WorldWideScience

Sample records for granule neurons electronic

  1. File list: DNS.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available DNS.Neu.50.AllAg.Cerebellar_granule_neurons mm9 DNase-seq Neural Cerebellar granule neurons... SRX685885,SRX685882,SRX685880 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Neu.50.AllAg.Cerebellar_granule_neurons.bed ...

  2. File list: Pol.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available Pol.Neu.50.AllAg.Cerebellar_granule_neurons mm9 RNA polymerase Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.50.AllAg.Cerebellar_granule_neurons.bed ...

  3. File list: Pol.Neu.20.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available Pol.Neu.20.AllAg.Cerebellar_granule_neurons mm9 RNA polymerase Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.20.AllAg.Cerebellar_granule_neurons.bed ...

  4. File list: Unc.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available Unc.Neu.50.AllAg.Cerebellar_granule_neurons mm9 Unclassified Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Neu.50.AllAg.Cerebellar_granule_neurons.bed ...

  5. File list: His.Neu.05.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available His.Neu.05.AllAg.Cerebellar_granule_neurons mm9 Histone Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.05.AllAg.Cerebellar_granule_neurons.bed ...

  6. File list: His.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available His.Neu.50.AllAg.Cerebellar_granule_neurons mm9 Histone Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.50.AllAg.Cerebellar_granule_neurons.bed ...

  7. File list: His.Neu.10.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available His.Neu.10.AllAg.Cerebellar_granule_neurons mm9 Histone Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.10.AllAg.Cerebellar_granule_neurons.bed ...

  8. File list: Oth.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available Oth.Neu.50.AllAg.Cerebellar_granule_neurons mm9 TFs and others Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.50.AllAg.Cerebellar_granule_neurons.bed ...

  9. File list: Pol.Neu.10.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available Pol.Neu.10.AllAg.Cerebellar_granule_neurons mm9 RNA polymerase Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.10.AllAg.Cerebellar_granule_neurons.bed ...

  10. File list: Oth.Neu.20.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available Oth.Neu.20.AllAg.Cerebellar_granule_neurons mm9 TFs and others Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.20.AllAg.Cerebellar_granule_neurons.bed ...

  11. File list: ALL.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available ALL.Neu.50.AllAg.Cerebellar_granule_neurons mm9 All antigens Neural Cerebellar granule neurons... SRX685885,SRX685882,SRX685880 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Neu.50.AllAg.Cerebellar_granule_neurons.bed ...

  12. File list: Oth.Neu.10.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available Oth.Neu.10.AllAg.Cerebellar_granule_neurons mm9 TFs and others Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.10.AllAg.Cerebellar_granule_neurons.bed ...

  13. File list: Unc.Neu.20.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available Unc.Neu.20.AllAg.Cerebellar_granule_neurons mm9 Unclassified Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Neu.20.AllAg.Cerebellar_granule_neurons.bed ...

  14. File list: Unc.Neu.10.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available Unc.Neu.10.AllAg.Cerebellar_granule_neurons mm9 Unclassified Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Neu.10.AllAg.Cerebellar_granule_neurons.bed ...

  15. File list: ALL.Neu.20.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available ALL.Neu.20.AllAg.Cerebellar_granule_neurons mm9 All antigens Neural Cerebellar granule neurons... SRX685885,SRX685882,SRX685880 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Neu.20.AllAg.Cerebellar_granule_neurons.bed ...

  16. File list: His.Neu.20.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available His.Neu.20.AllAg.Cerebellar_granule_neurons mm9 Histone Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.20.AllAg.Cerebellar_granule_neurons.bed ...

  17. File list: DNS.Neu.20.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available DNS.Neu.20.AllAg.Cerebellar_granule_neurons mm9 DNase-seq Neural Cerebellar granule neurons... SRX685885,SRX685882,SRX685880 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Neu.20.AllAg.Cerebellar_granule_neurons.bed ...

  18. File list: Oth.Neu.05.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available Oth.Neu.05.AllAg.Cerebellar_granule_neurons mm9 TFs and others Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.05.AllAg.Cerebellar_granule_neurons.bed ...

  19. File list: ALL.Neu.05.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available ALL.Neu.05.AllAg.Cerebellar_granule_neurons mm9 All antigens Neural Cerebellar granule neurons... SRX685885,SRX685878,SRX685882,SRX685877,SRX685880,SRX685883 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Neu.05.AllAg.Cerebellar_granule_neurons.bed ...

  20. File list: ALL.Neu.10.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available ALL.Neu.10.AllAg.Cerebellar_granule_neurons mm9 All antigens Neural Cerebellar granule neurons... SRX685882,SRX685880,SRX685883,SRX685885,SRX685877,SRX685878 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Neu.10.AllAg.Cerebellar_granule_neurons.bed ...

  1. File list: DNS.Neu.10.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available DNS.Neu.10.AllAg.Cerebellar_granule_neurons mm9 DNase-seq Neural Cerebellar granule neurons... SRX685882,SRX685880,SRX685883,SRX685885,SRX685877,SRX685878 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Neu.10.AllAg.Cerebellar_granule_neurons.bed ...

  2. A low-density culture method of cerebellar granule neurons with paracrine support applicable for the study of neuronal morphogenesis.

    Kubota, Kenta; Seno, Takeshi; Konishi, Yoshiyuki

    2013-11-20

    Cerebellar granule neuronal cultures have been used to study the molecular mechanisms underlying neuronal functions, including neuronal morphogenesis. However, a limitation of this system is the difficulty to analyze isolated neurons because these are required to be maintained at a high density. Therefore, in the present study, we aimed to develop a simple and cost-effective method for culturing low-density cerebellar granule neurons. Cerebellar granule cells at two different densities (low- and high-density) were co-cultivated in order for the low-density culture to be supported by the paracrine signals from the high-density culture. This method enabled morphology analysis of isolated cerebellar granule neurons without astrocytic feeder cultures or supplements such as B27. Using this method, we investigated the function of a polarity factor. Studies using hippocampal neurons suggested that glycogen synthase kinase-3 (GSK-3) is an essential regulator of neuronal polarity, and inhibition of GSK-3 results in the formation of multiple axons. Pharmacological inhibitors for GSK-3 (6-bromoindirubin-3'-oxime and lithium chloride) did not cause the formation of multiple axons of cerebellar granule neurons but significantly reduced their length. Consistent results were obtained by introducing kinase-dead form of GSK-3 beta (K85A). These results indicated that GSK-3 is not directly involved in the control of neuronal polarity in cerebellar granule neurons. Overall, this study provides a simple method for culturing low-density cerebellar granule neurons and insights in to the neuronal-type dependent function of GSK-3 in neuronal morphogenesis. © 2013 Elsevier B.V. All rights reserved.

  3. File list: InP.Neu.20.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available InP.Neu.20.AllAg.Cerebellar_granule_neurons mm9 Input control Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Neu.20.AllAg.Cerebellar_granule_neurons.bed ...

  4. File list: InP.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available InP.Neu.50.AllAg.Cerebellar_granule_neurons mm9 Input control Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Neu.50.AllAg.Cerebellar_granule_neurons.bed ...

  5. File list: NoD.Neu.10.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available NoD.Neu.10.AllAg.Cerebellar_granule_neurons mm9 No description Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Neu.10.AllAg.Cerebellar_granule_neurons.bed ...

  6. File list: InP.Neu.05.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available InP.Neu.05.AllAg.Cerebellar_granule_neurons mm9 Input control Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Neu.05.AllAg.Cerebellar_granule_neurons.bed ...

  7. File list: NoD.Neu.20.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available NoD.Neu.20.AllAg.Cerebellar_granule_neurons mm9 No description Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Neu.20.AllAg.Cerebellar_granule_neurons.bed ...

  8. File list: NoD.Neu.05.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available NoD.Neu.05.AllAg.Cerebellar_granule_neurons mm9 No description Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Neu.05.AllAg.Cerebellar_granule_neurons.bed ...

  9. File list: InP.Neu.10.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available InP.Neu.10.AllAg.Cerebellar_granule_neurons mm9 Input control Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Neu.10.AllAg.Cerebellar_granule_neurons.bed ...

  10. Conditional induction of Math1 specifies embryonic stem cells to cerebellar granule neuron lineage and promotes differentiation into mature granule neurons.

    Srivastava, Rupali; Kumar, Manoj; Peineau, Stéphane; Csaba, Zsolt; Mani, Shyamala; Gressens, Pierre; El Ghouzzi, Vincent

    2013-04-01

    Directing differentiation of embryonic stem cells (ESCs) to specific neuronal subtype is critical for modeling disease pathology in vitro. An attractive means of action would be to combine regulatory differentiation factors and extrinsic inductive signals added to the culture medium. In this study, we have generated mature cerebellar granule neurons by combining a temporally controlled transient expression of Math1, a master gene in granule neuron differentiation, with inductive extrinsic factors involved in cerebellar development. Using a Tetracyclin-On transactivation system, we overexpressed Math1 at various stages of ESCs differentiation and found that the yield of progenitors was considerably increased when Math1 was induced during embryonic body stage. Math1 triggered expression of Mbh1 and Mbh2, two target genes directly involved in granule neuron precursor formation and strong expression of early cerebellar territory markers En1 and NeuroD1. Three weeks after induction, we observed a decrease in the number of glial cells and an increase in that of neurons albeit still immature. Combining Math1 induction with extrinsic factors specifically increased the number of neurons that expressed Pde1c, Zic1, and GABAα6R characteristic of mature granule neurons, formed "T-shaped" axons typical of granule neurons, and generated synaptic contacts and action potentials in vitro. Finally, in vivo implantation of Math1-induced progenitors into young adult mice resulted in cell migration and settling of newly generated neurons in the cerebellum. These results show that conditional induction of Math1 drives ESCs toward the cerebellar fate and indicate that acting on both intrinsic and extrinsic factors is a powerful means to modulate ESCs differentiation and maturation into a specific neuronal lineage. Copyright © 2012 AlphaMed Press.

  11. CXCL12-mediated feedback from granule neurons regulates generation and positioning of new neurons in the dentate gyrus.

    Abe, Philipp; Wüst, Hannah M; Arnold, Sebastian J; van de Pavert, Serge A; Stumm, Ralf

    2018-03-14

    Adult hippocampal neurogenesis is implicated in learning and memory processing. It is tightly controlled at several levels including progenitor proliferation as well as migration, differentiation and integration of new neurons. Hippocampal progenitors and immature neurons reside in the subgranular zone (SGZ) and are equipped with the CXCL12-receptor CXCR4 which contributes to defining the SGZ as neurogenic niche. The atypical CXCL12-receptor CXCR7 functions primarily by sequestering extracellular CXCL12 but whether CXCR7 is involved in adult neurogenesis has not been assessed. We report that granule neurons (GN) upregulate CXCL12 and CXCR7 during dentate gyrus maturation in the second postnatal week. To test whether GN-derived CXCL12 regulates neurogenesis and if neuronal CXCR7 receptors influence this process, we conditionally deleted Cxcl12 and Cxcr7 from the granule cell layer. Cxcl12 deletion resulted in lower numbers, increased dispersion and abnormal dendritic growth of immature GN and reduced neurogenesis. Cxcr7 ablation caused an increase in progenitor proliferation and progenitor numbers and reduced dispersion of immature GN. Thus, we provide a new mechanism where CXCL12-signals from GN prevent dispersion and support maturation of newborn GN. CXCR7 receptors of GN modulate the CXCL12-mediated feedback from GN to the neurogenic niche. © 2018 Wiley Periodicals, Inc.

  12. Protective Effect of Edaravone in Primary Cerebellar Granule Neurons against Iodoacetic Acid-Induced Cell Injury

    Xinhua Zhou

    2015-01-01

    Full Text Available Edaravone (EDA is clinically used for treatment of acute ischemic stroke in Japan and China due to its potent free radical-scavenging effect. However, it has yet to be determined whether EDA can attenuate iodoacetic acid- (IAA- induced neuronal death in vitro. In the present study, we investigated the effect of EDA on damage of IAA-induced primary cerebellar granule neurons (CGNs and its possible underlying mechanisms. We found that EDA attenuated IAA-induced cell injury in CGNs. Moreover, EDA significantly reduced intracellular reactive oxidative stress production, loss of mitochondrial membrane potential, and caspase 3 activity induced by IAA. Taken together, EDA protected CGNs against IAA-induced neuronal damage, which may be attributed to its antiapoptotic and antioxidative activities.

  13. Oligodendrocyte ablation affects the coordinated interaction between granule and Purkinje neurons during cerebellum development

    Collin, Ludovic; Doretto, Sandrine; Malerba, Monica; Ruat, Martial; Borrelli, Emiliana

    2007-01-01

    Oligodendrocytes (OLs) are the glial cells of the central nervous system (CNS) classically known to be devoted to the formation of myelin sheaths around most axons of the vertebrate brain. We have addressed the role of these cells during cerebellar development, by ablating OLs in vivo. Previous analyses had indicated that OL ablation during the first six postnatal days results into a striking cerebellar phenotype, whose major features are a strong reduction of granule neurons and aberrant Purkinje cells development. These two cell types are highly interconnected during cerebellar development through the production of molecules that help their proliferation, differentiation and maintenance. In this article, we present data showing that OL ablation has major effects on the physiology of Purkinje (PC) and granule cells (GC). In particular, OL ablation results into a reduction of sonic hedgehog (Shh), Brain Derived Neurotrophic Factor (BDNF), and Reelin (Rln) expression. These results indicate that absence of OLs profoundly alters the normal cerebellar developmental program

  14. Electron microscopic analysis of the specific granule content of ...

    Knowledge about the stimulus for the release of atrial natriuretic peptide (ANP) from human atria is incomplete. Atrial stretch is known to be a stimulus and atrial tachyarrhythmias are thought to be another. The effects of atrial size (by twodimensional echocardiography) and atrial fibrillation on the atrial specific granule ...

  15. Single K ATP channel opening in response to action potential firing in mouse dentate granule neurons.

    Tanner, Geoffrey R; Lutas, Andrew; Martínez-François, Juan Ramón; Yellen, Gary

    2011-06-08

    ATP-sensitive potassium channels (K(ATP) channels) are important sensors of cellular metabolic state that link metabolism and excitability in neuroendocrine cells, but their role in nonglucosensing central neurons is less well understood. To examine a possible role for K(ATP) channels in modulating excitability in hippocampal circuits, we recorded the activity of single K(ATP) channels in cell-attached patches of granule cells in the mouse dentate gyrus during bursts of action potentials generated by antidromic stimulation of the mossy fibers. Ensemble averages of the open probability (p(open)) of single K(ATP) channels over repeated trials of stimulated spike activity showed a transient increase in p(open) in response to action potential firing. Channel currents were identified as K(ATP) channels through blockade with glibenclamide and by comparison with recordings from Kir6.2 knock-out mice. The transient elevation in K(ATP) p(open) may arise from submembrane ATP depletion by the Na(+)-K(+) ATPase, as the pump blocker strophanthidin reduced the magnitude of the elevation. Both the steady-state and stimulus-elevated p(open) of the recorded channels were higher in the presence of the ketone body R-β-hydroxybutyrate, consistent with earlier findings that ketone bodies can affect K(ATP) activity. Using perforated-patch recording, we also found that K(ATP) channels contribute to the slow afterhyperpolarization following an evoked burst of action potentials. We propose that activity-dependent opening of K(ATP) channels may help granule cells act as a seizure gate in the hippocampus and that ketone-body-mediated augmentation of the activity-dependent opening could in part explain the effect of the ketogenic diet in reducing epileptic seizures.

  16. Design of memristive interface between electronic neurons

    Gerasimova, S. A.; Mikhaylov, A. N.; Belov, A. I.; Korolev, D. S.; Guseinov, D. V.; Lebedeva, A. V.; Gorshkov, O. N.; Kazantsev, V. B.

    2018-05-01

    Nonlinear dynamics of two electronic oscillators coupled via a memristive device has been investigated. Such model mimics the interaction between synaptically coupled brain neurons with the memristive device imitating neuron axon. The synaptic connection is provided by the adaptive behavior of memristive device that changes its resistance under the action of spike-like activity. Mathematical model of such a memristive interface has been developed to describe and predict the experimentally observed regularities of forced synchronization of neuron-like oscillators.

  17. Sonic Hedgehog Signaling Drives Mitochondrial Fragmentation by Suppressing Mitofusins in Cerebellar Granule Neuron Precursors and Medulloblastoma.

    Malhotra, Anshu; Dey, Abhinav; Prasad, Niyathi; Kenney, Anna Marie

    2016-01-01

    Sonic hedgehog (Shh) signaling is closely coupled with bioenergetics of medulloblastoma, the most common malignant pediatric brain tumor. Shh-associated medulloblastoma arises from cerebellar granule neuron precursors (CGNP), a neural progenitor whose developmental expansion requires signaling by Shh, a ligand secreted by the neighboring Purkinje neurons. Previous observations show that Shh signaling inhibits fatty acid oxidation although driving increased fatty acid synthesis. Proliferating CGNPs and mouse Shh medulloblastomas feature high levels of glycolytic enzymes in vivo and in vitro. Because both of these metabolic processes are closely linked to mitochondrial bioenergetics, the role of Shh signaling in mitochondrial biogenesis was investigated. This report uncovers a surprising decrease in mitochondrial membrane potential (MMP) and overall ATP production in CGNPs exposed to Shh, consistent with increased glycolysis resulting in high intracellular acidity, leading to mitochondrial fragmentation. Ultrastructural examination of mitochondria revealed a spherical shape in Shh-treated cells, in contrast to the elongated appearance in vehicle-treated postmitotic cells. Expression of mitofusin 1 and 2 was reduced in these cells, although their ectopic expression restored the MMP to the nonproliferating state and the morphology to a fused, interconnected state. Mouse Shh medulloblastoma cells featured drastically impaired mitochondrial morphology, restoration of which by ectopic mitofusin expression was also associated with a decrease in the expression of Cyclin D2 protein, a marker for proliferation. This report exposes a novel role for Shh in regulating mitochondrial dynamics and rescue of the metabolic profile of tumor cells to that of nontransformed, nonproliferating cells and represents a potential avenue for development of medulloblastoma therapeutics. ©2015 American Association for Cancer Research.

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

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

    2013-01-01

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

  19. Adiponectin regulates contextual fear extinction and intrinsic excitability of dentate gyrus granule neurons through AdipoR2 receptors.

    Zhang, D; Wang, X; Wang, B; Garza, J C; Fang, X; Wang, J; Scherer, P E; Brenner, R; Zhang, W; Lu, X-Y

    2017-07-01

    Post-traumatic stress disorder (PTSD) is characterized by exaggerated fear expression and impaired fear extinction. The underlying molecular and cellular mechanisms of PTSD are largely unknown. The current pharmacological and non-pharmacological treatments for PTSD are either ineffective or temporary with high relapse rates. Here we report that adiponectin-deficient mice exhibited normal contextual fear conditioning but displayed slower extinction learning. Infusions of adiponectin into the dentate gyrus (DG) of the hippocampus in fear-conditioned mice facilitated extinction of contextual fear. Whole-cell patch-clamp recordings in brain slices revealed that intrinsic excitability of DG granule neurons was enhanced by adiponectin deficiency and suppressed after treatment with the adiponectin mimetic AdipoRon, which were associated with increased input resistance and hyperpolarized resting membrane potential, respectively. Moreover, deletion of AdipoR2, but not AdipoR1 in the DG, resulted in augmented fear expression and reduced extinction, accompanied by intrinsic hyperexcitability of DG granule neurons. Adiponectin and AdipoRon failed to induce facilitation of fear extinction and elicit inhibition of intrinsic excitability of DG neurons in AdipoR2 knockout mice. These results indicated that adiponectin action via AdipoR2 was both necessary and sufficient for extinction of contextual fear and intrinsic excitability of DG granule neurons, implying that enhancing or dampening DG neuronal excitability may cause resistance to or facilitation of extinction. Therefore, our findings provide a functional link between adiponectin/AdipoR2 activation, DG neuronal excitability and contextual fear extinction, and suggest that targeting adiponectin/AdipoR2 may be used to strengthen extinction-based exposure therapies for PTSD.

  20. The histone demethylase Kdm6b regulates a mature gene expression program in differentiating cerebellar granule neurons.

    Wijayatunge, Ranjula; Liu, Fang; Shpargel, Karl B; Wayne, Nicole J; Chan, Urann; Boua, Jane-Valeriane; Magnuson, Terry; West, Anne E

    2018-03-01

    The histone H3 lysine 27 (H3K27) demethylase Kdm6b (Jmjd3) can promote cellular differentiation, however its physiological functions in neurons remain to be fully determined. We studied the expression and function of Kdm6b in differentiating granule neurons of the developing postnatal mouse cerebellum. At postnatal day 7, Kdm6b is expressed throughout the layers of the developing cerebellar cortex, but its expression is upregulated in newborn cerebellar granule neurons (CGNs). Atoh1-Cre mediated conditional knockout of Kdm6b in CGN precursors either alone or in combination with Kdm6a did not disturb the gross morphological development of the cerebellum. Furthermore, RNAi-mediated knockdown of Kdm6b in cultured CGN precursors did not alter the induced expression of early neuronal marker genes upon cell cycle exit. By contrast, knockdown of Kdm6b significantly impaired the induction of a mature neuronal gene expression program, which includes gene products required for functional synapse maturation. Loss of Kdm6b also impaired the ability of Brain-Derived Neurotrophic Factor (BDNF) to induce expression of Grin2c and Tiam1 in maturing CGNs. Taken together, these data reveal a previously unknown role for Kdm6b in the postmitotic stages of CGN maturation and suggest that Kdm6b may work, at least in part, by a transcriptional mechanism that promotes gene sensitivity to regulation by BDNF. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Synchronous behavior of two coupled electronic neurons

    Pinto, R. D.; Varona, P.; Volkovskii, A. R.; Szuecs, A.; Abarbanel, Henry D. I.; Rabinovich, M. I.

    2000-01-01

    We report on experimental studies of synchronization phenomena in a pair of analog electronic neurons (ENs). The ENs were designed to reproduce the observed membrane voltage oscillations of isolated biological neurons from the stomatogastric ganglion of the California spiny lobster Panulirus interruptus. The ENs are simple analog circuits which integrate four-dimensional differential equations representing fast and slow subcellular mechanisms that produce the characteristic regular/chaotic spiking-bursting behavior of these cells. In this paper we study their dynamical behavior as we couple them in the same configurations as we have done for their counterpart biological neurons. The interconnections we use for these neural oscillators are both direct electrical connections and excitatory and inhibitory chemical connections: each realized by analog circuitry and suggested by biological examples. We provide here quantitative evidence that the ENs and the biological neurons behave similarly when coupled in the same manner. They each display well defined bifurcations in their mutual synchronization and regularization. We report briefly on an experiment on coupled biological neurons and four-dimensional ENs, which provides further ground for testing the validity of our numerical and electronic models of individual neural behavior. Our experiments as a whole present interesting new examples of regularization and synchronization in coupled nonlinear oscillators. (c) 2000 The American Physical Society

  2. Spin orbit torque based electronic neuron

    Sengupta, Abhronil, E-mail: asengup@purdue.edu; Choday, Sri Harsha; Kim, Yusung; Roy, Kaushik [School of Electrical and Computer Engineering, Purdue University, West Lafayette, Indiana 47907 (United States)

    2015-04-06

    A device based on current-induced spin-orbit torque (SOT) that functions as an electronic neuron is proposed in this work. The SOT device implements an artificial neuron's thresholding (transfer) function. In the first step of a two-step switching scheme, a charge current places the magnetization of a nano-magnet along the hard-axis, i.e., an unstable point for the magnet. In the second step, the SOT device (neuron) receives a current (from the synapses) which moves the magnetization from the unstable point to one of the two stable states. The polarity of the synaptic current encodes the excitatory and inhibitory nature of the neuron input and determines the final orientation of the magnetization. A resistive crossbar array, functioning as synapses, generates a bipolar current that is a weighted sum of the inputs. The simulation of a two layer feed-forward artificial neural network based on the SOT electronic neuron shows that it consumes ∼3× lower power than a 45 nm digital CMOS implementation, while reaching ∼80% accuracy in the classification of 100 images of handwritten digits from the MNIST dataset.

  3. Spin orbit torque based electronic neuron

    Sengupta, Abhronil; Choday, Sri Harsha; Kim, Yusung; Roy, Kaushik

    2015-01-01

    A device based on current-induced spin-orbit torque (SOT) that functions as an electronic neuron is proposed in this work. The SOT device implements an artificial neuron's thresholding (transfer) function. In the first step of a two-step switching scheme, a charge current places the magnetization of a nano-magnet along the hard-axis, i.e., an unstable point for the magnet. In the second step, the SOT device (neuron) receives a current (from the synapses) which moves the magnetization from the unstable point to one of the two stable states. The polarity of the synaptic current encodes the excitatory and inhibitory nature of the neuron input and determines the final orientation of the magnetization. A resistive crossbar array, functioning as synapses, generates a bipolar current that is a weighted sum of the inputs. The simulation of a two layer feed-forward artificial neural network based on the SOT electronic neuron shows that it consumes ∼3× lower power than a 45 nm digital CMOS implementation, while reaching ∼80% accuracy in the classification of 100 images of handwritten digits from the MNIST dataset

  4. Glucose deprivation stimulates Cu(2+) toxicity in cultured cerebellar granule neurons and Cu(2+)-dependent zinc release.

    Isaev, Nickolay K; Genrikhs, Elisaveta E; Aleksandrova, Olga P; Zelenova, Elena A; Stelmashook, Elena V

    2016-05-27

    Copper chloride (0.01mM, 2h) did not have significant influence on the survival of cerebellar granule neurons (CGNs) incubated in balanced salt solution. However, CuCl2 caused severe neuronal damage by glucose deprivation (GD). The glutamate NMDA-receptors blocker MK-801 partially and antioxidant N-acetyl-l-cysteine (NAC) or Zn(2+) chelator, N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) almost entirely protected CGNs from this toxic effect. Measurements of intracellular calcium ions using Fluo-4 AM, or zinc ions with FluoZin-3 AM demonstrated that 1 h-exposure to GD induced intensive increase of Fluo-4 but not FluoZin-3 fluorescence in neurons. The supplementation of solution with CuCl2 caused an increase of FluoZin-3, Fluo-4 and CellROX Green (reactive oxygen species probe) fluorescence by GD. The stimulation of Fluo-4 but not FluoZin-3 fluorescence by copper could be prevented partially by MK-801 and as well as CellROX Green fluorescence by NAC at GD. This data imply that during GD copper ions induce intense displacement zinc ions from intracellular stores, in addition free radical production, glutamate release and Ca(2+) overload of CGNs, that causes death of neurons as a result. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Inhibition of glycogen synthase kinase-3 reduces extension of the axonal leading process by destabilizing microtubules in cerebellar granule neurons.

    Inami, Yoshihiro; Omura, Mitsuru; Kubota, Kenta; Konishi, Yoshiyuki

    2018-07-01

    Recent studies have uncovered various molecules that play key roles in neuronal morphogenesis. Nevertheless, the mechanisms underlying the neuron-type-dependent regulation of morphogenesis remain unknown. We have previously reported that inhibition of glycogen synthase kinase-3 (GSK3) markedly reduced axonal length of cerebellar granule neurons (CGNs) in a neuron-type-dependent manner. In the present study, we investigated the mechanisms by which the growth of CGN axons was severely suppressed upon GSK3 inhibition. Using time-lapse imaging of cultured CGNs at early morphogenesis, we found that extension of the leading process was severely inhibited by the pharmacological inhibition of GSK3. The rate of somal migration was also reduced with a GSK3 inhibitor in dissociated culture as well as in microexplant culture. In addition, CGNs ectopically expressed with a catalytically inactive mutant of GSK3 exhibited a migration defect in vivo. In axonal leading processes of CGNs, detyrosination and acetylation of α-tubulin, which are known to correlate with microtubule stability, were decreased by GSK3 inhibition. A photoconversion analysis found that inhibition of GSK3 increases the turnover of microtubules. Furthermore, in the presence of paclitaxel, a microtubule-stabilizing reagent, inhibition of GSK3 recovered the axonal leading process extension that was reduced by paclitaxel. Our results suggest that GSK3 supports the extension of axonal processes by stabilizing microtubules, contrary to its function in other neuron-types, lending mechanical insight into neuron-type-dependent morphological regulation. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Axonal transport of TDP-43 mRNA granules in neurons is impaired by ALS-causing mutations

    Carrasco, Monica A.; Williams, Luis A.; Winborn, Christina S.; Han, Steve S. W.; Kiskinis, Evangelos; Winborn, Brett; Freibaum, Brian D.; Kanagaraj, Anderson; Clare, Alison J.; Badders, Nisha M.; Bilican, Bilada; Chaum, Edward; Chandran, Siddharthan; Shaw, Christopher E.; Eggan, Kevin C.; Maniatis, Tom; Taylor, J. Paul

    2014-01-01

    Summary The RNA binding protein TDP-43 regulates RNA metabolism at multiple levels, including transcription, RNA splicing, and mRNA stability. TDP-43 is a major component of the cytoplasmic inclusions characteristic of amyotrophic lateral sclerosis and some types of frontotemporal lobar degeneration. The importance of TDP-43 in disease is underscored by the fact that dominant missense mutations are sufficient to cause disease, although the role of TDP-43 in pathogenesis is unknown. Here we show that TDP-43 forms cytoplasmic mRNP granules that undergo bidirectional, microtubule-dependent transport in neurons in vitro and in vivo and facilitate delivery of target mRNA to distal neuronal compartments. TDP-43 mutations impair this mRNA transport function in vivo and in vitro, including in stem cell-derived motor neurons from ALS patients bearing any one of three different TDP-43 ALS-causing mutations. Thus, TDP43 mutations that cause ALS lead to partial loss of a novel cytoplasmic function of TDP-43. PMID:24507191

  7. Leading-process actomyosin coordinates organelle positioning and adhesion receptor dynamics in radially migrating cerebellar granule neurons.

    Trivedi, Niraj; Ramahi, Joseph S; Karakaya, Mahmut; Howell, Danielle; Kerekes, Ryan A; Solecki, David J

    2014-12-02

    During brain development, neurons migrate from germinal zones to their final positions to assemble neural circuits. A unique saltatory cadence involving cyclical organelle movement (e.g., centrosome motility) and leading-process actomyosin enrichment prior to nucleokinesis organizes neuronal migration. While functional evidence suggests that leading-process actomyosin is essential for centrosome motility, the role of the actin-enriched leading process in globally organizing organelle transport or traction forces remains unexplored. We show that myosin ii motors and F-actin dynamics are required for Golgi apparatus positioning before nucleokinesis in cerebellar granule neurons (CGNs) migrating along glial fibers. Moreover, we show that primary cilia are motile organelles, localized to the leading-process F-actin-rich domain and immobilized by pharmacological inhibition of myosin ii and F-actin dynamics. Finally, leading process adhesion dynamics are dependent on myosin ii and F-actin. We propose that actomyosin coordinates the overall polarity of migrating CGNs by controlling asymmetric organelle positioning and cell-cell contacts as these cells move along their glial guides.

  8. Effects of electron-beam irradation on some structural properties of granulated polymer blends

    Zenkiewicz, Marian; Czuprynska, Joanna; Polanski, Julian; Karasiewicz, Tomasz; Engelgard, Wlodzimierz

    2008-01-01

    The aim of this article was to show the effects of the electron radiation dose and presence of a compatibiliser on the peak melting temperature (T pm ) of the crystalline phase, crystallinity (X c ), and melt flow rate (MFR) of granulated blends of low-density polyethylene (LDPE), high-density polyethylene (HDPE), polypropylene (PP), polystyrene (PS), and polyethylene terephthalate (PET) as well as of blends of LDPE, HDPE, and PP. The purpose of applying the high-energy electron radiation with doses up to 300 kGy and of adding a compatibiliser was to enhance mechanical properties of the studied blends and, at the same time, to investigate the possibility of using this technique in the processes of recycling polymeric materials. As the compatibilisers, the styrene-ethylene/butylene-styrene elastomer grafted with maleic anhydride (SEBS-g-MA) and trimethylol propane trimethacrylate (TMPTA) were utilised; they were added at the amounts of 5, 10, and 15 wt% and 1, 2, and 3 wt%, respectively. The enhancement of mechanical properties was accompanied by the following effects, discussed in this article: (i) a decrease in the peak melting temperature upon the electron radiation for the crystalline phase of LDPE, HDPE, and PP that constituted the studied granulated blends and (ii) changes in MFR upon both the electron radiation and the addition of compatibilisers

  9. Talpid3-binding centrosomal protein Cep120 is required for centriole duplication and proliferation of cerebellar granule neuron progenitors.

    Chuanqing Wu

    Full Text Available Granule neuron progenitors (GNPs are the most abundant neuronal type in the cerebellum. GNP proliferation and thus cerebellar development require Sonic hedgehog (Shh secreted from Purkinje cells. Shh signaling occurs in primary cilia originating from the mother centriole. Centrioles replicate only once during a typical cell cycle and are responsible for mitotic spindle assembly and organization. Recent studies have linked cilia function to cerebellar morphogenesis, but the role of centriole duplication in cerebellar development is not known. Here we show that centrosomal protein Cep120 is asymmetrically localized to the daughter centriole through its interaction with Talpid3 (Ta3, another centrosomal protein. Cep120 null mutant mice die in early gestation with abnormal heart looping. Inactivation of Cep120 in the central nervous system leads to both hydrocephalus, due to the loss of cilia on ependymal cells, and severe cerebellar hypoplasia, due to the failed proliferation of GNPs. The mutant GNPs lack Hedgehog pathway activity. Cell biological studies show that the loss of Cep120 results in failed centriole duplication and consequently ciliogenesis, which together underlie Cep120 mutant cerebellar hypoplasia. Thus, our study for the first time links a centrosomal protein necessary for centriole duplication to cerebellar morphogenesis.

  10. Effects of pentylenetetrazole and glutamate on metabolism of [U-(13)C]glucose in cultured cerebellar granule neurons.

    Eloqayli, Haytham; Qu, Hong; Unsgård, Geirmund; Sletvold, Olav; Hadidi, Hakam; Sonnewald, Ursula

    2002-02-01

    This study was performed to analyze the effects of glutamate and the epileptogenic agent pentylenetetrazole (PTZ) on neuronal glucose metabolism. Cerebellar granule neurons were incubated for 2 h in medium containing 3 mM [U-(13)C]glucose, with and without 0.25 mM glutamate and/or 10 mM PTZ. In the presence of PTZ, decreased glucose consumption with unchanged lactate release was observed, indicating decreased glucose oxidation. PTZ also slowed down tricarboxylic acid (TCA) cycle activity as evidenced by the decreased amounts of labeled aspartate and [1,2-(13)C]glutamate. When glutamate was present, glucose consumption was also decreased. However, the amount of glutamate, derived from [U-(13)C]glucose via the first turn of the TCA cycle, was increased. The decreased amount of [1,2-(13)C]glutamate, derived from the second turn in the TCA cycle, and increased amount of aspartate indicated the dilution of label due to the entrance of unlabeled glutamate into TCA cycle. In the presence of glutamate plus PTZ, the effect of PTZ was enhanced by glutamate. Labeled alanine was detected only in the presence of glutamate plus PTZ, which indicated that oxaloacetate was a better amino acid acceptor than pyruvate. Furthermore, there was also evidence for intracellular compartmentation of oxaloacetate metabolism. Glutamate and PTZ caused similar metabolic changes, however, via different mechanisms. Glutamate substituted for glucose as energy substrate in the TCA cycle, whereas, PTZ appeared to decrease mitochondrial activity.

  11. Different Molecular Mechanisms Mediate Direct or Glia-Dependent Prion Protein Fragment 90-231 Neurotoxic Effects in Cerebellar Granule Neurons.

    Thellung, Stefano; Gatta, Elena; Pellistri, Francesca; Villa, Valentina; Corsaro, Alessandro; Nizzari, Mario; Robello, Mauro; Florio, Tullio

    2017-10-01

    Glia over-stimulation associates with amyloid deposition contributing to the progression of central nervous system neurodegenerative disorders. Here we analyze the molecular mechanisms mediating microglia-dependent neurotoxicity induced by prion protein (PrP)90-231, an amyloidogenic polypeptide corresponding to the protease-resistant portion of the pathological prion protein scrapie (PrP Sc ). PrP90-231 neurotoxicity is enhanced by the presence of microglia within neuronal culture, and associated to a rapid neuronal [Ca ++ ] i increase. Indeed, while in "pure" cerebellar granule neuron cultures, PrP90-231 causes a delayed intracellular Ca ++ entry mediated by the activation of NMDA receptors; when neuron and glia are co-cultured, a transient increase of [Ca ++ ] i occurs within seconds after treatment in both granule neurons and glial cells, then followed by a delayed and sustained [Ca ++ ] i raise, associated with the induction of the expression of inducible nitric oxide synthase and phagocytic NADPH oxidase. [Ca ++ ] i fast increase in neurons is dependent on the activation of multiple pathways since it is not only inhibited by the blockade of voltage-gated channel activity and NMDA receptors but also prevented by the inhibition of nitric oxide and PGE 2 release from glial cells. Thus, Ca ++ homeostasis alteration, directly induced by PrP90-231 in cerebellar granule cells, requires the activation of NMDA receptors, but is greatly enhanced by soluble molecules released by activated glia. In glia-enriched cerebellar granule cultures, the activation of inducible nitric oxide (iNOS) and NADPH oxidase represents the main mechanism of toxicity since their pharmacological inhibition prevented PrP90-231 neurotoxicity, whereas NMDA blockade by D(-)-2-amino-5-phosphonopentanoic acid is ineffective; conversely, in pure cerebellar granule cultures, NMDA blockade but not iNOS inhibition strongly reduced PrP90-231 neurotoxicity. These data indicate that amyloidogenic peptides

  12. P2X7, NMDA and BDNF receptors converge on GSK3 phosphorylation and cooperate to promote survival in cerebellar granule neurons.

    Ortega, Felipe; Pérez-Sen, Raquel; Morente, Verónica; Delicado, Esmerilda G; Miras-Portugal, Maria Teresa

    2010-05-01

    Glycogen synthase kinase-3 (GSK3) is a key player in the regulation of neuronal survival. Herein, we report evidence of an interaction between P2X7 receptors with NMDA and BDNF receptors at the level of GSK3 signalling and neuroprotection. The activation of these receptors in granule neurons led to a sustained pattern of GSK3 phosphorylation that was mainly PKC-dependent. BDNF was the most potent at inducing GSK3 phosphorylation, which was also dependent on PI3K. The P2X7 agonist, BzATP, exhibited additive effects with both NMDA and BDNF to rescue granule neurons from cell death induced by PI3K inhibition. This survival effect was mediated by the PKC-dependent GSK3 pathway. In addition, ERK1/2 proteins were also involved in BDNF protective effect. These results show the function of ATP in amplifying neuroprotective actions of glutamate and neurotrophins, and support the role of GSK3 as an important convergence point for these survival promoting factors in granule neurons.

  13. BarTeL, a Genetically Versatile, Bioluminescent and Granule Neuron Precursor-Targeted Mouse Model for Medulloblastoma.

    Gregory M Shackleford

    Full Text Available Medulloblastomas are the most common malignant pediatric brain tumor and have been divided into four major molecular subgroups. Animal models that mimic the principal molecular aberrations of these subgroups will be important tools for preclinical studies and allow greater understanding of medulloblastoma biology. We report a new transgenic model of medulloblastoma that possesses a unique combination of desirable characteristics including, among others, the ability to incorporate multiple and variable genes of choice and to produce bioluminescent tumors from a limited number of somatic cells within a normal cellular environment. This model, termed BarTeL, utilizes a Barhl1 homeobox gene promoter to target expression of a bicistronic transgene encoding both the avian retroviral receptor TVA and an eGFP-Luciferase fusion protein to neonatal cerebellar granule neuron precursor (cGNP cells, which are cells of origin for the sonic hedgehog (SHH subgroup of human medulloblastomas. The Barhl1 promoter-driven transgene is expressed strongly in mammalian cGNPs and weakly or not at all in mature granule neurons. We efficiently induced bioluminescent medulloblastomas expressing eGFP-luciferase in BarTeL mice by infection of a limited number of somatic cGNPs with avian retroviral vectors encoding the active N-terminal fragment of SHH and a stabilized MYCN mutant. Detection and quantification of the increasing bioluminescence of growing tumors in young BarTeL mice was facilitated by the declining bioluminescence of their uninfected maturing cGNPs. Inclusion of eGFP in the transgene allowed enriched sorting of cGNPs from neonatal cerebella. Use of a single bicistronic avian vector simultaneously expressing both Shh and Mycn oncogenes increased the medulloblastoma incidence and aggressiveness compared to mixed virus infections. Bioluminescent tumors could also be produced by ex vivo transduction of neonatal BarTeL cerebellar cells by avian retroviruses and

  14. Physical exercise prevents stress-induced activation of granule neurons and enhances local inhibitory mechanisms in the dentate gyrus.

    Schoenfeld, Timothy J; Rada, Pedro; Pieruzzini, Pedro R; Hsueh, Brian; Gould, Elizabeth

    2013-05-01

    Physical exercise is known to reduce anxiety. The ventral hippocampus has been linked to anxiety regulation but the effects of running on this subregion of the hippocampus have been incompletely explored. Here, we investigated the effects of cold water stress on the hippocampus of sedentary and runner mice and found that while stress increases expression of the protein products of the immediate early genes c-fos and arc in new and mature granule neurons in sedentary mice, it has no such effect in runners. We further showed that running enhances local inhibitory mechanisms in the hippocampus, including increases in stress-induced activation of hippocampal interneurons, expression of vesicular GABA transporter (vGAT), and extracellular GABA release during cold water swim stress. Finally, blocking GABAA receptors in the ventral hippocampus, but not the dorsal hippocampus, with the antagonist bicuculline, reverses the anxiolytic effect of running. Together, these results suggest that running improves anxiety regulation by engaging local inhibitory mechanisms in the ventral hippocampus.

  15. Mutant PrP Suppresses Glutamatergic Neurotransmission in Cerebellar Granule Neurons by Impairing Membrane Delivery of VGCC α2δ-1 Subunit

    Senatore, Assunta; Colleoni, Simona; Verderio, Claudia; Restelli, Elena; Morini, Raffaella; Condliffe, Steven B.; Bertani, Ilaria; Mantovani, Susanna; Canovi, Mara; Micotti, Edoardo; Forloni, Gianluigi; Dolphin, Annette C.; Matteoli, Michela; Gobbi, Marco; Chiesa, Roberto

    2012-01-01

    Summary How mutant prion protein (PrP) leads to neurological dysfunction in genetic prion diseases is unknown. Tg(PG14) mice synthesize a misfolded mutant PrP which is partially retained in the neuronal endoplasmic reticulum (ER). As these mice age, they develop ataxia and massive degeneration of cerebellar granule neurons (CGNs). Here, we report that motor behavioral deficits in Tg(PG14) mice emerge before neurodegeneration and are associated with defective glutamate exocytosis from granule neurons due to impaired calcium dynamics. We found that mutant PrP interacts with the voltage-gated calcium channel α2δ-1 subunit, which promotes the anterograde trafficking of the channel. Owing to ER retention of mutant PrP, α2δ-1 accumulates intracellularly, impairing delivery of the channel complex to the cell surface. Thus, mutant PrP disrupts cerebellar glutamatergic neurotransmission by reducing the number of functional channels in CGNs. These results link intracellular PrP retention to synaptic dysfunction, indicating new modalities of neurotoxicity and potential therapeutic strategies. PMID:22542184

  16. Characterization of two novel nuclear BTB/POZ domain zinc finger isoforms. Association with differentiation of hippocampal neurons, cerebellar granule cells, and macroglia

    Mitchelmore, Cathy; Kjaerulff, Karen M; Pedersen, Hans C

    2002-01-01

    BTB/POZ (broad complex tramtrack bric-a-brac/poxvirus and zinc finger) zinc finger factors are a class of nuclear DNA-binding proteins involved in development, chromatin remodeling, and cancer. However, BTB/POZ domain zinc finger factors linked to development of the mammalian cerebral cortex......, cerebellum, and macroglia have not been described previously. We report here the isolation and characterization of two novel nuclear BTB/POZ domain zinc finger isoforms, designated HOF(L) and HOF(S), that are specifically expressed in early hippocampal neurons, cerebellar granule cells, and gliogenic...

  17. Calcium detection in secretion granules of avian oviduct by scanning electron microscopy (SEM) and energy-dispersive X-ray microanalysis (EDX)

    Makita, T.; Hatsuoka, M.; Sugi, Y.

    1983-01-01

    Secretion granules in the shell gland, isthmus, and albumin-secreting region of the hen oviduct were analyzed with WET-scanning electron microscopy (SEM) and EDX, a combination of wide-angle backscattered electron detector (BED) and energy-dispersive X-ray microanalyzer (EDX). Glutaraldehyde-fixed but unhydrated, unstained, and uncoated samples were analyzed; Ca was localized in all secretion granules in all three sections of the hen oviduct studied

  18. An experimental electronic model for a neuronal cell

    Campos-Cantón, I; Martel-Gallegos, G; Rangel-López, A; Vertiz-Hérnandez, A; Zarazúa, S

    2014-01-01

    Over the last two decades, the study of information transmission in living beings has acquired great relevance, because it regulates and conducts the functioning of all of the organs in the body. In information transmission pathways, the neuron plays an important role in that it receives, transmits, and processes electrical signals from different parts of the human body; these signals are transmitted as electrical impulses called action potentials, and they transmit information from one neuron to another. In this work, and with the aim of developing experiments for teaching biological processes, we implemented an electronic circuit of the neuron cell device and its mathematical model based on piecewise linear functions. (paper)

  19. Tridimensional architecture of the collagen element in the arachnoid granulations in humans: a study on scanning electron microscopy

    Conegero Celso Ivan

    2003-01-01

    Full Text Available The arachnoid granulations of adult individual of both sexes were studied through scanning electron microscopy. The dura mater and arachnoid meninges of individuals were collected at the Service of Death Verification of São Paulo - USP and fixed in Karnovsky solution. After this period the material was prepared for analysis in electron microscope. Our results demonstrated that the arachnoid granulations are formed by a pedicle, body and apex, being surrounded by a capsule of connective tissue, which in turn is composed of, basically, bundles of collagen fibers that line pores of different shapes and sizes. The smaller pores are lined by tiny bundles and are located at the apical region of the granulation and the larger are lined by thicker bundles and are located at the lateral regions. In the body we verified that the bundles of collagen fibers compose a fibrous meshwork and in some regions these bundles have circular orientation, forming pores similar to those found at the region of the capsule.

  20. BNN27, a 17-Spiroepoxy Steroid Derivative, Interacts With and Activates p75 Neurotrophin Receptor, Rescuing Cerebellar Granule Neurons from Apoptosis.

    Pediaditakis, Iosif; Kourgiantaki, Alexandra; Prousis, Kyriakos C; Potamitis, Constantinos; Xanthopoulos, Kleanthis P; Zervou, Maria; Calogeropoulou, Theodora; Charalampopoulos, Ioannis; Gravanis, Achille

    2016-01-01

    Neurotrophin receptors mediate a plethora of signals affecting neuronal survival. The p75 pan-neurotrophin receptor controls neuronal cell fate after its selective activation by immature and mature isoforms of all neurotrophins. It also exerts pleiotropic effects interacting with a variety of ligands in different neuronal or non-neuronal cells. In the present study, we explored the biophysical and functional interactions of a blood-brain-barrier (BBB) permeable, C17-spiroepoxy steroid derivative, BNN27, with p75 NTR receptor. BNN27 was recently shown to bind to NGF high-affinity receptor, TrkA. We now tested the p75 NTR -mediated effects of BNN27 in mouse Cerebellar Granule Neurons (CGNs), expressing p75 NTR , but not TrkA receptors. Our findings show that BNN27 physically interacts with p75 NTR receptors in specific amino-residues of its extracellular domain, inducing the recruitment of p75 NTR receptor to its effector protein RIP2 and the simultaneous release of RhoGDI in primary neuronal cells. Activation of the p75 NTR receptor by BNN27 reverses serum deprivation-induced apoptosis of CGNs resulting in the decrease of the phosphorylation of pro-apoptotic JNK kinase and of the cleavage of Caspase-3, effects completely abolished in CGNs, isolated from p75 NTR null mice. In conclusion, BNN27 represents a lead molecule for the development of novel p75 NTR ligands, controlling specific p75 NTR -mediated signaling of neuronal cell fate, with potential applications in therapeutics of neurodegenerative diseases and brain trauma.

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

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

    2009-01-01

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

  2. Neuroprotection comparison of chlorogenic acid and its metabolites against mechanistically distinct cell death-inducing agents in cultured cerebellar granule neurons.

    Taram, Faten; Winter, Aimee N; Linseman, Daniel A

    2016-10-01

    While the number of patients diagnosed with neurodegenerative disorders like Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease is increasing, there are currently no effective treatments that significantly limit the neuronal cell death underlying these diseases. Chlorogenic acid (CGA), a polyphenolic compound found in high concentration in coffee, is known to possess antioxidant and free radical scavenging activity. In this study, we investigated the neuroprotective effects of CGA and its major metabolites in primary cultures of rat cerebellar granule neurons. We show that CGA and caffeic acid displayed a dramatic protective effect against the nitric oxide donor, sodium nitroprusside. In marked contrast, ferulic acid and quinic acid had no protective effect against this nitrosative stress. While CGA and quinic acid had no protective effect against glutamate-induced cell death, caffeic acid and ferulic acid significantly protected neurons from excitotoxicity. Finally, caffeic acid was the only compound to display significant protective activity against hydrogen peroxide, proteasome inhibition, caspase-dependent intrinsic apoptosis, and endoplasmic reticulum stress. These results indicate that caffeic acid displays a much broader profile of neuroprotection against a diverse range of stressors than its parent polyphenol, CGA, or the other major metabolites, ferulic acid and quinic acid. We conclude that caffeic acid is a promising candidate for testing in pre-clinical models of neurodegeneration. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. N-acetyl-l-cysteine and Mn2+ attenuate Cd2+-induced disturbance of the intracellular free calcium homeostasis in cultured cerebellar granule neurons.

    Isaev, Nickolay K; Avilkina, Svetlana; Golyshev, Sergey A; Genrikhs, Elisaveta E; Alexandrova, Olga P; Kapkaeva, Marina R; Stelmashook, Elena V

    2018-01-15

    Cadmium is a highly toxic heavy metal that is capable of accumulating in the body via direct exposure or through the alimentary and respiratory tract, leading to neurodegeneration. In this article, we show that the application of CdCl 2 (0.001-0.005mM) for 48h induced high dose-dependent death rate of cultured cerebellar granule neurons (CGNs). Unlike Trolox or vitamin E, antioxidant N-acetyl-l-cysteine (NAC, 1mM) and Mn 2+ (0.0025-0.005mM) significantly protected CGNs from this toxic effect. Using Fluo-4 AM, measurements of intracellular calcium ions demonstrated that 24h-exposure to Cd 2+ induced intensive increase of Fluo-4 fluorescence in neurons accompanied by mitochondria swelling. These data imply that the cadmium-induced Ca 2+ increase is an important element in the death of neurons due to toxic effect of cadmium and the mechanism of protective action of manganese and NAC is mediated by the prevention of increase in calcium levels. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Light and electron microscopic localization of GABAA-receptors on cultured cerebellar granule cells and astrocytes using immunohistochemical techniques

    Hansen, Gert Helge; Hösli, E; Belhage, B

    1991-01-01

    . At the light microscope level specific staining of GABAA-receptors was localized in various types of neurones in explant cultures of rat cerebellum using the indirect peroxidase-antiperoxidase (PAP) technique, whereas no specific staining was found in astrocytes. At the electron microscope level labeling...

  5. Forced swimming sabotages the morphological and synaptic maturation of newborn granule neurons and triggers a unique pro-inflammatory milieu in the hippocampus.

    Llorens-Martín, María; Jurado-Arjona, Jerónimo; Bolós, Marta; Pallas-Bazarra, Noemí; Ávila, Jesús

    2016-03-01

    Recent experimental data suggest that mood disorders are related to inflammatory phenomena and have led to the "inflammatory hypothesis of depression". Given that the hippocampus is one of the most affected areas in these disorders, we used a model of acute stress (the Porsolt test) to evaluate the consequences of forced swimming on two crucial events related to the pathophysiology of major depression: the functional maturation of newborn granule neurons; and the hippocampal inflammatory milieu. Using PSD95:GFP-expressing retroviruses, we found that forced swimming selectively alters the dendritic morphology of newborn neurons and impairs their connectivity by reducing the number and volume of their postsynaptic densities. In addition, acute stress triggered a series of morphological changes in microglial cells, together with an increase in microglial CD68 expression, thus suggesting the functional and morphological activation of this cell population. Furthermore, we observed an intriguing change in the hippocampal inflammatory milieu in response to forced swimming. Importantly, the levels of several molecules affected by acute stress (such as Interleukin-6 and eotaxin) have been described to also be altered in patients with depression and other mood disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Neuroprotective Effect of Total and Sequential Extract of Scrophularia striata Boiss. in Rat Cerebellar Granule Neurons Following Glutamate- Induced Neurotoxicity: An In-vitro Study

    Salavati, Parvin; Ramezani, Mina; Monsef-Esfahani, Hamid R; Hajiagha, Reza; Parsa, Maliheh; Tavajohi, Shoreh; Ostad, Seyed Nasser

    2013-01-01

    Neuroprotective effect of the extract from aerial parts of Scrophularia striata Boiss (Scrophulariaceae) was investigated against glutamate-induced neurotoxicity on cultured rat pups Cerebellar Granule Neurons (CGNs). CGNs from 8 days old Sprague-Dawley rat were prepared and cultured. The experiments were performed after 8 days in culture. The plant was collected from the northeastern part (Ruin region) of Iran and air-dried at room temperature. The total extract was prepared with maceration of prepared powder in ethanol 80% for three times. Sequential extracts were obtained using dried and powdered aerial parts with increasingly polar solvents: petroleum ether, chloroform, ethyl acetate and methanol 80% solution. Cultured cells were exposed to 125 μM of glutamate for 12 h following a 24 h of incubation with test fractions at concentration of 10 mcg/mL. Morphological assay was performed using invert light microscope after fixation and staining with haematoxylin. Neuronal viability was measured using MTT assay. Statistical analysis was done using SPSS software. One way analysis of variance (ANOVA) was performed by Tukey post-hoc test. Values were considered statistically significant when p-value ≤ 0.05. Results of this study showed a significant neuroprotective activity of high polarity methanolic fraction of aerial parts of Scrophularia striata against glutamate-induced neurotoxicity in a dosedependent manner. Treatment with 10 mcg/mL of the fractions showed the best result. PMID:24250613

  7. Impaired terminal differentiation of hippocampal granule neurons and defective contextual memory in PC3/Tis21 knockout mice.

    Stefano Farioli-Vecchioli

    Full Text Available Neurogenesis in the dentate gyrus of the adult hippocampus has been implicated in neural plasticity and memory, but the molecular mechanisms controlling the proliferation and differentiation of newborn neurons and their integration into the synaptic circuitry are still largely unknown. To investigate this issue, we have analyzed the adult hippocampal neurogenesis in a PC3/Tis21-null mouse model. PC3/Tis21 is a transcriptional co-factor endowed with antiproliferative and prodifferentiative properties; indeed, its upregulation in neural progenitors has been shown to induce exit from cell cycle and differentiation. We demonstrate here that the deletion of PC3/Tis21 causes an increased proliferation of progenitor cells in the adult dentate gyrus and an arrest of their terminal differentiation. In fact, in the PC3/Tis21-null hippocampus postmitotic undifferentiated neurons accumulated, while the number of terminally differentiated neurons decreased of 40%. As a result, PC3/Tis21-null mice displayed a deficit of contextual memory. Notably, we observed that PC3/Tis21 can associate to the promoter of Id3, an inhibitor of proneural gene activity, and negatively regulates its expression, indicating that PC3/Tis21 acts upstream of Id3. Our results identify PC3/Tis21 as a gene required in the control of proliferation and terminal differentiation of newborn neurons during adult hippocampal neurogenesis and suggest its involvement in the formation of contextual memories.

  8. Curcumin Pretreatment Induces Nrf2 and an Antioxidant Response and Prevents Hemin-Induced Toxicity in Primary Cultures of Cerebellar Granule Neurons of Rats

    Susana González-Reyes

    2013-01-01

    Full Text Available Curcumin is a bifunctional antioxidant derived from Curcuma longa. This study identifies curcumin as a neuroprotectant against hemin-induced damage in primary cultures of cerebellar granule neurons (CGNs of rats. Hemin, the oxidized form of heme, is a highly reactive compound that induces cellular injury. Pretreatment of CGNs with 5–30 μM curcumin effectively increased by 2.3–4.9 fold heme oxygenase-1 (HO-1 expression and by 5.6–14.3-fold glutathione (GSH levels. Moreover, 15 μM curcumin attenuated by 55% the increase in reactive oxygen species (ROS production, by 94% the reduction of GSH/glutathione disulfide (GSSG ratio, and by 49% the cell death induced by hemin. The inhibition of heme oxygenase system or GSH synthesis with tin mesoporphyrin and buthionine sulfoximine, respectively, suppressed the protective effect of curcumin against hemin-induced toxicity. These data strongly suggest that HO-1 and GSH play a major role in the protective effect of curcumin. Furthermore, it was found that 24 h of incubation with curcumin increases by 1.4-, 2.3-, and 5.2-fold the activity of glutathione reductase, glutathione S-transferase and superoxide dismutase, respectively. Additionally, it was found that curcumin was capable of inducing nuclear factor (erythroid-derived 2-like 2 (Nrf2 translocation into the nucleus. These data suggest that the pretreatment with curcumin induces Nrf2 and an antioxidant response that may play an important role in the protective effect of this antioxidant against hemin-induced neuronal death.

  9. Curcumin Pretreatment Induces Nrf2 and an Antioxidant Response and Prevents Hemin-Induced Toxicity in Primary Cultures of Cerebellar Granule Neurons of Rats

    González-Reyes, Susana; Guzmán-Beltrán, Silvia; Medina-Campos, Omar Noel; Pedraza-Chaverri, José

    2013-01-01

    Curcumin is a bifunctional antioxidant derived from Curcuma longa. This study identifies curcumin as a neuroprotectant against hemin-induced damage in primary cultures of cerebellar granule neurons (CGNs) of rats. Hemin, the oxidized form of heme, is a highly reactive compound that induces cellular injury. Pretreatment of CGNs with 5–30 μM curcumin effectively increased by 2.3–4.9 fold heme oxygenase-1 (HO-1) expression and by 5.6–14.3-fold glutathione (GSH) levels. Moreover, 15 μM curcumin attenuated by 55% the increase in reactive oxygen species (ROS) production, by 94% the reduction of GSH/glutathione disulfide (GSSG) ratio, and by 49% the cell death induced by hemin. The inhibition of heme oxygenase system or GSH synthesis with tin mesoporphyrin and buthionine sulfoximine, respectively, suppressed the protective effect of curcumin against hemin-induced toxicity. These data strongly suggest that HO-1 and GSH play a major role in the protective effect of curcumin. Furthermore, it was found that 24 h of incubation with curcumin increases by 1.4-, 2.3-, and 5.2-fold the activity of glutathione reductase, glutathione S-transferase and superoxide dismutase, respectively. Additionally, it was found that curcumin was capable of inducing nuclear factor (erythroid-derived 2)-like 2 (Nrf2) translocation into the nucleus. These data suggest that the pretreatment with curcumin induces Nrf2 and an antioxidant response that may play an important role in the protective effect of this antioxidant against hemin-induced neuronal death. PMID:24454990

  10. Inhibitors of the alpha-ketoglutarate dehydrogenase complex alter [1-13C]glucose and [U-13C]glutamate metabolism in cerebellar granule neurons.

    Santos, Sónia Sá; Gibson, Gary E; Cooper, Arthur J L; Denton, Travis T; Thompson, Charles M; Bunik, Victoria I; Alves, Paula M; Sonnewald, Ursula

    2006-02-15

    Diminished activity of the alpha-ketoglutarate dehydrogenase complex (KGDHC), an important component of the tricarboxylic acid (TCA) cycle, occurs in several neurological diseases. The effect of specific KGDHC inhibitors [phosphonoethyl ester of succinyl phosphonate (PESP) and the carboxy ethyl ester of succinyl phosphonate (CESP)] on [1-13C]glucose and [U-13C]glutamate metabolism in intact cerebellar granule neurons was investigated. Both inhibitors decreased formation of [4-13C]glutamate from [1-13C]glucose, a reduction in label in glutamate derived from [1-13C]glucose/[U-13C]glutamate through a second turn of the TCA cycle and a decline in the amounts of gamma-aminobutyric acid (GABA), aspartate, and alanine. PESP decreased formation of [U-13C]aspartate and total glutathione, whereas CESP decreased concentrations of valine and leucine. The findings are consistent with decreased KGDHC activity; increased alpha-ketoglutarate formation; increased transamination of alpha-ketoglutarate with valine, leucine, and GABA; and new equilibrium position of the aspartate aminotransferase reaction. Overall, the findings also suggest that some carbon derived from alpha-ketoglutarate may bypass the block in the TCA cycle at KGDHC by means of the GABA shunt and/or conversion of valine to succinate. The results suggest the potential of succinyl phosphonate esters for modeling the biochemical and pathophysiological consequences of reduced KGDHC activity in brain diseases.

  11. Immunophenotype of leukemic blasts with small peroxidase-positive granules detected by electron microscopy.

    Vainchenker, W; Villeval, J L; Tabilio, A; Matamis, H; Karianakis, G; Guichard, J; Henri, A; Vernant, J P; Rochant, H; Breton-Gorius, J

    1988-05-01

    Forty-three cases of undifferentiated leukemias by light microscopy examination were diagnosed as acute myeloblastic leukemias by ultrastructural revelation of peroxidase and were subsequently studied by immunological markers. In 41 of these cases, blasts were labeled by at least one of the antimyeloid MoAbs (My 7, My 9, and 80H5). An antimyeloperoxidase polyclonal antibody was used in 23 cases and was clearly positive in 11 of them, while cytochemistry by light microscopy was negative. These myeloblasts were frequently mixed with a minority of blasts from other lineages especially promegakaryoblasts. It is noteworthy that in 6 cases myeloid and lymphoid markers (E rosette receptor, common acute lymphoblastic leukemia antigen (cALLA), CD 9, CD 19 antigens (anti-B4 MoAb] were detected on a fraction of blast cells, suggesting a bilineage leukemia. However, in double labeling experiments, blasts with myeloperoxidase coexpressed lymphoid and myeloid markers including cALLA and CD 19 antigen. In one case, blasts had a typical non-B, non-T acute lymphoblastic leukemia phenotype (HLA-DR, CD 9, CD 19, cALLA positive) without staining by any of the antimyeloid MoAbs. However, 70% of the blasts were labeled by the antimyeloperoxidase antibody and expressed peroxidase-positive granules at ultrastructural level. In conclusion, most of the AML undiagnosed by optical cytochemistry are identified by antimyeloid antibodies. Some of these cases are also stained by some antilymphoid MoAbs. Use of antibodies against myeloperoxidase may improve the diagnosis of difficult cases of acute myeloblastic leukemia.

  12. Updates to a 13C metabolic flux analysis model for evaluating energy metabolism in cultured cerebellar granule neurons from neonatal rats.

    Jekabsons, Mika B; Gebril, Hoda M; Wang, Yan-Hong; Avula, Bharathi; Khan, Ikhlas A

    2017-10-01

    A hexose phosphate recycling model previously developed to infer fluxes through the major glucose consuming pathways in cultured cerebellar granule neurons (CGNs) from neonatal rats metabolizing [1,2- 13 C 2 ]glucose was revised by considering reverse flux through the non-oxidative pentose phosphate pathway (PPP) and symmetrical succinate oxidation within the tricarboxylic acid (TCA) cycle. The model adjusts three flux ratios to effect 13 C distribution in the hexose, pentose, and triose phosphate pools, and in TCA cycle malate to minimize the error between predicted and measured 13 C labeling in exported lactate (i.e., unlabeled, single-, double-, and triple-labeled; M, M1, M2, and M3, respectively). Inclusion of reverse non-oxidative PPP flux substantially increased the number of calculations but ultimately had relatively minor effects on the labeling of glycolytic metabolites. From the error-minimized solution in which the predicted M-M3 lactate differed by 0.49% from that measured by liquid chromatography-triple quadrupole mass spectrometry, the neurons exhibited negligible forward non-oxidative PPP flux. Thus, no glucose was used by the pentose cycle despite explicit consideration of hexose phosphate recycling. Mitochondria consumed only 16% of glucose while 45% was exported as lactate by aerobic glycolysis. The remaining 39% of glucose was shunted to pentose phosphates presumably for de novo nucleotide synthesis, but the proportion metabolized through the oxidative PPP vs. the reverse non-oxidative PPP could not be determined. The lactate exported as M1 (2.5%) and M3 (1.2%) was attributed to malic enzyme, which was responsible for 7.8% of pyruvate production (vs. 92.2% by glycolysis). The updated model is more broadly applicable to different cell types by considering bi-directional flux through the non-oxidative PPP. Its application to cultured neurons utilizing glucose as the sole exogenous substrate has demonstrated substantial oxygen-independent glucose

  13. Novel insights into pericarp, protein body globoids of aleurone layer, starchy granules of three cereals gained using atomic force microscopy and environmental scanning electronic microscopy.

    Antonini, Elena; Zara, Carolina; Valentini, Laura; Gobbi, Pietro; Ninfali, Paolino; Menotta, Michele

    2018-02-05

    In this study, we applied Environmental Scanning Electron Microscopy-Energy Dispersive Spectroscopy (ESEM-EDS) and Atomic Force Microscopy (AFM) analysis to three different cereal caryopses: barley, oat and einkorn wheat. The morphological structures, chemical elemental composition and surface characteristics of the three cereals were described. Regarding the morphology, barley showed the thickest pericarp, providing a strong barrier digestion and absorption of nutrients. The aleurone layer of each cereal type contained protein body globoids within its cells. Large type-A and small type-B starchy granules were revealed in the endosperm of barley and einkorn wheat, whereas irregular starchy granules were found in oats. The starchy granule elemental composition, detected by ESEM-EDS, was rather homogenous in the three cereals, whereas the pericarp and protein body globoids showed heterogeneity. In the protein body globoids, oats showed higher P and K concentrations than barley and einkorn wheat. Regarding the topographic profiles, detected by AFM, einkorn wheat starchy granules showed a surface profile that differed significantly from that of oats and barley, which were quite similar to one another. The present work provides insights into the morphological and chemical makeup of the three grains shedding light on the higher bio-accessibility of einkorn wheat nutrients compared to barley and oats, providing important suggestions for human nutrition and technological standpoints.

  14. Novel insights into pericarp, protein body globoids of aleurone layer, starchy granules of three cereals gained using atomic force microscopy and environmental scanning electronic microscopy

    Antonini, Elena; Zara, Carolina; Valentini, Laura; Gobbi, Pietro; Menotta, Michele

    2018-01-01

    In this study, we applied Environmental Scanning Electron Microscopy-Energy Dispersive Spectroscopy (ESEM-EDS) and Atomic Force Microscopy (AFM) analysis to three different cereal caryopses: barley, oat and einkorn wheat. The morphological structures, chemical elemental composition and surface characteristics of the three cereals were described. Regarding the morphology, barley showed the thickest pericarp, providing a strong barrier to digestion and absorption of nutrients. The aleurone layer of each cereal type contained protein body globoids within its cells. Large type-A and small type-B starchy granules were revealed in the endosperm of barley and einkorn wheat, whereas irregular starchy granules were found in oats. The starchy granule elemental composition, detected by ESEM-EDS, was rather homogenous in the three cereals, whereas the pericarp and protein body globoids showed heterogeneity. In the protein body globoids, oats showed higher P and K concentrations than barley and einkorn wheat. Regarding the topographic profiles, detected by AFM, einkorn wheat starchy granules showed a surface profile that differed significantly from that of oats and barley, which were quite similar to one another. The present work provides insights into the morphological and chemical makeup of the three grains shedding light on the higher bio-accessibility of einkorn wheat nutrients compared to barley and oats, providing important suggestions for human nutrition and technological standpoints. PMID:29569870

  15. Mechanism of the formation of hollow spherical granules using a high shear granulator.

    Asada, Takumi; Nishikawa, Mitsunori; Ochiai, Yasushi; Noguchi, Shuji; Kimura, Shin-Ichiro; Iwao, Yasunori; Itai, Shigeru

    2018-05-30

    Recently, we have developed a novel granulation technology to manufacture hollow spherical granules (HSGs) for controlled-release formulations; however, the mechanism of the granulation is still unclear. The aim of this study is to determine the mechanism of the formation of the HSGs using a high shear granulator. Samples of granulated material were collected at various times during granulation and were investigated using scanning electron microscope and X-ray computed tomography. It was observed that the granulation proceeded by drug layering to the polymer, followed by formation of a hollow in the granule. In addition, it was also found that generation of a crack in the adhered drug layer and air flow into the granules might be involved in forming the hollow in the structure. Observation of the granulation of formulations with different types of drugs and polymers indicated that negative pressure in the granules occurred and the granules caved in when the hollow was formed. The hollow-forming speed and the shell density of the hollow granules depended on the particular drug and polymer. Taken together, the granulation mechanism of HSGs was determined and this information will be valuable for HSGs technology development. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. An electronic implementation for Liao's chaotic delayed neuron model with non-monotonous activation function

    Duan Shukai; Liao Xiaofeng

    2007-01-01

    A new chaotic delayed neuron model with non-monotonously increasing transfer function, called as chaotic Liao's delayed neuron model, was recently reported and analyzed. An electronic implementation of this model is described in detail. At the same time, some methods in circuit design, especially for circuit with time delayed unit and non-monotonously increasing activation unit, are also considered carefully. We find that the dynamical behaviors of the designed circuits are closely similar to the results predicted by numerical experiments

  17. Neuronal synchrony detection on single-electron neural networks

    Oya, Takahide; Asai, Tetsuya; Kagaya, Ryo; Hirose, Tetsuya; Amemiya, Yoshihito

    2006-01-01

    Synchrony detection between burst and non-burst spikes is known to be one functional example of depressing synapses. Kanazawa et al. demonstrated synchrony detection with MOS depressing synapse circuits. They found that the performance of a network with depressing synapses that discriminates between burst and random input spikes increases non-monotonically as the static device mismatch is increased. We designed a single-electron depressing synapse and constructed the same network as in Kanazawa's study to develop noise-tolerant single-electron circuits. We examined the temperature characteristics and explored possible architecture that enables single-electron circuits to operate at T > 0 K

  18. Wallerian degeneration slow mouse neurons are protected against cell death caused by mechanisms involving mitochondrial electron transport dysfunction.

