory of Open Access Journals (Sweden)

    Golde Todd E

    2009-05-01

    Full Text Available Abstract The γ-secretase complex is a major therapeutic target for the prevention and treatment of Alzheimer's disease. Previous studies have shown that treatment of young APP mice with specific inhibitors of γ-secretase prevented formation of new plaques. It has not yet been shown directly whether existing plaques would be affected by γ-secretase inhibitor treatment. Similarly, alterations in neuronal morphology in the immediate vicinity of plaques represent a plaque-specific neurotoxic effect. Reversal of these alterations is an important endpoint of successful therapy whether or not a treatment affects plaque size. In the present study we used longitudinal imaging in vivo with multiphoton microscopy to study the effects of the orally active γ-secretase inhibitor LY-411575 in 10–11 month old APP:PS1 mice with established amyloid pathology and neuritic abnormalities. Neurons expressed YFP allowing fluorescent detection of morphology whereas plaques were labelled with methoxy-XO4. The same identified neurites and plaques were followed in weekly imaging sessions in living mice treated daily (5 mg/kg for 3 weeks with the compound. Although LY-411575 reduced Aβ levels in plasma and brain, it did not have an effect on the size of existing plaques. There was also no effect on the abnormal neuritic curvature near plaques, or the dystrophies in very close proximity to senile plaques. Our results suggest that therapeutics aimed at inhibition of Aβ generation are less effective for reversal of existing plaques than for prevention of new plaque formation and have no effect on the plaque-mediated neuritic abnormalities, at least under these conditions where Aβ production is suppressed but not completely blocked. Therefore, a combination therapy of Aβ suppression with agents that increase clearance of amyloid and/or prevent neurotoxicity might be needed for a more effective treatment in patients with pre-existing pathology.

  7. 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 < 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. 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.

  8. 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.

  9. 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

  10. 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.

  11. Sub-toxic concentrations of nano-ZnO and nano-TiO2 suppress neurite outgrowth in differentiated PC12 cells.

    Science.gov (United States)

    Irie, Tomohiko; Kawakami, Tsuyoshi; Sato, Kaoru; Usami, Makoto

    2017-01-01

    Nanomaterials have been extensively used in our daily life, and may also induce health effects and toxicity. Nanomaterials can translocate from the outside to internal organs, including the brain. For example, both nano-ZnO and nano-TiO2 translocate into the brain via the olfactory pathway in rodents, possibly leading to toxic effects on the brain. Although the effects of nano-ZnO and nano-TiO2 on neuronal viability or neuronal excitability have been studied, no work has focused on how these nanomaterials affect neuronal differentiation and development. In this study, we investigated the effects of nano-ZnO and nano-TiO2 on neurite outgrowth of PC12 cells, a useful model system for neuronal differentiation. Surprisingly, the number, length, and branching of differentiated PC12 neurites were significantly suppressed by the 7-day exposure to nano-ZnO (in the range of 1.0 × 10-4 to 1.0 × 10-1 µg/mL), at which the cell viability was not affected. The number and length were also significantly inhibited by the 7-day exposure to nano-TiO2 (1.0 × 10-3 to 1.0 µg/mL), which did not have cytotoxic effects. These results demonstrate that the neurite outgrowth in differentiated PC12 cells was suppressed by sub-cytotoxic concentrations of nano-ZnO or nano-TiO2.

  12. A beta-lactone related to lactacystin induces neurite outgrowth in a neuroblastoma cell line and inhibits cell cycle progression in an osteosarcoma cell line.

    Science.gov (United States)

    Fenteany, G; Standaert, R F; Reichard, G A; Corey, E J; Schreiber, S L

    1994-04-12

    Lactacystin, a microbial natural product, induces neurite outgrowth in Neuro 2A mouse neuroblastoma cells and inhibits progression of synchronized Neuro 2A cells and MG-63 human osteosarcoma cells beyond the G1 phase of the cell cycle. A related beta-lactone, clasto-lactacystin beta-lactone, formally the product of elimination of N-acetylcysteine from lactacystin, is also active, whereas the corresponding clastolactacystin dihydroxy acid is completely inactive. Structural analogs of lactacystin altered only in the N-acetylcysteine moiety are active, while structural or stereochemical modifications of the gamma-lactam ring or the hydroxyisobutyl group lead to partial or complete loss of activity. The inactive compounds do not antagonize the effects of lactacystin in either neurite outgrowth or cell cycle progression assays. The response to lactacystin involves induction of a predominantly bipolar morphology that is maximal 16-32 h after treatment and is distinct from the response to several other treatments that result in morphological differentiation. Neurite outgrowth in response to lactacystin appears to be dependent upon microtubule assembly, actin polymerization, and de novo protein synthesis. The observed structure-activity relationships suggest that lactacystin and its related beta-lactone may act via acylation of one or more relevant target molecule(s) in the cell.

  13. Myelin-associated glycoprotein interacts with neurons via a sialic acid binding site at ARG118 and a distinct neurite inhibition site.

    Science.gov (United States)

    Tang, S; Shen, Y J; DeBellard, M E; Mukhopadhyay, G; Salzer, J L; Crocker, P R; Filbin, M T

    1997-09-22

    Inhibitory components in myelin are largely responsible for the lack of regeneration in the mammalian CNS. Myelin-associated glycoprotein (MAG), a sialic acid binding protein and a component of myelin, is a potent inhibitor of neurite outgrowth from a variety of neurons both in vitro and in vivo. Here, we show that MAG's sialic acid binding site is distinct from its neurite inhibitory activity. Alone, sialic acid-dependent binding of MAG to neurons is insufficient to effect inhibition of axonal growth. Thus, while soluble MAG-Fc (MAG extracellular domain fused to Fc), a truncated form of MAG-Fc missing Ig-domains 4 and 5, MAG(d1-3)-Fc, and another sialic acid binding protein, sialoadhesin, each bind to neurons in a sialic acid- dependent manner, only full-length MAG-Fc inhibits neurite outgrowth. These results suggest that a second site must exist on MAG which elicits this response. Consistent with this model, mutation of arginine 118 (R118) in MAG to either alanine or aspartate abolishes its sialic acid-dependent binding. However, when expressed at the surface of either CHO or Schwann cells, R118-mutated MAG retains the ability to inhibit axonal outgrowth. Hence, MAG has two recognition sites for neurons, the sialic acid binding site at R118 and a distinct inhibition site which is absent from the first three Ig domains.

  14. Myelin-associated Glycoprotein Interacts with Neurons via a Sialic Acid Binding Site at ARG118 and a Distinct Neurite Inhibition Site

    Science.gov (United States)

    Tang, Song; Shen, Ying Jing; DeBellard, Maria Elena; Mukhopadhyay, Gitali; Salzer, James L.; Crocker, Paul R.; Filbin, Marie T.

    1997-01-01

    Inhibitory components in myelin are largely responsible for the lack of regeneration in the mammalian CNS. Myelin-associated glycoprotein (MAG), a sialic acid binding protein and a component of myelin, is a potent inhibitor of neurite outgrowth from a variety of neurons both in vitro and in vivo. Here, we show that MAG's sialic acid binding site is distinct from its neurite inhibitory activity. Alone, sialic acid–dependent binding of MAG to neurons is insufficient to effect inhibition of axonal growth. Thus, while soluble MAG-Fc (MAG extracellular domain fused to Fc), a truncated form of MAG-Fc missing Ig-domains 4 and 5, MAG(d1-3)-Fc, and another sialic acid binding protein, sialoadhesin, each bind to neurons in a sialic acid– dependent manner, only full-length MAG-Fc inhibits neurite outgrowth. These results suggest that a second site must exist on MAG which elicits this response. Consistent with this model, mutation of arginine 118 (R118) in MAG to either alanine or aspartate abolishes its sialic acid–dependent binding. However, when expressed at the surface of either CHO or Schwann cells, R118-mutated MAG retains the ability to inhibit axonal outgrowth. Hence, MAG has two recognition sites for neurons, the sialic acid binding site at R118 and a distinct inhibition site which is absent from the first three Ig domains. PMID:9298990

  15. Neurite Aggregation and Calcium Dysfunction in iPSC-Derived Sensory Neurons with Parkinson's Disease-Related LRRK2 G2019S Mutation.

    Science.gov (United States)

    Schwab, Andrew J; Ebert, Allison D

    2015-12-08

    Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most-common genetic determinants of Parkinson's disease (PD). The G2019S mutation is detected most frequently and is associated with increased kinase activity. Whereas G2019S mutant dopamine neurons exhibit neurite elongation deficits, the effect of G2019S on other neuronal subtypes is unknown. As PD patients also suffer from non-motor symptoms that may be unrelated to dopamine neuron loss, we used induced pluripotent stem cells (iPSCs) to assess morphological and functional properties of peripheral sensory neurons. LRRK2 G2019S iPSC-derived sensory neurons exhibited normal neurite length but had large microtubule-containing neurite aggregations. Additionally, LRRK2 G2019S iPSC-derived sensory neurons displayed altered calcium dynamics. Treatment with LRRK2 kinase inhibitors resulted in significant, but not complete, morphological and functional rescue. These data indicate a role for LRRK2 kinase activity in sensory neuron structure and function, which when disrupted, may lead to sensory neuron deficits in PD. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  16. 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

  17. Dock6, a Dock-C subfamily guanine nucleotide exchanger, has the dual specificity for Rac1 and Cdc42 and regulates neurite outgrowth.

    Science.gov (United States)

    Miyamoto, Yuki; Yamauchi, Junji; Sanbe, Atsushi; Tanoue, Akito

    2007-02-15

    Small GTPases of the Rho family, Rho, Rac, and Cdc42, are critical regulators of the changes in the actin cytoskeleton. Rho GTPases are typically activated by Dbl-homology (DH)-domain-containing guanine nucleotide exchange factors (GEFs). Recent genetic and biochemical studies revealed a new type of GEF for the Rho GTPases. This family is composed of 11 genes, designated as Dock1 to Dock11, and is structurally divided into four classes Dock-A, -B, -C, and -D. Dock-A and -B subfamilies are typically GEFs specific for Rac1, while the Dock-D subfamily is specific for Cdc42. Here we show that Dock6, a member of the Dock-C subfamily, exchanges GDP for GTP for Rac1 and Cdc42 in vitro and in vivo. Furthermore, we find that, in mouse N1E-115 neuroblastoma cells, expression of Dock6 is increased following differentiation. Transfection of the catalytic Dock Homology Region-2 (DHR-2) domain of Dock6 promotes neurite outgrowth mediated by Rac1 and Cdc42. Conversely, knockdown of endogenous Dock6 by small interference RNA reduces activation of Rac1 and Cdc42 and neurite outgrowth. Taken together, these results suggest that Dock6 differs from all of the identified Dock180-related proteins, in that it is the GEF specific for both Rac1 and Cdc42 and may be one of physiological regulators of neurite outgrowth.

  18. Particle length-dependent titanium dioxide nanomaterials toxicity and bioactivity

    Directory of Open Access Journals (Sweden)

    Buford Mary

    2009-12-01

    Full Text Available Abstract Background Titanium dioxide (TiO2 nanomaterials have considerable beneficial uses as photocatalysts and solar cells. It has been established for many years that pigment-grade TiO2 (200 nm sphere is relatively inert when internalized into a biological model system (in vivo or in vitro. For this reason, TiO2 nanomaterials are considered an attractive alternative in applications where biological exposures will occur. Unfortunately, metal oxides on the nanoscale (one dimension Results TiO2 nanospheres, short ( 15 μm nanobelts were synthesized, characterized and tested for biological activity using primary murine alveolar macrophages and in vivo in mice. This study demonstrates that alteration of anatase TiO2 nanomaterial into a fibre structure of greater than 15 μm creates a highly toxic particle and initiates an inflammatory response by alveolar macrophages. These fibre-shaped nanomaterials induced inflammasome activation and release of inflammatory cytokines through a cathepsin B-mediated mechanism. Consequently, long TiO2 nanobelts interact with lung macrophages in a manner very similar to asbestos or silica. Conclusions These observations suggest that any modification of a nanomaterial, resulting in a wire, fibre, belt or tube, be tested for pathogenic potential. As this study demonstrates, toxicity and pathogenic potential change dramatically as the shape of the material is altered into one that a phagocytic cell has difficulty processing, resulting in lysosomal disruption.

  19. Length dependent potentiation in electrically stimulated human ankle dorsiflexor muscles

    NARCIS (Netherlands)

    Mela, P.; Veltink, P.H.; Huijing, P.A.J.B.M.

    2002-01-01

    The purpose of this study was to investigate the short-term history effect of a decreasing frequency train on force and the influence of joint angle on such effect in human dorsiflexor muscles. Six able-bodied and three spinal cord injured (SCI) subjects took part in the study. Their isometric left

  20. Concentration and length dependence of DNA looping in transcriptional regulation.

    Directory of Open Access Journals (Sweden)

    Lin Han

    2009-05-01

    Full Text Available In many cases, transcriptional regulation involves the binding of transcription factors at sites on the DNA that are not immediately adjacent to the promoter of interest. This action at a distance is often mediated by the formation of DNA loops: Binding at two or more sites on the DNA results in the formation of a loop, which can bring the transcription factor into the immediate neighborhood of the relevant promoter. These processes are important in settings ranging from the historic bacterial examples (bacterial metabolism and the lytic-lysogeny decision in bacteriophage, to the modern concept of gene regulation to regulatory processes central to pattern formation during development of multicellular organisms. Though there have been a variety of insights into the combinatorial aspects of transcriptional control, the mechanism of DNA looping as an agent of combinatorial control in both prokaryotes and eukaryotes remains unclear. We use single-molecule techniques to dissect DNA looping in the lac operon. In particular, we measure the propensity for DNA looping by the Lac repressor as a function of the concentration of repressor protein and as a function of the distance between repressor binding sites. As with earlier single-molecule studies, we find (at least two distinct looped states and demonstrate that the presence of these two states depends both upon the concentration of repressor protein and the distance between the two repressor binding sites. We find that loops form even at interoperator spacings considerably shorter than the DNA persistence length, without the intervention of any other proteins to prebend the DNA. The concentration measurements also permit us to use a simple statistical mechanical model of DNA loop formation to determine the free energy of DNA looping, or equivalently, the for looping.

  1. Particle length-dependent titanium dioxide nanomaterials toxicity and bioactivity.

    Science.gov (United States)

    Hamilton, Raymond F; Wu, Nianqiang; Porter, Dale; Buford, Mary; Wolfarth, Michael; Holian, Andrij

    2009-12-31

    Titanium dioxide (TiO(2)) nanomaterials have considerable beneficial uses as photocatalysts and solar cells. It has been established for many years that pigment-grade TiO(2 )(200 nm sphere) is relatively inert when internalized into a biological model system (in vivo or in vitro). For this reason, TiO(2 )nanomaterials are considered an attractive alternative in applications where biological exposures will occur. Unfortunately, metal oxides on the nanoscale (one dimension 15 mum) nanobelts were synthesized, characterized and tested for biological activity using primary murine alveolar macrophages and in vivo in mice. This study demonstrates that alteration of anatase TiO(2 )nanomaterial into a fibre structure of greater than 15 mum creates a highly toxic particle and initiates an inflammatory response by alveolar macrophages. These fibre-shaped nanomaterials induced inflammasome activation and release of inflammatory cytokines through a cathepsin B-mediated mechanism. Consequently, long TiO(2 )nanobelts interact with lung macrophages in a manner very similar to asbestos or silica. These observations suggest that any modification of a nanomaterial, resulting in a wire, fibre, belt or tube, be tested for pathogenic potential. As this study demonstrates, toxicity and pathogenic potential change dramatically as the shape of the material is altered into one that a phagocytic cell has difficulty processing, resulting in lysosomal disruption.

  2. Length dependence of active force production in skeletal muscle.

    Science.gov (United States)

    Rassier, D E; MacIntosh, B R; Herzog, W

    1999-05-01

    The sliding filament and cross-bridge theories of muscle contraction provide discrete predictions of the tetanic force-length relationship of skeletal muscle that have been tested experimentally. The active force generated by a maximally activated single fiber (with sarcomere length control) is maximal when the filament overlap is optimized and is proportionally decreased when overlap is diminished. The force-length relationship is a static property of skeletal muscle and, therefore, it does not predict the consequences of dynamic contractions. Changes in sarcomere length during muscle contraction result in modulation of the active force that is not necessarily predicted by the cross-bridge theory. The results of in vivo studies of the force-length relationship suggest that muscles that operate on the ascending limb of the force-length relationship typically function in stretch-shortening cycle contractions, and muscles that operate on the descending limb typically function in shorten-stretch cycle contractions. The joint moments produced by a muscle depend on the moment arm and the sarcomere length of the muscle. Moment arm magnitude also affects the excursion (length change) of a muscle for a given change in joint angle, and the number of sarcomeres arranged in series within a muscle fiber determines the sarcomere length change associated with a given excursion.

  3. Automated condition-invariable neurite segmentation and synapse classification using textural analysis-based machine-learning algorithms.

    Science.gov (United States)

    Kandaswamy, Umasankar; Rotman, Ziv; Watt, Dana; Schillebeeckx, Ian; Cavalli, Valeria; Klyachko, Vitaly A

    2013-02-15

    High-resolution live-cell imaging studies of neuronal structure and function are characterized by large variability in image acquisition conditions due to background and sample variations as well as low signal-to-noise ratio. The lack of automated image analysis tools that can be generalized for varying image acquisition conditions represents one of the main challenges in the field of biomedical image analysis. Specifically, segmentation of the axonal/dendritic arborizations in brightfield or fluorescence imaging studies is extremely labor-intensive and still performed mostly manually. Here we describe a fully automated machine-learning approach based on textural analysis algorithms for segmenting neuronal arborizations in high-resolution brightfield images of live cultured neurons. We compare performance of our algorithm to manual segmentation and show that it combines 90% accuracy, with similarly high levels of specificity and sensitivity. Moreover, the algorithm maintains high performance levels under a wide range of image acquisition conditions indicating that it is largely condition-invariable. We further describe an application of this algorithm to fully automated synapse localization and classification in fluorescence imaging studies based on synaptic activity. Textural analysis-based machine-learning approach thus offers a high performance condition-invariable tool for automated neurite segmentation. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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.

  7. Piperine-like alkamides from Piper nigrum induce BDNF promoter and promote neurite outgrowth in Neuro-2a cells.

    Science.gov (United States)

    Yun, Young Sook; Noda, Sachie; Takahashi, Shigeru; Takahashi, Yuji; Inoue, Hideshi

    2018-01-01

    Black pepper (Piper nigrum) contains a variety of alkamides. Among them, piperine has been reported to have antidepressant-like effects in chronically stressed mice, but little is known about the biological activity of other alkamides. In this study, we investigated the effects of alkamides from white pepper (P. nigrum) on neuronal cells. Twelve alkamides were isolated from white pepper MeOH extracts, and their chemical structures were identified by NMR and MS analyses. The compounds were subjected to assays using the luciferase-reporter gene under the control of the BDNF promoter or cAMP response element in mouse neuroblastoma Neuro-2a cells. In both assays, marked reporter-inducing activity was observed for piperine (1), piperettine (2) and piperylin (7), all of which have in common an (E)-5-(buta-1,3-dien-1-yl)benzo[d] [1, 3] dioxole moiety. Piperettine (2) and piperylin (7) tended to increase endogenous BDNF protein levels. Furthermore, piperylin (7) promoted retinoic acid-induced neurite outgrowth. These results suggest that piperylin (7), or analogues thereof, may have a beneficial effect on disorders associated with dysregulation of BDNF expression, such as depression.

  8. 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.

  9. Fine needle aspiration cytology as an aid to diagnosis, categorization and treatment when pure neuritic leprosy presents as nerve abscess

    Science.gov (United States)

    Kiran, C M; Menon, Roshni

    2013-01-01

    Background: Pure neuritic leprosy (PNL) usually presents with neurological symptoms without skin involvement. Fine needle aspiration can play an important role in the management of PNL cases presenting as nerve abscesses. Aim: To assess the role of fine needle aspiration cytology (FNAC) in diagnosing and categorizing PNL cases presenting as nerve abscesses in the absence of neurological symptoms. Materials and Methods: Five patients with subcutaneous nerve related swellings without clinically evident neurological deficits were subjected to FNAC. As the cytological features were suggestive of nerve abscesses due to leprosy, Fite stain was performed in all cases. As none of the patients had any leprosy skin lesions, they were diagnosed as cases of PNL. Features like cellularity, caseous necrosis, presence or absence of lymphocytes, macrophages, epithelioid cells, granulomas, Langhans giant cells and nerve elements were analyzed with the bacteriological index, to categorize PNL according to the Ridley-Jopling classification. Results: Based on the cytological features and bacteriological indices, 3 cases were cytologically categorized into tuberculoid (TT)/borderline tuberculoid (BT) leprosy and the other two, as BT/borderline lepromatous (BL) and BL leprosy respectively in spite of having similar clinical presentation. Based on the cytological diagnoses, category-specific treatment could be instituted with clinical improvement. Conclusions: The simple and minimally invasive FNAC procedure allows diagnosis and a reasonably accurate categorization of PNL presenting as nerve abscess and therefore, highly useful in its clinical management. PMID:24648666

  10. Neurite Sprouting and Synapse Deterioration in the Aging C. elegans Nervous System

    Science.gov (United States)

    Toth, Marton; 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

    2012-01-01

    C. 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 dimunition 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. PMID:22745480

  11. Manganese As a Metal Accumulator

    Science.gov (United States)

    Manganese deposits in water distribution systems accumulate metals, radionuclides and oxyanions by a combination of surface complexation, adsorption and solid substitution, as well as a combination of oxidation followed by manganese reduction and sorption of the oxidized constitu...

  12. Evidence accumulation for spatial reasoning

    Science.gov (United States)

    Matsuyama, T.; Hwang, V. S. S.; Davis, L. S.

    1984-01-01

    The evidence accumulation proces of an image understanding system is described enabling the system to perform top-down(goal-oriented) picture processing as well as bottom-up verification of consistent spatial relations among objects.

  13. Inhibition of nerve growth factor-induced neurite outgrowth from PC12 cells by dexamethasone: signaling pathways through the glucocorticoid receptor and phosphorylated Akt and ERK1/2.

    Directory of Open Access Journals (Sweden)

    Kazuki Terada

    Full Text Available Glucocorticoids are important mediators of the stress response and are commonly employed as drugs for the suppression of immune rejection after organ transplantation. Previous investigations uncovered the possibility of mood depression in patients undergoing long-term treatment with synthetic glucocorticoids, including dexamethasone (DEX. Exogenous glucocorticoids and their synthetic derivatives can also adversely affect the development of the central nervous system. Although neurite extension from rat pheochromocytoma-derived PC12 cells and a variety of primary neurons is stimulated by nerve growth factor (NGF, and signaling pathways triggered by the binding of NGF to tyrosine kinase receptor type 1 (TrkA function in both neurite outgrowth and neuronal survival, the effect of DEX on the activation of regulatory proteins and pathways downstream of TrkA has not been well characterized. To analyze the influence of DEX on NGF-induced neurite outgrowth and signaling, PC12 cells, a widely utilized model of neuronal differentiation, were pretreated with the glucocorticoid prior to NGF induction. NGF-induced neurite outgrowth was attenuated by pretreatment with DEX, even in the absence of DEX after the addition of NGF. Moreover, DEX suppressed the phosphorylation of Akt and extracellular-regulated kinase 1/2 (ERK1/2 in the neurite outgrowth signaling cascade initiated by NGF. Finally, the glucocorticoid receptor (GR antagonist, RU38486, counteracted the inhibitory effect of DEX pretreatment, not only on the phosphorylation of Akt and ERK1/2, but also on neurite extension from PC12 cells. These results suggest that DEX binding to the GR impairs NGF-promoted neurite outgrowth by interfering with the activation/phosphorylation of Akt and ERK1/2. These novel findings are likely to be useful for elucidating the central nervous system depressive mechanism(s of action of DEX and other glucocorticoids.

  14. Inhibition of nerve growth factor-induced neurite outgrowth from PC12 cells by dexamethasone: signaling pathways through the glucocorticoid receptor and phosphorylated Akt and ERK1/2.

    Science.gov (United States)

    Terada, Kazuki; Kojima, Yoshitsugu; Watanabe, Takayuki; Izumo, Nobuo; Chiba, Koji; Karube, Yoshiharu

    2014-01-01

    Glucocorticoids are important mediators of the stress response and are commonly employed as drugs for the suppression of immune rejection after organ transplantation. Previous investigations uncovered the possibility of mood depression in patients undergoing long-term treatment with synthetic glucocorticoids, including dexamethasone (DEX). Exogenous glucocorticoids and their synthetic derivatives can also adversely affect the development of the central nervous system. Although neurite extension from rat pheochromocytoma-derived PC12 cells and a variety of primary neurons is stimulated by nerve growth factor (NGF), and signaling pathways triggered by the binding of NGF to tyrosine kinase receptor type 1 (TrkA) function in both neurite outgrowth and neuronal survival, the effect of DEX on the activation of regulatory proteins and pathways downstream of TrkA has not been well characterized. To analyze the influence of DEX on NGF-induced neurite outgrowth and signaling, PC12 cells, a widely utilized model of neuronal differentiation, were pretreated with the glucocorticoid prior to NGF induction. NGF-induced neurite outgrowth was attenuated by pretreatment with DEX, even in the absence of DEX after the addition of NGF. Moreover, DEX suppressed the phosphorylation of Akt and extracellular-regulated kinase 1/2 (ERK1/2) in the neurite outgrowth signaling cascade initiated by NGF. Finally, the glucocorticoid receptor (GR) antagonist, RU38486, counteracted the inhibitory effect of DEX pretreatment, not only on the phosphorylation of Akt and ERK1/2, but also on neurite extension from PC12 cells. These results suggest that DEX binding to the GR impairs NGF-promoted neurite outgrowth by interfering with the activation/phosphorylation of Akt and ERK1/2. These novel findings are likely to be useful for elucidating the central nervous system depressive mechanism(s) of action of DEX and other glucocorticoids.

  15. Double-Edge Sword of Sustained ROCK Activation in Prion Diseases through Neuritogenesis Defects and Prion Accumulation.

    Science.gov (United States)

    Alleaume-Butaux, Aurélie; Nicot, Simon; Pietri, Mathéa; Baudry, Anne; Dakowski, Caroline; Tixador, Philippe; Ardila-Osorio, Hector; Haeberlé, Anne-Marie; Bailly, Yannick; Peyrin, Jean-Michel; Launay, Jean-Marie; Kellermann, Odile; Schneider, Benoit

    2015-08-01

    In prion diseases, synapse dysfunction, axon retraction and loss of neuronal polarity precede neuronal death. The mechanisms driving such polarization defects, however, remain unclear. Here, we examined the contribution of RhoA-associated coiled-coil containing kinases (ROCK), key players in neuritogenesis, to prion diseases. We found that overactivation of ROCK signaling occurred in neuronal stem cells infected by pathogenic prions (PrPSc) and impaired the sprouting of neurites. In reconstructed networks of mature neurons, PrPSc-induced ROCK overactivation provoked synapse disconnection and dendrite/axon degeneration. This overactivation of ROCK also disturbed overall neurotransmitter-associated functions. Importantly, we demonstrated that beyond its impact on neuronal polarity ROCK overactivity favored the production of PrPSc through a ROCK-dependent control of 3-phosphoinositide-dependent kinase 1 (PDK1) activity. In non-infectious conditions, ROCK and PDK1 associated within a complex and ROCK phosphorylated PDK1, conferring basal activity to PDK1. In prion-infected neurons, exacerbated ROCK activity increased the pool of PDK1 molecules physically interacting with and phosphorylated by ROCK. ROCK-induced PDK1 overstimulation then canceled the neuroprotective α-cleavage of normal cellular prion protein PrPC by TACE α-secretase, which physiologically precludes PrPSc production. In prion-infected cells, inhibition of ROCK rescued neurite sprouting, preserved neuronal architecture, restored neuronal functions and reduced the amount of PrPSc. In mice challenged with prions, inhibition of ROCK also lowered brain PrPSc accumulation, reduced motor impairment and extended survival. We conclude that ROCK overactivation exerts a double detrimental effect in prion diseases by altering neuronal polarity and triggering PrPSc accumulation. Eventually ROCK emerges as therapeutic target to combat prion diseases.

  16. Double-Edge Sword of Sustained ROCK Activation in Prion Diseases through Neuritogenesis Defects and Prion Accumulation.

    Directory of Open Access Journals (Sweden)

    Aurélie Alleaume-Butaux

    2015-08-01

    Full Text Available In prion diseases, synapse dysfunction, axon retraction and loss of neuronal polarity precede neuronal death. The mechanisms driving such polarization defects, however, remain unclear. Here, we examined the contribution of RhoA-associated coiled-coil containing kinases (ROCK, key players in neuritogenesis, to prion diseases. We found that overactivation of ROCK signaling occurred in neuronal stem cells infected by pathogenic prions (PrPSc and impaired the sprouting of neurites. In reconstructed networks of mature neurons, PrPSc-induced ROCK overactivation provoked synapse disconnection and dendrite/axon degeneration. This overactivation of ROCK also disturbed overall neurotransmitter-associated functions. Importantly, we demonstrated that beyond its impact on neuronal polarity ROCK overactivity favored the production of PrPSc through a ROCK-dependent control of 3-phosphoinositide-dependent kinase 1 (PDK1 activity. In non-infectious conditions, ROCK and PDK1 associated within a complex and ROCK phosphorylated PDK1, conferring basal activity to PDK1. In prion-infected neurons, exacerbated ROCK activity increased the pool of PDK1 molecules physically interacting with and phosphorylated by ROCK. ROCK-induced PDK1 overstimulation then canceled the neuroprotective α-cleavage of normal cellular prion protein PrPC by TACE α-secretase, which physiologically precludes PrPSc production. In prion-infected cells, inhibition of ROCK rescued neurite sprouting, preserved neuronal architecture, restored neuronal functions and reduced the amount of PrPSc. In mice challenged with prions, inhibition of ROCK also lowered brain PrPSc accumulation, reduced motor impairment and extended survival. We conclude that ROCK overactivation exerts a double detrimental effect in prion diseases by altering neuronal polarity and triggering PrPSc accumulation. Eventually ROCK emerges as therapeutic target to combat prion diseases.

  17. High speed nanofluidic protein accumulator.

    Science.gov (United States)

    Wu, Dapeng; Steckl, Andrew J

    2009-07-07

    Highly efficient preconcentration is a crucial prerequisite to the identification of important protein biomarkers with extremely low abundance in target biofluids. In this work, poly(dimethylsiloxane) microchips integrated with 10 nm polycarbonate nanopore membranes were utilized as high-speed protein accumulators. Double-sided injection control of electrokinetic fluid flow in the sample channel resulted in highly localized protein accumulation at a very sharp point in the channel cross point. This greatly enhanced the ability to detect very low levels of initial protein concentration. Fluorescein labeled human serum albumin solutions of 30 and 300 pM accumulated to 3 and 30 microM in only 100 s. Initial solutions as low as 0.3 and 3 pM could be concentrated within 200 s to 0.3 and 3 microM, respectively. This demonstrates a approximately 10(5)-10(6) accumulation factor, and an accumulation rate as high as 5000/sec, yielding a >10x improvement over most results reported to date.

  18. The all-trans retinoic acid (atRA)-regulated gene Calmin (Clmn) regulates cell cycle exit and neurite outgrowth in murine neuroblastoma (Neuro2a) cells

    Energy Technology Data Exchange (ETDEWEB)

    Marzinke, Mark A. [Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706-1544 (United States); Clagett-Dame, Margaret, E-mail: dame@biochem.wisc.edu [Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706-1544 (United States); Pharmaceutical Science Division, University of Wisconsin-Madison, Madison, WI 53705-2222 (United States)

    2012-01-01

    The vitamin A metabolite all-trans retinoic acid (atRA) functions in nervous system development and regulates cell proliferation and differentiation. Neuroblastoma cells (SH-SY5Y and Neuro2a or N2A) exposed to atRA undergo growth inhibition and neuronal differentiation, both of which are preceded by an increase in Clmn mRNA. Treatment of N2A cells with atRA produces a reduction in phosphohistone 3 immunostaining and BrdU incorporation, both indicators of a reduction in cell proliferation. These effects are nearly eliminated in atRA-treated shClmn knockdown cells. Loss of Clmn in the mouse N2A cell line also results in a significant reduction of atRA-mediated neurite outgrowth, a response that can be rescued by reintroduction of the Clmn sequence. In contrast, ectopic overexpression of Clmn produces an increase in the cyclin dependent kinase inhibitor, p21{sup Cip1}, a decrease in cyclin D1 protein and an increase in hypophosphorylated Rb, showing that Clmn participates in G{sub 1}/S arrest. Clmn overexpression alone is sufficient to inhibit N2A cell proliferation, whereas both Clmn and atRA must be present to induce neurite outgrowth. This study shows that the atRA-responsive gene Clmn promotes exit from the cell cycle, a requisite event for neuronal differentiation. -- Highlights: Black-Right-Pointing-Pointer Calmin is a retinoic acid-responsive gene. Black-Right-Pointing-Pointer Calmin promotes cell cycle exit in N2A cells. Black-Right-Pointing-Pointer Calmin overexpression increases p21Cip1 and decreases cyclin D1. Black-Right-Pointing-Pointer Calmin is required for RA-induced growth inhibition and neurite outgrowth.

  19. 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.

  20. CD11b+GR1+ Myeloid Cells Secrete NGF and Promote Trigeminal Ganglion Neurite Growth: Implications for Corneal Nerve Regeneration

    Science.gov (United States)

    Sarkar, Joy; Chaudhary, Shweta; Jassim, Sarmad H.; Ozturk, Okan; Chamon, Wallace; Ganesh, Balaji; Tibrewal, Sapna; Gandhi, Sonal; Byun, Yong-Soo; Hallak, Joelle; Mahmud, Dolores L.; Mahmud, Nadim; Rondelli, Damiano; Jain, Sandeep

    2013-01-01

    Purpose. We characterized fluorescent bone marrow cells (YFP+ BMCs) in the thy1-YFP mouse and determine if they promote trigeminal ganglion (TG) cell neurite growth. Methods. Excimer laser annular keratectomy was performed in thy1-YFP mice, and corneas were imaged. BMCs were harvested from femur and tibia, and the expression of surface markers on YFP+ BMCs was analyzed by flow cytometry. The immunosuppressive action of BMCs (YFP+ and YFP−) was evaluated in an allogenic mixed lymphocyte reaction (MLR). Neurotrophic action of BMCs (YFP+ and YFP−) was determined in compartmental and transwell cultures of dissociated TG cells. Results. Following annular keratectomy, YFP+ BMCs infiltrated the cornea. YFP+ BMCs shared surface markers (CD11b+Gr1+Ly6C+Ly6G-F4/80low) with monocytic myeloid-derived suppressor cells (MDSCs), had similar morphology, and suppressed T-cell proliferation in allogenic MLR in a dose-dependent manner. YFP+ BMCs, but not YFP− BMCs, significantly increased growth of TG neurites in vitro. When cultured in a transwell with TG neurites, YFP+ BMCs expressed neurotrophins and secreted nerve growth factor (NGF) in conditioned medium. YFP+ BMCs that infiltrated the cornea maintained their phenotype and actions (neuronal and immune). Conclusions. YFP+ BMCs in thy1-YFP mice have immunophenotypic features of MDSCs. They secrete NGF and promote neuroregeneration. Their immunosuppressive and neurotrophic actions are preserved after corneal infiltration. These findings increase our understanding of the beneficial roles played by leukocyte trafficking in the cornea and may lead to therapeutic strategies that use NGF-secreting myeloid cells to repair diseased or injured neurons. PMID:23942970

  1. Surface Microstructures on Planar Substrates and Textile Fibers Guide Neurite Outgrowth: A Scaffold Solution to Push Limits of Critical Nerve Defect Regeneration?

