Morphologic Integration of Hilar Ectopic Granule Cells into Dentate Gyrus Circuitry in the Pilocarpine Model of Temporal Lobe Epilepsy

PubMed Central

Cameron, Michael C.; Zhan, Ren-Zhi; Nadler, J. Victor

2014-01-01

After pilocarpine-induced status epilepticus, many granule cells born into the postseizure environment migrate aberrantly into the dentate hilus. Hilar ectopic granule cells (HEGCs) are hyperexcitable and may therefore increase circuit excitability. This study determined the distribution of their axons and dendrites. HEGCs and normotopic granule cells were filled with biocytin during whole-cell patch clamp recording in hippocampal slices from pilocarpine-treated rats. The apical dendrite of 86% of the biocytin-labeled HEGCs extended to the outer edge of the dentate molecular layer. The total length and branching of HEGC apical dendrites that penetrated the molecular layer were significantly reduced compared with apical dendrites of normotopic granule cells. HEGCs were much more likely to have a hilar basal dendrite than normotopic granule cells. They were about as likely as normotopic granule cells to project to CA3 pyramidal cells within the slice, but were much more likely to send at least one recurrent mossy fiber into the molecular layer. HEGCs with burst capability had less well-branched apical dendrites than nonbursting HEGCs, their dendrites were more likely to be confined to the hilus, and some exhibited dendritic features similar to those of immature granule cells. HEGCs thus have many paths along which to receive synchronized activity from normotopic granule cells and to transmit their own hyperactivity to both normotopic granule cells and CA3 pyramidal cells. They may therefore contribute to the highly interconnected granule cell hubs that have been proposed as crucial to development of a hyperexcitable, potentially seizure-prone circuit. PMID:21455997

Echinococcus granulosus equinus: an ultrastructural study of the laminated layer, including changes on incubating cysts in various media.

PubMed

Richards, K S; Arme, C; Bridges, J F

1983-06-01

The microfibrillate component of the laminated layer of Echinococcus granulosus equinus contains, except for the zone adjacent to the germinal layer, aggregates of electron-dense bodies displaying a sub-structure of electron-lucent spheres. The tegumentary syncytial cytoplasm contains randomly distributed electron-dense granules, many occurring near the apical plasmalemma, although exocytosis was rarely seen. Granules, similar in size and sub-structure to the bodies of the aggregates, also occur in the internuncial connexions and tegumentary cytons, suggesting that they may be produced in the cytons and released into the laminated layer via the internuncial connexions and tegumentary cytoplasm. Cysts incubated for 0.5-2.5 h in serum- and non-serum-containing media showed differences from non-incubated cysts. The distal half of the syncytium contained a progressive increase in the number of granules (distal: proximal 1.9:1 at 2.5 h; cf. 1:1 in non-incubated cysts), and exocytosis of granules into the laminated layer adjacent to the cyst had occurred. This cannot be attributed wholly to serum proteins. Cysts incubated for 21 h appeared 'normal', suggesting re-establishment of an equilibrium. Since the matrix of the laminated layer is considered homologous to the glycocalyx of other cestodes, the possible protective role played by the granules/bodies, characteristic of Echinococcus spp., is discussed.

Analysis of the release process of phenylpropanolamine hydrochloride from ethylcellulose matrix granules.

PubMed

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

2002-11-01

The release properties of phenylpropanolamine hydrochloride (PPA) from ethylcellulose (EC, ethylcellulose 10 cps (EC#10) and/or 100 cps (EC#100)) matrix granules prepared by the extrusion granulation method were examined. The release process could be divided into two parts, and was well analyzed by applying square-root time law and cube root law equations, respectively. The validity of the treatments was confirmed by the fitness of the simulation curve with the measured curve. At the initial stage, PPA was released from the gel layer of swollen EC in the matrix granules. At the second stage, the drug existing below the gel layer dissolved, and was released through the gel layer. Also, the time and release ratio at the connection point of the simulation curves was examined to determine the validity of the analysis. Comparing the release properties of PPA from the two types of EC matrix granules, EC#100 showed more effective sustained release than EC#10. On the other hand, changes in the release property of the EC#10 matrix granule were relatively more clear than that of the EC#100 matrix granule. Thus, it was supposed that EC#10 is more available for controlled and sustained release formulations than EC#100.

New clinicopathological associations and histoprognostic markers in ILAE types of hippocampal sclerosis.

PubMed

Calderon-Garcidueñas, Ana Laura; Mathon, Bertrand; Lévy, Pierre; Bertrand, Anne; Mokhtari, Karima; Samson, Véronique; Thuriès, Valérie; Lambrecq, Virginie; Nguyen, Vi-Huong Michel; Dupont, Sophie; Adam, Claude; Baulac, Michel; Clémenceau, Stéphane; Duyckaerts, Charles; Navarro, Vincent; Bielle, Franck

2018-02-24

Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is a heterogeneous syndrome. Surgery results in seizure freedom for most pharmacoresistant patients, but the epileptic and cognitive prognosis remains variable. The 2013 International League Against Epilepsy (ILAE) histopathological classification of hippocampal sclerosis (HS) has fostered research to understand MTLE-HS heterogeneity. We investigated the associations between histopathological features (ILAE types, hypertrophic CA4 neurons, granule cell layer alterations, CD34 immunopositive cells) and clinical features (presurgical history, postsurgical outcome) in a monocentric series of 247 MTLE-HS patients treated by surgery. NeuN, GFAP and CD34 immunostainings and a double independent pathological examination were performed. 186 samples were type 1, 47 type 2, 7 type 3 and 7 samples were gliosis only but no neuronal loss (noHS). In the type 1, hypertrophic CA4 neurons were associated with a worse postsurgical outcome and granule cell layer duplication was associated with generalized seizures and episodes of status epilepticus. In the type 2, granule cell layer duplication was associated with generalized seizures. CD34+ stellate cells were more frequent in the type 2, type 3 and in noHS. These cells had a Nestin and SOX2 positive, immature neural immunophenotype. Patients with nodules of CD34+ cells had more frequent dysmnesic auras. CD34+ stellate cells in scarce pattern were associated with higher ratio of normal MRI and of stereo-electroencephalographic studies. CD34+ cells were associated with a trend for a better postsurgical outcome. Among CD34+ cases, we proposed a new entity of BRAF V600E positive HS and we described three hippocampal multinodular and vacuolating neuronal tumors. To conclude, our data identified new clinicopathological associations with ILAE types. They showed the prognostic value of CA4 hypertrophic neurons. They highlighted CD34+ stellate cells and BRAF V600E as biomarkers to further decipher MTLE-HS heterogeneity. © 2018 International Society of Neuropathology.

Comparison of waxy and normal potato starch remaining granules after chemical surface gelatinization: pasting behavior and surface morphology.

PubMed

Huang, Junrong; Chen, Zhenghong; Xu, Yalun; Li, Hongliang; Liu, Shuxing; Yang, Daqing; Schols, Henk A

2014-02-15

To understand the contribution of granule inner portion to the pasting property of starch, waxy potato starch and two normal potato starches and their acetylated starch samples were subjected to chemical surface gelatinization by 3.8 mol/L CaCl2 to obtain remaining granules. Native and acetylated, original and remaining granules of waxy potato starch had similar rapid visco analyzer (RVA) pasting profiles, while those of two normal potato starches behaved obviously different from each other. All remaining granules had lower peak viscosity than the corresponding original granules. Contribution of waxy potato starch granule's inner portion to the peak viscosity was significant more than those of normal potato starches. The shell structure appearing on the remaining granule surface for waxy potato starch was smoother and thinner than that for normal potato starches as observed by scanning electron microscopy, indicating a more regular structure of shell and a more ordered packing of shell for waxy potato starch granules. The blocklet size of waxy potato starch was smaller and more uniform than those of normal potato starches as shown by atomic force microscopy images of original and remaining granules. In general, our results provided the evidence for the spatial structure diversity between waxy and normal potato starch granules: outer layer and inner portion of waxy potato starch granule had similar structure, while outer layer had notably different structure from inner portion for normal potato starch granule. Copyright © 2013 Elsevier Ltd. All rights reserved.

Structure of Arabidopsis leaf starch is markedly altered following nocturnal degradation.

PubMed

Zhu, Fan; Bertoft, Eric; Wang, You; Emes, Michael; Tetlow, Ian; Seetharaman, Koushik

2015-03-06

Little is known about the thermal properties and internal molecular structure of transitory starch. In this study, granule morphology, thermal properties, and the cluster structure of Arabidopsis leaf starch at beginning and end of the light period were explored. The structural properties of building blocks and clusters were evaluated by using diverse chromatographic techniques. On the granular level, starch from end of day had larger granule size, thinner crystalline lamellae thickness, lower free surface energy of crystals, and lower tendency to retrograde than that from end of night. On the molecular level, the starch had lower amylose content, larger cluster size, and higher number of blocks per cluster at the end of day than at end of night. It is concluded that the core of the granules contains a more permanent molecular and less-ordered physical structure different from the transitory layers laid down around the core at daytime. Copyright © 2014 Elsevier Ltd. All rights reserved.

Analysis of the release process of phenylpropanolamine hydrochloride from ethylcellulose matrix granules IV.(1)) Evaluation of the controlled release properties for in vivo and in vitro release systems.

PubMed

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

2007-11-01

In the pharmaceutical preparation of a controlled release drug, it is very important and necessary to understand the release properties. The dissolution test is a very important and useful method for understanding and predicting drug-release properties. It was readily confirmed in the previous paper that the release process could be assessed quantitatively by a combination of the square-root time law and cube-root law equations for ethylcellulose (EC) matrix granules of phenylpropanolamine hydrochloride (PPA). In this paper EC layered granules were used in addition to EC matrix. The relationship between release property and the concentration of PPA in plasma after administration using beagle dogs were examined. Then it was confirmed that the correlativity for EC layered granules and EC matrix were similar each other. Therefore, it was considered that the dissolution test is useful for prediction of changes in concentration of PPA in the blood with time. And it was suggested that EC layered granules were suitable as a controlled release system as well as EC matrix.

Control of cerebellar granule cell output by sensory-evoked Golgi cell inhibition

PubMed Central

Duguid, Ian; Branco, Tiago; Chadderton, Paul; Arlt, Charlotte; Powell, Kate; Häusser, Michael

2015-01-01

Classical feed-forward inhibition involves an excitation–inhibition sequence that enhances the temporal precision of neuronal responses by narrowing the window for synaptic integration. In the input layer of the cerebellum, feed-forward inhibition is thought to preserve the temporal fidelity of granule cell spikes during mossy fiber stimulation. Although this classical feed-forward inhibitory circuit has been demonstrated in vitro, the extent to which inhibition shapes granule cell sensory responses in vivo remains unresolved. Here we combined whole-cell patch-clamp recordings in vivo and dynamic clamp recordings in vitro to directly assess the impact of Golgi cell inhibition on sensory information transmission in the granule cell layer of the cerebellum. We show that the majority of granule cells in Crus II of the cerebrocerebellum receive sensory-evoked phasic and spillover inhibition prior to mossy fiber excitation. This preceding inhibition reduces granule cell excitability and sensory-evoked spike precision, but enhances sensory response reproducibility across the granule cell population. Our findings suggest that neighboring granule cells and Golgi cells can receive segregated and functionally distinct mossy fiber inputs, enabling Golgi cells to regulate the size and reproducibility of sensory responses. PMID:26432880

Stimulus-Dependent State Transition between Synchronized Oscillation and Randomly Repetitive Burst in a Model Cerebellar Granular Layer

PubMed Central

Tanaka, Shigeru; Nagao, Soichi; Nishino, Tetsuro

2011-01-01

Information processing of the cerebellar granular layer composed of granule and Golgi cells is regarded as an important first step toward the cerebellar computation. Our previous theoretical studies have shown that granule cells can exhibit random alternation between burst and silent modes, which provides a basis of population representation of the passage-of-time (POT) from the onset of external input stimuli. On the other hand, another computational study has reported that granule cells can exhibit synchronized oscillation of activity, as consistent with observed oscillation in local field potential recorded from the granular layer while animals keep still. Here we have a question of whether an identical network model can explain these distinct dynamics. In the present study, we carried out computer simulations based on a spiking network model of the granular layer varying two parameters: the strength of a current injected to granule cells and the concentration of Mg2+ which controls the conductance of NMDA channels assumed on the Golgi cell dendrites. The simulations showed that cells in the granular layer can switch activity states between synchronized oscillation and random burst-silent alternation depending on the two parameters. For higher Mg2+ concentration and a weaker injected current, granule and Golgi cells elicited spikes synchronously (synchronized oscillation state). In contrast, for lower Mg2+ concentration and a stronger injected current, those cells showed the random burst-silent alternation (POT-representing state). It is suggested that NMDA channels on the Golgi cell dendrites play an important role for determining how the granular layer works in response to external input. PMID:21779155

Morphological Constraints on Cerebellar Granule Cell Combinatorial Diversity.

PubMed

Gilmer, Jesse I; Person, Abigail L

2017-12-13

Combinatorial expansion by the cerebellar granule cell layer (GCL) is fundamental to theories of cerebellar contributions to motor control and learning. Granule cells (GrCs) sample approximately four mossy fiber inputs and are thought to form a combinatorial code useful for pattern separation and learning. We constructed a spatially realistic model of the cerebellar GCL and examined how GCL architecture contributes to GrC combinatorial diversity. We found that GrC combinatorial diversity saturates quickly as mossy fiber input diversity increases, and that this saturation is in part a consequence of short dendrites, which limit access to diverse inputs and favor dense sampling of local inputs. This local sampling also produced GrCs that were combinatorially redundant, even when input diversity was extremely high. In addition, we found that mossy fiber clustering, which is a common anatomical pattern, also led to increased redundancy of GrC input combinations. We related this redundancy to hypothesized roles of temporal expansion of GrC information encoding in service of learned timing, and we show that GCL architecture produces GrC populations that support both temporal and combinatorial expansion. Finally, we used novel anatomical measurements from mice of either sex to inform modeling of sparse and filopodia-bearing mossy fibers, finding that these circuit features uniquely contribute to enhancing GrC diversification and redundancy. Our results complement information theoretic studies of granule layer structure and provide insight into the contributions of granule layer anatomical features to afferent mixing. SIGNIFICANCE STATEMENT Cerebellar granule cells are among the simplest neurons, with tiny somata and, on average, just four dendrites. These characteristics, along with their dense organization, inspired influential theoretical work on the granule cell layer as a combinatorial expander, where each granule cell represents a unique combination of inputs. Despite the centrality of these theories to cerebellar physiology, the degree of expansion supported by anatomically realistic patterns of inputs is unknown. Using modeling and anatomy, we show that realistic input patterns constrain combinatorial diversity by producing redundant combinations, which nevertheless could support temporal diversification of like combinations, suitable for learned timing. Our study suggests a neural substrate for producing high levels of both combinatorial and temporal diversity in the granule cell layer. Copyright © 2017 the authors 0270-6474/17/3712153-14$15.00/0.

Functional properties of granule cells with hilar basal dendrites in the epileptic dentate gyrus.

PubMed

Kelly, Tony; Beck, Heinz

2017-01-01

The maturation of adult-born granule cells and their functional integration into the network is thought to play a key role in the proper functioning of the dentate gyrus. In temporal lobe epilepsy, adult-born granule cells in the dentate gyrus develop abnormally and possess a hilar basal dendrite (HBD). Although morphological studies have shown that these HBDs have synapses, little is known about the functional properties of these HBDs or the intrinsic and network properties of the granule cells that possess these aberrant dendrites. We performed patch-clamp recordings of granule cells within the granule cell layer "normotopic" from sham-control and status epilepticus (SE) animals. Normotopic granule cells from SE animals possessed an HBD (SE + HBD + cells) or not (SE + HBD - cells). Apical and basal dendrites were stimulated using multiphoton uncaging of glutamate. Two-photon Ca 2+ imaging was used to measure Ca 2+ transients associated with back-propagating action potentials (bAPs). Near-synchronous synaptic input integrated linearly in apical dendrites from sham-control animals and was not significantly different in apical dendrites of SE + HBD - cells. The majority of HBDs integrated input linearly, similar to apical dendrites. However, 2 of 11 HBDs were capable of supralinear integration mediated by a dendritic spike. Furthermore, the bAP-evoked Ca 2+ transients were relatively well maintained along HBDs, compared with apical dendrites. This further suggests an enhanced electrogenesis in HBDs. In addition, the output of granule cells from epileptic tissue was enhanced, with both SE + HBD - and SE + HBD + cells displaying increased high-frequency (>100 Hz) burst-firing. Finally, both SE + HBD - and SE + HBD + cells received recurrent excitatory input that was capable of generating APs, especially in the absence of feedback inhibition. Taken together, these data suggest that the enhanced excitability of HBDs combined with the altered intrinsic and network properties of granule cells collude to promote excitability and synchrony in the epileptic dentate gyrus. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Isolation of Cytoplasmic Pituitary Granules with Gonadotropic Activity

PubMed Central

Hartley, Marshall W.; McShan, W. H.; Ris, Hans

1960-01-01

A fraction isolated from the anterior pituitary glands of rats castrate for 8 weeks contained essentially a single cytoplasmic constituent with which the major portion of the gonadotropic hormone activity was associated. The glands were homogenized in an 0.25 M sucrose + 7.3 per cent polyvinylpyrrolidone (PVP) solution and fractionated by differential centrifugation to give a heterogeneous small granule fraction which contained almost all the gonadotropic hormone activity. The active supernatant containing this small granule fraction was separated into layers by isopycnic gradient centrifugation on a continuous 6 to 45 per cent sucrose + 17.5 per cent "diodrast" + 5 x 10-4 M "versene" gradient at 100,000 g for 2 hours. Three layers were obtained and the pellet from the active bottom layer was sectioned, examined with the electron microscope, and found to contain 200 mµ granules, mitochondria, ergastoplasm, and other cellular debris. This layer was fractionated further by isopycnic and differential centrifugation to obtain a pellet which contained the major portion of the gonadotropic hormone activity. Because of the heterogeneity of this fraction, due to the contamination of the 200 mµ granules with mitochondria and other cellular debris, the active layer and the resuspended active pellet, obtained by centrifuging this layer first at 17,000 g then diluting the supernatant and centrifuging at 30,000 g for 1 hour, were filtered through Millipore HA paper with a pore size of 0.45 µ. The cytoplasmic material containing the gonadotropic hormone activity passed through the filter paper and this activity was recovered in the pellets obtained by centrifuging at 100,000 g for 1 hour. These active pellets consisted almost entirely of 200 mµ granules with a minimum amount of contamination, and they contained the major portion of the gonadotropic hormone activity with practically none remaining in the supernatant fraction. These results are discussed in view of their importance to the cytology of the pituitary gland. PMID:14400127

Effects of dissolved oxygen and pH on nitrous oxide production rates in autotrophic partial nitrification granules.

PubMed

Rathnayake, Rathnayake M L D; Oshiki, Mamoru; Ishii, Satoshi; Segawa, Takahiro; Satoh, Hisashi; Okabe, Satoshi

2015-12-01

The effects of dissolved oxygen (DO) and pH on nitrous oxide (N2O) production rates and pathways in autotrophic partial nitrification (PN) granules were investigated at the granular level. N2O was primarily produced by betaproteobacterial ammonia-oxidizing bacteria, mainly Nitrosomonas europaea, in the oxic surface layer (<200μm) of the autotrophic PN granules. N2O production increased with increasing bulk DO concentration owing to activation of the ammonia (i.e., hydroxylamine) oxidation in this layer. The highest N2O emissions were observed at pH 7.5, although the ammonia oxidation rate was unchanged between pH 6.5 and 8.5. Overall, the results of this study suggest that in situ analyses of PN granules are essential to gaining insight into N2O emission mechanisms in a granule. Copyright © 2015 Elsevier Ltd. All rights reserved.

Organisation and tyrosine hydroxylase and calretinin immunoreactivity in the main olfactory bulb of paca (Cuniculus paca): a large caviomorph rodent.

PubMed

Sasahara, Tais Harumi de Castro; Leal, Leonardo Martins; Spillantini, Maria Grazia; Machado, Márcia Rita Fernandes

2015-04-01

The majority of neuroanatomical and chemical studies of the olfactory bulb have been performed in small rodents, such as rats and mice. Thus, this study aimed to describe the organisation and the chemical neuroanatomy of the main olfactory bulb (MOB) in paca, a large rodent belonging to the Hystricomorpha suborder and Caviomorpha infraorder. For this purpose, histological and immunohistochemical procedures were used to characterise the tyrosine hydroxylase (TH) and calretinin (CR) neuronal populations and their distribution. The paca MOB has eight layers: the olfactory nerve layer (ONL), the glomerular layer (GL), the external plexiform layer (EPL; subdivided into the inner and outer sublayers), the mitral cell layer (MCL), the internal plexiform layer (IPL), the granule cell layer (GCL), the periventricular layer and the ependymal layer. TH-ir neurons were found mostly in the GL, and moderate numbers of TH-ir neurons were scattered in the EPL. Numerous varicose fibres were distributed in the IPL and in the GCL. CR-ir neurons concentrated in the GL, around the base of the olfactory glomeruli. Most of the CR-ir neurons were located in the MCL, IPL and GCL. Some of the granule cells had an apical dendrite with a growth cone. The CR immunoreactivity was also observed in the ONL with olfactory nerves strongly immunostained. This study has shown that the MOB organisation in paca is consistent with the description in other mammals. The characterisation and distribution of the population of TH and CR in the MOB is not exclusively to this species. This large rodent shares common patterns to other caviomorph rodent, as guinea pig, and to the myomorph rodents, as mice, rats and hamsters.

Imaging exocytosis of single glucagon-like peptide-1 containing granules in a murine enteroendocrine cell line with total internal reflection fluorescent microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ohara-Imaizumi, Mica; Aoyagi, Kyota; Akimoto, Yoshihiro

To analyze the exocytosis of glucagon-like peptide-1 (GLP-1) granules, we imaged the motion of GLP-1 granules labeled with enhanced yellow fluorescent protein (Venus) fused to human growth hormone (hGH-Venus) in an enteroendocrine cell line, STC-1 cells, by total internal reflection fluorescent (TIRF) microscopy. We found glucose stimulation caused biphasic GLP-1 granule exocytosis: during the first phase, fusion events occurred from two types of granules (previously docked granules and newcomers), and thereafter continuous fusion was observed mostly from newcomers during the second phase. Closely similar to the insulin granule fusion from pancreatic {beta} cells, the regulated biphasic exocytosis from two typesmore » of granules may be a common mechanism in glucose-evoked hormone release from endocrine cells.« less

Olfactory and cortical projections to bulbar and hippocampal adult-born neurons

PubMed Central

De La Rosa-Prieto, Carlos; De Moya-Pinilla, Miguel; Saiz-Sanchez, Daniel; Ubeda-banon, Isabel; Arzate, Dulce M.; Flores-Cuadrado, Alicia; Liberia, Teresa; Crespo, Carlos; Martinez-Marcos, Alino

2015-01-01

New neurons are continually generated in the subependymal layer of the lateral ventricles and the subgranular zone of dentate gyrus during adulthood. In the subventricular zone, neuroblasts migrate a long distance to the olfactory bulb where they differentiate into granule or periglomerular interneurons. In the hippocampus, neuroblasts migrate a short distance from the subgranular zone to the granule cell layer of the dentate gyrus to become granule neurons. In addition to the short-distance inputs, bulbar interneurons receive long-distance centrifugal afferents from olfactory-recipient structures. Similarly, dentate granule cells receive differential inputs from the medial and lateral entorhinal cortices through the perforant pathway. Little is known concerning these new inputs on the adult-born cells. In this work, we have characterized afferent inputs to 21-day old newly-born neurons. Mice were intraperitoneally injected with bromodeoxyuridine. Two weeks later, rhodamine-labeled dextran-amine was injected into the anterior olfactory nucleus, olfactory tubercle, piriform cortex and lateral and medial entorhinal cortices. One week later, animals were perfused and immunofluorescences were carried out. The data show that projection neurons from the mentioned structures, establish putative synaptic contacts onto 21-day-old neurons in the olfactory bulb and dentate gyrus, in some cases even before they start to express specific subpopulation proteins. Long-distance afferents reach middle and outer one-third portions of the molecular layer of the dentate gyrus and granule and, interestingly, periglomerular layers of the olfactory bulb. In the olfactory bulb, these fibers appear to establish presumptive axo-somatic contacts onto newly-born granule and periglomerular cells. PMID:25698936

Electrophysiological mapping of the accessory olfactory bulb of the rabbit (Oryctolagus cuniculus).

PubMed

van Groen, T; Ruardy, L; da Silva, F H

1986-07-01

Field potentials elicited by electrical stimulation of the vomeronasal nerve were measured in the accessory olfactory bulb of the rabbit. Maps were made of the distribution of surface field potentials and of the corresponding depth profiles. The surface maps followed closely the contours of the accessory olfactory bulb: at the frontal border the field potential tended to zero and at the center of the structure the field potential attained a maximum. Depth profiles of the field potentials through the accessory olfactory bulb presented a surface-negative wave and, in depth, a positive wave. The polarity reversal occurred at the deep part of the granule cell layer. The zero equipotential line followed closely the curvature of the granule cell layer. Current source density analysis of the depth profiles revealed a main sink at the external plexiform and granule cell layers. This indicates that the main activity in the accessory olfactory bulb is generated by the synapses between the mitral cells and the granule cells as is found in the main olfactory bulb.

Investigation of Oral Preparation That Is Expected to Improve Medication Administration: Preparation and Evaluation of Oral Gelling Tablet Using Sodium Alginate.

PubMed

Ito, Ikumi; Ito, Akihiko; Unezaki, Sakae

2017-01-01

We investigated the preparation of a gelling tablet that swells and forms a gel upon absorbing water, and hence would be easy for patients to swallow. We prepared naked tablets and compressed coated tablets by the direct tableting or wet granule-compression methods, using the commonly prescribed drug acetaminophen (AA) and sodium alginate (AG) as a thickening agent. The tablets quickly absorbed water, had favorable gelling properties, low adhesiveness, appropriate drug dissolution profile, and at the same time, were easy to swallow. In the case of naked tablets, water absorption increased upon granulation, but gelling of AG interfere when AA and AG were present together. There was no change in the adhesiveness, and more than 30 min were required to achieve a 25% dissolution ratio. Compressed coated tablets that were made with AA in the inner layer and granulated AG in the outer layer showed improved dissolution behavior, it was about 90% dissolution ratio in 30 min, owing to the water absorption property of AG, and decreased adhesiveness. In this case, there was a difference in the outer layer thickness. As the outer layer amount increased, dissolution slowed, but it did not depend on the compression pressure. Our gelling tablet can be prepared by using AA (main drug) in the inner layer and an appropriate thickness of granulated AG in the outer layer of compressed coated tablets.

Analysis of the release process of phenylpropanolamine hydrochloride from ethylcellulose matrix granules II. effects of the binder solution on the release process.

PubMed

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

2004-03-01

The release properties of phenylpropanolamine hydrochloride (PPA) from ethylcellulose (EC) matrix granules prepared by an extrusion granulation method were examined. The release process could be divided into two parts; the first and second stages were analyzed by applying square-root time law and cube-root law equations, respectively. The validity of the treatments was confirmed by the fitness of a simulation curve with the measured curve. In the first stage, PPA was released from the gel layer of swollen EC in the matrix granules. In the second stage, the drug existing below the gel layer dissolved and was released through the gel layer. The effect of the binder solution on the release from EC matrix granules was also examined. The binder solutions were prepared from various EC and ethanol (EtOH) concentrations. The media changed from a good solvent to a poor solvent with decreasing EtOH concentration. The matrix structure changed from loose to compact with increasing EC concentration. The preferable EtOH concentration region was observed when the release process was easily predictable. The time and release ratio at the connection point of the simulation curves were also examined to determine the validity of the analysis.

Measurement and characterization of external oil in the fried waxy maize starch granules using ATR-FTIR and XRD.

PubMed

Chen, Long; Tian, Yaoqi; Sun, Binghua; Cai, Canxin; Ma, Rongrong; Jin, Zhengyu

2018-03-01

Concerns regarding increased dietary oil uptake have prompted efforts to investigate the oil absorption and distribution in fried starchy foods. In the present study, attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, together with a chloroform-methanol method, was used to analyze the external and internal oil contents in fried starchy samples. The micromorphology of fried starchy samples was further investigated using scanning electron microscope (SEM), polarized light microscope (PLM) and confocal laser scanning microscopy (CLSM). The results indicated that large amounts of oil were absorbed in or within waxy maize starch, but the majority of oil was located near the surface layer of the starch granules. After defatting, the internal oil was thoroughly removed, while a small amount of external oil remained. As evidenced by the changes of the crystalline characteristics with the help of X-ray diffraction (XRD), the interaction between starch and lipids on the surface was confirmed to form V-type complex compounds during frying at high moisture. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hardened, environmentally disposable composite granules of coal cleaning refuse, coal combustion waste, and other wastes, and method preparing the same

DOEpatents

Burnet, George; Gokhale, Ashok J.

1990-07-10

A hardened, environmentally inert and disposable composite granule of coal cleaning refuse and coal combustion waste, and method for producing the same, wherein the coal combustion waste is first granulated. The coal cleaning refuse is pulverized into fine particles and is then bound, as an outer layer, to the granulated coal combustion waste granules. This combination is then combusted and sintered. After cooling, the combination results in hardened, environmentally inert and disposable composite granules having cores of coal combustion waste, and outer shells of coal cleaning refuse. The composite particles are durable and extremely resistant to environmental and chemical forces.

Hardened, environmentally disposable composite granules of coal cleaning refuse, coal combustion waste, and other wastes, and method preparing the same

DOEpatents

Burnet, G.; Gokhale, A.J.

1990-07-10

A hardened, environmentally inert and disposable composite granule of coal cleaning refuse and coal combustion waste and method for producing the same are disclosed, wherein the coal combustion waste is first granulated. The coal cleaning refuse is pulverized into fine particles and is then bound, as an outer layer, to the granulated coal combustion waste granules. This combination is then combusted and sintered. After cooling, the combination results in hardened, environmentally inert and disposable composite granules having cores of coal combustion waste, and outer shells of coal cleaning refuse. The composite particles are durable and extremely resistant to environmental and chemical forces. 3 figs.

Vigorous convection in a sunspot granular light bridge

NASA Astrophysics Data System (ADS)

Lagg, Andreas; Solanki, Sami K.; van Noort, Michiel; Danilovic, Sanja

2014-08-01

Context. Light bridges are the most prominent manifestation of convection in sunspots. The brightest representatives are granular light bridges composed of features that appear to be similar to granules. Aims: An in-depth study of the convective motions, temperature stratification, and magnetic field vector in and around light bridge granules is presented with the aim of identifying similarities and differences to typical quiet-Sun granules. Methods: Spectropolarimetric data from the Hinode Solar Optical Telescope were analyzed using a spatially coupled inversion technique to retrieve the stratified atmospheric parameters of light bridge and quiet-Sun granules. Results: Central hot upflows surrounded by cooler fast downflows reaching 10 km s-1 clearly establish the convective nature of the light bridge granules. The inner part of these granules in the near surface layers is field free and is covered by a cusp-like magnetic field configuration. We observe hints of field reversals at the location of the fast downflows. The quiet-Sun granules in the vicinity of the sunspot are covered by a low-lying canopy field extending radially outward from the spot. Conclusions: The similarities between quiet-Sun and light bridge granules point to the deep anchoring of granular light bridges in the underlying convection zone. The fast, supersonic downflows are most likely a result of a combination of invigorated convection in the light bridge granule due to radiative cooling into the neighboring umbra and the fact that we sample deeper layers, since the downflows are immediately adjacent to the slanted walls of the Wilson depression. The two movies are available in electronic form at http://www.aanda.org

Characterization of Pu-238 Heat Source Granule Containment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Richardson, Paul Dean II; Sanchez, Joey Leo; Wall, Angelique Dinorah

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 238PuO 2 granules. The granules are contained by 3 layers of encapsulation. A thin T-111 liner surrounds the 238PuO 2 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 thismore » 238PuO 2 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).« less

Critical evaluation of root causes of the reduced compactability after roll compaction/dry granulation.

PubMed

Mosig, Johanna; Kleinebudde, Peter

2015-03-01

The influence of lubrication and particle size on the reduced compactability after dry granulation was investigated. Powder cellulose, lactose, magnesium carbonate, and two types of microcrystalline cellulose were roll compacted, granulated, and sieved into particle fractions. Particle fractions were compressed into tablets using internal and external lubrication. Internal lubrication resulted in an overlubrication of the granule material compared with the powder material. This resulted in extraordinary high reduction of compactability after dry granulation for lubricant-sensitive materials. The granule size can cause differences in strength, whereby the degree of this effect was material dependent. The loss in strength with increasing compaction force was comparable for different particles sizes of one material, suggesting a change in material properties independently of the size. Granule hardening could be one reason as for higher compaction forces the integrity of the granule structure survived the compression step. The results demonstrated that granule lubrication mainly influence the degree of the reduced compactability after dry granulation and must be considered for the evaluation of mechanism for this phenomenon. Hardening of the material as well as size enlargement will cause the loss in strength after recompression, but the influence of both depends strongly on the material. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Somatic Arc protein expression in hippocampal granule cells is increased in response to environmental change but independent of task-specific learning.

PubMed

Cleland, J P; Willis, E F; Bartlett, P F; Vukovic, J

2017-09-29

Activated neurons express immediate-early genes, such as Arc. Expression of Arc in the hippocampal granule cell layer, an area crucial for spatial learning and memory, is increased during acquisition of spatial learning; however, it is unclear whether this effect is related to the task-specific learning process or to nonspecific aspects of the testing procedure (e.g. exposure to the testing apparatus and exploration of the environment). Herein, we show that Arc-positive cells numbers are increased to the same extent in the granule cell layer after both acquisition of a single spatial learning event in the active place avoidance task and exploration of the testing environment, as compared to naïve (i.e. caged) mice. Repeated exposure the testing apparatus and environment did not reduce Arc expression. Furthermore, Arc expression did not correlate with performance in both adult and aged animals, suggesting that exploration of the testing environment, rather than the specific acquisition of the active place avoidance task, induces Arc expression in the dentate granule cell layer. These findings thus suggest that Arc is an experience-induced immediate-early gene.

Linking macroscopic with microscopic neuroanatomy using synthetic neuronal populations.

PubMed

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

2014-10-01

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

Linking Macroscopic with Microscopic Neuroanatomy Using Synthetic Neuronal Populations

PubMed Central

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

2014-01-01

Dendritic morphology has been shown to have a dramatic impact on neuronal function. However, population features such as the inherent variability in dendritic morphology between cells belonging to the same neuronal type are often overlooked when studying computation in neural networks. While detailed models for morphology and electrophysiology exist for many types of single neurons, the role of detailed single cell morphology in the population has not been studied quantitatively or computationally. Here we use the structural context of the neural tissue in which dendritic trees exist to drive their generation in silico. We synthesize the entire population of dentate gyrus granule cells, the most numerous cell type in the hippocampus, by growing their dendritic trees within their characteristic dendritic fields bounded by the realistic structural context of (1) the granule cell layer that contains all somata and (2) the molecular layer that contains the dendritic forest. This process enables branching statistics to be linked to larger scale neuroanatomical features. We find large differences in dendritic total length and individual path length measures as a function of location in the dentate gyrus and of somatic depth in the granule cell layer. We also predict the number of unique granule cell dendrites invading a given volume in the molecular layer. This work enables the complete population-level study of morphological properties and provides a framework to develop complex and realistic neural network models. PMID:25340814

Corrosion behavior of HVOF coated sheets

NASA Astrophysics Data System (ADS)

Yilbas, B. S.; Abdul-Aleem, B. J.; Khalid, M.

2003-12-01

High velocity oxygen-fuel (HVOF) thermal spray coating finds application in industry due to its superior resistance to corrosion and thermal loading. In the HVOF process, the metallic powders at elevated temperature are sprayed at supersonic speed onto a substrate material. The powder granules sprayed impact onto each other, forming a mechanical bonding across the coating layer. In most of the cases, the distances among the particles (powder granules sprayed) are not the same, which in turn results in inhomogeneous structure across the coating layer. Moreover, the rate of oxidation of the powder granules during the spraying process varies. Consequently, the electrochemical response of the coating layer surfaces next to the base material and free to atmosphere differs. In the current study, the electrochemical response of a coating sheet formed during HVOF thermal spraying was investigated. NiCrMoNb alloy (similar to Inconel 625) wass used for the powder granules. Thermal spraying was carried out onto a smooth surface of stainless steel workpiece (without grid blasting), and later the coating layer was removed from the surface to obtain the coating sheet for the electrochemical tests. It was found that the corrosion rate of the smooth surface (surface next to the stainless steel surface before its removal) is considerably larger than that corresponding to the rough surface (free surface) of the coating sheet, and no specific patterns were observed for the pit sites.

Glomerular and Mitral-Granule Cell Microcircuits Coordinate Temporal and Spatial Information Processing in the Olfactory Bulb.

PubMed

Cavarretta, Francesco; Marasco, Addolorata; Hines, Michael L; Shepherd, Gordon M; Migliore, Michele

2016-01-01

The olfactory bulb processes inputs from olfactory receptor neurons (ORNs) through two levels: the glomerular layer at the site of input, and the granule cell level at the site of output to the olfactory cortex. The sequence of action of these two levels has not yet been examined. We analyze this issue using a novel computational framework that is scaled up, in three-dimensions (3D), with realistic representations of the interactions between layers, activated by simulated natural odors, and constrained by experimental and theoretical analyses. We suggest that the postulated functions of glomerular circuits have as their primary role transforming a complex and disorganized input into a contrast-enhanced and normalized representation, but cannot provide for synchronization of the distributed glomerular outputs. By contrast, at the granule cell layer, the dendrodendritic interactions mediate temporal decorrelation, which we show is dependent on the preceding contrast enhancement by the glomerular layer. The results provide the first insights into the successive operations in the olfactory bulb, and demonstrate the significance of the modular organization around glomeruli. This layered organization is especially important for natural odor inputs, because they activate many overlapping glomeruli.

DYNAMICS OF TURBULENT CONVECTION AND CONVECTIVE OVERSHOOT IN A MODERATE-MASS STAR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kitiashvili, I. N.; Mansour, N. N.; Wray, A. A.

We present results of realistic three-dimensional (3D) radiative hydrodynamic simulations of the outer layers of a moderate-mass star (1.47 M {sub ⊙}), including the full convection zone, the overshoot region, and the top layers of the radiative zone. The simulation results show that the surface granulation has a broad range of scales, from 2 to 12 Mm, and that large granules are organized in well-defined clusters, consisting of several granules. Comparison of the mean structure profiles from 3D simulations with the corresponding one-dimensional (1D) standard stellar model shows an increase of the stellar radius by ∼800 km, as well as significantmore » changes in the thermodynamic structure and turbulent properties of the ionization zones. Convective downdrafts in the intergranular lanes between granulation clusters reach speeds of more than 20 km s{sup −1}, penetrate through the whole convection zone, hit the radiative zone, and form an 8 Mm thick overshoot layer. Contrary to semi-empirical overshooting models, our results show that the 3D dynamic overshoot region consists of two layers: a nearly adiabatic extension of the convection zone and a deeper layer of enhanced subadiabatic stratification. This layer is formed because of heating caused by the braking of the overshooting convective plumes. This effect has to be taken into account in stellar modeling and the interpretation of asteroseismology data. In particular, we demonstrate that the deviations of the mean structure of the 3D model from the 1D standard model of the same mass and composition are qualitatively similar to the deviations for the Sun found by helioseismology.« less

Postnatal Migration of Cerebellar Interneurons

PubMed Central

Galas, Ludovic; Bénard, Magalie; Lebon, Alexis; Komuro, Yutaro; Schapman, Damien; Vaudry, Hubert; Vaudry, David; Komuro, Hitoshi

2017-01-01

Due to its continuing development after birth, the cerebellum represents a unique model for studying the postnatal orchestration of interneuron migration. The combination of fluorescent labeling and ex/in vivo imaging revealed a cellular highway network within cerebellar cortical layers (the external granular layer, the molecular layer, the Purkinje cell layer, and the internal granular layer). During the first two postnatal weeks, saltatory movements, transient stop phases, cell-cell interaction/contact, and degradation of the extracellular matrix mark out the route of cerebellar interneurons, notably granule cells and basket/stellate cells, to their final location. In addition, cortical-layer specific regulatory factors such as neuropeptides (pituitary adenylate cyclase-activating polypeptide (PACAP), somatostatin) or proteins (tissue-type plasminogen activator (tPA), insulin growth factor-1 (IGF-1)) have been shown to inhibit or stimulate the migratory process of interneurons. These factors show further complexity because somatostatin, PACAP, or tPA have opposite or no effect on interneuron migration depending on which layer or cell type they act upon. External factors originating from environmental conditions (light stimuli, pollutants), nutrients or drug of abuse (alcohol) also alter normal cell migration, leading to cerebellar disorders. PMID:28587295

Adsorption mechanism for xanthene dyes to cellulose granules.

PubMed

Tabara, Aya; Yamane, Chihiro; Seguchi, Masaharu

2012-01-01

The xanthene dyes, erythrosine, phloxine, and rose bengal, were adsorbed to charred cellulose granules. The charred cellulose granules were preliminarily steeped in ionic (NaOH, NaCl, KOH, KCl, and sodium dodecyl sulfate (SDS)), nonionic (glucose, sucrose, and ethanol), and amphipathic sucrose fatty acid ester (SFAE) solutions, and adsorption tests on the dye to the steeped and charred cellulose granules were conducted. Almost none of the dye was adsorbed when the solutions of ionic and amphipathic molecules were used, but were adsorbed in the case of steeping in the nonionic molecule solutions. Thin-layer chromatography (TLC) and the Fourier transform infra-red (FT-IR) profiles of SFAE which was adsorbed to the charred cellulose granules and extracted by ethyl ether suggested the presence of hydrophobic sites on the surface of the charred cellulose granules. We confirmed that the xanthene dyes could bind to the charred cellulose granules by ionic and hydrophobic bonds.

Aggregate Size and Architecture Determine Microbial Activity Balance for One-Stage Partial Nitritation and Anammox ▿

PubMed Central

Vlaeminck, Siegfried E.; Terada, Akihiko; Smets, Barth F.; De Clippeleir, Haydée; Schaubroeck, Thomas; Bolca, Selin; Demeestere, Lien; Mast, Jan; Boon, Nico; Carballa, Marta; Verstraete, Willy

2010-01-01

Aerobic ammonium-oxidizing bacteria (AerAOB) and anoxic ammonium-oxidizing bacteria (AnAOB) cooperate in partial nitritation/anammox systems to remove ammonium from wastewater. In this process, large granular microbial aggregates enhance the performance, but little is known about granulation so far. In this study, three suspended-growth oxygen-limited autotrophic nitrification-denitrification (OLAND) reactors with different inoculation and operation (mixing and aeration) conditions, designated reactors A, B, and C, were used. The test objectives were (i) to quantify the AerAOB and AnAOB abundance and the activity balance for the different aggregate sizes and (ii) to relate aggregate morphology, size distribution, and architecture putatively to the inoculation and operation of the three reactors. A nitrite accumulation rate ratio (NARR) was defined as the net aerobic nitrite production rate divided by the anoxic nitrite consumption rate. The smallest reactor A, B, and C aggregates were nitrite sources (NARR, >1.7). Large reactor A and C aggregates were granules capable of autonomous nitrogen removal (NARR, 0.6 to 1.1) with internal AnAOB zones surrounded by an AerAOB rim. Around 50% of the autotrophic space in these granules consisted of AerAOB- and AnAOB-specific extracellular polymeric substances. Large reactor B aggregates were thin film-like nitrite sinks (NARR, <0.5) in which AnAOB were not shielded by an AerAOB layer. Voids and channels occupied 13 to 17% of the anoxic zone of AnAOB-rich aggregates (reactors B and C). The hypothesized granulation pathways include granule replication by division and budding and are driven by growth and/or decay based on species-specific physiology and by hydrodynamic shear and mixing. PMID:19948857

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

PubMed

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

2018-01-03

Reelin controls neuronal migration and layer formation. Previous studies in reeler mice deficient in Reelin focused on the result of the developmental process in fixed tissue sections. It has remained unclear whether Reelin affects the migratory process, migration directionality, or migrating neurons guided by the radial glial scaffold. Moreover, Reelin has been regarded as an attractive signal because newly generated neurons migrate toward the Reelin-containing marginal zone. Conversely, Reelin might be a stop signal because migrating neurons in reeler , but not in wild-type mice, invade the marginal zone. Here, we monitored the migration of newly generated proopiomelanocortin-EGFP -expressing dentate granule cells in slice cultures from reeler , reeler -like mutants and wild-type mice of either sex using real-time microscopy. We discovered that not the actual migratory process and migratory speed, but migration directionality of the granule cells is controlled by Reelin. While wild-type granule cells migrated toward the marginal zone of the dentate gyrus, neurons in cultures from reeler and reeler -like mutants migrated randomly in all directions as revealed by vector analyses of migratory trajectories. Moreover, live imaging of granule cells in reeler slices cocultured to wild-type dentate gyrus showed that the reeler neurons changed their directions and migrated toward the Reelin-containing marginal zone of the wild-type culture, thus forming a compact granule cell layer. In contrast, directed migration was not observed when Reelin was ubiquitously present in the medium of reeler slices. These results indicate that topographically administered Reelin controls the formation of a granule cell layer. SIGNIFICANCE STATEMENT Neuronal migration and the various factors controlling its onset, speed, directionality, and arrest are poorly understood. Slice cultures offer a unique model to study the migration of individual neurons in an almost natural environment. In the present study, we took advantage of the expression of proopiomelanocortin-EGFP by newly generated, migrating granule cells to analyze their migratory trajectories in hippocampal slice cultures from wild-type mice and mutants deficient in Reelin signaling. We show that the compartmentalized presence of Reelin is essential for the directionality, but not the actual migratory process or speed, of migrating granule cells leading to their characteristic lamination in the dentate gyrus. Copyright © 2018 the authors 0270-6474/18/380137-12$15.00/0.

Elucidation of the internal physical and chemical microstructure of pharmaceutical granules using X-ray micro-computed tomography, Raman microscopy and infrared spectroscopy.

PubMed

Crean, Barry; Parker, Andrew; Roux, Delphine Le; Perkins, Mark; Luk, Shen Y; Banks, Simon R; Melia, Colin D; Roberts, Clive J

2010-11-01

X-ray micro-computed tomography (XMCT) was used in conjunction with confocal Raman mapping to measure the intra-granular pore size, binder volumes and to provide spatial and chemical maps of internal granular components in α-lactose monohydrate granules formulated with different molecular weights of polyvinyl pyrrolidone (PVP). Infrared spectroscopy was used to understand the molecular association of binder domains. Granules were prepared by high-shear aqueous granulation from α-lactose monohydrate and PVP K29/32 or K90. XMCT was used to visualise the granule microstructure, intra-granular binder distribution and measure intra-granular porosity, which was subsequently related to intrusion porosimetry measurements. Confocal Raman microscopy and infrared microscopy were employed to investigate the distribution of components within the granule and explore the nature of binder substrate interactions. XMCT data sets of internal granule microstructure provided values of residual porosity in the lactose:PVP K29/32 and lactose:PVP K90 granules of 32.41 ± 4.60% and 22.40 ± 0.03%, respectively. The binder volumes of the lactose:PVP K29/32 and lactose:PVP K90 granules were 2.98 ± 0.10% and 3.38 ± 0.07%, respectively, and were attributed to PVP-rich binder domains within the granule. Confocal Raman microscopy revealed anisotropic domains of PVP between 2 μm and 20 μm in size surrounded by larger particles of lactose, in both granule types. Raman data showed that PVP domains contained various amounts of lactose, whilst IR microscopy determined that the PVP was molecularly associated with lactose, rather than residual water. The work shows that XMCT can be applied to investigate granular microstructure and resolve the porosity and the excipient and binder volumes. Combining this technique with vibrational techniques provides further structural information and aids the interpretations of the XMCT images. When used complementarily, these techniques highlighted that porosity and binder volume were the most significant microstructural differences between the α-lactose monohydrate granules formulated with the different grades of PVP. Copyright © 2010 Elsevier B.V. All rights reserved.

The cerebellar Golgi cell and spatiotemporal organization of granular layer activity

PubMed Central

D'Angelo, Egidio; Solinas, Sergio; Mapelli, Jonathan; Gandolfi, Daniela; Mapelli, Lisa; Prestori, Francesca

2013-01-01

The cerebellar granular layer has been suggested to perform a complex spatiotemporal reconfiguration of incoming mossy fiber signals. Central to this role is the inhibitory action exerted by Golgi cells over granule cells: Golgi cells inhibit granule cells through both feedforward and feedback inhibitory loops and generate a broad lateral inhibition that extends beyond the afferent synaptic field. This characteristic connectivity has recently been investigated in great detail and been correlated with specific functional properties of these neurons. These include theta-frequency pacemaking, network entrainment into coherent oscillations and phase resetting. Important advances have also been made in terms of determining the membrane and synaptic properties of the neuron, and clarifying the mechanisms of activation by input bursts. Moreover, voltage sensitive dye imaging and multi-electrode array (MEA) recordings, combined with mathematical simulations based on realistic computational models, have improved our understanding of the impact of Golgi cell activity on granular layer circuit computations. These investigations have highlighted the critical role of Golgi cells in: generating dense clusters of granule cell activity organized in center-surround structures, implementing combinatorial operations on multiple mossy fiber inputs, regulating transmission gain, and cut-off frequency, controlling spike timing and burst transmission, and determining the sign, intensity and duration of long-term synaptic plasticity at the mossy fiber-granule cell relay. This review considers recent advances in the field, highlighting the functional implications of Golgi cells for granular layer network computation and indicating new challenges for cerebellar research. PMID:23730271

Mechanism of internal fertilization in Pegea socia (Tunicata, Thaliacea), a salp with a solid oviduct.