    Tokunaga, Shinji; Araki, Toshiyuki

    2012-03-01

    Ischemia elicits a variety of stress responses in neuronal cells, which result in cell death. wld(S) Mice bear a mutation that significantly delays Wallerian degeneration. This mutation also protects all neuronal cells against other types of stresses resulting in cell death, including ischemia. To clarify the types of stresses that neuronal cell bodies derived from wld(S) mice are protected from, we exposed primary cultured neurons derived from wld(S) mice to various components of hypoxic stress. We found that wld(S) mouse neurons are protected against cellular injury induced by reoxygenation following hypoxic stress. Furthermore, we found that wld(S) mouse neurons are protected against functional impairment of the mitochondrial electron transport chain. These data suggest that Wld(S) protein expression may provide protection against neuronal cell death caused by mechanisms involving mitochondrial electron transport dysfunction. Copyright © 2011 Wiley Periodicals, Inc.

  19. The forced swimming-induced behavioural immobility response involves histone H3 phospho-acetylation and c-Fos induction in dentate gyrus granule neurons via activation of the N-methyl-D-aspartate/extracellular signal-regulated kinase/mitogen- and stress-activated kinase signalling pathway.

    Chandramohan, Yalini; Droste, Susanne K; Arthur, J Simon C; Reul, Johannes M H M

    2008-05-01

    The hippocampus is involved in learning and memory. Previously, we have shown that the acquisition of the behavioural immobility response after a forced swim experience is associated with chromatin modifications and transcriptional induction in dentate gyrus granule neurons. Given that both N-methyl-D-aspartate (NMDA) receptors and the extracellular signal-regulated kinases (ERK) 1/2 signalling pathway are involved in neuroplasticity processes underlying learning and memory, we investigated in rats and mice whether these signalling pathways regulate chromatin modifications and transcriptional events participating in the acquisition of the immobility response. We found that: (i) forced swimming evoked a transient increase in the number of phospho-acetylated histone H3-positive [P(Ser10)-Ac(Lys14)-H3(+)] neurons specifically in the middle and superficial aspects of the dentate gyrus granule cell layer; (ii) antagonism of NMDA receptors and inhibition of ERK1/2 signalling blocked forced swimming-induced histone H3 phospho-acetylation and the acquisition of the behavioural immobility response; (iii) double knockout (DKO) of the histone H3 kinase mitogen- and stress-activated kinases (MSK) 1/2 in mice completely abolished the forced swimming-induced increases in histone H3 phospho-acetylation and c-Fos induction in dentate granule neurons and the behavioural immobility response; (iv) blocking mineralocorticoid receptors, known not to be involved in behavioural immobility in the forced swim test, did not affect forced swimming-evoked histone H3 phospho-acetylation in dentate neurons; and (v) the pharmacological manipulations and gene deletions did not affect behaviour in the initial forced swim test. We conclude that the forced swimming-induced behavioural immobility response requires histone H3 phospho-acetylation and c-Fos induction in distinct dentate granule neurons through recruitment of the NMDA/ERK/MSK 1/2 pathway.

  20. Early x-irradiation of rats. Part 2. Effect of granule cells and their dendrodendritic synapses in the olfactory bulb

    Halasz, N

    1987-01-01

    Low, repeated doses of X-rays from a Co/sup 60/ source were used to impair the development of the granule cells and their dendritic terminals in the olfactory bulb, and the resulting effect was studied under light and electron microscopes at 9 days of age. Irradiation of rats from embryonic day 18 (in utero) to postnatal day 5 resulted, among others, in maldevelopment of the (internal) granule cell and external plexiform layers. This was accompanied by a decrease in the number and the density of the granule cells, and the remaining granule cells contained less ribosomes, regardless of their position within the layer. This implies that both supposed subtypes of granule cells were effected. In the external plexiform layer, a reduced number of mature dendrodendritic synapses and signs of harmed granule gemmules were observed. The results suggest that intrauterinal plus postnatal irradiation with low, repeated doses of X-rays may be an effective tool impairing the development of prenatally forming neurons.

  1. THE STUDY OF THE KINETIC OF NATURAL ZEOLITE GRANULES GROWTH AT DIFFERENT WAYS OF GRANULATION

    Rybachuk VD

    2016-12-01

    . Natural zeolite granules were prepared by wet granulation using a laboratory rotary granulator NG-12, laboratory extruder, laboratory high-speed mixer-granulator and laboratory dragee pan NSD A-0.25. Microstructure and form of granules were established by electron microscope REM-106. Fractional composition and average grain size was determined using a standard set of sieves with the diameter of the holes 2.0; 1.0; 0.5 and 0.25 mm. Porosity determined on the basis of tapped density and the real density, which were defined on the device Pharma Test PTF PT-TD200, Germany by the method. Form factor calculated as the ratio of the share of grains in its width. The hardness of the granules was assessed by their ability to withstand compression. Results & discussion. The resulting granules have heterogeneous porous surface. Granules obtained using rotary granulator and extruder have elongated form of particles with form factor 1,6-1,7 and 2,5-2,8 respectively. Granules obtained in high speed mixer-granulator and dragee pan have nearly round shape with form factor 1.1-1.2. The size of the granules is affected by the concentration of the humidifier and the way of granulation. The increasing of concentrations of potato starch paste from 3% to 10%, lead to an increase of the average size of granules according to the method in average 3-5 times, the last was proved by the increase of fractions with a larger particle size. The largest average size of granules was obtained in the laboratory dragee pan, and the smallest - in the high-speed mixer-granulator. When using PVP solution of different concentrations the average grain size varied depending on the method of granulation within 120-1464 µm. The highest binding capacity showed PVP solutions, as evidenced by higher values of grain size at the same concentrations of humidifiers. Increased concentrations of both humidifiers more than 10% is inappropriate, because results in large particle size of granules. Study of influence of

  2. Correlation between microbial community and granule conductivity in anaerobic bioreactors for brewery wastewater treatment

    Shrestha, Pravin; Malvankar, Nikhil S.; Werner, Jeffrey

    2014-01-01

    Prior investigation of an upflow anaerobic sludge blanket (UASB) reactor treating brewery wastes suggested that direct interspecies electron transfer (DIET) significantly contributed to interspecies electron transfer to methanogens. To investigate DIET in granules further, the electrical conducti......Prior investigation of an upflow anaerobic sludge blanket (UASB) reactor treating brewery wastes suggested that direct interspecies electron transfer (DIET) significantly contributed to interspecies electron transfer to methanogens. To investigate DIET in granules further, the electrical...... conductivity and bacterial community composition of granules in fourteen samples from four different UASB reactors treating brewery wastes were investigated. All of the UASB granules were electrically conductive whereas control granules from ANAMMOX (ANaerobic AMMonium OXidation) reactors and microbial...... granules from an aerobic bioreactor designed for phosphate removal were not. There was a moderate correlation (r = 0.67) between the abundance of Geobacter species in the UASB granules and granule conductivity, suggesting that Geobacter contributed to granule conductivity. These results, coupled...

  3. Preparation of herpes simplex virus-infected primary neurons for transmission electron microscopy.

    Miranda-Saksena, Monica; Boadle, Ross; Cunningham, Anthony L

    2014-01-01

    Transmission electron microscopy (TEM) provides the resolution necessary to identify both viruses and subcellular components of cells infected with many types of viruses, including herpes simplex virus. Recognized as a powerful tool in both diagnostic and research-based virology laboratories, TEM has made possible the identification of new viruses and has contributed to the elucidation of virus life cycle and virus-host cell interaction. Whilst there are many sample preparation techniques for TEM, conventional processing using chemical fixation and resin embedding remains a useful technique, available in virtually all EM laboratories, for studying virus/cell ultrastructure. In this chapter, we describe the preparation of herpes simplex virus-infected primary neurons, grown on plastic cover slips, to allow sectioning of neurons and axons in their growth plane. This technique allows TEM examination of cell bodies, axons, growth cones, and varicosities, providing powerful insights into virus-cell interaction.

  4. Repeated intermittent alcohol exposure during the third trimester-equivalent increases expression of the GABA(A) receptor δ subunit in cerebellar granule neurons and delays motor development in rats.

    Diaz, Marvin R; Vollmer, Cyndel C; Zamudio-Bulcock, Paula A; Vollmer, William; Blomquist, Samantha L; Morton, Russell A; Everett, Julie C; Zurek, Agnieszka A; Yu, Jieying; Orser, Beverley A; Valenzuela, C Fernando

    2014-04-01

    Exposure to ethanol (EtOH) during fetal development can lead to long-lasting alterations, including deficits in fine motor skills and motor learning. Studies suggest that these are, in part, a consequence of cerebellar damage. Cerebellar granule neurons (CGNs) are the gateway of information into the cerebellar cortex. Functionally, CGNs are heavily regulated by phasic and tonic GABAergic inhibition from Golgi cell interneurons; however, the effect of EtOH exposure on the development of GABAergic transmission in immature CGNs has not been investigated. To model EtOH exposure during the 3rd trimester-equivalent of human pregnancy, neonatal pups were exposed intermittently to high levels of vaporized EtOH from postnatal day (P) 2 to P12. This exposure gradually increased pup serum EtOH concentrations (SECs) to ∼60 mM (∼0.28 g/dl) during the 4 h of exposure. EtOH levels gradually decreased to baseline 8 h after the end of exposure. Surprisingly, basal tonic and phasic GABAergic currents in CGNs were not significantly affected by postnatal alcohol exposure (PAE). However, PAE increased δ subunit expression at P28 as detected by immunohistochemical and western blot analyses. Also, electrophysiological studies with an agonist that is highly selective for δ-containing GABA(A) receptors, 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridine-3-ol (THIP), showed an increase in THIP-induced tonic current. Behavioral studies of PAE rats did not reveal any deficits in motor coordination, except for a delay in the acquisition of the mid-air righting reflex that was apparent at P15 to P18. These findings demonstrate that repeated intermittent exposure to high levels of EtOH during the equivalent of the last trimester of human pregnancy has significant but relatively subtle effects on motor coordination and GABAergic transmission in CGNs in rats. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. An ultra-low-voltage electronic implementation of inertial neuron model with nonmonotonous Liao's activation function.

    Kant, Nasir Ali; Dar, Mohamad Rafiq; Khanday, Farooq Ahmad

    2015-01-01

    The output of every neuron in neural network is specified by the employed activation function (AF) and therefore forms the heart of neural networks. As far as the design of artificial neural networks (ANNs) is concerned, hardware approach is preferred over software one because it promises the full utilization of the application potential of ANNs. Therefore, besides some arithmetic blocks, designing AF in hardware is the most important for designing ANN. While attempting to design the AF in hardware, the designs should be compatible with the modern Very Large Scale Integration (VLSI) design techniques. In this regard, the implemented designs should: only be in Metal Oxide Semiconductor (MOS) technology in order to be compatible with the digital designs, provide electronic tunability feature, and be able to operate at ultra-low voltage. Companding is one of the promising circuit design techniques for achieving these goals. In this paper, 0.5 V design of Liao's AF using sinh-domain technique is introduced. Furthermore, the function is tested by implementing inertial neuron model. The performance of the AF and inertial neuron model have been evaluated through simulation results, using the PSPICE software with the MOS transistor models provided by the 0.18-μm Taiwan Semiconductor Manufacturer Complementary Metal Oxide Semiconductor (TSM CMOS) process.

  6. Mining the granule proteome

    Albrethsen, Jakob; Goetze, Jens P; Johnsen, Anders H

    2015-01-01

    Proteomics of secretory granules is an emerging strategy for identifying secreted proteins, including potentially novel candidate biomarkers and peptide hormones. In addition, proteomics can provide information about the abundance, localization and structure (post-translational modification) of g...

  7. Comparison of Size Characterization of Barley Starch Granules Determined by Electron and Optical Microscopy, Low Angle Laser Light Scattering and Gravitational Field-Flow Fractionation

    Chmelík, Josef; Krumlová, Andrea; Budinská, Marcela; Kruml, Tomáš; Psota, V.; Bohačenko, I.; Mazal, P.; Vydrová, H.

    2001-01-01

    Roč. 107, č. 1 (2001), s. 11-17 ISSN 0046-9750 R&D Projects: GA AV ČR IAA4031805 Grant - others:Copernicus(BE) ERB IC-15-CT98-0909 Institutional research plan: CEZ:AV0Z4031919 Keywords : Barley * starch granules * size determination Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 0.862, year: 2001

  8. A unit density method of grain analysis used to identify GABEergic neurons for electron microscopic autoradiographs

    Burry, R.W.

    1982-01-01

    The distribution of electron microscopic autoradiographic grains over neurons in cerebellar cultures incubated with [ 3 H]gamma-aminobutyric acid ([ 3 H]GABA) was examined. With the unit density method of grain analysis, the number of grains over each structure was tested against the total grain density for the entire section. If an individual structure has a grain density higher than the expected grain density, it is considered one of the group of heavily labeled structures. The expected grain density for each structure is calculated based on the area for that structure, the total grain density and the Poisson distribution. A different expected grain density can be calculated for any P value required. The method provides an adequate population of structures for morphological analysis but excludes weakly labeled structures and thus may underestimate the number of labeled structures. The unit density method of grain analysis showed, as expected, a group of cell bodies and synapses that was labeled heavily. Cultures incubated with other [ 3 H]amino acids did not have any heavily labeled synaptic elements. In addition, serial section analysis of sections showed that synapses heavily labeled with [ 3 H]GABA are seen in adjacent sections. The advantage of the unit density method of grain analysis is that it can be used to separate two groups of metabolically different neurons even when no morphological differences are present. (Auth.)

  9. Atrial natriuretic peptide (ANP)-granules: ultrastructure ...

    ANP) are present in the four regions of the atrial-auricular complex (two atria and two auricles). ANP-immunoreactivity was detected in all granules from the four regions. Ultrastructurally, atrial myocytes show the presence of very electron dense ...

  10. Electronic bypass of spinal lesions: activation of lower motor neurons directly driven by cortical neural signals.

    Li, Yan; Alam, Monzurul; Guo, Shanshan; Ting, K H; He, Jufang

    2014-07-03

    Lower motor neurons in the spinal cord lose supraspinal inputs after complete spinal cord injury, leading to a loss of volitional control below the injury site. Extensive locomotor training with spinal cord stimulation can restore locomotion function after spinal cord injury in humans and animals. However, this locomotion is non-voluntary, meaning that subjects cannot control stimulation via their natural "intent". A recent study demonstrated an advanced system that triggers a stimulator using forelimb stepping electromyographic patterns to restore quadrupedal walking in rats with spinal cord transection. However, this indirect source of "intent" may mean that other non-stepping forelimb activities may false-trigger the spinal stimulator and thus produce unwanted hindlimb movements. We hypothesized that there are distinguishable neural activities in the primary motor cortex during treadmill walking, even after low-thoracic spinal transection in adult guinea pigs. We developed an electronic spinal bridge, called "Motolink", which detects these neural patterns and triggers a "spinal" stimulator for hindlimb movement. This hardware can be head-mounted or carried in a backpack. Neural data were processed in real-time and transmitted to a computer for analysis by an embedded processor. Off-line neural spike analysis was conducted to calculate and preset the spike threshold for "Motolink" hardware. We identified correlated activities of primary motor cortex neurons during treadmill walking of guinea pigs with spinal cord transection. These neural activities were used to predict the kinematic states of the animals. The appropriate selection of spike threshold value enabled the "Motolink" system to detect the neural "intent" of walking, which triggered electrical stimulation of the spinal cord and induced stepping-like hindlimb movements. We present a direct cortical "intent"-driven electronic spinal bridge to restore hindlimb locomotion after complete spinal cord injury.

  11. Behavioral experience induces zif268 expression in mature granule cells but suppresses its expression in immature granule cells

    Huckleberry, Kylie A.; Kane, Gary A.; Mathis, Rita J.; Cook, Sarah G.; Clutton, Jonathan E.; Drew, Michael R.

    2015-01-01

    Thousands of neurons are born each day in the dentate gyrus (DG), but many of these cells die before reaching maturity. Both death and survival of adult-born neurons are regulated by neuronal activity in the DG. The immediate-early gene (IEG) zif268 appears to be an important mediator of these effects, as its expression can be induced by neural activity and knockout of zif268 impairs survival of adult-born neurons (Richardson et al., 1992; Veyrac et al., 2013). Despite the apparent importance of zif268 for adult neurogenesis, its behavior-induced expression has not been fully characterized in adult-born neurons. Here we characterize behavior-evoked expression of zif268 in mature and newborn dentate granule cells (DGCs). We first quantified zif268 expression in doublecortin-positive (DCX+) immature neurons and in the general granule cell population after brief exposure to a novel environment (NE). In the general granule cell population, zif268 expression peaked 1 h after NE exposure and returned to baseline by 8 h post-exposure. However, in the DCX+ cells, zif268 expression was suppressed relative to home cage for at least 8 h post-exposure. We next asked whether suppression of zif268 in DCX+ immature cells occurs in other behavioral paradigms that recruit the hippocampus. Exposure to Morris water maze (MWM) training, an enriched environment, or a NE caused approximately equal suppression of zif268 expression in DCX+ cells and approximately equal activation of zif268 expression among the general granule cell population. The same behavioral procedures activated zif268 expression in 6-week-old BrdU-labeled adult-born neurons, indicating that zif268 suppression is specific to immature neurons. Finally, we asked whether zif268 suppression varied as a function of age within the DCX+ population, which ranges in age from 0 to approximately 4 weeks. NE exposure had no significant effect on zif268 expression in 2- or 4-week-old BrdU-labeled neurons, but it significantly

  12. An electronic implementation for Liao's chaotic delayed neuron model with non-monotonous activation function

    Duan Shukai [Department of Computer Science and Engineering, Chongqing University, Chongqing 400044 (China); School of Electronic and Information Engineering, Southwest University, Chongqing 400715 (China)], E-mail: duansk@swu.edu.cn; Liao Xiaofeng [Department of Computer Science and Engineering, Chongqing University, Chongqing 400044 (China)], E-mail: xfliao@cqu.edu.cn

    2007-09-10

    A new chaotic delayed neuron model with non-monotonously increasing transfer function, called as chaotic Liao's delayed neuron model, was recently reported and analyzed. An electronic implementation of this model is described in detail. At the same time, some methods in circuit design, especially for circuit with time delayed unit and non-monotonously increasing activation unit, are also considered carefully. We find that the dynamical behaviors of the designed circuits are closely similar to the results predicted by numerical experiments.

  13. PHB granules are attached to the nucleoid via PhaM in Ralstonia eutropha.

    Wahl, Andreas; Schuth, Nora; Pfeiffer, Daniel; Nussberger, Stephan; Jendrossek, Dieter

    2012-11-16

    Poly(3-hydroxybutyrate) (PHB) granules are important storage compounds of carbon and energy in many prokaryotes which allow survival of the cells in the absence of suitable carbon sources. Formation and subcellular localization of PHB granules was previously assumed to occur randomly in the cytoplasm of PHB accumulating bacteria. However, contradictionary results on subcellular localization of PHB granules in Ralstonia eutropha were published, recently. Here, we provide evidence by transmission electron microscopy that PHB granules are localized in close contact to the nucleoid region in R. eutropha during growth on nutrient broth. Binding of PHB granules to the nucleoid is mediated by PhaM, a PHB granule associated protein with phasin-like properties that is also able to bind to DNA and to phasin PhaP5. Over-expression of PhaM resulted in formation of many small PHB granules that were always attached to the nucleoid region. In contrast, PHB granules of ∆phaM strains became very large and distribution of granules to daughter cells was impaired. Association of PHB granules to the nucleoid region was prevented by over-expression of PhaP5 and clusters of several PHB granules were mainly localized near the cell poles. Subcellular localization of PHB granules is controlled in R. eutropha and depends on the presence and concentrations of at least two PHB granule associated proteins, PhaM and PhaP5.

  14. Chromospheric impact of an exploding solar granule

    Fischer, C. E.; Bello González, N.; Rezaei, R.

    2017-06-01

    Context. Observations of multi-wavelength and therefore height-dependent information following events throughout the solar atmosphere and unambiguously assigning a relation between these rapidly evolving layers are rare and difficult to obtain. Yet, they are crucial for our understanding of the physical processes that couple the different regimes in the solar atmosphere. Aims: We characterize the exploding granule event with simultaneous observations of Hinode spectroplarimetric data in the solar photosphere and Hinode broadband Ca II H images combined with Interface Region Imaging Spectrograph (IRIS) slit spectra. We follow the evolution of an exploding granule and its connectivity throughout the atmosphere and analyze the dynamics of a magnetic element that has been affected by the abnormal granule. Methods: In addition to magnetic flux maps we use a local correlation tracking method to infer the horizontal velocity flows in the photosphere and apply a wavelet analysis on several IRIS chromospheric emission features such as Mg II k2v and Mg II k3 to detect oscillatory phenomena indicating wave propagation. Results: During the vigorous expansion of the abnormal granule we detect radially outward horizontal flows, causing, together with the horizontal flows from the surrounding granules, the magnetic elements in the bordering intergranular lanes to be squeezed and elongated. In reaction to the squeezing, we detect a chromospheric intensity and velocity oscillation pulse which we identify as an upward traveling hot shock front propagating clearly through the IRIS spectral line diagnostics of Mg II h&k. Conclusions: Exploding granules can trigger upward-propagating shock fronts that dissipate in the chromosphere. Movies associated to Figs. A.1 and A.2 are available in electronic form at http://www.aanda.org

  15. High resolution of heterogeneity among human neutrophil granules: physical, biochemical, and ultrastructural properties of isolated fractions.

    Rice, W G; Kinkade, J M; Parmley, R T

    1986-08-01

    Previous studies on the fractionation of human neutrophil granules have identified two major populations: myeloperoxidase (MPO)-containing azurophil, or primary, granules and MPO-deficient specific, or secondary, granules. Peripheral blood neutrophils from individual donors were lysed in sucrose-free media by either hypotonic shock or nitrogen cavitation. Using a novel two-gradient Percoll density centrifugation system, the granule-rich postnuclear supernatant was rapidly (ten minutes) and reproducibly resolved into 13 granule fractions (L1 through L8 and H1 through H5). Granule flotation and recentrifugation experiments on both continuous, self-generated and multiple-step gradients using individual and mixed isolated fractions demonstrated that the banding patterns were isopycnic and nonartifactual. Isolated granules were intact based on the findings that biochemical latency of several granule enzymes was greater than 95%, and thin-sectioned electron micrographs demonstrated intact granule profiles. Biochemical analyses of the granule marker proteins MPO, beta-glucuronidase, lysozyme, and lactoferrin indicated that a number of the fractions were related to the major azurophil and specific granule populations. Lactoferrin was found in ten of 13 fractions (L1 through L8, H1 to H2), whereas MPO was found in every fraction. Consistent with these biochemical data, all fractions exhibited varying degrees of heterogeneity based on ultrastructural morphology and cytochemistry, including diaminobenzidine (DAB) reactivity for peroxidase and periodate-thiocarbohydrazide-silver proteinate (PA-TCH-SP) staining for complex glycoconjugates. A variable but significant percentage (23% to 70%) of the granules in fractions L1 through L8 and H1 and H2 showed DAB reactivity, while about 90% of the granules in fractions H3 through H5 were peroxidase positive. These results demonstrated that DAB-reactive granules spanned the entire range of granule size and density. Ultrastructural PA

  16. Collages of granulation pictures

    Dunn, R.B.; November, L.J.

    1985-01-01

    This paper describes two small-area selection schemes that the authors have applied to CCD observations of solar granulation. The first scheme, which the authors call the ''mosaic,'' divides the 128 x 128 array into 64 subarrays each containing 16 x 16 pixels. On each picture in the burst the RMS contrast of the fine structure is measured in each subarray and compared to the corresponding value in a table that contains the highest previous RMS values. The second scheme, which the authors call a ''collage,'' is similar except the RMS value is calculated smoothly within a sliding Gaussian window over the entire scene and the value of an individual pixel is gated into the final collage whenever the RMS contrast at that pixel location exceeds that of all previous frames taken during the burst

  17. Spontaneous calcium waves in granule cells in cerebellar slice cultures

    Apuschkin, Mia; Ougaard, Maria; Rekling, Jens C

    2013-01-01

    Multiple regions in the CNS display propagating correlated activity during embryonic and postnatal development. This activity can be recorded as waves of increased calcium concentrations in spiking neurons or glia cells, and have been suggested to be involved in patterning, axonal guidance and es......, that the propagating wave activity is carried through the tissue by axonal collaterals formed by neighboring granule cells, and further suggest that the correlated activity may be related to processes that ensure correct postnatal wiring of the cerebellar circuits....

  18. Difference in distribution of membrane proteins between low- and high-density secretory granules in parotid acinar cells

    Fujita-Yoshigaki, Junko; Katsumata, Osamu; Matsuki, Miwako; Yoshigaki, Tomoyoshi; Furuyama, Shunsuke; Sugiya, Hiroshi

    2006-01-01

    Secretory granules (SGs) are considered to be generated as immature granules and to mature by condensation of their contents. In this study, SGs of parotid gland were separated into low-, medium-, and high-density granule fractions by Percoll-density gradient centrifugation, since it was proposed that the density corresponds to the degree of maturation. The observation with electron microscopy showed that granules in the three fractions were very similar. The average diameter of high-density granules was a little but significantly larger than that of low-density granules. Although the three fractions contained amylase, suggesting that they are all SGs, distribution of membrane proteins was markedly different. Syntaxin6 and VAMP4 were localized in the low-density granule fraction, while VAMP2 was concentrated in the high-density granule fraction. Immunoprecipitation with anti-syntaxin6 antibody caused coprecipitation of VAMP2 from the medium-density granule fraction without solubilization, but not from Triton X-100-solubilized fraction, while VAMP4 was coprecipitated from both fractions. Therefore, VAMP2 is present on the same granules, but is separated from syntaxin6 and VAMP4, which are expected to be removed from immature granules. These results suggest that the medium-density granules are intermediates from low- to high-density granules, and that the membrane components of SGs dynamically change by budding and fusion during maturation

  19. The life cycle of platelet granules.

    Sharda, Anish; Flaumenhaft, Robert

    2018-01-01

    Platelet granules are unique among secretory vesicles in both their content and their life cycle. Platelets contain three major granule types-dense granules, α-granules, and lysosomes-although other granule types have been reported. Dense granules and α-granules are the most well-studied and the most physiologically important. Platelet granules are formed in large, multilobulated cells, termed megakaryocytes, prior to transport into platelets. The biogenesis of dense granules and α-granules involves common but also distinct pathways. Both are formed from the trans -Golgi network and early endosomes and mature in multivesicular bodies, but the formation of dense granules requires trafficking machinery different from that of α-granules. Following formation in the megakaryocyte body, both granule types are transported through and mature in long proplatelet extensions prior to the release of nascent platelets into the bloodstream. Granules remain stored in circulating platelets until platelet activation triggers the exocytosis of their contents. Soluble N -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, located on both the granules and target membranes, provide the mechanical energy that enables membrane fusion during both granulogenesis and exocytosis. The function of these core fusion engines is controlled by SNARE regulators, which direct the site, timing, and extent to which these SNAREs interact and consequently the resulting membrane fusion. In this review, we assess new developments in the study of platelet granules, from their generation to their exocytosis.

  20. Incorporation of a circulating protein into megakaryocyte and platelet granules

    Handagama, P. J.; George, J. N.; Shuman, M. A.; McEver, R. P.; Bainton, D. F.

    1987-01-01

    To determine whether or not proteins circulating in plasma can be incorporated into megakaryocytes and platelets, horseradish peroxidase (HRP) was injected intravenously into guinea pigs and these cells were examined for its uptake by electron microscopy and cytochemistry. Enriched samples of megakaryocytes enabled ultrastructural analysis of large numbers of these rare cells. In megakaryocytes, 50% of alpha granules contained HRP between 75 min and 7 hr after injection. At 24 hr, 25% of the megakaryocyte granules were peroxidase-positive, less were positive by 48 hr, and there were none at 4 days. Thus, the findings demonstrate that a circulating protein can be endocytosed by megakaryocytes and rapidly packaged into alpha granules. Platelet granules also contain HRP by 7 hr after injection, and they can secrete it in response to thrombin. Unfortunately, our present studies do not allow us to distinguish between direct endocytosis by the platelet and/or shedding of new platelets from recently labeled megakaryocytes. It is concluded that while some alpha granule proteins are synthesized by megakaryocytes, others may be acquired from plasma by endocytosis. In addition to providing evidence that some of the proteins of alpha granules may be of exogenous origin, this study has allowed the definition of a pathway whereby plasma proteins may be temporarily sequestered in megakaryocytes before reentering the circulation in platelets.

  1. Cascade reactor: granule fabrication processes

    Erlandson, O.D.; Winkler, E.O.; Maya, I.; Pitts, J.H.

    1985-01-01

    A key feature of Cascade is the granular blanket. Of the many blanket material options open to Cascade, fabrication of Li 2 O granules was felt to offer the greatest challenge. The authors explored available methods for initial Li 2 O granule fabrication. They identified three cost-effective processes for fabricating Li 2 O granules: the VSM drop-melt furnace process, which is based on melting and spheroidizing irregularly shaped Li 2 O feed granules; the LiOH process, which spheroidizes liquefied LiOH and uses GA Technologies' sphere-forming procedures; and the Li 2 CO 3 sol-gel process, used for making spherical fuel particles for the high-temperature gas-cooled reactor (HTGR). Each process is described below

  2. Collages of granulation pictures

    Dunn, R. B.; November, L. J.

    Two small-area selection schemes are applied to CCD observations of solar granulation. One procedure, referred to as mosaic, divides a 128 x 128 array into 64 subarrays of 16 x 16 pixels; the rms contrast of the fine structure is measured and compared in order to develop a mosaic of the subarrays. The second technique, collage, involves calculating rms values within a sliding Gaussian window and gating the pixel into the final image. Methods for assessing seeing quality, which involve the calculation of rms after high-pass filtering, are examined; a simple high-pass filter or an edge-locating function can be utilized for filtering. The rms map is then formed from the convolution of a Gaussian with either the high-pass or the Laplacian filters. The usefulness of the two procedures is demonstrated by applying the mosaic and collage processes to data recorded on July 17, 1983 with a CCD device on the NSO/Sac Peak Vacuum Tower Telescope.

  3. New developments in electron microscopy for serial image acquisition of neuronal profiles.

    Kubota, Yoshiyuki

    2015-02-01

    Recent developments in electron microscopy largely automate the continuous acquisition of serial electron micrographs (EMGs), previously achieved by laborious manual serial ultrathin sectioning using an ultramicrotome and ultrastructural image capture process with transmission electron microscopy. The new systems cut thin sections and capture serial EMGs automatically, allowing for acquisition of large data sets in a reasonably short time. The new methods are focused ion beam/scanning electron microscopy, ultramicrotome/serial block-face scanning electron microscopy, automated tape-collection ultramicrotome/scanning electron microscopy and transmission electron microscope camera array. In this review, their positive and negative aspects are discussed. © The Author 2015. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Mechanism of electron transfer in the bioadsorption of hexavalent chromium within Leersia hexandra Swartz granules by X-ray photoelectron spectroscopy

    Li Jianping, E-mail: likianping@263.net [College of Chemistry and Bioengineering, Guilin University of Technology, Guilin 541004 (China) and Guangxi Key Laboratory of Environmental Engineering, Protection and Assessment, Guilin 541004 (China); Lin Qingyu [College of Chemistry and Bioengineering, Guilin University of Technology, Guilin 541004 (China); Zhang Xuehong [Guangxi Key Laboratory of Environmental Engineering, Protection and Assessment, Guilin 541004 (China)

    2010-10-15

    Leersia hexandra Swartz biogranules were used to adsorb Cr(VI) from aqueous solutions. Batch biosorption experiments showed that the Cr(VI) concentration sharply decreases in the first 15 min. The main functional groups that may be involved in chromium sorption were determined using Fourier transform infrared spectroscopy. The use of X-ray photoelectron spectroscopy confirmed the reduction of Cr(VI) to Cr(III) through L. hexandra Sw. Results indicate that Cr(III) is the dominant species on the surface of the biogranules and that the redox reaction can be accomplished within 40 min. The mechanism of electron transfer during Cr(VI) reduction to Cr(III) was investigated. Protonation of the oxygen-containing groups produces electrostatic-sorption power over Cr(VI). The nitrogen-containing groups serve as the electron-donor groups in the process of reduction-sorption. Moreover, after the complete reduction of Cr(VI), the pH of the suspension significantly increases.

  5. Abnormal ion content, hydration and granule expansion of the secretory granules from cystic fibrosis airway glandular cells

    Baconnais, S.; Delavoie, F.; Zahm, J.M.; Milliot, M.; Terryn, C.; Castillon, N.; Banchet, V.; Michel, J.; Danos, O.; Merten, M.; Chinet, T.; Zierold, K.; Bonnet, N.; Puchelle, E.; Balossier, G.

    2005-01-01

    The absence or decreased expression of cystic fibrosis transmembrane conductance regulator (CFTR) induces increased Na + absorption and hyperabsorption of the airway surface liquid (ASL) resulting in a dehydrated and hyperviscous ASL. Although the implication of abnormal airway submucosal gland function has been suggested, the ion and water content in the Cystic Fibrosis (CF) glandular secretory granules, before exocytosis, is unknown. We analyzed, in non-CF and CF human airway glandular cell lines (MM-39 and KM4, respectively), the ion content in the secretory granules by electron probe X-ray microanalysis and the water content by quantitative dark field imaging on freeze-dried cryosections. We demonstrated that the ion content (Na + , Mg 2+ , P, S and Cl - ) is significantly higher and the water content significantly lower in secretory granules from the CF cell line compared to the non-CF cell line. Using videomicroscopy, we observed that the secretory granule expansion was deficient in CF glandular cells. Transfection of CF cells with CFTR cDNA or inhibition of non-CF cells with CFTR inh -172, respectively restored or decreased the water content and granule expansion, in parallel with changes in ion content. We hypothesize that the decreased water and increased ion content in glandular secretory granules may contribute to the dehydration and increased viscosity of the ASL in CF

  6. Recent results and prospects on superheated superconducting granules detectors

    Gonzalez-Mestres, L.; Perret-Gallix, D.

    1987-11-01

    The basic properties of superheated superconducting granules (SSG) detectors are reviewed. Recent results are presented and discussed. Granule samples of different sizes (10 μm -8 Ω.cm -6 Ω.cm) exhibit encouraging sensitivity to low energy β and γ sources (down to 55 Fe 6 KeV γ'S). All tests were performed with real-time read-out electronics, detecting single granule flips under the action of individual particles. Sensitivity is shown to depend on normal state resistivity. Irradiation of very large tin granules (45 μm ≤ Φ ≤ 400 μm) with α particles ( 241 Am, E ≅ 5.5 MeV) shows evidence for local heating, where the observed energy threshold is far below the one predicted by equilibrium thermodynamical calculations. Tests made at lower temperatures (T ≥ 450 mK) show the absence of avalanche effect (seen by other authors in different conditions) for several samples of tin granules. A theoretical discussion of the avalanche effect is presented. The understanding of the role of heat exchanges in the composite medium leads to the concept of 'localized micro-avalanche' and opens the way to drastic improvements of SSG performance for particle detection. Such a phenomenon should be obtained by a better thermal matching between dielectric and granules, working at temperatures where the released latent heat is slightly positive. Estimates of the behavior of the detector at very low T are also given, where a thin layer of normal electrons near the surface is shown to contribute to the heat capacity of a superheated granule. We discuss the main points to be studied in the near future, and give a brief evaluation of the present status of feasibility investigation for several proposed experiments (solar neutrinos, monopoles, dark matter, double β,...). An updated working program for SSG development is proposed

  7. Phenotypic properties and microbial diversity of methanogenic granules from a full-scale upflow anaerobic sludge bed reactor treating brewery wastewater.

    Díaz, Emiliano E; Stams, Alfons J M; Amils, Ricardo; Sanz, José L

    2006-07-01

    Methanogenic granules from an anaerobic bioreactor that treated wastewater of a beer brewery consisted of different morphological types of granules. In this study, the microbial compositions of the different granules were analyzed by molecular microbiological techniques: cloning, denaturing gradient gel electrophoresis and fluorescent in situ hybridization (FISH), and scanning and transmission electron microscopy. We propose here that the different types of granules reflect the different stages in the life cycle of granules. Young granules were small, black, and compact and harbored active cells. Gray granules were the most abundant granules. These granules have a multilayer structure with channels and void areas. The core was composed of dead or starving cells with low activity. The brown granules, which were the largest granules, showed a loose and amorphous structure with big channels that resulted in fractured zones and corresponded to the older granules. Firmicutes (as determined by FISH) and Nitrospira and Deferribacteres (as determined by cloning and sequencing) were the predominant Bacteria. Remarkably, Firmicutes could not be detected in the brown granules. The methanogenic Archaea identified were Methanosaeta concilii (70 to 90% by FISH and cloning), Methanosarcina mazei, and Methanospirillum spp. The phenotypic appearance of the granules reflected the physiological condition of the granules. This may be valuable to easily select appropriate seed sludges to start up other reactors.

  8. Trajectory Analysis Unveils Reelin's Role in the Directed Migration of Granule Cells in the Dentate Gyrus.

    Wang, Shaobo; Brunne, Bianka; Zhao, Shanting; Chai, Xuejun; Li, Jiawei; Lau, Jeremie; Failla, Antonio Virgilio; Zobiak, Bernd; Sibbe, Mirjam; Westbrook, Gary L; Lutz, David; Frotscher, Michael

    2018-01-03

    Reelin controls neuronal migration and layer formation. Previous studies in reeler mice deficient in Reelin focused on the result of the developmental process in fixed tissue sections. It has remained unclear whether Reelin affects the migratory process, migration directionality, or migrating neurons guided by the radial glial scaffold. Moreover, Reelin has been regarded as an attractive signal because newly generated neurons migrate toward the Reelin-containing marginal zone. Conversely, Reelin might be a stop signal because migrating neurons in reeler , but not in wild-type mice, invade the marginal zone. Here, we monitored the migration of newly generated proopiomelanocortin-EGFP -expressing dentate granule cells in slice cultures from reeler , reeler -like mutants and wild-type mice of either sex using real-time microscopy. We discovered that not the actual migratory process and migratory speed, but migration directionality of the granule cells is controlled by Reelin. While wild-type granule cells migrated toward the marginal zone of the dentate gyrus, neurons in cultures from reeler and reeler -like mutants migrated randomly in all directions as revealed by vector analyses of migratory trajectories. Moreover, live imaging of granule cells in reeler slices cocultured to wild-type dentate gyrus showed that the reeler neurons changed their directions and migrated toward the Reelin-containing marginal zone of the wild-type culture, thus forming a compact granule cell layer. In contrast, directed migration was not observed when Reelin was ubiquitously present in the medium of reeler slices. These results indicate that topographically administered Reelin controls the formation of a granule cell layer. SIGNIFICANCE STATEMENT Neuronal migration and the various factors controlling its onset, speed, directionality, and arrest are poorly understood. Slice cultures offer a unique model to study the migration of individual neurons in an almost natural environment. In the

  9. Electron microscopic localization of 3H-leucine in the neurons of the hypoglossal nerve during axonal reaction

    Gylybov, G.P.; Chuchkov, Ch.Kh.; Davidov, M.S.

    1978-01-01

    The uptake of tritium-labelled leucine in the neuronal organelles with the aim of a follow-up of the dynamics in the protein synthesis in the motoneurons affected during axonal reaction was investigated. The experiments were carried out with rats, of which one of the hypoglossal nerve was crushed and the other was left intact. The labelled amino-acid was injected in the lateral cerebral ventricle 30 to 40 min before the sacrificing of each animal. The examination of the histological preparations shows that the neurons of the hypoglossal nerve cumulate to a larger extent the labelled precursor in comparison with the neuroglia. The perinuclear region, the nucleus, the nucleolus and the axonal hillock show preponderance in the accumulation. The activity greatly decreases at the more remote parts of the axon. The electron=microscopic data confirm these results and supplement them by exactly determining the localization of the labels in the individual organelles. The highest activity was found in the mitochondria, in the Golgi apparatus and in the lysosomes. This can be viewed as the result of intensified transfer of proteins from the ribosomes toward these organelles. There is, however, another possibility - the directly elevated biosynthesis. The elevated activity of the protein synthesis in the cell organelles, assume the authors, is related not only to preserving their structural proteins but also to intensifying axonal transport. (A.B.)

  10. High Plasticity of New Granule Cells in the Aging Hippocampus

    Mariela F. Trinchero

    2017-10-01

    Full Text Available Summary: During aging, the brain undergoes changes that impair cognitive capacity and circuit plasticity, including a marked decrease in production of adult-born hippocampal neurons. It is unclear whether development and integration of those new neurons are also affected by age. Here, we show that adult-born granule cells (GCs in aging mice are scarce and exhibit slow development, but they display a remarkable potential for structural plasticity. Retrovirally labeled 3-week-old GCs in middle-aged mice were small, underdeveloped, and disconnected. Neuronal development and integration were accelerated by voluntary exercise or environmental enrichment. Similar effects were observed via knockdown of Lrig1, an endogenous negative modulator of neurotrophin receptors. Consistently, blocking neurotrophin signaling by Lrig1 overexpression abolished the positive effects of exercise. These results demonstrate an unparalleled degree of plasticity in the aging brain mediated by neurotrophins, whereby new GCs remain immature until becoming rapidly recruited to the network by activity. : Trinchero et al. show that development of new granule cells born in the adult hippocampus is strongly influenced by age. In the aging hippocampus, new neurons remain immature for prolonged intervals, yet voluntary exercise triggers their rapid growth and functional synaptogenesis. This extensive structural remodeling is mediated by neurotrophins. Keywords: adult neurogenesis, dentate gyrus, functional integration, neurotrophins, synaptogenesis, exercise

  11. Morphological Constraints on Cerebellar Granule Cell Combinatorial Diversity.

    Gilmer, Jesse I; Person, Abigail L

    2017-12-13

    Combinatorial expansion by the cerebellar granule cell layer (GCL) is fundamental to theories of cerebellar contributions to motor control and learning. Granule cells (GrCs) sample approximately four mossy fiber inputs and are thought to form a combinatorial code useful for pattern separation and learning. We constructed a spatially realistic model of the cerebellar GCL and examined how GCL architecture contributes to GrC combinatorial diversity. We found that GrC combinatorial diversity saturates quickly as mossy fiber input diversity increases, and that this saturation is in part a consequence of short dendrites, which limit access to diverse inputs and favor dense sampling of local inputs. This local sampling also produced GrCs that were combinatorially redundant, even when input diversity was extremely high. In addition, we found that mossy fiber clustering, which is a common anatomical pattern, also led to increased redundancy of GrC input combinations. We related this redundancy to hypothesized roles of temporal expansion of GrC information encoding in service of learned timing, and we show that GCL architecture produces GrC populations that support both temporal and combinatorial expansion. Finally, we used novel anatomical measurements from mice of either sex to inform modeling of sparse and filopodia-bearing mossy fibers, finding that these circuit features uniquely contribute to enhancing GrC diversification and redundancy. Our results complement information theoretic studies of granule layer structure and provide insight into the contributions of granule layer anatomical features to afferent mixing. SIGNIFICANCE STATEMENT Cerebellar granule cells are among the simplest neurons, with tiny somata and, on average, just four dendrites. These characteristics, along with their dense organization, inspired influential theoretical work on the granule cell layer as a combinatorial expander, where each granule cell represents a unique combination of inputs

  12. Denervation-induced homeostatic dendritic plasticity in morphological granule cell models

    Hermann Cuntz

    2014-03-01

    Full Text Available Neuronal death and subsequent denervation of target areas are major consequences of several neurological conditions such asischemia or neurodegeneration (Alzheimer's disease. The denervation-induced axonal loss results in reorganization of the dendritic tree of denervated neurons. The dendritic reorganization has been previously studied using entorhinal cortex lesion (ECL. ECL leads to shortening and loss of dendritic segments in the denervated outer molecular layer of the dentate gyrus. However, the functional importance of these long-term dendritic alterations is not yet understood and their impact on neuronal electrical properties remains unclear. Here we analyzed what happens to the electrotonic structure and excitability of dentate granule cells after lesion-induced alterations of their dendritic morphology, assuming all other parameters remain equal. We performed comparative electrotonic analysis in anatomically and biophysically realistic compartmental models of 3D-reconstructed healthy and denervated granule cells. Using the method of morphological modeling based on optimization principles minimizing the amount of wiring and maximizing synaptic democracy, we built artificial granule cells which replicate morphological features of their real counterparts. Our results show that somatofugal and somatopetal voltage attenuation in the passive cable model are strongly reduced in denervated granule cells. In line with these predictions, the attenuation both of simulated backpropagating action potentials and forward propagating EPSPs was significantly reduced in dendrites of denervated neurons. Intriguingly, the enhancement of action potential backpropagation occurred specifically in the denervated dendritic layers. Furthermore, simulations of synaptic f-I curves revealed a homeostatic increase of excitability in denervated granule cells. In summary, our morphological and compartmental modeling indicates that unless modified by changes of

  13. Expression of tryptophan 2,3-dioxygenase in mature granule cells of the adult mouse dentate gyrus

    Ohira, Koji

    2010-09-01

    Full Text Available Abstract New granule cells are continuously generated in the dentate gyrus of the adult hippocampus. During granule cell maturation, the mechanisms that differentiate new cells not only describe the degree of cell differentiation, but also crucially regulate the progression of cell differentiation. Here, we describe a gene, tryptophan 2,3-dioxygenase (TDO, whose expression distinguishes stem cells from more differentiated cells among the granule cells of the adult mouse dentate gyrus. The use of markers for proliferation, neural progenitors, and immature and mature granule cells indicated that TDO was expressed in mature cells and in some immature cells. In mice heterozygous for the alpha-isoform of calcium/calmodulin-dependent protein kinase II, in which dentate gyrus granule cells fail to mature normally, TDO immunoreactivity was substantially downregulated in the dentate gyrus granule cells. Moreover, a 5-bromo-2'-deoxyuridine labeling experiment revealed that new neurons began to express TDO between 2 and 4 wk after the neurons were generated, when the axons and dendrites of the granule cells developed and synaptogenesis occurred. These findings indicate that TDO might be required at a late-stage of granule cell development, such as during axonal and dendritic growth, synaptogenesis and its maturation.

  14. Measurement of total calcium in neurons by electron probe X-ray microanalysis.

    Pivovarova, Natalia B; Andrews, S Brian

    2013-11-20

    In this article the tools, techniques, and instruments appropriate for quantitative measurements of intracellular elemental content using the technique known as electron probe microanalysis (EPMA) are described. Intramitochondrial calcium is a particular focus because of the critical role that mitochondrial calcium overload plays in neurodegenerative diseases. The method is based on the analysis of X-rays generated in an electron microscope (EM) by interaction of an electron beam with the specimen. In order to maintain the native distribution of diffusible elements in electron microscopy specimens, EPMA requires "cryofixation" of tissue followed by the preparation of ultrathin cryosections. Rapid freezing of cultured cells or organotypic slice cultures is carried out by plunge freezing in liquid ethane or by slam freezing against a cold metal block, respectively. Cryosections nominally 80 nm thick are cut dry with a diamond knife at ca. -160 °C, mounted on carbon/pioloform-coated copper grids, and cryotransferred into a cryo-EM using a specialized cryospecimen holder. After visual survey and location mapping at ≤-160 °C and low electron dose, frozen-hydrated cryosections are freeze-dried at -100 °C for ~30 min. Organelle-level images of dried cryosections are recorded, also at low dose, by means of a slow-scan CCD camera and subcellular regions of interest selected for analysis. X-rays emitted from ROIs by a stationary, focused, high-intensity electron probe are collected by an energy-dispersive X-ray (EDX) spectrometer, processed by associated electronics, and presented as an X-ray spectrum, that is, a plot of X-ray intensity vs. energy. Additional software facilitates: 1) identification of elemental components by their "characteristic" peak energies and fingerprint; and 2) quantitative analysis by extraction of peak areas/background. This paper concludes with two examples that illustrate typical EPMA applications, one in which mitochondrial calcium analysis

  15. Physicochemical and tablet properties of Cyperus alulatus rhizomes starch granules.

    Paramakrishnan, N; Jha, S; Kumar, K Jayaram

    2015-05-01

    The starch extracted from rhizomes of Cyperus alulatus (CA) was characterized for its physicochemical, morphological and tableting properties. Rhizomes of CA yield a significant quantity of starch granules (CASG) i.e., 11.93%. CASG was characterized in terms of moisture, ash and amylose contents, solubility and swelling power, paste clarity and water retention capacity. The swelling power was found to be significantly improved with the increase in temperature. Scanning electron micrographs revealed that the granule's surface was smooth, the granules were spherical, mostly round, disc like, and the size range was 6.65-12.13 μm. Finger print region in FTIR spectra confirmed its carbohydrate nature. The evaluated micromeritic properties of extracted granule's bulk density, tapped density, Carr's index, Hausner ratio, true density and porosity render unique practicability of CASG being used as an adjuvant in pharmaceutical solid dosage forms. Tablets prepared by using CASG showed higher mechanical strength and more disintegration time, which depicted the characteristic binding nature of the starch granules. As CASG is imparting better binding properties in less concentration and also it can be used in combination with the established starches to get the synergistic effect; this starch can be used commercially in the tablet preparation. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Linking granulation performance with residence time and granulation liquid distributions in twin-screw granulation: An experimental investigation

    Kumar, Ashish; Alakarjula, Maija; Vanhoorne, Valérie

    2016-01-01

    Twin-screw granulation is a promising wet granulation technique for the continuous manufacturing of pharmaceutical solid dosage forms. A twin screw granulator displays a short residence time. Thus, the solid-liquid mixing must be achieved quickly by appropriate arrangement of transport and kneading...

  17. Multidimensional modelling of anaerobic granules

    Picioreanu, C.; Batstone, Damien J.; van Loosdrecht, M.C.M.

    2005-01-01

    A multispecies, two- and three-dimensional model was developed, based on a previously published planar biofilm model, and the biochemical structure of the ADM1. Several soluble substrates diffuse and react in the granule. Local pH is calculated from acid-base equilibria and charge balance. The mo...

  18. Transplantation of colon carcinoma into granulation tissue induces an invasive morphotype

    Dingemans, K. P.; Zeeman-Boeschoten, I. M.; Keep, R. F.; Das, P. K.

    1993-01-01

    The stroma surrounding many malignant tumors resembles granulation tissue. To test the hypothesis that such stroma stimulates tumor invasiveness, we compared, by electron microscopy and immunohistochemistry, the growth patterns of CC531 rat colon adenocarcinoma in 2 experimental situations: (i)

  19. Serglycin proteoglycan is not implicated in localizing exocrine pancreas enzymes to zymogen granules

    Niemann, Carsten U; Cowland, Jack B; Ralfkiaer, Elisabeth

    2009-01-01

    Storage and release of proteins from granules forms the basis of cellular functions as diverse as cell mediated cytotoxicity, neuronal communication, activation of muscle fibres, and release of hormones or digestive enzymes from endocrine and exocrine glands, such as the pancreas. Serglycin...... is the major intracellular proteoglycan of haematopoietic cells. Serglycin is important for localization of proteins in granules of different haematopoietic cell types. Previous reports have indicated a role for serglycin in granule formation and localization of zymogens in granules of the exocrine pancreas...... in rat. We here present data showing that serglycin is not present at the protein level in human or murine pancreas. Furthermore, the amount and localization of three exocrine pancreas zymogens (amylase, trypsinogen, and carboxypeptidase A) is not affected by the absence of serglycin in a serglycin knock...

  20. Measurement of the internal pH of mast cell granules using microvolumetric fluorescence and isotopic techniques

    De Young, M.B.; Nemeth, E.F.; Scarpa, A.

    1987-01-01

    The intragranular pH of isolated mast cell granules was measured. Because of the minute amounts of isolated granules available, two techniques were developed by modifying aminoacridine fluorescence and [ 14 C]methylamine accumulation techniques to permit measurements with microliter sample volumes. Granule purity was demonstrated by electron microscopy, ruthenium red exclusion, and biochemical (histamine, mast cell granule protease) analysis. The internal pH was determined to be 5.55 +/- 0.06, indicating that the pH environment within mast cell granules is not significantly different from that of previously studied granule types (i.e., chromaffin, platelet, pancreatic islet, and pituitary granules). Collapse of the pH gradient by NH+4 was demonstrated with both techniques. No evidence of Cl-/OH- or specific cation/H+ transport was found, and major chloride permeability could not be unequivocably demonstrated. Ca 2+ and Cl- at concentrations normally present extracellularly destabilized granules in the presence of NH+4, but this phenomenon does not necessarily indicate a role for these ions in the exocytotic release of granule contents from intact cells. The pH measurement techniques developed for investigating the properties of granules in mast cells may be useful for studying other granules that can be obtained only in limited quantities

  1. Intercellular communication within the rat anterior pituitary: XIV electron microscopic and immunohistochemical study on the relationship between the agranular cells and GnRH neurons in the dorsal pars tuberalis of the pituitary gland.

    Shirasawa, Nobuyuki; Sakuma, Eisuke; Wada, Ikuo; Naito, Akira; Horiuchi, Osamu; Mabuchi, Yoshio; Kanai, Miharu; Herbert, Damon C; Soji, Tsuyoshi

    2007-11-01

    Although numerous investigators in 1970s to 1980s have reported the distribution of LH-RH nerve fibers in the median eminence, a few LH-RH fibers have been shown to be present in the pars tuberalis. The significance of the finding remains to be elucidated, and there are few studies on the distribution of LH-RH neurons in the pars tuberalis, especially in the dorsal pars tuberalis (DPT). Adult male Wistar-Imamichi rats were separated into two groups: one for electron microscopy and the other for immunohistochemistry to observe LH-RH and neurofilaments. Pituitary glands attached to the brain were fixed by perfusion, and the sections were prepared parallel to the sagittal plane. The typical glandular structure of the pars tuberalis was evident beneath the bottom floor of the third ventricle, and the thick glandular structure was present in the foremost region. Closer to the anterior lobe, the glandular structure changed to be a thin layer, and it was again observed at the posterior portion. Then the pituitary stalk was surrounded with the dorsal, lateral, and ventral pars tuberalis. LH-RH and neurofilaments fibers were noted in the bottom floor, and some of them vertically descended to the gland. Adjacent to the glandular folliculostellate cells in the pars tuberalis, Herring bodies with numerous dense granules invading into the gland were present between the pituitary stalk and DPT. It was postulated that the "message" carried by LH-RH might have been transmitted to the cells in the DPT to aid in the modulation of LH release. Copyright 2007 Wiley-Liss, Inc.

  2. Behavioral experience induces zif268 expression in mature granule cells but suppresses its expression in immature granule cells

    Kylie A. Huckleberry

    2015-08-01

    Full Text Available Thousands of neurons are born each day in the dentate gyrus (DG, but many of these cells die before reaching maturity. Both death and survival of adult-born neurons are regulated by neuronal activity in DG. The immediate-early gene (IEG zif268 is an important mediator of these effects, as its expression is induced by neural activity and knockout of zif268 impairs survival of adult-born neurons (Veyrac et al., 2013. Despite the apparent importance of zif268 for adult neurogenesis, its behavior-induced expression has not been fully characterized in adult-born neurons. Here we characterize behavior-evoked expression of zif268 in mature and newborn dentate granule cells (DGCs. In the general granule cell population, zif268 expression peaked 1 hour after novel environment exposure and returned to baseline by 8 hours post-exposure. However, in the doublecortin-positive (DCX+ immature neurons, zif268 expression was suppressed relative to home cage for at least 8 hours post-exposure. We next determined that exposure to water maze training, an enriched environment, or a novel environment caused approximately equal suppression of zif268 expression in DCX+ cells and approximately equal activation of zif268 in the general DGC population and in 6-week-old adult-born neurons. Finally, we asked whether zif268 suppression varied as a function of age within the DCX+ population, which ranges in age from 0 to approximately 4 weeks. Novel environment exposure had no significant effect on zif268 expression in 2- or 4-week-old BrdU-labeled neurons, but it significantly suppressed zif268 expression in 3-week-old neurons. In summary, behavioral experience transiently activated expression of zif268 in mature DGCs but caused a more long-lasting suppression of zif268 expression in immature, adult-born DGCs. We hypothesize that zif268 suppression inhibits memory-related synaptic plasticity in immature DGCs or mediates learning-induced apoptosis of immature adult

  3. The functional morphology of color changing in a spider: development of ommochrome pigment granules.

    Insausti, Teresita C; Casas, Jérôme

    2008-03-01

    Studies on the formation of ommochrome pigment granules are very few, despite their generalized occurrence as screening pigments in insect eyes. This is particularly true for ommochrome granules responsible for epidermal coloration. The aims of this study were to characterize the localization of major body pigments in a color changing mimetic spider, Misumena vatia (Thomisidae), and to describe the formation and location of ommochrome pigment granules responsible for the spider's color change from white to yellow. The unpigmented cuticula of this spider is transparent. Both the guanine localized in guanine cells in the opisthosoma and the uric acid localized in epidermis cells in the prosoma are responsible for the white coloration. The bright yellow color is due to the combination of ommochrome pigment granules and the white reflectance from coincident guanine and/or uric acid. The formation of ommochrome pigment granules in epidermis cells proceeds via three distinctive steps. Translucent, UV fluorescent, progranules (type I) are produced by a dense network of endoplasmic reticulum associated with numerous mitochondria and glycogen rosettes. These progranules are present in white spiders only, and regularly distributed in the cytoplasm. The merging of several progranules of type I into a transient state (progranule type II) leads to the formation of granules (type III) characterized by their lack of fluorescence, their spherical sections and their osmophilic-electron-dense contents. They are found in yellow spiders and in the red stripes on the body sides. Their color varies from yellow to red. Thus, white spiders contain only type I granules, yellow tinted spiders contain type II and III granules and bright yellow spiders contain only type III granules. We present a synthetic view of the ontogeny of ommochrome granules. We discuss the physiology of color changing and the nature of the chemical compounds in the different types of granules. Extended studies on the

  4. Internal structure of normal maize starch granules revealed by chemical surface gelatinization.

    Pan, D D; Jane, J I

    2000-01-01

    Normal maize starch was fractionated into two sizes: large granules with diameters more than 5 microns and small granules with diameters less than 5 microns. The large granules were surface gelatinized by treating them with an aqueous LiCl solution (13 M) at 22-23 degrees C. Surface-gelatinized remaining granules were obtained by mechanical blending, and gelatinized surface starch was obtained by grinding with a mortar and a pestle. Starches of different granular sizes and radial locations, obtained after different degrees of surface gelatinization, were subjected to scanning electron microscopy, iodine potentiometric titration, gel-permeation chromatography, and amylopectin branch chain length analysis. Results showed that the remaining granules had a rough surface with a lamella structure. Amylose was more concentrated at the periphery than at the core of the granule. Amylopectin had longer long B-chains at the core than at the periphery of the granule. Greater proportions of the long B-chains were present at the core than at the periphery of the granule.

  5. Light and electron microscopic immunocytochemistry of neurons in the blowfly optic lobe reacting with antisera to RFamide and FMRFamide

    Nässel, D R; Ohlsson, Lisbeth; Johansson, K U

    1988-01-01

    Different antisera to the molluscan cardioexcitatory peptide FMRFamide, and its fragment, RFamide (Arg-Phe-NH2), label a distinct population of neurons in the optic lobe of the blowfly, Calliphora erythrocephala. Seven morphological types of RFamide/FMRFamide-like immunoreactive neurons could be ...

  6. Increased accuracy of starch granule type quantification using mixture distributions

    Tanaka, Emi; Ral, Jean-Phillippe F.; Li, Sean; Gaire, Raj; Cavanagh, Colin R.; Cullis, Brian R.; Whan, Alex

    2017-01-01

    Background The proportion of granule types in wheat starch is an important characteristic that can affect its functionality. It is widely accepted that granule types are either large, disc-shaped A-type granules or small, spherical B-type granules. Additionally, there are some reports of the tiny C-type granules. The differences between these granule types are due to its carbohydrate composition and crystallinity which is highly, but not perfectly, correlated with the granule size. A majority...

  7. A possible role of the non-GAT1 GABA transporters in transfer of GABA from GABAergic to glutamatergic neurons in mouse cerebellar neuronal cultures

    Suñol, C; Babot, Z; Cristòfol, R

    2010-01-01

    Cultures of dissociated cerebellum from 7-day-old mice were used to investigate the mechanism involved in synthesis and cellular redistribution of GABA in these cultures consisting primarily of glutamatergic granule neurons and a smaller population of GABAergic Golgi and stellate neurons......3 transporters. Only a small population of cells were immuno-stained for GAD while many cells exhibited VGlut-1 like immuno-reactivity which, however, never co-localized with GAD positive neurons. This likely reflects the small number of GABAergic neurons compared to the glutamatergic granule......M concentrations (95%). Essentially all neurons showed GABA like immunostaining albeit with differences in intensity. The results indicate that GABA which is synthesized in a small population of GAD-positive neurons is redistributed to essentially all neurons including the glutamatergic granule cells. GAT1...

  8. In vivo calcium imaging from dentate granule cells with wide-field fluorescence microscopy.

    Yuichiro Hayashi

    Full Text Available A combination of genetically-encoded calcium indicators and micro-optics has enabled monitoring of large-scale dynamics of neuronal activity from behaving animals. In these studies, wide-field microscopy is often used to visualize neural activity. However, this method lacks optical sectioning capability, and therefore its axial resolution is generally poor. At present, it is unclear whether wide-field microscopy can visualize activity of densely packed small neurons at cellular resolution. To examine the applicability of wide-field microscopy for small-sized neurons, we recorded calcium activity of dentate granule cells having a small soma diameter of approximately 10 micrometers. Using a combination of high numerical aperture (0.8 objective lens and independent component analysis-based image segmentation technique, activity of putative single granule cell activity was separated from wide-field calcium imaging data. The result encourages wider application of wide-field microscopy in in vivo neurophysiology.

  9. Distorted secretory granule composition in mast cells with multiple protease deficiency.

    Grujic, Mirjana; Calounova, Gabriela; Eriksson, Inger; Feyerabend, Thorsten; Rodewald, Hans-Reimer; Tchougounova, Elena; Kjellén, Lena; Pejler, Gunnar

    2013-10-01

    Mast cells are characterized by an abundance of secretory granules densely packed with inflammatory mediators such as bioactive amines, cytokines, serglycin proteoglycans with negatively charged glycosaminoglycan side chains of either heparin or chondroitin sulfate type, and large amounts of positively charged proteases. Despite the large biological impact of mast cell granules and their contents on various pathologies, the mechanisms that regulate granule composition are incompletely understood. In this study, we hypothesized that granule composition is dependent on a dynamic electrostatic interrelationship between different granule compounds. As a tool to evaluate this possibility, we generated mice in which mast cells are multideficient in a panel of positively charged proteases: the chymase mouse mast cell protease-4, the tryptase mouse mast cell protease-6, and carboxypeptidase A3. Through a posttranslational effect, mast cells from these mice additionally lack mouse mast cell protease-5 protein. Mast cells from mice deficient in individual proteases showed normal morphology. In contrast, mast cells with combined protease deficiency displayed a profound distortion of granule integrity, as seen both by conventional morphological criteria and by transmission electron microscopy. An assessment of granule content revealed that the distorted granule integrity in multiprotease-deficient mast cells was associated with a profound reduction of highly negatively charged heparin, whereas no reduction in chondroitin sulfate storage was observed. Taken together with previous findings showing that the storage of basic proteases conversely is regulated by anionic proteoglycans, these data suggest that secretory granule composition in mast cells is dependent on a dynamic interrelationship between granule compounds of opposite electrical charge.

  10. Evidence for evoked release of adenosine and glutamate from cultured cerebellar granule cells

    Schousboe, A.; Frandsen, A.; Drejer, J.

    1989-01-01

    Evoked release of [ 3 H]-D-aspartate which labels the neurotransmitter glutamate pool in cultured cerebellar granule cells was compared with evoked release of adenosine from similar cultures. It was found that both adenosine and [3H]-D-aspartate could be released from the neurons in a calcium dependent manner after depolarization of the cells with either 10-100 microM glutamate or 50 mM KCl. Cultures of cerebellar granule cells treated with 50 microM kainate to eliminate GABAergic neurons behaved in the same way. This together with the observation that cultured astrocytes did not exhibit a calcium dependent, potassium stimulated adenosine release strongly suggest that cerebellar granule cells release adenosine in a neurotransmitter-like fashion together with glutamate which is the classical neurotransmitter of these neurons. Studies of the metabolism of adenosine showed that in the granule cells adenosine is rapidly metabolized to ATP, ADP, and AMP, but in spite of this, adenosine was found to be released preferential to ATP

  11. An innovative method for the preparation of high API-loaded hollow spherical granules for use in controlled-release formulation.

    Asada, Takumi; Kobiki, Mitsuaki; Ochiai, Yasushi; Iwao, Yasunori; Itai, Shigeru

    2017-05-15

    The aim of this study was to prepare controlled-release (CR) granules with suitable particle strength, flowability, particle size distribution (PSD) and density characteristics for blending with other excipients. We also wanted these CR granules to contain large quantities of active pharmaceutical ingredient (API). A high shear mixer was used to mix an API with various polymers at various feed ratios, and the resulting granulated materials were sprayed with solvent. The wet granules were dried using a fluidized bed dryer to give CR granules. The API content of the granules was determined to be 95wt%. The granules were found to be spherical in shape with smooth surfaces by scanning electron microscopy. The inner structure of each granule was determined to be hollow by X-ray computed tomography, highlighting the unusual mechanism of this granulation process. The PSD of the granules was found to be dependent on that of the constituent polymer, and a narrow PSD was obtained by adjusting the PSD of the polymer. The dissolution profile of the granules was also dependent on the constituent polymer. Taken together, these results show that we have successfully developed a new manufacturing technology for the simple and low-cost preparation of ideal CR granules. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Medical image of the week: granulation tissue

    Ganesh A

    2014-03-01

    Full Text Available A 57 year old woman presented with a tickling sensation in the back of throat and intermittent bleeding from the healing stoma one month after decannulation of her tracheostomy tube. On bronchoscopy a granuloma with surrounding granulation tissue was present in the subglottic space (Figure 1. Argon plasma coagulation (APC was performed to cauterize the granulation tissue (Figure 2. Formation of granulation tissue after tracheostomy is a common complication which can result in tracheal stenosis. APC and electrocautery using flexible bronchoscopy has been shown to safely and effectively remove the granulation tissue.

  13. Acute ethanol exposure inhibits silencing of cerebellar Golgi cell firing induced by granule cell axon input

    Paolo eBotta

    2014-02-01

    Full Text Available Golgi cells (GoCs are specialized interneurons that provide inhibitory input to granule cells in the cerebellar cortex. GoCs are pacemaker neurons that spontaneously fire action potentials, triggering spontaneous inhibitory postsynaptic currents in granule cells and also contributing to the generation tonic GABAA receptor-mediated currents in granule cells. In turn, granule cell axons provide feedback glutamatergic input to GoCs. It has been shown that high frequency stimulation of granule cell axons induces a transient pause in GoC firing in a type 2-metabotropic glutamate receptor (mGluR2-dependent manner. Here, we investigated the effect ethanol on the pause of GoC firing induced by high frequency stimulation of granule cell axons. GoC electrophysiological recordings were performed in parasagittal cerebellar vermis slices from postnatal day 23 to 26 rats. Loose-patch cell-attached recordings revealed that ethanol (40 mM reversibly decreases the pause duration. An antagonist of mGluR2 reduced the pause duration but did not affect the effect of ethanol. Whole-cell voltage-clamp recordings showed that currents evoked by an mGluR2 agonist were not significantly affected by ethanol. Perforated-patch experiments in which hyperpolarizing and depolarizing currents were injected into GoCs demonstrated that there is an inverse relationship between spontaneous firing and pause duration. Slight inhibition of the Na+/K+ pump mimicked the effect of ethanol on pause duration. In conclusion, ethanol reduces the granule cell axon-mediated feedback mechanism by reducing the input responsiveness of GoCs. This would result in a transient increase of GABAA receptor-mediated inhibition of granule cells, limiting information flow at the input stage of the cerebellar cortex.

  14. Quantitative immuno-electron microscopic analysis of depolarization-induced expression of PGC-1alpha in cultured rat visual cortical neurons.

