Sample records for chromaffin granules

  1. Nonreutilizaton of adrenal chromaffin granule membranes following secretion

    The intracellular postexocytotic fate of the adrenal chromaffin granule membrane (reutilization vs. nonreutilization) was addressed through two experimental approaches. First, (3H) 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

  2. Platelet granule exocytosis: A comparison with chromaffin cells

    Jennifer eFitch-Tewfik


    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.

  3. Uptake of meta-iodobenzylguanidine by bovine chromaffin granule membranes

    meta-Iodobenzylguanidine, an adrenal imaging agent used for the scintigraphic detection of human pheochromocytoma, is a substrate for the monoamine uptake system of chromaffin granules. It is accumulated by bovine chromaffin granule membrane vesicles in the presence of ATP, and it can be released by an osmotic shock. The uptake is dependent upon the generation of an H+-electrochemical gradient by an ATP-dependent H+ pump since it is blocked by an H+ ionophore and since meta-iodobenzylguanidine uptake can be driven by imposing an artificial pH gradient (inside acidic) on the membrane vesicles. The transport is saturable and its Km value (2.0 microM at pH 8.0) is similar to that of noradrenaline (5.3 microM). Transport occurs through the monoamine transporter since it is blocked by the same inhibitors, tetrabenazine and reserpine, and also by the transporter substrates noradrenaline and serotonin. Noradrenaline inhibits meta-iodobenzylguanidine uptake competitively (Ki = 13 microM). In addition, meta-iodobenzylguanidine displaces dihydrotetrabenazine and reserpine from their binding sites on chromaffin granule membranes. It is thus likely that, after in vivo administration, [131I] meta-iodobenzylguanidine is ultimately stored in chromaffin granules and that it is translocated by the monoamine transporter

  4. Core structure, internal osmotic pressure and irreversible structural changes of chromaffin granules during osmometer behaviour.

    Südhof, T C


    In the adrenal medullary cells, catecholamines are stored in and secreted from specialized secretory vesicles, the chromaffin granules. In order to gain some understanding of both functions of chromaffin granules, it is important to characterize their biophysical organization. Using isolated bovine chromaffin granules we have investigated the osmometer behaviour of chromaffin granules by 31P-NMR and fluorescence spectroscopy, by turbidity measurements and by electron-microscopic determination of chromaffin granule size distributions. On the basis of the osmometer model we have formulated equations predicting the behaviour of the native catecholamine fluorescence quenching and of the size of chromaffin granules a a function of osmolarity and have shown experimentally that the granules' behaviour conforms to these. It was possible to estimate the osmotic activity of the chromaffin granule core solution and the mean absolute water space in chromaffin granules from the determination of the size distributions as a function of osmotic pressure. With NMR spectroscopy a selective line-broadening of the alpha-resonances was observed with increasing osmolarities, while the gamma-phosphorus resonances remained virtually unchanged. Possibly there is an increase in core viscosity with osmolarity which affects only the alpha- and beta-phosphorus groups. While suspending chromaffin granules from lower to higher osmolarities causes no lysis, moving them back to their original osmolarity at which they were previously stable lyses them, thereby releasing a maximum of 70% of their releasable protein. This 'hyperosmolar' lysis is independent of preincubation times in the higher osmolarities and of the absolute dilution applied but depends on dilution beyond the 405 to 322 mosM sucrose range. Under the experiment conditions no uptake of sucrose from the medium into the granules could be measured, thereby suggesting that hyperosmolar lysis is a phenomenon not due to solute penetration

  5. Analysis of the carbon-13 and proton NMR spectra of bovine chromaffin granules.

    Sharp, R R; Richards, E P


    Natural abundance carbon-13 and proton NMR spectra of bovine chromaffin granules have been obtained and analyzed using computer simulation techniques. High resolution spectra show the presence of a fluid aqueous phase containing epinephrine, ATP and a random coil protein. The protein spectrum contains unusually intense resonances due to glutamic acid and proline and has been simulated satisfactorily using the known amino acid composition of chromogranin A. The lipid phase of chromaffin granules gives rise to intense, but very broad, resonances in the carbon-13 spectrum. Protons in the lipid phase are also observable as a very rapid component of the proton-free induction decay (T2 approximately equal to 15 microns). Linewidths of the carbon-13 spectra have been used to set upper limits on rotational correlation times and on the motional anisotropy in the aqueous phase. These limits show that the aqueous phase is a simple solution (not a gel) that is isotropic over regions much larger than solute dimensions. No gel transition is observed between -3 and 25 degrees C. The carbon-13 spectra are definitely inconsistent with a lipoprotein matrix model and chromaffin granules previously proposed by Helle and Serck-Hanssen ((1975) Mol. Cell, Biochem. 6, 127-146). Relative carbon-13 intensities of ATP and epinephrine are not consistent with the known 1 : 4 mol ratio of these components. This fact suggests that epinephrine and ATP are not directly complexed in intact chromaffin granules. PMID:849474

  6. Characterization of the monoamine carrier of chromaffin granule membrane by binding of [2-3H]dihydrotetrabenazine.

    Scherman, D; Jaudon, P; Henry, J.P.


    [2-3H]Dihydrotetrabenazine (2-hydroxy-3-isobutyl-9, 10-dimethoxy-1,2,3,4,6,7-hexahydro-11b-H-benzo [a]-quinolizine), a derivative of the neuroleptic tetrabenazine, binds to the membrane of purified bovine chromaffin granules. Specific binding was characterized by Kd and Bmax values of 3.1 nM and 62 pmol/mg of membrane protein, respectively. It was reversible, with association and dissociation rate constants of 0.22 x 10(6) M-1 s-1 and 1.8 x 10(-3) s-1, respectively. Binding sites were present...

  7. Effect of heart failure on catecholamine granule morphology and storage in chromaffin cells.

    Mahata, Sushil K; Zheng, Hong; Mahata, Sumana; Liu, Xuefei; Patel, Kaushik P


    One of the key mechanisms involved in sympathoexcitation in chronic heart failure (HF) is the activation of the adrenal glands. Impact of the elevated catecholamines on the hemodynamic parameters has been previously demonstrated. However, studies linking the structural effects of such overactivation with secretory performance and cell metabolism in the adrenomedullary chromaffin cells in vivo have not been previously reported. In this study, HF was induced in male Sprague-Dawley rats by ligation of the left coronary artery. Five weeks after surgery, cardiac function was assessed by ventricular hemodynamics. HF rats showed increased adrenal weight and adrenal catecholamine levels (norepinephrine, epinephrine and dopamine) compared with sham-operated rats. Rats with HF demonstrated increased small synaptic and dense core vesicle in splanchnic-adrenal synapses indicating trans-synaptic activation of catecholamine biosynthetic enzymes, increased endoplasmic reticulum and Golgi lumen width to meet the demand of increased catecholamine synthesis and release, and more mitochondria with dilated cristae and glycogen to accommodate for the increased energy demand for the increased biogenesis and exocytosis of catecholamines from the adrenal medulla. These findings suggest that increased trans-synaptic activation of the chromaffin cells within the adrenal medulla may lead to increased catecholamines in the circulation which in turn contributes to the enhanced neurohumoral drive, providing a unique mechanistic insight for enhanced catecholamine levels in plasma commonly observed in chronic HF condition. PMID:27402067

  8. The chromaffin cells of Siren lacertina (Amphibia, Urodela): cytological characteristics and evidence of exocytosis.

    Accordi, F


    In the adrenal gland of Siren lacertina three types of chromaffin cells are described, on the basis of size, shape and electron density of the cytoplasmic granules: adrenaline-secreting cells, noradrenaline-secreting cells and small granulated chromaffin-cells. In A-cells exocytotic profiles are described, in which the granule membrane fuses with the plasma membrane and the granule core is discharged into the intercellular space.

  9. Histotopography of the chromaffin tissue of the mouse heart on critical stages of the normal cardioembryogenesis

    Dyagovets K.I.


    Full Text Available Background. Pheochromocytoma is tumor of chromaffin tissue, which is very hard to diagnose. Chromaffin tissue present not only in the adrenal gland, but also some cells determined in all organs of the head, neck and body. Heart population of chromaffin tissue has signs of the high developmental level during the embryonic period. It’s known, that chromaffin cells develop from neuroectoderm, like neural crest cells. There is an opinion that neural crest cells differentiate into the chromaffin tissue. Objective. Determine histotopography of the chromaffin tissue of the mouse heart on critical stages of the normal cardioembryogenesis. Methods. Embryonic mice hearts line С56BL/6 were fixed by 10%-formalin and then were subjected to the standard histological procedures. The sections 5 µm thickness were stained by the Vizel. Results and conclusion. It was established that among neural crest cells or condense mesenchyma determined cells with specific granules. These granules had specific semilunar shape and bilberry color. Cells which have same granules named like chromaffin cells. They differentiate from neural crest cells according to the opinions of some scientists. These cells have much less proliferation activity than neuroblasts. Chromaffin cells still had a few of phenotypic differences during the migration from the aortic arches. They might to be determined since the beginning of this migration. We observed that in our results. Summing up, there were defined two populations of chromaffin cells in embryo heart during the critical rotation and septation stages. They were located on subendocardial regions of the embryo heart mostly and had focal signs. Citation: Dyagovets KI. [Histotopography of the chromaffin tissue of the mouse heart on critical stages of the normal cardioembryogenesis]. Morphologia. 2015;9(4:26-30. Ukrainian.

  10. Adrenaline-, noradrenaline- and small granule- containing cells in the adrenal gland of Discoglossus pictus (Amphibia, Anura).

    Accordi, F; Gallo, V P


    In the adrenal gland of Discoglossus pictus, various types of chromaffin cells are described: noradrenaline cells, adrenaline cells and small granule-containing cells (on the basis of electron density and shape of the granules). The chromaffin cells occur in small groups, and have cytoplasmic processes which may surround them in the form of parallel layers. Their nerve supply is sparse. The possible function of SGC-cells, in relation to those described in other vertebrates, is discussed.

  11. Inhibition of catecholamine secretion by iron-rich and iron-deprived multiwalled carbon nanotubes in chromaffin cells.

    Gavello, Daniela; Fenoglio, Ivana; Fubini, Bice; Cesano, Federico; Premoselli, Federica; Renna, Annamaria; Carbone, Emilio; Carabelli, Valentina


    The assay of the toxic effects of carbon nanotubes (CNTs) on human health is a stringent need in view of their expected increasing exploitation in industrial and biomedical applications. Most studies so far have been focused on lung toxicity, as the respiratory tract is the main entry of airborne particulate, but there is also recent evidence on the existence of toxic effects of multiwalled carbon nanotubes (MWCNTs) on neuronal and neuroendocrine cells (Belyanskaya et al., 2009; Xu et al., 2009; Gavello et al., 2012). Commercial MWCNTs often contain large amounts of metals deriving from the catalyst used during their synthesis. Since metals, particularly iron, may contribute to the toxicity of MWCNTs, we compared here the effects of two short MWCNTs samples (<5μm length), differing only in their iron content (0.5 versus 0.05% w/w) on the secretory responses of neurotransmitters in mouse chromaffin cells. We found that both iron-rich (MWCNT+Fe) and iron-deprived (MWCNT-Fe) samples enter chromaffin cells after 24h exposure, even though incorporation was attenuated in the latter case (40% versus 78% of cells). As a consequence of MWCNT+Fe or MWCNT-Fe exposure (50-263μg/ml, 24h), catecholamine secretion of chromaffin cells is drastically impaired because of the decreased Ca(2+)-dependence of exocytosis, reduced size of ready-releasable pool and lowered rate of vesicle release. On the contrary, both MWCNTs were ineffective in changing the kinetics of neurotransmitter release of single chromaffin granules and their quantal content. Overall, our data indicate that both MWCNT samples dramatically impair secretion in chromaffin cells, thus uncovering a true depressive action of CNTs mainly associated to their structure and degree of aggregation. This cellular "loss-of-function" is only partially attenuated in iron-deprived samples, suggesting a minor role of iron impurities on MWCNTs toxicity in chromaffin cells exocytosis. PMID:23999117

  12. Membrane toxicity of abnormal prion protein in adrenal chromaffin cells of scrapie infected sheep.

    Gillian McGovern

    Full Text Available Transmissible spongiform encephalopathies (TSEs or prion diseases are associated with accumulations of disease specific PrP (PrP(d in the central nervous system (CNS and often the lymphoreticular system (LRS. Accumulations have additionally been recorded in other tissues including the peripheral nervous system and adrenal gland. Here we investigate the effect of sheep scrapie on the morphology and the accumulation of PrP(d in the adrenal medulla of scrapie affected sheep using light and electron microscopy. Using immunogold electron microscopy, non-fibrillar forms of PrP(d were shown to accumulate mainly in association with chromaffin cells, occasional nerve endings and macrophages. PrP(d accumulation was associated with distinctive membrane changes of chromaffin cells including increased electron density, abnormal linearity and invaginations. Internalisation of PrP(d from the chromaffin cell plasma membrane occurred in association with granule recycling following hormone exocytosis. PrP(d accumulation and internalisation from membranes is similarly associated with perturbations of membrane structure and trafficking in CNS neurons and tingible body macrophages of the LRS. These data suggest that a major toxic effect of PrP(d is at the level of plasma membranes. However, the precise nature of PrP(d-membrane toxicity is tissue and cell specific suggesting that the normal protein may act as a multi-functional scaffolding molecule. We further suggest that the co-localisation of PrP(d with exocytic granules of the hormone trafficking system may provide an additional source of infectivity in blood.

  13. Right atrial chromaffin paraganglioma in a dog.

    Wey, Aaron C; Moore, Frances M


    Cardiac neoplasia is relatively uncommon in canine patients, with the most common neoplasms including right atrial hemangiosarcoma and paragangliomas occurring at the heart base (i.e. chemodectomas or aortic body tumors). Intracardiac paragangliomas are rare neoplasms in humans and have seldom been documented in the veterinary literature. This report describes the clinical course and histopathological findings in an adult canine patient with an intracardiac chromaffin paraganglioma (non-adrenal pheochromocytoma) of the right atrium. PMID:22840732

  14. Protein mobility within secretory granules.

    Weiss, Annita Ngatchou; Bittner, Mary A; Holz, Ronald W; Axelrod, Daniel


    We investigated the basis for previous observations that fluorescent-labeled neuropeptide Y (NPY) is usually released within 200 ms after fusion, whereas labeled tissue plasminogen activator (tPA) is often discharged over many seconds. We found that tPA and NPY are endogenously expressed in small and different subpopulations of bovine chromaffin cells in culture. We measured the mobility of these proteins (tagged with fluorophore) within the lumen of individual secretory granules in living chromaffin cells, and related their mobilities to postfusion release kinetics. A method was developed that is not limited by standard optical resolution, in which a bright flash of strongly decaying evanescent field (∼64 nm exponential decay constant) produced by total internal reflection (TIR) selectively bleaches cerulean-labeled protein proximal to the glass coverslip within individual granules. Fluorescence recovery occurred as unbleached protein from distal regions within the 300 nm granule diffused into the bleached proximal regions. The fractional bleaching of tPA-cerulean (tPA-cer) was greater when subsequently probed with TIR excitation than with epifluorescence, indicating that tPA-cer mobility was low. The almost equal NPY-cer bleaching when probed with TIR and epifluorescence indicated that NPY-cer equilibrated within the 300 ms bleach pulse, and therefore had a greater mobility than tPA-cer. TIR-fluorescence recovery after photobleaching revealed a significant recovery of tPA-cer (but not NPY-cer) fluorescence within several hundred milliseconds after bleaching. Numerical simulations, which take into account bleach duration, granule diameter, and the limited number of fluorophores in a granule, are consistent with tPA-cer being 100% mobile, with a diffusion coefficient of 2 × 10(-10) cm(2)/s (∼1/3000 of that for a protein of similar size in aqueous solution). However, the low diffusive mobility of tPA cannot alone explain its slow postfusion release. In the

  15. Intranuclear bundles of microfilaments and microtubules in chromaffin cells of the auricle of the heart of a lungfish, Protopterus aethiopicus.

    Scheuermann, D W; Adriaensen, D; De Groodt-Lasseel, M H


    Intranuclear microtubular-microfilamentous rod-like inclusions were investigated in chromaffin cells of the auricle of the heart of lungfishes. In conventional electron microscopy, these inclusions reveal a wide variety in appearance, depending on their orientation to the plane of sectioning. Whereas originally they were merely interpreted as a bundle of microfilaments, application of a goniometer stage showed the rod- or spindle-shaped intranuclear inclusions to have a basic substructure of parallel arranged microtubules among microfilaments, which are clearly connected to chromatin granules, occasionally penetrating dense areas of chromatin. The chemical nature and biological significance of these structures, which so far remain enigmatic, are discussed. PMID:3227775

  16. Immunoreactive atrial natriuretic peptide and dopamine beta-hydroxylase in myocytes and chromaffin cells of the heart of the African lungfish, Protopterus aethiopicus.

    Larsen, T H; Helle, K B; Saetersdal, T


    The heart of the African lungfish, Protopterus aethiopicus, was examined for immunoreactive atrial natriuretic peptide (ANP) and dopamine beta-hydroxylase (D beta H) as markers for hormone secreting myocytes and chromaffin cells, respectively. Specific antibodies raised against rat alpha-ANP and rat D beta H were used for immunofluorescence microscopy and immunogold electron microscopy. D beta H-immunoreactive cells were restricted to subendocardial areas of the atrium whereas ANP immunoreactivity occurred throughout both the atrial and the ventricular myocardium, showing particularly strong staining intensity in the atrial myocytes. The granular ANP immunostaining in the atrial myocytes was frequently accumulated in the sarcoplasm. In the ventricular myocytes ANP immunoreactivity occurred as scattered granular staining throughout the sarcoplasm. ANP and D beta H immunofluorescence staining coincided with the presence of immunoreactive specific granules and secretory vesicles in the cardiac myocytes and chromaffin cells, respectively, as revealed by electron microscopy. The number of ANP-containing specific granules was generally high in the atrial myocytes, and they were frequently observed in clusters in subsarcolemmal areas. Granular frequency was considerably lower and the mean granular diameter was smaller (0.142 +/- 0.045 micron versus 0.213 +/- 0.049 micron) in the ventricular than in the atrial myocytes. The present results indicate that ANP and D beta H are phylogenetically highly conserved proteins from the dipnoi to the rat. The large amounts of ANP and of specific granules are consistent with an endocrine myocardium in the Protopterus heart. The presence of D beta H and secretory vesicles in the subendocardial chromaffin cells of the atrium suggests a local production of catecholamines from dopamine in the heart of this dipnoan. PMID:7926645

  17. Vesicle Pools: Lessons from Adrenal Chromaffin Cells

    David R Stevens


    Full Text Available The adrenal chromaffin cell serves as a model system to study fast Ca2+-dependent exocytosis. Membrane capacitance measurements in combination with Ca2+ uncaging offers a temporal resolution in the millisecond range and reveals that catecholamine release occurs in three distinct phases. Release of a readily releasable (RRP and a slowly releasable (SRP pool are followed by sustained release, due to maturation and release of vesicles which were not release-ready at the start of the stimulus. Trains of depolarizations, a more physiological stimulus, induce release from a small immediately releasable pool of vesicles residing adjacent to calcium channels, as well as from the RRP. The SRP is poorly activated by depolarization. A sequential model, in which non-releasable docked vesicles are primed to a slowly releasable state, and then further mature to the readily releasable state, has been proposed. The docked state, dependent on membrane proximity, requires SNAP-25, synaptotagmin and syntaxin. The ablation or modification of SNAP-25 and syntaxin, components of the SNARE complex, as well as of synaptotagmin, the calcium sensor, and modulators such complexins and Snapin alter the properties and/or magnitudes of different phases of release, and in particular can ablate the RRP. These results indicate that the composition of the SNARE complex and its interaction with modulatory molecules drives priming and provides a molecular basis for different pools of releasable vesicles.

  18. Permissive effect of dexamethasone on the increase of proenkephalin mRNA induced by depolarization of chromaffin cells

    In cultured bovine chromaffin cells, changes in the dynamic state of enkephalin stores elicited experimentally were studied by measuring cellular proenkephalin mRNA, as well as enkephalin precursors and authentic enkephalin content of cells and culture media. In parallel, tyrosine hydroxylase mRNA and catecholamine cell content were also determined. Low concentrations (0.5-100 pM) of dexamethasone increased the cell contents of proenkephalin mRNA and enkephalin-containing peptides. High concentrations of the hormone(1 μM) were required to increase the cell contents of tyrosine hydroxylase mRNA and catecholamines. Depolarization of the cells with 10 μM veratridine resulted in a depletion of enkephalin and catecholamine stores after 24 hr. The enkephalin, but not the catecholamine, content was restored by 48 hr. An increase in proenkephalin mRNA content might account for the recovery; this increase was curtailed by tetrodotoxin and enhanced by 10 pM dexamethasone. Tyrosine hydroxylase mRNA content was not significantly modified by depolarization, even in the presence of 1 μM dexamethasone. Aldosterone, progesterone, testosterone, or estradiol (1 μM) failed to change proenkephalin mRNA. Hence, dexamethasone appears to exert a specific permissive action on the stimulation of the proenkephalin gene elicited by depolarization. Though the catecholamines and enkephalins are localized in the same chromaffin granules and are coreleased by depolarization, the genes coding for the processes that are rate limiting in the production of these neuromodulators can be differentially regulated

  19. Direct and remote modulation of L-channels in chromaffin cells: distinct actions on alpha1C and alpha1D subunits?

    Baldelli, Pietro; Hernández-Guijo, Jesus Miguel; Carabelli, Valentina; Novara, Monica; Cesetti, Tiziana; Andrés-Mateos, Eva; Montiel, Carmen; Carbone, Emilio


    Understanding precisely the functioning of voltage-gated Ca2+ channels and their modulation by signaling molecules will help clarifying the Ca(2+)-dependent mechanisms controlling exocytosis in chromaffin cells. In recent years, we have learned more about the various pathways through which Ca2+ channels can be up- or down-modulated by hormones and neurotransmitters and how these changes may condition chromaffin cell activity and catecolamine release. Recently, the attention has been focused on the modulation of L-channels (CaV 1), which represent the major Ca2+ current component in rat and human chromaffin cells. L-channels are effectively inhibited by the released content of secretory granules or by applying mixtures of exogenous ATP, opioids, and adrenaline through the activation of receptor-coupled G proteins. This unusual inhibition persists in a wide range of potentials and results from a direct (membrane-delimited) interaction of G protein subunits with the L-channels co-localized in membrane microareas. Inhibition of L-channels can be reversed when the cAMP/PKA pathway is activated by membrane permeable cAMP analog or when cells are exposed to isoprenaline (remote action), suggesting the existence of parallel and opposite effects on L-channel gating by distinctly activated membrane autoreceptors. Here, the authors review the molecular components underlying these two opposing signaling pathways and present new evidence supporting the presence of two L-channel types in rat chromaffin cells (alpha1C and alpha1D), which open new interesting issues concerning Ca(2+)-channel modulation. In light of recent findings on the regulation of exocytosis by Ca(2+)-channel modulation, the authors explore the possible role of L-channels in the autocontrol of catecholamine release. PMID:15034224

  20. GPCRs of adrenal chromaffin cells & catecholamines: The plot thickens.

    Lymperopoulos, Anastasios; Brill, Ava; McCrink, Katie A


    The circulating catecholamines (CAs) epinephrine (Epi) and norepinephrine (NE) derive from two major sources in the whole organism: the sympathetic nerve endings, which release NE on effector organs, and the chromaffin cells of the adrenal medulla, which are cells that synthesize, store and release Epi (mainly) and NE. All of the Epi in the body and a significant amount of circulating NE derive from the adrenal medulla. The secretion of CAs from adrenal chromaffin cells is regulated in a complex way by a variety of membrane receptors, the vast majority of which are G protein-coupled receptors (GPCRs), including adrenergic receptors (ARs), which act as "presynaptic autoreceptors" in this regard. There is a plethora of CA-secretagogue signals acting on these receptors but some of them, most notably the α2ARs, inhibit CA secretion. Over the past few years, however, a few new proteins present in chromaffin cells have been uncovered to participate in CA secretion regulation. Most prominent among these are GRK2 and β-arrestin1, which are known to interact with GPCRs regulating receptor signaling and function. The present review will discuss the molecular and signaling mechanisms by which adrenal chromaffin cell-residing GPCRs and their regulatory proteins modulate CA synthesis and secretion. Particular emphasis will be given to the newly discovered roles of GRK2 and β-arrestins in these processes and particular points of focus for future research will be highlighted, as well. PMID:26851510

  1. Identification of a Munc13-sensitive step in chromaffin cell large dense-core vesicle exocytosis

    Man, Kwun-Nok Mimi; Imig, Cordelia; Walter, Alexander M;


    using chromaffin cells lacking individual isoforms. We show that particularly Munc13-2 plays a fundamental role in LDCV exocytosis, but in contrast to synapses lacking Munc13s, the corresponding chromaffin cells do not exhibit a vesicle docking defect. We further demonstrate that ubMunc13-2 and Munc13...

  2. The chromaffin cell: paradigm in cell, developmental and growth factor biology.

    Unsicker, K


    This article reviews the chromaffin cell in relation to studies that have elucidated fundamental phenomena in cell biology (the molecular anatomy of exocytosis) and developmental neuroscience (the principle of neuropoiesis in the development of the sympathoadrenal cell lineage). A final section addresses growth factor synthesis and storage in chromaffin cells and their implications for the treatment of neurological disorders, such as Parkinson's disease.