    Science.gov (United States)

    Weigel, Stefan; Tobler, Ursina; Yao, Li; Wiesli, Manuel; Lehnert, Thomas; Pandit, Abhay; Bruinink, Arie

    2012-01-01

    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. PMID:23251379

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

    Directory of Open Access Journals (Sweden)

    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.

  3. The proinflammatory cytokine, interleukin-17A, augments mitochondrial function and neurite outgrowth of cultured adult sensory neurons derived from normal and diabetic rats.

    Science.gov (United States)

    Habash, Tarek; Saleh, Ali; Roy Chowdhury, Subir K; Smith, Darrell R; Fernyhough, Paul

    2015-11-01

    Diabetic neuropathy comprises dying back of nerve endings that reflects impairment in axonal plasticity and regenerative nerve growth. Metabolic changes in diabetes can lead to a dysregulation of hormonal mediators, such as cytokines, that may constrain distal nerve fiber growth. Interleukin-17 (IL-17A), a proinflammatory and neurotropic cytokine produced by T-cells, was significantly reduced in sciatic nerve of streptozotocin (STZ)-diabetic rats. Thus we studied the effect of IL-17A on the phenotype of sensory neurons derived from age matched control or type 1 diabetic rats. The aims were to determine the ability of IL-17A to enhance neurite outgrowth in cultured sensory neurons, investigate the signaling pathways activated by IL-17A, study the role of mitochondria and mechanistically link to neurite outgrowth. IL-17A (10 ng/ml; psensory neurons derived from both control and streptozotocin (STZ)-diabetic rats. This enhancement was mediated by IL-17A-dependent activation of extracellular-regulated protein kinase (ERK) and phosphoinositide-3 kinase (PI-3K) signal transduction pathways. Pharmacological blockade of one of these activated pathways triggered complete inhibition of neurite outgrowth. IL-17A augmented mitochondrial bioenergetic function of sensory neurons derived from control or diabetic rats and this was also mediated via ERK or PI-3K. IL-17A-dependent elevation of bioenergetic function was associated with augmented expression of proteins of the mitochondrial electron transport system complexes. IL-17A enhanced axonal plasticity through activation of ERK and PI-3K pathways and was associated with augmented mitochondrial bioenergetic function in sensory neurons. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. An NCAM-derived FGF-receptor agonist, the FGL-peptide, induces neurite outgrowth and neuronal survival in primary rat neurons

    DEFF Research Database (Denmark)

    Neiiendam, Johanne Louise; Køhler, Lene Boding; Christensen, Claus

    2004-01-01

    factor receptor (FGFR). NCAM-mediated adhesion leads to activation of various intracellular signal transduction pathways, including the Ras-mitogen activated protein kinase (MAPK) and the phosphatidylinositol-3-kinase (PI3K)-Akt pathways. A synthetic peptide derived from the second fibronectin type III...... of the FGL peptide are shown to depend on activation of FGFR and the MAPK and PI3K intracellular signalling pathways, all three kinases being necessary for the effects of FGL on neurite outgrowth and neuronal survival....

  5. 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

  6. Lipiodol Accumulation in Hepatic Hemangioma

    Energy Technology Data Exchange (ETDEWEB)

    Chun, Ki Sung; Park, Jeong Mi; Ha, Hyun Kwon; Shinn, Kyung Sub; Bahk, Yong Whee; Shim, Kyu Sik [Catholic University College of Medicine, Seoul (Korea, Republic of)

    1989-04-15

    In order to establish different features of hemangioma, lipiodol was superselectively infused in three cases of hepatic hemangioma through the proper or a distal branch hepatic artery following hepatic angiogram. Thereafter a plain X-ray of the abdomen and CT were obtained. The present study revealed accumulation of lipiodol within abnormal vascular space of hemangioma to be multiple, stippled, dense and discrete. Follow-up plain abdomen and CT (6 months, 8 months, and 9 months, respectively) demonstrated very slow clearing of lipiodol accumulation without change in size. These findings are considered to be pathognomonic of hemangioma.

  7. (17) ACCUMULATION OF HEAVY METAL

    African Journals Online (AJOL)

    Adeyinka Odunsi

    The mean metal content of cassava leaf indicated that all the metals were higher in the leaf at high ... components of petroleum hydrocarbons ..... Atmos. Environ. 40: 5929-5941. Onder, S., Dursun, S., Gezgin, S. and. Demirbas, A. (2007). Determination. Accumulation of heavy metal pollutants on soil microbial population.

  8. 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.

  9. 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.

  10. 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.

  11. Neurite growth acceleration of adult Dorsal Root Ganglion neurons illuminated by low-level Light Emitting Diode light at 645 nm.

    Science.gov (United States)

    Burland, Marion; Paris, Lambert; Quintana, Patrice; Bec, Jean-Michel; Diouloufet, Lucie; Sar, Chamroeun; Boukhaddaoui, Hassan; Charlot, Benoit; Braga Silva, Jefferson; Chammas, Michel; Sieso, Victor; Valmier, Jean; Bardin, Fabrice

    2015-06-01

    The effect of a 645 nm Light Emitting Diode (LED) light irradiation on the neurite growth velocity of adult Dorsal Root Ganglion (DRG) neurons with peripheral axon injury 4-10 days before plating and without previous injury was investigated. The real amount of light reaching the neurons was calculated by taking into account the optical characteristics of the light source and of media in the light path. The knowledge of these parameters is essential to be able to compare results of the literature and a way to reduce inconsistencies. We found that 4 min irradiation of a mean irradiance of 11.3 mW/cm(2) (corresponding to an actual irradiance reaching the neurons of 83 mW/cm(2)) induced a 1.6-fold neurite growth acceleration on non-injured neurons and on axotomized neurons. Although the axotomized neurons were naturally already in a rapid regeneration process, an enhancement was found to occur while irradiating with the LED light, which may be promising for therapy applications. Dorsal Root Ganglion neurons (A) without previous injury and (B) subjected to a conditioning injury. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Distinctive effect on nerve growth factor-induced PC12 cell neurite outgrowth by two unique neolignan enantiomers from Illicium merrillianum

    Science.gov (United States)

    Tian, Xinhui; Yue, Rongcai; Zeng, Huawu; Li, Honglin; Shan, Lei; He, Weiwei; Shen, Yunheng; Zhang, Weidong

    2015-11-01

    Merrillianoid (1), a racemic neolignan possessing the characteristic benzo-2,7-dioxabicyclo[3.2.1]octane moiety, was isolated from the branches and leaves of Illicium merrillianum. Chiral separation of 1 gave two enantiomers (+)-1 and (-)-1. The structure of 1 was established by comprehensive spectroscopic analysis and single crystal X-ray diffraction. The absolute configurations of enantiomers were determined by quantum mechanical calculation. Compound (+)-1 exhibited a better neurotrophic activity than racemate 1 by promoting nerve growth factor (NGF) induced PC12 cell neurite outgrowth, while (-)-1 showed a distinctive inhibitory effect. Furthermore, a mechanism study indicated that the two enantiomers influenced NGF-induced neurite outgrowth of PC12 cells possibly by interacting with the trkA receptor, and extracellular signal regulated kinases 1/2 (ERK1/2) and mitogen-activated protein kinase (MEK) in Ras/ERK signal cascade. But the phosphorylation level of serine/threonine kinase Akt1 and Akt2 in PI3K/Akt signal pathway showed no significant difference between (+)-1 and (-)-1.

  13. Traffic-related air pollution impact on mouse brain accelerates myelin and neuritic aging changes with specificity for CA1 neurons.

    Science.gov (United States)

    Woodward, Nicholas C; Pakbin, Payam; Saffari, Arian; Shirmohammadi, Farimah; Haghani, Amin; Sioutas, Constantinos; Cacciottolo, Mafalda; Morgan, Todd E; Finch, Caleb E

    2017-05-01

    Traffic-related air pollution (TRAP) is associated with lower cognition and reduced white matter volume in older adults, specifically for particulate matter age differences of TRAP exposure, with focus on hippocampus for neuritic atrophy, white matter degeneration, and microglial activation. Young- and middle-aged mice (3 and 18 months female C57BL/6J) were exposed to nanoscale-PM (nPM, changes in the hippocampal CA1 region, with neurite atrophy (-25%), decreased MBP (-50%), and increased Iba1 (+50%), with dentate gyrus relatively unaffected. Exposure to nPM of young mice decreased GluA1 protein (-40%) and increased TNFa mRNA (10×). Older controls had age changes approximating nPM effects on young, with no response to nPM, suggesting an age-ceiling effect. The CA1 selective vulnerability in young mice parallels CA1 vulnerability in Alzheimer's disease. We propose that TRAP-associated human cognitive and white matter changes involve hippocampal responses to nPM that begin at younger ages. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Metal accumulating plants: Medium's role

    Science.gov (United States)

    Rabier, J.; Prudent, P.; Szymanska, B.; Mevy, J.-P.

    2003-05-01

    To evaluate phytoremediation potentialities by metal accumulation in tolerant plants, trials are carried out using in vitro cultures. Organie compounds influence on metal accumulation is studied with metals supplemented media. The tested compounds on zinc and lead absorption by Brassica juncea, are chelating agents (EDTA, citric acid) and soluble organic fractions of compost. EDTA seems to enhance the transfer of lead in plant but it is the opposite in the case of zinc. Citric acid stimulates root absorption for both zinc and lead. For the aqueous extracts of compost, variable effects are obtained according to the origin of compost (green wastes and food wastes). In'all tested conditions of cultures, zinc is mainly exported towards shoot while lead is stored in root.

  15. Growth-dependent and species-specific accumulation of polychlorinated biphenyls (PCBs) in tidal flat organisms collected from the Ariake Sea, Japan.

    Science.gov (United States)

    Nakata, H; Sakai, Y; Miyawaki, T

    2002-02-01

    The growth-related as well as species-specific accumulation of polychlorinated biphenyls (PCBs) was studied for tidal flat organisms collected from the Ariake Sea, western Japan. Elevated concentrations of PCBs were found in omnivore fishes, followed in decreasing order by crabs, herbivore fishes, and mussels. This revealed that trophic levels play an important role in PCB accumulation in these organisms. Age- and body length-dependent accumulations of PCBs were observed in herbivorous mudskippers, although a large range of concentrations was found in similar growth stage of fishes. High correlations have been found between concentrations and body length rather than age, which may indicate that the growth rate, which is strongly influenced by the feeding rate of diets, seems to be the predominant factor in determining PCB accumulation. Besides, based on PCB levels in eggs and the whole body in herbivore fishes, the transfer rate of PCBs was estimated to be approximately 10% of female body burdens. Comparison of PCB compositions between eggs and whole body suggests the selective transfer of lower-chlorinated congeners to eggs, which may be due to their instantaneous periods to achieve steady state between egg and whole body lipids. The relationship between BSAFs (biota-sediment accumulation factors) in organisms and log Kow revealed that omnivore mudskipper significantly accumulated PCBs in their body, which might be due to their greater feeding rate and/or higher trophic status in the tidal flat environment.

  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

    Directory of Open Access Journals (Sweden)

    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. Botanical drug puerarin coordinates with nerve growth factor in the regulation of neuronal survival and neuritogenesis via activating ERK1/2 and PI3K/Akt signaling pathways in the neurite extension process.

    Science.gov (United States)

    Zhao, Jia; Cheng, Yuan-Yuan; Fan, Wen; Yang, Chuan-Bin; Ye, Shui-Fen; Cui, Wei; Wei, Wei; Lao, Li-Xing; Cai, Jing; Han, Yi-Fan; Rong, Jian-Hui

    2015-01-01

    Nerve growth factor (NGF) regulates neuronal survival and differentiation by activating extracellular signal-regulated-kinases (ERK) 1/2 and phosphoinositide-3-kinase (PI3K)/Akt pathways in two distinct processes: latency process and neurite extension process. This study was designed to investigate whether botanical drug C-glucosylated isoflavone puerarin coordinates with NGF to regulate neuritogenesis via activating ERK1/2 and PI3K/Akt in neurite extension process. We investigated the neuroprotective and neurotrophic activities of puerarin in MPTP-lesioned mice and dopaminergic PC12 cells. The effects of puerarin on ERK1/2, Akt, Nrf2, and HO-1 were assessed by Western blotting. The neurite outgrowth was assayed by neurite outgrowth staining kit. Puerarin protected dopaminergic cells and ameliorated the behavioral impairments in MPTP-lesioned mice. Puerarin potentiated the effect of NGF on neuritogenesis in PC12 cells by >10-fold. Mechanistic studies revealed: (1) puerarin rapidly activated ERK1/2 and Akt, leading to the activation of Nrf2/heme oxygenase-1 (HO-1) pathways; (2) ERK1/2, PI3K/Akt, and HO-1 inhibitors attenuated the neuritogenic activity of puerarin. Notably, puerarin enhanced NGF-induced neuritogenesis in a timing-dependent manner. Puerarin effectively coordinated with NGF to stimulate neuritogenesis via activating ERK1/2 and PI3K/Akt pathways in neurite extension process. These results demonstrated a general mechanism supporting the therapeutic application of puerarin-related compounds in neurodegenerative diseases. © 2014 John Wiley & Sons Ltd.

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

    Science.gov (United States)

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

    2013-01-01

    In the injured adult mammalian central nervous system (CNS), products are generated that inhibit neuronal sprouting and regeneration. In recent years, most attention has focused on the myelin-associated inhibitory proteins (MAIs) Nogo-A, OMgp, and myelin-associated glycoprotein (MAG). Binding of MAIs to neuronal cell-surface receptors leads to activation of RhoA, growth cone collapse, and neurite outgrowth inhibition. In the present study, we identify low-density lipoprotein (LDL) receptor-related protein-1 (LRP1) as a high-affinity, endocytic receptor for MAG. In contrast with previously identified MAG receptors, binding of MAG to LRP1 occurs independently of terminal sialic acids. In primary neurons, functional inactivation of LRP1 with receptor-associated protein, depletion by RNA interference (RNAi) knock-down, or LRP1 gene deletion is sufficient to significantly reverse MAG and myelin-mediated inhibition of neurite outgrowth. Similar results are observed when LRP1 is antagonized in PC12 and N2a cells. By contrast, inhibiting LRP1 does not attenuate inhibition of neurite outgrowth caused by chondroitin sulfate proteoglycans. Mechanistic studies in N2a cells showed that LRP1 and p75NTR associate in a MAG-dependent manner and that MAG-mediated activation of RhoA may involve both LRP1 and p75NTR. LRP1 derivatives that include the complement-like repeat clusters CII and CIV bind MAG and other MAIs. When CII and CIV were expressed as Fc-fusion proteins, these proteins, purified full-length LRP1 and shed LRP1 all attenuated the inhibition of neurite outgrowth caused by MAG and CNS myelin in primary neurons. Collectively, our studies identify LRP1 as a novel MAG receptor that functions in neurite outgrowth inhibition.

  19. 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......Neurotrophic factors are secreted proteins responsible for migration, growth and survival of neurons during development, and for maintenance and plasticity of adult neurons. Here we present a novel secreted protein named Cometin which together with Meteorin defines a new evolutionary conserved...... protein family. During early mouse development, Cometin is found exclusively in the floor plate and from E13.5 also in dorsal root ganglions and inner ear but apparently not in the adult nervous system. In vitro, Cometin promotes neurite outgrowth from dorsal root ganglion cells which can be blocked...

  20. Type I bHLH Proteins Daughterless and Tcf4 Restrict Neurite Branching and Synapse Formation by Repressing Neurexin in Postmitotic Neurons

    Directory of Open Access Journals (Sweden)

    Mitchell D’Rozario

    2016-04-01

    Full Text Available Proneural proteins of the class I/II basic-helix-loop-helix (bHLH family are highly conserved transcription factors. Class I bHLH proteins are expressed in a broad number of tissues during development, whereas class II bHLH protein expression is more tissue restricted. Our understanding of the function of class I/II bHLH transcription factors in both invertebrate and vertebrate neurobiology is largely focused on their function as regulators of neurogenesis. Here, we show that the class I bHLH proteins Daughterless and Tcf4 are expressed in postmitotic neurons in Drosophila melanogaster and mice, respectively, where they function to restrict neurite branching and synapse formation. Our data indicate that Daughterless performs this function in part by restricting the expression of the cell adhesion molecule Neurexin. This suggests a role for these proteins outside of their established roles in neurogenesis.

  1. Astrocyte-to-neuron communication through integrin-engaged Thy-1/CBP/Csk/Src complex triggers neurite retraction via the RhoA/ROCK pathway.

    Science.gov (United States)

    Maldonado, H; Calderon, C; Burgos-Bravo, F; Kobler, O; Zuschratter, W; Ramirez, O; Härtel, S; Schneider, P; Quest, A F G; Herrera-Molina, R; Leyton, L

    2017-02-01

    Two key proteins for cellular communication between astrocytes and neurons are αvβ3 integrin and the receptor Thy-1. Binding of these molecules in the same (cis) or on adjacent (trans) cellular membranes induces Thy-1 clustering, triggering actin cytoskeleton remodeling. Molecular events that could explain how the Thy-1-αvβ3 integrin interaction signals have only been studied separately in different cell types, and the detailed transcellular communication and signal transduction pathways involved in neuronal cytoskeleton remodeling remain unresolved. Using biochemical and genetic approaches, single-molecule tracking, and high-resolution nanoscopy, we provide evidence that upon binding to αvβ3 integrin, Thy-1 mobility decreased while Thy-1 nanocluster size increased. This occurred concomitantly with inactivation and exclusion of the non-receptor tyrosine kinase Src from the Thy-1/C-terminal Src kinase (Csk)-binding protein (CBP)/Csk complex. The Src inactivation decreased the p190Rho GTPase activating protein phosphorylation, promoting RhoA activation, cofilin, and myosin light chain II phosphorylation and, consequently, neurite shortening. Finally, silencing the adaptor CBP demonstrated that this protein was a key transducer in the Thy-1 signaling cascade. In conclusion, these data support the hypothesis that the Thy-1-CBP-Csk-Src-RhoA-ROCK axis transmitted signals from astrocytic integrin-engaged Thy-1 (trans) to the neuronal actin cytoskeleton. Importantly, the β3 integrin in neurons (cis) was not found to be crucial for neurite shortening. This is the first study to detail the signaling pathway triggered by αvβ3, the endogenous Thy-1 ligand, highlighting the role of membrane-bound integrins as trans acting ligands in astrocyte-neuron communication. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. A Novel Small Molecule GDNF Receptor RET Agonist, BT13, Promotes Neurite Growth from Sensory Neurons in Vitro and Attenuates Experimental Neuropathy in the Rat

    Directory of Open Access Journals (Sweden)

    Yulia A. Sidorova

    2017-06-01

    Full Text Available Neuropathic pain caused by nerve damage is a common and severe class of chronic pain. Disease-modifying clinical therapies are needed as current treatments typically provide only symptomatic relief; show varying clinical efficacy; and most have significant adverse effects. One approach is targeting either neurotrophic factors or their receptors that normalize sensory neuron function and stimulate regeneration after nerve damage. Two candidate targets are glial cell line-derived neurotrophic factor (GDNF and artemin (ARTN, as these GDNF family ligands (GFLs show efficacy in animal models of neuropathic pain (Boucher et al., 2000; Gardell et al., 2003; Wang et al., 2008, 2014. As these protein ligands have poor drug-like properties and are expensive to produce for clinical use, we screened 18,400 drug-like compounds to develop small molecules that act similarly to GFLs (GDNF mimetics. This screening identified BT13 as a compound that selectively targeted GFL receptor RET to activate downstream signaling cascades. BT13 was similar to NGF and ARTN in selectively promoting neurite outgrowth from the peptidergic class of adult sensory neurons in culture, but was opposite to ARTN in causing neurite elongation without affecting initiation. When administered after spinal nerve ligation in a rat model of neuropathic pain, 20 and 25 mg/kg of BT13 decreased mechanical hypersensitivity and normalized expression of sensory neuron markers in dorsal root ganglia. In control rats, BT13 had no effect on baseline mechanical or thermal sensitivity, motor coordination, or weight gain. Thus, small molecule BT13 selectively activates RET and offers opportunities for developing novel disease-modifying medications to treat neuropathic pain.

  3. Extracellular vesicles from a muscle cell line (C2C12 enhance cell survival and neurite outgrowth of a motor neuron cell line (NSC-34

    Directory of Open Access Journals (Sweden)

    Roger D. Madison

    2014-02-01

    Full Text Available Introduction: There is renewed interest in extracellular vesicles over the past decade or 2 after initially being thought of as simple cellular garbage cans to rid cells of unwanted components. Although there has been intense research into the role of extracellular vesicles in the fields of tumour and stem cell biology, the possible role of extracellular vesicles in nerve regeneration is just in its infancy. Background: When a peripheral nerve is damaged, the communication between spinal cord motor neurons and their target muscles is disrupted and the result can be the loss of coordinated muscle movement. Despite state-of-the-art surgical procedures only approximately 10% of adults will recover full function after peripheral nerve repair. To improve upon such results will require a better understanding of the basic mechanisms that influence axon outgrowth and the interplay between the parent motor neuron and the distal end organ of muscle. It has previously been shown that extracellular vesicles are immunologically tolerated, display targeting ligands on their surface, and can be delivered in vivo to selected cell populations. All of these characteristics suggest that extracellular vesicles could play a significant role in nerve regeneration. Methods: We have carried out studies using 2 very well characterized cell lines, the C2C12 muscle cell line and the motor neuron cell line NSC-34 to ask the question: Do extracellular vesicles from muscle influence cell survival and/or neurite outgrowth of motor neurons? Conclusion: Our results show striking effects of extracellular vesicles derived from the muscle cell line on the motor neuron cell line in terms of neurite outgrowth and survival.

  4. Upregulation of reggie-1/flotillin-2 promotes axon regeneration in the rat optic nerve in vivo and neurite growth in vitro.

    Science.gov (United States)

    Koch, Jan C; Solis, Gonzalo P; Bodrikov, Vsevolod; Michel, Uwe; Haralampieva, Deana; Shypitsyna, Aleksandra; Tönges, Lars; Bähr, Mathias; Lingor, Paul; Stuermer, Claudia A O

    2013-03-01

    The ability of fish retinal ganglion cells (RGCs) to regenerate their axons was shown to require the re-expression and function of the two proteins reggie-1 and -2. RGCs in mammals fail to upregulate reggie expression and to regenerate axons after lesion suggesting the possibility that induced upregulation might promote regeneration. In the present study, RGCs in adult rats were induced to express reggie-1 by intravitreal injection of adeno-associated viral vectors (AAV2/1) expressing reggie-1 (AAV.R1-EGFP) 14d prior to optic nerve crush. Four weeks later, GAP-43-positive regenerating axons had crossed the lesion and grown into the nerve at significantly higher numbers and length (up to 5mm) than the control transduced with AAV.EGFP. Consistently, after transduction with AAV.R1-EGFP as opposed to AAV.EGFP, primary RGCs in vitro grew long axons on chondroitin sulfate proteoglycan (CSPG) and Nogo-A, both glial cell-derived inhibitors of neurite growth, suggesting that reggie-1 can provide neurons with the ability to override inhibitors of neurite growth. This reggie-1-mediated enhancement of growth was reproduced in mouse hippocampal and N2a neurons which generated axons 40-60% longer than their control counterparts. This correlates with the reggie-1-dependent activation of Src and PI3 kinase (PI3K), of the Rho family GTPase Rac1 and downstream effectors such as cofilin. This increased growth also depends on TC10, the GTPase involved in cargo delivery to the growth cone. Thus, the upregulation of reggie-1 in mammalian neurons provides nerve cells with neuron-intrinsic properties required for axon growth and successful regeneration in the adult mammalian CNS. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. 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.

  6. Extracellular vesicles from a muscle cell line (C2C12) enhance cell survival and neurite outgrowth of a motor neuron cell line (NSC-34).

    Science.gov (United States)

    Madison, Roger D; McGee, Christopher; Rawson, Renee; Robinson, Grant A

    2014-01-01

    There is renewed interest in extracellular vesicles over the past decade or 2 after initially being thought of as simple cellular garbage cans to rid cells of unwanted components. Although there has been intense research into the role of extracellular vesicles in the fields of tumour and stem cell biology, the possible role of extracellular vesicles in nerve regeneration is just in its infancy. When a peripheral nerve is damaged, the communication between spinal cord motor neurons and their target muscles is disrupted and the result can be the loss of coordinated muscle movement. Despite state-of-the-art surgical procedures only approximately 10% of adults will recover full function after peripheral nerve repair. To improve upon such results will require a better understanding of the basic mechanisms that influence axon outgrowth and the interplay between the parent motor neuron and the distal end organ of muscle. It has previously been shown that extracellular vesicles are immunologically tolerated, display targeting ligands on their surface, and can be delivered in vivo to selected cell populations. All of these characteristics suggest that extracellular vesicles could play a significant role in nerve regeneration. We have carried out studies using 2 very well characterized cell lines, the C2C12 muscle cell line and the motor neuron cell line NSC-34 to ask the question: Do extracellular vesicles from muscle influence cell survival and/or neurite outgrowth of motor neurons? Our results show striking effects of extracellular vesicles derived from the muscle cell line on the motor neuron cell line in terms of neurite outgrowth and survival.

  7. Biota-Sediment Accumulation Factor Data

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Biota-Sediment Accumulation Factor contains approximately 20,000 biota-sediment accumulation factors (BSAFs) from 20 locations (mostly Superfund sites) for...

  8. 47 CFR 32.3100 - Accumulated depreciation.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Accumulated depreciation. 32.3100 Section 32... Accumulated depreciation. (a) This account shall include the accumulated depreciation associated with the... with depreciation amounts concurrently charged to Account 6561, Depreciation expense—telecommunications...

  9. Markov models for accumulating mutations

    CERN Document Server

    Beerenwinkel, Niko

    2007-01-01

    We introduce and analyze a waiting time model for the accumulation of genetic changes. The continuous time conjunctive Bayesian network is defined by a partially ordered set of mutations and by the rate of fixation of each mutation. The partial order encodes constraints on the order in which mutations can fixate in the population, shedding light on the mutational pathways underlying the evolutionary process. We study a censored version of the model and derive equations for an EM algorithm to perform maximum likelihood estimation of the model parameters. We also show how to select the maximum likelihood poset. The model is applied to genetic data from different cancers and from drug resistant HIV samples, indicating implications for diagnosis and treatment.

  10. Electron-Positron Accumulator (EPA)

    CERN Multimedia

    Photographic Service

    1986-01-01

    After acceleration in the low-current linac LIL-W, the electrons and positrons are accumulated in EPA to obtain a sufficient intensity and a suitable time-structure, before being passed on to the PS for further acceleration to 3.5 GeV. Electrons circulate from right to left, positrons in the other direction. Dipole bending magnets are red, focusing quadrupoles blue, sextupoles for chromaticity-control orange. The vertical tube at the left of the picture belongs to an optical transport system carrying the synchrotron radiation to detectors for beam size measurement. Construction of EPA was completed in spring 1986. LIL-W and EPA were conceived for an energy of 600 MeV, but operation was limited to 500 MeV.

  11. Accumulation of uranium by biopigments

    Energy Technology Data Exchange (ETDEWEB)

    Sakaguchi, Takashi; Nakajima, Akira

    1987-01-01

    The uranium adsorbing abilities of various biopigments were investigated. Extremely high adsorption capacities for uranium were found in melanin and bioflavonols (quercetin and morin) having chelating positions with uranium. As a step towards improving the adsorption characteristics of the bioflavonols, quercetin and morin were immobilized on both Bemberg rayon fiber and polyaminostyrene, and the basic features of uranium adsorption by the immobilized bioflavonols were studied. The bioflavonols immobilized on Bemberg rayon fiber have a highly selective capacity to adsorb uranium. Uranium recovery from seawater by the immobilized bioflavonols was markedly affected by the pH value of the seawater, and the uptake at pH 8, which is the pH value of natural seawater, was difficult. However, this adsorbent can accumulate large amounts of uranium from non-saline water. Thus it can be used to remove and recover uranium from uranium refining waste water and other waste sources.

  12. APP expression, distribution and accumulation are altered by aluminum in a rodent model for Alzheimer's disease.

    Science.gov (United States)

    Walton, J R; Wang, M-X

    2009-11-01

    Up-regulated expression of amyloid precursor protein (APP) occurs early in the cascade of events that leads to amyloid plaque formation in the human brain. APP gene up-regulation, mediated by activated NF-kappaB, is a response to stress from nM concentrations of aluminum ions, aluminum-disregulated iron ions, reactive-oxygen species, cytokines, and physical trauma. We examined in vivo effects of aluminum on APP in aged rats, obtained from previously-reported longitudinal studies, that chronically ingested aluminum in amounts equivalent to total dietary aluminum levels that Americans routinely ingest. These rats exhibited two outcomes: one group remained cognitively-intact, scoring as well on a memory-discrimination task in old age as in middle age. The other developed cognitive deterioration, obtaining significantly lower mean performance scores in old age than in middle age and exhibiting abnormal behaviors associated with dementia. We compared the expression, distribution and accumulation of APP in hippocampal and cortical tissue of these two rat groups. Compared to results from cognitively-intact rats, hippocampal and cortical tissue from the cognitively-deteriorated rats showed elevated APP gene expression, significantly more dense APP deposits in cytoplasm of neural cells, and APP-immunoreactive neurites that were swollen and varicose. This study shows aluminum routinely derived from chronic oral ingestion, that gradually accumulates in brain regions important for memory-processing, is sufficient to increase APP levels in neural cells of those regions. Aluminum may thus launch the cascade that results in the formation of amyloid plaques in human brain.

  13. ACCUMULATION AND CONSUMPTION IN MICROECONOMIC SYSTEM

    Directory of Open Access Journals (Sweden)

    Serghey A. Amelkin

    2004-12-01

    Full Text Available Two main processes are common for an economic system. They are consumption and accumulation. The first one is described by utility function, either cardinal or ordinal one. The mathematical model for accumulation process can be constructed using wealth function introduced within the frame of irreversible microeconomics. Characteristics of utility and wealth functions are compared and a problem of extreme performance of resources exchange process is solved for a case when both the consumption and accumulation exist.

  14. Renewable Resources, Capital Accumulation, and Economic Growth

    National Research Council Canada - National Science Library

    Zhang, Wei-Bin

    2011-01-01

    .... Different from most of the neoclassical growth models with renewable resources which are based on microeconomic foundation and neglect physical capital accumulation, this study proposes a growth...

  15. 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.

  16. Iron Chelators and Antioxidants Regenerate Neuritic Tree and Nigrostriatal Fibers of MPP+/MPTP-Lesioned Dopaminergic Neurons.

    Directory of Open Access Journals (Sweden)

    Pabla Aguirre

    Full Text Available Neuronal death in Parkinson's disease (PD is often preceded by axodendritic tree retraction and loss of neuronal functionality. The presence of non-functional but live neurons opens therapeutic possibilities to recover functionality before clinical symptoms develop. Considering that iron accumulation and oxidative damage are conditions commonly found in PD, we tested the possible neuritogenic effects of iron chelators and antioxidant agents. We used three commercial chelators: DFO, deferiprone and 2.2'-dypyridyl, and three 8-hydroxyquinoline-based iron chelators: M30, 7MH and 7DH, and we evaluated their effects in vitro using a mesencephalic cell culture treated with the Parkinsonian toxin MPP+ and in vivo using the MPTP mouse model. All chelators tested promoted the emergence of new tyrosine hydroxylase (TH-positive processes, increased axodendritic tree length and protected cells against lipoperoxidation. Chelator treatment resulted in the generation of processes containing the presynaptic marker synaptophysin. The antioxidants N-acetylcysteine and dymetylthiourea also enhanced axodendritic tree recovery in vitro, an indication that reducing oxidative tone fosters neuritogenesis in MPP+-damaged neurons. Oral administration to mice of the M30 chelator for 14 days after MPTP treatment resulted in increased TH- and GIRK2-positive nigra cells and nigrostriatal fibers. Our results support a role for oral iron chelators as good candidates for the early treatment of PD, at stages of the disease where there is axodendritic tree retraction without neuronal death.

  17. Charge accumulation in lossy dielectrics: a review

    DEFF Research Database (Denmark)

    Rasmussen, Jørgen Knøster; McAllister, Iain Wilson; Crichton, George C

    1999-01-01

    such that the material parameters which influence charge accumulation are clearly identified; viz. the conductivity, permittivity and dimensions of the insulating media. The two former parameters, together with the applied voltage, govern both the magnitude and polarity of the accumulated charge....

  18. Functionalized Collagen Scaffold Neutralizing the Myelin-Inhibitory Molecules Promoted Neurites Outgrowth in Vitro and Facilitated Spinal Cord Regeneration in Vivo.

    Science.gov (United States)

    Li, Xing; Han, Jin; Zhao, Yannan; Ding, Wenyong; Wei, Jianshu; Han, Sufang; Shang, Xianping; Wang, Bin; Chen, Bing; Xiao, Zhifeng; Dai, Jianwu

    2015-07-01

    Research has demonstrated that many myelin-associated inhibitory molecules jointly contribute to the failure of adult spinal cord regeneration. Therapies comprehensively targeting the multiple inhibitory nature of the injured spinal cord are being concerned. Here, two collagen-binding proteins, CBD-EphA4LBD and CBD-PlexinB1LBD, were constructed, respectively, to neutralize the axon guidance molecules ephrinB3 and sema4D that inhibit the regeneration of nerve fibers. The two neutralizing proteins have proven their ability to specifically bind collagen and to continuously release from collagen scaffolds. They could also promote neurites outgrowth of cerebellar granular neurons and dorsal root ganglion neurons in vitro. Subsequently, the functionalized collagen scaffolds by physically absorbing NEP1-40 and immobilizing CBD-EphA4LBD and CBD-PlexinB1LBD were transplanted into a rat T10 complete spinal cord transection model. Our results showed that rats that received the treatment of transplanting the functionalized collagen scaffold exhibited great advantage on axonal regeneration and locomotion recovery after spinal cord injury.

  19. Development of a cell permeable competitive antagonist of RhoA and CRMP4 binding, TAT-C4RIP, to promote neurite outgrowth.