PubMed

Holland, L Z; Miller, R L

1994-03-01

The ovary of the salp Pegea socia (Bosc, 1802) is located at the end of an atrial diverticulum. The ovary consists of a single oocyte encased in a layer of follicle cells and is connected to the atrial epithelium by an oviduct. Transmission electron microscopy shows that the oocyte lacks a vitelline layer, cortical granules, and yolk granules and that the oviduct lacks a continuous lumen. What previous authors thought was a lumen is a line of dense intercellular junctions running down the center of the oviduct. The sperm nucleus in this species, as in other salps, is elongate. The tubular mitochondrion spirals about the sperm nucleus giving it a corkscrew-shape appearance. Sperm reach the ovary when the oocyte is still at the germinal vesicle stage. Many sperm swim up the atrial diverticulum and burrow through the cells of the atrial epithelium, oviduct, and follicular epithelium. Thus oviduct shortening, which occurs when the oocyte is in the meiotic divisions, is evidently unrelated to sperm moving up the oviduct. All previous authors, who argued either that a continuous lumen is necessary for sperm to move up the oviduct or that sperm bypass the oviduct, were incorrect. © 1994 Wiley-Liss, Inc. Copyright © 1994 Wiley-Liss, Inc.

Atomic force microscopy of pea starch: origins of image contrast.

PubMed

Ridout, Michael J; Parker, Mary L; Hedley, Cliff L; Bogracheva, Tatiana Y; Morris, Victor J

2004-01-01

Atomic force microscopy (AFM) has been used to image the internal structure of pea starch granules. Starch granules were encased in a nonpenetrating matrix of rapid-set Araldite. Images were obtained of the internal structure of starch exposed by cutting the face of the block and of starch in sections collected on water. These images have been obtained without staining, or either chemical or enzymatic treatment of the granule. It has been demonstrated that contrast in the AFM images is due to localized absorption of water within specific regions of the exposed fragments of the starch granules. These regions swell, becoming "softer" and higher than surrounding regions. The images obtained confirm the "blocklet model" of starch granule architecture. By using topographic, error signal and force modulation imaging modes on samples of the wild-type pea starch and the high amylose r near-isogenic mutant, it has been possible to demonstrate differing structures within granules of different origin. These architectural changes provide a basis for explaining the changed appearance and functionality of the r mutant. The growth-ring structure of the granule is suggested to arise from localized "defects" in blocklet distribution within the granule. It is proposed that these defects are partially crystalline regions devoid of amylose.

Study of heat-moisture treatment of potato starch granules by chemical surface gelatinization.

PubMed

Bartz, Josiane; da Rosa Zavareze, Elessandra; Dias, Alvaro Renato Guerra

2017-08-01

Native potato starch was subjected to heat-moisture treatment (HMT) at 12%, 15%, 18%, 21%, and 24% of moisture content at 110 °C for 1 h, and the effects on morphology, structure, and thermal and physicochemical properties were investigated. To reveal the internal structure, 30% and 50% of the granular surface were removed by chemical surface gelatinization in concentrated LiCl solution. At moisture contents of 12% and 15%, HTM reduced the gelatinization temperatures and relative crystallinity of the starches, while at moisture contents of 21% and 24 % both increased. The alterations on morphology, X-ray pattern, physicochemical properties, and increase of amylose content were more intense with the increase of moisture content of HMT. The removal of granular layers showed that the changes promoted by HMT occur throughout the whole granule and were pronounced at the core or peripheral region, depending of the moisture content applied during HMT. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Nanocrystallized SrHA/SrHA SrTiO3/SrTiO3 TiO2 multilayer coatings formed by micro-arc oxidation for photocatalytic application

NASA Astrophysics Data System (ADS)

Han, Y.; Chen, D. H.; Zhang, L.

2008-08-01

Novel photocatalytic coatings containing strontium hydroxyapatite (SrHA), strontium titanate (SrTiO3), and TiO2 were formed by micro-arc oxidation (MAO) in an aqueous electrolyte containing strontium acetate and β-glycerophosphate disodium at 530 V for 0.1-5 min. The structure evolution of the coatings was investigated as a function of processing time, and the photocatalytic activity of the coatings was evaluated by measuring the decomposition rate of methyl orange under ultraviolet irradiation. During the MAO processing of the coatings, it was observed that some granules appeared in the electrolyte adjacent to the anode and they increased in amount as the processing time was prolonged. The obtained results show that the granules are amorphous and poorly crystallized SrHA with negative charges. The coating prepared for 5 min presents a microporous structure of SrHA/SrHA-SrTiO3/SrTiO3-TiO2 multilayers, in which the SrHA outermost layer and the SrHA-SrTiO3 intermediate layer are nanocrystallized. It is suggested that formation of the granules, electro-migration of the granules onto the pre-formed layer, and crystallization of the adhered granules are possible mechanisms for the formation of a SrHA/SrHA-SrTiO3/SrTiO3-TiO2 multilayer coating. This coating shows much higher photocatalytic decomposition efficiency relative to the MAO-formed TiO2 coating, and is expected to have an important photocatalytic application.

Small-scale Magnetic Flux Emergence in the Quiet Sun

NASA Astrophysics Data System (ADS)

Moreno-Insertis, F.; Martinez-Sykora, J.; Hansteen, V. H.; Muñoz, D.

2018-06-01

Small bipolar magnetic features are observed to appear in the interior of individual granules in the quiet Sun, signaling the emergence of tiny magnetic loops from the solar interior. We study the origin of those features as part of the magnetoconvection process in the top layers of the convection zone. Two quiet-Sun magnetoconvection models, calculated with the radiation-magnetohydrodynamic (MHD) Bifrost code and with domain stretching from the top layers of the convection zone to the corona, are analyzed. Using 3D visualization as well as a posteriori spectral synthesis of Stokes parameters, we detect the repeated emergence of small magnetic elements in the interior of granules, as in the observations. Additionally, we identify the formation of organized horizontal magnetic sheets covering whole granules. Our approach is twofold, calculating statistical properties of the system, like joint probability density functions (JPDFs), and pursuing individual events via visualization tools. We conclude that the small magnetic loops surfacing within individual granules in the observations may originate from sites at or near the downflows in the granular and mesogranular levels, probably in the first 1 or 1.5 Mm below the surface. We also document the creation of granule-covering magnetic sheet-like structures through the sideways expansion of a small subphotospheric magnetic concentration picked up and pulled out of the interior by a nascent granule. The sheet-like structures that we found in the models may match the recent observations of Centeno et al.

Texture Analysis of Poly-Adenylated mRNA Staining Following Global Brain Ischemia and Reperfusion

PubMed Central

Szymanski, Jeffrey J.; Jamison, Jill T.; DeGracia, Donald J.

2011-01-01

Texture analysis provides a means to quantify complex changes in microscope images. We previously showed that cytoplasmic poly-adenylated mRNAs form mRNA granules in post-ischemic neurons and that these granules correlated with protein synthesis inhibition and hence cell death. Here we utilized the texture analysis software MaZda to quantify mRNA granules in photomicrographs of the pyramidal cell layer of rat hippocampal region CA3 around 1 hour of reperfusion after 10 min of normothermic global cerebral ischemia. At 1 hour reperfusion, we observed variations in the texture of mRNA granules amongst samples that were readily quantified by texture analysis. Individual sample variation was consistent with the interpretation that animal-to-animal variations in mRNA granules reflected the time-course of mRNA granule formation. We also used texture analysis to quantify the effect of cycloheximide, given either before or after brain ischemia, on mRNA granules. If administered before ischemia, cycloheximide inhibited mRNA granule formation, but if administered after ischemia did not prevent mRNA granulation, indicating mRNA granule formation is dependent on dissociation of polysomes. We conclude that texture analysis is an effective means for quantifying the complex morphological changes induced in neurons by brain ischemia and reperfusion. PMID:21477879

Morphometric studies of heavy ion damage in the brains of rodents

NASA Technical Reports Server (NTRS)

Kraft, L. M.; Cox, A. B.

1986-01-01

The relative biological effectiveness (RBE) of different heavy ions for the mammalian brain was determined in mice irradiated at 100 days of age with He-4, C-12, Ne-20, Fe-56, Ar-40, or Co-60 gamma photons (with the primary particle LET values ranging from 2 to 650). Brain preparations were examined 16 months later for volume changes in the external plexiform layer (P-zone) of the olfactory bulb and an internal region (G-zone), which consists of the granule cells, the internal plexiform layer, and the mitral cell layer. The result indicate that the volume changes did occur in the olfactory bulb, not only in absolute terms but also when expressed as the ratio of the structures to each other and to the bulb as a whole. While the observed increased neuronal loss in mice receiving 700 cGy of Co-60 support the earlier data from irradiated rabbits, the increases observed in bulbar volumes and in the volume ratios of the P and the G zones measured in the mice given lower doses (320 or 160 cGy of He or C), were not expected.

Intracellular Zn(2+) signaling in the dentate gyrus is required for object recognition memory.

PubMed

Takeda, Atsushi; Tamano, Haruna; Ogawa, Taisuke; Takada, Shunsuke; Nakamura, Masatoshi; Fujii, Hiroaki; Ando, Masaki

2014-11-01

The role of perforant pathway-dentate granule cell synapses in cognitive behavior was examined focusing on synaptic Zn(2+) signaling in the dentate gyrus. Object recognition memory was transiently impaired when extracellular Zn(2+) levels were decreased by injection of clioquinol and N,N,N',N'-tetrakis-(2-pyridylmethyl) ethylendediamine. To pursue the effect of the loss and/or blockade of Zn(2+) signaling in dentate granule cells, ZnAF-2DA (100 pmol, 0.1 mM/1 µl), an intracellular Zn(2+) chelator, was locally injected into the dentate molecular layer of rats. ZnAF-2DA injection, which was estimated to chelate intracellular Zn(2+) signaling only in the dentate gyrus, affected object recognition memory 1 h after training without affecting intracellular Ca(2+) signaling in the dentate molecular layer. In vivo dentate gyrus long-term potentiation (LTP) was affected under the local perfusion of the recording region (the dentate granule cell layer) with 0.1 mM ZnAF-2DA, but not with 1-10 mM CaEDTA, an extracellular Zn(2+) chelator, suggesting that the blockade of intracellular Zn(2+) signaling in dentate granule cells affects dentate gyrus LTP. The present study demonstrates that intracellular Zn(2+) signaling in the dentate gyrus is required for object recognition memory, probably via dentate gyrus LTP expression. Copyright © 2014 Wiley Periodicals, Inc.

Different morphologic formation patterns of dark patches in the black-spotted frog (Pelophylax nigromaculata) and the Asiatic toad (Bufo gargarizans).

PubMed

Guangming, Gan; Tao, Zhao; Chao, Li; Moyan, Zhao

2017-01-01

The black-spotted frog (Pelophylax nigromaculata) and Asiatic toad (Bufo gargarizans), two relatively distantly related species, live in different habitats with different adaptive dark patches. To explain the formation of dark patches, the distribution patterns of melanin granules were examined with light microscopy and transmission electron microscopy. Melanin granules were produced and gathered into the "cap" structures on top of the nuclei in most epidermal cells. The "cap" structures may play a role in forming the dorsal dark patches coupled with three-layer melanophores, which can give rise to three layers of interconnected melanin networks in the dorsal dermis in P. nigromaculata. Epidermal melanocytes are rare and do not have a definitive role in forming dorsal dark patches in either P. nigromaculata or B. gargarizans. In B. gargarizans, the dermal melanophores only give rise to a single-layered melanin network, which hardly results in dark patches in the dorsal skin. However, the dermal melanophores migrate twice and form into pseudostratified networks, leading to dark patch formation in the ventral skin in B. gargarizans. The melanin granules precisely coregulate dark patches in the dermis and/or epidermis in P. nigromaculata and B. gargarizans. The dark patch formation depends on melanin granules in the epidermis or/and dermis in P. nigromaculata and B. gargarizans.

Gap Junction Modulation of Low-Frequency Oscillations in the Cerebellar Granule Cell Layer.

PubMed

Robinson, Jennifer Claire; Chapman, C Andrew; Courtemanche, Richard

2017-08-01

Local field potential (LFP) oscillations in the granule cell layer (GCL) of the cerebellar cortex have been identified previously in the awake rat and monkey during immobility. These low-frequency oscillations are thought to be generated through local circuit interactions between Golgi cells and granule cells within the GCL. Golgi cells display rhythmic firing and pacemaking properties, and also are electrically coupled through gap junctions within the GCL. Here, we tested if gap junctions in the rat cerebellar cortex contribute to the generation of LFP oscillations in the GCL. We recorded LFP oscillations under urethane anesthesia, and examined the effects of local infusion of gap junction blockers on 5-15 Hz oscillations. Local infusion of the gap junction blockers carbenoxolone and mefloquine resulted in significant decreases in the power of oscillations over a 30-min period, but the power of oscillations was unchanged in control experiments following vehicle injections. In addition, infusion of gap junction blockers had no significant effect on multi-unit activity, suggesting that the attenuation of low-frequency oscillations was likely due to reductions in electrical coupling rather than a decreased excitability within the granule cell layer. Our results indicate that electrical coupling among the Golgi cell networks in the cerebellar cortex contributes to the local circuit mechanisms that promote the occurrence of GCL LFP slow oscillations in the anesthetized rat.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ohara-Imaizumi, Mica; Aoyagi, Kyota; Nakamichi, Yoko

We simultaneously analyzed insulin granule fusion with insulin fused to green fluorescent protein and the subplasma membrane Ca{sup 2+} concentration ([Ca{sup 2+}]{sub PM}) with the Ca{sup 2+} indicator Fura Red in rat {beta} cells by dual-color total internal reflection fluorescence microscopy. We found that rapid and marked elevation in [Ca{sup 2+}]{sub PM} caused insulin granule fusion mostly from previously docked granules during the high KCl-evoked release and high glucose-evoked first phase release. In contrast, the slow and sustained elevation in [Ca{sup 2+}]{sub PM} induced fusion from newcomers translocated from the internal pool during the low KCl-evoked release and glucose-evoked secondmore » phase release. These data suggest that the pattern of the [Ca{sup 2+}]{sub PM} rise directly determines the types of fusing granules.« less

Multi-layer porous fiber-reinforced composites for implants: in vitro calcium phosphate formation in the presence of bioactive glass.

PubMed

Nganga, Sara; Zhang, Di; Moritz, Niko; Vallittu, Pekka K; Hupa, Leena

2012-11-01

Glass-fiber-reinforced composites (FRCs), based on bifunctional methacrylate resin, have recently shown their potential for use as durable cranioplasty, orthopedic and oral implants. In this study we suggest a multi-component sandwich implant structure with (i) outer layers out of porous FRC, which interface the cortical bone, and (ii) inner layers encompassing bioactive glass granules, which interface with the cancellous bone. The capability of Bioglass(®) 45S5 granules (100-250μm) to induce calcium phosphate formation on the surface of the FRC was explored by immersing the porous FRC-Bioglass laminates in simulated body fluid (SBF) for up to 28d. In both static (agitated) and dynamic conditions, bioactive glass granules induced precipitation of calcium phosphate at the laminate surfaces as confirmed by scanning electron microscopy. The proposed dynamic flow system is useful for the in vitro simulation of bone-like apatite formation on various new porous implant designs containing bioactive glass and implant material degradation. Copyright © 2012 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Osseointegration of alumina bioceramic granules: A comparative experimental study

NASA Astrophysics Data System (ADS)

Rerikh, V. V.; Avetisyan, A. R.; Zaydman, A. M.; Anikin, K. A.; Bataev, V. A.; Nikulina, A. A.; Sadovoy, M. A.; Aronov, A. M.; Semantsova, E. S.

2016-08-01

To perform a comparative analysis of osseointegration of bioceramic alumina-based granules, hydroxyapatite-based granules, and deproteinized bone granules. The experiment was conducted on 52 adult male Kyoto-Wistar rats weighing 350 to 520 g. The animals were divided into five matched groups that differed only in the type of an implanted material. The granules were implanted in the lumbar vertebral bodies and in the distal right femur of each laboratory animal. Two months after surgery, the animals were euthanized, followed by tissue sampling for morphological studies. An examination of specimens from the groups with implanted alumina granules revealed the newly formed trabecular bone with remodeling signs. The bone tissue filled the intragranular space, tightly adhering to the granule surface. There was no connective tissue capsule on the border between bone tissue and alumina granules. Cylindrical bioceramic alumina-based granules with an open internal channel have a higher strength surpassing than that of analogs and the osseointegration ability close to that of hydroxyapatite and deproteinized bone granules.

Identification of human cysteine-rich secretory protein 3 (CRISP-3) as a matrix protein in a subset of peroxidase-negative granules of neutrophils and in the granules of eosinophils.

PubMed

Udby, Lene; Calafat, Jero; Sørensen, Ole E; Borregaard, Niels; Kjeldsen, Lars

2002-09-01

Cysteine-rich secretory protein 3 (CRISP-3; also known as SGP28) was originally discovered in human neutrophilic granulocytes. We have recently developed a sensitive sandwich enzyme-linked immunosorbent assay for CRISP-3 and demonstrated the presence of CRISP-3 in exocrine secretions. To investigate the subcellular localization and mobilization of CRISP-3 in human neutrophils, we performed subcellular fractionation of resting and activated neutrophils on three-layer Percoll density gradients, release-studies of granule proteins in response to different secretagogues, and double-labeling immunogold electron microscopy. CRISP-3 was found to be localized in a subset of granules with overlapping characteristics of specific and gelatinase granules and mobilized accordingly, thus confirming the hypothesis that peroxidase-negative granules exist as a continuum from specific to gelatinase granules regarding protein content and mobilization. CRISP-3 was found to be a matrix protein, which is stored in granules as glycosylated and as unglycosylated protein. The subcellular distribution of the two forms of CRISP-3 was identical. In addition, CRISP-3 was found as a granule protein in eosinophilic granulocytes. The presence of CRISP-3 in peroxidase-negative granules of neutrophils, in granules of eosinophils, and in exocrine secretions indicates a role in the innate host defense.

Preterm birth disrupts cerebellar development by affecting granule cell proliferation program and Bergmann glia.

PubMed

Iskusnykh, Igor Y; Buddington, Randal K; Chizhikov, Victor V

2018-08-01

Preterm birth is a leading cause of long-term motor and cognitive deficits. Clinical studies suggest that some of these deficits result from disruption of cerebellar development, but the mechanisms that mediate cerebellar abnormalities in preterm infants are largely unknown. Furthermore, it remains unclear whether preterm birth and precocious exposure to the ex-utero environment directly disrupt cerebellar development or indirectly by increasing the probability of cerebellar injury, including that resulting from clinical interventions and protocols associated with the care of preterm infants. In this study, we analyzed the cerebellum of preterm pigs delivered via c-section at 91% term and raised for 10 days, until term-equivalent age. The pigs did not receive any treatments known or suspected to affect cerebellar development and had no evidence of brain damage. Term pigs sacrificed at birth were used as controls. Immunohistochemical analysis revealed that preterm birth did not affect either size or numbers of Purkinje cells or molecular layer interneurons at term-equivalent age. The number of granule cell precursors and Bergmann glial fibers, however, were reduced in preterm pigs. Preterm pigs had reduced proliferation but not differentiation of granule cells. qRT-PCR analysis of laser capture microdissected external granule cell layer showed that preterm pigs had a reduced expression of Ccnd1 (Cyclin D1), Ccnb1 (Cyclin B1), granule cell master regulatory transcription factor Atoh1, and signaling molecule Jag1. In vitro rescue experiments identified Jag1 as a central granule cell gene affected by preterm birth. Thus, preterm birth and precocious exposure to the ex-utero environment disrupt cerebellum by modulating expression of key cerebellar developmental genes, predominantly affecting development of granule precursors and Bergmann glia. Copyright © 2018 Elsevier Inc. All rights reserved.

Neonatal isolation impairs neurogenesis in the dentate gyrus of the guinea pig.

PubMed

Rizzi, Simona; Bianchi, Patrizia; Guidi, Sandra; Ciani, Elisabetta; Bartesaghi, Renata

2007-01-01

In the current study we examined the effects of early isolation rearing on cell proliferation, survival and differentiation in the dentate gyrus of the guinea pig. Animals were assigned to either a standard (control) or an isolated environment a few days after birth (P5-P6), taking advantage of the precocious independence from maternal care of the guinea pig. On P14-P17 animals received one daily bromodeoxyuridine injection, to label dividing cells, and were sacrificed either on P18, to evaluate cell proliferation or on P45, to evaluate cell survival and differentiation. In P18 isolated animals we found a reduced cell proliferation (-35%) compared to controls and a lower expression of brain-derived neurotrophic factor (BDNF). Though in absolute terms P45 isolated animals had less surviving cells, they showed no differences in survival rate and phenotype percent distribution compared to controls. Looking at the location of the new neurons, we found that while in control animals 76% of them had migrated to the granule cell layer, in isolated animals only 55% of the new neurons had reached this layer. Examination of radial glia cells of P18 and P45 animals by vimentin immunohistochemistry showed that in isolated animals radial glia cells were reduced in density and had less and shorter processes. Granule cell count revealed that P45 isolated animals had less (-42%) granule cells than controls. Results show that isolation rearing reduces hippocampal cell proliferation, likely by reducing BDNF expression and hampers migration of the new neurons to the granule cell layer, likely by altering density/morphology of radial glia cells. The large reduction in granule cell number following isolation rearing emphasizes the role of environmental cues as relevant modulators of neurogenesis.

Topographic and age-related changes of the retinal epithelium and Bruch's membrane of rhesus monkeys.

PubMed

Gouras, Peter; Ivert, Lena; Neuringer, Martha; Mattison, Julie A

2010-07-01

To examine structural differences in the retinal pigmented epithelium (RPE) and Bruch's membrane of rhesus monkeys (Macaca mulatta) as a function of topography and age. The retinas of two old (24 and 26 years old) and two young (1 and 6 years old) female monkeys were examined by light fluorescence and electron microscopy at the macula, equator, and ora serrata. All monkeys lacked fluorescence and lipofuscin granules in the RPE at the ora serrata where photoreceptors are absent. The equator and macula showed intense fluorescence and many lipofuscin granules in the RPE of the old but not the young monkeys. At the ora, the RPE contained many dense round melanin granules throughout the cell. At the equator and macula, melanin granules were more apical, less frequent, and often elongated. Mitochondria were clustered at the basal side of the RPE cell near infolds of the plasma membrane. Both mitochondria and infolds tended to increase toward the macula. In all regions, the basal lamina of the RPE did not penetrate the extracellular space adjacent to infolds. The elastin layer of Bruch's membrane was wide at the ora and equator and thinner at the macula. In the old monkeys, drusen were found at all retinal regions between the basal lamina and the internal collagen layer of Bruch's membrane. The drusen were often membrane-bound with a basal lamina and contained material resembling structures in the RPE. Lack of fluorescence and lipofuscin in the RPE at the ora serrata, where photoreceptors are absent, confirms that RPE fluorescence occurs only where outer segments are phagocytized. Mitochondrial clustering indicates that the basal side of the RPE cell uses the most energy and this becomes maximal at the macula. The presence of age-related degenerative changes and drusen at all retinal locations in the older monkeys, even at the ora where RPE lipofuscin was absent, indicates that these processes are not dependent on local lipofuscin accumulation. Therefore lipofuscin toxicity may not be the sole cause of age-related RPE degeneration.

Migration and Differentiation of GFP-transplanted Bone Marrow-derived Cells into Experimentally Induced Periodontal Polyp in Mice.

PubMed

Matsuda, Saeka; Shoumura, Masahito; Osuga, Naoto; Tsujigiwa, Hidetsugu; Nakano, Keisuke; Okafuji, Norimasa; Ochiai, Takanaga; Hasegawa, Hiromasa; Kawakami, Toshiyuki

2016-01-01

Perforation of floor of the dental pulp is often encountered during root canal treatment in routine clinical practice of dental caries. If perforation were large, granulation tissue would grow to form periodontal polyp. Granulation tissue consists of proliferating cells however their origin is not clear. It was shown that the cells in granulation tissue are mainly from migration of undifferentiated mesenchymal cells of the bone marrow. Hence, this study utilized GFP bone marrow transplantation mouse model. The floor of the pulp chamber in maxillary first molar was perforated using ½ dental round bur. Morphological assessment was carried out by micro CT and microscopy and GFP cell mechanism was further assessed by immunohistochemistry using double fluorescent staining with GFP-S100A4; GFP-Runx2 and GFP-CD31. Results of micro CT revealed alveolar bone resorption and widening of periodontal ligament. Histopathological examination showed proliferation of fibroblasts with some round cells and blood vessels in the granulation tissue. At 2 weeks, the outermost layer of the granulation tissue was lined by squamous cells with distinct intercellular bridges. At 4 weeks, the granulation tissue became larger than the perforation and the outermost layer was lined by relatively typical stratified squamous epithelium. Double immunofluorescent staining of GFP and Runx2 revealed that both proteins were expressed in spindle-shaped cells. Double immunofluorescent staining of GFP and CD31 revealed that both proteins were expressed in vascular endothelial cells in morphologically distinct vessels. The results suggest that fibroblasts, periodontal ligament fibroblasts and blood vessels in granulation tissue were derived from transplanted-bone marrow cells. Thus, essential growth of granulation tissue in periodontal polyp was caused by the migration of undifferentiated mesenchymal cells derived from bone marrow, which differentiated into fibroblasts and later on differentiated into other cells in response to injury.

Respiration Gates Sensory Input Responses in the Mitral Cell Layer of the Olfactory Bulb

PubMed Central

Short, Shaina M.; Morse, Thomas M.; McTavish, Thomas S.; Shepherd, Gordon M.; Verhagen, Justus V.

2016-01-01

Respiration plays an essential role in odor processing. Even in the absence of odors, oscillating excitatory and inhibitory activity in the olfactory bulb synchronizes with respiration, commonly resulting in a burst of action potentials in mammalian mitral/tufted cells (MTCs) during the transition from inhalation to exhalation. This excitation is followed by inhibition that quiets MTC activity in both the glomerular and granule cell layers. Odor processing is hypothesized to be modulated by and may even rely on respiration-mediated activity, yet exactly how respiration influences sensory processing by MTCs is still not well understood. By using optogenetics to stimulate discrete sensory inputs in vivo, it was possible to temporally vary the stimulus to occur at unique phases of each respiration. Single unit recordings obtained from the mitral cell layer were used to map spatiotemporal patterns of glomerular evoked responses that were unique to stimulations occurring during periods of inhalation or exhalation. Sensory evoked activity in MTCs was gated to periods outside phasic respiratory mediated firing, causing net shifts in MTC activity across the cycle. In contrast, odor evoked inhibitory responses appear to be permitted throughout the respiratory cycle. Computational models were used to further explore mechanisms of inhibition that can be activated by respiratory activity and influence MTC responses. In silico results indicate that both periglomerular and granule cell inhibition can be activated by respiration to internally gate sensory responses in the olfactory bulb. Both the respiration rate and strength of lateral connectivity influenced inhibitory mechanisms that gate sensory evoked responses. PMID:28005923

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

PubMed

Pan, D D; Jane, J I

2000-01-01

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

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

PubMed Central

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

2018-01-01

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

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

PubMed

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

2018-02-05

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

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

PubMed Central

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

2009-01-01

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

Subcellular TSC22D4 localization in cerebellum granule neurons of the mouse depends on development and differentiation.

PubMed

Canterini, Sonia; Bosco, Adriana; Carletti, Valentina; Fuso, Andrea; Curci, Armando; Mangia, Franco; Fiorenza, Maria Teresa

2012-03-01

We previously demonstrated that TSC22D4, a protein encoded by the TGF-β1-activated gene Tsc22d4 (Thg-1pit) and highly expressed in postnatal and adult mouse cerebellum with multiple post-translationally modified protein forms, moves to nucleus when in vitro differentiated cerebellum granule neurons (CGNs) are committed to apoptosis by hyperpolarizing KCl concentrations in the culture medium. We have now studied TSC22D4 cytoplasmic/nuclear localization in CGNs and Purkinje cells: (1) during CGN differentiation/maturation in vivo, (2) during CGN differentiation in vitro, and (3) by in vitro culturing ex vivo cerebellum slices under conditions favoring/inhibiting CGN/Purkinje cell differentiation. We show that TSC22D4 displays both nuclear and cytoplasmic localizations in undifferentiated, early postnatal cerebellum CGNs, irrespectively of CGN proliferation/migration from external to internal granule cell layer, and that it specifically accumulates in the somatodendritic and synaptic compartments when CGNs mature, as indicated by TSC22D4 abundance at the level of adult cerebellum glomeruli and apparent lack in CGN nuclei. These features were also observed in cerebellum slices cultured in vitro under conditions favoring/inhibiting CGN/Purkinje cell differentiation. In vitro TSC22D4 silencing with siRNAs blocked CGN differentiation and inhibited neurite elongation in N1E-115 neuroblastoma cells, pinpointing the relevance of this protein to CGN differentiation.

Researching of the reduction of shock waves intensivity in the “pseudo boiling” layer

NASA Astrophysics Data System (ADS)

Pavlov, G. I.; Telyashov, D. A.; Kochergin, A. V.; Nakoryakov, P. V.; Sukhovaya, E. A.

2017-09-01

This article applies to the field of acoustics and deals with noise reduction of pulsating combustion chambers, in particular the reduction of the shock waves’ intensity with the help of pseudo boiling layer. In the course of work on a test stand that included a pulsator, a compressor with the receiver and a high pressure fan was simulated gas jet flowing from the chamber pulsating combustion and studied the effect of different types of fluidization on effect of reducing the sound pressure levels. Were obtained the experimental dependence of the sound pressure levels from parameters such as: height of the layer of granules; diameter of the used granules; amplitude of the pressure pulsations in the gas stream at the entrance to the camera; frequency of pressure pulsations. Based on the results of the study, it was concluded that the using of a pseudo boiling layer is promising for reducing shock wave noise.

Ultrastructural study on the embryonic development of the orthokeratinized epithelium and its cornified layer (lingual nail) on the ventral surface of the lingual apex in the domestic duck (Anas platyrhynchos f. domestica).

PubMed

Skieresz-Szewczyk, Kinga; Jackowiak, Hanna; Ratajczak, Marlena

2018-02-01

The lingual nail as the cornified layer of the orthokeratinized epithelium in birds is responsible for the collection of solid food by pecking. The aim of the present study is to determine the manner of orthokeratinized epithelium development and assess the degree of readiness of the epithelium to fulfill its mechanical function at hatching. Three developmental phases are distinguished, i.e. embryonic, transformation and pre-hatching stage. In the embryonic stage lasting until day 13 of incubation the epithelium is composed of several layers of undifferentiated cells. During the transformation stage, from day 14 to 20 of incubation, the epithelium becomes differentiated to form three layers. A characteristic feature is the formation of osmophilic granules in the superficial layer, referred to as periderm granules. Until the pre-hatching stage the fibrous cytoskeleton of epithelial cells and an impermeable epithelial barrier are gradually developed. In the pre-hatching stage, a cornified lingual nail is formed, while the periderm is exfoliated. At hatching the orthokeratinized epithelium and lingual nail are fully developed and ready to perform feeding activities. The presence of periderm, similarly as in the epidermis, indicates the ectodermal derivation of the oral cavity epithelium. Moreover, occurrence of osmophilic granules may be considered as evidence for the phylogenetic affinity of birds and reptiles. Copyright © 2018 Elsevier GmbH. All rights reserved.

Surface topography and ultrastructural architecture of the tegument of adult Carmyerius spatiosus Brandes, 1898.

PubMed

Anuracpreeda, Panat; Phutong, Sumittra; Ngamniyom, Arin; Panyarachun, Busaba; Sobhon, Prasert

2015-03-01

Adult Carmyerius spatiosus or stomach fluke has an elongate, cylindrical-shaped, straight to slightly curved body, with conical anterior end and truncated posterior end. The worm measures about 8.7-11.2mm in body length and 2.3-3.0mm in body width across the mid-section. When observed by SEM, the tegumental surface in all part of the body appears highly corrugated with ridges and furrows, and having no spines. The ventral surface has more complex corrugation than those of the dorsal surface. Both anterior and posterior suckers have thick edges covered with transverse folds and appear spineless. The genital pore is located at the anterior part of the body. There are two types of sensory papillae on the surface: type 1 is bulbous in shape with nipple-like tips; type 2 has a similar shape with short cilia on the tip. The dorsal surface exhibits similar surface features, but papillae appear less numerous and are smaller. When observed by TEM, the tegument is divided into four layers. The first layer includes the ridges and furrows which are covered by a trilaminate membrane underlined by a dense lamina and coated externally with the glycocalyx. The second layer of the tegument is a narrow region of cytoplasm that contains high concentrations of ovoid electron lucent tegumental granules (TG1), and disc-shaped electron dense tegumental granules (TG2) as well as lysosomes. TG1 close to the surface invariably exocytose their content into bottoms of the ridges, while some TG2 are fused and have their membrane joined up with the surface membrane. The third layer is the widest middle area of the tegument which contains numerous and evenly distributed mitochondria. Both TG1 and TG2 granules are present but in much fewer number than in the first and second layers. The fourth layer is the innermost zone that rests on and couples with a thick basal lamina. The cytoplasm in this layer is loosely packed and contains numerous infoldings of the basal plasma membrane with closely associated mitochondria. It also contains fairly large numbers of TG1 and TG2 granules which are produced and transported to the tegument by one type of tegumental cells lying in rows underneath the muscular layers. Copyright © 2014 Elsevier B.V. All rights reserved.

Phosphorylation of SNAP-23 regulates its dynamic membrane association during mast cell exocytosis

PubMed Central

Naskar, Pieu

2017-01-01

ABSTRACT Upon allergen challenge, mast cells (MCs) respond by releasing pre-stored mediators from their secretory granules by the transient mechanism of porosome-mediated cell secretion. The target SNARE SNAP-23 has been shown to be important for MC exocytosis, and our previous studies revealed the presence of one basal (Thr102) and two induced (Ser95 and Ser120) phosphorylation sites in its linker region. To study the role of SNAP-23 phosphorylation in the regulation of exocytosis, green fluorescence protein-tagged wild-type SNAP-23 (GFP-SNAP-23) and its phosphorylation mutants were transfected into rat basophilic leukemia (RBL-2H3) MCs. Studies on GFP-SNAP-23 transfected MCs revealed some dynamic changes in SNAP-23 membrane association. SNAP-23 was associated with plasma membrane in resting MCs, however, on activation a portion of it translocated to cytosol and internal membranes. These internal locations were secretory granule membranes. This dynamic change in the membrane association of SNAP-23 in MCs may be important for mediating internal granule-granule fusions in compound exocytosis. Further studies with SNAP-23 phosphorylation mutants revealed an important role for the phosphorylation at Thr102 in its initial membrane association, and of induced phosphorylation at Ser95 and Ser120 in its internal membrane association, during MC exocytosis. PMID:28784843

Ultrastructure of the platypus and echidna mandibular glands.

PubMed

Krause, W J

2011-10-01

The secretory units of the platypus and echidna mandibular glands consist of a single serous cell type. Secretory granules within the cells of the platypus mandibular gland stained intensely with the periodic acid-Schiff staining procedure but failed to stain with Alcian Blue, suggesting the granules contained neutral glycoproteins. Secretory granules within the mandibular glands of the echidna failed to stain with the methods used indicating little if any glycoprotein was associated with the secretory granules. Ultrastructurally, secretory granules of the platypus mandibular gland were electron dense with a central core of less electron-dense material and were membrane bound. In contrast, those of the echidna presented a lamellated appearance and also were limited by a membrane. These secretory granules appeared to form as a result of concentric layering of lamellae within cisternae of the Golgi membranes. The intralobular ductal system of the platypus was more extensively developed than that of the echidna. The striated ducts of both species were characterized by elaborate infoldings of the basolateral plasmalemma and an abundance of associated mitochondria. © 2011 Blackwell Verlag GmbH.

Comparison and Analysis of Membrane Fouling between Flocculent Sludge Membrane Bioreactor and Granular Sludge Membrane Bioreactor

PubMed Central

Zhi-Qiang, Chen; Jun-Wen, Li; Yi-Hong, Zhang; Xuan, Wang; Bin, Zhang

2012-01-01

The goal of this study is to investigate the effect of inoculating granules on reducing membrane fouling. In order to evaluate the differences in performance between flocculent sludge and aerobic granular sludge in membrane reactors (MBRs), two reactors were run in parallel and various parameters related to membrane fouling were measured. The results indicated that specific resistance to the fouling layer was five times greater than that of mixed liquor sludge in the granular MBR. The floc sludge more easily formed a compact layer on the membrane surface, and increased membrane resistance. Specifically, the floc sludge had a higher moisture content, extracellular polymeric substances concentration, and negative surface charge. In contrast, aerobic granules could improve structural integrity and strength, which contributed to the preferable permeate performance. Therefore, inoculating aerobic granules in a MBR presents an effective method of reducing the membrane fouling associated with floc sludge the perspective of from the morphological characteristics of microbial aggregates. PMID:22859954

Acetylated sialic acid residues and blood group antigens localise within the epithelium in microvillous atrophy indicating internal accumulation of the glycocalyx

PubMed Central

Phillips, A D; Brown, A; Hicks, S; Schüller, S; Murch, S H; Walker-Smith, J A; Swallow, D M

2004-01-01

Background: Microvillous atrophy, a disorder of intractable diarrhoea in infancy, is characterised by the intestinal epithelial cell abnormalities of abnormal accumulation of periodic acid-Schiff (PAS) positive secretory granules within the apical cytoplasm and the presence of microvillous inclusions. The identity of the PAS positive material is not known, and the aim of this paper was to further investigate its composition. Methods: Formaldehyde fixed sections were stained with alcian blue/PAS to identify the acidic or neutral nature of the material, phenylhydrazine blocking was employed to stain specifically for sialic acid, and saponification determined the presence of sialic acid acetylation. The specificity of sialic acid staining was tested by digestion with mild sulphuric acid. Expression of blood group related antigens was tested immunochemically. Results: Alcian blue/PAS staining identified a closely apposed layer of acidic material on the otherwise neutral (PAS positive) brush border in controls. In microvillous atrophy, a triple layer was seen with an outer acidic layer, an unstained brush border region, and accumulation within the epithelium of a neutral glycosubstance that contained acetylated sialic acid. Blood group antigens were detected on the brush border, in mucus, and within goblet cells in controls. In microvillous atrophy they were additionally expressed within the apical cytoplasm of epithelial cells mirroring the PAS abnormality. Immuno electron microscopy localised expression to secretory granules. Conclusions: A neutral, blood group antigen positive, glycosubstance that contains acetylated sialic acid accumulates in the epithelium in microvillous atrophy. Previous studies have demonstrated that the direct and indirect constitutive pathways are intact in this disorder and it is speculated that the abnormal staining pattern reflects accumulation of glycocalyx related material. PMID:15542511

Chromaffin granules in the rat adrenal medulla release their secretory content in a particulate fashion.

PubMed

Crivellato, Enrico; Belloni, Anna; Nico, Beatrice; Nussdorfer, Gastone G; Ribatti, Domenico

2004-03-01

Exocytosis is considered the main route of granule discharge in chromaffin cells. We recently provided ultrastructural evidence suggesting that piecemeal degranulation (PMD) occurs in mouse adrenal chromaffin cells. In the present study, we processed rat adrenal glands for transmission electron microscopy (TEM), and examined chromaffin cells for changes characteristic of PMD. Both adrenaline (A)- and noradrenaline (NA)-storing cells express ultrastructural features suggestive of a slow and particulate mode of granule discharge. In adrenaline-containing cells, some granules present enlarged dimensions accompanied by eroded or dissolved matrices. Likewise, a number of granules in NA-releasing cells show content reduction with variably expanded granule chambers. Dilated, empty granule containers are recognizable in the cytoplasm of both cell types. Characteristically, altered granules and empty containers are seen intermingled with normal, resting granules. In addition, chromaffin granules often show irregular profiles, with budding or tail-like projections of their limiting membranes. Thirty 150-nm-diameter membrane-bound vesicles with a moderately electron-dense or -lucent internal structure are observable in the cytoplasm of both cell types. These vesicles are seen among the granules and some of them are fused with the perigranule membranes in the process of attachment to or budding from the granules. These data add further support to the concept that PMD may be an alternative secretory pathway in adrenal chromaffin cells. Copyright 2004 Wiley-Liss, Inc.

A Method for Extracting Pigments from Squid Doryteuthis pealeii.

PubMed

DiBona, Christopher W; Williams, Thomas L; Dinneen, Sean R; Jones Labadie, Stephanie F; Deravi, Leila F

2016-11-09

Cephalopods can undergo rapid and adaptive changes in dermal coloration for sensing, communication, defense, and reproduction purposes. These capabilities are supported in part by the areal expansion and retraction of pigmented organs known as chromatophores. While it is known that the chromatophores contain a tethered network of pigmented granules, their structure-function properties have not been fully detailed. We describe a method for isolating the nanostructured granules in squid Doryteuthis pealeii chromatophores and demonstrate how their associated pigments can be extracted in acidic solvents. To accomplish this, the chromatophore containing dermal layer is first manually isolated using a superficial dissection, and the pigment granules are removed using sonication, centrifugation, and washing cycles. Pigments confined within the purified granules are then extracted via acidic methanol solutions, leaving nanostructures with smaller diameters that are void of visible color. This extraction procedure produces a 58% yield of soluble pigments isolated from granules. Using this method, the composition of the chromatophore pigments can be determined and used to provide insight into the mechanism of adaptive coloration in cephalopods.

Development of the cascade inertial-confinement-fusion reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pitts, J.H.

Caqscade, originally conceived as a football-shaped, steel-walled reactor containing a Li/sub 2/O granule blanket, is now envisaged as a double-cone-shaped reactor containing a two-layered (three-zone) flowing blanket of BeO and LiAlO/sub 2/ granules. Average blanket exit temperature is 1670 K and gross plant efficiency (net thermal conversion efficiency) using a Brayton cycle is 55%. The reactor has a low-activation SiC-tiled wall. It rotates at 50 rpm, and the granules are transported to the top of the heat exchanger using their peripheral speed; no conveyors or lifts are required. The granules return to the reactor by gravity. After considerable analysis andmore » experimentation, we continue to regard Cascade as a promising reactor concept with the advantages of safety, efficiency, and low activation.« less

Development of the cascade inertial-confinement-fusion reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pitts, J.H.

Cascade, originally conceived as a football-shaped, steel-walled reactor containing a Li/sub 2/O granule blanket, is now envisaged as a double-cone-shaped reactor containing a two-layered (three-zone) flowing blanket of BeO and LiAlO/sub 2/ granules. Average blanket exit temperature is 1670/sup 0/K and gross plant efficiency (net thermal conversion efficiency) using a Brayton cycle is 55%. The reactor has a low-activation SiC-tiled wall. It rotates at 50 rpm, and the granules are transported to the top of the heat exchanger using their peripheral speed; no conveyors or lifts are required. The granules return to the reactor by gravity. After considerable analysis andmore » experimentation, we continue to regard Cascade as a promising reactor concept with the advantages of safety, efficiency, and low activation.« less

Antimicrobial-Coated Granules for Disinfecting Water

NASA Technical Reports Server (NTRS)

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

2011-01-01

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

Why do gelatinized starch granules not dissolve completely? Roles for amylose, protein, and lipid in granule "ghost" integrity.

PubMed

Debet, Martine R; Gidley, Michael J

2007-06-13

After gelatinization in water, starch granules persist in swollen hydrated forms known as ghosts. Three potential mechanisms for ghost formation are tested. Proteins and lipids on the granule surface are found to be a determinant of ghost robustness, but not ghost formation. Proteins inside pre-made maize or wheat starch ghosts are degraded extensively by proteases without any apparent change in ghost properties, making an internal protein cross-linking mechanism unlikely. Waxy maize mutants with a range of amylose contents have ghost integrities that correlate with (low) apparent amylose levels. It is hypothesized that ghost formation is due to cross-linking of polysaccharide chains within swollen granules, most likely involving double helices formed from polymer chains that become free to move following heat-induced granule swelling. The size and robustness of granule ghosts is proposed to be determined by the relative rates of swelling and cross-linking, modulated by surface non-polysaccharide components.

Performance of double-layer biofilter packed with coal fly ash ceramic granules in treating highly polluted river water.

PubMed

Jing, Zhaoqian; Li, Yu-You; Cao, Shiwei; Liu, Yuyu

2012-09-01

To improve trickling filters' denitrification efficiency, a biofilter with a trickling upper layer and a submerged lower layer was developed and applied in treating highly polluted river water. It was packed with porous coal fly ash ceramic granules. Its start-up characteristics, influence of hydraulic loading rates (HLR), carbon/nitrogen (C/N) ratio and filter depth on pollutants removal were investigated. The results indicated this biofilter was started quickly in 16 days with river sediment as inoculum. Alternating nitrification and denitrification were achieved when water flowed downwards. COD and nitrogen were mainly removed in the upper layer and the lower layer, respectively. With HLR of 4.0-5.0m(3)/(m(2)d), chemical oxygen demand (COD), ammonium (NH(4)(+)-N) and total nitrogen (TN) in the effluent were below 50, 5 and 15 mg/L, respectively. This biofilter removed more than 80% of COD, 85% of NH(4)(+)-N and 60% of TN with C/N ratios ranging from 6 to 10. Copyright © 2012 Elsevier Ltd. All rights reserved.

Phosphorylation of SNAP-23 regulates its dynamic membrane association during mast cell exocytosis.

PubMed

Naskar, Pieu; Puri, Niti

2017-09-15

Upon allergen challenge, mast cells (MCs) respond by releasing pre-stored mediators from their secretory granules by the transient mechanism of porosome-mediated cell secretion. The target SNARE SNAP-23 has been shown to be important for MC exocytosis, and our previous studies revealed the presence of one basal (Thr 102 ) and two induced (Ser 95 and Ser 120 ) phosphorylation sites in its linker region. To study the role of SNAP-23 phosphorylation in the regulation of exocytosis, green fluorescence protein-tagged wild-type SNAP-23 (GFP-SNAP-23) and its phosphorylation mutants were transfected into rat basophilic leukemia (RBL-2H3) MCs. Studies on GFP-SNAP-23 transfected MCs revealed some dynamic changes in SNAP-23 membrane association. SNAP-23 was associated with plasma membrane in resting MCs, however, on activation a portion of it translocated to cytosol and internal membranes. These internal locations were secretory granule membranes. This dynamic change in the membrane association of SNAP-23 in MCs may be important for mediating internal granule-granule fusions in compound exocytosis. Further studies with SNAP-23 phosphorylation mutants revealed an important role for the phosphorylation at Thr 102 in its initial membrane association, and of induced phosphorylation at Ser 95 and Ser 120 in its internal membrane association, during MC exocytosis. © 2017. Published by The Company of Biologists Ltd.

Docking is not a prerequisite but a temporal constraint for fusion of secretory granules.

PubMed

Kasai, Kazuo; Fujita, Takuji; Gomi, Hiroshi; Izumi, Tetsuro

2008-07-01

We examined secretory granule dynamics using total internal reflection fluorescence microscopy in normal pancreatic beta cells and their mutants devoid of Rab27a and/or its effector, granuphilin, which play critical roles in the docking and recruitment of insulin granules to the plasma membrane. In the early phase of glucose stimulation in wild-type cells, we observed marked fusion of granules recruited from a relatively distant area, in parallel with that from granules located underneath the plasma membrane. Furthermore, despite a lack of granules directly attached to the plasma membrane, both spontaneous and evoked fusion was increased in granuphilin-null cells. In addition to these granuphilin-null phenotypes, Rab27a/granuphilin doubly deficient cells showed the decreases in granules located next to the docked area and in fusion from granules near the plasma membrane in the early phase of glucose-stimulated secretion, similar to Rab27a-mutated cells. Thus, the two proteins play nonoverlapping roles in insulin exocytosis: granuphilin acts on the granules underneath the plasma membrane, whereas Rab27a acts on those in a more distal area. These findings demonstrate that, in contrast to our conventional understanding, stable attachment of secretory granules to the plasma membrane is not prerequisite but temporally inhibitory for both spontaneous and evoked fusion.