    Meng, Hui; Liang, Huan Ling; Wong-Riley, Margaret

    2007-10-17

    Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC- 1alpha) is a coactivator of nuclear receptors and other transcription factors that regulate several metabolic processes, including mitochondrial biogenesis, energy homeostasis, respiration, and gluconeogenesis. PGC-1alpha plays a vital role in stimulating genes that are important to oxidative metabolism and other mitochondrial functions in brown adipose tissue and skeleton muscles, but the significance of PGC-1alpha in the brain remains elusive. The goal of our present study was to determine by means of quantitative immuno-electron microscopy the expression of PGC-1alpha in cultured rat visual cortical neurons under normal conditions as well as after depolarizing stimulation for varying periods of time. Our results showed that: (a) PGC-1alpha was normally located in both the nucleus and the cytoplasm. In the nucleus, PGC-1alpha was associated mainly with euchromatin rather than heterochromatin, consistent with active involvement in transcription. In the cytoplasm, it was associated mainly with free ribosomes. (b) Neuronal depolarization by KCl for 0.5 h induced a significant increase in PGC-1alpha labeling density in both the nucleus and the cytoplasm (Pneuronal activity by synthesizing more proteins in the cytoplasm and translocating them to the nucleus for gene activation. PGC-1alpha level in neurons is, therefore, tightly regulated by neuronal activity.

  15. Distribution of binder in granules produced by means of twin screw granulation

    Fonteyne, Margot; Fussell, Andrew Luke; Vercruysse, Jurgen

    2014-01-01

    According to the quality by design principle processes may not remain black-boxes and full process understanding is required. The granule size distribution of granules produced via twin screw granulation is often found to be bimodal. The aim of this study was to gain a better understanding...

  16. The paradox of high shear granulation : the formation of non-homogeneous granules

    Dries, Kaspar van den

    2004-01-01

    Wet granulation is a process used for the particle size enlargement of primary powders. The mixing of a liquid with the powder glues the primary particles together, which results in the formation of the granules. The mixing action can be performed in many ways, like tumbling (drum granulation),

  17. Surface Modification of Porous Titanium Granules for Improving Bioactivity.

    Karaji, Zahra Gorgin; Houshmand, Behzad; Faghihi, Shahab

    The highly porous titanium granules are currently being used as bone substitute material and for bone tissue augmentation. However, they suffer from weak bone bonding ability. The aim of this study was to create a nanostructured surface oxide layer on irregularly shaped titanium granules to improve their bioactivity. This could be achieved using optimized electrochemical anodic oxidation (anodizing) and heat treatment processes. The anodizing process was done in an ethylene glycol-based electrolyte at an optimized condition of 60 V for 3 hours. The anodized granules were subsequently annealed at 450°C for 1 hour. Scanning electron microscopy (SEM), energy-dispersive x-ray spectroscopy (EDS), and x-ray diffraction (XRD) were used to characterize the surface structure and morphology of the granules. The in vitro bioactivity of the samples was evaluated by immersion of specimens in simulated body fluid (SBF) for 1, 2, and 3 weeks. The human osteoblastic sarcoma cell line, MG63, was used to evaluate cell viability on the samples using dimethylthiazol-diphenyl tetrazolium bromide (MTT) assay. The results demonstrated the formation of amorphous nanostructured titanium oxide after anodizing, which transformed to crystalline anatase and rutile phases upon heat treatment. After immersion in SBF, spherical aggregates of amorphous calcium phosphate were formed on the surface of the anodized sample, which turned into crystalline hydroxyapatite on the surface of the anodized annealed sample. No cytotoxicity was detected among the samples. It is suggested that anodic oxidation followed by heat treatment could be used as an effective surface treatment procedure to improve bioactivity of titanium granules implemented for bone tissue repair and augmentation.

  18. APPLICATION OF GRANULATION TECHNOLOGY IN VARIOUS INDUSTRIES

    B. V. YEGOROV

    2017-10-01

    Full Text Available Science and practice proved the high efficiency of granulated mixed fodders. This article presents an overview of granulation technologies for various industries. This article discusses the application of granulation technologies in various industries. The processes of granulation are mass technological processes currently used in a wide range of industries: feed industry, food industry, pharmaceutical industry, fertilizer production, polyethylene, metal production, mining, etc. A wide range of different materials are granulated, including chemicals, iron ore, mixed fodder, and much more. Granulation is a process of pressing or shaping a material in the form of granulesGranulation is widely used in the production of pigments, dyes, synthetic detergents, catalysts, plastics, soot, chemical reagents, etc. The use of granular raw materials in the metallurgical industry helps not only to mechanize processes, but also to increase their intensity by increasing the contact surface of interacting media. Granular fertilizers retain their properties for a long time. In the mining industry, granulation processes are used at the stage of preparation and enrichment of raw materials and release of the finished product.  Particular attention is paid to the feed industry. Granulation allows to ensure stable homogeneity, to improve sanitary and hygienic parameters, to increase nutritional value, to increase the storage period, improve the physical properties. However, despite all the advantages, the existing granulation production lines have a relatively high productivity and, at the same time, a high energy intensity. In this regard, this article proposes a technology for improving the granulation of mixed fodders. According to a preliminary literary review, It should be concluded that improving the technology of the granulation process for feed production is a topical issue in the feed industry today. The development of technology for improving the

  19. Biochemical and microscopic evidence for the internalization and degradation of heparin-containing mast cell granules by bovine endothelial cells

    Atkins, F.M.; Friedman, M.M.; Metcalfe, D.D.

    1985-01-01

    Incubation of [ 35 S]heparin-containing mast cell granules with cultured bovine endothelial cells was followed by the appearance of 35 S-granule-associated radioactivity within the endothelial cells and a decrease in radioactivity in the extracellular fluid. These changes occurred during the first 24 hours of incubation and suggested ingestion of the mast cell granules by the endothelial cells. Periodic electron microscopic examination of the monolayers confirmed this hypothesis by demonstrating apposition of the granules to the plasmalemma of endothelial cells, which was followed by the engulfment of the granules by cytoplasmic projections. Under light microscopic examination, mast cell granules within endothelial cells then appeared to undergo degradation. The degradation of [ 35 S]heparin in mast cell granules was demonstrated by a decrease in the amount of intracellular [ 35 S]heparin proteoglycan after 24 hours and the appearance of free [ 35 S]sulfate in the extracellular compartment. Intact endothelial cells were more efficient at degrading [ 35 S]heparin than were cell lysates or cell supernatants. These data provide evidence of the ability of endothelial cells to ingest mast cell granules and degrade native heparin that is presented as a part of the mast cell granule

  20. Coating of waste containing ceramic granules

    Neumann, W.; Kofler, O.

    1979-01-01

    Simulated high-level waste granules produced by fluidized-bed calcination were overcoated by chemical vapor deposition (CVD) with pyrocarbon and nickel in laboratory-scale experiments. Successful development enables pyrocrbon deposition at temperatures of 600 to 800 0 K. The coated granules have excellent properties for long-term waste storage

  1. Multiphase flow in spout fluidized bed granulators

    Buijtenen, van M.S.

    2011-01-01

    Spout fluidized beds are frequently used for the production of granules or particles through granulation, which are widely applied, for example, in the production of detergents, pharmaceuticals, food and fertilizers (M¨orl et al. 2007). Spout fluidized beds have a number of advantageous properties,

  2. Twin screw wet granulation: Binder delivery.

    Saleh, Mohammed F; Dhenge, Ranjit M; Cartwright, James J; Hounslow, Michael J; Salman, Agba D

    2015-06-20

    The effects of three ways of binder delivery into the twin screw granulator (TSG) on the residence time, torque, properties of granules (size, shape, strength) and binder distribution were studied. The binder distribution was visualised through the transparent barrel using high speed imaging as well as quantified using offline technique. Furthermore, the effect of binder delivery and the change of screw configuration (conveying elements only and conveying elements with kneading elements) on the surface velocity of granules across the screw channel were investigated using particle image velocimetry (PIV). The binder was delivered in three ways; all solid binder incorporated with powder mixture, 50% of solid binder mixed with powder mixture and 50% mixed with water, all the solid binder dissolved in water. Incorporation of all solid binder with powder mixture resulted in the relatively longer residence time and higher torque, narrower granule size distribution, more spherical granules, weaker big-sized granules, stronger small-sized granules and better binder distribution compared to that in other two ways. The surface velocity of granules showed variation from one screw to another as a result of uneven liquid distribution as well as shown a reduction while introducing the kneading elements into the screw configuration. Copyright © 2015. Published by Elsevier B.V.

  3. NEDDylation promotes stress granule assembly.

    Jayabalan, Aravinth Kumar; Sanchez, Anthony; Park, Ra Young; Yoon, Sang Pil; Kang, Gum-Yong; Baek, Je-Hyun; Anderson, Paul; Kee, Younghoon; Ohn, Takbum

    2016-07-06

    Stress granules (SGs) harbour translationally stalled messenger ribonucleoproteins and play important roles in regulating gene expression and cell fate. Here we show that neddylation promotes SG assembly in response to arsenite-induced oxidative stress. Inhibition or depletion of key components of the neddylation machinery concomitantly inhibits stress-induced polysome disassembly and SG assembly. Affinity purification and subsequent mass-spectrometric analysis of Nedd8-conjugated proteins from translationally stalled ribosomal fractions identified ribosomal proteins, translation factors and RNA-binding proteins (RBPs), including SRSF3, a previously known SG regulator. We show that SRSF3 is selectively neddylated at Lys85 in response to arsenite. A non-neddylatable SRSF3 (K85R) mutant do not prevent arsenite-induced polysome disassembly, but fails to support the SG assembly, suggesting that the neddylation pathway plays an important role in SG assembly.

  4. Colchicine induced intraneuronal free zinc accumulation and dentate granule cell degeneration.

    Choi, Bo Young; Lee, Bo Eun; Kim, Jin Hee; Kim, Hyun Jung; Sohn, Min; Song, Hong Ki; Chung, Tae Nyoung; Suh, Sang Won

    2014-08-01

    Colchicine has been discovered to inhibit many inflammatory processes such as gout, familial Mediterranean fever, pericarditis and Behcet disease. Other than these beneficial anti-inflammatory effects, colchicine blocks microtubule-assisted axonal transport, which results in the selective loss of dentate granule cells of the hippocampus. The mechanism of the colchicine-induced dentate granule cell death and depletion of mossy fiber terminals still remains unclear. In the present study, we hypothesized that colchicine-induced dentate granule cell death may be caused by accumulation of labile intracellular zinc. 10 μg kg(-1) of colchicine was injected into the adult rat hippocampus and then brain sections were evaluated at 1 day or 1 week later. Neuronal cell death was evaluated by H&E staining or Fluoro-Jade B. Zinc accumulation and vesicular zinc were detected by N-(6-methoxy-8-quinolyl)-para-toluene sulfonamide (TSQ) staining. To test whether an extracellular zinc chelator can prevent this process, CaEDTA was injected into the hippocampus over a 5 min period with colchicine. To test whether other microtubule toxins also produce similar effects as colchicine, vincristine was injected into the hippocampus. The present study found that colchicine injection induced intracellular zinc accumulation in the dentate granule cells and depleted vesicular zinc from mossy fiber terminals. Injection of a zinc chelator, CaEDTA, did not block the zinc accumulation and neuronal death. Vincristine also produced intracellular zinc accumulation and neuronal death. These results suggest that colchicine-induced dentate granule cell death is caused by blocking axonal zinc flow and accumulation of intracellular labile zinc.

  5. Cultured neurons as model systems for biochemical and pharmacological studies on receptors for neurotransmitter amino acids

    Schousboe, A; Drejer, J; Hansen, Gert Helge

    1985-01-01

    By the use of primary cultures of neurons consisting of cerebral cortex interneurons or cerebellar granule cells it is possible to study biochemical and pharmacological aspects of receptors for GABA and glutamate. Cerebellar granule cells have been shown to express both high- and low-affinity GAB...

  6. MicroRNAs Promote Granule Cell Expansion in the Cerebellum Through Gli2.

    Constantin, Lena; Wainwright, Brandon J

    2015-12-01

    MicroRNAs (miRNAs) are important regulators of cerebellar function and homeostasis. Their deregulation results in cerebellar neuronal degeneration and spinocerebellar ataxia type 1 and contributes to medulloblastoma. Canonical miRNA processing involves Dicer, which cleaves precursor miRNAs into mature double-stranded RNA duplexes. In order to address the role of miRNAs in cerebellar granule cell precursor development, loxP-flanked exons of Dicer1 were conditionally inactivated using the granule cell precursor-specific Atoh1-Cre recombinase. A reduction of 87% in Dicer1 transcript was achieved in this conditional Dicer knockdown model. Although knockdown resulted in normal survival, mice had disruptions to the cortical layering of the anterior cerebellum, which resulted from the premature differentiation of granule cell precursors in this region during neonatal development. This defect manifested as a thinner external granular layer with ectopic mature granule cells, and a depleted internal granular layer. We found that expression of the activator components of the Hedgehog-Patched pathway, the Gli family of transcription factors, was perturbed in conditional Dicer knockdown mice. We propose that loss of Gli2 mRNA mediated the anterior-restricted defect in conditional Dicer knockdown mice and, as proof of principle, were able to show that miR-106b positively regulated Gli2 mRNA expression. These findings confirm the importance of miRNAs as positive mediators of Hedgehog-Patched signalling during granule cell precursor development.

  7. Polyhydroxyalkanoate (PHA) Granules Have no Phospholipids

    Bresan, Stephanie; Sznajder, Anna; Hauf, Waldemar; Forchhammer, Karl; Pfeiffer, Daniel; Jendrossek, Dieter

    2016-01-01

    Polyhydroxybutyrate (PHB) granules, also designated as carbonosomes, are supra-molecular complexes in prokaryotes consisting of a PHB polymer core and a surface layer of structural and functional proteins. The presence of suspected phospholipids in the surface layer is based on in vitro data of isolated PHB granules and is often shown in cartoons of the PHB granule structure in reviews on PHB metabolism. However, the in vivo presence of a phospholipid layer has never been demonstrated. We addressed this topic by the expression of fusion proteins of DsRed2EC and other fluorescent proteins with the phospholipid-binding domain (LactC2) of lactadherin in three model organisms. The fusion proteins specifically localized at the cell membrane of Ralstonia eutropha but did not co-localize with PHB granules. The same result was obtained for Pseudomonas putida, a species that accumulates another type of polyhydroxyalkanoate (PHA) granules related to PHB. Notably, DsRed2EC-LactC2 expressed in Magnetospirillum gryphiswaldense was detected at the position of membrane-enclosed magnetosome chains and at the cytoplasmic membrane but not at PHB granules. In conclusion, the carbonosomes of representatives of α-proteobacteria, β-proteobacteria and γ-proteobacteria have no phospholipids in vivo and we postulate that the PHB/PHA granule surface layers in natural producers generally are free of phospholipids and consist of proteins only. PMID:27222167

  8. Regularities of formation of granules at granulation of powdered materials in drum devices

    Kelbaliyev, G.I; Samedli, V.M.

    2008-01-01

    Full text:Granulation of powdered materials in the presence of binding agent is widely used in the most multi-tankage productions of chemical, food, pharmaceutical, metallurgical and agrarian technology. Granulation of powdered materials with participation of liquid phase is carried out in screw, disk, plase-shaped and drum devices and also in devices with mixers. In all cases a formation and growth of granules takes place owing to wetting of separate particles of powder leading to agglomeration and coagulation of particles in their contact with each other. It is apparent that in early stage of granule formation a growth and formation of granules takes place owing to adherence of small particles and agglomerates to larger granules. The content of liquid phase owing to which are appeared adhesive, capillary and surface forces, keeping particles on surface of granule exerts an essential influence on process of granule formation. Besides composition of mixture, its moisture and physical-chemical properties of initial components a mixing frequency degree of filling and angle of inclination of the device, ratio of liquid and hard phases which defines finally qualitative characteristics of the process exert an essential influence on formation of granules as a result of agglomeration of particles of powder. Powder lamination on granule surface is as consequence of its consolidation whereas as a result of consolidation and compression, a binding agent containing in pores squeezed out to a surface, which increases a possibility and probability of further sticking of dry particles of powder. In all cases the further growth and completeness of form of granule is determined by distribution of concentration of binding agent in volume of granule, i.e. moisture content or moisture of granule surface

  9. Stimulation of the N-methyl-D-aspartate receptor has a trophic effect on differentiating cerebellar granule cells

    Balázs, R; Hack, N; Jørgensen, Ole Steen

    1988-01-01

    N-methyl-D-aspartate (NMDA) supplementation of cerebellar cultures enriched in granule neurones (about 90%) prevented the extensive cell loss which occurs when cultivation takes place, in serum containing media, in the presence of 'low' K+ (5-15 mM). Estimation of tetanus toxin receptors and N-CA...

  10. Azurophil granule proteins constitute the major mycobactericidal proteins in human neutrophils and enhance the killing of mycobacteria in macrophages

    Jena, Prajna; Mohanty, Soumitra; Mohanty, Tirthankar

    2012-01-01

    Pathogenic mycobacteria reside in, and are in turn controlled by, macrophages. However, emerging data suggest that neutrophils also play a critical role in innate immunity to tuberculosis, presumably by their different antibacterial granule proteins. In this study, we purified neutrophil azurophil...... and specific granules and systematically analyzed the antimycobacterial activity of some purified azurophil and specific granule proteins against M. smegmatis, M. bovis-BCG and M. tuberculosis H37Rv. Using gel overlay and colony forming unit assays we showed that the defensin-depleted azurophil granule...... proteins (AZP) were more active against mycobacteria compared to other granule proteins and cytosolic proteins. The proteins showing antimycobacterial activity were identified by MALDI-TOF mass spectrometry. Electron microscopic studies demonstrate that the AZP disintegrate bacterial cell membrane...

  11. Convergent evolution of germ granule nucleators: A hypothesis.

    Kulkarni, Arpita; Extavour, Cassandra G

    2017-10-01

    Germ cells have been considered "the ultimate stem cell" because they alone, during normal development of sexually reproducing organisms, are able to give rise to all organismal cell types. Morphological descriptions of a specialized cytoplasm termed 'germ plasm' and associated electron dense ribonucleoprotein (RNP) structures called 'germ granules' within germ cells date back as early as the 1800s. Both germ plasm and germ granules are implicated in germ line specification across metazoans. However, at a molecular level, little is currently understood about the molecular mechanisms that assemble these entities in germ cells. The discovery that in some animals, the gene products of a small number of lineage-specific genes initiate the assembly (also termed nucleation) of germ granules and/or germ plasm is the first step towards facilitating a better understanding of these complex biological processes. Here, we draw on research spanning over 100years that supports the hypothesis that these nucleator genes may have evolved convergently, allowing them to perform analogous roles across animal lineages. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Application of tumbling melt granulation (TMG) method to prepare controlled-release fine granules.

    Maejima, T; Kubo, M; Osawa, T; Nakajima, K; Kobayashi, M

    1998-03-01

    The tumbling melt granulation (TMG) method was applied to prepare controlled-release fine granules of diltiazem hydrochloride (DH). The entire process, from the preparation of the cores by the adherence of DH to the sucrose crystal to the subsequent coating of the controlled-release layer, was performed without using any solvent. A mixture of meltable material, talc, and ethylcellulose was used for the controlled-release layer and controlled-release fine granules approximately 400 microns in diameter were obtained with excellent producibility. The dissolution rate of DH from these fine granules was similar to that of a once-a-day dosage form obtained in the market; further, the dependency of the dissolution profile on pH of the media was less. Thus, it was concluded that this TMG method was very useful for preparing not only controlled-release beads of granule size (usually 500 to 1400 microns) but also fine granules.

  13. Role of calcium oxide in sludge granulation and methanogenesis for the treatment of palm oil mill effluent using UASB reactor

    Ahmad, Anwar; Ghufran, Rumana; Wahid, Zularisam Abd.

    2011-01-01

    Graphical abstract: SEM micrograph of granules; Outer surface of the granule; Scanning electron micrographs of the granule: Archaea (Methanosarcina sp.) showing the arrangement of bacterial cells in granule surrounded by extracellular polymeric substances (EPS), the seed sludge and granules sampled on day 150. Highlights: ► Examine the treatability of POME and effects of CaO–CKD on the granulation process in UASB reactors. ► The main objective was to determine the influent CaO–CKD concentration and the relationship between the CaO concentration in the feed and biomass accumulation, specific granulation, methanogenic activity, and the density and composition of granules. ► The biomass concentration profiles along the reactors and the size distribution of granules were also measured to track and to assess granulation, methanogenesis, and COD removal on levels at the industrial scale. ► SEM micrograph are showing smooth surface of granule with a large opening cavities likely for biogas escape. - Abstract: The granulation process in palm oil mill effluent using calcium oxide-cement kiln dust (CaO–CKD) provides an attractive and cost effective treatment option. In this study the efficiency of CaO–CKD at doses of 1.5–20 g/l was tested in batch experiments and found that 10 g of CaO/l caused the greatest degradation of VFA, butyrate and acetate. An upflow anaerobic sludge blanket (UASB) reactor was operated continuously at 35 °C for 150 days to investigate the effect of CaO–CKD on sludge granulation and methanogenesis during start-up. The treatment of POME emphasized the influence of varying organic loading rates (OLR). Up to 94.9% of COD was removed when the reactor was fed with the 15.5–65.5 g-COD g/l at an OLR of 4.5–12.5 kg-COD/m 3 d, suggesting the feasibility of using CaO in an UASB process to treat POME. The ratio of volatile solids/total solids (VS/TS) and volatile fatty acids in the anaerobic sludge in the UASB reactor decreased

  14. Role of calcium oxide in sludge granulation and methanogenesis for the treatment of palm oil mill effluent using UASB reactor

    Ahmad, Anwar, E-mail: anwarak218@yahoo.co.uk [Faculty of Civil Engineering and Earth Resources, University Malaysia Pahang (UMP), Lebuhraya Tun Razak, 26300 Gambang, Kuantan, Pahang (Malaysia); Ghufran, Rumana; Wahid, Zularisam Abd. [Faculty of Civil Engineering and Earth Resources, University Malaysia Pahang (UMP), Lebuhraya Tun Razak, 26300 Gambang, Kuantan, Pahang (Malaysia)

    2011-12-30

    Graphical abstract: SEM micrograph of granules; Outer surface of the granule; Scanning electron micrographs of the granule: Archaea (Methanosarcina sp.) showing the arrangement of bacterial cells in granule surrounded by extracellular polymeric substances (EPS), the seed sludge and granules sampled on day 150. Highlights: Black-Right-Pointing-Pointer Examine the treatability of POME and effects of CaO-CKD on the granulation process in UASB reactors. Black-Right-Pointing-Pointer The main objective was to determine the influent CaO-CKD concentration and the relationship between the CaO concentration in the feed and biomass accumulation, specific granulation, methanogenic activity, and the density and composition of granules. Black-Right-Pointing-Pointer The biomass concentration profiles along the reactors and the size distribution of granules were also measured to track and to assess granulation, methanogenesis, and COD removal on levels at the industrial scale. Black-Right-Pointing-Pointer SEM micrograph are showing smooth surface of granule with a large opening cavities likely for biogas escape. - Abstract: The granulation process in palm oil mill effluent using calcium oxide-cement kiln dust (CaO-CKD) provides an attractive and cost effective treatment option. In this study the efficiency of CaO-CKD at doses of 1.5-20 g/l was tested in batch experiments and found that 10 g of CaO/l caused the greatest degradation of VFA, butyrate and acetate. An upflow anaerobic sludge blanket (UASB) reactor was operated continuously at 35 Degree-Sign C for 150 days to investigate the effect of CaO-CKD on sludge granulation and methanogenesis during start-up. The treatment of POME emphasized the influence of varying organic loading rates (OLR). Up to 94.9% of COD was removed when the reactor was fed with the 15.5-65.5 g-COD g/l at an OLR of 4.5-12.5 kg-COD/m{sup 3} d, suggesting the feasibility of using CaO in an UASB process to treat POME. The ratio of volatile solids

  15. Soft x-ray imaging of intracellular granules of filamentous cyanobacterium generating musty smell in Lake Biwa

    Takemoto, K; Mizuta, G; Namba, H; Yamamoto, A; Kihara, H; Yoshimura, M; Ichise, S

    2013-01-01

    A planktonic blue-green algae, which are currently identified as Phormidium tenue, was observed by a soft x-ray microscopy (XM) for comparing a musty smell generating green strain (PTG) and a non-smell brown strain (PTB). By XM, cells were clearly imaged, and several intracellular granules which could not be observed under a light microscope were visualized. The diameter of granules was about 0.5–1 μm, and one or a few granules were seen in a cell. XM analyses showed that width of cells and sizes of intracellular granules were quite different between PTG and PTB strains. To study the granules observed by XM, transmission in more detail, transmission electron microscopy (TEM) and indirect fluorescent-antibody technique (IFA) were applied. By TEM, carboxysomes, thylakoids and polyphosphate granules were observed. IFA showed the presence of carboxysomes. Results lead to the conclusion that intracellular granules observed under XM are carboxysomes or polyphosphate granules. These results demonstrate that soft XM is effective for analyzing fine structures of small organisms such as cyanobacterium, and for discriminating the strains which generates musty smells from others

  16. Morphological study of the solar granulation. Pt. 2

    Kawaguchi, I.

    1980-01-01

    A time sequence of granulation images of 46 min long has allowed us to make a detailed study of the evolution of granules in an area of approximately 17 x 17 on the solar surface; It is found that the granules evolve by repeated fragmentation into smaller granules or merging with adjacent ones and that there are few granules which appear in the intergranular lanes as new granules (Table III). The statistical nature of granules is as follows: (1) A family of granules is defined as a group of granules produced from a single granule by fragmentation or merging. The lifetime is estimated for single granules and for families of granules. The lifetime shows a close correlation with the maximum size of a single granule or with that of the largest granule belonging to a family (Figures 5 and 7). (2) The smaller the size, the more probably a granule will disappear without further fragmentation or merging. The granule whose size is larger than 2 will certainly split or merge as the next evolutional step (Table IV.). (orig.)

  17. Alkali-silica reactivity of expanded glass granules in structure of lightweight concrete

    Bumanis, G; Bajare, D; Korjakins, A; Locs, J

    2013-01-01

    Main component in the lightweight concrete, which provides its properties, is aggregate. A lot of investigations on alkali silica reaction (ASR) between cement and lightweight aggregates have been done with their results published in the academic literature. Whereas expanded glass granules, which is relatively new product in the market of building materials, has not been a frequent research object. Therefore lightweight granules made from waste glass and eight types of cement with different chemical and mineralogical composition were examined in this research. Expanded glass granules used in this research is commercially available material produced by Penostek. Lightweight concrete mixtures were prepared by using commercial chemical additives to improve workability of concrete. The aim of the study is to identify effect of cement composition to the ASR reaction which occurs between expanded glass granules and binder. Expanded glass granules mechanical and physical properties were determined. In addition, properties of fresh and hardened concrete were determined. The ASR test was processed according to RILEM AAR-2 testing recommendation. Tests with scanning electron microscope and microstructural investigations were performed for expanded glass granules and hardened concrete specimens before and after exposing them in alkali solution

  18. Atrial natriuretic peptide (ANP)-granules: ultrastructure ...

    AJB SERVER

    2006-12-29

    Dec 29, 2006 ... morphometry and function. Eliane Florencio ... granules is greatest in the right atrium followed by the left atrium and left auricle and right auricle, in this order. ... family: Atrial natriuretic peptide (ANP), Urodilatin, Brain natriuretic ...

  19. Analysis of carbohydrate storage granules in the diazotrophic cyanobacterium Cyanothece sp. PCC 7822

    Welkie, David G. [Purdue Univ., West Lafayette, IN (United States); Sherman, Debra M. [Purdue Univ., West Lafayette, IN (United States); Chrisler, William B. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Orr, Galya [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Sherman, Louis A. [Purdue Univ., West Lafayette, IN (United States)

    2013-10-19

    The unicellular diazotrophic cyanobacteria of the genus Cyanothece demonstrate oscillations in nitrogenase activity and H2 production when grown under 12h light-12h dark cycles. We established that Cyanothece sp. PCC 7822 allows for the construction of knock-out mutants and our objective was to improve the growth characteristics of this strain and to identify the nature of the intracellular storage granules. We report the physiological and morphological effects of reduction in nitrate and phosphate concentrations in BG-11 media on this strain. We developed a series of BG-11-derived growth media and monitored batch culture growth, nitrogenase activity and nitrogenase-mediated hydrogen production, culture synchronicity, and intracellular storage content. Reduction in NaNO3 and K2HPO4 concentrations from 17.6 and 0.23 mM to 4.41 and 0.06 mM, respectively, improved growth characteristics such as cell size and uniformity, and enhanced the rate of cell division. Cells grown in this low NP BG-11 were less complex, a parameter that related to the composition of the intracellular storage granules. Cells grown in low NP BG-11 had less polyphosphate, fewer polyhydroxybutyrate granules and many smaller granules became evident. Biochemical analysis and transmission electron microscopy using the histocytochemical PATO technique demonstrated that these small granules contained glycogen. The glycogen levels and the number of granules per cell correlated nicely with a 2.3 to 3.3-fold change from the minimum at L0 to the maximum at D0. The differences in granule morphology and enzymes between Cyanothece ATCC 51142 and Cyanothece PCC 7822 provide insights into the formation of large starch-like granules in some cyanobacteria.

  20. Actinomyces associated with persistent vaginal granulation tissue.

    Wai, Clifford Y; Nihira, Mikio A; Drewes, Peter G; Chang, Joe S; Siddiqui, Momin T; Hemsell, David L

    2005-01-01

    BACKGROUND: We report a case of symptomatic actinomycosis associated with vaginal suture erosion and granulation tissue refractory to conservative management, in an outpatient setting. CASE: Three months after total vaginal hysterectomy and uterosacral ligament vaginal vault suspension, a woman complained of painless, intermittent vaginal discharge and spotting. Despite cauterization of granulation tissue, vaginal spotting persisted for another month. On re-examination, braided polyester sutu...

  1. Mathematical model of melt flow channel granulator

    A. A. Kiselev

    2016-01-01

    Full Text Available Granulation of carbohydrate-vitamin-mineral supplements based on molasses is performed at a high humidity (26 %, so for a stable operation of granulator it is necessary to reveal its melt flow pattern. To describe melt non-isothermal flow in the granulator a mathematical model with following initial equations: continuity equation, motion equation and rheological equation – was developed. The following assumptions were adopted: the melt flow in the granulator is a steady laminar flow; inertial and gravity forces can be ignored; melt is an incompressible fluid; velocity gradient in the flow direction is much smaller than in the transverse direction; the pressure gradient over the cross section of the channel is constant; the flow is hydrodynamically fully developed; effects impact on the channel inlet and outlet may be neglected. Due to the assumptions adopted, it can be considered that in this granulator only velocity components in the x-direction are significant and all the members of the equation with the components and their derivatives with respect to the coordinates y and z can be neglected. The resulting solutions were obtained: the equation for the mean velocity, the equation for determining the volume flow, the formula for calculating of mean time of the melt being in the granulator, the equation for determining the shear stress, the equation for determining the shear rate and the equation for determining the pressure loss. The results of calculations of the equations obtained are in complete agreement with the experimental data; deviation range is 16–19 %. The findings about the melt movement pattern in granulator allowed developing a methodology for calculating a rational design of the granulator molding unit.

  2. Digestion of Starch Granules from Maize, Potato and Wheat by Larvae of the the Yellow Mealworm, Tenebrio molitor and the Mexican Bean Weevil, Zabrotes subfasciatus

    Meireles, Elaine A.; Carneiro, Cíntia N. B.; DaMatta, Renato A.; Samuels, Richard I.; Silva, Carlos P.

    2009-01-01

    Scanning electron microscopy images were taken of starch granules from different sources following exposure in vivo and in vitro to gut α-amylases isolated from Tenebrio molitor L. (Coleoptera: Tenebrionidae) and Zabrotes subfasciatus Boheman (Coleoptera: Bruchidae). One α-amylase was isolated from whole larval midguts of T. molitor using non-denaturing SDS-PAGE, while two other α-amylase fractions were isolated from whole larval midguts of Z. subfasciatus using hydrophobic interaction chromatography., Digested starch granules from larvae fed on maize, potato or wheat were isolated from midgut contents. Combinations of starch granules with isolated α-amylases from both species showed similar patterns of granule degradation. In vitro enzymatic degradation of maize starch granules by the three different α-amylase fractions began by creating small holes and crater-like areas on the surface of the granules. Over time, these holes increased in number and area resulting in extensive degradation of the granule structure. Granules from potato did not show formation of pits and craters on their surface, but presented extensive erosion in their interior. For all types of starch, as soon as the interior of the starch granule was reached, the inner layers of amylose and amylopectin were differentially hydrolyzed, resulting in a striated pattern. These data support the hypothesis that the pattern of starch degradation depends more on the granule type than on the α-amylase involved. PMID:19619014

  3. Excess influx of Zn(2+) into dentate granule cells affects object recognition memory via attenuated LTP.

    Suzuki, Miki; Fujise, Yuki; Tsuchiya, Yuka; Tamano, Haruna; Takeda, Atsushi

    2015-08-01

    The influx of extracellular Zn(2+) into dentate granule cells is nonessential for dentate gyrus long-term potentiation (LTP) and the physiological significance of extracellular Zn(2+) dynamics is unknown in the dentate gyrus. Excess increase in extracellular Zn(2+) in the hippocampal CA1, which is induced with excitation of zincergic neurons, induces memory deficit via excess influx of Zn(2+) into CA1 pyramidal cells. In the present study, it was examined whether extracellular Zn(2+) induces object recognition memory deficit via excess influx of Zn(2+) into dentate granule cells. KCl (100 mM, 2 µl) was locally injected into the dentate gyrus. The increase in intracellular Zn(2+) in dentate granule cells induced with high K(+) was blocked by co-injection of CaEDTA and CNQX, an extracellular Zn(2+) chelator and an AMPA receptor antagonist, respectively, suggesting that high K(+) increases the influx of Zn(2+) into dentate granule cells via AMPA receptor activation. Dentate gyrus LTP induction was attenuated 1 h after KCl injection into the dentate gyrus and also attenuated when KCl was injected 5 min after the induction. Memory deficit was induced when training of object recognition test was performed 1 h after KCl injection into the dentate gyrus and also induced when KCl was injected 5 min after the training. High K(+)-induced impairments of LTP and memory were rescued by co-injection of CaEDTA. These results indicate that excess influx of Zn(2+) into dentate granule cells via AMPA receptor activation affects object recognition memory via attenuated LTP induction. Even in the dentate gyrus where is scarcely innervated by zincergic neurons, it is likely that extracellular Zn(2+) homeostasis is strictly regulated for cognition. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Simulating spinal border cells and cerebellar granule cells under locomotion--a case study of spinocerebellar information processing.

    Anton Spanne

    Full Text Available The spinocerebellar systems are essential for the brain in the performance of coordinated movements, but our knowledge about the spinocerebellar interactions is very limited. Recently, several crucial pieces of information have been acquired for the spinal border cell (SBC component of the ventral spinocerebellar tract (VSCT, as well as the effects of SBC mossy fiber activation in granule cells of the cerebellar cortex. SBCs receive monosynaptic input from the reticulospinal tract (RST, which is an important driving system under locomotion, and disynaptic inhibition from Ib muscle afferents. The patterns of activity of RST neurons and Ib afferents under locomotion are known. The activity of VSCT neurons under fictive locomotion, i.e. without sensory feedback, is also known, but there is little information on how these neurons behave under actual locomotion and for cerebellar granule cells receiving SBC input this is completely unknown. But the available information makes it possible to simulate the interactions between the spinal and cerebellar neuronal circuitries with a relatively large set of biological constraints. Using a model of the various neuronal elements and the network they compose, we simulated the modulation of the SBCs and their target granule cells under locomotion and hence generated testable predictions of their general pattern of modulation under this condition. This particular system offers a unique opportunity to simulate these interactions with a limited number of assumptions, which helps making the model biologically plausible. Similar principles of information processing may be expected to apply to all spinocerebellar systems.

  5. Proneurotrophin-3 promotes cell cycle withdrawal of developing cerebellar granule cell progenitors via the p75 neurotrophin receptor.

    Zanin, Juan Pablo; Abercrombie, Elizabeth; Friedman, Wilma J

    2016-07-19

    Cerebellar granule cell progenitors (GCP) proliferate extensively in the external granule layer (EGL) of the developing cerebellum prior to differentiating and migrating. Mechanisms that regulate the appropriate timing of cell cycle withdrawal of these neuronal progenitors during brain development are not well defined. The p75 neurotrophin receptor (p75(NTR)) is highly expressed in the proliferating GCPs, but is downregulated once the cells leave the cell cycle. This receptor has primarily been characterized as a death receptor for its ability to induce neuronal apoptosis following injury. Here we demonstrate a novel function for p75(NTR) in regulating proper cell cycle exit of neuronal progenitors in the developing rat and mouse EGL, which is stimulated by proNT3. In the absence of p75(NTR), GCPs continue to proliferate beyond their normal period, resulting in a larger cerebellum that persists into adulthood, with consequent motor deficits.

  6. Granule size control and targeting in pulsed spray fluid bed granulation.

    Ehlers, Henrik; Liu, Anchang; Räikkönen, Heikki; Hatara, Juha; Antikainen, Osmo; Airaksinen, Sari; Heinämäki, Jyrki; Lou, Honxiang; Yliruusi, Jouko

    2009-07-30

    The primary aim of the study was to investigate the effects of pulsed liquid feed on granule size. The secondary aim was to increase knowledge of this technique in granule size targeting. Pulsed liquid feed refers to the pump changing between on- and off-positions in sequences, called duty cycles. One duty cycle consists of one on- and off-period. The study was performed with a laboratory-scale top-spray fluid bed granulator with duty cycle length and atomization pressure as studied variables. The liquid feed rate, amount and inlet air temperature were constant. The granules were small, indicating that the powder has only undergone ordered mixing, nucleation and early growth. The effect of atomizing pressure on granule size depends on inlet air relative humidity, with premature binder evaporation as a reason. The duty cycle length was of critical importance to the end product attributes, by defining the extent of intermittent drying and rewetting. By varying only the duty cycle length, it was possible to control granule nucleation and growth, with a wider granule size target range in increased relative humidity. The present study confirms that pulsed liquid feed in fluid bed granulation is a useful tool in end product particle size targeting.

  7. Study of light scattering by a granulated coated sphere - a model of granulated blood cells

    Yurkin, M.A.; de Kanter, D.; Hoekstra, A.G.

    2008-01-01

    We performed extensive simulations of light scattering by granulated coated sphere model using the discrete dipole approximation and varying model parameters in the ranges of sizes and refractive indices of granulated blood cells. We compared these results with predictions of Maxwell-Garnett

  8. Investigation of Physicochemical Drug Properties to Prepare Fine Globular Granules Composed of Only Drug Substance in Fluidized Bed Rotor Granulation.

    Mise, Ryohei; Iwao, Yasunori; Kimura, Shin-Ichiro; Osugi, Yukiko; Noguchi, Shuji; Itai, Shigeru

    2015-01-01

    The effect of some drug properties (wettability and particle size distribution) on granule properties (mean particle size, particle size distribution, sphericity, and granule strength) were investigated in a high (>97%) drug-loading formulation using fluidized bed rotor granulation. Three drugs: acetaminophen (APAP); ibuprofen (IBU); and ethenzamide (ETZ) were used as model drugs based on their differences in wettability and particle size distribution. Granules with mean particle sizes of 100-200 µm and a narrow particle size distribution (PSD) could be prepared regardless of the drug used. IBU and ETZ granules showed a higher sphericity than APAP granules, while APAP and ETZ granules exhibited higher granule strength than IBU. The relationship between drug and granule properties suggested that the wettability and the PSD of the drugs were critical parameters affecting sphericity and granule strength, respectively. Furthermore, the dissolution profiles of granules prepared with poorly water-soluble drugs (IBU and ETZ) showed a rapid release (80% release in 20 min) because of the improved wettability with granulation. The present study demonstrated for the first time that fluidized bed rotor granulation can prepare high drug-loaded (>97%) globular granules with a mean particle size of less than 200 µm and the relationship between physicochemical drug properties and the properties of the granules obtained could be readily determined, indicating the potential for further application of this methodology to various drugs.

  9. Atividade das fosfodiesterases em tecido de granulação submetido a irradiação de elétrons - estudo experimental em ratos Activity of phosphodiesterases in granulation tissue submitted to electron irradiation - experimental study in rats

    Frab Norberto BÓSCOLO

    2001-09-01

    Full Text Available Os autores estudaram o efeito de baixas doses de radiação de elétrons na atividade de fosfodiesterases presentes no tecido de granulação, induzido por esponja de PVC, subcutaneamente, na região dorsal de 84 ratos Wistar, divididos em dois grupos, controle e irradiado. A atividade enzimática foi avaliada segundo a evolução do tecido de granulação aos 5, 7, 10, 14, 17, 20 e 24 dias. Os animais foram irradiados com um feixe de elétrons de 6 MeV, dose de 1 Gy, 3 dias após a implantação da esponja, sendo que no momento da irradiação, foram protegidos por uma lâmina de 4 mm de chumbo, tendo sido irradiada somente a área correspondente ao local onde encontrava-se a esponja. Considerando-se a dose e o tipo de radiação empregada, pode-se concluir que houve influência direta da radiação na atividade da enzima 5’-nucleotidase e da ATPase no início do processo de reparação tecidual, aos 5 e 7 dias. Já a enzima fosfatase alcalina não sofreu a ação direta da radiação. É possível que o principal fator tenha sido danos nos constituintes celulares que são responsáveis pela formação do tecido de granulação, determinando a produção enzimática conforme a necessidade.The present study evaluated the effect of low doses of electron radiation on the activity of phosphodiesterases in granulation tissue. In order to induce growth of granulation tissue, a PVC sponge disk was introduced under the dorsal skin of 84 Wistar rats. The rats were divided in two groups, control and irradiated. The enzymatic activity was evaluated according to the evolution of the granulation tissue after 5, 7, 10, 14, 17, 20 and 24 days. Irradiation was carried out 3 days after the implantation of the sponge, by means of a linear accelerator, with energy of 6 MeV, and dose of 1.0 Gy. The results of this study showed that 5’-nucleotidase and ATPase had their activity directly affected by irradiation only in the beginning of the tissue repairing

  10. Status epilepticus increases mature granule cells in the molecular layer of the dentate gyrus in rats★

    Liang, Zhaoliang; Gao, Fei; Wang, Fajun; Wang, Xiaochen; Song, Xinyu; Liu, Kejing; Zhan, Ren-Zhi

    2013-01-01

    Enhanced neurogenesis in the dentate gyrus of the hippocampus following seizure activity, especially status epilepticus, is associated with ectopic residence and aberrant integration of newborn granule cells. Hilar ectopic granule cells may be detrimental to the stability of dentate circuitry by means of their electrophysiological properties and synaptic connectivity. We hypothesized that status epilepticus also increases ectopic granule cells in the molecular layer. Status epilepticus was induced in male Sprague-Dawley rats by intraperitoneal injection of pilocarpine. Immunostaining showed that many doublecortin-positive cells were present in the molecular layer and the hilus 7 days after the induction of status epilepticus. At least 10 weeks after status epilepticus, the estimated number of cells positive for both prospero homeobox protein 1 and neuron-specific nuclear protein in the hilus was significantly increased. A similar trend was also found in the molecular layer. These findings indicate that status epilepticus can increase the numbers of mature and ectopic newborn granule cells in the molecular layer. PMID:25206705

  11. Wolfram syndrome 1 gene (WFS1) product localizes to secretory granules and determines granule acidification in pancreatic beta-cells.

    Hatanaka, Masayuki; Tanabe, Katsuya; Yanai, Akie; Ohta, Yasuharu; Kondo, Manabu; Akiyama, Masaru; Shinoda, Koh; Oka, Yoshitomo; Tanizawa, Yukio

    2011-04-01

    Wolfram syndrome is an autosomal recessive disorder characterized by juvenile-onset insulin-dependent diabetes mellitus and optic atrophy. The gene responsible for the syndrome (WFS1) encodes an endoplasmic reticulum (ER) resident transmembrane protein. The Wfs1-null mouse exhibits progressive insulin deficiency causing diabetes. Previous work suggested that the function of the WFS1 protein is connected to unfolded protein response and to intracellular Ca(2+) homeostasis. However, its precise molecular function in pancreatic β-cells remains elusive. In our present study, immunofluorescent and electron-microscopic analyses revealed that WFS1 localizes not only to ER but also to secretory granules in pancreatic β-cells. Intragranular acidification was assessed by measuring intracellular fluorescence intensity raised by the acidotrophic agent, 3-[2,4-dinitroanilino]-3'-amino-N-methyldipropyramine. Compared with wild-type β-cells, there was a 32% reduction in the intensity in WFS1-deficient β-cells, indicating the impairment of granular acidification. This phenotype may, at least partly, account for the evidence that Wfs1-null islets have impaired proinsulin processing, resulting in an increased circulating proinsulin level. Morphometric analysis using electron microscopy evidenced that the density of secretory granules attached to the plasma membrane was significantly reduced in Wfs1-null β-cells relative to that in wild-type β-cells. This may be relevant to the recent finding that granular acidification is required for the priming of secretory granules preceding exocytosis and may partly explain the fact that glucose-induced insulin secretion is profoundly impaired in young prediabetic Wfs1-null mice. These results thus provide new insights into the molecular mechanisms of β-cell dysfunction in patients with Wolfram syndrome.

  12. Stress granules at the intersection of autophagy and ALS.

    Monahan, Zachary; Shewmaker, Frank; Pandey, Udai Bhan

    2016-10-15

    Amyotrophic lateral sclerosis (ALS) is a progressive, fatal disease caused by loss of upper and lower motor neurons. The majority of ALS cases are classified as sporadic (80-90%), with the remaining considered familial based on patient history. The last decade has seen a surge in the identification of ALS-causing genes - including TARDBP (TDP-43), FUS, MATR3 (Matrin-3), C9ORF72 and several others - providing important insights into the molecular pathways involved in pathogenesis. Most of the protein products of ALS-linked genes fall into two functional categories: RNA-binding/homeostasis and protein-quality control (i.e. autophagy and proteasome). The RNA-binding proteins tend to be aggregation-prone with low-complexity domains similar to the prion-forming domains of yeast. Many also incorporate into stress granules (SGs), which are cytoplasmic ribonucleoprotein complexes that form in response to cellular stress. Mutant forms of TDP-43 and FUS perturb SG dynamics, lengthening their cytoplasmic persistence. Recent evidence suggests that SGs are regulated by the autophagy pathway, suggesting a unifying connection between many of the ALS-linked genes. Persistent SGs may give rise to intractable aggregates that disrupt neuronal homeostasis, thus failure to clear SGs by autophagic processes may promote ALS pathogenesis. This article is part of a Special Issue entitled SI:Autophagy. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. A Survey of Sludge Granulation Theories Under Anaerobic Conditions

    Jalal Shayegan

    2011-01-01

    Full Text Available This paper surveys the different theories developed on anaerobic sludge granulation. The theories are generally categorized as physical, microbial, and thermodynamic approaches. In the physical approach to the granulation process, granulation is described by such physical conditions of the reactor as upflow velocity of gas and liquid streams, suspended solids in the effluent flow, and excess sludge removal. Microbial theories are based on the properties of specific organisms and on granule properties (granule structure and its microbiology. The thermodynamic approach studies such factors as hydrophobia, electrophoretic mobility, effective energy in granule adhesion process, and effect of proton transferring activities on bacterial membrane surfaces.

  14. Study of granulated nickel alloy superplasticity

    Anoshkin, N.F.; Fatkullin, O.Kh.; Ermanok, M.Z.; Sharshagin, N.A.

    1982-01-01

    Peculiarities of the structure and properties of compact material obtained from granules of the EhI 698 and ZhS6U alloys in the form of pressed rods are investigated. It is shown, that granule metallurgy is the most rational technology method, ensuring the receipt of stable fine-grained structure in the initial blank. After appropriate thermal treatment the products obtained by the method of granule metallyrgy have more high strength characteristics at the room temperature and heat resistance, than typical for the products produced by traditional technology. Creation of specialized vertical presses providing low rates of deformation as well as their equipment by vacuum mechanizms which permit to use a tool from molybdenum alloys is necessary for successful introduction into production of the processes of plastic metal working under conditions of superplasticity

  15. Antimicrobial-Coated Granules for Disinfecting Water

    Akse, James R.; Holtsnider, John T.; Kliestik, Helen

    2011-01-01

    Methods of preparing antimicrobialcoated granules for disinfecting flowing potable water have been developed. Like the methods reported in the immediately preceding article, these methods involve chemical preparation of substrate surfaces (in this case, the surfaces of granules) to enable attachment of antimicrobial molecules to the surfaces via covalent bonds. A variety of granular materials have been coated with a variety of antimicrobial agents that include antibiotics, bacteriocins, enzymes, bactericides, and fungicides. When employed in packed beds in flowing water, these antimicrobial-coated granules have been proven effective against gram-positive bacteria, gram-negative bacteria, fungi, and viruses. Composite beds, consisting of multiple layers containing different granular antimicrobial media, have proven particularly effective against a broad spectrum of microorganisms. These media have also proven effective in enhancing or potentiating the biocidal effects of in-line iodinated resins and of very low levels of dissolved elemental iodine.

  16. Biosorption of Sr(II) from aqueous solutions using aerobic granules. Equilibrium and mechanisms

    Li Wang; Xiang Liu; Xiao-feng Chen; Duu-Jong Lee; Joo-Hwa Tay; Yi Zhang; Chun-li Wan

    2015-01-01

    Aqueous strontium biosorption using aerobic granules was investigated. Parameters affecting the biosorption were optimized, including initial pH, biomass dosage, temperature, and rotation speed. The equilibrium data were fitted using Langmuir and Freundlich models, and both could well describe the process (R 2 = 0.987 and 0.989, respectively). Ion exchange and water-desorption experiments were conducted, and ion exchange together with physical adsorption were found to be the main mechanisms. The aerobic granules were characterized with methods including scanning electron microscopy, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy. The results showed that surface complexation could also be involved in the Sr(II) biosorption. (author)

  17. Lemongrass Oil Granules AS Aedes Aegypti Larvicide

    Mulyani, Sri

    2014-01-01

    One way to prevent the spread of Haemorrhage Dengue Fever is the use of abate. The use of abate as larvicides often complained causing an unpleasant smell, and can cause resistance. Lemongrass oil is reported to have activity as larvicides, and this study aims to make granules of lemongrass oil preparation, as well as determining the value of LC50, LC90 against larvae of Ae. aegypti instar III. The granules of lemongrass oil preparation are made with lactose filler and binder CMC-Na. Larvicid...

  18. Method of producing granulated ceramic nuclear fuels

    Wilkinson, W.L.

    1976-01-01

    For the production of granulated ceramic nuclear fuels with a grain size spectrum as narrow as possible it is proposed to suspend the nuclear fuel powder in a non-aqueous solvent with small content of hydrogen (e.g. chloridized hydrocarbons) while adding a binding agent and then dry it by means of rays. As binding agent polybutyl methane acrylate in dibutyl phthalate is proposed. The method is described by the example of UO 2 -powder in trichloroethylene. The dry granulated material is produced in one working step. (UWI) [de

  19. Arachnoid granulation affected by subarachnoid hemorrhage

    R.P. Chopard

    1993-11-01

    Full Text Available The purpose of this study was to investigate using light microscopy the fibro-cellular components of arachnoid granulations affected by mild and severe subarachnoid hemorrage. The erythrocytes were in the channels delimitated by collagenous and elastic bundles and arachnoid cells, showing their tortuous and intercommunicating row from the pedicle to the fibrous capsule. The core portion of the pedicle and the center represented a principal route to the bulk outflow of cerebrospinal fluid and erythrocytes. In the severe hemorrhage, the fibrocellular components are desorganized, increasing the extracellular channels. We could see arachnoid granulations without erythrocytes, which cells showed big round nucleous suggesting their transformation into phagocytic cells.

  20. Creep of granulated loose-fill insulation

    Rasmussen, Torben Valdbjørn

    This report presents a proposal for a standardised method for creep tests and the necessary theoretical framework that can be used to describe creep of a granulated loose-fill material. Furthermore results from a round robin test are shown. The round robin test was carried out in collaboration...... with SP-Building Physics in Sweden and VTT Building Technology in Finland. For the round robin test a cellulosic fibre insulation material was used. The proposed standardised method for creep tests and theories are limited to cases when the granulated loose-fill material is exposed to a constant...

  1. Molecular composition of IMP1 ribonucleoprotein granules

    Jønson, Lars; Vikesaa, Jonas; Krogh, Anders

    2007-01-01

    Localized mRNAs are transported to sites of local protein synthesis in large ribonucleoprotein (RNP) granules, but their molecular composition is incompletely understood. Insulin-like growth factor II mRNA-binding protein (IMP) zip code-binding proteins participate in mRNA localization, and in mo......Localized mRNAs are transported to sites of local protein synthesis in large ribonucleoprotein (RNP) granules, but their molecular composition is incompletely understood. Insulin-like growth factor II mRNA-binding protein (IMP) zip code-binding proteins participate in mRNA localization...

  2. Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress

    Gould, Elizabeth; Tanapat, Patima; McEwen, Bruce S.; Flügge, Gabriele; Fuchs, Eberhard

    1998-01-01

    Although granule cells continue to be added to the dentate gyrus of adult rats and tree shrews, this phenomenon has not been demonstrated in the dentate gyrus of adult primates. To determine whether neurons are produced in the dentate gyrus of adult primates, adult marmoset monkeys (Callithrix jacchus) were injected with BrdU and perfused 2 hr or 3 weeks later. BrdU is a thymidine analog that is incorporated into proliferating cells during S phase. A substantial number of cells in the dentate gyrus of adult monkeys incorporated BrdU and ≈80% of these cells had morphological characteristics of granule neurons and expressed a neuronal marker by the 3-week time point. Previous studies suggest that the proliferation of granule cell precursors in the adult dentate gyrus can be inhibited by stress in rats and tree shrews. To test whether an aversive experience has a similar effect on cell proliferation in the primate brain, adult marmoset monkeys were exposed to a resident-intruder model of stress. After 1 hr in this condition, the intruder monkeys were injected with BrdU and perfused 2 hr later. The number of proliferating cells in the dentate gyrus of the intruder monkeys was compared with that of unstressed control monkeys. We found that a single exposure to this stressful experience resulted in a significant reduction in the number of these proliferating cells. Our results suggest that neurons are produced in the dentate gyrus of adult monkeys and that the rate of precursor cell proliferation can be affected by a stressful experience. PMID:9501234

  3. Plantain starch granules morphology, crystallinity, structure transition, and size evolution upon acid hydrolysis.

    Hernández-Jaimes, C; Bello-Pérez, L A; Vernon-Carter, E J; Alvarez-Ramirez, J

    2013-06-05

    Plantain native starch was hydrolysed with sulphuric acid for twenty days. Hydrolysis kinetics was described by a logistic function, with a zero-order rate during the first seven days, followed by a slower kinetics dynamics at longer times. X-ray diffraction results revealed a that gradual increase in crystallinity occurred during the first seven days, followed by a decrease to values similar to those found in the native starch. Differential scanning calorimetry analysis suggested a sharp structure transition by the seventh day probably due to a molecular rearrangement of the starch blocklets and inhomogeneous erosion of the amorphous regions and semi crystalline lamellae. Scanning electron micrographs showed that starch granules morphology was continually degraded from an initial oval-like shape to irregular shapes due to aggregation effects. Granule size distribution broadened as hydrolysis time proceeded probably due to fragmentation and agglomeration phenomena of the hydrolysed starch granules. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Nano-structured silica coated mesoporous carbon micro-granules for potential application in water filtration

    Das, Avik; Sen, D.; Mazumder, S.; Ghosh, A. K.

    2017-05-01

    A novel nano-composite spherical micro-granule has been synthesized using a facile technique of solvent evaporation induced assembly of nanoparticles for potential application in water filtration. The spherical micro-granule is comprised of nano-structured shell of hydrophilic silica encapsulating a hydrophobic mesoporous carbon at the core. Hierarchical structure of such core-shell micro-granules has been rigorously characterized using small-angle neutron and X-ray scattering techniques and complemented with scanning electron microscopy. The hydrophilic silica envelope around the carbon core helps in incorporation of such granules into the hydrophilic polymeric ultra-filtration membrane. The interstitial micro-pores present in the silica shell can serve as water transport channels and the mesoporus carbon core enhances the separation performance due its well adsorption characteristics. It has been found that the incorporation of such granules inside the ultra-filtration membrane indeed enhances the water permeability as well as the separation performance in a significant way.

  5. Cdk5 regulates accurate maturation of newborn granule cells in the adult hippocampus.

    Sebastian Jessberger

    2008-11-01

    Full Text Available Newborn granule cells become functionally integrated into the synaptic circuitry of the adult dentate gyrus after a morphological and electrophysiological maturation process. The molecular mechanisms by which immature neurons and the neurites extending from them find their appropriate position and target area remain largely unknown. Here we show that single-cell-specific knockdown of cyclin-dependent kinase 5 (cdk5 activity in newborn cells using a retrovirus-based strategy leads to aberrant growth of dendritic processes, which is associated with an altered migration pattern of newborn cells. Even though spine formation and maturation are reduced in cdk5-deficient cells, aberrant dendrites form ectopic synapses onto hilar neurons. These observations identify cdk5 to be critically involved in the maturation and dendrite extension of newborn neurons in the course of adult neurogenesis. The data presented here also suggest a mechanistic dissociation between accurate dendritic targeting and subsequent synapse formation.

  6. Vaccine adjuvants: Tailor-made mast-cell granules

    Gunzer, Matthias

    2012-03-01

    Mast cells induce protective immune responses through secretion of stimulatory granules. Microparticles modelled after mast-cell granules are now shown to replicate and enhance the functions of their natural counterparts and to direct the character of the resulting immunity.

  7. Breakage and drying behaviour of granules in a continuous fluid bed dryer: Influence of process parameters and wet granule transfer.

    De Leersnyder, F; Vanhoorne, V; Bekaert, H; Vercruysse, J; Ghijs, M; Bostijn, N; Verstraeten, M; Cappuyns, P; Van Assche, I; Vander Heyden, Y; Ziemons, E; Remon, J P; Nopens, I; Vervaet, C; De Beer, T

    2018-03-30

    Although twin screw granulation has already been widely studied in recent years, only few studies addressed the subsequent continuous drying which is required after wet granulation and still suffers from a lack of detailed understanding. The latter is important for optimisation and control and, hence, a cost-effective practical implementation. Therefore, the aim of the current study is to increase understanding of the drying kinetics and the breakage and attrition phenomena during fluid bed drying after continuous twin screw granulation. Experiments were performed on a continuous manufacturing line consisting of a twin-screw granulator, a six-segmented fluid bed dryer, a mill, a lubricant blender and a tablet press. Granulation parameters were fixed in order to only examine the effect of drying parameters (filling time, drying time, air flow, drying air temperature) on the size distribution and moisture content of granules (both of the entire granulate and of size fractions). The wet granules were transferred either gravimetrically or pneumatically from the granulator exit to the fluid bed dryer. After a certain drying time, the moisture content reached an equilibrium. This drying time was found to depend on the applied airflow, drying air temperature and filling time. The moisture content of the granules decreased with an increasing drying time, airflow and drying temperature. Although smaller granules dried faster, the multimodal particle size distribution of the granules did not compromise uniform drying of the granules when the target moisture content was achieved. Extensive breakage of granules was observed during drying. Especially wet granules were prone to breakage and attrition during pneumatic transport, either in the wet transfer line or in the dry transfer line. Breakage and attrition of granules during transport and drying should be anticipated early on during process and formulation development by performing integrated experiments on the granulator

  8. Sodium phenylbutyrate coated granules (Pheburane). Defective urea synthesis: a welcome formulation.

    2015-02-01

    Compared with Ammonaps granules, Pheburane coated granules mask the unpleasant taste of sodium phenylbutyrate. A more precise dosing device is provided with the coated granules than with the uncoated granules (Ammonaps).

  9. Detection and Analysis of the Quality of Ibuprofen Granules

    Yu-bin, Ji; Xin, LI; Guo-song, Xin; Qin-bing, Xue

    2017-12-01

    The Ibuprofen Granules comprehensive quality testing to ensure that it is in accordance with the provisions of Chinese pharmacopoeia. With reference of Chinese pharmacopoeia, the Ibuprofen Granules is tested by UV, HPLC, in terms of grain size checking, volume deviation, weight loss on drying detection, dissolution rate detection, and quality evaluation. Results indicated that Ibuprofen Granules conform to the standards. The Ibuprofen Granules are qualified and should be permitted to be marketed.

  10. Cysteamine depletes prolactin (PRL) but does not alter the structure of PRL-containing granules in the anterior pituitary

    Weinstein, L.A.; Landis, D.M.; Sagar, S.M.; Millard, W.J.; Martin, J.B.

    1984-01-01

    Cysteamine causes a profound depletion of PRL in the anterior pituitary and in the systemic circulation, as measured by RIA and bioassay. However, electron microscopic study of PRL-containing cells in rat anterior pituitary does not reveal changes in secretory granule or cytoplasmic structure during the interval of depressed PRL content and of subsequent recovery to normal levels. In contrast to the results obtained by RIA, PRL-like immunoreactivity as detected by immunocyto-chemistry is present and similar to that of control preparations after cysteamine administration. We suggest that cysteamine alters PRL structure in secretory granules, probably by interacting with the disulfide bonds of PRL, thereby altering bioactivity and immunoreactivity. The presence of cysteamine-altered PRL in secretory granules does not seem to trigger degradation of granules by the lysosomal system

  11. Tracheostomy Decannulation: Suprastomal Granulation Tissue in ...

    Background: Suprastomal granulation tissue is a complication of tracheostomy which may make decannulation difficult and presents a therapeutic challenge to the Otorhinolaryngologists. The aims of this study therefore were to evaluate tracheostomy in black African population, determine the prevalence of suprastomal ...

  12. 21 CFR 520.1468 - Naproxen granules.

    2010-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1468 Naproxen granules. (a... musculoskeletal system of the horse. (2)(i) For oral maintenance therapy following initial intravenous dosage...

  13. Water Filtration through Homogeneous Granulated Charge

    A. M. Krautsou

    2005-01-01

    Full Text Available General relationship for calculation of water filtration through homogeneous granulated charge has been obtained. The obtained relationship has been compared with experimental data. Discrepancies between calculated and experimental values do not exceed 6 % throughout the entire investigated range.

  14. Multiple zebrafish atoh1 genes specify a diversity of neuronal types in the zebrafish cerebellum.

    Kidwell, Chelsea U; Su, Chen-Ying; Hibi, Masahiko; Moens, Cecilia B

    2018-06-01

    A single Atoh1 basic-helix-loop-helix transcription factor specifies multiple neuron types in the mammalian cerebellum and anterior hindbrain. The zebrafish genome encodes three paralagous atoh1 genes whose functions in cerebellum and anterior hindbrain development we explore here. With use of a transgenic reporter, we report that zebrafish atoh1c-expressing cells are organized in two distinct domains that are separated both by space and developmental time. An early isthmic expression domain gives rise to an extracerebellar population in rhombomere 1 and an upper rhombic lip domain gives rise to granule cell progenitors that migrate to populate all four granule cell territories of the fish cerebellum. Using genetic mutants we find that of the three zebrafish atoh1 paralogs, atoh1c and atoh1a are required for the full complement of granule neurons. Surprisingly, the two genes are expressed in non-overlapping granule cell progenitor populations, indicating that fish use duplicate atoh1 genes to generate granule cell diversity that is not detected in mammals. Finally, live imaging of granule cell migration in wildtype and atoh1c mutant embryos reveals that while atoh1c is not required for granule cell specification per se, it is required for granule cells to delaminate and migrate away from the rhombic lip. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. The influence of granulating solvents on drug release from tablets ...

    ... significantly lower than the other wet granulated tablets, but higher than the matrix tablets. The granulating solvent influenced the release of drug which increased with increase in the water content. Key Words: Grewia gum: Granulating solvents; Release mechanisms. Journal of Pharmacy and Bioresources Vol.1(1) 2004: ...

  16. 21 CFR 520.905b - Fenbendazole granules.

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Fenbendazole granules. 520.905b Section 520.905b... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.905b Fenbendazole granules. (a) Specifications. Each gram of granules contains 222 milligrams (mg) fenbendazole. (b) Sponsor. See...

  17. ALS mutant SOD1 interacts with G3BP1 and affects stress granule dynamics.

    Gal, Jozsef; Kuang, Lisha; Barnett, Kelly R; Zhu, Brian Z; Shissler, Susannah C; Korotkov, Konstantin V; Hayward, Lawrence J; Kasarskis, Edward J; Zhu, Haining

    2016-10-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Mutations in Cu/Zn superoxide dismutase (SOD1) are responsible for approximately 20 % of the familial ALS cases. ALS-causing SOD1 mutants display a gain-of-toxicity phenotype, but the nature of this toxicity is still not fully understood. The Ras GTPase-activating protein-binding protein G3BP1 plays a critical role in stress granule dynamics. Alterations in the dynamics of stress granules have been reported in several other forms of ALS unrelated to SOD1. To our surprise, the mutant G93A SOD1 transgenic mice exhibited pathological cytoplasmic inclusions that co-localized with G3BP1-positive granules in spinal cord motor neurons. The co-localization was also observed in fibroblast cells derived from familial ALS patient carrying SOD1 mutation L144F. Mutant SOD1, unlike wild-type SOD1, interacted with G3BP1 in an RNA-independent manner. Moreover, the interaction is specific for G3BP1 since mutant SOD1 showed little interaction with four other RNA-binding proteins implicated in ALS. The RNA-binding RRM domain of G3BP1 and two particular phenylalanine residues (F380 and F382) are critical for this interaction. Mutant SOD1 delayed the formation of G3BP1- and TIA1-positive stress granules in response to hyperosmolar shock and arsenite treatment in N2A cells. In summary, the aberrant mutant SOD1-G3BP1 interaction affects stress granule dynamics, suggesting a potential link between pathogenic SOD1 mutations and RNA metabolism alterations in ALS.

  18. Novel in situ self-assembly nanoparticles for formulating a poorly water-soluble drug in oral solid granules, improving stability, palatability, and bioavailability

    Guo S

    2016-04-01

    Full Text Available Shujie Guo,1 Kevin Pham,2 Diana Li,2 Scott R Penzak,3 Xiaowei Dong2 1State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Pharmaceutical Sciences, 3Department of Pharmacotherapy, University of North Texas Health Science Center, Fort Worth, TX, USA Purpose: The purpose of this study was to develop a novel lipid-based nanotechnology to formulate poorly water-soluble drugs in oral solid granules to improve stability, palatability, and bioavailability. Materials and methods: In one method, we prepared ritonavir (RTV nanoparticles (NPs by a microemulsion-precursor method and then converted the RTV NPs to solid granules by wet granulation to produce RTV NP-containing granules. In the other innovative method, we did not use water in the formulation preparation, and discovered novel in situ self-assembly nanoparticles (ISNPs. We prepared RTV ISNP granules that did not initially contain NPs, but spontaneously produced RTV ISNPs when the granules were introduced to water with gentle agitation. We fully characterized these RTV nanoformulations. We also used rats to test the bioavailability of RTV ISNP granules. Finally, an Astree electronic tongue was used to assess the taste of the RTV ISNP granules. Results: RTV NP-containing granules only had about 1% drug loading of RTV in the solid granules. In contrast, RTV ISNP granules achieved over 16% drug loading and were stable at room temperature over 24 weeks. RTV ISNPs had particle size between 160 nm and 300 nm with narrow size distribution. RTV ISNPs were stable in simulated gastric fluid for 2 hours and in simulated intestinal fluid for another 6 hours. The data from the electronic tongue showed that the RTV ISNP granules were similar in taste to blank ISNP granules, but were much different from RTV solution. RTV ISNP granules increased RTV bioavailability

  19. Amylolytic hydrolysis of native starch granules affected by granule surface area.

    Kim, J C; Kong, B W; Kim, M J; Lee, S H

    2008-11-01

    Initial stage of hydrolysis of native starch granules with various amylolytic enzymes, alpha-amylase from Bacillus subtilis, glucoamylase I (GA-I) and II (GA-II) from Aspergillus niger, and beta-amylase from sweet potato showed that the reaction was apparently affected by a specific surface area of the starch granules. The ratios of the reciprocal of initial velocity of each amylolytic hydrolysis for native potato and maize starch to that for rice with the amylolytic enzymes were nearly equivalent to the ratio of surface area per mass of the 2 starch granules to that of rice, that is, 6.94 and 2.25, respectively. Thus, the reciprocal of initial velocity of each enzymatic hydrolysis as expressed in a Lineweaver-Burk plot was a linear function of the reciprocal of surface area for each starch granule. As a result, it is concluded that amylolytic hydrolysis of native starch granules is governed by the specific surface area, not by the mass concentration, of each granule.