  3. The effect of CdSe-ZnS quantum dots on calcium currents and catecholamine secretion in mouse chromaffin cells.

    Gosso, Sara; Gavello, Daniela; Giachello, Carlo N G; Franchino, Claudio; Carbone, Emilio; Carabelli, Valentina


    Semiconductor nanocrystal quantum dots (QDs) possess an enormous potential of applications in nanomedicine, drug delivery and bioimaging which derives from their unique photoemission and photostability characteristics. In spite of this, however, their interactions with biological systems and impact on human health are still largely unknown. Here we used neurosecretory mouse chromaffin cells of the adrenal gland for testing the effects of CdSe-ZnS core-shell quantum dots (5-36 nM) on Ca(2+) channels functionality and Ca(2+)-dependent neurosecretion. Prolonged exposure (24 h) to commonly used concentrations of CdSe-ZnS QDs (≥16 nM) showed that the semiconductor nanocrystal is effectively internalized into the cells without affecting cell integrity (no changes of membrane resistance and cell capacitance). QDs reduced the size of Ca(2+) currents by ∼28% in a voltage-independent manner without affecting channel gating. Correspondingly, depolarization-evoked exocytosis, measured at +10 mV, where Ca(2+) currents are maximal, was reduced by 29%. CdSe-ZnS QDs reduced the size of the readily releasable pool (RRP) of secretory vesicles by 32%, the frequency of release by 33% and the overall quantity of released catecholamines by 61%, as measured by carbon fibers amperometry. In addition, the Ca(2+)-dependence of exocytosis was reduced, whereas the catecholamine content of single granules, as well as the kinetics of release, remained unaltered. These data suggest that exposure to CdSe-ZnS QDs impairs Ca(2+) influx and severely interferes with the functionality of the exocytotic machinery, compromising the overall catecholamine supply from chromaffin cells. PMID:21872323

  4. Chaos evidence in catecholamine secretion at chromaffin cells

    Highlights: ► Nonlinear behavior in protein secretion. ► Nonlinear characterization of complex behavior in catecholamine secretion. ► Chaos in chromaffin cells activity at the adrenaline secretion. ► Preliminary evidences on the chaotic behavior in catecholamine secretion. - Abstract: Chromaffin cells secrete catecholamine molecules via exocytosis process. Each exocytotic event is characterized by a current spike, which corresponds to the amount of released catecholamine from secretory vesicles after fusing to plasma membrane. The current spike might be measured by the oxidation of catecholamine molecules and can be experimentally detected through amperometry technique. In this contribution, the secretion of catecholamine, namely adrenaline, of a set of bovine chromaffin cells is measured individually at each single cell. The aim is to study quantitative results of chaotic behavior in catecholamine secretion. For analysis, time series were obtained from amperometric measurements of each single chromaffin cell. Three analysis techniques were exploited: (i) A low-order attractor was generated by means of phase space reconstruction, Average Mutual Information (AMI) and False Nearest Neighbors (FNN) were used to compute embedding lag and embedding dimension, respectively. (ii) The properties of power spectrum density of time series were studied by Fast Fourier Transform (FFT) looking for possible dominant frequencies in power spectrum. (iii) Maximun Lyapunov Exponent (MLE) analysis was done to study the divergence of trajectories of the time series. Nevertheless, in order to dismiss the possibility of positiveness of MLE are due to the inherent noise in experiments, seven surrogate data sets computed using the Amplitude Adjusted Fourier Transform (AAFT) algorithm was computed. The phase space reconstruction showed that, in all cases, the trajectories lie in an embedding subspace suggesting oscillatory nature. The FFT analysis showed high dispersion of the power

  5. Granulation of fine powder

    Chen, Ching-Fong


    A mixture of fine powder including thorium oxide was converted to granulated powder by forming a first-green-body and heat treating the first-green-body at a high temperature to strengthen the first-green-body followed by granulation by crushing or milling the heat-treated first-green-body. The granulated powder was achieved by screening through a combination of sieves to achieve the desired granule size distribution. The granulated powder relies on the thermal bonding to maintain its shape and structure. The granulated powder contains no organic binder and can be stored in a radioactive or other extreme environment. The granulated powder was pressed and sintered to form a dense compact with a higher density and more uniform pore size distribution.

  6. Analgesia induced by isolated bovine chromaffin cells implanted in rat spinal cord.

    Sagen, J.; Pappas, G. D.; Pollard, H B


    Chromaffin cells synthesize and secrete several neuroactive substances, including catecholamines and opioid peptides, that, when injected into the spinal cord, induce analgesia. Moreover, the release of these substances from the cells can be stimulated by nicotine. Since chromaffin cells from one species have been shown to survive when transplanted to the central nervous system of another species, these cells are ideal candidates for transplantation to alter pain sensitivity. Bovine chromaffi...

  7. Cell contact-mediated regulation of tyrosine hydroxylase synthesis in cultured bovine adrenal chromaffin cells


    The specific activity of tyrosine hydroxylase (TH) in bovine adrenal chromaffin cells can be controlled by changing cell density. Chromaffin cells initially plated at low density (2-3 X 10(4) cells/cm2), and subsequently replated at a 10-fold higher density showed a sixfold increase in specific TH activity within 48 h, resulting from enhanced synthesis (increased number of TH molecules as demonstrated by immunotitration and blockade by cycloheximide) rather than activation. The density-mediat...

  8. Inhibition by the Chromaffin Cell-Derived Peptide Serine-Histogranin in the Rat's Dorsal Horn

    Hentall, Ian D.; Hargraves, Walter A.; Sagen, Jacqueline


    The heptadecapeptide histogranin, synthesized by adrenal chromaffin cells, is implicated in the analgesia produced by transplanting chromaffin cells into the spinal cord, including block of hyperalgesia mediated by NMDA-subtype glutamate receptors. To examine the neurophysiological basis for this analgesia, we applied the stable analog [Ser1]-histogranin (SHG) by iontophoresis near extracellularly recorded wide-dynamic range (WDR) neurons in anesthetized rats. When SHG was applied during peri...

  9. Mining the granule proteome

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


    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...... granule proteins and peptides. Analytical strategies within this research line include so-called 'subtractive proteomics', 'peptidomics' and granule purification by the use of multiple gradient centrifugations. Here we review the literature, and describe the challenges and opportunities in proteomics of...

  10. Anaerobic sludge granulation

    Hulshoff Pol, L.W.; Castro Lopes, de S.I.; Lettinga, G.; Lens, P.N.L.


    This paper reviews different theories on anaerobic sludge granulation in UASB-reactors that have been proposed during the past two decades
    This paper reviews different theories on anaerobic sludge granulation in UASB-reactors that have been proposed during the past two decades. The initial stage

  11. Stimulation of catecholamine secretion from cultured chromaffin cells by an ionophore-mediated rise in intracellular sodium.

    Suchard, S J; Lattanzio, F A; Rubin, R W; Pressman, B C


    The significance of intracellular Na+ concentration in catecholamine secretion of cultured bovine adrenal chromaffin cells was investigated using the monovalent carboxylic ionophore monensin. This ionophore, which is known to mediate a one-for-one exchange of intracellular K+ for extracellular Na+, induces a slow, prolonged release of catecholamines which, at 6 h, amounts of 75-90% of the total catecholamines; carbachol induces a rapid pulse of catecholamine secretion of 25-35%. Although secretory granule numbers appear to be qualitatively reduced after carbachol, multiple carbachol, or Ba2+ stimulation, overall granule distribution remains similar to that in untreated cells. Monensin-stimulated catecholamine release requires extracellular Na+ but not Ca2+ whereas carbachol-stimulated catecholamine release requires extracellular Ca2+ and is partially dependent on extracellular Na+. Despite its high selectivity for monovalent ions, monensin is considerably more effective in promoting catecholamine secretion than the divalent ionophores, A23187 and ionomycin, which mediate a more direct entry of extracellular Ca2+ into the cell. We propose that the monensin-stimulated increase in intracellular Na+ levels causes an increase in the availability of intracellular Ca2+ which, in turn, stimulates exocytosis. This hypothesis is supported by the comparable stimulation of catecholamine release by ouabain which inhibits the outwardly directed Na+ pump and thus permits intracellular Na+ to accumulate. The relative magnitudes of the secretion elicited by monensin, carbachol, and the calcium ionophores, are most consistent with the hypothesis that, under normal physiological conditions, Na+ acts by decreasing the propensity of Ca2+-sequestering sites to bind the Ca2+ that enters the cell as a result of acetylcholine stimulation. PMID:7130269

  12. Calcium channels in chromaffin cells: focus on L and T types.

    Marcantoni, A; Carabelli, V; Comunanza, V; Hoddah, H; Carbone, E


    Voltage-gated Ca2+ channels (Cav) are highly expressed in the adrenal chromaffin cells of mammalian species. Besides shaping action potential waveforms, they are directly involved in the excitation-secretion coupling underlying catecholamine release and, possibly, control other Ca2+-dependent events that originate near the membrane. These functions are shared by a number of Cav channel types (L, N, P/Q, R and T) which have different structure-function characteristics and whose degree of expression changes remarkably among mammalian species. Understanding precisely the functioning of each voltage-gated Ca2+ channels is a crucial task that helps clarifying the Ca2+-dependent mechanisms controlling exocytosis during physiological and pathological conditions. In this paper, we focus on classical and new roles that L- and T-type channels play in the control of chromaffin cell excitability and neurotransmitter release. Interestingly, L-type channels are shown to be implicated in the spontaneous autorhythmicity of chromaffin cells, while T-type channels, which are absent in adult chromaffin cells, are coupled with secretion and can be recruited following long-term beta-adrenergic stimulation or chronic hypoxia. This suggests that like other cells, adrenal chromaffin cells undergo effective remodelling of membrane ion channels and cell functioning during prolonged stress conditions. PMID:18021322

  13. Effect of Twin Screw Granulator Process Parameters on Granule Attributes

    Xu, Haosheng; Sayin, Ridade; Litster, James


    Twin screw wet granulation has been considered as an efficient and effective technique of manufacturing granules (agglomerates made up of small particles) and has been widely applied in pharmaceutical industry. However, narrow granule size distributions are difficult to achieve. This study aims to elucidate the effect of process parameters such as liquid feed rate and screw configuration on the granule attributes through granule characterization. The methods used are sieve analysis (for size ...

  14. Specific insulin binding in bovine chromaffin cells; demonstration of preferential binding to adrenalin-storing cells

    Serck-Hanssen, G.; Soevik, O.


    Insulin binding was studied in subpopulations of bovine chromaffin cells enriched in adrenalin-producing cells (A-cells) or noradrenalin-producing cells (NA-cells). Binding of /sup 125/I-insulin was carried out at 15/sup 0/C for 3 hrs in the absence or presence of excess unlabeled hormone. Four fractions of cells were obtained by centrifugation on a stepwise bovine serum albumin gradient. The four fractions were all shown to bind insulin in a specific manner and the highest binding was measured in the cell layers of higher densities, containing mainly A-cells. The difference in binding of insulin to the four subpopulations of chromaffin cells seemed to be related to differences in numbers of receptors as opposed to receptor affinities. The authors conclude that bovine chromaffin cells possess high affinity binding sites for insulin and that these binding sites are mainly confined to A-cells. 24 references, 2 figures, 1 table.

  15. Analgesia Induced by Isolated Bovine Chromaffin Cells Implanted in Rat Spinal Cord

    Sagen, Jacqueline; Pappas, George D.; Pollard, Harvey B.


    Chromaffin cells synthesize and secrete several neuroactive substances, including catecholamines and opioid peptides, that, when injected into the spinal cord, induce analgesia. Moreover, the release of these substances from the cells can be stimulated by nicotine. Since chromaffin cells from one species have been shown to survive when transplanted to the central nervous system of another species, these cells are ideal candidates for transplantation to alter pain sensitivity. Bovine chromaffin cells were implanted into the subarachnoid space of the lumbar spinal region in adult rats. Pain sensitivity and response to nicotine stimulation was determined at various intervals following cell implantation. Low doses of nicotine were able to induce potent analgesia in implanted animals as early as one day following their introduction into the host spinal cord. This response could be elicited at least through the 4 months the animals were tested. The induction of analgesia by nicotine in implanted animals was dose related. This analgesia was blocked by the opiate antagonist naloxone and partially attenuated by the adrenergic antagonist phentolamine. These results suggest that the analgesia is due to the stimulated release of opioid peptides and catecholamines from the implanted bovine chromaffin cells and may provide a new therapeutic approach for the relief of pain.

  16. Dopamine receptors on adrenal chromaffin cells modulate calcium uptake and catecholamine release

    Bigornia, L.; Suozzo, M.; Ryan, K.A.; Napp, D.; Schneider, A.S.


    The presence of dopamine-containing cells in sympathetic ganglia, i.e., small, intensely fluorescent cells, has been known for some time. However, the role of dopamine as a peripheral neurotransmitter and its mechanism of action are not well understood. Previous studies have demonstrated the presence of D2 dopamine receptors on the surface of bovine adrenal chromaffin cells using radioligand binding methods and dopamine receptor inhibition of catecholamine release from perfused adrenal glands. In the present study, we provide evidence confirming a role of dopamine receptors as inhibitory modulators of adrenal catecholamine release from bovine chromaffin cell cultures and further show that the mechanism of modulation involves inhibition of stimulated calcium uptake. Apomorphine gave a dose-dependent inhibition (IC50 = 1 microM) of 45Ca2+ uptake stimulated by either nicotine (10 microM) or membrane depolarization with an elevated K+ level (60 mM). This inhibition was reversed by a series of specific (including stereospecific) dopamine receptor antagonists: haloperidol, spiperone, sulpiride, and (+)-butaclamol, but not (-)-butaclamol. In addition, the calcium channel agonist Bay K 8644 was used to stimulate uptake of 45Ca2+ into chromaffin cells, and this uptake was also inhibited by the dopamine receptor agonist apomorphine. The combined results suggest that dopamine receptors on adrenal chromaffin cells alter Ca2+ channel conductance, which, in turn, modulates catecholamine release.

  17. Voltage-independent autocrine modulation of L-type channels mediated by ATP, opioids and catecholamines in rat chromaffin cells.

    Hernández-Guijo, J M; Carabelli, V; Gandía, L; García, A G; Carbone, E


    The inhibition of L-type channels induced by either bath application of ATP, opioids and catecholamines or by endogenously released neurotransmitters was investigated in rat chromaffin cells with whole-cell recordings (5 mM Ba2+). In both cases, the L-type current, isolated pharmacologically using omega-toxin peptides and potentiated by Bay K 8644, was inhibited by approximately 50% with nearly no changes to the activation-inactivation kinetics. Inhibition was voltage independent at a wide range of potentials (-20 to +50 mV) and insensitive to depolarizing prepulses (+100 mV, 50 ms). Onset and offset of the inhibition were fast (time constants: tau(on) approximately 0.9 s, tau(off) approximately 3.6 s), indicating a rapid mechanism of channel modulation. Whether induced exogenously or from the released granules content in conditions of stopped cell superfusion, the neurotransmitter action was reversible and largely prevented by either intracellular GDP-beta-S, cell treatment with pertussis toxin or simultaneous application of P2y,2x delta/mu-opioidergic and alpha/beta-adrenergic antagonists. This suggests the existence of converging modulatory pathways by which autoreceptors-activated G-proteins reduce the activity of L-type channels through fast interactions. The autocrine inhibition of L-type currents, which was absent in superfused isolated cells, was effective on cell clusters, suggesting that L-type channels may be potently inhibited by cell exocytosis under physiological conditions resembling the intact adrenal glands. PMID:10564365

  18. Stimulation of Adrenal Chromaffin Cell Proliferation by Hypercalcemia Induced by Intravenous Infusion of Calcium Gluconate in Rats

    Isobe, Kaori; Ito, Tsuneo; Komatsu, Shun-ichiro; Asanuma, Kentaro; Fujii, Etsuko; Kato, Chie; Adachi, Kenji; Kato, Atsuhiko; Sugimoto, Tetsuro; Suzuki, Masami


    Increased incidence of adrenal pheochromocytoma is frequently encountered in rat carcinogenicity studies. In some of the studies, the finding is judged to be due to a rat-specific mechanism of carcinogenesis caused by a disturbance of calcium homeostasis. However, direct evidence that the proliferation of chromaffin cells in the adrenal medulla is induced solely by hypercalcemia is not available. In this study, calcium gluconate was intravenously infused for 7 days to rat chromaffin cells by ...

  19. Altered excitability of cultured chromaffin cells following exposure to multi-walled carbon nanotubes.

    Gavello, Daniela; Vandael, David H F; Cesa, Roberta; Premoselli, Federica; Marcantoni, Andrea; Cesano, Federico; Scarano, Domenica; Fubini, Bice; Carbone, Emilio; Fenoglio, Ivana; Carabelli, Valentina


    We studied the effects of multi-walled carbon nanotubes (MWCNTs) on the electrophysiological properties of cultured mouse chromaffin cells, a model of spontaneously firing cells. The exposure of chromaffin cells to MWCNTs at increasing concentrations (30-263 μg/ml) for 24 h reduced, in a dose-dependent way, both the cell membrane input resistance and the number of spontaneously active cells (from 80-52%). Active cells that survived from the toxic effects of MWCNTs exhibited more positive resting potentials, higher firing frequencies and unaltered voltage-gated Ca(2+), Na(+) and K+ current amplitudes. MWCNTs slowed down the inactivation kinetics of Ca(2+)-dependent BK channels. These electrophysiological effects were accompanied by MWCNTs internalization, as confirmed by transmission electron microscopy, indicating that most of the toxic effects derive from a dose-dependent MWCNTs-cell interaction that damages the spontaneous cell activity. PMID:21322767

  20. Laminin increases both levels and activity of tyrosine hydroxylase in calf adrenal chromaffin cells


    We have investigated the effects of substrate-bound laminin on levels of enzymes of the catecholamine biosynthetic pathway in primary cultures of calf adrenal chromaffin cells. Laminin increases the levels of the enzymes tyrosine hydroxylase, dopamine-beta-hydroxylase, and phenylethanolamine-N-methyl-transferase. This effect is selective, in that levels of other enzymes (lactate dehydrogenase, aromatic amino acid decarboxylase, and acetylcholinesterase) are not increased. The effect of lamini...

  1. Pannexin 1 channels: new actors in the regulation of catecholamine release from adrenal chromaffin cells

    Momboisse, Fanny; Olivares, María José; Báez-Matus, Ximena; Guerra, María José; Flores-Muñoz, Carolina; Sáez, Juan C.; Martínez, Agustín D.; Cárdenas, Ana M.


    Chromaffin cells of the adrenal gland medulla synthesize and store hormones and peptides, which are released into the blood circulation in response to stress. Among them, adrenaline is critical for the fight-or-flight response. This neurosecretory process is highly regulated and depends on cytosolic [Ca2+]. By forming channels at the plasma membrane, pannexin-1 (Panx1) is a protein involved in many physiological and pathological processes amplifying ATP release and/or Ca2+ signals. Here, we show that Panx1 is expressed in the adrenal gland where it plays a role by regulating the release of catecholamines. In fact, inhibitors of Panx1 channels, such as carbenoxolone (Cbx) and probenecid, reduced the secretory activity induced with the nicotinic agonist 1,1-dimethyl-4-phenyl-piperazinium (DMPP, 50 μM) in whole adrenal glands. A similar inhibitory effect was observed in single chromaffin cells using Cbx or 10Panx1 peptide, another Panx1 channel inhibitors. Given that the secretory response depends on cytosolic [Ca2+] and Panx1 channels are permeable to Ca2+, we studied the possible implication of Panx1 channels in the Ca2+ signaling occurring during the secretory process. In support of this possibility, Panx1 channel inhibitors significantly reduced the Ca2+ signals evoked by DMPP in single chromaffin cells. However, the Ca2+ signals induced by caffeine in the absence of extracellular Ca2+ was not affected by Panx1 channel inhibitors, suggesting that this mechanism does not involve Ca2+ release from the endoplasmic reticulum. Conversely, Panx1 inhibitors significantly blocked the DMPP-induce dye uptake, supporting the idea that Panx1 forms functional channels at the plasma membrane. These findings indicate that Panx1 channels participate in the control the Ca2+ signal that triggers the secretory response of adrenal chromaffin cells. This mechanism could have physiological implications during the response to stress. PMID:25237296

  2. Morphological aspects of chromaffin tissue: the differential fixation of adrenaline and noradrenaline.

    Kobayashi, S; Coupland, R. E.


    The morphological aspects of chromaffin tissue are reviewed, based mainly on our studies on the mouse adrenal gland. Particular attention was focused on the differential fixation of adrenaline and noradrenaline, and on the uptake and storage of [3H]dopa, [3H]dopamine and related substances in the adrenaline-storing (A) and noradrenaline-storing (NA) cells. Scanning electron microscopy combined with the NaOH-maceration method was useful for demonstrating the 3-dimensional organisation of nerve...

  3. A new diamond biosensor with integrated graphitic microchannels for detecting quantal exocytic events from chromaffin cells.

    Picollo, Federico; Gosso, Sara; Vittone, Ettore; Pasquarelli, Alberto; Carbone, Emilio; Olivero, Paolo; Carabelli, Valentina


    An MeV ion-microbeam lithographic technique can be successfully employed for the fabrication of an all-carbon miniaturized cellular biosensor based on graphitic microchannels embedded in a single-crystal diamond matrix. The device is functionally characterized for the in vitro recording of quantal exocytic events from single chromaffin cells, with high sensitivity and signal-to-noise ratio, opening promising perspectives for the realization of monolithic all-carbon cellular biosensors. PMID:23847004

  4. Cytosolic organelles shape calcium signals and exo-endocytotic responses of chromaffin cells.

    García, Antonio G; Padín, Fernando; Fernández-Morales, José C; Maroto, Marcos; García-Sancho, Javier


    The concept of stimulus-secretion coupling was born from experiments performed in chromaffin cells 50 years ago. Stimulation of these cells with acetylcholine enhances calcium (Ca(2+)) entry and this generates a transient elevation of the cytosolic Ca(2+) concentration ([Ca(2+)](c)) that triggers the exocytotic release of catecholamines. The control of the [Ca(2+)](c) signal is complex and depends on various classes of plasmalemmal calcium channels, cytosolic calcium buffers, the uptake and release of Ca(2+) from cytoplasmic organelles, such as the endoplasmic reticulum, mitochondria, chromaffin vesicles and the nucleus, and Ca(2+) extrusion mechanisms, such as the plasma membrane Ca(2+)-stimulated ATPase, and the Na(+)/Ca(2+) exchanger. Computation of the rates of Ca(2+) fluxes between the different cell compartments support the proposal that the chromaffin cell has developed functional calcium tetrads formed by calcium channels, cytosolic calcium buffers, the endoplasmic reticulum, and mitochondria nearby the exocytotic plasmalemmal sites. These tetrads shape the Ca(2+) transients occurring during cell activation to regulate early and late steps of exocytosis, and the ensuing endocytotic responses. The different patterns of catecholamine secretion in response to stress may thus depend on such local [Ca(2+)](c) transients occurring at different cell compartments, and generated by redistribution and release of Ca(2+) by cytoplasmic organelles. In this manner, the calcium tetrads serve to couple the variable energy demands due to exo-endocytotic activities with energy production and protein synthesis. PMID:22209033

  5. Calcium channel types contributing to chromaffin cell excitability, exocytosis and endocytosis.

    Mahapatra, S; Calorio, C; Vandael, D H F; Marcantoni, A; Carabelli, V; Carbone, E


    Voltage gated Ca(2+) channels are effective voltage sensors of plasma membrane which convert cell depolarizations into Ca(2+) signaling. The chromaffin cells of the adrenal medulla utilize a large number of Ca(2+) channel types to drive the Ca(2+)-dependent release of catecholamines into blood circulation, during normal or stress-induced conditions. Some of the Ca(2+) channels expressed in chromaffin cells (L, N, P/Q, R and T), however, do not control only vesicle fusion and catecholamine release. They also subserve a variety of key activities which are vital for the physiological and pathological functioning of the cell, like: (i) shaping the action potentials of electrical oscillations driven either spontaneously or by ACh stimulation, (ii) controlling the action potential frequency of tonic or bursts firing, (iii) regulating the compensatory and excess endocytosis following robust exocytosis and (iv) driving the remodeling of Ca(2+) signaling which occurs during stressors stimulation. Here, we will briefly review the well-established properties of voltage-gated Ca(2+) channels accumulated over the past three decades focusing on the most recent discoveries on the role that L- (Cav1.2, Cav1.3) and T-type (Cav3.2) channels play in the control of excitability, exocytosis and endocytosis of chromaffin cells in normal and stress-mimicking conditions. PMID:22317919

  6. Isolation of RNP granules

    Jønson, Lars; Nielsen, Finn Cilius; Christiansen, Jan


    be regarded as a supramolecular assembly of RNA and protein, probably representing several overlapping post-transcriptional operons. The present protocol describes how RNP granules may be isolated by the transgenic expression of a 3X FLAG version of an RNA-binding protein under tetracycline control...... via the tetracycline receptor/operator complex. In this way, inclusion of an appropriate tetracycline concentration ensures expression of the tagged version at the endogenous level, and the 3X FLAG tag is a convenient "handle" for the subsequent immunoprecipitation by immobilized anti-FLAG antibody....

  7. Granulation techniques and technologies: recent progresses.

    Shanmugam, Srinivasan


    Granulation, the process of particle enlargement by agglomeration technique, is one of the most significant unit operations in the production of pharmaceutical dosage forms, mostly tablets and capsules. Granulation process transforms fine powders into free-flowing, dust-free granules that are easy to compress. Nevertheless, granulation poses numerous challenges due to high quality requirement of the formed granules in terms of content uniformity and physicochemical properties such as granule size, bulk density, porosity, hardness, moisture, compressibility, etc. together with physical and chemical stability of the drug. Granulation process can be divided into two types: wet granulation that utilize a liquid in the process and dry granulation that requires no liquid. The type of process selection requires thorough knowledge of physicochemical properties of the drug, excipients, required flow and release properties, to name a few. Among currently available technologies, spray drying, roller compaction, high shear mixing, and fluid bed granulation are worth of note. Like any other scientific field, pharmaceutical granulation technology also continues to change, and arrival of novel and innovative technologies are inevitable. This review focuses on the recent progress in the granulation techniques and technologies such as pneumatic dry granulation, reverse wet granulation, steam granulation, moisture-activated dry granulation, thermal adhesion granulation, freeze granulation, and foamed binder or foam granulation. This review gives an overview of these with a short description about each development along with its significance and limitations. PMID:25901297

  8. [Research of aerobic granule characteristics with different granule age].