ELKS, a Protein Structurally Related to the Active Zone-associated Protein CAST, Is Expressed in Pancreatic β Cells and Functions in Insulin Exocytosis: Interaction of ELKS with Exocytotic Machinery Analyzed by Total Internal Reflection Fluorescence MicroscopyV⃞

PubMed Central

Ohara-Imaizumi, Mica; Ohtsuka, Toshihisa; Matsushima, Satsuki; Akimoto, Yoshihiro; Nishiwaki, Chiyono; Nakamichi, Yoko; Kikuta, Toshiteru; Nagai, Shintaro; Kawakami, Hayato; Watanabe, Takashi; Nagamatsu, Shinya

2005-01-01

The cytomatrix at the active zone (CAZ) has been implicated in defining the site of Ca2+-dependent exocytosis of neurotransmitters. Here, we demonstrate the expression and function of ELKS, a protein structurally related to the CAZ protein CAST, in insulin exocytosis. The results of confocal and immunoelectron microscopic analysis showed that ELKS is present in pancreatic β cells and is localized close to insulin granules docked on the plasma membrane-facing blood vessels. Total internal reflection fluorescence microscopy imaging in insulin-producing clonal cells revealed that the ELKS clusters are less dense and unevenly distributed than syntaxin 1 clusters, which are enriched in the plasma membrane. Most of the ELKS clusters were on the docking sites of insulin granules that were colocalized with syntaxin 1 clusters. Total internal reflection fluorescence images of single-granule motion showed that the fusion events of insulin granules mostly occurred on the ELKS cluster, where repeated fusion was sometimes observed. When the Bassoon-binding region of ELKS was introduced into the cells, the docking and fusion of insulin granules were markedly reduced. Moreover, attenuation of ELKS expression by small interfering RNA reduced the glucose-evoked insulin release. These data suggest that the CAZ-related protein ELKS functions in insulin exocytosis from pancreatic β cells. PMID:15888548

Characterization of Pu-238 heat source granule containment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Richardson Ii, P D; Thronas, D L; Romero, J P

2008-01-01

The Milliwatt Radioisotopic Thermoelectric Generator (RTG) provides power for permissive-action links. These nuclear batteries convert thermal energy to electrical energy using a doped silicon-germanium thermopile. The thermal energy is provided by a heat source made of {sup 238}Pu, in the form of {sup 238}PuO{sub 2} granules. The granules are contained in 3 layers of encapsulation. A thin T-111 liner surrounds the {sup 238}PuO{sub 2} granules and protects the second layer (strength member) from exposure to the fuel granules. The T-111 strength member contains the fuel under impact condition. An outer clad of Hastelloy-C protects the T-111 from oxygen embrittlement. Themore » T-111 strength member is considered the critical component in this {sup 238}PuO{sub 2} containment system. Any compromise in the strength member is something that needs to be characterized. Consequently, the T-111 strength member is characterized upon it's decommissioning through Scanning Electron Microscopy (SEM), and Metallography. SEM is used in 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 photomicrographs. SEM may further be used to examine polished Metallography mounts to characterize elements using the SEM mode of Energy Dispersive X-ray Spectroscopy (EDS). This paper describes the characterization of the metallurgical condition of decommissioned RTG heat sources.« less

Ultrastructural identification of Langerhans cells in normal swine epidermis.

PubMed Central

Romano, J; Balaguer, L

1991-01-01

Langerhans cells of the epidermis of 6-month-old white crossbred farm pigs were identified by electron microscopy. Ultrastructurally they were similar to those described in other mammals. They were present in basal and suprabasal layers and were characterised by a lobulated nucleus and an electrolucent cytoplasm with occasional dendritic processes, and the absence of tonofilaments and specialised unions with surrounding keratinocytes. They were specifically identified by the presence of characteristic rod or racquet-shaped intracytoplasmic granules. Intraepidermal clear cells without specific granules were present, although no melanocytes were observed. This is the first report of the presence of Birbeck granules in porcine Langerhans cells. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:1817140

Seizure frequency correlates with loss of dentate gyrus GABAergic neurons in a mouse model of temporal lobe epilepsy

PubMed Central

Buckmaster, Paul S.; Abrams, Emily; Wen, Xiling

2018-01-01

Epilepsy occurs in one of 26 people. Temporal lobe epilepsy is common and can be difficult to treat effectively. It can develop after brain injuries that damage the hippocampus. Multiple pathophysiological mechanisms involving the hippocampal dentate gyrus have been proposed. This study evaluated a mouse model of temporal lobe epilepsy to test which pathological changes in the dentate gyrus correlate with seizure frequency and help prioritize potential mechanisms for further study. FVB mice (n = 127) that had experienced status epilepticus after systemic treatment with pilocarpine 31–61 days earlier were video-monitored for spontaneous, convulsive seizures 9 hr/day every day for 24–36 days. Over 4,060 seizures were observed. Seizure frequency ranged from an average of one every 3.6 days to one every 2.1 hr. Hippocampal sections were processed for Nissl stain, Prox1-immunocytochemistry, GluR2-immunocytochemistry, Timm stain, glial fibrillary acidic protein-immunocytochemistry, glutamic acid decarboxylase in situ hybridization, and parvalbumin-immunocytochemistry. Stereological methods were used to measure hilar ectopic granule cells, mossy cells, mossy fiber sprouting, astrogliosis, and GABAergic interneurons. Seizure frequency was not significantly correlated with the generation of hilar ectopic granule cells, the number of mossy cells, the extent of mossy fiber sprouting, the extent of astrogliosis, or the number of GABAergic interneurons in the molecular layer or hilus. Seizure frequency significantly correlated with the loss of GABAergic interneurons in or adjacent to the granule cell layer, but not with the loss of parvalbumin-positive interneurons. These findings prioritize the loss of granule cell layer interneurons for further testing as a potential cause of temporal lobe epilepsy. PMID:28425097

Seizure frequency correlates with loss of dentate gyrus GABAergic neurons in a mouse model of temporal lobe epilepsy.

PubMed

Buckmaster, Paul S; Abrams, Emily; Wen, Xiling

2017-08-01

Epilepsy occurs in one of 26 people. Temporal lobe epilepsy is common and can be difficult to treat effectively. It can develop after brain injuries that damage the hippocampus. Multiple pathophysiological mechanisms involving the hippocampal dentate gyrus have been proposed. This study evaluated a mouse model of temporal lobe epilepsy to test which pathological changes in the dentate gyrus correlate with seizure frequency and help prioritize potential mechanisms for further study. FVB mice (n = 127) that had experienced status epilepticus after systemic treatment with pilocarpine 31-61 days earlier were video-monitored for spontaneous, convulsive seizures 9 hr/day every day for 24-36 days. Over 4,060 seizures were observed. Seizure frequency ranged from an average of one every 3.6 days to one every 2.1 hr. Hippocampal sections were processed for Nissl stain, Prox1-immunocytochemistry, GluR2-immunocytochemistry, Timm stain, glial fibrillary acidic protein-immunocytochemistry, glutamic acid decarboxylase in situ hybridization, and parvalbumin-immunocytochemistry. Stereological methods were used to measure hilar ectopic granule cells, mossy cells, mossy fiber sprouting, astrogliosis, and GABAergic interneurons. Seizure frequency was not significantly correlated with the generation of hilar ectopic granule cells, the number of mossy cells, the extent of mossy fiber sprouting, the extent of astrogliosis, or the number of GABAergic interneurons in the molecular layer or hilus. Seizure frequency significantly correlated with the loss of GABAergic interneurons in or adjacent to the granule cell layer, but not with the loss of parvalbumin-positive interneurons. These findings prioritize the loss of granule cell layer interneurons for further testing as a potential cause of temporal lobe epilepsy. © 2017 Wiley Periodicals, Inc.

Teaching Population Balances for Chemical Engineering Students: Application to Granulation Processes

ERIC Educational Resources Information Center

Bucala, Veronica; Pina, Juliana

2007-01-01

The population balance equation (PBE) is a useful tool to predict particle size distributions in granulation processes. When PBE is taught to advanced chemical engineering students, the internal coordinates (particle properties) are particularly hard to understand. In this paper, the flow of particles along different coordinates is carefully…

Microstructure of anammox granules and mechanisms endowing their intensity revealed by microscopic inspection and rheometry.

PubMed

Lin, Ximao; Wang, Yayi

2017-09-01

The anammox process represents a sustainable and cost-effective technique for nitrogen removal from wastewater, where granulation of anammox bacteria could be of great benefit to the system performance. However, knowledge of the specific properties of anammox granules is currently unsatisfactory. In this study, the organization of anammox granules was comprehensively studied from macro to micro scale with a range of microscale techniques. Scanning and transmission electron microscopy and multiple fluorescence labeling combined with confocal laser scanning microscopy were included. Simultaneously, the associated mechanical properties were studied in-depth by rheometry in combination with selective enzymatic hydrolysis. Anammox granules follow a tertiary organization regime, where interactions between individual anammox bacteria made up the primary base, then, the grouping of anammox bacterial cells encapsulated within a thin extracellular polymeric substance (EPS) layer comprised a second arrangement level, and, finally, the cementing of these groups together with other bacteria and polymers gave rise to compact aggregates. α-Polysaccharides and proteins were considered the backbones of anammox granules, contributing greatly to their excellent intensity. β-Polysaccharides concentrated at the outer rims of anammox granules and combined with other macromolecules to form a buffer zone or protective barrier, beneath which anammox bacteria proliferated. Divalent cationic bridging for EPS binding was prevalent and of great significance within the dense anammox granules, while there was also much weak monovalent ionic interaction. The specific organization and composition of anammox granules endows them with excellent intensity and integrity, which can be of importance for full-scale reactor operations where diverse shocks can be expected. Copyright © 2017 Elsevier Ltd. All rights reserved.

Exocyst sec5 regulates exocytosis of newcomer insulin granules underlying biphasic insulin secretion.

PubMed

Xie, Li; Zhu, Dan; Kang, Youhou; Liang, Tao; He, Yu; Gaisano, Herbert Y

2013-01-01

The exocyst complex subunit Sec5 is a downstream effector of RalA-GTPase which promotes RalA-exocyst interactions and exocyst assembly, serving to tether secretory granules to docking sites on the plasma membrane. We recently reported that RalA regulates biphasic insulin secretion in pancreatic islet β cells in part by tethering insulin secretory granules to Ca(2+) channels to assist excitosome assembly. Here, we assessed β cell exocytosis by patch clamp membrane capacitance measurement and total internal reflection fluorescence microscopy to investigate the role of Sec5 in regulating insulin secretion. Sec5 is present in human and rodent islet β cells, localized to insulin granules. Sec5 protein depletion in rat INS-1 cells inhibited depolarization-induced release of primed insulin granules from both readily-releasable pool and mobilization from the reserve pool. This reduction in insulin exocytosis was attributed mainly to reduction in recruitment and exocytosis of newcomer insulin granules that undergo minimal docking time at the plasma membrane, but which encompassed a larger portion of biphasic glucose stimulated insulin secretion. Sec5 protein knockdown had little effect on predocked granules, unless vigorously stimulated by KCl depolarization. Taken together, newcomer insulin granules in β cells are more sensitive than predocked granules to Sec5 regulation.

Influence of raw material properties upon critical quality attributes of continuously produced granules and tablets.

PubMed

Fonteyne, Margot; Wickström, Henrika; Peeters, Elisabeth; Vercruysse, Jurgen; Ehlers, Henrik; Peters, Björn-Hendrik; Remon, Jean Paul; Vervaet, Chris; Ketolainen, Jarkko; Sandler, Niklas; Rantanen, Jukka; Naelapää, Kaisa; De Beer, Thomas

2014-07-01

Continuous manufacturing gains more and more interest within the pharmaceutical industry. The International Conference of Harmonisation (ICH) states in its Q8 'Pharmaceutical Development' guideline that the manufacturer of pharmaceuticals should have an enhanced knowledge of the product performance over a range of raw material attributes, manufacturing process options and process parameters. This fits further into the Process Analytical Technology (PAT) and Quality by Design (QbD) framework. The present study evaluates the effect of variation in critical raw material properties on the critical quality attributes of granules and tablets, produced by a continuous from-powder-to-tablet wet granulation line. The granulation process parameters were kept constant to examine the differences in the end product quality caused by the variability of the raw materials properties only. Theophylline-Lactose-PVP (30-67.5-2.5%) was used as model formulation. Seven different grades of theophylline were granulated. Afterward, the obtained granules were tableted. Both the characteristics of granules and tablets were determined. The results show that differences in raw material properties both affect their processability and several critical quality attributes of the resulting granules and tablets. Copyright © 2014 Elsevier B.V. All rights reserved.

PtdIns(4,5)P2 is not required for secretory granule docking.

PubMed

Omar-Hmeadi, Muhmmad; Gandasi, Nikhil R; Barg, Sebastian

2018-06-01

Phosphoinositides (PtdIns) play important roles in exocytosis and are thought to regulate secretory granule docking by co-clustering with the SNARE protein syntaxin to form a docking receptor in the plasma membrane. Here we tested this idea by high-resolution total internal reflection imaging of EGFP-labeled PtdIns markers or syntaxin-1 at secretory granule release sites in live insulin-secreting cells. In intact cells, PtdIns markers distributed evenly across the plasma membrane with no preference for granule docking sites. In contrast, syntaxin-1 was found clustered in the plasma membrane, mostly beneath docked granules. We also observed rapid accumulation of syntaxin-1 at sites where granules arrived to dock. Acute depletion of plasma membrane phosphatidylinositol (4,5) bisphosphate (PtdIns(4,5)P 2 ) by recruitment of a 5'-phosphatase strongly inhibited Ca 2+ -dependent exocytosis, but had no effect on docked granules or the distribution and clustering of syntaxin-1. Cell permeabilization by α-toxin or formaldehyde-fixation caused PtdIns marker to slowly cluster, in part near docked granules. In summary, our data indicate that PtdIns(4,5)P 2 accelerates granule priming, but challenge a role of PtdIns in secretory granule docking or clustering of syntaxin-1 at the release site. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Regulation of RNA granule dynamics by phosphorylation of serine-rich, intrinsically disordered proteins in C. elegans

PubMed Central

Wang, Jennifer T; Smith, Jarrett; Chen, Bi-Chang; Schmidt, Helen; Rasoloson, Dominique; Paix, Alexandre; Lambrus, Bramwell G; Calidas, Deepika; Betzig, Eric; Seydoux, Geraldine

2014-01-01

RNA granules have been likened to liquid droplets whose dynamics depend on the controlled dissolution and condensation of internal components. The molecules and reactions that drive these dynamics in vivo are not well understood. In this study, we present evidence that a group of intrinsically disordered, serine-rich proteins regulate the dynamics of P granules in C. elegans embryos. The MEG (maternal-effect germline defective) proteins are germ plasm components that are required redundantly for fertility. We demonstrate that MEG-1 and MEG-3 are substrates of the kinase MBK-2/DYRK and the phosphatase PP2APPTR−½. Phosphorylation of the MEGs promotes granule disassembly and dephosphorylation promotes granule assembly. Using lattice light sheet microscopy on live embryos, we show that GFP-tagged MEG-3 localizes to a dynamic domain that surrounds and penetrates each granule. We conclude that, despite their liquid-like behavior, P granules are non-homogeneous structures whose assembly in embryos is regulated by phosphorylation. DOI: http://dx.doi.org/10.7554/eLife.04591.001 PMID:25535836

Determining the Influence of Granule Size on Simulation Parameters and Residual Shear Stress Distribution in Tablets by Combining the Finite Element Method into the Design of Experiments.

PubMed

Hayashi, Yoshihiro; Kosugi, Atsushi; Miura, Takahiro; Takayama, Kozo; Onuki, Yoshinori

2018-01-01

The influence of granule size on simulation parameters and residual shear stress in tablets was determined by combining the finite element method (FEM) into the design of experiments (DoE). Lactose granules were prepared using a wet granulation method with a high-shear mixer and sorted into small and large granules using sieves. To simulate the tableting process using the FEM, parameters simulating each granule were optimized using a DoE and a response surface method (RSM). The compaction behavior of each granule simulated by FEM was in reasonable agreement with the experimental findings. Higher coefficients of friction between powder and die/punch (μ) and lower by internal friction angle (α y ) were generated in the case of small granules, respectively. RSM revealed that die wall force was affected by α y . On the other hand, the pressure transmissibility rate of punches value was affected not only by the α y value, but also by μ. The FEM revealed that the residual shear stress was greater for small granules than for large granules. These results suggest that the inner structure of a tablet comprising small granules was less homogeneous than that comprising large granules. To evaluate the contribution of the simulation parameters to residual stress, these parameters were assigned to the fractional factorial design and an ANOVA was applied. The result indicated that μ was the critical factor influencing residual shear stress. This study demonstrates the importance of combining simulation and statistical analysis to gain a deeper understanding of the tableting process.

Distribution of caspase-14 in epidermis and hair follicles is evolutionarily conserved among mammals.

PubMed

Alibardi, Lorenzo; Tschachler, Erwin; Eckhart, Leopold

2005-10-01

Caspase-14, a member of the caspase family of cysteine proteases, is almost exclusively expressed in the epidermis. Studies on human and mouse cells and tissues have implicated caspase-14 in terminal differentiation of epidermal keratinocytes and in the formation of the stratum corneum. Here we investigated evolutionary aspects of the role of caspase-14 by analyzing its distribution in the epidermis and hair follicles of representative species of placental mammals, marsupials, and monotremes. Immunocytochemical staining showed that caspase-14 is consistently expressed in the granular and corneous layer of the epidermis of all mammalian species investigated. Ultrastructural analysis using gold-labeled anticaspase-14 antibodies revealed that caspase-14 is associated preferentially with keratin bundles and amorphous material of keratohyalin granules, but is also present in nuclei of transitional cells of the granular layer and in corneocytes. In hair follicles, caspase-14 was diffusely present in cornifying cells of the outer root sheath, in the companion layer, and, most abundantly, in the inner root sheath of all mammalian species here analyzed. In Henle and Huxley layers of the inner root sheath, labeling was seen in nuclei and, more diffusely, among trichohyalin granules of cornifying cells. In summary, the tissue expression pattern and the intracellular localization of caspase-14 are highly conserved among diverse mammalian species, suggesting that this enzyme is involved in a molecular process that appeared early in the evolution of mammalian skin. The association of caspase-14 with keratohyalin and trichohyalin granules may indicate a specific role of caspase-14 in the maturation of these keratinocyte-specific structures.

A severe form of epidermal nevus syndrome associated with brainstem and cerebellar malformations and neonatal medulloblastoma.

PubMed

Okumura, Akihisa; Lee, Tsubasa; Ikeno, Mitsuru; Shimojima, Keiko; Kajino, Kazunori; Inoue, Yuka; Yoshikawa, Naomi; Suganuma, Hiroki; Suzuki, Mitsuyoshi; Hisata, Ken; Shoji, Hiromichi; Takanashi, Jun-ichi; Barkovich, A James; Shimizu, Toshiaki; Yamamoto, Toshiyuki; Hayashi, Masaharu

2012-11-01

Here we report a boy with epidermal nevus syndrome associated with brainstem and cerebellar malformations and neonatal medulloblastoma. The patient had epidermal nevi and complicated brain malformations including macrocephaly with polymicrogyria, dysmorphic and enlarged midbrain tectum, enlarged cerebellar hemispheres with small and maloriented folia. The patient died after surgical resection of medulloblastoma which was newly recognized on MRI at 51 days of age. Postmortem pathological examinations showed very unique and bizarre malformation of the midbrain and hindbrain. The cerebellar cortex exhibited a coarse, irregular and bumpy surface, blurred border between the Purkinje cell layer and internal granule cell layer, and many foci of heterotopia in the cerebellar white matter. The brainstem showed multiple anomalies, including enlargement of superior colliculi, hypoplasia of pyramidal tracts and dysplasia of inferior olivary nuclei. The unusual constellation of brain malformations of our patient will widen the spectrum of epidermal nevus syndrome. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Synaptic reorganization of inhibitory hilar interneuron circuitry after traumatic brain injury in mice

PubMed Central

Hunt, Robert F.; Scheff, Stephen W.; Smith, Bret N.

2011-01-01

Functional plasticity of synaptic networks in the dentate gyrus has been implicated in the development of posttraumatic epilepsy and in cognitive dysfunction after traumatic brain injury, but little is known about potentially pathogenic changes in inhibitory circuits. We examined synaptic inhibition of dentate granule cells and excitability of surviving GABAergic hilar interneurons 8–13 weeks after cortical contusion brain injury in transgenic mice that express enhanced green fluorescent protein in a subpopulation of inhibitory neurons. Whole-cell voltage-clamp recordings in granule cells revealed a reduction in spontaneous and miniature IPSC frequency after head injury; no concurrent change in paired-pulse ratio was found in granule cells after paired electrical stimulation of the hilus. Despite reduced inhibitory input to granule cells, action potential and EPSC frequencies were increased in hilar GABA neurons from slices ipsilateral to the injury, versus those from control or contralateral slices. Further, increased excitatory synaptic activity was detected in hilar GABA neurons ipsilateral to the injury after glutamate photostimulation of either the granule cell or CA3 pyramidal cell layers. Together, these findings suggest that excitatory drive to surviving hilar GABA neurons is enhanced by convergent input from both pyramidal and granule cells, but synaptic inhibition of granule cells is not fully restored after injury. This rewiring of circuitry regulating hilar inhibitory neurons may reflect an important compensatory mechanism, but it may also contribute to network destabilization by increasing the relative impact of surviving individual interneurons in controlling granule cell excitability in the posttraumatic dentate gyrus. PMID:21543618

GSK-3β Overexpression Alters the Dendritic Spines of Developmentally Generated Granule Neurons in the Mouse Hippocampal Dentate Gyrus.

PubMed

Pallas-Bazarra, Noemí; Kastanauskaite, Asta; Avila, Jesús; DeFelipe, Javier; Llorens-Martín, María

2017-01-01

The dentate gyrus (DG) plays a crucial role in hippocampal-related memory. The most abundant cellular type in the DG, namely granule neurons, are developmentally generated around postnatal day P6 in mice. Moreover, a unique feature of the DG is the occurrence of adult hippocampal neurogenesis, a process that gives rise to newborn granule neurons throughout life. Adult-born and developmentally generated granule neurons share some maturational aspects but differ in others, such as in their positioning within the granule cell layer. Adult hippocampal neurogenesis encompasses a series of plastic changes that modify the function of the hippocampal trisynaptic network. In this regard, it is known that glycogen synthase kinase 3β (GSK-3β) regulates both synaptic plasticity and memory. By using a transgenic mouse overexpressing GSK-3β in hippocampal neurons, we previously demonstrated that the overexpression of this kinase has deleterious effects on the maturation of newborn granule neurons. In the present study, we addressed the effects of GSK-3β overexpression on the morphology and number of dendritic spines of developmentally generated granule neurons. To this end, we performed intracellular injections of Lucifer Yellow in developmentally generated granule neurons of wild-type and GSK-3β-overexpressing mice and analyzed the number and morphologies of dendritic spines (namely, stubby, thin and mushroom). GSK-3β overexpression led to a general reduction in the number of dendritic spines. In addition, it caused a slight reduction in the percentage, head diameter and length of thin spines, whereas the head diameter of mushroom spines was increased.

GSK-3β Overexpression Alters the Dendritic Spines of Developmentally Generated Granule Neurons in the Mouse Hippocampal Dentate Gyrus

PubMed Central

Pallas-Bazarra, Noemí; Kastanauskaite, Asta; Avila, Jesús; DeFelipe, Javier; Llorens-Martín, María

2017-01-01

The dentate gyrus (DG) plays a crucial role in hippocampal-related memory. The most abundant cellular type in the DG, namely granule neurons, are developmentally generated around postnatal day P6 in mice. Moreover, a unique feature of the DG is the occurrence of adult hippocampal neurogenesis, a process that gives rise to newborn granule neurons throughout life. Adult-born and developmentally generated granule neurons share some maturational aspects but differ in others, such as in their positioning within the granule cell layer. Adult hippocampal neurogenesis encompasses a series of plastic changes that modify the function of the hippocampal trisynaptic network. In this regard, it is known that glycogen synthase kinase 3β (GSK-3β) regulates both synaptic plasticity and memory. By using a transgenic mouse overexpressing GSK-3β in hippocampal neurons, we previously demonstrated that the overexpression of this kinase has deleterious effects on the maturation of newborn granule neurons. In the present study, we addressed the effects of GSK-3β overexpression on the morphology and number of dendritic spines of developmentally generated granule neurons. To this end, we performed intracellular injections of Lucifer Yellow in developmentally generated granule neurons of wild-type and GSK-3β-overexpressing mice and analyzed the number and morphologies of dendritic spines (namely, stubby, thin and mushroom). GSK-3β overexpression led to a general reduction in the number of dendritic spines. In addition, it caused a slight reduction in the percentage, head diameter and length of thin spines, whereas the head diameter of mushroom spines was increased. PMID:28344548

The effect of trichlorfon and methylazoxymethanol on the development of guinea pig cerebellum.

PubMed

Mehl, Anna; Schanke, Tore M; Torvik, Ansgar; Fonnum, Frode

2007-03-01

The pesticide trichlorfon (125 mg/kg on days 42-44 in gestation) gives hypoplasia of the brain of the offspring without any significant reduction in their body weights. The hypoplasia may be caused by trichlorfon itself or by its metabolite dichlorvos. This period of development coincides with the growth spurt period of guinea pig brain. The largest changes occurred in the cerebellum. Electron microscopic examination of the cerebellar cortex showed increased apoptotic death of cells in the granule cell layer after trichlorfon treatment. A reduction in thickness of the external germinal layer of the cerebellar cortex and an elevated amount of pyknotic and karyorrhexic cells in the granule cell layer was found. There was a significant reduction in choline esterase, choline acetyltransferase and glutamate decarboxylase activities in the cerebellum. Methylazoxymethanol (15 mg/kg body weight, day 43) was examined for comparison and caused similar hypoplasia of the guinea pig cerebellum, but did also induce a reduction in body weight. Trichloroethanol, the main metabolite of trichlorfon, did not give brain hypoplasia.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mehl, Anna; Schanke, Tore M.; Torvik, Ansgar

The pesticide trichlorfon (125 mg/kg on days 42-44 in gestation) gives hypoplasia of Brain of the offspring without any significant reduction in their body weights. The hypoplasia may be caused by trichlorfon itself or by its metabolite dichlorvos. This period of development coincides with the growth spurt period of guinea pig brain. The largest changes occurred in the cerebellum. Electron microscopic examination of the cerebellar cortex showed increased apoptotic death of cells in the granule cell layer after trichlorfon treatment. A reduction in thickness of the external germinal layer of the cerebellar cortex and an elevated amount of pyknotic andmore » karyorrhexic cells in the granule cell layer was found. There was a significant reduction in choline esterase, choline acetyltransferase and glutamate decarboxylase activities in the cerebellum. Methylazoxymethanol (15 mg/kg body weight, day 43) was examined for comparison and caused similar hypoplasia of the guinea pig cerebellum, but did also induce a reduction in body weight. Trichloroethanol, the main metabolite of trichlorfon, did not give brain hypoplasia.« less

Localization of α1-2 Fucose Glycan in the Mouse Olfactory Pathway.

PubMed

Kondoh, Daisuke; Kamikawa, Akihiro; Sasaki, Motoki; Kitamura, Nobuo

2017-01-01

Glycoconjugates in the olfactory system play critical roles in neuronal formation, and α1-2 fucose (α1-2Fuc) glycan mediates neurite outgrowth and synaptic plasticity. Histochemical findings of α1-2Fuc glycan in the mouse olfactory system detected using Ulex europaeus agglutinin-I (UEA-I) vary. This study histochemically assessed the main olfactory and vomeronasal pathways in male and female ICR and C57BL/6J mice aged 3-4 months using UEA-I. Ulex europaeus agglutinin-I reacted with most receptor cells arranged mainly at the basal region of the olfactory epithelium. The olfactory nerve layer and glomerular layer of the main olfactory bulb were speckled with positive UEA-I staining, and positive fibers were scattered from the glomerular to the internal plexiform layer. The lateral olfactory tract and rostral migratory stream were also positive for UEA-I. We identified superficial short-axon cells, interneurons of the external plexiform layer, external, middle and internal tufted cells, mitral cells and granule cells as the origins of the UEA-I-positive fibers in the main olfactory bulb. The anterior olfactory nucleus, anterior piriform cortex and olfactory tubercle were negative for UEA-I. Most receptor cells in the vomeronasal epithelium and most glomeruli of the accessory olfactory bulb were positive for UEA-I. Our findings indicated that α1-2Fuc glycan is located within the primary and secondary, but not the ternary, pathways of the main olfactory system, in local circuits of the main olfactory bulb and within the primary, but not secondary, pathway of the vomeronasal system. © 2016 S. Karger AG, Basel.

Cerebellar microfolia and other abnormalities of neuronal growth, migration, and lamination in the Pit1dw-J homozygote mutant mouse

NASA Technical Reports Server (NTRS)

Sekiguchi, M.; Abe, H.; Moriya, M.; Tanaka, O.; Nowakowski, R. S.

1998-01-01

The Snell dwarf mouse (Pit1dw-J homozygote) has a mutation in the Pit1 gene that prevents the normal formation of the anterior pituitary. In neonates and adults there is almost complete absence of growth hormone (GH), prolactin (PRL), thyroxin (T4), and thyroid-stimulating hormone (TSH). Since these hormones have been suggested to play a role in normal development of the central nervous system (CNS), we have investigated the effects of the Pit1dw-J mutation on the cerebellum and hippocampal formation. In the cerebellum, there were abnormalities of both foliation and lamination. The major foliation anomalies were 1) changes in the relative size of specific folia and also the proportional sizes of the anterior vs posterior cerebellum; and 2) the presence of between one and three microfolia per half cerebellum. The microfolia were all in the medial portion of the hemisphere in the caudal part of the cerebellum. Each microfolium was just rostral to a normal fissure and interposed between the fissure and a normal gyrus. Lamination abnormalities included an increase in the number of single ectopic granule cells in the molecular layer in both cerebellar vermis (86%) and hemisphere (40%) in comparison with the wild-type mouse. In the hippocampus of the Pit1dw-J homozygote mouse, the number of pyramidal cells was decreased, although the width of the pyramidal cell layer throughout areas CA1-CA3 appeared to be normal, but less densely populated than in the wild-type mouse. Moreover, the number of granule cells that form the granule cell layer was decreased from the wild-type mouse and some ectopic granule cells (occurring both as single cells and as small clusters) were observed in the innermost portion of the molecular layer. The abnormalities observed in the Pit1dw-J homozygote mouse seem to be caused by both direct and indirect effects of the deficiency of TSH (or T4), PRL, or GH rather than by a direct effect of the deletion of Pit1.

Mitigation of divertor heat flux by high-frequency ELM pacing with non-fuel pellet injection in DIII-D

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bortolon, A.; Maingi, R.; Mansfield, D. K.

Experiments have been conducted on DIII-D investigating high repetition rate injection of non-fuel pellets as a tool for pacing Edge Localized Modes (ELMs) and mitigating their transient divertor heat loads. Effective ELM pacing was obtained with injection of Li granules in different H-mode scenarios, at frequencies 3–5 times larger than the natural ELM frequency, with subsequent reduction of strike-point heat flux. However, in scenarios with high pedestal density (~6 × 10 19 m –3), the magnitude of granule triggered ELMs shows a broad distribution, in terms of stored energy loss and peak heat flux, challenging the effectiveness of ELM mitigation.more » Furthermore, transient heat-flux deposition correlated with granule injections was observed far from the strike-points. As a result, field line tracing suggest this phenomenon to be consistent with particle loss into the mid-plane far scrape-off layer, at toroidal location of the granule injection.« less

Mitigation of divertor heat flux by high-frequency ELM pacing with non-fuel pellet injection in DIII-D

DOE PAGES

Bortolon, A.; Maingi, R.; Mansfield, D. K.; ...

2017-03-23

Experiments have been conducted on DIII-D investigating high repetition rate injection of non-fuel pellets as a tool for pacing Edge Localized Modes (ELMs) and mitigating their transient divertor heat loads. Effective ELM pacing was obtained with injection of Li granules in different H-mode scenarios, at frequencies 3–5 times larger than the natural ELM frequency, with subsequent reduction of strike-point heat flux. However, in scenarios with high pedestal density (~6 × 10 19 m –3), the magnitude of granule triggered ELMs shows a broad distribution, in terms of stored energy loss and peak heat flux, challenging the effectiveness of ELM mitigation.more » Furthermore, transient heat-flux deposition correlated with granule injections was observed far from the strike-points. As a result, field line tracing suggest this phenomenon to be consistent with particle loss into the mid-plane far scrape-off layer, at toroidal location of the granule injection.« less

Modulation of dendrodendritic interactions and mitral cell excitability in the mouse accessory olfactory bulb by vaginocervical stimulation.

PubMed

Otsuka, T; Ishii, K; Osako, Y; Okutani, F; Taniguchi, M; Oka, T; Kaba, H

2001-05-01

When female mice are mated, they form a memory to the pheromonal signal of their male partner. The neural changes underlying this memory occur in the accessory olfactory bulb, depend upon vaginocervical stimulation at mating and involve changes at the reciprocal synapses between mitral and granule cells. However, the action of vaginocervical stimulation on the reciprocal interactions between mitral and granule cells remains to be elucidated. We have examined the effects of vaginocervical stimulation on paired-pulse depression of amygdala-evoked field potentials recorded in the external plexiform layer of the accessory olfactory bulb (AOB) and the single-unit activity of mitral cells antidromically stimulated from the amygdala in urethane-anaesthetized female mice. Artificial vaginocervical stimulation reduced paired-pulse depression (considered to be due to feedback inhibition of the mitral cell dendrites from the granule cells via reciprocal dendrodendritic synapses) recorded in the AOB external plexiform layer. As would be expected from this result, vaginocervical stimulation also enhanced the spontaneous activity of a proportion of the mitral cells tested. These results suggest that vaginocervical stimulation reduces dendrodendritic feedback inhibition to mitral cells and enhances their activity.

Altered expression of heat shock protein 110 family members in mouse hippocampal neurons following trimethyltin treatment in vivo and in vitro.

PubMed

Yoneyama, Masanori; Iwamoto, Naoko; Nagashima, Reiko; Sugiyama, Chie; Kawada, Koichi; Kuramoto, Nobuyuki; Shuto, Makoto; Ogita, Kiyokazu

2008-10-01

The heat shock protein (Hsp) 110 family is composed of HSP105, APG-1, and APG-2. As the response of these proteins to neuronal damage is not yet fully understood, in the present study, we assessed their expression in mouse hippocampal neurons following trimethyltin chloride (TMT) treatment in vivo and in vitro. Although each of these three Hsps had a distinct regional distribution within the hippocampus, a low level of all of them was observed in the granule cell layer of the dentate gyrus in naïve animals. TMT was effective in markedly increasing the level of these Hsps in the granule cell layer, at least 16h to 4days after the treatment. In the dentate granule cell layer on day 2 after TMT treatment, HSP105 was expressed mainly in the perikarya of NeuN-positive cells (intact neurons); whereas APG-1 and APG-2 were predominantly found in NeuN-negative cells (damaged neurons as evidenced by signs of cell shrinkage and condensation of chromatin). Assessments using primary cultures of mouse hippocampal neurons exposed to TMT revealed that whereas HSP105 was observed in intact neurons rather than in damaged neurons, APG-1 and APG-2 were detected in both damaged neurons and intact neurons. Taken together, our data suggest that APG-1 and APG-2 may play different roles from HSP105 in neurons damaged by TMT.

Hierarchical architecture of the inner layers of selected extant rhynchonelliform brachiopods.

PubMed

Gaspard, Danièle; Nouet, Julius

2016-11-01

In spite of several attempts for a best knowledge of the phylum, brachiopods remain, compared with molluscs, among those least analysed in terms of biomineralization. The lack of economic impact for extant species is probably liable for that situation. Much attention has been on the microstructure of calcite biomaterials (rhynchonelliforms and craniiforms). Here, we emphasize the sub-micrometric structure of selected examples of rhynchonelliform shells using Atomic Force Microscopy (AFM) to complement Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray (EDX) analyses. The hierarchical organization of the shell layers (secondary and/or tertiary elements) is highlighted for species non-yet observed from this point of view, and is compared to a few already mentioned in the literature. Previous analysis revealed that granules are composed of a complex aggregation of sub-units in intimate relation with an intracrystalline matrix. Their shape, size and probably early orientation depend on the species as well as age and living environments of the specimens studied. The control of the inorganic part of the composite fibrous elements is constrained by the deposition of nearly arched shape or polygonal protein membranes at the inner boundary of the primary layer, prior to the deposition of the first granules, membranes becoming proteinaceous sheathes progressively enshrining fibres. The diverse orientations of the granules in fibrous neighbours thus further increase arguments in favour of the tendency to improve the shell strength. Copyright © 2016 Elsevier Inc. All rights reserved.

Structure of the solar photosphere studied from the radiation hydrodynamics code ANTARES.

PubMed

Leitner, P; Lemmerer, B; Hanslmeier, A; Zaqarashvili, T; Veronig, A; Grimm-Strele, H; Muthsam, H J

2017-01-01

The ANTARES radiation hydrodynamics code is capable of simulating the solar granulation in detail unequaled by direct observation. We introduce a state-of-the-art numerical tool to the solar physics community and demonstrate its applicability to model the solar granulation. The code is based on the weighted essentially non-oscillatory finite volume method and by its implementation of local mesh refinement is also capable of simulating turbulent fluids. While the ANTARES code already provides promising insights into small-scale dynamical processes occurring in the quiet-Sun photosphere, it will soon be capable of modeling the latter in the scope of radiation magnetohydrodynamics. In this first preliminary study we focus on the vertical photospheric stratification by examining a 3-D model photosphere with an evolution time much larger than the dynamical timescales of the solar granulation and of particular large horizontal extent corresponding to [Formula: see text] on the solar surface to smooth out horizontal spatial inhomogeneities separately for up- and downflows. The highly resolved Cartesian grid thereby covers [Formula: see text] of the upper convection zone and the adjacent photosphere. Correlation analysis, both local and two-point, provides a suitable means to probe the photospheric structure and thereby to identify several layers of characteristic dynamics: The thermal convection zone is found to reach some ten kilometers above the solar surface, while convectively overshooting gas penetrates even higher into the low photosphere. An [Formula: see text] wide transition layer separates the convective from the oscillatory layers in the higher photosphere.

Structure of the solar photosphere studied from the radiation hydrodynamics code ANTARES

NASA Astrophysics Data System (ADS)

Leitner, P.; Lemmerer, B.; Hanslmeier, A.; Zaqarashvili, T.; Veronig, A.; Grimm-Strele, H.; Muthsam, H. J.

2017-09-01

The ANTARES radiation hydrodynamics code is capable of simulating the solar granulation in detail unequaled by direct observation. We introduce a state-of-the-art numerical tool to the solar physics community and demonstrate its applicability to model the solar granulation. The code is based on the weighted essentially non-oscillatory finite volume method and by its implementation of local mesh refinement is also capable of simulating turbulent fluids. While the ANTARES code already provides promising insights into small-scale dynamical processes occurring in the quiet-Sun photosphere, it will soon be capable of modeling the latter in the scope of radiation magnetohydrodynamics. In this first preliminary study we focus on the vertical photospheric stratification by examining a 3-D model photosphere with an evolution time much larger than the dynamical timescales of the solar granulation and of particular large horizontal extent corresponding to 25''×25'' on the solar surface to smooth out horizontal spatial inhomogeneities separately for up- and downflows. The highly resolved Cartesian grid thereby covers ˜4 Mm of the upper convection zone and the adjacent photosphere. Correlation analysis, both local and two-point, provides a suitable means to probe the photospheric structure and thereby to identify several layers of characteristic dynamics: The thermal convection zone is found to reach some ten kilometers above the solar surface, while convectively overshooting gas penetrates even higher into the low photosphere. An ≈145 km wide transition layer separates the convective from the oscillatory layers in the higher photosphere.

Morphometric studies of heavy ion damage in the brains of rodents

NASA Astrophysics Data System (ADS)

Kraft, L. M.; Cox, A. B.

As an approach to determining the relative biological effectiveness (RBE) of each of five different heavy ions for the mammalian brain, histological preparations of brains from mice exposed to various HZE particles at different doses and primary LET∞ values were examined by means of semi-automated image analysis for volume changes in specific regions of the olfactory bulb. The mice were irradiated at 100 days of age and euthanatized about 500 days (16 months) later. Exposures were: 60Co gamma photons (LET∞ = 1-2 keV/μm), 4He (LET∞ = 6 keV/μm, 12C (LET∞ = 80 keV/μm), 20Ne (LET∞ = 150 keV/μm, 56Fe (LET∞ = 180 keV/μm, and 40Ar (LET∞ = 650 keV/μm). Animals receiving particle radiation were exposed in an extended Bragg peak region except for iron where the plateau region was used. The zones measured in the olfactory bulb were 1) the external plexiform layer (zone) and 2) an internal region consisting of the granule cells, internal plexiform layer, and layer of mitral cells. These studies indicated that volume changes did indeed occur, not only in absolute terms but alos when expressed as the ratio of the structures to each other and to the bulb as a whole. Although this study is exploratory in character, the data obtained may nevertheless contribute to a determination of risk factors due to late effects from HZE particles.

Slow fusion pore expansion creates a unique reaction chamber for co-packaged cargo

PubMed Central

Bittner, Mary A.; Lawrence, Daniel A.

2017-01-01

A lumenal secretory granule protein, tissue plasminogen activator (tPA), greatly slows fusion pore dilation and thereby slows its own discharge. We investigated another outcome of the long-lived narrow fusion pore: the creation of a nanoscale chemical reaction chamber for granule contents in which the pH is suddenly neutralized upon fusion. Bovine adrenal chromaffin cells endogenously express both tPA and its primary protein inhibitor, plasminogen activator inhibitor 1 (PAI). We found by immunocytochemistry that tPA and PAI are co-packaged in the same secretory granule. It is known that PAI irreversibly and covalently inactivates tPA at neutral pH. We demonstrate with zymography that the acidic granule lumen protects tPA from inactivation by PAI. Immunocytochemistry, total internal reflection fluorescence (TIRF) microscopy, and polarized TIRF microscopy demonstrated that co-packaged PAI and tPA remain together in granules for many seconds in the nanoscale reaction chamber, more than enough time to inhibit tPA and create a new secreted protein species. PMID:28882880

Numerical study of a stochastic particle algorithm solving a multidimensional population balance model for high shear granulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Braumann, Andreas; Kraft, Markus, E-mail: mk306@cam.ac.u; Wagner, Wolfgang

2010-10-01

This paper is concerned with computational aspects of a multidimensional population balance model of a wet granulation process. Wet granulation is a manufacturing method to form composite particles, granules, from small particles and binders. A detailed numerical study of a stochastic particle algorithm for the solution of a five-dimensional population balance model for wet granulation is presented. Each particle consists of two types of solids (containing pores) and of external and internal liquid (located in the pores). Several transformations of particles are considered, including coalescence, compaction and breakage. A convergence study is performed with respect to the parameter that determinesmore » the number of numerical particles. Averaged properties of the system are computed. In addition, the ensemble is subdivided into practically relevant size classes and analysed with respect to the amount of mass and the particle porosity in each class. These results illustrate the importance of the multidimensional approach. Finally, the kinetic equation corresponding to the stochastic model is discussed.« less

Structure of a bimetallic strip produced by plasma spraying of a TiAl powder on a niobium sheet

NASA Astrophysics Data System (ADS)

Povarova, K. B.; Antonova, A. V.; Burmistrov, V. I.; Safronov, B. V.; Perfilov, L. S.; Chukanov, A. P.

2007-10-01

Ti-48 at % Al alloy granules produced by centrifugal spraying are milled into a powder with a particle size of 40 100 μm, and are applied onto a niobium foil using plasma spraying in an argon atmosphere. The fabricated TiAl/Nb bimetallic strip consists of a 100-μm-thick niobium layer and a porous 300-to 400-μm-thick TiAl layer formed by flattened particles. Directly after the preparation of the bimetallic strip, the surface of the TiAl porous layer is rough. Vacuum annealing at 1000, 1100, and 1200°C for 0.5 1.5 h leads to intense pore healing. After deposition and annealing, the interlayer adhesion is strong. The preparation of TiAl granules and spraying of the powder is accompanied by aluminum depletion of the Ti-48 at % Al alloy to 42 45 at % and an increase in the fraction of the α2-Ti3Al phase in the deposited layer. The prepared material has a duplex structure. An intermediate diffuse layer characterized by a variable composition and thickness is formed at the interface. This layer consists of two solid solutions; one of them, which is formed at the TiAl layer, is an α2-Ti3Al-based solid solution of niobium and the other, which is formed at the niobium foil, is a niobium-based solid solution of titanium and aluminum.

Dendrodendritic Synapses in the Mouse Olfactory Bulb External Plexiform Layer

PubMed Central

Bartel, Dianna L.; Rela, Lorena; Hsieh, Lawrence; Greer, Charles A.

2014-01-01

Odor information relayed by olfactory bulb projection neurons, mitral and tufted cells (M/T), is modulated by pairs of reciprocal dendrodendritic synaptic circuits in the external plexiform layer (EPL). Interneurons, which are accounted for largely by granule cells, receive depolarizing input from M/T dendrites and in turn inhibit current spread in M/T dendrites via hyperpolarizing reciprocal dendrodendritic synapses. Because the location of dendrodendritic synapses may significantly affect the cascade of odor information, we assessed synaptic properties and density within sublaminae of the EPL and along the length of M/T secondary dendrites. In electron micrographs the M/T to granule cell synapse appeared to predominate and were equivalent in both the outer and inner EPL. However, the dendrodendritic synapses from granule cell spines onto M/T dendrites, were more prevalent in the outer EPL. In contrast, individual gephyrin-IR puncta, a postsynaptic scaffolding protein at inhibitory synapses used here as a proxy for the granule to M/T dendritic synapse was equally distributed throughout the EPL. Of significance to the organization of intrabulbar circuits, gephyrin-IR synapses are not uniformly distributed along M/T secondary dendrites. Synaptic density, expressed as a function of surface area, increases distal to the cell body. Furthermore, the distributions of gephyrin-IR puncta are heterogeneous and appear as clusters along the length of the M/T dendrites. Consistent with computational models, our data suggest that temporal coding in M/T cells is achieved by precisely located inhibitory input and that distance from the soma is compensated with an increase in synaptic density. PMID:25420934

Two new species of Eimeria Schneider, 1875 (Apicomplexa: Eimeriidae) from emerald tree skinks, Lamprolepis smaragdina (Lesson) (Sauria: Scincidae) from Papua New Guinea and the Philippines.

PubMed

McAllister, Chris T; Seville, R Scott; Duszynski, Donald W; Bush, Sarah E; Fisher, Robert N; Austin, Christopher C

2013-10-01

Two new species of Eimeria Schneider, 1875, from emerald tree skinks, Lamprolepis smaragdina (Lesson) are described from specimens collected in Papua New Guinea (PNG) and the Philippines. Oöcysts of Eimeria nuiailan n. sp. from the only L. smaragdina from PNG are ovoidal, with a smooth, colourless, bi-layered wall, measure 23.7 × 19.1 μm, and have a length/width (L/W) ratio of 1.3; both micropyle and oöcyst residuum are absent, but a fragmented polar granule is present. Sporocysts are ovoidal to ellipsoidal, 11.9 × 7.0 μm, L/W 1.7, and the wall is composed of two valves joined by a longitudinal suture; neither Stieda nor sub-Stieda bodies are present; a sporocyst residuum is present as a compact mass of granules. Sporozoites are elongate, 14.6 × 2.6 μm, and contain anterior and posterior refractile bodies with a nucleus between them. Oöcysts of Eimeria auffenbergi n. sp. from L. smaragdina collected in the Philippines are ovoidal, with a smooth, colourless, bi-layered wall, measure 19.9 × 15.8 μm, L/W 1.3; both micropyle and oöcyst residuum are absent, but one to four polar granules are present. Sporocysts are ovoidal to ellipsoidal, 10.3 × 5.8 μm, L/W 1.8, and the wall is composed of two valves joined by a longitudinal suture; neither Stieda nor sub-Stieda bodies are present; a sporocyst residuum is composed of dispersed granules.

Two new species of Eimeria Schneider, 1875 (Apicomplexa: Eimeriidae) from emerald tree skinks, Lamprolepis smaragdina (Lesson) (Sauria: Scincidae) from Papua New Guinea and the Philippines

USGS Publications Warehouse

McAllister, Chris T.; Seville, R. Scott; Duszynski, Donald W.; Bush, Sarah E.; Fisher, Robert N.; Austin, Christopher C.

2013-01-01

Two new species of Eimeria Schneider, 1875, from emerald tree skinks, Lamprolepis smaragdina (Lesson) are described from specimens collected in Papua New Guinea (PNG) and the Philippines. Oöcysts of Eimeria nuiailan n. sp. from the only L. smaragdina from PNG are ovoidal, with a smooth, colourless, bi-layered wall, measure 23.7 × 19.1 μm, and have a length/width (L/W) ratio of 1.3; both micropyle and oöcyst residuum are absent, but a fragmented polar granule is present. Sporocysts are ovoidal to ellipsoidal, 11.9 × 7.0 μm, L/W 1.7, and the wall is composed of two valves joined by a longitudinal suture; neither Stieda nor sub-Stieda bodies are present; a sporocyst residuum is present as a compact mass of granules. Sporozoites are elongate, 14.6 × 2.6 μm, and contain anterior and posterior refractile bodies with a nucleus between them. Oöcysts of Eimeria auffenbergi n. sp. from L. smaragdina collected in the Philippines are ovoidal, with a smooth, colourless, bi-layered wall, measure 19.9 × 15.8 μm, L/W 1.3; both micropyle and oöcyst residuum are absent, but one to four polar granules are present. Sporocysts are ovoidal to ellipsoidal, 10.3 × 5.8 μm, L/W 1.8, and the wall is composed of two valves joined by a longitudinal suture; neither Stieda nor sub-Stieda bodies are present; a sporocyst residuum is composed of dispersed granules.

Dynamic superconcentration at critical-point double-layer gates of conducting nanoporous granules due to asymmetric tangential fluxes

PubMed Central

Wang, Shau-Chun; Wei, Hsien-Hung; Chen, Hsiao-Ping; Tsai, Min-Hsuan; Yu, Chun-Ching; Chang, Hsueh-Chia

2008-01-01

A transient 106-fold concentration of double-layer counterions by a high-intensity electric field is demonstrated at the exit pole of a millimeter-sized conducting nanoporous granule that permits ion permeation. The phenomenon is attributed to a unique counterion screening dynamics that transforms half of the surface field into a converging one toward the ejecting pole. The resulting surface conduction flux then funnels a large upstream electro-osmotic convective counterion flux into the injecting hemisphere toward the zero-dimensional gate of the ejecting hemisphere to produce the superconcentration. As the concentrated counterion is ejected into the electroneutral bulk electrolyte, it attracts co-ions and produce a corresponding concentration of the co-ions. This mechanism is also shown to trap and concentrate co-ion microcolloids of micron sizes too (macroions) and hence has potential application in bead-based molecular assays. PMID:19693364

Discovery of Transcription Factors Novel to Mouse Cerebellar Granule Cell Development Through Laser-Capture Microdissection.