  20. Human oocyte cryopreservation and the fate of cortical granules.

    Ghetler, Yehudith; Skutelsky, Ehud; Ben Nun, Isaac; Ben Dor, Liah; Amihai, Dina; Shalgi, Ruth

    2006-07-01

    To examine the effect of the commonly used oocyte cryopreservation protocol on the cortical granules (CGs) of human immature germinal vesicle (GV) and mature metaphase II (MII) oocytes. Laboratory study. IVF unit. Unfertilized, intracytoplasmic sperm injected (ICSI) oocytes, and immature oocytes were cryopreserved using a slow freezing-rapid thawing program with 1,2-propanediol (PROH) as a cryoprotectant. Cortical granule exocytosis (CGE) was assessed by either confocal microscopy or transmission electron microscopy (TEM). The survival rates of frozen-thawed oocytes (mature and immature) were significantly lower compared with zygotes. Both mature and immature oocytes exhibited increased fluorescence after cryopreservation, indicating the occurrence of CGE. Mere exposure of oocytes to cryoprotectants induced CGE of 70% the value of control zygotes. The TEM revealed a drastic reduction in the amount of CGs at the cortex of frozen-thawed GV and MII oocytes, as well as appearance of vesicles in the ooplasm. The commonly used PROH freezing protocol for human oocytes resulted in extensive CGE. This finding explains why ICSI is needed to achieve fertilization of frozen-thawed human oocytes.

  1. COUP-TFI mitotically regulates production and migration of dentate granule cells and modulates hippocampal Cxcr4 expression.

    Parisot, Joséphine; Flore, Gemma; Bertacchi, Michele; Studer, Michèle

    2017-06-01

    Development of the dentate gyrus (DG), the primary gateway for hippocampal inputs, spans embryonic and postnatal stages, and involves complex morphogenetic events. We have previously identified the nuclear receptor COUP-TFI as a novel transcriptional regulator in the postnatal organization and function of the hippocampus. Here, we dissect its role in DG morphogenesis by inactivating it in either granule cell progenitors or granule neurons. Loss of COUP-TFI function in progenitors leads to decreased granule cell proliferative activity, precocious differentiation and increased apoptosis, resulting in a severe DG growth defect in adult mice. COUP-TFI-deficient cells express high levels of the chemokine receptor Cxcr4 and migrate abnormally, forming heterotopic clusters of differentiated granule cells along their paths. Conversely, high COUP-TFI expression levels downregulate Cxcr4 expression, whereas increased Cxcr4 expression in wild-type hippocampal cells affects cell migration. Finally, loss of COUP-TFI in postmitotic cells leads to only minor and transient abnormalities, and to normal Cxcr4 expression. Together, our results indicate that COUP-TFI is required predominantly in DG progenitors for modulating expression of the Cxcr4 receptor during granule cell neurogenesis and migration. © 2017. Published by The Company of Biologists Ltd.

  2. Dendrites of cerebellar granule cells correctly recognize their target axons for synaptogenesis in vitro.

    Ito, Shoko; Takeichi, Masatoshi

    2009-08-04

    Neural circuits are generated by precisely ordered synaptic connections among neurons, and this process is thought to rely on the ability of neurons to recognize specific partners. However, it is also known that neurons promiscuously form synapses with nonspecific partners, in particular when cultured in vitro, causing controversies about neural recognition mechanisms. Here we reexamined whether neurons can or cannot select particular partners in vitro. In the cerebellum, granule cell (GC) dendrites form synaptic connections specifically with mossy fibers, but not with climbing fibers. We cocultured GC neurons with pontine or inferior olivary axons, the major sources for mossy and climbing fibers, respectively, as well as with hippocampal axons as a control. The GC neurons formed synapses with pontine axons predominantly at the distal ends of their dendrites, reproducing the characteristic morphology of their synapses observed in vivo, whereas they failed to do so when combined with other axons. In the latter case, synaptic proteins could accumulate between axons and dendrites, but these synapses were randomly distributed throughout the contact sites, and also their synaptic vesicle recycling was anomalous. These observations suggest that GC dendrites can select their authentic partners for synaptogenesis even in vitro, forming the synapses with a GC-specific nature only with them.

  3. Pleomorphic (giant cell) carcinoma of the intestine. An immunohistochemical and electron microscopic study

    Bak, Martin; Teglbjaerg, P S

    1989-01-01

    reaction for neuron-specific enolase (NSE) was found in three tumors and a positive reaction for chromogranin was found in one tumor. On electron microscopic study, intracytoplasmic whorls of intermediate filaments were seen in the perinuclear area. Dense core "neurosecretory" granules were rarely seen......Pleomorphic (giant cell) carcinomas have been described in the lungs, thyroid, pancreas, and gallbladder. Two pleomorphic carcinomas of the small bowel and two of the large bowel are presented. On light microscopic study, the carcinomas were solid, without squamous or glandular differentiation...

  4. Calcium phosphate granules in the hepatopancreas of the blue crab Callinectes sapidus.

    Becker, G L; Chen, C H; Greenawalt, J W; Lehninger, A L

    1974-05-01

    The hepatopancreas of the adult male blue crab Callinectes sapidus in intermolt was found to contain substantial amounts of calcium, magnesium, and inorganic phosphorus, averaging about 260, 20, and 250 microg-atoms per g wet tissue, respectively, accounting for over 10% of the tissue dry weight. Electron microscopy of the intact tissue showed three qualitatively different granular structures having electron densities suggestive of high mineral content. After fractionation of the tissue using centrifugal techniques, almost 95% of the total mineral was found to reside in a heavy, nonmitochondrial particulate fraction(s). The bulk of the low-speed pellet consisted of relatively dense, roughly spherical granules 1-5 microm in diameter, which could be considerably purified by repeated suspension in water and low-speed sedimentation. In the electron microscope the isolated granules appeared basically similar to one of the three characteristic types of electron-dense granules seen in the intact tissue. Although the freshly isolated granules lost approximately 50% of their wet weight when dried at 105 degrees C, only 10% more was lost upon dry ashing at 450 degrees C, suggesting a fairly low content of organic material. Chemical analysis revealed calcium, magnesium, and inorganic phosphate at 5.7, 2.1, and 4.4 microg-atoms per mg dried granules, respectively, accounting for 69% of the dry weight of the fraction. By specific enzymatic assays, the freshly isolated granules were found to contain ATP, ADP, and AMP at levels of 0.13, 0.03, and 0.01 micromol/mg, or 8% of their total dry weight. The remainder of the total phosphorus contributed an additional 3%, whereas carbonate, citrate, oxalate, and protein each constituted no more than 1%. The mineral granules of the crab hepatopancreas appear to function as storage forms of calcium and phosphate during the intermolt period. This tissue appears promising as a model for study of the cellular events associated with biological

  5. Microbial Community Composition and Ultrastructure of Granules from a Full-Scale Anammox Reactor

    Gonzalez-Gil, Graciela

    2014-12-11

    Granules in anammox reactors contain besides anammox bacteria other microbial communities whose identity and relationship with the anammox bacteria are not well understood. High calcium concentrations are often supplied to anammox reactors to obtain sufficient bacterial aggregation and biomass retention. The aim of this study was to provide the first characterization of bacterial and archaeal communities in anammox granules from a full-scale anammox reactor and to explore on the possible role of calcium in such aggregates. High magnification imaging using backscattered electrons revealed that anammox bacteria may be embedded in calcium phosphate precipitates. Pyrosequencing of 16S rRNA gene fragments showed, besides anammox bacteria (Brocadiacea, 32 %), substantial numbers of heterotrophic bacteria Ignavibacteriacea (18 %) and Anaerolinea (7 %) along with heterotrophic denitrifiers Rhodocyclacea (9 %), Comamonadacea (3 %), and Shewanellacea (3 %) in the granules. It is hypothesized that these bacteria may form a network in which heterotrophic denitrifiers cooperate to achieve a well-functioning denitrification system as they can utilize the nitrate intrinsically produced by the anammox reaction. This network may provide a niche for the proliferation of archaea. Hydrogenotrophic methananogens, which scavenge the key fermentation product H2, were the most abundant archaea detected. Cells resembling the polygon-shaped denitrifying methanotroph Candidatus Methylomirabilis oxyfera were observed by electron microscopy. It is hypothesized that the anammox process in a full-scale reactor triggers various reactions overall leading to efficient denitrification and a sink of carbon as biomass in anammox granules.

  6. Microbial community composition and ultrastructure of granules from a full-scale anammox reactor.

    Gonzalez-Gil, Graciela; Sougrat, Rachid; Behzad, Ali R; Lens, Piet N L; Saikaly, Pascal E

    2015-07-01

    Granules in anammox reactors contain besides anammox bacteria other microbial communities whose identity and relationship with the anammox bacteria are not well understood. High calcium concentrations are often supplied to anammox reactors to obtain sufficient bacterial aggregation and biomass retention. The aim of this study was to provide the first characterization of bacterial and archaeal communities in anammox granules from a full-scale anammox reactor and to explore on the possible role of calcium in such aggregates. High magnification imaging using backscattered electrons revealed that anammox bacteria may be embedded in calcium phosphate precipitates. Pyrosequencing of 16S rRNA gene fragments showed, besides anammox bacteria (Brocadiacea, 32%), substantial numbers of heterotrophic bacteria Ignavibacteriacea (18%) and Anaerolinea (7%) along with heterotrophic denitrifiers Rhodocyclacea (9%), Comamonadacea (3%), and Shewanellacea (3%) in the granules. It is hypothesized that these bacteria may form a network in which heterotrophic denitrifiers cooperate to achieve a well-functioning denitrification system as they can utilize the nitrate intrinsically produced by the anammox reaction. This network may provide a niche for the proliferation of archaea. Hydrogenotrophic methananogens, which scavenge the key fermentation product H2, were the most abundant archaea detected. Cells resembling the polygon-shaped denitrifying methanotroph Candidatus Methylomirabilis oxyfera were observed by electron microscopy. It is hypothesized that the anammox process in a full-scale reactor triggers various reactions overall leading to efficient denitrification and a sink of carbon as biomass in anammox granules.

  7. Granulation of snow: From tumbler experiments to discrete element simulations

    Steinkogler, Walter; Gaume, Johan; Löwe, Henning; Sovilla, Betty; Lehning, Michael

    2015-06-01

    It is well known that snow avalanches exhibit granulation phenomena, i.e., the formation of large and apparently stable snow granules during the flow. The size distribution of the granules has an influence on flow behavior which, in turn, affects runout distances and avalanche velocities. The underlying mechanisms of granule formation are notoriously difficult to investigate within large-scale field experiments, due to limitations in the scope for measuring temperatures, velocities, and size distributions. To address this issue we present experiments with a concrete tumbler, which provide an appropriate means to investigate granule formation of snow. In a set of experiments at constant rotation velocity with varying temperatures and water content, we demonstrate that temperature has a major impact on the formation of granules. The experiments showed that granules only formed when the snow temperature exceeded -1∘C. No evolution in the granule size was observed at colder temperatures. Depending on the conditions, different granulation regimes are obtained, which are qualitatively classified according to their persistence and size distribution. The potential of granulation of snow in a tumbler is further demonstrated by showing that generic features of the experiments can be reproduced by cohesive discrete element simulations. The proposed discrete element model mimics the competition between cohesive forces, which promote aggregation, and impact forces, which induce fragmentation, and supports the interpretation of the granule regime classification obtained from the tumbler experiments. Generalizations, implications for flow dynamics, and experimental and model limitations as well as suggestions for future work are discussed.

  8. Super-resolution microscopy as a potential approach to diagnosis of platelet granule disorders.

    Westmoreland, D; Shaw, M; Grimes, W; Metcalf, D J; Burden, J J; Gomez, K; Knight, A E; Cutler, D F

    2016-04-01

    Many platelet functions are dependent on bioactive molecules released from their granules. Deficiencies of these granules in number, shape or content are associated with bleeding. The small size of these granules is such that imaging them for diagnosis has traditionally required electron microscopy. However, recently developed super-resolution microscopes provide sufficient spatial resolution to effectively image platelet granules. When combined with automated image analysis, these methods provide a quantitative, unbiased, rapidly acquired dataset that can readily and reliably reveal differences in platelet granules between individuals. To demonstrate the ability of structured illumination microscopy (SIM) to efficiently differentiate between healthy volunteers and three patients with Hermansky-Pudlak syndrome. Blood samples were taken from three patients with Hermansky-Pudlak syndrome and seven controls. Patients 1-3 have gene defects in HPS1, HPS6 and HPS5, respectively; all controls were healthy volunteers. Platelet-rich plasma was isolated from blood and the platelets fixed, stained for CD63 and processed for analysis by immunofluorescence microscopy, using a custom-built SIM microscope. SIM can successfully resolve CD63-positive structures in fixed platelets. A determination of the number of CD63-positive structures per platelet allowed us to conclude that each patient was significantly different from all of the controls with 99% confidence. A super-resolution imaging approach is effective and rapid in objectively differentiating between patients with a platelet bleeding disorder and healthy volunteers. CD63 is a useful marker for predicting Hermansky-Pudlak syndrome and could be used in the diagnosis of patients suspected of other platelet granule disorders. © 2016 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

  9. Factors Involved in Sludge Granulation under Anaerobic Conditions

    Jalal Shayegan

    2011-03-01

    Full Text Available This paper investigates the effects of factors involved in sludge anaerobic granulation. Granulated sludge formation is the main parameter contributing to the success of UASB reactors. Anaerobic granulation leads to reduced reactor size, space requirement, and investment costs. Operation costs are also greatly reduced due to lack of aeration. An important parameter affecting process performance is the size of sludge granules; the factors involved in granule size will be investigated. Some of the important parameters of anaerobic sludge granulation are: existence of growth cores as inert particles or granulated sludge, process operational conditions (Sludge Loading Rate and Organic Loading Rate, Loading rate increase and …, and environment conditions (nutrients, temperature, pH, combination and ….

  10. Giant renin secretory granules in beige mouse renal afferent arterioles

    Jensen, B L; Rasch, Ruth; Nyengaard, Jens Randel

    1997-01-01

    The mutant beige mouse (C57BL/6 bg) has a disease characterised by abnormally enlarged cytoplasmic granules in a variety of cells. With the purpose of establishing a suitable cellular model for studying renin secretion, the present study was undertaken to compare renin granule morphology in beige...... (average granular volume 0.681 microm3), whereas 1-2 large granules were present per cell in beige mice. The volume of afferent arteriole that contained secretory granules was lower in the beige mice. We conclude that the beige mouse synthesizes, stores and releases active renin. Renin secretory granules...... in beige mice are grossly enlarged with 1-2 granules per juxtaglomerular cell. Compared with control mice, a similar amount of total renin granule volume per afferent arteriole is contained in a smaller part of beige mouse afferent arteriole. Granular cells from beige mice could therefore be a valuable...

  11. Balloon cells associated with granule cell dispersion in the dentate gyrus in hippocampal sclerosis.

    Thom, M; Martinian, L; Caboclo, L O; McEvoy, A W; Sisodiya, S M

    2008-06-01

    Granule cell dispersion (GCD) is a common finding in hippocampal sclerosis in patients with intractable focal epilepsy. It is considered to be an acquired, post-developmental rather than a pre-existing abnormality, involving dispersion of either mature or newborn neurones, but the precise factors regulating it and its relationship to seizures are unknown. We present two cases of GCD with associated CD34-immunopositive balloon cells, a cell phenotype associated with focal cortical dysplasia type IIB, considered to be a developmental cortical lesion promoting epilepsy. This observation opens up the debate regarding the origin of balloon cells and CD34 expression and their temporal relationship to seizures.

  12. Increased accuracy of starch granule type quantification using mixture distributions.

    Tanaka, Emi; Ral, Jean-Phillippe F; Li, Sean; Gaire, Raj; Cavanagh, Colin R; Cullis, Brian R; Whan, Alex

    2017-01-01

    The proportion of granule types in wheat starch is an important characteristic that can affect its functionality. It is widely accepted that granule types are either large, disc-shaped A-type granules or small, spherical B-type granules. Additionally, there are some reports of the tiny C-type granules. The differences between these granule types are due to its carbohydrate composition and crystallinity which is highly, but not perfectly, correlated with the granule size. A majority of the studies that have considered granule types analyse them based on a size threshold rather than chemical composition. This is understandable due to the expense of separating starch into different types. While the use of a size threshold to classify granule type is a low-cost measure, this results in misclassification. We present an alternative, statistical method to quantify the proportion of granule types by a fit of the mixture distribution, along with an R package, a web based app and a video tutorial for how to use the web app to enable its straightforward application. Our results show that the reliability of the genotypic effects increase approximately 60% using the proportions of the A-type and B-type granule estimated by the mixture distribution over the standard size-threshold measure. Although there was a marginal drop in reliability for C-type granules. The latter is likely due to the low observed genetic variance for C-type granules. The determination of the proportion of granule types from size-distribution is better achieved by using the mixing probabilities from the fit of the mixture distribution rather than using a size-threshold.

  13. Light and electron microscopy of contacts between primary afferent fibres and neurones with axons ascending the dorsal columns of the feline spinal cord.

    Maxwell, D J; Koerber, H R; Bannatyne, B A

    1985-10-01

    In addition to primary afferent fibres, the dorsal columns of the cat spinal cord contain ascending second-order axons which project to the dorsal column nuclei. The aim of the present study was to obtain morphological evidence that certain primary afferent axons form monosynaptic contacts with cells of origin of this postsynaptic dorsal column pathway. In ten adult cats, neurones with axons ascending the dorsal columns were retrogradely labelled with horseradish peroxidase using a pellet implantation method in the thoracic dorsal columns. In the lumbosacral regions of the same animals, primary afferent fibres were labelled intra-axonally with ionophoretic application of horseradish peroxidase. Tissue containing labelled axons was prepared for light and combined light and electron microscopy. Ultrastructural examination demonstrated that slowly adapting (Type I), hair follicle, Pacinian corpuscle and group Ia muscle spindle afferents formed monosynaptic contacts with labelled cells and light microscopical analysis suggested that they also received monosynaptic input from rapidly adapting (Krause) afferents. This evidence suggests that sensory information from large-diameter cutaneous and muscle spindle afferent fibres is conveyed disynaptically via the postsynaptic dorsal column pathway to the dorsal column nuclei. Some of the input to this pathway is probably modified in the spinal cord as the majority of primary afferent boutons forming monosynaptic contacts were postsynaptic to other axon terminals. The postsynaptic dorsal column system appears to constitute a major somatosensory pathway in the cat.

  14. Electron-microscopic characteristics of neuroendocrine neurons in the amygdaloid body of the brain in male rats and female rats at different stages of the estral cycle.

    Akhmadeev, A V; Kalimullina, L B

    2008-01-01

    The ultrastructural features of neuroendocrine neurons in the dorsomedial nucleus (DMN) of the amygdaloid body of the brain - one of the major zones of sexual dimorphism - in 12 Wistar rats weighing 250-300 g were studied in three males and nine females at different stages of the estral cycle. On the basis of ultrastructural characteristics, analysis of the functional states of an average of 50 DMN neurons were studied in each animal. A morphofunctional classification reflecting hormone-dependent variations in neuron activity is proposed. DMN neurons were found to be in different structural-functional states, which could be classified as the states of rest, moderate activity, elevated activity, tension (maximal activity), decreased activity (types 1 and 2, depending on prior history), return to the initial state, and apoptosis. At the estrus stage, there was a predominance of neurons in the states of elevated activity (40% of all cells) and maximal activity (26%). At the metestrus stage, neurons in the state of decreased activity type 1 (with increased nuclear heterochromatin content) predominated (30% of cells), while 25% and 20% of cells were in the states of maximal activity and elevated activity respectively. In diestrus, neurons in the resting state, in moderate and elevated activity, in maximal activity, and in decreased activity type 1 were present in essentially identical proportions (18%, 21%, 18%, 20%, and 16% respectively). In males, 35% and 22% of neurons were in the states of elevated and maximal activity respectively. Neuron death was seen only in males.

  15. Microbial granulation for lactic acid production

    Kim, Dong-Hoon; Lee, Mo-Kwon; Hwang, Yuhoon

    2016-01-01

    This work investigated the formation of microbial granules to boost the productivity of lactic acid (LA). The flocculated form of LA-producing microbial consortium, dominated by Lactobacillus sp. (91.5% of total sequence), was initially obtained in a continuous stirred-tank reactor (CSTR), which...... increased, reaching 67 g L-fermenter−1h−1 at HRT 0.17 h. The size of LA-producing granules and hydrophobicity gradually increased with decrease in HRT, reaching 6.0 mm and 60%, respectively. These biogranules were also found to have high settling velocities and low porosities, ranging 2.69-4.73 cm s−1 and 0...

  16. Autoradiographic detection of [125I]-secondary antiserum: a sensitive light and electron microscopic labeling method compatible with peroxidase immunocytochemistry for dual localization of neuronal antigens

    Pickel, V.M.; Chan, J.; Milner, T.A.

    1986-01-01

    We examined whether autoradiographic localization of [ 125 I]-antirabbit immunoglobulin (IgG) was suitable for light and electron microscopic detection of a rabbit antiserum to the catecholamine-synthesizing enzyme, tyrosine hydroxylase (TH), and whether autoradiographic and peroxidase labeling could be combined for simultaneous immunocytochemical identification of TH and neuropeptides in brain. Adult rat brains were fixed by aortic arch perfusion with acrolein and paraformaldehyde. Vibratome sections of the fixed tissues were incubated with various dilutions of TH antiserum followed by [ 125 I]-secondary IgG. These sections were then directly processed for autoradiography or were incubated with rabbit antiserum to substance P (SP) or methionine [Met5]-enkephalin (ME). These latter sections were then processed by the peroxidase-antiperoxidase (PAP) or conjugated peroxidase methods followed by autoradiography. Exposure periods of 12-20 days for light microscopy or 90 days for electron microscopy yielded substantial accumulations of silver grains even at the highest (1:30,000) dilution of TH antiserum. At this dilution, immunoreactivity for TH was virtually nondetectable by PAP and conjugated peroxidase methods. The differential sensitivities of the autoradiographic versus peroxidase methods provided a means for separable identification of rabbit antiserum to TH and to SP or ME. Ultrastructural analysis of the catecholaminergic neurons in the medial nuclei of the solitary tract (NTS) showed selective cytoplasmic localization of silver grains for [ 125 I]-labeling of TH in perikarya, dendrites, and terminals. Within single thin sections prepared for dual labeling, the peroxidase marker for SP and for ME was differentially localized with respect to autoradiographic labeling of TH

  17. Oscillating behavior of carbohydrate granule formation and dinitrogen fixation in the cyanobacterium Cyanothece sp. strain ATCC 51142

    Schneegurt, M. A.; Sherman, D. M.; Nayar, S.; Sherman, L. A.; Mitchell, C. A. (Principal Investigator)

    1994-01-01

    It has been shown that some aerobic, unicellular, diazotrophic cyanobacteria temporally separate photosynthetic O2 evolution and oxygen-sensitive N2 fixation. Cyanothece sp. ATCC strain 51142 is an aerobic, unicellular, diazotrophic cyanobacterium that fixes N2 during discrete periods of its cell cycle. When the bacteria are maintained under diurnal light-dark cycles, N2 fixation occurs in the dark. Similar cycling is observed in continuous light, implicating a circadian rhythm. Under N2-fixing conditions, large inclusion granules form between the thylakoid membranes. Maximum granulation, as observed by electron microscopy, occurs before the onset of N2 fixation, and the granules decrease in number during the period of N2 fixation. The granules can be purified from cell homogenates by differential centrifugation. Biochemical analyses of the granules indicate that these structures are primarily carbohydrate, with some protein. Further analyses of the carbohydrate have shown that it is a glucose polymer with some characteristics of glycogen. It is proposed that N2 fixation is driven by energy and reducing power stored in these inclusion granules. Cyanothece sp. strain ATCC 51142 represents an excellent experimental organism for the study of the protective mechanisms of nitrogenase, metabolic events in cyanobacteria under normal and stress conditions, the partitioning of resources between growth and storage, and biological rhythms.

  18. PTEN deletion from adult-generated dentate granule cells disrupts granule cell mossy fiber axon structure.

    LaSarge, Candi L; Santos, Victor R; Danzer, Steve C

    2015-03-01

    Dysregulation of the mTOR-signaling pathway is implicated in the development of temporal lobe epilepsy. In mice, deletion of PTEN from hippocampal dentate granule cells leads to mTOR hyperactivation and promotes the rapid onset of spontaneous seizures. The mechanism by which these abnormal cells initiate epileptogenesis, however, is unclear. PTEN-knockout granule cells develop abnormally, exhibiting morphological features indicative of increased excitatory input. If these cells are directly responsible for seizure genesis, it follows that they should also possess increased output. To test this prediction, dentate granule cell axon morphology was quantified in control and PTEN-knockout mice. Unexpectedly, PTEN deletion increased giant mossy fiber bouton spacing along the axon length, suggesting reduced innervation of CA3. Increased width of the mossy fiber axon pathway in stratum lucidum, however, which likely reflects an unusual increase in mossy fiber axon collateralization in this region, offsets the reduction in boutons per axon length. These morphological changes predict a net increase in granule cell innervation of CA3. Increased diameter of axons from PTEN-knockout cells would further enhance granule cell communication with CA3. Altogether, these findings suggest that amplified information flow through the hippocampal circuit contributes to seizure occurrence in the PTEN-knockout mouse model of temporal lobe epilepsy. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Spatio-temporal Dynamics and Mechanisms of Stress Granule Assembly.

    Daisuke Ohshima

    2015-06-01

    Full Text Available Stress granules (SGs are non-membranous cytoplasmic aggregates of mRNAs and related proteins, assembled in response to environmental stresses such as heat shock, hypoxia, endoplasmic reticulum (ER stress, chemicals (e.g. arsenite, and viral infections. SGs are hypothesized as a loci of mRNA triage and/or maintenance of proper translation capacity ratio to the pool of mRNAs. In brain ischemia, hippocampal CA3 neurons, which are resilient to ischemia, assemble SGs. In contrast, CA1 neurons, which are vulnerable to ischemia, do not assemble SGs. These results suggest a critical role SG plays in regards to cell fate decisions. Thus SG assembly along with its dynamics should determine the cell fate. However, the process that exactly determines the SG assembly dynamics is largely unknown. In this paper, analyses of experimental data and computer simulations were used to approach this problem. SGs were assembled as a result of applying arsenite to HeLa cells. The number of SGs increased after a short latent period, reached a maximum, then decreased during the application of arsenite. At the same time, the size of SGs grew larger and became localized at the perinuclear region. A minimal mathematical model was constructed, and stochastic simulations were run to test the modeling. Since SGs are discrete entities as there are only several tens of them in a cell, commonly used deterministic simulations could not be employed. The stochastic simulations replicated observed dynamics of SG assembly. In addition, these stochastic simulations predicted a gamma distribution relative to the size of SGs. This same distribution was also found in our experimental data suggesting the existence of multiple fusion steps in the SG assembly. Furthermore, we found that the initial steps in the SG assembly process and microtubules were critical to the dynamics. Thus our experiments and stochastic simulations presented a possible mechanism regulating SG assembly.

  20. Registering parameters and granules of wave observations: IMAGE RPI success story

    Galkin, I. A.; Charisi, A.; Fung, S. F.; Benson, R. F.; Reinisch, B. W.

    2015-12-01

    . Numerical data products include plasmagram-derived records containing signatures of local and remote signal propagation, as well as field-aligned profiles of electron density in the plasmasphere. Registered granules of RPI observations are available in ESPAS for their content-targeted search and retrieval.

  1. Granule fraction inhomogeneity of calcium carbonate/sorbitol in roller compacted granules

    Bacher, Charlotte; Olsen, P.M.; Bertelsen, P.

    2008-01-01

    The granule fraction inhomogeneity of roller compacted granules was examined on mixtures of three different morphologic forms of calcium carbonate and three particle sizes of sorbitol. The granule fraction inhomogeneity was determined by the distribution of the calcium carbonate in each of the 10...... size fractions between 0 and 2000 µm and by calculating the demixing potential. Significant inhomogeneous occurrence of calcium carbonate in the size fractions was demonstrated, depending mostly on the particles sizes of sorbitol but also on the morphological forms of calcium carbonate......, the ability of the powder to agglomerate in the roller compactor was demonstrated to be related to the ability of the powder to be compacted into a tablet, thus the most compactable calcium carbonate and the smallest sized sorbitol improved the homogeneity by decreasing the demixing potential....

  2. Reliable activation of immature neurons in the adult hippocampus.

    Lucas A Mongiat

    Full Text Available Neurons born in the adult dentate gyrus develop, mature, and connect over a long interval that can last from six to eight weeks. It has been proposed that, during this period, developing neurons play a relevant role in hippocampal signal processing owing to their distinctive electrical properties. However, it has remained unknown whether immature neurons can be recruited into a network before synaptic and functional maturity have been achieved. To address this question, we used retroviral expression of green fluorescent protein to identify developing granule cells of the adult mouse hippocampus and investigate the balance of afferent excitation, intrinsic excitability, and firing behavior by patch clamp recordings in acute slices. We found that glutamatergic inputs onto young neurons are significantly weaker than those of mature cells, yet stimulation of cortical excitatory axons elicits a similar spiking probability in neurons at either developmental stage. Young neurons are highly efficient in transducing ionic currents into membrane depolarization due to their high input resistance, which decreases substantially in mature neurons as the inward rectifier potassium (Kir conductance increases. Pharmacological blockade of Kir channels in mature neurons mimics the high excitability characteristic of young neurons. Conversely, Kir overexpression induces mature-like firing properties in young neurons. Therefore, the differences in excitatory drive of young and mature neurons are compensated by changes in membrane excitability that render an equalized firing activity. These observations demonstrate that the adult hippocampus continuously generates a population of highly excitable young neurons capable of information processing.

  3. Competition from newborn granule cells does not drive axonal retraction of silenced old granule cells in the adult hippocampus

    Carla M Lopez

    2012-11-01

    Full Text Available In the developing nervous system synaptic refinement, typified by the neuromuscular junction where supernumerary connections are eliminated by axon retraction leaving the postsynaptic target innervated by a single dominant input, critically regulates neuronal circuit formation. Whether such competition based pruning continues in established circuits of mature animals remains unknown. This question is particularly relevant in the context of adult neurogenesis where newborn cells must integrate into preexisting circuits, and thus, potentially compete with functionally mature synapses to gain access to their postsynaptic targets. The hippocampus plays an important role in memory formation/retrieval and the dentate gyrus subfield (DG exhibits continued neurogenesis into adulthood. Therefore, this region contains both mature granule cells (old GCs and immature recently born GCs that are generated throughout adult life (young GCs, providing a neurogenic niche model to examine the role of competition in synaptic refinement. Recent work from an independent group in developing animals indicated that embryonically/early postnatal generated GCs placed at a competitive disadvantage by selective expression of tetanus toxin (TeTX to prevent synaptic release rapidly retracted their axons, and that this retraction was driven by competition from newborn GCs lacking TeTX. In contrast, following 3-6 months of selective TeTX expression in old GCs of adult mice we did not observe any evidence of axon retraction. Indeed ultrastructural analyses indicated that the terminals of silenced GCs even maintained synaptic contact with their postsynaptic targets. Furthermore, we did not detect any significant differences in the electrophysiological properties between old GCs in control and TeTX conditions. Thus, our data demonstrate a remarkable stability in the face of a relatively prolonged period of altered synaptic competition between two populations of neurons within the

  4. Neuron Morphology Influences Axon Initial Segment Plasticity.

    Gulledge, Allan T; Bravo, Jaime J

    2016-01-01

    In most vertebrate neurons, action potentials are initiated in the axon initial segment (AIS), a specialized region of the axon containing a high density of voltage-gated sodium and potassium channels. It has recently been proposed that neurons use plasticity of AIS length and/or location to regulate their intrinsic excitability. Here we quantify the impact of neuron morphology on AIS plasticity using computational models of simplified and realistic somatodendritic morphologies. In small neurons (e.g., dentate granule neurons), excitability was highest when the AIS was of intermediate length and located adjacent to the soma. Conversely, neurons having larger dendritic trees (e.g., pyramidal neurons) were most excitable when the AIS was longer and/or located away from the soma. For any given somatodendritic morphology, increasing dendritic membrane capacitance and/or conductance favored a longer and more distally located AIS. Overall, changes to AIS length, with corresponding changes in total sodium conductance, were far more effective in regulating neuron excitability than were changes in AIS location, while dendritic capacitance had a larger impact on AIS performance than did dendritic conductance. The somatodendritic influence on AIS performance reflects modest soma-to-AIS voltage attenuation combined with neuron size-dependent changes in AIS input resistance, effective membrane time constant, and isolation from somatodendritic capacitance. We conclude that the impact of AIS plasticity on neuron excitability will depend largely on somatodendritic morphology, and that, in some neurons, a shorter or more distally located AIS may promote, rather than limit, action potential generation.

  5. Successive neuron loss in the thalamus and cortex in a mouse model of infantile neuronal ceroid lipofuscinosis.

    Kielar, Catherine; Maddox, Lucy; Bible, Ellen; Pontikis, Charlie C; Macauley, Shannon L; Griffey, Megan A; Wong, Michael; Sands, Mark S; Cooper, Jonathan D

    2007-01-01

    Infantile neuronal ceroid lipofuscinosis (INCL) is caused by deficiency of the lysosomal enzyme, palmitoyl protein thioesterase 1 (PPT1). We have investigated the onset and progression of pathological changes in Ppt1 deficient mice (Ppt1-/-) and the development of their seizure phenotype. Surprisingly, cortical atrophy and neuron loss occurred only late in disease progression but were preceded by localized astrocytosis within individual thalamic nuclei and the progressive loss of thalamic neurons that relay different sensory modalities to the cortex. This thalamic neuron loss occurred first within the visual system and only subsequently in auditory and somatosensory relay nuclei or the inhibitory reticular thalamic nucleus. The loss of granule neurons and GABAergic interneurons followed in each corresponding cortical region, before the onset of seizure activity. These findings provide novel evidence for successive neuron loss within the thalamus and cortex in Ppt1-/- mice, revealing the thalamus as an important early focus of INCL pathogenesis.

  6. Comparison of starch granule development and physicochemical properties of starches in wheat pericarp and endosperm.

    Yu, Xurun; Zhou, Liang; Zhang, Jing; Yu, Heng; Xiong, Fei; Wang, Zhong

    2015-01-01

    The objectives of this study were: (i) to characterize structural development of starch granule in pericarp and endosperm during wheat caryopsis growth; (ii) to compare physicochemical properties of starches in pericarp and endosperm; (iii) to further discover the relationships between pericarp starches and endosperm starches. Wheat pericarp and endosperm at different development stages were observed by light microscopy and scanning electron microscopy, respectively. Structural properties of starches were determined using X-ray power diffraction and (13) C solid nuclear magnetic resonance. Pericarp starch granules (PSG) accumulated in amyloplasts and chloroplasts, and showed a typical accumulation peak at 5 days after fertilization (DAF), and then gradually decomposed during 5-22 DAF. PSG in the abdominal region showed a higher rate of decomposition compared to the dorsal region of pericarp. Endosperm starch granules (ESG) accumulated in amyloplasts, and occurred in endosperm cells at 5 DAF, then rapidly enriched the endosperm cells until 22 DAF. Compared with ESG, PSG were compound granules of irregular shape and small size distribution. The results also suggested lower amylose content and V-type single-helix content and higher proportions of double helices for PSG compared to ESG. Based on the structural development of PSG and ESG, we speculated that the saccharides resulting from decomposition of PSG, on one hand, enabled the pericarp to survive before maturity of wheat caryopsis and, on the other hand, provided extra nutrition for the growth of ESG. © 2014 Society of Chemical Industry.

  7. Development and Evaluation of Taste Masked Granular Formulation of Satranidazole by Melt Granulation Technique

    Harshal Ashok Pawar

    2014-01-01

    Full Text Available Drugs from nitroimidazole category are generally bitter in taste. Oral formulation with bitter taste is not palatable. Geriatrics and pediatrics patients usually suffer from swallowing difficulties. Many other patients in some disease conditions avoid swallowing tablets. Satranidazole is a new nitro-imidazole derivative with bitter taste and is available in market as film coated tablet. The purpose of this research was to mask the bitter taste of Satranidazole by coating complexation with low melting point wax and Eudragit EPO. Different types of wax (glyceryl monostearate, stearic acid and cetyl alcohol were tried for taste masking. The drug to stearic acid ratio 1 : 2 was found to be optimum on the basis of taste evaluation and in vitro release. The formulated granules were found to possess good flow property. FTIR studies confirmed that there was no interaction between drug and excipients. Scanning Electron Microscopy of drug and the optimized batch of granules was performed. The in vitro release of drug from granules was compared with marketed tablet formulation. The taste masked granules of optimized batch showed 87.65% release of drug in 1 hr which is comparable to that of marketed tablet formulation.

  8. Linking macroscopic with microscopic neuroanatomy using synthetic neuronal populations.

    Schneider, Calvin J; Cuntz, Hermann; Soltesz, Ivan

    2014-10-01

    Dendritic morphology has been shown to have a dramatic impact on neuronal function. However, population features such as the inherent variability in dendritic morphology between cells belonging to the same neuronal type are often overlooked when studying computation in neural networks. While detailed models for morphology and electrophysiology exist for many types of single neurons, the role of detailed single cell morphology in the population has not been studied quantitatively or computationally. Here we use the structural context of the neural tissue in which dendritic trees exist to drive their generation in silico. We synthesize the entire population of dentate gyrus granule cells, the most numerous cell type in the hippocampus, by growing their dendritic trees within their characteristic dendritic fields bounded by the realistic structural context of (1) the granule cell layer that contains all somata and (2) the molecular layer that contains the dendritic forest. This process enables branching statistics to be linked to larger scale neuroanatomical features. We find large differences in dendritic total length and individual path length measures as a function of location in the dentate gyrus and of somatic depth in the granule cell layer. We also predict the number of unique granule cell dendrites invading a given volume in the molecular layer. This work enables the complete population-level study of morphological properties and provides a framework to develop complex and realistic neural network models.

  9. Visualization and understanding of the granulation liquid mixing and distribution during continuous twin screw granulation using NIR chemical imaging.

    Vercruysse, Jurgen; Toiviainen, Maunu; Fonteyne, Margot; Helkimo, Niko; Ketolainen, Jarkko; Juuti, Mikko; Delaet, Urbain; Van Assche, Ivo; Remon, Jean Paul; Vervaet, Chris; De Beer, Thomas

    2014-04-01

    Over the last decade, there has been increased interest in the application of twin screw granulation as a continuous wet granulation technique for pharmaceutical drug formulations. However, the mixing of granulation liquid and powder material during the short residence time inside the screw chamber and the atypical particle size distribution (PSD) of granules produced by twin screw granulation is not yet fully understood. Therefore, this study aims at visualizing the granulation liquid mixing and distribution during continuous twin screw granulation using NIR chemical imaging. In first instance, the residence time of material inside the barrel was investigated as function of screw speed and moisture content followed by the visualization of the granulation liquid distribution as function of different formulation and process parameters (liquid feed rate, liquid addition method, screw configuration, moisture content and barrel filling degree). The link between moisture uniformity and granule size distributions was also studied. For residence time analysis, increased screw speed and lower moisture content resulted to a shorter mean residence time and narrower residence time distribution. Besides, the distribution of granulation liquid was more homogenous at higher moisture content and with more kneading zones on the granulator screws. After optimization of the screw configuration, a two-level full factorial experimental design was performed to evaluate the influence of moisture content, screw speed and powder feed rate on the mixing efficiency of the powder and liquid phase. From these results, it was concluded that only increasing the moisture content significantly improved the granulation liquid distribution. This study demonstrates that NIR chemical imaging is a fast and adequate measurement tool for allowing process visualization and hence for providing better process understanding of a continuous twin screw granulation system. Copyright © 2013 Elsevier B.V. All

  10. FIB/SEM technology and high-throughput 3D reconstruction of dendritic spines and synapses in GFP-labeled adult-generated neurons

    Carles eBosch

    2015-05-01

    Full Text Available The fine analysis of synaptic contacts is usually performed using transmission electron microscopy (TEM and its combination with neuronal labeling techniques. However, the complex 3D architecture of neuronal samples calls for their reconstruction from serial sections. Here we show that focused ion beam/scanning electron microscopy (FIB/SEM allows efficient, complete, and automatic 3D reconstruction of identified dendrites, including their spines and synapses, from GFP/DAB-labeled neurons, with a resolution comparable to that of TEM. We applied this technology to analyze the synaptogenesis of labeled adult-generated granule cells (GCs in mice. 3D reconstruction of spines in GCs aged 3–4 and 8–9 weeks revealed two different stages of spine development and unexpected features of synapse formation, including vacant and branched spines and presynaptic terminals establishing synapses with up to 10 spines. Given the reliability, efficiency, and high resolution of FIB/SEM technology and the wide use of DAB in conventional EM, we consider FIB/SEM fundamental for the detailed characterization of identified synaptic contacts in neurons in a high-throughput manner.

  11. Signaling from the secretory granule to the nucleus: Uhmk1 and PAM.

    Francone, Victor P; Ifrim, Marius F; Rajagopal, Chitra; Leddy, Christopher J; Wang, Yanping; Carson, John H; Mains, Richard E; Eipper, Betty A

    2010-08-01

    Neurons and endocrine cells package peptides in secretory granules (large dense-core vesicles) for storage and stimulated release. Studies of peptidylglycine alpha-amidating monooxygenase (PAM), an essential secretory granule membrane enzyme, revealed a pathway that can relay information from secretory granules to the nucleus, resulting in alterations in gene expression. The cytosolic domain (CD) of PAM, a type 1 membrane enzyme essential for the production of amidated peptides, is basally phosphorylated by U2AF homology motif kinase 1 (Uhmk1) and other Ser/Thr kinases. Proopiomelanocortin processing in AtT-20 corticotrope tumor cells was increased when Uhmk1 expression was reduced. Uhmk1 was concentrated in the nucleus, but cycled rapidly between nucleus and cytosol. Endoproteolytic cleavage of PAM releases a soluble CD fragment that localizes to the nucleus. Localization of PAM-CD to the nucleus was decreased when PAM-CD with phosphomimetic mutations was examined and when active Uhmk1 was simultaneously overexpressed. Membrane-tethering Uhmk1 did not eliminate its ability to exclude PAM-CD from the nucleus, suggesting that cytosolic Uhmk1 could cause this response. Microarray analysis demonstrated the ability of PAM to increase expression of a small subset of genes, including aquaporin 1 (Aqp1) in AtT-20 cells. Aqp1 mRNA levels were higher in wild-type mice than in mice heterozygous for PAM, indicating that a similar relationship occurs in vivo. Expression of PAM-CD also increased Aqp1 levels whereas expression of Uhmk1 diminished Aqp1 expression. The outlines of a pathway that ties secretory granule metabolism to the transcriptome are thus apparent.

  12. Giant arachnoid granulation in a patient with benign intracranial hypertension

    Kiroglu, Yilmaz; Yaqci, Baki; Cirak, Bayram; Karabulut, Nevzat

    2008-01-01

    We report magnetic resonance (MR), computed tomography (CT) and angiographic imaging of an unusual giant arachnoid granulation in the superior sagittal sinus in a man with headache and vertigo. Intrasinus pressure measurements revealed a significant pressure gradient across the lesion. MR imaging is useful to identify giant arachnoid granulation and dural sinus thrombosis, whereas dural sinus pressure measurement in certain cases of giant arachnoid granulations can be used to evaluate the lesion as the cause of the patient's symptoms. (orig.)

  13. Giant arachnoid granulation in a patient with benign intracranial hypertension

    Kiroglu, Yilmaz; Yaqci, Baki; Cirak, Bayram; Karabulut, Nevzat [Pamukkale University, Department of Radiology, School of Medicine, Denizli (Turkey)

    2008-10-15

    We report magnetic resonance (MR), computed tomography (CT) and angiographic imaging of an unusual giant arachnoid granulation in the superior sagittal sinus in a man with headache and vertigo. Intrasinus pressure measurements revealed a significant pressure gradient across the lesion. MR imaging is useful to identify giant arachnoid granulation and dural sinus thrombosis, whereas dural sinus pressure measurement in certain cases of giant arachnoid granulations can be used to evaluate the lesion as the cause of the patient's symptoms. (orig.)

  14. Corticosterone Facilitates Fluoxetine-Induced Neuronal Plasticity in the Hippocampus

    Kobayashi, Katsunori; Ikeda, Yumiko; Asada, Minoru; Inagaki, Hirofumi; Kawada, Tomoyuki; Suzuki, Hidenori

    2013-01-01

    The hippocampal dentate gyrus has been implicated in a neuronal basis of antidepressant action. We have recently shown a distinct form of neuronal plasticity induced by the serotonergic antidepressant fluoxetine, that is, a reversal of maturation of the dentate granule cells in adult mice. This “dematuration” is induced in a large population of dentate neurons and maintained for at least one month after withdrawal of fluoxetine, suggesting long-lasting strong influence of dematuration on brain functioning. However, reliable induction of dematuration required doses of fluoxetine higher than suggested optimal doses for mice (10 to 18 mg/kg/day), which casts doubt on the clinical relevance of this effect. Since our previous studies were performed in naive mice, in the present study, we reexamined effects of fluoxetine using mice treated with chronic corticosterone that model neuroendocrine pathophysiology associated with depression. In corticosterone-treated mice, fluoxetine at 10 mg/kg/day downregulated expression of mature granule cell markers and attenuated strong frequency facilitation at the synapse formed by the granule cell axon mossy fiber, suggesting the induction of granule cell dematuration. In addition, fluoxetine caused marked enhancement of dopaminergic modulation at the mossy fiber synapse. In vehicle-treated mice, however, fluoxetine at this dose had no significant effects. The plasma level of fluoxetine was comparable to that in patients taking chronic fluoxetine, and corticosterone did not affect it. These results indicate that corticosterone facilitates fluoxetine-induced plastic changes in the dentate granule cells. Our finding may provide insight into neuronal mechanisms underlying enhanced responsiveness to antidepressant medication in certain pathological conditions. PMID:23675498

  15. Properties of bilateral spinocerebellar activation of cerebellar cortical neurons

    Pontus eGeborek

    2014-10-01

    Full Text Available We aimed to explore the cerebellar cortical inputs from two spinocerebellar pathways, the spinal border cell-component of the ventral spinocerebellar tract (SBC-VSCT and the dorsal spinocerebellar tract (DSCT, respectively, in the sublobule C1 of the cerebellar posterior lobe. The two pathways were activated by electrical stimulation of the contralateral lateral funiculus (coLF and the ipsilateral LF (iLF at lower thoracic levels. Most granule cells in sublobule C1 did not respond at all but part of the granule cell population displayed high-intensity responses to either coLF or iLF stimulation. As a rule, Golgi cells and Purkinje cell simple spikes responded to input from both LFs, although Golgi cells could be more selective. In addition, a small population of granule cells responded to input from both the coLF and the iLF. However, in these cases, similarities in the temporal topography and magnitude of the responses suggested that the same axons were stimulated from the two LFs, i.e. that the axons of individual spinocerebellar neurons could be present in both funiculi. This was also confirmed for a population of spinal neurons located within known locations of SBC-VSCT neurons and dorsal horn DSCT neurons. We conclude that bilateral spinocerebellar responses can occur in cerebellar granule cells, but the VSCT and DSCT systems that provide the input can also be organized bilaterally. The implications for the traditional functional separation of VSCT and DSCT systems and the issue whether granule cells primarily integrate functionally similar information or not are discussed.

  16. Motor Neurons

    Hounsgaard, Jorn

    2017-01-01

    Motor neurons translate synaptic input from widely distributed premotor networks into patterns of action potentials that orchestrate motor unit force and motor behavior. Intercalated between the CNS and muscles, motor neurons add to and adjust the final motor command. The identity and functional...... in in vitro preparations is far from complete. Nevertheless, a foundation has been provided for pursuing functional significance of intrinsic response properties in motoneurons in vivo during motor behavior at levels from molecules to systems....

  17. Rab3A, a possible marker of cortical granules, participates in cortical granule exocytosis in mouse eggs

    Bello, Oscar Daniel; Cappa, Andrea Isabel; Paola, Matilde de; Zanetti, María Natalia [Instituto de Histología y Embriología, CONICET – Universidad Nacional de Cuyo, Av. Libertador 80, 5500 Mendoza (Argentina); Fukuda, Mitsunori [Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578 (Japan); Fissore, Rafael A. [Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, 661 North Pleasant Street, Amherst, MA 01003 (United States); Mayorga, Luis S. [Instituto de Histología y Embriología, CONICET – Universidad Nacional de Cuyo, Av. Libertador 80, 5500 Mendoza (Argentina); Michaut, Marcela A., E-mail: mmichaut@gmail.com [Instituto de Histología y Embriología, CONICET – Universidad Nacional de Cuyo, Av. Libertador 80, 5500 Mendoza (Argentina); Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Cuyo (Argentina)

    2016-09-10

    Fusion of cortical granules with the oocyte plasma membrane is the most significant event to prevent polyspermy. This particular exocytosis, also known as cortical reaction, is regulated by calcium and its molecular mechanism is still not known. Rab3A, a member of the small GTP-binding protein superfamily, has been implicated in calcium-dependent exocytosis and is not yet clear whether Rab3A participates in cortical granules exocytosis. Here, we examine the involvement of Rab3A in the physiology of cortical granules, particularly, in their distribution during oocyte maturation and activation, and their participation in membrane fusion during cortical granule exocytosis. Immunofluorescence and Western blot analysis showed that Rab3A and cortical granules have a similar migration pattern during oocyte maturation, and that Rab3A is no longer detected after cortical granule exocytosis. These results suggested that Rab3A might be a marker of cortical granules. Overexpression of EGFP-Rab3A colocalized with cortical granules with a Pearson correlation coefficient of +0.967, indicating that Rab3A and cortical granules have almost a perfect colocalization in the egg cortical region. Using a functional assay, we demonstrated that microinjection of recombinant, prenylated and active GST-Rab3A triggered cortical granule exocytosis, indicating that Rab3A has an active role in this secretory pathway. To confirm this active role, we inhibited the function of endogenous Rab3A by microinjecting a polyclonal antibody raised against Rab3A prior to parthenogenetic activation. Our results showed that Rab3A antibody microinjection abolished cortical granule exocytosis in parthenogenetically activated oocytes. Altogether, our findings confirm that Rab3A might function as a marker of cortical granules and participates in cortical granule exocytosis in mouse eggs. - Highlights: • Rab3A has a similar migration pattern to cortical granules in mouse oocytes. • Rab3A can be a marker of

  18. Microbial granulation for lactic acid production.

    Kim, Dong-Hoon; Lee, Mo-Kwon; Hwang, Yuhoon; Im, Wan-Taek; Yun, Yeo-Myeong; Park, Chul; Kim, Mi-Sun

    2016-01-01

    This work investigated the formation of microbial granules to boost the productivity of lactic acid (LA). The flocculated form of LA-producing microbial consortium, dominated by Lactobacillus sp. (91.5% of total sequence), was initially obtained in a continuous stirred-tank reactor (CSTR), which was fed with 2% glucose and operated at a hydraulic retention time (HRT) of 12 h and pH 5.0 ± 0.1 under a thermophilic condition (50°C). The mixed liquor in the CSTR was then transferred to an up-flow anaerobic sludge blanket reactor (UASB). The fermentation performance and granulation process were monitored with a gradual decrease of HRT from 8.0 to 0.17 h, corresponding to an increase in the substrate loading from 60 to 2,880 g glucose L(-1) d(-1) . As the operation continued, the accumulation of biomass in the UASB was clearly observed, which changed from flocculent to granular form with decrease in HRT. Up to the HRT decrease to 0.5 h, the LA concentration was maintained at 19-20 g L(-1) with over 90% of substrate removal efficiency. However, further decrease of HRT resulted in a decrease of LA concentration with increase in residual glucose. Nevertheless, the volumetric LA productivity continuously increased, reaching 67 g L-fermenter (-1) h(-1) at HRT 0.17 h. The size of LA-producing granules and hydrophobicity gradually increased with decrease in HRT, reaching 6.0 mm and 60%, respectively. These biogranules were also found to have high settling velocities and low porosities, ranging 2.69-4.73 cm s(-1) and 0.39-0.92, respectively. © 2015 Wiley Periodicals, Inc.

  19. Fragile X protein mitigates TDP-43 toxicity by remodeling RNA granules and restoring translation.

    Coyne, Alyssa N; Yamada, Shizuka B; Siddegowda, Bhavani Bagevalu; Estes, Patricia S; Zaepfel, Benjamin L; Johannesmeyer, Jeffrey S; Lockwood, Donovan B; Pham, Linh T; Hart, Michael P; Cassel, Joel A; Freibaum, Brian; Boehringer, Ashley V; Taylor, J Paul; Reitz, Allen B; Gitler, Aaron D; Zarnescu, Daniela C

    2015-12-15

    RNA dysregulation is a newly recognized disease mechanism in amyotrophic lateral sclerosis (ALS). Here we identify Drosophila fragile X mental retardation protein (dFMRP) as a robust genetic modifier of TDP-43-dependent toxicity in a Drosophila model of ALS. We find that dFMRP overexpression (dFMRP OE) mitigates TDP-43 dependent locomotor defects and reduced lifespan in Drosophila. TDP-43 and FMRP form a complex in flies and human cells. In motor neurons, TDP-43 expression increases the association of dFMRP with stress granules and colocalizes with polyA binding protein in a variant-dependent manner. Furthermore, dFMRP dosage modulates TDP-43 solubility and molecular mobility with overexpression of dFMRP resulting in a significant reduction of TDP-43 in the aggregate fraction. Polysome fractionation experiments indicate that dFMRP OE also relieves the translation inhibition of futsch mRNA, a TDP-43 target mRNA, which regulates neuromuscular synapse architecture. Restoration of futsch translation by dFMRP OE mitigates Futsch-dependent morphological phenotypes at the neuromuscular junction including synaptic size and presence of satellite boutons. Our data suggest a model whereby dFMRP is neuroprotective by remodeling TDP-43 containing RNA granules, reducing aggregation and restoring the translation of specific mRNAs in motor neurons. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Disintegration of aerobic granules induced by trans-2-decenoic acid.

    Cai, Pei-Jie; Xiao, Xiang; He, Yan-Rong; Li, Wen-Wei; Yu, Lei; Yu, Han-Qing

    2013-01-01

    One current major hurdle to practical implementation of aerobic granule technology is the frequent occurrence of granule disintegration during long-term operation. However, the mechanism behind this is largely unclear today. Here, 2-decenoic acid, which has been previously demonstrated to be released by Pseudomonas aeruginosa and disperse biofilms, was found to also induce the disintegration of aerobic granules. A comparison of the solution compositions from samples of only trans-2-decenoic acid, only aerobic granules, and granules added with trans-2-decenoic acid shows that bacteria and extracellular polymeric substances (EPS) were stripped from granule surface upon trans-2-decenoic acid dosing. Due to the possible toxicity of trans-2-decenoic acid at a saturation concentration, the disintegrated granules and the milky suspension in the disintegration test showed a significantly lower oxygen uptake rate than the un-integrated granules. This work suggests that trans-2-decenoic acid released by microbes might play a critical role in regulating the disintegration of aerobic granules. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Anatomical evidence for direct fiber projections from the cerebellar nucleus interpositus to rubrospinal neurons. A quantitative EM study in the rat combining anterograde and retrograde intra-axonal tracing methods

    Dekker, J.J.

    1981-01-01

    A quantitative electron microscopic (EM) study combining the anterograde intra-axonal transport of radioactive amino acids and the retrograde intra-axonal transport of the enzyme horseradish peroxidase (HRP) was performed in the magnocellular red nucleus of the rat to obtain anatomical evidence as to whether there is a direct projection from the cerebellar nucleus interpositus to the cells in the red nucleus that give rise to the rubrospinal tract. Large asymmetrical synaptic terminals were radioactively labeled in the magnocellular red nucleus following injections of [ 3 H]leucine into the cerebellar nucleus interpositus. In these same animals, the postsynaptic target neurons were labeled with HRP granules after injection of this substance in the rubrospinal tract. A quantitative analysis showed that more than 85% of the large and giant neurons in the magnocellular red nucleus were labeled with HRP granules and also received synaptic contacts from radioactively-labeled terminals. Thus, it can be concluded that in the rat, afferents from the cerebellar nucleus interpositus establish asymmetrical synaptic contacts with large and giant rubrospinal neurons, thus confirming and extending the previous physiological evidence of such direct monosynaptic connections. (Auth.)

  2. New developments on transition radiation detectors using superconducting granules

    Yuan, L.C.L.

    1977-01-01

    By raising slightly either the temperature or the magnetic field to above that of the critical temperature or the critical magnetic field, the type I superconducting granules would still remain in the superconducting state which becomes a metastable state and is called the superheated superconducting state. If a relativistic charged particle incident on such a granule which is located in a colloidal suspension has imported to it an energy that is above the threshold energy (for state flipping) of the granule then it would flip to the normal state. The threshold energy of a granule is a function of the square of its radius, whereas the energy loss of a charged particle due to ionization is linearly proportional to the radius. The size of the granule can be pre-determined to be such that its threshold energy is slightly above the ionization loss of a relativistic charged particle. Then the traversal of the charged particle through such a granule would not affect the superconducting state of the granule unless a transition x-ray radiation is emitted at the surface of the granule by the traversing particle and the x-ray transition radiation is immediately absorbed either in total or partially by the metallic granule causing it to flip to the normal state. The total intensity of the x-ray transition radiation is linearly proportional to the Lorentz factor γ of the traversing particle, and the number of granules flipped would also be a measure of γ. Three methods for detecting the flipping of granules from the superconducting state to the normal state are described. They include the frequency measuring method, the SQUID method, and the pulse method with low noise amplifier system

  3. The biology and dynamics of mammalian cortical granules

    Liu Min

    2011-11-01

    Full Text Available Abstract Cortical granules are membrane bound organelles located in the cortex of unfertilized oocytes. Following fertilization, cortical granules undergo exocytosis to release their contents into the perivitelline space. This secretory process, which is calcium dependent and SNARE protein-mediated pathway, is known as the cortical reaction. After exocytosis, the released cortical granule proteins are responsible for blocking polyspermy by modifying the oocytes' extracellular matrices, such as the zona pellucida in mammals. Mammalian cortical granules range in size from 0.2 um to 0.6 um in diameter and different from most other regulatory secretory organelles in that they are not renewed once released. These granules are only synthesized in female germ cells and transform an egg upon sperm entry; therefore, this unique cellular structure has inherent interest for our understanding of the biology of fertilization. Cortical granules are long thought to be static and awaiting in the cortex of unfertilized oocytes to be stimulated undergoing exocytosis upon gamete fusion. Not till recently, the dynamic nature of cortical granules is appreciated and understood. The latest studies of mammalian cortical granules document that this organelle is not only biochemically heterogeneous, but also displays complex distribution during oocyte development. Interestingly, some cortical granules undergo exocytosis prior to fertilization; and a number of granule components function beyond the time of fertilization in regulating embryonic cleavage and preimplantation development, demonstrating their functional significance in fertilization as well as early embryonic development. The following review will present studies that investigate the biology of cortical granules and will also discuss new findings that uncover the dynamic aspect of this organelle in mammals.

  4. Performance of mesophilic anaerobic granules for removal of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) from aqueous solution

    An Chunjiang; He Yanling; Huang Guohe; Liu Yonghong

    2010-01-01

    The performance of mesophilic anaerobic granules to degrade octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) was investigated under various conditions. The results of batch experiments showed that anaerobic granules were capable of removing HMX from aqueous solution with high efficiency. Both biotic and abiotic mechanisms contributed to the removal of HMX by anaerobic granules under mesophilic conditions. Adsorption appeared to play a significant role in the abiotic process. Furthermore, HMX could be biodegraded by anaerobic granules as the sole substrate. After 16 days of incubation, 99.04% and 96.42% of total HMX could be removed by 1 g VSS/L acclimated and unacclimated granules, respectively. Vancomycin, an inhibitor of acetogenic bacteria, caused a significant inhibition of HMX biotransformation, while 2-bromoethanesulfonic acid, an inhibitor of methanogenic bacteria, only resulted in a slight decrease of metabolic activity. The presence of the glucose, as a suitable electron donor and carbon source, was found to enhance the degradation of HMX by anaerobic granules. Our study showed that sulfate had little adverse effects on biotransformation of HMX by anaerobic granules. However, nitrate had significant inhibitory effect on the extent of HMX removal especially in the initial period. This study offered good prospects of using high-rate anaerobic technology in the treatment of munition wastewater.

  5. Efeito do tamanho dos grânulos nas características estruturais e físico-químicas do amido de trigo Effect of granule size on the structural and physicochemical characteristics of wheat starch

    Patrícia Guedes Yonemoto

    2007-12-01

    Full Text Available A distribuição de tamanho dos grânulos influencia diretamente a composição química do amido, afetando sua funcionalidade, características de gelatinização, susceptibilidade enzimática, e cristalinidade. Os grânulos de amido de trigo possuem distribuição bimodal de tamanho e são divididos em grânulos tipo A (10-40 µm e B (15 µm e pequenos (Granule size distribution directly influences the chemical composition of starch, affecting its functionality, characteristics of gelatinization, enzymatic susceptibility and crystallinity. Wheat starch granules exhibit a bimodal size distribution and are divided into type A (10-40 µm and type B (15 µm and small granules (<10 µm. Starches of different sizes were analyzed to determine their lysophospholipid and amylose content, X-ray patterns, enzymatic susceptibility, swelling power, and thermal and pasting properties. They were also examined under a scanning electron microscope. Independent of the cultivar studied, large granules showed an average diameter of 22 µm and were lentil-shaped, while small granules showed an average diameter of 6 µm and were spherical. The large granules exhibited lower lysophospholipids content, higher amylose content and a lower index of crystallinity (IC than the small granules. Despite their higher crystallinity, small granules were more susceptible to hydrolysis than large ones, suggesting that the enzymatic susceptibility of small granules is related to its larger surface area.

  6. Functional circuits of new neurons in the dentate gyrus

    Carmen eVivar

    2013-02-01

    Full Text Available The hippocampus is crucial for memory formation. New neurons are added throughout life to the hippocampal dentate gyrus (DG, a brain area considered important for differential storage of similar experiences and contexts. To better understand the functional contribution of adult neurogenesis to pattern separation processes, we recently used a novel synapse specific trans-neuronal tracing approach to identify the (sub cortical inputs to new dentate granule cells. It was observed that newly born neurons receive sequential innervation from structures important for memory function. Initially, septal-hippocampal cells provide input to new neurons, followed after about one month by perirhinal and lateral entorhinal cortex. These cortical areas are deemed relevant to encoding of novel environmental information and may enable pattern separation. Here, we review the developmental time-course and proposed functional relevance of new neurons, within the context of their unique neural circuitry.  

  7. Somatostatin receptors in rat hippocampus: localization to intrinsic neurons

    Palacios, J.M.; Reubi, J.C.; Maurer, R.

    1986-01-01

    The effect of neurotoxic chemical and electrolytical lesions on somatostatin (SS) receptor binding in the septo-hippocampal afferents, pyramidal and granule cells of the rat hippocampus was examined by autoradiography using the stable SS analogue 125 I-204-090 as radioligand. Electrolytical lesions of the septum did not result in modification of SS binding in the hippocampus. In contrast, both granule cell lesion with colchicine and pyramidal or pyramidal and granule cell lesions with increasing kainic acid doses did result in a specific decrease of binding in the dentate gyrus and hippocampus (CA 1 and CA 3 ). These results suggest that SS receptors in the hippocampus are probably associated with elements from intrinsic neurons. (Author)

  8. Metatranscriptomics reveals the molecular mechanism of large granule formation in granular anammox reactor

    Bagchi, Samik; Lamendella, Regina; Strutt, Steven; Van Loosdrecht, Mark C. M.; Saikaly, Pascal

    2016-01-01

    to formation of large granules. Size distribution analysis revealed the spatial distribution of granules in which large granules having higher abundance of anammox bacteria (genus Brocadia) dominated the bottom biomass. Metatranscriptomics analysis detected all

  9. Completely assembled virus particles detected by transmission electron microscopy in proximal and mid-axons of neurons infected with herpes simplex virus type 1, herpes simplex virus type 2 and pseudorabies virus

    Huang Jialing; Lazear, Helen M.; Friedman, Harvey M.

    2011-01-01

    The morphology of alphaherpesviruses during anterograde axonal transport from the neuron cell body towards the axon terminus is controversial. Reports suggest that transport of herpes simplex virus type 1 (HSV-1) nucleocapsids and envelope proteins occurs in separate compartments and that complete virions form at varicosities or axon termini (subassembly transport model), while transport of a related alphaherpesvirus, pseudorabies virus (PRV) occurs as enveloped capsids in vesicles (assembled transport model). Transmission electron microscopy of proximal and mid-axons of primary superior cervical ganglion (SCG) neurons was used to compare anterograde axonal transport of HSV-1, HSV-2 and PRV. SCG cell bodies were infected with HSV-1 NS and 17, HSV-2 2.12 and PRV Becker. Fully assembled virus particles were detected intracellularly within vesicles in proximal and mid-axons adjacent to microtubules after infection with each virus, indicating that assembled virions are transported anterograde within axons for all three alphaherpesviruses.

  10. Granule properties of paracetamol made with Bombax ceiba gum ...

    Bombax ceiba gum was extracted from the calyx of the Bombax flower using both hot and cold water extraction method. The gum was used as binder to prepare paracetamol granules in concentrations of 1, 1.5, 2, and 3 %. Acacia gum was used to prepare the standard at the same concentrations. The granule properties of ...

  11. Proximate analysis of Sweet Potato Toasted Granules | Meludu ...

    Sweet potato is an important root crop in the food system of many African countries. The yield, nutrition and economic potential of sweet potato have been identified as very high. In this study, sweet potato was processed and toasted into granules. The proximate analysis performed on the toasted granules showed protein, ...

  12. Application of granulating of tires; Aplicaciones de granulado de NFUs

    Jimenez Justicia, A.

    2001-07-01

    At present, used tires are mainly used as fuel, retreading and granulating of tires. In this article. I will focus on the last option, talking about some of the multiple applications and going into detail of the making process of the granulation of used tires in a recycling plant. (Author)

  13. Roll compaction and granulation system for nuclear fuel material

    Goldmann, L.H. Jr.; Holley, C.C.

    1981-01-01

    A roll compaction and roll granulation system has been designed and fabricated to replace conventional preslugging and crushing operations typically used in the fabrication of mixed oxide nuclear fuel pellets. This equipment will be of maintenance advantage with only the compaction and granulation rolls inside containment. The prototype is being tested and the results will be reported within a year

  14. Nonreutilizaton of adrenal chromaffin granule membranes following secretion

    Nobiletti, J.B.

    1985-01-01

    The intracellular postexocytotic fate of the adrenal chromaffin granule membrane (reutilization vs. nonreutilization) was addressed through two experimental approaches. First, ( 3 H) leucine pulse-chase labeling experiments were conducted in two systems - the isolated retrograde perfused cat adrenal gland and cultured bovine adrenal chromaffin cells to compare chromaffin granule soluble dopamine-B-hydroxylase (DBH) turnover (marker for granule soluble content turnover) to that of membrane-bound DBH (marker for granule membrane turnover). Experiments in cat adrenal glands showed that at all chase periods the granule distribution of radiolabeled DBH was in agreement with the DBH activity distribution (73% membrane-bound/27% soluble) - a result consistent with parallel turnover of soluble and membrane-bound DBH. Experiments in cultured bovine cells showed that labeled soluble and membrane-bound DBH had parallel turnover patterns and at all chase period, the distribution of radiolabeled DBH between the soluble contents and membranes was similar to the DBH activity distribution (50% soluble/50% membrane-bound). The above experiments showed that the soluble contents and membranes turnover in parallel and are consistent with nonreutilization of chromaffin granule membranes following exocytosis. Isolated retrograde perfused bovine adrenal glands were subjected to repetitive acetylcholine stimulation to induce exocytosis and then the dense and less-dense chromaffin granule fractions were isolated. Since both approaches gave results consistent with membrane nonreutilization, the authors conclude that once a chromaffin granule is involved in exocytosis, its membrane is not reutilized for the further synthesis, storage, and secretion of catecholamines

  15. Autophagy meets fused in sarcoma-positive stress granules.

    Matus, Soledad; Bosco, Daryl A; Hetz, Claudio

    2014-12-01

    Mutations in fused in sarcoma and/or translocated in liposarcoma (FUS, TLS or FUS) are linked to familial cases of amyotrophic lateral sclerosis (ALS). Mutant FUS selectively accumulates into discrete cytosolic structures known as stress granules under various stress conditions. In addition, mutant FUS expression can alter the dynamics and morphology of stress granules. Although the link between mutant FUS and stress granules is well established, the mechanisms modulating stress granule formation and disassembly in the context of ALS are poorly understood. In this issue of Neurobiology of Aging, Ryu et al. uncover the impact of autophagy on the potential toxicity of mutant FUS-positive stress granules. The authors provide evidence indicating that enhanced autophagy activity reduces the number of stress granules, which in the case of cells containing mutant FUS-positive stress granules, is neuroprotective. Overall, this study identifies an intersection between the proteostasis network and alterations in RNA metabolism in ALS through the dynamic assembly and disassembly of stress granules. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Osseous drill holes to promote granulation tissue: Radiologic appearance

    Resnik, C.S.; Reiner, B.I.; Diaconis, J.N.; Goldberg, N.H.

    1991-01-01

    Skin grafting following extensive soft-tissue loss is often delayed until adequate granulation tissue can be generated. Surgical drill holes into the marrow cavity promote development of granulation tissue. This article illustrates the radiology appearance of these drill holes in four patients. (orig.)

  17. Method for the treatment of waste water with sludge granules

    Van Loosdrecht, M.C.; De Kreuk, M.K.