    Zhou, Man; Yang, Chang-Zhu; Pu, Wen-Hong; Luo, Ying-Dong; Gong, Jian-Yu


    In the SBR reactor, we studied the different style, physicochemical characteristic, pollutants removal and microbial activity between the short age and long age aerobic granule, respectively. The short age aerobic granule was cultivated from activated floccules sludge and the other was gotten from aerobic granular sludge which was operated stably more than one year. The results indicated that the wet density, the specific gravity and integrated coefficient (IC) of the short age aerobic granule were 1.066 g x cm(-1), 1.013 g x cm(-3) and 98.7%, respectively. And that of long age were 1.026 g x cm(-3), 1.010 g x cm(-3) and 98.4%, respectively. All of them were higher than the long age aerobic granule. The mean diameters of them were 1.9 mm and 2.2 mm, respectively. The settling velocity of short age and long age aerobic granule were 0.005-0.032 m x s(-1) and 0.003-0.028 m x s(-1), respectively, and two kinds of aerobic granule settling velocity increased with the diameter increased. SVI of the former was lower. The COD removal rates of two aerobic granules were above 90%, and the NH4(+) -N removal rates of them were about 85%. The results of the COD effluent concentration, NH4(+) -N effluent concentration and the pollutants concentration in a typical cycle indicated that the short age aerobic granule had better pollutants removal efficiency. The TP removal rates of them were between 40% -90% and 32% -85%, respectively. The TN removal rates of them were about 80%. The SOUR(H) SOUR(NH4) and SOUR(NO2) of the short age aerobic granule were 26.4, 14.8 and 11.2 mg x (h x g)(-1), respectively. And that of long age were 25.2, 14.4 and 8.4 mg x (h x g)(-1), respectively. In summary, the aerobic granule had significantly different physical and chemical characteristics because of different granule age, and the short age aerobic granule exhibited better pollutants removal ability, higher microbial activity and more stability than the long age aerobic granule. PMID:22624385

  9. Granulated zeolite plant "Alusil", Zvornik

    Stanković Mirjana S.


    Full Text Available The IGPC's Engineering Department designed basic technological and machine projects for a granulated zeolite production plant, on the basis of which a pilot plant with an initial capacity of 5,000 t/y was constructed in 1984, within Birač - Zvornik production complex. The technology in these projects was developed in the laboratories of the IGPC.Several goals were realized by designing a granulated zeolite production plant. This technology is one of the newest state of the art high tech technologies. The product meets all quality demands, as well as environmental regulations, by which granulated zeolite production for various uses was developed. The granulated zeolite production process is fully automatized, and the product has uniform quality. There is no waste material in granulated zeolite production, because all products with unsatisfactory quality are returned to the process. The production process can be controlled manually, which is necessary during start - up, and repairs.

  10. Functional chromaffin cell plasticity in response to stress: focus on nicotinic, gap junction, and voltage-gated Ca2+ channels.

    Guérineau, Nathalie C; Desarménien, Michel G; Carabelli, Valentina; Carbone, Emilio


    An increase in circulating catecholamines constitutes one of the mechanisms whereby human body responds to stress. In response to chronic stressful situations, the adrenal medullary tissue exhibits crucial morphological and functional changes that are consistent with an improvement of chromaffin cell stimulus-secretion coupling efficiency. Stimulus-secretion coupling encompasses multiple intracellular (chromaffin cell excitability, Ca(2+) signaling, exocytosis, endocytosis) and intercellular pathways (splanchnic nerve-mediated synaptic transmission, paracrine and endocrine communication, gap junctional coupling), each of them being potentially subjected to functional remodeling upon stress. This review focuses on three chromaffin cell incontrovertible actors, the cholinergic nicotinic receptors and the voltage-dependent T-type Ca(2+) channels that are directly involved in Ca(2+)-dependent events controlling catecholamine secretion and electrical activity, and the gap junctional communication involved in the modulation of catecholamine secretion. We show here that these three actors react differently to various stressors, sometimes independently, sometimes in concert or in opposition. PMID:22252244

  11. Transplants of immunologically isolated xenogeneic chromaffin cells provide a long-term source of pain-reducing neuroactive substances.

    Sagen, J; Wang, H; Tresco, P A; Aebischer, P


    Adrenal medullary chromaffin cells are a potential source of neuroactive substances for transplantation into the CNS to alleviate neurochemical deficits. In particular, work in our laboratory has suggested that adrenal medullary transplants in the spinal subarachnoid space can alleviate pain by providing sustained local delivery of catecholamines and opioid peptides. One of the major limitations for clinical application of neural transplantation is the availability of donor material in sufficient quantities. This limitation may be overcome by the use of xenogeneic donors if long-term graft rejection can be prevented. The purpose of this study was to assess whether xenogeneic chromaffin cells immunologically isolated by semipermeable membranes could survive and continue to reduce pain when transplanted into the CNS. Isolated bovine chromaffin cells were encapsulated by semipermeable polymer membranes and implanted into the rat spinal subarachnoid space. Pain sensitivity was assessed at several intervals up to 3 months following implantation. Results indicated that encapsulated bovine chromaffin cell implants, but not empty control capsules, could repeatedly reduce pain sensitivity with nicotine stimulation for the duration of the study. This response was dose related, indicating that pharmacologic integrity of the transplanted chromaffin cells is retained. The analgesia induced by encapsulated chromaffin cell implants could be attenuated by the opiate antagonist naloxone and the alpha-adrenergic antagonist phentolamine, suggesting the involvement of both opioid peptides and catecholamines in mediating this response. In addition, in vitro neurochemical studies of recultured capsules revealed sustained release of Met-enkephalin and catecholamines from encapsulated cells 3 months following implantation into the spinal subarachnoid space.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7684773

  12. The BAR Domain Protein PICK1 Controls Vesicle Number and Size in Adrenal Chromaffin Cells

    da Silva Pinheiro, Paulo César; Jansen, Anna M; de Wit, Heidi;


    Protein Interacting with C Kinase 1 (PICK1) is a Bin/Amphiphysin/Rvs (BAR) domain protein involved in AMPA receptor trafficking. Here, we identify a selective role for PICK1 in the biogenesis of large, dense core vesicles (LDCVs) in mouse chromaffin cells. PICK1 colocalized with syntaxin-6, a......, consistent with an upstream role for PICK1. Disrupting lipid binding of the BAR domain (2K-E mutation) or of the PDZ domain (CC-GG mutation) was sufficient to reproduce the secretion phenotype of the null mutant. The same mutations are known to eliminate PICK1 function in receptor trafficking, indicating...

  13. Granulopoiesis and granules of human neutrophils.

    Cowland, Jack B; Borregaard, Niels


    Granules are essential for the ability of neutrophils to fulfill their role in innate immunity. Granule membranes contain proteins that react to environmental cues directing neutrophils to sites of infection and initiate generation of bactericidal oxygen species. Granules are densely packed with proteins that contribute to microbial killing when liberated to the phagosome or extracellularly. Granules are, however, highly heterogeneous and are traditionally subdivided into azurophil granules, specific granules, and gelatinase granules in addition to secretory vesicles. This review will address issues pertinent to formation of granules, which is a process intimately connected to maturation of neutrophils from their precursors in the bone marrow. We further discuss possible mechanisms by which decisions are made regarding sorting of proteins to constitutive secretion or storage in granules and how degranulation of granule subsets is regulated. PMID:27558325

  14. Internal Ca2+ mobilization and secretion in bovine adrenal chromaffin cells

    Cheek, T R; Thastrup, Ole


    Since secretion from intact bovine adrenal chromaffin cells in response to depolarization by nicotine is triggered by a rise in the concentration of intracellular Ca2+ ([Ca2+]i) to about 200-300 nM above basal, it has been assumed that the failure of the inositol 1,4,5-trisphosphate (InsP3......+ store. The role of this Ca2+ store in secretion from bovine adrenal chromaffin cells is therefore unclear. In order to investigate in more detail the role of the InsP3-sensitive Ca2+ store in secretion from these cells, we have used a combination of an InsP3-mobilizing muscarinic agonist and the...... sesquiterpene lactone thapsigargin (TG), which releases internal Ca2+ without concomitant breakdown of inositol lipids or protein kinase C activation, to examine the events which follow depletion of the releasable Ca2+ store in these cells. Monitoring [Ca2+]i using Fura-2 demonstrated that TG released Ca2+ from...

  15. Congener specific effects by polychlorinated biphenyls on catecholamine content and release in chromaffin cells

    Messeri, M.D. [Medizinisches Institut fuer Umwelthygiene an der Heinrich-Heine-Univ., Duesseldorf (Germany); Bickmeyer, U. [Medizinisches Institut fuer Umwelthygiene an der Heinrich-Heine-Univ., Duesseldorf (Germany); Weinsberg, F. [Physiologisches Institut, Universitaetskrankenhaus Hamburg Eppendorf, Martinistasse 52, D-20246 Hamburg (Germany); Wiegand, H. [Medizinisches Institut fuer Umwelthygiene an der Heinrich-Heine-Univ., Duesseldorf (Germany)


    The effects of the non-planar polychlorinated biphenyl (PCB) congener 2,2`,4,4`-tetrachlorobiphenyl (2,4-TCB) and of the coplanar PCB congener 3,3`,4,4`-tetrachlorobiphenyl (3,4-TCB) were investigated on the catecholamine content and release from bovine adrenal chromaffin cells in culture. Each congener was tested at three concentrations (20, 50 and 100 {mu}M) and two exposure periods (24 h and 5 days). Catecholamine release induced by K{sup +}-stimulation as well as catecholamine content of Triton X-100 treated cell cultures were examined using high-performance liquid chromatography (HPLC). 2,4-TCB showed dose- and time-dependent effects. 2,4-TCB at 100 {mu}M reduced the K{sup +}-stimulated catecholamine release after 24 h of exposure. After 5 days of exposure, 2,4 TCB at 50 and 100 {mu}M drastically reduced the K{sup +}-stimulated catecholamine release. 3,4-TCB even at a concentration of 100 {mu}M over exposure of either 24 h or 5 days had no effects on the K{sup +}-stimulated secretion. When chromaffin cells, exposed to 2,4-TCB, were lysed with 0.5% Triton X-100, a dose- and time-dependent reduction of the catecholamine content appeared. The 3,4-TCB did not reduce the catecholamine content. Conversely there seemed to be a trend towards an increase in catecholamine content. Spontaneous release of catecholamines was strongly increased by the non-planar 2,4 TCB, while the coplanar 3,4 TCB showed no effects on this parameter. Furthermore, the effects of 2,4 TCB appeared to be reversible after replacing the highest concentration (100 {mu}M) of the TCB-solution with culture-medium at the end of the 24-h exposure. Thus, K{sup +}-stimulated catecholamine release and the catecholamine content of bovine adrenal chromaffin cells was effectively reduced by the non-planar PCB congener whereas spontaneous catecholamine release was strongly increased. The coplanar PCB congener was ineffective at the same conditions. (orig.). With 5 figs., 2 tabs.

  16. Vesicle Motion during Sustained Exocytosis in Chromaffin Cells: Numerical Model Based on Amperometric Measurements.

    Daungruthai Jarukanont

    Full Text Available Chromaffin cells release catecholamines by exocytosis, a process that includes vesicle docking, priming and fusion. Although all these steps have been intensively studied, some aspects of their mechanisms, particularly those regarding vesicle transport to the active sites situated at the membrane, are still unclear. In this work, we show that it is possible to extract information on vesicle motion in Chromaffin cells from the combination of Langevin simulations and amperometric measurements. We developed a numerical model based on Langevin simulations of vesicle motion towards the cell membrane and on the statistical analysis of vesicle arrival times. We also performed amperometric experiments in bovine-adrenal Chromaffin cells under Ba2+ stimulation to capture neurotransmitter releases during sustained exocytosis. In the sustained phase, each amperometric peak can be related to a single release from a new vesicle arriving at the active site. The amperometric signal can then be mapped into a spike-series of release events. We normalized the spike-series resulting from the current peaks using a time-rescaling transformation, thus making signals coming from different cells comparable. We discuss why the obtained spike-series may contain information about the motion of all vesicles leading to release of catecholamines. We show that the release statistics in our experiments considerably deviate from Poisson processes. Moreover, the interspike-time probability is reasonably well described by two-parameter gamma distributions. In order to interpret this result we computed the vesicles' arrival statistics from our Langevin simulations. As expected, assuming purely diffusive vesicle motion we obtain Poisson statistics. However, if we assume that all vesicles are guided toward the membrane by an attractive harmonic potential, simulations also lead to gamma distributions of the interspike-time probability, in remarkably good agreement with experiment. We

  17. Clearance of germ granules in the soma

    Sugimoto, Asako


    Germ granules are ribonucleoprotein complexes specifically segregated into germ cell lineages in diverse organisms. Recent studies indicate that multiple mechanisms are involved in the clearance of germ granules and their components in somatic cells in Caenorhabditis elegans embryos.

  18. Ultrastructure of Maize Starch Granules. A Review

    Gallant, Daniel J.; Bouchet, Brigitte


    History of starch granule ultrastructure and the principal data obtained on maize starch granules are analyzed. New results are developed: i) growth and development of the maize starch granules during maturation depend on the maize varieties and the tissue site in the kernel, especially the horny and flloury endosperms; ii) cytochemical studies of the starch granules differing from their amylose/amylopectin ratio show important differences in the distribution of their crystalline and amorph...


    Saikh Mahammed Athar Alli


    To have updated handy reference as source of outstanding knowledge on foam binder granulation process in granulating the material(s). Granulation considered being important unit operation for producing pharmaceutical oral dosage forms. Revolutionising binder application methodology as advancement of wet granulation process best owed said process. It is a modified version of atomised spraying method and gaining wide acceptance. Product and process development calls for method of optimisation i...

  20. Cultures of Cerebellar Granule Neurons



    Authors: Parizad M. Bilimoria and Azad Bonni1 Corresponding author ([]()) ### INTRODUCTION Primary cultures of granule neurons from the post-natal rat cerebellum provide an excellent model system for molecular and cell biological studies of neuronal development and function. The cerebellar cortex, with its highly organized structure and few neuronal subtypes, offers a well-characterized neural circuitry. Many fundamental insight...

  1. Variation of granule mass fraction with coordination number in wet granulation process

    Papiya Roy; Manish Vashishtha; Rajesh Khanna; Duwuri Subbarao


    In granulation, fine particles combine to form a coarse granule in the form of a particle matrix partially or fully saturated with a binder liquid. The final product of granulation possesses a wide variety of granule size distributions with surface mean diameters which differ with operating conditions. The final granule size depends on the operating conditions, e.g. operating gas velocity, inlet air temperature, initial feed particle size, and viscosity of the binder. The objective of this paper is to find out the uniformity in the relation between the granule mass fraction in the final granule size distribution and the number of feed particles present in the granules. The total number of granules obtained depends on the experimental conditions but the granule mass fraction and the number of feed particles forming a single granule are independent of operating variables, feed material and method of granulation. The paper purports further to compare the uniform nature of mass fraction of the granules in final granule size distribution and the primary particles required to form that particular granule size irrespective of experimental conditions of granulation.

  2. A new diamond biosensor with integrated graphitic microchannels for detecting quantal exocytic events from chromaffin cells

    Picollo, Federico; Vittone, Ettore; Pasquarelli, Alberto; Carbone, Emilio; Olivero, Paolo; Carabelli, Valentina


    The quantal release of catecholamines from neuroendocrine cells is a key mechanism which has been investigated with a broad range of materials and devices, among which carbon-based materials such as carbon fibers, diamond-like carbon, carbon nanotubes and nanocrystalline diamond. In the present work we demonstrate that a MeV-ion-microbeam lithographic technique can be successfully employed for the fabrication of an all-carbon miniaturized cellular bio-sensor based on graphitic micro-channels embedded in a single-crystal diamond matrix. The device was functionally characterized for the in vitro recording of quantal exocytic events from single chromaffin cells, with high sensitivity and signal-to-noise ratio, opening promising perspectives for the realization of monolithic all-carbon cellular biosensors.

  3. Rab3 proteins involved in vesicle biogenesis and priming in embryonic mouse chromaffin cells

    Schonn, Jean-Sébastien; van Weering, Jan R T; Mohrmann, Ralf;


    the size of the releasable vesicle pools but does not alter their fusion kinetics, consistent with an altered function in vesicle priming. The sustained release component has a sigmoid shape in ABCD(-/-) cells when normalized to the releasable pool size, indicating that vesicle priming follows at a...... higher rate after an initial delay. Rescue experiments showed that short-term (4-6 hours) overexpression of Rab3A or Rab3C suffices to rescue vesicle priming and secretion, but it does not restore the number of secretory vesicles. We conclude that Rab3 proteins play two distinct stimulating roles for...... LDCV fusion in embryonic chromaffin cells, by facilitating vesicle biogenesis and stabilizing the primed vesicle state....

  4. Mobilisation of store Ca2+ activates tyrosine hydroxylase in bovine adrenal chromaffin cells

    Full text: Many receptor agonists are able to activate tyrosine hydroxylase (TOH) in bovine adrenal chromaffin cells. The majority of these are dependent on extracellular Ca2+ for this action. Entry of extracellular Ca2+ through voltage-operated Ca2+ channels is very effective at activating TOH. The contribution of the intracellular Ca2+ stores to TOH activation however is not known. Previous studies have shown that mobilisation of intracellular Ca2+ stores is effective at increasing phosphorylation of TOH, but its effect on TOH activity has not been studied. Therefore, in the present study, the effect of mobilisation of store Ca2+ on TOH activity was investigated using primary cultures of bovine adrenal chromaffin cells. Cells were prepared from abattoir tissue and cultured for 3-6 days. TOH activity was determined over 10 minutes, measuring the 14CO2 produced following the hydroxylation and rapid decarboxylation of 14C-tyrosine offered to intact cells. Caffeine increased TOH activity in a concentration-dependent manner with a maximum response of 100% increase at 20mM. This effect was not due to osmolarity since 20mM sucrose had no effect.Nor was it due to inhibition of phosphodiesterases, since the effect of caffeine was still seen in the presence of 1mM IBMX. However,caffeine-induced TOH activation was substantially reduced in the absence of extracellular Ca2+. The results suggest that TOH activity can be increased by mobilising intracellular Ca2+ stores, but that this effect involves extracellular Ca2+ influx, possibly through store-operated channels. Copyright (2001) Australian Neuroscience Society

  5. Inhibition by the chromaffin cell-derived peptide serine-histogranin in the rat's dorsal horn.

    Hentall, Ian D; Hargraves, Walter A; Sagen, Jacqueline


    The heptadecapeptide histogranin, synthesized by adrenal chromaffin cells, is implicated in the analgesia produced by transplanting chromaffin cells into the spinal cord, including block of hyperalgesia mediated by NMDA-subtype glutamate receptors. To examine the neurophysiological basis for this analgesia, we applied the stable analog [Ser(1)]-histogranin (SHG) by iontophoresis near extracellularly recorded wide-dynamic range (WDR) neurons in anesthetized rats. When SHG was applied during peripheral electrical stimulation of A and C fibers at 0.1Hz, the C-fiber response was significantly inhibited but the A-fiber response was unaffected. SHG also opposed the NMDA-receptor-dependent post-tetanic facilitation (wind-up) of C-fiber responses produced by increasing the rate of peripheral afferent stimulation to 1Hz for 20s. To test whether block of NMDA-subtype receptors could be wholly or partially responsible for this suppression, SHG was applied during sequential pulsed iontophoresis of three agonists targeting distinct excitatory synaptic receptors: NMDA, kainate and substance P. All three excitatory effects were reversed by SHG; this reversal outlasted the 10-30min observation period when higher SHG doses were applied (>60nA). Histogranin therefore probably produces prolonged spinal analgesia by opposing the basal and potentiating synaptic effects of C-fibers on dorsal horn neurons. Actions besides or in addition to NMDA-receptor antagonism (e.g., agonism at inhibitory postsynaptic receptors or block of voltage-gated cation channels on C-fibers) are implied by the diversity of excitatory transmitters opposed by SHG. PMID:17442490

  6. L-type calcium channels in adrenal chromaffin cells: role in pace-making and secretion.

    Marcantoni, A; Baldelli, P; Hernandez-Guijo, J M; Comunanza, V; Carabelli, V; Carbone, E


    Voltage-gated L-type (Cav1.2 and Cav1.3) channels are widely expressed in cardiovascular tissues and represent the critical drug-target for the treatment of several cardiovascular diseases. The two isoforms are also abundantly expressed in neuronal and neuroendocrine tissues. In the brain, Cav1.2 and Cav1.3 channels control synaptic plasticity, somatic activity, neuronal differentiation and brain aging. In neuroendocrine cells, they are involved in the genesis of action potential generation, bursting activity and hormone secretion. Recent studies have shown that Cav1.2 and Cav1.3 are also expressed in chromaffin cells but their functional role has not yet been identified despite that L-type channels possess interesting characteristics, which confer them an important role in the control of catecholamine secretion during action potentials stimulation. In intact rat adrenal glands L-type channels are responsible for adrenaline and noradrenaline release following splanchnic nerve stimulation or nicotinic receptor activation. L-type channels can be either up- or down-modulated by membrane autoreceptors following distinct second messenger pathways. L-type channels are tightly coupled to BK channels and activate at relatively low-voltages. In this way they contribute to the action potential hyperpolarization and to the pace-maker current controlling action potential firings. L-type channels are shown also to regulate the fast secretion of the immediate readily releasable pool of vesicles with the same Ca(2+)-efficiency of other voltage-gated Ca(2+) channels. In mouse adrenal slices, repeated action potential-like stimulations drive L-type channels to a state of enhanced stimulus-secretion efficiency regulated by beta-adrenergic receptors. Here we will review all these novel findings and discuss the possible implication for a specific role of L-type channels in the control of chromaffin cells activity. PMID:17561252

  7. Non-Faradaic Electrochemical Detection of Exocytosis from Mast and Chromaffin Cells Using Floating-Gate MOS Transistors

    Krishna Jayant; Amit Singhai; Yingqiu Cao; Joshua B. Phelps; Manfred Lindau; David A. Holowka; Baird, Barbara A.; Edwin C. Kan


    We present non-faradaic electrochemical recordings of exocytosis from populations of mast and chromaffin cells using chemoreceptive neuron MOS (CνMOS) transistors. In comparison to previous cell-FET-biosensors, the CνMOS features control (CG), sensing (SG) and floating gates (FG), allows the quiescent point to be independently controlled, is CMOS compatible and physically isolates the transistor channel from the electrolyte for stable long-term recordings. We measured exocytosis from RBL-2H3 ...

  8. Discrete changes of cell membrane capacitance observed under conditions of enhanced secretion in bovine adrenal chromaffin cells.

    Neher, E; Marty, A.


    The capacitance of the surface membrane of small adrenal chromaffin cells was measured with patch-clamp pipettes. Continuous and discrete changes of capacitance were observed. They were interpreted as changes of surface area connected to exocytotic or endocytotic processes. Most of the measurements were performed in the "whole-cell" recording configuration [Hamill, O. P., Marty, A., Neher, E., Sakmann, B. & Sigworth, F. J. (1981) Pflügers Arch. 391, 85-100], which allows the intracellular Ca2...

  9. Stimulation of catecholamine secretion from cultured chromaffin cells by an ionophore-mediated rise in intracellular sodium


    The significance of intracellular Na+ concentration in catecholamine secretion of cultured bovine adrenal chromaffin cells was investigated using the monovalent carboxylic ionophore monensin. This ionophore, which is known to mediate a one-for-one exchange of intracellular K+ for extracellular Na+, induces a slow, prolonged release of catecholamines which, at 6 h, amounts of 75-90% of the total catecholamines; carbachol induces a rapid pulse of catecholamine secretion of 25-35%. Although secr...

  10. Process optimization for continuous extrusion wet granulation.

    Tan, Li; Carella, Anthony J; Ren, Yukun; Lo, Julian B


    Three granulating binders in high drug-load acetaminophen blends were evaluated using high shear granulation and extrusion granulation. A polymethacrylate binder enhanced tablet tensile strength with rapid disintegration in simulated gastric fluid, whereas polyvinylpyrrolidone and hydroxypropyl cellulose binders produced less desirable tablets. Using the polymethacrylate binder, the extrusion granulation process was studied regarding the effects of granulating liquid, injection rate and screw speed on granule properties. A full factorial experimental design was conducted to allow the statistical analysis of interactions between extrusion process parameters. Response variables considered in the study included extruder power consumption (screw loading), granule bulk/tapped density, particle size distribution, tablet hardness, friability, disintegration time and dissolution. PMID:20367553


    Saikh Mahammed Athar Alli


    Full Text Available To have updated handy reference as source of outstanding knowledge on foam binder granulation process in granulating the material(s. Granulation considered being important unit operation for producing pharmaceutical oral dosage forms. Revolutionising binder application methodology as advancement of wet granulation process best owed said process. It is a modified version of atomised spraying method and gaining wide acceptance. Product and process development calls for method of optimisation involving multidisciplinary activity and creates difficulties as several rudiments needed to be achievable, associated with umpteen features. Depth knowledge on process and formulation properties, monitoring granulation behaviour and its performance, is prerequisite. In this regard, information collected and presented as a handy note. Presented note will give insight on associated technicality and will assist researchers in getting optimised granule, having applicability in product evolution. This considered being offering outstanding knowledge and helping hand for getting granule with excellent feature.

  12. Nanocrystalline diamond microelectrode arrays fabricated on sapphire technology for high-time resolution of quantal catecholamine secretion from chromaffin cells.

    Carabelli, V; Gosso, S; Marcantoni, A; Xu, Y; Colombo, E; Gao, Z; Vittone, E; Kohn, E; Pasquarelli, A; Carbone, E


    The quantal release of oxidizable molecules can be successfully monitored by means of polarized carbon fiber microelectrodes (CFEs) positioned in close proximity to the cell membrane. To partially overcome certain CFE limitations, mainly related to their low spatial resolution and lack of optical transparency, we developed a planar boron-doped nanocrystalline diamond (NCD) prototype, grown on a transparent sapphire wafer. Responsiveness to applied catecholamines as well as the electrochemical and optical properties of the NCD-based device were first characterized by cyclic voltammetry and optical transmittance measurements. By stimulating chromaffin cells positioned on the device with external KCl, well-resolved quantal exocytotic events could be detected either from one NCD microelectrode, or simultaneously from an array of four microelectrodes, indicating that the chip is able to monitor secretory events (amperometric spikes) from a number of isolated chromaffin cells. Spikes detected by the planar NCD device had comparable amplitudes, kinetics and vesicle diameter distributions as those measured by conventional CFEs from the same chromaffin cell. PMID:20570501

  13. CaV1.3 as pacemaker channels in adrenal chromaffin cells: specific role on exo- and endocytosis?

    Comunanza, Valentina; Marcantoni, Andrea; Vandael, David H; Mahapatra, Satyajit; Gavello, Daniela; Carabelli, Valentina; Carbone, Emilio


    Voltage-gated L-type calcium channels (LTCCs) are expressed in adrenal chromaffin cells. Besides shaping the action potential (AP), LTCCs are involved in the excitation-secretion coupling controlling catecholamine release and in Ca (2+) -dependent vesicle retrieval. Of the two LTCCs expressed in chromaffin cells (CaV1.2 and CaV1.3), CaV1.3 possesses the prerequisites for pacemaking spontaneously firing cells: low-threshold, steep voltage-dependence of activation and slow inactivation. By using CaV1 .3 (-/-) KO mice and the AP-clamp it has been possible to resolve the time course of CaV1.3 pacemaker currents, which is similar to that regulating substantia nigra dopaminergic neurons. In mouse chromaffin cells CaV1.3 is coupled to fast-inactivating BK channels within membrane nanodomains and controls AP repolarization. The ability to carry subthreshold Ca (2+) currents and activate BK channels confers to CaV1.3 the unique feature of driving Ca (2+) loading during long interspike intervals and, possibly, to control the Ca (2+) -dependent exocytosis and endocytosis processes that regulate catecholamine secretion and vesicle recycling. PMID:21084859

  14. The Effect of the Chopper on Granules from Wet High-Shear Granulation Using a PMA-1 Granulator

    Briens, Lauren; Logan, Ryan


    Chopper presence and then chopper speed was varied during wet high shear granulation of a placebo formulation using a PMA-1 granulator while also varying the impeller speed. The granules were extensively analyzed for differences due to the chopper. The effect of the chopper on the granules varied with impeller speed from no effect at a low impeller speed of 300 rpm to flow interruptions at an impeller speed of 700 rpm to minimal impact at very high impeller speeds as caking at the bowl perime...