PubMed

Zhang, Peter G Y; Yeung, Joanna; Gupta, Ishita; Ramirez, Miguel; Ha, Thomas; Swanson, Douglas J; Nagao-Sato, Sayaka; Itoh, Masayoshi; Kawaji, Hideya; Lassmann, Timo; Daub, Carsten O; Arner, Erik; de Hoon, Michiel; Carninci, Piero; Forrest, Alistair R R; Hayashizaki, Yoshihide; Goldowitz, Dan

2018-06-01

Laser-capture microdissection was used to isolate external germinal layer tissue from three developmental periods of mouse cerebellar development: embryonic days 13, 15, and 18. The cerebellar granule cell-enriched mRNA library was generated with next-generation sequencing using the Helicos technology. Our objective was to discover transcriptional regulators that could be important for the development of cerebellar granule cells-the most numerous neuron in the central nervous system. Through differential expression analysis, we have identified 82 differentially expressed transcription factors (TFs) from a total of 1311 differentially expressed genes. In addition, with TF-binding sequence analysis, we have identified 46 TF candidates that could be key regulators responsible for the variation in the granule cell transcriptome between developmental stages. Altogether, we identified 125 potential TFs (82 from differential expression analysis, 46 from motif analysis with 3 overlaps in the two sets). From this gene set, 37 TFs are considered novel due to the lack of previous knowledge about their roles in cerebellar development. The results from transcriptome-wide analyses were validated with existing online databases, qRT-PCR, and in situ hybridization. This study provides an initial insight into the TFs of cerebellar granule cells that might be important for development and provide valuable information for further functional studies on these transcriptional regulators.

Polyhydroxyalkanoate-associated phasins as phylogenetically heterogeneous, multipurpose proteins.

PubMed

Maestro, Beatriz; Sanz, Jesús M

2017-11-01

Polyhydroxyalkanoates (PHAs) are natural polyesters of increasing biotechnological importance that are synthesized by many prokaryotic organisms as carbon and energy storage compounds in limiting growth conditions. PHAs accumulate intracellularly in form of inclusion bodies that are covered with a proteinaceous surface layer (granule-associated proteins or GAPs) conforming a network-like surface of structural, metabolic and regulatory polypeptides, and configuring the PHA granules as complex and well-organized subcellular structures that have been designated as 'carbonosomes'. GAPs include several enzymes related to PHA metabolism (synthases, depolymerases and hydroxylases) together with the so-called phasins, an heterogeneous group of small-size proteins that cover most of the PHA granule and that are devoid of catalytic functions but nevertheless play an essential role in granule structure and PHA metabolism. Structurally, phasins are amphiphilic proteins that shield the hydrophobic polymer from the cytoplasm. Here, we summarize the characteristics of the different phasins identified so far from PHA producer organisms and highlight the diverse opportunities that they offer in the Biotechnology field. © 2017 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Anaerobic granule-based biofilms formation reduces propionate accumulation under high H2 partial pressure using conductive carbon felt particles.

PubMed

Xu, Heng; Wang, Cuiping; Yan, Kun; Wu, Jing; Zuo, Jiane; Wang, Kaijun

2016-09-01

Syngas based co-digestion is not only more economically attractive than separate syngas methanation but also able to upgrade biogas and increase overall CH4 amount simultaneously. However, high H2 concentration in the syngas could inhibit syntrophic degradation of propionate, resulting in propionate accumulation and even failure of the co-digestion system. In an attempt to reduce propionate accumulation via enhancing both H2 interspecies transfer (HIT) and direct interspecies electron transfer (DIET) pathways, layered granule-based biofilms induced by conductive carbon felt particles (CCFP) was employed. The results showed that propionate accumulation was effectively reduced with influent COD load up to 7gL(-1)d(-1). Two types of granule-based biofilms, namely biofilm adhered to CCFP (B-CCFP) and granules formed by self-immobilization (B-SI) were formed in the reactor. Clostridium, Syntrophobacter, Methanospirillum were possibly involved in HIT and Clostridium, Geobacter, Anaerolineaceae, Methanosaeta in DIET, both of which might be responsible for the high-rate propionate degradation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Roll Compaction/Dry Granulation of Dibasic Calcium Phosphate Anhydrous-Does the Morphology of the Raw Material Influence the Tabletability of Dry Granules?

PubMed

Grote, Simon; Kleinebudde, Peter

2018-04-01

The influence of raw material particle morphology on the tabletabilty of dry granules was investigated. Therefore, dibasic calcium phosphate anhydrous was used as a model material. One milled grade, 2 agglomerated grades with different porosities, and a functionalized structure, that is, an agglomerate formed by very small primary particles, were included. Particle size, density, and specific surface area of raw materials were measured. The starting materials and 2 fractions of dry granules were compressed to tablets. The tabletability of granules was compared to that of the powders and the influence of specific compaction force, granule size, and lubrication on tablet tensile strength was evaluated. All materials showed a loss in tabletability induced by a previous compaction step but to a varying extent. Only in case of the functionalized calcium phosphate morphology, this effect depended on the specific compaction force. In contrast to the other materials, the tabletability of functionalized calcium phosphate was influenced by the granule size. This effect was not related to an overlubrication as internal and external lubrication resulted in similar tensile strengths. A clear influence of the particle morphology on tablet strength was demonstrated by the study. The functionalized structure showed aspects of a more plastic deformation behavior. The functionalized dibasic calcium phosphate and the more porous agglomerate performed as potential filler/binder in the field of roll compaction/dry granulation. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Clean recycle and utilization of hazardous iron-bearing waste in iron ore sintering process.

PubMed

Gan, Min; Ji, Zhiyun; Fan, Xiaohui; Chen, Xuling; Zhou, Yang; Wang, Guojing; Tian, Ye; Jiang, Tao

2018-04-18

Applying recycled iron-bearing waste materials (RIM) into iron ore sintering process is the general disposal approach worldwide, while its use is still a thorny problem. Results showed that adding RIM increased contents of hazardous elements (K, Na, Pb, Zn, and Cl) in sinter product, and also enhanced emission concentration of PM 2.5 in flue gas; increasing reaction temperature, and contents of CaO & coke breeze in raw mixtures improved hazardous elements removal. Based on these features, a novel method through granulating natural iron ores and RIM separately and distributing granulated RIM in bottom sintering layers was proposed for clean RIM cycle. When recycling 5% RIM, granulating RIM separately with higher contents of CaO and coke breeze removed hazardous elements effectively, the contents of which in sinter were reduced to comparable level of the case without RIM. Moreover, distributing RIM in bottom sintering layer reached intensive release of hazardous elements and PM 2.5 during sintering, which reduced the flue gas volume needing purification by about 2/3. Through activated carbon purification, about 60% of PM 2.5 comprised high contents of hazardous elements was removed. Novel technique eliminated the negative impact of RIM and has the prospect to reach clean recycle in sinter-making plants. Copyright © 2018. Published by Elsevier B.V.

Nicotinic receptor abnormalities in the cerebellar cortex in autism.

PubMed

Lee, M; Martin-Ruiz, C; Graham, A; Court, J; Jaros, E; Perry, R; Iversen, P; Bauman, M; Perry, E

2002-07-01

Autism is a common developmental disorder associated with structural and inferred neurochemical abnormalities of the brain. Cerebellar abnormalities frequently have been identified, based on neuroimaging or neuropathology. Recently, the cholinergic neurotransmitter system has been implicated on the basis of nicotinic receptor loss in the cerebral cortex. Cerebellar cholinergic activities were therefore investigated in autopsy tissue from a series of autistic individuals. The presynaptic cholinergic enzyme, choline acetyltransferase, together with nicotinic and muscarinic receptor subtypes were compared in the cerebellum from age-matched mentally retarded autistic (eight), normal control (10) and non-autistic mentally retarded individuals (11). The nicotinic receptor binding the agonist epibatidine (the high affinity receptor subtype, consisting primarily of alpha3 and alpha4, together with beta2 receptor subunits) was significantly reduced by 40-50% in the granule cell, Purkinje and molecular layers in the autistic compared with the normal group (P < 0.05). There was an opposite increase (3-fold) in the nicotinic receptor binding alpha-bungarotoxin (to the alpha7 subunit) which reached significance in the granule cell layer (P < 0.05). These receptor changes were paralleled by a significant reduction (P < 0.05) and non-significant increase, respectively, of alpha4 and alpha7 receptor subunit immunoreactivity measured using western blotting. Immunohistochemically loss of alpha(4 )reactivity was apparent from Purkinje and the other cell layers, with increased alpha7 reactivity in the granule cell layer. There were no significant changes in choline acetyltransferase activity, or in muscarinic M1 and M2 receptor subtypes in autism. In the non-autistic mentally retarded group, the only significant abnormality was a reduction in epibatidine binding in the granule cell and Purkinje layers. In two autistic cases examined histologically, Purkinje cell loss was observed in multiple lobules throughout the vermis and hemispheres. This was more severe in one case with epilepsy, which also showed vermis folial malformation. The case with less severe Purkinje cell loss also showed cerebellar white matter thinning and demyelination. These findings indicate a loss of the cerebellar nicotinic alpha4 receptor subunit in autism which may relate to the loss of Purkinje cells, and a compensatory increase in the alpha7 subunit. It remains to be determined how these receptor abnormalities are involved in neurodevelopment in autism and what is the relationship to mental function. Since nicotinic receptor agonists enhance attentional function and also induce an elevation in the high affinity receptor, nicotinic therapy in autism may be worth considering.

Chromospheric impact of an exploding solar granule

NASA Astrophysics Data System (ADS)

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

2017-06-01

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

Thermal insulation for high temperature microwave sintering operations and method thereof

DOEpatents

Holcombe, Cressie E.; Dykes, Norman L.; Morrow, Marvin S.

1995-01-01

Superior microwave transparent thermal insulations for high temperature microwave sintering operations were prepared. One embodiment of the thermal insulation comprises granules of boron nitride coated with a very thin layer of glassy carbon made by preparing a glassy carbon precursor and blending it with boron nitride powder to form a mixture. The blended mixture is granulated to form a grit which is dried and heated to form the granules of boron nitride coated with a glassy carbon. Alternatively, grains of glassy carbon are coated with boron nitride by blending a mixture of a slurry comprising boron nitride, boric acid binder, and methyl alcohol with glassy carbon grains to form a blended mixture. The blended mixture is dried to form grains of glassy carbon coated with boron nitride. In addition, a physical mixture of boron nitride powder and glassy carbon grains has also been shown to be an excellent thermal insulation material for microwave processing and sintering.

Method of preparing thermal insulation for high temperature microwave sintering operations

DOEpatents

Holcombe, Cressie E.; Dykes, Norman L.; Morrow, Marvin S.

1996-01-01

Superior microwave transparent thermal insulations for high temperature microwave sintering operations were prepared. One embodiment of the thermal insulation comprises granules of boron nitride coated with a very thin layer of glassy carbon made by preparing a glassy carbon precursor and blending it with boron nitride powder to form a mixture. The blended mixture is granulated to form a grit which is dried and heated to form the granules of boron nitride coated with a glassy carbon. Alternatively, grains of glassy carbon are coated with boron nitride by blending a mixture of a slurry comprising boron nitride, boric acid binder, and methyl alcohol with glassy carbon grains to form a blended mixture. The blended mixture is dried to form grains of glassy carbon coated with boron nitride. In addition, a physical mixture of boron nitride powder and glassy carbon grains has also been shown to be an excellent thermal insulation material for microwave processing and sintering.

Rodent renal structure differs among species.

PubMed

Ichii, Osamu; Yabuki, Akira; Ojima, Toshimichi; Matsumoto, Mitsuharu; Suzuki, Shusaku

2006-05-01

In the present study, we histologically and morphometrically investigated species differences in renal structure using laboratory rodents (mice, gerbils, hamsters, rats, and guinea pigs). Morphometric parameters were as follows, 1) diameter of the cortical renal corpuscles, 2) diameter of the juxtamedullary renal corpuscles, 3) percentage of the renal corpuscles with a cuboidal parietal layer, 4) number of nuclei in proximal convoluted tubules (PCTs) per unit area of cortex, 5) semi-quantitative score of the periodic acid-Schiff (PAS) -positive granules in PCTs, and 6) semi-quantitative score of the PAS-positive granules in proximal straight tubules (PSTs). Significant species differences were detected for each parameter, and particularly severe differences were observed in the PAS-positive granules of PCTs and PSTs. Granular scores varied among species and sexes. Vacuolar structures that did not stain with PAS or hematoxylin-eosin were observed in the renal proximal tubules. The appearance and localization of these vacuolar structures differed remarkably between species and sexes.

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

PubMed

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

2016-07-19

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

Proceedings of IEEE International Symposium on Information Theory Held in San Antonio, Texas on January 17 - 22, 1993

DTIC Science & Technology

1993-01-22

elementary con- index p must have memory m > i. We also show that a syndrome stituents of the state group -2k, called " granules ." The controller former...0. dual granules p-1 A syndrome map f: GZ -. GZ//C for a group code C may be Em, - ® H rli,i+j) constructed by setting f(g) gC for g E GZ, where the...syndrome ,=o i4Ejh-jl,& set S is the set GCZ//C of left cosets of C in G7 and the "identity" such that the value of a granule r1ij+j) depends only on

Ultrastructure of the embryonic snake skin and putative role of histidine in the differentiation of the shedding complex.

PubMed

Alibardi, Lorenzo

2002-02-01

The morphogenesis and ultrastructure of the epidermis of snake embryos were studied at progressive stages of development through hatching to determine the time and modality of differentiation of the shedding complex. Scales form as symmetric epidermal bumps that become slanted and eventually very overlapped. During the asymmetrization of the bumps, the basal cells of the forming outer surface of the scale become columnar, as in an epidermal placode, and accumulate glycogen. Small dermal condensations are sometimes seen and probably represent primordia of the axial dense dermis of the growing tip of scales. Deep, dense, and superficial loose dermal regions are formed when the epidermis is bilayered (periderm and basal epidermis) and undifferentiated. Glycogen and lipids decrease from basal cells to differentiating suprabasal cells. On the outer scale surface, beneath the peridermis, a layer containing dense granules and sparse 25-30-nm thick coarse filaments is formed. The underlying clear layer does not contain keratohyalin-like granules but has a rich cytoskeleton of intermediate filaments. Small denticles are formed and they interdigitate with the oberhautchen spinulae formed underneath. On the inner scale surface the clear layer contains dense granules, coarse filaments, and does not form denticles with the aspinulated oberhautchen. On the inner side surface the oberhautchen only forms occasional spinulae. The sloughing of the periderm and embryonic epidermis takes place in ovo 5-6 days before hatching. There follow beta-, mesos-, and alpha-layers, not yet mature before hatching. No resting period is present but a new generation is immediately produced so that at 6-10 h posthatching an inner generation and a new shedding complex are forming beneath the outer generation. The first shedding complex differentiates 10-11 days before hatching. In hatchlings 6-10 h old, tritiated histidine is taken up in the epidermis 4 h after injection and is found mainly in the shedding complex, especially in the apposed membranes of the clear layer and oberhautchen cells. This indicates that a histidine-rich protein is produced in preparation for shedding, as previously seen in lizard epidermis. The second shedding (first posthatching) takes place at 7-9 days posthatching. It is suggested that the shedding complex in lepidosaurian reptiles has evolved after the production of a histidine-rich protein and of a beta-keratin layer beneath the former alpha-layer. Copyright 2002 Wiley-Liss, Inc.

A Reorganized GABAergic Circuit in a Model of Epilepsy: Evidence from Optogenetic Labeling and Stimulation of Somatostatin Interneurons

PubMed Central

Peng, Zechun; Zhang, Nianhui; Wei, Weizheng; Huang, Christine S.; Cetina, Yliana; Otis, Thomas S.

2013-01-01

Axonal sprouting of excitatory neurons is frequently observed in temporal lobe epilepsy, but the extent to which inhibitory interneurons undergo similar axonal reorganization remains unclear. The goal of this study was to determine whether somatostatin (SOM)-expressing neurons in stratum (s.) oriens of the hippocampus exhibit axonal sprouting beyond their normal territory and innervate granule cells of the dentate gyrus in a pilocarpine model of epilepsy. To obtain selective labeling of SOM-expressing neurons in s. oriens, a Cre recombinase-dependent construct for channelrhodopsin2 fused to enhanced yellow fluorescent protein (ChR2-eYFP) was virally delivered to this region in SOM-Cre mice. In control mice, labeled axons were restricted primarily to s. lacunosum-moleculare. However, in pilocarpine-treated animals, a rich plexus of ChR2-eYFP-labeled fibers and boutons extended into the dentate molecular layer. Electron microscopy with immunogold labeling demonstrated labeled axon terminals that formed symmetric synapses on dendritic profiles in this region, consistent with innervation of granule cells. Patterned illumination of ChR2-labeled fibers in s. lacunosum-moleculare of CA1 and the dentate molecular layer elicited GABAergic inhibitory responses in dentate granule cells in pilocarpine-treated mice but not in controls. Similar optical stimulation in the dentate hilus evoked no significant responses in granule cells of either group of mice. These findings indicate that under pathological conditions, SOM/GABAergic neurons can undergo substantial axonal reorganization beyond their normal territory and establish aberrant synaptic connections. Such reorganized circuitry could contribute to functional deficits in inhibition in epilepsy, despite the presence of numerous GABAergic terminals in the region. PMID:24005292

Mineral-bearing vesicle transport in sea urchin embryos.

PubMed

Vidavsky, Netta; Masic, Admir; Schertel, Andreas; Weiner, Steve; Addadi, Lia

2015-12-01

Sea urchin embryos sequester calcium from the sea water. This calcium is deposited in a concentrated form in granule bearing vesicles both in the epithelium and in mesenchymal cells. Here we use in vivo calcein labeling and confocal Raman spectroscopy, as well as cryo-FIB-SEM 3D structural reconstructions, to investigate the processes occurring in the internal cavity of the embryo, the blastocoel. We demonstrate that calcein stained granules are also present in the filopodial network within the blastocoel. Simultaneous fluorescence imaging and Raman spectroscopy show that these granules do contain a calcium mineral. By tracking the movements of these granules, we show that the granules in the epithelium and primary mesenchymal cells barely move, but those in the filopodial network move long distances. We could however not detect any unidirectional movement of the filopodial granules. We also show the presence of mineral containing multivesicular vesicles that also move in the filopodial network. We conclude that the filopodial network is an integral part of the mineral transport process, and possibly also for sequestering calcium and other ions. Although much of the sequestered calcium is deposited in the mineralized skeleton, a significant amount is used for other purposes, and this may be temporarily stored in these membrane-delineated intracellular deposits. Copyright © 2015 Elsevier Inc. All rights reserved.

Influence of dissolved oxygen concentration on the start-up of the anammox-based process: ELAN®.

PubMed

Morales, N; Val del Río, A; Vázquez-Padín, J R; Gutiérrez, R; Fernández-González, R; Icaran, P; Rogalla, F; Campos, J L; Méndez, R; Mosquera-Corral, A

2015-01-01

The anammox-based process ELAN® was started-up in two different sequencing batch reactor (SBR) pilot plant reactors treating municipal anaerobic digester supernatant. The main difference in the operation of both reactors was the dissolved oxygen (DO) concentration in the bulk liquid. SBR-1 was started at a DO value of 0.4 mg O2/L whereas SBR-2 was started at DO values of 3.0 mg O2/L. Despite both reactors working at a nitrogen removal rate of around 0.6 g N/(L d), in SBR-1, granules represented only a small fraction of the total biomass and reached a diameter of 1.1 mm after 7 months of operation, while in SBR-2 the biomass was mainly composed of granules with an average diameter of 3.2 mm after the same operational period. Oxygen microelectrode profiling revealed that granules from SBR-2 where only fully penetrated by oxygen with DO concentrations of 8 mg O2/L while granules from SBR-1 were already oxygen penetrated at DO concentrations of 1 mg O2/L. In this way granules from SBR-2 performed better due to the thick layer of ammonia oxidizing bacteria, which accounted for up to 20% of all the microbial populations, which protected the anammox bacteria from non-suitable liquid media conditions.

Cell-type-specific expression of NFIX in the developing and adult cerebellum.

PubMed

Fraser, James; Essebier, Alexandra; Gronostajski, Richard M; Boden, Mikael; Wainwright, Brandon J; Harvey, Tracey J; Piper, Michael

2017-07-01

Transcription factors from the nuclear factor one (NFI) family have been shown to play a central role in regulating neural progenitor cell differentiation within the embryonic and post-natal brain. NFIA and NFIB, for instance, promote the differentiation and functional maturation of granule neurons within the cerebellum. Mice lacking Nfix exhibit delays in the development of neuronal and glial lineages within the cerebellum, but the cell-type-specific expression of this transcription factor remains undefined. Here, we examined the expression of NFIX, together with various cell-type-specific markers, within the developing and adult cerebellum using both chromogenic immunohistochemistry and co-immunofluorescence labelling and confocal microscopy. In embryos, NFIX was expressed by progenitor cells within the rhombic lip and ventricular zone. After birth, progenitor cells within the external granule layer, as well as migrating and mature granule neurons, expressed NFIX. Within the adult cerebellum, NFIX displayed a broad expression profile, and was evident within granule cells, Bergmann glia, and interneurons, but not within Purkinje neurons. Furthermore, transcriptomic profiling of cerebellar granule neuron progenitor cells showed that multiple splice variants of Nfix are expressed within this germinal zone of the post-natal brain. Collectively, these data suggest that NFIX plays a role in regulating progenitor cell biology within the embryonic and post-natal cerebellum, as well as an ongoing role within multiple neuronal and glial populations within the adult cerebellum.

Four new species of coccidia (Apicomplexa: Eimeriidae) from Owen Stanley Skinks, Papuascincus stanleyanus (Sauria: Scincidae), from Papua New Guinea

USGS Publications Warehouse

McAllister, Chris T.; Duszynski, Donald W.; Fisher, Robert N.; Austin, Christopher C.

2014-01-01

Between September and November 1991, 12 Owen Stanley skinks, Papuascincus stanleyanus (Booulenger) were collected from various localities on Papua New Guinea and examined for coccidians. Six (50%) were found to harbour four eimerians that we describe here as new. Oocysts of Eimeria burseyi sp. n. were elongate to ellipsoidal with a bilayered wall and measured (length x width, L x W) 36.0 x 24.0 microm, with a L/W ratio of 1.5. Both micropyle and oocyst residuum were absent, but a polar granule was present. Oocysts of Eimeria goldbergi sp. n. were ellipsoidal, with a bilayered wall, and measured 21.4 x 16.1 microm; L/W ratio was 1.3. Both micropyle and oocyst residuum were absent, but a single or fragmented polar granule was present. Oocysts of Eimeria boulengeri sp. n. were spheroidal to slightly subspheroidal, with a thin, single-layered wall that readily collapses, and measured 16.0 microm, L/W ratio was 1.0. Both micropyle and oocyst residuum were absent, but usually one (sometimes two) polar granule(s) were present. Oocysts of Eimeria niuginiensis sp. n. were oblong to tapered with a bilayered wall, and measured 20.0 x 13.1 microm; L/W ratio was 1.5. A micropyle, oocyst residuum and polar granule were absent. To our knowledge, these represent the only coccidians ever described from P. stanleyanus.

Entorhinal Denervation Induces Homeostatic Synaptic Scaling of Excitatory Postsynapses of Dentate Granule Cells in Mouse Organotypic Slice Cultures

PubMed Central

Vlachos, Andreas; Becker, Denise; Jedlicka, Peter; Winkels, Raphael; Roeper, Jochen; Deller, Thomas

2012-01-01

Denervation-induced changes in excitatory synaptic strength were studied following entorhinal deafferentation of hippocampal granule cells in mature (≥3 weeks old) mouse organotypic entorhino-hippocampal slice cultures. Whole-cell patch-clamp recordings revealed an increase in excitatory synaptic strength in response to denervation during the first week after denervation. By the end of the second week synaptic strength had returned to baseline. Because these adaptations occurred in response to the loss of excitatory afferents, they appeared to be in line with a homeostatic adjustment of excitatory synaptic strength. To test whether denervation-induced changes in synaptic strength exploit similar mechanisms as homeostatic synaptic scaling following pharmacological activity blockade, we treated denervated cultures at 2 days post lesion for 2 days with tetrodotoxin. In these cultures, the effects of denervation and activity blockade were not additive, suggesting that similar mechanisms are involved. Finally, we investigated whether entorhinal denervation, which removes afferents from the distal dendrites of granule cells while leaving the associational afferents to the proximal dendrites of granule cells intact, results in a global or a local up-scaling of granule cell synapses. By using computational modeling and local electrical stimulations in Strontium (Sr2+)-containing bath solution, we found evidence for a lamina-specific increase in excitatory synaptic strength in the denervated outer molecular layer at 3–4 days post lesion. Taken together, our data show that entorhinal denervation results in homeostatic functional changes of excitatory postsynapses of denervated dentate granule cells in vitro. PMID:22403720

Surface Modification of Porous Titanium Granules for Improving Bioactivity.

PubMed

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

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

Agronomic Effectiveness of Granulated and Powdered P-Exchanged Mg-Al LDH Relative to Struvite and MAP.

PubMed

Everaert, Maarten; Degryse, Fien; McLaughlin, Mike J; De Vos, Dirk; Smolders, Erik

2017-08-16

Layered double hydroxides (LDHs) used to recover P from wastewater have recently been proposed as new slow-release fertilizers. Here, the use of P-exchanged Mg-Al LDHs as powdered or granulated fertilizer is explored and compared with monoammonium phosphate (MAP), a fully water-soluble fertilizer, and with struvite, a recycled phosphate fertilizer with lower solubility. First, these three fertilizers were compared in a 100-day incubation experiment using P diffusion visualization and chemical analysis to assess P release from either granules or powdered fertilizer in three different soils. By the end of the incubation, 74-90% of P remained within the LDH granule, confirming a slow release. Second, a pot experiment was performed with wheat (Triticum aestivum) in an acid and a calcareous soil. The granular treatment resulted in a considerably higher P uptake for MAP compared to LDH and struvite. For the powder treatments, the P uptake was less than for granular MAP and was largely unaffected by the chemical form. The LDHs and struvite showed a lower agronomic effectiveness than granular MAP, but the benefits of their use in P recycling, potential residual value, and environmental benefits may render these slow-release fertilizers attractive.

Magnetization reversal mechanism of magnetic tunnel junctions

NASA Astrophysics Data System (ADS)

Liu, Cun-Ye; Li, Jian; Wang, Yue; Chen, Jian-Yong; Xu, Qing-Yu; Ni, Gang; Sang, Hai; Du, You-Wei

2002-01-01

Using the ion-beam-sputtering technique, we have fabricated Fe/Al2O3/Fe magnetic tunnelling junctions (MTJs). We have observed double-peaked shapes of curves, which have a level summit and a symmetrical feature, showing the magnetoresistance of the junction as a function of applied field. We have measured the tunnel conductance of MTJs which have insulating layers of different thicknesses. We have studied the dependence of the magnetoresistance of MTJs on tunnel conductance. The microstructures of hard- and soft-magnetic layers and interfaces of ferromagnets and insulators were probed. Analysing the influence of MJT microstructures, including those having clusters or/and granules in magnetic and non-magnetic films, a magnetization reversal mechanism (MRM) is proposed, which suggests that the MRM of tunnelling junctions may be explained by using a group-by-group reversal model of magnetic moments of the mesoscopical particles. We discuss the influence of MTJ microstructures, including those with clusters or/and granules in the ferromagnetic and non-magnetic films, on the MRM.

Disruption of the midkine gene (Mdk) resulted in altered expression of a calcium binding protein in the hippocampus of infant mice and their abnormal behaviour.

PubMed

Nakamura, E; Kadomatsu, K; Yuasa, S; Muramatsu, H; Mamiya, T; Nabeshima, T; Fan, Q W; Ishiguro, K; Igakura, T; Matsubara, S; Kaname, T; Horiba, M; Saito, H; Muramatsu, T

1998-12-01

Midkine (MK) is a growth factor implicated in the development and repair of various tissues, especially neural tissues. However, its in vivo function has not been clarified. Knockout mice lacking the MK gene (Mdk) showed no gross abnormalities. We closely analysed postnatal brain development in Mdk(-/-) mice using calcium binding proteins as markers to distinguish neuronal subpopulations. Intense and prolonged calretinin expression was found in the dentate gyrus granule cell layer of the hippocampus of infant Mdk(-/-) mice. In infant Mdk(+/+) mice, calretinin expression in the granule cell layer was weaker, and had disappeared by 4 weeks after birth, when calretinin expression still persisted in Mdk(-/-) mice. Furthermore, 4 weeks after birth, Mdk(-/-) mice showed a deficit in their working memory, as revealed by a Y-maze test, and had an increased anxiety, as demonstrated by the elevated plus-maze test. Midkine plays an important role in the regulation of postnatal development of the hippocampus.

Mitotic events in cerebellar granule progenitor cells that expand cerebellar surface area are critical for normal cerebellar cortical lamination in mice.

PubMed

Chang, Joshua C; Leung, Mark; Gokozan, Hamza Numan; Gygli, Patrick Edwin; Catacutan, Fay Patsy; Czeisler, Catherine; Otero, José Javier

2015-03-01

Late embryonic and postnatal cerebellar folial surface area expansion promotes cerebellar cortical cytoarchitectural lamination. We developed a streamlined sampling scheme to generate unbiased estimates of murine cerebellar surface area and volume using stereologic principles. We demonstrate that, during the proliferative phase of the external granular layer (EGL) and folial surface area expansion, EGL thickness does not change and thus is a topological proxy for progenitor self-renewal. The topological constraints indicate that, during proliferative phases, migration out of the EGL is balanced by self-renewal. Progenitor self-renewal must, therefore, include mitotic events yielding 2 cells in the same layer to increase surface area (β events) and mitotic events yielding 2 cells, with 1 cell in a superficial layer and 1 cell in a deeper layer (α events). As the cerebellum grows, therefore, β events lie upstream of α events. Using a mathematical model constrained by the measurements of volume and surface area, we could quantify intermitotic times for β events on a per-cell basis in postnatal mouse cerebellum. Furthermore, we found that loss of CCNA2, which decreases EGL proliferation and secondarily induces cerebellar cortical dyslamination, shows preserved α-type events. Thus, CCNA2-null cerebellar granule progenitor cells are capable of self-renewal of the EGL stem cell niche; this is concordant with prior findings of extensive apoptosis in CCNA2-null mice. Similar methodologies may provide another layer of depth to the interpretation of results from stereologic studies.

Kinetics and mass-transfer phenomena in anaerobic granular sludge.

PubMed

Gonzalez-Gil, G; Seghezzo, L; Lettinga, G; Kleerebezem, R

2001-04-20

The kinetic properties of acetate-degrading methanogenic granular sludge of different mean diameters were assessed at different up-flow velocities (V(up)). Using this approach, the influence of internal and external mass transfer could be estimated. First, the apparent Monod constant (K(S)) for each data set was calculated by means of a curve-fitting procedure. The experimental results revealed that variations in the V(up) did not affect the apparent K(S)-value, indicating that external mass-transport resistance normally can be neglected. With regard to the granule size, a clear increase in K(S) was found at increasing granule diameters. The experimental data were further used to validate a dynamic mathematical biofilm model. The biofilm model was able to describe reaction-diffusion kinetics in anaerobic granules, using a single value for the effective diffusion coefficient in the granules. This suggests that biogas formation did not influence the diffusion-rates in the granular biomass. Copyright 2001 John Wiley & Sons, Inc.

Surface histology, topography, and ultrastructure of the tegument of adult Orthocoelium parvipapillatum (Stiles & Goldberger, 1910).

PubMed

Anuracpreeda, Panat; Chawengkirttikul, Runglawan; Sobhon, Prasert

2016-07-01

Adult Orthocoelium parvipapillatum are common parasites that reside in the rumen and reticulum of ruminants, i.e., cattle, sheep, goats, and buffaloes. The fluke is conical-shaped and slightly concave ventrally and convex dorsally, and measures bout 2.4-3.9 mm in length and 1.0-2.3 mm in width across the mid-section. The tegument of the adult worm is examined using light microscopy (LM) and scanning (SEM) and transmission electron microscopy (TEM). Under LM, the tegument appears as a thick homogeneous layer containing folds alternated with grooves without spines. SEM revealed that the tegumental surface is highly corrugated with ridges and furrows and appears spineless. Two types of sensory papillae are observed, i.e., type 1 is bulbous in shape with nipple-like tips and type 2 has a similar shape with short cilia. In TEM, the tegument has a typical syncytial organization and is divided into four layers. The first layer of the tegument contains ridges and furrows covered by a trilaminate membrane coated externally with the glycocalyx. The second layer is a strait area of cytoplasm that includes numerous ovoid electron-lucent (TG1) and disc-shaped electron-dense (TG2) tegumental granules and lysosomes. The third layer is the widest middle area which contains several evenly distributed mitochondria, TG1 and TG2. The fourth layer rests on a thick basal lamina and contains numerous infoldings of the basal plasma membrane with closely associated mitochondria. Both granules are produced and transported to the tegument by one type of tegumental cells lying in rows below the muscular layers.

Evaluation of bovine (Bos indicus) ovarian potential for in vitro embryo production in the Adamawa plateau (Cameroon)

PubMed Central

Kouamo, J.; Dawaye, S.M.; Zoli, A.P.; Bah, G.S.

2014-01-01

An abattoir study was conducted to evaluate the ovarian potential of 201 local zebu cattle from Ngaoundere, Adamawa region (Cameroon) for in vitro embryo production (IVEP). The ovaries were excised, submerged in normal saline solution (0.9%) and transported to the laboratory for a detailed evaluation. Follicles on each ovary were counted, their diameters (Φ) measured and were grouped into 3 categories: small (Φ < 3 mm), medium (3 ≥ Φ ≤ 8 mm) and large (Φ > 8 mm). Each ovary was then sliced into a petri dish; the oocytes were recovered in Dulbecco’s phosphate buffered saline, examined under a stereoscope (x10) and graded into four groups based on the morphology of cumulus oophorus cells and cytoplasmic changes of the oocytes. Grade I (GI): oocytes with more than 4 layers of bunch of compact cumulus cells mass with evenly granulated cytoplasm; grade II (GII): oocyte with at least 2-4 layers of compact cumulus cell mass with evenly granulated cytoplasm; grade III (GIII): oocyte with at least one layer of compact cumulus cell mass with evenly granulated cytoplasm; grade IV (GIV): denuded oocyte with no cumulus cells or incomplete layer of cumulus cell or expanded cells and having dark or unevenly granulated cytoplasm. The effects of both ovarian (ovarian localization, corpus luteum, size and weight of ovary) and non-ovarian factors (breed, age, body condition score (BCS) and pregnancy status of cow) on the follicular population and oocyte recovery rate were determined. There were an average of 16.75±0.83 follicles per ovary. The small, medium and large follicles were 8.39±0.60, 8.14±0.43 and 0.21±0.02 respectively. Oocyte recovery was 10.97±0.43 per ovary (65%). Oocytes graded I, II, III and IV were 3.53±0.19 (32.21%), 2.72±0.15 (24.82%), 2.24±0.15 (20.43%) and 2.47±0.20 (22.54%) respectively. The oocyte quality index was 2.26. Younger non pregnant cows having BCS of 3 and large ovaries presented higher number of follicles and oocyte quality (P < 0.05) compared with other animals. Oocytes with quality (grade I and II) acceptable for IVEP constituted 57.15% of the harvest. This study indicated that factors such as age, pregnancy status, BCS and ovarian size must be taken into account to increase the potential of the ovary for IVEP. PMID:26623353

Fabrication and physicochemical characterization of porous composite microgranules with selenium oxyanions and risedronate sodium for potential applications in bone tumors.

PubMed

Kolmas, Joanna; Pajor, Kamil; Pajchel, Lukasz; Przekora, Agata; Ginalska, Grażyna; Oledzka, Ewa; Sobczak, Marcin

2017-01-01

Nanocrystalline hydroxyapatite containing selenite ions (SeHA; 9.6 wt.% of selenium) was synthesized using wet method and subject to careful physicochemical analysis by powder X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, solid-state nuclear magnetic resonance, wavelength dispersive X-ray fluorescence, and inductively coupled plasma optical emission spectrometry. SeHA was then used to develop the selenium-containing hydroxyapatite/alginate (SeHA/ALG) composite granules. Risedronate sodium (RIS) was introduced to the obtained spherical microgranules of a size of about 1.1-1.5 mm in 2 ways: during the granules' preparation (RIS solution added to a suspension of ALG and SeHA), and as a result of SeHA/ALG granules soaking in aqueous RIS solution. The analysis made using 13 C and 31 P cross-polarization magic angle spinning nuclear magnetic resonance confirmed the presence of RIS and its interaction with calcium ions. Then, the release of selenium (inductively coupled plasma optical emission spectrometry) and RIS (high-performance liquid chromatography) from microgranules was examined. Moreover, cytotoxicity of fabricated granules was assessed by MTT test. Selenium release was biphasic: the first stage was short and ascribed to a "burst release" probably from a hydrated surface layer of SeHA crystals, while the next stage was significantly longer and ascribed to a sustained release of selenium from the crystals' interior. The study showed that the method of obtaining microgranules containing RIS significantly affects its release profile. Performed cytotoxicity test revealed that fabricated granules had high antitumor activity against osteosarcoma cells. However, because of the "burst release" of selenium during the first 10 h, the granules significantly reduced viability of normal osteoblasts as well.

Latent structure analysis in the pharmaceutical process of tablets prepared by wet granulation.

PubMed

Uehara, Naoto; Hayashi, Yoshihiro; Mochida, Hiroshi; Otoguro, Saori; Onuki, Yoshinori; Obata, Yasuko; Takayama, Kozo

2016-01-01

Granule characteristics are some of the important intermediate qualities that determine tablet properties. However, the relationships between granule and tablet characteristics are poorly understood. The aim of this study was to elucidate relationships among formulation factors, granule characteristics, and tablet properties using a non-linear response surface method (RSM) incorporating a thin-plate spline interpolation (RSM-S) and a Bayesian network (BN). Tablets containing lactose (Lac), cornstarch (CS), and microcrystalline cellulose (MCC) were prepared by wet granulation. Ten formulations were prepared by an extreme vertices design. The angle of repose (Y 1 ), compressibility (Y 2 ), cohesion force (Y 3 ), internal friction angle (Y 4 ), and mean particle size (Y 5 ) were measured as granule characteristics. Tensile strength (TS) and disintegration time (DT) were measured as tablet properties. RSM-S results showed that TS increased with increasing amounts of MCC and Lac. DT decreased with increasing amounts of MCC and CS. The optimal BN models were predicted using four evaluation indices -Y 3 was shown to be the most important factor for TS, whereas Y 2 , Y 3 , and Y 4 were relatively important for predicting DT. Moreover, tablets with excellent tablet properties (i.e. high TS and low DT) were produced by relatively high Y 1 , low Y 2 , high Y 3 , high Y 4 , and middle Y 5 values, and resulted from the middle of MCC, middle-to-low CS, low Lac, and middle-to-low magnesium stearate (Mg-St) amounts. The RSM-S and BN techniques are useful for revealing complex relationships among formulation factors, granule characteristics, and tablet properties.

Method of preparing thermal insulation for high temperature microwave sintering operations

DOEpatents

Holcombe, C.E.; Dykes, N.L.; Morrow, M.S.

1996-07-16

Superior microwave transparent thermal insulations for high temperature microwave sintering operations were prepared. One embodiment of the thermal insulation comprises granules of boron nitride coated with a very thin layer of glassy carbon made by preparing a glassy carbon precursor and blending it with boron nitride powder to form a mixture. The blended mixture is granulated to form a grit which is dried and heated to form the granules of boron nitride coated with a glassy carbon. Alternatively, grains of glassy carbon are coated with boron nitride by blending a mixture of a slurry comprising boron nitride, boric acid binder, and methyl alcohol with glassy carbon grains to form a blended mixture. The blended mixture is dried to form grains of glassy carbon coated with boron nitride. In addition, a physical mixture of boron nitride powder and glassy carbon grains has also been shown to be an excellent thermal insulation material for microwave processing and sintering. 1 fig.

Thermal insulation for high temperature microwave sintering operations and method thereof

DOEpatents

Holcombe, C.E.; Dykes, N.L.; Morrow, M.S.

1995-09-12

Superior microwave transparent thermal insulations for high temperature microwave sintering operations were prepared. One embodiment of the thermal insulation comprises granules of boron nitride coated with a very thin layer of glassy carbon made by preparing a glassy carbon precursor and blending it with boron nitride powder to form a mixture. The blended mixture is granulated to form a grit which is dried and heated to form the granules of boron nitride coated with a glassy carbon. Alternatively, grains of glassy carbon are coated with boron nitride by blending a mixture of a slurry comprising boron nitride, boric acid binder, and methyl alcohol with glassy carbon grains to form a blended mixture. The blended mixture is dried to form grains of glassy carbon coated with boron nitride. In addition, a physical mixture of boron nitride powder and glassy carbon grains has also been shown to be an excellent thermal insulation material for microwave processing and sintering. 1 fig.

Integration of aerobic granular sludge and mesh filter membrane bioreactor for cost-effective wastewater treatment.

PubMed

Li, Wen-Wei; Wang, Yun-Kun; Sheng, Guo-Ping; Gui, Yong-Xin; Yu, Lei; Xie, Tong-Qing; Yu, Han-Qing

2012-10-01

Conventional MBR has been mostly based on floc sludge and the use of costly microfiltration membranes. Here, a novel aerobic granule (AG)-mesh filter MBR (MMBR) process was developed for cost-effective wastewater treatment. During 32-day continuous operation, a predominance of granules was maintained in the system, and good filtration performance was achieved at a low trans-membrane pressure (TMP) of below 0.025 m. The granules showed a lower fouling propensity than sludge flocs, attributed to the formation of more porous biocake layer at mesh surface. A low-flux and low-TMP filtration favored a stable system operation. In addition, the reactor had high pollutant removal efficiencies, with a 91.4% chemical oxygen demand removal, 95.7% NH(4)(+) removal, and a low effluent turbidity of 4.1 NTU at the stable stage. This AG-MMBR process offers a promising technology for low-cost and efficient treatment of wastewaters. Copyright © 2012 Elsevier Ltd. All rights reserved.

ZIO impregnation and cytochemical localization of thiamine pyrophosphatase and acid phosphatase activities in small granule-containing (SGC) cells of rat superior cervical ganglia.

PubMed

Chau, Y P; Lu, K S

1994-10-01

Cytochemical relationship between Golgi complex and dense-cored granules (DCGs) of small granule-containing (SGC) cells in rat superior cervical ganglia was examined in electron microscopy by zinc-iodide-osmium tetroxide (ZIO) method and by enzyme cytochemistry for thiamine pyrophosphatase (TPPase) and acid phosphatase (ACPase). After ZIO impregnation, all the saccules of Golgi apparatus and some of tubular rough endoplasmic reticulum (rER) were stained. DCGs in periphery of SGC cells were not stained, but varying degrees of dense deposits occurred in the DCGs in vicinity of Golgi trans-saccules. Both TPPase and ACPase activities were localized in one or two stacked layers of saccules on the trans side of the Golgi complex. No reaction products were demonstrated in the DCGs. From these results, we suggest that the DCGs of SGC cells in rat superior cervical ganglia are derived from the Golgi complex, and that lysosomal cleavage of protein contents in the DCGs may occur in the trans Golgi saccules.

Interactions between Inhibitory Interneurons and Excitatory Associational Circuitry in Determining Spatio-Temporal Dynamics of Hippocampal Dentate Granule Cells: A Large-Scale Computational Study

PubMed Central

Hendrickson, Phillip J.; Yu, Gene J.; Song, Dong; Berger, Theodore W.

2015-01-01

This paper reports on findings from a million-cell granule cell model of the rat dentate gyrus that was used to explore the contributions of local interneuronal and associational circuits to network-level activity. The model contains experimentally derived morphological parameters for granule cells, which each contain approximately 200 compartments, and biophysical parameters for granule cells, basket cells, and mossy cells that were based both on electrophysiological data and previously published models. Synaptic input to cells in the model consisted of glutamatergic AMPA-like EPSPs and GABAergic-like IPSPs from excitatory and inhibitory neurons, respectively. The main source of input to the model was from layer II entorhinal cortical neurons. Network connectivity was constrained by the topography of the system, and was derived from axonal transport studies, which provided details about the spatial spread of axonal terminal fields, as well as how subregions of the medial and lateral entorhinal cortices project to subregions of the dentate gyrus. Results of this study show that strong feedback inhibition from the basket cell population can cause high-frequency rhythmicity in granule cells, while the strength of feedforward inhibition serves to scale the total amount of granule cell activity. Results furthermore show that the topography of local interneuronal circuits can have just as strong an impact on the development of spatio-temporal clusters in the granule cell population as the perforant path topography does, both sharpening existing clusters and introducing new ones with a greater spatial extent. Finally, results show that the interactions between the inhibitory and associational loops can cause high frequency oscillations that are modulated by a low-frequency oscillatory signal. These results serve to further illustrate the importance of topographical constraints on a global signal processing feature of a neural network, while also illustrating how rich spatio-temporal and oscillatory dynamics can evolve from a relatively small number of interacting local circuits. PMID:26635545

DEVELOPMENT OF A FABRICATION PROCESS FOR SOL-GEL/METAL HYDRIDE COMPOSITE GRANULES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hansen, E; Eric Frickey, E; Leung Heung, L

An external gelation process was developed to produce spherical granules that contain metal hydride particles in a sol-gel matrix. Dimensionally stable granules containing metal hydrides are needed for applications such as hydrogen separation and hydrogen purification that require columns containing metal hydrides. Gases must readily flow through the metal hydride beds in the columns. Metal hydrides reversibly absorb and desorb hydrogen and hydrogen isotopes. This is accompanied by significant volume changes that cause the metal hydride to break apart or decrepitate. Repeated cycling results in very fine metal hydride particles that are difficult to handle and contain. Fine particles tendmore » to settle and pack making it more difficult to flow gases through a metal hydride bed. Furthermore, the metal hydrides can exert a significant force on the containment vessel as they expand. These problems associated with metal hydrides can be eliminated with the granulation process described in this report. Small agglomerates of metal hydride particles and abietic acid (a pore former) were produced and dispersed in a colloidal silica/water suspension to form the feed slurry. Fumed silica was added to increase the viscosity of the feed slurry which helped to keep the agglomerates in suspension. Drops of the feed slurry were injected into a 27-foot tall column of hot ({approx}70 C), medium viscosity ({approx}3000 centistokes) silicone oil. Water was slowly evaporated from the drops as they settled. The drops gelled and eventually solidified to form spherical granules. This process is referred to as external gelation. Testing was completed to optimize the design of the column, the feed system, the feed slurry composition, and the operating parameters of the column. The critical process parameters can be controlled resulting in a reproducible fabrication technique. The residual silicone oil on the surface of the granules was removed by washing in mineral spirits. The granules were dried in air at 40 C. The granules were heated to 230 C for 30 minutes in argon to remove the remaining water and organic materials. The resulting product was spherical composite granules (100 to 2000 micron diameter) with a porous silica matrix containing small agglomerates of metal hydride particles. Open porosity in the silica matrix allows hydrogen to permeate rapidly through the matrix but the pores are small enough to contain the metal hydride particles. Additional porosity around the metal hydride particles, induced using abietic acid as a pore former, allows the particles to freely expand and contract without fracturing the brittle sol-gel matrix. It was demonstrated that the granules readily absorb and desorb hydrogen while remaining integral and dimensionally stable. Microcracking was observed after the granules were cycled in hydrogen five times. The strength of the granules was improved by coating them with a thin layer of a micro-porous polymer sol-gel that would allow hydrogen to freely pass through the coating but would filter out metal hydride poisons such as water and carbon monoxide. It was demonstrated that if a thin sol-gel coating was applied after the granules were cycled, the coating not only improved the strength of the granules but the coated granules retained their strength after additional hydrogen cycling tests. This additional strength is needed to extend the lifetime of the granules and to survive the compressive load in a large column of granules. Additional hydrogen adsorption tests are planned to evaluate the performance of coated granules after one hundred cycles. Tests will also be performed to determine the effects of metal hydride poisons on the granules. The results of these tests will be documented in a separate report. The process that was developed to form these granules could be scaled to a production process. The process to form granules from a mixture of metal hydride particles and pore former such as abietic acid can be scaled up using commercial granulators. The current laboratory-scale external gelation column produces approximately one gram of granules per hour. To increase the production output from a single column, multiple feed injection systems in a larger diameter column could be used.« less

Alternating anoxic feast/aerobic famine condition for improving granular sludge formation in sequencing batch airlift reactor at reduced aeration rate.