    2004-01-01

    The invention relates to a method for the treatment of waste water comprising an organic nutrient. According to the invention, the waste water is in a first step fed to sludge granules, after the supply of the waste water to be treated the sludge granules are fluidised in the presence of an

  18. Consolidating nanoparticles in micron-sized granules using spray drying

    Lindeloev, J S; Wahlberg, M

    2011-01-01

    Suspensions of nanoparticles (SiO 2 , SiC, TiO2, CNT, Nanoclay and Hydroxyapatite) were spray dried to produce dry granulated products. The nanoparticles were consolidated in granules making them more convenient and safer to use in further processing compared to handling of nanopowders.

  19. Azurophil granule proteins constitute the major mycobactericidal proteins in human neutrophils and enhance the killing of mycobacteria in macrophages.

    Prajna Jena

    Full Text Available Pathogenic mycobacteria reside in, and are in turn controlled by, macrophages. However, emerging data suggest that neutrophils also play a critical role in innate immunity to tuberculosis, presumably by their different antibacterial granule proteins. In this study, we purified neutrophil azurophil and specific granules and systematically analyzed the antimycobacterial activity of some purified azurophil and specific granule proteins against M. smegmatis, M. bovis-BCG and M. tuberculosis H37Rv. Using gel overlay and colony forming unit assays we showed that the defensin-depleted azurophil granule proteins (AZP were more active against mycobacteria compared to other granule proteins and cytosolic proteins. The proteins showing antimycobacterial activity were identified by MALDI-TOF mass spectrometry. Electron microscopic studies demonstrate that the AZP disintegrate bacterial cell membrane resulting in killing of mycobacteria. Exogenous addition of AZP to murine macrophage RAW 264.7, THP-1 and peripheral blood monocyte-derived macrophages significantly reduced the intracellular survival of mycobacteria without exhibiting cytotoxic activity on macrophages. Immunofluorescence studies showed that macrophages actively endocytose neutrophil granular proteins. Treatment with AZP resulted in increase in co-localization of BCG containing phagosomes with lysosomes but not in increase of autophagy. These data demonstrate that neutrophil azurophil proteins may play an important role in controlling intracellular survival of mycobacteria in macrophages.

  20. The number of granule cells in rat hippocampus is reduced after chronic mild stress and re-established after chronic escitalopram treatment

    Jayatissa, Magdalena N; Bisgaard, Christina; West, Mark J

    2008-01-01

    mild stress and chronic escitalopram treatment. Furthermore, we investigated which classes of immature granule cells are affected by stress and targeted by escitalopram. Rats were initially exposed to 2weeks of CMS and 4weeks of escitalopram treatment with concurrent exposure to stress. The behavioral...... changes, indicating a decrease in sensitivity to a reward, were assessed in terms of sucrose consumption. We found a significant 22.4% decrease in the total number of granule cells in the stressed rats. This decrease was reversed in the stressed escitalopram treated rats that responded to the treatment......, but not in the rats that did not respond to escitalopram treatment. These changes were not followed by alterations in the volume of the granule cell layer. We also showed a differential regulation of dentate neurons, in different stages of development, by chronic stress and chronic escitalopram treatment. Our study...

  1. [Mirror neurons].

    Rubia Vila, Francisco José

    2011-01-01

    Mirror neurons were recently discovered in frontal brain areas of the monkey. They are activated when the animal makes a specific movement, but also when the animal observes the same movement in another animal. Some of them also respond to the emotional expression of other animals of the same species. These mirror neurons have also been found in humans. They respond to or "reflect" actions of other individuals in the brain and are thought to represent the basis for imitation and empathy and hence the neurobiological substrate for "theory of mind", the potential origin of language and the so-called moral instinct.

  2. Hilar mossy cell circuitry controlling dentate granule cell excitability

    Seiichiro eJinde

    2013-02-01

    Full Text Available Glutamatergic hilar mossy cells of the dentate gyrus can either excite or inhibit distant granule cells, depending on whether their direct excitatory projections to granule cells or their projections to local inhibitory interneurons dominate. However, it remains controversial whether the net effect of mossy cell loss is granule cell excitation or inhibition. Clarifying this controversy has particular relevance to temporal lobe epilepsy, which is marked by dentate granule cell hyperexcitability and extensive loss of dentate hilar mossy cells. Two diametrically opposed hypotheses have been advanced to explain this granule cell hyperexcitability – the dormant basket cell and the irritable mossy cell hypotheses. The dormant basket cell hypothesis proposes that mossy cells normally exert a net inhibitory effect on granule cells and therefore their loss causes dentate granule cell hyperexcitability. The irritable mossy cell hypothesis takes the opposite view that mossy cells normally excite granule cells and that the surviving mossy cells in epilepsy increase their activity, causing granule cell excitation. The inability to eliminate mossy cells selectively has made it difficult to test these two opposing hypotheses. To this end, we developed a transgenic toxin-mediated, mossy cell-ablation mouse line. Using these mutants, we demonstrated that the extensive elimination of hilar mossy cells causes granule cell hyperexcitability, although the mossy cell loss observed appeared insufficient to cause clinical epilepsy. In this review, we focus on this topic and also suggest that different interneuron populations may mediate mossy cell-induced translamellar lateral inhibition and intralamellar recurrent inhibition. These unique local circuits in the dentate hilar region may be centrally involved in the functional organization of the dentate gyrus.

  3. A review on granules initiation and development inside UASB Reactor and the main factors affecting granules formation process

    Habeeb, S.A.; Latiff, Ab Aziz Bin Abdul; Daud, Zawawi Bin; Ahmad, Zulkifli Bin [Civil and Environmental Engineering, University Tun Hussein Onn Malaysia (Malaysia)

    2011-07-01

    Decades of investigations and explorations in the field of anaerobic wastewater treatment have resulted in significant indications about the role importance of sludge granules in biodegradation anaerobic process. It is believed that the development of anaerobic granules is reflecting an important role on the performance of reactor. An overview on the concept of up-flow anaerobic sludge bed (UASB) reactor operation as well as the main parts that reactor consists of is briefly explained in this paper, whereas the major theories of anaerobic granules formation are listed by related researchers. The correlations and compositions of such sludge granule have been specifically explained. It is believed that the extracellular polymer (ECP) is totally responsible of bacterial cell correlations and the formation of bacterial communities in the form of granules. In addition, the dependable factors for the performance of anaerobic granules formation process e.g. temperature, organic loading rate, pH, and alkalinity, nutrients, and cations and heavy metals have been discussed in this paper. Strong evidences proved that the process of gas production in the form of biogas is related to the methanogens activities, which are practically found in the core of granules. The aim of this review is to explore and assess the mechanisms of granules initiation and development inside UASB reactor.

  4. Joint Effects of Granule Size and Degree of Substitution on Octenylsuccinated Sweet Potato Starch Granules As Pickering Emulsion Stabilizers.

    Li, Jinfeng; Ye, Fayin; Lei, Lin; Zhou, Yun; Zhao, Guohua

    2018-05-02

    The granules of sweet potato starch were size fractionated into three portions with significantly different median diameters ( D 50 ) of 6.67 (small-sized), 11.54 (medium-sized), and 16.96 μm (large-sized), respectively. Each portion was hydrophobized at the mass-based degrees of substitution (DS m ) of approximately 0.0095 (low), 0.0160 (medium), and 0.0230 (high). The Pickering emulsion-stabilizing capacities of modified granules were tested, and the resultant emulsions were characterized. The joint effects of granule size and DS m on emulsifying capacity (EC) were investigated by response surface methodology. For small-, medium-, and large-sized fractions, their highest emulsifying capacities are comparable but, respectively, encountered at high (0.0225), medium (0.0158), and low (0.0095) DS m levels. The emulsion droplet size increased with granule size, and the number of freely scattered granules in emulsions decreased with DS m . In addition, the term of surface density of the octenyl succinic group (SD -OSG ) was first proposed for modified starch granules, and it was proved better than DS m in interpreting the emulsifying capacities of starch granules with varying sizes. The present results implied that, as the particulate stabilizers, the optimal DS m of modified starch granules is size specific.

  5. High-shear granulation as a manufacturing method for cocrystal granules

    Rehder, Sönke; Christensen, Niels Peter Aae; Rantanen, Jukka

    2013-01-01

    and the respective excipients). The drug release was slightly decreased by cocrystal formation, most likely due to the lower solubility of the cocrystal. In the presence of calcium hydrogenphosphate however, no influence of cocrystal formation on either compactability or on drug release were observed, compared...... with the reference tablets. It was concluded that high-shear wet granulation is a valuable, however complex, manufacturing method for cocrystals. Cocrystal formation may influence compactability and drug release and thus affect drug performance and should be investigated during pre-formulation.......Cocrystal formation allows the tailoring of physicochemical as well as of mechanical properties of an API. However, there is a lack of large-scale manufacturing methods of cocrystals. Therefore, the objective of this work was to examine the suitability of high-shear wet granulation...

  6. Three-dimensional ultrastructural analyses of anterior pituitary gland expose spatial relationships between endocrine cell secretory granule localization and capillary distribution.

    Yoshitomi, Munetake; Ohta, Keisuke; Kanazawa, Tomonoshin; Togo, Akinobu; Hirashima, Shingo; Uemura, Kei-Ichiro; Okayama, Satoko; Morioka, Motohiro; Nakamura, Kei-Ichiro

    2016-10-31

    Endocrine and endothelial cells of the anterior pituitary gland frequently make close appositions or contacts, and the secretory granules of each endocrine cell tend to accumulate at the perivascular regions, which is generally considered to facilitate secretory functions of these cells. However, three-dimensional relationships between the localization pattern of secretory granules and blood vessels are not fully understood. To define and characterize these spatial relationships, we used scanning electron microscopy (SEM) three-dimensional reconstruction method based on focused ion-beam slicing and scanning electron microscopy (FIB/SEM). Full three-dimensional cellular architectures of the anterior pituitary tissue at ultrastructural resolution revealed that about 70% of endocrine cells were in apposition to the endothelial cells, while almost 30% of endocrine cells were entirely isolated from perivascular space in the tissue. Our three-dimensional analyses also visualized the distribution pattern of secretory granules in individual endocrine cells, showing an accumulation of secretory granules in regions in close apposition to the blood vessels in many cases. However, secretory granules in cells isolated from the perivascular region tended to distribute uniformly in the cytoplasm of these cells. These data suggest that the cellular interactions between the endocrine and endothelial cells promote an uneven cytoplasmic distribution of the secretory granules.

  7. Nucleoli and stress granules: connecting distant relatives.

    Mahboubi, Hicham; Stochaj, Ursula

    2014-10-01

    Nucleoli and cytoplasmic stress granules (SGs) are subcellular compartments that modulate the response to endogenous and environmental signals to control cell survival. In our opinion, nucleoli and SGs are functionally linked; they are distant relatives that combine forces when cellular homeostasis is threatened. Several lines of evidence support this idea; nucleoli and SGs share molecular building blocks, are regulated by common signaling pathways and communicate when vital cellular functions become compromised. Together, nucleoli and SGs orchestrate physiological responses that are directly relevant to stress and human health. As both compartments have established roles in neurodegenerative diseases, cancer and virus infections, we propose that these conditions will benefit from therapeutic interventions that target simultaneously nucleoli and SGs. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. The Solar-flux Third Granulation Signature

    Gray, David F.; Oostra, Benjamin

    2018-01-01

    The velocity shifts of spectral lines as a function of line strength, so-called the third signature of granulation, are investigated using three published solar-flux atlases. We use flux atlases because we wish to treat the Sun as a star, against which stellar observations can be compared and judged. The atlases are critiqued and compared to the lower-resolution observations taken with the Elginfield stellar spectrograph. Third-signature plots are constructed for the 6020–6340 Å region. No dependence on excitation potential or wavelength is found over this wavelength span. The shape of the plots from the three solar atlases is essentially the same, with rms line-core velocity differences of 30–35 m s‑1. High-resolution atlas data are degraded to the level of the Elginfield spectrograph and compared to direct observations taken with that spectrograph. The line-core velocities show good agreement, with rms differences of 38 m s‑1. A new standard curve is derived and compared with the previously published one. Only small differences in shape are found, but a significant (+97 m s‑1) change in the zero point is indicated. The bisector of the Fe I 6253 line is mapped onto the third-signature plots and flux deficits are derived, which measure the granule/lane flux imbalance. The lower spectral resolution lowers the flux deficit area slightly and moves the peak of the deficit 0.3–0.5 km s‑1 toward higher velocities. These differences, while significant, are not large compared to measurement errors for stellar data.

  9. Ocular Injury due to Potassium Permanganate Granules

    Chareenun Chirapapaisan

    2018-02-01

    Full Text Available Purpose: We report a rare case of ocular injury due to potassium permanganate (KMnO4 granules in a child. Methods: This is a retrospective case report. Results: A 2-year-old boy was transferred to our emergency room with severe pain in his right eye, inflamed eyelids, and brownish stains on his fingers. Chemical injury was suspected. Copious eye irrigation was immediately performed. Diffuse brownish splotches were then observed at the inferior bulbar conjunctiva. Otherwise, systemic organs were intact. Complete eye exam under general anesthesia revealed a 5-mm epithelial defect at the central cornea, along with generalized conjunctival injection and limbal ischemia, inferiorly. Multiple semi-dissolved granules of KMnO4 trapped in the inferior fornix were identified. The chemical particles were gradually washed out and removed; however, the brownish stains remained. The patient received preservative-free steroid, antibiotic eye drops, and lubricants as regular management for mild to moderate degree of ocular burn. Pseudomembrane developed early and transformed into symblepharon within a few days after the injury. Membrane adhesion was lysed, and more aggressive medications were then substituted. Commercial amniotic membrane (PROKERA® was also applied to promote wound healing and to prevent recurrence of symblepharon. The ocular surface was eventually restored, and corneal transparency was preserved. Conclusion: Ocular injury with the granular form of KMnO4 is rare. Its toxicity is comparable to concentrated KMnO4 solution. However, the dissolved particles that had been absorbed in the stained conjunctiva were continuously released and damaged the ocular surface more than we primarily anticipated. Awareness of this condition and prompt management yield a good treatment outcome.

  10. Organization of spinocerebellar projection map in three types of agranular cerebellum: Purkinje cells vs. granule cells as organizer element

    Arsenio Nunes, M.L.; Sotelo, C.; Wehrle, R.

    1988-01-01

    The organization of the spinocerebellar projection was analysed by the anterograde axonal WGA-HRP (horseradish peroxidase-wheat germ agglutinin conjugate) tracing method in three different types of agranular cerebellar cortex either induced experimentally by X-irradiation or occurring spontaneously in weaver (wv/wv) and staggerer (sg/sg) mutant mice. The results of this study show that in the X-irradiated rat and weaver mouse, in both of which the granule cells are directly affected and die early in development, the spinal axons reproduce, with few differences, the normal spinocerebellar pattern. Conversely, in staggerer mouse, in which the Purkinje cells are intrinsically affected and granule neurons do not seem to be primarily perturbed by the staggerer gene action, the spinocerebellar organization is severely modified. These findings appear somewhat paradoxical because if granule cells, the synaptic targets of mossy spinocerebellar fibers, were necessary for the organization of spinocerebellar projection, the staggerer cerebellum would exhibit a much more normal projectional map than the weaver and the X-irradiated cerebella. It is, therefore, obvious that granule cells, and even specific synaptogenesis, are not essential for the establishment of the normal spinocerebellar topography. On the other hand, the fact that the Purkinje cells are primarily affected in the unique agranular cortex in which the spinocerebellar organization is severely modified suggests that these neurons could be the main element in the organization of the spinocerebellar projection map. This hypothesis is discussed in correlation with already-reported findings on the zonation of the cerebellar cortex by biochemically different clusters of Purkinje cells

  11. Preventing effect of L-type calcium channel blockade on electrophysiological alterations in dentate gyrus granule cells induced by entorhinal amyloid pathology.

    Hamid Gholami Pourbadie

    Full Text Available The entorhinal cortex (EC is one of the earliest affected brain regions in Alzheimer's disease (AD. EC-amyloid pathology induces synaptic failure in the dentate gyrus (DG with resultant behavioral impairment, but there is little known about its impact on neuronal properties in the DG. It is believed that calcium dyshomeostasis plays a pivotal role in the etiology of AD. Here, the effect of the EC amyloid pathogenesis on cellular properties of DG granule cells and also possible neuroprotective role of L-type calcium channel blockers (CCBs, nimodipine and isradipine, were investigated. The amyloid beta (Aβ 1-42 was injected bilaterally into the EC of male rats and one week later, electrophysiological properties of DG granule cells were assessed. Voltage clamp recording revealed appearance of giant sIPSC in combination with a decrease in sEPSC frequency which was partially reversed by CCBs in granule cells from Aβ treated rats. EC amyloid pathogenesis induced a significant reduction of input resistance (Rin accompanied by a profound decreased excitability in the DG granule cells. However, daily administration of CCBs, isradipine or nimodipine (i.c.v. for 6 days, almost preserved the normal excitability against Aβ. In conclusion, lower tendency to fire AP along with reduced Rin suggest that DG granule cells might undergo an alteration in the membrane ion channel activities which finally lead to the behavioral deficits observed in animal models and patients with early-stage Alzheimer's disease.

  12. UNCERTAINTY HANDLING IN DISASTER MANAGEMENT USING HIERARCHICAL ROUGH SET GRANULATION

    H. Sheikhian

    2015-08-01

    Full Text Available Uncertainty is one of the main concerns in geospatial data analysis. It affects different parts of decision making based on such data. In this paper, a new methodology to handle uncertainty for multi-criteria decision making problems is proposed. It integrates hierarchical rough granulation and rule extraction to build an accurate classifier. Rough granulation provides information granules with a detailed quality assessment. The granules are the basis for the rule extraction in granular computing, which applies quality measures on the rules to obtain the best set of classification rules. The proposed methodology is applied to assess seismic physical vulnerability in Tehran. Six effective criteria reflecting building age, height and material, topographic slope and earthquake intensity of the North Tehran fault have been tested. The criteria were discretized and the data set was granulated using a hierarchical rough method, where the best describing granules are determined according to the quality measures. The granules are fed into the granular computing algorithm resulting in classification rules that provide the highest prediction quality. This detailed uncertainty management resulted in 84% accuracy in prediction in a training data set. It was applied next to the whole study area to obtain the seismic vulnerability map of Tehran. A sensitivity analysis proved that earthquake intensity is the most effective criterion in the seismic vulnerability assessment of Tehran.

  13. Assessment of physical properties of granules with paracetamol and caffeine

    Michal Szumilo

    2017-09-01

    Full Text Available Caffeine increases the analgesic properties of acetaminophen and therefore it is reasonable to use both substances together in one drug form in stronger pain. Currently, there are no commercially available pharmaceutical combination products containing acetaminophen and caffeine, which is present as granules. The aim of the study was to obtain twelve different granules with these therapeutic substances and determine the effect of various excipients on the quality of the drug form. All the granules were made by wet granulation. Two types of binders were used: polyethylene glycol 6000 (PEG and polyvinylpyrrolidone K30 (PVP as well as different types of fillers. The physical properties of granules were assessed in accordance to the requirements of the European Pharmacopoeia 8th ed. The highest apparent density was found in preparations containing calcium hydrophosphate (0.609 g/mL and the lowest – containing mannitol (0.353 g/mL as a filler. The Hausner ratio of most prepared granules ranged from 1.05 to 1.11, while the compressibility index ranged from 4.59 to 10.48%. The evaluation of properties of individual granules helped to indicate formulation with good features, which perhaps will be a good alternative to currently available painkillers with caffeine and acetaminophen.

  14. Characterization of depolarization-coupled release of glutamate from cultured mouse cerebellar granule cells using DL-threo-beta-benzyloxyaspartate (DL-TBOA) to distinguish between the vesicular and cytoplasmic pools

    Bak, Lasse K; Schousboe, Arne; Waagepetersen, Helle S

    2003-01-01

    Release of preloaded [3H]D-aspartate in response to depolarization induced by N-methyl-D-aspartate (NMDA) or the endogenous agonist glutamate was characterized using cultured glutamatergic cerebellar granule neurons. Release from the vesicular and the cytoplasmic glutamate pools, respectively, wa...

  15. Zinc sulfide in intestinal cell granules of Ancylostoma caninum adults

    Gianotti, A.J.; Clark, D.T.; Dash, J. (Portland State Univ., OR (USA))

    1991-04-01

    A source of confusion has existed since the turn of the century about the reddish brown, weakly birefringent 'sphaerocrystals' located in the intestines of strongyle nematodes, Strongylus and Ancylostoma. X-ray diffraction and energy dispersive spectrometric analyses were used for accurate determination of the crystalline order and elemental composition of the granules in the canine hookworm Ancylostoma caninum. The composition of the intestinal pigmented granules was identified unequivocally as zinc sulfide. It seems most probable that the granules serve to detoxify high levels of metallic ions (specifically zinc) present due to the large intake of host blood.

  16. Mechanistic modelling of the drying behaviour of single pharmaceutical granules

    Thérèse F.C. Mortier, Séverine; Beer, Thomas De; Gernaey, Krist

    2012-01-01

    The trend to move towards continuous production processes in pharmaceutical applications enhances the necessity to develop mechanistic models to understand and control these processes. This work focuses on the drying behaviour of a single wet granule before tabletting, using a six...... phase (submodel 2), the water inside the granule evaporates. The second submodel contains an empirical power coefficient, b. A sensitivity analysis was performed to study the influence of parameters on the moisture content of single pharmaceutical granules, which clearly points towards the importance...

  17. Electronics

    2001-01-01

    International Acer Incorporated, Hsin Chu, Taiwan Aerospace Industrial Development Corporation, Taichung, Taiwan American Institute of Taiwan, Taipei, Taiwan...Singapore and Malaysia .5 - 4 - The largest market for semiconductor products is the high technology consumer electronics industry that consumes up...Singapore, and Malaysia . A new semiconductor facility costs around $3 billion to build and takes about two years to become operational

  18. Iron coated pottery granules for arsenic removal from drinking water.

    Dong, Liangjie; Zinin, Pavel V; Cowen, James P; Ming, Li Chung

    2009-09-15

    A new media, iron coated pottery granules (ICPG) has been developed for As removal from drinking water. ICPG is a solid phase media that produces a stable Fe-Si surface complex for arsenic adsorption. Scanning electron microscopy (SEM) was used to document the physical attributes (grain size, pore size and distribution, surface roughness) of the ICPG media. Several advantages of the ICPG media such as (a) its granular structure, (b) its ability to absorb As via the F(0) coating on the granules' surface; (c) the inexpensive preparation process for the media from clay material make ICPG media a highly effective media for removing arsenic at normal pH. A column filtration test demonstrated that within the stability region (flow rate lower than 15L/h, EBCT >3 min), the concentration of As in the influent was always lower than 50 microg/L. The 2-week system ability test showed that the media consistently removed arsenic from test water to below the 5 microg/L level. The average removal efficiencies for total arsenic, As(III), and As(V) for a 2-week test period were 98%, 97%, and 99%, respectively, at an average flow rate of 4.1L/h and normal pH. Measurements of the Freundlich and Langmuir isotherms at normal pH show that the Freundlich constants of the ICPG are very close to those of ferric hydroxide, nanoscale zero-valent iron and much higher than those of nanocrystalline titanium dioxide. The parameter 1/n is smaller than 0.55 indicating a favorable adsorption process [K. Hristovski, A. Baumgardner, P. Westerhoff, Selecting metal oxide nanomaterials for arsenic removal in fixed bed columns: from nanopowders to aggregated nanoparticle media, J. Hazard. Mater. 147 (2007) 265-274]. The maximum adsorption capacity (q(e)) of the ICPG from the Langmuir isotherm is very close to that of nanoscale zero-valent indicating that zero-valent iron is involved in the process of the As removal from the water. The results of the toxicity characteristic leaching procedure (TCLP

  19. Iron coated pottery granules for arsenic removal from drinking water

    Dong Liangjie; Zinin, Pavel V.; Cowen, James P.; Ming, Li Chung

    2009-01-01

    A new media, iron coated pottery granules (ICPG) has been developed for As removal from drinking water. ICPG is a solid phase media that produces a stable Fe-Si surface complex for arsenic adsorption. Scanning electron microscopy (SEM) was used to document the physical attributes (grain size, pore size and distribution, surface roughness) of the ICPG media. Several advantages of the ICPG media such as (a) its granular structure, (b) its ability to absorb As via the F(0) coating on the granules' surface; (c) the inexpensive preparation process for the media from clay material make ICPG media a highly effective media for removing arsenic at normal pH. A column filtration test demonstrated that within the stability region (flow rate lower than 15 L/h, EBCT >3 min), the concentration of As in the influent was always lower than 50 μg/L. The 2-week system ability test showed that the media consistently removed arsenic from test water to below the 5 μg/L level. The average removal efficiencies for total arsenic, As(III), and As(V) for a 2-week test period were 98%, 97%, and 99%, respectively, at an average flow rate of 4.1 L/h and normal pH. Measurements of the Freundlich and Langmuir isotherms at normal pH show that the Freundlich constants of the ICPG are very close to those of ferric hydroxide, nanoscale zero-valent iron and much higher than those of nanocrystalline titanium dioxide. The parameter 1/n is smaller than 0.55 indicating a favorable adsorption process [K. Hristovski, A. Baumgardner, P. Westerhoff, Selecting metal oxide nanomaterials for arsenic removal in fixed bed columns: from nanopowders to aggregated nanoparticle media, J. Hazard. Mater. 147 (2007) 265-274]. The maximum adsorption capacity (q e ) of the ICPG from the Langmuir isotherm is very close to that of nanoscale zero-valent indicating that zero-valent iron is involved in the process of the As removal from the water. The results of the toxicity characteristic leaching procedure (TCLP) analysis

  20. Early natural stimulation through environmental enrichment accelerates neuronal development in the mouse dentate gyrus.

    Na Liu

    Full Text Available The dentate gyrus is the primary afferent into the hippocampal formation, with important functions in learning and memory. Granule cells, the principle neuronal type in the dentate gyrus, are mostly formed postnatally, in a process that continues into adulthood. External stimuli, including environmental enrichment, voluntary exercise and learning, have been shown to significantly accelerate the generation and maturation of dentate granule cells in adult rodents. Whether, and to what extent, such environmental stimuli regulate the development and maturation of dentate granule cells during early postnatal development is largely unknown. Furthermore, whether natural stimuli affect the synaptic properties of granule cells had been investigated neither in newborn neurons of the adult nor during early development. To examine the effect of natural sensory stimulation on the dentate gyrus, we reared newborn mice in an enriched environment (EE. Using immunohistochemistry, we showed that dentate granule cells from EE-reared mice exhibited earlier morphological maturation, manifested as faster peaking of doublecortin expression and elevated expression of mature neuronal markers (including NeuN, calbindin and MAP2 at the end of the second postnatal week. Also at the end of the second postnatal week, we found increased density of dendritic spines across the entire dentate gyrus, together with elevated levels of postsynaptic scaffold (post-synaptic density 95 and receptor proteins (GluR2 and GABA(ARγ2 of excitatory and inhibitory synapses. Furthermore, dentate granule cells of P14 EE-reared mice had lower input resistances and increased glutamatergic and GABAergic synaptic inputs. Together, our results demonstrate that EE-rearing promotes morphological and electrophysiological maturation of dentate granule cells, underscoring the importance of natural environmental stimulation on development of the dentate gyrus.

  1. Electrophysiological characterization of granule cells in the dentate gyrus immediately after birth

    Andrea ePedroni

    2014-02-01

    Full Text Available Granule cells (GCs in the dentate gyrus are generated mainly postnatally. Between embryonic day 10 and 14, neural precursors migrate from the primary dentate matrix to the dentate gyrus where they differentiate into neurons. Neurogenesis reaches a peak at the end of the first postnatal week and it is completed at the end of the first postnatal month. This process continues at a reduced rate throughout life. Interestingly, immediately after birth, GCs exhibit a clear GABAergic phenotype. Only later they integrate the classical glutamatergic trisynaptic hippocampal circuit. Here, whole patch clamp recordings, in current clamp mode, were performed from immature GCs, intracellularly loaded with biocytin (in hippocampal slices from P0-P3 old rats in order to compare their morphological characteristics with their electrophysiological properties. The vast majority of GCs were very immature with small somata, few dendritic branches terminating with small varicosities and growth cones. In spite of their immaturity their axons reached often the CA3 area. Immature GCs generated, upon membrane depolarization, either rudimentary sodium spikes or more clear overshooting action potentials that fired repetitively. They exhibited also low threshold calcium spikes. In addition, most spiking neurons showed spontaneous synchronized network activity, reminiscent of giant depolarizing potentials (GDPs generated in the hippocampus by the synergistic action of glutamate and GABA, both depolarizing and excitatory. This early synchronized activity, absent during adult neurogenesis, may play a crucial role in the refinement of local neuronal circuits within the developing dentate gyrus.

  2. Does Thermal Granulation Drive Tephra Jets?

    White, J. D.; Zimanowski, B.; Buettner, R.; Sonder, I.; Dellino, P.

    2011-12-01

    Surtseyan tephra jets, also called cypressoid or cock's tail plumes, comprise a characteristic mixture of ash with bombs travelling roughly ballistic paths that tip the individual fingers of the projecting jet. Jets of similar form but smaller scale are generated by littoral magma-water interactions, confirming the general inference that surtseyan tephra jets are a characteristic product of explosive magma-water interaction, and suggesting that magmatic volatiles play a subsidiary role, if any, in their formation. Surtseyan jets have been inferred to result from both intense fuel-coolant interactions, and from simple boiling of water entrained into rising magma, and little new information has become available to test these two positions since they were clearly developed in the 1980s. Recent experiments in which magma is poured into standing water have produced vigorous jetting of hot water as melt solidifies and undergoes extensive thermal granulation. We present high-resolution hi-speed video of these jets, which we see as having the following origin. As thermal granulation takes place, a fracture network advances into the melt/glass body, and water invading the cracks at the rate of propagation is heated nearly instantaneously. Vapor produced at the contact expands and drives outward through cooled cracks, condensing as it moves to the exterior of the magma body where it is emitted as a jet of hot water. In ocean ridge hydrothermal systems a diffuse crack network inducts cold water, which is heated and expelled in focused jets. Focusing of hot outflow in experiments is inferred to result, as suggested for ridge hydrothermal systems, from thermoelastic closure of cracks near the one(s) feeding the jet. From the cooled products of our experimental runs, we know that thermal contraction produces a network of curved cracks with modal spacing of 1-2 mm, which separate domains of unbroken glass. It is during growth of this crack network that cold water enters, is

  3. Neurons other than motor neurons in motor neuron disease.

    Ruffoli, Riccardo; Biagioni, Francesca; Busceti, Carla L; Gaglione, Anderson; Ryskalin, Larisa; Gambardella, Stefano; Frati, Alessandro; Fornai, Francesco

    2017-11-01

    Amyotrophic lateral sclerosis (ALS) is typically defined by a loss of motor neurons in the central nervous system. Accordingly, morphological analysis for decades considered motor neurons (in the cortex, brainstem and spinal cord) as the neuronal population selectively involved in ALS. Similarly, this was considered the pathological marker to score disease severity ex vivo both in patients and experimental models. However, the concept of non-autonomous motor neuron death was used recently to indicate the need for additional cell types to produce motor neuron death in ALS. This means that motor neuron loss occurs only when they are connected with other cell types. This concept originally emphasized the need for resident glia as well as non-resident inflammatory cells. Nowadays, the additional role of neurons other than motor neurons emerged in the scenario to induce non-autonomous motor neuron death. In fact, in ALS neurons diverse from motor neurons are involved. These cells play multiple roles in ALS: (i) they participate in the chain of events to produce motor neuron loss; (ii) they may even degenerate more than and before motor neurons. In the present manuscript evidence about multi-neuronal involvement in ALS patients and experimental models is discussed. Specific sub-classes of neurons in the whole spinal cord are reported either to degenerate or to trigger neuronal degeneration, thus portraying ALS as a whole spinal cord disorder rather than a disease affecting motor neurons solely. This is associated with a novel concept in motor neuron disease which recruits abnormal mechanisms of cell to cell communication.

  4. Removal of 4-chlorophenol from synthetic wastewater by the granulated graphene oxide nano particles

    A Eslami

    2016-09-01

    Full Text Available Abstract Introduction: 4-chlorophenols one of the most common pollutants in wastewater is generated from the chemical and petrochemical industries. It is due to the presence of chloride and benzene ring is resistant to biodegradation. In this study, the use of granulated graphene oxide nano particles as an adsorbent nanostructure with better properties than other adsorbents for Removal of 4- chlorophenol from aqueous solution were investigated Methods: This research was implemented during the year 2013-2014 where the Granules of Graphene oxide nanoparticles were prepared using sodium silicate and X-ray diffraction techniques and electron microscope were used to identify the morphology and structure of the adsorbent of.  Parameters  affecting the adsorption process such as initial concentration of  4-chlorophenol(5,10,15,20,25,30mg/L, amount of adsorbent(20,40,60,80% by weight, contact time (3,5,10,20,30 min and pH(4,6,7,8,9 were investigated by changing one factor at a time. Finally, the data fitness with Langmuir and Freundlich isotherms were showed. Results: Adsorption process reached to equilibrium after 20 minutes. 2 g/L of graphene oxide granules at 3 minutes and 7 = pH could remove 5 mg/L 4-chlorophenol up to 58%. Freundlich isotherm have describing adsorption process and R2 =0.92. Conclusion: Absorbed process by the granules of Graphene oxide nanoparticles is low-cost high-efficiency and it could used to reduce and eliminate environmental pollutants particularly aqueous solutions.  

  5. LXR agonist rescued the deficit in the proliferation of the cerebellar granule cells induced by dexamethasone

    Bian, Xuting; Zhong, Hongyu; Li, Fen; Cai, Yulong; Li, Xin; Wang, Lian; Fan, Xiaotang, E-mail: fanxiaotang2005@163.com

    2016-09-02

    Dexamethasone (DEX) exposure during early postnatal life produces permanent neuromotor and intellectual deficits and stunts cerebellar growth. The liver X receptor (LXR) plays important roles in CNS development. However, the effects of LXR on the DEX-mediated impairment of cerebellar development remain undetermined. Thus, mice were pretreated with LXR agonist TO901317 (TO) and were later exposed to DEX to evaluate its protective effects on DEX-mediated deficit during cerebellar development. The results showed that an acute exposure of DEX on postnatal day 7 resulted in a significant impairment in cerebellar development and decreased the proliferation of granule neuron precursors in the external granule layer of cerebellum. This effect was attenuated by pretreatment with TO. We further found that the decrease in the proliferation caused by DEX occurred via up-regulation of glucocorticoid receptor and p27kip1, which could be partially prevented by LXR agonist pretreatment. Overall, our results suggest that LXR agonist pretreatment could protect against DEX-induced deficits in cerebellar development in postnatal mice and may thus be perspective recruited to counteract such GC side effects.

  6. LXR agonist rescued the deficit in the proliferation of the cerebellar granule cells induced by dexamethasone

    Bian, Xuting; Zhong, Hongyu; Li, Fen; Cai, Yulong; Li, Xin; Wang, Lian; Fan, Xiaotang

    2016-01-01

    Dexamethasone (DEX) exposure during early postnatal life produces permanent neuromotor and intellectual deficits and stunts cerebellar growth. The liver X receptor (LXR) plays important roles in CNS development. However, the effects of LXR on the DEX-mediated impairment of cerebellar development remain undetermined. Thus, mice were pretreated with LXR agonist TO901317 (TO) and were later exposed to DEX to evaluate its protective effects on DEX-mediated deficit during cerebellar development. The results showed that an acute exposure of DEX on postnatal day 7 resulted in a significant impairment in cerebellar development and decreased the proliferation of granule neuron precursors in the external granule layer of cerebellum. This effect was attenuated by pretreatment with TO. We further found that the decrease in the proliferation caused by DEX occurred via up-regulation of glucocorticoid receptor and p27kip1, which could be partially prevented by LXR agonist pretreatment. Overall, our results suggest that LXR agonist pretreatment could protect against DEX-induced deficits in cerebellar development in postnatal mice and may thus be perspective recruited to counteract such GC side effects.

  7. a-Band Oscillations in Intracellular Membrane Potentials of Dentate Gyrus Neurons in Awake Rodents

    Anderson, Ross W.; Strowbridge, Ben W.

    2014-01-01

    The hippocampus and dentate gyrus play critical roles in processing declarative memories and spatial information. Dentate granule cells, the first relay in the trisynaptic circuit through the hippocampus, exhibit low spontaneous firing rates even during locomotion. Using intracellular recordings from dentate neurons in awake mice operating a…

  8. The life cycle of platelet granules [version 1; referees: 2 approved

    Anish Sharda

    2018-02-01

    Full Text Available Platelet granules are unique among secretory vesicles in both their content and their life cycle. Platelets contain three major granule types—dense granules, α-granules, and lysosomes—although other granule types have been reported. Dense granules and α-granules are the most well-studied and the most physiologically important. Platelet granules are formed in large, multilobulated cells, termed megakaryocytes, prior to transport into platelets. The biogenesis of dense granules and α-granules involves common but also distinct pathways. Both are formed from the trans-Golgi network and early endosomes and mature in multivesicular bodies, but the formation of dense granules requires trafficking machinery different from that of α-granules. Following formation in the megakaryocyte body, both granule types are transported through and mature in long proplatelet extensions prior to the release of nascent platelets into the bloodstream. Granules remain stored in circulating platelets until platelet activation triggers the exocytosis of their contents. Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE proteins, located on both the granules and target membranes, provide the mechanical energy that enables membrane fusion during both granulogenesis and exocytosis. The function of these core fusion engines is controlled by SNARE regulators, which direct the site, timing, and extent to which these SNAREs interact and consequently the resulting membrane fusion. In this review, we assess new developments in the study of platelet granules, from their generation to their exocytosis.

  9. Study of ATM Phosphorylation by Cdk5 in Neuronal Cells.

    She, Hua; Mao, Zixu

    2017-01-01

    The phosphatidylinositol-3-kinase-like kinase ATM (ataxia-telangiectasia mutated) plays a central role in coordinating the DNA damage responses including cell cycle checkpoint control, DNA repair, and apoptosis. Mutations of ATM cause a spectrum of defects ranging from neurodegeneration to cancer predisposition. We previously showed that Cdk5 (cyclin-dependent kinase 5) is activated by DNA damage and directly phosphorylates ATM at serine 794 in postmitotic neurons. Phosphorylation at serine 794 precedes and is required for ATM autophosphorylation at serine 1981, and activates ATM kinase activity. Cdk5-ATM pathway plays a crucial role in DNA damage-induced neuronal injury. This chapter describes protocols used in analyzing ATM phosphorylation by Cdk5 in CGNs (cerebellar granule neurons) and its effects on neuronal survival.

  10. Survival of adult neurons lacking cholesterol synthesis in vivo.

    Fünfschilling, Ursula; Saher, Gesine; Xiao, Le; Möbius, Wiebke; Nave, Klaus-Armin

    2007-01-02

    Cholesterol, an essential component of all mammalian plasma membranes, is highly enriched in the brain. Both during development and in the adult, brain cholesterol is derived from local cholesterol synthesis and not taken up from the circulation. However, the contribution of neurons and glial cells to total brain cholesterol metabolism is unknown. Using conditional gene inactivation in the mouse, we disrupted the squalene synthase gene (fdft1), which is critical for cholesterol synthesis, in cerebellar granule cells and some precerebellar nuclei. Mutant mice showed no histological signs of neuronal degeneration, displayed ultrastructurally normal synapses, and exhibited normal motor coordination. This revealed that these adult neurons do not require cell-autonomous cholesterol synthesis for survival or function. We conclude that at least some adult neurons no longer require endogenous cholesterol synthesis and can fully meet their cholesterol needs by uptake from their surrounding. Glia are a likely source of cholesterol in the central nervous system.

  11. Survival of adult neurons lacking cholesterol synthesis in vivo

    Möbius Wiebke

    2007-01-01

    Full Text Available Abstract Background Cholesterol, an essential component of all mammalian plasma membranes, is highly enriched in the brain. Both during development and in the adult, brain cholesterol is derived from local cholesterol synthesis and not taken up from the circulation. However, the contribution of neurons and glial cells to total brain cholesterol metabolism is unknown. Results Using conditional gene inactivation in the mouse, we disrupted the squalene synthase gene (fdft1, which is critical for cholesterol synthesis, in cerebellar granule cells and some precerebellar nuclei. Mutant mice showed no histological signs of neuronal degeneration, displayed ultrastructurally normal synapses, and exhibited normal motor coordination. This revealed that these adult neurons do not require cell-autonomous cholesterol synthesis for survival or function. Conclusion We conclude that at least some adult neurons no longer require endogenous cholesterol synthesis and can fully meet their cholesterol needs by uptake from their surrounding. Glia are a likely source of cholesterol in the central nervous system.

  12. Rac1 regulates neuronal polarization through the WAVE complex

    Tahirovic, Sabina; Hellal, Farida; Neukirchen, Dorothee

    2010-01-01

    the physiological function of Rac1 in neuronal development, we have generated a conditional knock-out mouse, in which Rac1 is ablated in the whole brain. Rac1-deficient cerebellar granule neurons, which do not express other Rac isoforms, showed impaired neuronal migration and axon formation both in vivo...... and in vitro. In addition, Rac1 ablation disrupts lamellipodia formation in growth cones. The analysis of Rac1 effectors revealed the absence of the Wiskott-Aldrich syndrome protein (WASP) family verprolin-homologous protein (WAVE) complex from the plasma membrane of knock-out growth cones. Loss of WAVE...... function inhibited axon growth, whereas overexpression of a membrane-tethered WAVE mutant partially rescued axon growth in Rac1-knock-out neurons. In addition, pharmacological inhibition of the WAVE complex effector Arp2/3 also reduced axon growth. We propose that Rac1 recruits the WAVE complex...

  13. Analyzing dendritic growth in a population of immature neurons in the adult dentate gyrus using laminar quantification of disjointed dendrites

    Shira eRosenzweig

    2011-03-01

    Full Text Available In the dentate gyrus of the hippocampus, new granule neurons are continuously produced throughout adult life. A prerequisite for the successful synaptic integration of these neurons is the sprouting and extension of dendrites into the molecular layer of the dentate gyrus. Thus, studies aimed at investigating the developmental stages of adult neurogenesis often use dendritic growth as an important indicator of neuronal health and maturity. Based on the known topography of the dentate gyrus, characterized by distinct laminar arrangement of granule neurons and their extensions, we have developed a new method for analysis of dendritic growth in immature adult-born granule neurons. The method is comprised of laminar quantification of cell bodies, primary, secondary and tertiary dendrites separately and independently from each other. In contrast to most existing methods, laminar quantification of dendrites does not require the use of exogenous markers and does not involve arbitrary selection of individual neurons. The new method relies on immonuhistochemical detection of endogenous markers such as doublecortin to perform a comprehensive analysis of a sub-population of immature neurons. Disjointed, orphan dendrites that often appear in the thin histological sections are taken into account. Using several experimental groups of rats and mice, we demonstrate here the suitable techniques for quantifying neurons and dendrites, and explain how the ratios between the quantified values can be used in a comparative analysis to indicate variations in dendritic growth and complexity.

  14. A review of monitoring methods for pharmaceutical wet granulation.

    Hansuld, E M; Briens, L

    2014-09-10

    High-shear wet granulation is commonly used in the pharmaceutical industry to improve powder properties for downstream processes such as tabletting. Granule growth, however, is difficult to predict because the process is sensitive to raw material properties and operating conditions. Development of process analytical technologies is encouraged by regulatory bodies to improve process understanding and monitor quality online. The primary technologies investigated for high-shear wet granulation monitoring include power consumption, near-infrared spectroscopy, Raman spectroscopy, capacitance measurements, microwave measurements, imaging, focused beam reflectance measurements, spatial filter velocimetry, stress and vibration measurements, as well as acoustic emissions. This review summarizes relevant research related to each of these technologies and discusses the challenges associated with each approach as a possible process analytical technology tool for high-shear wet granulation. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Evaluation of Grade 120 Granulated Ground blast Furnace Slag.

    1999-06-01

    This study evaluates Grade 120 Granulated Ground Blast Furnace Slag (GGBFS) and its effect on the properties of hydraulic cement concretes used in structural and pavement construction. Several mix designs, structural and pavement, were used for this ...

  16. Treatment of hyper-granulated limb wounds in horses

    O. A. Bader

    2011-01-01

    Full Text Available This study was performed to investigate the different methods of treating hyper granulation tissue on experimentally induced wounds in equine limbs. Wounds were induced by removal of a skin patch and subcutaneous tissue for about 5-7 cm width and 6-8 cm in length from the dorsal and lateral aspect of the fore and hind limbs below the carpal and tarsal joints. The wounds were left open without treatment and the animals were trained 2-2.5 hours every day for about 3-5 weeks until hyper granulation tissue was developed. The schedule for the treatment of hyper granulation was divided into five groups each contained eight wounds of hyper granulation tissue; each main group was divided into two subgroups. The subgroups of first, second, third, fourth and fifth groups were treated by the following schedules: bandage alone; copper sulphate ointment 10%; silver nitrate ointment 2%; red mercury ointment 11%; and laser therapy (at a total dose of 9.72 Joule / cm2 respectively. While the second subgroups were treated by surgical resection of the hyper granulation tissue, followed by the same treatments applied on the first subgroup. The bandage for all experimental groups was changed every 48 hours until healing was occurred. The clinical and histological observation of the first group revealed that the healing take long period comparing with other groups. The mean of wound healing were 65 days in non surgical removal of hyper granulation tissue subgroup, while 57 days in surgical removed of hyper granulation tissue subgroup. The results of the second, third, fourth groups revealed that the caustic material especially red mercury has a role in healing processes through depressing the hyper granulation tissue. The mean of wound healing of the second group was 42.25 days in non surgical removal of hyper granulation tissue subgroup while 37.25 days in surgically removed hyper granulation tissue subgroup. In the third group the mean of wound healing was 45

  17. In vitro binding of puroindolines to wheat starch granules

    Sørensen, Helle Aagaard; Darlington, H.F.; Shewry, P.R.

    2001-01-01

    Puroindoline (pin) preparations made from flours of hard and soft wheats contained a mixture of pin-a, 0.19/0.53 alpha -amylase inhibitor, and purothionins. Starch granule preparations from the same cultivars were treated with proteinase to remove surface proteins and incubated with solutions...... of the pin preparations. Binding of pin-a and purothionins but not the 0.19/0.53 inhibitor was observed with no apparent differences between the behavior of the pin preparations or starch granule preparations from hard or soft types. No binding was observed when several other proteins (bovine serum albumin......, total albumins, a commercial preparation of wheat alpha -amylase inhibitors, and barley beta -amylase) were incubated with the starch granules under the same conditions, indicating that in vitro binding can be used to study specific starch granule and protein interactions....

  18. A Review of Granulation Process for Blast Furnace Slag

    Yu Pengfei

    2016-01-01

    Full Text Available Molten slags of blast furnace is a second resources with great value of 1600~1 800 MJ sensible heat per ton. At present, water-quenching process plays a leading role in recovering waste heat of the molten slags. However, this method not only cost lots of water, but also recover little sensible heat and can pollute the surrounding environment. Dry granulation process, as an environmentally friendly method with high-efficiency heat recovery, have attracted widespread attentions. In this paper, the water quenching and dry granulation processes were discussed in detail. After a thorough comparative analysis of various treatment technologies, it can be concluded that centrifugal granulation affiliated with dry granulation is the optimum process, with smaller slag particle size (about 2mm, more glassy phase and higher recovery rate.

  19. Kit systems for granulated decontamination formulations

    Tucker, Mark D.

    2010-07-06

    A decontamination formulation and method of making that neutralizes the adverse health effects of both chemical and biological compounds, especially chemical warfare (CW) and biological warfare (BW) agents, and toxic industrial chemicals. The formulation provides solubilizing compounds that serve to effectively render the chemical and biological compounds, particularly CW and BW compounds, susceptible to attack, and at least one reactive compound that serves to attack (and detoxify or kill) the compound. The formulation includes at least one solubilizing agent, a reactive compound, a sorbent additive, and water. A highly adsorbent sorbent additive (e.g., amorphous silica, sorbitol, mannitol, etc.) is used to "dry out" one or more liquid ingredients into a dry, free-flowing powder that has an extended shelf life, and is more convenient to handle and mix in the field. The formulation can be pre-mixed and pre-packaged as a multi-part kit system, where one or more of the parts are packaged in a powdered, granulated form for ease of handling and mixing in the field.

  20. Development of granules from Phyllanthus niruri spray-dried extract

    Tatiane Pereira de Souza

    2009-12-01

    Full Text Available The aim of this study was to develop granules from Phyllanthus niruri spray-dried extract using dry and wet granulation and to assess techniques to enable the production of granules with improved technological characteristics and yields. Granules were characterized by granulometry, reological parameters, compression and hygroscopic behavior. Independent of the granulation technique, technologically developed granules presented particle diameter, bulk and tapped densities and compressibility indexes suitable for a solid dosage form. The compression behavior showed plastic and fragmentary deformation for granules produced by the dry granulation technique and predominantly plastic deformation for wet granulation. Concerning the humidity sorption, the study showed that granules absorb less humidity than the spray-dried extract. However, granules with Eudragit® E 100 were the least hygroscopic.O objetivo deste estudo foi desenvolver grânulos de extrato Phyllantus niruri seco por aspersão e por granulação úmida e avaliar técnicas que possibilitem a produção de grânulos com características tecnológicas e rendimentos aperfeiçoados. Os grânulos foram caracterizados por granulometria, parâmetros reológicos, compressão e comportamento higroscópico. Independentemente da técnica de granulação, os grânulos tecnologicamente desenvolvidos apresentaram diâmetro de partículas, densidades aparente e compactada e índices de compressibilidade adequados para a formulação sólida. O comportamento de compressão mostrou deformação plástica e elástica para os grânulos produzidos por técnicas de granulação seca e, predominantemente, deformação plástica para a granulação úmida. Com relação à absorção da umidade, o estudo mostrou que os grânulos absorvem menos umidade do que o extrato seco por aspersão. Entretanto, os grânulos com Eudragit E 100 foram os menos higroscópicos.

  1. Sludge granulation during anaerobic treatment of pre-hydrolysed ...

    An upflow anaerobic sludge bed (UASB) digester was operated at different hydraulic retention times (HRT) ranging from 26.7 h to 2.2 h, while the organic load rate (OLR) ranged from 0.9 to 7.3 kgCOD/m3·d. Sludge granulation was observed after day 150 of operation, at an HRT of 3.4 h, when small granules of less than 2 ...

  2. Superheated superconducting granules: a detector for particle physics and astrophysics

    Gonzalez-Mestres, L.; Perret-Gallix, D.

    1987-01-01

    A general introduction to superheated superconducting granules (SSG) detectors is given and some recent results on their basic properties are presented. Granules recently made by industrial producers exhibit good metastability properties and show sensitivity, better than naively expected, to photons and ionizing particles. The behaviour of SSG detectors at very low temperatures is also discussed. We finally sketch a critical review of proposed applications to the cross-disciplinary frontier between particle physics and astrophysics

  3. Effect of granular activated carbon on the aerobic granulation of sludge and its mechanism.

    Tao, Jia; Qin, Lian; Liu, Xiaoying; Li, Bolin; Chen, Junnan; You, Juan; Shen, Yitian; Chen, Xiaoguo

    2017-07-01

    The granulation of activated sludge and effect of granular activated carbon (GAC) was investigated under the alternative anaerobic and aerobic conditions. The results showed that GAC accelerated the granulation, but had no obvious effect on the bacterial community structure of granules. The whole granulation process could be categorized into three phases, i.e. lag, granulation and granule maturation phase. During lag period GAC provided nuclei for sludge to attach, and thus enhanced the morphological regularization of sludge. During granulation period the granule size increased significantly due to the growth of bacteria in granules. GAC reduced the compression caused by the inter-particle collisions and thus accelerate the granulation. GAC has no negative effect on the performance of SBR, and thus efficient simultaneous removal of COD, nitrogen and phosphorus were obtained during most of the operating time. Copyright © 2017. Published by Elsevier Ltd.

  4. Metabolism of Mannose in Cultured Primary Rat Neurons.

    Rastedt, Wiebke; Blumrich, Eva-Maria; Dringen, Ralf

    2017-08-01

    Glucose is the main peripheral substrate for energy production in the brain. However, as other hexoses are present in blood and cerebrospinal fluid, we have investigated whether neurons have the potential to metabolize, in addition to glucose, also the hexoses mannose, fructose or galactose. Incubation of primary cerebellar granule neurons in the absence of glucose caused severe cell toxicity within 24 h, which could not be prevented by application of galactose or fructose, while the cells remained viable during incubation in the presence of either mannose or glucose. In addition, cultured neurons produced substantial and almost identical amounts of lactate after exposure to either glucose or mannose, while lactate production was low in the presence of fructose and hardly detectable during incubations without hexoses or with galactose as carbon source. Determination of the K M values of hexokinase in lysates of cultured neurons for the hexoses revealed values in the micromolar range for mannose (32 ± 2 µM) and glucose (59 ± 10 µM) and in the millimolar range for fructose (4.4 ± 2.3 mM), demonstrating that mannose is efficiently phosphorylated by neuronal hexokinase. Finally, cultured neurons contained reasonable specific activity of the enzyme phosphomannose isomerase, which is required for isomerization of the hexokinase product mannose-6-phosphate into the glycolysis intermediate fructose-6-phosphate. These data demonstrate that cultured cerebellar granule neurons have the potential and express the required enzymes to efficiently metabolize mannose, while galactose and fructose serve at best poorly as extracellular carbon sources for neurons.

  5. PHYSICAL PROPERTIES OF LARGE AND SMALL GRANULES IN SOLAR QUIET REGIONS

    Yu Daren; Xie Zongxia; Hu Qinghua [Harbin Institute of Technology, Harbin 150001 (China); Yang Shuhong; Zhang Jun; Wang Jingxiu, E-mail: caddiexie@hotmail.com, E-mail: zjun@ourstar.bao.ac.cn [Key Laboratory of Solar Activity, National Astronomical Observatories, Chinese Academy of Sciences, Beijing 100012 (China)

    2011-12-10

    The normal mode observations of seven quiet regions obtained by the Hinode spacecraft are analyzed to study the physical properties of granules. An artificial intelligence technique is introduced to automatically find the spatial distribution of granules in feature spaces. In this work, we investigate the dependence of granular continuum intensity, mean Doppler velocity, and magnetic fields on granular diameter. We recognized 71,538 granules by an automatic segmentation technique and then extracted five properties: diameter, continuum intensity, Doppler velocity, and longitudinal and transverse magnetic flux density to describe the granules. To automatically explore the intrinsic structures of the granules in the five-dimensional parameter space, the X-means clustering algorithm and one-rule classifier are introduced to define the rules for classifying the granules. It is found that diameter is a dominating parameter in classifying the granules and two families of granules are derived: small granules with diameters smaller than 1.''44, and large granules with diameters larger than 1.''44. Based on statistical analysis of the detected granules, the following results are derived: (1) the averages of diameter, continuum intensity, and Doppler velocity in the upward direction of large granules are larger than those of small granules; (2) the averages of absolute longitudinal, transverse, and unsigned flux density of large granules are smaller than those of small granules; (3) for small granules, the average of continuum intensity increases with their diameters, while the averages of Doppler velocity, transverse, absolute longitudinal, and unsigned magnetic flux density decrease with their diameters. However, the mean properties of large granules are stable; (4) the intensity distributions of all granules and small granules do not satisfy Gaussian distribution, while that of large granules almost agrees with normal distribution with a peak at 1.04 I

  6. Plant RNA Regulatory Network and RNA Granules in Virus Infection

    Kristiina Mäkinen

    2017-12-01

    Full Text Available Regulation of post-transcriptional gene expression on mRNA level in eukaryotic cells includes translocation, translation, translational repression, storage, mRNA decay, RNA silencing, and nonsense-mediated decay. These processes are associated with various RNA-binding proteins and cytoplasmic ribonucleoprotein complexes many of which are conserved across eukaryotes. Microscopically visible aggregations formed by ribonucleoprotein complexes are termed RNA granules. Stress granules where the translationally inactive mRNAs are stored and processing bodies where mRNA decay may occur present the most studied RNA granule types. Diverse RNP-granules are increasingly being assigned important roles in viral infections. Although the majority of the molecular level studies on the role of RNA granules in viral translation and replication have been conducted in mammalian systems, some studies link also plant virus infection to RNA granules. An increasing body of evidence indicates that plant viruses require components of stress granules and processing bodies for their replication and translation, but how extensively the cellular mRNA regulatory network is utilized by plant viruses has remained largely enigmatic. Antiviral RNA silencing, which is an important regulator of viral RNA stability and expression in plants, is commonly counteracted by viral suppressors of RNA silencing. Some of the RNA silencing suppressors localize to cellular RNA granules and have been proposed to carry out their suppression functions there. Moreover, plant nucleotide-binding leucine-rich repeat protein-mediated virus resistance has been linked to enhanced processing body formation and translational repression of viral RNA. Many interesting questions relate to how the pathways of antiviral RNA silencing leading to viral RNA degradation and/or repression of translation, suppression of RNA silencing and viral RNA translation converge in plants and how different RNA granules and

  7. Plant RNA Regulatory Network and RNA Granules in Virus Infection.

    Mäkinen, Kristiina; Lõhmus, Andres; Pollari, Maija

    2017-01-01

    Regulation of post-transcriptional gene expression on mRNA level in eukaryotic cells includes translocation, translation, translational repression, storage, mRNA decay, RNA silencing, and nonsense-mediated decay. These processes are associated with various RNA-binding proteins and cytoplasmic ribonucleoprotein complexes many of which are conserved across eukaryotes. Microscopically visible aggregations formed by ribonucleoprotein complexes are termed RNA granules. Stress granules where the translationally inactive mRNAs are stored and processing bodies where mRNA decay may occur present the most studied RNA granule types. Diverse RNP-granules are increasingly being assigned important roles in viral infections. Although the majority of the molecular level studies on the role of RNA granules in viral translation and replication have been conducted in mammalian systems, some studies link also plant virus infection to RNA granules. An increasing body of evidence indicates that plant viruses require components of stress granules and processing bodies for their replication and translation, but how extensively the cellular mRNA regulatory network is utilized by plant viruses has remained largely enigmatic. Antiviral RNA silencing, which is an important regulator of viral RNA stability and expression in plants, is commonly counteracted by viral suppressors of RNA silencing. Some of the RNA silencing suppressors localize to cellular RNA granules and have been proposed to carry out their suppression functions there. Moreover, plant nucleotide-binding leucine-rich repeat protein-mediated virus resistance has been linked to enhanced processing body formation and translational repression of viral RNA. Many interesting questions relate to how the pathways of antiviral RNA silencing leading to viral RNA degradation and/or repression of translation, suppression of RNA silencing and viral RNA translation converge in plants and how different RNA granules and their individual

  8. Reduction of the immunostainable length of the hippocampal dentate granule cells’ primary cilia in 3xAD-transgenic mice producing human Aβ1-42 and tau

    Chakravarthy, Balu; Gaudet, Chantal; Ménard, Michel; Brown, Leslie; Atkinson, Trevor; LaFerla, Frank M.; Ito, Shingo; Armato, Ubaldo; Dal Prà, Ilaria; Whitfield, James

    2012-01-01

    Highlights: ► Aβ and tau-induced neurofibrillary tangles play a key role in Alzheimer’s disease. ► Aβ 1-42 and mutant tau protein together reduce the primary cilium length. ► This shortening likely reduces cilium-dependent neurogenesis and memory function. ► This provides a model of an Aβ/tau targeting of a neuronal signaling organelle. -- Abstract: The hippocampal dentate gyrus is one of the two sites of continuous neurogenesis in adult rodents and humans. Virtually all dentate granule cells have a single immobile cilium with a microtubule spine or axoneme covered with a specialized cell membrane loaded with receptors such as the somatostatin receptor 3 (SSTR3), and the p75 neurotrophin receptor (p75 NTR ). The signals from these receptors have been reported to stimulate neuroprogenitor proliferation and the post-mitotic maturation of newborn granule cells into functioning granule cells. We have found that in 6–24-months-old triple transgenic Alzheimer’s disease model mice (3xTg-AD) producing both Aβ 1-42 and the mutant human tau protein tau P301L, the dentate granule cells still had immunostainable SSTR3- and p75 NTR -bearing cilia but they were only half the length of the immunostained cilia in the corresponding wild-type mice. However, the immunostainable length of the granule cell cilia was not reduced either in 2xTg-AD mice accumulating large amounts of Aβ 1-42 or in mice accumulating only a mutant human tau protein. Thus it appears that a combination of Aβ 1-42 and tau protein accumulation affects the levels of functionally important receptors in 3xTg-AD mice. These observations raise the important possibility that structural and functional changes in granule cell cilia might have a role in AD.

  9. The GAD-given Right of Dentate Gyrus Granule Cells to Become GABAergic

    Mody, Istvan

    2002-01-01

    low-affinity neurotrophin receptor p75NTR, perhaps as part of a programmed developmental switch, can convert the phenotype of the sympathetic neuron from noradrenergic to cholinergic 4. Other examples of two fast neurotransmitters released from the same neuron include GABA and glycine in interneurons of the spinal cord 5 and glutamate and dopamine in ventral midbrain dopamine neurons 6. Of all CNS neurons, the granule cells of the dentate gyrus appear to be the champions of neurotransmitter colocalization: glutamate, enkephalin, dynorphin, zinc, and finally GABA 2, 7, 8, 9. With this many transmitters in a single neuron, there are probably different ways in which they can be released. Dynorphin and other opioid peptides can be released directly from the dendrites to inhibit excitatory transmission 8. A similar mechanism may take place for GABA, as described in cortical GABAergic neurons 10. PMID:15309121

  10. Localization of SERBP1 in stress granules and nucleoli.

    Lee, Yu-Jen; Wei, Hung-Ming; Chen, Ling-Yun; Li, Chuan

    2014-01-01

    SERPINE1 mRNA-binding protein 1 (SERBP1) is an arginine-methylated RNA-binding protein whose modification affects protein interaction and intracellular localization. In the present study, we show that, under normal growth conditions without stress, SERBP1 interacts with arginine-methylated and stress granule-associated proteins such as heterogeneous nuclear ribonucleoprotein A1, fragile X mental retardation protein and fragile X mental retardation syndrome-related protein 1 in an RNA-dependent manner. We also show that, after arsenite treatment, a proportion of full-length SERBP1 protein co-localizes with the typical stress granule marker T-cell intracellular antigen-1 in the cytoplasmic stress granules. Truncated SERBP1 with an N-terminal, central RG or C-terminal deletion, or single-domain segments comprising the N-terminal, central or C-terminal region, were recruited to stress granules upon arsenite treatment but with reduced efficiency. In addition, upon arsenite treatment, the localization of SERBP1 changed from a diffuse cytoplasmic localization to nuclear-dominant (concentrated in the nucleolus) A similar distribution was observed when cells were treated with the methylation inhibitor adenosine periodate, and was also detected for N- or C-terminal domain deletions and all three single-domain fragments even without stress induction. We further demonstrate that adenosine periodate treatment delays the association/dissociation of SERBP1 with stress granules. Hypomethylation retains SERBP1 in the nucleus/nucleolus regardless of arsenite treatment. Our study indicates that arginine methylation is correlated with recruitment of SERBP to stress granules and nucleoli and its retention therein. To our knowledge, this is the first report of an RNA-binding protein that is shifted simultaneously to cytoplasmic stress granules and nucleoli, two ribonucleoprotein-enriched subcellular compartments, upon stress. © 2013 FEBS.

  11. A chimeric path to neuronal synchronization

    Essaki Arumugam, Easwara Moorthy; Spano, Mark L.

    2015-01-01

    Synchronization of neuronal activity is associated with neurological disorders such as epilepsy. This process of neuronal synchronization is not fully understood. To further our understanding, we have experimentally studied the progression of this synchronization from normal neuronal firing to full synchronization. We implemented nine FitzHugh-Nagumo neurons (a simplified Hodgkin-Huxley model) via discrete electronics. For different coupling parameters (synaptic strengths), the neurons in the ring were either unsynchronized or completely synchronized when locally coupled in a ring. When a single long-range connection (nonlocal coupling) was introduced, an intermediate state known as a chimera appeared. The results indicate that (1) epilepsy is likely not only a dynamical disease but also a topological disease, strongly tied to the connectivity of the underlying network of neurons, and (2) the synchronization process in epilepsy may not be an "all or none" phenomenon, but can pass through an intermediate stage (chimera).

  12. A chimeric path to neuronal synchronization

    Essaki Arumugam, Easwara Moorthy; Spano, Mark L. [School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona 85287-9709 (United States)

    2015-01-15

    Synchronization of neuronal activity is associated with neurological disorders such as epilepsy. This process of neuronal synchronization is not fully understood. To further our understanding, we have experimentally studied the progression of this synchronization from normal neuronal firing to full synchronization. We implemented nine FitzHugh-Nagumo neurons (a simplified Hodgkin-Huxley model) via discrete electronics. For different coupling parameters (synaptic strengths), the neurons in the ring were either unsynchronized or completely synchronized when locally coupled in a ring. When a single long-range connection (nonlocal coupling) was introduced, an intermediate state known as a chimera appeared. The results indicate that (1) epilepsy is likely not only a dynamical disease but also a topological disease, strongly tied to the connectivity of the underlying network of neurons, and (2) the synchronization process in epilepsy may not be an “all or none” phenomenon, but can pass through an intermediate stage (chimera)

  13. A chimeric path to neuronal synchronization

    Essaki Arumugam, Easwara Moorthy; Spano, Mark L.

    2015-01-01

    Synchronization of neuronal activity is associated with neurological disorders such as epilepsy. This process of neuronal synchronization is not fully understood. To further our understanding, we have experimentally studied the progression of this synchronization from normal neuronal firing to full synchronization. We implemented nine FitzHugh-Nagumo neurons (a simplified Hodgkin-Huxley model) via discrete electronics. For different coupling parameters (synaptic strengths), the neurons in the ring were either unsynchronized or completely synchronized when locally coupled in a ring. When a single long-range connection (nonlocal coupling) was introduced, an intermediate state known as a chimera appeared. The results indicate that (1) epilepsy is likely not only a dynamical disease but also a topological disease, strongly tied to the connectivity of the underlying network of neurons, and (2) the synchronization process in epilepsy may not be an “all or none” phenomenon, but can pass through an intermediate stage (chimera)

  14. Morphological, thermal and physicochemical characteristics of small granules starch from Mirabilis jalapa L

    Pumacahua-Ramos, Augusto [Department of Food Engineering, Universidad Peruana Unión, Juliaca (Peru); Paulista State University, IBILCE/UNESP, São Jose do Rio Preto, SP (Brazil); State University of Ponta Grossa–UEPG, Av. Carlos Cavalcanti, 4748, ZIP 84030-900 Ponta Grossa, PR (Brazil); Demiate, Ivo Mottin [State University of Ponta Grossa–UEPG, Av. Carlos Cavalcanti, 4748, ZIP 84030-900 Ponta Grossa, PR (Brazil); Schnitzler, Egon, E-mail: egons@uepg.br [State University of Ponta Grossa–UEPG, Av. Carlos Cavalcanti, 4748, ZIP 84030-900 Ponta Grossa, PR (Brazil); Bedin, Ana Cláudia [State University of Ponta Grossa–UEPG, Av. Carlos Cavalcanti, 4748, ZIP 84030-900 Ponta Grossa, PR (Brazil); Telis-Romero, Javier; Lopes-Filho, José Francisco [Paulista State University, IBILCE/UNESP, São Jose do Rio Preto, SP (Brazil)

    2015-02-20

    Highlights: • New source of small granules starch was studied. • DSC analysis allowed to determine the gelatinisation of starch from M. jalapa seeds. • Structural characteristics of granules were analysed by XRD and MEV techniques. • The rheological and thermal behaviour were analysed by RVA and TG–DTA. - Abstract: Some physicochemical and thermal properties of starch from Mirabilis jalapa L, seeds were evaluated. The starch was extracted after hulling and grinding the seeds and the flour obtained was suspended in 0.1% (m/v) NaOH solution for 12 h at 30 °C; it was then centrifuged, re-suspended, washed with deionised water and dried in an oven with circulating air at 40 °C for 12 h. The micro-images of starch granules were performed by using scanning electron (SEM) and non-contact atomic force microscopy (NC-AFM) techniques; X-ray diffraction and mid-infrared spectroscopy were both used to evaluate the relative crystallinity of the starch granules. Thermal analyses TG/DTG and DSC, were applied for the analysis of thermal behaviour of this starch and the cooking behaviour of its aqueous solution was studied by using a viscometer RVA. Thermogravimetry showed that once dehydrated, the starch was stable up to 292 °C after which two steps of decomposition occurred, which were attributed to decomposition and oxidation of organic matter, respectively. The gelatinisation temperature and enthalpy, as assessed by DSC analysis, were 82.1 °C and 5.67 J g{sup −1}, respectively. RVA analysis showed pasting temperature of 76.4 °C, with a low viscosity peak at 95 °C, low breakdown, and high tendency to retrograde during cooling. Microscopic results reveal that the starch granules had a spherical shape and 67.4% of them presented diameters smaller than 890 nm. The X-ray diffractogram showed a typical A-type pattern and a relative crystallinity of 34% with a FTIR of 1047/1022 cm{sup −1} and a ratio of 1.38.