  15. The extrusion properties of potato granules

    Kooi, Eng Teong


    Potato granules from different sources were found, on extrusion, to produce potato snacks of variable quality. In some instances strip formation was unsatisfactory, in other instances blistering of the snack occurred on frying. In total, about 20-25 batches of potato granules were examined and classified in relation to these two phenomena. The amylose/amylopectin ratios of these samples of potato granules were determined by the semi-micro potentiometric iodine titration technique, but it was ...

  16. Stress granules, P-bodies and cancer

    Anderson, Paul; Kedersha, Nancy; Ivanov, Pavel


    Cancer cells are exposed to adverse conditions in the tumor microenvironment, and utilize post-transcriptional control mechanisms to re-program gene expression in ways that enhance cell survival. Stress granules and processing bodies are RNA-containing granules that contribute to this process by modulating cellular signaling pathways, metabolic machinery, and stress response programs. This review examines evidence implicating RNA granules in the pathogenesis of cancer and discusses their pote...

  17. Medical image of the week: granulation tissue

    Ganesh A


    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.

  18. Brevenal inhibits pacific ciguatoxin-1B-induced neurosecretion from bovine chromaffin cells.

    César Mattei

    Full Text Available Ciguatoxins and brevetoxins are neurotoxic cyclic polyether compounds produced by dinoflagellates, which are responsible for ciguatera and neurotoxic shellfish poisoning (NSP respectively. Recently, brevenal, a natural compound was found to specifically inhibit brevetoxin action and to have a beneficial effect in NSP. Considering that brevetoxin and ciguatoxin specifically activate voltage-sensitive Na+ channels through the same binding site, brevenal has therefore a good potential for the treatment of ciguatera. Pacific ciguatoxin-1B (P-CTX-1B activates voltage-sensitive Na+ channels and promotes an increase in neurotransmitter release believed to underpin the symptoms associated with ciguatera. However, the mechanism through which slow Na+ influx promotes neurosecretion is not fully understood. In the present study, we used chromaffin cells as a model to reconstitute the sequence of events culminating in ciguatoxin-evoked neurosecretion. We show that P-CTX-1B induces a tetrodotoxin-sensitive rise in intracellular Na+, closely followed by an increase in cytosolic Ca2+ responsible for promoting SNARE-dependent catecholamine secretion. Our results reveal that brevenal and beta-naphtoyl-brevetoxin prevent P-CTX-1B secretagogue activity without affecting nicotine or barium-induced catecholamine secretion. Brevenal is therefore a potent inhibitor of ciguatoxin-induced neurotoxic effect and a potential treatment for ciguatera.

  19. MiR-124 is differentially expressed in derivatives of the sympathoadrenal cell lineage and promotes neurite elongation in chromaffin cells.

    Shtukmaster, Stella; Narasimhan, Priyanka; El Faitwri, Tehani; Stubbusch, Jutta; Ernsberger, Uwe; Rohrer, Hermann; Unsicker, Klaus; Huber, Katrin


    The neural-crest-derived sympathoadrenal cell lineage gives rise to sympathetic neurons and to endocrine chromaffin cells of the adrenal medulla. Both cell types express a largely overlapping set of genes, including those coding for the molecular machinery related to the synthesis and exocytotic release of catecholamines. During their early development, sympathetic neurons and chromaffin cells rely on a shared transcription factor network that controls the establishment of these common features. Despite many similarities, mature sympathetic neurons and chromaffin cells significantly differ regarding their morphology and function. Most prominently, sympathetic neurons possess axons that are absent in mammalian adrenal chromaffin cells. The molecular mechanism underlying the divergent development of sympathoadrenal cells into neuronal and endocrine cells remains elusive. Mutational inactivation of the ribonuclease dicer hints at the importance of microRNAs in this diversification. We show here that miR-124 is detectable in developing sympathetic neurons but absent in chromaffin cell precursors. We further demonstrate that miR-124 promotes neurite elongation when transfected into cultured chromaffin cells indicating its capability to support the establishment of a neuronal morphology in non-neuronal sympathoadrenal cells. Our results also show that treatment of PC12 cells with the neurotrophin nerve growth factor leads to an upregulation of miR-124 expression and that inhibition of miR-124 reduces nerve-growth-factor-induced neurite outgrowth in PC12 cells. Thus, our data indicate that miR-124 contributes to the establishment of specific neuronal features in developing sympathoadrenal cells. PMID:27094431

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

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


    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 of...... binder distribution within granules produced via twin screw granulation in order to investigate if an inhomogeneous spread of binder is causing this bimodal size distribution. Theophylline-lactose-polyvinylpyrrolidone K30 (PVP) (30-67.5-2.5%, w/w) was used as a model formulation. The intra...

  1. Effects of inorganic mercury (Hg{sup 2+}) on calcium channel currents and catecholamine release from bovine chromaffin cells

    Weinsberg, F. [Medical Inst. of Environmental Hygiene, Heinrich Heine University, Duesseldorf (Germany); Bickmeyer, U. [Medical Inst. of Environmental Hygiene, Heinrich Heine University, Duesseldorf (Germany); Wiegand, H. [Medical Inst. of Environmental Hygiene, Heinrich Heine University, Duesseldorf (Germany)


    The effects of Hg{sup 2+} on calcium channel currents and the potassium-evoked catecholamine release of bovine chromaffin cells in culture were examined. The effects of Cd{sup 2+} were studied for comparison. Calcium channel currents were recorded in the whole-cell configuration of the patch-clamp technique. In a concentration of 100 {mu}M, Hg{sup 2+} blocked the currents completely; 100 {mu}M Cd{sup 2+} had the same effect. Potassium-evoked catecholamine release from chromaffin cells was measured at different timepoints with HPLC under control conditions and in the presence of different Hg{sup 2+} concentrations. Low Hg{sup 2+} concentrations (0.1 and 1 {mu}M) did not affect the amount of the catecholamines epinephrine (E) and norepinephrine (NE) which was released. Under identical conditions 1 {mu}M Cd{sup 2+} also had no effect on release. With 10 {mu}M Hg{sup 2+} there was a time-dependent increase in the potassium-evoked catecholamine release (by 27% after 8 min). The E/NE ratio was not altered. In contrast to this, the release was slightly reduced with 10 {mu}M Cd{sup 2+}. In the presence of 100 {mu}M Hg{sup 2+}, there was a reduction of the release during an early phase, followed by an increase. The calcium channel block by 100 {mu}M Cd{sup 2+} also reduced the release significantly. Catecholamine release of bovine chromaffin cells is driven into two opposite directions by Hg{sup 2+}. On the one hand, a calcium channel block reduces the release, while on the other hand effects occur which can increase the release. Both tendencies occur simultaneously, but have different concentration- and time-dependencies. The catecholamine output at a given timepoint reflects the `sum` of these different effects. (orig.)

  2. Characterization of a novel, hydrophilic dihydropyridine, NKY-722, as a Ca2+ antagonist in bovine cultured adrenal chromaffin cells.

    Ohue, T.; Lee, K; Koshimura, K.; Miwa, S


    1. To characterize NKY-722, a novel hydrophilic dihydropyridine derivative, as a Ca2+ antagonist, we examined its effects on 45Ca2+ influx, intracellular free Ca2+ concentrations [( Ca2+]i), and release of noradrenaline and adrenaline in bovine cultured adrenal chromaffin cells. 2. NKY-722 had little effect on basal 45Ca2+ influx into the resting cells, but inhibited high K+ (35.9 mM)-evoked 45Ca2+ influx in a concentration-dependent manner with an IC50 value of 5.2 nM. 3. NKY-722 inhibited h...

  3. Effects of opioid peptides and morphine on histamine-induced catecholamine secretion from cultured, bovine adrenal chromaffin cells.

    Livett, B. G.; Marley, P. D.


    The effect of opioid peptides and morphine on histamine-induced catecholamine secretion has been studied in monolayer cultures of dispersed, bovine adrenal chromaffin cells. Histamine-induced a dose-dependent secretion of both adrenaline and noradrenaline with a threshold dose of approximately 5 nM, an EC50 of 150 nM and maximal secretion at 10 microM. Catecholamine secretion induced by 1 microM histamine was completely dependent on extracellular calcium, was inhibited in a dose-dependent man...

  4. MRI feature of dural sinus arachnoid granulations

    Objective: To evaluate the MRI feature of dural sinus arachnoid granulations. Methods: All of the brain MRI studies in 2010 were retrospectively analyzed with emphasis on the distribution, size and signal characteristics of dural sinus arachnoid granulations. Results: Superior sagittal sinus was the most location followed by transverse sinus, straight sinus, and sigmoid sinus. The size ranged from 2 mm to 16 mm with the majority smaller than 8 mm in diameter. All of arachnoid granulations were hypointense on T1WI and FLAIR-weighted images slightly higher than cerebrospinal fluid, hyperintense on T2WI slightly lower than cerebrospinal fluid. Most of them did not enhance with contrast with the larger ones showing punctate or linear enhancement. Filling defects were seen on cerebral MRV. Conclusion: MRI characteristics of arachnoid granulations are reliable for distinguishing arachnoid granulations from other lesions of dural sinus. (authors)

  5. Electrochemical performance of granulated titania nanoparticles

    Wilhelm, O.; Pratsinis, S. E.; de Chambrier, E.; Crouzet, M.; Exnar, I.

    The electrochemical performance of Li-ion insertion into electrodes made of various sizes of anatase titania nanoparticles embedded in larger granulated entities (1-10 μm) is investigated. The granules are formed by spray drying of a suspension containing titania nanoparticles made by hydrolyzing titanium tetraisopropoxide (TTIP). Depending on the three process steps, i.e. hydrolysis-condensation, hydrothermal processing and spray drying, different properties for the electrode made from these granules can be achieved in terms of phase composition, specific surface area (SSA) and specific charge capacity. Hydrothermally processed (HP) particles are more resistant to calcination than sol-gel precipitated (SGP) ones and have a higher SSA which leads to a better performance with respect to specific charge capacity. Electrodes made from granulated nanoparticles have superior specific charge capacity than from non-granulated ones as the former have more inter-particle contacts.

  6. Dry reprocessing MOX granules: DMOXG

    In DMOXG (Dry reprocessing of Mixed-OXide Granule), spent fuels are to be dissolved in molten salt (NaCl-2CsCl, 650degC) and to be electrolysed to eliminate and recover noble FP metals before the main process of fuel treatment. The U and Pu, after oxidized by chlorine and oxygen gas, will be recovered as oxides to fabricate MOX fuels. Compared to Purex process which has been adopted in Japan as a first generation of reprocessing plant, DMOXG process as a next generation will be simple and compact in design with an expected lower cost of construction. This will be favorable to Japan as a seismically active country. The paper pursues (1) compact facility, (2) reduction of low level wastes, (3) the same level of safety as Purex process and compares the relevant important techniques which appear in future development with already established techniques in Purex process. (S. Ohno)

  7. NP04634 prevents cell damage caused by calcium overload and mitochondrial disruption in bovine chromaffin cells.

    Valero, Teresa; del Barrio, Laura; Egea, Javier; Cañas, Noelia; Martínez, Ana; García, Antonio G; Villarroya, Mercedes; López, Manuela G


    Marine sponges are becoming a rich source of potential new medicines. NP04634 is a synthetic derivative of 11,19 dideoxyfistularin, a natural product of the Mediterranean sponge Aplysina cavernicola. We report the cytoprotective effects of this new compound in isolated bovine chromaffin cells exposed to cytotoxic stimuli that have been related to neuronal cell death, i.e. Ca(2+) overload and mitochondrial dysfunction. Cell death was achieved by: (i) causing Ca(2+) overload through voltage-dependent calcium channels by exposing the cells to 30 mM K(+), 5 mM Ca(2+) plus 0.3 microM FPL64176 (an L-type Ca(2+)-channel activator); (ii) incubating the cells with veratridine, causing cytosolic Ca(2+) concentration ([Ca(2+)](c)) oscillations and mitochondrial disruption; and (iii) blocking mitochondrial complexes I and V using a combination of 30 microM rotenone and 10 microM oligomycin. At 10 microM, NP04634 caused significant protection against 30K(+)/5Ca(2+)/FPL-induced toxicity. NP04634 caused a concentration-dependent reduction in [Ca(2+)](c) induced by 70 mM K(+) in cells loaded with Fluo-4; maximum blockade was 67% at 30 microM. Veratridine caused continuous [Ca(2+)](c) oscillations that translated into 43.4+/-2% cell death. In this model, NP04634 caused 42% and 67% protection at 3 and 10 microM, respectively. NP04634 reduced [Ca(2+)](c) oscillations and mitochondrial depolarization caused by veratridine. NP04634 at 10 microM also protected against mitochondrial disruption caused by rotenone plus oligomycin. In conclusion, NP04634 is a novel compound of marine origin with cytoprotective properties that might have potential therapeutic implications under pathological circumstances involving Ca(2+) overload and mitochondrial disruption, such as in certain neurodegenerative diseases and/or stroke. PMID:19233161

  8. Trifluoperazine reduces inward ionic currents and secretion by separate mechanisms in bovine chromaffin cells.

    Clapham, D E; Neher, E


    Using patch-clamp techniques, excitation and secretion in chromaffin cells were studied by measurement of unitary inward currents and of stimulus-evoked increments in membrane capacitance. The effect of the calmodulin inhibitor trifluoperazine (TFP) on Na, Ca and acetylcholine-induced (ACh) currents as well as on capacitance increments was investigated. TFP in concentrations up to 10 microM had no effect on Na channel currents. TFP was a potent anticholinergic agent. TFP in concentrations of 100 nM-1 microM decreased net ACh-induced currents by a slow block or allosteric modification of the channel. The effect was only partially reversible. Recovery from desensitization was retarded in direct relation to [TFP]. At the single channel level, TFP was found to slightly shorten open times in 0.5 and 20 microM-ACh. As reported previously, desensitization can be modelled by at least two desensitized states, as reflected by the bursting and clustering behaviour of single channels. TFP shortened clusters mainly by reducing the number of bursts per cluster. Whole-cell Ca currents (ICa) were reduced in 10 microM-TFP from an average of 29 microA cm-2-13 microA cm-2. Changes in capacitance of 1-200 fF were elicited in controls by maximal activation of the Ca current. We interpreted these steps to be the summed result of many exocytotic vesicular fusion events. Capacitance steps depended on ICa and were absent when extracellular Ca was removed. Application of 10 microM-TFP inhibited capacitance steps. The block of capacitance steps by TFP was shown to be independent of the reduction of ACh and Ca inward ionic currents. We conclude that the prevention of exocytosis by TFP is not completely described by its inhibition of electrical excitability but also results from intracellular actions. PMID:6090644

  9. Asthma pregnancy alters postnatal development of chromaffin cells in the rat adrenal medulla.

    Xiu-Ming Wu

    Full Text Available BACKGROUND: Adrenal neuroendocrine plays an important role in asthma. The activity of the sympathoadrenal system could be altered by early life events. The effects of maternal asthma during pregnancy on the adrenal medulla of offspring remain unknown. METHODOLOGY/PRINCIPAL FINDINGS: This study aims to explore the influence of maternal asthma during pregnancy on the development and function of adrenal medulla in offspring from postnatal day 3 (P3 to postnatal day 60 (P60. Asthmatic pregnant rats (AP, nerve growth factor (NGF-treated pregnant rats (NP and NGF antibody-treated pregnant rats (ANP were sensitized and challenged with ovalbumin (OVA; NP and ANP were treated with NGF and NGF antibody respectively. Offspring rats from the maternal group were divided into four groups: offspring from control pregnant rats (OCP, offspring from AP (OAP, offspring from NP (ONP, and offspring from ANP (OANP. The expressions of phenylethanolamine N-methyltransferase (PNMT protein in adrenal medulla were analyzed. The concentrations of epinephrine (EPI, corticosterone and NGF in serum were measured. Adrenal medulla chromaffin cells (AMCC were prone to differentiate into sympathetic nerve cells in OAP and ONP. Both EPI and PNMT were decreased in OAP from P3 to P14, and then reached normal level gradually from P30 to P60, which were lower from birth to adulthood in ONP. Corticosterone concentration increased significantly in OAP and ONP. CONCLUSION/SIGNIFICANCE: Asthma pregnancy may promote AMCC to differentiate into sympathetic neurons in offspring rats and inhibit the synthesis of EPI, resulting in dysfunction of bronchial relaxation.

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

    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

  11. Analysis of the release process of phenylpropanolamine hydrochloride from ethylcellulose matrix granules V. Release properties of ethylcellulose layered matrix granules.

    Fukui, Atsuko; Fujii, Ryuta; Yonezawa, Yorinobu; Sunada, Hisakazu


    In the pharmaceutical preparation of a controlled release drug, it is very important and necessary to understand the release properties. In previous papers, a combination of the square-root time law and cube-root law equations was confirmed to be a useful equation for qualitative treatment. It was also confirmed that the combination equation could analyze the release properties of layered granules as well as matrix granules. The drug release property from layered granules is different from that of matrix granules. A time lag occurs before release, and the entire release property of layered granules was analyzed using the combination of the square-root time law and cube-root law equations. It is considered that the analysis method is very useful and efficient for both matrix and layered granules. Comparing the granulation methods, it is easier to control the manufacturing process by tumbling granulation (method B) than by tumbling-fluidized bed granulation (method C). Ethylcellulose (EC) layered granulation by a fluidized bed granulator might be convenient for the preparation of controlled release dosage forms as compared with a tumbling granulator, because the layered granules prepared by the fluidized bed granulator can granulate and dry at the same time. The time required for drying by the fluidized bed granulator is shorter than that by the tumbling granulator, so the fluidized bed granulator is convenient for preparation of granules in handling and shorter processing time than the tumbling granulator. It was also suggested that the EC layered granules prepared by the fluidized bed granulator were suitable for a controlled release system as well as the EC matrix granules. PMID:18379102

  12. Non-Faradaic Electrochemical Detection of Exocytosis from Mast and Chromaffin Cells Using Floating-Gate MOS Transistors.

    Jayant, Krishna; Singhai, Amit; Cao, Yingqiu; Phelps, Joshua B; Lindau, Manfred; Holowka, David A; Baird, Barbara A; Kan, Edwin C


    We present non-faradaic electrochemical recordings of exocytosis from populations of mast and chromaffin cells using chemoreceptive neuron MOS (CνMOS) transistors. In comparison to previous cell-FET-biosensors, the CνMOS features control (CG), sensing (SG) and floating gates (FG), allows the quiescent point to be independently controlled, is CMOS compatible and physically isolates the transistor channel from the electrolyte for stable long-term recordings. We measured exocytosis from RBL-2H3 mast cells sensitized by IgE (bound to high-affinity surface receptors FcεRI) and stimulated using the antigen DNP-BSA. Quasi-static I-V measurements reflected a slow shift in surface potential () which was dependent on extracellular calcium ([Ca]o) and buffer strength, which suggests sensitivity to protons released during exocytosis. Fluorescent imaging of dextran-labeled vesicle release showed evidence of a similar time course, while un-sensitized cells showed no response to stimulation. Transient recordings revealed fluctuations with a rapid rise and slow decay. Chromaffin cells stimulated with high KCl showed both slow shifts and extracellular action potentials exhibiting biphasic and inverted capacitive waveforms, indicative of varying ion-channel distributions across the cell-transistor junction. Our approach presents a facile method to simultaneously monitor exocytosis and ion channel activity with high temporal sensitivity without the need for redox chemistry. PMID:26686301

  13. Dynamin-2 regulates fusion pore expansion and quantal release through a mechanism that involves actin dynamics in neuroendocrine chromaffin cells.

    Arlek M González-Jamett

    Full Text Available Over the past years, dynamin has been implicated in tuning the amount and nature of transmitter released during exocytosis. However, the mechanism involved remains poorly understood. Here, using bovine adrenal chromaffin cells, we investigated whether this mechanism rely on dynamin's ability to remodel actin cytoskeleton. According to this idea, inhibition of dynamin GTPase activity suppressed the calcium-dependent de novo cortical actin and altered the cortical actin network. Similarly, expression of a small interfering RNA directed against dynamin-2, an isoform highly expressed in chromaffin cells, changed the cortical actin network pattern. Disruption of dynamin-2 function, as well as the pharmacological inhibition of actin polymerization with cytochalasine-D, slowed down fusion pore expansion and increased the quantal size of individual exocytotic events. The effects of cytochalasine-D and dynamin-2 disruption were not additive indicating that dynamin-2 and F-actin regulate the late steps of exocytosis by a common mechanism. Together our data support a model in which dynamin-2 directs actin polymerization at the exocytosis site where both, in concert, adjust the hormone quantal release to efficiently respond to physiological demands.

  14. Differentiation in neuroblastoma: diffusion-limited hypoxia induces neuro-endocrine secretory protein 55 and other markers of a chromaffin phenotype.

    Fredrik Hedborg

    Full Text Available BACKGROUND: Neuroblastoma is a childhood malignancy of sympathetic embryonal origin. A high potential for differentiation is a hallmark of neuroblastoma cells. We have previously presented data to suggest that in situ differentiation in tumors frequently proceeds along the chromaffin lineage and that decreased oxygen (hypoxia plays a role in this. Here we explore the utility of Neuro-Endocrine Secretory Protein 55 (NESP55, a novel member of the chromogranin family, as a marker for this process. METHODOLOGY/PRINCIPAL FINDINGS: Immunohistochemical analyses and in situ hybridizations were performed on human fetal tissues, mouse xenografts of human neuroblastoma cell lines, and on specimens of human neuroblastoma/ganglioneuroma. Effects of anaerobic exposure on gene expression by cultured neuroblastoma cells was analyzed with quantitative real-time PCR. Fetal sympathetic nervous system expression of NESP55 was shown to be specific for chromaffin cell types. In experimental and clinical neuroblastoma NESP55 immunoreactivity was specific for regions of chronic hypoxia. NESP55 expression also correlated strikingly with morphological evidence of differentiation and with other chromaffin-specific patterns of gene expression, including IGF2 and HIF2α. Anaerobic culture of five neuroblastoma cell lines resulted in an 18.9-fold mean up-regulation of NESP55. CONCLUSIONS/SIGNIFICANCE: The data confirms that chronic tumor hypoxia is a key microenvironmental factor for neuroblastoma cell differentiation, causing induction of chromaffin features and NESP55 provides a reliable marker for this neuronal to neuroendocrine transition. The hypoxia-induced phenotype is the predominant form of differentiation in stroma-poor tumors, while in stroma-rich tumors the chromaffin phenotype coexists with ganglion cell-like differentiation. The findings provide new insights into the biological diversity which is a striking feature of this group of tumors.

  15. The evolution of granule fracture strength as a function of impeller tip speed and granule size for a novel reverse-phase wet granulation process.

    Wade, J B; Martin, G P; Long, D F


    The feasibility of a novel reverse-phase wet granulation process has been established previously and several potential advantages over the conventional process have been highlighted (Wade et al., 2014a,b,b). Due to fundamental differences in the growth mechanism and granule consolidation behaviour between the two processes the reverse-phase approach generally formed granules with a greater mass mean diameter and a lower intragranular porosity than those formed by the conventional granulation process under the same liquid saturation and impeller tip speed conditions. The lower intragranular porosity was hypothesised to result in an increase in the granule strength and subsequent decrease in tablet tensile strength. Consequently, the aim of this study was to compare the effect of impeller tip speed and granule size on the strength and compaction properties of granules prepared using both the reverse-phase and conventional granulation processes. For the conventional granulation process an increase in the impeller tip speed from 1.57 to 4.71 ms(-1) (200-600 RPM) resulted in an increase in the mean granule strength (pimpeller tip speed had no effect (p>0.05) on mean granule strength whereas, like the conventional process, an increase in granule size fraction from 425-600 to 2000-3350 μm resulted in a decrease (p0.05) for either granulation approach. These data support the rejection of the original hypothesis which stated that an increase in granule strength may result in a decrease in the tablet tensile strength. The similar tablet tensile strength observed between the conventional and reverse-phase granulation processes indicated that while mechanistic differences exist in the formation of the granules, which resulted in significant granule-scale fracture strength differences, the granule compaction properties at pharmaceutically relevant tableting pressures were unaffected. PMID:25888799

  16. A Granule Model for Evaluating Adhesion of Pharmaceutical Binders

    Hossein Orafai


    Granule capability is defined in terms of the strength of individual granule and friability of granulation batch to withstand breaking, abrasion and compactibility. Binder(s) are added to perform the above properties .The common methods to asses their capability are to test crushing strength of the granules directly and to make statistical analysis and /or testing the friability of bulk granulation. In this work four substrate models including polymethylmetacrylate beads(PMMA),glass powder, a...