    Science.gov (United States)

    Khazaei, Mohammad R; Montcalm, Samuel; Di Polo, Adriana; Fournier, Alyson E; Durocher, Yves; Ong Tone, Stephan

    2015-02-01

    Neurons fail to re-extend their processes within the central nervous system environment in vivo, and this is partly because of inhibitory proteins expressed within myelin debris and reactive astrocytes that actively signal to the injured nerve cells to limit their growth. The ability of the trans-acting activator of transcription (TAT) protein transduction domain (PTD) to transport macromolecules across biological membranes raises the possibility of developing it as a therapeutic delivery tool for nerve regeneration. Most studies have produced TAT PTD fusion protein in bacteria, which can result in problems such as protein solubility, the formation of inclusion bodies and the lack of eukaryotic posttranslational modifications. While some groups have investigated the production of TAT PTD fusion protein in mammalian cells, these strategies are focused on generating TAT PTD fusions that are targeted to the secretory pathway, where furin protease as well as other proteases can cleave the TAT PTD. As an alternative to mutating the furin cleavage site in the TAT PTD, we describe a novel method to generate cytosolic TAT PTD fusion proteins and purify them from cell lysates. Here, we use this method to generate TAT-C4RIP, a cell permeable competitive antagonist of binding between the small GTPase RhoA and the cytosolic phosphoprotein Collapsin response mediator protein 4 (CRMP4). We demonstrate that TAT-C4RIP transduces cells in vitro and in vivo and retains its biological activity to attenuate myelin inhibition in an in vitro neurite outgrowth assay.

  20. Pure neuritic leprosy: Resolving diagnostic issues in acid fast bacilli (AFB)-negative nerve biopsies: A single centre experience from South India.

    Science.gov (United States)

    Hui, Monalisa; Uppin, Megha S; Challa, Sundaram; Meena, A K; Kaul, Subhash

    2015-01-01

    Demonstration of lepra bacilli is essential for definite or unequivocal diagnosis of pure neuritic leprosy (PNL) on nerve biopsy. However, nerves always do not show bacilli owing to the changes of previous therapy or due to low bacillary load in tuberculoid forms. In absence of granuloma or lepra bacilli, other morphologic changes in endoneurium and perineurium can be of help in making a probable diagnosis of PNL and treating the patient with multidrug therapy. Forty-six biopsies of PNL were retrospectively reviewed and histologic findings were compared with 25 biopsies of non leprosy neuropathies (NLN) including vasculitic neuropathy and chronic inflammatory demyelinating polyneuropathy (CIDP). The distribution of endoneurial infiltrate and fibrosis, perineurial thickening, and myelin abnormalities were compared between PNL and NLN biopsies and analyzed by Chi-square test. Out of 46 PNL casses, 24 (52.17 %) biopsies were negative for acid fast bacilli (AFB). In these cases, the features which favor a diagnosis of AFB-negative PNL were endoneurial infiltrate (51.1%), endoneurial fibrosis (54.2%), perineurial thickening (70.8%), and reduced number of myelinated nerve fibers (75%). Nerve biopsy is an efficient tool to diagnose PNL and differentiate it from other causes of NLN. In absence of AFB, the diagnosis of PNL is challenging. In this article, we have satisfactorily evaluated the various hisopthological features and found that endoneurial inflammation, dense fibrosis, and reduction in the number of myelinated nerve fibers are strong supportive indicators of PNL regardless of AFB positivity.

  1. IMPACT is a developmentally regulated protein in neurons that opposes the eukaryotic initiation factor 2α kinase GCN2 in the modulation of neurite outgrowth.

    Science.gov (United States)

    Roffé, Martín; Hajj, Glaucia N M; Azevedo, Hátylas F; Alves, Viviane S; Castilho, Beatriz A

    2013-04-12

    The product of the mouse Imprinted and Ancient gene, IMPACT, is preferentially expressed in neurons. We have previously shown that IMPACT overexpression inhibits the activation of the protein kinase GCN2, which signals amino acid starvation. GCN2 phosphorylates the α-subunit of eukaryotic translation initiation factor 2 (eIF2α), resulting in inhibition of general protein synthesis but increased translation of specific messages, such as ATF4. GCN2 is also involved in the regulation of neuronal functions, controlling synaptic plasticity, memory, and feeding behavior. We show here that IMPACT abundance increases during differentiation of neurons and neuron-like N2a cells, whereas GCN2 displays lowered activation levels. Upon differentiation, IMPACT associates with translating ribosomes, enhances translation initiation, and down-regulates the expression of ATF4. We further show that endogenous IMPACT promotes neurite outgrowth whereas GCN2 is a strong inhibitor of spontaneous neuritogenesis. Together, these results uncover the participation of the GCN2-IMPACT module of translational regulation in a highly controlled step in the development of the nervous system.

  2. IMPACT Is a Developmentally Regulated Protein in Neurons That Opposes the Eukaryotic Initiation Factor 2α Kinase GCN2 in the modulation of Neurite Outgrowth*

    Science.gov (United States)

    Roffé, Martín; Hajj, Glaucia N. M.; Azevedo, Hátylas F.; Alves, Viviane S.; Castilho, Beatriz A.

    2013-01-01

    The product of the mouse Imprinted and Ancient gene, IMPACT, is preferentially expressed in neurons. We have previously shown that IMPACT overexpression inhibits the activation of the protein kinase GCN2, which signals amino acid starvation. GCN2 phosphorylates the α-subunit of eukaryotic translation initiation factor 2 (eIF2α), resulting in inhibition of general protein synthesis but increased translation of specific messages, such as ATF4. GCN2 is also involved in the regulation of neuronal functions, controlling synaptic plasticity, memory, and feeding behavior. We show here that IMPACT abundance increases during differentiation of neurons and neuron-like N2a cells, whereas GCN2 displays lowered activation levels. Upon differentiation, IMPACT associates with translating ribosomes, enhances translation initiation, and down-regulates the expression of ATF4. We further show that endogenous IMPACT promotes neurite outgrowth whereas GCN2 is a strong inhibitor of spontaneous neuritogenesis. Together, these results uncover the participation of the GCN2-IMPACT module of translational regulation in a highly controlled step in the development of the nervous system. PMID:23447528

  3. Aflatoxin Accumulation in a Maize Diallel Cross

    Directory of Open Access Journals (Sweden)

    W. Paul Williams

    2015-06-01

    Full Text Available Aflatoxins, produced by the fungus Aspergillus flavus, occur naturally in maize. Contamination of maize grain with aflatoxin is a major food and feed safety problem and greatly reduces the value of the grain. Plant resistance is generally considered a highly desirable approach to reduction or elimination of aflatoxin in maize grain. In this investigation, a diallel cross was produced by crossing 10 inbred lines with varying degrees of resistance to aflatoxin accumulation in all possible combinations. Three lines that previously developed and released as sources of resistance to aflatoxin accumulation were included as parents. The 10 parental inbred lines and the 45 single crosses making up the diallel cross were evaluated for aflatoxin accumulation in field tests conducted in 2013 and 2014. Plants were inoculated with an A. flavus spore suspension seven days after silk emergence. Ears were harvested approximately 60 days later and concentration of aflatoxin in the grain determined. Parental inbred lines Mp717, Mp313E, and Mp719 exhibited low levels (3–12 ng/g of aflatoxin accumulation. In the diallel analysis, both general and specific combining ability were significant sources of variation in the inheritance of resistance to aflatoxin accumulation. General combining ability effects for reduced aflatoxin accumulation were greatest for Mp494, Mp719, and Mp717. These lines should be especially useful in breeding for resistance to aflatoxin accumulation. Breeding strategies, such as reciprocal recurrent selection, would be appropriate.

  4. Electrical and thermal spin accumulation in germanium

    Science.gov (United States)

    Jain, A.; Vergnaud, C.; Peiro, J.; Le Breton, J. C.; Prestat, E.; Louahadj, L.; Portemont, C.; Ducruet, C.; Baltz, V.; Marty, A.; Barski, A.; Bayle-Guillemaud, P.; Vila, L.; Attané, J.-P.; Augendre, E.; Jaffrès, H.; George, J.-M.; Jamet, M.

    2012-07-01

    In this letter, we first show electrical spin injection in the germanium conduction band at room temperature and modulate the spin signal by applying a gate voltage to the channel. The corresponding signal modulation agrees well with the predictions of spin diffusion models. Then, by setting a temperature gradient between germanium and the ferromagnet, we create a thermal spin accumulation in germanium without any charge current. We show that temperature gradients yield larger spin accumulations than electrical spin injection but, due to competing microscopic effects, the thermal spin accumulation remains surprisingly unchanged under the application of a gate voltage.

  5. Manganese accumulation in the brain: MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Uchino, A.; Nomiyama, K.; Takase, Y.; Nakazono, T.; Nojiri, J.; Kudo, S. [Saga Medical School, Department of Radiology, Saga (Japan); Noguchi, T. [Kyushu University, Department of Clinical Radiology, Graduate School of Medicine, Fukuoka (Japan)

    2007-09-15

    Manganese (Mn) accumulation in the brain is detected as symmetrical high signal intensity in the globus pallidi on T1-weighted MR images without an abnormal signal on T2-weighted images. In this review, we present several cases of Mn accumulation in the brain due to acquired or congenital diseases of the abdomen including hepatic cirrhosis with a portosystemic shunt, congenital biliary atresia, primary biliary cirrhosis, congenital intrahepatic portosystemic shunt without liver dysfunction, Rendu-Osler-Weber syndrome with a diffuse intrahepatic portosystemic shunt, and patent ductus venosus. Other causes of Mn accumulation in the brain are Mn overload from total parenteral nutrition and welding-related Mn intoxication. (orig.)

  6. Microbial accumulation of uranium, radium, and cesium

    Energy Technology Data Exchange (ETDEWEB)

    Strandberg, G.W.; Shumate, S.E. II; Parrott, J.R. Jr.; North, S.E.

    1981-05-01

    Diverse microbial species varied considerably in their ability to accumulate uranium, cesium, and radium. Mechanistic differences in uranium uptake by Saccharomyces cerevisiae and Pseudomonas aeruginosa were indicated. S. serevisiae exhibited a slow (hours) surface accumulation of uranium which was subject to environmental factors, while P. aeruginosa accumulated uranium rapidly (minutes) as dense intracellular deposits and did not appear to be affected by environmental parameters. Metabolism was not required for uranium uptake by either organism. Cesium and radium were concentrated to a considerably lesser extent than uranium by the several species tested.

  7. 46 CFR 58.30-25 - Accumulators.

    Science.gov (United States)

    2010-10-01

    ... pressure vessel in which energy is stored under high pressure in the form of a gas or a gas and hydraulic... result in contamination of the hydraulic fluid and loss of gas through absorption. (c) Each accumulator...

  8. INDUSTRIAL HYDRAULIC ACCUMULATORS AND APPLICATION CIRCUITS

    Directory of Open Access Journals (Sweden)

    Mustafa GÖLCÜ

    2002-01-01

    Full Text Available Important developments in industrial hydraulic technologies extended their application areas including big power transmission systems. Efficient and powerful systems have been developed using sensitive control units. However, it is necessary to provide safe operating working conditions since some systems can not work properly in some situations. For instance, lack of the fluid in the system or leakage of the fluid from the system may cause serious damage in the circuit. When the pressure reaches the high levels, instantaneous shock strokes may also occur. Hydraulic accumulators are used to prevent such kind of problems. In this study, types of accumulators used in hydraulic circuits are introduced and necessary formulas for selection of the accumulators are presented with an example. The usage of accumulators in different circuits is shown with figures.

  9. Rock bed heat accumulators. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Riaz, M.

    1977-12-01

    The principal objectives of the research program on rock bed heat accumulators (or RBHA) are: (1) to investigate the technical and economic feasibility of storing large amounts of thermal energy (in the tens of MWt range) at high temperature (up to 500/sup 0/C) over extended periods of time (up to 6 months) using native earth or rock materials; (2) to conduct studies to establish the performance characteristics of large rock bed heat accumulators at various power and temperature levels compatible with thermal conversion systems; and (3) to assess the materials and environmental problems associated with the operation of such large heat accumulators. Results of the study indicate that rock bed heat accumulators for seasonal storage are both technically and economically feasible, and hence could be exploited in various applications in which storage plays an essential role such as solar power and total energy systems, district and cogeneration heating systems.

  10. Tear film MMP accumulation and corneal disease

    OpenAIRE

    Smith, V; Rishmawi, H; Hussein, H; Easty, D

    2001-01-01

    BACKGROUND/AIMS—Matrix metalloproteinases (MMPs) accumulate in the tears of patients with active peripheral ulcerative keratitis (PUK) but it is unknown whether these enzymes have a central role in disease progression. The aims of the present investigation were to determine the source of these enzymes and to ascertain whether their accumulation in tears is a phenomenon specific to PUK or a general feature of other anterior segment diseases.
METHODS—The experimental samples were obtained from ...

  11. Land Accumulation Dynamics in Developing Country Agriculture

    OpenAIRE

    Henderson, Heath; Corral, Leonardo; Simning, Eric; Winters, Paul

    2014-01-01

    Understanding land accumulation dynamics is relevant for policy makers interested in the economic effects of land inequality in developing country agriculture. We thus explore and simultaneously test the leading theories of microlevel land accumulation dynamics using unique panel data from Paraguay. The results suggest that farm growth varies systematically with farm size --a formal rejection of stochasticgrowth theories (that is, Gibrat's Law)-- and that titled land area may have considerabl...

  12. Caracterização etiológica e clínica das neurites ópticas infecciosas Etiological and clinical characteristics of infectious optic neuritis

    Directory of Open Access Journals (Sweden)

    Marco Aurélio Lana-Peixoto

    1997-06-01

    Full Text Available As neurites ópticas infecciosas (NOI foram estudadas em relação aos aspectos etiológicos, epidemiológicos e clínicos, com o intuito de detectar características que possam diferencia-las das neurites ópticas desmielinizantes (NOD, que apresentam nítida tendência para conversão em esclerose múltipla. Entre 105 casos de NOI, 51 não apresentavam qualquer evidência de envolvimento da coróide ou retina e poderiam ser confundidos com NOD. Envolvimento bilateral foi encontrado em 23 pacientes (45,1%, sendo simultâneo em 18 (78,3% casos. A relação entre sexos foi 2M: IF. As idades variaram ente 1 a 82 anos, com mediana de 34,8 anos. Um terço dos pacientes tinha idades até 20 anos, e em um terço dos pacientes as idades eram igual ou maior que 50 anos. Sífilis foi encontrada em 19 pacientes sendo a causa mais comum das NOI, enquanto infecções virais diversas foram responsabilizadas em 41,2%. A acuidade visual foi gravemente afetada na maioria dos casos, sendo pior que 20/200 em 57,3% dos olhos acometidos. Distúrbios da visão cromática foram encontrados em 91,8%, enquanto o exame do campo visual revelou anormalidades em 92,6% dos olhos, predominando os defeitos centrais (40,7%. O disco óptico estava anormal em 90,5% dos olhos examinados, sendo atrofia óptica o principal achado fundoscópico. O presente estudo demonstra que a maior tendência a bilateralidade e simultaneidade das NOI, sua maior prevalência no sexo masculino, na infância e em adultos após os 50 anos de idade, assim como a maior severidade do comprometimento das funções visuais diferem substancialmente das características relatadas nas NOD. O conhecimento destas diferenças pode auxiliar na diferente abordagem terapêutica e prognostica das duas distintas condições.Fifty-one patients with infectious optic neuritis (ION with no associated choroidal or retinal involvement were studied in relation to the etiologic agents, and to the epidemiological and

  13. Sodium accumulation in Atriplex. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Norton, J.A.; Caldwell, M.M.; Richardson, S.G.

    1984-09-01

    This study was undertaken to determine the ecological significance and the significance to arid land reclamation of sodium accumulation and nonaccumulation in Atriplex. There was a continuum in the genetic tendency of Atriplex canescens to accumulate sodium, from populations which accumulated almost no sodium to populations which accumulated up to 7% in the leaves. There were also substantial differences in sodium uptake between populations of A. tridentata, A. falcata and A. gardneri, with some populations having less than 0.1% leaf sodium and other populations having up to 5 or 6%. In three experiments (a field study, a greenhouse pot study and a hydroponics study) there were no significant differences in salinity tolerance between sodium accumulating and nonaccumulating A. canescens: both genotypes were highly salt tolerant. There was a significant buildup of sodium in the soil beneath sodium accumulating Atriplex plants, both in natural populations and on revegetated oil shale study plots. The sodium buildup was not sufficient to be detrimental to the growth or establishment of most herbaceous species, but with older Atriplex plants or with more saline soil, the buildup could potentially be detrimental. 14 references, 42 figures, 3 tables.

  14. Altered neurite morphology and cholinergic function of induced pluripotent stem cell-derived neurons from a patient with Kleefstra syndrome and autism

    Science.gov (United States)

    Nagy, J; Kobolák, J; Berzsenyi, S; Ábrahám, Z; Avci, H X; Bock, I; Bekes, Z; Hodoscsek, B; Chandrasekaran, A; Téglási, A; Dezső, P; Koványi, B; Vörös, E T; Fodor, L; Szél, T; Németh, K; Balázs, A; Dinnyés, A; Lendvai, B; Lévay, G; Román, V

    2017-01-01

    The aim of the present study was to establish an in vitro Kleefstra syndrome (KS) disease model using the human induced pluripotent stem cell (hiPSC) technology. Previously, an autism spectrum disorder (ASD) patient with Kleefstra syndrome (KS-ASD) carrying a deleterious premature termination codon mutation in the EHMT1 gene was identified. Patient specific hiPSCs generated from peripheral blood mononuclear cells of the KS-ASD patient were differentiated into post-mitotic cortical neurons. Lower levels of EHMT1 mRNA as well as protein expression were confirmed in these cells. Morphological analysis on neuronal cells differentiated from the KS-ASD patient-derived hiPSC clones showed significantly shorter neurites and reduced arborization compared to cells generated from healthy controls. Moreover, density of dendritic protrusions of neuronal cells derived from KS-ASD hiPSCs was lower than that of control cells. Synaptic connections and spontaneous neuronal activity measured by live cell calcium imaging could be detected after 5 weeks of differentiation, when KS-ASD cells exhibited higher sensitivity of calcium responses to acetylcholine stimulation indicating a lower nicotinic cholinergic tone at baseline condition in KS-ASD cells. In addition, gene expression profiling of differentiated neuronal cells from the KS-ASD patient revealed higher expression of proliferation-related genes and lower mRNA levels of genes involved in neuronal maturation and migration. Our data demonstrate anomalous neuronal morphology, functional activity and gene expression in KS-ASD patient-specific hiPSC-derived neuronal cultures, which offers an in vitro system that contributes to a better understanding of KS and potentially other neurodevelopmental disorders including ASD. PMID:28742076

  15. Scorpion venom heat-resistant peptide (SVHRP) enhances neurogenesis and neurite outgrowth of immature neurons in adult mice by up-regulating brain-derived neurotrophic factor (BDNF).

    Science.gov (United States)

    Wang, Tao; Wang, Shi-Wei; Zhang, Yue; Wu, Xue-Fei; Peng, Yan; Cao, Zhen; Ge, Bi-Ying; Wang, Xi; Wu, Qiong; Lin, Jin-Tao; Zhang, Wan-Qin; Li, Shao; Zhao, Jie

    2014-01-01

    Scorpion venom heat-resistant peptide (SVHRP) is a component purified from Buthus martensii Karsch scorpion venom. Although scorpions and their venom have been used in Traditional Chinese Medicine (TCM) to treat chronic neurological disorders, the underlying mechanisms of these treatments remain unknown. We applied SVHRP in vitro and in vivo to understand its effects on the neurogenesis and maturation of adult immature neurons and explore associated molecular mechanisms. SVHRP administration increased the number of 5-bromo-2'-dexoxyuridine (BrdU)-positive cells, BrdU-positive/neuron-specific nuclear protein (NeuN)-positive neurons, and polysialylated-neural cell adhesion molecule (PSA-NCAM)-positive immature neurons in the subventricular zone (SVZ) and subgranular zone (SGZ) of hippocampus. Furthermore immature neurons incubated with SVHRP-pretreated astrocyte-conditioned medium exhibited significantly increased neurite length compared with those incubated with normal astrocyte-conditioned medium. This neurotrophic effect was further confirmed in vivo by detecting an increased average single area and whole area of immature neurons in the SGZ, SVZ and olfactory bulb (OB) in the adult mouse brain. In contrast to normal astrocyte-conditioned medium, higher concentrations of brain-derived neurotrophic factor (BDNF) but not nerve growth factor (NGF) or glial cell line-derived neurotrophic factor (GDNF) was detected in the conditioned medium of SVHRP-pretreated astrocytes, and blocking BDNF using anti-BDNF antibodies eliminated these SVHRP-dependent neurotrophic effects. In SVHRP treated mouse brain, more glial fibrillary acidic protein (GFAP)-positive cells were detected. Furthermore, immunohistochemistry revealed increased numbers of GFAP/BDNF double-positive cells, which agrees with the observed changes in the culture system. This paper describes novel effects of scorpion venom-originated peptide on the stem cells and suggests the potential therapeutic values of SVHRP.

  16. Rostro-caudal maturation of glial cells in the accessory olfactory system during development: involvement in outgrowth of GnRH neurites.

    Science.gov (United States)

    Geller, Sarah; Lomet, Didier; Caraty, Alain; Tillet, Yves; Duittoz, Anne; Vaudin, Pascal

    2017-10-03

    During mammalian embryonic development, GnRH neurones differentiate from the nasal placode and migrate through the nasal septum towards the forebrain. We previously showed that a category of glial cells, the olfactory ensheathing cells (OEC), forms the microenvironment of migrating GnRH neurones. Here, to characterize the quantitative and qualitative importance of this glial, we investigated the spatiotemporal maturation of glial cells in situ and the role of maturing glia in GnRH neurones development ex vivo. More than 90% of migrating GnRH neurones were found to be associated with glial cells. There was no change in the cellular microenvironment of GnRH neurones in the regions crossed during embryonic development as glial cells formed the main microenvironment of these neurones (53.4%). However, the phenotype of OEC associated with GnRH neurones changed across regions. The OEC progenitors immunoreactive to brain lipid binding protein formed the microenvironment of migrating GnRH neurones from the vomeronasal organ to the telencephalon and were also present in the diencephalon. However, during GnRH neurone migration, maturation of OEC to [GFAP+] state (glial fibrillary acid protein) was only observed in the nasal septum. Inducing depletion of OEC in maturation, using transgenic mice expressing herpes simplex virus thymidine kinase driven by the GFAP promoter, had no impact on neurogenesis or on triggering GnRH neurones migration in nasal explant culture. Nevertheless, depletion of [GFAP+] cells decreased GnRH neurites outgrowth by 57.4%. This study suggests that specific maturation of OEC in the nasal septum plays a role in morphological differentiation of GnRH neurones. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  17. RabGEF1/Rabex-5 Regulates TrkA-Mediated Neurite Outgrowth and NMDA-Induced Signaling Activation in NGF-Differentiated PC12 Cells.

    Directory of Open Access Journals (Sweden)

    See-Ying Tam

    Full Text Available Nerve growth factor (NGF binds to its cognate receptor TrkA and induces neuronal differentiation by activating distinct downstream signal transduction events. RabGEF1 (also known as Rabex-5 is a guanine nucleotide exchange factor for Rab5, which regulates early endosome fusion and vesicular trafficking in endocytic pathways. Here, we used the antisense (AS expression approach to induce an NGF-dependent sustained knockdown of RabGEF1 protein expression in stable PC12 transfectants. We show that RabGEF1 is a negative regulator of NGF-induced neurite outgrowth and modulates other cellular and signaling processes that are activated by the interaction of NGF with TrkA receptors, such as cell cycle progression, cessation of proliferation, and activation of NGF-mediated downstream signaling responses. Moreover, RabGEF1 can bind to Rac1, and the activation of Rac1 upon NGF treatment is significantly enhanced in AS transfectants, suggesting that RabGEF1 is a negative regulator of NGF-induced Rac1 activation in PC12 cells. Furthermore, we show that RabGEF1 can also interact with NMDA receptors by binding to the NR2B subunit and its associated binding partner SynGAP, and negatively regulates activation of nitric oxide synthase activity induced by NMDA receptor stimulation in NGF-differentiated PC12 cells. Our data suggest that RabGEF1 is a negative regulator of TrkA-dependent neuronal differentiation and of NMDA receptor-mediated signaling activation in NGF-differentiated PC12 cells.

  18. Pure neuritic leprosy: Resolving diagnostic issues in acid fast bacilli (AFB-negative nerve biopsies: A single centre experience from South India

    Directory of Open Access Journals (Sweden)

    Monalisa Hui

    2015-01-01

    Full Text Available Background and Purpose: Demonstration of lepra bacilli is essential for definite or unequivocal diagnosis of pure neuritic leprosy (PNL on nerve biopsy. However, nerves always do not show bacilli owing to the changes of previous therapy or due to low bacillary load in tuberculoid forms. In absence of granuloma or lepra bacilli, other morphologic changes in endoneurium and perineurium can be of help in making a probable diagnosis of PNL and treating the patient with multidrug therapy. Materials and Methods: Forty-six biopsies of PNL were retrospectively reviewed and histologic findings were compared with 25 biopsies of non leprosy neuropathies (NLN including vasculitic neuropathy and chronic inflammatory demyelinating polyneuropathy (CIDP. The distribution of endoneurial infiltrate and fibrosis, perineurial thickening, and myelin abnormalities were compared between PNL and NLN biopsies and analyzed by Chi-square test. Results: Out of 46 PNL casses, 24 (52.17 % biopsies were negative for acid fast bacilli (AFB. In these cases, the features which favor a diagnosis of AFB-negative PNL were endoneurial infiltrate (51.1%, endoneurial fibrosis (54.2%, perineurial thickening (70.8%, and reduced number of myelinated nerve fibers (75%. Interpretation and Conclusion: Nerve biopsy is an efficient tool to diagnose PNL and differentiate it from other causes of NLN. In absence of AFB, the diagnosis of PNL is challenging. In this article, we have satisfactorily evaluated the various hisopthological features and found that endoneurial inflammation, dense fibrosis, and reduction in the number of myelinated nerve fibers are strong supportive indicators of PNL regardless of AFB positivity.

  19. Impact of slope inclination on salt accumulation

    Science.gov (United States)

    Nachshon, Uri

    2017-04-01

    Field measurements indicated on high variability in salt accumulation along natural and cultivated slopes, even for relatively homogeneous soil conditions. It was hypothesised that slope inclination has an impact on the location of salt accumulation along the slope. A set of laboratory experiments and numerical models were used to explore the impact of slope inclination on salt accumulation. It was shown, experimentally, that for conditions of saline water source at the lower boundary of the slope - salt accumulates in low concentrations and homogeneously along the entire slope, for moderate slopes. However, as inclination increases high salt concentrations were observed at the upper parts of the slope, leaving the lower parts of the slope relatively free of salt. The traditional flow and transport models did not predict the experimental observations as they indicated also for the moderate slopes on salt accumulation in the elevated parts of the slope, away of the saline water source. Consequently - a conceptual model was raised to explain the laboratory observations. It was suggested that the interactions between slope angle, evaporation rates, hydraulic conductivity of the medium and distribution of wetness along the slope affect the saline water flow path through the medium. This lead to preferential flow path close to the soil-atmosphere interface for the steep slopes, which leads to constant wash of the salts from the evaporation front upward towards the slope upper parts, whereas for the moderate slopes, flow path is below the soil-atmosphere interface, therefore salt that accumulates at the evaporation front is not being transported upward. Understanding of salt dynamics along slopes is important for agricultural and natural environments, as well as for civil engineering purposes. Better understanding of the salt transport processes along slopes will improve our ability to minimize and to cope with soil salinization processes. The laboratory experiments and

  20. Neurotrophic effect of citrus 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone: promotion of neurite outgrowth via cAMP/PKA/CREB pathway in PC12 cells.

    Directory of Open Access Journals (Sweden)

    Hui-Chi Lai

    Full Text Available 5-Hydroxy-3,6,7,8,3',4'-hexamethoxyflavone (5-OH-HxMF, a hydroxylated polymethoxyflavone, is found exclusively in the Citrus genus, particularly in the peels of sweet orange. In this research, we report the first investigation of the neurotrophic effects and mechanism of 5-OH-HxMF in PC12 pheochromocytoma cells. We found that 5-OH-HxMF can effectively induce PC12 neurite outgrowth accompanied with the expression of neuronal differentiation marker protein growth-associated protein-43(GAP-43. 5-OH-HxMF caused the enhancement of cyclic AMP response element binding protein (CREB phosphorylation, c-fos gene expression and CRE-mediated transcription, which was inhibited by 2-naphthol AS-E phosphate (KG-501, a specific antagonist for the CREB-CBP complex formation. Moreover, 5-OH-HxMF-induced both CRE transcription activity and neurite outgrowth were inhibited by adenylate cyclase and protein kinase A (PKA inhibitor, but not MEK1/2, protein kinase C (PKC, phosphatidylinositol 3-kinase (PI3K or calcium/calmodulin-dependent protein kinase (CaMK inhibitor. Consistently, 5-OH-HxMF treatment increased the intracellular cAMP level and downstream component, PKA activity. We also found that addition of K252a, a TrKA antagonist, significantly inhibited NGF- but not 5-OH-HxMF-induced neurite outgrowth. These results reveal for the first time that 5-OH-HxMF is an effective neurotrophic agent and its effect is mainly through a cAMP/PKA-dependent, but TrKA-independent, signaling pathway coupling with CRE-mediated gene transcription. A PKC-dependent and CREB-independent pathway was also involved in its neurotrophic action.

  1. Selenium accumulation in the cockle Anadara trapezia

    Energy Technology Data Exchange (ETDEWEB)

    Jolley, Dianne F. [GEOQUEST, Department of Chemistry, University of Wollongong, NSW 2522 (Australia)]. E-mail: djolley@uow.edu.au; Maher, William A. [Ecochemistry Laboratory, Division of Science and Design, University of Canberra ACT 2601 (Australia); Kyd, Jennelle [Immunological Research Group, Division of Science and Design, University of Canberra ACT 2601 (Australia)

    2004-11-01

    An extensive study on Se accumulation in a population of Anadara trapezia from a marine lake is reported. The effects of organism mass, gender, reproductive cycle, and season on Se accumulation and tissue distribution were investigated. Analyses showed that gender and reproductive cycle had no significant effect on Se accumulation. A. trapezia showed a strong positive correlation between Se burden and tissue mass. Constant Se concentrations were observed within individual populations but varied spatially with sediment Se concentrations. Se concentrations in tissues decreased from gills > gonad/intestine > mantle > muscle > foot, which remained constant over 12 months, however, significantly lower concentrations were observed in the summer compared to winter. A. trapezia is a good biomonitor for Se, as gender and size do not effect concentration, however, season of collection must be reported if changes in Se bioavailability are to be identified in short term studies, or during intersite comparisons. - Capsule: The marine bivalve Anadara trapezia is a good bioindicator for marine selenium contamination.

  2. Recent progress on the ATHENA Positron Accumulator

    CERN Document Server

    Jørgensen, L V; Watson, T L; Charlton, M; Collier, M

    2002-01-01

    The Positron Accumulator for the ATHENA anti-hydrogen experiment at CERN, Geneva has recently been upgraded with a new 50 mCi /sup 22/Na beta /sup +/-radioactive source. Following this, rapid progress has been made in optimizing and characterizing the properties of the positron plasma. The rotating wall technique has also been implemented in the accumulation region and has been shown to lead to compression of better than a factor of 10 in density and markedly increased lifetimes, even when using the N/sub 2/ buffer gas as a cooling gas. Using these techniques we have routinely accumulated up to 2 * 10/sup 8/ positrons in a few minutes. The positron plasma has a FWHM of only 3-4 mm when using the rotating wall which compares with a FWHM of 15 mm without the rotating wall. (13 refs).

  3. Carbon accumulation in pristine and drained mires

    Energy Technology Data Exchange (ETDEWEB)

    Maekilae, M.

    2011-07-01

    The carbon accumulation of 73 peat columns from 48 pristine and drained mires was investigated using a total of 367 dates and age-depth models derived from bulk density measurements. Peat columns were collected from mires of varying depth, age, degree of natural state and nutrient conditions in aapa mire and raised bog regions and coastal mires from southern and central Finland and Russian Karelia. Particular attention was paid to the accumulation of carbon over the last 300 years, as this period encompasses the best estimates of the oxic layer (acrotelm) age across the range of sites investigated. In general, drained mires are initially more nutrient-rich than pristine mires. Organic matter decomposes more rapidly at drained sites than at pristine sites, resulting in thinner peat layers and carbon accumulation but a higher dry bulk density and carbon content. The average carbon accumulation was calculated as 24.0 g m-2 yr-1 at pristine sites and 19.4 g m-2 yr-1 at drained sites, while for peat layers younger than 300 years the respective figures were 45.3 and 34.5 g m-2 yr-1 at pristine and drained sites. For the <300-year-old peat layers studied here, the average thickness was 19 cm less and the carbon accumulation rate 10.8 g m-2 yr-1 lower in drained areas than in pristine areas. The amount carbon accumulation of surface peat layers depends upon the mire site type, vegetation and natural state; variations reflect differences in plant communities as well as factors that affect biomass production and decay rates. The highest accumulation rates and thus carbon binding for layers younger than 300 years were measured in the ombrotrophic mire site types (Sphagnum fuscum bog and Sphagnum fuscum pine bog), and the second highest rates in wet, treeless oligotrophic and minerotrophic mire site types. The lowest values of carbon accumulation over the last 300 years were obtained for the most transformed, sparsely forested and forested mire site types, where the water

  4. Stationarity Testing of Accumulated Ethernet Traffic

    Directory of Open Access Journals (Sweden)

    Zhiping Lu

    2013-01-01

    Full Text Available We investigate the stationarity property of the accumulated Ethernet traffic series. We applied several widely used stationarity and unit root tests, such as Dickey-Fuller test and its augmented version, Phillips-Perron test, as well as the Kwiatkowski-Phillips-Schmidt-Shin test and some of its generalizations, to the assessment of the stationarity of the traffic traces at the different time scales. The quantitative results in this research provide evidence that when the time scale increases, the accumulated traffic series are more stationary.

  5. Implications of metal accumulation mechanisms to phytoremediation.

    Science.gov (United States)

    Memon, Abdul R; Schröder, Peter

    2009-03-01

    Trace elements (heavy metals and metalloids) are important environmental pollutants, and many of them are toxic even at very low concentrations. Pollution of the biosphere with trace elements has accelerated dramatically since the Industrial Revolution. Primary sources are the burning of fossil fuels, mining and smelting of metalliferous ores, municipal wastes, agrochemicals, and sewage. In addition, natural mineral deposits containing particularly large quantities of heavy metals are found in many regions. These areas often support characteristic plant species thriving in metal-enriched environments. Whereas many species avoid the uptake of heavy metals from these soils, some of them can accumulate significantly high concentrations of toxic metals, to levels which by far exceed the soil levels. The natural phenomenon of heavy metal tolerance has enhanced the interest of plant ecologists, plant physiologists, and plant biologists to investigate the physiology and genetics of metal tolerance in specialized hyperaccumulator plants such as Arabidopsis halleri and Thlaspi caerulescens. In this review, we describe recent advances in understanding the genetic and molecular basis of metal tolerance in plants with special reference to transcriptomics of heavy metal accumulator plants and the identification of functional genes implied in tolerance and detoxification. Plants are susceptible to heavy metal toxicity and respond to avoid detrimental effects in a variety of different ways. The toxic dose depends on the type of ion, ion concentration, plant species, and stage of plant growth. Tolerance to metals is based on multiple mechanisms such as cell wall binding, active transport of ions into the vacuole, and formation of complexes with organic acids or peptides. One of the most important mechanisms for metal detoxification in plants appears to be chelation of metals by low-molecular-weight proteins such as metallothioneins and peptide ligands, the phytochelatins. For

  6. Macrodamage Accumulation Model for a Human Femur

    Directory of Open Access Journals (Sweden)

    Farah Hamandi

    2017-01-01

    Full Text Available The objective of this study was to more fully understand the mechanical behavior of bone tissue that is important to find an alternative material to be used as an implant and to develop an accurate model to predict the fracture of the bone. Predicting and preventing bone failure is an important area in orthopaedics. In this paper, the macrodamage accumulation models in the bone tissue have been investigated. Phenomenological models for bone damage have been discussed in detail. In addition, 3D finite element model of the femur prepared from imaging data with both cortical and trabecular structures is delineated using MIMICS and ANSYS® and simulated as a composite structure. The damage accumulation occurring during cyclic loading was analyzed for fatigue scenario. We found that the damage accumulates sooner in the multiaxial than in the uniaxial loading condition for the same number of cycles, and the failure starts in the cortical bone. The damage accumulation behavior seems to follow a three-stage growth: a primary phase, a secondary phase of damage growth marked by linear damage growth, and a tertiary phase that leads to failure. Finally, the stiffness of the composite bone comprising the cortical and trabecular bone was significantly different as expected.