  15. The influence of substrate transport limitation on porosity and methanogenic activity of anaerobic sludge granules

    Alphenaar, P.A. (Agricultural Univ., Wageningen (Netherlands). Dept. of Environmental Technology); Perez, M.C. (Agricultural Univ., Wageningen (Netherlands). Dept. of Environmental Technology); Lettinga, G. (Agricultural Univ., Wageningen (Netherlands). Dept. of Environmental Technology)

    1993-05-01

    The relationship between porosity, diameter and methanogenic activity of anaerobic granules has been investigated. Experiments with different granular sludges revealed that substrate transport limitations increase with the diameter of the granules. As a consequence, autolysis can occur in the core of the granule, producing hollow granules. The porosity measurements revealed that the hollow centre is not available for substrate transport. Possibly as an effect of bacterial lysis, the porosity decreases in the more interior layers of the granules. This results in a inactive inner part of the large granules, which is not involved in the treatment process; the specific methanogenic activity decreases with granule size. No marked difference in substrate affinity is observed between granules of different sizes, which probably indicates that for large granules only the exterior is biological active. (orig.)

  16. Ablation of BRaf impairs neuronal differentiation in the postnatal hippocampus and cerebellum.

    Verena Pfeiffer

    Full Text Available This study focuses on the role of the kinase BRaf in postnatal brain development. Mice expressing truncated, non-functional BRaf in neural stem cell-derived brain tissue demonstrate alterations in the cerebellum, with decreased sizes and fuzzy borders of the glomeruli in the granule cell layer. In addition we observed reduced numbers and misplaced ectopic Purkinje cells that showed an altered structure of their dendritic arborizations in the hippocampus, while the overall cornus ammonis architecture appeared to be unchanged. In male mice lacking BRaf in the hippocampus the size of the granule cell layer was normal at postnatal day 12 (P12 but diminished at P21, as compared to control littermates. This defect was caused by a reduced ability of dentate gyrus progenitor cells to differentiate into NeuN positive granule cell neurons. In vitro cell culture of P0/P1 hippocampal cells revealed that BRaf deficient cells were impaired in their ability to form microtubule-associated protein 2 positive neurons. Together with the alterations in behaviour, such as autoaggression and loss of balance fitness, these observations indicate that in the absence of BRaf all neuronal cellular structures develop, but neuronal circuits in the cerebellum and hippocampus are partially disturbed besides impaired neuronal generation in both structures.

  17. Granulation of Cu-Al-Fe-Ni Bronze

    Pisarek B.P.

    2014-08-01

    Full Text Available With the increase in wall thickness of the casting of iron-nickel-aluminium-bronze, by the reduction of the cooling rate the size of κII phase precipitates increases. This process, in the case of complex aluminium bronzes with additions of Cr, Mo and W is increased. Crystallization of big κII phase, during slow cooling of the casting, reduces the concentration of additives introduced to the bronze matrix and hardness. Undertaken research to develop technology of thick-walled products (g> 6 mm of complex aluminium bronzes. Particular attention was paid to the metallurgy of granules. As a result, a large cooling speed of the alloy, and also high-speed solidification casting a light weight of the granules allows: to avoid micro-and macrosegregation, decreasing the particle size, increase the dispersion of phases in multiphase alloys. Depending on the size granules as possible is to provide finished products with a wall thickness greater than 6 mm by infiltration of liquid alloy of granules (composites. Preliminary studies was conducted using drip method granulate of CuAl10Fe5Ni5 bronze melted in a INDUTHERM-VC 500 D Vacuum Pressure Casting Machine. This bronze is a starting alloy for the preparation of the complex aluminium bronzes with additions of Cr, Mo, W and C or Si. Optimizations of granulation process was carried out. As the process control parameters taken a casting temperature t (°C and the path h (mm of free-fall of the metal droplets in the surrounding atmosphere before it is intensively cooled in a container of water. The granulate was subjected to a sieve analysis. For the objective function was assume maximize of the product of Um*n, the percentage weight “Um” and the quantity of granules ‘n’ in the mesh fraction. The maximum value of the ratio obtained for mesh fraction a sieve with a mesh aperture of 6.3 mm. In the intensively cooled granule of bronze was identified microstructure composed of phases: β and fine bainite

  18. Pelletizing of NaF granules as adsorbent for fluorides of nuclear fuel materials, (1)

    Kimura, Syojiro; Tsutsui, Tenson; Kanagawa, Akira.

    1976-01-01

    The pelletizing of NaF granules on laboratory scale used for recovery and purification of fluorides of nuclear fuel materials are investigated, particularity experimental studies on how to pelletize, fluidity of granules and flow rate of the granules in mortar of tablet machine are carried out. As result, added quantity of H 2 O as binder at granulation process of spherical NaF granule influence to yield of NaF granules. The proper quantity of H 2 O to NaF powder is about 18--19%. Friction coefficient of unfixed shape NaF granule is higher than that of spherical granule, in opposition, density of the former granule is lower. So fluidity of unfixed shape NaF granule is low, flow rate of the granules through feeder of tablet machine is slow, and arching on mortar of the tablet machine occurs. Then, some further operation for getting better fluidity needs for pelletizing of NaF granules using unfixed shape granule. The other hand, using spherical NaF granule, continuous pelletizing by commercial tablet machine can be carried out. (auth.)

  19. Electroconvulsive stimulation results in long-term survival of newly generated hippocampal neurons in rats

    Olesen, Mikkel Vestergaard; Wörtwein, Gitta; Folke, Jonas

    2017-01-01

    Electroconvulsive stimulation (ECS) is one of the strongest stimulators of hippocampal neurogenesis in rodents that represents a plausible mechanism for the efficacy of electroconvulsive therapy (ECT) in major depressive disorder. Using design-based stereological cell counting, we recently...... in neurogenesis facilitates the behavioral outcome of the forced swim test (FST), an animal model of depression. The results showed that ECS in conjunction with CRS stimulates hippocampal neurogenesis, and that a significant quantity of the newly formed hippocampal neurons survives up to 12 months. The new Brd......U-positive neurons showed time-dependent attrition of ∼40% from day 1 to 3 months, with no further decline between 3 and 12 months. ECS did not affect the number of pre-existing dentate granule neurons or the volume of the dentate granule cell layer, suggesting no damaging effect of the treatment. Finally, we found...

  20. Studi Awal Desain Pabrik Pupuk Organik Granul Dari Organic Waste

    Zulfatul Hanna

    2015-12-01

    Full Text Available 800x600 Banyak pertanian di Indonesia yang masih bergantung pada penggunaan pupuk kimia. Padahal penggunaan pupuk kimia yang berlebihan dapat menyebabkan penurunan bahan organik tanah. Untuk menyeimbangkannnya saat ini petani juga sedang menggalakkan penggunaan pupuk organik. Sehingga membuat kebutuhan pupuk organik meningkat setiap tahunnya. Pendirian pabrik pupuk organik granul ini dapat memenuhi kebutuhan pupuk organik untuk petani. Prosess pembuatan pupuk organik granul terdiri dari pencampuran bahan baku, yakni sampah organik, kotoran sapi, kotoran domba, dan dipotong dengan rotary knife cutter. Tahap berikutnya adalah proses fermentasi, dengan penambahan bioactivator agar meningkatkan kandungan C-organik, phosphor, dan kalium. Selanjutnya adalah proses granulasi, pembesaran dari partikel dengan proses aglomerasi. Ukuran yang diharapkan pada proses granulasi ini adalah 2-4 mm sehingga produk undersize maupun oversize akan dikembalikan ke dalam granulator setelah melewati screener. Selanjutnya pupuk organik granul dikeringkan. Selanjutnya produk dipisahkan berdasarkan ukurannya lalu didinginkan di Rotary cooler. Setelah keluar dari Rotary Cooler suhu keluaran sekitar 40 oC dan masih mengandung kadar air sebesar 13,7%. Produk dari rotary cooler siap untuk di packaging dan masuk ke dalam pupuk organik granul storage. Dari analisa ekonomi didapatkan BEP sebesar 45% dengan POT sesudah pajak sebesar 4,8 tahun. Normal 0 false false false IN X-NONE X-NONE MicrosoftInternetExplorer4

  1. Platelet granule exocytosis: A comparison with chromaffin cells

    Jennifer eFitch-Tewfik

    2013-06-01

    Full Text Available The rapid secretion of bioactive amines from chromaffin cells constitutes an important component of the fight or flight response of mammals to stress. Platelets respond to stresses within the vasculature by rapidly secreting cargo at sites of injury, inflammation, or infection. Although chromaffin cells derive from the neural crest and platelets from bone marrow megakaryocytes, both have evolved a heterogeneous assemblage of granule types and a mechanism for efficient release. This article will provide an overview of granule formation and exocytosis in platelets with an emphasis on areas in which the study of chromaffin cells has influenced that of platelets and on similarities between the two secretory systems. Commonalities include the use of transporters to concentrate bioactive amines and other cargos into granules, the role of cytoskeletal remodeling in granule exocytosis, and the use of granules to provide membrane for cytoplasmic projections. The SNAREs and SNARE accessory proteins used by each cell type will also be considered. Finally, we will discuss the newly appreciated role of dynamin family proteins in regulated fusion pore formation. This evaluation of the comparative cell biology of regulated exocytosis in platelets and chromaffin cells demonstrates a convergence of mechanisms between two disparate cell types both tasked with responding rapidly to physiological stimuli.

  2. Preparation of porcelain tile granulates by more environmentally sustainable processes

    Gil, C.; Silvestre, D.; Piquer, J.; Garcia-Ten, J.; Quereda, E.; Vicente, M. J.

    2012-07-01

    This study examines the feasibility of manufacturing glazed porcelain tiles with a more environmentally friendly manufacturing process, by reducing water and thermal energy consumption. The process studied in this paper is dry milling in a pendulum mill, with subsequent granulation (in order to obtain a press powder with similar flow ability to that of spray dried powders). The different morphology of the new granulate with respect to the standard spray-dried granulate modifies the microstructure of the green compacts and thus, their behaviour and fired tile properties. In order to obtain porcelain tiles with the required properties (water absorption, mechanical strength,) changes have been made in the raw materials mixture and in the processing variables. Finally, porcelain tiles measuring 50x50 cm have been manufactured at industrial scale with the new granulate using a conventional firing cycle, obtaining quality levels identical to those provided by the spray-dried granulate. These results open the possibility of preparing porcelain tile body compositions through a manufacturing process alternative to the standard one, more environmentally friendly and with lower costs. (Author)

  3. Neuron Morphology Influences Axon Initial Segment Plasticity123

    2016-01-01

    In most vertebrate neurons, action potentials are initiated in the axon initial segment (AIS), a specialized region of the axon containing a high density of voltage-gated sodium and potassium channels. It has recently been proposed that neurons use plasticity of AIS length and/or location to regulate their intrinsic excitability. Here we quantify the impact of neuron morphology on AIS plasticity using computational models of simplified and realistic somatodendritic morphologies. In small neurons (e.g., dentate granule neurons), excitability was highest when the AIS was of intermediate length and located adjacent to the soma. Conversely, neurons having larger dendritic trees (e.g., pyramidal neurons) were most excitable when the AIS was longer and/or located away from the soma. For any given somatodendritic morphology, increasing dendritic membrane capacitance and/or conductance favored a longer and more distally located AIS. Overall, changes to AIS length, with corresponding changes in total sodium conductance, were far more effective in regulating neuron excitability than were changes in AIS location, while dendritic capacitance had a larger impact on AIS performance than did dendritic conductance. The somatodendritic influence on AIS performance reflects modest soma-to-AIS voltage attenuation combined with neuron size-dependent changes in AIS input resistance, effective membrane time constant, and isolation from somatodendritic capacitance. We conclude that the impact of AIS plasticity on neuron excitability will depend largely on somatodendritic morphology, and that, in some neurons, a shorter or more distally located AIS may promote, rather than limit, action potential generation. PMID:27022619

  4. Pattern separation: a common function for new neurons in hippocampus and olfactory bulb.

    Sahay, Amar; Wilson, Donald A; Hen, René

    2011-05-26

    While adult-born neurons in the olfactory bulb (OB) and the dentate gyrus (DG) subregion of the hippocampus have fundamentally different properties, they may have more in common than meets the eye. Here, we propose that new granule cells in the OB and DG may function as modulators of principal neurons to influence pattern separation and that adult neurogenesis constitutes an adaptive mechanism to optimally encode contextual or olfactory information. See the related Perspective from Aimone, Deng, and Gage, "Resolving New Memories: A Critical Look at the Dentate Gyrus, Adult Neurogenesis, and Pattern Separation," in this issue of Neuron. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. A natural form of learning can increase and decrease the survival of new neurons in the dentate gyrus.

    Olariu, Ana; Cleaver, Kathryn M; Shore, Lauren E; Brewer, Michelle D; Cameron, Heather A

    2005-01-01

    Granule cells born in the adult dentate gyrus undergo a 4-week developmental period characterized by high susceptibility to cell death. Two forms of hippocampus-dependent learning have been shown to rescue many of the new neurons during this critical period. Here, we show that a natural form of associative learning, social transmission of food preference (STFP), can either increase or decrease the survival of young granule cells in adult rats. Increased numbers of pyknotic as well as phospho-Akt-expressing BrdU-labeled cells were seen 1 day after STFP training, indicating that training rapidly induces both cell death and active suppression of cell death in different subsets. A single day of training for STFP increased the survival of 8-day-old BrdU-labeled cells when examined 1 week later. In contrast, 2 days of training decreased the survival of BrdU-labeled cells and the density of immature neurons, identified with crmp-4. This change from increased to decreased survival could not be accounted for by the ages of the cells. Instead, we propose that training may initially increase young granule cell survival, then, if continued, cause them to die. This complex regulation of cell death could potentially serve to maintain granule cells that are actively involved in memory consolidation, while rapidly using and discarding young granule cells whose training is complete to make space for new naïve neurons. Published 2005 Wiley-Liss, Inc.

  6. [Protective effect of compound bismuth and magnesium granules on aspirin-induced gastric mucosal injury in rats].

    Mu, F H; Hu, F L; Wei, H; Zhang, Y Y; Yang, G B; Lei, X Y; Yang, Y P; Sun, W N; Cui, M H

    2016-02-01

    To investigate the protective effect of compound bismuth and magnesium granules on aspirin-induced gastric mucosal injury in rats and its possible mechanism. Acute gastric mucosal injury model was developed with intraperitoneal injection of aspirin in Wistar rats. The rats were divided into normal control group, injury group, sucralfate protection group, compound bismuth and magnesium granules protection group and its herbal components protection group(each group 12 rats). In the protection groups, drugs as mentioned above were administered by gavage before treated with intraperitoneal injection of aspirin. To evaluate the extent of gastric mucosal injury and the protective effect of drugs, gastric mucosal lesion index, gastric mucosal blood flow, content of gastric mucosal hexosamine, prostaglandins (PG), nitric oxide(NO), tumor necrosis factor (TNF), and interleukin (IL) -1, 2, 8 were measured in each group, and histological changes were observed by gross as well as under microscope and electron microscope. Contents of hexosamine, NO, and PG in all the protection groups were significantly higher than those in the injury group (all Pcompound bismuth and magnesium granules group was significantly higher than that in the sucralfate group ((11.29±0.51) vs(10.80±0.36)nmol/ml, Pcompound bismuth and magnesium granules group were significantly lower than those in the sucralfate group ((328.17±6.56) vs(340.23±8.05)pg/ml, PCompound bismuth and magnesium granules and its herbal components may have significant protective effect on aspirin-induced gastric mucosal injury.

  7. Contrasting Pathology of the Stress Granule Proteins TIA-1 and G3BP in Tauopathies

    Vanderweyde, Tara; Yu, Haung; Varnum, Megan; Liu-Yesucevitz, Liqun; Citro, Allison; Ikezu, Tsuneya; Duff, Karen; Wolozin, Benjamin

    2012-01-01

    Stress induces aggregation of RNA-binding proteins to form inclusions, termed stress granules (SGs). Recent evidence suggests that SG proteins also colocalize with neuropathological structures, but whether this occurs in Alzheimer’s disease is unknown. We examined the relationship between SG proteins and neuropathology in brain tissue from P301L Tau transgenic mice, as well as in cases of Alzheimer’s disease and FTDP-17. The pattern of SG pathology differs dramatically based on the RNA-binding protein examined. SGs positive for T-cell intracellular antigen-1 (TIA-1) or tristetraprolin (TTP) initially do not colocalize with tau pathology, but then merge with tau inclusions as disease severity increases. In contrast, G3BP (ras GAP-binding protein) identifies a novel type of molecular pathology that shows increasing accumulation in neurons with increasing disease severity, but often is not associated with classic markers of tau pathology. TIA-1 and TTP both bind phospho-tau, and TIA-1 overexpression induces formation of inclusions containing phospho-tau. These data suggest that SG formation might stimulate tau pathophysiology. Thus, study of RNA-binding proteins and SG biology highlights novel pathways interacting with the pathophysiology of AD, providing potentially new avenues for identifying diseased neurons and potentially novel mechanisms regulating tau biology. PMID:22699908

  8. Removal of strontium ions from solutions using granulated zeolites

    Bronic, J.; Subotic, B.

    1992-01-01

    The ion-exchange process on columns filled with granulated zeolites is determined by several physico-chemical parameters. The influence of these parameters (zeolite type, concentration of exchangeable ions in solution, temperature, flow rate, etc.) on the kinetics of ion-exchange process was studied by measuring the Sr 2+ ion concentration in solution before and after passing through a column filled with various granulated zeolites (zeolite 13X, zeolite A and synthetic mordenite). Using the experimental technique of radioactive labeling by 89 Sr, the distribution of Sr 2+ ions in column fillings were also determined. From the results obtained, the optimal conditions for the most efficient removal of strontium ions from solutions using granulated zeolites can be defined. (author) 24 refs.; 9 figs

  9. Enterovirus Control of Translation and RNA Granule Stress Responses.

    Lloyd, Richard E

    2016-03-30

    Enteroviruses such as poliovirus (PV) and coxsackievirus B3 (CVB3) have evolved several parallel strategies to regulate cellular gene expression and stress responses to ensure efficient expression of the viral genome. Enteroviruses utilize their encoded proteinases to take over the cellular translation apparatus and direct ribosomes to viral mRNAs. In addition, viral proteinases are used to control and repress the two main types of cytoplasmic RNA granules, stress granules (SGs) and processing bodies (P-bodies, PBs), which are stress-responsive dynamic structures involved in repression of gene expression. This review discusses these processes and the current understanding of the underlying mechanisms with respect to enterovirus infections. In addition, the review discusses accumulating data suggesting linkage exists between RNA granule formation and innate immune sensing and activation.

  10. Superheated superconducting granule detector tested with nuclear recoil measurements

    Berger, C.; Czapek, G.; Diggelmann, U.; Flammer, I.; Frei, D.; Furlan, M.; Gabutti, A.; Janos, S.; Moser, U.; Pretzl, K.; Schmiemann, K.; Perret-Gallix, D.; Brandt, B. van den; Konter, J.A.; Mango, S.

    1993-01-01

    The presented results are part of a superheated superconducting granule (SSG) detector development for neutrino and dark matter. The aim of the experiment was to measure the sensitivity of the detector to nuclear recoil energies when exposed to a 70 MeV neutron beam. The detector consists of a small readout coil (diameter 5 mm, length 10 mm) filled with aluminum granules of average diameter 23 μm embedded in an Al 2 O 3 granulate with a 6% volume filling factor. The neutron scattering angles were determined using a scintillator hodoscope. Coincidences between the SSG and the hodoscope signals have been clearly established. Data were taken at an operating temperature of 120 mK for different SSG intrinsic thresholds. The results prove the sensitivity of the detector to nuclear recoils around 10 keV. (orig.)

  11. [Pharmacological availability of erythromycin granules for children's use].

    Korenev, S V; Garsheva, G B; Nesterova, L Ia; Grakovskaia, L K; Tentsova, A I

    1990-08-01

    Pharmaceutical availability of erythromycin granules with polymeric coating of different composition+ was studied. With an account of the ++anatomo-physiological features of a child organism and the properties of the antibiotic, acetylphthalyl cellulose in combination with hydroxypropyl methylcellulose or methyl cellulose was used as a film forming agent. The coated granules were estimated by such parameters as the time of disintegration and the rate of dissolution in various media. The results of the study showed that coating of the erythromycin granules with the film composed of acetylphthalyl cellulose and hydroxypropyl methylcellulose in the ratio of 8 to 2 provided the required protection of the antibiotic in acid media and high pharmaceutical availability of the drug.

  12. Olfactory granule cell development in normal and hyperthyroid rats.

    Brunjes, P C; Schwark, H D; Greenough, W T

    1982-10-01

    Dendritic development was examined in olfactory bulbs of both normal 7-, 14-, 21- and 60-day-old rats and littermates treated on postnatal days 1-4 with 1 microgram/g body weight of L-thyroxine sodium. Tissue was processed via the Golgi-Cox technique and subjected to quantitative analyses of mitral and internal layer granule cell development. These populations of granule cells were selected because their pattern of late proliferation suggested potentially greater susceptibility to postnatal hormonal alterations. Although neonatal hyperthyroidism induces widespread acceleration of maturation, including precocious chemosensitivity, granule cell development was unaffected relative to littermate controls. Both normal and hyperthyroid groups exhibited an inverted U-shaped pattern of cellular development, with rapid dendritic dendritic growth and expansion occurring during the earliest ages tested, but with loss of processes and dendritic field size occurring after day 21.

  13. Study and development of NiAl intermetallic coating on hypo-eutectoid steel using highly activated composite granules of the Ni-Al system

    Shahzad, Aamir; Zadorozhnyy, Vladislav Yu.; Pavlov, Mikhail D.; Semenov, Dmitri V.; Kaloshkin, Sergey D. [National Univ. of Science and Technology (MISIS), Moscow (Russian Federation)

    2018-01-15

    NiAl intermetallic coating thickness of about 50 μm was fabricated on hypo-eutectoid steel by mechanical alloying using pre-activated Ni-Al composite granules as coating material. First, Ni and Al powders were mixed with the composition of Ni-50 at.% Al and mechanically activated in a planetary ball mill, until the composite granules of this powder mixture, having maximum activity (9 cm sec{sup -1}), were formed after 120 min of milling at 200 rpm. The composite granules were then taken out from the planetary ball mill just before the critical time, i. e. the time at which these granules synthesize and convert to an intermetallic NiAl compound. The highly activated composite granules of Ni-Al were then put into the vial of a vibratory ball mill with the substrate on top of the chamber. After mechanical alloying for 60 min in the vibratory ball mill, the composite granules were synthesized fully and heat was produced during the synthesis which helped producing a thick and strong adhesive coating of NiAl intermetallic on the steel substrate. The main advantage of this technique is that not only is time saved but also there is no need for any post mechanical alloying process such as annealing or laser treatment etc. to get homogeneous, strongly bonded intermetallic coatings. X-ray diffraction analysis clearly indicates the formation of NiAl phase. Micro-hardness of the coating and substrate was also measured. The cross-sectional microstructure of the composite granules and the final coating were studied by scanning electron microscopy.

  14. Pigment granule translocation in red ovarian chromatophores from the palaemonid shrimp Macrobrachium olfersi (Weigmann, 1836): functional roles for the cytoskeleton and its molecular motors.

    Milograna, Sarah Ribeiro; Ribeiro, Márcia Regina; Baqui, Munira Muhammad Abdel; McNamara, John Campbell

    2014-12-01

    The binding of red pigment concentrating hormone (RPCH) to membrane receptors in crustacean chromatophores triggers Ca²⁺/cGMP signaling cascades that activate cytoskeletal motors, driving pigment granule translocation. We investigate the distributions of microfilaments and microtubules and their associated molecular motors, myosin and dynein, by confocal and transmission electron microscopy, evaluating a functional role for the cytoskeleton in pigment translocation using inhibitors of polymer turnover and motor activity in vitro. Microtubules occupy the chromatophore cell extensions whether the pigment granules are aggregated or dispersed. The inhibition of microtubule turnover by taxol induces pigment aggregation and inhibits re-dispersion. Phalloidin-FITC actin labeling, together with tannic acid fixation and ultrastructural analysis, reveals that microfilaments form networks associated with the pigment granules. Actin polymerization induced by jasplaquinolide strongly inhibits RPCH-induced aggregation, causes spontaneous pigment dispersion, and inhibits pigment re-dispersion. Inhibition of actin polymerization by latrunculin-A completely impedes pigment aggregation and re-dispersion. Confocal immunocytochemistry shows that non-muscle myosin II (NMMII) co-localizes mainly with pigment granules while blebbistatin inhibition of NMMII strongly reduces the RPCH response, also inducing spontaneous pigment dispersion. Myosin II and dynein also co-localize with the pigment granules. Inhibition of dynein ATPase by erythro-9-(2-hydroxy-3-nonyl) adenine induces aggregation, inhibits RPCH-triggered aggregation, and inhibits re-dispersion. Granule aggregation and dispersion depend mainly on microfilament integrity although microtubules may be involved. Both cytoskeletal polymers are functional only when subunit turnover is active. Myosin and dynein may be the molecular motors that drive pigment aggregation. These mechanisms of granule translocation in crustacean

  15. UVC-induced stress granules in mammalian cells.

    Mohamed Taha Moutaoufik

    Full Text Available Stress granules (SGs are well characterized cytoplasmic RNA bodies that form under various stress conditions. We have observed that exposure of mammalian cells in culture to low doses of UVC induces the formation of discrete cytoplasmic RNA granules that were detected by immunofluorescence staining using antibodies to RNA-binding proteins. UVC-induced cytoplasmic granules are not Processing Bodies (P-bodies and are bone fide SGs as they contain TIA-1, TIA-1/R, Caprin1, FMRP, G3BP1, PABP1, well known markers, and mRNA. Concomitant with the accumulation of the granules in the cytoplasm, cells enter a quiescent state, as they are arrested in G1 phase of the cell cycle in order to repair DNA damages induced by UVC irradiation. This blockage persists as long as the granules are present. A tight correlation between their decay and re-entry into S-phase was observed. However the kinetics of their formation, their low number per cell, their absence of fusion into larger granules, their persistence over 48 hours and their slow decay, all differ from classical SGs induced by arsenite or heat treatment. The induction of these SGs does not correlate with major translation inhibition nor with phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α. We propose that a restricted subset of mRNAs coding for proteins implicated in cell cycling are removed from the translational apparatus and are sequestered in a repressed form in SGs.

  16. Molecular neuron based on the Franck–Condon blockade

    Timm, C; Di Ventra, M

    2013-01-01

    Electronic realizations of neurons are of great interest as building blocks for neuromorphic computation. Electronic neurons should send signals into the input and output lines when subject to an input signal exceeding a given threshold, in such a way that they may affect all other parts of a neural network. Here, we propose a design for a neuron that is based on molecular-electronics components and thus promises a very high level of integration. We employ the Monte Carlo technique to simulate typical time evolutions of this system and thereby show that it indeed functions as a neuron. (paper)

  17. Mutant human FUS Is ubiquitously mislocalized and generates persistent stress granules in primary cultured transgenic zebrafish cells.

    Jamie Rae Acosta

    Full Text Available FUS mutations can occur in familial amyotrophic lateral sclerosis (fALS, a neurodegenerative disease with cytoplasmic FUS inclusion bodies in motor neurons. To investigate FUS pathology, we generated transgenic zebrafish expressing GFP-tagged wild-type or fALS (R521C human FUS. Cell cultures were made from these zebrafish and the subcellular localization of human FUS and the generation of stress granule (SG inclusions examined in different cell types, including differentiated motor neurons. We demonstrate that mutant FUS is mislocalized from the nucleus to the cytosol to a similar extent in motor neurons and all other cell types. Both wild-type and R521C FUS localized to SGs in zebrafish cells, demonstrating an intrinsic ability of human FUS to accumulate in SGs irrespective of the presence of disease-associated mutations or specific cell type. However, elevation in relative cytosolic to nuclear FUS by the R521C mutation led to a significant increase in SG assembly and persistence within a sub population of vulnerable cells, although these cells were not selectively motor neurons.

  18. Giant arachnoid granulation: differential diagnosis of acute headache

    Peters, S.A.; Heyer, C.M.; Frombach, E.

    2007-01-01

    Full text: We present a case of intense, rapidly evolving headache clinically mimicking meningitis, subarachnoid haemorrhage or venous sinus thrombosis. Clinical examination, standard blood work and central nervous system studies were non-contributory and effectively ruled out these diagnoses. Cranial multidetector CT studies before and after application of intravenous contrast medium performed prior to lumbar tap disclosed a non-enhancing ovoid mass filling the superior sagittal sinus. This lesion posed a differential to venous sinus thrombosis, but ultimately fulfilled the criteria of a giant arachnoid granulation. The imaging characteristics and differential diagnosis of giant arachnoid granulations are discussed

  19. Method of production of granulates of ceramic nuclear fuels

    Wilkinson, W.L.

    1975-01-01

    To obtain a classified granulate of ceramic nuclear fuels with narrow grain size spectrum, the nuclear fuel powder is made into a slurry in a non-aqueous solvent with a water content as low as possible (e.g. chlorated hydrocarbon), a binder added to it, and spray-dried. The dry granulate desired is already obtained by this working stage. Polybutyl methacrylate in dibutylphthalate is proposed as binder. An example in which uranium dioxide powder is slurried in trichloro-ethylene is described in detail. (UWI/LH) [de

  20. Removal of cesium radioisotopes from solutions using granulated zeolites

    Bronic, J.; Subotic, B.

    1991-01-01

    The influence of type of zeolite and the flow rate of solution through the column on the removal efficiency of radioactive cesium ions from solution has been investigated. The analysis of the change in the concentration of cesium ions in the solutions and distribution of cesium ions in the column fillings (granulated zeolites), after passing the solutions through the columns filled with various granulated zeolites (zeolite 4A, zeolite 13X, synthetic mordenite) was performed. On the basis of the results of this study, the conditions for the most efficient removal of cesium ions from solutions have been discussed. (author) 35 refs.; 9 figs.; 1 tab

  1. Comparative effects of PBDEs and PCBs on intracellular signaling in rat cerebellar granule neurons

    Polybrominated diphenyl ethers (PBDEs) are synthetic chemicals that do not occur in nature and are structurally similar to polychlorinated biphenyls (PCBs; Figure I) and several chlorinated pesticides. They are comprised of two phenyl rings linked by oxygen and are resistant to p...

  2. Phenotypic properties and microbial diversity of methanogenic granules from a full-scale UASB reactor treating brewery wastewater

    Diaz, E.E.; Stams, A.J.M.; Amils, R.; Sanz, J.L.

    2006-01-01

    Methanogenic granules from an anaerobic bioreactor that treated wastewater of a beer brewery consisted of different morphological types of granules. In this study, the microbial compositions of the different granules were analyzed by molecular microbiological techniques: cloning, denaturing gradient

  3. Spike timing precision of neuronal circuits.

    Kilinc, Deniz; Demir, Alper

    2018-04-17

    Spike timing is believed to be a key factor in sensory information encoding and computations performed by the neurons and neuronal circuits. However, the considerable noise and variability, arising from the inherently stochastic mechanisms that exist in the neurons and the synapses, degrade spike timing precision. Computational modeling can help decipher the mechanisms utilized by the neuronal circuits in order to regulate timing precision. In this paper, we utilize semi-analytical techniques, which were adapted from previously developed methods for electronic circuits, for the stochastic characterization of neuronal circuits. These techniques, which are orders of magnitude faster than traditional Monte Carlo type simulations, can be used to directly compute the spike timing jitter variance, power spectral densities, correlation functions, and other stochastic characterizations of neuronal circuit operation. We consider three distinct neuronal circuit motifs: Feedback inhibition, synaptic integration, and synaptic coupling. First, we show that both the spike timing precision and the energy efficiency of a spiking neuron are improved with feedback inhibition. We unveil the underlying mechanism through which this is achieved. Then, we demonstrate that a neuron can improve on the timing precision of its synaptic inputs, coming from multiple sources, via synaptic integration: The phase of the output spikes of the integrator neuron has the same variance as that of the sample average of the phases of its inputs. Finally, we reveal that weak synaptic coupling among neurons, in a fully connected network, enables them to behave like a single neuron with a larger membrane area, resulting in an improvement in the timing precision through cooperation.

  4. Effect of matrix granulation and wax coating on the dissolution rates ...

    disintegrating) granules consisting of paracetamol (drug) and acrylatemethacrylate copolymer, a matrix forming material. The effect of coating the matrix granules with wax on the drug release profiles was also investigated. The objective was to ...

  5. Effect of particle size of granules on some mechanical properties of ...

    PRECIOUS

    2009-11-02

    Nov 2, 2009 ... granules on some tablet mechanical properties of paracetamol tablets. Granules ... massing paracetamol powder (200 g) with 20% (w/w) of maize starch mucilage as binder. .... The resulting tablets were stored overnight in a.

  6. Formulation of a poorly water-soluble drug in sustained-release hollow granules with a high viscosity water-soluble polymer using a fluidized bed rotor granulator.

    Asada, Takumi; Yoshihara, Naoki; Ochiai, Yasushi; Kimura, Shin-Ichiro; Iwao, Yasunori; Itai, Shigeru

    2018-04-25

    Water-soluble polymers with high viscosity are frequently used in the design of sustained-release formulations of poorly water-soluble drugs to enable complete release of the drug in the gastrointestinal tract. Tablets containing matrix granules with a water-soluble polymer are preferred because tablets are easier to handle and the multiple drug-release units of the matrix granules decreases the influences of the physiological environment on the drug. However, matrix granules with a particle size of over 800 μm sometimes cause a content uniformity problem in the tableting process because of the large particle size. An effective method of manufacturing controlled-release matrix granules with a smaller particle size is desired. The aim of this study was to develop tablets containing matrix granules with a smaller size and good controlled-release properties, using phenytoin as a model poorly water-soluble drug. We adapted the recently developed hollow spherical granule granulation technology, using water-soluble polymers with different viscosities. The prepared granules had an average particle size of 300 μm and sharp particle size distribution (relative width: 0.52-0.64). The values for the particle strength of the granules were 1.86-1.97 N/mm 2 , and the dissolution profiles of the granules were not affected by the tableting process. The dissolution profiles and the blood concentration levels of drug released from the granules depended on the viscosity of the polymer contained in the granules. We succeeded in developing the desired controlled-release granules, and this study should be valuable in the development of sustained-release formulations of poorly water-soluble drugs. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Constitutively polarized granules prime KHYG-1 NK cells.

    Suck, Garnet; Branch, Donald R; Aravena, Paola; Mathieson, Mark; Helke, Simone; Keating, Armand

    2006-09-01

    The major mechanism for NK cell lysis of tumor cells is granule-mediated cytotoxicity. Polarization of granules is a prelude to the release of their cytotoxic contents in response to target-cell binding. We describe the novel observation of constitutive granule polarization in the cytotoxic NK cell line, KHYG-1. Continuous degranulation of KHYG-1 cells, however, does not occur and still requires target-cell contact. Disruption of microtubules with colcemid is sufficient to disperse the granules in KHYG-1 and significantly decreases cytotoxicity. A similar effect is not obtained by inhibiting extracellular signal-related kinase 2 (ERK2), the most distal kinase investigated in the cytolytic pathway. Disruption of microtubules significantly down-regulates activation receptors, NKp44 and NKG2D, implicating them as potential microtubule-trafficking receptors. Such changes in upstream receptor expression may have caused deactivation of ERK2, since NKG2D cross-linking also leads to receptor down-regulation and diminished ERK phosphorylation. Thus, a functional role for NKG2D in KHYG-1 cytotoxicity is demonstrated. Moreover, the novel primed state may contribute to the high cytotoxicity exhibited by KHYG-1.

  8. Thermal effects on granules and direct determination of swelling ...

    STORAGESEVER

    2009-08-04

    Aug 4, 2009 ... DEA. UAA. Abidjan. Côte d'Ivoire, pp. 25-28. Larrigue S, Alvarez G, Cuvelier G, Flick D (2008). Swelling kinetics of waxy maize and starches at high temperatures and heating rates. Carbohydr. Polym. 73: 148-155. Leach HW, MC Cowen LD, Schoch JJ (1959). Structure of the starch granule swelling and ...

  9. Glass foam granulate as growing medium for tomato and cucumber

    Blok, C.; Winkel, van A.; Chizhmak, S.

    2011-01-01

    Glass foam granulate was evaluated for use as a horticultural rooting medium with laboratory tests and cultivation experiments. The laboratory tests included moisture characteristics, rehydration rate and pH buffering analyses. Cucumbers and later on tomatoes were propagated in rockwool propagation

  10. ATP storage and uptake by isolated pancreatic zymogen granules

    Haanes, Kristian Agmund; Novak, Ivana

    2010-01-01

    ATP is released from pancreatic acini in response to cholinergic and hormonal stimulation. The same stimuli cause exocytosis of ZG (zymogen granules) and release of digestive enzymes. The aim of the present study was to determine whether ZG stored ATP and to characterize the uptake mechanism for ...

  11. Effect of Drug Active Substance Particles on Wet Granulation Process.

    Bělohlav, Z.; Břenková, L.; Hanika, Jiří; Durdil, P.; Rapek, P.; Tomášek, V.

    2007-01-01

    Roč. 85, A7 (2007) , s. 974-980 ISSN 0263-8762 Institutional research plan: CEZ:AV0Z40720504 Keywords : wet granulation * control * active substance Subject RIV: CI - Industrial Chemistry, Chemical Engineering Impact factor: 0.837, year: 2007

  12. Measurement of the moisture content of the granulated sugar by ...

    AJB SERVER

    2007-01-18

    Jan 18, 2007 ... The moisture content of granulated sugar is a critical parameter for its transformation into cubes. To the best of our ... resolve this, a new method using infrared transphotometry technique based on the attenuation of an infrared ... contribution of other interactions to the attenuation of the incident wave, i.e. ...

  13. Granulated Silica Method for the Fiber Preform Production

    Sönke Pilz

    2017-07-01

    Full Text Available During the past few years, we have studied the granulated silica method as a versatile and cost effective way of fiber preform production and the sol-gel method. Until now, we have used the sol-gel technology together with an iterative re-melting and milling step in order to produce rare earth or transition metal doped granular material for the granulated silica method. Here, we present that the iterative re-melting (laser-assisted and milling step is no longer needed to reach a high homogeneity. The sol-gel method also offers a high degree of compositional flexibility with respect to dopants; it further facilitates achieving high concentrations, even in cases when several dopants are used. We employed optical active doped sol-gel derived granulate for the fiber core, whereas pure or index-raised granulated silica has been employed for the cladding. Based on the powder-in-tube technique, where silica glass tubes are appropriately filled with these granular materials, fibers has been directly drawn (“fiber rapid prototyping”, or eventually after an additional optional quality enhancing vitrification step. The powder-in-tube technique is also ideally suited for the preparation of microstructured optical fibers.

  14. Iron-based granules in body of bumblebees

    Jandacka, P.; Kasparova, B.; Jirásková, Yvonna; Dedkova, K.; Mamulová-Kutláková, K.; Kukutschová, J.

    2015-01-01

    Roč. 28, č. 1 (2015), s. 89-99 ISSN 0966-0844 R&D Projects: GA ČR(CZ) GAP108/11/1350 Institutional support: RVO:68081723 Keywords : Magnetoreception * Bumblebee * Biomineralisation * Iron granules Subject RIV: BO - Biophysics Impact factor: 2.134, year: 2015

  15. Automation system for production of UO2 granules

    Swaminathan, N.; Setty, C.R.P.; Banerjee, P.K.; Husnain, G.; Rao, K.C.M.; Satyanarayana, A.

    1990-01-01

    Precompaction of UO 2 powder into slugs and granulation of the slugs were used to be carried out in two different work centres involving manual loading/handling of powder and compacts which resulted in a very high level of air-borne activity. This has been simplified by integrating both the operations into one work centre on both the precompaction presses. In the present system, UO 2 powder is transferred to feed hopper through the use of high vac. feeder. The powder in metered quantities is fed into the shoe by deploying screw feeder driven by a compact hydraulic motor. The die cavity is filled with just the right quantity of powder to prevent spillage. The compacts are pushed on to the granulator through a set of guides mounted on the die platform. The granulated powder is made to pass through Vibro screen for separating the fines before collecting in a replaceable S.S. Container. This container is mounted on the final compacting press by using job crane installed on the press. The replaceable container handling facility drastically cuts down the manual handling of UO 2 granules and also eliminates spillage, air borne activity. The development and fabrication of hydraulically operated screw feeder, feed shoe, replaceable container and the job crane structure etc., were completely carried out at Nuclear Fuel Complex, Hyderabad. Paper deals in detail the design of the system developed, present operational experiences and further improvements planned. (author). 6 figs

  16. Contribution of granule bound starch synthase in kernel modification ...

    The role of gbssI and gbssII genes, encoding granule bound starch synthase enzyme I and II, respectively, in quality protein maize (QPM) were studied at different days after pollination (DAP). Total RNA was used for first strand cDNA synthesis using the ImpromIISriptTM reverse transcriptase. No detectable levels of gbssI ...

  17. Population balance modelling of fluidized bed melt granulation: an overview

    Tan, H.S.; Goldschmidt, M.J.V.; Boerefijn, R.; Hounslow, M.J.; Salman, A.; Kuipers, J.A.M.

    2005-01-01

    This paper presents an overview of the work undertaken by our group to identify and quantify the rates processes active in fluidized bed melt granulation (FBMG). The process involves the identification and development of physically representative models to mechanistically describe FBMG using both

  18. Measurement of the moisture content of the granulated sugar by ...

    The moisture content of granulated sugar is a critical parameter for its transformation into cubes. To the best of our knowledge there is no easy-to-use method for the determination of this parameter. To resolve this, a new method using infrared transphotometry technique based on the attenuation of an infrared radiation ...

  19. Metabolic changes induced by Bushenhouxue Granules on striatum ...

    Background: Parkinson's disease is a neurodegenerative disease, while its mechanism is still unclear. Long-term levodopa-based treatment leads to decreased response or loss of response, as well as severe side effects. Our previous study has proved that Bushenhuoxue Granules have effects on Parkinson's disease, but ...

  20. EVIDENCE FOR GRANULATION IN EARLY A-TYPE STARS

    Kallinger, Thomas; Matthews, Jaymie M.

    2010-01-01

    Stars with spectral types earlier than about F0 on (or close) to the main sequence have long been believed to lack observable surface convection, although evolutionary models of A-type stars do predict very thin surface convective zones. We present evidence for granulation in two δ Scuti stars of spectral type A2: HD 174936 and HD 50844. Recent analyses of space-based CoRoT data revealed up to some 1000 frequencies in the photometry of these stars. The frequencies were interpreted as individual pulsation modes. If true, there must be large numbers of nonradial modes of very high degree l which should suffer cancellation effects in disk-integrated photometry (even of high space-based precision). The p-mode interpretation of all the frequencies in HD 174936 and HD 50844 depends on the assumption of white (frequency-independent) noise. Our independent analyses of the data provide an alternative explanation: most of the peaks in the Fourier spectra are the signature of non-white granulation background noise, and less than about 100 of the frequencies are actual stellar p-modes in each star. We find granulation timescales which are consistent with scaling relations that describe cooler stars with known surface convection. If the granulation interpretation is correct, the hundreds of low-amplitude Fourier peaks reported in recent studies are falsely interpreted as independent pulsation modes and a significantly lower number of frequencies are associated with pulsation, consistent with only modes of low degree.

  1. 21 CFR 520.2520f - Trichlorfon granules.

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Trichlorfon granules. 520.2520f Section 520.2520f Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL.... Do not fast horses before or after treatment. Treatment of mares in late pregnancy is not recommended...

  2. The herpes simplex virus 2 virion-associated ribonuclease vhs interferes with stress granule formation.

    Finnen, Renée L; Hay, Thomas J M; Dauber, Bianca; Smiley, James R; Banfield, Bruce W

    2014-11-01

    In a previous study, it was observed that cells infected with herpes simplex virus 2 (HSV-2) failed to accumulate stress granules (SGs) in response to oxidative stress induced by arsenite treatment. As a follow-up to this observation, we demonstrate here that disruption of arsenite-induced SG formation by HSV-2 is mediated by a virion component. Through studies on SG formation in cells infected with HSV-2 strains carrying defective forms of UL41, the gene that encodes vhs, we identify vhs as a virion component required for this disruption. Cells infected with HSV-2 strains producing defective forms of vhs form SGs spontaneously late in infection. In addition to core SG components, these spontaneous SGs contain the viral immediate early protein ICP27 as well as the viral serine/threonine kinase Us3. As part of these studies, we reexamined the frameshift mutation known to reside within the UL41 gene of HSV-2 strain HG52. We demonstrate that this mutation is unstable and can rapidly revert to restore wild-type UL41 following low-multiplicity passaging. Identification of the involvement of virion-associated vhs in the disruption of SG formation will enable mechanistic studies on how HSV-2 is able to counteract antiviral stress responses early in infection. In addition, the ability of Us3 to localize to stress granules may indicate novel roles for this viral kinase in the regulation of translation. Eukaryotic cells respond to stress by rapidly shutting down protein synthesis and storing mRNAs in cytoplasmic stress granules (SGs). Stoppages in protein synthesis are problematic for all viruses as they rely on host cell machinery to synthesize viral proteins. Thus, many viruses target SGs for disruption or modification. Infection by herpes simplex virus 2 (HSV-2) was previously observed to disrupt SG formation induced by oxidative stress. In this follow-up study, we identify virion host shutoff protein (vhs) as a viral protein involved in this disruption. The

  3. Granule-by-granule reconstruction of a sandpile from x-ray microtomography data

    Seidler, G. T.; Martinez, G.; Seeley, L. H.; Kim, K. H.; Behne, E. A.; Zaranek, S.; Chapman, B. D.; Heald, S. M.; Brewe, D. L.

    2000-01-01

    Mesoscale disordered materials are ubiquitous in industry and in the environment. Any fundamental understanding of the transport and mechanical properties of such materials must follow from a thorough understanding of their structure. However, in the overwhelming majority of cases, experimental characterization of such materials has been limited to first- and second-order structural correlation functions, i.e., the mean filling fraction and the structural autocorrelation function. We report here the successful combination of synchrotron x-ray microtomography and image processing to determine the full three-dimensional real-space structure of a model disordered material, a granular bed of relatively monodisperse glass spheres. Specifically, we determine the center location and the local connectivity of each granule. This complete knowledge of structure can be used to calculate otherwise inaccessible high-order correlation functions. We analyze nematic order parameters for contact bonds to characterize the geometric anisotropy or fabric induced by the sample boundary conditions. Away from the boundaries we find short-range bond orientational order exhibiting characteristics of the underlying polytetrahedral structure

  4. THE EFFECT OF DRY GRANULATION ON THE CONSOLIDATION AND COMPACTION OF CRYSTALLINE LACTOSE

    RIEPMA, KA; VROMANS, H; ZUURMAN, K; LERK, CF

    1993-01-01

    The consolidation and compaction properties of granule fractions prepared by dry granulation (slugging) of alpha-lactose monohydrate and roller dried beta-lactose, respectively, were studied. The results showed that the compactibility of the granule fractions was determined by the type of lactose

  5. THE RELATIONSHIP BETWEEN BULK-DENSITY AND COMPACTIBILITY OF LACTOSE GRANULATIONS

    ZUURMAN, K; RIEPMA, KA; BOLHUIS, GK; VROMANS, H; LERK, CF

    1994-01-01

    The relationship between the bulk density and the compactibility of lactose granulations was studied. The granulations were prepared from different alpha-lactose monohydrate and roller dried beta-lactose powders by wet granulation, using different techniques with only water as a binder, or by

  6. The consequences of granulate heterogeneity towards breakage and attrition upon fluid-bed drying

    Nieuwmeyer, Florentine; Maarschalk, Kees van der Voort; Vromans, Herman

    High-shear granulated lactose granulates were dried in it fluid-bed dryer at various conditions. Granules were characterized by water content and size analysis. It is shown that the drying process is very dynamic in terms of growth and breakage phenomena. Granular size heterogeneity, composition and

  7. TABLETING PROPERTIES OF EXPERIMENTAL AND COMMERCIALLY AVAILABLE LACTOSE GRANULATIONS FOR DIRECT COMPRESSION

    BOLHUIS, GK; ZUURMAN, K

    1995-01-01

    Lactose granulations (125-250 mu m) were prepared from two different alpha-lactose monohydrate powders and one roller dried beta-lactose powder respectively, by wet granulation with only water as a binder. As an effect of the granulation process, the flow properties improved, but the compactibility

  8. Magnetic resonance microscopy of iron transport in methanogenic granules

    Bartacek, Jan; Vergeldt, Frank J.; Gerkema, Edo; Jenicek, Pavel; Lens, Piet N. L.; Van As, Henk

    2009-10-01

    Interactions between anaerobic biofilms and heavy metals such as iron, cobalt or nickel are largely unknown. Magnetic resonance imaging (MRI) is a non-invasive method that allows in situ studies of metal transport within biofilm matrixes. The present study investigates quantitatively the penetration of iron (1.75 mM) bound to ethylenediaminetetraacetate (EDTA) into the methanogenic granules (spherical biofilm). A spatial resolution of 109 × 109 × 218 μm 3 and a temporal resolution of 11 min are achieved with 3D Turbo Spin Echo (TSE) measurements. The longitudinal relaxivity, i.e. the slope the dependence of the relaxation rate (1/ T1) on the concentration of paramagnetic metal ions, was used to measure temporal changes in iron concentration in the methanogenic granules. It took up to 300 min for the iron-EDTA complex ([FeEDTA] 2-) to penetrate into the methanogenic granules (3-4 mm in diameter). The diffusion was equally fast in all directions with irregularities such as diffusion-facilitating channels and diffusion-resistant zones. Despite these irregularities, the overall process could be modeled using Fick's equations for diffusion in a sphere, because immobilization of [FeEDTA] 2- in the granular matrix (or the presence of a reactive barrier) was not observed. The effective diffusion coefficient ( D ejf) of [FeEDTA] 2- was found to be 2.8 × 10 -11 m 2 s -1, i.e. approximately 4% of D ejf of [FeEDTA] 2- in water. The Fickian model did not correspond to the processes taking place in the core of the granule (3-5% of the total volume of the granule), where up to 25% over-saturation by iron (compare to the concentration in the bulk solution) occurred.

  9. GRANULATION AND BRIQUETTING OF SOLID PRODUCTS FROM FLUE GAS DESULFURIZATION

    Jan J. Hycnar

    2015-11-01

    Full Text Available Most flue gas desulfurization products can be characterized by significant solubility in water and dusting in dry state. These characteristics can cause a considerable pollution of air, water, and soil. Among many approaches to utilization of this waste, the process of agglomeration using granulation or briquetting has proved very effective. Using desulfurization products a new material of aggregate characteristics has been acquired, and this material is resistant to water and wind erosion as well as to the conditions of transportation and storage. The paper presents the results of industrial trials granulation and briquetting of calcium desulphurization products. The granulation of a mixture of phosphogypsum used with fly ash (in the share 1:5. The resulting granules characterized by a compressive strength of 41.6 MPa, the damping resistance of 70% and 14.2% abrasion. The granulate was used for the production of cement mix. The produced concrete mortar have a longer setting and hardening time, as compared to the traditional ash and gypsum mortar, and have a higher or comparable flexural and compressive strength during hardening. Briquetting trials made of a product called synthetic gypsum or rea-gypsum both in pure form and with the addition of 5% and 10% of the limestone dust. Briquettes have a high initial strength and resistance to abrasion. The values ​​of these parameters increased after 72 hours of seasoning. It was found that higher hardiness of briquettes with rea-gypsum was obtained with the impact of atmospheric conditions and higher resistance to elution of water-soluble components in comparison to ash briquettes.

  10. Cold experiments on ligament formation for blast furnace slag granulation

    Liu Junxiang; Yu Qingbo; Li Peng; Du Wenya

    2012-01-01

    Rotary cup atomization for molten slag granulation is an attractive alternative to water quenching. However, the mechanism of disintegration of molten slag must be assessed. In the present study, a glycerol/water mixture was substituted for molten slag, and the mechanism of ligament formation in a rotary cup was investigated using photos taken by a high-speed camera. The effects of the angular speed and inner depth of the rotary cup on ligament disintegration was investigated. The results showed that one state of disintegration may transform into another state as the angular speed of the rotary cup increases at a given liquid flow rate. During ligament formation, the number of ligaments increased with an increase in the angular speed of the rotary cup, and a decrease in the diameter of ligament and liquid drop was observed. Moreover, the initial point of disintegration of the ligament moved to the lip of the rotary cup as the angular speed increased. An equation describing the relationship between the diameter of the liquid drop and various factors was used to predict the diameter of the liquid drop. A rotary cup with an inner depth of 30 mm was the best choice for granulation. The results of the present study will be useful for designing devices used in molten slag granulation. - Highlights: ►The results can be used in the granulation of molten blast furnace slag. ► The three different states of disintegration occur as the angular speed of rotary cup increases. ► The mechanism of ligament disintegration is analyzed. ► Eq. can be used to predict the diameter of liquid drop. ► A rotary cup with an inner depth of 30 mm is optimal for granulation.

  11. From synapse to nucleus and back again--communication over distance within neurons.

    Fainzilber, Mike; Budnik, Vivian; Segal, Rosalind A; Kreutz, Michael R

    2011-11-09

    How do neurons integrate intracellular communication from synapse to nucleus and back? Here we briefly summarize aspects of this topic covered by a symposium at Neuroscience 2011. A rich repertoire of signaling mechanisms link both dendritic terminals and axon tips with neuronal soma and nucleus, using motor-dependent transport machineries to traverse the long intracellular distances along neuronal processes. Activation mechanisms at terminals include localized translation of dendritic or axonal RNA, proteolytic cleavage of receptors or second messengers, and differential phosphorylation of signaling moieties. Signaling complexes may be transported in endosomes, or as non-endosomal complexes associated with importins and dynein. Anterograde transport of RNA granules from the soma to neuronal processes, coupled with retrograde transport of proteins translated locally at terminals or within processes, may fuel ongoing bidirectional communication between soma and synapse to modulate synaptic plasticity as well as neuronal growth and survival decisions.

  12. MORPHOLOGICAL AND ANATOMICAL STUDY OF GRANULES WITH SEEDS EPIDERMIS OF PLANTAGO OVATA FORSSK

    J. V. Daironas

    2017-01-01

    Full Text Available The results of a morphological and anatomical study of granules from the epidermis of Plantago ovata seeds are presented in the article. Morphological and microscopic diagnostic signs are important for establishing the authenticity of medicinal plant material and drugs made from it.The aim is the identification of morphological and microscopic diagnostic characteristics of the seed epidermis of Plantago ovata, minimal and sufficient to establish the authenticity of the granular pieces of the plant’s epidermis.Materials and methods. The study of morphological and anatomical characteristics as well as histochemical study were conducted according to the procedures of the State Pharmacopoeia of the Russian Federation XIII edition. Microscope “Micromed-1” and digital camera MD300 Electronic Eyepiece (Jincheng were used. Photos were edited in Adobe Photoshop CS6.Results and discussion. Morphological signs of the epidermis of Plantago ovata seeds include its light yellow or pinkish-yellow color and a presence of a pigmented spot of pink or light brown color on the epidermis of the convex side of the seeds and along the seed. These signs are applicable for diagnosis and are also found in crushed raw materials. Granules are rough lumps, consisting of stuck together epidermis pieces. They are characterized by a yellowish or light brown color and the presence of a pigmented spot. The microscopic diagnostic signs include the structure of the upper and lower epidermis, the presence of cells with mucus and starch grains. The upper epidermis consists of large polygonal cells with straight thin anticlinal walls. The cells are covered with a smooth cuticle and are filled with mucus. The lower epidermis consists of elongated rectangular cells. Cells with mucus swell rapidly in the radial direction. Biometric characteristics of anatomical diagnostic signs were established.Conclusion. As the result of a morphological and anatomical study the diagnostic signs

  13. Correlative two-photon and serial block face scanning electron microscopy in neuronal tissue using 3D near-infrared branding maps.

    Lees, Robert M; Peddie, Christopher J; Collinson, Lucy M; Ashby, Michael C; Verkade, Paul

    2017-01-01

    Linking cellular structure and function has always been a key goal of microscopy, but obtaining high resolution spatial and temporal information from the same specimen is a fundamental challenge. Two-photon (2P) microscopy allows imaging deep inside intact tissue, bringing great insight into the structural and functional dynamics of cells in their physiological environment. At the nanoscale, the complex ultrastructure of a cell's environment in tissue can be reconstructed in three dimensions (3D) using serial block face scanning electron microscopy (SBF-SEM). This provides a snapshot of high resolution structural information pertaining to the shape, organization, and localization of multiple subcellular structures at the same time. The pairing of these two imaging modalities in the same specimen provides key information to relate cellular dynamics to the ultrastructural environment. Until recently, approaches to relocate a region of interest (ROI) in tissue from 2P microscopy for SBF-SEM have been inefficient or unreliable. However, near-infrared branding (NIRB) overcomes this by using the laser from a multiphoton microscope to create fiducial markers for accurate correlation of 2P and electron microscopy (EM) imaging volumes. The process is quick and can be user defined for each sample. Here, to increase the efficiency of ROI relocation, multiple NIRB marks are used in 3D to target ultramicrotomy. A workflow is described and discussed to obtain a data set for 3D correlated light and electron microscopy, using three different preparations of brain tissue as examples. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Clarithromycin highly-loaded gastro-floating fine granules prepared by high-shear melt granulation can enhance the efficacy of Helicobacter pylori eradication.

    Aoki, Hajime; Iwao, Yasunori; Mizoguchi, Midori; Noguchi, Shuji; Itai, Shigeru

    2015-05-01

    In an effort to develop a new gastro-retentive drug delivery system (GRDDS) without a large amount of additives, 75% clarithromycin (CAM) loaded fine granules were prepared with three different hydrophobic binders by high-shear melt granulation and their properties were evaluated. Granules containing the higher hydrophobic binder showed sustained drug release and were able to float over 24h. The synchrotron X-ray CT measurement indicated that both the high hydrophobicity of the binder and the void space inside the granules might be involved in their buoyancy. In an in vivo experiment, the floating granules more effectively eradicated Helicobacter pylori than a CAM suspension by remaining in the stomach for a longer period. In short, CAM highly-loaded gastro-floating fine granules can enhance the eradication efficiency of H. pylori compared with CAM alone. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Ultrastructure and electrophoretic protein pattern of a nuclear fraction enriched in interchromatin granule conglomerations

    Krzyzowska-Gruca, S.; Zborek, A.; Gruca, S.

    1986-01-01

    Rats were injected with a cytostatic 1-nitro-9/3'-dimethylpropyloamine/acridine.2HCl to induce aggregation of interchromatin granules (IG). The conglomerations of IG were well preserved in isolated liver nuclei and in nuclear structures deprived of chromatin. This feature enabled obtaining a nuclear fraction enriched in IG. The method consisted in extraction of isolated nuclei with a non-ionic detergent and digestion with DNase I in a high ionic strength. Each step of isolation was ultrastructurally monitored using both the routine electron microscopy as well as a preferential staining of IG with bismuth. Presence of spots of tightly packed granules within IG conglomerations in the final fraction like in the nuclei in situ was a good ultrastructural marker of IG. The resulting fraction consisted predominantly of IG conglomerations. Their preferential staining with bismuth was well preserved. Minute amounts of fibrillar material originating from nuclear matrix and residual nuclei could be observed. Protein composition of the fraction enriched in IG was studied by SDS-polyacrylamide gel electrophoresis. After electrotransfer, nitrocellulose filters were fixed with glutaraldehyde and stained with bismuth method in order to identify IG proteins. The results of ultrastructural and cytochemical studies in comparison to electrophoretic protein pattern are discussed.

  16. Sequestration of highly expressed mRNAs in cytoplasmic granules, P-bodies, and stress granules enhances cell viability.

    Anna Lavut

    Full Text Available Transcriptome analyses indicate that a core 10%-15% of the yeast genome is modulated by a variety of different stresses. However, not all the induced genes undergo translation, and null mutants of many induced genes do not show elevated sensitivity to the particular stress. Elucidation of the RNA lifecycle reveals accumulation of non-translating mRNAs in cytoplasmic granules, P-bodies, and stress granules for future regulation. P-bodies contain enzymes for mRNA degradation; under stress conditions mRNAs may be transferred to stress granules for storage and return to translation. Protein degradation by the ubiquitin-proteasome system is elevated by stress; and here we analyzed the steady state levels, decay, and subcellular localization of the mRNA of the gene encoding the F-box protein, UFO1, that is induced by stress. Using the MS2L mRNA reporter system UFO1 mRNA was observed in granules that colocalized with P-bodies and stress granules. These P-bodies stored diverse mRNAs. Granules of two mRNAs transported prior to translation, ASH1-MS2L and OXA1-MS2L, docked with P-bodies. HSP12 mRNA that gave rise to highly elevated protein levels was not observed in granules under these stress conditions. ecd3, pat1 double mutants that are defective in P-body formation were sensitive to mRNAs expressed ectopically from strong promoters. These highly expressed mRNAs showed elevated translation compared with wild-type cells, and the viability of the mutants was strongly reduced. ecd3, pat1 mutants also exhibited increased sensitivity to different stresses. Our interpretation is that sequestration of highly expressed mRNAs in P-bodies is essential for viability. Storage of mRNAs for future regulation may contribute to the discrepancy between the steady state levels of many stress-induced mRNAs and their proteins. Sorting of mRNAs for future translation or decay by individual cells could generate potentially different phenotypes in a genetically identical

  17. Impact of fill-level in twin-screw granulation on critical quality attributes of granules and tablets.

    Meier, Robin; Moll, Klaus-Peter; Krumme, Markus; Kleinebudde, Peter

    2017-06-01

    In a previous study a change of the fill-level in the barrel exerted a huge influence on the twin-screw granulation (TSG) process of a high drug loaded, simplified formulation. The present work investigated this influence systematically. The specific feed load (SFL) indicating the mass per revolution as surrogate parameter for the fill-level was applied and the correlation to the real volumetric fill level of an extruder could be demonstrated by a newly developed method. A design of experiments was conducted to examine the combined influence of SFL and screw speed on the process and on critical quality attributes of granules and tablets. The same formulation was granulated at constant liquid level with the same screw configuration and led to distinctively different results by only changing the fill-level and the screw speed. The power consumption of the extruder increased at higher SFLs with hardly any influence of screw speed. At low SFL the median residence time was mainly fill-level dependent and at higher SFL mainly screw speed dependent. Optimal values for the product characteristics were found at medium values for the SFL. Granule size distributions shifted from mono-modal and narrow shape to broader and even bimodal distributions of larger median granule sizes, when exceeding or falling below a certain fill-level. Deviating from the optimum fill-level, tensile strength of tablets decreased by about 25% and disintegration times of tablets increased for more than one third. At low fill-levels, material accumulation in front of the kneading zone was detected by pressure measurements and was assumed to be responsible for the unfavored product performance. At high fill-levels, granule consolidation due to higher propensity of contact with the result of higher material temperature was accounted for inferior product performance. The fill-level was found to be an important factor in assessment and development of twin-screw granulation processes as it impacted

  18. Neurons of the dentate molecular layer in the rabbit hippocampus.

    Francisco J Sancho-Bielsa

    Full Text Available The molecular layer of the dentate gyrus appears as the main entrance gate for information into the hippocampus, i.e., where the perforant path axons from the entorhinal cortex synapse onto the spines and dendrites of granule cells. A few dispersed neuronal somata appear intermingled in between and probably control the flow of information in this area. In rabbits, the number of neurons in the molecular layer increases in the first week of postnatal life and then stabilizes to appear permanent and heterogeneous over the individuals' life span, including old animals. By means of Golgi impregnations, NADPH histochemistry, immunocytochemical stainings and intracellular labelings (lucifer yellow and biocytin injections, eight neuronal morphological types have been detected in the molecular layer of developing adult and old rabbits. Six of them appear as interneurons displaying smooth dendrites and GABA immunoreactivity: those here called as globoid, vertical, small horizontal, large horizontal, inverted pyramidal and polymorphic. Additionally there are two GABA negative types: the sarmentous and ectopic granular neurons. The distribution of the somata and dendritic trees of these neurons shows preferences for a definite sublayer of the molecular layer: small horizontal, sarmentous and inverted pyramidal neurons are preferably found in the outer third of the molecular layer; vertical, globoid and polymorph neurons locate the intermediate third, while large horizontal and ectopic granular neurons occupy the inner third or the juxtagranular molecular layer. Our results reveal substantial differences in the morphology and electrophysiological behaviour between each neuronal archetype in the dentate molecular layer, allowing us to propose a new classification for this neural population.

  19. Spiking Neurons for Analysis of Patterns

    Huntsberger, Terrance

    2008-01-01

    Artificial neural networks comprising spiking neurons of a novel type have been conceived as improved pattern-analysis and pattern-recognition computational systems. These neurons are represented by a mathematical model denoted the state-variable model (SVM), which among other things, exploits a computational parallelism inherent in spiking-neuron geometry. Networks of SVM neurons offer advantages of speed and computational efficiency, relative to traditional artificial neural networks. The SVM also overcomes some of the limitations of prior spiking-neuron models. There are numerous potential pattern-recognition, tracking, and data-reduction (data preprocessing) applications for these SVM neural networks on Earth and in exploration of remote planets. Spiking neurons imitate biological neurons more closely than do the neurons of traditional artificial neural networks. A spiking neuron includes a central cell body (soma) surrounded by a tree-like interconnection network (dendrites). Spiking neurons are so named because they generate trains of output pulses (spikes) in response to inputs received from sensors or from other neurons. They gain their speed advantage over traditional neural networks by using the timing of individual spikes for computation, whereas traditional artificial neurons use averages of activity levels over time. Moreover, spiking neurons use the delays inherent in dendritic processing in order to efficiently encode the information content of incoming signals. Because traditional artificial neurons fail to capture this encoding, they have less processing capability, and so it is necessary to use more gates when implementing traditional artificial neurons in electronic circuitry. Such higher-order functions as dynamic tasking are effected by use of pools (collections) of spiking neurons interconnected by spike-transmitting fibers. The SVM includes adaptive thresholds and submodels of transport of ions (in imitation of such transport in biological

  20. Retrograde monosynaptic tracing reveals the temporal evolution of inputs onto new neurons in the adult dentate gyrus and olfactory bulb

    Deshpande, Aditi; Bergami, Matteo; Ghanem, Alexander; Conzelmann, Karl-Klaus; Lepier, Alexandra; Götz, Magdalena; Berninger, Benedikt

    2013-01-01

    Identifying the connectome of adult-generated neurons is essential for understanding how the preexisting circuitry is refined by neurogenesis. Changes in the pattern of connectivity are likely to control the differentiation process of newly generated neurons and exert an important influence on their unique capacity to contribute to information processing. Using a monosynaptic rabies virus-based tracing technique, we studied the evolving presynaptic connectivity of adult-generated neurons in the dentate gyrus (DG) of the hippocampus and olfactory bulb (OB) during the first weeks of their life. In both neurogenic zones, adult-generated neurons first receive local connections from multiple types of GABAergic interneurons before long-range projections become established, such as those originating from cortical areas. Interestingly, despite fundamental similarities in the overall pattern of evolution of presynaptic connectivity, there were notable differences with regard to the development of cortical projections: although DG granule neuron input originating from the entorhinal cortex could be traced starting only from 3 to 5 wk on, newly generated neurons in the OB received input from the anterior olfactory nucleus and piriform cortex already by the second week. This early glutamatergic input onto newly generated interneurons in the OB was matched in time by the equally early innervations of DG granule neurons by glutamatergic mossy cells. The development of connectivity revealed by our study may suggest common principles for incorporating newly generated neurons into a preexisting circuit. PMID:23487772

  1. Neuronal Migration Disorders

    ... Understanding Sleep The Life and Death of a Neuron Genes At Work In The Brain Order Publications ... birth defects caused by the abnormal migration of neurons in the developing brain and nervous system. In ...

  2. Motor Neuron Diseases

    ... and other neurodegenerative diseases to better understand the function of neurons and other support cells and identify candidate therapeutic ... and other neurodegenerative diseases to better understand the function of neurons and other support cells and identify candidate therapeutic ...

  3. Riding the glial monorail: a common mechanism for glial-guided neuronal migration in different regions of the developing mammalian brain.

    Hatten, M E

    1990-05-01

    In vitro studies from our laboratory indicate that granule neurons, purified from early postnatal mouse cerebellum, migrate on astroglial fibers by forming a 'migration junction' with the glial fiber along the length of the neuronal soma and extending a motile 'leading process' in the direction of migration. Similar dynamics are seen for hippocampal neurons migrating along hippocampal astroglial fibers in vitro. In heterotypic recombinations of neurons and glia from mouse cerebellum and rat hippocampus, neurons migrate on astroglial processes with a cytology and neuron-glia relationship identical to that of homotypic neuronal migration in vitro. In all four cases, the migrating neuron presents a stereotyped posture, speed and mode of movement, suggesting that glial fibers provide a generic pathway for neuronal migration in developing brain. Studies on the molecular basis of glial-guided migration suggest that astrotactin, a neuronal antigen that functions as a neuron-glia ligand, is likely to play a crucial role in the locomotion of the neuron along glial fibers. The navigation of neurons from glial fibers into cortical layers, in turn, is likely to involve neuron-neuron adhesion ligands.

  4. Statistical properties of solar granulation from the SOUP instrument on Spacelab 2

    Topka, K.; Title, A.; Tarbell, T.; Ferguson, S.; Shine, R.