PubMed

Wan, Junfeng; Bessière, Yolaine; Spérandio, Mathieu

2009-12-01

In this study the influence of a pre-anoxic feast period on granular sludge formation in a sequencing batch airlift reactor is evaluated. Whereas a purely aerobic SBR was operated as a reference (reactor R2), another reactor (R1) was run with a reduced aeration rate and an alternating anoxic-aerobic cycle reinforced by nitrate feeding. The presence of pre-anoxic phase clearly improved the densification of aggregates and allowed granular sludge formation at reduced air flow rate (superficial air velocity (SAV)=0.63cms(-1)). A low sludge volume index (SVI(30)=45mLg(-1)) and a high MLSS concentration (9-10gL(-1)) were obtained in the anoxic/aerobic system compared to more conventional results for the aerobic reactor. A granular sludge was observed in the anoxic/aerobic system whilst only flocs were observed in the aerobic reference even when operated at a high aeration rate (SAV=2.83cms(-1)). Nitrification was maintained efficiently in the anoxic/aerobic system even when organic loading rate (OLR) was increased up to 2.8kgCODm(-3)d(-1). In the contrary nitrification was unstable in the aerobic system and dropped at high OLR due to competition between autotrophic and heterotrophic growth. The presence of a pre-anoxic period positively affected granulation process via different mechanisms: enhancing heterotrophic growth/storage deeper in the internal anoxic layer of granule, reducing the competition between autotrophic and heterotrophic growth. These processes help to develop dense granular sludge at a moderate aeration rate. This tends to confirm that oxygen transfer is the most limiting factor for granulation at reduced aeration. Hence the use of an alternative electron acceptor (nitrate or nitrite) should be encouraged during feast period for reducing energy demand of the granular sludge process.

Layered composites made from bimetallic strips produced by plasma spraying of TiAl on niobium

NASA Astrophysics Data System (ADS)

Burmistrov, V. I.; Antonova, A. V.; Povarova, K. B.; Bannykh, I. O.

2007-12-01

The production and structure of a multilayer TiAl/Nb composite material made from bimetallic TiAl/Nb strips fabricated by plasma spraying of TiAl granules onto niobium plates are studied. Here, 3-mm-and 2-mm-thick plates of a layered composite material (LCM) are produced by hot isostatic pressing of a stack of 35 bimetallic plates followed by hot rolling (the total degree of reduction is 78.6 and 85.7%, respectively). The LCM consists of discontinuous TiAl layers separated by niobium layers, and the adhesion between the layers is good. Diffusional intermediate layers form at the TiAl/Nb interfaces in the 3-mm-thick LCM and consist of the following two solid solutions: an α2-Ti3Al-based solid solution contains up to 28 at % Nb, and a niobiumbased solid solution contains up to 27 at % Ti and 32 at % Al. The diffusional intermediate layers in the 2-mmthick LCM plates consist of an α2-Ti3Al-based solid solution with up to 16.0 at % Nb; a τ-Ti3Al2Nb-or Ti4Al3Nb-based solid solution with 51.5 at % Ti, 32 at % Al, and 16.5 at % Nb; and a niobium-based solid solution with up to 22 at % Ti and 30.5 at % Al. When a bimetallic TiAl/Nb strip is fabricated by plasma spraying of granules of the Ti-48 at % Al alloy, this alloy is depleted of aluminum to 42 45 at %, and the fraction of the α2-Ti3Al phase in the sprayed layer increases. When the LCM is produced by hot isostatic pressing followed by hot rolling, the layer of plain niobium (Nb1) dissolves up to 5 at % Ti and 7 at % Al.

Lime utilization in the laboratory, field, and design of pavement layers : final report.

DOT National Transportation Integrated Search

2017-01-01

The objective of this study was to review and report the best practices of using lime (i.e., granulated lime, hydrated lime, and slurry lime) to dry soil, in working tables, and in pavement applications. The project also reviewed and documented the i...

Partial nitrification of non-ammonium-rich wastewater within biofilm filters under ambient temperature.

PubMed

Wang, Hongyu; He, Jiajie; Yang, Kai

2010-01-01

This study evaluated the partial nitrification performances of two biofilm filters over a synthetic non-ammonium-rich wastewater at a 20°C room temperature under both limited DO (∼2.0 mg/L) and unlimited DO (∼4.0 mg/L) conditions. The two filters were each of 80 cm long and used different biofilm carriers: activated carbon and ceramic granule. Results showed that partial nitrification was accomplished for both filters under the limited DO condition. However, the effluent NO(2)-N was higher in the ceramic granule filter than in the activated carbon filter, and was less susceptible to the influent COD/N changes. Further investigation into the water phase COD and NH(4)-N depth profiles and bacteria population within the two filters showed that by putting upper filter layer (upstream) to confront relatively higher influent COD/N ratios, the filtration process naturally put lower filter layers (downstream) relatively more favorable for nitrifying bacteria (ammonia oxidizing bacteria in this study) to prosper, making the filter depth left for nitrification a crucial factor for the effectiveness of nitrification with a filter. The potentially different porous flow velocities of the two filters might be the reason to cause their different partial nitrification performances, with a lower porous flow velocity (the ceramic granule filter) favoring partial nitrification more. In summation, DO, filter depth, and filtration speed should be played together to successfully operate a biofilm filter for partial nitrification.

Use of a continuous twin screw granulation and drying system during formulation development and process optimization.

PubMed

Vercruysse, J; Peeters, E; Fonteyne, M; Cappuyns, P; Delaet, U; Van Assche, I; De Beer, T; Remon, J P; Vervaet, C

2015-01-01

Since small scale is key for successful introduction of continuous techniques in the pharmaceutical industry to allow its use during formulation development and process optimization, it is essential to determine whether the product quality is similar when small quantities of materials are processed compared to the continuous processing of larger quantities. Therefore, the aim of this study was to investigate whether material processed in a single cell of the six-segmented fluid bed dryer of the ConsiGma™-25 system (a continuous twin screw granulation and drying system introduced by GEA Pharma Systems, Collette™, Wommelgem, Belgium) is predictive of granule and tablet quality during full-scale manufacturing when all drying cells are filled. Furthermore, the performance of the ConsiGma™-1 system (a mobile laboratory unit) was evaluated and compared to the ConsiGma™-25 system. A premix of two active ingredients, powdered cellulose, maize starch, pregelatinized starch and sodium starch glycolate was granulated with distilled water. After drying and milling (1000 μm, 800 rpm), granules were blended with magnesium stearate and compressed using a Modul™ P tablet press (tablet weight: 430 mg, main compression force: 12 kN). Single cell experiments using the ConsiGma™-25 system and ConsiGma™-1 system were performed in triplicate. Additionally, a 1h continuous run using the ConsiGma™-25 system was executed. Process outcomes (torque, barrel wall temperature, product temperature during drying) and granule (residual moisture content, particle size distribution, bulk and tapped density, hausner ratio, friability) as well as tablet (hardness, friability, disintegration time and dissolution) quality attributes were evaluated. By performing a 1h continuous run, it was detected that a stabilization period was needed for torque and barrel wall temperature due to initial layering of the screws and the screw chamber walls with material. Consequently, slightly deviating granule and tablet quality attributes were obtained during the start-up phase of the 1h run. For the single cell runs, granule and tablet properties were comparable with results obtained during the second part of the 1h run (after start-up). Although deviating granule quality (particle size distribution and Hausner ratio) was observed due to the divergent design of the ConsiGma™-1 unit and the ConsiGma™-25 system (horizontal set-up) used in this study, tablet quality produced from granules processed with the ConsiGma™-1 system was predictive for tablet quality obtained during continuous production using the ConsiGma™-25 system. Copyright © 2014 Elsevier B.V. All rights reserved.

Immunocytochemical and autoradiographic studies on the process of keratinization in avian epidermis suggests absence of keratohyalin.

PubMed

Alibardi, Lorenzo

2004-02-01

The process of keratinization in apteric avian epidermis and in scutate scales of some avian species has been studied by autoradiography for histidine and immunohistochemistry for keratins and other epidermal proteins. Acidic or basic alpha-keratins are present in basal, spinosus, and transitional layers, but are not seen in the corneous layer. Keratinization-specific alpha-keratins (AE2-positive) are observed in the corneous layer of apteric epidermis but not in that of scutate scales, which contain mainly beta-keratin. Alpha-keratin bundles accumulate along the plasma membrane of transitional cells of apteric epidermis. In contrast to the situation in scutate scales, in the transitional layer and in the lowermost part of the corneous layer of apteric epidermis, filaggrin-like, loricrin-like, and transglutaminase immunoreactivities are present. The lack of isopeptide bond immunoreactivity suggests that undetectable isopeptide bonds are present in avian keratinocytes. Using immunogold ultrastructural immunocytochemistry a low but localized loricrin-like and, less, filaggrin-like labeling is seen over round-oval granules or vesicles among keratin bundles of upper spinosus and transitional keratinocytes of apteric epidermis. Filaggrin-and loricrin-labeling are absent in alpha-keratin bundles localized along the plasma membrane and in the corneous layer, formerly considered keratohyalin. Using ultrastructural autoradiography for tritiated histidine, occasional trace grains are seen among these alpha-keratin bundles. A different mechanism of redistribution of matrix and corneous cell envelope proteins probably operates in avian keratinocytes as compared to that of mammals. Keratin bundles are compacted around the lipid-core of apteric epidermis keratinocytes, which do not form complex chemico/mechanical-resistant corneous cell envelopes as in mammalian keratinocytes. These observations suggest that low amounts of matrix proteins are present among keratin bundles of avian keratinocytes and that keratohyalin granules are absent. Copyright 2003 Wiley-Liss, Inc.

Immobilization of Pseudomonas sp. DG17 onto sodium alginate–attapulgite–calcium carbonate

PubMed Central

Wang, Hong Qi; Hua, Fei; Zhao, Yi Cun; Li, Yi; Wang, Xuan

2014-01-01

A strain of Pseudomonas sp. DG17, capable of degrading crude oil, was immobilized in sodium alginate–attapulgite–calcium carbonate for biodegradation of crude oil contaminated soil. In this work, proportion of independent variables, the laboratory immobilization parameters, the micromorphology and internal structure of the immobilized granule, as well as the crude oil biodegradation by sodium alginate–attapulgite–calcium carbonate immobilized cells and sodium alginate–attapulgite immobilized cells were studied to build the optimal immobilization carrier and granule-forming method. The results showed that the optimal concentrations of sodium alginate–attapulgite–calcium carbonate and calcium chloride were 2.5%–3.5%, 0.5%–1%, 3%–7% and 2%–4%, respectively. Meanwhile, the optimal bath temperature, embedding cell amount, reaction time and multiplication time were 50–60 °C, 2%, 18 h and 48 h, respectively. Moreover, biodegradation was enhanced by immobilized cells with a total petroleum hydrocarbon removal ranging from 33.56% ± 3.84% to 56.82% ± 3.26% after 20 days. The SEM results indicated that adding calcium carbonate was helpful to form internal honeycomb-like pores in the immobilized granules. PMID:26019567

The Smo/Smo model: hedgehog-induced medulloblastoma with 90% incidence and leptomeningeal spread.

PubMed

Hatton, Beryl A; Villavicencio, Elisabeth H; Tsuchiya, Karen D; Pritchard, Joel I; Ditzler, Sally; Pullar, Barbara; Hansen, Stacey; Knoblaugh, Sue E; Lee, Donghoon; Eberhart, Charles G; Hallahan, Andrew R; Olson, James M

2008-03-15

Toward the goal of generating a mouse medulloblastoma model with increased tumor incidence, we developed a homozygous version of our ND2:SmoA1 model. Medulloblastomas form in 94% of homozygous Smo/Smo mice by 2 months of age. Tumor formation is, thus, predictable by age, before the symptomatic appearance of larger lesions. This high incidence and early onset of tumors is ideal for preclinical studies because mice can be enrolled before symptom onset and with a greater latency period before late-stage disease. Smo/Smo tumors also display leptomeningeal dissemination of neoplastic cells to the brain and spine, which occurs in many human cases. Despite an extended proliferation of granule neuron precursors (GNP) in the postnatal external granular layer (EGL), the internal granular layer formed normally in Smo/Smo mice and tumor formation occurred only in localized foci on the superficial surface of the molecular layer. Thus, tumor formation is not simply the result of over proliferation of GNPs within the EGL. Moreover, Smo/Smo medulloblastomas were transplantable and serially passaged in vivo, demonstrating the aggressiveness of tumor cells and their transformation beyond a hyperplastic state. The Smo/Smo model is the first mouse medulloblastoma model to show leptomeningeal spread. The adherence to human pathology, high incidence, and early onset of tumors thus make Smo/Smo mice an efficient model for preclinical studies.

Observing secretory granules with a multiangle evanescent wave microscope.

PubMed Central

Rohrbach, A

2000-01-01

In total internal reflection fluorescence microscopy (TIRFM), fluorophores near a surface can be excited with evanescent waves, which decay exponentially with distance from the interface. Penetration depths of evanescent waves from 60 nm to 300 nm were generated by varying the angle of incidence of a laser beam. With a novel telecentric multiangle evanescent wave microscope, we monitored and investigated both single secretory granules and pools of granules in bovine chromaffin cells. By measuring the fluorescence intensity as a function of penetration depth, it is possible through a Laplace transform to obtain the fluorophore distribution as a function of axial position. We discuss the extent to which it is possible to determine distances and diameters of granules with this microscopy technique by modeling the fluorescent volumes of spheres in evanescent fields. The anisotropic near-field detection of fluorophores and the influence of the detection point-spread function are considered. The diameters of isolated granules between 70 nm and 300 nm have been reconstructed, which is clearly beyond the resolution limit of a confocal microscope. Furthermore, the paper demonstrates how evanescent waves propagate along surfaces and scatter at objects with a higher refractive index. TIRFM will have a limited applicability for quantitative measurements when the parameters used to define evanescent waves are not optimally selected. PMID:10777760

Two new species of coccidia (Apicomplexa: Eimeriidae) from leaf-tailed geckos, Uroplatus spp. (Sauria: Gekkonidae) from Madagascar, including a new host of Eimeria brygooi Upton and Barnard, 1987

PubMed Central

McAllister, Chris T.; Seville, R. Scott; Hartdegen, Ruston

2016-01-01

During May and June 2015, four common leaf-tailed geckos, Uroplatus fimbriatus (Schneider), five satanic leaf-tailed geckos, Uroplatus phantasticus (Boulenger), and four mossy leaf-tailed geckos, Uroplatus sikorae Boettger originally collected from Madagascar and housed at the Dallas Zoo, USA, had their faeces examined for coccidian parasites. Eight (62%) geckos were found to be passing oöcysts, including a new eimerian, a new isosporan and a previously described eimerian. Three of four (75%) U. fimbratus (type host) and one of five (20%) U. phantasticus were infected with Eimeria schneideri n. sp.; oöcysts were subspheroidal to ellipsoidal with a bi-layered wall and measured (length × width, L × W) 15.1 × 13.5 µm, with a length/width (L/W) ratio of 1.1. A micropyle and oöcyst residuum were absent but 1–many polar granules were present. Sporocysts were ovoidal, 6.9 × 5.3 µm, L/W 1.3. Stieda, sub-Stieda and para-Stieda bodies were absent. A globular sporocyst residuum was present as dispersed granules. Four of five (80%) U. phantasticus harbored Isospora boulengeri n. sp.; oöcysts were subpheroidal to ellipsoidal with a bi-layered wall and measured 17.3 × 16.0 µm, L/W 1.1. A micropyle and oöcyst residuum were absent but a polar granule was present. Sporocysts were ellipsoidal, 9.5 × 6.9 µm, L/W 1.4. Stieda and sub-Stieda bodies were present but a para-Stieda body was absent. A globular sporocyst residuum was present with dispersed granules. In addition, one of four (25%) U. sikorae was infected with an eimerian indistinguishable from Eimeria brygooi Upton and Barnard, 1987, previously reported from Madagascar day gecko, Phelsuma grandis Gray and golddust day gecko, Phelsuma laticauda (Boettger) from Madagascar. These are the first coccidians described from Uroplatus spp. PMID:27638735

Overexpression of Lin28b in Neural Stem Cells is Insufficient for Brain Tumor Formation, but Induces Pathological Lobulation of the Developing Cerebellum.

PubMed

Wefers, Annika K; Lindner, Sven; Schulte, Johannes H; Schüller, Ulrich

2017-02-01

LIN28B is a homologue of the RNA-binding protein LIN28A and regulates gene expression during development and carcinogenesis. It is strongly upregulated in a variety of brain tumors, such as medulloblastoma, embryonal tumor with multilayered rosettes (ETMR), atypical teratoid/rhabdoid tumor (AT/RT), or glioblastoma, but the effect of an in vivo overexpression of LIN28B on the developing central nervous system is unknown. We generated transgenic mice that either overexpressed Lin28b in Math1-positive cerebellar granule neuron precursors or in a broad range of Nestin-positive neural precursors. Sections of the cerebellar vermis from adult Math1-Cre::lsl-Lin28b mice had an additional subfissure in lobule IV. Vermes from p0 and p7 Nestin-Cre::lsl-Lin28b mice appeared normal, but we found a pronounced vermal hypersublobulation at p15 and p21 in these mice. Also, the external granule cell layer (EGL) was thicker at p15 than in controls, contained more proliferating cells, and persisted up to p21. Consistently, some Pax6- and NeuN-positive cells were present in the EGL of Nestin-Cre::lsl-Lin28b mice even at p21, and we detected more NeuN-positive granule neuron precursors in the molecular layer (ML) as compared to control. Finally, we found some residual Pax2-positive precursors of inhibitory interneurons in the ML of Nestin-Cre::lsl-Lin28b mice at p21, which have already disappeared in controls. We conclude that while overexpression of LIN28B in Nestin-positive cells does not lead to tumor formation, it results in a protracted development of granule cells and inhibitory interneurons and leads to a hypersublobulation of the cerebellar vermis.

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

PubMed

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

2016-04-01

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

Role of mammalian homologue of Caenorhabditis elegans unc-13-1 (Munc13-1) in the recruitment of newcomer insulin granules in both first and second phases of glucose-stimulated insulin secretion in mouse islets.

PubMed

Xie, L; Zhu, D; Gaisano, H Y

2012-10-01

We have previously reported that the haplodeficient Munc13-1(+/-) mouse exhibits impaired biphasic glucose-stimulated insulin secretion (GSIS), causing glucose intolerance mimicking type 2 diabetes. Glucagon-like peptide-1 (GLP-1) can bypass these insulin-secretory defects in type 2 diabetes, but the mechanism of exocytotic events mediated by GLP-1 in rescuing insulin secretion is unclear. The total internal reflection fluorescence microscopy (TIRFM) technique was used to examine single insulin granule fusion events in mouse islet beta cells. There was no difference in the density of docked granules in the resting state between Munc13-1(+/+) and Munc13-1(+/-) mouse islet beta cells. While exocytosis of previously docked granules in Munc13-1(+/-) beta cells is reduced during high-K(+) stimulation as expected, we now find a reduction in additional exocytosis events that account for the major portion of GSIS, namely two types of newcomer granules, one which has a short docking time (short-dock) and another undergoing no docking before exocytosis (no-dock). As mammalian homologue of Caenorhabditis elegans unc-13-1 (Munc13-1) is a phorbol ester substrate, phorbol ester could partially rescue biphasic GSIS in Munc13-1-deficient beta cells by enhancing recruitment of short-dock newcomer granules for exocytosis. The more effective rescue of biphasic GSIS by GLP-1 than by phorbol was due to increased recruitment of both short-dock and no-dock newcomer granules. Phorbol ester and GLP-1 potentiation of biphasic GSIS are brought about by recruitment of distinct populations of newcomer granules for exocytosis, which may be mediated by Munc13-1 interaction with syntaxin-SNARE complexes other than that formed by syntaxin-1A.

Endothelial cells in the oral mucosa of Bufo marinus.

PubMed Central

Loo, S K; Yeo, B C; Kovac, H

1980-01-01

The oral mucosa of the cane toad (Bufo marinus) is lined by a pseudostratified columnar ciliated epithelium containing an intraepithelial network of capillaries, which penetrates it to the bases of the distal layer of cells. The capillaries are lined by fenestrated endothelium lying on a complete basal lamina. A connective tissue sheath, approximately 1 micrometer thick, surrounds the capillaries and separates them from the surrounding epithelial cells. Endothelial cells resemble those in lymphatic capillaries in that they show microvillus-like processes or folds projecting into the lumen and also have extremely attenuated and fenestrated cytoplasm except in the nuclear region. Numerous pinocytotic vesicles, bundles of filaments and many electrondense granules occur in the cytoplasm. These granules are oval or round in shape and approximately 250-400 micrometer in diameter. Histochemical tests on the endothelial cells show that the granules do not contain pigment, as both the Schmorl and argentaffin reactions are negative. Both the Sudan black B and Luxol fast blue reactions are also negative showing the lack of stainable lipids. The formaldehyde-induced fluorescence, the argentaffin reactions and lead haematoxylin reactions are negative, indicating that they do not have the characteristics of endocrine cells. The acid phosphatase reaction gives a positive result, localized to the site of the granules by electron microscopy and suggesting that these granules in amphibian capillaries may have a lysosomal function. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 Fig. 16 PMID:6773911

Determination of external and internal mass transfer limitation in nitrifying microbial aggregates.

PubMed

Wilén, Britt-Marie; Gapes, Daniel; Keller, Jürg

2004-05-20

In this article we present a study of the effects of external and internal mass transfer limitation of oxygen in a nitrifying system. The oxygen uptake rates (OUR) were measured on both a macro-scale with a respirometric reactor using off-gas analysis (Titrimetric and Off-Gas Analysis (TOGA) sensor) and on a micro-scale with microsensors. These two methods provide independent, accurate measurements of the reaction rates and concentration profiles around and in the granules. The TOGA sensor and microsensor measurements showed a significant external mass transfer effect at low dissolved oxygen (DO) concentrations in the bulk liquid while it was insignificant at higher DO concentrations. The oxygen distribution with anaerobic or anoxic conditions in the center clearly shows major mass transfer limitation in the aggregate interior. The large drop in DO concentration of 22-80% between the bulk liquid and aggregate surface demonstrates that the external mass transfer resistance is also highly important. The maximum OUR even for floccular biomass was only attained at much higher DO concentrations (approximately 8 mg/L) than typically used in such systems. For granules, the DO required for maximal activity was estimated to be >20 mg/L, clearly indicating the effects of the major external and internal mass transfer limitations on the overall biomass activity. Smaller aggregates had a larger volumetric OUR indicating that the granules may have a lower activity in the interior part of the aggregate. Copyright 2004 Wiley Periodicals, Inc.

Spatiotemporal expression of MANF in the developing rat brain.

PubMed

Wang, Haiping; Ke, Zunji; Alimov, Alexander; Xu, Mei; Frank, Jacqueline A; Fang, Shengyun; Luo, Jia

2014-01-01

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an evolutionarily conserved neurotrophic factor which exhibited neuroprotective properties. Recent studies suggested that MANF may play a role in the neural development of Drosophila and zebra fishes. In this study, we investigated the spatiotemporal expression of MANF in the brain of postnatal and adult rats. MANF expression appeared wide spread and mainly localized in neurons. In the cerebral cortex, neurons in layer IV and VI displayed particularly strong MANF immunoreactivity. In the hippocampus, intensive MANF expression was observed throughout the subfields of Cornu Amonis (CA1, CA2, and CA3) and the granular layer of the dentate gyrus (DG). In the substantia nigra, high MANF expression was shown in the substantia nigra pars compacta (SNpc). In the thalamus, the anterodorsal thalamic nucleus (ADTN) exhibited the highest MANF immunoreactivity. In the hypothalamus, intensive MANF immunoreactivity was shown in the supraoptic nucleus (SON) and tuberomammillary nucleus (TMN). In the cerebellum, MANF was localized in the external germinal layer (EGL), Purkinje cell layer (PCL), internal granule layer (IGL) and the deep cerebellar nuclei (DCN). We examined the developmental expression of MANF on postnatal day (PD) 3, 5, 7, 9, 15, 21, 30 and adulthood. In general, the levels of MANF were high in the early PDs (PD3 and PD5), and declined gradually as the brain matured; MANF expression in the adult brain was the lowest among all time points examined. However, in some structures, such as PCL, IGL, SON, TMN and locus coeruleus (LC), high expression of MANF sustained throughout the postnatal period and persisted into adulthood. Our results indicated that MANF was developmentally regulated and may play a role in the maturation of the central nervous system (CNS).

Spatiotemporal Expression of MANF in the Developing Rat Brain

PubMed Central

Wang, Haiping; Ke, Zunji; Alimov, Alexander; Xu, Mei; Frank, Jacqueline A.; Fang, Shengyun; Luo, Jia

2014-01-01

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an evolutionarily conserved neurotrophic factor which exhibited neuroprotective properties. Recent studies suggested that MANF may play a role in the neural development of Drosophila and zebra fishes. In this study, we investigated the spatiotemporal expression of MANF in the brain of postnatal and adult rats. MANF expression appeared wide spread and mainly localized in neurons. In the cerebral cortex, neurons in layer IV and VI displayed particularly strong MANF immunoreactivity. In the hippocampus, intensive MANF expression was observed throughout the subfields of Cornu Amonis (CA1, CA2, and CA3) and the granular layer of the dentate gyrus (DG). In the substantia nigra, high MANF expression was shown in the substantia nigra pars compacta (SNpc). In the thalamus, the anterodorsal thalamic nucleus (ADTN) exhibited the highest MANF immunoreactivity. In the hypothalamus, intensive MANF immunoreactivity was shown in the supraoptic nucleus (SON) and tuberomammillary nucleus (TMN). In the cerebellum, MANF was localized in the external germinal layer (EGL), Purkinje cell layer (PCL), internal granule layer (IGL) and the deep cerebellar nuclei (DCN). We examined the developmental expression of MANF on postnatal day (PD) 3, 5, 7, 9, 15, 21, 30 and adulthood. In general, the levels of MANF were high in the early PDs (PD3 and PD5), and declined gradually as the brain matured; MANF expression in the adult brain was the lowest among all time points examined. However, in some structures, such as PCL, IGL, SON, TMN and locus coeruleus (LC), high expression of MANF sustained throughout the postnatal period and persisted into adulthood. Our results indicated that MANF was developmentally regulated and may play a role in the maturation of the central nervous system (CNS). PMID:24587361

To Be or Not To Be a Poly(3-Hydroxybutyrate) (PHB) Depolymerase: PhaZd1 (PhaZ6) and PhaZd2 (PhaZ7) of Ralstonia eutropha, Highly Active PHB Depolymerases with No Detectable Role in Mobilization of Accumulated PHB

PubMed Central

Sznajder, Anna

2014-01-01

The putative physiological functions of two related intracellular poly(3-hydroxybutyrate) (PHB) depolymerases, PhaZd1 and PhaZd2, of Ralstonia eutropha H16 were investigated. Purified PhaZd1 and PhaZd2 were active with native PHB granules in vitro. Partial removal of the proteinaceous surface layer of native PHB granules by trypsin treatment or the use of PHB granules isolated from ΔphaP1 or ΔphaP1-phaP5 mutant strains resulted in increased specific PHB depolymerase activity, especially for PhaZd2. Constitutive expression of PhaZd1 or PhaZd2 reduced or even prevented the accumulation of PHB under PHB-permissive conditions in vivo. Expression of translational fusions of enhanced yellow fluorescent protein (EYFP) with PhaZd1 and PhaZd2 in which the active-site serines (S190 and Ser193) were replaced with alanine resulted in the colocalization of only PhaZd1 fusions with PHB granules. C-terminal fusions of inactive PhaZd2(S193A) with EYFP revealed the presence of spindle-like structures, and no colocalization with PHB granules was observed. Chromosomal deletion of phaZd1, phaZd2, or both depolymerase genes had no significant effect on PHB accumulation and mobilization during growth in nutrient broth (NB) or NB-gluconate medium. Moreover, neither proteome analysis of purified native PHB granules nor lacZ fusion studies gave any indication that PhaZd1 or PhaZd2 was detectably present in the PHB granule fraction or expressed at all during growth on NB-gluconate medium. In conclusion, PhaZd1 and PhaZd2 are two PHB depolymerases with a high capacity to degrade PHB when artificially expressed but are apparently not involved in PHB mobilization in the wild type. The true in vivo functions of PhaZd1 and PhaZd2 remain obscure. PMID:24907326

To be or not to be a poly(3-hydroxybutyrate) (PHB) depolymerase: PhaZd1 (PhaZ6) and PhaZd2 (PhaZ7) of Ralstonia eutropha, highly active PHB depolymerases with no detectable role in mobilization of accumulated PHB.

PubMed

Sznajder, Anna; Jendrossek, Dieter

2014-08-01

The putative physiological functions of two related intracellular poly(3-hydroxybutyrate) (PHB) depolymerases, PhaZd1 and PhaZd2, of Ralstonia eutropha H16 were investigated. Purified PhaZd1 and PhaZd2 were active with native PHB granules in vitro. Partial removal of the proteinaceous surface layer of native PHB granules by trypsin treatment or the use of PHB granules isolated from ΔphaP1 or ΔphaP1-phaP5 mutant strains resulted in increased specific PHB depolymerase activity, especially for PhaZd2. Constitutive expression of PhaZd1 or PhaZd2 reduced or even prevented the accumulation of PHB under PHB-permissive conditions in vivo. Expression of translational fusions of enhanced yellow fluorescent protein (EYFP) with PhaZd1 and PhaZd2 in which the active-site serines (S190 and Ser193) were replaced with alanine resulted in the colocalization of only PhaZd1 fusions with PHB granules. C-terminal fusions of inactive PhaZd2(S193A) with EYFP revealed the presence of spindle-like structures, and no colocalization with PHB granules was observed. Chromosomal deletion of phaZd1, phaZd2, or both depolymerase genes had no significant effect on PHB accumulation and mobilization during growth in nutrient broth (NB) or NB-gluconate medium. Moreover, neither proteome analysis of purified native PHB granules nor lacZ fusion studies gave any indication that PhaZd1 or PhaZd2 was detectably present in the PHB granule fraction or expressed at all during growth on NB-gluconate medium. In conclusion, PhaZd1 and PhaZd2 are two PHB depolymerases with a high capacity to degrade PHB when artificially expressed but are apparently not involved in PHB mobilization in the wild type. The true in vivo functions of PhaZd1 and PhaZd2 remain obscure. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

New neurons generated from running are broadly recruited into neuronal activation associated with three different hippocampus-involved tasks

PubMed Central

Clark, Peter J.; Bhattacharya, Tushar K.; Miller, Daniel S.; Kohman, Rachel A.; DeYoung, Erin K.; Rhodes, Justin S.

2012-01-01

Running increases the formation of new neurons in the adult rodent hippocampus. However, the function of new neurons generated from running is currently unknown. One hypothesis is that new neurons from running contribute to enhanced cognitive function by increasing plasticity in the adult hippocampus. An alternative hypothesis is that new neurons generated from running incorporate into experience-specific hippocampal networks that only become active during running. The purpose of this experiment was to determine if new neurons generated from running are selectively activated by running, or can become recruited into granule cell activity occurring during performance on other behavioral tasks that engage the hippocampus. Therefore, the activation of new 5–6 week neurons was detected using BrdU, NeuN, and Zif268 triple-label immunohistochemistry in cohorts of female running and sedentary adult C57BL/6J mice following participation in one of three different tasks: the Morris water maze, novel environment exploration, or wheel running. Results showed that running and sedentary mice displayed a nearly equivalent proportion of new neurons that expressed Zif268 following each task. Since running approximately doubled the number of new neurons, the results demonstrated that running mice had a greater number of new neurons recruited into the Zif268 induction in the granule cell layer following each task than sedentary mice. The results suggest that new neurons incorporated into hippocampal circuitry from running are not just activated by wheel running itself, but rather become broadly recruited into granule cell layer activity during distinct behavioral experiences. PMID:22467337

Selective vulnerability of dentate granule cells prior to amyloid deposition in PDAPP mice: digital morphometric analyses.

PubMed

Wu, Chi-Cheng; Chawla, Faisal; Games, Dora; Rydel, Russell E; Freedman, Stephen; Schenk, Dale; Young, Warren G; Morrison, John H; Bloom, Floyd E

2004-05-04

Increasing evidence from mouse models of Alzheimer's disease shows that overexpression of a mutant form of the amyloid precursor protein (APP) and its product, beta-amyloid peptide, initiate pathological changes before amyloid deposition. To evaluate the cytological basis for one of these early changes, namely reduced volume of the dentate gyrus (DG), we have used high-throughput diOlistic cell loading and 3D neuronal reconstruction to investigate potential dendritic pathology of granule cells (GCs) in 90-day-old PDAPP mice. Labeled GCs from fixed hippocampal slices were selected randomly and imaged digitally by using confocal laser-scanning microscopy. The dendritic complexity of GCs was quantified according to subordinate morphological parameters, including soma position within the granule cell layer (superficial versus deep) and topographic location within the DG (dorsal versus ventral blade) along the anterior-posterior hippocampal axis. Initial analysis, which included all sampled GC types, revealed a 12% reduction of total dendritic length in PDAPP mice compared with littermate controls. Further analysis, performed with refined subgroups, found that superficially located GCs in the dorsal blade were profoundly altered, exhibiting a 23% loss in total dendritic length, whereas neurons in the ventral blade were unaffected. Superficial GCs were particularly vulnerable (a 32% reduction) in the posterior region of the DG. Furthermore, the dendritic reductions of this select group were uniformly localized within middle-to-outer portions of the dentate molecular layer. We conclude that substantial dendritic pathology is evident in 90-day-old PDAPP mice for a spatially defined subset of GCs well before amyloid accumulation occurs.

Selective vulnerability of dentate granule cells prior to amyloid deposition in PDAPP mice: Digital morphometric analyses

PubMed Central

Wu, Chi-Cheng; Chawla, Faisal; Games, Dora; Rydel, Russell E.; Freedman, Stephen; Schenk, Dale; Young, Warren G.; Morrison, John H.; Bloom, Floyd E.

2004-01-01

Increasing evidence from mouse models of Alzheimer's disease shows that overexpression of a mutant form of the amyloid precursor protein (APP) and its product, β-amyloid peptide, initiate pathological changes before amyloid deposition. To evaluate the cytological basis for one of these early changes, namely reduced volume of the dentate gyrus (DG), we have used high-throughput diOlistic cell loading and 3D neuronal reconstruction to investigate potential dendritic pathology of granule cells (GCs) in 90-day-old PDAPP mice. Labeled GCs from fixed hippocampal slices were selected randomly and imaged digitally by using confocal laser-scanning microscopy. The dendritic complexity of GCs was quantified according to subordinate morphological parameters, including soma position within the granule cell layer (superficial versus deep) and topographic location within the DG (dorsal versus ventral blade) along the anterior-posterior hippocampal axis. Initial analysis, which included all sampled GC types, revealed a 12% reduction of total dendritic length in PDAPP mice compared with littermate controls. Further analysis, performed with refined subgroups, found that superficially located GCs in the dorsal blade were profoundly altered, exhibiting a 23% loss in total dendritic length, whereas neurons in the ventral blade were unaffected. Superficial GCs were particularly vulnerable (a 32% reduction) in the posterior region of the DG. Furthermore, the dendritic reductions of this select group were uniformly localized within middle-to-outer portions of the dentate molecular layer. We conclude that substantial dendritic pathology is evident in 90-day-old PDAPP mice for a spatially defined subset of GCs well before amyloid accumulation occurs. PMID:15118092

[Removal of PO4(3-) from solution, wastewater and seawater by modification and granulation magnesium and aluminium layered double hydroxide].

PubMed

Xing, Kun; Wang, Hai-Zeng

2013-04-01

Powder layered double hydroxide of Mg-Al LDH were prepared by hydrothermal technology with 500 kg x batch(-1), modified and granulated (MG Mg-Al CLDH) by deposition method. After the modification and granulation, the fixed bed can not be accumulated and clogged by the adsorbents. The PO4(3-) is removed from aqueous solution, wastewater and seawater by MG Mg-Al CLDH with column experiments. It shows that MG Mg-Al CLDH is an effective adsorbent. After removal, the water quality can satisfy with the first degree of integrated wastewater discharge or seawater standards. The mechanism of removal PO4(3-) is ion exchange and 'memory effect'. The breakthrough adsorption capacity of PO4(3-) from solution is 13.49 mg x g(-1), more than 6 times higher than that by Mg-Al LDH without modification. The exhausted MG Mg-Al CLDH can be desorbed with 0.1 mol x L(-1) NaOH and 3 mol x L(-1) NaCl and regenerated with 25% MgCl2. The regeneration rate is 126.24%. The breakthrough curves are influenced by bed depth, flow rate, initial concentration and initial pH. The adsorption processes are controlled by film diffusion. When the initial concentration is as low as 0.38 micromol x L(-1), PO4(3-) can be removed from seawater to satisfy with the first degree of seawater quality. So this work is very useful for the practical application of Mg-Al LDH and the removal of phosphorus.

Physical structure and absorption properties of tailor-made porous starch granules produced by selected amylolytic enzymes

PubMed Central

Jung, Yi-seul; Lee, Byung-Hoo

2017-01-01

Porous starch granules (PSGs) with various pores and cavity sizes were prepared by amylolysis enzymes. The greatest hydrolysis rate on corn starch granule was observed with α-amylase, followed by gluco- and β-amylases. Temperature increase enhanced glucoamylase reaction rate more drastically than other enzyme treatments. Final hydrolysis level with glucoamylase reached to 66.9%, close to 67.5% of α-amylolysis. The α-amylase-treated PSGs displayed the greatest pore size and ratio of cavity-to-granule diameters. Gelatinization onset temperatures of PSGs increased to 72.1 (α-), 68.7 (β-), and 68.1°C (gluco-amylolysis) after 8 h; enthalpy changes of β- and gluco-amylase-treated PSGs increased to 13.4, and 13.1 J/g but α-amylase-treated one showed slightly reduced value of 8.5 J/g. Water holding capacities of PSGs were 209.7 (α-), 94.6 (β-), and 133.8% (gluco-amylolysis), and the untreated control had 89.1%; oil holding capacities of them showed 304.5, 182.7, and 211.5%, respectively, while the untreated control had 161.8%. Thus, enzyme types and their reaction conditions can be applied to generate desirable cavity and pore sizes in starch granules. This biocatalytic approach could contribute to develop tailor-made PSGs with distinct internal structure for specific uses in wide range of food, pharmaceutical and other industrial applications. PMID:28727742

Localization of Poly(3-Hydroxybutyrate) (PHB) Granule-Associated Proteins during PHB Granule Formation and Identification of Two New Phasins, PhaP6 and PhaP7, in Ralstonia eutropha H16

PubMed Central

Pfeiffer, Daniel

2012-01-01

Poly(3-hydroxybutyrate) (PHB) granules are covered by a surface layer consisting of mainly phasins and other PHB granule-associated proteins (PGAPs). Phasins are small amphiphilic proteins that determine the number and size of accumulated PHB granules. Five phasin proteins (PhaP1 to PhaP5) are known for Ralstonia eutropha. In this study, we identified three additional potential phasin genes (H16_B1988, H16_B2296, and H16_B2326) by inspection of the R. eutropha genome for sequences with “phasin 2 motifs.” To determine whether the corresponding proteins represent true PGAPs, fusions with eYFP (enhanced yellow fluorescent protein) were constructed. Similar fusions of eYFP with PhaP1 to PhaP5 as well as fusions with PHB synthase (PhaC1), an inactive PhaC1 variant (PhaC1-C319A), and PhaC2 were also made. All fusions were investigated in wild-type and PHB-negative backgrounds. Colocalization with PHB granules was found for all PhaC variants and for PhaP1 to PhaP5. Additionally, eYFP fusions with H16_B1988 and H16_B2326 colocalized with PHB. Fusions of H16_B2296 with eYFP, however, did not colocalize with PHB granules but did colocalize with the nucleoid region. Notably, all fusions (except H16_B2296) were soluble in a ΔphaC1 strain. These data confirm that H16_B1988 and H16_B2326 but not H16_B2296 encode true PGAPs, for which we propose the designation PhaP6 (H16_B1988) and PhaP7 (H16_B2326). When localization of phasins was investigated at different stages of PHB accumulation, fusions of PhaP6 and PhaP7 were soluble in the first 3 h under PHB-permissive conditions, although PHB granules appeared after 10 min. At later time points, the fusions colocalized with PHB. Remarkably, PHB granules of strains expressing eYFP fusions with PhaP5, PhaP6, or PhaP7 localized predominantly near the cell poles or in the area of future septum formation. This phenomenon was not observed for the other PGAPs (PhaP1 to PhaP4, PhaC1, PhaC1-C319A, and PhaC2) and indicated that some phasins can have additional functions. A chromosomal deletion of phaP6 or phaP7 had no visible effect on formation of PHB granules. PMID:22923598

Localization of poly(3-hydroxybutyrate) (PHB) granule-associated proteins during PHB granule formation and identification of two new phasins, PhaP6 and PhaP7, in Ralstonia eutropha H16.

PubMed

Pfeiffer, Daniel; Jendrossek, Dieter

2012-11-01

Poly(3-hydroxybutyrate) (PHB) granules are covered by a surface layer consisting of mainly phasins and other PHB granule-associated proteins (PGAPs). Phasins are small amphiphilic proteins that determine the number and size of accumulated PHB granules. Five phasin proteins (PhaP1 to PhaP5) are known for Ralstonia eutropha. In this study, we identified three additional potential phasin genes (H16_B1988, H16_B2296, and H16_B2326) by inspection of the R. eutropha genome for sequences with "phasin 2 motifs." To determine whether the corresponding proteins represent true PGAPs, fusions with eYFP (enhanced yellow fluorescent protein) were constructed. Similar fusions of eYFP with PhaP1 to PhaP5 as well as fusions with PHB synthase (PhaC1), an inactive PhaC1 variant (PhaC1-C319A), and PhaC2 were also made. All fusions were investigated in wild-type and PHB-negative backgrounds. Colocalization with PHB granules was found for all PhaC variants and for PhaP1 to PhaP5. Additionally, eYFP fusions with H16_B1988 and H16_B2326 colocalized with PHB. Fusions of H16_B2296 with eYFP, however, did not colocalize with PHB granules but did colocalize with the nucleoid region. Notably, all fusions (except H16_B2296) were soluble in a ΔphaC1 strain. These data confirm that H16_B1988 and H16_B2326 but not H16_B2296 encode true PGAPs, for which we propose the designation PhaP6 (H16_B1988) and PhaP7 (H16_B2326). When localization of phasins was investigated at different stages of PHB accumulation, fusions of PhaP6 and PhaP7 were soluble in the first 3 h under PHB-permissive conditions, although PHB granules appeared after 10 min. At later time points, the fusions colocalized with PHB. Remarkably, PHB granules of strains expressing eYFP fusions with PhaP5, PhaP6, or PhaP7 localized predominantly near the cell poles or in the area of future septum formation. This phenomenon was not observed for the other PGAPs (PhaP1 to PhaP4, PhaC1, PhaC1-C319A, and PhaC2) and indicated that some phasins can have additional functions. A chromosomal deletion of phaP6 or phaP7 had no visible effect on formation of PHB granules.

Model cerebellar granule cells can faithfully transmit modulated firing rate signals

PubMed Central

Rössert, Christian; Solinas, Sergio; D'Angelo, Egidio; Dean, Paul; Porrill, John

2014-01-01

A crucial assumption of many high-level system models of the cerebellum is that information in the granular layer is encoded in a linear manner. However, granule cells are known for their non-linear and resonant synaptic and intrinsic properties that could potentially impede linear signal transmission. In this modeling study we analyse how electrophysiological granule cell properties and spike sampling influence information coded by firing rate modulation, assuming no signal-related, i.e., uncorrelated inhibitory feedback (open-loop mode). A detailed one-compartment granule cell model was excited in simulation by either direct current or mossy-fiber synaptic inputs. Vestibular signals were represented as tonic inputs to the flocculus modulated at frequencies up to 20 Hz (approximate upper frequency limit of vestibular-ocular reflex, VOR). Model outputs were assessed using estimates of both the transfer function, and the fidelity of input-signal reconstruction measured as variance-accounted-for. The detailed granule cell model with realistic mossy-fiber synaptic inputs could transmit information faithfully and linearly in the frequency range of the vestibular-ocular reflex. This was achieved most simply if the model neurons had a firing rate at least twice the highest required frequency of modulation, but lower rates were also adequate provided a population of neurons was utilized, especially in combination with push-pull coding. The exact number of neurons required for faithful transmission depended on the precise values of firing rate and noise. The model neurons were also able to combine excitatory and inhibitory signals linearly, and could be replaced by a simpler (modified) integrate-and-fire neuron in the case of high tonic firing rates. These findings suggest that granule cells can in principle code modulated firing-rate inputs in a linear manner, and are thus consistent with the high-level adaptive-filter model of the cerebellar microcircuit. PMID:25352777

Distribution of CaMKIIα expression in the brain in vivo, studied by CaMKIIα-GFP mice

PubMed Central

Wang, Xinjun; Zhang, Chunzhao; Szábo, Gábor; Sun, Qian-Quan

2013-01-01

To facilitate the study of the CaMKIIα function in vivo, a CaMKIIα-GFP transgenic mouse line was generated. Here, our goal is to provide the first neuroanatomical characterization of GFP expression in the CNS of this line of mouse. Overall, CaMKIIα -GFP expression is strong and highly heterogeneous, with the dentate gyrus of the hippocampus as the most abundantly expressed region. In the hippocampus, around 70% of granule and pyramidal neurons expressed strong GFP. In the neocortex, presumed pyramidal neurons were GFP positive: around 32% of layer II/III and 35% of layer VI neurons expressed GFP, and a lower expression rate was found in other layers. In the thalamus and hypothalamus, strong GFP signals were detected in the neuropil. GFP-positive cells were also found in many other regions such as the spinal trigeminal nucleus, cerebellum and basal ganglia. We further compared the GFP expression with specific antibody staining for CaMKIIα and GABA. We found that GFP+ neurons were mostly positive for CaMKIIα-IR throughout the brain, with some exceptions throughout the brain, especially in the deeper layers of neocortex. GFP and GABA-IR marked distinct neuronal populations in most brain regions with the exception of granule cells in the olfactory bulb, purkinje cells in the cerebellar, and some layer I cells in neocortex. In conclusion, GFP expression in the CaMKIIα-GFP mice is similar to the endogenous expression of CaMKIIα protein, thus these mice can be used in in vivo and in vitro physiological studies in which visualization of CaMKIIα- neuronal populations is required. PMID:23632380

CHRONIC DEVELOPMENTAL LEAD EXPOSURE REDUCES NEUROGENESIS IN ADULT RAT HIPPOCAMPUS BUT DOES NOT IMPAIR SPATIAL LEARNING.

EPA Science Inventory

It has long been heralded that the mature brain does not generate new neurons, it only loses them as a function of injury, disease and age. An exciting recent finding in neuroscience has been that the dentate granule cell layer of the hippocampus has the distinctive property of ...

Mechanical Parameters of Rubber-Sand Mixtures for Numerical Analysis of a Road Embankment

NASA Astrophysics Data System (ADS)

Kowalska, Magdalena; Chmielewski, Maciej

2017-10-01

Waste production is one of the greatest problems of the modern world. It is inevitably related to the increase of industrialization. One of the most difficult, and growing in amounts, waste is scrap tyres. The most common method of utilization of end-of-life tyres by their incineration raises much concern in terms of air pollution. More sustainable seems to reuse the tyre derived products - rubber in particular - in civil engineering, where the interesting properties of this material may be effectively utilized. This paper presents results of direct shear strength tests on sand-rubber mixtures, which were next applied to a numerical FEM (finite element method) model of a road embankment built on soft ground. The laboratory tests, conducted for two types of scrap tyre rubber granulates (0.5 - 2 mm and 1 - 5 mm in size) mixed with medium fluvial sand in various proportions (5, 10, 30 and 50% by weight), proved that the unit weight of the mixtures is distinctly smaller that the unit weight of sand alone and at 50% rubber content it drops by half. The internal angle of friction stays almost unchanged for the mixtures with up to 10% of rubber (33 - 37°), but decreases by about 10° when the rubber content increases to 50%. In most of the cases analysed, the cohesion intercept is higher in case of sand-rubber mixtures when compared to sand alone. The numerical model simulated a 4.5 m high embankment with a 3 m thick layer made of sand-rubber mixtures, containing 0%, 10% or 30% of the waste product, founded on a weak subsoil (with a 3 m layer of organic soil). The results showed that stability factor of the structure built with the layer containing 30% of the coarser rubber granulate has increased from 1.60 - for sand only, to 2.15. The embankment was also able to carry load increased from 32 kPa to 45.5 kPa and its base showed much smaller settlement. The results prove that the use of tyre derived aggregates in embankment construction is not only an effective way of utilization of this problematic waste, but can also improve behaviour of such a structure.

A new species of Caryospora Léger, 1904 (Apicomplexa: Eimeriidae) from the endangered Round Island boa Casarea dussumieri (Schlegel) (Serpentes: Bolyeridae) of Round Island, Mauritius: an endangered parasite?

PubMed

Daszak, Peter; Ball, Stanley J; Streicker, Daniel G; Jones, Carl G; Snow, Keith R

2011-02-01

A new species of Caryospora Léger, 1904 (Apicomplexa: Eimeriidae), C. durelli n. sp., is described from the endangered Round Island boa Casarea dussumieri (Schlegel) (Serpentes: Bolyeridae) from Round Island, Mauritius. Six of 11 hosts were infected. Oöcysts are spherical to subspherical, 19.2 × 18.2 (17.5-21 × 16-21) μm, n = 20, and have a shape index (mean length/mean width) of 1.05 (1.02-1.09). The bi-layered wall is composed of an outer layer of c.0.6 μm thick and an inner layer of c.0.4 μm thick. A micropyle, oöcyst residuum and polar granule are absent. Sporocysts are ellipsoidal, 14.7 × 11.0 (13-16 × 9.5-11.5) μm, n = 20, and have a shape index of 1.33. Both Stieda and substieda bodies are present. The sporocyst residuum measures c.12 × 4.5 μm, is surrounded by sporozoites and composed of numerous granules. Refractile bodies are present but not clearly visible. This is the first coccidian parasite reported from the family Bolyeridae and the first species of Caryospora durrelli [corrected] reported from the Mascarenes. Conservation issues concerning parasites of endangered host species are discussed.