  7. Plastic Accumulation in the Mediterranean Sea

    Science.gov (United States)

    Cózar, Andrés; Sanz-Martín, Marina; Martí, Elisa; González-Gordillo, J. Ignacio; Ubeda, Bárbara; Gálvez, José Á.; Irigoien, Xabier; Duarte, Carlos M.

    2015-01-01

    Concentrations of floating plastic were measured throughout the Mediterranean Sea to assess whether this basin can be regarded as a great accumulation region of plastic debris. We found that the average density of plastic (1 item per 4 m2), as well as its frequency of occurrence (100% of the sites sampled), are comparable to the accumulation zones described for the five subtropical ocean gyres. Plastic debris in the Mediterranean surface waters was dominated by millimeter-sized fragments, but showed a higher proportion of large plastic objects than that present in oceanic gyres, reflecting the closer connection with pollution sources. The accumulation of floating plastic in the Mediterranean Sea (between 1,000 and 3,000 tons) is likely related to the high human pressure together with the hydrodynamics of this semi-enclosed basin, with outflow mainly occurring through a deep water layer. Given the biological richness and concentration of economic activities in the Mediterranean Sea, the affects of plastic pollution on marine and human life are expected to be particularly frequent in this plastic accumulation region. PMID:25831129

  8. Mitochondrial accumulation of APP and Abeta

    DEFF Research Database (Denmark)

    Pavlov, Pavel F; Petersen, Anna Camilla Hansson; Glaser, Elzbieta

    2009-01-01

    Accumulating evidence suggest that alterations in energy metabolism are among the earliest events that occur in the Alzheimer disease (AD) affected brain. Energy consumption is drastically decreased in the AD-affected regions of cerebral cortex and hippocampus pointing towards compromised mitocho...

  9. Plastic accumulation in the Mediterranean sea.

    Directory of Open Access Journals (Sweden)

    Andrés Cózar

    Full Text Available Concentrations of floating plastic were measured throughout the Mediterranean Sea to assess whether this basin can be regarded as a great accumulation region of plastic debris. We found that the average density of plastic (1 item per 4 m2, as well as its frequency of occurrence (100% of the sites sampled, are comparable to the accumulation zones described for the five subtropical ocean gyres. Plastic debris in the Mediterranean surface waters was dominated by millimeter-sized fragments, but showed a higher proportion of large plastic objects than that present in oceanic gyres, reflecting the closer connection with pollution sources. The accumulation of floating plastic in the Mediterranean Sea (between 1,000 and 3,000 tons is likely related to the high human pressure together with the hydrodynamics of this semi-enclosed basin, with outflow mainly occurring through a deep water layer. Given the biological richness and concentration of economic activities in the Mediterranean Sea, the affects of plastic pollution on marine and human life are expected to be particularly frequent in this plastic accumulation region.

  10. Electric charger for an accumulator or battery

    NARCIS (Netherlands)

    Robers, E.W.J.; Molenaar, B.A.M.; Smit, W.; Bech, L.P.; Bouman, C.

    2009-01-01

    The invention relates to an electric charger for an accumulator or a battery or the like, which is adapted for rapid charging during an on-period and comprises for this purpose control means for starting and ending the on-period. The charger is provided with a circuit for converting a supply voltage

  11. Accumulating Project Management Knowledge Using Process Theory

    NARCIS (Netherlands)

    Niederman, Fred; March, Salvatore T.; Mueller, Benjamin

    2016-01-01

    Process theory has become an important mechanism for the accumulation of knowledge in a number of disciplines. In contrast with variance theory, which focuses on co-variation of dependent and independent variables, process theory focuses on sequences of activities, their duration and the intervals

  12. Plastic accumulation in the Mediterranean sea.

    Science.gov (United States)

    Cózar, Andrés; Sanz-Martín, Marina; Martí, Elisa; González-Gordillo, J Ignacio; Ubeda, Bárbara; Gálvez, José Á; Irigoien, Xabier; Duarte, Carlos M

    2015-01-01

    Concentrations of floating plastic were measured throughout the Mediterranean Sea to assess whether this basin can be regarded as a great accumulation region of plastic debris. We found that the average density of plastic (1 item per 4 m2), as well as its frequency of occurrence (100% of the sites sampled), are comparable to the accumulation zones described for the five subtropical ocean gyres. Plastic debris in the Mediterranean surface waters was dominated by millimeter-sized fragments, but showed a higher proportion of large plastic objects than that present in oceanic gyres, reflecting the closer connection with pollution sources. The accumulation of floating plastic in the Mediterranean Sea (between 1,000 and 3,000 tons) is likely related to the high human pressure together with the hydrodynamics of this semi-enclosed basin, with outflow mainly occurring through a deep water layer. Given the biological richness and concentration of economic activities in the Mediterranean Sea, the affects of plastic pollution on marine and human life are expected to be particularly frequent in this plastic accumulation region.

  13. Immunohistochemical evaluation of iron accumulation in term ...

    African Journals Online (AJOL)

    Classical immunohistochemical studies on placenta have shown that there is a linear increase in iron storage in the placenta in the first half of a normal pregnancy, however, these stocks are decreased in normal 3rd trimester placenta. Iron accumulation in term placentas of preeclamptic and normal pregnancies were ...

  14. Differential nitrate accumulation, nitrate reduction, nitrate reductase ...

    African Journals Online (AJOL)

    Differential nitrate accumulation, nitrate reduction, nitrate reductase activity, protein production and carbohydrate biosynthesis in response to potassium and sodium ... due to the positive effects of potassium on the enzyme activity, sugars transport, water and nutrient transport, protein synthesis and carbohydrate metabolism.

  15. Reduced collagen accumulation after major surgery

    DEFF Research Database (Denmark)

    Jorgensen, L N; Kallehave, F; Karlsmark, T

    1996-01-01

    .01)). This decline was significantly higher in the six patients who had a postoperative infection (median 3.02 (range -0.06 to 6.14) versus 0.36 (range -1.56 to 12.60) micrograms/cm, P = 0.02). This study shows that major surgery is associated with impairment of subcutaneous collagen accumulation in a test wound...

  16. Differential nitrate accumulation, nitrate reduction, nitrate reductase ...

    African Journals Online (AJOL)

    use

    2011-12-07

    Dec 7, 2011 ... biosynthesis. Carbohydrate metabolism produces both the carbon skeletons and ferredoxin for nitrate assimilation. Inhibition of photosynthesis prevents the production of the reduced ferredoxin required for nitrite reduction in chloroplasts, which leads to nitrate and nitrite accumulation (Commichau et al., ...

  17. Accumulation of nanocarriers in the ovary

    DEFF Research Database (Denmark)

    Schädlich, Andreas; Hoffmann, Stefan; Mueller, Thomas

    2012-01-01

    ovaries after intravenous (i.v.) administration. Studies in different mouse species and Wistar rats were conducted and a high local accumulation of nanoparticles, nanocapsules and nanoemulsions in specific locations of the ovaries was found in all animals. We characterised the enrichment by in vivo and ex...

  18. Temporal accumulation of oriented visual features

    DEFF Research Database (Denmark)

    Pugeault, Nicolas; Krüger, Norbert

    2011-01-01

    In this paper we present a framework for accumulating on-line a model of a moving object (e.g., when manipulated by a robot). The proposed scheme is based on Bayesian filtering of local features, filtering jointly position, orientation and appearance information. The work presented here is novel...

  19. Accumulation pattern of total nonstructural carbohydrate in ...

    African Journals Online (AJOL)

    The pattern of total nonstructural carbohydrate (TNC) accumulation in strawberry (Fragaria ananassa Duch.) nursery runner plants, cv. eCamarosaf, was determined for three growing seasons. Plant growth and fruit production patterns were also evaluated. The experiments were carried out on plants propagated in high ...

  20. Contextual investigation of factors affecting sludge accumulation ...

    African Journals Online (AJOL)

    Pit latrines in slums areas of Uganda fill up faster than might be expected from some estimates owing to inappropriate use and failure to consider critical factors affecting sludge accumulation rates at the planning, design and construction stages. This study sought to investigate factors affecting filling rates of lined pit latrines ...

  1. Contextual investigation of factors affecting sludge accumulation ...

    African Journals Online (AJOL)

    ABSTRACT. Pit latrines in slums areas of Uganda fill up faster than might be expected from some estimates owing to inappropriate use and failure to consider critical factors affecting sludge accumulation rates at the planning, design and construction stages. This study sought to investigate factors affecting filling rates of ...

  2. Intracellular accumulation of norfloxacin in Mycobacterium smegmatis.

    Science.gov (United States)

    Corti, S; Chevalier, J; Cremieux, A

    1995-01-01

    To evaluate the intracellular accumulation of norfloxacin in mycobacteria, two methods were used with Mycobacterium smegmatis. A radiometric method (K. V. Cundy, C. E. Fasching, K. E. Willard, and L. R. Peterson, J. Antimicrob. Chemother. 28:491-497, 1991) was used without great modification, but the fluorometric method (P. G. S. Mortimer and L. J. V. Piddock, J. Antimicrob. Chemother. 28:639-653, 1991) was changed considerably. Indeed, adsorption of the quinolone to the bacterial surface was characterized by measuring the level of accumulation of 0 degree C. Taking into account the adsorption, the pH of the washing buffer was increased from 7.0 to 9.0 to improve the desorption of norfloxacin from the cell surface. Both the fluorometric method, with the technical improvement, and the radiometric method could be used to estimate the intracellular accumulation of norfloxacin, which resulted from the difference between the whole uptake measured at 37 degrees C and the adsorption measured at 0 degrees C. A total of 35 ng of norfloxacin per mg of cells (dry weight) penetrated into the M. smegmatis cell, and the steady state was achieved in 5 min. Use of inhibitors of the proton motive force revealed that transport of norfloxacin was energy independent. Thus, the same mechanisms of quinolone accumulation that occur in eubacteria seem to occur in mycobacteria, at least in M. smegmatis. PMID:8585727

  3. Accumulation pattern of total nonstructural carbohydrate in ...

    African Journals Online (AJOL)

    Umukoro

    1977-09-09

    Sep 9, 1977 ... predominant soluble nonstructural carbohydrates in roots and crowns of strawberry plants (Bringhurst et al., 1960;. Macias-Rodriguez et al., 2002). Starch accumulation in roots is influenced by temperature; moreover, total non- structural carbohydrate (TNC) concentration in strawberry roots increases with ...

  4. On Ruckle's Conjecture on Accumulation Games

    NARCIS (Netherlands)

    Alpern, S.; Fokkink, R.J.; Kikuta, K.

    2010-01-01

    In an accumulation game, the Hider secretly distributes his given total wealth $h$ among $n$ locations, while the Searcher picks $r$ locations and confiscates the material placed there. The Hider wins if what is left at the remaining $n-r$ locations is at least 1; otherwise the Searcher wins.

  5. Plastic Accumulation in the Mediterranean Sea

    KAUST Repository

    Cózar, Andrés

    2015-04-01

    Concentrations of floating plastic were measured throughout the Mediterranean Sea to assess whether this basin can be regarded as a great accumulation region of plastic debris. We found that the average density of plastic (1 item per 4 m2), as well as its frequency of occurrence (100% of the sites sampled), are comparable to the accumulation zones described for the five subtropical ocean gyres. Plastic debris in the Mediterranean surface waters was dominated by millimeter-sized fragments, but showed a higher proportion of large plastic objects than that present in oceanic gyres, reflecting the closer connection with pollution sources. The accumulation of floating plastic in the Mediterranean Sea (between 1,000 and 3,000 tons) is likely related to the high human pressure together with the hydrodynamics of this semi-enclosed basin, with outflow mainly occurring through a deep water layer. Given the biological richness and concentration of economic activities in the Mediterranean Sea, the affects of plastic pollution on marine and human life are expected to be particularly frequent in this plastic accumulation region.

  6. Accumulation of Radiocesium in Eleutherococcus sciadophylloides

    Energy Technology Data Exchange (ETDEWEB)

    Sugiura, Y.; Takenaka, C.; Kanasashi, T. [Graduate School of Bioagricultural Sciences, Nagoya University, 464-8601, Nagoya City, Aichi Prefecture (Japan); Deguchi, S. [School of Agricultural Sciences, Nagoya University, Nagoya City, Aichi Prefecture, 464-8601 (Japan); Matsuda, Y. [Graduate School of Bioresources, Mie University, Tsu City, Mie Prefecture, 514-0102 (Japan); Ozawa, H. [Fukushima Prefectural Forestry Research Centre, Koriyama City Fukushima Prefecture, 963-0112 (Japan)

    2014-07-01

    1. Introduction: After Fukushima Daiichi Nuclear Power Plant accident, radiocesium ({sup 137}Cs) had deposited on forests in Fukushima Prefecture. In order to comprehend radiocesium circulation in forest ecosystem, it is important to understand about properties of {sup 137}Cs accumulation of each plant species. In addition, {sup 137}Cs accumulator plants would be candidates of phyto-remediation, which is a remediation method using plants to remove pollutants from environment. We aimed to find {sup 137}Cs accumulator plants and to clarify the accumulate mechanisms. 2. Materials and Methods: We collected soil and plant samples at 22 points in Fukushima Prefecture more than once a year from May 2011 to October 2013. Surface (0-5 cm) soils were collected at the same site as the plant sampling. The soil samples were air-dried for 2-3 weeks and then passed through a 2 mm sieve. Foliar samples were washed with tap water to remove soil particles and rinsed with deionized water for {sup 137}Cs and other elements analysis. The samples were dried at 80 deg. C for 48 hr and ground with a mill mixer. {sup 137}Cs activities in soil and plant samples were determined by means of high-purity Ge detector (HPGe). The elements concentrations of the plant samples were determined by inductively coupled plasma mass spectrometry (ICP-MS) after wet digestion with HNO{sub 3}. 3. Results and Discussion: As a whole trend, evergreen tree species such as Camellia japonica and Cryptomeria japonica contained {sup 137}Cs at high concentration due to the deposited {sup 137}Cs on old leaves and foliar absorption. The activities in leaves of deciduous tree species were lower than those in evergreen trees. However, we confirmed that a deciduous tree species, Eleutherococcus sciadophylloides, collected in 2012 and 2013 accumulated {sup 137}Cs, whereas that collected in 2011 did not accumulate {sup 137}Cs. The {sup 137}Cs concentration of E. sciadophylloides in 2012 and 2013 were higher than those of

  7. Role of taurine accumulation in keratinocyte hydration.

    Science.gov (United States)

    Janeke, Guido; Siefken, Wilfried; Carstensen, Stefanie; Springmann, Gunja; Bleck, Oliver; Steinhart, Hans; Höger, Peter; Wittern, Klaus-Peter; Wenck, Horst; Stäb, Franz; Sauermann, Gerhard; Schreiner, Volker; Doering, Thomas

    2003-08-01

    Epidermal keratinocytes are exposed to a low water concentration at the stratum corneum-stratum granulosum interface. When epithelial tissues are osmotically perturbed, cellular protection and cell volume regulation is mediated by accumulation of organic osmolytes such as taurine. Previous studies reported the presence of taurine in the epidermis of several animal species. Therefore, we analyzed human skin for the presence of the taurine transporter (TAUT) and studied the accumulation of taurine as one potential mechanism protecting epidermal keratinocytes from dehydration. According to our results, TAUT is expressed as a 69 kDa protein in human epidermis but not in the dermis. For the epidermis a gradient was evident with maximal levels of TAUT in the outermost granular keratinocyte layer and lower levels in the stratum spinosum. No TAUT was found in the basal layer or in the stratum corneum. Keratinocyte accumulation of taurine was induced by experimental induction of skin dryness via application of silica gel to human skin. Cultured human keratinocytes accumulated taurine in a concentration- and osmolarity-dependent manner. TAUT mRNA levels were increased after exposure of human keratinocytes to hyperosmotic culture medium, indicating osmosensitive TAUT mRNA expression as part of the adaptation of keratinocytes to hyperosmotic stress. Keratinocyte uptake of taurine was inhibited by beta-alanine but not by other osmolytes such as betaine, inositol, or sorbitol. Accumulation of taurine protected cultured human keratinocytes from both osmotically induced and ultraviolet-induced apoptosis. Our data indicate that taurine is an important epidermal osmolyte required to maintain keratinocyte hydration in a dry environment.

  8. Accumulation of carbon in northern mire ecosystems

    Energy Technology Data Exchange (ETDEWEB)

    Tolonen, K.; Turunen, J.; Alm, J. [Joensuu Univ. (Finland). Dept. of Biology; Korhola, A. [Helsinki Univ. (Finland). Lab. of Physical Geography; Jungner, H. [Helsinki Univ. (Finland). Dating Lab.; Vasander, H. [Helsinki Univ. (Finland). Dept. of Forest Ecology

    1996-12-31

    The basic feature in the functional ecology of any mire ecosystem is retardation of the effective decay of organic material resulting in a conspicuous accumulation of plant debris as peat overtime. The carbon accumulation process is slow, and climatic change may have an impact on the carbon cycle of peatlands, therefore, it has been of interest to study the rate of carbon accumulation by geological methods from dated peat strata. The approach is hampered by several facts. First, the mires vary enormously as to their vegetation and hydrology and hence their production and decay properties. It follows that a great number of study sites are needed. Second, the peat in mires expands both vertically and laterally, and this requires a spatial reconstruction of carbon accumulation within a mire basin. Third, simple geological methods cannot account for the actual rate of carbon accumulation in peat, and finally, an additional carbon sink in the mire ecosystems can be the mineral subsoil beneath peat. The proposed warming will perhaps shift northwards the existing climatic mire regimes and, thus, the northern aapa fens will change to Sphagnum bogs that are more effective in sequestering carbon, but distinctly less effective in their CH{sub 4} and N{sub 2}O emanation. The role of mire fires in more remote northern areas may then become another important factor. The answer to the important question of future total sequestration of carbon to peatlands depends on the precipitation and its seasonal distribution pattern. Most climatic scenarios predict a decrease in the evaporation surplus during the summer at northern regions. Presumably, the consequent lowering of the water table would improve growth of forest on mires and simultaneously decrease the methane fluxes from peat. The combined net effect could be a clear restraining of the radiative forcing

  9. Membrane progesterone receptor beta (mPRβ/Paqr8) promotes progesterone-dependent neurite outgrowth in PC12 neuronal cells via non-G protein-coupled receptor (GPCR) signaling.

    Science.gov (United States)

    Kasubuchi, Mayu; Watanabe, Keita; Hirano, Kanako; Inoue, Daisuke; Li, Xuan; Terasawa, Kazuya; Konishi, Morichika; Itoh, Nobuyuki; Kimura, Ikuo

    2017-07-12

    Recently, sex steroid membrane receptors garnered world-wide attention because they may be related to sex hormone-mediated unknown rapid non-genomic action that cannot be currently explained by their genomic action via nuclear receptors. Progesterone affects cell proliferation and survival via non-genomic effects. In this process, membrane progesterone receptors (mPRα, mPRβ, mPRγ, mPRδ, and mPRε) were identified as putative G protein-coupled receptors (GPCRs) for progesterone. However, the structure, intracellular signaling, and physiological functions of these progesterone receptors are still unclear. Here, we identify a molecular mechanism by which progesterone promotes neurite outgrowth through mPRβ (Paqr8) activation. Mouse mPRβ mRNA was specifically expressed in the central nervous system. It has an incomplete GPCR topology, presenting 6 transmembrane domains and did not exhibit typical GPCR signaling. Progesterone-dependent neurite outgrowth was exhibited by the promotion of ERK phosphorylation via mPRβ, but not via other progesterone receptors such as progesterone membrane receptor 1 (PGRMC-1) and nuclear progesterone receptor in nerve growth factor-induced neuronal PC12 cells. These findings provide new insights of regarding the non-genomic action of progesterone in the central nervous system.

  10. Performance of [18F]flutemetamol amyloid imaging against the neuritic plaque component of CERAD and the current (2012) NIA-AA recommendations for the neuropathologic diagnosis of Alzheimer's disease.

    Science.gov (United States)

    Salloway, Stephen; Gamez, Jose E; Singh, Upinder; Sadowsky, Carl H; Villena, Teresa; Sabbagh, Marwan N; Beach, Thomas G; Duara, Ranjan; Fleisher, Adam S; Frey, Kirk A; Walker, Zuzana; Hunjan, Arvinder; Escovar, Yavir M; Agronin, Marc E; Ross, Joel; Bozoki, Andrea; Akinola, Mary; Shi, Jiong; Vandenberghe, Rik; Ikonomovic, Milos D; Sherwin, Paul F; Farrar, Gill; Smith, Adrian P L; Buckley, Christopher J; Thal, Dietmar Rudolf; Zanette, Michelle; Curtis, Craig

    2017-01-01

    Performance of the amyloid tracer [ 18 F]flutemetamol was evaluated against three pathology standard of truth (SoT) measures including neuritic plaques (CERAD "original" and "modified" and the amyloid component of the 2012 NIA-AA guidelines). After [ 18 F]flutemetamol imaging, 106 end-of-life patients who died underwent postmortem brain examination for amyloid plaque load. Blinded positron emission tomography scan interpretations by five independent electronically trained readers were compared with pathology measures. By SoT, sensitivity and specificity of majority image interpretations were, respectively, 91.9% and 87.5% with "original CERAD," 90.8% and 90.0% with "modified CERAD," and 85.7% and 100% with the 2012 NIA-AA criteria. The high accuracy of either CERAD criteria suggests that [ 18 F]flutemetamol predominantly reflects neuritic amyloid plaque density. However, the use of CERAD criteria as the SoT can result in some false-positive results because of the presence of diffuse plaques, which are accounted for when the positron emission tomography read is compared with the 2012 NIA-AA criteria.

  11. 26 CFR 1.535-3 - Accumulated earnings credit.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Accumulated earnings credit. 1.535-3 Section 1... Accumulated earnings credit. (a) In general. As provided in section 535(a) and § 1.535-1, the accumulated earnings credit, provided by section 535(c), reduces taxable income in computing accumulated taxable income...

  12. Energy Balance and Operating Features of the Heat Accumulator

    Directory of Open Access Journals (Sweden)

    Pavel Fiala

    2006-01-01

    Full Text Available There are described design and realization of a heat accumulator in the article which joins advantages and eliminates disadvantages of water and gravel accumulators. Inside the accumulator there are suppressed heat convection and conduction between layers of storage matter, so there is the temperature stratification along a height of such accumulator. The article deals with operating features as well.

  13. Solar-Panel Dust Accumulation and Cleanings

    Science.gov (United States)

    2005-01-01

    Air-fall dust accumulates on the solar panels of NASA's Mars Exploration Rovers, reducing the amount of sunlight reaching the solar arrays. Pre-launch models predicted steady dust accumulation. However, the rovers have been blessed with occasional wind events that clear significant amounts of dust from the solar panels. This graph shows the effects of those panel-cleaning events on the amount of electricity generated by Spirit's solar panels. The horizontal scale is the number of Martian days (sols) after Spirit's Jan. 4, 2005, (Universal Time) landing on Mars. The vertical scale indicates output from the rover's solar panels as a fraction of the amount produced when the clean panels first opened. Note that the gradual declines are interrupted by occasional sharp increases, such as a dust-cleaning event on sol 420.

  14. [Characteristics of mycotoxin accumulation in lichens].

    Science.gov (United States)

    Burkin, A A; Kononenko, G P

    2013-01-01

    The levels and frequencies of mycotoxin accumulation in lichens belonging to 20 genera of the families Cladoniaceae, Nephromataceae, Parmeliaceae, Peltigeraceae, Telosshistaceae, and Umbilicari- aceae were characterized using enzyme immunoassay. Alternariol, sterigmatocystin, mycophenolic acid, cit- rinin, cyclopiazonic acid, and emodin were regularly detected in all genera, except for Peltigera, at an average level of more than 1000 ng/g (i.e., 0.0001%). The necessity for the safety monitoring of drugs based on lichen extractives is discussed.

  15. Accumulation and subsequent utilization of waste heat

    Science.gov (United States)

    Koloničný, Jan; Richter, Aleš; Pavloková, Petra

    2016-06-01

    This article aims to introduce a special way of heat accumulation and primary operating characteristics. It is the unique way in which the waste heat from flue gas of biogas cogeneration station is stored in the system of storage tanks, into the heat transfer oil. Heat is subsequently transformed into water, from which is generated the low-pressure steam. Steam, at the time of peak electricity needs, spins the special designed turbine generator and produces electrical energy.

  16. Aflatoxin Accumulation in a Maize Diallel Cross

    OpenAIRE

    W. Paul Williams; Gary L. Windham

    2015-01-01

    Aflatoxins, produced by the fungus Aspergillus flavus , occur naturally in maize. Contamination of maize grain with aflatoxin is a major food and feed safety problem and greatly reduces the value of the grain. Plant resistance is generally considered a highly desirable approach to reduction or elimination of aflatoxin in maize grain. In this investigation, a diallel cross was produced by crossing 10 inbred lines with varying degrees of resistance to aflatoxin accumulation in all possible comb...

  17. Arsenic accumulation by edible aquatic macrophytes.

    Science.gov (United States)

    Falinski, K A; Yost, R S; Sampaga, E; Peard, J

    2014-01-01

    Edible aquatic macrophytes grown in arsenic (As)-contaminated soil and sediment were investigated to determine the extent of As accumulation and potential risk to humans when consumed. Nasturtium officinale (watercress) and Diplazium esculentum (warabi) are two aquatic macrophytes grown and consumed in Hawaii. Neither has been assessed for potential to accumulate As when grown in As-contaminated soil. Some former sugarcane plantation soils in eastern Hawaii have been shown to have concentrations of total As over 500 mg kg(-1). It was hypothesized that both species will accumulate more As in contaminated soils than in non-contaminated soils. N. officinale and D. esculentum were collected in areas with and without As-contaminated soil and sediment. High soil As concentrations averaged 356 mg kg(-1), while low soil As concentrations were 0.75 mg kg(-1). Average N. officinale and D. esculentum total As concentrations were 0.572 mg kg(-1) and 0.075 mg kg(-1), respectively, corresponding to hazard indices of 0.12 and 0.03 for adults. Unlike previous studies where watercress was grown in As-contaminated water, N. officinale did not show properties of a hyperaccumulator, yet plant concentrations in high As areas were more than double those in low As areas. There was a slight correlation between high total As in sediment and soil and total As concentrations in watercress leaves and stems, resulting in a plant uptake factor of 0.010, an order of magnitude higher than previous studies. D. esculentum did not show signs of accumulating As in the edible fiddleheads. Hawaii is unique in having volcanic ash soils with extremely high sorption characteristics of As and P that limit release into groundwater. This study presents a case where soils and sediments were significantly enriched in total As concentration, but the water As concentration was below detection limits. © 2013 Published by Elsevier Inc.

  18. Extrapulmonary sites of radiogallium accumulation in sarcoidosis

    Energy Technology Data Exchange (ETDEWEB)

    Sulavik, S.B.; Palestro, C.J.; Spencer, R.P.; Swyer, A.J.; Goldsmith, S.J.; Tierstein, A.S. (Univ. of Connecticut Health Center, Farmington (USA))

    1990-12-01

    In an effort to detect extrapulmonary sites of radiogallium accumulation in cases of sarcoidosis, 145 separate Ga-67 citrate studies of 114 patients with biopsy-proven sarcoidosis were examined. The most characteristic extrapulmonary radiogallium uptake pattern was the panda sign in 47 patients (41%). The most common site of prominent extrapulmonary radiogallium uptake was the lacrimal glands in 101 patients (88%). Second most common was activity in one or more superficial lymph node regions such as the cervical, axillary, femoral, or inguinal in 19 patients (17%). Other extrapulmonary sites included breast uptake in 6 out of 80 women (8%), prominent splenic and nasal uptake in 9 (8%) patients, periportal accumulation in 7 (6%), and cutaneous/subcutaneous activity in 4 (4%). Because many of these individuals were receiving corticosteroids, the natural (untreated) prevalence of extrapulmonary findings may be even higher. Although the sensitivity and specificity of extrapulmonary radiogallium accumulation has still to be determined, many of the sites may be accessible to biopsy both for diagnostic purposes and to follow the effects of medications. It is therefore suggested that whole-body imaging be performed when radiogallium is administered to patients with suspected or known sarcoidosis.

  19. Linear Deterministic Accumulator Models of Simple Choice

    Directory of Open Access Journals (Sweden)

    Andrew eHeathcote

    2012-08-01

    Full Text Available We examine theories of simple choice as a race among evidence accumulation processes. We focus on the class of deterministic race models, which assume that the effects of fluctuations in the parameters of the accumulation processes between choice trials (between-choice noise dominate the effects of fluctuations occurring while making a choice (within-choice noise in behavioural data (i.e., response times and choices. The latter deterministic approximation, when combined with the assumption that accumulation is linear, leads to a class of models that can be readily applied to simple-choice behaviour because they are computationally tractable. We develop a new and mathematically simple exemplar within the class of linear deterministic models, the Lognormal Race (LNR. We then examine how the LNR, and another widely applied linear deterministic model, Brown and Heathcote’s (2008 LBA, account for a range of benchmark simple-choice effects in lexical-decision task data reported by Wagenmakers, Ratcliff, Gomez and McKoon (2008.

  20. Anthocyanins facilitate tungsten accumulation in Brassica

    Energy Technology Data Exchange (ETDEWEB)

    Hale, K.L.

    2002-11-01

    Accumulation of molybdenum in Brassica was recently found to be correlated with anthocyanin content, involving the formation of a blue complex. Here the role of anthocyanins in tungsten sequestration was investigated using three species of Brassica: B. rapa (cv. Fast plants), B. juncea (Indian mustard) and B. oleracea (red cabbage). Seedlings of B. rapa and B. juncea turned blue when supplied with colourless tungstate. The blue compound co-localized with anthocyanins in the peripheral cell layers, and the degree of blueness was correlated with anthocyanin content. The direct involvement of anthocyanins in the blue coloration was evident when purified anthocyanins showed a colour change from pink to blue in vitro upon addition of tungstate, over a wide pH range. Anthocyanin production was upregulated 3-fold by W in B. juncea, possibly reflecting a function for anthocyanins in W tolerance or sequestration. The presence of anthocyanins facilitated W accumulation in B. rapa: anthocyanin-containing seedlings accumulated 3-fold more W than an anthocyaninless mutant. There was no correlation between anthocyanin content and W tolerance under these conditions. The nature of the interaction between anthocyanins and tungstate was investigated. X-ray absorption spectroscopy showed no change in the local chemical environment of Wupon uptake of tungstate by the plant; HPLC analysis of purified anthocyanin with or without tungstate showed no peak shift after metal treatment.

  1. [Asenic accumulation following realgar administration in rats].

    Science.gov (United States)

    Li, Chunying; Liang, Aihua; Wang, Jinhua; Xue, Baoyun; Li, Hua; Yang, Bin; Wang, Jingyu; Xie, Qing; Nilsen, Odd Georg; Zhang, Boli

    2011-07-01

    To explore arsenic accumulation and toxicity mechanism following long-term use of realgar and provide scientific basis for safety use of realgar in clinic. The realgar which was used in the study contains 90% insoluble asenic sulfide (As2S2) and 1.696 mg x kg(-1) soluble arsenic. Two separate experiments were performed: 1) Twenty-eight fasting SD rats were orally given a single dose of realgar at the dose of 0.8 g x kg(-1) and the other four rats were given ultra-filtrated water served as control group. Blood, hearts, livers, kidneys, lungs and brains of four rats were taken out at 0.5, 1, 2, 4, 8, 16, 36 h respectively after treatment. Asenic quantity of each organ or blood sample was measured. 2) Forty SD rats were randomly divided into four groups: control group and realgar 0.02, 0.08, 0.16 g x kg(-1) groups, each group containing 5 females and 5 males. The rats were intra-gastrically treated with realgar once a day for successively 90 days, while the control group was given ultra-filtrated water. Asenic amount in blood, liver, kidney and brain of each rat was measured in fasting rats at 16 h after last dosing. Asenic amount of blood, liver, kidney, heart, lung and brain increased after single dosing of realgar at dose of 0.16 g x kg(-1), with the order from high to low blood > kidney > lung > liver > heart > brain. Asenic amount was much higher in blood than that in other organs. The feature of asenic distribution in blood following realgar administration may be the basis for its use for leukemia Ninety-day oral treatment of realgar led to significant accumulation of asenic in blood, kidney, liver and brain. The highest asenic accumulation times was found in kidney followed by liver, which was assumed to be associated with nephrotoxicity and hepatotoxicity of realgar. The highest amount of asenic was observed in blood after 90 day's administration of realgar, and the amount of asenic in organs was in the order of blood > kidney > liver > brain. Asenic can be

  2. Accumulating exercise and postprandial health in adolescents.

    Science.gov (United States)

    Bond, Bert; Williams, Craig A; Jackman, Sarah R; Woodward, Adam; Armstrong, Neil; Barker, Alan R

    2015-09-01

    To examine the influence of exercise intensity on postprandial health outcomes in adolescents when exercise is accumulated throughout the day. 19 adolescents (9 male, 13.7±0.4 years old) completed three 1-day trials in a randomised order: (1) rest (CON); or four bouts of (2) 2×1 min cycling at 90% peak power with 75 s recovery (high-intensity interval exercise; HIIE); or (3) cycling at 90% of the gas exchange threshold (moderate-intensity exercise; MIE), which was work-matched to HIIE. Each bout was separated by 2 hours. Participants consumed a high fat milkshake for breakfast and lunch. Postprandial triacylglycerol (TAG), glucose, systolic blood pressure (SBP) and fat oxidation were assessed throughout the day. There was no effect of trial on total area under the curve (TAUC) for TAG (P=0.87). TAUC-glucose was lower in HIIE compared to CON (P=0.03, ES=0.42) and MIE (P=0.04, ES=0.41), with no difference between MIE and CON (P=0.89, ES=0.04). Postprandial SBP was lower in HIIE compared to CON (P=0.04, ES=0.50) and MIE (P=0.04, ES=0.40), but not different between MIE and CON (P=0.52, ES=0.11). Resting fat oxidation was increased in HIIE compared to CON (P=0.01, ES=0.74) and MIE (P=0.05, ES=0.51), with no difference between MIE and CON (P=0.37, ES=0.24). Neither exercise trial attenuated postprandial lipaemia. However, accumulating brief bouts of HIIE, but not MIE, reduced postprandial plasma glucose and SBP, and increased resting fat oxidation in adolescent boys and girls. The intensity of accumulated exercise may therefore have important implications for health outcomes in youth. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Test Plan - Solids Accumulation Scouting Studies

    Energy Technology Data Exchange (ETDEWEB)

    Duignan, M. R.; Steeper, T. J.; Steimke, J. L.; Fowley, M. D.