    1988-01-01

    The Solar Optical Universal Polarimeter (SOUP) on Spacelab 2 collected movies of solar granulation completely free from atmospheric blurring, and are not degraded by pointint jitter (the pointing stability was 0.003 sec root mean square). The movies illustrate that the solar five minute oscillation has a major role in the appearance of solar granulation and that exploding granules are a common feature of the granule evolution. Using 3-D Fourier filtering techniques the oscillations were removed and it was demonstrated that the autocorrelation lifetime of granulation is a factor of two greater in magnetic field regions than in field-free quiet sun. Horizontal velocities were measured and flow patterns were observed on the scale of meso- and super granulation. In quiet regions the mean flow velocity is 370 m/s while in the magnetic regions it is about 125 m/s. It was also found that the root mean square (RMS) fluctuating horizonal velocity field is substantially greater in quiet sun than in strong magnetic field regions. By superimposing the location of exploding granules on the average flow maps it was found that they appear almost exclusively in the center of mesogranulation size flow cells. Because of the nonuniformity of the distribution of exploding granules, the evolution of the granulation pattern in mesogranule cell centers and boundaries differs fundamentally. It is clear from this study there is neither a typical granule nor a typical granule evolution

  5. Statistical properties of solar granulation from the SOUP instrument on Spacelab 2

    Topka, K.; Title, A.; Tarbell, T.; Ferguson, S.; Shine, R.

    1988-11-01

    The Solar Optical Universal Polarimeter (SOUP) on Spacelab 2 collected movies of solar granulation completely free from atmospheric blurring, and are not degraded by pointint jitter (the pointing stability was 0.003 sec root mean square). The movies illustrate that the solar five minute oscillation has a major role in the appearance of solar granulation and that exploding granules are a common feature of the granule evolution. Using 3-D Fourier filtering techniques the oscillations were removed and it was demonstrated that the autocorrelation lifetime of granulation is a factor of two greater in magnetic field regions than in field-free quiet sun. Horizontal velocities were measured and flow patterns were observed on the scale of meso- and super granulation. In quiet regions the mean flow velocity is 370 m/s while in the magnetic regions it is about 125 m/s. It was also found that the root mean square (RMS) fluctuating horizonal velocity field is substantially greater in quiet sun than in strong magnetic field regions. By superimposing the location of exploding granules on the average flow maps it was found that they appear almost exclusively in the center of mesogranulation size flow cells. Because of the nonuniformity of the distribution of exploding granules, the evolution of the granulation pattern in mesogranule cell centers and boundaries differs fundamentally. It is clear from this study there is neither a typical granule nor a typical granule evolution.

  6. Anaerobic granule-based biofilms formation reduces propionate accumulation under high H2 partial pressure using conductive carbon felt particles.

    Xu, Heng; Wang, Cuiping; Yan, Kun; Wu, Jing; Zuo, Jiane; Wang, Kaijun

    2016-09-01

    Syngas based co-digestion is not only more economically attractive than separate syngas methanation but also able to upgrade biogas and increase overall CH4 amount simultaneously. However, high H2 concentration in the syngas could inhibit syntrophic degradation of propionate, resulting in propionate accumulation and even failure of the co-digestion system. In an attempt to reduce propionate accumulation via enhancing both H2 interspecies transfer (HIT) and direct interspecies electron transfer (DIET) pathways, layered granule-based biofilms induced by conductive carbon felt particles (CCFP) was employed. The results showed that propionate accumulation was effectively reduced with influent COD load up to 7gL(-1)d(-1). Two types of granule-based biofilms, namely biofilm adhered to CCFP (B-CCFP) and granules formed by self-immobilization (B-SI) were formed in the reactor. Clostridium, Syntrophobacter, Methanospirillum were possibly involved in HIT and Clostridium, Geobacter, Anaerolineaceae, Methanosaeta in DIET, both of which might be responsible for the high-rate propionate degradation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Localization of MTT formazan in lipid droplets. An alternative hypothesis about the nature of formazan granules and aggregates

    G Diaz

    2009-08-01

    Full Text Available MTT (3-(4, 5-dimethyl-2-thiazolyl-2, 5-dihphenyltetrazolium bromide assay is a widely used method to assess cell viability and proliferation. MTT is readily taken up by cells and enzymatically reduced to formazan, a dark compound which accumulates in cytoplasmic granules. Formazan is later eliminated by the cell by a mechanisms often indicated as exocytosis, that produces characteristic needle-like aggregates on the cell surface. The shape of formazan aggregates and the rate of exocytosis change in the presence of bioactive amyloid b peptides (Ab and cholesterol. Though the cellular mechanisms involved in MTT reduction have been extensively investigated, the exact nature of formazan granules and the process of exocytosis are still obscure. Using Nile Red, which stains differentially neutral and polar lipids, and a fluorescent analog of cholesterol (NBD-cholesterol, we found that formazan localized in lipid droplets, consistent with the lipophilic nature of formazan. However, formazan granules and aggregates were also found to form after killing cells with paraformaldehyde fixation. Moreover, formazan aggregates were also obtained in cell-free media, using ascorbic acid to reduce MTT. The density and shape of formazan aggregates obtained in cell-free media was sensitive to cholesterol and Ab. In cells, electron microscopy failed to detect the presence of secretory vesicles, but revealed unusual fibers of 50 nm of diameter extending throughout the cytoplasm. Taken together, these findings suggest that formazan efflux is driven by physico-chemical interactions at molecular level without involving higher cytological mechanisms.

  8. Differential 3’ processing of specific transcripts expands regulatory and protein diversity across neuronal cell types

    Jereb, Saša; Hwang, Hun-Way; Van Otterloo, Eric; Govek, Eve-Ellen; Fak, John J; Yuan, Yuan; Hatten, Mary E

    2018-01-01

    Alternative polyadenylation (APA) regulates mRNA translation, stability, and protein localization. However, it is unclear to what extent APA regulates these processes uniquely in specific cell types. Using a new technique, cTag-PAPERCLIP, we discovered significant differences in APA between the principal types of mouse cerebellar neurons, the Purkinje and granule cells, as well as between proliferating and differentiated granule cells. Transcripts that differed in APA in these comparisons were enriched in key neuronal functions and many differed in coding sequence in addition to 3’UTR length. We characterize Memo1, a transcript that shifted from expressing a short 3’UTR isoform to a longer one during granule cell differentiation. We show that Memo1 regulates granule cell precursor proliferation and that its long 3’UTR isoform is targeted by miR-124, contributing to its downregulation during development. Our findings provide insight into roles for APA in specific cell types and establish a platform for further functional studies. PMID:29578408

  9. Behavior of hollow balls containing granules bouncing repeatedly off the ground

    Hu, Min; Mu, Qing-song; Luo, Ning; Li, Gang; Peng, Ning-bo

    2013-07-01

    An experimental study of the behavior of hollow balls filled with some granules (mung beans or millets) bouncing repeatedly off a static flat horizontal surface is presented. We observed that the bounce number of the ball is limited and decreases regularly with an increasing number of granules. Moreover, for two balls containing a different kind of granules, their bounce numbers are basically equal when the two balls have the same mass of granules. While there is no clear relationship between the first rebound height of one ball and the number of granules, there appears an exponential decay of the second rebound height with an increase of the granule number. Furthermore, a two-dimensional numerical model has been created to find out the law of the ball's rebound height and the dissipation law of the granule nested system. A generalized prediction equation to reasonably explain the law of the bounce number has also been proposed.

  10. The converse magnetoelectric coupling in asymmetric granule/matrix composite film with Ni/PZT component

    Chen, Bo; Su, Ning-Ning; Cui, Wen-Li; Yan, Shi-Nong

    2018-04-01

    In this work, a type of asymmetric granule/matrix composite film is designed, where the Ni granule is dispersed in PZT matrix, meanwhile the top and bottom electrode is constituted by Au and SRO respectively. Predicted through the electrostatic screening model and mean field approximation, considerable electrostatic charge is induced on Ni granule surface by ferroelectric PZT polarization. Predicted through the spin splitting model and spherical shell approximation, both the magnetization and magnetic anisotropy of Ni granule are modulated by ferroelectric PZT polarization. As the volume fraction of Ni granule is increased, the electric modulation of magnetization and magnetic anisotropy is reduced and enhanced respectively. As the dimension of granule/matrix composite is varied, such modulation is retained. Due to the large area-volume ratio of nano-granule, this work benefits to realize the converse magnetoelectric coupling in nanoscale.

  11. MICROMORPHOLOGICAL STUDIES OF STARCH GRANULES IN SELECTED PROCESSED INDIGENOUS FLOUR OF SOUTH WESTERN NIGERIA

    Adeniyi A. JAYEOLA

    2013-06-01

    Full Text Available Starch granules of yam stem tubers, plantain fruits and cassava root tubers were studied using the light microscope and then compared. Yam and plantain, both monocotyledons, had morphologically similar granules between locations, being mostly oval in shape while the granules of cassava, a dicot, were predominantly globular but varied between locations. Differences in processing methods between locations might be responsible for the observed variation in cassava granules. There is a suggestion that starch granule morphology might follow lineages in a broad sense. The unique micromorphology of cassava starch granule could make it easily detectable when adulterated, substituted or contaminated with yam or plantain granules and this could provide a cost effective clue in forensic determination.

  12. GRANULATION TRIALS OF WASTE THE DUST SILICON CARBIDE FOR UTILIZATION IN METALLURGY

    Gabriel Borowski

    2016-09-01

    Full Text Available The article presents the results of laboratory granulation tests of dust silicon carbide and the results of research on the selection of the binder and the properties of the granules obtained. The research material was a waste of the silicon carbide powder with a high fragmentation, mixed with a cement or an organic modified starch specimen. Six tests were performed in a disc granulator with 100 cm in diameter. In each series of trial specified: the type and share of the binder, the diameter of the granules, tenderness, type of structure and mechanical properties. Good granules of silicon carbide obtained with the addition of cement binder with 4% of the mass fraction and at least 24 hours of seasoning. The binder should be added twice by powdering, first in a stirred granulator, and again after manufacture. It was found that the resulting granules may be used as a replacement of ferrosilicon in the process of steelmaking.

  13. Glomerular and Mitral-Granule Cell Microcircuits Coordinate Temporal and Spatial Information Processing in the Olfactory Bulb.

    Cavarretta, Francesco; Marasco, Addolorata; Hines, Michael L; Shepherd, Gordon M; Migliore, Michele

    2016-01-01

    The olfactory bulb processes inputs from olfactory receptor neurons (ORNs) through two levels: the glomerular layer at the site of input, and the granule cell level at the site of output to the olfactory cortex. The sequence of action of these two levels has not yet been examined. We analyze this issue using a novel computational framework that is scaled up, in three-dimensions (3D), with realistic representations of the interactions between layers, activated by simulated natural odors, and constrained by experimental and theoretical analyses. We suggest that the postulated functions of glomerular circuits have as their primary role transforming a complex and disorganized input into a contrast-enhanced and normalized representation, but cannot provide for synchronization of the distributed glomerular outputs. By contrast, at the granule cell layer, the dendrodendritic interactions mediate temporal decorrelation, which we show is dependent on the preceding contrast enhancement by the glomerular layer. The results provide the first insights into the successive operations in the olfactory bulb, and demonstrate the significance of the modular organization around glomeruli. This layered organization is especially important for natural odor inputs, because they activate many overlapping glomeruli.

  14. Progressive behavioral changes during the maturation of rats with early radiation-induced hypoplasia of fascia dentata granule cells

    Mickley, G.A.; Ferguson, J.L.; Mulvihill, M.A.; Nemeth, T.J.

    1989-01-01

    Localized exposure of the neonatal rat brain to X-rays produces neuronal hypoplasia specific to the granule cell layer of the hippocampal dentate gyrus. This brain damage causes locomotor hyperactivity, slowed acquisition of passive avoidance tasks and long bouts of spontaneous turning (without reversals) in a bowl apparatus. Here we report how these behavioral deficits change as a function of subject aging and behavioral test replications. Portions of the neonatal rat cerebral hemispheres were X-irradiated in order to selectively damage the granule cells of the dentate gyrus. The brains of experimental animals received a fractionated dose of X rays (13 Gy total) over postnatal days 1 to 16 and control animals were sham-irradiated. Rats between the ages of 71-462 days were tested 3 separate times on each of the following 3 behavioral tests: (1) spontaneous locomotion, (2) passive avoidance acquisition, and (3) spontaneous circling in a large plastic hemisphere. Rats with radiation-induced damage to the fascia dentata exhibited long bouts of slow turns without reversals. Once they began, irradiated subjects perseverated in turning to an extent significantly greater than sham-irradiated control subjects. This irradiation effect was significant during all test series. Moreover, in time, spontaneous perseverative turning was significantly potentiated in rats with hippocampal damage but increased only slightly in controls. Early radiation exposure produced locomotor hyperactivity in young rats. While activity levels of controls remained fairly stable throughout the course of the experiment, the hyperactivity of the irradiated animals decreased significantly as they matured

  15. Glomerular and mitral-granule cell microcircuits coordinate temporal and spatial information processing in the olfactory bulb

    Francesco Cavarretta

    2016-07-01

    Full Text Available The olfactory bulb processes inputs from olfactory receptor neurons (ORNs through two levels: the glomerular layer at the site of input, and the granule cell level at the site of output to the olfactory cortex. The sequence of action of these two levels has not yet been examined. We analyze this issue using a novel computational framework that is scaled up, in three-dimensions (3D, with realistic representations of the interactions between layers, activated by simulated natural odors, and constrained by experimental and theoretical analyses. We suggest that the postulated functions of glomerular circuits have as their primary role transforming a complex and disorganized input into a contrast-enhanced and normalized representation, but cannot provide for synchronization of the distributed glomerular outputs. By contrast, at the granule cell layer, the dendrodendritic interactions mediate temporal decorrelation, which we show is dependent on the preceding contrast enhancement by the glomerular layer. The results provide the first insights into the successive operations in the olfactory bulb, and demonstrate the significance of the modular organization around glomeruli. This layered organization is especially important for natural odor inputs, because they activate many overlapping glomeruli.

  16. Comparative sensitivity of rat cerebellar neurons to dysregulation of divalent cation homeostasis and cytotoxicity caused by methylmercury

    Edwards, Joshua R.; Marty, M. Sue; Atchison, William D.

    2005-01-01

    The objective of the present study was to determine the relative effectiveness of methylmercury (MeHg) to alter divalent cation homeostasis and cause cell death in MeHg-resistant cerebellar Purkinje and MeHg-sensitive granule neurons. Application of 0.5-5 μM MeHg to Purkinje and granule cells grown in culture caused a concentration- and time-dependent biphasic increase in fura-2 fluorescence. At 0.5 and 1 μM MeHg, the elevations of fura-2 fluorescence induced by MeHg were biphasic in both cell types, but significantly delayed in Purkinje as compared to granule cells. Application of the heavy-metal chelator, TPEN, to Purkinje cells caused a precipitous decline in a proportion of the fura-2 fluorescence signal, indicating that MeHg causes release of Ca 2+ and non-Ca 2+ divalent cations. Purkinje cells were also more resistant than granule cells to the neurotoxic effects of MeHg. At 24.5 h after-application of 5 μM MeHg, 97.7% of Purkinje cells were viable. At 3 μM MeHg there was no detectable loss of Purkinje cell viability. In contrast, only 40.6% of cerebellar granule cells were alive 24.5 h after application of 3 μM MeHg. In conclusion, Purkinje neurons in primary cultures appear to be more resistant to MeHg-induced dysregulation of divalent cation homeostasis and subsequent cell death when compared to cerebellar granule cells. There is a significant component of non-Ca 2+ divalent cation released by MeHg in Purkinje neurons

  17. Self-organizing of critical state in granulated superconductors

    Ginzburg, S.L.; Savitskaya, N.E.

    2000-01-01

    Critical state in granulated superconductors was studied on the basis of two mathematical models - the system of differential equations for calibration and invariant difference of phases and a simplified model describing the system of associated images and equivalent to the standard models to study self-organizing criticality. The critical state of granulated superconductors in all studied cases was shown to be self-organized. Besides, it is shown that the applied models are practically equivalent ones, that is they both show similar critical behavior and lead to coincidence of noncritical phenomena. For the first time one showed that the occurrence of self-organized critically within the system of nonlinear differential equations and its equivalence to self-organized critically in the standard models [ru

  18. Block-based approach to modelling of granulated fertilizers' quality

    Kohonen, J.; Reinikainen, S. P.; Høskuldsson, Agnar

    2009-01-01

    be defined through testing the flow rate with, e.g., seed drill. Besides the chemical composition, flowability can be considered as one of the most important characteristics. There are numerous factors affecting the flowability of a granulated fertilizer, several of them related to the particle size......Fertilizer manufacturing is a customer-driven industry, where the quality of a product is a key factor in order to survive the competition. However, measuring the most important feature with granulated fertilizers, flowability, is tedious, time-consuming and thus expensive. Flowability can...... size distribution. The goals are to find a reliable model for flowability using this data and to find the most important variables and to identify the effect of blocks to the quality....

  19. Spray Drying Processing: granules production and drying kinetics of droplets

    Mondragon, R.; Julia, J. E.; Barba, A.; Jarque, J. C.

    2013-01-01

    Spray drying is a unit operation very common in many industrial processes. For each particular application, the resulting granulated material must possess determined properties that depend on the conditions in which the spray drying processing has been carried out, and whose dependence must be known in order to optimize the quality of the material obtained. The large number of variables that influence on the processes of matter and energy transfer and on the formation of granular material has required a detailed analysis of the drying process. Over the years there have been many studies on the spray drying processing of all kind of materials and the influence of process variables on the drying kinetics of the granulated material properties obtained. This article lists the most important works published for both the spray drying processing and the drying of individual droplets, as well as studies aimed at modeling the drying kinetics of drops. (Author)

  20. Contaminated fluid filtration plant using pneumatically renewable granulated material

    Lucas, J.-C.; Messirejean, Pierre.

    1980-01-01

    This invention concerns a plant for the filtration of a contaminated fluid flow using a granulated material capable of absorbing or adsorbing the contaminants. This plant includes a filtration box within which there is at least one appreciably vertical filtering bed filled with the material and crossed by the fluid flow, loading and discharge compartments respectively located at the top and bottom of the box, each in communication with the filtering bed and an air-actuated transfer system for loading and discharging this bed through these compartments. Facilities of this kind are used mainly in the nuclear and chemical engineering industries to rid their waste of radio-iodines, generally constituted by elementary iodine and methyl iodide, or of toxic gases that contaminate them. The granulated material, whose job it is to trap these contaminants by adsorption or absorption, is generally composed of active carbon or zeolites whose utilisation time is limited [fr

  1. Organic-mineral binder for molybdenum concentrate granulation

    Guro, Vitaliy P.; Ibragimova, Matluba A.; Safarov, Edgorjon T.

    2016-01-01

    Process of pyrite cinders production from Mo middlings consists of molybdenite concentrate granulation, firing to oxidize sulfide minerals and to recover Re-oxide. If kaolin binder is used a pyrite cinders dilution with Mo takes place. So, the development of organic binding agents, alternative to kaolin, is an actual issue. The approach is based on the comparison of the hydrophilic, strength and technological features of the hydrometallurgical processing of pellets. The new batch is developed. It differs from the traditional mixture by polymer burning and minimizing Mo dilution, thus aiming to maximize Re, Au, Ag recovery. The composition of the new organic-mineral batch is as follows: 97.3 % of molybdenite concentrate, 2 % of kaolin and 0.7 % of SK polymer. Keywords: molybdenum middlings, binder, organic additive, batch, granulation.

  2. Multivariate modelling of the tablet manufacturing process with wet granulation for tablet optimization and in-process control

    Westerhuis, J.A; Coenegracht, P.M J; Lerk, C.F

    1997-01-01

    The process of tablet manufacturing with granulation is described as a two-step process. The first step comprises wet granulation of the powder mixture, and in the second step the granules are compressed into tablets. For the modelling of the pharmaceutical process of wet granulation and tableting,

  3. Lewis M. Rutherfurd and the First Photograph of Solar Granulation

    Harvey, J. W.; Briggs, John W.; Prosser, Sian

    2017-08-01

    A major astronomical controversy of the mid-19th century was discordant descriptions of the small scale structure of the solar surface. Visual observers contradicted each other by describing the surface as consisting of “corrugations”, “willow leaves”, “rice grains”, “cumuli”, “thatch”, “granules”, etc. Early photographs of the solar surface were not good enough to settle the controversy. The French astronomer Jules Janssen is credited with the first 1876 photographs that clearly showed what we now call solar granulation (1876, CRAS 82, 1363). Upon seeing these images, New Yorker Lewis M. Rutherfurd (1878, MNRAS 38, 410) praised the high quality of Janssen’s images but asserted that he had also photographed granulation as early as 1871 using collodion wet plates. He sent copies of his best photograph to the Royal Astronomical Society to support his assertion. Curious about his claim, Briggs and Harvey set up Rutherfurd’s 13-inch achromatic refractor on Kitt Peak and found that it easily showed well-resolved solar granulation, so his claim might well have been justified. But without his plates we could not confirm the claim. For 140 years the copies of Rutherfurd’s best solar photograph remained in the archives of the Royal Astronomical Society and were recently discovered by Prosser (RAS Photographs A3/001B and A3/002). By coincidence a few days later, Briggs found the original August 11, 1871 plate. Despite poor condition these photographs show solar granulation. There are at least two other possible early claimants (Reade; Vogel) but their plates are almost certainly lost. Rutherfurd was a master of astronomical instrumentation and photography. He was reticent about his work, letting results speak for themselves, so it is satisfying to find that he was justified in making his claim of priority.

  4. Lipopolysaccharide-binding protein: localization in secretory granules of Paneth cells in the mouse small intestine

    Hansen, Gert H; Rasmussen, Karina; Niels-Christiansen, Lise-Lotte

    2009-01-01

    Lipopolysaccharide (LPS)-binding protein (LBP) is an acute-phase protein involved in the host's response to endotoxin and mainly synthesized and secreted to the blood by the liver. But in addition, LBP is also made by extrahepatic cells, including the enterocyte-like cell line Caco-2. To study...... in closer detail the synthesis and storage of LBP in the intestinal mucosal epithelium, we performed an immunolocalization of LBP in mouse small intestine. By immunofluorescence microscopy, an antibody recognizing the 58-60 kDa protein of LBP distinctly labeled a small population of cells located deep...... into the crypts. This cell population was also positive for lysozyme and alpha-defensin 4, identifying Paneth cells as the main intestinal LBP-producing cells. By immunogold electron microscopy, intense labeling was observed in the secretory granules of these cells. We conclude that Paneth cells express LBP...

  5. Granule cell dispersion is not a predictor of surgical outcome in temporal lobe epilepsy with mesial temporal sclerosis.

    da Costa Neves, Rafael Scarpa; Jardim, Anaclara Prada; Caboclo, Luís Otávio; Lancellotti, Carmen; Marinho, Taissa Ferrari; Hamad, Ana Paula; Marinho, Murilo; Centeno, Ricardo; Cavalheiro, Esper Abrão; Scorza, Carla Alessandra; Targas Yacubian, Elza Márcia

    2013-01-01

    The aim of this retrospective study of a series of patients with mesial temporal lobe epilepsy (MTLE) and mesial temporal sclerosis (MTS) was to analyze the association of granule cell dispersion (GCD) with surgical prognosis, patterns of MTS and clinical data. Hippocampal specimens from 66 patients with MTLE and unilateral MTS and from 13 controls were studied. Quantitative neuropathological evaluation was performed on NeuN-stained hippocampal sections. Patients' clinical data, types of MTS and surgical outcome were reviewed. GCD occurred in 45.5% of cases and was not correlated with clinical variable. More severe neuronal loss was observed in patients with GCD. Except for MTS Type 2 - observed only in four no- GCD patients - groups did not differ with respect to the types of MTS. Surgical outcome was similar in both groups. In conclusion, GCD was associated with the degree of hippocampal cell loss, but was not a predictor of surgical outcome.

  6. Studies on the influence of laser beams on wound granulation

    Brunner, R.

    1982-01-01

    The influence of laser light of law energy on wound healing was tested on 204 rats in a blind study. The growth of granulation tissue in a polyvinylchloride cylinder implanted on the backs of the animals served as parameter for wound healing. Irradiation was carried out with a helium-neon laser (wavelength 632.8 nm) at daily doses of 0.5 J/cm 2 , 1.5 J/cm 2 , 4 J/cm 2 , 10 J/cm 2 and 20 J/cm 2 , and with incoherent non-linear polarized red light (wavelength 630 nm) with a daily dose of 4 J/cm 2 . This was repeated 8 times. Laser irradiation caused a statistically significant increase in wet and dry granulation tissue weight of 25% in the dose range 1.5 J/cm 2 to 20 J/cm 2 . At 0.5 J/cm 2 the effect was less, but the least effect was achieved by non-linear polarized incoherent red light. Bacteriological evaluation of wound germ counts revealed a marginally lower presence of high germ cell densities. In irradiated animals, histological and enzyme cytochemical findings revealed, in addition to a significant findings revealed, in addition to a significant increase in mast cells, a smaller increase in fibroblast count and a slight decrease in granulocytic and histiocytic elements. The biochemical evaluation of granulation tissue revealed no differences in collagen content between irradiated and unirradiated animals. (orig.) [de

  7. First results on quiet and magnetic granulation from SOUP

    Title, A. M.; Tarbell, T. D.; Acton, L.; Duncan, D.; Ferguson, S. H.; Finch, M.; Frank, Z.; Kelly, G.; Lindgren, R.; Morrill, M.

    1987-01-01

    The flight of Solar Optical Universal Polarimeter (SOUP) on Spacelab 2 allowed the collection of time sequences of diffraction limited (0.5 arc sec) granulation images with excellent pointing (0.003 arc sec) and completely free of the distortion that plagues groundbased images. The p-mode oscillations are clearly seen in the data. Using Fourier transforms in the temporal and spatial domain, it was shown that the p-modes dominate the autocorrelation lifetime in magnetic regions. When these oscillations are removed the autocorrelation lifetime is found to be 500 sec in quiet and 950 sec in magnetic regions. In quiet areas exploding granules are seen to be common. It is speculated that a significant fraction of granule lifetimes are terminated by nearby explosions. Using local correlation tracking techniques it was able to measure horizontal displacements, and thus transverse velocities, in the magnetic field. In quiet sun it is possible to detect both super and mesogranulation. Horizontal velocities are as great as 1000 m/s and the average velocity is 400 m/s. In magnetic regions horizontal velocities are much less, about 100 m/s.

  8. Recreating the synthesis of starch granules in yeast

    Pfister, Barbara; Sánchez-Ferrer, Antoni; Diaz, Ana; Lu, Kuanjen; Otto, Caroline; Holler, Mirko; Shaik, Farooque Razvi; Meier, Florence; Mezzenga, Raffaele; Zeeman, Samuel C

    2016-01-01

    Starch, as the major nutritional component of our staple crops and a feedstock for industry, is a vital plant product. It is composed of glucose polymers that form massive semi-crystalline granules. Its precise structure and composition determine its functionality and thus applications; however, there is no versatile model system allowing the relationships between the biosynthetic apparatus, glucan structure and properties to be explored. Here, we expressed the core Arabidopsis starch-biosynthesis pathway in Saccharomyces cerevisiae purged of its endogenous glycogen-metabolic enzymes. Systematic variation of the set of biosynthetic enzymes illustrated how each affects glucan structure and solubility. Expression of the complete set resulted in dense, insoluble granules with a starch-like semi-crystalline organization, demonstrating that this system indeed simulates starch biosynthesis. Thus, the yeast system has the potential to accelerate starch research and help create a holistic understanding of starch granule biosynthesis, providing a basis for the targeted biotechnological improvement of crops. DOI: http://dx.doi.org/10.7554/eLife.15552.001 PMID:27871361

  9. [Multi-mathematical modelings for compatibility optimization of Jiangzhi granules].

    Yang, Ming; Zhang, Li; Ge, Yingli; Lu, Yanliu; Ji, Guang

    2011-12-01

    To investigate into the method of "multi activity index evaluation and combination optimized of mult-component" for Chinese herbal formulas. According to the scheme of uniform experimental design, efficacy experiment, multi index evaluation, least absolute shrinkage, selection operator (LASSO) modeling, evolutionary optimization algorithm, validation experiment, we optimized the combination of Jiangzhi granules based on the activity indexes of blood serum ALT, ALT, AST, TG, TC, HDL, LDL and TG level of liver tissues, ratio of liver tissue to body. Analytic hierarchy process (AHP) combining with criteria importance through intercriteria correlation (CRITIC) for multi activity index evaluation was more reasonable and objective, it reflected the information of activity index's order and objective sample data. LASSO algorithm modeling could accurately reflect the relationship between different combination of Jiangzhi granule and the activity comprehensive indexes. The optimized combination of Jiangzhi granule showed better values of the activity comprehensive indexed than the original formula after the validation experiment. AHP combining with CRITIC can be used for multi activity index evaluation and LASSO algorithm, it is suitable for combination optimized of Chinese herbal formulas.

  10. First results on quiet and magnetic granulation from SOUP

    Title, A. M.; Tarbell, T. D.; Acton, L.; Duncan, D.; Ferguson, S. H.; Finch, M.; Frank, Z.; Kelly, G.; Lindgren, R.; Morrill, M.

    1987-09-01

    The flight of Solar Optical Universal Polarimeter (SOUP) on Spacelab 2 allowed the collection of time sequences of diffraction limited (0.5 arc sec) granulation images with excellent pointing (0.003 arc sec) and completely free of the distortion that plagues groundbased images. The p-mode oscillations are clearly seen in the data. Using Fourier transforms in the temporal and spatial domain, it was shown that the p-modes dominate the autocorrelation lifetime in magnetic regions. When these oscillations are removed the autocorrelation lifetime is found to be 500 sec in quiet and 950 sec in magnetic regions. In quiet areas exploding granules are seen to be common. It is speculated that a significant fraction of granule lifetimes are terminated by nearby explosions. Using local correlation tracking techniques it was able to measure horizontal displacements, and thus transverse velocities, in the magnetic field. In quiet sun it is possible to detect both super and mesogranulation. Horizontal velocities are as great as 1000 m/s and the average velocity is 400 m/s. In magnetic regions horizontal velocities are much less, about 100 m/s.

  11. Cochlear nucleus neuron analysis in individuals with presbycusis.

    Hinojosa, Raul; Nelson, Erik G

    2011-12-01

    The aim of this study was to analyze the cochlear nucleus neuron population in individuals with normal hearing and presbycusis. Retrospective study of archival human temporal bone and brain stem tissues. Using strict inclusion criteria, the temporal bones and cochlear nuclei from six normal hearing individuals and four individuals with presbycusis were selected for analysis. The spiral ganglion cell population, the cochlear nucleus neuron population, and the cell body size of the neurons were quantified in these cases. A relationship was not observed between age and the spiral ganglion cell population in the normal hearing group. Presbycusis subjects exhibited a reduced spiral ganglion cell population. The mean cochlear nucleus neuron population was observed to be significantly higher in the presbycusis group (mean ± standard deviation: 114,170 ± 10,570) compared to the normal hearing group (91,470 ± 9,510) (P = .019). This difference was predominantly the result of greater multipolar and granule cell neuron populations. Only the fusiform neuron type exhibited a significantly different mean cell body cross-sectional area between the normal hearing group (242 ± 27) and the presbycusis group (300 ± 37) (P = .033). This investigation is the first time, to our knowledge, that the populations of the eight neuron types in the cochlear nucleus have been quantified in both normal hearing individuals and individuals with presbycusis. The data support the concept that presbycusis is not an effect of aging alone but instead may be a condition that predisposes one to hearing loss with advancing age and is characterized by a congenitally elevated cochlear nucleus neuron population. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

  12. A comparative study of the influence of alpha-lactose monohydrate particle morphology on granule and tablet properties after roll compaction/dry granulation.

    Grote, Simon; Kleinebudde, Peter

    2018-05-29

    The influence of particle morphology and size of alpha-lactose monohydrate on dry granules and tablets was studied. Four different morphologies were investigated: Two grades of primary crystals, which differed in their particle size and structure (compact crystals vs. agglomerates). The materials were roll compacted at different specific compaction forces and changes in the particle size distribution and the specific surface area were measured. Afterwards, two fractions of granules were pressed to tablets and the tensile strength was compared to that from tablets compressed from the raw materials. The specific surface area was increased induced by roll compaction/dry granulation for all materials. At increased specific compaction forces, the materials showed sufficient size enlargement. The morphology of lactose determined the strength of direct compressed tablets. In contrast, the strength of granule tablets was leveled by the previous compression step during roll compaction/dry granulation. Thus, the tensile strength of tablets compressed directly from the powder mixtures determined whether materials exhibited a loss in tabletability after roll compaction/dry granulation or not. The granule size had only a slight influence on the strength of produced tablets. In some cases, the fraction of smaller granules showed a higher tensile strength compared to the larger fraction.

  13. GABA regulates synaptic integration of newly generated neurons in the adult brain

    Ge, Shaoyu; Goh, Eyleen L. K.; Sailor, Kurt A.; Kitabatake, Yasuji; Ming, Guo-Li; Song, Hongjun

    2006-02-01

    Adult neurogenesis, the birth and integration of new neurons from adult neural stem cells, is a striking form of structural plasticity and highlights the regenerative capacity of the adult mammalian brain. Accumulating evidence suggests that neuronal activity regulates adult neurogenesis and that new neurons contribute to specific brain functions. The mechanism that regulates the integration of newly generated neurons into the pre-existing functional circuitry in the adult brain is unknown. Here we show that newborn granule cells in the dentate gyrus of the adult hippocampus are tonically activated by ambient GABA (γ-aminobutyric acid) before being sequentially innervated by GABA- and glutamate-mediated synaptic inputs. GABA, the major inhibitory neurotransmitter in the adult brain, initially exerts an excitatory action on newborn neurons owing to their high cytoplasmic chloride ion content. Conversion of GABA-induced depolarization (excitation) into hyperpolarization (inhibition) in newborn neurons leads to marked defects in their synapse formation and dendritic development in vivo. Our study identifies an essential role for GABA in the synaptic integration of newly generated neurons in the adult brain, and suggests an unexpected mechanism for activity-dependent regulation of adult neurogenesis, in which newborn neurons may sense neuronal network activity through tonic and phasic GABA activation.

  14. Neurotoxicity of amphetamine derivatives is mediated by caspase pathway activation in rat cerebellar granule cells

    Jimenez, Andres; Jorda, Elvira G.; Verdaguer, Ester; Pubill, David; Sureda, Francesc X.; Canudas, Anna M.; Escubedo, Elena; Camarasa, Jordi; Camins, Antoni; Pallas, Merce

    2004-01-01

    The neurotoxic action of the abuse drugs methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA) on cerebellar granule neurones (CGNs) culture was examined. Treatment for 48 h with METH or MDMA (1-5 mM) induced a higher decrease in viability than 24 h treatment. z.VAD.fmk (100 μM) but not MK-801 nor NBQX recovered control viability values. In both cases, cell death was characterised as apoptotic rather than necrotic by morphology cell observation. Apoptosis measured by flow cytometry indicated an increase in the hypodiploid population after 48 h treatment with METH and MDMA. Apoptosis was reverted by the presence of z.VAD.fmk (100 μM) but not by 10 μM MK-801 or NBQX. Similar results were obtained by analysing nuclear chromatine condensation. These results ruled out excitotoxic participation in amphetamine derivative-induced neurotoxicity in CGNs. Participation of radical oxygen species (ROS) was evaluated using α-tocopherol (1-15 μM) and cytometric studies. The co-treatment with 4 mM METH or MDMA for 48 h partially reverted neurotoxic action and apoptotic features, indicating ROS implication in CGNs death by amphetamine derivatives. Alteration of mitochondrial function induced cytochrome C (Cyt C) release after 48-h treatment with METH and MDMA (4 mM). There was also indication of caspase-3-like activation, measured by immunoanalysis and biochemically. Finally, neurodegenerative action caused by amphetamine derivatives may be prevented by using caspase inhibitors

  15. Melting of fuel element racks and their recycling as granulate

    Quade, U.; Kluth, T.; Kreh, R.

    1998-01-01

    In order to increase the storage capacity for spent fuel elements in the Spanish NPPs of Almaraz and Asco, the existing racks were replaced by compact one in 1991/1993. The 28 racks from Almaraz NPP were cut on site, packed in 200-I-drums and taken to intermediate storage. For the remaining 28 racks of Asco NPP, ENRESA preferred the melting alternative. To demonstrate the recycling path melting in Germany, a test campaign with six racks was performed in 1997. As a result of this test melt, the limits for Carla melting plant were modified to 200 Bq/g total, α, β, γ 100 Bq/g nuclear fuels, max. 3g/100 kg 2,000 Bq/g total Fe55, H 3 , C-14 and Ni63. After the test melt campaign, the German authorities licensed the import and treatment of the remaining 22 racks on the condition that the waste resulting from the melting process as well as the granules produced were taken back to Spain. The shipment from Asco via France to Germany has been carried out in F 20-ft-IPII containers in accordance with ADR. Size reduction to chargeable dimensions was carried out by a plasma burner and hydraulic shears. For melting, a 3.2 Mg medium frequency induction furnace, operated in a separate housing, was used. For granules production outside this housing, the liquid iron was cast into a 5Mg ladle and then, through a water jet, into the granulating basin. The total mass of 287,659 Kg of 28 fuel elements racks and components of the storage basin yielded 297,914 kg of iron granulate. Secondary waste from melting amounted to 9,920 kg, corresponding to 3.45% of the input mass. The granulating process produced 6,589 kg, corresponding to 2.28% of the total mass to be melted. Radiological analysis of samples taken from the melt and different waste components confirmed the main nuclides Co60, Cs134 and Cs137. Fe55 was highly overestimated by the preliminary analysis. (Author) 2 refs

  16. The role of immunohistochemistry, electron microscopy, and ultrastructural cytochemistry in the diagnosis of mixed carcinoma-neuroendocrine neoplasms.

    Graham, A R; Payne, C M; Nagle, R B; Angel, E

    1987-02-01

    We studied four mixed carcinoma-neuroendocrine neoplasms from gastrointestinal tract and pancreas by routine light microscopy (LM), immunohistochemistry (IH), electron microscopy (EM), and ultrastructural cytochemistry (UC). By LM, the individual tumors showed fairly pure neuroendocrine (carcinoid) or epithelial (papillary) patterns, mixed neuroendocrine-carcinoma features and poorly-differentiated tumor in sheets and nests which did not lend itself to morphologic characterization. IH demonstrated mixed expression, within different areas of the same neoplasm, of epithelial antigens (keratins and carcinoembryonic antigen [CEA]) and neuroendocrine markers (neuron-specific enolase [NSE], bombesin and neurohormonal peptides). By EM, each tumor showed ultrastructural features of epithelial and neuroendocrine differentiation which varied substantially in terms of number of cells involved and their distribution; two of the neoplasms showed biphasic differentiation within single cells. The nature of the neurosecretory granules was verified with the uranaffin reaction (UR). This study illustrates the value of combining LM, IH, EM and UC for the identification of mixed carcinoma-neuroendocrine lesions.

  17. Rice starch granule amylolysis--differentiating effects of particle size, morphology, thermal properties and crystalline polymorph.

    Dhital, Sushil; Butardo, Vito M; Jobling, Stephen A; Gidley, Michael J

    2015-01-22

    The underlying mechanism of amylolysis of rice starch granules was investigated using isolated starch granules from wild-type, as well as SBEIIb mutant and down-regulated lines. Fused granule agglomerates isolated from mutant and transgenic lines were hydrolysed at similar rates by amylases, and had similar crystalline patterns and thermal properties as individual granules. Surface pores, a feature previously only reported for A-polymorphic starch granules, were also observed in B- and C-polymorphic rice starch granules. Although the microscopic patterns of hydrolysis among granules with different crystalline polymorphs were qualitatively similar, the extent and the rate of amylolysis were different, suggesting that B-type crystalline polymorphs are intrinsically more resistant to enzymatic hydrolysis than A-type in rice starch granules. It is proposed that the slightly longer branch lengths of amylopectin which leads to the formation of more stable B-type double helical structures compared to their A-type counterparts is the major parameter, with other factors such as granule size, surface pores and interior channels having secondary roles, in determining the rate of enzymatic hydrolysis of rice starch granules. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Formation of tRNA granules in the nucleus of heat-induced human cells

    Miyagawa, Ryu; Mizuno, Rie; Watanabe, Kazunori; Ijiri, Kenichi

    2012-01-01

    Highlights: ► tRNAs are tranlocated into the nucleus in heat-induced HeLa cells. ► tRNAs form the unique granules in the nucleus. ► tRNA ganules overlap with nuclear stress granules. -- Abstract: The stress response, which can trigger various physiological phenomena, is important for living organisms. For instance, a number of stress-induced granules such as P-body and stress granule have been identified. These granules are formed in the cytoplasm under stress conditions and are associated with translational inhibition and mRNA decay. In the nucleus, there is a focus named nuclear stress body (nSB) that distinguishes these structures from cytoplasmic stress granules. Many splicing factors and long non-coding RNA species localize in nSBs as a result of stress. Indeed, tRNAs respond to several kinds of stress such as heat, oxidation or starvation. Although nuclear accumulation of tRNAs occurs in starved Saccharomyces cerevisiae, this phenomenon is not found in mammalian cells. We observed that initiator tRNA Met (Meti) is actively translocated into the nucleus of human cells under heat stress. During this study, we identified unique granules of Meti that overlapped with nSBs. Similarly, elongator tRNA Met was translocated into the nucleus and formed granules during heat stress. Formation of tRNA granules is closely related to the translocation ratio. Then, all tRNAs may form the specific granules.

  19. Impact of functionalized particle structure on roll compaction/dry granulation and tableting of calcium carbonate.

    Grote, Simon; Kleinebudde, Peter

    2018-06-10

    The influence of a functionalized raw material particle structure on the granulation behavior and tabletabilty of calcium carbonate (CaCO 3 ) was investigated. Therefore, a milled grade of CaCO 3 was compared to different binary mixtures of milled and functionalized CaCO 3 . Relevant properties of raw materials, ribbons and granules were measured. The starting materials and two fractions of dry granules were compressed to tablets. The tabletability of granules was compared to that of the powders and the influence of specific compaction force and granule size on tablet tensile strength was evaluated. Adding functionalized particles drastically influenced the granulation and tableting behavior of CaCO 3 . Increasing proportions increased the ribbon porosity and granule size. Tensile strength of tablets from powder mixtures and granules was increased as well. Nevertheless, adding functionalized CaCO 3 led to a loss in tabletability induced by a previous compaction step to an extent depending on its proportion in the formulation. A clear influence of the particle morphology on granulation and tableting behavior was demonstrated by the study. The functionalized structure showed aspects of a more plastic deformation behavior. Adding functionalized CaCO 3 to a mixture, even in small amounts, seemed to be beneficial to increase granule size and tablet strength. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Control over the morphology and segregation of Zebrafish germ cell granules during embryonic development

    Nakkrasae La-Iad

    2008-05-01

    Full Text Available Abstract Background Zebrafish germ cells contain granular-like structures, organized around the cell nucleus. These structures share common features with polar granules in Drosophila, germinal granules in Xenopus and chromatoid bodies in mice germ cells, such as the localization of the zebrafish Vasa, Piwi and Nanos proteins, among others. Little is known about the structure of these granules as well as their segregation in mitosis during early germ-cell development. Results Using transgenic fish expressing a fluorescently labeled novel component of Zebrafish germ cell granules termed Granulito, we followed the morphology and distribution of the granules. We show that whereas these granules initially exhibit a wide size variation, by the end of the first day of development they become a homogeneous population of medium size granules. We investigated this resizing event and demonstrated the role of microtubules and the minus-end microtubule dependent motor protein Dynein in the process. Last, we show that the function of the germ cell granule resident protein the Tudor domain containing protein-7 (Tdrd7 is required for determination of granule morphology and number. Conclusion Our results suggest that Zebrafish germ cell granules undergo a transformation process, which involves germ cell specific proteins as well as the microtubular network.

  1. Somatic Arc protein expression in hippocampal granule cells is increased in response to environmental change but independent of task-specific learning.

    Cleland, J P; Willis, E F; Bartlett, P F; Vukovic, J

    2017-09-29

    Activated neurons express immediate-early genes, such as Arc. Expression of Arc in the hippocampal granule cell layer, an area crucial for spatial learning and memory, is increased during acquisition of spatial learning; however, it is unclear whether this effect is related to the task-specific learning process or to nonspecific aspects of the testing procedure (e.g. exposure to the testing apparatus and exploration of the environment). Herein, we show that Arc-positive cells numbers are increased to the same extent in the granule cell layer after both acquisition of a single spatial learning event in the active place avoidance task and exploration of the testing environment, as compared to naïve (i.e. caged) mice. Repeated exposure the testing apparatus and environment did not reduce Arc expression. Furthermore, Arc expression did not correlate with performance in both adult and aged animals, suggesting that exploration of the testing environment, rather than the specific acquisition of the active place avoidance task, induces Arc expression in the dentate granule cell layer. These findings thus suggest that Arc is an experience-induced immediate-early gene.

  2. The transformation from anammox granules to deammonification granules in micro-aerobic system by facilitating indigenous ammonia oxidizing bacteria.

    Wang, Xiaolong; Gao, Dawen

    2018-02-01

    Granular deammonification process is a good way to retain aerobic and anaerobic ammonia oxidizing bacteria (AOB and anammox bacteria) and exhaust flocculent nitrite oxidizing bacteria (NOB). In this study, to facilitate indigenous AOB growth on anammox granules, by stepwise reducing influent nitrite, anammox granules were effectively transformed into deammonification granules in a micro-aerobic EGSB in 100 days. Total nitrogen removal efficiency of 90% and nitrogen removal rate of 2.3 g N/L/d were reached at stable deammonification stage. High influent FA and limited oxygen supply contributed suppression for Nitrospira-like NOB. In transition stages, Proteobacteria and Chloroflexi were always dominated. Anammox abundance decreased, while AOB abundance grew fast. Anammox bacteria and AOB were dominated by Brocadia fulgida and Nitrosomonas europaea, respectively. Denitrification activity and bacteria existed although without influent organic. The final AOB abundance was about 4.55-13.8 times more than anammox bacteria abundance, with almost equal potential activities. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. BACE1 Deficiency Causes Abnormal Neuronal Clustering in the Dentate Gyrus

    Hailong Hou

    2017-07-01

    Full Text Available BACE1 is validated as Alzheimer's β-secretase and a therapeutic target for Alzheimer's disease. In examining BACE1-null mice, we discovered that BACE1 deficiency develops abnormal clusters of immature neurons, forming doublecortin-positive neuroblasts, in the developing dentate gyrus, mainly in the subpial zone (SPZ. Such clusters were rarely observed in wild-type SPZ and not reported in other mouse models. To understand their origins and fates, we examined how neuroblasts in BACE1-null SPZ mature and migrate during early postnatal development. We show that such neuroblasts are destined to form Prox1-positive granule cells in the dentate granule cell layer, and mainly mature to form excitatory neurons, but not inhibitory neurons. Mechanistically, higher levels of reelin potentially contribute to abnormal neurogenesis and timely migration in BACE1-null SPZ. Altogether, we demonstrate that BACE1 is a critical regulator in forming the dentate granule cell layer through timely maturation and migration of SPZ neuroblasts.

  4. Electron cryotomography of vitrified cells with a Volta phase plate.

    Fukuda, Yoshiyuki; Laugks, Ulrike; Lučić, Vladan; Baumeister, Wolfgang; Danev, Radostin

    2015-05-01

    Electron cryotomography provides a means of studying the three dimensional structure of pleomorphic objects, such as organelles or cells, with a resolution of 1-3nm. A limitation in the study of radiation sensitive biological samples is the low signal-to-noise ratio of the tomograms which may obscure fine details. To overcome this limitation, the recently developed Volta phase plate (VPP) was applied in electron cryotomographic studies of a wide range of cellular structures, from magnetotactic bacteria to primary cultured neurons. The results show that the VPP improves contrast significantly and consequently the signal-to-noise ratio of the tomograms, moreover it avoids disturbing fringing artifacts typical for Zernike phase plates. The contrast improvement provided by the VPP was also confirmed in projection images of relatively thick (∼400nm) samples. In order to investigate the respective contributions of the VPP and the energy filter, images acquired with different combinations of the two were compared. Zero-loss energy filtering reduced the background noise in thicker areas of the sample and improved the contrast of features such as poly-β-hydroxybutyrate granules in magnetotactic bacteria, whereas the VPP provided an overall contrast improvement for all sample areas. After 3D reconstruction, tomograms acquired with the combination of a VPP and an energy filter showed structural features in neuronal processes with outstanding clarity. We also show that the VPP can be combined with focused ion beam milling to examine structures embedded deeply inside cells. Thus, we expect that VPP will become a standard element of the electron cryotomography workflow. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Downstream processing from melt granulation towards tablets: In-depth analysis of a continuous twin-screw melt granulation process using polymeric binders.

    Grymonpré, W; Verstraete, G; Vanhoorne, V; Remon, J P; De Beer, T; Vervaet, C

    2018-03-01

    The concept of twin-screw melt granulation (TSMG) has steadily (re)-gained interest in pharmaceutical formulation development as an intermediate step during tablet manufacturing. However, to be considered as a viable processing option for solid oral dosage forms there is a need to understand all critical sources of variability which could affect this granulation technique. The purpose of this study was to provide an in-depth analysis of the continuous TSMG process in order to expose the critical process parameters (CPP) and elucidate the impact of process and formulation parameters on the critical quality attributes (CQA) of granules and tablets during continuous TSMG. A first part of the study dealt with the screening of various amorphous polymers as binder for producing high-dosed melt granules of two model drug (i.e. acetaminophen and hydrochlorothiazide). The second part of this study described a quality-by-design (QbD) approach for melt granulation of hydrochlorothiazide in order to thoroughly evaluate TSMG, milling and tableting stage of the continuous TSMG line. Using amorphous polymeric binders resulted in melt granules with high milling efficiency due to their brittle behaviour without producing excessive amounts of fines, providing high granule yields with low friability. Therefore, it makes them extremely suitable for further downstream processing. One of the most important CPP during TSMG with polymeric binders was the granulation-torque, which - in case of polymers with high T g - increased during longer granulation runs to critical levels endangering the continuous process flow. However, by optimizing both screw speed and throughput or changing to polymeric binders with lower T g it was possible to significantly reduce this risk. This research paper highlighted that TSMG must be considered as a viable option during formulation development of solid oral dosage forms based on the robustness of the CQA of both melt granules and tablets. Copyright © 2017

  6. Cultured subventricular zone progenitor cells transduced with neurogenin-2 become mature glutamatergic neurons and integrate into the dentate gyrus.

    Xia Chen

    Full Text Available We have previously shown that transplantation of immature DCX+/NeuN+/Prox1+ neurons (found in the neonatal DG, but not undifferentiated neuronal progenitor cells (NPCs from ventral subventricular zone (SVZ, results in neuronal maturation in vivo within the dentate niche. Here we investigated whether we could enhance the integration of SVZ NPCs by forced expression of the proneural gene Neurogenin 2 (NEUROG2. NPCs cultured from neonatal GFP-transgenic rat SVZ for 7 days in a non-differentiating medium were transduced with a retrovirus encoding NEUROG2 and DsRed or the DsRed reporter gene alone (control. By 3 days post-transduction, the NEUROG2-transduced cells maintained in culture contained mostly immature neurons (91% DCX+; 76% NeuN+, whereas the control virus-transduced cells remained largely undifferentiated (30% DCX+; <1% NeuN+. At 6 weeks following transplantation into the DG of adult male rats, there were no neurons among the transplanted cells treated with the control virus but the majority of the NEUROG2-transduced DsRed+ SVZ cells became mature neurons (92% NeuN+; DCX-negative. Although the NEUROG2-transduced SVZ cells did not express the dentate granule neuron marker Prox1, most of the NEUROG2-transduced SVZ cells (78% expressed the glutamatergic marker Tbr1, suggesting the acquisition of a glutamatergic phenotype. Moreover, some neurons extended dendrites into the molecular layer, grew axons containing Ankyrin G+ axonal initial segments, and projected into the CA3 region, thus resembling mature DG granule neurons. A proportion of NEUROG2 transduced cells also expressed c-Fos and P-CREB, two markers of neuronal activation. We conclude that NEUROG2-transduction is sufficient to promote neuronal maturation and integration of transplanted NPCs from SVZ into the DG.

  7. Iron and cell death in Parkinson's disease: a nuclear microscopic study into iron-rich granules in the parkinsonian substantia nigra of primate models

    Thong, P.S.P.; Watt, F. E-mail: phywattf@nus.edu.sg; Ponraj, D.; Leong, S.K.; He, Y.; Lee, T.K.Y

    1999-09-02

    . This shows that localised iron increase may be an early event contributing to cell death. (4) The iron content in granules found in both the MPTP-injected and contra-lateral SNs is correlated with the degree of bulk SN cell loss (assessed by TH-immunohistochemistry) in individual models. This indicates a correlation between localised iron increase and cell loss, at least at the whole SN level. Our results are consistent with the observation that in Parkinson's disease (PD), neuronal cell death seems to be related to their neuromelanin content and support the proposal that iron-melanin interaction may play a role in oxidative neuronal cell death. Indeed, iron-saturated neuromelanin granules may act as centres of free radical production, contributing to localised cell death.

  8. Neuronal degeneration in autonomic nervous system of Dystonia musculorum mice

    Liu Kang-Jen

    2011-01-01

    Full Text Available Abstract Background Dystonia musculorum (dt is an autosomal recessive hereditary neuropathy with a characteristic uncoordinated movement and is caused by a defect in the bullous pemphigoid antigen 1 (BPAG1 gene. The neural isoform of BPAG1 is expressed in various neurons, including those in the central and peripheral nerve systems of mice. However, most previous studies on neuronal degeneration in BPAG1-deficient mice focused on peripheral sensory neurons and only limited investigation of the autonomic system has been conducted. Methods In this study, patterns of nerve innervation in cutaneous and iridial tissues were examined using general neuronal marker protein gene product 9.5 via immunohistochemistry. To perform quantitative analysis of the autonomic neuronal number, neurons within the lumbar sympathetic and parasympathetic ciliary ganglia were calculated. In addition, autonomic neurons were cultured from embryonic dt/dt mutants to elucidate degenerative patterns in vitro. Distribution patterns of neuronal intermediate filaments in cultured autonomic neurons were thoroughly studied under immunocytochemistry and conventional electron microscopy. Results Our immunohistochemistry results indicate that peripheral sensory nerves and autonomic innervation of sweat glands and irises dominated degeneration in dt/dt mice. Quantitative results confirmed that the number of neurons was significantly decreased in the lumbar sympathetic ganglia as well as in the parasympathetic ciliary ganglia of dt/dt mice compared with those of wild-type mice. We also observed that the neuronal intermediate filaments were aggregated abnormally in cultured autonomic neurons from dt/dt embryos. Conclusions These results suggest that a deficiency in the cytoskeletal linker BPAG1 is responsible for dominant sensory nerve degeneration and severe autonomic degeneration in dt/dt mice. Additionally, abnormally aggregated neuronal intermediate filaments may participate in

  9. Influence of raw material properties upon critical quality attributes of continuously produced granules and tablets

    Fonteyne, Margot; Wickström, Henrika; Peeters, Elisabeth

    2014-01-01

    over a range of raw material attributes, manufacturing process options and process parameters. This fits further into the Process Analytical Technology (PAT) and Quality by Design (QbD) framework. The present study evaluates the effect of variation in critical raw material properties on the critical......-Lactose-PVP (30-67.5-2.5%) was used as model formulation. Seven different grades of theophylline were granulated. Afterward, the obtained granules were tableted. Both the characteristics of granules and tablets were determined. The results show that differences in raw material properties both affect...... quality attributes of granules and tablets, produced by a continuous from-powder-to-tablet wet granulation line. The granulation process parameters were kept constant to examine the differences in the end product quality caused by the variability of the raw materials properties only. Theophylline...

  10. Evolution of vacuolar proton pyrophosphatase domains and volutin granules: clues into the early evolutionary origin of the acidocalcisome

    Valerio Alejandro

    2011-10-01

    Full Text Available Abstract Background Volutin granules appear to be universally distributed and are morphologically and chemically identical to acidocalcisomes, which are electron-dense granular organelles rich in calcium and phosphate, whose functions include storage of phosphorus and various metal ions, metabolism of polyphosphate, maintenance of intracellular pH, osmoregulation and calcium homeostasis. Prokaryotes are thought to differ from eukaryotes in that they lack membrane-bounded organelles. However, it has been demonstrated that as in acidocalcisomes, the calcium and polyphosphate-rich intracellular "volutin granules (polyphosphate bodies" in two bacterial species, Agrobacterium tumefaciens, and Rhodospirillum rubrum, are membrane bound and that the vacuolar proton-translocating pyrophosphatases (V-H+PPases are present in their surrounding membranes. Volutin granules and acidocalcisomes have been found in organisms as diverse as bacteria and humans. Results Here, we show volutin granules also occur in Archaea and are, therefore, present in the three superkingdoms of life (Archaea, Bacteria and Eukarya. Molecular analyses of V-H+PPase pumps, which acidify the acidocalcisome lumen and are diagnostic proteins of the organelle, also reveal the presence of this enzyme in all three superkingdoms suggesting it is ancient and universal. Since V-H+PPase sequences contained limited phylogenetic signal to fully resolve the ancestral nodes of the tree, we investigated the divergence of protein domains in the V-H+PPase molecules. Using Protein family (Pfam database, we found a domain in the protein, PF03030. The domain is shared by 31 species in Eukarya, 231 in Bacteria, and 17 in Archaea. The universal distribution of the V-H+PPase PF03030 domain, which is associated with the V-H+PPase function, suggests the domain and the enzyme were already present in the Last Universal Common Ancestor (LUCA. Conclusion The importance of the V-H+PPase function and the

  11. In vivo Anomalous Diffusion and Weak Ergodicity Breaking of Lipid Granules

    Jeon, J.-H.; Tejedor, V.; Burov, S.

    2011-01-01

    Combining extensive single particle tracking microscopy data of endogenous lipid granules in living fission yeast cells with analytical results we show evidence for anomalous diffusion and weak ergodicity breaking. Namely we demonstrate that at short times the granules perform subdiffusion...... according to the laws of continuous time random walk theory. The associated violation of ergodicity leads to a characteristic turnover between two scaling regimes of the time averaged mean squared displacement. At longer times the granule motion is consistent with fractional Brownian motion....

  12. Proteome profiling of human neutrophil granule subsets, secretory vesicles, and cell membrane

    Rørvig, Sara; Østergaard, Ole; Heegaard, Niels Henrik Helweg

    2013-01-01

    granules, SVs, and plasma membrane has been performed before. Here, we performed subcellular fractionation on freshly isolated human neutrophils by nitrogen cavitation and density centrifugation on a four-layer Percoll gradient. Granule subsets were pooled and subjected to SDS-PAGE, and gel pieces were in...... subcellular proteome profiles presented here may be used as a database in combination with the mRNA array database to predict and test the presence and localization of proteins in neutrophil granules and membranes....

  13. High level waste containing granules coated and embedded in metal as an alternative to HLW glasses

    Neumann, W.

    1980-01-01

    Simulated high level waste containing granules were overcoated with pyrocarbon or nickel respectively. The coatings were performed by the use of chemical vapour deposition in a fluidized bed. The coated granules were embedded in an aluminium-silicon-alloy to improve the dissipation of radiation induced heat. The metal-granules-composites obtained were of improved product stability related to the high level waste containing glasses. (orig.) [de

  14. Role of the Caenorhabditis elegans multidrug resistance gene, mrp-4, in gut granule differentiation.

    Currie, Erin; King, Brian; Lawrenson, Andrea L; Schroeder, Lena K; Kershner, Aaron M; Hermann, Greg J

    2007-11-01

    Caenorhabditis elegans gut granules are lysosome-related organelles with birefringent contents. mrp-4, which encodes an ATP-binding cassette (ABC) transporter homologous to mammalian multidrug resistance proteins, functions in the formation of gut granule birefringence. mrp-4(-) embryos show a delayed appearance of birefringent material in the gut granule but otherwise appear to form gut granules properly. mrp-4(+) activity is required for the extracellular mislocalization of birefringent material, body-length retraction, and NaCl sensitivity, phenotypes associated with defective gut granule biogenesis exhibited by embryos lacking the activity of GLO-1/Rab38, a putative GLO-1 guanine nucleotide exchange factor GLO-4, and the AP-3 complex. Multidrug resistance protein (MRP)-4 localizes to the gut granule membrane, consistent with it playing a direct role in the transport of molecules that compose and/or facilitate the formation of birefringent crystals within the gut granule. However, MRP-4 is also present in oocytes and early embryos, and our genetic analyses indicate that its site of action in the formation of birefringent material may not be limited to just the gut granule in embryos. In a search for genes that function similarly to mrp-4(+), we identified WHT-2, another ABC transporter that acts in parallel to MRP-4 for the formation of birefringent material in the gut granule.

  15. Common spectrum of polypeptides occurs in secretion granule membranes of different exocrine glands

    Cameron, R.S.; Cameron, P.L.; Castle, J.D.

    1986-01-01

    A highly purified membrane preparation from rat parotid secretion granules has been used as a comparative probe to examine the extent of compositional overlap in granule membranes of three other exocrine secretory tissues - pancreatic, lacrimal, and submandibular - from several standpoints. First, indirect immunofluorescent studies using a polyclonal polyspecific anti-parotid granule membrane antiserum has indicated a selective staining of granule membrane profiles in all acinar cells of all tissues. Second, highly purified granule membrane subfractions have been isolated from each exocrine tissue; comparative two-dimensional (isoelectric focusing; SDS) PAGE of radioiodinated granule membranes has identified 10-15 polypeptides of identical pI and apparent molecular mass. These species are likely to be integral membrane components since they are not extracted by either saponin-sodium sulfate or sodium carbonate (pH 11.5) treatments, and they do not have counterparts in the granule content. Finally, the identity among selected parotid and pancreatic radioiodinated granule membrane polypeptides has been documented using two-dimensional peptide mapping of chymotryptic and tryptic digests. These findings clearly indicate that exocrine secretory granules, irrespective of the nature of stored secretion, comprise a type of vesicular carrier with a common (and probably refined) membrane composition. Conceivably, the polypeptides identified carry out general functions related to exocrine secretion

  16. The Effect of Wetting on The Course of The Drum Granulation

    Błaszczyk Michał

    2017-06-01

    Full Text Available This paper presents the results of experimental drum granulation of silica flour with the use of wetting liquids with different values of surface tension. Additionally, different liquid jet breakup and different residual moisture of the bed were applied in the tests. The process was conducted periodically in two stages: wetting and proper granulation, during which no liquid was supplied to the bed. The condition of the granulated material after the period of wetting (particle size distribution and moisture of separate fractions and a change in the particle size distribution during the further conduct of the process (granulation kinetics were determined.

  17. Who Regulates Whom? An Overview of RNA Granules and Viral Infections

    Natalia Poblete-Durán

    2016-06-01

    Full Text Available After viral infection, host cells respond by mounting an anti-viral stress response in order to create a hostile atmosphere for viral replication, leading to the shut-off of mRNA translation (protein synthesis and the assembly of RNA granules. Two of these RNA granules have been well characterized in yeast and mammalian cells, stress granules (SGs, which are translationally silent sites of RNA triage and processing bodies (PBs, which are involved in mRNA degradation. This review discusses the role of these RNA granules in the evasion of anti-viral stress responses through virus-induced remodeling of cellular ribonucleoproteins (RNPs.

  18. Three novel proteins co-localise with polyhydroxybutyrate (PHB) granules in Rhodospirillum rubrum S1.

    Narancic, Tanja; Scollica, Elisa; Cagney, Gerard; O'Connor, Kevin E

    2018-04-01

    Polyhydroxybutyrate (PHB), a biodegradable polymer accumulated by bacteria is deposited intracellularly in the form of inclusion bodies often called granules. The granules are supramolecular complexes harbouring a varied number of proteins on their surface, which have specific but incompletely characterised functions. By comparison with other organisms that produce biodegradable polymers, only two phasins have been described to date for Rhodosprillum rubrum, raising the possibility that more await discovery. Using a comparative proteomics strategy to compare the granules of wild-type R. rubrum with a PHB-negative mutant housing artificial PHB granules, we identified four potential PHB granules' associated proteins. These were: Q2RSI4, an uncharacterised protein; Q2RWU9, annotated as an extracellular solute-binding protein; Q2RQL4, annotated as basic membrane lipoprotein; and Q2RQ51, annotated as glucose-6-phosphate isomerase. In silico analysis revealed that Q2RSI4 harbours a Phasin_2 family domain and shares low identity with a single-strand DNA-binding protein from Sphaerochaeta coccoides. Fluorescence microscopy found that three proteins Q2RSI4, Q2EWU9 and Q2RQL4 co-localised with PHB granules. This work adds three potential new granule associated proteins to the repertoire of factors involved in bacterial storage granule formation, and confirms that proteomics screens are an effective strategy for discovery of novel granule associated proteins.

  19. Layered growth with bottom-spray granulation for spray deposition of drug.

    Er, Dawn Z L; Liew, Celine V; Heng, Paul W S

    2009-07-30

    The gap in scientific knowledge on bottom-spray fluidized bed granulation has emphasized the need for more studies in this area. This paper comparatively studied the applicability of a modified bottom-spray process and the conventional top-spray process for the spray deposition of a micronized drug during granulation. The differences in circulation pattern, mode of growth and resultant granule properties between the two processes were highlighted. The more ordered and consistent circulation pattern of particles in a bottom-spray fluidized bed was observed to give rise to layered granule growth. This resulted in better drug content uniformity among the granule batches and within a granule batch. The processes' sensitivities to wetting and feed material characteristics were also compared and found to differ markedly. Less robustness to differing process conditions was observed for the top-spray process. The resultant bottom-spray granules formed were observed to be less porous, more spherical and had good flow properties. The bottom-spray technique can thus be potentially applied for the spray deposition of drug during granulation and was observed to be a good alternative to the conventional technique for preparing granules.

  20. Comparison of Ca2+ and Mg2+ enhancing aerobic granulation in SBR

    Liu Lin; Gao Dawen; Zhang Min; Fu Yuan

    2010-01-01

    Two sequencing batch reactors (SBRs) were operated to investigate the effect of Ca 2+ and Mg 2+ augmentation on aerobic granulation. Reactor R1 was augmented with Ca 2+ at 40 mg/L, while Mg 2+ was added to the reactor R2 with 40 mg/L. Results showed that the reactor R1 had a faster granulation process compared with R2, and the mature granules in R1 showed better physical characteristics. However, the mature granules in R2 had the higher production yield of polysaccharides and proteins, and aerobic granules in R2 experienced a faster substrate biodegradation. Microbial and genetic characteristics in mature granules were analyzed using polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis (DGGE) techniques. The results revealed that Mg 2+ addition led to higher microbial diversity in mature granules. In addition, an uncultured bacterium (AB447697) was major specie in R1, and β-proteobacterium was dominant in R2. It can be concluded that Ca 2+ had an important effect on physical properties of aerobic granules, while Mg 2+ played a key role on biological properties during the sludge granulation.

  1. Titanium Granules for Augmentation of the Maxillary Sinus

    Lyngstadaas, Ståle Petter; Verket, Anders; Pinholt, Else Marie

    2015-01-01

    BACKGROUND: Biomaterials are commonly used to augment the maxillary sinus floor prior to or in conjunction with dental implant installation. Recently, porous titanium granules (PTGs) have been used in oral implant surgery to stabilize implants and function as an osteoconductive matrix. PURPOSE...... in the study. RESULTS: One immobile implant was removed. The mean marginal bone loss was 0.5 mm and 0.8 mm, on the mesial and distal side, respectively. Histologically, all biopsies demonstrated bone ingrowth. CONCLUSIONS: The results suggest that PTG can be safely and effectively used as augmentation material...

  2. Identification of the Polyhydroxybutyrate Granules in Mammalian Cultured Cells

    Elustondo, Pia; Zakharian, Eleonora; Pavlov, Evgeny

    2012-01-01

    Poly-3-hydroxybutyrate (PHB) is a biological polyester present in bacteria and eukaryotic cells. Long-chain (or storage) sPHB (up to 100,000 residues) is typically present in PHB-accumulating bacteria and localized in specialized granules known as carbonosomes. In these organisms, sPHB plays a major role as carbon and energy storage. On the other hand, short-chain (or complexed) cPHB (10–100 residues) is present in eukaryotic organisms, including mammals as well as in many bacteria. Previous ...

  3. The Significance of Arachnoid Granulation in Patients With Idiopathic Intracranial Hypertension.

    Watane, Gaurav Vishwasrao; Patel, Bhumi; Brown, Derek; Taheri, M Reza

    The aim of this article was to study the significance of arachnoid granulations (AGs) in patients with idiopathic intracranial hypertension (IIH). In an institutional review board-approved retrospective chart review study, 79 patients with clinical diagnosis of idiopathic increased intracranial pressure were compared with 63 patients with a diagnosis of multiple sclerosis. Inclusion criteria also included available magnetic resonance imaging (MRI) of the brain, older than 18 years, and female sex. Patients with elevated intracranial pressure due to other causes were excluded. The electronic medical records were mined for presence of the following: body mass index, age, headache, vision changes, tinnitus, and vertigo. The MRI of the brain was reviewed for the presence of the following features: empty sella, prominent cerebrospinal fluid space in the optic sheaths, tortuosity of the optic nerves and enlarged Meckel cave. In addition, the number, size, and location of AGs associated with major venous drainage sinuses were documented in all patients. Using statistical analysis, association between various imaging and clinical signs were evaluated. The association between AG and various imaging and clinical signs were evaluated. The percentage of patients with AG were significantly higher in patients with IIH. Patients with IIH tended to have 0 to 3 AG. The most common imaging findings observed in MRI of the brain of patients with IIH were empty sella and prominent cerebrospinal fluid space in the optic sheaths. The prevalence of these MRI findings in patients with IIH was inversely proportional to the number of AG. A similar inverse trend was also noted with the opening pressure of patients with IIH and number of AG. The study establishes that there is a relationship between presence of AG and IIH. Arachnoid granulation seems to act in a compensatory mechanism in patients with IIH.