Temperature variation in metal ceramic technology analyzed using time domain optical coherence tomography

NASA Astrophysics Data System (ADS)

Sinescu, Cosmin; Topala, Florin I.; Negrutiu, Meda Lavinia; Duma, Virgil-Florin; Podoleanu, Adrian G.

2014-01-01

The quality of dental prostheses is essential in providing good quality medical services. The metal ceramic technology applied in dentistry implies ceramic sintering inside the dental oven. Every ceramic material requires a special sintering chart which is recommended by the producer. For a regular dental technician it is very difficult to evaluate if the temperature inside the oven remains the same as it is programmed on the sintering chart. Also, maintaining the calibration in time is an issue for the practitioners. Metal ceramic crowns develop a very accurate pattern for the ceramic layers depending on the temperature variation inside the oven where they are processed. Different patterns were identified in the present study for the samples processed with a variation in temperature of +30 °C to +50 °C, respectively - 30 0°C to -50 °C. The OCT imagistic evaluations performed for the normal samples present a uniform spread of the ceramic granulation inside the ceramic materials. For the samples sintered at a higher temperature an alternation between white and darker areas between the enamel and opaque layers appear. For the samples sintered at a lower temperature a decrease in the ceramic granulation from the enamel towards the opaque layer is concluded. The TD-OCT methods can therefore be used efficiently for the detection of the temperature variation due to the ceramic sintering inside the ceramic oven.

Electropulse treatment of water solution of humic substances in a layer iron granules in process of water treatment

NASA Astrophysics Data System (ADS)

Lobanova, G. L.; Yurmazova, T. A.; Shiyan, L. N.; Machekhina, K. I.

2016-02-01

The present work is a part of a continuations study of the physical and chemical processes complex in natural waters containing humic-type organic substances at the influence of pulsed electrical discharges in a layer of iron pellets. The study of humic substances processing in the iron granules layer by means of pulsed electric discharge for the purpose of water purification from organic compounds humic origin from natural water of the northern regions of Russia is relevant for the water treatment technologies. In case of molar humate sodium - iron ions (II) at the ratio 2:3, reduction of solution colour and chemical oxygen demand occur due to the humate sodium ions and iron (II) participation in oxidation-reduction reactions followed by coagulation insoluble compounds formation at a pH of 6.5. In order to achieve this molar ratio and the time of pulsed electric discharge, equal to 10 seconds is experimentally identified. The role of secondary processes that occur after disconnection of the discharge is shown. The time of contact in active erosion products with sodium humate, equal to 1 hour is established. During this time, the value of permanganate oxidation and iron concentration in solution achieves the value of maximum permissible concentrations and further contact time increase does not lead to the controlled parameters change.

Trace element distribution in the rat cerebellum

NASA Astrophysics Data System (ADS)

Kwiatek, W. M.; Long, G. J.; Pounds, J. G.; Reuhl, K. R.; Hanson, A. L.; Jones, K. W.

1990-04-01

Spatial distributions and concentrations of trace elements (TE) in the brain are important because TE perform catalytic and structural functions in enzymes which regulate brain function and development. We have investigated the distributions of TE in rat cerebellum. Structures were sectioned and analyzed by the Synchrotron Radiation Induced X-ray Emission (SRIXE) method using the NSLS X-26 white-light microprobe facility. Advantages important for TE analysis of biological specimens with X-ray microscopy include short time of measurement, high brightness and flux, good spatial resolution, multielemental detection, good sensitivity, and nondestructive irradiation. Trace elements were measured in thin rat brain sections of 20 μm thickness. The analyses were performed on sample volumes as small as 0.2 nl with Minimum Detectable Limits (MDL) of 50 ppb wet weight for Fe, 100 ppb wet weight for Cu, and Zn, and 1 ppm wet weight for Pb. The distribution of TE in the molecular cell layer, granule cell layer and fiber tract of rat cerebella was investigated. Both point analyses and two-dimensional semiquantitative mapping of the TE distribution in a section were used. All analyzed elements were observed in each structure of the cerebellum except mercury which was not observed in granule cell layer or fiber tract. This approach permits an exacting correlation of the TE distribution in complex structure with the diet, toxic elements, and functional status of the animal.

Emulsion stabilizing capacity of intact starch granules modified by heat treatment or octenyl succinic anhydride.

PubMed

Timgren, Anna; Rayner, Marilyn; Dejmek, Petr; Marku, Diana; Sjöö, Malin

2013-03-01

Starch granules are an interesting stabilizer candidate for food-grade Pickering emulsions. The stabilizing capacity of seven different intact starch granules for making oil-in-water emulsions has been the topic of this screening study. The starches were from quinoa; rice; maize; waxy varieties of rice, maize, and barley; and high-amylose maize. The starches were studied in their native state, heat treated, and modified by octenyl succinic anhydride (OSA). The effect of varying the continuous phase, both with and without salt in a phosphate buffer, was also studied. Quinoa, which had the smallest granule size, had the best capacity to stabilize oil drops, especially when the granules had been hydrophobically modified by heat treatment or by OSA. The average drop diameter (d 32) in these emulsions varied from 270 to 50 μm, where decreasing drop size and less aggregation was promoted by high starch concentration and absence of salt in the system. Of all the starch varieties studied, quinoa had the best overall emulsifying capacity, and OSA modified quinoa starch in particular. Although the size of the drops was relatively large, the drops themselves were in many instances extremely stable. In the cases where the system could stabilize droplets, even when they were so large that they were visible to the naked eye, they remained stable and the measured droplet sizes after 2 years of storage were essentially unchanged from the initial droplet size. This somewhat surprising result has been attributed to the thickness of the adsorbed starch layer providing steric stabilization. The starch particle-stabilized Pickering emulsion systems studied in this work has potential practical application such as being suitable for encapsulation of ingredients in food and pharmaceutical products.

Sensorimotor Representations in Cerebellar Granule Cells in Larval Zebrafish Are Dense, Spatially Organized, and Non-temporally Patterned.

PubMed

Knogler, Laura D; Markov, Daniil A; Dragomir, Elena I; Štih, Vilim; Portugues, Ruben

2017-05-08

A fundamental question in neurobiology is how animals integrate external sensory information from their environment with self-generated motor and sensory signals in order to guide motor behavior and adaptation. The cerebellum is a vertebrate hindbrain region where all of these signals converge and that has been implicated in the acquisition, coordination, and calibration of motor activity. Theories of cerebellar function postulate that granule cells encode a variety of sensorimotor signals in the cerebellar input layer. These models suggest that representations should be high-dimensional, sparse, and temporally patterned. However, in vivo physiological recordings addressing these points have been limited and in particular have been unable to measure the spatiotemporal dynamics of population-wide activity. In this study, we use both calcium imaging and electrophysiology in the awake larval zebrafish to investigate how cerebellar granule cells encode three types of sensory stimuli as well as stimulus-evoked motor behaviors. We find that a large fraction of all granule cells are active in response to these stimuli, such that representations are not sparse at the population level. We find instead that most responses belong to only one of a small number of distinct activity profiles, which are temporally homogeneous and anatomically clustered. We furthermore identify granule cells that are active during swimming behaviors and others that are multimodal for sensory and motor variables. When we pharmacologically change the threshold of a stimulus-evoked behavior, we observe correlated changes in these representations. Finally, electrophysiological data show no evidence for temporal patterning in the coding of different stimulus durations. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Fabrication and physicochemical characterization of porous composite microgranules with selenium oxyanions and risedronate sodium for potential applications in bone tumors

PubMed Central

Kolmas, Joanna; Pajor, Kamil; Pajchel, Lukasz; Przekora, Agata; Ginalska, Grażyna; Oledzka, Ewa; Sobczak, Marcin

2017-01-01

Nanocrystalline hydroxyapatite containing selenite ions (SeHA; 9.6 wt.% of selenium) was synthesized using wet method and subject to careful physicochemical analysis by powder X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, solid-state nuclear magnetic resonance, wavelength dispersive X-ray fluorescence, and inductively coupled plasma optical emission spectrometry. SeHA was then used to develop the selenium-containing hydroxyapatite/alginate (SeHA/ALG) composite granules. Risedronate sodium (RIS) was introduced to the obtained spherical microgranules of a size of about 1.1–1.5 mm in 2 ways: during the granules’ preparation (RIS solution added to a suspension of ALG and SeHA), and as a result of SeHA/ALG granules soaking in aqueous RIS solution. The analysis made using 13C and 31P cross-polarization magic angle spinning nuclear magnetic resonance confirmed the presence of RIS and its interaction with calcium ions. Then, the release of selenium (inductively coupled plasma optical emission spectrometry) and RIS (high-performance liquid chromatography) from microgranules was examined. Moreover, cytotoxicity of fabricated granules was assessed by MTT test. Selenium release was biphasic: the first stage was short and ascribed to a “burst release” probably from a hydrated surface layer of SeHA crystals, while the next stage was significantly longer and ascribed to a sustained release of selenium from the crystals’ interior. The study showed that the method of obtaining microgranules containing RIS significantly affects its release profile. Performed cytotoxicity test revealed that fabricated granules had high antitumor activity against osteosarcoma cells. However, because of the “burst release” of selenium during the first 10 h, the granules significantly reduced viability of normal osteoblasts as well. PMID:28848343

Sirolimus-eluting Biodegradable Poly-l-Lactic Acid Stent to Suppress Granulation Tissue Formation in the Rat Urethra.

PubMed

Kim, Kun Yung; Park, Jung-Hoon; Kim, Do Hoon; Tsauo, Jiaywei; Kim, Min Tae; Son, Woo-Chan; Kang, Sung-Gwon; Kim, Dong-Hyun; Song, Ho-Young

2018-01-01

Purpose To investigate the use of sirolimus-eluting biodegradable stents (SEBSs) to suppress granulation tissue formation after stent placement in a rat urethral model. Materials and Methods All experiments were approved by the animal research committee. A total of 36 male Sprague-Dawley rats were randomized into three equal groups after biodegradable stent placement. Group A received control biodegradable stents. Groups B and C received stents coated with 90 µg/cm 2 and 450 µg/cm 2 sirolimus, respectively. Six rats in each group were sacrificed after 4 weeks; the remaining rats were sacrificed after 12 weeks. The therapeutic effectiveness of SEBSs was assessed by comparing the results of retrograde urethrography and histologic examination. Analysis of variance with post hoc comparisons was used to evaluate statistical differences. Results SEBS placement was technically successful in all rats. Urethrographic and histologic examinations revealed significantly less granulation tissue formation at both time points in the rats receiving SEBSs (groups B and C) compared with those that received control stents (group A) (P < .05 for all). There were no significant differences in urethrographic and histologic findings between groups B and C (P > .05 for all). However, the mean number of epithelial layers in group B was higher than that in group C at 4 weeks after stent placement (P < .001). Apoptosis increased in group C compared with groups A and B (P < .05 for all). Conclusion The use of SEBSs suppressed granulation tissue formation secondary to stent placement in a rat urethral model; local therapy with SEBSs may be used to decrease stent-related granulation tissue formation. © RSNA, 2017.

[Fusion of reconstructed titanic plate, vertebral pedical screws and autogenous granulated cancellous bone graft in posterior occipitocervical region].

PubMed

Zhong, Dejun; Song, Yueming

2006-08-01

To explore the technique of fusing the reconstructed titanic plate, the C2 pedical screws, and the autogenous granulated cancellous bone graft in the occipitocervical region. From April 2002 to January 2005, 19 patients aged 31-67 years with occipitocervical instability underwent the occipitocervical fusion using the reconstructed plate, C2 pedical screws, and autogenous granulated cancellous bone graft. Of the patients, 8 had complex occipitocervical deformity, 8 had old atlantoaxial fracture and dislocation, 2 had rheumatoid arthritis and anterior dislocation of the atlantoaxial joint, and 1 had cancer of the deltoid process of the axis. No complication occurred during and after operation. The follow-up for an average of 16 months in 19 patients showed that all the patients achieved solid bony fusion in the occipitocervical region. There was no broken plate, broken screw, looseness of the internal fixation or neurovascular injury. The fixation of the C2 pedical screws with the reconstructed titanic plate is reliable, the insertion is easy, and the autogenous granulated cancellous bone graft has a high fusion rate, thus resulting in a satisfactory effect in the occipitocervical fusion.

Development and in vitro evaluation of carboxymethyl chitosan based drug delivery system for the controlled release of propranolol hydrochloride

NASA Astrophysics Data System (ADS)

Hernawan; Nur Hayati, Septi; Nisa, Khoirun; Wheni Indrianingsih, Anastasia; Darsih, Cici; Kismurtono, Muhammad

2017-12-01

Propranolol hydrochloride is a nonselective β-adrenergic drug and has been used as angina pectoris, antihypertensive, and that of many other cardiovascular disorders. It has a relatively short plasma half-life and duration of action are considered too short in certain circumstances. Thus, it’s fascinating to elongate the action. The tablet formula was based on extended-release by a propranolol hydrochloride based carboxymethyl chitosan matrix. Here we used direct compression technique with internal wet granulation to prepare the tablets. The tablets were evaluated for physical properties (hardness, weight variation test, friability) and in vitro release studies. There was no interaction observed between propranolol hydrochloride and excipients. Dissolution profiles of each formulation were followed zero order model. In conclusion, these results strongly suggest that in appropriate proportions carboxymethyl chitosan with internal granulation is suitable for formulating propranolol hydrochloride controlled release.

Hippocampal subfield volume changes in subtypes of attention deficit hyperactivity disorder.

PubMed

Al-Amin, Mamun; Zinchenko, Artyom; Geyer, Thomas

2018-04-15

Attention-deficit hyperactivity disorder (ADHD) is accompanied by reduction of total hippocampal volume. However, disorder-related fine-grained structural alterations of hippocampal subfields remain unclear. Here we compared hippocampal subfield volumes in a large sample of patients with ADHD and healthy controls. We used T1-weighted structural 3-Tesla MRI images of 880 individuals (7-21 years old) from the ADHD-200 database. The images were acquired from 553 healthy individuals and 327 children and adolescents with combined (N = 196) and inattentive (N = 131) ADHD subtypes. Hippocampal subfields were segmented into the cornu amonis regions (CA1, CA2/3, CA4), fimbria, hippocampal fissure, presubiculum, subiculum, hippocampal tail, parasubiculum, granule cell layers of the dentate gyrus, molecular layer within the subiculum and the CA fields, and the hippocampal-amygdala transition area using an automatic algorithm available in Freesurfer 6.0. We found a significant reduction of total hippocampal volume in the combined ADHD group compared to healthy controls. This reduction was due to the atrophy of CA1, CA4, molecular layer, granule cell layers of the dentate gyrus, presubiculum, subiculum, and hippocampal tail. These differences were exclusively driven by the corresponding brain volume reduction in the combined ADHD-subtype, while hippocampal volumes in inattentive ADHD showed no reliable differences relative to controls. Finally, there were negative correlations between the reduced hippocampal subfields and behavioral ADHD indices. The present results point to a clear dissociation between inattentive and combined subtypes of ADHD. Therefore, hippocampal subfields may contribute towards understanding the pathophysiology of ADHD. Copyright © 2018 Elsevier B.V. All rights reserved.

Association of Factor V Secretion with Protein Kinase B Signaling in Platelets from Horses with Atypical Equine Thrombasthenia.

PubMed

Norris, J W; Pombo, M; Shirley, E; Blevins, G; Tablin, F

2015-01-01

Two congenital bleeding diatheses have been identified in Thoroughbred horses: Glanzmann thrombasthenia (GT) and a second, novel diathesis associated with abnormal platelet function in response to collagen and thrombin stimulation. Platelet dysfunction in horses with this second thrombasthenia results from a secretory defect. Two affected and 6 clinically normal horses. Ex vivo study. Washed platelets were examined for (1) expression of the αIIb-β3 integrin; (2) fibrinogen binding capacity in response to ADP and thrombin; (3) secretion of dense and α-granules; (4) activation of the mammalian target of rapamycin (mTOR)-protein kinase B (AKT) signaling pathway; and (5) cellular distribution of phosphatidylinositol-4-phosphate-3-kinase, class 2B (PIK3C2B) and SH2 containing inositol-5'-phosphatase 1 (SHIP1). Platelets from affected horses expressed normal amounts of αIIb-β3 integrin and bound fibrinogen normally in response to ADP, but bound 80% less fibrinogen in response to thrombin. α-granules only released 50% as much Factor V as control platelets, but dense granules released their contents normally. Protein kinase B (AKT) phosphorylation was reduced after thrombin activation, but mTOR Complex 2 (mTORC2) and phosphoinositide-dependent kinase 1 (PDK1) signaling were normal. SH2-containing inositol-5'-phosphatase 1 (SHIP1) did not localize to the cytoskeleton of affected platelets and was decreased overall consistent with reduced AKT phosphorylation. Defects in fibrinogen binding, granule secretion, and signal transduction are unique to this thrombasthenia, which we designate as atypical equine thrombasthenia. Copyright © The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.

Rescue of neuronal migration deficits in a mouse model of fetal Minamata disease by increasing neuronal Ca2+ spike frequency.

PubMed

Fahrion, Jennifer K; Komuro, Yutaro; Li, Ying; Ohno, Nobuhiko; Littner, Yoav; Raoult, Emilie; Galas, Ludovic; Vaudry, David; Komuro, Hitoshi

2012-03-27

In the brains of patients with fetal Minamata disease (FMD), which is caused by exposure to methylmercury (MeHg) during development, many neurons are hypoplastic, ectopic, and disoriented, indicating disrupted migration, maturation, and growth. MeHg affects a myriad of signaling molecules, but little is known about which signals are primary targets for MeHg-induced deficits in neuronal development. In this study, using a mouse model of FMD, we examined how MeHg affects the migration of cerebellar granule cells during early postnatal development. The cerebellum is one of the most susceptible brain regions to MeHg exposure, and profound loss of cerebellar granule cells is detected in the brains of patients with FMD. We show that MeHg inhibits granule cell migration by reducing the frequency of somal Ca(2+) spikes through alterations in Ca(2+), cAMP, and insulin-like growth factor 1 (IGF1) signaling. First, MeHg slows the speed of granule cell migration in a dose-dependent manner, independent of the mode of migration. Second, MeHg reduces the frequency of spontaneous Ca(2+) spikes in granule cell somata in a dose-dependent manner. Third, a unique in vivo live-imaging system for cell migration reveals that reducing the inhibitory effects of MeHg on somal Ca(2+) spike frequency by stimulating internal Ca(2+) release and Ca(2+) influxes, inhibiting cAMP activity, or activating IGF1 receptors ameliorates the inhibitory effects of MeHg on granule cell migration. These results suggest that alteration of Ca(2+) spike frequency and Ca(2+), cAMP, and IGF1 signaling could be potential therapeutic targets for infants with MeHg intoxication.

Rescue of neuronal migration deficits in a mouse model of fetal Minamata disease by increasing neuronal Ca2+ spike frequency

PubMed Central

Fahrion, Jennifer K.; Ohno, Nobuhiko; Littner, Yoav; Raoult, Emilie; Galas, Ludovic; Vaudry, David; Komuro, Hitoshi

2012-01-01

In the brains of patients with fetal Minamata disease (FMD), which is caused by exposure to methylmercury (MeHg) during development, many neurons are hypoplastic, ectopic, and disoriented, indicating disrupted migration, maturation, and growth. MeHg affects a myriad of signaling molecules, but little is known about which signals are primary targets for MeHg-induced deficits in neuronal development. In this study, using a mouse model of FMD, we examined how MeHg affects the migration of cerebellar granule cells during early postnatal development. The cerebellum is one of the most susceptible brain regions to MeHg exposure, and profound loss of cerebellar granule cells is detected in the brains of patients with FMD. We show that MeHg inhibits granule cell migration by reducing the frequency of somal Ca2+ spikes through alterations in Ca2+, cAMP, and insulin-like growth factor 1 (IGF1) signaling. First, MeHg slows the speed of granule cell migration in a dose-dependent manner, independent of the mode of migration. Second, MeHg reduces the frequency of spontaneous Ca2+ spikes in granule cell somata in a dose-dependent manner. Third, a unique in vivo live-imaging system for cell migration reveals that reducing the inhibitory effects of MeHg on somal Ca2+ spike frequency by stimulating internal Ca2+ release and Ca2+ influxes, inhibiting cAMP activity, or activating IGF1 receptors ameliorates the inhibitory effects of MeHg on granule cell migration. These results suggest that alteration of Ca2+ spike frequency and Ca2+, cAMP, and IGF1 signaling could be potential therapeutic targets for infants with MeHg intoxication. PMID:22411806

Histological and morphological observations on tongue of Scincella tsinlingensis (Reptilia, Squamata, Scincidae).

PubMed

Yang, Chun; Wang, Limin

2016-01-01

The histology and morphology characteristics of the tongue in Scincella tsinlingensis were studied by light and electronic microscopy. Under light microscopy, the tongue consists of tip, lingual body and radix in sequence. Numerous lingual papillae widely distribute on the surface of the dorsal and ventral flanks in the tongue, in addition to some regions of the tip. The papillae's surface is covered with the epithelial layer. The lamina propria and dense connective tissue are distinct existing under the epithelial layer. There are many lingual glands spread over the lamina propria. Tongue muscle is developed and composed of distinct intrinsic muscle, hyoglossus and genioglossus. By scanning electron microscopy, at higher magnification, the epithelial cells of the dorsal surface in the divaricate tongue tips show numerous microvilli, micro-ridges and micro-pores. The surface of dorsal side of the papillae in lingual body is covered with abundant of micro-ridges and taste bud lacuna. On the surface of the papillae in radix, micro-facets and micro-ridges are compactly distributed, as well as scattered mucilage-pores. The lingual epithelium is divided into four layers observed by the transmission electron microscope. Cells of basal layer are irregularly elliptical in shape, with sparse organelles in the cytoplasm. The deep intermediate layer is not always distinct. Small numbers of organelles are scattered into the cytoplasm. The cells of the superficial intermediate layer gradually flatten, as do their nuclei. The cytoplasm contains many keratohyalin granules. Cell membranes are formed processes around cells and joined by abundant desmosomes to the cell membranes of adjacent cells. The cells located on the extreme free-surface side of the keratinized layer have fallen off. The basal lamina is intercalated between the basal layer and the lamina propria. The lamina propria of lingual body contains lingual gland. A large part of the cytoplasm is occupied by mucus granules which located in the distal part of the cell. The connective tissue contains myelinated nerve fibers, vessel and muscle cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

Acral peeling skin syndrome: report of two cases.

PubMed

García, Elena García; Carreño, Rosario Granados; Martínez González, Miguel A; Reyes, José Jiménez

2005-01-01

Peeling skin syndrome is a rare dermatosis characterized by spontaneous and painless peeling of the skin. The authors report two patients with history of spontaneous, asymptomatic, and noninflammatory peeling skin of the acral surfaces after soaking in water. On light microscopy, blisters were located in the mid layers of the stratum corneum, above the granular layer. Ultrastructural examination revealed increased intercellular lipids and abnormal, "moth-eaten," keratohyalin granules, but the authors were unable to determine whether the separation initiated within the horny cells or between adjacent cells. These patients represented a localized variant of peeling skin syndrome.

High-resolution structural and elemental analyses of calcium storage structures synthesized by the noble crayfish Astacus astacus.

PubMed

Luquet, Gilles; Salomé, Murielle; Ziegler, Andreas; Paris, Céline; Percot, Aline; Dauphin, Yannicke

2016-11-01

During premolt, crayfish develop deposits of calcium ions, called gastroliths, in their stomach wall. The stored calcium is used for the calcification of parts of the skeleton regularly renewed for allowing growth. Structural and molecular analyses of gastroliths have been primarily performed on three crayfish species, Orconectes virilis, Procambarus clarkii, and more recently, Cherax quadricarinatus. We have performed high-resolution analyses of gastroliths from the native noble crayfish, Astacus astacus, focusing on the microstructure, the mineralogical and elemental composition and distribution in a comparative perspective. Field emission scanning electron microscopy (FESEM) and atomic force microscopy (AFM) observations showed a classical layered microstructure composed of 200-nm diameter granules aligned along fibers. These granules are themselves composed of agglomerated nanogranules of 50nm-mean diameters. Denser regions of bigger fused granules are also present. Micro-Raman spectroscopy show that if A. astacus gastroliths, similarly to the other analyzed gastroliths, are mainly composed of amorphous calcium carbonate (ACC), they are also rich in amorphous calcium phosphate (ACP). The presence of a carotenoid pigment is also observed in A. astacus gastrolith contrary to C. quadricarinatus. Energy-dispersive X-ray spectroscopy (EDX) analyses demonstrate the presence of minor elements such as Mg, Sr, Si and P. The distribution of this last element is particularly heterogeneous. X-ray absorption near edge structure spectroscopy (XANES) reveals an alternation of layers more or less rich in phosphorus evidenced in the mineral phase as well as in the organic matrix in different molecular forms. Putative functions of the different P-comprising molecules are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Omega-3 Fatty Acids Supplementation: Therapeutic Potential in a Mouse Model of Stargardt Disease.

PubMed

Prokopiou, Ekatherine; Kolovos, Panagiotis; Kalogerou, Maria; Neokleous, Anastasia; Nicolaou, Orthodoxia; Sokratous, Kleitos; Kyriacou, Kyriacos; Georgiou, Tassos

2018-06-01

To evaluate the therapeutic effects of omega-3 (ω3) fatty acids on retinal degeneration in the ABCA4-/- model of Stargardt disease when the blood level of arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio is between 1 and 1.5. Eight-month-old mice were allocated to three groups: wild type (129S1), ABCA4-/- untreated, and ABCA4-/- ω3 treated. ω3 treatment lasted 3 months and comprised daily gavage administration of EPA and docosahexaenoic acid (DHA). Blood and retinal fatty acid analysis was performed using gas chromatography to adjust the blood AA/EPA ∼1 to 1.5. Eyecups were histologically examined using transmission electron microscopy and confocal microscopy to evaluate lipofuscin granules and the photoreceptor layer. Retinal N-retinylidene-N-retinylethanolamine (A2E), a major component of retinal pigment epithelium lipofuscin, was quantified using liquid chromatography and tandem mass spectrometry, in addition to retinal proteomic analysis to determine changes in inflammatory proteins. EPA levels increased and AA levels decreased in the blood and retinas of the treatment group. Significantly less A2E and lipofuscin granules were observed in the treatment group. The thickness of the outer nuclear layer was significantly greater in the treatment group (75.66 ± 4.80 μm) than in the wild-type (61.40 ± 1.84 μm) or untreated ABCA4-/- (56.50 ± 3.24 μm) groups. Proteomic analysis indicated lower levels of complement component 3 (C3) in the treatment group, indicative of lower complement-induced inflammatory response. Three months of ω3 supplementation (AA/EPA ∼1-1.5) reduces A2E levels, lipofuscin granules, and C3 levels in the ABCA4-/- mouse model of Stargardt disease, consistent with slowing of the disease.

Cathodic Potential Dependence of Electrochemical Reduction of SiO2 Granules in Molten CaCl2

NASA Astrophysics Data System (ADS)

Yang, Xiao; Yasuda, Kouji; Nohira, Toshiyuki; Hagiwara, Rika; Homma, Takayuki

2016-09-01

As part of an ongoing fundamental study to develop a new process for producing solar-grade silicon, this paper examines the effects of cathodic potential on reduction kinetics, current efficiency, morphology, and purity of Si product during electrolysis of SiO2 granules in molten CaCl2 at 1123 K (850 °C). SiO2 granules were electrolyzed potentiostatically at different cathodic potentials (0.6, 0.8, 1.0, and 1.2 V vs Ca2+/Ca). The reduction kinetics was evaluated based on the growth of the reduced Si layer and the current behavior during electrolysis. The results suggest that a more negative cathodic potential is favorable for faster reduction. Current efficiencies in 60 minutes are greater than 65 pct at all the potentials examined. Si wires with sub-micron diameters are formed, and their morphologies show little dependence on the cathodic potential. The impurities in the Si product can be controlled at low level. The rate-determining step for the electrochemical reduction of SiO2 granules in molten CaCl2 changes with time. At the initial stage of electrolysis, the electron transfer is the rate-determining step. At the later stage, the diffusion of O2- ions is the rate-determining step. The major cause of the decrease in reduction rate with increasing electrolysis time is the potential drop from the current collector to the reaction front due to the increased contact resistance among the reduced Si particles.

Correlation between loose density and compactibility of granules prepared by various granulation methods.

PubMed

Murakami, H; Yoneyama, T; Nakajima, K; Kobayashi, M

2001-03-23

The objectives of this study were to prepare the lactose granules by various granulation methods using polyethylene glycol 6000 (PEG 6000) as a binder and to evaluate the effects of granulation methods on the compressibility and compactibility of granules in tabletting. Lactose was granulated by seven granulation methods -- four wet granulations including wet massing granulation, wet high-speed mixer granulation, wet fluidized bed granulation and wet tumbling fluidized bed granulation; and three melt granulations including melt high-speed mixer granulation, melt fluidized bed granulation and melt tumbling fluidized bed granulation. The loose density, angle of repose, granule size distribution, mean diameter of granules, and the tensile strength and porosity of tablets were evaluated. The compactibilities of granules were varied by the granulation methods. However, the difference in compactibility of granules could not be explained due to the difference in compressibility, since there was no difference in Heckel plots due to granulation methods. Among their granule properties, the loose density of granules seemed to have a correlation with the tablet strength regardless of the granulation methods.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bian, Xuting; Zhong, Hongyu; Li, Fen

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

Membrane interactions between secretion granules and plasmalemma in three exocrine glands

PubMed Central

Tanaka, Y; De Camilli, P; Meldolesi, J

1980-01-01

Three types of membrane interactions were studied in three exocrine systems (the acinar cells of the rat parotid, rat lacrimal gland, and guinea pig pancrease) by freeze- fracture and thin-section electron microscopy: exocytosis, induced in vivo by specific pharmacological stimulations; the mutual apposition of secretory granule membranes in the intact cell; membrane appositions induced in vitro by centrifugation of the isolated granules. In all three glandular cells, the distribution of intramembrane particles (IMP) on the fracture faces of the luminal plasmagranule membrane particles (IMP) on the fracture faces of the lumenal plasmalemma appeared random before stimulation. However, after injection of secretagogues, IMP were rapidly clearly from the areas of granule- plasmalemma apposition in the parotid cells and, especially, in lacrimocytes. In the latter, the cleared areas appeared as large bulges toward the lumen, whereas in the parotid they were less pronounced. Exocytotic openings were usually large and the fracture faces of their rims were covered with IMP. In contrast, in stimulated pancreatic acinar cells, the IMP distribution remained apparently random after stimulation. Exocytoses were established through the formation of narrown necks, and no images which might correspond to early stages of membrane fusion were revealed. Within the cytoplasm of parotid and lacrimal cells (but not in the pancreas), both at rest and after stimulation, secretion granules were often closely apposed by means of flat, circular areas, also devoid of IMP. In thin sections, the images corresponding to IMP-free areas were close granule-granule and granule-plasmalemma appositions, sometimes with focal merging of the membrane outer layers to yield pentalaminar structures. Isolated secretion granules were forced together in vitro by centrifugation. Under these conditions, increasing the centrifugal force from 1,600 to 50,000 g for 10 min resulted in a progressive, statistically significant increase of the frequency of IMP-free flat appositions between parotid granules. In contrast, no such areas were seen between freeze-fractured pancreatic granules, although some focal pentalaminar appositions appeared in section after centrifugation at 50 and 100,000 g for 10 min. On the basis of the observation that, in secretory cells, IMP clearing always develops in deformed membrane areas (bulges, depressions, flat areas), it is suggested that it might result from the forced mechanical apposition of the interacting membranes. This might be a preliminary process not sufficient to initiate fusion. In the pancreas, IMP clearing could occur over surface areas too small to be detected. In stimulated parotid and lacrimal glands they were exceptional. These structures were either attached at the sites of continuity between granule and plasma membranes, or free in the acinar lumen, with a preferential location within exocytotic pockets or in their proximity. Experiments designed to investigate the nature of these blisters and vesicles revealed that they probably arise artifactually during glutaraldehyde fixation. In fact, (a) they were large and numerous in poorly fixed samples but were never observed in thin sections of specimens fixed in one step with glutaraldehyde and OsO(4); and (b) no increase in concentration of phospholipids was observed in the parotid saliva and pancreatic juice after stimulation of protein discharge, as was to be expected if release of membrane material were occurring after exocytosis. PMID:7380885

Defective pigment granule biogenesis and aberrant behavior caused by mutations in the Drosophila AP-3beta adaptin gene ruby.

PubMed Central

Kretzschmar, D; Poeck, B; Roth, H; Ernst, R; Keller, A; Porsch, M; Strauss, R; Pflugfelder, G O

2000-01-01

Lysosomal protein trafficking is a fundamental process conserved from yeast to humans. This conservation extends to lysosome-like organelles such as mammalian melanosomes and insect eye pigment granules. Recently, eye and coat color mutations in mouse (mocha and pearl) and Drosophila (garnet and carmine) were shown to affect subunits of the heterotetrameric adaptor protein complex AP-3 involved in vesicle trafficking. Here we demonstrate that the Drosophila eye color mutant ruby is defective in the AP-3beta subunit gene. ruby expression was found in retinal pigment and photoreceptor cells and in the developing central nervous system. ruby mutations lead to a decreased number and altered size of pigment granules in various cell types in and adjacent to the retina. Humans with lesions in the related AP-3betaA gene suffer from Hermansky-Pudlak syndrome, which is caused by defects in a number of lysosome-related organelles. Hermansky-Pudlak patients have a reduced skin pigmentation and suffer from internal bleeding, pulmonary fibrosis, and visual system malfunction. The Drosophila AP-3beta adaptin also appears to be involved in processes other than eye pigment granule biogenesis because all ruby allele combinations tested exhibited defective behavior in a visual fixation paradigm. PMID:10790396

Cell wall biogenesis in Oocystis: experimental alteration of microfibril assembly and orientation.

PubMed

Montezinos, D; Brown, R M

1978-01-01

Cell wall biogenesis in the unicellular green alga Oocystis apiculata has been studied. Under normal growth conditions, a cell wall with ordered microfibrils is synthesized. In each layer there are rows of parallel microfibrils. Layers are nearly perpendicular to each other. Terminal linear synthesizing complexes are located in the plasma membrane, and they are capable of bidirectional synthesis of cellulose microfibrils. Granule bands associated with the inner leaflet of the plasma membrane appear to control the orientation of newly synthesized microfibrils. Subcortical microtubules also are present during wall synthesis. Patterns of cell wall synthesis were studied after treatment with EDTA and EGTA as well as divalent cations (MgSO4, CaSO4, Cacl2). 0.1 M EDTA treatment for 15 min results in the disassociation of the terminal complexes from the ends of microfibrils. EDTA-treated cells followed by 15 min treatment with MgSO4 results in reaggregation of the linear complexes into a paired state, remote from the original ends to which they were associated. After 90 min treatment with MgSO4, normal synthesis resumes. EGTA and calcium salts do not affect the linear complexes or microfibril orientation. Treatments with colchicine and vinblastine sulphate do not depolymerize the microtubles, but the wall microfibril orientation is altered. With colchicine or vinblastine, the change in orientation from layer to layer is inhibited. The process is reversible upon removal of the drugs. Lumicolchicine has no effect upon microfibril orientation, but granule bands are disorganized. Treatment with coumarin, a known inhibitor of cellulose synthesis, causes the loss of visualization of subunits of the terminal complexes. The possibility of the existence of a membrane-associated colchicine-sensitive orientation protein for cellulose microfibrils is discussed. Transmembrane modulation of microfibril synthesis and orientation is presented.

Fine structure of the dorsal lingual epithelium of the juvenile hawksbill turtle, Eretmochelys imbricata bissa.

PubMed

Iwasaki, S; Asami, T; Wanichanon, C

1996-04-01

Various species of turtles are adapted to different environments, such as freshwater, seawater, and terrestrial habitats. Comparisons of histological and ultrastructural features of the tongue of the juvenile Hawksbill turtle, Eretmochelys imbricata bissa, with those of freshwater turtles should reveal some aspects of the relationship between the structure of the lingual epithelium and the environment. The light microscope, scanning electron microscope and transmission electron microscope were used. Light microscopy revealed that the mucosal epithelium of the tongue was of the keratinized, stratified squamous type. Under the scanning electron microscope, no lingual papillae were visible on the dorsal surface of the tongue. Micropits and the thickening of cell margins were clearly seen on the surface of cells located on the outermost side. The transmission electron microscope revealed that the cells in the intermediate layer were gradually flattened from the basal side to the surface side, as were their nuclei. In the shallow intermediate layer, the cells were significantly flattened, and their nuclei were condensed or had disappeared. The cytoplasm contained keratohyalin granules, tonofibrils, free ribosomes, mitochondria, and rough endoplasmic reticulum. Numerous free ribosomes were attached to the surface of small keratohyalin granules. The cells of the keratinized layer were significantly flattened, and their nuclei had completely disappeared. Most of cytoplasm was filled with keratin fibers of high electron density. Keratin fibers of the shedding cells, which were located on the outermost side of the keratinized layer, appeared looser, and each fiber, which was somewhat thicker than the tonofibrils and tonofilaments, was clearly distinguishable. The lingual epithelium of the juvenile Hawksbill turtle differs significantly from that of the adult freshwater turtle, in spite of the similarity in gross morphology of the tongues of these species.

Evaluation of the tissue reaction to a new bilayered collagen matrix in vivo and its translation to the clinic.

PubMed

Ghanaati, Shahram; Schlee, Markus; Webber, Matthew J; Willershausen, Ines; Barbeck, Mike; Balic, Ela; Görlach, Christoph; Stupp, Samuel I; Sader, Robert A; Kirkpatrick, C James

2011-02-01

This study evaluates a new collagen matrix that is designed with a bilayered structure in order to promote guided tissue regeneration and integration within the host tissue. This material induced a mild tissue reaction when assessed in a murine model and was well integrated within the host tissue, persisting in the implantation bed throughout the in vivo study. A more porous layer was rapidly infiltrated by host mesenchymal cells, while a layer designed to be a barrier allowed cell attachment and host tissue integration, but at the same time remained impermeable to invading cells for the first 30 days of the study. The tissue reaction was favorable, and unlike a typical foreign body response, did not include the presence of multinucleated giant cells, lymphocytes, or granulation tissue. In the context of translation, we show preliminary results from the clinical use of this biomaterial applied to soft tissue regeneration in the treatment of gingival tissue recession and exposed roots of human teeth. Such a condition would greatly benefit from guided tissue regeneration strategies. Our findings demonstrate that this material successfully promoted the ingrowth of gingival tissue and reversed gingival tissue recession. Of particular importance is the fact that the histological evidence from these human studies corroborates our findings in the murine model, with the barrier layer preventing unspecific tissue ingrowth, as the scaffold becomes infiltrated by mesenchymal cells from adjacent tissue into the porous layer. Also in the clinical situation no multinucleated giant cells, no granulation tissue and no evidence of a marked inflammatory response were observed. In conclusion, this bilayered matrix elicits a favorable tissue reaction, demonstrates potential as a barrier for preferential tissue ingrowth, and achieves a desirable therapeutic result when applied in humans for soft tissue regeneration.

Reduction of the plastidial phosphorylase in potato (Solanum tuberosum L.) reveals impact on storage starch structure during growth at low temperature.

PubMed

Orawetz, Tom; Malinova, Irina; Orzechowski, Slawomir; Fettke, Joerg

2016-03-01

Tubers of potato (Solanum tuberosum L.), one of the most important crops, are a prominent example for an efficient production of storage starch. Nevertheless, the synthesis of this storage starch is not completely understood. The plastidial phosphorylase (Pho1; EC 2.4.1.1) catalyzes the reversible transfer of glucosyl residues from glucose-1-phosphate to the non-reducing end of α-glucans with the release of orthophosphate. Thus, the enzyme is in principle able to act during starch synthesis. However, so far under normal growth conditions no alterations in tuber starch metabolism were observed. Based on analyses of other species and also from in vitro experiments with potato tuber slices it was supposed, that Pho1 has a stronger impact on starch metabolism, when plants grow under low temperature conditions. Therefore, we analyzed the starch content, granule size, as well as the internal structure of starch granules isolated from potato plants grown under low temperatures. Besides wild type, transgenic potato plants with a strong reduction in the Pho1 activity were analyzed. No significant alterations in starch content and granule size were detected. In contrast, when plants were cultivated at low temperatures the chain length distributions of the starch granules were altered. Thus, the granules contained more short glucan chains. That was not observed in the transgenic plants, revealing that Pho1 in wild type is involved in the formation of the short glucan chains, at least at low temperatures. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Influence of granulating method on physical and mechanical properties, compression behavior, and compactibility of lactose and microcrystalline cellulose granules.

PubMed

Horisawa, E; Danjo, K; Sunada, H

2000-06-01

The physical and mechanical properties of lactose (LC) and microcrystalline cellulose (MCC) granules prepared by various granulating methods were determined, and their effects on the compression and strength of the tablets were examined. From the force-displacement curve obtained in a crushing test on a single granule, all LC granules appeared brittle, and MCC granules were somewhat plastically deformable. Inter-granular porosity epsilon inter clearly decreased with greater spherical granule shape for both materials. Decrease in intragranular porosity epsilon intra enhanced the crushing force of a single granule Fg. Agitating granulation brought about the most compactness and hardness of granules. In granule compression tests, the initial slope of Heckel plots K1 appeared closely related to ease of filling voids in a granule bed by the slippage or rolling of granules. The reciprocal of the slope in the succeeding step 1/K2 in compression of MCC granules indicated positive correlation to Fg, while in LC granules, no such obvious relation was evident. 1/K2 differed only slightly among granulating methods. Tensile strength of tablets Tt obtained by compression of various LC granules was low as a whole and was little influenced by granulating method. For MCC granules, which are plastically deformable, tablet strength greatly depended on granulation. Granules prepared by extruding or dry granulation gave strong tablets. Tablets prepared from granules made by the agitating method showed particularly low Tt. From stereomicroscopic observation, the contact area between granule particles in a tablet appeared smaller; this would explain the decrease in inter-granular bond formation.

Numerical Control Device for Preparation Nano-Carbon Granule Coating Superhydrophobic Template and Its Application

NASA Astrophysics Data System (ADS)

Shang, G. R.; Li, Y.

2017-12-01

It is one of the ways for changing surface property by fabricating superhydrophibic coating with the help of template that is made of depositing nano-carbon particles of fuel flame on substrate such as pure copper or aluminium alloy. In the process of making template, it is difficult to keep the deposition layer uniformed. In this work, the problem was solved by manufacturing a set of numerical control equipment. It has been proved by application test that the deposition layer was uniformed by means of this facility. The contact angle is more than 150°. A new way has been developed for making superhydrohibic template.

Evaluation of rate of swelling and erosion of verapamil (VRP) sustained-release matrix tablets.

PubMed

Khamanga, Sandile M; Walker, Roderick B

2006-01-01

Tablets manufactured in-house were compared to a marketed sustained-release product of verapamil to investigate the rate of hydration, erosion, and drug-release mechanism by measuring the wet and subsequent dry weights of the products. Swelling and erosion rates depended on the polymer and granulating fluid used, which ultimately pointed to their permeability characteristics. Erosion rate of the marketed product was highest, which suggests that the gel layer that formed around these tablets was weak as opposed to the robust and resistant layers of test products. Anomalous and near zero-order transport mechanisms were dominant in tests and commercial product, respectively.

Altered cerebellar development in nuclear receptor TAK1/ TR4 null mice is associated with deficits in GLAST(+) glia, alterations in social behavior, motor learning, startle reactivity, and microglia.

PubMed

Kim, Yong-Sik; Harry, G Jean; Kang, Hong Soon; Goulding, David; Wine, Rob N; Kissling, Grace E; Liao, Grace; Jetten, Anton M

2010-09-01

Previously, deficiency in the expression of the nuclear orphan receptor TAK1 was found to be associated with delayed cerebellar granule cell migration and Purkinje cell maturation with a permanent deficit in foliation of lobules VI–VII, suggesting a role for TAK1 in cerebellum development. In this study, we confirm that TAK1-deficient (TAK1(−/−)) mice have a smaller cerebellum and exhibit a disruption of lobules VI–VII. We extended these studies and show that at postnatal day 7, TAK1(−/−) mice exhibit a delay in monolayer maturation of dysmorphic calbindin 28K-positive Purkinje cells. The astrocyte-specific glutamate transporter (GLAST) was expressed within Bergmann fibers and internal granule cell layer at significantly lower levels in the cerebellum of TAK1(−/−) mice. At PND21, Golgi-positive Purkinje cells in TAK1(−/−) mice displayed a smaller soma (18%) and shorter distance to first branch point (35%). Neuronal death was not observed in TAK1(−/−) mice at PND21; however, activated microglia were present in the cerebellum, suggestive of earlier cell death. These structural deficits in the cerebellum were not sufficient to alter motor strength, coordination, or activity levels; however, deficits in acoustic startle response, prepulse startle inhibition, and social interactions were observed. Reactions to a novel environment were inhibited in a light/dark chamber, open-field, and home-cage running wheel. TAK1(−/−) mice displayed a plateau in performance on the running wheel, suggesting a deficit in learning to coordinate performance on a motor task. These data indicate that TAK1 is an important transcriptional modulator of cerebellar development and neurodevelopmentally regulated behavior.

Using a million cell simulation of the cerebellum: network scaling and task generality.

PubMed

Li, Wen-Ke; Hausknecht, Matthew J; Stone, Peter; Mauk, Michael D

2013-11-01

Several factors combine to make it feasible to build computer simulations of the cerebellum and to test them in biologically realistic ways. These simulations can be used to help understand the computational contributions of various cerebellar components, including the relevance of the enormous number of neurons in the granule cell layer. In previous work we have used a simulation containing 12000 granule cells to develop new predictions and to account for various aspects of eyelid conditioning, a form of motor learning mediated by the cerebellum. Here we demonstrate the feasibility of scaling up this simulation to over one million granule cells using parallel graphics processing unit (GPU) technology. We observe that this increase in number of granule cells requires only twice the execution time of the smaller simulation on the GPU. We demonstrate that this simulation, like its smaller predecessor, can emulate certain basic features of conditioned eyelid responses, with a slight improvement in performance in one measure. We also use this simulation to examine the generality of the computation properties that we have derived from studying eyelid conditioning. We demonstrate that this scaled up simulation can learn a high level of performance in a classic machine learning task, the cart-pole balancing task. These results suggest that this parallel GPU technology can be used to build very large-scale simulations whose connectivity ratios match those of the real cerebellum and that these simulations can be used guide future studies on cerebellar mediated tasks and on machine learning problems. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cytologic appearance of retinal cells included in a fine-needle aspirate of a meningioma around the optic nerve of a dog.

PubMed

Tvedten, Harold; Hillström, Anna

2013-06-01

A 6-year-old Wirehair Dachshund had a meningioma around the optic nerve that caused exophthalmos. A benign mesenchymal tumor was suspected based on the cytologic pattern of a fine-needle aspirate, and a meningioma was diagnosed by histopathologic examination. In addition to the meningioma cells, the cytologic smears included groups of cells from apparently 4 layers of normal retina. In particular, uniform rod-shaped structures in the cytologic sample could suggest rod-shaped bacteria, but these structures were identified as cylindrical outer segments of photoreceptor rod cells. Other retinal structures recognized included pigmented epithelial layer cells with their uniquely formed pigment granules, the characteristic bi-lobed, cleaved nuclei from the outer nuclear layer, and nerve tissue likely from the outer plexiform layer of the retina. © 2013 American Society for Veterinary Clinical Pathology.

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

PubMed

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

2008-05-01

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

A ketogenic diet rescues hippocampal memory defects in a mouse model of Kabuki syndrome.

PubMed

Benjamin, Joel S; Pilarowski, Genay O; Carosso, Giovanni A; Zhang, Li; Huso, David L; Goff, Loyal A; Vernon, Hilary J; Hansen, Kasper D; Bjornsson, Hans T

2017-01-03

Kabuki syndrome is a Mendelian intellectual disability syndrome caused by mutations in either of two genes (KMT2D and KDM6A) involved in chromatin accessibility. We previously showed that an agent that promotes chromatin opening, the histone deacetylase inhibitor (HDACi) AR-42, ameliorates the deficiency of adult neurogenesis in the granule cell layer of the dentate gyrus and rescues hippocampal memory defects in a mouse model of Kabuki syndrome (Kmt2d +/βGeo ). Unlike a drug, a dietary intervention could be quickly transitioned to the clinic. Therefore, we have explored whether treatment with a ketogenic diet could lead to a similar rescue through increased amounts of beta-hydroxybutyrate, an endogenous HDACi. Here, we report that a ketogenic diet in Kmt2d +/βGeo mice modulates H3ac and H3K4me3 in the granule cell layer, with concomitant rescue of both the neurogenesis defect and hippocampal memory abnormalities seen in Kmt2d +/βGeo mice; similar effects on neurogenesis were observed on exogenous administration of beta-hydroxybutyrate. These data suggest that dietary modulation of epigenetic modifications through elevation of beta-hydroxybutyrate may provide a feasible strategy to treat the intellectual disability seen in Kabuki syndrome and related disorders.

Tracheal replacement in rabbits with a new composite silicone-metallic prosthesis.