    2012-05-10

    This plan documents the highlights of the Solids Accumulations Scouting Studies test; a project, from Washington River Protection Solutions (WRPS), that began on February 1, 2012. During the last 12 weeks considerable progress has been made to design and plan methods that will be used to estimate the concentration and distribution of heavy fissile solids in accumulated solids in the Hanford double-shell tank (DST) 241-AW-105 (AW-105), which is the primary goal of this task. This DST will be one of the several waste feed delivery staging tanks designated to feed the Pretreatment Facility (PTF) of the Waste Treatment and Immobilization Plant (WTP). Note that over the length of the waste feed delivery mission AW-105 is currently identified as having the most fill empty cycles of any DST feed tanks, which is the reason for modeling this particular tank. At SRNL an existing test facility, the Mixing Demonstration Tank, which will be modified for the present work, will use stainless steel particles in a simulant that represents Hanford waste to perform mock staging tanks transfers that will allow solids to accumulate in the tank heel. The concentration and location of the mock fissile particles will be measured in these scoping studies to produce information that will be used to better plan larger scaled tests. Included in these studies is a secondary goal of developing measurement methods to accomplish the primary goal. These methods will be evaluated for use in the larger scale experiments. Included in this plan are the several pretest activities that will validate the measurement techniques that are currently in various phases of construction. Aspects of each technique, e.g., particle separations, volume determinations, topographical mapping, and core sampling, have been tested in bench-top trials, as discussed herein, but the actual equipment to be employed during the full test will need evaluation after fabrication and integration into the test facility.

  4. Electrochemical accumulators batteries; Accumulateurs electrochimiques batteries

    Energy Technology Data Exchange (ETDEWEB)

    Ansart, F.; Castillo, S.; Laberty- Robert, C.; Pellizon-Birelli, M. [Universite Paul Sabatier, Lab. de Chimie des Materiaux Inorganiques et Energetiques, CIRIMAT, UMR CNRS 5085, 31 - Toulouse (France)] [and others

    2000-07-01

    It is necessary to storage the electric power in batteries to join the production and the utilization. In this domain progresses are done every days in the technics and also in the available materials. These technical days present the state of the art in this domain. Many papers were presented during these two days giving the research programs and recent results on the following subjects: the lithium batteries, the electrolytes performances and behaviour, lead accumulators, economic analysis of the electrochemical storage market, the batteries applied to the transportation sector and the telephones. (A.L.B.)

  5. Storing wind energy into electrical accumulators

    Science.gov (United States)

    Dordescu, M.; Petrescu, D. I.; Erdodi, G. M.

    2016-12-01

    Shall be determined, in this work, the energy stored in the accumulators electrical, AE, at a wind system operating at wind speeds time-varying. mechanical energy caught in the turbine from the wind, (TV), is transformed into electrical energy by the generator synchronous with the permanent magnets, GSMP. The Generator synchronous with the permanent magnets saws, via a rectifier, energy in a battery AE, finished in a choice of two: variant 1-unregulated rectifier and variant of the 2-controlled rectifier and task adapted. Through simulation determine the differences between the two versions

  6. Selenium accumulation and metabolism in algae.

    Science.gov (United States)

    Schiavon, Michela; Ertani, Andrea; Parrasia, Sofia; Vecchia, Francesca Dalla

    2017-08-01

    Selenium (Se) is an intriguing element because it is metabolically required by a variety of organisms, but it may induce toxicity at high doses. Algae primarily absorb selenium in the form of selenate or selenite using mechanisms similar to those reported in plants. However, while Se is needed by several species of microalgae, the essentiality of this element for plants has not been established yet. The study of Se uptake and accumulation strategies in micro- and macro-algae is of pivotal importance, as they represent potential vectors for Se movement in aquatic environments and Se at high levels may affect their growth causing a reduction in primary production. Some microalgae exhibit the capacity of efficiently converting Se to less harmful volatile compounds as a strategy to cope with Se toxicity. Therefore, they play a crucial role in Se-cycling through the ecosystem. On the other side, micro- or macro-algae enriched in Se may be used in Se biofortification programs aimed to improve Se content in human diet via supplementation of valuable food. Indeed, some organic forms of selenium (selenomethionine and methylselenocysteine) are known to act as anticarcinogenic compounds and exert a broad spectrum of beneficial effects in humans and other mammals. Here, we want to give an overview of the developments in the current understanding of Se uptake, accumulation and metabolism in algae, discussing potential ecotoxicological implications and nutritional aspects. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Primitive Accumulation and Temporalities of Capitalism

    Directory of Open Access Journals (Sweden)

    Joanna Bednarek

    2015-04-01

    Full Text Available The main thesis of the article is the statement that capitalism is composed of many different, incoherent temporalities, as well as that apprehension of capitalism from the angle of primitive accumulation enables the more accurate grasp of the modes of its functioning, including the complexity created by the interactions of the temporalities mentionned. The problem of primitive accumulation is, as Sandro Mezzadra proves, a good starting point for analysing this issue. It allows us to pose two questions: first, the question of the relation between the historical dimension and the structural logic of capitalism; second, the question of hierarchical relation between the center and the periphery of the capitalist system.Dipesh Chakrabarty’s project of ‘provincializing Europe’ proves helpful here, as it’s goal is deconstruction of the categories of progress, modernization and the capital with its abstract structure. The aim is not to negate the fact that capitalist abstraction is a real force, but to show that this force develops by means of constant assimiliation of the other – redefined as ‘backward’ or archaic. The linear scheme is in force, because it is the main mechanism of imposing the power of capital; as such, it is not politically neutral.

  8. Normative evidence accumulation in unpredictable environments

    Science.gov (United States)

    Glaze, Christopher M; Kable, Joseph W; Gold, Joshua I

    2015-01-01

    In our dynamic world, decisions about noisy stimuli can require temporal accumulation of evidence to identify steady signals, differentiation to detect unpredictable changes in those signals, or both. Normative models can account for learning in these environments but have not yet been applied to faster decision processes. We present a novel, normative formulation of adaptive learning models that forms decisions by acting as a leaky accumulator with non-absorbing bounds. These dynamics, derived for both discrete and continuous cases, depend on the expected rate of change of the statistics of the evidence and balance signal identification and change detection. We found that, for two different tasks, human subjects learned these expectations, albeit imperfectly, then used them to make decisions in accordance with the normative model. The results represent a unified, empirically supported account of decision-making in unpredictable environments that provides new insights into the expectation-driven dynamics of the underlying neural signals. DOI: http://dx.doi.org/10.7554/eLife.08825.001 PMID:26322383

  9. Sequential evidence accumulation in decision making

    Directory of Open Access Journals (Sweden)

    Daniel Hausmann

    2008-03-01

    Full Text Available Judgments and decisions under uncertainty are frequently linked to a prior sequential search for relevant information. In such cases, the subject has to decide when to stop the search for information. Evidence accumulation models from social and cognitive psychology assume an active and sequential information search until enough evidence has been accumulated to pass a decision threshold. In line with such theories, we conceptualize the evidence threshold as the ``desired level of confidence'' (DLC of a person. This model is tested against a fixed stopping rule (one-reason decision making and against the class of multi-attribute information integrating models. A series of experiments using an information board for horse race betting demonstrates an advantage of the proposed model by measuring the individual DLC of each subject and confirming its correctness in two separate stages. In addition to a better understanding of the stopping rule (within the narrow framework of simple heuristics, the results indicate that individual aspiration levels might be a relevant factor when modelling decision making by task analysis of statistical environments.

  10. Hericium erinaceus (Bull.: Fr) Pers. cultivated under tropical conditions: isolation of hericenones and demonstration of NGF-mediated neurite outgrowth in PC12 cells via MEK/ERK and PI3K-Akt signaling pathways.

    Science.gov (United States)

    Phan, Chia-Wei; Lee, Guan-Serm; Hong, Sok-Lai; Wong, Yuin-Teng; Brkljača, Robert; Urban, Sylvia; Abd Malek, Sri Nurestri; Sabaratnam, Vikineswary

    2014-12-01

    Hericium erinaceus (Bull.: Fr.) Pers. is an edible and medicinal mushroom used traditionally to improve memory. In this study, we investigated the neuritogenic effects of hericenones isolated from H. erinaceus and the mechanisms of action involved. H. erinaceus was cultivated and the secondary metabolites were elucidated by high performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR). The secondary metabolites were tested for neurite outgrowth activity (if any). Rat pheochromocytoma (PC12) cells were employed and the nerve growth factor (NGF) level was also determined. The signaling pathways involved in the mushroom-induced neuritogenesis were investigated using several pharmacological inhibitors. Hericenones B-E (1-4), erinacerin A (5) and isohericerin (6) were isolated from the basidiocarps of H. erinaceus. The hericenones did not promote neurite outgrowth but when induced with a low concentration of NGF (5 ng mL(-1)), the neuritogenic activity was comparable to that of the positive control (50 ng mL(-1) of NGF). Hericenone E was able to stimulate NGF secretion which was two-fold higher than that of the positive control. The neuritogenesis process was partially blocked by the tyrosine kinase receptor (Trk) inhibitor, K252a, suggesting that the neuritogenic effect was not solely due to NGF. Hericenone E also increased the phosphorylation of extracellular-signal regulated kinases (ERKs) and protein kinase B (Akt). Taken together, this study suggests that hericenone E potentiated NGF-induced neuritogenesis in PC12 cells via the MEK/ERK and PI3K/Akt pathways.

  11. Chain-length dependent para-phenyelene film- and needle-growth on dielectrics

    DEFF Research Database (Denmark)

    Balzer, Frank; Rubahn, Horst-Günter

    2004-01-01

    Surface unit cells of vacuum grown ultrathin films of blue-light emitting para-phenylene oligomers on alkali halides and on muscovite mica have been determined using low energy electron diffraction. Both, films from upright and from laying molecules are grown on alkali halide (1 0 0) and mica (0...

  12. The MX/G/1 queue with queue length dependent service times

    Directory of Open Access Journals (Sweden)

    Bong Dae Choi

    2001-01-01

    Full Text Available We deal with the MX/G/1 queue where service times depend on the queue length at the service initiation. By using Markov renewal theory, we derive the queue length distribution at departure epochs. We also obtain the transient queue length distribution at time t and its limiting distribution and the virtual waiting time distribution. The numerical results for transient mean queue length and queue length distributions are given.

  13. Alkyl chain length-dependent surface reaction of dodecahydro-N-alkylcarbazoles on Pt model catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Gleichweit, Christoph; Amende, Max; Bauer, Udo; Schernich, Stefan; Höfert, Oliver; Lorenz, Michael P. A.; Zhao, Wei; Bachmann, Philipp; Papp, Christian, E-mail: christian.papp@fau.de [Lehrstuhl für Physikalische Chemie II, Friedrich-Alexander-Universität Erlangen-Nürnberg, Egerlandstrasse 3, 91058 Erlangen (Germany); Müller, Michael; Koch, Marcus [Lehrstuhl für Chemische Reaktionstechnik, Friedrich-Alexander-Universität Erlangen-Nürnberg, Egerlandstrasse 3, 91058 Erlangen (Germany); Wasserscheid, Peter [Lehrstuhl für Chemische Reaktionstechnik, Friedrich-Alexander-Universität Erlangen-Nürnberg, Egerlandstrasse 3, 91058 Erlangen (Germany); Erlangen Catalysis Resource Center, Friedrich-Alexander-Universität Erlangen-Nürnberg, Egerlandstrasse 3, 91058 Erlangen (Germany); Libuda, Jörg; Steinrück, Hans-Peter [Lehrstuhl für Physikalische Chemie II, Friedrich-Alexander-Universität Erlangen-Nürnberg, Egerlandstrasse 3, 91058 Erlangen (Germany); Erlangen Catalysis Resource Center, Friedrich-Alexander-Universität Erlangen-Nürnberg, Egerlandstrasse 3, 91058 Erlangen (Germany)

    2014-05-28

    The concept of liquid organic hydrogen carriers (LOHC) holds the potential for large scale chemical storage of hydrogen at ambient conditions. Herein, we compare the dehydrogenation and decomposition of three alkylated carbazole-based LOHCs, dodecahydro-N-ethylcarbazole (H{sub 12}-NEC), dodecahydro-N-propylcarbazole (H{sub 12}-NPC), and dodecahydro-N-butylcarbazole (H{sub 12}-NBC), on Pt(111) and on Al{sub 2}O{sub 3}-supported Pt nanoparticles. We follow the thermal evolution of these systems quantitatively by in situ high-resolution X-ray photoelectron spectroscopy. We show that on Pt(111) the relevant reaction steps are not affected by the different alkyl substituents: for all LOHCs, stepwise dehydrogenation to NEC, NPC, and NBC is followed by cleavage of the C–N bond of the alkyl chain starting at 380–390 K. On Pt/Al{sub 2}O{sub 3}, we discern dealkylation on defect sites already at 350 K, and on ordered, (111)-like facets at 390 K. The dealkylation process at the defects is most pronounced for NEC and least pronounced for NBC.

  14. Ribosome reinitiation can explain length-dependent translation of messenger RNA.

    Science.gov (United States)

    Rogers, David W; Böttcher, Marvin A; Traulsen, Arne; Greig, Duncan

    2017-06-01

    Models of mRNA translation usually presume that transcripts are linear; upon reaching the end of a transcript each terminating ribosome returns to the cytoplasmic pool before initiating anew on a different transcript. A consequence of linear models is that faster translation of a given mRNA is unlikely to generate more of the encoded protein, particularly at low ribosome availability. Recent evidence indicates that eukaryotic mRNAs are circularized, potentially allowing terminating ribosomes to preferentially reinitiate on the same transcript. Here we model the effect of ribosome reinitiation on translation and show that, at high levels of reinitiation, protein synthesis rates are dominated by the time required to translate a given transcript. Our model provides a simple mechanistic explanation for many previously enigmatic features of eukaryotic translation, including the negative correlation of both ribosome densities and protein abundance on transcript length, the importance of codon usage in determining protein synthesis rates, and the negative correlation between transcript length and both codon adaptation and 5' mRNA folding energies. In contrast to linear models where translation is largely limited by initiation rates, our model reveals that all three stages of translation-initiation, elongation, and termination/reinitiation-determine protein synthesis rates even at low ribosome availability.

  15. Comment on "Length-dependent translation of messenger RNA by ribosomes"

    CERN Document Server

    Zhang, Yunxin

    2011-01-01

    In recent paper [Phys. Rev. E {\\bf 83}, 042903 (2011)], a simple model for the translation of messenger RNA by ribosomes is provided, and the expression of translational ratio of protein is given. In this comments, varied methods to get this ratio are addressed. Depending on a different method, we find that, roughly speaking, this translational ratio decays exponentially with mRNA length in prokaryotic cell, and reciprocally with mRNA length in eukaryotic cells.

  16. An uncommon cause of bifacial weakness and non-length-dependent demyelinating neuropathy

    Directory of Open Access Journals (Sweden)

    Madhu Nagappa

    2015-01-01

    Full Text Available Tangier disease is a rare metabolic disorder that causes neuropathy in half of the affected individuals. We present the clinical, electrophysiological, and histopathological findings in a middle-aged gentleman of Tangier disease who was initially diagnosed as leprosy and treated with antileprosy drugs. The presence of a demyelinating electrophysiology in a patient with predominant upper limb involvement and facial diplegia should raise the suspicion of Tangier disease. Estimation of serum lipids should form a part of routine evaluation in order to avoid misdiagnosis.

  17. Alkyl chain length-dependent surface reaction of dodecahydro-N-alkylcarbazoles on Pt model catalysts

    Science.gov (United States)

    Gleichweit, Christoph; Amende, Max; Bauer, Udo; Schernich, Stefan; Höfert, Oliver; Lorenz, Michael P. A.; Zhao, Wei; Müller, Michael; Koch, Marcus; Bachmann, Philipp; Wasserscheid, Peter; Libuda, Jörg; Steinrück, Hans-Peter; Papp, Christian

    2014-05-01

    The concept of liquid organic hydrogen carriers (LOHC) holds the potential for large scale chemical storage of hydrogen at ambient conditions. Herein, we compare the dehydrogenation and decomposition of three alkylated carbazole-based LOHCs, dodecahydro-N-ethylcarbazole (H12-NEC), dodecahydro-N-propylcarbazole (H12-NPC), and dodecahydro-N-butylcarbazole (H12-NBC), on Pt(111) and on Al2O3-supported Pt nanoparticles. We follow the thermal evolution of these systems quantitatively by in situ high-resolution X-ray photoelectron spectroscopy. We show that on Pt(111) the relevant reaction steps are not affected by the different alkyl substituents: for all LOHCs, stepwise dehydrogenation to NEC, NPC, and NBC is followed by cleavage of the C-N bond of the alkyl chain starting at 380-390 K. On Pt/Al2O3, we discern dealkylation on defect sites already at 350 K, and on ordered, (111)-like facets at 390 K. The dealkylation process at the defects is most pronounced for NEC and least pronounced for NBC.

  18. Length-dependent thermal conductivity in suspended single-layer graphene.

    Science.gov (United States)

    Xu, Xiangfan; Pereira, Luiz F C; Wang, Yu; Wu, Jing; Zhang, Kaiwen; Zhao, Xiangming; Bae, Sukang; Tinh Bui, Cong; Xie, Rongguo; Thong, John T L; Hong, Byung Hee; Loh, Kian Ping; Donadio, Davide; Li, Baowen; Özyilmaz, Barbaros

    2014-04-16

    Graphene exhibits extraordinary electronic and mechanical properties, and extremely high thermal conductivity. Being a very stable atomically thick membrane that can be suspended between two leads, graphene provides a perfect test platform for studying thermal conductivity in two-dimensional systems, which is of primary importance for phonon transport in low-dimensional materials. Here we report experimental measurements and non-equilibrium molecular dynamics simulations of thermal conduction in suspended single-layer graphene as a function of both temperature and sample length. Interestingly and in contrast to bulk materials, at 300 K, thermal conductivity keeps increasing and remains logarithmically divergent with sample length even for sample lengths much larger than the average phonon mean free path. This result is a consequence of the two-dimensional nature of phonons in graphene, and provides fundamental understanding of thermal transport in two-dimensional materials.

  19. Anomalous length dependence of conductance of aromatic nanoribbons with amine anchoring groups

    KAUST Repository

    Bilić, Ante

    2012-09-06

    Two sets of aromatic nanoribbons, based around a common hexagonal scaffolding, with single and dual terminal amine groups have been considered as potential molecular wires in a junction formed by gold leads. Charge transport through the two-terminal device has been modeled using density functional theory (with and without self-interaction correction) and the nonequilibrium Green\\'s function method. The effects of wire length, multiple terminal contacts, and pathways across the junction have been investigated. For nanoribbons with the oligopyrene motif and conventional single amine terminal groups, an increase in the wire length causes an exponential drop in the conductance. In contrast, for the nanoribbons with the oligoperylene motif and dual amine anchoring groups the predicted conductance rises with the wire length over the whole range of investigated lengths. Only when the effects of self-interaction correction are taken into account, the conductance of the oligoperylene ribbons exhibits saturation for longer members of the series. The oligoperylene nanoribbons, with dual amine groups at both terminals, show the potential to fully harness the highly conjugated system of π molecular orbitals across the junction. © 2012 American Physical Society.

  20. Length-dependent conformational transitions of polyglutamine repeats as molecular origin of fibril initiation.

    Science.gov (United States)

    Heck, Benjamin S; Doll, Franziska; Hauser, Karin

    2014-01-01

    Polyglutamine (polyQ) sequences are found in a variety of proteins with normal function. However, their repeat expansion is associated with a number of neurodegenerative diseases, also called polyQ diseases. The length of the polyQ sequence, varying in the number of consecutive glutamines among different diseases, is critical for inducing fibril formation. We performed a systematic spectroscopic study to analyze the conformation of polyQ model peptides in dependence of the glutamine sequence lengths (K2QnK2 with n=10, 20, 30). Complementary FTIR- and CD-spectra were measured in a wide concentration range and repeated heating and cooling cycles revealed the thermal stability of formed β-sheets. The shortest glutamine sequence K2Q10K2 shows solely random structure for concentrations up to 10 mg/ml. By increasing the peptide length to K2Q20K2, a significant fraction of β-sheet is observed even at low concentrations of 0.01 mg/ml. The higher the concentration, the more the structural composition is dominated by the intermolecular β-sheet. The formation of highly thermostable β-sheet is much more pronounced in K2Q30K2. K2Q30K2 precipitates at a concentration of 0.3 mg/ml. Our spectroscopic study shows that the aggregation tendency is enhanced with increased glutamine repeat expansion and that the concentration plays another critical factor in the β-sheet formation. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. The DTH8-Hd1 Module Mediates Day-Length-Dependent Regulation of Rice Flowering.

    Science.gov (United States)

    Du, Anping; Tian, Wei; Wei, Menghao; Yan, Wei; He, Hang; Zhou, Da; Huang, Xi; Li, Shigui; Ouyang, Xinhao

    2017-07-05

    Photoperiodic flowering is one of the most important pathways to govern flowering in rice (Oryza sativa), in which Heading date 1 (Hd1), an ortholog of the Arabidopsis CONSTANS gene, encodes a pivotal regulator. Hd1 promotes flowering under short-day conditions (SD) but represses flowering under long-day conditions (LD) by regulating the expression of Heading date 3a (Hd3a), the FLOWERING LOCUS T (FT) ortholog in rice. However, the molecular mechanism of how Hd1 changes its regulatory activity in response to day length remains largely unknown. In this study, we demonstrated that the repression of flowering in LD by Hd1 is dependent on the transcription factor DAYS TO HEADING 8 (DTH8). Loss of DTH8 function results in the activation of Hd3a by Hd1, leading to early flowering. We found that Hd1 directly interacts with DTH8 and that the formation of the DTH8-Hd1 complex is necessary for the transcriptional repression of Hd3a by Hd1 in LD, implicating that the switch of Hd1 function is mediated by DTH8 in LD rather than in SD. Furthermore, we revealed that DTH8 associates with the Hd3a promoter to modulate the level of H3K27 trimethylation (H3K27me3) at the Hd3a locus. In the presence of the DTH8-Hd1 complex, the H3K27me3 level was increased at Hd3a, whereas loss of DTH8 function resulted in decreased H3K27me3 level at Hd3a. Taken together, our findings indicate that, in response to day length, DTH8 plays a critical role in mediating the transcriptional regulation of Hd3a by Hd1 through the DTH8-Hd1 module to shape epigenetic modifications in photoperiodic flowering. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

  2. Gain length dependence on phase shake in the VUV-FEL at the TESLA Test Facility

    Energy Technology Data Exchange (ETDEWEB)

    Pflueger, J. [DESY/HASYLAB, Hamburg (Germany); Schneidmiller, E.A. [Automatic Systems Corporation, Samara (Russian Federation); Pierini, P. [INFN, Milano (Italy)

    1995-12-31

    The TTF VUV FEL, which is in its design stage at DESY, consists of a 30 m long SASE FEL which will radiate around 6 nm, driven by a superconducting linac with final energy of 1 GeV. One of the important issues in its design is the undulator performance, which is studied in this paper. The present setup, including FODO lattice, is discussed in this paper. Results of simulations, including the realistic wiggler field errors and beam stearing, are presented. Dependence of the performance, in particular the gain and saturation length as well as the saturation peak power, on the wiggler field errors is discussed.

  3. Fast Water Transport in CNTs: length dependence and entrane/exit effects

    DEFF Research Database (Denmark)

    Walther, Jens Honore; Koumoutsakos, Petros

    , for the first time, that under imposed pressures of the order of 1 bar, water entry into the CNT cavity and exit from the CNT end, can occur only on pre-wetted membranes. We conduct large scale simulations for up to 500nm long CNTs and observe a previously unseen dependence of the flow enhancement rates......Superfast water transport in carbon nanotube (CNT) membranes has been reported in experimental studies. We use Molecular Dynamics simulations to elucidate the mechanisms of water entry, exit and transport in 2nm-diameter hydrophobic CNTs embedded in a hydrophilic membrane matrix. We demonstrate...

  4. Chain-length-dependent intermolecular packing in polyphenylenes: a high pressure study

    CERN Document Server

    Heimel, G; Oehzelt, M; Hummer, K; Koppelhuber-Bitschnau, B; Porsch, F; Ambrosch-Draxl, C; Resel, R

    2003-01-01

    We report on pressure-induced structural changes in crystalline oligo(para-phenylenes) containing two to six phenyl rings. The results are discussed with particular emphasis put on the implications these changes in intermolecular distances and molecular arrangement have on important bulk properties of this class of materials, such as optical response and charge transport. We performed energy dispersive x-ray diffraction in a systematic study on polycrystalline powders of biphenyl, para-terphenyl, p-quaterphenyl, p-quinquephenyl and p-sexiphenyl under hydrostatic pressure up to 60 kbar. Revisiting the crystal structures at ambient conditions reveals details in the packing principle. A linear relationship between the density at ambient conditions and the number of phenyl rings is found. High pressure data not only yields pressure-dependent lattice parameters and hints towards pressure-induced changes in the molecular arrangement but also allows for an analysis of the equations of state of these substances as a ...

  5. Conductance of Conjugated Molecular Wires: Length Dependence, Anchoring Groups, and Band Alignment

    DEFF Research Database (Denmark)

    Peng, Guowen; Strange, Mikkel; Thygesen, Kristian Sommer

    2009-01-01

    . In comparison, the corresponding values for amine-terminated thiophene are calculated to be β = 0.160 Å−1 and Gc = 0.038G0. These results show that (1) the contact resistance is mainly determined by the anchoring group and (2) the decay constant, which determines the conductance in the long wire limit......, is not solely determined by the intrinsic band gap of the molecular wire but also depends on the anchoring group. This is because the alignment of the metal Fermi level with respect to the molecular levels is controlled by charge transfer and interface dipoles which in turn are determined by the local chemistry...

  6. Observation of Query Pulse Length Dependent Ramsey Interference in Rubidium Vapor Using Pulsed Raman Excitation

    Science.gov (United States)

    2011-11-07

    diode laser, AOM for generating Raman beams and a buffer gas filled Rb cell. FCL: fiber collimating lens, FCP: fiber coupler , NDF: neutral density...filter, OF: optical fiber, P: prism (out-of-plane as discussed in the text), PP: prism polarizer, PBS: polarizing beam splitter, PD: photodiode, and HWP...interference can also be observed without the prism polarizer since the effect is manifested in both Raman beams. The prism polarizer allows us to observe

  7. Performance Comparisons of Improved Regular Repeat Accumulate (RA and Irregular Repeat Accumulate (IRA Turbo Decoding

    Directory of Open Access Journals (Sweden)

    Ahmed Abdulkadhim Hamad

    2017-08-01

    Full Text Available In this paper, different techniques are used to improve the turbo decoding of regular repeat accumulate (RA and irregular repeat accumulate (IRA codes. The adaptive scaling of a-posteriori information produced by Soft-output Viterbi decoder (SOVA is proposed. The encoded pilots are another scheme that applied for short length RA codes. This work also suggests a simple and a fast method to generate a random interleaver having a free 4 cycle Tanner graph. Progressive edge growth algorithm (PEG is also studied and simulated to create the Tanner graphs which have a great girth.

  8. Millennially Averaged Accumulation Rates for Lake Vostok, Version 1

    Data.gov (United States)

    National Aeronautics and Space Administration — This data set consists of inferred accumulation rates from three radar layers (26, 35 and 41 thousand years old) in the Vostok Subglacial Lake region. Accumulation...

  9. Accumulation of sunscreen in human skin after daily applications

    DEFF Research Database (Denmark)

    Bodekær, Mette; Akerström, Ulf; Wulf, Hans Christian

    2012-01-01

    Sunscreen applied to the skin provides a considerable sun protection factor (SPF) even after 8 h. Sunscreen use for consecutive days may therefore result in an accumulation of the product. This study investigated the consequences of accumulation for SPF.......Sunscreen applied to the skin provides a considerable sun protection factor (SPF) even after 8 h. Sunscreen use for consecutive days may therefore result in an accumulation of the product. This study investigated the consequences of accumulation for SPF....

  10. Uncertainty on Fatigue Damage Accumulation for Composite Materials

    DEFF Research Database (Denmark)

    Toft, Henrik Stensgaard; Sørensen, John Dalsgaard

    2009-01-01

    In the present paper stochastic models for fatigue damage accumulation for composite materials are presented based on public available constant and variable amplitude fatigue tests. The methods used for estimating the SN-curve and accumulated fatigue damage are presented.......In the present paper stochastic models for fatigue damage accumulation for composite materials are presented based on public available constant and variable amplitude fatigue tests. The methods used for estimating the SN-curve and accumulated fatigue damage are presented....

  11. 47 CFR 32.3300 - Accumulated depreciation-nonoperating.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Accumulated depreciation-nonoperating. 32.3300....3300 Accumulated depreciation—nonoperating. (a) This account shall include the accumulated amortization and depreciation associated with the investment contained in Account 2006, Nonoperating Plant. (b...

  12. 40 CFR 273.15 - Accumulation time limits.

    Science.gov (United States)

    2010-07-01

    ... of accumulation of such quantities of universal waste as necessary to facilitate proper recovery... the purpose of accumulation of such quantities of universal waste as necessary to facilitate proper recovery, treatment, or disposal. (c) A small quantity handler of universal waste who accumulates universal...

  13. recent trends in accumulation rate, elemental and isotopic ...

    African Journals Online (AJOL)

    al. 1990). Quarternary sediments accumulated along the lake, on the east of. Speke Gulf, south of Mwanza Gulf, north of. Kagera River and east of Nyanza Gulf ..... accumulation rate values in Magu Bay fall within the range of reported accumulation rates in lakes that are experiencing eutrophication. ACKNOWLEDGEMENT.

  14. Fluctuations, Environment, Mutations Accumulation and Ageing

    Science.gov (United States)

    Biecek, Przemysław; Cebrat, Stanisław

    We present a model of evolution of the age structured population based on the Monte Carlo method. We have assumed that the health status of an individual is described by variance of its fluctuations. Each expressed deleterious mutation increases the fluctuations. Additionally, the fluctuations of the environment are superimposed on the fluctuations of individuals in the population. An individual dies if the combination of both stochastic processes trespass the limit (level of homeostasis) set as the model parameter. The genes are switched on chronologically, what leads to accumulating defective genes expressed during the late periods of life in the genetic pool of the population. That results in the specific age structured population, in accordance with the predictions of Medawar's hypothesis of ageing and the results of the Penna model simulations. A decrease of the variation of the environmental noise increases the average expected lifespan of individuals.

  15. Human accumulation of mercury in Greenland

    DEFF Research Database (Denmark)

    Johansen, Poul; Mulvad, Gert; Pedersen, Henning Sloth

    2007-01-01

    In the Arctic, the traditional diet exposes its people to a high intake of mercury especially from marine mammals. To determine whether the mercury is accumulated in humans, we analyzed autopsy samples of liver, kidney and spleen from adult ethnic Greenlanders who died between 1990 and 1994 from...... a wide range of causes, natural and violent. Liver, kidney and spleen samples from between 33 and 71 case subjects were analyzed for total mercury and methylmercury, and liver samples also for selenium. Metal levels in men and women did not differ and were not related to age except in one case, i.......e. for total mercury in liver, where a significant declining concentration with age was observed. The highest total mercury levels were found in kidney followed by liver and spleen. Methylmercury followed the same pattern, but levels were much lower, constituting only 19% of the total mercury concentration...

  16. Partial connectivity increases cultural accumulation within groups.

    Science.gov (United States)

    Derex, Maxime; Boyd, Robert

    2016-03-15

    Complex technologies used in most human societies are beyond the inventive capacities of individuals. Instead, they result from a cumulative process in which innovations are gradually added to existing cultural traits across many generations. Recent work suggests that a population's ability to develop complex technologies is positively affected by its size and connectedness. Here, we present a simple computer-based experiment that compares the accumulation of innovations by fully and partially connected groups of the same size in a complex fitness landscape. We find that the propensity to learn from successful individuals drastically reduces cultural diversity within fully connected groups. In comparison, partially connected groups produce more diverse solutions, and this diversity allows them to develop complex solutions that are never produced in fully connected groups. These results suggest that explanations of ancestral patterns of cultural complexity may need to consider levels of population fragmentation and interaction patterns between partially isolated groups.

  17. Truncating mutations of SPAST associated with hereditary spastic paraplegia indicate greater accumulation and toxicity of the M1 isoform of spastin.

    Science.gov (United States)

    Solowska, Joanna M; Rao, Anand N; Baas, Peter W

    2017-07-01

    The SPAST gene, which produces two isoforms (M1 and M87) of the microtubule-severing protein spastin, is the chief gene mutated in hereditary spastic paraplegia. Haploinsufficiency is a popular explanation for the disease, in part because most of the >200 pathogenic mutations of the gene are truncating and expected to produce only vanishingly small amounts of shortened proteins. Here we studied two such mutations, N184X and S245X, and our results suggest another possibility. We found that the truncated M1 proteins can accumulate to notably higher levels than their truncated M87 or wild-type counterparts. Reminiscent of our earlier studies on a pathogenic mutation that generates full-length M1 and M87 proteins, truncated M1 was notably more detrimental to neurite outgrowth than truncated M87, and this was true for both N184X and S245X. The greater toxicity and tendency to accumulate suggest that, over time, truncated M1 could damage the corticospinal tracts of human patients. Curiously, the N184X mutation triggers the reinitiation of translation at a third start codon in SPAST, resulting in synthesis of a novel M187 spastin isoform that is able to sever microtubules. Thus microtubule severing may not be as reduced as previously assumed in the case of that mutation. © 2017 Solowska 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).

  18. Tipping news in information accumulation system

    Science.gov (United States)

    Shin, J. K.

    2010-05-01

    As a continuous opinion dynamics model, the information accumulation system (IAS) includes three basic mechanisms of the news, the inheritance and the diffusion as contributing to the information accumulation process of a system. A system is composed of agents who diffuse information through internal interaction, while each of them has incomplete memory or inheritance rate. The news comes from external sources of information, such as mass media. Previously the model IAS was studied only for the small news problems. In this study, a tipping news problem is considered. A key question of the problem is: what is the minimum strength of advertisement that can tip the minority opinion to a majority one? Dynamics of the IAS is briefly revisited with a special interest on nonlinear behavior of the model. In particular, it is shown that a discrete map of the IAS for a single color problem can be transformed into a logistic map, from which the dynamics of the IAS can be better understood. To show the applicability of the IAS model, the result is applied to explain the concept of the critical population size, which claims that there is a minimum population size for a social knowledge system to be continuously inherited without being lost. And critical size of the tipping news is found analytically in terms of IAS parameters. Some of the key results from the present study are compared in detail with the results from the Brownian particle model, which is believed to be the most similar model to the IAS. The concept of tipping news is used to show that a traditional society can tip at an exceptionally low inter-community exposure. Finally, the result was applied to the language competition problem.