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

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


    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 as a manufactu......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 as a...... manufacturing method for cocrystal granules on a batch scale. Furthermore, the cocrystal granules were characterized regarding their mechanical properties as well as their dissolution behavior. High-shear wet granulation was found to be a feasible manufacturing method for cocrystal granules. Cocrystal formation...... depended on the exposure time of the solids to the granulation liquid (water), the amount of liquid, the impeller speed of the granulator, and on the excipients (hydroxyl propylcellulose, microcrystalline cellulose, calcium hydrogenphosphate) used in the formulation. Storage stability was strongly...

  18. Heterogeneous distribution of exocytotic microdomains in adrenal chromaffin cells resolved by high-density diamond ultra-microelectrode arrays.

    Gosso, Sara; Turturici, Marco; Franchino, Claudio; Colombo, Elisabetta; Pasquarelli, Alberto; Carbone, Emilio; Carabelli, Valentina


    Here we describe the ability of a high-density diamond microelectrode array targeted to resolve multi-site detection of fast exocytotic events from single cells. The array consists of nine boron-doped nanocrystalline diamond ultra-microelectrodes (9-Ch NCD-UMEA) radially distributed within a circular area of the dimensions of a single cell. The device can be operated in voltammetric or chronoamperometric configuration. Sensitivity to catecholamines, tested by dose-response calibrations, set the lowest detectable concentration of adrenaline to ∼5 μm. Catecholamine release from bovine or mouse chromaffin cells could be triggered by electrical stimulation or external KCl-enriched solutions. Spikes detected from the cell apex using carbon fibre microelectrodes showed an excellent correspondence with events measured at the bottom of the cell by the 9-Ch NCD-UMEA, confirming the ability of the array to resolve single quantal secretory events. Subcellular localization of exocytosis was provided by assigning each quantal event to one of the nine channels based on its location. The resulting mapping highlights the heterogeneous distribution of secretory activity in cell microdomains of 12-27 μm2. In bovine chromaffin cells, secretion was highly heterogeneous with zones of high and medium activity in 54% of the cell surface and zones of low or no activity in the remainder. The 'non-active' ('silent') zones covered 24% of the total and persisted for 6-8 min, indicating stable location. The 9-Ch NCD-UMEA therefore appears suitable for investigating the microdomain organization of neurosecretion with high spatial resolution. PMID:24879870

  19. Denitrification in USB reactor with granulated biomass.

    Pagácová, P; Galbová, K; Drtil, M; Jonatová, I


    Denitrification of low concentrations of NO(3)-N (20 mg L(-1)), with methanol as an organic carbon source (COD:NO(3)-N=6) in laboratory upflow sludge bed reactor (USB), was tested as a possibility for wastewater post-treatment. By gradual increase of volumetric loading (Bv) and hydraulic loading (gamma), anoxic biomass spontaneously granulated out even from flocculate activated sludge and from anaerobic granulated sludge as well. Anaerobic granulated biomass derived from high-rate anaerobic IC reactor was a far better inoculum for anoxic granulation and for denitrification in the USB reactor. The maximum level of Bv and gamma was remarkably higher with the use of anaerobic granulated inoculum, (19-22 kg COD m(-3)d(-1); 3.2-3.7 kg NO(3)-Nm(-3)d(-1); 2.8-3.2m(3)m(-2)h(-1); SVI=15 mL g(-1)) in comparison to inoculum from flocculate activated sludge (4.2-8.1 kg CO Dm(-3)d(-1); 0.7-1.4 kg NO(3)-Nm(-3)d(-1); 0.7-1.15m(3)m(-2)h(-1); SVI=40-95 mL g(-1)). PMID:19716692

  20. Formation of volutin granules in Corynebacterium glutamicum.

    Pallerla, Srinivas Reddy; Knebel, Sandra; Polen, Tino; Klauth, Peter; Hollender, Juliane; Wendisch, Volker F; Schoberth, Siegfried M


    Volutin granules are intracellular storages of complexed inorganic polyphosphate (poly P). Histochemical staining procedures differentiate between pathogenic corynebacteria such as Corynebacterum diphtheriae (containing volutin) and non-pathogenic species, such as C. glutamicum. Here we report that strains ATCC13032 and MH20-22B of the non-pathogenic C. glutamicum also formed subcellular entities (18-37% of the total cell volume) that had the typical characteristics of volutin granules: (i) volutin staining, (ii) green UV fluorescence when stained with 4',6-diamidino-2-phenylindole, (iii) electron-dense and rich in phosphorus when determined with transmission electron microscopy and X-ray microanalysis, and (iv) 31P NMR poly P resonances of isolated granules dissolved in EDTA. MgCl2 addition to the growth medium stimulated granule formation but did not effect expression of genes involved in poly P metabolism. Granular volutin fractions from lysed cells contained polyphosphate glucokinase as detected by SDS-PAGE/MALDI-TOF, indicating that this poly P metabolizing enzyme is present also in intact poly P granules. The results suggest that formation of volutin is a more widespread phenomenon than generally accepted. PMID:15668011

  1. Microelectrode arrays of diamond-insulated graphitic channels for real time detection of exocytotic events from cultured chromaffin cells and slices of adrenal glands

    Picollo, F; Bernardi, E; Marcantoni, A; Pasquarelli, A; Carbone, E; Olivero, P; Carabelli, V


    A microstructured graphitic 4x4 multielectrode array was embedded in a single crystal diamond substrate (4x4 {uG-SCD MEA) for real-time monitoring of exocytotic events from cultured chromaffin cells and adrenal slices. The current approach relies on the development of a parallel ion beam lithographic technique, which assures the time effective fabrication of extended arrays with reproducible electrode dimensions. The reported device is suitable for performing amperometric and voltammetric recordings with high sensitivity and temporal resolution, by simultaneously acquiring data from 16 rectangularly shaped microelectrodes (20x3.5 um^2) separated by 200 um gaps. Taking advantage of the array geometry we addressed the following specific issues: i) detect both the spontaneous and KCl-evoked secretion simultaneously from several chromaffin cells directly cultured on the device surface, ii) resolve the waveform of different subsets of exocytotic events, iii) monitoring quantal secretory events from thin slices of ...

  2. 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...

  3. Arachnoid granulation affected by subarachnoid hemorrhage

    R.P. Chopard


    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.

  4. Mitochondrial RNA granules: Compartmentalizing mitochondrial gene expression.

    Jourdain, Alexis A; Boehm, Erik; Maundrell, Kinsey; Martinou, Jean-Claude


    In mitochondria, DNA replication, gene expression, and RNA degradation machineries coexist within a common nondelimited space, raising the question of how functional compartmentalization of gene expression is achieved. Here, we discuss the recently characterized "mitochondrial RNA granules," mitochondrial subdomains with an emerging role in the regulation of gene expression. PMID:26953349

  5. 21 CFR 520.1468 - Naproxen granules.


    ... 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...

  6. Simulation of the spray drying of single granules: The correlation between microscopic forces and granule morphology

    Breinlinger, T.; Hashibon, A.; Kraft, T


    In the ceramic industry, spray drying is an important process transforming fine primary powder into processable granular material. Granule formation at spray drying has been investigated in the past and plausible explanatory models have been established for the governing mechanisms of granule formation. In this study, we use numerical modeling via coupled discrete element method and computational fluid dynamics simulations to investigate this formation process. The focus lies on the evolution...

  7. In planta modification of potato starch granule biogenesis by different granule-bound fusion proteins

    Nazarian, F.


    Starch is composed of amylose and amylopectin and it is deposited in amyloplasts/choloroplasts as semi-crystalline granules. Many biosynthetic enzymes are involved in starch degradation and biosynthesis. Some microbial starch degrading enzymes have a Starch Binding Domain (SBD) which has affinity for the starch granules on its own. In our laboratory, expression of SBD alone or fused to other effector proteins has been demonstrated. In industry, starch is modified after harvesting by chemical,...

  8. Thermoelectric phenomena in small granulated semiconductors

    Full text: The results of theoretical and experimental studies of the thermoelectric phenomena in the granulated semiconductors have been presented. A model of the heterogeneous semiconductor medium consisting of di phasic granules, which are the crystal semiconductor grains covered by the oxide nanofilms has been proposed. This effective medium model (EMM) consisting of the set of contacting granules has been constructed. Each granule phase is characterized by its own conductivity σi, heat conductivity χi, Seebeck factor αi, characteristic size di and, accordingly, efficiency of thermoelectric transformation Zi (i=1,2). On the basis of the linear Onsager thermodynamics the expressions for the estimation of σeff, χeff, αeff and Zeff are constructed, and their values depending on degree of asymmetry of characteristics of the granule components are analyzed. In framework of this method the more complicated ternary media is considered too. The possibilities of acquisition of the optimal medium characteristics under various technological conditions and under action of ionising radiation (electrons and γ-irradiation) have been studied. The developed model has been tested on the samples of polycrystalline and microgranular silicon with the various size of grains. The thermoelectric parameters of these materials have been studied. Conditions of obtaining of the big αeff and Zeff values are found. It is shown that radiation is a fine tool to control the properties of the effective medium and can be considered as a technology factor. A satisfactory agreement of EMM both with the previous experiments [1], and with the present ones has been obtained. (authors) References: 1. B.M.Abdurakhmanov, M.M.Adilov, M.H.Ashurov, H.B.Ashurov, B.L.Oksengendler. Appl. Solar Energy. 2011. V.47.No 2. P.139.

  9. Proteoglycan modifications by granulation tissue in culture.

    Quintner, M I; Kollar, E J; Rossomando, E F


    To study the process of tissue remodeling that occurs during wound healing, radioactive proteoglycan ([35S]-PGS) was used to assay for enzymatic activities present in the extracellular fluid of healing tissue. Mice, wounded by removal of a 2 x 1.5 cm patch of skin from the dorsal surface, were sacrificed after 3 days of healing. Granulation tissue (1 cm2) was removed, spread onto a sterile wire mesh support and placed in the center well of an organ culture dish. To each well was added 1 ml MCDB medium supplemented with 10% fetal calf serum and antibiotics and 5-20 microliters of [35S]-PGS (100,000 cpm/10 microliters). Medium, removed from the well by aspiration after 24 and 48 h of culture, was boiled 5 min at 100 degrees C and stored frozen at -20 degrees C. Alterations of the PGS were assayed with a Sepharose 4B column (1 x 50 cm) which had an excluded and included volume of 17 and 46 ml, respectively. PGS, incubated without cells or with tissues from unwounded animals, eluted at 26 ml. PGS, incubated with granulation tissue and cultured for either 24 or 48 h, eluted from the Sepharose 4B at 29 ml, a 10% increase in elution volume, suggesting that the size or shape of the PGS has been altered by enzymes secreted by the cells of the granulation tissue. In contrast, PGS incubated with tissues from unwounded animals or without granulation tissue showed no changes. These data suggest that enzymatic activities secreted by cells of granulation tissue may be involved in remodeling during healing. PMID:6749574

  10. The dissolution of granulated wood ash in forest soils

    The purpose of this study was to examine the dissolution of granulated wood ash in forest soils. The study was based on comparison between ash granules collected from different forest sites and the original granules. The sites differed in drainage conditions and type of vegetation. The ash granules were spread 1 to 3 years before sampling. Three different types of ash granules were studied. One ash was granulated by adding molasses and lignosulfonate, the second by adding cement and the third by adding only water. The result of this study shows that the ash granulated with the water soluble binders molasses and lignosulfonate, was more easily dissolved than the other two granulated ashes. The former type of ash was almost totally dissolved after three years in moist environment and it had increased the pH level by 1.4 units in the humus layer of well drained sites. The ash granulated with cement did not influence the pH level in the humus layer during a two year period. The granules without any extra binders were almost as hard and insoluble as the granules with cement added. Independent of granulation method the soluble salts in the ash were quickly leached from the granules. This led to a decrease in the relative contents of K, Na, S and Cl during the time after spreading. In the ash granulated with water soluble binders, the relative alkalinity content and the relative contents of Ca and Mg decreased approximately by 20 % during the time after spreading. Corresponding figures for the other two ashes was only a few percent. During the time after spreading the relative contents of Al, Fe, P and the heavy metals Zn, Pb, Cr and Cd has increased, by approximately 30 %, in the ash granulated with water soluble binders. (25 refs., 5 figs., 13 tabs.)

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

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


    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...

  12. Shigella flexneri modulates stress granule composition and inhibits stress granule aggregation.

    Vonaesch, Pascale; Campbell-Valois, François-Xavier; Dufour, Alexandre; Sansonetti, Philippe J; Schnupf, Pamela


    Invasion and multiplication of the facultative, cytosolic, enteropathogen Shigella flexneri within the colonic epithelial lining leads to an acute inflammatory response, fever and diarrhea. During the inflammatory process, infected cells are subjected to numerous stresses including heat, oxidative stress and genotoxic stress. The evolutionarily conserved pathway of cellular stress management is the formation of stress granules that store translationally inactive cellular mRNAs and interfere with cellular signalling pathways by sequestering signalling components. In this study, we investigated the ability of S. flexneri-infected cells to form stress granules in response to exogenous stresses. We found that S. flexneri infection inhibits movement of the stress granule markers eIF3 and eIF4B into stress granules and prevents the aggregation of G3BP1 and eIF4G-containing stress granules. This inhibition occurred only with invasive, but not with non-invasive bacteria and occurred in response to stresses that induce translational arrest through the phosphorylation of eIF2α and by treating cells with pateamine A, a drug that induces stress granules by inhibiting the eIF4A helicase. The S. flexneri-mediated stress granule inhibition could be largely phenocopied by the microtubule-destabilizing drug nocodazole and while S. flexneri infection did not lead to microtubule depolymerization, infection greatly enhanced acetylation of alpha-tubulin. Our data suggest that qualitative differences in the microtubule network or subversion of the microtubule-transport machinery by S. flexneri may be involved in preventing the full execution of this cellular stress response. PMID:27282465

  13. Biogenic calcite granules--are brachiopods different?

    Pérez-Huerta, Alberto; Dauphin, Yannicke; Cusack, Maggie


    Brachiopods are still one of the least studied groups of organisms in terms of biomineralization despite recent studies indicating the presence of highly complex biomineral structures, particularly in taxa with calcitic shells. Here, we analyze the nanostructure of calcite biominerals, fibers and semi-nacre tablets, in brachiopod shells by high-resolution scanning electron microscopy (SEM) and atomic force microscopy (AFM). We demonstrate that basic mechanisms of carbonate biomineralization are not uniform within the phylum, with semi-nacre tablets composed of spherical aggregates with sub-rounded granules and fibers composed of large, triangular or rod-like particles composed of small sub-rounded granules (40-60 nm). Additionally, proteinaceous envelopes surrounding calcite fibers have been shown for the first time to have a dual function: providing a micro-environment in which granules are produced and acting as the organic template for particle orientation as fiber components. In summary, these new findings in brachiopod shells reveal a complex and distinctive style of biomineralization among carbonate-producing organisms. PMID:23026148

  14. Zymophagy: Selective Autophagy of Secretory Granules

    Maria I. Vaccaro


    Full Text Available Timing is everything. That's especially true when it comes to the activation of enzymes created by the pancreas to break down food. Pancreatic enzymes are packed in secretory granules as precursor molecules called zymogens. In physiological conditions, those zymogens are activated only when they reach the gut, where they get to work releasing and distributing nutrients that we need to survive. If this process fails and the enzymes are prematurely activated within the pancreatic cell, before they are released from the gland, they break down the pancreas itself causing acute pancreatitis. This is a painful disease that ranges from a mild and autolimited process to a severe and lethal condition. Recently, we demonstrated that the pancreatic acinar cell is able to switch on a refined mechanism that could explain the autolimited form of the disease. This is a novel selective form of autophagy named zymophagy, a cellular process to specifically detect and degrade secretory granules containing activated enzymes before they can digest the organ. In this work, we revise the molecules and mechanisms that mediate zymophagy, a selective autophagy of secretory granules.

  15. 31P nuclear magnetic resonance study of the metabolic pools of adenosine triphosphate in cultured bovine adrenal medullary chromaffin cells

    31P NMR was used to resolve and determine the relative quantity and mobility of ATP in the cytosolic and vesicular compartments of isolated adrenomedullary chromaffin cells. The cells were cultured on microcarrier beads and superfused with an oxygenated medium-thereby permitting dense suspensions of viable cells to be maintained in the NMR probe for extended time periods. Under these conditions, distinct 31P signals could be seen for ATP within the vesicular and the cytosolic pools. Comparison of the integrated areas of the β-phosphate resonances from the two ATP pools indicated 77% of the endogenous ATP was in the vesicular pool. From this observation and the assumption that the concentration of ATP in the vesicle is 87.5 mM, the concentration of ATP calculated to be in the cytoplasmic pool was ∼ 4 mM. The pH in the vesicle determined from the chemical shift of the γ-phosphate resonance of vesicular ATP was 5.84 ± 0.17, slightly higher than the intragranular pH measured in hypoxic cells. Spin-lattice relaxation times of ATP 31P resonances in the vesicular pool were from 12 to 14 times shorter than the ATP resonances in the cytosol, corresponding to a decrease in molecular mobility due to incorporation of ATP within a catecholamine-storage complex

  16. Muted protein is involved in the targeting of CD63 to large dense-core vesicles of chromaffin cells.

    Zhenhua, Hao; Wei, Li


    Large dense-core vesicles (LDCVs) are characterized as a class of lysosome-related organelles (LROs), which undergo regulated release and play important roles in development, metabolism and homeostasis. The Muted protein is a subunit of the biogenesis of lysosome-related organelles complex-1 (BLOC-1), which functions in the biogenesis of lysosomes and LROs. CD63 is a membrane component of lysosomes and LROs. Whether and how CD63 is sorted into LDCVs is largely unknown. In this study, we aim to identify the localization of CD63 in chromaffin cells by colocalization, living cell imaging and cell fractionation. We found that a proportion of CD63-YFP colocalized with NPY-dsRed labeled LDCVs. By sucrose density gradient fractionation, a proportion of CD63 was found to be highly enriched in LDCVs fractions. The Muted mutant mouse is a model of Hermansky-Pudlak syndrome (HPS). We also found that the level of CD63 was significantly decreased in Muted-deficient adrenal glands, suggesting that the Muted protein is important for the steady-state level of CD63. Our results suggest that CD63 is a membrane component of LDCVs and the stability of CD63 is dependent on the Muted protein, which provides a clue to the pathogenesis of LRO defects in HPS. PMID:27531610

  17. Localized secretion of ATP and opioids revealed through single Ca2+ channel modulation in bovine chromaffin cells.

    Carabelli, V; Carra, I; Carbone, E


    In bovine chromaffin cells, the Ca2+ channels involved in exocytosis are effectively inhibited by ATP and opioids that are coreleased with catecholamines during cell activity. This autocrine loop causes a delay in Ca2+ channel activation that is quickly removed by preceding depolarizations. Changes in Ca2+ channel gating by secreted products thus make it possible to correlate Ca2+ channel activity to secretory events. Here, using cell-attached patch recordings, we found a remarkable correlation between delayed Ca2+ channel openings and neurotransmitter secretion induced by either local or whole-cell Ba2+ stimulation. The action is specific for N- and P/Q-type channels and largely prevented by PTX and mixtures of purinergic and opioid receptor antagonists. Overall, our data provide evidence that exocytosis, viewed through the autocrine inhibition of non-L-type channels, is detectable in membrane patches of approximately 1 microm2 distributed over 30%-40% of the total cell surface, while Ca2+ channels and autoreceptors are uniformly distributed over most of the cell membrane. PMID:9655512

  18. Comparison of Different Granulation Techniques for Lactose Monohydrate

    Pankaj Patel


    Full Text Available The objective of this study was directed to improve the physical and technical properties of poorly flowing and highly cohesive Lactose monohydrate to solve the most important problem that affects tablet manufacture. To overcome all the problems related to lactose granulation is required. Granulation is one of the most important unit operations in the production of pharmaceutical oral dosage forms. Granulation process will improve flow and compression characteristics, reduce segregation, improve content uniformity, and eliminate excessive amounts of fine particles. The results will be improved yields, reduced tablet defects, increased productivity. Pharmaceutical products are processed all over the world using the direct-compressing, wet-granulation, or dry granulation methods. Which method is chosen depends on the ingredients individual characteristics and ability to properly flow, compresses, eject, and disintegrate. Then the proper granulation process can be applied. The objective of present article was to focus on the best possible granulation technology that gives good results based on evaluation of different granule properties, namely the Carr’s index, Hausner’s index, Angle of repose, were evaluated for granule prepared by different binders and different techniques. Finally, the tabletting process showed low values of ejection forces, good tablet properties (weight uniformity, hardness, friability, and disintegration indicating good compressibility of the prepared granules using Fluidized Bed Processor (HPMC 2.5% as binder and Coprocessing of Lactose.

  19. Second Harmonic Generation Mediated by Aligned Water in Starch Granules.

    Cisek, Richard; Tokarz, Danielle; Krouglov, Serguei; Steup, Martin; Emes, Michael J; Tetlow, Ian J; Barzda, Virginijus


    The origin of second harmonic generation (SHG) in starch granules was investigated using ab initio quantum mechanical modeling and experimentally examined using polarization-in, polarization-out (PIPO) second harmonic generation microscopy. Ab initio calculations revealed that the largest contribution to the SHG signal from A- and B-type allomorphs of starch originates from the anisotropic organization of hydroxide and hydrogen bonds mediated by aligned water found in the polymers. The hypothesis was experimentally tested by imaging maize starch granules under various hydration and heat treatment conditions that alter the hydrogen bond network. The highest SHG intensity was found in fully hydrated starch granules, and heat treatment diminished the SHG intensity. The PIPO SHG imaging showed that dried starch granules have a much higher nonlinear optical susceptibility component ratio than fully hydrated granules. In contrast, deuterated starch granules showed a smaller susceptibility component ratio demonstrating that SHG is highly sensitive to the organization of the hydroxyl and hydrogen bond network. The polarization SHG imaging results of potato starch granules, representing starch allomorph B, were compared to those of maize starch granules representing allomorph A. The results showed that the amount of aligned water was higher in the maize granules. Nonlinear microscopy of starch granules provides evidence that varying hydration conditions leads to significant changes in the nonlinear susceptibility ratio as well as the SHG intensity, supporting the hypothesis from ab initio calculations that the dominant contribution to SHG is due to the ordered hydroxide and hydrogen bond network. PMID:25427055

  20. Fast exocytosis mediated by T- and L-type channels in chromaffin cells: distinct voltage-dependence but similar Ca2+ -dependence.

    Carabelli, V; Marcantoni, A; Comunanza, V; Carbone, E


    Expression, spatial distribution and specific roles of different Ca(2+) channels in stimulus-secretion coupling of chromaffin cells are intriguing issues still open to discussion. Most of the evidence supports a role of high-voltage activated (HVA) Ca(2+) channels (L-, N-, P/Q- and R-types) in the control of exocytosis: some suggesting a preferential coupling of specific Ca(2+) channel subunits with the secretory apparatus, others favoring the idea of a contribution to secretion proportional to the expression density and gating properties of Ca(2+) channels. In this work we review recent findings and bring new evidence in favor of the hypothesis that also the LVA (low-voltage-activated, T-type) Ca(2+) channels effectively control fast exocytosis near resting potential in adrenal chromaffin cells of adult rats. T-type channels recruited after long-term treatments with pCPT-cAMP (or chronic hypoxia) are shown to control exocytosis with the same efficacy of L-type channels, which are the dominant Ca(2+) channel types expressed in rodent chromaffin cells. A rigorous comparison of T- and L-type channel properties shows that, although operating at different potentials and with different voltage-sensitivity, the two channels possess otherwise similar Ca(2+)-dependence of exocytosis, size and kinetics of depletion of the immediately releasable pool and mobilize vesicles of the same quantal size. Thus, T- and L-type channels are coupled with the same Ca(2+)-efficiency to the secretory apparatus and deplete the same number of vesicles ready for release. The major difference of the secretory signals controlled by the two channels appear to be the voltage range of operation, suggesting the idea that stressful conditions (hypoxia and persistent beta-adrenergic stimulation) can lower the threshold of cell excitability by recruiting new Ca(2+) channels and activate an additional source of catecholamine secretion. PMID:17340096


    Gabriel I.Tardos


    Granulation is a unit operation by which larger granules are produced from fine, powdery particles to improve appearance, flow properties and mixedness, reduce dustiness and, in general, produce engineered particles with superior attributes. Agglomeration in wet granulation is achieved by introducing a "binder" fluid onto a shearing mass of fine powders. This paper gives a general overview of the process with emphasis on a simplified granulation model based on a dimensionless parameter containing inertia and viscous dissipation energies between colliding particles: the so-called Stokes number. The model incorporates most common features of all granulation devices (mixers) used in the pharmaceutical industry.Also described in the paper is a computer simulation that captures the movement of flowing powder in an ideal mixer-granulator with constant shear rate. A fraction of the total number of particles is wet (covered by binder and therefore "sticky") while the rest of the particles are dry. The numerical simulation depicts two distinct regimes of agglomeration found in a typical granulator: granule growth and subsequent breakup. During granule growth-simulations, final granule size and shape distributions are obtained by analyzing the size and shape of formed granules using a pattern-recognition technique. A second kind of simulation, also using rapid granular flow modeling, follows the rotation and deformation of an "agglomerate" held together by a liquid binder. Results from these simulations yield critical values of the Stokes number. Below the critical value, the agglomerates are stable and only rotate in response to shear while above the critical value they break into two or more pieces. At the critical value, they attain a steady elongated shape. Using values of the critical Stokes number, the model predicts the size of formed granules.The existence of the critical state in which granules attain a characteristic elongated shape is used to measure shear forces

  2. The hemodynamically-regulated vascular microenvironment promotes migration of the steroidogenic tissue during its interaction with chromaffin cells in the zebrafish embryo.