PubMed

Dodge-Khatami, Ali; Niessen, Hans W M; Koole, Leo H; Klein, Marloes G; van Gulik, Thomas M; de Mol, Bas A J M

2003-09-01

A new composite silicone-metallic prosthesis was tested, studying the potential for respiratory epithelial covering over the biocompatible inner lining, in a rabbit survival model. Seven New Zealand White rabbits underwent near-total excision of their trachea and implantation of a sterile prosthesis. After 2 months, they were sacrificed and the prostheses were retrieved. Specimens were fixed and histologically examined for tissue reaction around the prosthesis, at the anastomotic lines, and particularly for the presence or absence of epithelialization of the inner lumen over the biocompatible surface. All rabbits survived the operation. At 2 months, the outer layer of the prosthesis was consistently covered with fibrosis and neutrophils. The inner layer showed necrotic cells and scant re-epithelialization over the biocompatible lining, up to 5 mm beyond the anastomosis, with no evidence of organized respiratory epithelium in the middle sections. The new prosthesis is a viable temporary solution for airway replacement in rabbits. Granulation tissue was not observed at the anastomosis, and re-epithelialization did occur, but failed to achieve full-length luminal covering. The potential for granulation tissue does not yet make this an ideal long-term solution. Improvements in prosthesis design or biocompatibility are required, and need to be re-evaluated before applicability for chronic use.

Microstructure of the feather in Japanese Jungle Crows (Corvus macrorhynchos) with distinguishing gender differences.

PubMed

Lee, Eunok; Aoyama, Masato; Sugita, Shoei

2009-09-01

Assessing gender difference in Japanese Jungle Crows (Corvus macrorhynchos) is difficult by gross observation because both sexes have black plumage colors. Careful observation of the plumage, however, reveals that it is actually iridescent glossy purple and dark-green in color, and that these colors are more marked in adult males than in females. In birds, such iridescent structural colors are generally produced in the feather barbules, where light is scattered constructively by laminar arrays consisting of alternating layers of materials with different refractive indices, namely keratin, melanin and air. We have investigated differences in the microstructure of the feathers of male and female Jungle Crows by means of scanning and transmission electron microscopy. Male birds had more barbs than females, and the length of the prongs was shorter in males than in females. The density of the melanin granules in the cross-section of barbules was higher in males than in females. Moreover, only in males did the melanin granules show an ordered arrangement beneath a keratin cortex layer at the edges of barbules. These results demonstrate that there are microstructural differences in the feathers of male and female Jungle Crows and suggest that the Jungle Crows' feathers may have iridescent coloring that differs according to gender.

A novel DPP6 isoform (DPP6-E) can account for differences between neuronal and reconstituted A-type K(+) channels.

PubMed

Maffie, Jonathon; Blenkinsop, Timothy; Rudy, Bernardo

2009-01-16

The channels mediating most of the somatodendritic A-type K(+) current in neurons are thought to be ternary complexes of Kv4 pore-forming subunits and two types of auxiliary subunits, the K(+) channel interacting proteins (KChIPs) and dipeptidyl-peptidase-like (DPPL) proteins. The channels expressed in heterologous expression systems by mixtures of Kv4.2, KChIP1 and DPP6-S resemble in many properties the A-type current in hippocampal CA1 pyramidal neurons and cerebellar granule cells, neurons with prominent A-type K(+) currents. However, the native currents have faster kinetics. Moreover, the A-type currents in neurons in intermediary layers of the superior colliculus have even faster inactivating rates. We have characterized a new DPP6 spliced isoform, DPP6-E, that produces in heterologous cells ternary Kv4 channels with very fast kinetics. DPP6-E is selectively expressed in a few neuronal populations in brain including cerebellar granule neurons, hippocampal pyramidal cells and neurons in intermediary layers of the superior colliculus. The effects of DPP6-E explain past discrepancies between reconstituted and native Kv4 channels in some neurons, and contributes to the diversity of A-type K(+) currents in neurons.

Theoretical and experimental analysis of AlGaInP micro-LED array with square-circle anode

NASA Astrophysics Data System (ADS)

Tian, Chao; Wang, Weibiao; Liang, Jingqiu; Liang, Zhongzhu; Qin, Yuxin; Lv, Jinguang

2015-04-01

An array of 320 × 240 micro-light-emitting diodes (micro-LEDs) based on an AlGaInP epitaxial wafer and with a unit size of 100 µm×100 µm was designed and fabricated. The optimum width of the isolation groove between adjacent light-emitting units was determined based on a compromise between full isolation of each LED and maximization of the light emitting area, and was found to be 20 µm. The grooves were filled with a mixed Si granule-polyurethane composite medium, because this type of insulating material can reflect part of the emitted light from the sidewall to the window layer in each light-emitting unit, and could thus improve lighting output efficiency. The 10-µm-wide square-circle anode was designed to increase the light emitting area while simultaneously being simple to fabricate. The device current used was in the 0.42-1.06 mA range to guarantee internal quantum efficiency of more than 85%, with a corresponding voltage range of 2-2.3 V. The layered temperature distribution in a single unit was simulated under a drive voltage of 2.2 V, and the maximum device temperature was 341 K. The micro-opto-electro-mechanical systems (MOEMS) technology-based fabrication process, experimental images of the device and device test results are presented here.

Theoretical and experimental analysis of AlGaInP micro-LED array with square-circle anode

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tian, Chao; University of Chinese Academy of Sciences, Beijing 100049; Wang, Weibiao, E-mail: wangwbcn@163.com

An array of 320 × 240 micro-light-emitting diodes (micro-LEDs) based on an AlGaInP epitaxial wafer and with a unit size of 100 µm×100 µm was designed and fabricated. The optimum width of the isolation groove between adjacent light-emitting units was determined based on a compromise between full isolation of each LED and maximization of the light emitting area, and was found to be 20 µm. The grooves were filled with a mixed Si granule-polyurethane composite medium, because this type of insulating material can reflect part of the emitted light from the sidewall to the window layer in each light-emitting unit,more » and could thus improve lighting output efficiency. The 10-µm-wide square-circle anode was designed to increase the light emitting area while simultaneously being simple to fabricate. The device current used was in the 0.42–1.06 mA range to guarantee internal quantum efficiency of more than 85%, with a corresponding voltage range of 2–2.3 V. The layered temperature distribution in a single unit was simulated under a drive voltage of 2.2 V, and the maximum device temperature was 341 K. The micro-opto-electro-mechanical systems (MOEMS) technology-based fabrication process, experimental images of the device and device test results are presented here.« less

The timing of cortical granule fusion, content dispersal, and endocytosis during fertilization of the hamster egg: an electrophysiological and histochemical study.

PubMed

Kline, D; Stewart-Savage, J

1994-03-01

To determine the temporal relationship between cortical granule exocytosis and the repetitive calcium transients, which are characteristic of mammalian fertilization, we monitored membrane addition from exocytosis during fertilization of hamster eggs. Continuous measurement of membrane capacitance by applying a 3.1-nA alternating current at 375 Hz showed addition of cortical granule membrane. Simultaneous measurement of membrane potential revealed each calcium transient by the appearance of transient hyperpolarizing responses due to calcium-activated potassium channels in the egg. The initial membrane capacitance of the eggs averaged 736 +/- 44 pF (mean +/- SD; n = 7) and an increase in capacitance of 61 +/- 19 pF occurred within 4 sec of the start of the first hyperpolarizing response (HR) after fertilization. Immediately after the first increase in capacitance there was a gradual decline in membrane capacitance in all eggs and in five/seven eggs the capacitance returned to the unfertilized level in 7.8 +/- 4.4 min. The gradual decline in capacitance after the first increase indicated endocytosis, which was confirmed by the internalization of fluorescently labeled dextran. Superimposed on the gradual decline in membrane capacitance were smaller increases in capacitance that occurred with the second and later HRs. The total increase in capacitance from the first three events averaged 72 +/- 19 pF, representing an average increase in capacitance of about 10% of the capacitance of the unfertilized egg. By labeling eggs before and after permeabilization with two different fluorochromes attached to Lens culinaris agglutinin, we demonstrate that the dispersal of the cortical granules contents does not occur immediately after exocytosis. Our results demonstrate that cortical granule exocytosis in hamster eggs is closely coupled to the periodic increases in calcium, that the contents of the cortical granules are slow to disperse, and that after exocytosis, the surface area of the egg returns to the unfertilized level because of a period of endocytosis.

Protein Mobility within Secretory Granules

PubMed Central

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

2014-01-01

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 cm2/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 accompanying study, we suggest that, additionally, tPA itself stabilizes the fusion pore with dimensions that restrict its own exit. PMID:24988337

A New Host for Caryospora lampropeltis (Apicomplexa: Eimeriidae) from the Eastern Hognose Snake, Heterodon platirhinos (Ophidia: Colubroidea: Dipsadinae), from Arkansas, U.S.A., with a Summary of Hosts of This Coccidian

PubMed Central

Seville, R. Scott; Connior, Matthew B.

2016-01-01

Between May 2012 and July 2013, four eastern hognose snakes (Heterodon platirhinos) were collected from Arkansas (n = 2) and Oklahoma (n = 2), U.S.A., and examined for coccidians. A single H. platirhinos from Arkansas was found to be passing oocysts of Caryospora lampropeltis Anderson, Duszynski, and Marquardt. Oocysts of C. lampropeltis were spheroidal to slightly subspheroidal with a rough, colourless, bi-layered wall, measure 23.5 × 22.8 µm, and have a length/width (L/W) ratio of 1.0; both micropyle and oocyst residuum were absent, but a prominent polar granule was present. Sporocysts are ovoidal, 16.8 × 12.8 µm, L/W 1.3; a prominent Stieda and subStieda body was present; a sporocyst residuum was present and composed of numerous spheroidal granules dispersed into small and large granules. Sporozoites lie lengthwise and parallel in a semi-spiral in sporocyst; a spheroidal anterior refractile and posterior refractile body is present; a single nucleus is located between the 2 refractile bodies. This represents the first report of a caryosporan reported from H. platirhinos as well as the only known coccidian from this host. A summary of hosts of C. lampropeltis is provided. PMID:27917072

A wave model for rigid-frame porous materials using lumped parameter concepts

NASA Astrophysics Data System (ADS)

Rossetti, S.; Gardonio, P.; Brennan, M. J.

2005-08-01

The work presented in this paper concerns the behaviour of porous media when exposed to a normal incidence sound field. A propagating wave model based on lumped parameter concepts of acoustic mass, stiffness and damping is used to investigate the absorption phenomena due to the wave propagation in the layer(s) and interference effects due to the wave reflection-transmission at the interfaces of the layer(s). Results from the theoretical model have been validated by measurements on samples of consolidated rubber granulate material. Two typical installations where a layer of porous material is placed next to a rigid wall, and where it is placed at a distance from a rigid wall are used as reference cases. The geometrical and physical properties of porous materials can be described by such parameters as the non-dimensional shape factor and the porosity. The propagating model introduced is used to investigate the effect of these two parameters on acoustic absorption and thus relate the physical properties to the acoustic behaviour.

Enhancing tablet disintegration characteristics of a highly water-soluble high-drug-loading formulation by granulation process.

PubMed

Pandey, Preetanshu; Levins, Christopher; Pafiakis, Steve; Zacour, Brian; Bindra, Dilbir S; Trinh, Jade; Buckley, David; Gour, Shruti; Sharif, Shasad; Stamato, Howard

2018-07-01

The objective of this study was to improve the disintegration and dissolution characteristics of a highly water-soluble tablet matrix by altering the manufacturing process. A high disintegration time along with high dependence of the disintegration time on tablet hardness was observed for a high drug loading (70% w/w) API when formulated using a high-shear wet granulation (HSWG) process. Keeping the formulation composition mostly constant, a fluid-bed granulation (FBG) process was explored as an alternate granulation method using a 2 (4-1) fractional factorial design with two center points. FBG batches (10 batches) were manufactured using varying disingtegrant amount, spray rate, inlet temperature (T) and atomization air pressure. The resultant final blend particle size was affected significantly by spray rate (p = .0009), inlet T (p = .0062), atomization air pressure (p = .0134) and the interaction effect between inlet T*spray rate (p = .0241). The compactibility of the final blend was affected significantly by disintegrant amount (p < .0001), atomization air pressure (p = .0013) and spray rate (p = .05). It was observed that the fluid-bed batches gave significantly lower disintegration times than the HSWG batches, and mercury intrusion porosimetry data revealed that this was caused by the higher internal pore structure of tablets manufactured using the FBG batches.

"Reticular" and "Areticular" Nissl Bodies in Sympathetic Neurons of a Lizard

PubMed Central

Smith, Stuart W.

1959-01-01

Sympathetic ganglia of the horned lizard, Phrynosoma cornutum, were fixed in OsO4 and imbedded in methacrylate. Thin sections were cut for electron microscopy. Some adjacent thick sections were cut for light microscopy and were stained in acidified, dilute thionine both before and after digestion by RNase. In the light microscope two types of Nissl bodies are found, both removable by RNase: (1) a deep, diffuse, indistinctly bounded, metachromatic variety, and (2) a superficial, dense, sharply delimited, orthochromatic sort. Electron microscopically, the former ("reticular" Nissl bodies) corresponds to the granulated endoplasmic reticular structure of Nissl material previously described by others, whereas the latter ("areticular" Nissl bodies) comprises compact masses of particles of varying internal density and devoid of elements of endoplasmic reticulum. The constituent particles of the areticular Nissl material are 4 to 8 x the diameter of single ribonucleoprotein granules of the reticular Nissl substance and seem, near zones of junction with the reticular type, to arise by clustering of such granules with subsequent partial dispersion of the substance of the granules into an added, less dense material. It is suggested that the observed orthochromasia of the areticular Nissl substance is due to accumulation of a large amount of protein bound to RNA and, further, that these Nissl bodies may represent storage depots of RNA and protein. PMID:13673051

Effect of steroid hormones on Bufo arenarum oviduct. Ultrastructural study.

PubMed

Medina, Marcela Fátima; Crespo, Claudia Alejandra; Ramos, Inés; Cisint, Susana Beatriz; Fernández, Silvia Nélida

2007-06-01

The endocrine regulation of the mucosa of the oviductal pars convoluta was analyzed by ultrastructural studies demonstrating that ovariectomy, together with a decrease in ovarian steroids circulating levels, caused a marked regression in this portion of Bufo arenarum oviduct. Twenty-five days after ovariectomy, a decrease in the depth of the epithelial and glandular layers was observed due to the notable loss of secretory cells, whose number was clearly smaller than in nonovariectomized females. The remaining secretory cells showed involution signs, with few secretory granules in their cytoplasm, little endoplasmic reticulum near poorly developed Golgi complexes and a large amount of lipid droplets. Cells in an advanced autolysis state were found in the lumen. These characteristics evidence a nonfunctional state of the pars convoluta. Treatment with 5alpha-dihydrotestosterone (DHT) completely reversed the ovariectomy effect, inducing pars convoluta growths and restoring the characteristics of epithelial and glandular secretory cells in the whole pars convoluta, with micrographs similar to the control. These same effects were observed after treatment with estradiol-17beta (E2), progesterone (P) o E(2)+P in the glandular layer of the whole pars convoluta, but only in the epithelial layer of the most anterior region of this duct. In the secretory cells of other segments these treatments induced the formation of granules of high electron density and homogeneous aspect. Each steroid had a particular effect on the pars convoluta. Although E2 and DHT induced the development of the organoids involved in the proteins biosynthesis, P and DHT acted as secretagogues. (c) 2007 Wiley-Liss, Inc.

Detection of component segregation in granules manufactured by high shear granulation with over-granulation conditions using near-infrared chemical imaging.

PubMed

Koide, Tatsuo; Nagato, Takuya; Kanou, Yoshiyuki; Matsui, Kou; Natsuyama, Susumu; Kawanishi, Toru; Hiyama, Yukio

2013-01-30

The objective of this study was to evaluate the high shear granulation process using near-infrared (NIR) chemical imaging technique and to make the findings available for pharmaceutical development. We prepared granules and tablets made under appropriate- and over-granulation conditions with high shear granulation and observed these granules and tablets using NIR chemical imaging system. We found an interesting phenomenon: lactose agglomeration and segregation of ingredients occurred in experimental tablets when over-granulation conditions, including greater impeller rotation speeds and longer granulation times, were employed. Granules prepared using over-granulation conditions were larger and had progressed to the consolidation stage; segregation between ethenzamide and lactose occurred within larger granules. The segregation observed here is not detectable using conventional analytical technologies such as high pressure liquid chromatography (HPLC) because the content of the granules remained uniform despite the segregation. Therefore, granule visualization using NIR chemical imaging is an effective method for investigating and evaluating the granulation process. Copyright © 2012 Elsevier B.V. All rights reserved.

ELECTRON MICROSCOPY OF HELA CELLS INFECTED WITH ADENOVIRUSES

PubMed Central

Harford, Carl G.; Hamlin, Alice; Parker, Esther; van Ravenswaay, Theodore

1956-01-01

HeLa cells were infected with adenoviruses (types 1–4) and sectioned for electron microscopy after intervals of 20 to 48 hours. Clusters of virus-like particles were found within the nuclei of infected cultures but not in those of uninfected controls. The particles were often arranged in rows as if in crystalline formation. Maximal diameter of particles was approximately 65 mµ, and internal bodies were demonstrated. Lesions of infected cells included target-like structures of the nuclear membrane, large nuclear vacuoles (type 2), and increased numbers of large irregular electron-dense granules in the cytoplasm 48 hours after infection. Examination of infected cultures by light microscopy, using the Feulgen reaction, showed intranuclear inclusion bodies and a cytopathogenic effect consisting of clumping of cells without pyknosis of nuclei. A lipide stain showed numerous cytoplasmic granules that were not identical with the large, irregular, electron-dense granules of the cytoplasm. Practically all the cells showed the viral cytopathogenic effect, but only a minority of cells were found to contain virus-like particles or intranuclear inclusion bodies. PMID:13357696

MODster: Namespaces and Redirection for Earth Science Data

NASA Astrophysics Data System (ADS)

Frew, J.; Metzger, D.; Slaughter, P.

2005-12-01

MODster is a distributed, decentralized inventory server for Earth science data granules (standard units of data content and structure.) MODster connects data granule users (people who know which specific granule they want, but who don't know who has it or how to get it) with data granule providers (people or institutions that keep granules accessible online.) * If you're a provider, you can tell MODster which granules you have and where they live (i.e., their URLs.) * If you're a user, you can ask MODster for a granule, and it will transparently redirect your request to whomever has it. The key to making this work is a standard granule namespace. A granule namespace is a naming convention that associates particular names with particular granules, regardless of where those granules live. Different Earth science data products have their own granule namespaces. For example, in the MODIS granule namespace, the granule name "MOD43A2.A1998365.h5.v8.001.1999001090020.hdf" always refers to version 1 of the 5th horizontal and 8th vertical tile of the Level 3 16-day Bi-directional Reflectance Distribution Function product, acquired by the MODIS Terra sensor on 31 December 1998 and generated on 01 January 1999 at 9:00:20 AM. A MODster URL is simply a standard way of referring to a data product namespace and one of its granules. MODster URLs have the general form "http://server/namespace/granule" where "granule" is a granule name that conforms to a granule namespace, "namespace" is a MODster namespace, which is the name of a granule namespace whose conventions are known to MODster, and "server" is a MODster server, which is an HTTP server that can redirect namespace/granule requests to granule providers. A MODster URL with no granule component gets a description of the MODster namespace, its authority (the persons or institutions responsible for documenting and maintaining the naming convention), and also any services for that MODster namespace that the MODster server supports. Our current MODster implementation allows granule providers to explicitly register their granules, and can also crawl provider sites looking for granules whose names match specific rules or regular expressions.

Glinide, but Not Sulfonylurea, Can Evoke Insulin Exocytosis by Repetitive Stimulation: Imaging Analysis of Insulin Exocytosis by Secretagogue-Induced Repetitive Stimulations

PubMed Central

Aoyagi, Kyota; Ohara-Imaizumi, Mica; Nishiwaki, Chiyono; Nakamichi, Yoko; Nagamatsu, Shinya

2009-01-01

To investigate the different effects between sulfonylurea (SU) and glinide drugs in insulin secretion, pancreatic β-cells were repeatedly stimulated with SU (glimepiride) or glinide (mitiglinide). Total internal reflection fluorescent (TIRF) microscopy revealed that secondary stimulation with glimepiride, but not glucose and mitiglinide, failed to evoke fusions of insulin granules although primary stimulation with glucose, glimepiride, and mitiglinide induced equivalent numbers of exocytotic responses. Glimepiride, but not glucose and mitiglinide, induced abnormally sustained [Ca2+]i elevations and reductions of docked insulin granules on the plasma membrane. Our data suggest that the effect of glinide on insulin secretory mechanisms is similar to that of glucose. PMID:20069052

PHYSICAL PROPERTIES OF LARGE AND SMALL GRANULES IN SOLAR QUIET REGIONS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu Daren; Xie Zongxia; Hu Qinghua

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 themore » five-dimensional parameter space, the X-means clustering algorithm and one-rule classifier are introduced to define the rules for classifying the granules. It is found that diameter is a dominating parameter in classifying the granules and two families of granules are derived: small granules with diameters smaller than 1.''44, and large granules with diameters larger than 1.''44. Based on statistical analysis of the detected granules, the following results are derived: (1) the averages of diameter, continuum intensity, and Doppler velocity in the upward direction of large granules are larger than those of small granules; (2) the averages of absolute longitudinal, transverse, and unsigned flux density of large granules are smaller than those of small granules; (3) for small granules, the average of continuum intensity increases with their diameters, while the averages of Doppler velocity, transverse, absolute longitudinal, and unsigned magnetic flux density decrease with their diameters. However, the mean properties of large granules are stable; (4) the intensity distributions of all granules and small granules do not satisfy Gaussian distribution, while that of large granules almost agrees with normal distribution with a peak at 1.04 I{sub 0}.« less

Histochemistry and ultrastructure of the metacercarial cysts of blackspot trematodes Uvulifer ambloplitis and Neascus pyriformis.

PubMed

Wittrock, D D; Bruce, C S; Johnson, A D

1991-06-01

Cysts of Uvulifer ambloplitis from green sunfish, Lepomis cyanellus, and Neascus pyriformis from red shiners, Notropis lutrensis, were studied with light-level histochemistry and scanning and transmission electron microscopy. Cysts of both species are bilayered, consisting of an outer host capsule and an inner parasite cyst; the space between these layers is filled with a viscous material. The outer portion of the host capsule of both species is composed of fibrocytes, melanin granules, and collagen fibrils, and the inner portion of layers of flattened fibrocytes. The parasite cyst of U. ambloplitis is formed of 2 layers, an outer dense layer and an inner light layer, whereas the parasite cyst of N. pyriformis is made of 3 layers. A thin outer light-staining layer is present in addition to the 2 layers observed in U. ambloplitis. Results of histochemical staining were the same for both species. The host capsule stained positively for proteins and neutral and acid mucopolysaccharides. The viscous material was positive for neutral and acid mucopolysaccharides but not for proteins. The parasite cyst gave a strong positive reaction for neutral mucopolysaccharides but was negative for acid mucopolysaccharides and proteins.

Ultrastructure of the filiform papillae on the tongue of the hamster.

PubMed Central

Fernandez, B; Suarez, I; Zapata, A

1978-01-01

The fine structure of the filiform papillae on the hamster tongue is described level by level from the basal layer to the surface. We did not observe two distinct types of cells with different morphology or components which could be held responsible for the production of two different types of keratin as have been described in other animals, but rather a uniformity of cell structures in each layer and only the so-called "smooth" type of keratin. However, keratin granules were more abundant in the anterior part of the papilla. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 PMID:689988

Expression of the alpha and beta subunits of Ca2+/calmodulin kinase II in the cerebellum of jaundiced Gunn rats during development: a quantitative light microscopic analysis.

PubMed

Conlee, J W; Shapiro, S M; Churn, S B

2000-04-01

The homozygous (jj) jaundiced Gunn rat model for hyperbilirubinemia displays pronounced cerebellar hypoplasia. To examine the cellular mechanisms involved in bilirubin toxicity, this study focused on the effect of hyperbilirubinemia on calcium/calmodulin-dependent kinase II (CaM kinase II). CaM kinase II is a neuronally enriched enzyme which performs several important functions. Immunohistochemical analysis of alternating serial sections were performed using monoclonal antibodies for the alpha and beta subunits of CaM kinase II. Measurements were made of the total numbers of stained cells in each of the deep cerebellar nuclei and of Purkinje and granule cell densities in cerebellar lobules II, VI, and IX. The beta subunit was present in Purkinje cells and deep cerebellar nuclei of both groups at all ages, but only granule cells which had migrated through the Purkinje cell layer showed staining for beta subunit; external granule cells were completely negative. Many Purkinje cells had degenerated in the older animals, and the percent of granule cells stained for beta subunit was significantly reduced. The alpha subunit was found exclusively in Purkinje cells, although its appearance was delayed in the jaundiced animals. Sulfadimethoxine was administered to some jj rats 24 h or 15 days prior to sacrifice to increase brain bilirubin concentration. Results showed that bilirubin exposure modulated both alpha and beta CaM kinase II subunit expression in selective neuronal populations, but sulfadimethoxine had no acute effect on enzyme immunoreactivity. Thus, developmental expression of the alpha and beta subunits of CaM kinase II was affected by chronic bilirubin exposure during early postnatal development of jaundiced Gunn rats.

The life cycle of platelet granules.

PubMed

Sharda, Anish; Flaumenhaft, Robert

2018-01-01

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

The influence of porosity and structural parameters on different kinds of gas hydrate dissociation

PubMed Central

Misyura, S. Y.

2016-01-01

Methane hydrate dissociation at negative temperatures was studied experimentally for different artificial and natural samples, differing by macro- and micro-structural parameters. Four characteristic dissociation types are discussed in the paper. The internal kinetics of artificial granule gas hydrates and clathrate hydrates in coal is dependent on the porosity, defectiveness and gas filtration rate. The density of pores distribution in the crust of formed ice decreases by the several orders of magnitude and this change significantly the rate of decay. Existing models for describing dissociation at negative temperatures do not take into account the structural parameters of samples. The dissociation is regulated by internal physical processes that must be considered in the simulation. Non-isothermal dissociation with constant external heat flux was simulated numerically. The dissociation is simulated with consideration of heat and mass transfer, kinetics of phase transformation and gas filtering through a porous medium of granules for the negative temperatures. It is shown that the gas hydrate dissociation in the presence of mainly microporous structures is fundamentally different from the disintegration of gas hydrates containing meso and macropores. PMID:27445113

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

PubMed

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

2015-01-01

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

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

PubMed

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

2006-07-01

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

The combined effect of wet granulation process parameters and dried granule moisture content on tablet quality attributes.

PubMed

Gabbott, Ian P; Al Husban, Farhan; Reynolds, Gavin K

2016-09-01

A pharmaceutical compound was used to study the effect of batch wet granulation process parameters in combination with the residual moisture content remaining after drying on granule and tablet quality attributes. The effect of three batch wet granulation process parameters was evaluated using a multivariate experimental design, with a novel constrained design space. Batches were characterised for moisture content, granule density, crushing strength, porosity, disintegration time and dissolution. Mechanisms of the effect of the process parameters on the granule and tablet quality attributes are proposed. Water quantity added during granulation showed a significant effect on granule density and tablet dissolution rate. Mixing time showed a significant effect on tablet crushing strength, and mixing speed showed a significant effect on the distribution of tablet crushing strengths obtained. The residual moisture content remaining after granule drying showed a significant effect on tablet crushing strength. The effect of moisture on tablet tensile strength has been reported before, but not in combination with granulation parameters and granule properties, and the impact on tablet dissolution was not assessed. Correlations between the energy input during granulation, the density of granules produced, and the quality attributes of the final tablets were also identified. Understanding the impact of the granulation and drying process parameters on granule and tablet properties provides a basis for process optimisation and scaling. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

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

2016-09-01

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. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Cytoplasmic RNA Granules in Somatic Maintenance.

PubMed

Moujaber, Ossama; Stochaj, Ursula

2018-05-30

Cytoplasmic RNA granules represent subcellular compartments that are enriched in protein-bound RNA species. RNA granules are produced by evolutionary divergent eukaryotes, including yeast, mammals, and plants. The functions of cytoplasmic RNA granules differ widely. They are dictated by the cell type and physiological state, which in turn is determined by intrinsic cell properties and environmental factors. RNA granules provide diverse cellular functions. However, all of the granules contribute to aspects of RNA metabolism. This is exemplified by transcription, RNA storage, silencing, and degradation, as well as mRNP remodeling and regulated translation. Several forms of cytoplasmic mRNA granules are linked to normal physiological processes. For instance, they may coordinate protein synthesis and thereby serve as posttranscriptional "operons". RNA granules also participate in cytoplasmic mRNA trafficking, a process particularly well understood for neurons. Many forms of RNA granules support the preservation of somatic cell performance under normal and stress conditions. On the other hand, severe insults or disease can cause the formation and persistence of RNA granules that contribute to cellular dysfunction, especially in the nervous system. Neurodegeneration and many other diseases linked to RNA granules are associated with aging. Nevertheless, information related to the impact of aging on the various types of RNA granules is presently very limited. This review concentrates on cytoplasmic RNA granules and their role in somatic cell maintenance. We summarize the current knowledge on different types of RNA granules in the cytoplasm, their assembly and function under normal, stress, or disease conditions. Specifically, we discuss processing bodies, neuronal granules, stress granules, and other less characterized cytoplasmic RNA granules. Our focus is primarily on mammalian and yeast models, because they have been critical to unravel the physiological role of various RNA granules. RNA granules in plants and pathogens are briefly described. We conclude our viewpoint by summarizing the emerging concepts for RNA granule biology and the open questions that need to be addressed in future studies. © 2018 S. Karger AG, Basel.

Method of sintering ceramic materials

DOEpatents

Holcombe, Cressie E.; Dykes, Norman L.

1992-01-01

A method for sintering ceramic materials is described. A ceramic article is coated with layers of protective coatings such as boron nitride, graphite foil, and niobium. The coated ceramic article is embedded in a container containing refractory metal oxide granules and placed within a microwave oven. The ceramic article is heated by microwave energy to a temperature sufficient to sinter the ceramic article to form a densified ceramic article having a density equal to or greater than 90% of theoretical density.

Inhibition of presynaptic activity by zinc released from mossy fiber terminals during tetanic stimulation.

PubMed

Minami, Akira; Sakurada, Naomi; Fuke, Sayuri; Kikuchi, Kazuya; Nagano, Tetsuo; Oku, Naoto; Takeda, Atsushi

2006-01-01

Zinc exists in high densities in the giant boutons of hippocampal mossy fibers. On the basis of the evidence that zinc decreases extracellular glutamate concentration in the hippocampus, the presynaptic action of zinc released from mossy fibers during high-frequency (tetanic) stimulation was examined using hippocampal slices. The increase in zinc-specific fluorescent signals was observed in both extracellular and intracellular compartments in the mossy fiber terminals during the delivery of tetanic stimuli (100 Hz, 1 sec) to the dentate granule cell layer, suggesting that zinc released from mossy fibers is immediately retaken up by mossy fibers. When mossy fiber terminals were preferentially double-stained with zinc and calcium indicators and tetanic stimuli (100 Hz, 1 sec) were delivered to the dentate granule cell layer, the increase in calcium orange signal during the stimulation was enhanced in mossy fiber terminals by addition of CaEDTA, a membrane-impermeable zinc chelator, and was suppressed by addition of zinc. The decrease in FM4-64 signal (vesicular exocytosis) during tetanic stimulation (10 Hz, 180 sec), which induced mossy fiber long-term potentiation, was also enhanced in mossy fiber terminals by addition of CaEDTA and was suppressed by addition of zinc. The present study demonstrates that zinc released from mossy fibers may be a negative-feedback factor against presynaptic activity during tetanic stimulation.

A highly stable (SnOx-Sn)@few layered graphene composite anode of sodium-ion batteries synthesized by oxygen plasma assisted milling

NASA Astrophysics Data System (ADS)

Cheng, Deliang; Liu, Jiangwen; Li, Xiang; Hu, Renzong; Zeng, Meiqing; Yang, Lichun; Zhu, Min

2017-05-01

The (SnOx-Sn)@few layered graphene ((SnOx-Sn)@FLG) composite has been synthesized by oxygen plasma-assisted milling. Owing to the synergistic effect of rapid plasma heating and ball mill grinding, SnOx (1 ≤ x ≤ 2) nanoparticles generated from the reaction of Sn with oxygen are tightly wrapped by FLG nanosheets which are simultaneously exfoliated from expanded graphite, forming secondary micro granules. Inside the granules, the small size of the SnOx nanoparticles enables the fast kinetics for Na+ transfer. The in-situ formed FLG and residual Sn nanoparticles improve the electrical conductivity of the composite, meanwhile alleviate the aggregation of SnOx nanoparticles and relieve the volume change during the cycling, which is beneficial for the cyclic stability for the Na+ storage. As an anode material for sodium-ion batteries, the (SnOx-Sn)@FLG composite exhibits a high reversible capacity of 448 mAh g-1 at a current density of 100 mA g-1 in the first cycle, with 82.6% capacity retention after 250 cycles. Even when the current density increases to 1000 mA g-1, this composite retains 316.5 mAh g-1 after 250 cycles. With superior Na+ storage stability, the (SnOx-Sn)@FLG composite can be a promising anode material for high performance sodium-ion batteries.

Numerical analysis of temperature field in the high speed rotary dry-milling process

NASA Astrophysics Data System (ADS)

Wu, N. X.; Deng, L. J.; Liao, D. H.

2018-01-01

For the effect of the temperature field in the ceramic dry granulation. Based on the Euler-Euler mathematical model, at the same time, made ceramic dry granulation experiment equipment more simplify and established physical model, the temperature of the dry granulation process was simulated with the granulation time. The relationship between the granulation temperature and granulation effect in dry granulation process was analyzed, at the same time, the correctness of numerical simulation was verified by measuring the fluidity index of ceramic bodies. Numerical simulation and experimental results showed that when granulation time was 4min, 5min, 6min, maximum temperature inside the granulation chamber was: 70°C, 85°C, 95°C. And the equilibrium of the temperature in the granulation chamber was weakened, the fluidity index of the billet particles was: 56.4. 89.7. 81.6. Results of the research showed that when granulation time was 5min, the granulation effect was best. When the granulation chamber temperature was more than 85°C, the fluidity index and the effective particles quantity of the billet particles were reduced.

Maintained LTP and Memory Are Lost by Zn2+ Influx into Dentate Granule Cells, but Not Ca2+ Influx.

PubMed

Takeda, Atsushi; Tamano, Haruna; Hisatsune, Marie; Murakami, Taku; Nakada, Hiroyuki; Fujii, Hiroaki

2018-02-01

The idea that maintained LTP and memory are lost by either increase in intracellular Zn 2+ in dentate granule cells or increase in intracellular Ca 2+ was examined to clarify significance of the increases induced by excess synapse excitation. Both maintained LTP and space memory were impaired by injection of high K + into the dentate gyrus, but rescued by co-injection of CaEDTA, which blocked high K + -induced increase in intracellular Zn 2+ but not high K + -induced increase in intracellular Ca 2+ . High K + -induced disturbances of LTP and intracellular Zn 2+ are rescued by co-injection of 6-cyano-7-nitroquinoxakine-2,3-dione, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist, but not by co-injection of blockers of NMDA receptors, metabotropic glutamate receptors, and voltage-dependent calcium channels. Furthermore, AMPA impaired maintained LTP and the impairment was also rescued by co-injection of CaEDTA, which blocked increase in intracellular Zn 2+ , but not increase in intracellular Ca 2+ . NMDA and glucocorticoid, which induced Zn 2+ release from the internal stores, did not impair maintained LTP. The present study indicates that increase in Zn 2+ influx into dentate granule cells through AMPA receptors loses maintained LTP and memory. Regulation of Zn 2+ influx into dentate granule cells is more critical for not only memory acquisition but also memory retention than that of Ca 2+ influx.

Nonlinear electrokinetic phenomena in microfluidic devices

NASA Astrophysics Data System (ADS)

Ben, Yuxing

This thesis addresses nonlinear electrokinetic mechanisms for transporting fluid and particles in microfluidic devices for potential applications in biomedical chips, microelectronic cooling and micro-fuel cells. Nonlinear electrokinetics have many advantages, such as low voltage, low power, high velocity, and no significant gas formation in the electrolyte. However, they involve new and complex charging and flow mechanisms that are still not fully understood or explored. Linear electrokinetic fingering that occurs when a fluid with a lower electrolyte concentration advances into one with a higher concentration is first analyzed. Unlike earlier miscible fingering theories, the linear stability analysis is carried out in the self-similar coordinates of the diffusing front. This new spectral theory is developed for small-amplitude gravity and viscous miscible fingering phenomena in general and applied to electrokinetic miscible fingering specifically. Transient electrokinetic fingering is shown to be insignificant in sub-millimeter micro-devices. Nonlinear electroosmotic flow around an ion-exchange spherical granule is studied next. When an electric field is applied across a conducting and ion-selective porous granule in an electrolyte solution, a polarized surface layer with excess counter-ions is created. The flux-induced polarization produces a nonlinear slip velocity to produce micro-vortices around this sphere. This polarization layer is reduced by convection at high velocity. Two velocity scalings at low and high electric fields are derived and favorably compared with experimental results. A mixing device based on this mechanism is shown to produce mixing efficiency 10-100 times higher than molecular diffusion. Finally, AC nonlinear electrokinetic flow on planar electrodes is studied. Two double layer charging mechanisms are responsible for the flow---one due to capacitive charging of ions from the bulk electrolyte and one due to Faradaic reactions at the electrode that consume or produce ions in the double layer. Faradaic charging is analyzed for specific reactions. From the theory, particular electrokinetic flows above the electrodes are selected for micropumps and bioparticle trapping by specifying the electrode geometry and the applied voltage and frequency.

Expression of erythropoietin and its receptor in the brain of late-gestation fetal sheep, and responses to asphyxia caused by umbilical cord occlusion.

PubMed

Castillo-Meléndez, Margie; Yan, Edwin; Walker, David W

2005-01-01

Asphyxia and hypoxia are common threats faced by the fetus in utero. In late-gestation fetal sheep, asphyxia produced by umbilical cord occlusion (UCO) results in widespread lipid peroxidation and apoptosis. Adaptive mechanisms that might limit fetal brain damage include induction of the hemopoietic cytokine, erythropoietin (EPO). In unanesthetized fetal sheep, we investigated if 1 or 2 bouts of brief asphyxia (UCO for 10 min) induced EPO and EPO type I receptor (EPO-R) expressions, with the second UCO repeated 48 h after the first. Fetal brains were recovered 48 h after either sham, 1 x or 2 x UCO at 129-133 (term approximately 147) days of gestation and prepared for immunocytochemistry. In age-matched control brain, low levels of EPO and EPO-R proteins were present in oligodendrocytes (OLs), periventricular and cortical white matter (WM), with no EPO and very low EPO-R expression in neurons. After 1 x UCO, EPO and EPO-R expressions were increased in astrocytes (periventricular and cortical WM, striatum, corpus callosum), choroid plexus epithelial cells, scattered neurons in cortical layers IV-VI, hippocampal CA1 neurons, and in the molecular and granule layers of the cerebellum. After 2 x UCO, higher levels of EPO and EPO-R occurred in the periventricular and cortical WM, corpus callosum, hippocampal CA1, and in neurons of all cortical layers. Paradoxically, EPO and EPO-R were now lower in hippocampal CA1 neurons and cerebellar molecular and granule cell layers. Few OLs expressed EPO or EPO-R after 1 x or 2 x UCO. Thus, brief asphyxia induces EPO and EPO-R in fetal astrocytes, but only after repeated asphyxial insult in neurons. Whether this is a response to increased injury, or represents an adaptive response that limits further cell death and brain damage awaits further investigation.

Effects of simulated microgravity on otoliths growth and microstructure of Larval Zebrafish, Danio rerio

NASA Astrophysics Data System (ADS)

Li, Xiaoyan; Wang, Gaohong; Liu, Yongding

2012-07-01

Otolith is the vestibular endorgan that takes part in gravitational signal initiation. Environmental change can leave mark on otolith microstructure. In this study, we use zebrafish from embryo stage of 10hpf to middle larval stage of 12dpf to investigate the effect of microgravity on otolith development. It was found that otoliths size of microgravity group was larger than the control before 6dpf, but after that both groups kept nearly the same size. Surface scanning of otolith morphology with SEM showed that otolith of microgravity group were much smoother than the control. After etching with HCl, we found both groups formed daily increments, but microgravity group lack clear check marks in some special developmental stage. Widths between increments were wider, and granule shape was much sharper in microgravity group. Analysis of crystal orientation disclosed the increments of microgravity group formed irregularly. The surface etched with PKb also exhibited different granule size and orientation: the granules in the control had nearly the same size and direction, while the particles in microgravity were smaller and orientated differently along the translucent ring. The organic leftover were also found between layers in microgravity group. These results suggest that microgravity can affect otolith development, the component and structural mode of inorganic and organic parts change with different gravitation environment, which may be involved in orientation adjustment of SMS (Space Movement Sickness).

Chronic corticosterone administration reduces dendritic complexity in mature, but not young granule cells in the rat dentate gyrus.

PubMed

Yau, Suk-Yu; Li, Ang; Tong, Jian-Bin; Bostrom, Crystal; Christie, Brian R; Lee, Tatia M C; So, Kwok-Fai

2016-09-21

Our previous work has shown that exposure to the stress hormone corticosterone (40 mg/kg CORT) for two weeks induces dendritic atrophy of pyramidal neurons in the hippocampal CA3 region and behavioral deficits. However, it is unclear whether this treatment also affects the dentate gyrus (DG), a subregion of the hippocampus comprising a heterogeneous population of young and mature neurons. We examined the effect of CORT treatment on the dendritic complexity of mature and young granule cells in the DG. We utilized a Golgi staining method to investigate the dendritic morphology and spine density of young neurons in the inner granular cell layer (GCL) and mature neurons in the outer GCL in response to CORT application. The expressions of glucocorticoid receptors during neuronal maturation were examined using Western blot analysis in a primary hippocampal neuronal culture. Sholl analysis revealed that CORT treatment decreased the number of intersections and shortened the dendritic length in mature, but not young, granule cells. However, the spine density of mature and young neurons was not affected. Western blot analysis showed a progressive increase in the protein levels of glucocorticoid receptors (GRs) in the cultured primary hippocampal neurons during neuronal maturation. These data suggest that mature neurons are likely more vulnerable to chronic exposure to CORT; this may be due to their higher expression of GRs when compared to younger DG neurons.

CaMKIIalpha 3' untranslated region-directed mRNA translocation in living neurons: visualization by GFP linkage

NASA Technical Reports Server (NTRS)

Rook, M. S.; Lu, M.; Kosik, K. S.

2000-01-01

The CaMKIIalpha mRNA extends into distal hippocampal dendrites, and the 3' untranslated region (3'UTR) is sufficient to mediate this localization. We labeled the 3'UTR of the CaMKIIalpha mRNA in hippocampal cultures by using a green fluorescent protein (GFP)/MS2 bacteriophage tagging system. The CaMKIIalpha 3'UTR formed discrete granules throughout the dendrites of transfected cells. The identity of the fluorescent granules was verified by in situ hybridization. Over 30 min time periods these granules redistributed without a net increase in granule number; with depolarization there is a tendency toward increased numbers of granules in the dendrites. These observations suggest that finer time resolution of granule motility might reveal changes in the motility characteristics of granules after depolarization. So that motile granules could be tracked, shorter periods of observation were required. The movements of motile granules can be categorized as oscillatory, unidirectional anterograde, or unidirectional retrograde. Colocalization of CaMKIIalpha 3'UTR granules and synapses suggested that oscillatory movements allowed the granules to sample several local synapses. Neuronal depolarization increased the number of granules in the anterograde motile pool. Based on the time frame over which the granule number increased, the translocation of granules may serve to prepare the dendrite for mounting an adequate local translation response to future stimuli. Although the resident pool of granules can respond to signals that induce local translation, the number of granules in a dendrite might reflect its activation history.

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

PubMed

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

2017-07-01

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

Mechanisms of objectionable textural changes by microwave reheating of foods: a review.

PubMed

Mizrahi, Shimon

2012-01-01

Microwave reheating, compared to a conventional method, is notorious for lack of crust formation and severe toughening of flour and starch-based products. This review discusses how the typical thermal characteristics of microwave heating are involved in affecting the texture as well as the possible role of non-thermal effects. While low surface temperature is the well known mechanism why microwave heating is incapable of crust formation, the most severe toughening problems are caused by internal boiling. Beside moisture loss, the internally generated steam causes 2 main textural effects when it is vented out. The first is the replacing of non-condensable gases (air) in the product voids with a condensable one (steam). When the latter is condensed by cooling, a vacuum may be created in the voids causing their collapse and a formation of a more compact and tougher structure. The second textural effect involves amylose extraction from starch granules and its redistribution to eventually form a rich layer on the walls of the structural foam cells of the baked goods. Relatively fast crystallization of the amylose seems to be the main cause of toughening a short while after microwave heating. This mechanism is relevant mainly to products where starch is an important structural element. Structural disruptions by localize excessive steam pressure at hot-spots are also discussed in this review as well as methods of preventing or alleviating the most objectionable textural changes. The most effective ways of preventing these undesirable changes are by avoiding internal boiling and/or by manipulating the starch content and properties. © 2011 Institute of Food Technologists®

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

PubMed

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

2018-03-30

Although twin screw granulation has already been widely studied in recent years, only few studies addressed the subsequent continuous drying which is required after wet granulation and still suffers from a lack of detailed understanding. The latter is important for optimisation and control and, hence, a cost-effective practical implementation. Therefore, the aim of the current study is to increase understanding of the drying kinetics and the breakage and attrition phenomena during fluid bed drying after continuous twin screw granulation. Experiments were performed on a continuous manufacturing line consisting of a twin-screw granulator, a six-segmented fluid bed dryer, a mill, a lubricant blender and a tablet press. Granulation parameters were fixed in order to only examine the effect of drying parameters (filling time, drying time, air flow, drying air temperature) on the size distribution and moisture content of granules (both of the entire granulate and of size fractions). The wet granules were transferred either gravimetrically or pneumatically from the granulator exit to the fluid bed dryer. After a certain drying time, the moisture content reached an equilibrium. This drying time was found to depend on the applied airflow, drying air temperature and filling time. The moisture content of the granules decreased with an increasing drying time, airflow and drying temperature. Although smaller granules dried faster, the multimodal particle size distribution of the granules did not compromise uniform drying of the granules when the target moisture content was achieved. Extensive breakage of granules was observed during drying. Especially wet granules were prone to breakage and attrition during pneumatic transport, either in the wet transfer line or in the dry transfer line. Breakage and attrition of granules during transport and drying should be anticipated early on during process and formulation development by performing integrated experiments on the granulator, dryer and mill. Copyright © 2018 Elsevier B.V. All rights reserved.

Oxytocin Depolarizes Fast-Spiking Hilar Interneurons and Induces GABA Release onto Mossy Cells of the Rat Dentate Gyrus

PubMed Central

Harden, Scott W.; Frazier, Charles J.

2016-01-01

Delivery of exogenous oxytocin (OXT) to central oxytocin receptors (OXT-Rs) is currently being investigated as a potential treatment for conditions such as post-traumatic stress disorder (PTSD), depression, social anxiety, and autism spectrum disorder (ASD). Despite significant research implicating central OXT signaling in modulation of mood, affect, social behavior, and stress response, relatively little is known about the cellular and synaptic mechanisms underlying these complex actions, particularly in brain regions which express the OXT-R but lie outside of the hypothalamus (where OXT-synthesizing neurons reside). We report that bath application of low concentrations of the selective OXT-R agonist Thr4,Gly7-OXT (TGOT) reliably and robustly drives GABA release in the dentate gyrus in an action potential dependent manner. Additional experiments led to identification of a small subset of small hilar interneurons that are directly depolarized by acute application of TGOT. From a physiological perspective, TGOT-responsive hilar interneurons have high input resistance, rapid repolarization velocity during an action potential, and a robust afterhyperpolarization. Further, they fire irregularly (or stutter) in response to moderate depolarization, and fire quickly with minimal spike frequency accommodation in response to large current injections. From an anatomical perspective, TGOT responsive hilar interneurons have dense axonal arborizations in the hilus that were found close proximity with mossy cell somata and/or proximal dendrites, and also invade the granule cell layer. Further, they have primary dendrites that always extend into the granule cell layer, and sometimes have clear arborizations in the molecular layer. Overall, these data reveal a novel site of action for OXT in an important limbic circuit, and represent a significant step towards better understanding how endogenous OXT may modulate flow of information in hippocampal networks. PMID:27068005

Neuronal nitric oxide synthase in the olfactory system of an adult teleost fish Oreochromis mossambicus.

PubMed

Singru, Praful S; Sakharkar, Amul J; Subhedar, Nishikant

2003-07-11

The aim of the present study is to explore the distribution of nitric oxide synthase in the olfactory system of an adult teleost, Oreochromis mossambicus using neuronal nitric oxide synthase (nNOS) immunocytochemistry and nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) histochemistry methods. Intense nNOS immunoreactivity was noticed in several olfactory receptor neurons (ORNs), in their axonal extensions over the olfactory nerve and in some basal cells of the olfactory epithelium. nNOS containing fascicles of the ORNs enter the bulb from its rostral pole, spread in the olfactory nerve layer in the periphery of the bulb and display massive innervation of the olfactory glomeruli. Unilateral ablation of the olfactory organ resulted in dramatic loss of nNOS immunoreactivity in the olfactory nerve layer of the ipsilateral bulb. In the olfactory bulb of intact fish, some granule cells showed intense immunoreactivity; dendrites arising from the granule cells could be traced to the glomerular layer. Of particular interest is the occurrence of nNOS immunoreactivity in the ganglion cells of the nervus terminalis. nNOS containing fibers were also encountered in the medial olfactory tracts as they extend to the telencephalon. The NADPHd staining generally coincides with that of nNOS suggesting that it may serve as a marker for nNOS in the olfactory system of this fish. However, mismatch was encountered in the case of mitral cells, while all are nNOS-negative, few were NADPHd positive. The present study for the first time revealed the occurrence of nNOS immunoreactivity in the ORNs of an adult vertebrate and suggests a role for nitric oxide in the transduction of odor stimuli, regeneration of olfactory epithelium and processing of olfactory signals.