  19. Accumulation Characteristics of Pb by Zea Mays of Different Genotyoes

    Directory of Open Access Journals (Sweden)

    QIN Rong-lin

    2016-05-01

    Full Text Available To determine the characteristics of lead(Pb accumulation by different maize genotypes, two low accumulation genotypes(Quchen 11, Quchen 3 and two high accumulation maize genotypes(Jingfeng 8, Xuyu 1446 were used in a field experiment under Pb stress(2 000 mg·kg-1. The following parameters were measured including the change of plant biomass , Pb contents in different plant parts, total Pb uptake,Pb accumulation and translocation of different maize varieties,soil pH value and available Pb contents in soils. The results showed that: (1Compared with the control, the Pb stress caused a decrease at differnet levels on the biomass of roots, stems, leaves and grains of the four maize genotypes. The plant biomass decreased by 9.65%~20.46%. And the decrease level on the plant biomass of the low accumulation maize genotypes was less than the high accumulation maize genotypes. (2The Pb contents were found highest in the roots(95.39~121.02 mg·kg-1, followed by the leaves(25.56~43.21 mg·kg-1 and stems(14.06~25.41 mg·kg-1, and lest in the grains(2.52~5.38 mg·kg-1. Moreover, the Pb contents in roots were higher of low accumulation maize genotypes than high accumulation maize genotypes. In contrast, the Pb contents in the stems, leaves and grains were less of the low accumulation maize genotypes than the high accumulation maize genotypes. The total Pb accumulation of maize was 4.46~7.94 mg per plant, and which was significant less of the low accumulation maize genotypes than the high accumulation maize genotypes. (3For the four maize genotypes, both the accumulation factor and translocation factor of Pb were less than 1, and were smaller of the low accumulation maize genotypes than the high accumulation maize genotypes. (4The pH values in soils were 6.60~6.82, which were significant higher of the low accumulation maize genotypes than the high accumulation maize genotypes, the available Pb contents in soils were 969.86~1 116.15 mg·kg-1。

  20. Trehalose Accumulation Triggers Autophagy during Plant Desiccation.

    Directory of Open Access Journals (Sweden)

    Brett Williams

    2015-12-01

    Full Text Available Global climate change, increasingly erratic weather and a burgeoning global population are significant threats to the sustainability of future crop production. There is an urgent need for the development of robust measures that enable crops to withstand the uncertainty of climate change whilst still producing maximum yields. Resurrection plants possess the unique ability to withstand desiccation for prolonged periods, can be restored upon watering and represent great potential for the development of stress tolerant crops. Here, we describe the remarkable stress characteristics of Tripogon loliiformis, an uncharacterised resurrection grass and close relative of the economically important cereals, rice, sorghum, and maize. We show that T. loliiformis survives extreme environmental stress by implementing autophagy to prevent Programmed Cell Death. Notably, we identified a novel role for trehalose in the regulation of autophagy in T.loliiformis. Transcriptome, Gas Chromatography Mass Spectrometry, immunoblotting and confocal microscopy analyses directly linked the accumulation of trehalose with the onset of autophagy in dehydrating and desiccated T. loliiformis shoots. These results were supported in vitro with the observation of autophagosomes in trehalose treated T. loliiformis leaves; autophagosomes were not detected in untreated samples. Presumably, once induced, autophagy promotes desiccation tolerance in T.loliiformis, by removal of cellular toxins to suppress programmed cell death and the recycling of nutrients to delay the onset of senescence. These findings illustrate how resurrection plants manipulate sugar metabolism to promote desiccation tolerance and may provide candidate genes that are potentially useful for the development of stress tolerant crops.

  1. Vinpocetine attenuates lipid accumulation and atherosclerosis formation

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Yujun [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States); Li, Jian-Dong [Center for Inflammation, Immunity and Infection, and Department of Biology, Georgia State University, Atlanta, GA 30303 (United States); Yan, Chen, E-mail: Chen_Yan@urmc.rochester.edu [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States)

    2013-05-10

    Highlights: •Vinpocetine attenuates hyperlipidemia-induced atherosclerosis in a mouse model. •Vinpocetine antagonizes ox-LDL uptake and accumulation in macrophages. •Vinpocetine blocks the induction of ox-LDL receptor LOX-1 in vitro and in vivo. -- Abstract: Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent anti-inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis.

  2. ISABELLE, accumulators, bunched beams and cosmictrons

    Energy Technology Data Exchange (ETDEWEB)

    Month, M

    1977-12-05

    An elaboration of the ISABELLE concept as the model for a high energy, high luminosity proton-proton facility is given. Its place in the total high energy physics program is discussed. Certain features of the ISABELLE design which have not been consolidated, in particular injection and modes of beam operation, are considered. A new scheme is reviewed, one which could provide quick beam turn-on after construction, one in which there is a high probability of reaching and perhaps even exceeding the design objectives, one which should provide comparatively more flexible and reliable operation for physics, and finally one whose presence opens up a window to a much higher energy region. The new system involves the use of a physically separate current accumulator, allowing, therefore, the optimal utilization of the superconducting structures. The fact that an obvious addition to the complex will permit pp collisions in the 4 TeV center-of-mass energy region, which corresponds to an equivalent lab energy of approximately 10/sup 16/ eV, i.e., cosmic ray energies, prompts the added structure to be referred to as the COSMICTRON. The facility operated in the ''new'' manner proposed is considered to be ''the best ISABELLE that can be built.''

  3. Silver tolerance and accumulation in yeasts.

    Science.gov (United States)

    Kierans, M; Staines, A M; Bennett, H; Gadd, G M

    1991-01-01

    Debaryomyces hansenii (NCYC 459 and strain 75-21), Candida albicans (3153A), Saccharomyces cerevisiae (X2180-1B), Rhodotorula rubra (NCYC 797) and Aureobasidium pullulans (IMI 45533 and ATCC 42371) were grown on solid medium supplemented with varying concentrations of AgNO3. Although Ag+ is highly toxic towards yeasts, growth on solid media was still possible at Ag concentrations of 1-2 mM. Further subculture on higher Ag concentrations (up to 5 mM) resulted in elevated tolerance. The extent of Ag tolerance depended on whether Ag-containing plates were exposed to light prior to inoculation since light-mediated reduction of Ag+ to Ag0 resulted in the production of a less toxic silver species. Experimental organisms exhibited blackening of colonies and the surrounding agar during growth on AgNO3-containing medium especially at the highest Ag concentrations tested. All organisms accumulated Ag from the medium; electron microscopy revealed that silver was deposited as electron-dense granules in and around cell walls and in the external medium. X-ray microprobe analysis indicated that these granules were metallic Ag0 although AgCl was also present in some organisms. Volatile and non-volatile reducing compounds were produced by several test organisms which presumably effected Ag+ reduction to Ag0.

  4. Earthworms accumulate alanine in response to drought.

    Science.gov (United States)

    Holmstrup, Martin; Slotsbo, Stine; Henriksen, Per G; Bayley, Mark

    2016-09-01

    Earthworms have ecologically significant functions in tropical and temperate ecosystems and it is therefore important to understand how these animals survive during drought. In order to explore the physiological responses to dry conditions, we simulated a natural drought incident in a laboratory trial exposing worms in slowly drying soil for about one month, and then analyzed the whole-body contents of free amino acids (FAAs). We investigated three species forming estivation chambers when soils dry out (Aporrectodea tuberculata, Aporrectodea icterica and Aporrectodea longa) and one species that does not estivate during drought (Lumbricus rubellus). Worms subjected to drought conditions (Aporrectodea species and 300μmolg(-1) dry weight in L. rubellus. Proline was only weakly upregulated in some species as were a few other FAAs. Species forming estivation chambers (Aporrectodea spp.) did not show a better ability to conserve body water than the non-estivating species (L. rubellus) at the same drought level. These results suggest that the accumulation of alanine is an important adaptive trait in drought tolerance of earthworms in general. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Childhood obesity and human capital accumulation.

    Science.gov (United States)

    Palermo, Tia M; Dowd, Jennifer B

    2012-12-01

    The prevalence of childhood obesity has tripled in the United States over the last 25 years, and in addition to increased risks of many chronic diseases, obesity may also be linked to lower skill attainment, poor social competency, and poorer labor outcomes. Any causal links between obesity and human capital accumulation could have important consequences for both health and economic well-being over the life course. We investigate the association of obesity and cognitive and non-cognitive outcomes among US children and adolescents aged 5 to 19 using the Child Development Supplement of the Panel Survey of Income Dynamics. We perform OLS and individual fixed effects regressions to address unobserved time invariant heterogeneity in the relationship between overweight/obesity and abilities. Results provide limited support for the hypothesis that obesity negatively affects non-cognitive but not cognitive outcomes and suggest that discrimination rather than a biological mechanism contributes to negative outcomes found in the literature on adults. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Interaction and accumulation of manganese and cadmium in the manganese accumulator Lupinus albus.

    Science.gov (United States)

    Zornoza, Pilar; Sánchez-Pardo, Beatriz; Carpena, Ramón O

    2010-09-01

    The effects of the interaction between Mn and Cd on the growth of the white lupin (Lupinus albus), uptake of these metals, their accumulation, and effects on heavy metal stress indicators were studied under glasshouse conditions. Plants were grown with and without Mn and/or Cd for 4 weeks. The absence of Mn and Cd led to lipid peroxidation-induced loss of flavonoids and anthocyanins in the roots, reduced the size of the plant canopy, and led to the appearance of proteoid roots. Sensitivity to Cd in white lupin was enhanced by a low Mn supply, despite lower Cd uptake and accumulation (leaf Mn:Cd concentration ratio <3), as evidenced by increased lipid peroxidation in the leaves and strong inhibition of growth. However, when the Mn supply was adequate, the plants showed few symptoms of Cd toxicity, even though Cd uptake and accumulation increased. A Mn:Cd ratio of up to 20 was enough to minimize Cd stress in the leaf, reflecting the plants' relative tolerance to Cd under such conditions. Irrespective of the Mn supply, the increase in antioxidant compounds observed in the roots of Cd-treated plants might act as a protective mechanism by minimizing the oxidative stress caused by Cd exposure. In summary, high leaf Mn concentrations seem to render white lupins more tolerant to Cd stress. Copyright 2010 Elsevier GmbH. All rights reserved.

  7. Topically applied ceramide accumulates in skin glyphs

    Directory of Open Access Journals (Sweden)

    Zhang Q

    2015-07-01

    Full Text Available Qihong Zhang,1 Carol R Flach,1 Richard Mendelsohn,1 Guangru Mao,2 Apostolos Pappas,2 M Catherine Mack,2 Russel M Walters,2 Michael D Southall2 1Department of Chemistry, Rutgers University, Newark, 2Johnson & Johnson Consumer Companies, Inc., Skillman, NJ, USAAbstract: Ceramides (CERs, structural components of the stratum corneum (SC, impart essential barrier properties to this thin outer layer of the epidermis. Variations in CER species within this layer have been linked to several skin diseases. A recent proliferation of CER-containing topical skin-care products warrants the elucidation of CER penetration profiles in both healthy and diseased skin. In the current study, the spatial distributions of CER concentration profiles, following topical application of two species of CER, were tracked using infrared imaging. Suspensions of single-chain perdeuterated sphingosine and phytosphingosine CER in oleic acid were applied, in separate experiments, to the surface of healthy intact ex vivo human skin using Franz diffusion cells. Following either a 24- or 48-hour incubation period at 34°C, infrared images were acquired from microtomed skin sections. Both CER species accumulated in glyph regions of the skin and penetrated into the SC, to a limited extent, only in these regions. The concentration profiles observed herein were independent of the CER species and incubation time utilized in the study. As a result, a very heterogeneous, sparse, spatial distribution of CERs in the SC was revealed. In contrast, oleic acid was found to be fairly homogeneously distributed throughout the SC and viable epidermis, albeit at lower concentrations in the latter. A more uniform, lateral distribution of CERs in the SC would likely be important for barrier efficacy or enhancement.Keywords: stratum corneum, infrared imaging, topical delivery, oleic acid

  8. Desmosterol accumulation in users of amiodarone.

    Science.gov (United States)

    Simonen, P; Lehtonen, J; Lampi, A-M; Piironen, V; Stenman, U-H; Kupari, M; Gylling, H

    2018-01-01

    Amiodarone is an effective and widely used antiarrhythmic drug with many possible adverse effects including hypercholesterolaemia and hepatotoxicity. Our aim was to evaluate how long-term amiodarone treatment affects cholesterol metabolism. The study population consisted of 56 cardiac patients, of whom 20 were on amiodarone (amiodarone + group) and 36 did not use the drug (amiodarone - group). We also studied a control group of 124 individuals selected randomly from the population. Cholesterol metabolism was evaluated by analysis of serum noncholesterol sterols by gas-liquid chromatography and gas chromatography-mass spectrometry. Comparisons of serum lipids and noncholesterol sterols across the three groups showed increased serum triglyceride in users of amiodarone but no statistically significant group differences in total, LDL or HDL cholesterol or serum proprotein convertase subtilisin/kexin type 9 concentrations. Nor did the groups differ in the ratios of cholestanol or plant sterols to cholesterol in serum, suggesting that cholesterol absorption was unaltered. However, all users of amiodarone had very markedly elevated serum desmosterol concentrations: the desmosterol-to-cholesterol ratio (102 × μmol mmol-1 ) averaged 1030.7 ± 115.7 (mean ± SE) in the amiodarone + group versus 82.7 ± 3.4 and 75.9 ± 1.4 in the amiodarone - and the population control groups (P amiodarone was associated with on average 12-fold serum desmosterol concentrations compared with the control groups. This observation is fully novel and suggests that amiodarone interferes with the conversion of desmosterol to cholesterol in the cholesterol synthesis pathway. Whether accumulation of desmosterol plays a role in amiodarone-induced hepatotoxicity deserves to be studied in the future. © 2017 The Association for the Publication of the Journal of Internal Medicine.

  9. Aluminium accumulation and immunosuppressive effect in recipients of kidney transplants.

    OpenAIRE

    Nordal, K.P.; Dahl, E; Albrechtsen, D; Halse, J.; Leivestad, T.; Tretli, S; Flatmark, A.

    1988-01-01

    Aluminium that has accumulated in the body is thought to have a generalised cytotoxic effect. A prospective study of aluminium accumulation in bone-that is, subclinical aluminium toxicity--was carried out in 94 recipients of kidney allografts, who were followed up for three years. Subclinical aluminium toxicity was found in 66 patients. A significantly smaller proportion of patients with aluminium accumulation experienced a rejection episode: 30 (58%) nu 12 (86%) who received grafts from cada...

  10. EFFECTS OF PRETREATMENTS ON CALCIUM ACCUMULATION ONTO GAC

    OpenAIRE

    Miño, Esteban R.; Okuda, Tetsuji; NISHIJIMA, Wataru; OKADA, Mitsumasa

    2007-01-01

    The effect of coagulation and ozonation as pretreatments for granular activated carbon (GAC) filtration on calcium accumulation onto GAC was studied. Three kinds of FA solutions extracted from commercial leaf mold for horticulture were used: FA itself, FA after coagulation (FA-c) and FA after ozonation (FA-oz). Coagulation used as pretreatment before GAC filtration significantly decreased calcium accumulation onto GAC while ozonation caused a small increase on calcium accumulation onto GA...

  11. Bicarbonate trigger for inducing lipid accumulation in algal systems

    Science.gov (United States)

    Gardner, Robert; Peyton, Brent; Cooksey, Keith E.

    2015-08-04

    The present invention provides bicarbonate containing and/or bicarbonate-producing compositions and methods to induce lipid accumulation in an algae growth system, wherein the algae growth system is under light-dark cycling condition. By adding said compositions at a specific growth stage, said methods lead to much higher lipid accumulation and/or significantly reduced total time required for accumulating lipid in the algae growth system.

  12. Drug accumulation in the presence of the multidrug resistance pump

    DEFF Research Database (Denmark)

    Ayesh, S; Litman, Thomas; Stein, W D

    1997-01-01

    We studied the interaction between the multidrug transporter, P-glycoprotein, and two compounds that interact with it: vinblastine, a classical substrate of the pump, and verapamil, a classical reverser. Steady-state levels of accumulation of these two drugs were determined in a multidrug resistant...... P388 leukemia cell line, P388/ADR. The time course of accumulation of these drugs, and the effect of energy starvation and the presence of chloroquine on the level of their steady-state accumulation were quite disparate. Vinblastine inhibited the accumulation of verapamil whereas it enhanced...

  13. No saturation in the accumulation of alien species worldwide

    National Research Council Canada - National Science Library

    Hanno Seebens; Tim M Blackburn; Ellie E Dyer; Piero Genovesi; Philip E Hulme; Jonathan M Jeschke; Shyama Pagad; Petr Pysek; Marten Winter; Margarita Arianoutsou; Sven Bacher; Bernd Blasius; Giuseppe Brundu; César Capinha; Laura Celesti-grapow; Wayne Dawson; Stefan Dullinger; Nicol Fuentes; Heinke Jäger; John Kartesz; Marc Kenis; Holger Kreft; Ingolf Kühn; Bernd Lenzner; Andrew Liebhold; Alexander Mosena; Dietmar Moser; Misako Nishino; David Pearman; Jan Pergl; Wolfgang Rabitsch; Julissa Rojas-sandoval; Alain Roques; Stephanie Rorke; Silvia Rossinelli; Helen E Roy; Riccardo Scalera; Stefan Schindler; Katerina Stajerová; Barbara Tokarska-guzik; Mark Van Kleunen; Kevin Walker; Patrick Weigelt; Takehiko Yamanaka; Franz Essl

    2017-01-01

      Although research on human-mediated exchanges of species has substantially intensified during the last centuries, we know surprisingly little about temporal dynamics of alien species accumulations...

  14. Aquatic mosses used as indicators and accumulators of metals

    Energy Technology Data Exchange (ETDEWEB)

    Cenci, R.M.

    2001-07-01

    Living organisms, especially vegetables, can be used to monitor environmental pollutants either as bio-indicators or bio-accumulators. This project, using aquatic mosses of the species Fontinalis antipyretica, allowed an accurate diagnosis of water quality in lakes and rivers, at the same time mosses accumulated great amounts of heavy metals. The results showed that Fontinalis antipyretica had the ability to accumulate great amounts of trace elements in a short time (few days and/or few weeks), whereas the release occurred in medium time (few months). Aquatic mosses, in a period of 28 days, accumulated a total mass, for all considered elements, of 4 g kg{sup -1} (dry weight).

  15. Dust Accumulation on MER Solar Panels

    Science.gov (United States)

    Guinness, E. A.; Arvidson, R. E.; McEwen, A. S.; Cull, S.

    2011-12-01

    underlying solar panels. The laboratory and HiRISE data suggest that the Spirit solar panels may have had a dust layer on the order of only 10s of micrometers thick. Further investigation of rover image data sets for the presence or absence of specular reflections as correlated with solar cell power output will yield more quantitative information on the amounts of atmospheric dust accumulation throughout the Spirit and Opportunity missions.

  16. Atmospheric mercury accumulation and washoff processes on impervious urban surfaces

    Science.gov (United States)

    Eckley, C.S.; Branfireun, B.; Diamond, M.; Van Metre, P.C.; Heitmuller, F.

    2008-01-01

    The deposition and transport of mercury (Hg) has been studied extensively in rural environments but is less understood in urbanized catchments, where elevated atmospheric Hg concentrations and impervious surfaces may efficiently deliver Hg to waterways in stormwater runoff. We determined the rate at which atmospheric Hg accumulates on windows, identified the importance of washoff in removing accumulated Hg, and measured atmospheric Hg concentrations to help understand the relationship between deposition and surface accumulation. The main study location was Toronto, Ontario. Similar samples were also collected from Austin, Texas for comparison of Hg accumulation between cities. Windows provided a good sampling surface because they are ubiquitous in urban environments and are easy to clean/blank allowing the assessment of contemporary Hg accumulation. Hg Accumulation rates were spatially variable ranging from 0.82 to 2.7 ng m-2 d-1 in Toronto and showed similar variability in Austin. The highest accumulation rate in Toronto was at the city center and was 5?? higher than the rural comparison site (0.58 ng m-2 d-1). The atmospheric total gaseous mercury (TGM) concentrations were less than 2?? higher between the rural and urban locations (1.7 ?? 0.3 and 2.7 ?? 1.1 ng m-3, respectively). The atmospheric particulate bound fraction (HgP), however, was more than 3?? higher between the rural and urban sites, which may have contributed to the higher urban Hg accumulation rates. Windows exposed to precipitation had 73 ?? 9% lower accumulation rates than windows sheltered from precipitation. Runoff collected from simulated rain events confirmed that most Hg accumulated on windows was easily removed and that most of the Hg in washoff was HgP. Our results indicate that the Hg flux from urban catchments will respond rapidly to changes in atmospheric concentrations due to the mobilization of the majority of the surface accumulated Hg during precipitation events. ?? 2008 Elsevier

  17. A Water Accumulation Flooding Potentiality Index (WAFPI) for rating ...

    African Journals Online (AJOL)

    The Water Accumulation Flooding Potentiality Index (WAFPI) is a qualitative risk assessment method based on a factorial scoring system that is aimed at dividing the land into classes that are similar in their susceptibility to flooding due to accumulating water. Such an assessment precedes quantitative flood modeling work, ...

  18. Heavy metal accumulation by carrageenan and agar producing algae

    Energy Technology Data Exchange (ETDEWEB)

    Burdin, K.S. [Moscow State Univ. (Russian Federation). Faculty of Biology; Bird, K.T. [North Carolina Univ., Wilmington, NC (United States). Center for Marine Science Research

    1994-09-01

    The accumulation of six heavy metals Cu, Cd, Ni, Zn, Mn and Pb was measured in living and lzophilized algal thalli. The agar producing algae were Gracilaria tikvahiae and Gelidium pusillum. The carrageenan producing macroalgae were Agardhiella subulata and the gametophyte and tetrasporophyte phases of Chondrus crispus. These produce primarily iota, kappa and lambda carrageenans, respectively. At heavy metal concentrations of 0.5 mg L{sup -1}, living thalli of Gracilaria tikvahiae generally showed the greatest amount of accumulation of the 6 heavy metals tested. The accumulation of Pb was greater in the living thalli of all four species than in the lyophilized thalli. Except for Agardhiella subulata, lyophilized thalli showed greater accumulation of Ni, Cu and Zn. There was no difference in heavy metal accumulation between living and lyophilized thalli in the accumulation of Cd. Manganese showed no accumulation at the tested concentration. There did not appear to be a relationship between algal hydrocolloid characteristics and the amounts of heavy metals accumulated. (orig.)

  19. In Vivo Inhibition of Lipid Accumulation in Caenorhabditis elegans

    Science.gov (United States)

    Sulistiyani; Purwakusumah, E. P.; Andrianto, D.

    2017-03-01

    This is a preliminary research report on the use of Caenorhabditis elegans as a model to establish anti-obesity screening assay of the natural plant resources. Nematode C. elegans has been used as experimental animal model for understanding lipid accumulation. The objective of this research was to investigate the effect of selected plant extracts on lipid accumulation in C. elegans. Currently no report could be found regarding lipid accumulation in C.elegans treated with ethanolic leaf extracts of jabon merah (Anthocephalus macrophyllus), jati belanda (Guazuma ulmifolia), and Mindi (Melia Azedarach) plants. Lipid accumulation was determined qualitatively using lipid staining method and quantitatively by colorimetry using sulpho-phospho-vanillin reagent. Data showed that lipid accumulation was inhibited up to 72% by extract of M. azedarach, about 35% by both of A. macrophyllus and G. ulmifolia extracts, and up to 25% by orlistat (a synthetic slimming drug). Ethanolic extract of A. macrophyllus, G. ulmifolia, and M. azedarach leaves were shown to inhibit lipid accumulation in C. elegans and M. azedarach leaves extracts was the most effective inhibitor. C.elegans were shown to be an effective model for in vivo lipid accumulation mechanism and potential to be used as a rapid screening assay for bioactive compounds with lipid accumulation inhibitory activity.

  20. 30 CFR 77.1104 - Accumulations of combustible materials.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Accumulations of combustible materials. 77.1104 Section 77.1104 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE..., grease, lubricants, paints, or flammable liquids shall not be allowed to accumulate where they can create...

  1. Thallium-201 accumulation in cerebral candidiasis: Unexpected finding on SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Tonami, N.; Matsuda, H.; Ooba, H.; Yokoyama, K.; Hisada, K.; Ikeda, K.; Yamashita, J. (Kanazawa Univ. (Japan))

    1990-06-01

    The authors present an unexpected finding of Tl-201 uptake in the intracerebral lesions due to candidiasis. SPECT demonstrated the extent of the lesions and a high target-to-background ratio. The regions where abnormal Tl-201 accumulation was seen were nearly consistent with CT scans of those enhanced by a contrast agent. After treatment, most of the abnormal Tl-201 accumulation disappeared.

  2. Effect of temperature on accumulation of chlorophylls and leaf ...

    African Journals Online (AJOL)

    The effects of temperature on leaf colour, accumulation of chlorophylls and leaf ultrastructures of an albino tea cultivar 'Xiaxueya' were investigated. The study showed that the shoot albino phenomenon of 'Xiaoxueya' was controlled by temperature. The development of chloroplast from etioplast and the accumulation of ...

  3. 7 CFR 1773.39 - Utility plant and accumulated depreciation.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 12 2010-01-01 2010-01-01 false Utility plant and accumulated depreciation. 1773.39... Procedures and Documentation § 1773.39 Utility plant and accumulated depreciation. (a) General. The audit of... depreciation reserves; (4) Examined direct purchases of special equipment and general plant; (5) Determined the...

  4. 47 CFR 36.503 - Accumulated depreciation-Account 3100.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Accumulated depreciation-Account 3100. 36.503 Section 36.503 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES... Accumulated depreciation—Account 3100. (a) Amounts recorded in this account shall be separated on the basis of...

  5. Carbohydrate Reserves And Metal Accumulation Of The Nile Tilapia ...

    African Journals Online (AJOL)

    This study investigated the carbohydrate reserves and metal accumulation of the Nile tilapia, Oreochromis niloticus after exposure to sublethal concentrations of heavy metals such as copper, lead and zinc for a 12-week period, using static renewable toxicity tests. The concentrations of the metals accumulated in the tissue ...

  6. Total lipid accumulation and fatty acid profiles of microalga Spirulina ...

    African Journals Online (AJOL)

    Nutrient limitation in terms of nitrogen and phosphorus increased lipid accumulation under depleted growth in Spirulina strains. Nitrogen limitation was found more effective than phosphorus in accumulating lipid. The fatty acid profile was variable: palmitic (48%), linolenic (21%) and linoleic acids (15%) were the most ...

  7. Accumulation of poly-beta-hydroxybutyrate in Spirulina platensis.

    OpenAIRE

    Campbell, J; Stevens, S E; Balkwill, D L

    1982-01-01

    Poly-beta-hydroxybutyrate has been identified in the cyanobacterium Spirulina platensis. The addition of reduced carbon compounds to the growth medium was not required for poly-beta-hydroxybutyrate accumulation. Poly-beta-hydroxybutyrate accumulated during exponential growth to 6% of the total dry weight and then decreased during the stationary phase.

  8. 40 CFR 273.35 - Accumulation time limits.

    Science.gov (United States)

    2010-07-01

    ... of accumulation of such quantities of universal waste as necessary to facilitate proper recovery... the purpose of accumulation of such quantities of universal waste as necessary to facilitate proper recovery, treatment, or disposal. (c) A large quantity handler of universal waste must be able to...

  9. Simple non-invasive assessment of advanced glycation endproduct accumulation

    NARCIS (Netherlands)

    Meerwaldt, R; Graaff, R; Links, TP; Jager, JJ; Alderson, NL; Thorpe, [No Value; Baynes, JW; Gans, ROB; Smit, AJ

    Aims/hypothesis. The accumulation of AGE is thought to play a role in the pathogenesis of chronic complications of diabetes mellitus and renal failure. All current measurements of AGE accumulation require invasive sampling. We exploited the fact that several AGE exhibit autofluorescence to develop a

  10. 26 CFR 1.1502-43 - Consolidated accumulated earnings tax.

    Science.gov (United States)

    2010-04-01

    ... that the group's earnings and profits are permitted to accumulate beyond the reasonable needs of its... either any of its members or any other corporation by permitting earnings and profits to accumulate... profits. For purposes of this paragraph (a) and paragraph (d) of this section, the following rules apply...

  11. Trace element accumulation in lotic dragonfly nymphs: Genus matters.

    Directory of Open Access Journals (Sweden)

    Dean E Fletcher

    Full Text Available Constituents of coal combustion waste (CCW expose aquatic organisms to complex mixtures of potentially toxic metals and metalloids. Multi-element trace element analyses were used to distinguish patterns of accumulation among 8 genera of dragonfly nymphs collected from two sites on a CCW contaminated coastal plain stream. Dragonfly nymphs are exceptional for comparing trace element accumulation in syntopic macroinvertebrates that are all predators within the same order (Odonata and suborder (Anisoptera, but differ vastly in habitat use and body form. Sixteen trace element (Be, V, Cr, Ni, Cu, Zn, As, Se, Sr, Cd, Sb, Cs, Ba, Hg, Tl, and Pb were analyzed and trophic position and basal carbon sources assessed with stable isotope analyses (C and N. Trophic positions varied within relatively narrow ranges. Size did not appear to influence trophic position. Trophic position rarely influenced trace element accumulation within genera and did not consistently correlate with accumulation among genera. Patterns between δ13C and trace element accumulation were generally driven by differences between sites. An increase in trace element accumulation was associated with a divergence of carbon sources between sites in two genera. Higher trace element concentrations tended to accumulate in nymphs from the upstream site, closer to contaminant sources. Influences of factors such as body form and habitat use appeared more influential on trace element accumulation than phylogeny for several elements (Ni, Ba, Sr, V, Be, Cd, and Cr as higher concentrations accumulated in sprawler and the climber-sprawler genera, irrespective of family. In contrast, As and Se accumulated variably higher in burrowers, but accumulation in sprawlers differed between sites. Greater variation between genera than within genera suggests genus as an acceptable unit of comparison in dragonfly nymphs. Overall, taxonomic differences in trace element accumulation can be substantial, often exceeding

  12. Social Capital Accumulation among Puerto Rican Mothers in Urban Neighborhoods

    Directory of Open Access Journals (Sweden)

    Phillip J. Granberry

    2017-03-01

    Full Text Available Social capital provides access to material and personal resources through participation in social networks and other social structures. Social capital may not function equally for all populations, especially those living in residentially segregated urban neighborhoods with increased levels of poverty. This is because inequalities exist in social capital accumulation and are found where disadvantaged socioeconomic groups cluster. Using probabilistic household survey data consisting of 205 Puerto Rican mothers in Springfield, Massachusetts in 2013, this research tests hypotheses regarding the association of social capital accumulation with Puerto Rican mothers’ individual, neighborhood, and social network characteristics. Logistic regression results suggested that Puerto Rican mothers who were employed and lived in neighborhoods with other Latinos were more likely to accumulate social capital. In addition, mothers who participated in activities of their children also had increased social capital accumulation. This neighborhood effect on social capital accumulation may promote bonding social capital but not bridging social capital among these Puerto Rican mothers.

  13. Inertia-induced accumulation of flotsam in the subtropical gyres

    Science.gov (United States)

    Beron-Vera, F. J.; Olascoaga, M. J.; Lumpkin, R.

    2016-12-01

    Recent surveys of marine plastic debris density have revealed high levels in the center of the subtropical gyres. Earlier studies have argued that the formation of great garbage patches is due to Ekman convergence in such regions. In this work we report a tendency so far overlooked of drogued and undrogued drifters to accumulate distinctly over the subtropical gyres, with undrogued drifters accumulating in the same areas where plastic debris accumulate. We show that the observed accumulation is too fast for Ekman convergence to explain it. We demonstrate that the accumulation is controlled by finite-size and buoyancy (i.e., inertial) effects on undrogued drifter motion subjected to ocean current and wind drags. We infer that the motion of flotsam in general is constrained by similar effects. This is done by using a newly proposed Maxey-Riley equation which models the submerged (surfaced) drifter portion as a sphere of the fractional volume that is submerged (surfaced).

  14. Choline metabolism in glycinebetaine accumulating and non-accumulating near-isogenic lines of Zea mays and Sorghum bicolor.

    Science.gov (United States)

    Peel, Gregory J; Mickelbart, Michael V; Rhodes, David

    2010-03-01

    Glycinebetaine (GB) is a compatible solute that is accumulated by some plant species, especially under conditions leading to tissue osmotic stress. Genetic modification for accumulation of GB in an attempt to produce more stress tolerant plants has been a focus for several groups in recent years. However, attempts to increase tissue GB concentrations have been unsuccessful, with many transgenic lines accumulating far lower concentrations than naturally-occurring GB accumulators. A better understanding of the metabolic regulation of GB synthesis is necessary for successful molecular breeding and biotechnology. We utilized previously developed near-isogenic lines for GB accumulation to characterize the biochemical basis for GB deficiency in maize and sorghum. Salinity resulted in increased accumulation of choline in both accumulating and non-accumulating lines. When grown in the presence of NaCl, GB-non-accumulating lines had increased concentrations of choline and phosphocholine, but not GB. Decreased GB synthesis can be explained from the increased concentrations of phosphocholine in planta and the strong inhibition of N-phosphoethanolamine methyltransferase by phosphocholine observed in vitro. The lack of GB accumulation in GB-/- homozygous NILs was not due to the lack of the putative choline monooxygenase (the enzyme responsible for choline oxidation to betaine aldehyde) gene or protein that we describe. The previously identified bet1 locus does not appear to be choline monooxygenase. However, the lack of GB synthesis does affect the synthesis and turnover of choline moieties in GB non-accumulating lines, which may lead to alterations in overall 1-carbon metabolism in plants. Copyright 2009 Elsevier Ltd. All rights reserved.

  15. Phytosiderophores determine thresholds for iron and zinc accumulation in biofortified rice endosperm while inhibiting the accumulation of cadmium.

    Science.gov (United States)

    Banakar, Raviraj; Alvarez Fernandez, Ana; Díaz-Benito, Pablo; Abadia, Javier; Capell, Teresa; Christou, Paul

    2017-10-13

    Nicotianamine (NA) and 2'-deoxymugenic acid (DMA) are metal-chelating ligands that promote the accumulation of metals in rice endosperm, but it is unclear how these phytosiderophores regulate the levels of different metals and limit their accumulation. In this study, transgenic rice plants producing high levels of NA and DMA accumulated up to 4-fold more iron (Fe) and 2-fold more zinc (Zn) in the endosperm compared with wild-type plants. The distribution of Fe and Zn in vegetative tissues suggested that both metals are sequestered as a buffering mechanism to avoid overloading the seeds. The buffering mechanism involves the modulation of genes encoding metal transporters in the roots and aboveground vegetative tissues. As well as accumulating more Fe and Zn, the endosperm of the transgenic plants accumulated less cadmium (Cd), suggesting that higher levels of Fe and Zn competitively inhibit Cd accumulation. Our data show that although there is a strict upper limit for Fe (~22.5 µg g-1 dry weight) and Zn (~84 µg g-1 dry weight) accumulation in the endosperm, the careful selection of strategies to increase endosperm loading with essential minerals can also limit the accumulation of toxic metals such as Cd, thus further increasing the nutritional value of rice. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  16. A comparative study of aluminium and nutrient concentrations in mistletoes on aluminium-accumulating and non-accumulating hosts.