  4. New gentle-wing high-shear granulator: impact of processing variables on granules and tablets characteristics of high-drug loading formulation using design of experiment approach.

    Fayed, Mohamed H; Abdel-Rahman, Sayed I; Alanazi, Fars K; Ahmed, Mahrous O; Tawfeek, Hesham M; Al-Shdefat, Ramadan I

    2017-10-01

    The aim of this work was to study the application of design of experiment (DoE) approach in defining design space for granulation and tableting processes using a novel gentle-wing high-shear granulator. According to quality-by-design (QbD) prospective, critical attributes of granules, and tablets should be ensured by manufacturing process design. A face-centered central composite design has been employed in order to investigate the effect of water amount (X 1 ), impeller speed (X 2 ), wet massing time (X 3 ), and water addition rate (X 4 ) as independent process variables on granules and tablets characteristics. Acetaminophen was used as a model drug and granulation experiments were carried out using dry addition of povidone k30. The dried granules have been analyzed for their size distribution, density, and flow pattern. Additionally, the produced tablets have been investigated for; weight uniformity, breaking force, friability and percent capping, disintegration time, and drug dissolution. Results of regression analysis showed that water amount, impeller speed and wet massing time have significant (p tablets characteristics. However, the water amount had the most pronounced effect as indicated by its higher parameter estimate. On the other hand, water addition rate showed a minimal impact on granules and tablets properties. In conclusion, water amount, impeller speed, and wet massing time could be considered as critical process variables. Thus, understanding the relationship between these variables and quality attributes of granules and corresponding tablets provides the basis for adjusting granulation variables in order to optimize product performance.

  5. Distribution Profile of Inositol 1,4,5-Trisphosphate Receptor/Ca2+ Channels in α and β Cells of Pancreas: Dominant Localization in Secretory Granules and Common Error in Identification of Secretory Granule Membranes.

    Hur, Yong Suk; Yoo, Seung Hyun

    2015-01-01

    The α and β cells of pancreatic islet release important hormones in response to intracellular Ca increases that result from Ca releases through the inositol 1,4,5-trisphoshate receptor (IP3R)/Ca channels. Yet no systematic studies on distribution of IP3R/Ca channels have been done, prompting us to investigate the distribution of all 3 IP3R isoforms. Immunogold electron microscopy was performed to determine the presence and the relative concentrations of all 3 IP3R isoforms in 2 major organelles secretory granules (SGs) and the endoplasmic reticulum of α and β cells of rat pancreas. All 3 IP3R isoforms were present in SG membranes of both cells, and the IP3R concentrations in SGs were ∼2-fold higher than those in the endoplasmic reticulum. Moreover, large halos shown in the electron microscope images of insulin-containing SGs of β cells were gap spaces that resulted from separation of granule membranes from the surrounding cytoplasm. These results strongly suggest the important roles of SGs in IP3-induced, Ca-dependent regulatory secretory pathway in pancreas. Moreover, the accurate location of SG membranes of β cells was further confirmed by the location of another integral membrane protein synaptotagmin V and of membrane phospholipid PI(4,5)P2.

  6. Propidium iodide (PI) stains Nissl bodies and may serve as a quick marker for total neuronal cell count.

    Niu, Junfei; Li, Chunman; Wu, Haihui; Feng, Xianling; Su, Qingning; Li, Shihe; Zhang, Lihong; Yew, David Tai Wai; Cho, Eric Yu Pang; Sha, Ou

    2015-03-01

    Propidium iodide (PI) reacts with both DNA and RNA and is a commonly used fluorescent reagent for nucleic acid staining. The aim of the study was to compare the cellular staining patterns of PI with that of Nissl staining in rat nervous tissues and to report a modified staining method that selectively labels Nissl bodies in neurons. Cryosections and paraffin sections of different tissues of normal Sprague-Dawley rats, including trigeminal ganglia, dorsal root ganglia, spinal cord, liver, and small intestine, were stained by either PI or the hematoxylin and eosin method. Some sections were treated with RNase or DNase before the above staining, and some were double stained with PI and a Nissl stain. The sections were observed by light, fluorescence or confocal microscopy. Results showed strong PI signals detected as patterns of granules in the neuronal cytoplasm of all nervous tissues, whereas the staining of neuronal nuclei was weaker. In contrast, nuclei of neuroglial cells were strongly stained by PI, while the cytoplasm was not obviously stained. Pretreatment of the neural tissue with RNase abolished the PI signals. Furthermore, the PI positive granules in neuronal cytoplasm co-localized with Nissl bodies stained by the fluorescent Nissl stain. When the tissue was pretreated with DNase, PI only stained the cytoplasmic granules of neurons, but not that of glial cells. Our results show that PI stains Nissl bodies and may serve as an economical and convenient neuron marker for neuronal cell counting when specific neural markers such as antibodies are not readily available. Copyright © 2015. Published by Elsevier GmbH.

  7. Kappe neurons, a novel population of olfactory sensory neurons

    Ahuja, Gaurav; Nia, Shahrzad Bozorg; Zapilko, Veronika; Shiriagin, Vladimir; Kowatschew, Daniel; Oka, Yuichiro; Korsching, Sigrun I.

    2014-01-01

    Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report here a novel, fourth olfactory sensory neuron population in zebrafish, which we named kappe neurons for their characteristic shape. Kappe neurons ar...

  8. Trim9 Deletion Alters the Morphogenesis of Developing and Adult-Born Hippocampal Neurons and Impairs Spatial Learning and Memory.

    Winkle, Cortney C; Olsen, Reid H J; Kim, Hyojin; Moy, Sheryl S; Song, Juan; Gupton, Stephanie L

    2016-05-04

    During hippocampal development, newly born neurons migrate to appropriate destinations, extend axons, and ramify dendritic arbors to establish functional circuitry. These developmental stages are recapitulated in the dentate gyrus of the adult hippocampus, where neurons are continuously generated and subsequently incorporate into existing, local circuitry. Here we demonstrate that the E3 ubiquitin ligase TRIM9 regulates these developmental stages in embryonic and adult-born mouse hippocampal neurons in vitro and in vivo Embryonic hippocampal and adult-born dentate granule neurons lacking Trim9 exhibit several morphological defects, including excessive dendritic arborization. Although gross anatomy of the hippocampus was not detectably altered by Trim9 deletion, a significant number of Trim9(-/-) adult-born dentate neurons localized inappropriately. These morphological and localization defects of hippocampal neurons in Trim9(-/-) mice were associated with extreme deficits in spatial learning and memory, suggesting that TRIM9-directed neuronal morphogenesis may be involved in hippocampal-dependent behaviors. Appropriate generation and incorporation of adult-born neurons in the dentate gyrus are critical for spatial learning and memory and other hippocampal functions. Here we identify the brain-enriched E3 ubiquitin ligase TRIM9 as a novel regulator of embryonic and adult hippocampal neuron shape acquisition and hippocampal-dependent behaviors. Genetic deletion of Trim9 elevated dendritic arborization of hippocampal neurons in vitro and in vivo Adult-born dentate granule cells lacking Trim9 similarly exhibited excessive dendritic arborization and mislocalization of cell bodies in vivo These cellular defects were associated with severe deficits in spatial learning and memory. Copyright © 2016 the authors 0270-6474/16/364940-19$15.00/0.

  9. Effect of Aggregated β-Amyloid (1-42 on Synaptic Plasticity of Hippocampal Dentate Gyrus Granule Cells in Vivo

    Shirin Babri

    2012-12-01

    Full Text Available Introduction: Alzheimer’s disease (AD is a common neurodegenerative disorder in elderly people with an impairment of cognitive decline and memory loss. β-amyloid (Aβ as a potent neurotoxic peptide has a pivotal role in the pathogenesis of AD. This disease begins with impairment in synaptic functions before developing into later neuro­degeneration and neuronal loss. The aim of this study was to evaluate the synaptic plasticity and electrophysiological function of granule cells in hippocampal dentate gyrus (DG after intracerebroventricular (i.c.v. administration of aggregated Aβ (1-42 peptide in vivo. Methods: Animals were divided to control and Aβ (1-42 groups. Long-term potentia­tion (LTP in perforant path-DG synapses was assessed in order to investigate the effect of aggregated Aβ (1-42 on synaptic plasticity. Field excitatory post-synaptic potential (fEPSP slope and population spike (PS amplitude were measured. Results: Administration of Aβ (1-42 significantly decreased fEPSP slope and PS amplitude in Aβ (1-42 group comparing with the control group and had no effect on baseline activity of neurons. Conclusion: The present study indicates that administration of aggregated form of Aβ (1-42 into the lateral ventricle effectively inhibits LTP in granular cells of the DG in hippocampus in vivo.

  10. A realistic bi-hemispheric model of the cerebellum uncovers the purpose of the abundant granule cells during motor control.

    Pinzon-Morales, Ruben-Dario; Hirata, Yutaka

    2015-01-01

    The cerebellar granule cells (GCs) have been proposed to perform lossless, adaptive spatio-temporal coding of incoming sensory/motor information required by downstream cerebellar circuits to support motor learning, motor coordination, and cognition. Here we use a physio-anatomically inspired bi-hemispheric cerebellar neuronal network (biCNN) to selectively enable/disable the output of GCs and evaluate the behavioral and neural consequences during three different control scenarios. The control scenarios are a simple direct current motor (1 degree of freedom: DOF), an unstable two-wheel balancing robot (2 DOFs), and a simulation model of a quadcopter (6 DOFs). Results showed that adequate control was maintained with a relatively small number of GCs (< 200) in all the control scenarios. However, the minimum number of GCs required to successfully govern each control plant increased with their complexity (i.e., DOFs). It was also shown that increasing the number of GCs resulted in higher robustness against changes in the initialization parameters of the biCNN model (i.e., synaptic connections and synaptic weights). Therefore, we suggest that the abundant GCs in the cerebellar cortex provide the computational power during the large repertoire of motor activities and motor plants the cerebellum is involved with, and bring robustness against changes in the cerebellar microcircuit (e.g., neuronal connections).

  11. A realistic bi-hemispheric model of the cerebellum uncovers the purpose of the abundant granule cells during motor control

    Ruben Dario Pinzon Morales

    2015-05-01

    Full Text Available The cerebellar granule cells (GCs have been proposed to perform lossless, adaptive spatio-temporal coding of incoming sensory/motor information required by downstream cerebellar circuits to textcolor{red}{support} motor learning, motor coordination, and cognition. Here we use a physio-anatomically inspired bi-hemispheric cerebellar neuronal network (biCNN to selectively enable/disable the output of GCs and evaluate the behavioral and neural consequences during three different control scenarios. The control scenarios are a simple direct current motor (1 degree of freedom: DOF, an unstable two-wheel balancing robot (2 DOFs, and a simulation model of a quadcopter (6 DOFs. Results showed that adequate control was maintained with a relatively small number of GCs ($<$ 200 in all the control scenarios. However, the minimum number of GCs required to successfully govern each control plant increased with their complexity (i.e., DOFs. It was also shown that increasing the number of GCs resulted in higher robustness against changes in the initialization parameters of the biCNN model (i.e., synaptic connections and synaptic weights. Therefore, we suggest that the abundant GCs in the cerebellar cortex provide the computational power during the large repertoire of motor activities and motor plants the cerebellum is involved with, and bring robustness against changes in the cerebellar microcircuit (e.g., neuronal connections.

  12. Volutin granules of Eimeria parasites are acidic compartments and have physiological and structural characteristics similar to acidocalcisomes

    Medeiros, Lia Carolina Soares; Gomes, Fabio; Maciel, Luis Renato Maia; Seabra, Sergio Henrique; Docampo, Roberto; Moreno, Silvia; Plattner, Helmut; Hentschel, Joachim; Kawazoe, Urara; Barrabin, Hector; de Souza, Wanderley; DaMatta, Renato Augusto; Miranda, Kildare

    2012-01-01

    The structural organization of parasites has been the subject of investigation by many groups and has lead to the identification of structures and metabolic pathways that may represent targets for anti-parasitic drugs. A specific group of organelles named acidocalcisomes has been identified in a number of organisms, including the apicomplexan parasites such as Toxoplasma and Plasmodium, where they have been shown to be involved in cation homeostasis, polyphosphate metabolism, and osmoregulation. Their structural counterparts in the apicomplexan parasite Eimeria have not been fully characterized. In this work, the ultrastructural and chemical properties of acidocalcisomes in Eimeria were characterized. Electron microscopy analysis of Eimeria parasites showed the dense organelles called volutin granules similar to acidocalcisomes. Immunolocalization of the vacuolar proton pyrophosphatase, considered as a marker for acidocalcisomes, showed labeling in vesicles of size and distribution similar to the dense organelles seen by electron microscopy. Spectrophotometric measurements of the kinetics of proton uptake showed a vacuolar proton pyrophosphatase activity. X-ray mapping revealed significant amounts of Na, Mg, P, K, Ca, and Zn in their matrix. The results suggest that volutin granules of Eimeria parasites are acidic, dense organelles and possess structural and chemical properties analogous to those of other acidocalcisomes, suggesting a similar functional role in these parasites. PMID:21699625

  13. Tribology of swollen starch granule suspensions from maize and potato.

    Zhang, Bin; Selway, Nichola; Shelat, Kinnari J; Dhital, Sushil; Stokes, Jason R; Gidley, Michael J

    2017-01-02

    The tribological properties of suspensions of cooked swollen starch granules are characterised for systems based on maize starch and potato starch. These systems are known as granule 'ghosts' due to the release (and removal) of polymer from their structure during cooking. Maize starch ghosts are less swollen than potato starch ghosts, resulting in a higher packing concentration and greater mechanical stability. In a soft-tribological contact, maize ghost suspensions reduce friction compared to the solvent (water), generate bell-shaped tribological profiles characteristic of particle entrainment and show a marked concentration dependence, whereas potato ghost suspensions exhibit lubrication behaviour similar to water. Microscopy analysis of the samples following tribological testing suggests that this is due to the rapid break-up of potato ghosts under the shear and rolling conditions within the tribological contact. A reduction in the small deformation moduli (associated with a weak gel structure) is also observed when the potato ghost suspensions are subjected to steady shear using parallel plate rheometry; both microscopy and particle size analysis show that this is accompanied by the partial shear-induced breakage of ghost particles. This interplay between particle microstructure and the resultant rheological and lubrication dynamics of starch ghost suspensions contributes to an enhanced mechanistic understanding of textural and other functional properties of cooked starches in food and other applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Modifying the properties of finely ground limestone by tumbling granulation

    Macho, Oliver; Eckert, Maroš; Tomášová, Barbora; Peciar, Peter; Ščasný, Martin; Fekete, Roman; Peciar, Marián

    2016-06-01

    Calcium carbonate in the form of finely ground limestone is a material that has found its application in a wide range of industries, in the chemical, rubber, agricultural, and paper industries, is used for desulfurization of boilers and other. In civil engineering, ground limestone is used for the production of building materials, plaster and mortar mixtures, as a filler in concrete mixtures, in road construction, and as an essential component of mastic asphalt. This paper deals with examining the modification of the properties of finely ground limestone by the tumbling agglomeration method. It has been shown that the components of concrete with a round grain have a positive effect on the pumping of concrete in comparison with an elongated grain or the rough surface of crushed stone. The experiments will be carried out on a granulation plate using a variety of granulation liquid. The agglomerates and their properties were compared with untreated finely ground limestone, with a focus on detecting changes in compressibility, density and particle size. The output of this paper is a description and graphical representation of the changes in the properties of ground limestone before and after the agglomeration process.

  15. PKCalpha regulates platelet granule secretion and thrombus formation in mice.

    Konopatskaya, Olga; Gilio, Karen; Harper, Matthew T; Zhao, Yan; Cosemans, Judith M E M; Karim, Zubair A; Whiteheart, Sidney W; Molkentin, Jeffery D; Verkade, Paul; Watson, Steve P; Heemskerk, Johan W M; Poole, Alastair W

    2009-02-01

    Platelets are central players in atherothrombosis development in coronary artery disease. The PKC family provides important intracellular mechanisms for regulating platelet activity, and platelets express several members of this family, including the classical isoforms PKCalpha and PKCbeta and novel isoforms PKCdelta and PKCtheta. Here, we used a genetic approach to definitively demonstrate the role played by PKCalpha in regulating thrombus formation and platelet function. Thrombus formation in vivo was attenuated in Prkca-/- mice, and PKCalpha was required for thrombus formation in vitro, although this PKC isoform did not regulate platelet adhesion to collagen. The ablation of in vitro thrombus formation in Prkca-/- platelets was rescued by the addition of ADP, consistent with the key mechanistic finding that dense-granule biogenesis and secretion depend upon PKCalpha expression. Furthermore, defective platelet aggregation in response to either collagen-related peptide or thrombin could be overcome by an increase in agonist concentration. Evidence of overt bleeding, including gastrointestinal and tail bleeding, was not seen in Prkca-/- mice. In summary, the effects of PKCalpha ablation on thrombus formation and granule secretion may implicate PKCalpha as a drug target for antithrombotic therapy.

  16. Enteric coating of granules containing the probiotic Lactobacillus acidophilus

    Pyar Hassan

    2014-06-01

    Full Text Available In the present study, a capsule formulation composed of enteric coated granules of Lactobacillus acidophilus ATCC 4962 was developed using Eudragit L30D-55 as enteric polymer. Optimization of the capsule formulation was achieved with a maximum viable cell count after 2 h of incubation in acid medium and disintegration time of 1 h in buffer pH 6.8. The amount of Eudragit L30D-55 in the capsules correlated with gastric juice resistance. The best protective qualities against artificial gastric juice were observed when capsules were prepared from granules composed of L. acidophilus, corn starch, lactose monohydrate, polyvinylpyrrolidone and coated with 12.5 % (m/V of Eudragit L30D-55. Capsule formulation of L. acidophilus in edible broth medium suspension serves as a cheap alternative to the expensive freeze-drying procedure for preparing L. acidophilus. In addition, the enteric coating using Eudragit L30D-55 could protect probiotics from the acidic gastric environment and enhance the bioactivity of probiotics along with replacement of pathogenic microbes in human intestine

  17. Biodiesel production from microbial granules in sequencing batch reactor.

    Liu, Lin; Hong, Yuling; Ye, Xin; Wei, Lili; Liao, Jie; Huang, Xu; Liu, Chaoxiang

    2018-02-01

    Effect of reaction variables of in situ transesterification on the biodiesel production, and the characteristic differences of biodiesel obtained from aerobic granular sludge (AG) and algae-bacteria granular consortia (AAG) were investigated. The results indicated that the effect of variables on the biodiesel yield decreased in the order of methanol quantity > catalyst concentration > reaction time, yet the parameters change will not significantly affect biodiesel properties. The maximum biodiesel yield of AAG was 66.21 ± 1.08 mg/g SS, what is significant higher than that of AG (35.44 ± 0.92 mg/g SS). Although methyl palmitate was the dominated composition of biodiesel obtained from both granules, poly-unsaturated fatty acid in the AAG showed a higher percentage (21.86%) than AG (1.2%) due to Scenedesmus addition. Further, microbial analysis confirmed that the composition of biodiesel obtained from microbial granules was also determined by bacterial community, and Xanthomonadaceae and Rhodobacteraceae were the dominant bacteria of AG and AAG, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Modifying the properties of finely ground limestone by tumbling granulation

    Macho Oliver

    2016-06-01

    Full Text Available Calcium carbonate in the form of finely ground limestone is a material that has found its application in a wide range of industries, in the chemical, rubber, agricultural, and paper industries, is used for desulfurization of boilers and other. In civil engineering, ground limestone is used for the production of building materials, plaster and mortar mixtures, as a filler in concrete mixtures, in road construction, and as an essential component of mastic asphalt. This paper deals with examining the modification of the properties of finely ground limestone by the tumbling agglomeration method. It has been shown that the components of concrete with a round grain have a positive effect on the pumping of concrete in comparison with an elongated grain or the rough surface of crushed stone. The experiments will be carried out on a granulation plate using a variety of granulation liquid. The agglomerates and their properties were compared with untreated finely ground limestone, with a focus on detecting changes in compressibility, density and particle size. The output of this paper is a description and graphical representation of the changes in the properties of ground limestone before and after the agglomeration process.

  19. BAD and KATP channels regulate neuron excitability and epileptiform activity.

    Martínez-François, Juan Ramón; Fernández-Agüera, María Carmen; Nathwani, Nidhi; Lahmann, Carolina; Burnham, Veronica L; Danial, Nika N; Yellen, Gary

    2018-01-25

    Brain metabolism can profoundly influence neuronal excitability. Mice with genetic deletion or alteration of Bad ( B CL-2 a gonist of cell d eath) exhibit altered brain-cell fuel metabolism, accompanied by resistance to acutely induced epileptic seizures; this seizure protection is mediated by ATP-sensitive potassium (K ATP ) channels. Here we investigated the effect of BAD manipulation on K ATP channel activity and excitability in acute brain slices. We found that BAD's influence on neuronal K ATP channels was cell-autonomous and directly affected dentate granule neuron (DGN) excitability. To investigate the role of neuronal K ATP channels in the anticonvulsant effects of BAD, we imaged calcium during picrotoxin-induced epileptiform activity in entorhinal-hippocampal slices. BAD knockout reduced epileptiform activity, and this effect was lost upon knockout or pharmacological inhibition of K ATP channels. Targeted BAD knockout in DGNs alone was sufficient for the antiseizure effect in slices, consistent with a 'dentate gate' function that is reinforced by increased K ATP channel activity. © 2018, Martínez-François et al.

  20. Soft chitosan microbeads scaffold for 3D functional neuronal networks.

    Tedesco, Maria Teresa; Di Lisa, Donatella; Massobrio, Paolo; Colistra, Nicolò; Pesce, Mattia; Catelani, Tiziano; Dellacasa, Elena; Raiteri, Roberto; Martinoia, Sergio; Pastorino, Laura

    2018-02-01

    The availability of 3D biomimetic in vitro neuronal networks of mammalian neurons represents a pivotal step for the development of brain-on-a-chip experimental models to study neuronal (dys)functions and particularly neuronal connectivity. The use of hydrogel-based scaffolds for 3D cell cultures has been extensively studied in the last years. However, limited work on biomimetic 3D neuronal cultures has been carried out to date. In this respect, here we investigated the use of a widely popular polysaccharide, chitosan (CHI), for the fabrication of a microbead based 3D scaffold to be coupled to primary neuronal cells. CHI microbeads were characterized by optical and atomic force microscopies. The cell/scaffold interaction was deeply characterized by transmission electron microscopy and by immunocytochemistry using confocal microscopy. Finally, a preliminary electrophysiological characterization by micro-electrode arrays was carried out. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. State of the art of aerobic granulation in continuous flow bioreactors.

    Kent, Timothy R; Bott, Charles B; Wang, Zhi-Wu

    In the wake of the success of aerobic granulation in sequential batch reactors (SBRs) for treating wastewater, attention is beginning to turn to continuous flow applications. This is a necessary step given the advantages of continuous flow treatment processes and the fact that the majority of full-scale wastewater treatment plants across the world are operated with aeration tanks and clarifiers in a continuous flow mode. As in SBRs, applying a selection pressure, based on differences in either settling velocity or the size of the biomass, is essential for successful granulation in continuous flow reactors (CFRs). CFRs employed for aerobic granulation come in multiple configurations, each with their own means of achieving such a selection pressure. Other factors, such as bioaugmentation and hydraulic shear force, also contribute to aerobic granulation to some extent. Besides the formation of aerobic granules, long-term stability of aerobic granules is also a critical issue to be addressed. Inorganic precipitation, special inocula, and various operational optimization strategies have been used to improve granule long-term structural integrity. Accumulated studies reviewed in this work demonstrate that aerobic granulation in CFRs is capable of removing a wide spectrum of contaminants and achieving properties generally comparable to those in SBRs. Despite the notable research progress made toward successful aerobic granulation in lab-scale CFRs, to the best of our knowledge, there are only three full-scale tests of the technique, two being seeded with anammox-supported aerobic granules and the other with conventional aerobic granules; two other process alternatives are currently in development. Application of settling- or size-based selection pressures and feast/famine conditions are especially difficult to implement to these and similar mainstream systems. Future research efforts needs to be focused on the optimization of the granule-to-floc ratio, enhancement of

  2. NEURON and Python.

    Hines, Michael L; Davison, Andrew P; Muller, Eilif

    2009-01-01

    The NEURON simulation program now allows Python to be used, alone or in combination with NEURON's traditional Hoc interpreter. Adding Python to NEURON has the immediate benefit of making available a very extensive suite of analysis tools written for engineering and science. It also catalyzes NEURON software development by offering users a modern programming tool that is recognized for its flexibility and power to create and maintain complex programs. At the same time, nothing is lost because all existing models written in Hoc, including graphical user interface tools, continue to work without change and are also available within the Python context. An example of the benefits of Python availability is the use of the xml module in implementing NEURON's Import3D and CellBuild tools to read MorphML and NeuroML model specifications.

  3. Preparation of porcelain tile granulates by more environmentally sustainable processes

    García-Ten, J.

    2012-04-01

    Full Text Available This study examines the feasibility of manufacturing glazed porcelain tiles with a more environmentally friendly manufacturing process, by reducing water and thermal energy consumption. The process studied in this paper is dry milling in a pendulum mill, with subsequent granulation (in order to obtain a press powder with similar flowability to that of spraydried powders. The different morphology of the new granulate with respect to the standard spray-dried granulate modifies the microstructure of the green compacts and thus, their behaviour and fired tile properties. In order to obtain porcelain tiles with the required properties (water absorption, mechanical strength,… changes have been made in the raw materials mixture and in the processing variables. Finally, porcelain tiles measuring 50x50 cm have been manufactured at industrial scale with the new granulate using a conventional firing cycle, obtaining quality levels identical to those provided by the spray-dried granulate. These results open the possibility of preparing porcelain tile body compositions through a manufacturing process alternative to the standard one, more environmentally friendly and with lower costs.

    En el presente trabajo se ha estudiado la viabilidad de fabricar gres porcelánico esmaltado utilizando un sistema de preparación de la composición del soporte más respetuoso con el medio ambiente, lo que implica una reducción importante de los consumos de agua y de energía térmica. El proceso que se estudia en el presente trabajo es el consistente en la molienda vía seca en molino pendular y en la posterior granulación (para obtener un polvo de prensas con fluidez similar a la de los polvos atomizados. La distinta morfología de los nuevos gránulos obtenidos respecto al polvo atomizado actual, modifica la microestuctura en crudo de las piezas y, con ello, el comportamiento y propiedades finales de las baldosas obtenidas. Por ello, ha sido necesario

  4. Spinal cord: motor neuron diseases.

    Rezania, Kourosh; Roos, Raymond P

    2013-02-01

    Spinal cord motor neuron diseases affect lower motor neurons in the ventral horn. This article focuses on the most common spinal cord motor neuron disease, amyotrophic lateral sclerosis, which also affects upper motor neurons. Also discussed are other motor neuron diseases that only affect the lower motor neurons. Despite the identification of several genes associated with familial amyotrophic lateral sclerosis, the pathogenesis of this complex disease remains elusive. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Neuronal-glial trafficking

    Bachelard, H.S.

    2001-01-01

    Full text: The name 'glia' originates from the Greek word for glue, because astro glia (or astrocytes) were thought only to provide an anatomical framework for the electrically-excitable neurones. However, awareness that astrocytes perform vital roles in protecting the neurones, which they surround, emerged from evidence that they act as neuroprotective K + -sinks, and that they remove potentially toxic extracellular glutamate from the vicinity of the neurones. The astrocytes convert the glutamate to non-toxic glutamine which is returned to the neurones and used to replenish transmitter glutamate. This 'glutamate-glutamine cycle' (established in the 1960s by Berl and his colleagues) also contributes to protecting the neurones against a build-up of toxic ammonia. Glial cells also supply the neurones with components for free-radical scavenging glutathione. Recent studies have revealed that glial cells play a more positive interactive role in furnishing the neurones with fuels. Studies using radioactive 14 C, 13 C-MRS and 15 N-GCMS have revealed that glia produce alanine, lactate and proline for consumption by neurones, with increased formation of neurotransmitter glutamate. On neuronal activation the release of NH 4 + and glutamate from the neurones stimulates glucose uptake and glycolysis in the glia to produce more alanine, which can be regarded as an 'alanine-glutamate cycle' Use of 14 C-labelled precursors provided early evidence that neurotransmitter GABA may be partly derived from glial glutamine, and this has been confirmed recently in vivo by MRS isotopomer analysis of the GABA and glutamine labelled from 13 C-acetate. Relative rates of intermediary metabolism in glia and neurones can be calculated using a combination of [1- 13 C] glucose and [1,2- 13 C] acetate. When glutamate is released by neurones there is a net neuronal loss of TCA intermediates which have to be replenished. Part of this is derived from carboxylation of pyruvate, (pyruvate carboxylase

  6. Granulation for Coking Wastewater Treatment in a Coupled Anaerobic-Aerobic Reactor

    Dong, Chunjuan; Lv, Bingnan

    2018-06-01

    A coupled anaerobic-aerobic granular bio-film reactor was employed with two operation stages: Stage I, granular sludge was formed from digestion sludge using brewery wastewater, and Stage II, granular sludge was acclimatized using coking wastewater. Two oxygenation methods (i.e. A and B) were employed to acclimatize the granules. For method A, dissolved O 2 was supplied through a continuous oxygenation way of 800-15000ml-min-1 . And for method B, dissolved O2 was supplied of 800-15000ml-min-1 18-12 times at 20-60min intervals, 1h each time. The experimental results showed that granules could quickly form in 10d in the EGSB reactor seeded with digestion sludge and little loose granules lack of nutrition, and it was the key factor for granules forming to add little loose granules. It took only about 6 months for granules acclimation using coking wastewater. Both oxygenation methods could run well when acclimatizing the granules. However, method A could have comparatively high and stable operation effect. The actual coking wastewater had distinct inhibition effect on the granules, but the supplement of some oxygen could promote the recovery of SMA, and NaHCO3 supplement could also weaken the inhibition effect of the CWW. Method A had more strongly activity recovery ability than method B.

  7. Microtubule-dependent association of AKAP350A and CCAR1 with RNA stress granules

    Kolobova, Elena; Efimov, Andrey; Kaverina, Irina; Rishi, Arun K.; Schrader, John W.; Ham, Amy-Joan; Larocca, M. Cecilia; Goldenring, James R.

    2009-01-01

    Recent investigations have highlighted the importance of subcellular localization of mRNAs to cell function. While AKAP350A, a multifunctional scaffolding protein, localizes to the Golgi apparatus and centrosomes, we have now identified a cytosolic pool of AKAP350A. Analysis of AKAP350A scaffolded complexes revealed two novel interacting proteins, CCAR1 and caprin-1. CCAR1, caprin-1 and AKAP350A along with G3BP, a stress granule marker, relocate to RNA stress granules after arsenite treatment. Stress also caused loss of AKAP350 from the Golgi and fragmentation of the Golgi apparatus. Disruption of microtubules with nocodazole altered stress granule formation and changed their morphology by preventing fusion of stress granules. In the presence of nocodazole, arsenite induced smaller granules with the vast majority of AKAP350A and CCAR1 separated from G3BP-containing granules. Similar to nocodazole treatment, reduction of AKAP350A or CCAR1 expression also altered the size and number of G3BP-containing stress granules induced by arsenite treatment. A limited set of 69 mRNA transcripts was immunoisolated with AKAP350A even in the absence of stress, suggesting the association of AKAP350A with mRNA transcripts. These results provide the first evidence for the microtubule dependent association of AKAP350A and CCAR1 with RNA stress granules

  8. Granulation in red giants: observations by the Kepler mission and three-dimensional convection simulations

    Mathur, S.; Hekker, S.; Trampedach, R.; Ballot, J.; Kallinger, T.; Buzasi, D.; Garcia, R.A.; Huber, D.; Jimenez, A.; Mosser, B.; Bedding, T.R.; Elsworth, Y.; Regulo, C.; Stello, D.; Chaplin, W.J.; de Ridder, J.; Hale, S.J.; Kinemuchi, K.; Kjeldsen, H.; Mullally, F.; Thompson, S.E.

    2011-01-01

    The granulation pattern that we observe on the surface of the Sun is due to hot plasma rising to the photosphere where it cools down and descends back into the interior at the edges of granules. This is the visible manifestation of convection taking place in the outer part of the solar convection

  9. Metatranscriptomics reveals the molecular mechanism of large granule formation in granular anammox reactor

    Bagchi, Samik

    2016-06-20

    Granules enriched with anammox bacteria are essential in enhancing the treatment of ammonia-rich wastewater, but little is known about how anammox bacteria grow and multiply inside granules. Here, we combined metatranscriptomics, quantitative PCR and 16S rRNA gene sequencing to study the changes in community composition, metabolic gene content and gene expression in a granular anammox reactor with the objective of understanding the molecular mechanism of anammox growth and multiplication that led to formation of large granules. Size distribution analysis revealed the spatial distribution of granules in which large granules having higher abundance of anammox bacteria (genus Brocadia) dominated the bottom biomass. Metatranscriptomics analysis detected all the essential transcripts for anammox metabolism. During the later stage of reactor operation, higher expression of ammonia and nitrite transport proteins and key metabolic enzymes mainly in the bottom large granules facilitated anammox bacteria activity. The high activity resulted in higher growth and multiplication of anammox bacteria and expanded the size of the granules. This conceptual model for large granule formation proposed here may assist in the future design of anammox processes for mainstream wastewater treatment.

  10. Effect of particle size of granules on some mechanical properties of ...

    Solid dosage forms are invariably multiparticulate systems of heterogenous particle size distribution. The purpose of this study was to investigate the effect of particle size distribution of paracetamol granules on some tablet mechanical properties of paracetamol tablets. Granules were formed by wet massing paracetamol ...

  11. N-methyl-D-aspartate promotes the survival of cerebellar granule cells in culture

    Balázs, R; Jørgensen, Ole Steen; Hack, N

    1988-01-01

    Our previous studies on the survival-promoting influence of elevated concentrations of extracellular K+ ([K+]e) on cultured cerebellar granule cells led to the proposal that depolarization in vitro mimics the effect of the earliest afferent inputs received by the granule cells in vivo. This, in t...

  12. Simultaneous recovery of calcium phosphate granules and methane in anaerobic treatment of black water

    Cunha Costa, da J.M.R.; Tervahauta, T.; Weijden, van der R.D.; Hernández Leal, L.; Zeeman, G.; Buisman, C.J.N.

    2017-01-01

    Calcium phosphate (CaP) granules were discovered in the anaerobic treatment of vacuum collected black water (BW), using upflow anaerobic sludge blanket (UASB) technology. This allows simultaneous recovery of CaP granules and methane in the UASB reactor. However, the role of BW composition on CaP

  13. OPTIMIZATION OF TABLET FORMULATIONS BASED ON STARCH LACTOSE GRANULATIONS FOR USE IN TROPICAL COUNTRIES

    BOS, CE; BOLHUIS, GK; LERK, CF

    1991-01-01

    Several granulations consisting of alpha-lactose monohydrate 200 mesh and native starch (corn, potato, rice or tapioca) were prepared. The influence of starch concentration, storage temperature and relative humidity on the physical properties of the tablets prepared from these granulations was

  14. A Single-Granule-Level Approach Reveals Ecological Heterogeneity in an Upflow Anaerobic Sludge Blanket Reactor.

    Kyohei Kuroda

    Full Text Available Upflow anaerobic sludge blanket (UASB reactor has served as an effective process to treat industrial wastewater such as purified terephthalic acid (PTA wastewater. For optimal UASB performance, balanced ecological interactions between syntrophs, methanogens, and fermenters are critical. However, much of the interactions remain unclear because UASB have been studied at a "macro"-level perspective of the reactor ecosystem. In reality, such reactors are composed of a suite of granules, each forming individual micro-ecosystems treating wastewater. Thus, typical approaches may be oversimplifying the complexity of the microbial ecology and granular development. To identify critical microbial interactions at both macro- and micro- level ecosystem ecology, we perform community and network analyses on 300 PTA-degrading granules from a lab-scale UASB reactor and two full-scale reactors. Based on MiSeq-based 16S rRNA gene sequencing of individual granules, different granule-types co-exist in both full-scale reactors regardless of granule size and reactor sampling depth, suggesting that distinct microbial interactions occur in different granules throughout the reactor. In addition, we identify novel networks of syntrophic metabolic interactions in different granules, perhaps caused by distinct thermodynamic conditions. Moreover, unseen methanogenic relationships (e.g. "Candidatus Aminicenantes" and Methanosaeta are observed in UASB reactors. In total, we discover unexpected microbial interactions in granular micro-ecosystems supporting UASB ecology and treatment through a unique single-granule level approach.

  15. A Single-Granule-Level Approach Reveals Ecological Heterogeneity in an Upflow Anaerobic Sludge Blanket Reactor

    Mei, Ran; Narihiro, Takashi; Bocher, Benjamin T. W.; Yamaguchi, Takashi; Liu, Wen-Tso

    2016-01-01

    Upflow anaerobic sludge blanket (UASB) reactor has served as an effective process to treat industrial wastewater such as purified terephthalic acid (PTA) wastewater. For optimal UASB performance, balanced ecological interactions between syntrophs, methanogens, and fermenters are critical. However, much of the interactions remain unclear because UASB have been studied at a “macro”-level perspective of the reactor ecosystem. In reality, such reactors are composed of a suite of granules, each forming individual micro-ecosystems treating wastewater. Thus, typical approaches may be oversimplifying the complexity of the microbial ecology and granular development. To identify critical microbial interactions at both macro- and micro- level ecosystem ecology, we perform community and network analyses on 300 PTA–degrading granules from a lab-scale UASB reactor and two full-scale reactors. Based on MiSeq-based 16S rRNA gene sequencing of individual granules, different granule-types co-exist in both full-scale reactors regardless of granule size and reactor sampling depth, suggesting that distinct microbial interactions occur in different granules throughout the reactor. In addition, we identify novel networks of syntrophic metabolic interactions in different granules, perhaps caused by distinct thermodynamic conditions. Moreover, unseen methanogenic relationships (e.g. “Candidatus Aminicenantes” and Methanosaeta) are observed in UASB reactors. In total, we discover unexpected microbial interactions in granular micro-ecosystems supporting UASB ecology and treatment through a unique single-granule level approach. PMID:27936088

  16. Hypoglycemic and anti-hyperglycemic activity of Triphalādi granules in mice

    Ankush Gunjal

    2016-01-01

    Conclusion: Triphalādi granules have significant hypoglycemic and anti-hyperglycemic activity in mice with minimal effect on BSL below normal range. The studies suggest the potential role of Triphalādi granules as an alternative adjuvant therapy in diabetic individuals for the control of the blood glucose level.

  17. Impact of full range of amylose contents on the architecture of starch granules*

    Goldstein, Avi; Annor, George; Putaux, Jean Luc

    2016-01-01

    The effects of amylose deposition on crystalline regions of barley starch granules were studied in granules containing zero to 99.1% amylose using "waxy" (WBS, 0% amylose), normal (NBS, 18% amylose) and amylose-only barley lines (AOS, 99.1% amylose). The effects were probed after hydrolysis of am...

  18. Performance of single carbon granules as perspective for larger scale capacitive bioanodes

    Borsje, Casper; Liu, Dandan; Sleutels, Tom H.J.A.; Buisman, Cees J.N.; Heijne, ter Annemiek

    2016-01-01

    The use of high surface area electrodes, like carbon-based felt or granules, in Bioelectrochemical Systems is crucial for high volumetric current production. In case activated carbon granules are used, charge can also be stored in the form of an electric double layer in the pores, which has been

  19. LUBRICANT SENSITIVITY IN RELATION TO BULK-DENSITY FOR GRANULATIONS BASED ON STARCH OR CELLULOSE

    BOS, CE; VROMANS, H; LERK, CF

    1991-01-01

    The study described in this paper was concerned with the susceptibility to lubrication with magnesium stearate of tablets compressed from granulations based on native starches or on modified celluloses. Different properties of the granulations, like particle size, flowability and surface area, were

  20. Calcium phosphate granulation in anaerobic treatment of black water: a new approach to phosphorus recovery

    Tervahauta, T.H.; Weijden, van der R.D.; Flemming, R.L.; Hernández, L.; Zeeman, G.; Buisman, C.J.N.

    2014-01-01

    Recovery of phosphorus from wastewater as calcium phosphate could diminish the need for mining of scarce phosphate rock resources. This study introduces a novel approach to phosphorus recovery by precipitation of calcium phosphate granules in anaerobic treatment of black water. The granules formed

  1. Effects of Traditional Chinese Medicine Wei-Wei-Kang-Granule on ...

    Wei-Wei-Kang-Granule(WWKG) is a traditional Chinese medicine (TCM) preparation for the treatment of chronic atrophic gastritis (CAG). We examined the pathologic change and the effects of Wei-Wei-Kang-Granule (WWKG) on the expression of EGFR (epiderminal growth factor receptors) and NF-kB (nuclear transcription ...

  2. Hyperactivity of newborn Pten knock-out neurons results from increased excitatory synaptic drive.

    Williams, Michael R; DeSpenza, Tyrone; Li, Meijie; Gulledge, Allan T; Luikart, Bryan W

    2015-01-21

    Developing neurons must regulate morphology, intrinsic excitability, and synaptogenesis to form neural circuits. When these processes go awry, disorders, including autism spectrum disorder (ASD) or epilepsy, may result. The phosphatase Pten is mutated in some patients having ASD and seizures, suggesting that its mutation disrupts neurological function in part through increasing neuronal activity. Supporting this idea, neuronal knock-out of Pten in mice can cause macrocephaly, behavioral changes similar to ASD, and seizures. However, the mechanisms through which excitability is enhanced following Pten depletion are unclear. Previous studies have separately shown that Pten-depleted neurons can drive seizures, receive elevated excitatory synaptic input, and have abnormal dendrites. We therefore tested the hypothesis that developing Pten-depleted neurons are hyperactive due to increased excitatory synaptogenesis using electrophysiology, calcium imaging, morphological analyses, and modeling. This was accomplished by coinjecting retroviruses to either "birthdate" or birthdate and knock-out Pten in granule neurons of the murine neonatal dentate gyrus. We found that Pten knock-out neurons, despite a rapid onset of hypertrophy, were more active in vivo. Pten knock-out neurons fired at more hyperpolarized membrane potentials, displayed greater peak spike rates, and were more sensitive to depolarizing synaptic input. The increased sensitivity of Pten knock-out neurons was due, in part, to a higher density of synapses located more proximal to the soma. We determined that increased synaptic drive was sufficient to drive hypertrophic Pten knock-out neurons beyond their altered action potential threshold. Thus, our work contributes a developmental mechanism for the increased activity of Pten-depleted neurons. Copyright © 2015 the authors 0270-6474/15/350943-17$15.00/0.

  3. Roll Compaction/Dry Granulation of Dibasic Calcium Phosphate Anhydrous-Does the Morphology of the Raw Material Influence the Tabletability of Dry Granules?

    Grote, Simon; Kleinebudde, Peter

    2018-04-01

    The influence of raw material particle morphology on the tabletabilty of dry granules was investigated. Therefore, dibasic calcium phosphate anhydrous was used as a model material. One milled grade, 2 agglomerated grades with different porosities, and a functionalized structure, that is, an agglomerate formed by very small primary particles, were included. Particle size, density, and specific surface area of raw materials were measured. The starting materials and 2 fractions of dry granules were compressed to tablets. The tabletability of granules was compared to that of the powders and the influence of specific compaction force, granule size, and lubrication on tablet tensile strength was evaluated. All materials showed a loss in tabletability induced by a previous compaction step but to a varying extent. Only in case of the functionalized calcium phosphate morphology, this effect depended on the specific compaction force. In contrast to the other materials, the tabletability of functionalized calcium phosphate was influenced by the granule size. This effect was not related to an overlubrication as internal and external lubrication resulted in similar tensile strengths. A clear influence of the particle morphology on tablet strength was demonstrated by the study. The functionalized structure showed aspects of a more plastic deformation behavior. The functionalized dibasic calcium phosphate and the more porous agglomerate performed as potential filler/binder in the field of roll compaction/dry granulation. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  4. Electron microscopy of primary cell cultures in solution and correlative optical microscopy using ASEM

    Hirano, Kazumi; Kinoshita, Takaaki; Uemura, Takeshi; Motohashi, Hozumi; Watanabe, Yohei; Ebihara, Tatsuhiko; Nishiyama, Hidetoshi; Sato, Mari; Suga, Mitsuo; Maruyama, Yuusuke; Tsuji, Noriko M.; Yamamoto, Masayuki; Nishihara, Shoko; Sato, Chikara

    2014-01-01

    Correlative light-electron microscopy of cells in a natural environment of aqueous liquid facilitates high-throughput observation of protein complex formation. ASEM allows the inverted SEM to observe the wet sample from below, while an optical microscope observes it from above quasi-simultaneously. The disposable ASEM dish with a silicon nitride (SiN) film window can be coated variously to realize the primary-culture of substrate-sensitive cells in a few milliliters of culture medium in a stable incubator environment. Neuron differentiation, neural networking, proplatelet-formation and phagocytosis were captured by optical or fluorescence microscopy, and imaged at high resolution by gold-labeled immuno-ASEM with/without metal staining. Fas expression on the cell surface was visualized, correlated to the spatial distribution of F-actin. Axonal partitioning was studied using primary-culture neurons, and presynaptic induction by GluRδ2-N-terminus-linked fluorescent magnetic beads was correlated to the presynaptic-marker Bassoon. Further, megakaryocytes secreting proplatelets were captured, and P-selectins with adherence activity were localized to some of the granules present by immuno-ASEM. The phagocytosis of lactic acid bacteria by dendritic cells was also imaged. Based on these studies, ASEM correlative microscopy promises to allow the study of various mesoscopic-scale dynamics in the near future. - Highlights: • In situ correlative light electron microscopy of samples in open solution by ASEM. • Primary cultures for in-solution CLEM by developing SiN-film coating methods • First visualization of fluorescent magnetic beads in aqueous solution by CLEM. • Presynaptic induction of neurons by GluRδ2-N-terminus-coated beads studied by CLEM. • Axonal partitioning, bacterial phagocytosis, platelet formation imaged by CLEM

  5. Electron microscopy of primary cell cultures in solution and correlative optical microscopy using ASEM

    Hirano, Kazumi; Kinoshita, Takaaki [Laboratory of Cell Biology, Department of Bioinformatics, Faculty of Engineering, Soka University, 1-236 Tangi-machi, Hachioji, Tokyo 192-8577 (Japan); Uemura, Takeshi [Department of Molecular Neurobiology and Pharmacology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Department of Molecular and Cellular Physiology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan); Motohashi, Hozumi [Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-cho, Aoba-ku, Sendai 980-8575 (Japan); Watanabe, Yohei; Ebihara, Tatsuhiko [Biomedical Research Institute, National Institute of Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba 305-8566 (Japan); Nishiyama, Hidetoshi [JEOL Ltd., 1-2 Musashino 3-chome, Akishima, Tokyo 196-8558 (Japan); Sato, Mari [Biomedical Research Institute, National Institute of Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba 305-8566 (Japan); Suga, Mitsuo [JEOL Ltd., 1-2 Musashino 3-chome, Akishima, Tokyo 196-8558 (Japan); Maruyama, Yuusuke; Tsuji, Noriko M. [Biomedical Research Institute, National Institute of Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba 305-8566 (Japan); Yamamoto, Masayuki [Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai 980-8575 (Japan); Nishihara, Shoko, E-mail: shoko@soka.ac.jp [Laboratory of Cell Biology, Department of Bioinformatics, Faculty of Engineering, Soka University, 1-236 Tangi-machi, Hachioji, Tokyo 192-8577 (Japan); Sato, Chikara, E-mail: ti-sato@aist.go.jp [Biomedical Research Institute, National Institute of Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba 305-8566 (Japan)

    2014-08-01

    Correlative light-electron microscopy of cells in a natural environment of aqueous liquid facilitates high-throughput observation of protein complex formation. ASEM allows the inverted SEM to observe the wet sample from below, while an optical microscope observes it from above quasi-simultaneously. The disposable ASEM dish with a silicon nitride (SiN) film window can be coated variously to realize the primary-culture of substrate-sensitive cells in a few milliliters of culture medium in a stable incubator environment. Neuron differentiation, neural networking, proplatelet-formation and phagocytosis were captured by optical or fluorescence microscopy, and imaged at high resolution by gold-labeled immuno-ASEM with/without metal staining. Fas expression on the cell surface was visualized, correlated to the spatial distribution of F-actin. Axonal partitioning was studied using primary-culture neurons, and presynaptic induction by GluRδ2-N-terminus-linked fluorescent magnetic beads was correlated to the presynaptic-marker Bassoon. Further, megakaryocytes secreting proplatelets were captured, and P-selectins with adherence activity were localized to some of the granules present by immuno-ASEM. The phagocytosis of lactic acid bacteria by dendritic cells was also imaged. Based on these studies, ASEM correlative microscopy promises to allow the study of various mesoscopic-scale dynamics in the near future. - Highlights: • In situ correlative light electron microscopy of samples in open solution by ASEM. • Primary cultures for in-solution CLEM by developing SiN-film coating methods • First visualization of fluorescent magnetic beads in aqueous solution by CLEM. • Presynaptic induction of neurons by GluRδ2-N-terminus-coated beads studied by CLEM. • Axonal partitioning, bacterial phagocytosis, platelet formation imaged by CLEM.

  6. Toxoplasma gondii: Biochemical and biophysical characterization of recombinant soluble dense granule proteins GRA2 and GRA6

    Bittame, Amina; Effantin, Grégory; Pètre, Graciane; Ruffiot, Pauline; Travier, Laetitia; Schoehn, Guy; Weissenhorn, Winfried; Cesbron-Delauw, Marie-France; Gagnon, Jean; Mercier, Corinne

    2015-01-01

    The most prominent structural feature of the parasitophorous vacuole (PV) in which the intracellular parasite Toxoplasma gondii proliferates is a membranous nanotubular network (MNN), which interconnects the parasites and the PV membrane. The MNN function remains unclear. The GRA2 and GRA6 proteins secreted from the parasite dense granules into the PV have been implicated in the MNN biogenesis. Amphipathic alpha-helices (AAHs) predicted in GRA2 and an alpha-helical hydrophobic domain predicted in GRA6 have been proposed to be responsible for their membrane association, thereby potentially molding the MMN in its structure. Here we report an analysis of the recombinant proteins (expressed in detergent-free conditions) by circular dichroism, which showed that full length GRA2 displays an alpha-helical secondary structure while recombinant GRA6 and GRA2 truncated of its AAHs are mainly random coiled. Dynamic light scattering and transmission electron microscopy showed that recombinant GRA6 and truncated GRA2 constitute a homogenous population of small particles (6–8 nm in diameter) while recombinant GRA2 corresponds to 2 populations of particles (∼8–15 nm and up to 40 nm in diameter, respectively). The unusual properties of GRA2 due to its AAHs are discussed. - Highlights: • Toxoplasma gondii: soluble GRA2 forms 2 populations of particles. • T. gondii: the dense granule protein GRA2 folds intrinsically as an alpha-helix. • T. gondii: monomeric soluble GRA6 forms particles of 6–8 nm in diameter. • T. gondii: monomeric soluble GRA6 is random coiled. • Unusual biophysical properties of the dense granule protein GRA2 from T. gondii

  7. Toxoplasma gondii: Biochemical and biophysical characterization of recombinant soluble dense granule proteins GRA2 and GRA6

    Bittame, Amina [CNRS, UMR 5163, 38042 Grenoble (France); Université Grenoble Alpes, 38042 Grenoble (France); Effantin, Grégory [Université Grenoble Alpes, Institut de Biologie Structurale (IBS), 38044 Grenoble (France); CNRS, IBS, 38044 Grenoble (France); CEA, IBS, 38044 Grenoble (France); Unit for Virus Host-Cell Interactions (UVHCI), UMI 3265 (UJF-EMBL-CNRS), 38027 Grenoble (France); Pètre, Graciane; Ruffiot, Pauline; Travier, Laetitia [CNRS, UMR 5163, 38042 Grenoble (France); Université Grenoble Alpes, 38042 Grenoble (France); Schoehn, Guy; Weissenhorn, Winfried [Université Grenoble Alpes, Institut de Biologie Structurale (IBS), 38044 Grenoble (France); CNRS, IBS, 38044 Grenoble (France); CEA, IBS, 38044 Grenoble (France); Unit for Virus Host-Cell Interactions (UVHCI), UMI 3265 (UJF-EMBL-CNRS), 38027 Grenoble (France); Cesbron-Delauw, Marie-France; Gagnon, Jean [CNRS, UMR 5163, 38042 Grenoble (France); Université Grenoble Alpes, 38042 Grenoble (France); Mercier, Corinne, E-mail: corinne.mercier@ujf-grenoble.fr [CNRS, UMR 5163, 38042 Grenoble (France); Université Grenoble Alpes, 38042 Grenoble (France)

    2015-03-27

    The most prominent structural feature of the parasitophorous vacuole (PV) in which the intracellular parasite Toxoplasma gondii proliferates is a membranous nanotubular network (MNN), which interconnects the parasites and the PV membrane. The MNN function remains unclear. The GRA2 and GRA6 proteins secreted from the parasite dense granules into the PV have been implicated in the MNN biogenesis. Amphipathic alpha-helices (AAHs) predicted in GRA2 and an alpha-helical hydrophobic domain predicted in GRA6 have been proposed to be responsible for their membrane association, thereby potentially molding the MMN in its structure. Here we report an analysis of the recombinant proteins (expressed in detergent-free conditions) by circular dichroism, which showed that full length GRA2 displays an alpha-helical secondary structure while recombinant GRA6 and GRA2 truncated of its AAHs are mainly random coiled. Dynamic light scattering and transmission electron microscopy showed that recombinant GRA6 and truncated GRA2 constitute a homogenous population of small particles (6–8 nm in diameter) while recombinant GRA2 corresponds to 2 populations of particles (∼8–15 nm and up to 40 nm in diameter, respectively). The unusual properties of GRA2 due to its AAHs are discussed. - Highlights: • Toxoplasma gondii: soluble GRA2 forms 2 populations of particles. • T. gondii: the dense granule protein GRA2 folds intrinsically as an alpha-helix. • T. gondii: monomeric soluble GRA6 forms particles of 6–8 nm in diameter. • T. gondii: monomeric soluble GRA6 is random coiled. • Unusual biophysical properties of the dense granule protein GRA2 from T. gondii.

  8. Cathodic Potential Dependence of Electrochemical Reduction of SiO2 Granules in Molten CaCl2

    Yang, Xiao; Yasuda, Kouji; Nohira, Toshiyuki; Hagiwara, Rika; Homma, Takayuki

    2016-09-01

    As part of an ongoing fundamental study to develop a new process for producing solar-grade silicon, this paper examines the effects of cathodic potential on reduction kinetics, current efficiency, morphology, and purity of Si product during electrolysis of SiO2 granules in molten CaCl2 at 1123 K (850 °C). SiO2 granules were electrolyzed potentiostatically at different cathodic potentials (0.6, 0.8, 1.0, and 1.2 V vs Ca2+/Ca). The reduction kinetics was evaluated based on the growth of the reduced Si layer and the current behavior during electrolysis. The results suggest that a more negative cathodic potential is favorable for faster reduction. Current efficiencies in 60 minutes are greater than 65 pct at all the potentials examined. Si wires with sub-micron diameters are formed, and their morphologies show little dependence on the cathodic potential. The impurities in the Si product can be controlled at low level. The rate-determining step for the electrochemical reduction of SiO2 granules in molten CaCl2 changes with time. At the initial stage of electrolysis, the electron transfer is the rate-determining step. At the later stage, the diffusion of O2- ions is the rate-determining step. The major cause of the decrease in reduction rate with increasing electrolysis time is the potential drop from the current collector to the reaction front due to the increased contact resistance among the reduced Si particles.

  9. Effect of neurotrophin-3 precursor on glutamate-induced calcium homeostasis deregulation in rat cerebellum granule cells.

    Safina, Dina R; Surin, Alexander M; Pinelis, Vsevolod G; Kostrov, Sergey V

    2015-12-01

    Neurotrophin-3 (NT-3) belongs to the family of highly conserved dimeric growth factors that controls the differentiation and activity of various neuronal populations. Mammals contain both the mature (NT-3) and the precursor (pro-NT-3) forms of neurotrophin. Members of the neurotrophin family are involved in the regulation of calcium homeostasis in neurons; however, the role of NT-3 and pro-NT-3 in this process remains unclear. The current study explores the effects of NT-3 and pro-NT-3 on disturbed calcium homeostasis and decline of mitochondrial potential induced by a neurotoxic concentration of glutamate (Glu; 100 µM) in the primary culture of rat cerebellar granule cells. In this Glu excitotoxicity model, mature NT-3 had no effect on the induced changes in Ca²⁺ homeostasis. In contrast, pro-NT-3 decreased the period of delayed calcium deregulation (DCD) and concurrent strong mitochondrial depolarization. According to the amplitude of the increase in the intracellular free Ca²⁺ concentration ([Ca²⁺]i ) and Fura-2 fluorescence quenching by Mn²⁺ within the first 20 sec of exposure to Glu, pro-NT-3 had no effect on the initial rate of Ca²⁺ entry into neurons. During the lag period preceding DCD, the mean amplitude of [Ca²⁺]i rise was 1.2-fold greater in the presence of pro-NT-3 than in the presence of Glu alone (1.67 ±  0.07 and 1.39 ± 0.04, respectively, P < 0.05). The Glu-induced changes in Са²⁺ homeostasis in the presence of pro-NT-3 likely are due to the decreased rate of Са²⁺ removal from the cytosol during the DCD latency period. © 2015 Wiley Periodicals, Inc.

  10. Prenatal nicotine and maternal deprivation stress de-regulate the development of CA1, CA3, and dentate gyrus neurons in hippocampus of infant rats.

    Hong Wang

    Full Text Available Adverse experiences by the developing fetus and in early childhood are associated with profound effects on learning, emotional behavior, and cognition as a whole. In this study we investigated the effects of prenatal nicotine exposure (NIC, postnatal maternal deprivation (MD or the combination of the two (NIC+MD to determine if hippocampal neuron development is modulated by exposure to drugs of abuse and/or stress. Growth of rat offspring exposed to MD alone or NIC+MD was repressed until after weaning. In CA1 but not CA3 of postnatal day 14 (P14 pups, MD increased pyramidal neurons, however, in dentate gyrus (DG, decreased granule neurons. NIC had no effect on neuron number in CA1, CA3 or DG. Unexpectedly, NIC plus MD combined caused a synergistic increase in the number of CA1 or CA3 neurons. Neuron density in CA regions was unaffected by treatment, but in the DG, granule neurons had a looser packing density after NIC, MD or NIC+MD exposure. When septotemporal axes were analyzed, the synergism of stress and drug exposure in CA1 and CA3 was associated with rostral, whereas MD effects were predominantly associated with caudal neurons. TUNEL labeling suggests no active apoptosis at P14, and doublecortin positive neurons and mossy fibers were diminished in NIC+MD relative to controls. The laterality of the effect of nicotine and/or maternal deprivation in right versus left hippocampus was also analyzed and found to be insiginificant. We report for the first time that early life stressors such as postnatal MD and prenatal NIC exposure, when combined, may exhibit synergistic consequences for CA1 and CA3 pyramidal neuron development, and a potential antagonistic influence on developing DG neurons. These results suggest that early stressors may modulate neurogenesis, apoptosis, or maturation of glutamatergic neurons in the hippocampus in a region-specific manner during critical periods of neurodevelopment.

  11. Shear Resistance Variations in Experimentally Sheared Mudstone Granules: A Possible Shear-Thinning and Thixotropic Mechanism

    Hu, Wei; Xu, Qiang; Wang, Gonghui; Scaringi, Gianvito; Mcsaveney, Mauri; Hicher, Pierre-Yves

    2017-11-01

    We present results of ring shear frictional resistance for mudstone granules of different size obtained from a landslide shear zone. Little rate dependency of shear resistance was observed in sand-sized granules in any wet or dry test, while saturated gravel-sized granules exhibited significant and abrupt reversible rate-weakening (from μ = 0.6 to 0.05) at about 2 mm/s. Repeating resistance variations occurred also under constant shear displacement rate. Mudstone granules generate mud as they are crushed and softened. Shear-thinning and thixotropic behavior of the mud can explain the observed behavior: with the viscosity decreasing, the mud can flow through the coarser soil pores and migrate out from the shear zone. This brings new granules into contact which produces new mud. Thus, the process can start over. Similarities between experimental shear zones and those of some landslides in mudstone suggest that the observed behavior may play a role in some landslide kinematics.

  12. Nitrate removal from aquaculture effluents using woodchip bioreactors improved by adding sulfur granules and crushed seashells

    von Ahnen, Mathis; Pedersen, Per Bovbjerg; Dalsgaard, Johanne

    2018-01-01

    This study examined the effects on nitrate removal when adding sulfur granules and crushed seashells to a woodchip bioreactor treating aquaculture effluents. Using a central composite design, the two components were added at three levels (0.000, 0.125 and 0.250 m3/m3 bioreactor volume) to 13......, the inclusion of crushed seashells together with sulfur granules helped to maintain the pH above 7.4 and prevent a production (i.e., release) of nitrite. According to the modeled response surfaces, a sulfur granule:crushed seashell:woodchip mixture ratio containing about 0.2 m3 sulfur granules and 0.1 m3...... crushed seashells per m3 reactor volume would give the best results with respect to high N removal and minimal nitrite release. In conclusion, the study showed that N removal in woodchip bioreactors may be improved by adding sulfur granules and seashells, contributing to the optimization of woodchip...

  13. On-line monitoring of fluid bed granulation by photometric imaging.

    Soppela, Ira; Antikainen, Osmo; Sandler, Niklas; Yliruusi, Jouko

    2014-11-01

    This paper introduces and discusses a photometric surface imaging approach for on-line monitoring of fluid bed granulation. Five granule batches consisting of paracetamol and varying amounts of lactose and microcrystalline cellulose were manufactured with an instrumented fluid bed granulator. Photometric images and NIR spectra were continuously captured on-line and particle size information was extracted from them. Also key process parameters were recorded. The images provided direct real-time information on the growth, attrition and packing behaviour of the batches. Moreover, decreasing image brightness in the drying phase was found to indicate granule drying. The changes observed in the image data were also linked to the moisture and temperature profiles of the processes. Combined with complementary process analytical tools, photometric imaging opens up possibilities for improved real-time evaluation fluid bed granulation. Furthermore, images can give valuable insight into the behaviour of excipients or formulations during product development. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Evaluation of an in-line particle imaging tool for monitoring twin-screw granulation performance

    Kumar, Ashish; Dhondt, Jens; De Leersnyder, Fien

    2015-01-01

    system. Off-line sieving was used as reference particle size analysis method. A twin-screw granulator which is part of the Consigma system was used to granulate a placebo formulation composed of lactose and polyvinylpyrrolidone (PVP; 97.5:2.5% w/w). PVP was dissolvedin water, which was used......). The volumetric size distribution obtained from the in-line measurements of the granules leaving the twin-screw granulator using the Eyecon™ camera was compared with the off-line measurements obtainedby sieving of the granule samples collected before and after the drying unit operation. For the intermediate size...... range (diameter 250–1000 μm), the Eyecon™ measurements showed to be promising as they were in agreement with off-line measurement results obtained before the drying unit. However, the image analysis algorithm and data post-processing of the Eyecon™ images for the fines and oversized ranges require...

  15. Conceptual framework for model-based analysis of residence time distribution in twin-screw granulation

    Kumar, Ashish; Vercruysse, Jurgen; Vanhoorne, Valerie

    2015-01-01

    Twin-screw granulation is a promising continuous alternative for traditional batchwise wet granulation processes. The twin-screw granulator (TSG) screws consist of transport and kneading element modules. Therefore, the granulation to a large extent is governed by the residence time distribution...... within each module where different granulation rate processes dominate over others. Currently, experimental data is used to determine the residence time distributions. In this study, a conceptual model based on classical chemical engineering methods is proposed to better understand and simulate...... the residence time distribution in a TSG. The experimental data were compared with the proposed most suitable conceptual model to estimate the parameters of the model and to analyse and predict the effects of changes in number of kneading discs and their stagger angle, screw speed and powder feed rate...

  16. Single neuron computation

    McKenna, Thomas M; Zornetzer, Steven F

    1992-01-01

    This book contains twenty-two original contributions that provide a comprehensive overview of computational approaches to understanding a single neuron structure. The focus on cellular-level processes is twofold. From a computational neuroscience perspective, a thorough understanding of the information processing performed by single neurons leads to an understanding of circuit- and systems-level activity. From the standpoint of artificial neural networks (ANNs), a single real neuron is as complex an operational unit as an entire ANN, and formalizing the complex computations performed by real n

  17. Mesmerising mirror neurons.

    Heyes, Cecilia

    2010-06-01

    Mirror neurons have been hailed as the key to understanding social cognition. I argue that three currents of thought-relating to evolution, atomism and telepathy-have magnified the perceived importance of mirror neurons. When they are understood to be a product of associative learning, rather than an adaptation for social cognition, mirror neurons are no longer mesmerising, but they continue to raise important questions about both the psychology of science and the neural bases of social cognition. Copyright 2010 Elsevier Inc. All rights reserved.

  18. The mirror neuron system.

    Cattaneo, Luigi; Rizzolatti, Giacomo

    2009-05-01

    Mirror neurons are a class of neurons, originally discovered in the premotor cortex of monkeys, that discharge both when individuals perform a given motor act and when they observe others perform that same motor act. Ample evidence demonstrates the existence of a cortical network with the properties of mirror neurons (mirror system) in humans. The human mirror system is involved in understanding others' actions and their intentions behind them, and it underlies mechanisms of observational learning. Herein, we will discuss the clinical implications of the mirror system.

  19. Insulin reduces neuronal excitability by turning on GABA(A channels that generate tonic current.

    Zhe Jin

    Full Text Available Insulin signaling to the brain is important not only for metabolic homeostasis but also for higher brain functions such as cognition. GABA (γ-aminobutyric acid decreases neuronal excitability by activating GABA(A channels that generate phasic and tonic currents. The level of tonic inhibition in neurons varies. In the hippocampus, interneurons and dentate gyrus granule cells normally have significant tonic currents under basal conditions in contrast to the CA1 pyramidal neurons where it is minimal. Here we show in acute rat hippocampal slices that insulin (1 nM "turns on" new extrasynaptic GABA(A channels in CA1 pyramidal neurons resulting in decreased frequency of action potential firing. The channels are activated by more than million times lower GABA concentrations than synaptic channels, generate tonic currents and show outward rectification. The single-channel current amplitude is related to the GABA concentration resulting in a single-channel GABA affinity (EC(50 in intact CA1 neurons of 17 pM with the maximal current amplitude reached with 1 nM GABA. They are inhibited by GABA(A antagonists but have novel pharmacology as the benzodiazepine flumazenil and zolpidem are inverse agonists. The results show that tonic rather than synaptic conductances regulate basal neuronal excitability when significant tonic conductance is expressed and demonstrate an unexpected hormonal control of the inhibitory channel subtypes and excitability of hippocampal neurons. The insulin-induced new channels provide a specific target for rescuing cognition in health and disease.

  20. Formation of tRNA granules in the nucleus of heat-induced human cells

    Miyagawa, Ryu [Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Department of Biological Science, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8654 (Japan); Mizuno, Rie [Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Watanabe, Kazunori, E-mail: watanabe@ric.u-tokyo.ac.jp [Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Ijiri, Kenichi [Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Department of Biological Science, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8654 (Japan)

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer tRNAs are tranlocated into the nucleus in heat-induced HeLa cells. Black-Right-Pointing-Pointer tRNAs form the unique granules in the nucleus. Black-Right-Pointing-Pointer tRNA ganules overlap with nuclear stress granules. -- Abstract: The stress response, which can trigger various physiological phenomena, is important for living organisms. For instance, a number of stress-induced granules such as P-body and stress granule have been identified. These granules are formed in the cytoplasm under stress conditions and are associated with translational inhibition and mRNA decay. In the nucleus, there is a focus named nuclear stress body (nSB) that distinguishes these structures from cytoplasmic stress granules. Many splicing factors and long non-coding RNA species localize in nSBs as a result of stress. Indeed, tRNAs respond to several kinds of stress such as heat, oxidation or starvation. Although nuclear accumulation of tRNAs occurs in starved Saccharomyces cerevisiae, this phenomenon is not found in mammalian cells. We observed that initiator tRNA{sup Met} (Meti) is actively translocated into the nucleus of human cells under heat stress. During this study, we identified unique granules of Meti that overlapped with nSBs. Similarly, elongator tRNA{sup Met} was translocated into the nucleus and formed granules during heat stress. Formation of tRNA granules is closely related to the translocation ratio. Then, all tRNAs may form the specific granules.