    Chih-Wei Chou

    Full Text Available BACKGROUND: While the endothelium-organ interaction is critical for regulating cellular behaviors during development and disease, the role of blood flow in these processes is only partially understood. The dorsal aorta performs paracrine functions for the timely migration and differentiation of the sympatho-adrenal system. However, it is unclear how the adrenal cortex and medulla achieve and maintain specific integration and whether hemodynamic forces play a role. METHODOLOGY AND PRINCIPAL FINDINGS: In this study, the possible modulation of steroidogenic and chromaffin cell integration by blood flow was investigated in the teleostean counterpart of the adrenal gland, the interrenal gland, in the zebrafish (Danio rerio. Steroidogenic tissue migration and angiogenesis were suppressed by genetic or pharmacologic inhibition of blood flow, and enhanced by acceleration of blood flow upon norepinephrine treatment. Repressed steroidogenic tissue migration and angiogenesis due to flow deficiency were recoverable following restoration of flow. The regulation of interrenal morphogenesis by blood flow was found to be mediated through the vascular microenvironment and the Fibronectin-phosphorylated Focal Adhesion Kinase (Fn-pFak signaling. Moreover, the knockdown of krüppel-like factor 2a (klf2a or matrix metalloproteinase 2 (mmp2, two genes regulated by the hemodynamic force, phenocopied the defects in migration, angiogenesis, the vascular microenvironment, and pFak signaling of the steroidogenic tissue observed in flow-deficient embryos, indicating a direct requirement of mechanotransduction in these processes. Interestingly, epithelial-type steroidogenic cells assumed a mesenchymal-like character and downregulated β-Catenin at cell-cell junctions during interaction with chromaffin cells, which was reversed by inhibiting blood flow or Fn-pFak signaling. Blood flow obstruction also affected the migration of chromaffin cells, but not through

  3. Flow of formulation granules through a conical hopper

    Mazumder B


    Full Text Available Gravity flow characteristics of various pharmaceutical granules through static conical hoppers of different cone angles were studied. Mass flow rate depends on properties of granules and cone angles when environmental conditions such as temperature and relative humidity are kept within a fixed range. The granules were made with active pharmaceutical ingredients as per Indian pharmacopoeia with other additives like binders and diluents. Lubricants were added with the granules to observe their effects on mass flow rate. Magnesium stearate and colloidal silicon dioxide of different proportions were used as lubricants after granulation. A new dimensionally analyzed equation was developed to predict flow rate of the granules. The developed equation agreed well with the experimental data with a percentage deviation of ±10%.

  4. Information granules and entropy theory in information systems

    LIANG JiYe; QIAN YuHua


    Information granulation and entropy theory are two main approaches to research uncertainty of an information system,which have been widely applied in many practical issues.In this paper,the characterizations and representations of information granules under various binary relations are investigated in information systems,an axiom definition of information granulation is presented,and some existing definitions of information granulation become its special forms.Entropy theory in information systems is further developed and the granulation monotonicity of each of them is proved.Moreover,the complement relationship between information granulation and entropy is established.This investigation unifies the results of measures for uncertainties in complete information systems and incomplete information systems.

  5. Structurization of dust precipitations and aerodynamical resistance in granulated mediums

    The processes of structurization of dust precipitations in the granulated mediums formed by glass spheres in diameter of 2 and 3 mm are studied. Distinction in the distribution of dust masses and air resistance is found after comparison with the filters filled with cylindrical granules. Going from the obtained research results, the conclusions on the possibility of use of the various adsorbents with different geometric forms and volumetric dimensions in the granulated filtering mediums in air filters at nuclear power plants are formulated.

  6. Application of the Molecular Combing Technique to Starch Granules

    Zhong-Dong Liu; Liu Boxiang; Jian-Hui Chen; You-Ning Sun; Xiao-Ling Lv; Ze-Sheng Zhang; Pin Sun; Pin Zhang; Yang-Li Wang; Hua Li


    The molecular combing technique was used to dissociate the nanostructural units of starch granules from the starch fragments after a gelatinization process. With the help of atomic force microscopy (AFM), we observed that some nanostructural chains were just flowing out of the granules. It proves that there are substantive nanostructural units in the starch granules, a phenomenon not previously observed, so these nanostructural units were defined as suspected intermediates. Furthermore, we co...

  7. Aerobic granules: microbial landscape and architecture, stages, and practical implications.

    Gonzalez-Gil, Graciela; Holliger, Christof


    For the successful application of aerobic granules in wastewater treatment, granules containing an appropriate microbial assembly able to remove contaminants should be retained and propagated within the reactor. To manipulate and/or optimize this process, a good understanding of the formation and dynamic architecture of the granules is desirable. Models of granules often assume a spherical shape with an outer layer and an inner core, but limited information is available regarding the extent of deviations from such assumptions. We report on new imaging approaches to gain detailed insights into the structural characteristics of aerobic granules. Our approach stained all components of the granule to obtain a high quality contrast in the images; hence limitations due to thresholding in the image analysis were overcome. A three-dimensional reconstruction of the granular structure was obtained that revealed the mesoscopic impression of the cavernlike interior of the structure, showing channels and dead-end paths in detail. In "old" granules, large cavities allowed for the irrigation and growth of dense microbial colonies along the path of the channels. Hence, in some areas, paradoxically higher biomass content was observed in the inner part of the granule compared to the outer part. Microbial clusters "rooting" from the interior of the mature granule structure indicate that granules mainly grow via biomass outgrowth and not by aggregation of small particles. We identify and discuss phenomena contributing to the life cycle of aerobic granules. With our approach, volumetric tetrahedral grids are generated that may be used to validate complex models of granule formation. PMID:24657859

  8. 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)


    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.)

  9. Ultrastructural similarity between bat and human mast cell secretory granules.

    Oliani, S M; Vugman, I; Jamur, M C


    Mast cells in the tongue of the bat (Artibeus lituratus) show a well-developed Golgi area and abundant mitochondria in the granule-free perinuclear cytoplasm. Rough endoplasmic reticulum profiles, free ribosomes, mitochondria, bundles of filaments and a great number of secretory granules are found throughout the remaining cytoplasm. The granules, of various shapes and sizes, are simple containing an electron-dense, homogeneous matrix, coarse particles or cylindrical scrolls, or combinations (cylindrical scrolls with either electron-dense, homogeneous matrix or coarse particle contents). Up to now, scroll-containing granules have been considered to be a unique feature of human mast cells. PMID:8453310

  10. Effect of alkaline treatment on the ultrastructure of starch granules

    Starch is a plant polysaccharide that occurs as discrete and partially crystalline microscopic granules. The development of different extraction methods to isolate granules with high purity and well-defined physical properties has increased due to the wide utilization of starch as an ingredient in the food industry. Alternatives to the pattern alkaline extraction protocol have been investigated in order to improve the extraction yield while maintaining the functional properties of the starch granules. In this work, we focused our efforts on the evaluation of the effect of alkaline treatments on the ultrastructure of Araucaria angustifolia (pinhao) starch granules during their extraction. (author)

  11. Structural processes during starch granule hydration by synchrotron radiation microdiffraction.

    Lemke, H; Burghammer, M; Flot, D; Rössle, M; Riekel, C


    Starch granule hydration has been examined on the level of a single potato starch granule by static and dynamic synchrotron radiation (SR) microdiffraction techniques. A cryofrozen, hydrated granule was mapped through a 5 microm SR-beam in order to investigate its internal organization. The edge of the granule showed fiber texture scattering due to radially oriented amylopectin helices. The variation of fiber texture across the granule center supports the model of concentric shells. The crystalline phase appears, however, to increase strongly toward the granule center due to a random amylopectin fraction, which could be related to crystallization of short-range ordered amylopectin during hydration. During gelatinization, the shell structure breaks down and remaining fiber-textured amylopectin domains belong probably to the swollen starch granule envelope. Hydration of a granule was initiated by a microdrop generator and followed in situ by SR-microdiffraction. A fast hydration process with a half time of about 7 s seems to reflect the porous nature of starch granules. The size of the hydrated domains suggests that this process is limited to the level of amylopectin side chain clusters. Longer hydration times are assumed to involve remaining short-range ordered amylopectin and results in larger domains. PMID:15244446

  12. Application of the Molecular Combing Technique to Starch Granules

    Zhong-Dong Liu


    Full Text Available The molecular combing technique was used to dissociate the nanostructural units of starch granules from the starch fragments after a gelatinization process. With the help of atomic force microscopy (AFM, we observed that some nanostructural chains were just flowing out of the granules. It proves that there are substantive nanostructural units in the starch granules, a phenomenon not previously observed, so these nanostructural units were defined as suspected intermediates. Furthermore, we conclude that blocklets of starch granules are formed through twisting or distortion of nanochains.

  13. Automated kymograph analysis for profiling axonal transport of secretory granules.

    Mukherjee, Amit; Jenkins, Brian; Fang, Cheng; Radke, Richard J; Banker, Gary; Roysam, Badrinath


    This paper describes an automated method to profile the velocity patterns of small organelles (BDNF granules) being transported along a selected section of axon of a cultured neuron imaged by time-lapse fluorescence microscopy. Instead of directly detecting the granules as in conventional tracking, the proposed method starts by generating a two-dimensional spatio-temporal map (kymograph) of the granule traffic along an axon segment. Temporal sharpening during the kymograph creation helps to highlight granule movements while suppressing clutter due to stationary granules. A voting algorithm defined over orientation distribution functions is used to refine the locations and velocities of the granules. The refined kymograph is analyzed using an algorithm inspired from the minimum set cover framework to generate multiple motion trajectories of granule transport paths. The proposed method is computationally efficient, robust to significant levels of noise and clutter, and can be used to capture and quantify trends in transport patterns quickly and accurately. When evaluated on a collection of image sequences, the proposed method was found to detect granule movement events with 94% recall rate and 82% precision compared to a time-consuming manual analysis. Further, we present a study to evaluate the efficacy of velocity profiling by analyzing the impact of oxidative stress on granule transport in which the fully automated analysis correctly reproduced the biological conclusion generated by manual analysis. PMID:21330183

  14. A study of fly ash-lime granule unfired brick

    P. Chindaprasirt; K. Pimraksa [Khon Kaen University (Thailand). Department of Civil Engineering


    In this paper, the properties of fly ash-lime granule unfired bricks are studied. Granules were prepared from mixtures of fly ash and lime at fly ash to hydrated lime ratios of 100:0 (Ca/Si = 0.2), 95:5 (Ca/Si = 0.35) and 90:10 (Ca/Si = 0.5). After a period of moist curing, the microstructure and mineralogy of the granules were studied. Microstructure examination reveals that new phases in the form of needle-like particles are formed at the surface of granule. The granules were used to make unfired bricks using hydrothermal treatment at temperature of 130 {+-} 5{sup o}C and pressure of 0.14 MPa. The microstructures, mineralogical compositions, mechanical properties and environmental impact of bricks were determined. The results reveal that the strengths of unfired bricks are dependent on the fineness of fly ash. The strength is higher with an increase in fly ash fineness. The strengths of the fly ash-lime granule unfired brick are excellent at 47.0-62.5 MPa. The high strength is due to the formation of new products consisting mainly of hibschite and Al-substituted 11 {angstrom} tobermorite. The main advantage of utilization of granule is the ability to increase the pozzolanic reaction of fly ash through moisture retained in the granule. In addition, the heavy elements, in particular Cd, Ni, Pb and Zn are efficiently retained in the fly ash-lime granule unfired brick.

  15. Aerobic granulation of pure bacterial strain Bacillus thuringiensis

    Sunil S ADAV; Duu-Jong LEE


    The objective of this study is to cultivate aer-obic granules by pure bacterial strain, Bacillus thuringien-sis, in a sequencing batch reactor. Stable granules sized 2.0-2.2 mm were formed in the reactor after a five-week cultivation. These granules exhibited excellent settling attributes, and degraded phenol at rates of 1.49 and concentration, respectively. Confocal laser scanning microscopic test results show that Bacillus thuringiensis was distributed over the initial small aggregates, and the outer edge of the granule was away from the core regime in the following stage.

  16. Granuphilin exclusively mediates functional granule docking to the plasma membrane

    Mizuno, Kouichi; Fujita, Takuji; Gomi, Hiroshi; Izumi, Tetsuro


    In regulated exocytosis, it is generally assumed that vesicles must stably “dock” at the plasma membrane before they are primed to become fusion-competent. However, recent biophysical analyses in living cells that visualize fluorescent secretory granules have revealed that exocytic behaviors are not necessarily uniform: some granules beneath the plasma membrane are resistant to Ca2+ -triggered release, while others are accelerated to fuse without a pause for stable docking. These findings suggest that stable docking is unnecessary, and can even be inhibitory or nonfunctional, for fusion. Consistently, pancreatic β cells deficient in the Rab27 effector, granuphilin, lack insulin granules directly attached to the plasma membrane in electron micrographs but nevertheless exhibit augmented exocytosis. Here we directly compare the exocytic behaviors between granuphilin-positive and -negative insulin granules. Although granuphilin makes granules immobile and fusion-reluctant beneath the plasma membrane, those granuphilin-positive, docked granules release a portion of granuphilin upon fusion, and fuse at a frequency and time course similar to those of granuphilin-negative undocked granules. Furthermore, granuphilin forms a 180-nm cluster at the site of each docked granule, along with granuphilin-interacting Rab27a and Munc18-1 clusters. These findings indicate that granuphilin is an exclusive component of the functional and fusion-inhibitory docking machinery of secretory granules. PMID:27032672

  17. In planta modification of potato starch granule biogenesis by different granule-bound fusion proteins

    Nazarian, F.


    Starch is composed of amylose and amylopectin and it is deposited in amyloplasts/choloroplasts as semi-crystalline granules. Many biosynthetic enzymes are involved in starch degradation and biosynthesis. Some microbial starch degrading enzymes have a Starch Binding Domain (SBD) which has affinity fo

  18. Role of [Na+]i and [Ca2+]i in nicotine-induced norepinephrine release from bovine adrenal chromaffin cells.

    Gerber, S H; Haunstetter, A; Krüger, C; Kaufmann, A; Nobiling, R; Haass, M


    Intracellular free sodium ([Na+]i) and calcium ([Ca2+]i) concentrations were determined by sodium-binding benzofuran isophthalate (SBFI) and fura 2 microfluorimetry, respectively, in bovine adrenal chromaffin cells (BCC). Validation of SBFI microfluorimetry by in vitro and in vivo calibration revealed a reliable assessment of [Na+]i within a range of 1-30 mM in single BCC. Nicotine (0.1-10 microM) induced concentration-dependent increases of both [Na+]i (from 3.3 +/- 0.1 to 25.6 +/- 0.4 mM, n = 76, P < 0.001) and [Ca2+]i (from 64 +/- 1 to 467 +/- 16 nM, n = 87, P < 0.001), which were accompanied by an increase in [3H]norepinephrine (NE) release. Consistent with an exocytotic release mechanism, nicotine-induced increments of [Ca2+]i and [3H]NE release were reduced under calcium-free conditions and by gadolinium chloride (40 microM), whereas [Na+]i was not affected. In contrast, a parallel attenuation of nicotine-evoked changes in [Na+]i, [Ca2+]i, and [3H]NE release was observed during reduction of the extracellular sodium concentration. The nicotine-evoked responses were neutralized by the nicotinic receptor antagonist hexamethonium (100 microM) but not by blockade of voltage-dependent sodium channels (1 microM tetrodotoxin). In conclusion, the nicotine-induced exocytotic release of [3H]NE is triggered by an increase in [Ca2+]i, which is facilitated by sodium influx through the nicotinic receptor ionophore. PMID:7573386

  19. Microbial granulation for lactic acid production

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


    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−1d−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...

  20. New developments on transition radiation detectors using superconducting granules

    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

  1. Sustained Exocytosis after Action Potential-Like Stimulation at Low Frequencies in Mouse Chromaffin Cells Depends on a Dynamin-Dependent Fast Endocytotic Process

    Moya-Díaz, José; Álvarez, Yanina D.; Montenegro, Mauricio; Bayonés, Lucas; Belingheri, Ana V.; González-Jamett, Arlek M.; Cárdenas, Ana M.; Marengo, Fernando D.


    Under basal conditions the action potential firing rate of adrenal chromaffin cells is lower than 0.5 Hz. The maintenance of the secretory response at such frequencies requires a continuous replenishment of releasable vesicles. However, the mechanism that allows such vesicle replenishment remains unclear. Here, using membrane capacitance measurements on mouse chromaffin cells, we studied the mechanism of replenishment of a group of vesicles released by a single action potential-like stimulus (APls). The exocytosis triggered by APls (ETAP) represents a fraction (40%) of the immediately releasable pool, a group of vesicles highly coupled to voltage dependent calcium channels. ETAP was replenished with a time constant of 0.73 ± 0.11 s, fast enough to maintain synchronous exocytosis at 0.2–0.5 Hz stimulation. Regarding the mechanism involved in rapid ETAP replenishment, we found that it depends on the ready releasable pool; indeed depletion of this vesicle pool significantly delays ETAP replenishment. On the other hand, ETAP replenishment also correlates with a dynamin-dependent fast endocytosis process (τ = 0.53 ± 0.01 s). In this regard, disruption of dynamin function markedly inhibits the fast endocytosis and delays ETAP replenishment, but also significantly decreases the synchronous exocytosis during repetitive APls stimulation at low frequencies (0.2 and 0.5 Hz). Considering these findings, we propose a model in where both the transfer of vesicles from ready releasable pool and fast endocytosis allow rapid ETAP replenishment during low stimulation frequencies. PMID:27507935

  2. Tracheal granulation as a cause of unrecognized airway narrowing

    Gaurav Bhatia; Valsamma Abraham; Linjo Louis


    Tracheostomy is one of the most common elective surgical procedures performed in critically ill patients. The most frequent late complication after tracheostomy is the development of granulation tissue, a complication that may cause airway occlusion or result in airway stenosis. We report the successful management of a patient with tracheal granulation presenting as an unrecognised cause of difficulty breathing.

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

    Suspensions of nanoparticles (SiO2, 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.

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

    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.)

  5. Roll compaction and granulation system for nuclear fuel material

    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

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

    Jimenez Justicia, A.


    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)

  7. A Calculus on Granules from Rough Inclusions in Information Systems

    Lech Polkowski


    Indiscernibility relations induced in information systems in the sense of Pawlak,define granules of knowledge as unions of their equivalence classes,leading to regular structures like Boolean algebras. Apart from Boolean operations on granules, under afixed set of attributes,that induce the partition topology on their collection, one may search for more flexible schemes that would induce in collections of granules some non-trivial topologies and in particular quasi-metrics on granules, allowing for richer structures. A way of realization of this program has been proposed as the paradigm of rough mereology; although abstract, stemming from an alternative set theory, yet it offers a calculus based on kind of quasi-metrics that allows for discussing granules from the point of view of their closeness. In thiswork, we would liketopresent theideas of this approach and basic results with short discussion of applications.

  8. Compressional Behavior of a Mixture of Granules Containing High Load of Phyllanthus niruri Spray-Dried Extract and Granules of Adjuvants: Comparison between Eccentric and Rotary Tablet Machines

    Spaniol, Bárbara; Bica, Vinicius Claudino; Ruppenthal, Lisias Rafael; Volpato, Maria Ramos; Petrovick, Pedro Ros


    The purpose of this paper was to evaluate the compressional behavior of granules containing high load of a Phyllanthus niruri spray-dried extract in eccentric (ETM) and rotary (RTM) tablet presses. Tablets were constituted by spray-dried extract granules (SDEG, 92%), excipient granules (EXCG, 7.92%), and magnesium stearate (0.08%). SDEG was obtained by dry granulation and EXCG, composed of microcrystalline cellulose (62.9%) and sodium starch glycolate (37.1%), by wet granulation. Particle siz...

  9. Hilar mossy cell circuitry controlling dentate granule cell excitability

    Seiichiro Jinde


    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.

  10. A highly sustainable and versatile granulation method of nanodrugs via their electrostatic adsorption onto chitosan microparticles as the granulation substrates.

    Yang, Yue; Hadinoto, Kunn


    Nanodrugs play important roles in enhancing the sustainability of pharmaceutical manufacturing via their ability to enhance the bioavailability of poorly soluble drugs, resulting in less drug wastage and less mass/energy consumed in their manufacturing. Despite their sustainability enhancement capability, solid dosage form manufacturing of nanodrugs remains lacking from the sustainability perspective. One example is the granulation of nanodrugs prior to tablet preparation, where existing methods (e.g. wet granulation, spray granulation, spray drying) require high energy and time expenses, or are highly intricate often leading to product inconsistencies. Herein we present an alternative nanodrug granulation method via electrostatic adsorption of the nanodrugs onto chitosan microparticles acting as granulation substrates. The method is sustainable involving only mixing of aqueous suspensions of the nanodrugs and substrates under ambient conditions, followed by washing and drying. We investigate the effects of substrate's physical characteristics and nanodrug to substrate ratio on the nanodrug loading in the granules, content uniformity, nanodrug recovery, and granule flowability. Ciprofloxacin and curcumin nanoplexes prepared by drug-polyelectrolyte complexation are used as the model nanodrugs with neutrally, positively, and negatively charged chitosan microparticles as the substrates. Granules having 25% (w/w) nanodrug loading at 50% (w/w) recovery with good flowability have been successfully prepared. PMID:23727594

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

    S. A. Habeeb, AB. Aziz Bin Abdul Latiff, Zawawi Bin Daud, Zulkifli Bin Ahmad


    Full Text Available 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.

  12. Dissociation of Ca sup 2+ entry and Ca sup 2+ mobilization responses to angiotensin II in bovine adrenal chromaffin cells

    Stauderman, K.A.; Pruss, R.M. (Merrell Dow Research Institute, Cincinnati, OH (USA))


    In fura-2-loaded bovine adrenal chromaffin cells, 0.5 microM angiotensin II (AII) stimulated a 185 +/- 19 nM increase of intracellular-free calcium (( Ca2+)i) approximately 3 s after addition. The time from the onset of the response until achieving 50% recovery (t 1/2) was 67 +/- 10 s. Concomitantly, AII stimulated both the release of 45Ca2+ from prelabeled cells, and a 4-5-fold increase of (3H)inositol 1,4,5-trisphosphate (( 3H)Ins(1,4,5)P3) levels. In the presence of 50 microM LaCl3, or when extracellular-free Ca2+ (( Ca2+)o) was less than 100 nM, AII still rapidly increased (Ca2+)i by 95-135 nM, but the t 1/2 for recovery was then only 23-27 s. In medium with 1 mM MnCl2 present, AII also stimulated a small amount of Mn2+ influx, as judged by quenching of the fura-2 signal. When (Ca2+)o was normal (1.1 mM) or low (less than 60 nM), 1-2 microM ionomycin caused (Ca2+)i to increase 204 +/- 26 nM, while also releasing 45-55% of bound 45Ca2+. With low (Ca2+)o, ionomycin pretreatment abolished both the (Ca2+)i increase and 45Ca2+ release stimulated by AII. However, after ionomycin pretreatment in normal medium, AII produced a La3+-inhibitable increase of (Ca2+)i (103 +/- 13 nM) with a t 1/2 of 89 +/- 8 s, but no 45Ca2+ release. No pretreatment condition altered AII-induced formation of (3H)Ins(1,4,5)P3. We conclude that AII increased (Ca2+)i via rapid and transient Ca2+ mobilization from Ins(1,4,5)P3- and ionomycin-sensitive stores, accompanied (and/or followed) by Ca2+ entry through a La3+-inhibitable divalent cation pathway. Furthermore, the ability of AII to activate Ca2+ entry in the absence of Ca2+ mobilization (i.e. after ionomycin pretreatment) suggests a receptor-linked stimulus other than Ca2+ mobilization initiates Ca2+ entry.

  13. A granulation model using diosgenin wastewater in an upflow anaerobic sludge blanket reactor

    Jianguo BAO; Hui LIU; Yanxin WANG; Lijun ZHANG


    An enhanced start-up of an upfiow anaerobic sludge blanket (UASB) reactor for diosgenin wastewater treatment was designed and experimentally tested. Gran-ular sludge was formed on day 35 in the reactor with high concentrations of chloride (4000-7000 mg/L) and COD (5000-13000mg/L) as substrate. A new model for the granulation was proposed which divides the formation of anaerobic granules into six consecutive stages; they include semi-embryonic granule formation, embryonic granule formation, single-nucleus granule formation, multi-nuclei granule formation, granule growth and granule maturation. A model of the granule structure was also proposed based on scanning electron microscope observation. The microspores occurring on the surface and further leading into the interior of the granules were considered as the channels and the passage of the materials and the products of the microorganisms' metabolism inside the granules.

  14. A Granule Model for Evaluating Adhesion of Pharmaceutical Binders

    Hossein Orafai


    Full Text Available Granule capability is defined in terms of the strength of individual granule and friability of granulation batch to withstand breaking, abrasion and compactibility. Binder(s are added to perform the above properties .The common methods to asses their capability are to test crushing strength of the granules directly and to make statistical analysis and /or testing the friability of bulk granulation. In this work four substrate models including polymethylmetacrylate beads(PMMA,glass powder, acetaminophen, and para-aminobebzoic acid were chosen. The binder models were corn starch, gelatin, methylcellulose (MC and hydroxypropylmethylcellulose (HPMC. After massing the substrates with the binder solutions, discs were produced by the mean of the mold technique. The discs were dried and conditioned and then tested for tensile strength while the failed areas were scanned by SEM. Various granulations were made and the results of friability and crush strength were compared with the discs strength .The bond areas in the SEM showed the trend with the binder concentration .A comparison of the standard deviation shows that discs have much lower level of the strength than granules. The resulting discs showed a higher performance which is related to the stems for the discs shape .In conclusion, this method is a simple and is applicable to differentiate efficacy of binder under studies.

  15. Uncertainty Handling in Disaster Management Using Hierarchical Rough Set Granulation

    Sheikhian, H.; Delavar, M. R.; Stein, A.


    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.

  16. Opposite action of beta1- and beta2-adrenergic receptors on Ca(V)1 L-channel current in rat adrenal chromaffin cells.