    Science.gov (United States)

    Scalon, M C; Haridasan, M; Franco, A C

    2013-09-01

    Mistletoes offer a unique model to study interactions among Al and nutrients in vascular plants, because they grow and reproduce on hosts with distinct Al uptake strategies. We investigated Al distribution and nutrient relations of mistletoes on Al-accumulating and non-accumulating hosts. We hypothesised that mistletoes would exhibit similar leaf nutrient and Al concentrations as their host plants, but a strong compartmentalisation of Al when growing on Al-accumulators. We measured concentrations of N, P, K, Ca, Mg, Cu, Fe, Mn, Zn in leaves and Al in leaves, seeds and branches of Phthirusa ovata and Psittacanthus robustus infecting Miconia albicans, an Al-accumulator, and Ph. ovata infecting Byrsonima verbascifolia, a non-Al-accumulator. High leaf concentrations of Al in Ph. ovata only occurred while parasitizing the Al-accumulating host; there was no accumulation in branches or seeds. In P. robustus, large concentrations of Al were found in leaves, branches and seeds. Mistletoe seed viability and leaf nutrient concentrations were not affected by Al accumulation. Passive uptake of Al, Ca, Mg, Mn and Cu in mistletoes was evidenced by significant correlations between mistletoes and host leaf concentrations, but not of N, P and K. Al was retranslocated to different plant organs in P. robustus, whereas it was mostly restricted to leaves in Ph. ovata. We suggest that Al might have some specific function in P. robustus, which only parasitizes Al-accumulator hosts, while the host generalist Ph. ovata can be considered a facultative Al-accumulator. © 2013 German Botanical Society and The Royal Botanical Society of the Netherlands.

  17. Micronutrient Accumulation in Conilon Coffee Berries with Different Maturation Cycles

    Directory of Open Access Journals (Sweden)

    Wellington Braida Marré

    2015-10-01

    Full Text Available ABSTRACT The number of days between anthesis and maturation of conilon coffee berries varies according to the genotype. Thus, it is believed that periods of greater nutrient demand for fruit formation also vary according to the genotype, directly influencing fertilizer management. The goal of this study was to establish accumulation curves for the micronutrients boron, copper, iron, manganese, and zinc in conilon coffee trees with different maturation cycles. The experiment was conducted in Nova Venécia, State of Espírito Santo, Brazil, during the reproductive cycle of the 2010/2011 crop year. Four coffee genotypes with different maturation cycles (early, intermediate, late, and super-late were studied. A completely randomized experimental design was used with five replications. The treatments correspond to the accumulation of B, Cu, Fe, Mn, and Zn in the berries every 28 days in the period from flowering to harvest. The early, intermediate, and late genotypes accumulated Fe, Cu, and Mn in a similar manner, with sigmoid curves, whereas the super-late genotype accumulated these nutrients exponentially. Zn was accumulated by all four genotypes following a sigmoid curve. The early, intermediate, and late genotypes accumulated B linearly, whereas the super-late genotype accumulated B following a sigmoid curve. The maturation cycle of the genotype must be taken into account to apply the correct rate of micronutrient fertilization in coffee plantations.

  18. Flavonoid accumulation patterns of transparent testa mutants of arabidopsis

    Science.gov (United States)

    Peer, W. A.; Brown, D. E.; Tague, B. W.; Muday, G. K.; Taiz, L.; Murphy, A. S.

    2001-01-01

    Flavonoids have been implicated in the regulation of auxin movements in Arabidopsis. To understand when and where flavonoids may be acting to control auxin movement, the flavonoid accumulation pattern was examined in young seedlings and mature tissues of wild-type Arabidopsis. Using a variety of biochemical and visualization techniques, flavonoid accumulation in mature plants was localized in cauline leaves, pollen, stigmata, and floral primordia, and in the stems of young, actively growing inflorescences. In young Landsberg erecta seedlings, aglycone flavonols accumulated developmentally in three regions, the cotyledonary node, the hypocotyl-root transition zone, and the root tip. Aglycone flavonols accumulated at the hypocotyl-root transition zone in a developmental and tissue-specific manner with kaempferol in the epidermis and quercetin in the cortex. Quercetin localized subcellularly in the nuclear region, plasma membrane, and endomembrane system, whereas kaempferol localized in the nuclear region and plasma membrane. The flavonoid accumulation pattern was also examined in transparent testa mutants blocked at different steps in the flavonoid biosynthesis pathway. The transparent testa mutants were shown to have precursor accumulation patterns similar to those of end product flavonoids in wild-type Landsberg erecta, suggesting that synthesis and end product accumulation occur in the same cells.

  19. Anomalous accumulation rates resulting from ice flow over Lake Vostok

    Science.gov (United States)

    Leonard, K. C.; Studinger, M.; Bell, R. E.; Tremblay, B.

    2004-12-01

    The accumulation rate of snow is crucial to the development of accurate age-depth models for ice-cores. The dating of the Vostok ice-core generally assumes that accumulation rates vary linearly between the core site and the ice divide 250 km to the west [Jouzel et al., 1996; Lorius et al., 1985; Petit et al., 1999], an assumption which impacts the timing of prominent climatic transitions. We present evidence for a local accumulation rate anomaly at the ice surface above the western shoreline of Lake Vostok. A significant thickening between isochronous layers results from this geographically fixed high accumulation zone which can be stratigraphically traced to a depth of 820-1100 m in the Vostok ice-core, a portion known for its high accumulation rates and paleoclimate records that deviate from other Antarctic ice-core records. This non-climatic accumulation anomaly in the Vostok ice-core impacts the flow dependent age models and subsequent interpretations of sequencing of global climate shifts during the last glacial. These previously unreported geographically fixed accumulation rate anomalies are introduced into ice-cores drilled away from ice domes (i.e., Byrd and Vostok) and should be considered in age depth models.

  20. FRACTAL MODEL OF DAMAGE ACCUMULATION IN SOLID BODES

    Directory of Open Access Journals (Sweden)

    Alim. Abed Al-Zobaede

    2014-01-01

    Full Text Available The paper considers a model of damage accumulation in parts of machines and structures which is based on a theory of fractals. Hidden process of destruction prior to the formation of macroscopic cracks is usually associated with the accumulation of micro-damages. Various models of damage accumulation and crack growth under the influence of power and thermal loads. However, models describing the accumulation process of micro-damages and their outgrowth into macro-crack are practically non-existent. Fractal structures with self-similarity are an adequate model of the fracture process. The MacDonald correlation function describing the medium structure allows to present the self-similarity of structures within a certain range of scales.The paper reviews models of damage accumulation near an opening in a composite medium and at layer boundaries. The Cantor model in a forward algorithm and a backward algorithm have been used in order to describe the model of damage accumulation. As it is known, the Cantor fractal (Cantor dust is obtained by using a recursive algorithm being applied to fracture mechanics can be regarded as a model of stepwise formation of dispersed micro-damages. The process of damage accumulation (latent destruction phase and its transition in the formation process of macro-cracks and their unification in a through-thickness crack can be described, for example, by the Paris' law.

  1. Oil and Protein Accumulation in Soybean Grains under Salinity Stress

    Directory of Open Access Journals (Sweden)

    Kazem GHASSEMI-GOLEZANI

    2010-06-01

    Full Text Available Two factorial experiments based on randomized complete block design (RCBD with three replications were conducted in 2007 and 2008, to evaluate grain development (four harvests and rate and duration of oil and protein accumulation in three soybean cultivars (Williams, Zan and L17 under a non-saline (control and three saline (3, 6 and 9 ds/m NaCl conditions. Six seeds were sown in each pot filled with 900 g perlite, using 144 pots for each experiment. After emergence, seedlings were thinned and 4 plants were kept in each pot. Rate of oil accumulation up to maturity was not significantly affected by salinity. With increasing salinity, rate and percentage of protein accumulation, duration of oil and protein accumulation and oil and protein content per grain decreased, but oil percentage increased. Oil and protein yields per plant decreased as salinity increased. These reductions were mainly attributed to the short duration of protein and oil accumulation and grain yield per plant under saline conditions. Williams had the highest rate and duration of protein accumulation and rate of oil accumulation, but L17 had the highest grain yield per plant. Consequently, differences in protein and oil yields per plant between these two cultivars were not statistically significant. However, Zan had the lowest protein and oil yields, due to the lowest grain yield per plant.

  2. Oil and Protein Accumulation in Soybean Grains under Salinity Stress

    Directory of Open Access Journals (Sweden)

    Kazem GHASSEMI-GOLEZANI

    2010-06-01

    Full Text Available Two factorial experiments based on randomized complete block design (RCBD with three replications were conducted in 2007 and 2008, to evaluate grain development (four harvests and rate and duration of oil and protein accumulation in three soybean cultivars (�Williams�, �Zan� and �L17� under a non-saline (control and three saline (3, 6 and 9 ds/m NaCl conditions. Six seeds were sown in each pot filled with 900 g perlite, using 144 pots for each experiment. After emergence, seedlings were thinned and 4 plants were kept in each pot. Rate of oil accumulation up to maturity was not significantly affected by salinity. With increasing salinity, rate and percentage of protein accumulation, duration of oil and protein accumulation and oil and protein content per grain decreased, but oil percentage increased. Oil and protein yields per plant decreased as salinity increased. These reductions were mainly attributed to the short duration of protein and oil accumulation and grain yield per plant under saline conditions. �Williams� had the highest rate and duration of protein accumulation and rate of oil accumulation, but �L17� had the highest grain yield per plant. Consequently, differences in protein and oil yields per plant between these two cultivars were not statistically significant. However, �Zan� had the lowest protein and oil yields, due to the lowest grain yield per plant.

  3. Arbuscular mycorrhizal fungi: effects on plant terpenoid accumulation.

    Science.gov (United States)

    Welling, M T; Liu, L; Rose, T J; Waters, D L E; Benkendorff, K

    2016-07-01

    Arbuscular mycorrhizal fungi (AMF) are a diverse group of soil-dwelling fungi that form symbiotic associations with land plants. AMF-plant associations promote the accumulation of plant terpenoids beneficial to human health, although how AMF mediate terpenoid accumulation is not fully understood. A critical assessment and discussion of the literature relating to mechanisms by which AMF influence plant terpenoid accumulation, and whether this symbiosis can be harnessed in horticultural ecosystems was performed. Modification of plant morphology, phosphorus availability and gene transcription involved with terpenoid biosynthetic pathways were identified as key mechanisms associated with terpenoid accumulation in AMF-colonised plants. In order to exploit AMF-plant symbioses in horticultural ecosystems it is important to consider the specificity of the AMF-plant association, the predominant factor affecting terpenoid accumulation, as well as the end use application of the harvested plant material. Future research should focus on resolving the relationship between ecologically matched AMF genotypes and terpenoid accumulation in plants to establish if these associations are effective in promoting mechanisms favourable for plant terpenoid accumulation. © 2015 German Botanical Society and The Royal Botanical Society of the Netherlands.

  4. Ozone injury in soybeans. Isoflavonoid accumulation is related to necrosis

    Energy Technology Data Exchange (ETDEWEB)

    Keen, N.T.; Taylor, O.C.

    1975-04-01

    Fumigation of soybean leaves (Glycine max (L.) Merr.) with ozone caused stippling and silvering at the same time that large accumulations of the isoflavonoid compounds daidzein, coumestrol, and sojagol occurred. Nitrogen dioxide and sulfur dioxide caused lesser accumulation of the isoflavonoids, and peroxyacetyl nitrate did not result in significant accumulation. Visible toxicity and chemical changes in ozone-fumigated leaves were similar to the hypersensitive disease defense reaction of soybean leaves to the pathogen Pseudomonas glycinea, except that the phytoalexin hydroxyphaseollin was not produced in the ozone-treated leaves. (auth)

  5. EMG Pattern Recognition based on Evidence Accumulation for Prosthesis Control

    Energy Technology Data Exchange (ETDEWEB)

    Lee, S.P. [Daewoo Electronics Co., Ltd., Seoul (Korea, Republic of); Park, S.H. [Yonsei University, Seoul (Korea, Republic of)

    1997-12-01

    We present a method of electromyography(EMG) pattern recognition to identify motion commands for the control of a prosthetic arm by evidence accumulation with multiple parameters. Integral absolute value, variance, autoregressive(AR) model coefficients, linear cepstrum coefficients, and adaptive cepstrum vector are extracted as feature parameters from several time segments of the EMG signals. Pattern recognition is carried out through the evidence accumulation procedure using the distances measured with reference parameters. A fuzzy mapping function is designed to transform the distances for the application of the evidence accumulation method. Results are presented to support the feasibility of the suggested approach for EMG pattern recognition. (author). 29 refs., 11 figs., 7 tabs.

  6. Cadmium uptake and speciation changes in the rhizosphere of cadmium accumulator and non-accumulator oilseed rape varieties.

    Science.gov (United States)

    Su, Dechun; Xing, Jianping; Jiao, Weiping; Wong, Woonchung

    2009-01-01

    Characteristics of cadmium (Cd) uptake kinetics and distribution of Cd speciation in the rhizosphere for Cd accumulator and non-accumulator oilseed rape varieties were investigated under nutrient solution and rhizobox soil culture conditions. The results showed that the maximal influx (V(max)) for Cd2+ and Km were significantly different for the two oilseed rape varieties. The value of V(max) for Cd accumulator oilseed rape Zhucang Huazi was two-fold greater than that for oilseed rape Chuan you II-93. The exchangeable Cd concentration in the rhizosphere was significantly lower than in non-rhizospheric soils supplemented with CdSO4 for both the varieties. Carbonate-bound Cd in the rhizosphere of Cd accumulator oilseed rape was significantly higher than that in the rhizosphere of non-accumulator oilseed rape and non-rhizospheric soil. Cd accumulator oilseed rape had a higher Cd2+ affinity and more ability to uptake insoluble Cd in the soil than the non-accumulator oilseed rape.

  7. Characteristics of cadmium accumulation and tolerance in novel Cd-accumulating crops, Avena strigosa and Crotalaria juncea.

    Science.gov (United States)

    Uraguchi, Shimpei; Watanabe, Izumi; Yoshitomi, Akiko; Kiyono, Masako; Kuno, Katsuji

    2006-01-01

    Characteristics of accumulation and tolerance of cadmium (Cd) in green manure crops were investigated to identify Cd-accumulating crops and to clarify the mechanisms involved in Cd accumulation and tolerance. Seedlings of eight crop species were treated with Cd (1 mg l(-1) or 5 mg l(-1)) in the growing medium for 4 d. Cd concentration in leaves of Avena strigosa Schreb. cv. New-oat, Crotalaria juncea L. and Tagetes erecta L. cv. African-tall was greater than values used to define Cd-hyperaccumulation (>100 mg Cd kg(-1) DW). However, in leaves of T. erecta, lipid peroxidation level increased significantly, and the activities of superoxide dismutase, ascorbate peroxidase, glutathione reductase, and catalase were depressed by both Cd treatments. By contrast, A. strigosa and C. juncea exhibited high Cd tolerance. Avena strigosa leaves showed higher activities of antioxidative enzymes such as superoxide dismutase and ascorbate peroxidase than those of other species tested. Crotalaria juncea showed higher amounts of total soluble phenolics which, in leaves, were doubled by 5 mg l(-1) Cd treatment. When two Cd-tolerant accumulators (A. strigosa and C. juncea) and the non-accumulator (C. spectabilis) were treated with lower Cd concentrations for 4 weeks, A. strigosa and C. juncea exhibited superior Cd accumulation in the shoots with greater biomass production compared with C. spectabilis. These results indicate that A. strigosa and C. juncea possess the greater potential for Cd accumulation and tolerance than common crops.

  8. Accumulated Growing Degree Days, Contiguous United States, 1981 - Current Year

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — The USA National Phenology Network has available a series of gridded products enabling researchers to analyze current year Accumulated Growing Degree Days (AGDD)...

  9. Inertia-induced accumulation of flotsam in the subtropical gyres

    CERN Document Server

    Beron-Vera, Francisco J; Lumpkin, Rick

    2016-01-01

    Recent surveys of marine plastic debris density have revealed high levels in the center of the subtropical gyres. Earlier studies have argued that the formation of great garbage patches is due to Ekman convergence in such regions. In this work we report, for the first time, a tendency of satellite-tracked surface drifting buoys which have lost their sea anchors (drogues) to accumulate in the same regions of the world oceans that plastic debris accumulate. We show that the observed accumulation is too fast for Ekman convergence to explain it. We demonstrate that the accumulation is controlled by finite-size and buoyancy (i.e., inertial) effects on undrogued drifter motion subjected to ocean current and wind drags. We infer that the motion of flotsam in general is constrained by similar effects.

  10. Accumulation of mercury by the marine copepod Acartia clausi

    National Research Council Canada - National Science Library

    弘田, 禮一郎; 浅田, 順子; 田島, 静子; 藤木, 素士

    1983-01-01

    .... Such results srggest that methylmercury in the sea watre is accumulated rapidly by Acartia clausi, and that the concentration of methylmercury in copepods and sea watre reached equilibrium within the experimental period (24 hours).

  11. Relationship Between Accumulation and Influx of Pollutants in Highway Ponds

    DEFF Research Database (Denmark)

    Bentzen, Thomas Ruby; Larsen, Torben; Rasmussen, Michael R.

    The paper discusses the long term mass balance of pollutants in highway ponds. The accumulations of five polycyclic aromatic hydrocarbons (PAHs) and six heavy metals have been measured in eight Danish detention ponds, which receive runoff from highways only. For each pollutant the accumulation has...... been compared to the long-term influx, estimated from short-term measurements of concentrations in highway runoff. The results show that a large proportion of the incoming heavy metals in short-term runoff events has accumulated in the ponds. This is not the case for the toxic organic compounds....... The results also show that the accumulation rates for the heavy metals depend significantly on the relative pond area (pond area divided by catchment area). The conclusion is that the mass balances of heavy metals and PAHs in highway ponds can be estimated with acceptable accuracy from a combination of short...

  12. LIPID ACCUMULATION OF CHLORELLA VULGARIS UNDER DIFFERENT PHOSPHATE CONCENTRATIONS

    Directory of Open Access Journals (Sweden)

    Magdalena Karolina Rokicka

    2017-04-01

    Full Text Available The cultivation and utilization of microalgae is now a intensively developing area of research. Some species of microalgae, under appropriate conditions, accumulate large amounts of lipids in the cells. This lipids have a suitable profile of fatty acids for biodiesel production. The culture of microalgae for lipids accumulation should be performed in certain physicochemical conditions. The aim of the study was to determine the effect of variable ortophophates concentrations in the culture medium for lipids accumulation of microalgae Chlorella vulgaris and to determine of parameters of the phosphoric shock in the medium. The study confirmed the possibility of the use of the phosphoric shock in the medium to maximize lipids accumulation by the microalgae Chlorella vulgaris. In the study, 45.23% of the oil was obtained from the biomass from the culture with phosphoric shock in the medium and 18% less of the oil was obtained from the biomass from the standard culture.

  13. Factors associated with pentosidine accumulation in the human vitreous

    NARCIS (Netherlands)

    Van Deemter, Marielle; Bank, Ruud A.; Vehof, Jelle; Hooymans, Johanna M. M.; Los, Leonoor I.

    Purpose: To explore factors associated with pentosidine accumulation in the human vitreous. Methods: Vitreous samples were obtained during trans pars plana vitrectomy for macular hole or rhegmatogenous retinal detachment. Patient characteristics included age, gender, and diabetes mellitus. Ocular

  14. Transfer and accumulation of lead, zinc, cadmium and copper in ...

    African Journals Online (AJOL)

    Transfer and accumulation of lead, zinc, cadmium and copper in plants growing in abandoned mining-district area. HK Chakroun, F Souissi, JL Bouchardon, R Souissi, J Moutte, O Faure, E Remon, S Abdeljaoued ...

  15. A Transformational Approach to Parametric Accumulated-Cost Static Profiling

    DEFF Research Database (Denmark)

    Haemmerlé, Rémy; López García, Pedro; Liqat, Umer

    2016-01-01

    on the concept of cost centers and a program transformation that allows the static inference of functions that return bounds on these accumulated costs depending on input data sizes, for each cost center of interest. Such information is much more useful to the software developer than the traditional resource......Traditional static resource analyses estimate the total resource usage of a program, without executing it. In this paper we present a novel resource analysis whose aim is instead the static profiling of accumulated cost, i.e., to discover, for selected parts of the program, an estimate or bound...... of the resource usage accumulated in each of those parts. Traditional resource analyses are parametric in the sense that the results can be functions on input data sizes. Our static profiling is also parametric, i.e., our accumulated cost estimates are also parameterized by input data sizes. Our proposal is based...

  16. Changes in brain amyloid-β accumulation after donepezil administration.

    Science.gov (United States)

    Ishibashi, Kenji; Miura, Yoshiharu; Wagatsuma, Kei; Ishiwata, Kiichi; Ishii, Kenji

    2017-11-01

    Recent studies using the mouse model of Alzheimer's disease (AD) have shown that donepezil administration reduces brain amyloid-β (Aβ) accumulation. This study investigated whether donepezil administration can reduce brain Aβ accumulation in human patients with AD. Ten patients with AD underwent two (11)C-Pittsburgh Compound B positron emission tomography sessions approximately one year apart to measure brain Aβ accumulation before and after donepezil treatment. Volumes-of-interest were placed on Aβ-preferred regions, and the standardized uptake value ratio (SUVR) was calculated considering the cerebellum as a reference region. Three and seven patients received 10mg and 5mg of donepezil, respectively. SUVR was significantly higher in the second than in the first session (P=0.026). This study showed that one year of donepezil administration does not reduce brain Aβ accumulation in human patients with AD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Exploration of the ability of Coleus blumei to accumulate aluminum.

    Science.gov (United States)

    Panizza de León, Amalia; Carrillo González, Rogelio; Bernal González, Marisela; Vaca Mier, Mabel; Durán-Domínguez-de-Bazúa, Carmen

    2011-01-01

    In this study, the capacity of an ornamental species (Coleus blumei) to extract and accumulate aluminum was evaluated. The analyzed parameters were amount of soluble aluminum, radical growth, tolerance rate, bioaccumulation factor, and tissues aluminum concentration. The main limiting factor for aluminum accumulation is the availability of the metal. However, Coleus blumei can grow and accumulate up to 1445.7 mg kg(-1) of aluminum dry base. This plant can play an important role in the treatment of polluted water with metals, since it can grow in conditions with a pH of around 4.8. The aluminum tolerance rate showed for this plant ranged between 18.8% and 25%. Therefore, this species behaves as a non-accumulator, even though the bioaccumulation factor was 3098.5 L kg(-1).

  18. Regulation and accumulation of secondary metabolites in plant ...

    African Journals Online (AJOL)

    Symbiotic fungi usually perform compatible and friendly interactions with host plants, which contribute to growth promotion and secondary metabolites accumulation simultaneously, such as alkaloids and terpenoid with pharmacological characteristics. Especially, some secondary metabolites derived from root exudation act ...

  19. Anandamide, but not 2-arachidonoylglycerol, accumulates during in vivo neurodegeneration

    DEFF Research Database (Denmark)

    Hansen, H.H.; Lastres-Becker, I.; Berrendero, F.

    2001-01-01

    Endogenous cannabinoid receptor ligands (endocannabinoids) may rescue neurons from glutamate excitotoxicity. As these substances also accumulate in cultured immature neurons following neuronal damage, elevated endocannabinoid concentrations may be interpreted as a putative neuroprotective respons...

  20. Effects of zinc exposure on the accumulation, haematology and ...

    African Journals Online (AJOL)

    Effects of zinc exposure on the accumulation, haematology and immunology of Mozambique tilapia, Oreochromis mossambicus. Ekrem Şanver Çelik, Hasan Kaya, Sevdan Yilmaz, Mehmet Akbulut, Arınç Tulgar ...

  1. Perlite as a carrier of phosphate-accumulating bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Ivankovic, T.; Hrenovic, J.; Sekovanic, L.; Tofant, A.

    2009-07-01

    The phosphate (P)-accumulating bacteria are important for biological P removal from wastewater. Currently, attention is being drawn to the immobilisation of desired bacteria on different carriers in order to achieve a better efficiency of the wastewater treatment. In this study, two size fractions (0.1-1 and 0.1-2 mm) of different forms of expanded perlite (original, autoclaved and magnesium-exchanged) were investigates as possible carriers of P accumulating bacterium. (Author)

  2. MODELING OF TEMPERATURE FIELDS IN A SOLID HEAT ACCUMULLATORS

    Directory of Open Access Journals (Sweden)

    S. S. Belimenko

    2016-10-01

    Full Text Available Purpose. Currently, one of the priorities of energy conservation is a cost savings for heating in commercial and residential buildings by the stored thermal energy during the night and its return in the daytime. Economic effect is achieved due to the difference in tariffs for the cost of electricity in the daytime and at night. One of the most common types of devices that allow accumulating and giving the resulting heat are solid heat accumulators. The main purpose of the work: 1 software development for the calculation of the temperature field of a flat solid heat accumulator, working due to the heat energy accumulation in the volume of thermal storage material without phase transition; 2 determination the temperature distribution in its volumes at convective heat transfer. Methodology. To achieve the study objectives a heat transfer theory and Laplace integral transform were used. On its base the problems of determining the temperature fields in the channels of heat accumulators, having different cross-sectional shapes were solved. Findings. Authors have developed the method of calculation and obtained solutions for the determination of temperature fields in channels of the solid heat accumulator in conditions of convective heat transfer. Temperature fields over length and thickness of channels were investigated. Experimental studies on physical models and industrial equipment were conducted. Originality. For the first time the technique of calculating the temperature field in the channels of different cross-section for the solid heat accumulator in the charging and discharging modes was proposed. The calculation results are confirmed by experimental research. Practical value. The proposed technique is used in the design of solid heat accumulators of different power as well as full-scale production of them was organized.

  3. Plants use macronutrients accumulated in leaf-cutting ant nests

    OpenAIRE

    da S.L Sternberg, Leonel; Pinzon, Maria Camila; Moreira, Marcelo Z.; Moutinho, Paulo; Rojas, Enith I.; Herre, Edward Allen

    2006-01-01

    Leaf-cutting ants (Atta spp.) are known for their extensive defoliation in neo-tropical forests and savannahs. Debate about the costs and benefits of their activities has been largely dominated by their detrimental effects on agriculture and agroforestry. However, the large accumulation of nutrients and changes in soil properties near their nests might benefit plants growing near them. Here, we test whether trees use nutrients that accumulate in debris piles near, or refuse chambers within, l...

  4. Enhancement of uranium-accumulating ability of microorganisms by irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Sakaguchi, Takashi; Nakajima, Akira; Tsuruta, Takehiko [Miyazaki Medical Coll., Kiyotake (Japan)

    1998-01-01

    Some microorganisms having excellent ability to accumulate uranium were isolated, from soil and water systems in and around the Ningyo-toge Station of Power Reactor and Nuclear Fuel Development Corporation. The enhancement of uranium-accumulating ability of microorganisms by electron-beam irradiation was examined, and the ability of JW-046 was increased 3-5% by the irradiation. The irradiation affect the growth of some of microorganisms tested. (author)

  5. The effect of chewing gum on dental plaque accumulation

    OpenAIRE

    Karami Nogourani M.; Banihashemi M

    2010-01-01

    "nBackground and Aims: Studies show that sucrose containing chewing gums are cariogenic. The aim of this study was to evaluate the effect of two commercial chewing gums with and without sucrose on dental plaque accumulation compared with the control group. "nMaterials and Methods: In this clinical study, plaque accumulation during three 7-day periods (with two weeks interval) was recorded (Sillness & Loe Index) in a group of 23 volunteer male dental students who chewed in th...

  6. Accumulation by fish of contaminants released from dredged sediments

    Science.gov (United States)

    Seelye, James G.; Hesselberg, Robert J.; Mac, Michael J.

    1982-01-01

    Inasmuch as the process of dredging and disposing of dredged materials causes a resuspension of these materials and an increase in bioavailability of associated contaminants, we conducted a series of experiments to examine the potential accumulation by fish of contaminants from suspended sediments. In the first experiment we compared accumulation of contaminants by yellow perch of hatchery and lake origin and found that after 10 days of exposure to nonaerated sediments, fish of hatchery origin accumulated PCBs and Fe, while fish of lake origin accumulated As, Cr, Fe, and Na. Two additional exposures were conducted to evaluate the effects of aerating the sediments prior to measuring bioavailability of associated contaminants. Fish of hatchery origin exposed to nonaerated sediments for 10 days accumulated PCBs and Hg, while fish of hatchery origin exposed to aerated sediments for 10 days accumulated PCBs, DDE, Zn, Fe, Cs, and Se. These results demonstrated not only the potential for uptake of contaminants by fish as a result of dredging but also the potential utility of fish bioassays in evaluating proposed dredging operations.

  7. Distributed and accumulated reinforcement arrangements: evaluations of efficacy and preference.

    Science.gov (United States)

    DeLeon, Iser G; Chase, Julie A; Frank-Crawford, Michelle A; Carreau-Webster, Abbey B; Triggs, Mandy M; Bullock, Christopher E; Jennett, Heather K

    2014-01-01

    We assessed the efficacy of, and preference for, accumulated access to reinforcers, which allows uninterrupted engagement with the reinforcers but imposes an inherent delay required to first complete the task. Experiment 1 compared rates of task completion in 4 individuals who had been diagnosed with intellectual disabilities when reinforcement was distributed (i.e., 30-s access to the reinforcer delivered immediately after each response) and accumulated (i.e., 5-min access to the reinforcer after completion of multiple consecutive responses). Accumulated reinforcement produced response rates that equaled or exceeded rates during distributed reinforcement for 3 participants. Experiment 2 used a concurrent-chains schedule to examine preferences for each arrangement. All participants preferred delayed, accumulated access when the reinforcer was an activity. Three participants also preferred accumulated access to edible reinforcers. The collective results suggest that, despite the inherent delay, accumulated reinforcement is just as effective and is often preferred by learners over distributed reinforcement. © Society for the Experimental Analysis of Behavior.

  8. Phytomass production and nutrient accumulation by green manure species

    Directory of Open Access Journals (Sweden)

    José Carlos Soares Mangaravite

    2014-10-01

    Full Text Available Green manuring is recognized as a viable alternative to improve nutrient cycling in soils. The aim of this study was to evaluate the phytomass production and nutrient accumulation in shoots of the summer green manures jack bean [Canavalia ensiformis (L. DC.], dwarf pigeon pea (Cajanus cajanvar var. Flavus DC., dwarf mucuna [Mucuna deeringiana (Bort Merr] and sunn hemp (Crotalaria juncea L., under nitrogen fertilization and/or inoculation with N-fixing bacteria. A split plot design was arranged with the four Fabaceae species as main plots and nitrogen fertilization (with and without and inoculation with diazotrophic bacteria (with and without as the subplots, in a 2² factorial. The experiment was arranged as a randomized complete block design with four replications. In the conditions of this trial, the sunn hemp had the highest production of shoot phytomass (12.4 Mg ha-1 and nutrient accumulation, while the dwarf mucuna had the lowest production of shoot phytomass (3.9 Mg ha-1 and nutrient accumulation. The results showed no effect of nitrogen fertilization or inoculation with N-fixing bacteria on the production of shoot phytomass and nutrient accumulation, except for inoculation without nitrogen fertilization, resulting in greater P accumulation (p <0.05 in the sunn hemp and greater Zn and Mn accumulation in the dwarf mucuna. These findings indicate that N fertilization or inoculation with N2-fixing bacteria for Fabaceae are low efficiency practices in the edaphoclimatic conditions of this study.

  9. A kinetic analysis of cadmium accumulation in a Cd hyper-accumulator fern, Athyrium yokoscense and tobacco plants.

    Science.gov (United States)

    Yoshihara, Toshihiro; Suzui, Nobuo; Ishii, Satomi; Kitazaki, Mayu; Yamazaki, Haruaki; Kitazaki, Kazuyoshi; Kawachi, Naoki; Yin, Yong-Gen; Ito-Tanabata, Sayuri; Hashida, Shin-nosuke; Shoji, Kazuhiro; Shimada, Hiroaki; Goto, Fumiyuki; Fujimaki, Shu

    2014-05-01

    Cadmium (Cd) accumulations in a Cd hyper-accumulator fern, Athyrium yokoscense (Ay), and tobacco, Nicotiana tabacum (Nt), were kinetically analysed using the positron-emitting tracer imaging system under two medium conditions (basal and no-nutrient). In Ay, maximumly 50% and 15% of the total Cd accumulated in the distal roots and the shoots under the basal condition, respectively. Interestingly, a portion of the Cd in the distal roots returned to the medium. In comparison with Ay, a little fewer Cd accumulations in the distal roots and clearly higher Cd migration to the shoots were observed in Nt under the basal condition (maximumly 40% and 70% of the total Cd, respectively). The no-nutrient condition down-regulated the Cd migration in both species, although the regulation was highly stricter in Ay than in Nt (almost no migration in Ay and around 20% migration in Nt). In addition, the present work enabled to estimate physical and physiological Cd accumulation capacities in the distal roots, and demonstrated condition-dependent changes especially in Ay. These results clearly suggested occurrences of species-/condition-specific regulations in each observed parts. It is probable that integration of these properties govern the specific Cd tolerance/accumulation in Ay and Nt. © 2013 John Wiley & Sons Ltd.

  10. Apolipoprotein E promotes lipid accumulation and differentiation in human adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lasrich, Dorothee; Bartelt, Alexander [Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany); Grewal, Thomas, E-mail: thomas.grewal@sydney.edu.au [Faculty of Pharmacy A15, The University of Sydney, Sydney, NSW 2006 (Australia); Heeren, Joerg, E-mail: heeren@uke.de [Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany)

    2015-09-10

    Several studies in mice indicate a role for apolipoprotein E (APOE) in lipid accumulation and adipogenic differentiation in adipose tissue. However, little is yet known if APOE functions in a similar manner in human adipocytes. This prompted us to compare lipid loading and expression of adipocyte differentiation markers in APOE-deficient and control adipocytes using the differentiated human mesenchymal stem cell line hMSC-Tert as well as primary human and mouse adipocytes as model systems. Differentiated hMSC-Tert were stably transduced with or without siRNA targeting APOE while murine adipocytes were isolated from wild type and Apoe knockout mice. Human APOE knockdown hMSC-Tert adipocytes accumulated markedly less triglycerides compared to control cells. This correlated with strongly decreased gene expression levels of adipocyte markers such as adiponectin (ADIPOQ) and fatty acid binding protein 4 (FABP4) as well as the key transcription factor driving adipocyte differentiation, peroxisome proliferator activator receptor gamma (PPARG), in particular the PPARG2 isoform. Similarly, differentiation of murine Apoe-deficient adipocytes was characterized by reduced gene expression of Adipoq, Fabp4 and Pparg. Interestingly, incubation of APOE-deficient hMSC-Tert adipocytes with conditioned media from APOE3-overexpressing adipocytes or APOE-containing Very Low Density Lipoprotein (VLDL) partially restored triglyceride accumulation, but were unable to induce adipocyte differentiation, as judged by expression of adipocyte markers. Taken together, depletion of endogenous APOE in human adipocytes severely impairs lipid accumulation, which is associated with an inability to initiate differentiation. - Highlights: • Immortalized human mesenchymal stem cells were used to study adipocyte development. • Knockdown of endogenous APOE lead to impaired lipid accumulation and adipogenesis. • APOE supplementation partially restored lipid accumulation but not differentiation.