    Cesetti, T; Hernández-Guijo, J M; Baldelli, P; Carabelli, V; Carbone, E


    Voltage-gated Ca(2+) channels of chromaffin cells are modulated by locally released neurotransmitters through autoreceptor-activated G-proteins. Clear evidence exists in favor of a Ca(2+) channel gating inhibition mediated by purinergic, opioidergic, and alpha-adrenergic autoreceptors. Few and contradictory data suggest also a role of beta-adrenergic autoreceptors (beta-ARs), the action of which, however, remains obscure. Here, using patch-perforated recordings, we show that rat chromaffin cells respond to the beta-AR agonist isoprenaline (ISO) by either upmodulating or downmodulating the amplitude of Ca(2+) currents through two distinct modulatory pathways. ISO (1 microm) could cause either fast inhibition (approximately 25%) or slow potentiation (approximately 25%), or a combination of the two actions. Both effects were completely prevented by propranolol. Slow potentiation was more evident in cells pretreated with pertussis toxin (PTX) or when beta(1)-ARs were selectively stimulated with ISO + ICI118,551. Potentiation was absent when the beta(2)-AR-selective agonist zinterol (1 microm), the protein kinase A (PKA) inhibitor H89, or nifedipine was applied, suggesting that potentiation is associated with a PKA-mediated phosphorylation of L-channels (approximately 40% L-current increase) through beta(1)-ARs. The ISO-induced inhibition was fast and reversible, preserved in cell treated with H89, and mimicked by zinterol. The action of zinterol was mostly on L-channels (38% inhibition). Zinterol action preserved the channel activation kinetics, the voltage-dependence of the I-V characteristic, and was removed by PTX, suggesting that beta(2)AR-mediated channel inhibition was mainly voltage independent and coupled to G(i)/G(o)-proteins. Sequential application of zinterol and ISO mimicked the dual action (inhibition/potentiation) of ISO alone. The two kinetically and pharmacologically distinct beta-ARs signaling uncover alternative pathways, which may serve the autocrine

  17. In vitro binding of puroindolines to wheat starch granules

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


    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...... 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. Pressing behaviour of spray dried alumina-zirconia granules

    In this study, spray drying of alumina-zirconia slurries on a pilot scale, and their pressing behaviour were investigated. Slurries were prepared at 50 wt-% solid loading. An acrylic polymer emulsion, polyethylene glycol, and stearic acid were used as a binder, plasticizer, and lubricant, respectively. Granules produced had a mean size of 85 μm with spherical morphology and smooth surfaces with considerably good flow behaviour. When polyethylene glycol was not used, granules were rather hard such that it was very difficult to break down the granule structure even at a pressure of 195 MPa. (orig.)

  19. Microstructure of starch granule related to kernel hardness in corn

    M. Gaytán-Martínez; J. D. Figueroa-Cárdenas; M. L. Reyes-Vega; F. Rincón-Sánchez; E. Morales-Sánchez


    The kernel hardness of 21 corn (Zea mays L.) cultivars was studied in relation to texture, flotation index, size and arrangement of the starch granules within the endosperm, using scanning electron microscope. Hardness (7.6 – 16.9 kg-f) was related to the size and the arrangement of the starch granules within the endosperm. Hard corn had large and small polygonal granules in a compact protein matrix. Data obtained from scanning electron microscopy showed a positive correlation of hardness wit...

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

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


    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.

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

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


    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 oxygen-comprising gas, and in a third step, the sludge granules are allowed to settle in a settling step. This makes it possible to effectively remove not only organic nutrients but optionally also nitroge...

  2. A Post-Docking Role of Synaptotagmin 1-C2B Domain Bottom Residues R398/399 in Mouse Chromaffin Cells

    Kedar, Girish H; Munch, Anders S; van Weering, Jan R T;


    synaptic transmission, Syt1-R398/399Q (RQ), in syt1 null mutant cells. Ultrastructural morphometry revealed that Syt1-RQ fully restored the docking defect observed previously in syt1 null mutant cells, similar to wild type Syt1 (Syt1-wt). Small unilamellar lipid vesicles (SUVs) that contained the v......-SNARE Synaptobrevin2 and Syt1-R398/399Q also docked to t-SNARE-containing giant vesicles (GUVs), similar to Syt1-wt. However, unlike Syt1-wt, Syt1-RQ-induced docking was strictly PI(4,5)P2-dependent. Unlike docking, neither synchronized secretion in chromaffin cells nor Ca2+-triggered SUV–GUV fusion was restored by...

  3. Prolonged exposure of chromaffin cells to nitric oxide down-regulates the activity of soluble guanylyl cyclase and corresponding mRNA and protein levels

    Ferrero, Rut; Torres, Magdalena


    Background Soluble guanylyl cyclase (sGC) is the main receptor for nitric oxide (NO) when the latter is produced at low concentrations. This enzyme exists mainly as a heterodimer consisting of one α and one β subunit and converts GTP to the second intracellular messenger cGMP. In turn, cGMP plays a key role in regulating several physiological processes in the nervous system. The aim of the present study was to explore the effects of a NO donor on sGC activity and its protein and subunit mRNA levels in a neural cell model. Results Continuous exposure of bovine adrenal chromaffin cells in culture to the nitric oxide donor, diethylenetriamine NONOate (DETA/NO), resulted in a lower capacity of the cells to synthesize cGMP in response to a subsequent NO stimulus. This effect was not prevented by an increase of intracellular reduced glutathione level. DETA/NO treatment decreased sGC subunit mRNA and β1 subunit protein levels. Both sGC activity and β1 subunit levels decreased more rapidly in chromaffin cells exposed to NO than in cells exposed to the protein synthesis inhibitor, cycloheximide, suggesting that NO decreases β1 subunit stability. The presence of cGMP-dependent protein kinase (PKG) inhibitors effectively prevented the DETA/NO-induced down regulation of sGC subunit mRNA and partially inhibited the reduction in β1 subunits. Conclusions These results suggest that activation of PKG mediates the drop in sGC subunit mRNA levels, and that NO down-regulates sGC activity by decreasing subunit mRNA levels through a cGMP-dependent mechanism, and by reducing β1 subunit stability. PMID:12350235

  4. Microelectrode Arrays of Diamond-Insulated Graphitic Channels for Real-Time Detection of Exocytotic Events from Cultured Chromaffin Cells and Slices of Adrenal Glands.

    Picollo, Federico; Battiato, Alfio; Bernardi, Ettore; Marcantoni, Andrea; Pasquarelli, Alberto; Carbone, Emilio; Olivero, Paolo; Carabelli, Valentina


    A microstructured graphitic 4 × 4 multielectrode array was embedded in a single-crystal diamond substrate (4 × 4 μG-SCD MEA) for real-time monitoring of exocytotic events from cultured chromaffin cells and adrenal slices. The current approach relies on the development of a parallel ion beam lithographic technique, which assures the time-effective fabrication of extended arrays with reproducible electrode dimensions. The reported device is suitable for performing amperometric and voltammetric recordings with high sensitivity and temporal resolution, by simultaneously acquiring data from 16 rectangularly shaped microelectrodes (20 × 3.5 μm(2)) separated by 200 μm gaps. Taking advantage of the array geometry we addressed the following specific issues: (i) detect both the spontaneous and KCl-evoked secretion simultaneously from several chromaffin cells directly cultured on the device surface, (ii) resolve the waveform of different subsets of exocytotic events, and (iii) monitoring quantal secretory events from thin slices of the adrenal gland. The frequency of spontaneous release was low (0.12 and 0.3 Hz, respectively, for adrenal slices and cultured cells) and increased up to 0.9 Hz after stimulation with 30 mM KCl in cultured cells. The spike amplitude as well as rise and decay time were comparable with those measured by carbon fiber microelectrodes and allowed to identify three different subsets of secretory events associated with "full fusion" events, "kiss-and-run" and "kiss-and-stay" exocytosis, confirming that the device has adequate sensitivity and time resolution for real-time recordings. The device offers the significant advantage of shortening the time to collect data by allowing simultaneous recordings from cell populations either in primary cell cultures or in intact tissues. PMID:27376596

  5. Conceptual framework for model-based analysis of residence time distribution in twin-screw granulation

    Kumar, Ashish; Vercruysse, Jurgen; Vanhoorne, Valerie;


    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 w...

  6. Statistics of Local Seismic Emission from the Solar Granulation

    Lindsey, Charles


    We apply computational seismic holography to high-frequency helioseismic observations of the quiet Sun from SDO/HMI to locate predominant sources of seismic emission with respect to the structure of the solar granulation. The regions of greatest seismic emission are the edges of photospheric granules. Seismic emission from regions whose continuum brightnesses are 95-100% of the mean, as resolved by HMI, are about 2.5 times as emissive as regions whose brightnesses are 100-104% of the mean. The greater seismic emissivity from regions whose brightnesses are somewhat less than the mean is roughly in line with expectations from an understanding that attributes most seismic emission to cool plumes plummeting from the edges of granules. However, seismic emission from regions whose continuum brightnesses significantly exceed 104% of the mean is also remarkably high. This unexpected feature of high-frequency seismic emission from the solar granulation begs to be understood.

  7. In vitro binding of puroindolines to wheat starch granules

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


    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....

  8. Heterogeneity of secretory granules of silent pituitary adenomas

    Holck, S; Wewer, U M; Albrechtsen, R


    Silent pituitary adenomas were compared with hormonally active tumors taking into account the size, number, and ultrastructural characteristics of secretory granules (SG). The study group (a total of 79 primary pituitary adenomas) comprised 27 silent, 21 growth hormone (GH)-producing-, 16 prolactin...... (PRL)-producing-, 5 GH-PRL-producing- and 10 adrenocorticotropic hormone (ACTH)-producing adenomas. The SG of silent adenomas were significantly smaller than SG in endocrine active adenomas. All hormonally inactive tumors also contained small (mean, 94 nm) specific cytoplasmic granules, designated...... "silent adenoma granules" (SIG). The fine structural features of the SIG included: a flocculent, granular material occupying an eccentric position in a larger vesicle limited by a double membrane. In the silent adenomas this particular granule was present in up to 90% of the adenoma cells and constituted...

  9. Kit systems for granulated decontamination formulations

    Tucker, Mark D.


    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.

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

    Tatiane Pereira de Souza


    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.

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

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


    (the calcium carbonate: calcium carbonate bonds) and consequently exposed the weakest areas of bond formation on the surface of the granules. Accordingly, the non-uniform allocation of the interparticulate attractive forces in a tablet would cause a lowering of the compactibility. Furthermore, 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....

  12. Experimental investigation on ligament formation for molten slag granulation

    During the dry granulation for molten blast furnace slag, rotary cup is used to atomize the molten slag. In this study, the mechanism of ligament formation for molten slag granulation was investigated. The results indicated that the transition equations from direct drop formation to ligament formation and ligament formation to sheet formation, obtained from glycerol/water mixture, can identify the type of disintegration for molten blast furnace slag granulation. Due to short wavelength of dilational wave along molten slag ligaments, the diameter of slag particles decreased with an increase in angular speed, and more and more slag particles were far away from the center of rotary cup. The slag particles diameter decreased with an increase in rotary cup diameter. The empirical equation can be used to predict the diameter of slag particles obtained by ligament formation for molten slag granulation at high angular speed. Because of slight change in viscosity and surface tension when the temperature of molten slag was over than 1300 °C, there was no change in diameter and mass fraction of slag particles with an increase in molten slag temperature. All the results could provide guidance for the design of industrial plant for molten blast furnace slag granulation. - Highlights: • Dry granulation for molten blast furnace slag is an attractive alternative to wet granulation. • Transition equation can be used to identify state of disintegration for molten slag granulation. • The diameter of slag particles decreased as an increase in angular speed and diameter of rotary cup. • There was no change in diameter of slag particles with an increase in molten slag temperature

  13. Development of giant granules in platelets during prolonged storage.

    White, J. G.; Clawson, C. C.


    Giant granules are uncommon in normal human platelets but are frequently observed in platelets from patients with the Chédiak-Higashi syndrome, some case of May-Hegglin anomaly, and individuals with chronic refractory anemia (preleukemia) or myelomonocytic leukema. However, the numbers of platelets containing the giant granule anomaly are so low that it has been impossible to isolate them in sufficient quantity to identify the mechanisms involved in their formation. Recently conditions were f...

  14. Preventive effect of Ganfujian granule on experimental hepatocarcinoma in rats

    Yan Qian; Chang-Quan Ling


    AIM: To investigate the inhibitory effect of dietary and medicinal formula Ganfujian granule on diethylnitrosamine (DEN)-induced hepatocarcinoma in rats.METHODS: Male SD rats had free access to water containing 0.1 g/L DEN for 16 weeks, during which the rats fed with standard diet or administration of Ganfujian granule (30.4 g/Kg in diet). At weeks 4, 8, 12 and 16 of hepatocarcinogenesis 5 rats of each group were sacrificed, and at week 20 another 30 rats were sacrificed from each group. The end point for survival observation was at week 28.Immunochemistry methods were used to examine the effect of Ganfujian granule on the process of hepatocarcinogenesis including proliferation of hepatocytes and cell cycle modulation.RESULTS: Ganfujian granule could reduce and delay the incidence of hepatocarcinoma in rats and prolong the survival of animals. In addition, Ganfujian granule had a marked inhibitory effect on high expression of cyclin dependent kinase (CDK4) during the whole process of hepatocarcinogenesis and cyclin D1 at week 16 and the number of proliferating cell nuclear antigen (PCNA) positive cells in different stages of hepatocarcinogenesis.CONCLUSION: Ganfujian granule can reduce and delay the incidence of hepatocarcinoma in rats by exerting direct or indirect effects on cell cycle and inhibiting uncontrolled proliferation of hepatocytes.

  15. Diversion of Stress Granules and P-Bodies During Viral Infection

    Reineke, Lucas C.; Lloyd, Richard E.


    RNA granules are structures within cells that impart key regulatory measures on gene expression. Two general types of RNA granules are conserved from yeast to mammals: stress granules (SGs), which contain many translation initiation factors, and processing bodies (P-bodies, PBs), which are enriched for proteins involved in RNA turnover. Because of the inverse relationship between appearance of RNA granules and persistence of translation, many viruses must subvert RNA granule function for repl...

  16. Physical Properties of Large and Small Granules in Solar Quiet Regions

    Yu, Daren; Xie, Zongxia; Hu, Qinghua; Yang, Shuhong; Zhang, Jun; Wang, Jingxiu


    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 1farcs44, and large granules with diameters larger than 1farcs44. 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 0.

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

    S. A. Habeeb, AB. Aziz Bin Abdul Latiff, Zawawi Bin Daud, Zulkifli Bin Ahmad


    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 p...

  18. Granule characterization during fluid bed drying by development of a near infrared method to determine water content and median granule size

    Nieuwmeyer, Florentine J. S.; Damen, Michiel; Gerich, Ad; Rusmini, Federica; van der Voort, Kees Maarschalk; Vromans, Herman


    Purpose. Water content and granule size are recognized as critical process and product quality parameters during drying. The purpose of this study was to enlighten the granule behavior during fluid bed drying by monitoring the major events i.e. changes in water content and granule size. Methods. NIR

  19. Recent results and prospects on superheated superconducting granules detectors

    The basic properties of superheated superconducting granules (SSG) detectors are reviewed. Recent results are presented and discussed. Granule samples of different sizes (10 μm -8Ω.cm -6 Ω.cm) exhibit encouraging sensitivity to low energy β and γ sources (down to 55Fe 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 (241Am, 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

  20. Cultivation of aerobic granules for simultaneous nitrification and denitrification by seeding different inoculated sludge

    WANG Fang; YANG Feng-lin; LIU Yi-hui; ZHANG Xing-wen


    Cultivation of aerobic granules for simultaneous nitrification and denitrification in two sequencing batch airlift bioreactors was studied. Conventional activated floc and anaerobic granules served as main two inoculated sludge in the systems. Morphological variations of sludge in the reactors were observed. It was found that the cultivation of aerobic granules was closely associated with the kind of inoculated sludge. Round and regular aerobic granules were prevailed in both reactors, and the physical characteristics of the aerobic granules in terms of settling ability, specific gravity, and ratio of water containing were distinct when the inoculate sludge was different.Aerobic granules formed by seeding activated floc are more excellent in simultaneous nitrification and denitrification than that by aerobic granules formed from anaerobic granules. It was concluded that inoculated sludge plays a crucial role in the cultivation of aerobic granules for simultaneous nitrification and denitrification.

  1. Aerobic Granulation in Sequencing Batch Reactor (SBR Treating Saline Wastewater

    Ensieh Taheri


    Full Text Available Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background and Objectives: Aerobic sludge granulation is an advanced phenomenonin which its mechanisms have not been understood. Granulation can be a promising and novel biological wastewater treatment technology to eliminate organic and inorganic materials in future. High salinity is a parameter which leads to plasmolisatian and reduction of the cell activity. This could be a problem for biological treatment of the saline wastewater. Aerobic granule was formed and investigated during this study. Materials and Methods: This study is an intervention study on the treatment of wastewater with 500-10000 mg/L concentration of NaCl by sequencing batch reactor. Asynthesized wastewater including nutrient required for microorganism's growth was prepared. Input and output pH and EC were measured. Range of pH and DO varied between 7-8, and 2-5 mg/L, respectively. SEM technology was used to identify graduals properties.Results: In terms of color, granules divided into two groups of light brown and black. Granule ranged in 3-7mm with the sediment velocity of 0.9-1.35 m/s and density of 32-60 g/L.Properties of granules were varied. Filamentous bacteria and fungi were dominant in some granules. However non filamentous bacteria were dominant in others. EDX analysis indicated the presence of Ca and PO4.Conclusion: Granules with non filamentous bacterial were compact and settled faster. Presence of different concentrations of salinity leaded to plasmolysis of the bacterial cells and increased concentrations of EPS  in the system as a result  of which granulation accelerated. /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso

  2. Innovative powder production and granulation for advanced MOX fuel forming

    In accordance with a long ranged research and development plan on the MOX fuel production for future FBR, we have been investigating the innovative MOX processing. Along with this plan, a new idea for realizing the serial processing, (1) crushing the solidified solute, and (2) granulation, in one vessel, are being proposed. An innovative design of a new system and the granulation examination were attempted. In order to establish the granulation technology, JAEA selected a candidate of machine, which has a rotating three lobes impeller (the crusher) driven from top outside of the casing, so as to fit our new system. This machine is mounted on a circular pan which sustains the evaporation dish, forming a vessel. The evaporation dish filled by solidified solute is moved from the Microwave oven into this vessel after the de-nitration. The rotary impeller is inserted on the solidified solute and crushes it until a reasonable powder state is obtained. The impeller is also utilized as the granulator after completion of the crushing. Namely, giving a slow rotation under showering, those powder changes into particles. Thus, the crushing and granulation are combined through the rotary impeller. As a result, the air flow assisted transfer of powder from the crusher to the granulator becomes unnecessary. According to the cold testing employing WO3 powder, the practical granulation was successfully carried out. The size of formed particle was larger than 100 m, and the flow-ability was ranged 80-90, being better than averaged value of conventional MOX particles produced by microwave direct heating method. The merits of the new granulation system are, (1) dispersion, scatter, and deposit of MOX powder which appear in the conventional transfer route are easy to prevent, and (2) running and control of job are easy. Due to the establishment of granulation technology by the system, it contributes the improvement of processing efficiency, lowering the construction and maintenance

  3. Microbial community variation in cryoconite granules on Qaanaaq Glacier, NW Greenland.

    Uetake, Jun; Tanaka, Sota; Segawa, Takahiro; Takeuchi, Nozomu; Nagatsuka, Naoko; Motoyama, Hideaki; Aoki, Teruo


    Cryoconite granules are aggregations of microorganisms with mineral particles that form on glacier surfaces. To understand the processes by which the granules develop, this study focused on the altitudinal distribution of the granules and photosynthetic microorganisms on the glacier, bacterial community variation with granules size and environmental factors affecting the growth of the granules. Size-sorted cryoconite granules collected from five different sites on Qaanaaq Glacier were analyzed. C and N contents were significantly higher in large (diameter greater than 250 μm) granules than in smaller (diameter 30-249 μm) granules. Bacterial community structures, based on 16S rRNA gene amplicon sequencing, were different between the smaller and larger granules. The filamentous cyanobacterium Phormidesmis priestleyi was the dominant bacterial species in larger granules. Multivariate analysis suggests that the abundance of mineral particles on the glacier surface is the main factor controlling growth of these cyanobacteria. These results show that the supply of mineral particles on the glacier enhances granule development, that P. priestleyi is likely the key species for primary production and the formation of the granules and that the bacterial community in the granules changes over the course of the granule development. PMID:27306554

  4. Lysophospholipids in pig pancreatic zymogen granules in relation to exocytosis

    A hypothesis to explain the stimulatory role of cyclic AMP (adenosine 3' : 5'-monophosphate) in pancreatic enzyme secretion has been tested. In this hypothesis cyclic AMP would activate a phospholipase activity, which would lead to a locally increased lysophospholipid formation, resulting in a fusion between the zymogen granule membrane and the apical plasma membrane. Cyclic AMP added to isolated pig pancreatic zymogen granules leads to an increased lysis of these granules, but the slowness of this effect makes its physiological significance dubious. In pancreatic homogenates or zymogen granules no stimulating effect of cyclic AMP on lipase or phospholipase activity could be demonstrated. Isolated zymogen granules have a high lysophospholipid content (27% of total phospholipids), consisting of the 1-acyl and 2-acyl forms of lysophosphatidylcholine and lysophosphatidylethanolamine. Experiments with radioactive phosphatidylcholine indicate that the lysophospholipids are due to the action of endogenous (phospho)lipases during the isolation procedure. It is concluded that these experiments do not lend support to the above hypothesis for the mechanism of action of cyclic AMP in pancreatic enzyme secretion. (orig.)


    龚伊红; R.R.Hcrberman; C.W.Reynolds


    Antisexum against purified cytoplasmic granules from rat LGL tumor cells, and protein A-gold inmmnoelec-tron microscopy were used to study the secretory events in lysis of YAC-1 tumor cells by rat LGL tumor cells or by isolated LGL from normal rats. After 30 min incubation of effector and target cells together, gold-labeled cyto-plasmic granules were often seen concentrated in the area of the LGL adjacent to the ~ YAC-1 Within 60min,the grantees were observed to move to the cell border near the conjugazed site. At this point, fine granules were fused with file cell membrane, and subsequently released file gold-labeled contents into the junction between the LGL and the target cell. Gold particles could be seen at the B-T interface, on the surface,or sometimes on the target cell surface.These data provide direct evidence for the hypothesis that under conditions of active cytotoxicity,natural killer cells secrete their cytoplasmic granule contents leading to the deposition of granule material on the target cell surface and the eventual lysis of the cell.

  6. Understanding the impact of influent nitrogen concentration on granule size and microbial community in a granule-based enhanced biological phosphorus removal system.

    Zou, Jinte; Li, Yongmei; Zhang, Lili; Wang, Ruyi; Sun, Jing


    To better understand the effect of influent nitrogen concentration on granule size and microbial community in a granule-based enhanced biological phosphorus removal system, three influent nitrogen concentrations were tested while carbon concentration was an unlimited factor. The results show that although ammonium and phosphate were well removed in the tested nitrogen concentration range (20-50 mg L(-1)), granule size, the amount of phosphate accumulating organisms (PAOs) and microbial activity were affected significantly. A possible mechanism for the effect of influent nitrogen concentration on granule size is proposed based on the experimental results. The increase in proteins/polysaccharides ratio caused by high influent nitrogen concentration plays a crucial role in granule breakage. The small granule size then weakens simultaneous nitrification-denitrification, which further causes higher nitrate concentration in the effluent and lower amount of PAOs in sludge. Consequently, phosphate concentration in the anaerobic phase decreases, which plays the secondary role in granule breakage. PMID:25496940

  7. Relative dispersion of trapped ion granulations in sheared flows

    The life time of trapped ion granulations (trapped ions correlated by resonance) in sheared flows is calculated. The dynamics of trapped ion granulations, in the presence of sheared flows, is formulated in terms of two point correlation function of phase space density fluctuations. The evolution equation is closed by a simplified closure calculation of the triplet term. Based on the closed equation, the life time of the relative dispersion of trapped ion granulations is calculated. The result shows that 1) a relevant time scale enters via a hybrid of decorrelation and shearing, (Δωcv'y2)1/3 and 2) small scale singularities in the absence of collisional dissipation enters through logarithmic divergence. (author)

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

    Lloyd, Richard E


    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. PMID:27043612

  9. Cystatin F Ensures Eosinophil Survival by Regulating Granule Biogenesis

    Matthews, Stephen P.; McMillan, Sarah J.; Colbert, Jeff D.; Lawrence, Rachel A.; Watts, Colin


    Summary Eosinophils are now recognized as multifunctional leukocytes that provide critical homeostatic signals to maintain other immune cells and aid tissue repair. Paradoxically, eosinophils also express an armory of granule-localized toxins and hydrolases believed to contribute to pathology in inflammatory disease. How eosinophils deliver their supporting functions while avoiding self-inflicted injury is poorly understood. We have demonstrated that cystatin F (CF) is a critical survival factor for eosinophils. Eosinophils from CF null mice had reduced lifespan, reduced granularity, and disturbed granule morphology. In vitro, cysteine protease inhibitors restored granularity, demonstrating that control of cysteine protease activity by CF is critical for normal eosinophil development. CF null mice showed reduced pulmonary pathology in a model of allergic lung inflammation but also reduced ability to combat infection by the nematode Brugia malayi. These data identify CF as a “cytoprotectant” that promotes eosinophil survival and function by ensuring granule integrity. Video Abstract PMID:27067058

  10. FTIR-ATR imaging of TAED-detergent granules

    Complete text of publication follows. The microstructure of detergents products for textile cleaning determines to a large extent their physical properties of these products. Release of a certain compound at a given time can improve the washing effect. Tetraacetylethylenediamine (TAED) is an important ingredient of washing powder/tablets. Its function is to enhance the bleaching effect to remove stains on clothing at lower temperatures. TAED granules are post-dosed to the formulation and consist of 4 compounds e.g.; TAED, sodium sulphate, a polymer and clay. To elucidate the microstructure of the detergents granules Fourier Transform Infrared (FTIR) microscopy using an Attenuated Total Reflection (ATR) crystal and Light Microscopy (LM) were used for characterization. FTIR-ATR-imaging was performed to elucidate the location of the different compounds. A Ge-crystal was brought in contact with the surface of interest. A principal component analysis was performed on the FTIR-ATR image, thus revealing the spatial distribution of the compounds (Figure 1) within the detergent granule. The full spectra obtained in a pixel can be used for identification. Figure 1 shows the distribution of the different compounds present in the TAED granule. The structure of the granule on the right is very porous. It shows large TAED particles partially encapsulated by sulphate and surrounded by the embedding material. The clay and copolymer compounds are mainly located around inner TAED particles. Combing techniques like FTIR-ATR imaging and LM results in useful information about the spatial distribution of chemical compounds within TAED granules. The FTIR spectra are used for positively identifying the chemical compounds.

  11. Application of high OLR-fed aerobic granules for the treatment of low-strength wastewater: performance, granule morphology and microbial community.