  11. Lead Tolerance and Accumulation in White Poplar Cultivated In Vitro

    Directory of Open Access Journals (Sweden)

    Branislav Kovačević

    2013-06-01

    Full Text Available Background and Purpose: This paper analyses the lead tolerance and accumulation in white poplar genotypes in vitro, in order to optimize genotype evaluation and other procedures in their implementation in phytoremediation projects and landscaping in areas endangered by lead accumulation. Material and Methods: The lead tolerance and accumulation of five white poplar genotypes after 35 days in vitro cultivation on media supplemented with lead was examined. The following Pb(NO32 concentrations were used: 0, 10-6, 10-5, 10-4 and 10-3 M. Tolerance analysis (described by tolerance indices was based on morphological parameters, biomass accumulation and the content of photosynthetic pigments, while lead accumulation was described by shoot lead accumulation and shoot lead content. Results and Conclusions: The chosen lead concentrations appeared not to be lethal. Moreover, the obtained results showed that the tested lead concentrations had a positive effect on: number of formed roots, shoot moisture content and shoot height. The best differentiation among the examined genotypes was gained by the tolerance index based on the shoot height on 10-4 M Pb(NO32. The shoot lead accumulation and shoot lead content significantly increased on 10-4 and 10-3 M Pb(NO32 media. Thus, the concentration of 10-4 M Pb(NO32 is recommended for further research. Two examined genotypes of horticultural value (LCM and LBM achieved a significantly higher lead shoot content compared to the wide spread genotype “Villafranca” (almost 200% and 125% higher, respectively.

  12. Carbon accumulation in Rhodotorula glutinis induced by nitrogen limitation.

    Science.gov (United States)

    Cescut, Julien; Fillaudeau, Luc; Molina-Jouve, Carole; Uribelarrea, Jean-Louis

    2014-01-01

    Oleaginous microorganisms, such as bacterium, yeast and algal species, can represent an alternative oil source for biodiesel production. The composition of their accumulated lipid is similar to the lipid of an oleaginous plant with a predominance of unsaturated fatty acid. Moreover this alternative to conventional biodiesel production does not create competition for land use between food and oleo-chemical industry supplies. Despite this promising potential, development of microbial production processes are at an early stage. Nutritional limited conditions, such as nitrogen limitation, with an excess of carbon substrate is commonly used to induce lipid accumulation metabolism. Nitrogen limitation implies modification of the carbon-to-nitrogen ratio in culture medium, which impacts on carbon flow distribution in the metabolic network. The goal of the present study is to improve our knowledge of carbon flow distribution in oleaginous yeast metabolism by focusing carbon distribution between carbohydrate and lipid pools in order to optimize microbial lipid production. The dynamic effects of limiting nitrogen consumption flux according to carbon flow were studied to trigger lipid accumulation in the oleaginous yeast Rhodotorula glutinis. With a decrease of the specific nitrogen consumption rate from 0.052 Nmol.CmolX (-1).h(-1) to 0.003 Nmol.CmolX (-1).h(-1), a short and transitory intracellular carbohydrate accumulation occurred before the lipid accumulation phase. This phenomenon was studied in fed-batch culture under optimal operating conditions, with a mineral medium and using glucose as carbon source. Two different strategies of decreasing nitrogen flow on carbohydrate accumulation were investigated: an instantaneous decrease and a progressive decrease of nitrogen flow. Lipid production performance in these fed-batch culture strategies with R. glutinis were higher than those reported in the previous literature; the catalytic specific lipid production rate was 0

  13. Ultra-High-Speed Image Signal Accumulation Sensor

    Directory of Open Access Journals (Sweden)

    Takeharu Goji Etoh

    2010-04-01

    Full Text Available Averaging of accumulated data is a standard technique applied to processing data with low signal-to-noise ratios (SNR, such as image signals captured in ultra-high-speed imaging. The authors propose an architecture layout of an ultra-high-speed image sensor capable of on-chip signal accumulation. The very high frame rate is enabled by employing an image sensor structure with a multi-folded CCD in each pixel, which serves as an in situ image signal storage. The signal accumulation function is achieved by direct connection of the first and the last storage elements of the in situ storage CCD. It has been thought that the multi-folding is achievable only by driving electrodes with complicated and impractical layouts. Simple configurations of the driving electrodes to overcome the difficulty are presented for two-phase and four-phase transfer CCD systems. The in situ storage image sensor with the signal accumulation function is named Image Signal Accumulation Sensor (ISAS.

  14. Morphological Studies of Synechocystis sp. UNIWG under Polyhydroxyalkanoate Accumulating Conditions

    Directory of Open Access Journals (Sweden)

    Yew, S. P.

    2005-01-01

    Full Text Available Some cyanobacteria are capable of producing polyhydroxyalkanoate (PHA, among which is the unicellular Synechocystis sp. Here, we report the identification and preliminary characterization of a newly isolated strain of Synechocystis sp. UNIWG that is capable of accumulating unusually high number of PHA granules. This cyanobacterium was isolated from oil-contaminated brackish water sample from Wadi Gaza, Palestine. Surprisingly, Nile Blue A staining of PHA-accumulating cells failed to reveal the accumulated PHA granules. Ultrastructural analysis of Synechocystis sp. UNIWG cells grown under nitrogen limiting conditions revealed the presence of up to 17 electron-transparent granules in the cell cytoplasm. Gas chromatography analysis further revealed that these cells contain up to 14 wt% poly(3-hydroxybutyrate of the cell dry weight. Ultrastructural analysis also revealed that Synechocystis sp. UNIWG cells from the growth phase were covered with a dense layer of pilus like structures. However, these pilus-like structures were not observed in cells from the PHA-accumulation phase. The possible roles of these pilus-like structures and PHA accumulation for the survival of this cyanobacterium is discussed here.

  15. Accumulation of heavy metals by vegetables grown in mine wastes

    Energy Technology Data Exchange (ETDEWEB)

    Cobb, G.P.; Sands, K.; Waters, M.; Wixson, B.G.; Dorward-King, E.

    2000-03-01

    Lead, cadmium, arsenic, and zinc were quantified in mine wastes and in soils mixed with mine wastes. Metal concentrations were found to be heterogeneous in the wastes. Iceberg lettuce, Cherry Belle radishes, Roma bush beans, and Better Boy tomatoes were cultivated in mine wastes and in waste-amended soils. Lettuce and radishes had 100% survival in the 100% mine waste treatments compared to 0% and 25% survival for tomatoes and beans, respectively. Metal concentrations were determined in plant tissues to determine uptake and distribution of metals in the edible plant parts. Individual soil samples were collected beneath each plant to assess metal content in the immediate plant environment. This analysis verified heterogeneous metal content of the mine wastes. The four plant species effectively accumulated and translocated lead, cadmium, arsenic, and zinc. Tomato and bean plants contained the four metals mainly in the roots and little was translocated to the fruits. Radish roots accumulated less metals compared to the leaves, whereas lettuce roots and leaves accumulated similar concentrations of the four metals. Lettuce leaves and radish roots accumulated significantly more metals than bean and tomato fruits. This accumulation pattern suggests that consumption of lettuce leaves or radish roots from plants grown in mine wastes would pose greater risks to humans and wildlife than would consumption of beans or tomatoes grown in the same area. The potential risk may be mitigated somewhat in humans, as vegetables grown in mine wastes exhibited stunted growth and chlorosis.

  16. Expression of human A53T alpha-synuclein in the rat substantia nigra using a novel AAV1/2 vector produces a rapidly evolving pathology with protein aggregation, dystrophic neurite architecture and nigrostriatal degeneration with potential to model the pathology of Parkinson's disease

    OpenAIRE

    Sun Xuan; Reyes M Gabriela; Johnston Tom H; Koprich James B; Brotchie Jonathan M

    2010-01-01

    Abstract Background The pathological hallmarks of Parkinson's disease (PD) include the presence of alpha-synuclein (α-syn) rich Lewy bodies and neurites and the loss of dopaminergic (DA) neurons of the substantia nigra (SN). Animal models of PD based on viral vector-mediated over-expression of α-syn have been developed and show evidence of DA toxicity to varying degrees depending on the type of virus used, its concentration, and the serotype of vector employed. To date these models have been ...

  17. Brain lipopigment accumulation in normal and pathological aging.

    Science.gov (United States)

    Riga, Dan; Riga, Sorin; Halalau, Florin; Schneider, Francisc

    2006-05-01

    A principal marker of brain vulnerability, stress, aging, and related pathology is represented by lipopigments (LPs)--lipofuscin, and ceroid. During ontogenesis, neuronal LP accumulations are significantly correlated with important changes in nerve cell morphology and biochemistry. In the aged neurons, LPs are present in all cellular compartments. Moreover, neuronal LP accumulations coexist with glial LP storage, especially in microglia. Owing to their transporting properties, and the migration capacity of microglia, glial cells deposit LP clusters in pericapillary areas. Thus, LP conglomerates appear in the whole nervous tissue, creating specific patterns of LP architectonics. Direct interrelations, critical LP concentrations, which generate cascades of negative subcellular events, and indirect impairment correlations determine characteristic neuropathologic aging profiles. These specific and associated negative neuropathologic consequences of LP accumulation have multiple and detrimental impacts on neuron and glia homeostasis, ranging from neuronal function to central nervous system physiology.

  18. Arbuscular mycorrhizal fungi decrease radiocesium accumulation in Medicago truncatula

    Energy Technology Data Exchange (ETDEWEB)

    Gyuricza, Veronika; Declerck, Stephane [Universite catholique de Louvain, Earth and Life Institute (ELI), Laboratoire de Mycologie, Croix du Sud 3, 1348 Louvain-la-Neuve (Belgium); Dupre de Boulois, Herve, E-mail: herve.dupre@uclouvain.b [Universite catholique de Louvain, Earth and Life Institute (ELI), Laboratoire de Mycologie, Croix du Sud 3, 1348 Louvain-la-Neuve (Belgium)

    2010-08-15

    The role of arbuscular mycorrhizal fungi (AMF) in plant radiocesium uptake and accumulation remains ambiguous. This is probably due to the presence of other soil microorganisms, the variability of soil characteristics and plant nutritional status or the availability of its chemical analogue, potassium (K). Here, we used an in vitro culture system to study the impact of increased concentration of K on radiocesium accumulation in non K-starved mycorrhizal and non-mycorrhizal Medicago truncatula plants. In the presence of AMF radiocesium uptake decreased regardless of the concentration of K, and its translocation from root to shoot was also significantly lower. Potassium also reduced the accumulation of radiocesium in plants but to a lesser extent than mycorrhization, and without any effect on translocation. These results suggest that AMF in combination with K can play a key role in reducing radiocesium uptake and its subsequent translocation to plant shoots, thereby representing good potential for improved phytomanagement of contaminated areas.

  19. Evidence accumulation as a model for lexical selection.

    Science.gov (United States)

    Anders, R; Riès, S; van Maanen, L; Alario, F X

    2015-11-01

    We propose and demonstrate evidence accumulation as a plausible theoretical and/or empirical model for the lexical selection process of lexical retrieval. A number of current psycholinguistic theories consider lexical selection as a process related to selecting a lexical target from a number of alternatives, which each have varying activations (or signal supports), that are largely resultant of an initial stimulus recognition. We thoroughly present a case for how such a process may be theoretically explained by the evidence accumulation paradigm, and we demonstrate how this paradigm can be directly related or combined with conventional psycholinguistic theory and their simulatory instantiations (generally, neural network models). Then with a demonstrative application on a large new real data set, we establish how the empirical evidence accumulation approach is able to provide parameter results that are informative to leading psycholinguistic theory, and that motivate future theoretical development. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Optimal Backpressure Scheduling in Wireless Networks using Mutual Information Accumulation

    CERN Document Server

    Yang, Jing; Draper, Stark C

    2011-01-01

    In this paper we develop scheduling policies that maximize the stability region of a wireless network under the assumption that mutual information accumulation is implemented at the physical layer. When the link quality between nodes is not sufficiently high that a packet can be decoded within a single slot, the system can accumulate information across multiple slots, eventually decoding the packet. The result is an expanded stability region. The accumulation process over weak links is temporally coupled and therefore does not satisfy the independent and identically distributed (i.i.d) assumption that underlies many previous analysis in this area. Therefore the problem setting also poses new analytic challenges. We propose two dynamic scheduling algorithms to cope with the non-i.i.d nature of the decoding. The first performs scheduling every $T$ slots, and approaches the boundary of the stability region as $T$ gets large, but at the cost of increased average delay. The second introduces virtual queues for eac...

  1. Stability, accumulation and cytotoxicity of an albumin-cisplatin adduct

    DEFF Research Database (Denmark)

    Møller, Charlotte; Tastesen, Hanne Sørup; Gammelgaard, Bente

    2010-01-01

    The accumulation and cytotoxicity of a 10 µmol L¿¹ equimolar human serum albumin-cisplatin adduct (HSA-Pt) was investigated in suspension Ehrlich Ascites Tumor Cells (EATC) and adherent Ehrlich Lettré Ascites Cells (Lettré). HSA-Pt did not induce apoptosis nor was it taken up by the cells to any...... significant amount within 24 h incubation. The accumulation and cytotoxicity of HSA-Pt was compared to 10 µmol L¿¹ cisplatin for which a larger accumulation and cytotoxicity were observed in EATC compared to Lettré. The experiment was performed with cell medium exchange every fourth hour as HSA......-Pt and cisplatin were not stable in RPMI-1640 with 10% serum. The stability was determined using size exclusion chromatography-inductively coupled plasma-mass spectrometry (SEC-ICP-MS) and after 4 h new platinum peaks were observed. These findings indicate that before conducting cell experiments, the stability...

  2. LOFT reflood as a function of accumulator initial gas volume

    Energy Technology Data Exchange (ETDEWEB)

    Rhodes, H.F.

    1978-06-01

    The effect of the initial gas volume in the LOFT accumulators on the time to start of core reflood, after a LOCA, has been studied. The bases of the calculations are the data used and results presented in the Safety Analysis Report, Rev.1, August 1977, and the data in the RELAP and TOODEE2 program input and output listings. The results of this study show that an initial nitrogen volume of 12 cu ft, or more (at 600 psig initial pressure), would cause start of core reflood in time to prevent the cladding temperature from reaching 2200/sup 0/F. The 12 cu ft initial volume will expand from 600 psig, initial pressure, to about 10 psig (containment pressure shortly after start of LOCA is approximately 8 psig) when all ECC liquid has been expelled from the accumulator. This pressure margin is considered too small; the ECC flowrate will be zero before the accumulator is empty.

  3. Dental wax decreases calculus accumulation in small dogs.

    Science.gov (United States)

    Smith, Mark M; Smithson, Christopher W

    2014-01-01

    A dental wax was evaluated after unilateral application in 20 client-owned, mixed and purebred small dogs using a clean, split-mouth study model. All dogs had clinical signs of periodontal disease including plaque, calculus, and/or gingivitis. The wax was randomly applied to the teeth of one side of the mouth daily for 30-days while the contralateral side received no treatment. Owner parameters evaluated included compliance and a subjective assessment of ease of wax application. Gingivitis, plaque and calculus accumulation were scored at the end of the study period. Owners considered the wax easy to apply in all dogs. Compliance with no missed application days was achieved in 8 dogs. The number of missed application days had no effect on wax efficacy. There was no significant difference in gingivitis or plaque accumulation scores when comparing treated and untreated sides. Calculus accumulation scores were significantly less (22.1 %) for teeth receiving the dental wax.

  4. Intestinal mucus accumulation in a child with acutemyeloblastic leukemia

    Directory of Open Access Journals (Sweden)

    Namık Özbek

    2009-12-01

    Full Text Available Intestinal mucus accumulation is a very rare situation observed in some solid tumors, intestinal inflammation, mucosal hyperplasia, elevated intestinal pressure, and various other diseases. However, it has never been described in acute myeloblastic leukemia. The pathogenesis of intestinal mucus accumulation is still not clear. Here, we report a 14-year-old girl with acute myeloblastic leukemia and febrile neutropenia in addition to typhlitis. She was also immobilized due to joint contractures of the lower extremities and had intestinal mucus accumulation, which was, at first, misdiagnosed as intestinal parasitosis. We speculate that typhlitis, immobilization and decreased intestinal motility due to usage of antiemetic drugs might have been the potential etiologic factors in this case. However, its impact on prognosis of the primary disease is unknown.

  5. Antimony Accumulation Risk in Lettuce Grown in Brazilian Urban Gardens

    Directory of Open Access Journals (Sweden)

    Silvia Mancarella

    2016-08-01

    Full Text Available More than 80% of the Brazilian population inhabits urban areas. Diffused poverty and the lack of fresh vegetables have generated malnutrition and unbalanced diets. Thus, the interest in growing food locally, in urban allotments and community gardens, has increased. However, urban agriculture may present some risks caused by the urban pollution. Road traffic is considered the biggest source of heavy metals in urban areas. Hence, the objective of the study was the assessment of the accumulation of heavy metals in an urban garden in the city of Recife, at different distances from a road with high traffic burden. The results showed that the distance from the street decreased the accumulation of many potentially toxic elements. Furthermore, the human health risk was estimated, revealing that greater danger was associated with the accumulation of antimony. Concentration of other elements in the leaf tissues were within previously reported thresholds.

  6. Positive effects of duckweed polycultures on starch and protein accumulation.

    Science.gov (United States)

    Li, Yang; Zhang, Fantao; Daroch, Maurycy; Tang, Jie

    2016-10-01

    The effect of duckweed species composition (Lemna aequinoctialis 5505, Landoltia punctata 5506 and Spirodela polyrhiza 5507) in polyculture and monoculture on biomass and starch/protein content were investigated at different levels of temperature, light intensity, nitrogen and phosphorus concentrations. The three growth parameters significantly affect duckweed biomass accumulation. Different combinations of duckweed species greatly varied in starch/protein content. Although all the polycultures showed a median relative growth rate and the majority of the polycultures showed a median and starch/protein content as compared with their respective monocultures, some of the polycultures were found to promote the accumulation of starch/protein at different growth conditions. These findings indicated that proper combination of duckweed species could facilitate desirable biomass accumulation and improve biomass quality. The present study provides useful references for future large-scale duckweed cultivation. © 2016 The Author(s).

  7. Biochemical responses and accumulation of cadmium in Spirodela polyrhiza.

    Science.gov (United States)

    Rolli, N M; Suvarnakhandi, S S; Mulgund, G S; Ratageri, R H; Taranath, T C

    2010-07-01

    The present study focused on biochemical responses of Spirodela polyrhiza to cadmium stresses and its accumulation. The laboratory experiments were conducted for the assessment of biochemical responses and accumulation of cadmium in plants at its various concentrations (0.1, 0.5, 1.5 and 2.0 ppm) at the regular interval for twelve days exposure. Spirodela showed visible symptoms like withering of roots and chlorosis at higher concentration (2.0 ppm), however the plant showed normal growth at lower concentration (0.1 ppm). The estimation of biochemical parameters (total chlorophyll, protein and carbohydrate) of test plants showed a significant increase at lower concentration (0.1 ppm) of cadmium. The biochemical changes decrease with increase in exposure concentration and duration. The toxic effect of cadmium is directly proportional to its concentration and duration. The accumulation of cadmium by Spirodela polyrhiza was maximum at four days exposure duration and gradually decreases.

  8. Gas hydrate accumulation at the Hakon Mosby Mud Volcano

    Science.gov (United States)

    Ginsburg, G.D.; Milkov, A.V.; Soloviev, V.A.; Egorov, A.V.; Cherkashev, G.A.; Vogt, P.R.; Crane, K.; Lorenson, T.D.; Khutorskoy, M.D.

    1999-01-01

    Gas hydrate (GH) accumulation is characterized and modeled for the Hakon Mosby mud volcano, ca. 1.5 km across, located on the Norway-Barents-Svalbard margin. Pore water chemical and isotopic results based on shallow sediment cores as well as geothermal and geomorphological data suggest that the GH accumulation is of a concentric pattern controlled by and formed essentially from the ascending mud volcano fluid. The gas hydrate content of sediment peaks at 25% by volume, averaging about 1.2% throughout the accumulation. The amount of hydrate methane is estimated at ca. 108 m3 STP, which could account for about 1-10% of the gas that has escaped from the volcano since its origin.

  9. A model for estimating carbon accumulation in cork products

    Directory of Open Access Journals (Sweden)

    Ana C. Dias

    2014-08-01

    Full Text Available Aim of study: This study aims to develop a calculation model for estimating carbon accumulation in cork products, both whilst in use and when in landfills, and to apply the model to Portugal as an example.Area of study: The model is applicable worldwide and the case-study is Portugal.Material and methods: The model adopts a flux-data method based on a lifetime analysis and quantifies carbon accumulation in cork products according to three approaches that differ on how carbon stocks (or emissions are allocated to cork product consuming and producing countries. These approaches are: stock-change, production and atmospheric-flow. The effect on carbon balance of methane emissions from the decay of cork products in landfills is also evaluated.Main results: The model was applied to Portugal and the results show that carbon accumulation in cork products in the period between 1990 and 2010 varied between 24 and 92 Gg C year-1. The atmospheric-flow approach provided the highest carbon accumulation over the whole period due to the net export of carbon in cork products. The production approach ranked second because exported cork products were mainly manufactured from domestically produced cork. The net carbon balance in cork products was also a net carbon accumulation with all the approaches, ranging from 5 to 81 Gg C eq year-1.Research highlights: The developed model can be applied to other countries and may be a step forward to consider carbon accumulation in cork products in national greenhouse gas inventories, as well as in future climate agreements.Keywords: Atmospheric-flow approach; Greenhouse gas balance; Modelling; Production approach; Stock-change approach.

  10. Accumulation and fragmentation of plastic debris in global environments.

    Science.gov (United States)

    Barnes, David K A; Galgani, Francois; Thompson, Richard C; Barlaz, Morton

    2009-07-27

    One of the most ubiquitous and long-lasting recent changes to the surface of our planet is the accumulation and fragmentation of plastics. Within just a few decades since mass production of plastic products commenced in the 1950s, plastic debris has accumulated in terrestrial environments, in the open ocean, on shorelines of even the most remote islands and in the deep sea. Annual clean-up operations, costing millions of pounds sterling, are now organized in many countries and on every continent. Here we document global plastics production and the accumulation of plastic waste. While plastics typically constitute approximately 10 per cent of discarded waste, they represent a much greater proportion of the debris accumulating on shorelines. Mega- and macro-plastics have accumulated in the highest densities in the Northern Hemisphere, adjacent to urban centres, in enclosed seas and at water convergences (fronts). We report lower densities on remote island shores, on the continental shelf seabed and the lowest densities (but still a documented presence) in the deep sea and Southern Ocean. The longevity of plastic is estimated to be hundreds to thousands of years, but is likely to be far longer in deep sea and non-surface polar environments. Plastic debris poses considerable threat by choking and starving wildlife, distributing non-native and potentially harmful organisms, absorbing toxic chemicals and degrading to micro-plastics that may subsequently be ingested. Well-established annual surveys on coasts and at sea have shown that trends in mega- and macro-plastic accumulation rates are no longer uniformly increasing: rather stable, increasing and decreasing trends have all been reported. The average size of plastic particles in the environment seems to be decreasing, and the abundance and global distribution of micro-plastic fragments have increased over the last few decades. However, the environmental consequences of such microscopic debris are still poorly

  11. Regional Antarctic snow accumulation over the past 1000 years

    Directory of Open Access Journals (Sweden)

    E. R. Thomas

    2017-11-01

    Full Text Available Here we present Antarctic snow accumulation variability at the regional scale over the past 1000 years. A total of 79 ice core snow accumulation records were gathered and assigned to seven geographical regions, separating the high-accumulation coastal zones below 2000 m of elevation from the dry central Antarctic Plateau. The regional composites of annual snow accumulation were evaluated against modelled surface mass balance (SMB from RACMO2.3p2 and precipitation from ERA-Interim reanalysis. With the exception of the Weddell Sea coast, the low-elevation composites capture the regional precipitation and SMB variability as defined by the models. The central Antarctic sites lack coherency and either do not represent regional precipitation or indicate the model inability to capture relevant precipitation processes in the cold, dry central plateau. Our results show that SMB for the total Antarctic Ice Sheet (including ice shelves has increased at a rate of 7 ± 0.13 Gt decade−1 since 1800 AD, representing a net reduction in sea level of ∼ 0.02 mm decade−1 since 1800 and ∼ 0.04 mm decade−1 since 1900 AD. The largest contribution is from the Antarctic Peninsula (∼ 75 % where the annual average SMB during the most recent decade (2001–2010 is 123 ± 44 Gt yr−1 higher than the annual average during the first decade of the 19th century. Only four ice core records cover the full 1000 years, and they suggest a decrease in snow accumulation during this period. However, our study emphasizes the importance of low-elevation coastal zones, which have been under-represented in previous investigations of temporal snow accumulation.

  12. Rabbit blastocysts accumulate (/sup 3/H)prostaglandins in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Jones, M.A.; Harper, M.J.

    1984-08-01

    Rabbit blastocysts obtained on days 5, 6, and 6.8 of pregnancy were incubated in vitro in Tyrode's buffer with /sup 3/H-labeled prostaglandins (PGs). Accumulation of PGs was studied, using Whatman GF/F filters to separate bound and free ligands. The uptake and efflux of (/sup 3/H)PGs were studied as a function of PG type, incubation time, temperature, and effect of metabolic inhibitors as well as age and number of blastocysts. Blastocysts of the same age accumulated approximately the same amount of (/sup 3/H)PGE2 and (/sup 3/H)PGF2 alpha from their environment; however, there was no apparent saturation over a PG concentration range of 1-1000 nM. Both the uptake and efflux of PG were age dependent, with older blastocysts accumulating more PGs. Approximately 90% of the (/sup 3/H)PGs appear to be transported into the blastocoelic fluid, with little PG remaining in the blastomeres. PG accumulation was relatively insensitive to azide, ouabain, cyanide, or bromcresol green, but was affected by incubation at 0 C or the addition of indomethacin (10 micrograms/ml). No catabolism of the accumulated PGs was observed. The release of PGE2 in general did not differ from that of PGF2 alpha, except on day 6.8 of pregnancy when PGE2 was released more rapidly than on day 6. The authors conclude that rabbit blastocysts can accumulate PGs from their environment, which may imply a storage potential in the blastocyst and release before implantation.

  13. Accumulation and fragmentation of plastic debris in global environments

    Science.gov (United States)

    Barnes, David K. A.; Galgani, Francois; Thompson, Richard C.; Barlaz, Morton

    2009-01-01

    One of the most ubiquitous and long-lasting recent changes to the surface of our planet is the accumulation and fragmentation of plastics. Within just a few decades since mass production of plastic products commenced in the 1950s, plastic debris has accumulated in terrestrial environments, in the open ocean, on shorelines of even the most remote islands and in the deep sea. Annual clean-up operations, costing millions of pounds sterling, are now organized in many countries and on every continent. Here we document global plastics production and the accumulation of plastic waste. While plastics typically constitute approximately 10 per cent of discarded waste, they represent a much greater proportion of the debris accumulating on shorelines. Mega- and macro-plastics have accumulated in the highest densities in the Northern Hemisphere, adjacent to urban centres, in enclosed seas and at water convergences (fronts). We report lower densities on remote island shores, on the continental shelf seabed and the lowest densities (but still a documented presence) in the deep sea and Southern Ocean. The longevity of plastic is estimated to be hundreds to thousands of years, but is likely to be far longer in deep sea and non-surface polar environments. Plastic debris poses considerable threat by choking and starving wildlife, distributing non-native and potentially harmful organisms, absorbing toxic chemicals and degrading to micro-plastics that may subsequently be ingested. Well-established annual surveys on coasts and at sea have shown that trends in mega- and macro-plastic accumulation rates are no longer uniformly increasing: rather stable, increasing and decreasing trends have all been reported. The average size of plastic particles in the environment seems to be decreasing, and the abundance and global distribution of micro-plastic fragments have increased over the last few decades. However, the environmental consequences of such microscopic debris are still poorly

  14. Iron accumulates in Huntington's disease neurons: protection by deferoxamine.

    Directory of Open Access Journals (Sweden)

    Jianfang Chen

    Full Text Available Huntington's disease (HD is a progressive neurodegenerative disorder caused by a polyglutamine-encoding CAG expansion in the huntingtin gene. Iron accumulates in the brains of HD patients and mouse disease models. However, the cellular and subcellular sites of iron accumulation, as well as significance to disease progression are not well understood. We used independent approaches to investigate the location of brain iron accumulation. In R6/2 HD mouse brain, synchotron x-ray fluorescence analysis revealed iron accumulation as discrete puncta in the perinuclear cytoplasm of striatal neurons. Further, perfusion Turnbull's staining for ferrous iron (II combined with transmission electron microscope ultra-structural analysis revealed increased staining in membrane bound peri-nuclear vesicles in R6/2 HD striatal neurons. Analysis of iron homeostatic proteins in R6/2 HD mice revealed decreased levels of the iron response proteins (IRPs 1 and 2 and accordingly decreased expression of iron uptake transferrin receptor (TfR and increased levels of neuronal iron export protein ferroportin (FPN. Finally, we show that intra-ventricular delivery of the iron chelator deferoxamine results in an improvement of the motor phenotype in R6/2 HD mice. Our data supports accumulation of redox-active ferrous iron in the endocytic / lysosomal compartment in mouse HD neurons. Expression changes of IRPs, TfR and FPN are consistent with a compensatory response to an increased intra-neuronal labile iron pool leading to increased susceptibility to iron-associated oxidative stress. These findings, together with protection by deferoxamine, support a potentiating role of neuronal iron accumulation in HD.

  15. ION EFFECTS IN THE APS PARTICLE ACCUMULATOR RING

    Energy Technology Data Exchange (ETDEWEB)

    Calvey, J.; Harkay, K.; Yao, CY.

    2017-06-25

    Trapped ions in the APS Particle Accumulator Ring (PAR) lead to a positive coherent tune shift in both planes, which increases along the PAR cycle as more ions accumulate. This effect has been studied using an ion simulation code developed at SLAC. After modifying the code to include a realistic vacuum profile, multiple ionization, and the effect of shaking the beam to measure the tune, the simulation agrees well with our measurements. This code has also been used to evaluate the possibility of ion instabilities at the high bunch charge needed for the APS-Upgrade.

  16. Hyperforin accumulates in the translucent glands of Hypericum perforatum

    DEFF Research Database (Denmark)

    Soelberg, Jens; Jørgensen, Lise Bolt; Jäger, Anna K

    2007-01-01

    BACKGROUND AND AIMS: Hypericum perforatum contains the therapeutically important compounds hypericin and hyperforin. Hypericin is known to accumulate in the dark glands. This investigation aimed to determine the accumulation site of hyperforin. METHODS: Dark and translucent glands as well as non......-secretory tissue in leaves were manually isolated under the microscope. Hyperforin content was quantified by UV HPLC. Secretory structures were surveyed anatomically. KEY RESULTS: The hyperforin content of intact leaves was found to be about 3 mg g(-1) fresh tissue, whereas a content of about 7 mg g(-1) fresh...

  17. Uptake, metabolism, accumulation and toxicity of cyanide in willow trees

    DEFF Research Database (Denmark)

    Larsen, Morten; Ucisik, Ahmed Süheyl; Trapp, Stefan

    2005-01-01

    Chemicals taken up into plants may be accumulated so leading to toxic effects. Uptake and phytotoxicity of free cyanide was determined with the willow-tree transpiration test. Willow sets were grown in sand and irrigated with varying levels of cyanide (CN). Toxicity was determined by measuring...... transpiration. At CN concentrations below 10 mg/L, no toxic effects were observed. At 20 mg/L, transpiration was reduced to approximately 50% after 96 h. With 30, 40 and 50 mg/L, the transpiration decreased with a similar rate to plant...... in the plant tissue. This relation between external dose and internal accumulation is nonlinear and explains the toxic effects observed....

  18. Accumulation of advanced glycation end products in canine atherosclerosis.

    Science.gov (United States)

    Chiers, K; Vandenberge, V; Ducatelle, R

    2010-07-01

    Atherosclerosis is an uncommon lesion in animals and particularly in dogs. Prominent atherosclerotic lesions of the coronary arteries are described in three dogs. These comprised an expansion of the tunica media by the accumulation of foam cells and/or cholesterol crystals, with subsequent narrowing of the vascular lumen. Immunohistochemical analysis revealed the accumulation of advanced glycation end products (AGEs) in foam cells, macrophages and lymphocytes. As in man, these findings suggest a possible role of AGEs in the development of canine atherosclerosis. (c) 2009 Elsevier Ltd. All rights reserved.

  19. Accumulation and chemical states of radiocesium by fungus Saccharomyces cerevisiae

    Science.gov (United States)

    Ohnuki, Toshihiko; Sakamoto, Fuminori; Kozai, Naofumi; Yamasaki, Shinya; Yu, Qianqian

    2014-05-01

    After accident of Fukushima Daiichi Nuclear Power Plant, the fall-out radiocesium was deposited on the ground. Filamentous fungus is known to accumulate radiocesium in environment, even though many minerals are involved in soil. These facts suggest that fungus affect the migration behavior of radiocesium in the environment. However, accumulation mechanism of radiocesium by fungus is not understood. In the present study, accumulation and chemical states change of Cs by unicellular fungus of Saccharomyces cerevisiae have been studied to elucidate the role of microorganisms in the migration of radiocesium in the environment. Two different experimental conditions were employed; one is the accumulation experiments of radiocesium by S. cerevisiae from the agar medium containing 137Cs and a mineral of zeolite, vermiculite, smectite, mica, or illite. The other is the experiments using stable cesium to examine the chemical states change of Cs. In the former experiment, the cells were grown on membrane filter of 0.45 μm installed on the agar medium. After the grown cells were weighed, radioactivity in the cells was measured by an autoradiography technique. The mineral weight contents were changed from 0.1% to 1% of the medium. In the latter experiment, the cells were grown in the medium containing stable Cs between 1 mM and 10mM. The Cs accumulated cells were analyzed by SEM-EDS and EXAFS. The adsorption experiments of cesium by the cells under resting condition were also conducted to test the effect of cells metabolic activity. Without mineral in the medium, cells of S. cerevisiae accumulated 1.5x103 Bq/g from the medium containing 137Cs of 2.6x102 Bq/g. When mineral was added in the medium, concentration of 137Cs in the cells decreased. The concentration of 137Cs in the cells from the medium containing different minerals were in the following order; smectite, illite, mica > vermiculite > zeolite. This order was nearly the same as the inverse of distribution coefficient of

  20. Effects of Zinc Exposure on Accumulation, Haematology and ...

    African Journals Online (AJOL)

    BILGISAYAR1

    2013-02-13

    Feb 13, 2013 ... A decrease was found in nitroblue tetrazolium (NBT) activity with medium and high concentrations; in the lysozyme and myeloperoxidase activities was found with high concentrations (P<0.05). In this study, the highest zinc accumulation rate was found in the liver tissue, and the lowest rate was found in the ...