    Ma, Jingyun; Quan, Xiangchun; Li, Huai


    Aerobic granules, pre-cultivated at the organic loading rate (OLR) of 3.0 kg COD/(m3 x day), were used to treat low-strength wastewater in two sequencing batch reactors at low OLRs of 1.2 and 0.6 kg COD/(m3 x day), respectively. Reactor performance, evolution of granule morphology, structure and microbial community at low OLRs under long-term operation (130 days) were investigated. Results showed that low OLRs did not cause significant damage to granule structure as a dominant granule morphology with size over 540 microm was maintained throughout the operation. Aerobic granules at sizes of about 750 microm were finally obtained at the low OLRs. The granule reactors operated at low OLRs demonstrated effective COD and ammonia removals (above 90%), smaller granule sizes and less biomass. The contents of extracellular polymeric substances in the granules were decreased while the ratios of exopolysaccharide/exoprotein were increased (above 1.0). The granules cultivated at the low OLRs showed a smoother surface and more compact structure than the seeded granules. A significant shift in microbial community was observed but the microbial diversity remained relatively stable. Confocal Laser Scanning Microscopy observation showed that the live cells were spread throughout the whole granule, while the dead cells were mainly concentrated in the outer layer of the granule, and the proteins, polysaccharides and lipids were mainly located in the central regime of the granule. In conclusion, granules cultivated at high OLRs show potential for treating low-strength organic wastewater steadily under long-term operation. PMID:24520692

  12. Nuclear recoil measurements in Superheated Superconducting Granule detectors

    Schmiemann, K.


    The response of Superheated Superconducting Granule (SSG) devices to nuclear recoils has been explored by irradiating SSG detectors with a 70Me$\\!$V neutron beam. In the past we have tested Al SSG and more recently, measurements have been performed with Sn and Zn detectors. The aim of the experiments was to test the sensitivity of SSG detectors to recoil energies down to a few ke$\\!$V. In this paper, the preliminary results of the neutron irradiation of a SSG detector made of Sn granules 15-2...

  13. Obtaining high thermally conductive materials by pressing from the granulate

    Ditts, A.; Revva, I.; Pautova, Y.; Pogrebenkov, V.; Nepochatov, Y.; Galashov, E.; Tarnovskiy, R.


    This work contains results of investigation of obtaining high thermally conductive ceramics from commercial powders of aluminum nitride and yttrium oxide by the method of monoaxial compaction of granulate. The principal scheme of preparation is proposed and technological properties of granulate are defined. Compaction conditions for simple items to use as heat removal in microelectronics and power electrical engineering have been established. Investigations of thermophysical properties of obtained ceramics and its structure by the XRD and SEM methods have been carried out. Ceramics with thermal conductivity from 172 to 174 W/m·K has been obtained as result of this work.

  14. Rapid start-up and improvement of granulation in SBR

    Jalali, Sajjad; Shayegan, Jalal; Rezasoltani, Samira


    Background The aim of this study is to accelerate and improve aerobic granulation within a Sequencing Batch Reactor (SBR) by cationic polymer addition. Methods To identify whether the polymer additive is capable of enhancing granule formation, two SBRs (R1 and R2, each 0.15 m in diameter and 2 m in height) are used by feeding synthetic wastewater. The cationic polymer with concentration of 30 to 2 ppm is added to R2, while no cationic polymer is added to R1. Results Results show that the cati...

  15. Semi-granules and schielding for off-line scheduling

    Le Goff, Bernard; Le Guernic, Paul; Araoz Durand, Julian


    In the framework of parallel programming, we use a type of directed graph, which we call the pin-graph, as a model for various applications : the vertices represent the elementary tasks ; the arcs represent the internal dependences ; and the pins represent communication with the outside. The connectivity of pins-graphs is studied in order to classify them into two classes. A pin-graph in the first class is called a semi-granule. The elementary tasks of a semi-granule can be ordered into a seq...

  16. Fate of aerobic bacterial granules with fungal contamination under different organic loading conditions

    Li, AJ; Zhang, T.; LI, XY


    Aerobic sludge granulation is an attractive new technology for biological wastewater treatment. However, the instability of aerobic granules caused by fungal growth is still one of the main problems encountered in granular bioreactors. In this study, laboratory experiments were conducted to investigate the fate and transformation of aerobic granules under different organic loading conditions. Bacterial granules (2-3 mm) in a poor condition with fungi-like black filamentous growth were seeded ...

  17. Granulated metrial gland cells in the uterine wall and placenta of the pregnant woodmouse, Apodemus sylvaticus.

    Stewart, I J; Clarke, J R


    The differentiation of the decidua and the fetal placenta in the woodmouse, Apodemus sylvaticus, was studied with particular attention to the differentiation and migration of granulated metrial gland cells. Numerous granulated metrial gland cells, characterised by their glycoprotein-containing cytoplasmic granules, were found to differentiate in the decidua basalis and metrial gland of the uterine wall during the first half of pregnancy. Many granulated metrial gland cells appeared to pass in...

  18. Electron microscope observations on the cytoplasmic granules of a freshwater teleost (Pimelodus maculatus) leucocyte.

    Ferri, S; Hernandez Blazquez, F J


    In the present study, a hitherto undescribed granule type in the leucocytes of the freshwater teleost Pimelodus maculatus is reported. This membrane bounded elliptic granule contains straight tubules measuring from 8 to 10 nm in diameter. Almost all granules present 1 or 2 electron dense inclusions more often than not with a geometrical form. A comparison with the granules found in Prochilodus scrofa leucocytes is made. PMID:3631529

  19. Starch Granule and Protein Accumulation during Seed Development of Ginkgo biloba L.

    Jin, Biao; Xie, Yan; Lu, Yan; Wang, Di; Zhang, Min; Wang, Li


    We investigated starch and protein formation and accumulation in the seed of Ginkgo biloba L. In the testa, starch granules and protein bodies (PBs) started to form and accumulate 30 days after pollination; they decreased in size and completely disappeared before maturity. In the endosperm, starch granules began to accumulate 45 days after pollination, and the number and size of starch granules increased gradually within 65 days after pollination. Starch granules, which were mainly produced i...

  20. Stress induces the assembly of RNA granules in the chloroplast of Chlamydomonas reinhardtii

    Uniacke, James; Zerges, William


    Eukaryotic cells under stress repress translation and localize these messenger RNAs (mRNAs) to cytoplasmic RNA granules. We show that specific stress stimuli induce the assembly of RNA granules in an organelle with bacterial ancestry, the chloroplast of Chlamydomonas reinhardtii. These chloroplast stress granules (cpSGs) form during oxidative stress and disassemble during recovery from stress. Like mammalian stress granules, cpSGs contain poly(A)-binding protein and the small, but not the lar...

  1. CSR-1 and P granules suppress sperm-specific transcription in the C. elegans germline

    Campbell, Anne C.; Updike, Dustin L.


    Germ granules (P granules) in C. elegans are required for fertility and function to maintain germ cell identity and pluripotency. Sterility in the absence of P granules is often accompanied by the misexpression of soma-specific proteins and the initiation of somatic differentiation in germ cells. To investigate whether this is caused by the accumulation of somatic transcripts, we performed mRNA-seq on dissected germlines with and without P granules. Strikingly, we found that somatic transcrip...

  2. Characterization of proinsulin- and proglucagon-converting activities in isolated islet secretory granules


    The conversion of proglucagon and proinsulin by secretory granules isolated from both prelabeled and unlabeled anglerfish islets was investigated. Either granules isolated from tissue labeled with [3H]tryptophan and [14C]isoleucine or [35S]cysteine, or lysed granules from unlabeled tissue to which exogenously labeled prohormones had been added were incubated under various conditions. Acetic acid extracts of these granule preparations were analyzed for prohormone and hormone content by gel fil...

  3. Investigation on Side-Spray Fluidized Bed Granulation with Swirling Airflow

    Wong, Poh Mun; Chan, Lai Wah; Heng, Paul Wan Sia


    Top-spray fluidized bed granulation with axial fluidization airflow from the bottom of the granulator is well-established in the pharmaceutical industry. The application of swirling airflow for fluidized bed granulation was more recently introduced. This study examined the effects of various process parameters on the granules produced by side-spray fluidized bed with swirling airflow using the central composite and Box–Behnken design of experiment. Influence of the amount of binder solution, ...

  4. The immediately releasable pool of mouse chromaffin cell vesicles is coupled to P/Q-type calcium channels via the synaptic protein interaction site.

    Yanina D Álvarez

    Full Text Available It is generally accepted that the immediately releasable pool is a group of readily releasable vesicles that are closely associated with voltage dependent Ca(2+ channels. We have previously shown that exocytosis of this pool is specifically coupled to P/Q Ca(2+ current. Accordingly, in the present work we found that the Ca(2+ current flowing through P/Q-type Ca(2+ channels is 8 times more effective at inducing exocytosis in response to short stimuli than the current carried by L-type channels. To investigate the mechanism that underlies the coupling between the immediately releasable pool and P/Q-type channels we transiently expressed in mouse chromaffin cells peptides corresponding to the synaptic protein interaction site of Cav2.2 to competitively uncouple P/Q-type channels from the secretory vesicle release complex. This treatment reduced the efficiency of Ca(2+ current to induce exocytosis to similar values as direct inhibition of P/Q-type channels via ω-agatoxin-IVA. In addition, the same treatment markedly reduced immediately releasable pool exocytosis, but did not affect the exocytosis provoked by sustained electric or high K(+ stimulation. Together, our results indicate that the synaptic protein interaction site is a crucial factor for the establishment of the functional coupling between immediately releasable pool vesicles and P/Q-type Ca(2+ channels.

  5. Characterization of Pu-238 Heat Source Granule Containment

    Richardson, Paul Dean II [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Sanchez, Joey Leo [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Wall, Angelique Dinorah [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Chavarria, Rene [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)


    The Milliwatt Radioisotopic Themoelectric Generator (RTG) provides power for permissive-action links. Essentially these are nuclear batteries that convert thermal energy to electrical energy using a doped silicon-germanium thermopile. The thermal energy is provided by a heat source made of 238Pu, in the form of 238PuO2 granules. The granules are contained by 3 layers of encapsulation. A thin T-111 liner surrounds the 238PuO2 granules and protects the second layer (strength member) from exposure to the fuel granules. An outer layer of Hastalloy-C protects the T-111 from oxygen embrittlement. The T-111 strength member is considered the critical component in this 238PuO2 containment system. Any compromise in the strength member seen during destructive testing required by the RTG surveillance program is characterized. The T-111 strength member is characterized through Scanning Electron Microscopy (SEM), and Metallography. SEM is used in the Secondary Electron mode to reveal possible grain boundary deformation and/or cracking in the region of the strength member weld. Deformation and cracking uncovered by SEM are further characterized by Metallography. Metallography sections are mounted and polished, observed using optical microscopy, then documented in the form of microphotographs. SEM mat further be used to examine polished Metallography mounts to characterize elements using the SEM mode of Energy Dispersive X-ray spectroscopy (EDS).

  6. F-Granulation Generalized Rough Entropy and Image Analysis

    Pal, Sankar K.


    Role of f-granulation in handling uncertainty in machine intelligence and its significance as a facet of natural computation are discussed. Its modeling through judicious integration of rough and fuzzy sets is explained. Several tasks like case generation, clustering, classification and segmentation are described in rough-fuzzy framework demonstrating the role of f-granulation and the resulting merits. A definition of generalized rough sets is given considering both the set and granules as crisp and/or fuzzy. Based on that new entropy measures are defined using exponential and logarithmic gain functions. The superiority of rough-fuzzy integration, in terms of performance and computation time, is illustrated for the tasks of case mining in large data sets, segmenting brain MR images, and classifying remotely sensed images as examples. Neighbourhood rough sets are capable of better dimensionality reduction. The effect of fuzzy-granules and generalizations in rough sets is demonstrated for image segmentation. The article includes some of the results published elsewhere.

  7. Some peculiarities of thermoelectric transformation of energy in granulated semiconductors

    The work presents a model of equivalent medium that allows one to estimate the thermoelectric characteristics of nonuniform semiconductor materials. The model describes experimental results obtained on microgranular silicon and defines ways of achieving high values of thermoelectric Q factor in transformers of thermal energy based on granulated semiconductors in a temperature range that can be easily achieved using solar concentrators. (author)

  8. Block-based approach to modelling of granulated fertilizers' quality

    Kohonen, J.; Reinikainen, S. P.; Høskuldsson, Agnar


    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...

  9. Iron-based granules in body of bumblebees

    Jandacka, P.; Kasparova, B.; Jirásková, Yvonna; Dedkova, K.; Mamulová-Kutláková, K.; Kukutschová, J.


    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: 2.503, year: 2014

  10. Glass foam granulate as growing medium for tomato and cucumber

    Blok, C.; Winkel, van A.; Chizhmak, S.


    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

  11. Scale-Up to High Shear Wet Granulation Process

    Belohlav, Z.; Brenková, L.; Durdil, P.; Hanika, Jiří; Lehotský, M.; Rápek, P.; Tomášek, V.

    Praha : Process Engineering Publisher, 2004, s. 993. ISBN 80-86059-40-5. [International Congress of Chemical and Process Engineering CHISA 2004 /16./. Praha (CZ), 22.08.2004-26.08.2004] Institutional research plan: CEZ:AV0Z4072921 Keywords : scale-up * pharmaceutical industry * granulation process Subject RIV: CI - Industrial Chemistry, Chemical Engineering

  12. Deubiquitination and the regulation of stress granule assembly.

    Nostramo, R; Herman, P K


    Stress granules (SGs) are evolutionarily conserved ribonucleoprotein (RNP) structures that form in response to a variety of environmental and cellular cues. The presence of these RNP granules has been linked to a number of human diseases, including neurodegenerative disorders like amyotrophic lateral sclerosis (ALS) and spinocerebellar ataxia type 2 (Li et al., J Cell Biol 201:361-372, 2013; Nonhoff et al., Mol Biol Cell 18:1385-1396, 2007). Understanding how the assembly of these granules is controlled could, therefore, suggest possible routes of therapy for patients afflicted with these conditions. Interestingly, several reports have identified a potential role for protein deubiquitination in the assembly of these RNP granules. In particular, recent work has found that a specific deubiquitinase enzyme, Ubp3, is required for efficient SG formation in S. cerevisiae (Nostramo et al., Mol Cell Biol 36:173-183, 2016). This same enzyme has been linked to SGs in other organisms, including humans and the fission yeast, Schizosaccharomyces pombe (Takahashi et al., Mol Cell Biol 33:815-829, 2013; Wang et al., RNA 18:694-703, 2012). At first glance, these observations suggest that a striking degree of conservation exists for a ubiquitin-based mechanism controlling SG assembly. However, the devil is truly in the details here, as the precise nature of the involvement of this deubiquitinating enzyme seems to vary in each organism. Here, we briefly review these differences and attempt to provide an overarching model for the role of ubiquitin in SG formation. PMID:26852120

  13. Mechanisms underlying the beneficial effects of Kaiyu Granule for depression

    Xi Jin; Yidan Zhang; Qiaoying Li; Jianjun Zhao


    The proprietary Chinese medicine preparation Kaiyu Granule is made of bupleurum, nutgrass ga-lingale rhizome, szechwan lovage rhizome, turmeric root tuber, white peony alba, cape jasmine fruit, fried semen ziziphi jujubae, and prepared liquorice root. It is a common recipe for the clinical treatment of depression in China. In this study, after 21 days of unpredictable stress exposure, Wistar rats exhibited similar behavioral changes to patients with depression. Moreover, G-protein-coupled inwardly rectifying K+channel 1 mRNA and protein expression were significantly reduced in rat hippocampal CA1 and CA3 regions. However, G-protein-coupled inwardly rectifying K+channel 1 mRNA, protein expression, and rat behavior were clearly better after administration of 12, 8, or 4 g/kg of Kaiyu Granule when depression model rats underwent stress. 12 g/kg of Kaiyu Granule had the most obvious effects on the increased expression of G-protein-coupled inwardly rectifying K+channel 1 mRNA and protein in rat hippocampal CA1 and CA3 regions. These results suggested that Kaiyu Granule improved depression by affecting G-protein-coupled inwardly fying K+channel 1 expression in the rat hippocampus.

  14. Mechanisms underlying the beneficial effects of Kaiyu Granule for depression.

    Jin, Xi; Zhang, Yidan; Li, Qiaoying; Zhao, Jianjun


    The proprietary Chinese medicine preparation Kaiyu Granule is made of bupleurum, nutgrass galingale rhizome, szechwan lovage rhizome, turmeric root tuber, white peony alba, cape jasmine fruit, fried semen ziziphi jujubae, and prepared liquorice root. It is a common recipe for the clinical treatment of depression in China. In this study, after 21 days of unpredictable stress exposure, Wistar rats exhibited similar behavioral changes to patients with depression. Moreover, G-protein-coupled inwardly rectifying K(+) channel 1 mRNA and protein expression were significantly reduced in rat hippocampal CA1 and CA3 regions. However, G-protein-coupled inwardly rectifying K(+) channel 1 mRNA, protein expression, and rat behavior were clearly better after administration of 12, 8, or 4 g/kg of Kaiyu Granule when depression model rats underwent stress. 12 g/kg of Kaiyu Granule had the most obvious effects on the increased expression of G-protein-coupled inwardly rectifying K(+) channel 1 mRNA and protein in rat hippocampal CA1 and CA3 regions. These results suggested that Kaiyu Granule improved depression by affecting G-protein-coupled inwardly rectifying K(+) channel 1 expression in the rat hippocampus. PMID:25206645

  15. Process of extracting volatile ingredients from powdered or granulated material

    Bronder, G.A.


    A process of treating powdered or granulated shale to produce oil is described consisting in separating the shale into portions adjacent to each other and translating them in one direction and simultaneously subjecting them to heat. The vapors generated from the shale are collected. Shale from one portion is forced to mix with the next adjacent portion simultaneously with the translation of the portions.

  16. Jingtong Granule: A Chinese Patent Medicine for Cervical Radiculopathy

    Liguo Zhu; Jinghua Gao; Jie Yu; Minshan Feng; Jinyu Li; Shangquan Wang; Xu Wei


    Objective. This paper systematically assessed the efficacy and safety of Jingtong granule (JG) for cervical radiculopathy (CR). Methods. Randomized controlled trials comparing JG with no intervention, placebo, or conventional therapies were retrieved. The trials testing JG combined with conventional therapies versus conventional therapies were also enrolled. Study selection, methodological assessment, data extraction, and analysis were conducted in accordance with the Cochrane standards. The ...

  17. Biological Hydrogen Production Using Chloroform-treated Methanogenic Granules

    Hu, Bo; Chen, Shulin

    In fermentative hydrogen production, the low-hydrogen-producing bacteria retention rate limits the suspended growth reactor productivity because of the long hydraulic retention time (HRT) required to maintain adequate bacteria population. Traditional bacteria immobilization methods such as calcium alginate entrapment have many application limitations in hydrogen fermentation, including limited duration time, bacteria leakage, cost, and so on. The use of chloroform-treated anaerobic granular sludge as immobilized hydrogen-producing bacteria in an immobilized hydrogen culture may be able to overcome the limitations of traditional immobilization methods. This paper reports the findings on the performance of fed-batch cultures and continuous cultures inoculated with chloroform-treated granules. The chloroform-treated granules were able to be reused over four fed-batch cultures, with pH adjustment. The upflow reactor packed with chloroform-treated granules was studied, and the HRT of the upflow reactor was found to be as low as 4 h without any decrease in hydrogen production yield. Initial pH and glucose concentration of the culture medium significantly influenced the performance of the reactor. The optimum initial pH of the culture medium was neutral, and the optimum glucose concentration of the culture medium was below 20 g chemical oxygen demand/L at HRT 4 h. This study also investigated the possibility of integrating immobilized hydrogen fermentation using chloroform-treated granules with immobilized methane production using untreated granular sludge. The results showed that the integrated batch cultures produced 1.01 mol hydrogen and 2 mol methane per mol glucose. Treating the methanogenic granules with chloroform and then using the treated granules as immobilized hydrogen-producing sludge demonstrated advantages over other immobilization methods because the treated granules provide hydrogen-producing bacteria with a protective niche, a long duration of an active

  18. Two Distinct Waxy Alleles Impact the Granule-Bound Starch Synthase in Sorghum

    The granule-bound starch synthase (GBSS) is the enzyme responsible for amylose synthesis in starch granules. Loss of GBSS activity results in starch granules containing mostly amylopectin and little or no amylose, a phenotype described as waxy. Previously, two phenotypic classes of waxy alleles we...

  19. Continuous and sustainable granulation of nanopharmaceuticals by spray coagulation encapsulation in alginate.

    Hadinoto, Kunn; Yang, Yue


    Nanopharmaceuticals (NPs) have emerged as an attractive formulation strategy for bioavailability enhancement of poorly soluble drugs. Their oral solid dosage form preparation requires them to undergo granulation before they can be processed into tablets. Existing NP granulation methods (e.g., spray drying, spray granulation), however, are lacking in sustainability due to their high energy expense and low mass efficiency. Herein we developed a one-step continuous NP granulation process via encapsulation by spray coagulation (ESC) in alginate, which transforms the NP immediately upon their preparation, thus removing the need for NP recovery prior to granulation, resulting in a highly sustainable process. Moreover, unlike spray-dried NP granules, the ESC-prepared granules are readily compacted into tablets owed to their larger size, thus further enhancing the overall sustainability of the solid dosage form preparation. Crystalline fenofibrate nanoparticles prepared by confined impinging jet crystallization were used as the model NP. Granules containing 25% NPs by mass with size ≈ 300 ± 100 μm were successfully prepared at >80% yield. The NPs maintain their fast dissolution (relative to native microcrystalline fenofibrate) after granulation. The tableted NP granules, having uniform dosage, exhibit similar drug release profiles as the free granules indicating complete granule disassociation from the tablets. PMID:25089512

  20. 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 ...

  1. 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... ...

  2. 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 ...

  3. 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... ...

  4. File list: Unc.Neu.05.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available Unc.Neu.05.AllAg.Cerebellar_granule_neurons mm9 Unclassified Neural Cerebellar granule neurons... ...

  5. 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 ...

  6. 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... ...

  7. 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... ...

  8. 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... ...

  9. 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 ...

  10. 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... ...

  11. 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... ...

  12. 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... ...

  13. 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 ...

  14. 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... ...

  15. 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... ...

  16. File list: DNS.Neu.05.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Full Text Available DNS.Neu.05.AllAg.Cerebellar_granule_neurons mm9 DNase-seq Neural Cerebellar granule neurons... SRX685885,SRX685878,SRX685882,SRX685877,SRX685880,SRX685883 ...

  17. 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... ...

  18. 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... ...

  19. 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 ...

  20. 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 ...

  1. 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... ...

  2. 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... ...

  3. A Kinetic Study of the Polymorphic Transformation of Nimodipine and Indomethacin during High Shear Granulation

    Guo, Zhen; Ma, Mingxin; Wang, Tianyi; Chang, Di; Jiang, Tongying; Wang, Siling


    The objective of the present study was to investigate the mechanism, kinetics, and factors affecting the polymorphic transformation of nimodipine (NMD) and indomethacin (IMC) during high shear granulation. Granules containing active pharmaceutical ingredient, microcrystalline cellulose, and low-substituted hydroxypropylcellulose were prepared with ethanolic hydroxypropylcellulose solution, and the effects of independent process variables including impeller speed and granulating temperature we...

  4. Comparison of four enhancement strategies for aerobic granulation in sequencing batch reactors

    Aerobic granules were developed in four identical sequencing batch reactors (SBRs) with synthetic wastewater to compare different strategies for the enhancement of granulation. The SBRs were operated by (a) increasing organic loading rate in R1; (b) reducing settling time in R2; (c) extending starvation period in R3; and (d) increasing shear force in R4. The results showed that four operational strategies were able to enhance aerobic granulation successfully in SBR, but that also showed different effect on the granulation process and characteristics of mature aerobic granules. The rapidest granulation was observed by using short settling time (R2) and the granules had higher extracellular polymeric substance (EPS) than other reactors. Extended starvation period (R3) and high shear force (R4) resulted in longer granulation period and the granules with higher integrity and smaller size. Higher organic loading rate (R1) resulted in the granules with larger size and higher K value. The maximum specific COD removal rates (qmax) of the granules in all SBRs were at a similar level (0.13-0.16 g COD/h-g VSS) but the granules in R1 and R2 had higher apparent half rate constant (K) of 18 and 16 mg/L, than those in R3 and R4 (2.8 and 3.3 mg/L).

  5. Cold experiments on ligament formation for blast furnace slag granulation

    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.


    Jan J. Hycnar


    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.

  7. 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


    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. PMID:25703356

  8. Nitrifying and denitrifying bacteria in aerobic granules formed in sequencing batch airlift reactors

    WANG Fang; YANG Fenglin; QI Aijiu


    The purpose of this study was to investigate nitrifying bacteria and denitrifying bacteria isolated from aerobic granules.Aerobic granules were formed in an internal-circulate sequencing batch airlift reactor(SBAR)and biodegradation of NH3 -N was analyzed in the reactor.Bacteria were isolated and determined from aerobic granules using selected media.The growth properties and morphology of bacteria colonies were observed by controlling aerobic or anaerobic conditions in the culture medium.It was found that bacteria in aerobic granules were diverse and some of them were facultative aerobes.The diversity of bacteria in aerobic granules was a premise of simultaneous nitrification and denitrification.

  9. Statistical properties of solar granulation from the SOUP instrument on Spacelab 2

    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

  10. Effects of extracellular polymer substances on aerobic granulation in sequencing batch reactors

    WANG Zhi-ping; LIU Li-li; YAO Jie; SUN Li-xin; CAI Wei-min


    The effects of extracellular polymeric substances (EPS) on aerobic granulation in sequencing batch reactors (SBR) were investigated by evaluating the EPS content, and the relationship between EPS composition and surface properties of glucose-fed aerobic granules. The results show that aerobic granular sludge contains more EPS than seed sludge, and it is about 47 mg/gMLSS. Corresponding to the changes of EPS, the surface charge of microorganisms in granules increases from -0. 732 to -0. 845 meq/gMLSS, whereas the hydrophobicry changes significantly from 48.46% to 73. 16%. It is obviously that changes of EPS in sludge alter the negative surface charge and hydrophobieity of microorganisms in granules, enhance the polymeric interaction and promote the aerobic granulation. Moreover, EPS can serve as carbon and energy reserves in granulation, thus the growth between the interior and exterior bacteria is balanced, and the integrality of granules is maintained.SEM observation of the granules exhibits that EPS in granules are ropy ; by mixing with bacteria, compact matrix structure can be formed. The distribution of EPS in granules profiles the importance of EPS storage. It can be concluded that EPS play a crucial role in aerobic granulation.