Cellular stress induces cytoplasmic RNA granules in fission yeast.

PubMed

Nilsson, Daniel; Sunnerhagen, Per

2011-01-01

Severe stress causes plant and animal cells to form large cytoplasmic granules containing RNA and proteins. Here, we demonstrate the existence of stress-induced cytoplasmic RNA granules in Schizosaccharomyces pombe. Homologs to several known protein components of mammalian processing bodies and stress granules are found in fission yeast RNA granules. In contrast to mammalian cells, poly(A)-binding protein (Pabp) colocalizes in stress-induced granules with decapping protein. After glucose deprivation, protein kinase A (PKA) is required for accumulation of Pabp-positive granules and translational down-regulation. This is the first demonstration of a role for PKA in RNA granule formation. In mammals, the translation initiation protein eIF2α is a key regulator of formation of granules containing poly(A)-binding protein. In S. pombe, nonphosphorylatable eIF2α does not block but delays granule formation and subsequent clearance after exposure to hyperosmosis. At least two separate pathways in S. pombe appear to regulate stress-induced granules: pka1 mutants are fully proficient to form granules after hyperosmotic shock; conversely, eIF2α does not affect granule formation in glucose starvation. Further, we demonstrate a Pka1-dependent link between calcium perturbation and RNA granules, which has not been described earlier in any organism.

Deficiency of Starch Synthase IIIa and IVb Alters Starch Granule Morphology from Polyhedral to Spherical in Rice Endosperm1

PubMed Central

Toyosawa, Yoshiko; Kawagoe, Yasushi; Matsushima, Ryo; Ogawa, Masahiro; Fukuda, Masako; Kumamaru, Toshihiro; Okazaki, Yozo; Kusano, Miyako; Saito, Kazuki; Toyooka, Kiminori; Sato, Mayuko; Ai, Yongfeng; Fujita, Naoko

2016-01-01

Starch granule morphology differs markedly among plant species. However, the mechanisms controlling starch granule morphology have not been elucidated. Rice (Oryza sativa) endosperm produces characteristic compound-type granules containing dozens of polyhedral starch granules within an amyloplast. Some other cereal species produce simple-type granules, in which only one starch granule is present per amyloplast. A double mutant rice deficient in the starch synthase (SS) genes SSIIIa and SSIVb (ss3a ss4b) produced spherical starch granules, whereas the parental single mutants produced polyhedral starch granules similar to the wild type. The ss3a ss4b amyloplasts contained compound-type starch granules during early developmental stages, and spherical granules were separated from each other during subsequent amyloplast development and seed dehydration. Analysis of glucan chain length distribution identified overlapping roles for SSIIIa and SSIVb in amylopectin chain synthesis, with a degree of polymerization of 42 or greater. Confocal fluorescence microscopy and immunoelectron microscopy of wild-type developing rice seeds revealed that the majority of SSIVb was localized between starch granules. Therefore, we propose that SSIIIa and SSIVb have crucial roles in determining starch granule morphology and in maintaining the amyloplast envelope structure. We present a model of spherical starch granule production. PMID:26747287

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

PubMed

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

1986-08-01

Previous studies on the fractionation of human neutrophil granules have identified two major populations: myeloperoxidase (MPO)-containing azurophil, or primary, granules and MPO-deficient specific, or secondary, granules. Peripheral blood neutrophils from individual donors were lysed in sucrose-free media by either hypotonic shock or nitrogen cavitation. Using a novel two-gradient Percoll density centrifugation system, the granule-rich postnuclear supernatant was rapidly (ten minutes) and reproducibly resolved into 13 granule fractions (L1 through L8 and H1 through H5). Granule flotation and recentrifugation experiments on both continuous, self-generated and multiple-step gradients using individual and mixed isolated fractions demonstrated that the banding patterns were isopycnic and nonartifactual. Isolated granules were intact based on the findings that biochemical latency of several granule enzymes was greater than 95%, and thin-sectioned electron micrographs demonstrated intact granule profiles. Biochemical analyses of the granule marker proteins MPO, beta-glucuronidase, lysozyme, and lactoferrin indicated that a number of the fractions were related to the major azurophil and specific granule populations. Lactoferrin was found in ten of 13 fractions (L1 through L8, H1 to H2), whereas MPO was found in every fraction. Consistent with these biochemical data, all fractions exhibited varying degrees of heterogeneity based on ultrastructural morphology and cytochemistry, including diaminobenzidine (DAB) reactivity for peroxidase and periodate-thiocarbohydrazide-silver proteinate (PA-TCH-SP) staining for complex glycoconjugates. A variable but significant percentage (23% to 70%) of the granules in fractions L1 through L8 and H1 and H2 showed DAB reactivity, while about 90% of the granules in fractions H3 through H5 were peroxidase positive. These results demonstrated that DAB-reactive granules spanned the entire range of granule size and density. Ultrastructural PA-TCH-SP staining of isolated granule fractions revealed patterns similar to those of granules in intact neutrophils at different stages of development. Granules from human acute promyelocytic leukemia cells (HL-60) exhibited a surprisingly low density compared with typical azurophil granules from normal, mature neutrophils. The data suggest that both functional and maturational differences contribute to granule heterogeneity, and provide a new practical and conceptual framework for further defining the phenomenon of neutrophil granule heterogeneity.

Visualizing melanosomes, lipofuscin, and melanolipofuscin in human retinal pigment epithelium using serial block face scanning electron microscopy.

PubMed

Pollreisz, Andreas; Messinger, Jeffrey D; Sloan, Kenneth R; Mittermueller, Tamara J; Weinhandl, Alexandra S; Benson, Emily K; Kidd, Grahame J; Schmidt-Erfurth, Ursula; Curcio, Christine A

2018-01-01

To assess serial section block-face scanning electron microscopy (SBFSEM) for retinal pigment epithelium (RPE) ultrastructure, we determined the number and distribution within RPE cell bodies of melanosomes (M), lipofuscin (L), and melanolipofuscin (ML). Eyes of 4 Caucasian donors (16M, 32F, 76F, 84M) with unremarkable maculas were sectioned and imaged using an SEM fitted with an in-chamber automated ultramicrotome. Aligned image stacks were generated by alternately imaging an epoxy resin block face using backscattered electrons, then removing a 125 nm-thick layer. Series of 249-499 sections containing 5-24 nuclei were examined per eye. Trained readers manually assigned boundaries of individual cells and x,y,z locations of M, L, and ML. A Density Recovery Profile was computed in three dimensions for M, L, and ML. The number of granules per RPE cell body in 16M, 32F, 76F, and 84M eyes, respectively, was 465 ± 127 (mean ± SD), 305 ± 92, 79 ± 40, and 333 ± 134 for L; 13 ± 9; 6 ± 7, 131 ± 55, and 184 ± 66 for ML; and 29 ± 19, 24 ± 12, 12 ± 7, and 7 ± 3 for M. Granule types were spatially organized, with M near apical processes. The effective radius, a sphere of decreased probability for granule occurrence, was 1 μm for L, ML, and M combined. In conclusion, SBFEM reveals that adult human RPE has hundreds of L, LF, and M and that granule spacing is regulated by granule size alone. When obtained for a larger sample, this information will enable hypothesis testing about organelle turnover and regulation in health, aging, and disease, and elucidate how RPE-specific signals are generated in clinical optical coherence tomography and autofluorescence imaging. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fetuin-A/Albumin-Mineral Complexes Resembling Serum Calcium Granules and Putative Nanobacteria: Demonstration of a Dual Inhibition-Seeding Concept

PubMed Central

Young, David; Young, John D.

2009-01-01

Serum-derived granulations and purported nanobacteria (NB) are pleomorphic apatite structures shown to resemble calcium granules widely distributed in nature. They appear to be assembled through a dual inhibitory-seeding mechanism involving proteinaceous factors, as determined by protease (trypsin and chymotrypsin) and heat inactivation studies. When inoculated into cell culture medium, the purified proteins fetuin-A and albumin fail to induce mineralization, but they will readily combine with exogenously added calcium and phosphate, even in submillimolar amounts, to form complexes that will undergo morphological transitions from nanoparticles to spindles, films, and aggregates. As a mineralization inhibitor, fetuin-A is much more potent than albumin, and it will only seed particles at higher mineral-to-protein concentrations. Both proteins display a bell-shaped, dose-dependent relationship, indicative of the same dual inhibitory-seeding mechanism seen with whole serum. As ascertained by both seeding experiments and gel electrophoresis, fetuin-A is not only more dominant but it appears to compete avidly for nanoparticle binding at the expense of albumin. The nanoparticles formed in the presence of fetuin-A are smaller than their albumin counterparts, and they have a greater tendency to display a multi-layered ring morphology. In comparison, the particles seeded by albumin appear mostly incomplete, with single walls. Chemically, spectroscopically, and morphologically, the protein-mineral particles resemble closely serum granules and NB. These particles are thus seen to undergo an amorphous to crystalline transformation, the kinetics and completeness of which depend on the protein-to-mineral ratios, with low ratios favoring faster conversion to crystals. Our results point to a dual inhibitory-seeding, de-repression model for the assembly of particles in supersaturated solutions like serum. The presence of proteins and other inhibitory factors tend to block apatite nuclei formation or to stabilize the nascent nuclei as amorphous or semi-crystalline spherical nanoparticles, until the same inhibitory influences are overwhelmed or de-repressed, whereby the apatite nuclei grow in size to coalesce into crystalline spindles and films—a mechanism that may explain not only the formation of calcium granules in nature but also normal or ectopic calcification in the body. PMID:19956594

In Situ Detection, Isolation, and Physiological Properties of a Thin Filamentous Microorganism Abundant in Methanogenic Granular Sludges: a Novel Isolate Affiliated with a Clone Cluster, the Green Non-Sulfur Bacteria, Subdivision I

PubMed Central

Sekiguchi, Yuji; Takahashi, Hiroki; Kamagata, Yoichi; Ohashi, Akiyoshi; Harada, Hideki

2001-01-01

We previously showed that very thin filamentous bacteria affiliated with the division green non-sulfur bacteria were abundant in the outermost layer of thermophilic methanogenic sludge granules fed with sucrose and several low-molecular-weight fatty acids (Y. Sekiguchi, Y. Kamagata, K. Nakamura, A. Ohashi, H. Harada, Appl. Environ. Microbiol. 65:1280–1288, 1999). Further 16S ribosomal DNA (rDNA) cloning-based analysis revealed that the microbes were classified within a unique clade, green non-sulfur bacteria (GNSB) subdivision I, which contains a number of 16S rDNA clone sequences from various environmental samples but no cultured representatives. To investigate their function in the community and physiological traits, we attempted to isolate the yet-to-be-cultured microbes from the original granular sludge. The first attempt at isolation from the granules was, however, not successful. In the other thermophilic reactor that had been treating fried soybean curd-manufacturing wastewater, we found filamentous microorganisms to outgrow, resulting in the formation of projection-like structures on the surface of granules, making the granules look like sea urchins. 16S rDNA-cloning analysis combined with fluorescent in situ hybridization revealed that the projections were comprised of the uncultured filamentous cells affiliated with the GNSB subdivision I and Methanothermobacter-like cells and the very ends of the projections were comprised solely of the filamentous cells. By using the tip of the projection as the inoculum for primary enrichment, a thermophilic, strictly anaerobic, filamentous bacterium, designated strain UNI-1, was successfully isolated with a medium supplemented with sucrose and yeast extract. The strain was a very slow growing bacterium which is capable of utilizing only a limited range of carbohydrates in the presence of yeast extract and produced hydrogen from these substrates. The growth was found to be significantly stimulated when the strain was cocultured with a hydrogen-utilizing methanogen, Methanothermobacter thermautotrophicus, suggesting that the strain is a sugar-fermenting bacterium, the growth of which is dependent on hydrogen consumers in the granules. PMID:11722931

Local corticotropin releasing hormone (CRH) signals to its receptor CRHR1 during postnatal development of the mouse olfactory bulb.

PubMed

Garcia, Isabella; Bhullar, Paramjit K; Tepe, Burak; Ortiz-Guzman, Joshua; Huang, Longwen; Herman, Alexander M; Chaboub, Lesley; Deneen, Benjamin; Justice, Nicholas J; Arenkiel, Benjamin R

2016-01-01

Neuropeptides play important physiological functions during distinct behaviors such as arousal, learning, memory, and reproduction. However, the role of local, extrahypothalamic neuropeptide signaling in shaping synapse formation and neuronal plasticity in the brain is not well understood. Here, we characterize the spatiotemporal expression profile of the neuropeptide corticotropin-releasing hormone (CRH) and its receptor CRHR1 in the mouse OB throughout development. We found that CRH-expressing interneurons are present in the external plexiform layer, that its cognate receptor is expressed by granule cells, and show that both CRH and CRHR1 expression enriches in the postnatal period when olfaction becomes important towards olfactory-related behaviors. Further, we provide electrophysiological evidence that CRHR1-expressing granule cells functionally respond to CRH ligand, and that the physiological circuitry of CRHR1 knockout mice is abnormal, leading to impaired olfactory behaviors. Together, these data suggest a physiologically relevant role for local CRH signaling towards shaping the neuronal circuitry within the mouse OB.

Recycled tire crumb rubber anodes for sustainable power production in microbial fuel cells

NASA Astrophysics Data System (ADS)

Wang, Heming; Davidson, Matthew; Zuo, Yi; Ren, Zhiyong

One of the greatest challenges facing microbial fuel cells (MFCs) in large scale applications is the high cost of electrode material. We demonstrate here that recycled tire crumb rubber coated with graphite paint can be used instead of fine carbon materials as the MFC anode. The tire particles showed satisfactory conductivity after 2-4 layers of coating. The specific surface area of the coated rubber was over an order of magnitude greater than similar sized graphite granules. Power production in single chamber tire-anode air-cathode MFCs reached a maximum power density of 421 mW m -2, with a coulombic efficiency (CE) of 25.1%. The control graphite granule MFC achieved higher power density (528 mW m -2) but lower CE (15.6%). The light weight of tire particle could reduce clogging and maintenance cost but posts challenges in conductive connection. The use of recycled material as the MFC anodes brings a new perspective to MFC design and application and carries significant economic and environmental benefit potentials.

Species and distribution of inorganic and organic phosphorus in enhanced phosphorus removal aerobic granular sludge.

PubMed

Huang, Wenli; Huang, Weiwei; Li, Huifang; Lei, Zhongfang; Zhang, Zhenya; Tay, Joo Hwa; Lee, Duu-Jong

2015-10-01

The species and distribution of phosphorus (P) in an enhanced biological phosphorus removal (EBPR)-aerobic granular sludge (AGS) were fractionated and further analyzed. Results showed that microbial cells, extracellular polymeric substances (EPS) and mineral precipitates contributed about 73.7%, 17.6% and 5.3-6.4% to the total P (TP) of EBPR-AGS, respectively. Inorganic P (IP) species were orthophosphate, pyrophosphate and polyphosphate among which polyphosphate was the major P species in the AGS, cells and EPS. Monoester and diester phosphates were identified as the organic P (OP) species in the AGS and cells. Hydroxyapatite (Ca5(PO4)3OH) and calcium phosphate (Ca2(PO4)3) were the dominant P minerals accumulated in the core of the granules. Cells along with polyphosphate were mainly in the outer layer of AGS while EPS were distributed in the whole granules. Based on the above results, the distribution of IP and OP species in AGS has been conceived. Copyright © 2015 Elsevier Ltd. All rights reserved.

A new coccidian parasite, Isospora samoaensis, from the Wattled Honeyeater (Foulehaio carunculata) from American Samoa

USGS Publications Warehouse

Adamczyk, Kelly J.; McQuistion, Thomas E.; LaPointe, Dennis

2004-01-01

A new species of Isospora is described from the feces of the wattled honeyeater, Foulehaio carunculata from American Samoa. Numerous oocysts of similar morphology were found in a single adult wattled honeyeater. Sporulated oocysts are ovoid, 28.9 × 26.1 (25-32 × 23-30) µm, with a smooth, colorless, bilayered wall; the inner wall is slightly thicker and darker than the outer wall. The average shape index is 1.1. No micropyle or oocyst residuum are present but the oocyst contains one or two ovoid polar granules. Sporocysts are ovoid, 17.1 × 10.9 (16-18 × 10-11) µm with a smooth single layered wall and an average shape index of 1.6. The Stieda body is broad, dome-like with a rather rectangular-shaped substieda body. Within the sporocyst is a large amorphous residuum composed of coarse granules and 4 randomly arranged, sausage-shaped sporozoites with a subspherical, posterior refractile body and a centrally located nucleus.

Profilin1 activity in cerebellar granule neurons is required for radial migration in vivo

PubMed Central

Kullmann, Jan A; Wickertsheim, Ines; Minnerup, Lara; Costell, Mercedes; Friauf, Eckhard; Rust, Marco B

2015-01-01

Neuron migration defects are an important aspect of human neuropathies. The underlying molecular mechanisms of such migration defects are largely unknown. Actin dynamics has been recognized as an important determinant of neuronal migration, and we recently found that the actin-binding protein profilin1 is relevant for radial migration of cerebellar granule neurons (CGN). As the exploited brain-specific mutants lacked profilin1 in both neurons and glial cells, it remained unknown whether profilin1 activity in CGN is relevant for CGN migration in vivo. To test this, we capitalized on a transgenic mouse line that expresses a tamoxifen-inducible Cre variant in CGN, but no other cerebellar cell type. In these profilin1 mutants, the cell density was elevated in the molecular layer, and ectopic CGN occurred. Moreover, 5-bromo-2′-deoxyuridine tracing experiments revealed impaired CGN radial migration. Hence, our data demonstrate the cell autonomous role of profilin1 activity in CGN for radial migration. PMID:25495756

Preparation of novel layer-stack hexagonal CdO micro-rods by a pre-oxidation and subsequent evaporation process

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peng, Kun, E-mail: kpeng@hnu.edu.cn; Hunan Province Key Laboratory for Spray Deposition Technology and Application, Hunan University, Changsha 410082; Jiang, Pan

2014-12-15

Graphical abstract: Layer-stack hexagonal cadmium oxide (CdO) micro-rods were prepared. - Highlights: • Novel hexagonal layer-stack structure CdO micro-rods were synthesized by a thermal evaporation method. • The pre-oxidation, vapor pressure and substrate nature play a key role on the formation of CdO rods. • The formation mechanism of CdO micro-rods was explained. - Abstract: Novel layer-stack hexagonal cadmium oxide (CdO) micro-rods were prepared by pre-oxidizing Cd granules and subsequent thermal oxidation under normal atmospheric pressure. X-ray diffraction (XRD) and scanning electron microscopy (SEM) were performed to characterize the phase structure and microstructure. The pre-oxidation process, vapor pressure and substratemore » nature were the key factors for the formation of CdO micro-rods. The diameter of micro-rod and surface rough increased with increasing of thermal evaporation temperature, the length of micro-rod increased with the increasing of evaporation time. The formation of hexagonal layer-stack structure was explained by a vapor–solid mechanism.« less

Evaluation of beta-lactose, PVP K12 and PVP K90 as excipients to prepare piroxicam granules using two wet granulation techniques.

PubMed

Albertini, Beatrice; Cavallari, Cristina; Passerini, Nadia; González-Rodríguez, M L; Rodriguez, Lorenzo

2003-11-01

The present investigation aimed at evaluating the use of different excipients, beta-lactose and polyvinylpyrrolidone of two molecular weights (PVP K12 and PVP K90), in the production of improved release piroxicam granules, by wet granulation using both water and steam as granulation liquid. The formulations examined were: piroxicam (Px)/beta-lactose; Px/PVP K12 and Px/PVP K90, each one at a 1:9 weight ratio. The most significant difference between beta-lactose and PVP is that, using the first excipient, both steam and water granules were produced while, when PVP were employed, only steam granules were obtained. Image analysis revealed that beta-lactose steam granules had a larger surface area with respect to water granules, whereas lower values of this parameter were observed in PVP-s granules, confirming the Scanning Electron Microscopy micrographs and the fractal analysis results. As regards the enhancement of the dissolution profiles, the best result was obtained using beta-lactose steam granules followed by PVP K12 ones, even if the reactive dimension values indicated that during the dissolution process PVP K12 granules modified the surface more than beta-lactose granules. As regards PVP K90, this excipient was the one less influencing the granule morphology and the dissolution behaviour. Differential Scanning Calorimetry analysis suggested the partial amorphisation of the drug in the granules containing the three excipients. This result was then confirmed by X-ray powder diffraction analysis. Therefore, beta-lactose and PVP K12 could be proposed as useful excipients to enhance the dissolution rate of Px from granules prepared using the steam granulation technique.

Improvements to the CATS Cloud-Aerosol Data Products and Implications for the Space-Based Lidar Data Record

NASA Astrophysics Data System (ADS)

Yorks, J. E.; McGill, M. J.; Nowottnick, E. P.; Palm, S. P.; Hlavka, D. L.; Selmer, P. A.; Rodier, S. D.; Vaughan, M.; Pauly, R.

2017-12-01

The Cloud-Aerosol Transport System (CATS) is an elastic backscatter lidar that has generated over 175 billion laser pulses on-orbit from the International Space Station (ISS) since February 2015. The CATS instrument was designed to demonstrate new in-space technologies for future Earth Science missions while also providing properties of clouds and aerosols such as: layer height/thickness, backscatter, optical depth, extinction, and feature type. Despite the "tech demo" nature of CATS and the lack of a funded science team, the research community is increasingly embracing CATS data. New CATS data products, the most acurrate yet, were released in the summer of 2017. The major algorithm changes made in L1B Version 2-08 (V2-08) focused on the backscatter calibration and the inclusion of a new flag to notify users of granules with depolarization ratio values of poor quality. Several changes were made to the molecular folding correction factor and calibration algorithms that result in favorable comparisons between CATS, CALIPSO, and modeled Rayleigh 1064 nm backscatter profiles. Given that the 1064 nm attenuated total backscatter and depolarization ratio are used to retrieve nearly all L2O data products, the accuracy of the L2O products has also improved. Several changes were made in CATS L2O Version 2-00 data products to improve cloud and aerosol detection. The CATS L2O data now includes layer detection at both 5 and 60 km horizontal resolutions to increase daytime detection of thin cirrus and aerosol layers over land. Horizontal persistence tests prevent superficial "striping" that was visible in vertical feature mask images for horizontally homogeneous cloud and aerosol layers. Also, the absolute uncertainties for all the L2O parameters are now reported in the CATS data products. Given the uncertain status of continued CALIPSO operations, these updated CATS data products may be the only space-based lidar data record that continues into the 2018 timeframe.

Intracisternal granules in the adipokinetic cells of locusts are not degraded and apparently function as supplementary stores of secretory material.

PubMed

Harthoorn, L F; Diederen, J H; Oudejans, R C; Verstegen, M M; Vullings, H G; Van der Horst, D J

2000-01-01

The intracisternal granules in locust adipokinetic cells appear to represent accumulations of secretory material within cisternae of the rough endoplasmic reticulum. An important question is whether these granules are destined for degradation or represent stores of (pro)hormones. Two strategies were used to answer this question. First, cytochemistry was applied to elucidate the properties of intracisternal granules. The endocytic tracers horseradish peroxidase and wheat-germ agglutinin-conjugated horseradish peroxidase were used to facilitate the identification of endocytic, autophagic, and lysosomal organelles, which may be involved in the degradation of intracisternal granules. No intracisternal granules could be found within autophagosomes, and granules fused with endocytic and lysosomal organelles were not observed, nor could tracer be found within the granules. The lysosomal enzyme acid phosphatase was absent from the granules. Second, biochemical analysis of the content of intracisternal granules revealed that these granules contain prohormones as well as hormones. Prohormones were present in relatively higher amounts compared with ordinary secretory granules. Since the intracisternal granules in locust adipokinetic cells are not degraded and contain intact (pro)hormones it is concluded that they function as supplementary stores of secretory material.

Three-Dimensional Porous Particles Composed of Curved, Two-Dimensional, Nano-Sized Layers for Li-Ion Batteries

NASA Technical Reports Server (NTRS)

Yushin, Gleb; Evanoff, Kara; Magasinski, Alexander

2012-01-01

Thin Si films coated on porous 3D particles composed of curved 2D graphene sheets have been synthesized utilizing techniques that allow for tunable properties. Since graphene exhibits specific surface area up to 100 times higher than carbon black or graphite, the deposition of the same mass of Si on graphene is much faster in comparison -- a factor which is important for practical applications. In addition, the distance between graphene layers is tunable and variation in the thickness of the deposited Si film is feasible. Both of these characteristics allow for optimization of the energy and power characteristics. Thicker films will allow higher capacity, but slower rate capabilities. Thinner films will allow more rapid charging, or higher power performance. In this innovation, uniform deposition of Si and C layers on high-surface area graphene produced granules with specific surface area (SSA) of 5 sq. m/g.

Influence of metronidazole particle properties on granules prepared in a high-shear mixer-granulator.

PubMed

Di Martino, Piera; Censi, Roberta; Malaj, Ledjan; Martelli, Sante; Joiris, Etienne; Barthélémy, Christine

2007-02-01

Metronidazole is a good example of high-dose drug substance with poor granulating and tableting properties. Tablets are generally produced by liquid granulation; however, the technological process failure is quite frequent. In order to verify how the metronidazole particle characteristics can influence granule properties, three metronidazole batches differing for crystal habit, mean particle size, BET surface area and wettability were selected, primarily designed according to their different elongation ratio: needle-shaped, stick-shaped, and isodimensional. In the presence of lactose monohydrate and pregelatinized maize starch, respectively as diluent and binder, they were included in a formula for wet granulation in a high-shear mixer-granulator. In order to render the process comparable as far as possible, all parameters and experimental conditions were maintained constant. Four granule batches were obtained: granules from placebo (G-placebo), granules from needle-shaped crystals (G-needle-shaped), granules from stick-shaped crystals (G-stick-shaped), and granules from isodimensional crystals (G-isodimensional). Different granule properties were considered, in particular concerning porosity, friability, loss on drying (LOD), and flowability. In order to study their tabletability and compressibility, the different granules obtained were then compressed in a rotary press. The best tabletability was obtained with the isodimensional batch, while the poorest was exhibited by the stick-shaped one. Differences in tabletability are in good accordance with compressibility results: to a better tabletability corresponds an important granule ability to undergo a volume reduction as a result of an applied pressure. In particular, it was proposed that the greatest compressibility of the G-isodimensional must be related to the greatest granule porosity percentage.

Evaluation of the physicochemical properties and compaction behavior of melt granules produced in microwave-induced and conventional melt granulation in a single pot high shear processor.

PubMed

Loh, Z H; Sia, B Y; Heng, Paul W S; Lee, C C; Liew, Celine V

2011-12-01

Recently, microwave-induced melt granulation was shown to be a promising alternative to conventional melt granulation with improved process monitoring capabilities. This study aimed to compare the physicochemical and compaction properties of granules produced from microwave-induced and conventional melt granulation. Powder admixtures comprising equivalent proportions by weight of lactose 200 M and anhydrous dicalcium phosphate were granulated with polyethylene glycol 3350 under the influence of microwave-induced and conventional heating in a 10-L single pot high shear processor. The properties of the granules and compacts produced from the two processes were compared. Relative to conventional melt granulation, the rates at which the irradiated powders heated up in microwave-induced melt granulation were lower. Agglomerate growth proceeded at a slower rate, and this necessitated longer massing durations for growth induction. These factors prompted greater evaporative moisture losses from the melt granules. Additionally, nonuniform heating of the powders under the influence of microwaves led to increased inter-batch variations in the binder contents of resultant melt granules and a reliance of content homogeneity on massing duration. Agglomerate growth proceeded more rapidly under the influence of conventional heating due to the enhanced heating capabilities of the powders. Melt granules produced using the conventional method possessed higher moisture contents and improved content homogeneity. The compaction behavior of melt granules were affected by their mean sizes, porosities, flow properties, binder, and moisture contents. The last two factors were responsible for the disparities in compaction behavior of melt granules produced from microwave-induced and conventional melt granulation.

Drosophila Vps16A is required for trafficking to lysosomes and biogenesis of pigment granules.

PubMed

Pulipparacharuvil, Suprabha; Akbar, Mohammed Ali; Ray, Sanchali; Sevrioukov, Evgueny A; Haberman, Adam S; Rohrer, Jack; Krämer, Helmut

2005-08-15

Mutations that disrupt trafficking to lysosomes and lysosome-related organelles cause multiple diseases, including Hermansky-Pudlak syndrome. The Drosophila eye is a model system for analyzing such mutations. The eye-color genes carnation and deep orange encode two subunits of the Vps-C protein complex required for endosomal trafficking and pigment-granule biogenesis. Here we demonstrate that dVps16A (CG8454) encodes another Vps-C subunit. Biochemical experiments revealed a specific interaction between the dVps16A C-terminus and the Sec1/Munc18 homolog Carnation but not its closest homolog, dVps33B. Instead, dVps33B interacted with a related protein, dVps16B (CG18112). Deep orange bound both Vps16 homologs. Like a deep orange null mutation, eye-specific RNAi-induced knockdown of dVps16A inhibited lysosomal delivery of internalized ligands and interfered with biogenesis of pigment granules. Ubiquitous knockdown of dVps16A was lethal. Together, these findings demonstrate that Drosophila Vps16A is essential for lysosomal trafficking. Furthermore, metazoans have two types of Vps-C complexes with non-redundant functions.

Effect of different excipients on the physical characteristics of granules and tablets with carbamazepine prepared with polyethylene glycol 6000 by fluidized hot-melt granulation (FHMG).

PubMed

Kraciuk, Radosław; Sznitowska, Malgorzata

2011-12-01

The objective of this study was to investigate the properties of granules and tablets with carbamazepine which were prepared employing a fluidized hot-melt granulation (FHMG) technique. The FHMG process was carried out at 65°C. Macrogol 6000 (PEG 6000) was used as a binder at the content 10% (w/w) of the granulated mass. Granules containing up to 70% (w/w) of the drug and 20-90% (w/w) of a filler (lactose, mannitol, calcium hydrogen phosphate (Di-Cafos), pregelatinized starch, and microcrystalline cellulose (MCC)) were produced. When the drug content was 30% (w/w), the yield of the process was satisfying (>95%) and flowability of the granules was better than placebo granules or drug-loaded granules prepared by wet granulation. Type of a filler had strong impact on physical properties of granules, and size distribution of the particles was the most homogenous when lactose or Di-Cafos were used. The FHMG technique enabled preparation of granules with better compressability compared with the wet-granulated product or with non-granulated powders. Tablets with shorter disintegration time than 10 min were obtained with 2.0% crospovidone added as a disintegrant. In comparison to tablets prepared from the wet-granulated mass, employment of the FHMG method resulted in tablets with faster dissolution of carbamazepine (more than 80% of the drug released within 15 min). This was achieved with mannitol or lactose/MCC, as fillers.

Structural micro-porous carbon anode for rechargeable lithium-ion batteries

DOEpatents

Delnick, Frank M.; Even, Jr., William R.; Sylwester, Alan P.; Wang, James C. F.; Zifer, Thomas

1995-01-01

A secondary battery having a rechargeable lithium-containing anode, a cathode and a separator positioned between the cathode and anode with an organic electrolyte solution absorbed therein is provided. The anode comprises three-dimensional microporous carbon structures synthesized from polymeric high internal phase emulsions or materials derived from this emulsion source, i.e., granules, powders, etc.

[Preparation and evaluation of taste masked orally disintegrating tablets with granules made by the wet granulation method].

PubMed

Kawano, Yayoi; Ito, Akihiko; Sasatsu, Masanaho; Machida, Yoshiharu; Onishi, Hiraku

2010-12-01

Using furosemide (FU) as a model drug, we examined the wet granulation method as a way to improve the taste masking and physical characteristics of orally disintegrating tablets (ODTs). In the wet granulation method, yogurt powder (YO) was used as a corrective and maltitol (MA) was used as a binding agent. The taste masked FU tablets were prepared using the direct compression method. Microcrystalline cellulose (Avicel® PH-302) and mannitol were added as excipients at a mixing ratio of 1/1 by weight. Based on the results of sensory test on taste, the prepared granules markedly improved the taste of FU, and a sufficient masking effect was obtained at the YO/FU ratio of 1 or more. Furthermore, it was found that the masking effect achieved by YO granules made with the wet granulation method was similar to or better than that produced by the granules made with dry granulation method. All types of tablets displayed sufficient hardness (over 3.5×10(-2) kN), and rapidly disintegrating tablets were obtained with YO granules produced at a mixing ratio of FU/YO=1/1, which disintegrated within 20 s. Disintegration time lengthened as the mixing ratio of YO to FU increased. In the mixing ratio of FU/YO=1/1, the hardness of tablets with granules made by the wet granulation method exceeded that of tablets with granules made by the dry granulation method, with minimal differences in disintegration time. The hardness and disintegration time of the tablets with granules made by the wet granulation method could be controlled by varying the compression force. In conclusion, YO was found to be a useful additive for masking unpleasant tastes. FU ODTs with improved taste, rapid disintegration and greater hardness could be prepared with YO-containing granules made by the wet granulation method using MA as a binding agent.

Rapid Feedforward Inhibition and Asynchronous Excitation Regulate Granule Cell Activity in the Mammalian Main Olfactory Bulb

PubMed Central

Burton, Shawn D.

2015-01-01

Granule cell-mediated inhibition is critical to patterning principal neuron activity in the olfactory bulb, and perturbation of synaptic input to granule cells significantly alters olfactory-guided behavior. Despite the critical role of granule cells in olfaction, little is known about how sensory input recruits granule cells. Here, we combined whole-cell patch-clamp electrophysiology in acute mouse olfactory bulb slices with biophysical multicompartmental modeling to investigate the synaptic basis of granule cell recruitment. Physiological activation of sensory afferents within single glomeruli evoked diverse modes of granule cell activity, including subthreshold depolarization, spikelets, and suprathreshold responses with widely distributed spike latencies. The generation of these diverse activity modes depended, in part, on the asynchronous time course of synaptic excitation onto granule cells, which lasted several hundred milliseconds. In addition to asynchronous excitation, each granule cell also received synchronous feedforward inhibition. This inhibition targeted both proximal somatodendritic and distal apical dendritic domains of granule cells, was reliably recruited across sniff rhythms, and scaled in strength with excitation as more glomeruli were activated. Feedforward inhibition onto granule cells originated from deep short-axon cells, which responded to glomerular activation with highly reliable, short-latency firing consistent with tufted cell-mediated excitation. Simulations showed that feedforward inhibition interacts with asynchronous excitation to broaden granule cell spike latency distributions and significantly attenuates granule cell depolarization within local subcellular compartments. Collectively, our results thus identify feedforward inhibition onto granule cells as a core feature of olfactory bulb circuitry and establish asynchronous excitation and feedforward inhibition as critical regulators of granule cell activity. SIGNIFICANCE STATEMENT Inhibitory granule cells are involved critically in shaping odor-evoked principal neuron activity in the mammalian olfactory bulb, yet little is known about how sensory input activates granule cells. Here, we show that sensory input to the olfactory bulb evokes a barrage of asynchronous synaptic excitation and highly reliable, short-latency synaptic inhibition onto granule cells via a disynaptic feedforward inhibitory circuit involving deep short-axon cells. Feedforward inhibition attenuates local depolarization within granule cell dendritic branches, interacts with asynchronous excitation to suppress granule cell spike-timing precision, and scales in strength with excitation across different levels of sensory input to normalize granule cell firing rates. PMID:26490853

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fujita-Yoshigaki, Junko; Katsumata, Osamu; Matsuki, Miwako

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

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

PubMed

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

2012-11-16

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

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

PubMed

2015-02-01

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

Rocks of the early lunar crust

NASA Technical Reports Server (NTRS)

James, O. B.

1980-01-01

Data are summarized which suggest a model for the early evolution of the lunar crust. According to the model, during the final stages of accretion, the outer part of the moon melted to form a magma ocean approximately 300 km deep. This ocean fractionated to form mafic and ultramafic cumulates at depth and an overlying anorthositic crust made up of ferroan anorthosites. Subsequent partial melting in the primitive mantle underlying the crystallized magma ocean produced melts which segregated, moved upward, intruded the primordial crust, and crystallized to form layered plutons consisting of Mg-rich plutonic rocks. Intense impact bombardment at the lunar surface mixed and melted the rocks of the two suites to form a thick layer of granulated debris, granulitic breccias, and impact-melt rocks.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bello, Oscar Daniel; Cappa, Andrea Isabel; Paola, Matilde de

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

Heat Transfer Retardation at Elevated Temperatures. Phase I. Analysis of Heat Transfer Retardation Configurations and Materials.

DTIC Science & Technology

1983-09-01

perature level effects the flow of the lignin (naturally found in cork) which acts as a binder. Then the bound cork granules are carbonized in an inert...distribution unlimited 17. DISTRIBUTION STATEMENT ( of the abstract entered In Stock 20. it different Inro Report) Same as block 16 I$. SUPPLEMENTARY NOTES 19...applications and was used to estimate the retardation characteristics in terms of an overall thermal resistance and unit weight. Multi-layer

Method of sintering ceramic materials

DOEpatents

Holcombe, C.E.; Dykes, N.L.

1992-11-17

A method for sintering ceramic materials is described. A ceramic article is coated with layers of protective coatings such as boron nitride, graphite foil, and niobium. The coated ceramic article is embedded in a container containing refractory metal oxide granules and placed within a microwave oven. The ceramic article is heated by microwave energy to a temperature sufficient to sinter the ceramic article to form a densified ceramic article having a density equal to or greater than 90% of theoretical density. 2 figs.

Surface Localization of Zein Storage Proteins in Starch Granules from Maize Endosperm1

PubMed Central

Mu-Forster, Chen; Wasserman, Bruce P.

1998-01-01

Starch granules from maize (Zea mays) contain a characteristic group of polypeptides that are tightly associated with the starch matrix (C. Mu-Forster, R. Huang, J.R. Powers, R.W. Harriman, M. Knight, G.W. Singletary, P.L. Keeling, B.P. Wasserman [1996] Plant Physiol 111: 821–829). Zeins comprise about 50% of the granule-associated proteins, and in this study their spatial distribution within the starch granule was determined. Proteolysis of starch granules at subgelatinization temperatures using the thermophilic protease thermolysin led to selective removal of the zeins, whereas granule-associated proteins of 32 kD or above, including the waxy protein, starch synthase I, and starch-branching enzyme IIb, remained refractory to proteolysis. Granule-associated proteins from maize are therefore composed of two distinct classes, the surface-localized zeins of 10 to 27 kD and the granule-intrinsic proteins of 32 kD or higher. The origin of surface-localized δ-zein was probed by comparing δ-zein levels of starch granules obtained from homogenized whole endosperm with granules isolated from amyloplasts. Starch granules from amyloplasts contained markedly lower levels of δ-zein relative to granules prepared from whole endosperm, thus indicating that δ-zein adheres to granule surfaces after disruption of the amyloplast envelope. Cross-linking experiments show that the zeins are deposited on the granule surface as aggregates. In contrast, the granule-intrinsic proteins are prone to covalent modification, but do not form intermolecular cross-links. We conclude that individual granule intrinsic proteins exist as monomers and are not deposited in the form of multimeric clusters within the starch matrix. PMID:9536075

Insensitivity of compaction properties of brittle granules to size enlargement by roller compaction.

PubMed

Wu, Sy-Juen; Sun, Changquan 'Calvin'

2007-05-01

Pharmaceutical granules prepared by roller compaction often exhibit significant loss of tabletability, that is, reduction in tensile strength, when compared to virgin powder. This may be attributed to granule size enlargement for highly plastic materials, for example, microcrystalline cellulose. The sensitivity of powder compaction properties on granule size variations impacts the robustness of the dry granulation process. We hypothesize that such sensitivity of compaction properties on granule size is minimum for brittle materials because extensive fracture of brittle granules during compaction minimizes differences in initial granule size. We tested the hypothesis using three common brittle excipients. Results show that the fine (44-106 microm), medium (106-250 microm), and coarse (250-500 microm) granules exhibit essentially identical tabletability below a certain critical compaction pressure, 100, 140, and 100 MPa for spray-dried lactose monohydrate, anhydrous dibasic calcium phosphate, and mannitol, respectively. Above respective critical pressure, tabletability lines diverge with smaller granules exhibiting slightly higher tablet tensile strength at identical compaction conditions. Overall, tabletability of brittle granules is insensitive to granule size enlargement. The results provide a scientific basis to the common practice of incorporating brittle filler to a typical tablet formulation processed by roller compaction granulation. (c) 2007 Wiley-Liss, Inc. and the American Pharmacists Association.

Roll compaction/dry granulation: comparison between roll mill and oscillating granulator in dry granulation.

PubMed

Sakwanichol, Jarunee; Puttipipatkhachorn, Satit; Ingenerf, Gernot; Kleinebudde, Peter

2012-01-01

Different experimental factorial designs were employed to evaluate granule properties obtained from oscillating granulator and roll mill. Four oscillating-granulator parameters were varied, i.e. rotor speed, oscillating angle, aperture of mesh screen and rotor type. Six roll-mill parameters that were throughput, speed ratio in both first and second stages, gap between roll pair in both stages and roll-surface texture were also investigated. Afterwards, the granule properties obtained from two milling types with similar median particle size were compared. All milling parameters in both milling types affected significantly the median particle size, size distribution and amount of fine particles (P < 0.05), except the rotor types of oscillating granulator on fines. Only three milling parameters influenced significantly the flowability (P < 0.05). These were the throughput and the gap size in the first stage of roll mill and the sieve size of oscillating granulator. In comparison between milling types, the differences of granule properties were not practically relevant. However, the roll mill had much higher capacity than the oscillating granulator about seven times, resulting in improving energy savings per unit of product. Consequently, the roll mill can be applied instead of oscillating granulator for roll compaction/dry granulation technique.

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

PubMed

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

2017-05-15

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

Enhancement of ibuprofen dissolution via wet granulation with beta-cyclodextrin.

PubMed

Ghorab, M K; Adeyeye, M C

2001-08-01

The purpose was to investigate the effect of wet granulation with beta-cyclodextrin (betaCD) on the enhancement of ibuprofen (IBU) dissolution. The effect of the granulation variables on the physical properties as well as the dissolution of tablets prepared from these granules was also examined. Granulation was performed using three granulating solvents: water, ethanol (95 vol%), and isopropanol. Granules were either oven-dried for 2 h or air-dried for 3 days. The granules or respective physical mixtures were compressed into tablets. Powder X-ray diffraction showed that oven-dried granulation resulted in less amorphous entities thatfacilitated IBU-betaCD complexation in solution and enhanced the dissolution of the corresponding tablets compared to the physical mixture with or without oven drying. In contrast, air-dried granulation did not cause any differences in the X-ray diffraction pattern (crystallinity) or the dissolution compared to the physical mixture without drying. Isopropanol and water, as granulating solvents, enhanced the dissolution of the oven-dried batches more than ethanol. The Differential scanning calorimetry (DSC) and Thermogravimetric analysis (TGA) data showed that tablets prepared from oven-dried granules, but not air-dried granules, had lower AH values and percent loss in weight, respectively, than those prepared from the physical mixture as a result of the expulsion of the water molecules from the betaCD cavity and enhancement of the complexation in solution. These results showed that oven-dried granulation of IBU and betaCD provided faster IBU dissolution than the physical mixture; air-dried granulation did not substantially affect the dissolution of IBU.

The biological significance of storage granules in rat parathyroid cells.

PubMed

Setoguti, T; Inoue, Y; Wild, P

1995-10-01

Both prosecretory and storage granules are concomitantly formed at the trans Golgi network including the innermost Golgi cisterna. Prosecretory granules develop into small secretory granules that release their contents by exocytosis finely regulated by a complex mechanism for maintaining calcium homeostasis. In the rat parathyroid cells, storage granules are large secretory granules storing parathyroid hormone for an emergency supply. The hormone is rapidly discharged by exocytosis when serum calcium concentration is decreased. The granules are constantly produced even under conditions of low serum calcium concentration in the regions of 8 mg/dl. The granule content is constantly hydrolyzed when not discharged, leading to a decreased core and finally to the formation of vacuolar bodies. The fate of the vacuolar bodies is unknown. Hypercalcemic conditions accelerate hydrolysis. The threshold value of calcium concentration required for the release of storage granule contents is between 8.0 and 7.5 mg/dl and that of calcium concentration for accelerating degradation of storage granules is about 11.5 mg/dl. Sympathetic stimulation causes storage granules to be discharged regardless of hypercalcemia or hypocalcemia. Parasympathetic stimulation accelerates hydrolysis. The degradation of storage granules seems to be closely associated with an intracellular regulatory mechanism for parathyroid hormone secretion.

Specific aerobic granules can be developed in a completely mixed tank reactor by bioaugmentation using micro-mycelial pellets of Phanerochaete chrysosporium.

PubMed

Hailei, Wang; Ping, Li; Qianlong, Jin; Ge, Qin

2014-03-01

Aerobic granules were firstly developed in a completely mixed tank reactor (CMTR) by seeding micro-mycelial pellets (MMPs) of Phanerochaete chrysosporium. During phenol wastewater treatment, sludge granulation rate reached 67 % after 15-day operation. The granules in CMTR are different from aerobic granules described in literature in morphology, and a majority of them are rod-shaped or rodlike sludge besides spherical granules. The polymorphic granules, having no essential difference with aerobic granules previously reported, achieve advantages over conventional activated sludge in settling ability, biomass concentration, density, integrity coefficient and removal ability to phenol wastewater. The optimized parameters for sludge granulation in CMTR including temperature, inoculum quantity, rotary speed and superficial air upflow velocity are 30 °C, 5–7 g/l, 150 rpm, and 0.5 cm/s, respectively. Analysis on sludge granulation mechanism indicates that MMPs not only result in the formation of aerobic granules containing MMPs as nuclei, but also induce the formation of biogranules which do not have MMP at their cores. The work challenges the general belief that the homogenous circular flow pattern of microbial aggregates is necessary for aerobic sludge granulation.

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

PubMed Central

2012-01-01

Background Poly(3-hydroxybutyrate) (PHB) granules are important storage compounds of carbon and energy in many prokaryotes which allow survival of the cells in the absence of suitable carbon sources. Formation and subcellular localization of PHB granules was previously assumed to occur randomly in the cytoplasm of PHB accumulating bacteria. However, contradictionary results on subcellular localization of PHB granules in Ralstonia eutropha were published, recently. Results Here, we provide evidence by transmission electron microscopy that PHB granules are localized in close contact to the nucleoid region in R. eutropha during growth on nutrient broth. Binding of PHB granules to the nucleoid is mediated by PhaM, a PHB granule associated protein with phasin-like properties that is also able to bind to DNA and to phasin PhaP5. Over-expression of PhaM resulted in formation of many small PHB granules that were always attached to the nucleoid region. In contrast, PHB granules of ∆phaM strains became very large and distribution of granules to daughter cells was impaired. Association of PHB granules to the nucleoid region was prevented by over-expression of PhaP5 and clusters of several PHB granules were mainly localized near the cell poles. Conclusion Subcellular localization of PHB granules is controlled in R. eutropha and depends on the presence and concentrations of at least two PHB granule associated proteins, PhaM and PhaP5. PMID:23157596

Insulin Storage and Glucose Homeostasis in Mice Null for the Granule Zinc Transporter ZnT8 and Studies of the Type 2 Diabetes–Associated Variants

PubMed Central

Nicolson, Tamara J.; Bellomo, Elisa A.; Wijesekara, Nadeeja; Loder, Merewyn K.; Baldwin, Jocelyn M.; Gyulkhandanyan, Armen V.; Koshkin, Vasilij; Tarasov, Andrei I.; Carzaniga, Raffaella; Kronenberger, Katrin; Taneja, Tarvinder K.; da Silva Xavier, Gabriela; Libert, Sarah; Froguel, Philippe; Scharfmann, Raphael; Stetsyuk, Volodymir; Ravassard, Philippe; Parker, Helen; Gribble, Fiona M.; Reimann, Frank; Sladek, Robert; Hughes, Stephen J.; Johnson, Paul R.V.; Masseboeuf, Myriam; Burcelin, Remy; Baldwin, Stephen A.; Liu, Ming; Lara-Lemus, Roberto; Arvan, Peter; Schuit, Frans C.; Wheeler, Michael B.; Chimienti, Fabrice; Rutter, Guy A.

2009-01-01

OBJECTIVE Zinc ions are essential for the formation of hexameric insulin and hormone crystallization. A nonsynonymous single nucleotide polymorphism rs13266634 in the SLC30A8 gene, encoding the secretory granule zinc transporter ZnT8, is associated with type 2 diabetes. We describe the effects of deleting the ZnT8 gene in mice and explore the action of the at-risk allele. RESEARCH DESIGN AND METHODS Slc30a8 null mice were generated and backcrossed at least twice onto a C57BL/6J background. Glucose and insulin tolerance were measured by intraperitoneal injection or euglycemic clamp, respectively. Insulin secretion, electrophysiology, imaging, and the generation of adenoviruses encoding the low- (W325) or elevated- (R325) risk ZnT8 alleles were undertaken using standard protocols. RESULTS ZnT8−/− mice displayed age-, sex-, and diet-dependent abnormalities in glucose tolerance, insulin secretion, and body weight. Islets isolated from null mice had reduced granule zinc content and showed age-dependent changes in granule morphology, with markedly fewer dense cores but more rod-like crystals. Glucose-stimulated insulin secretion, granule fusion, and insulin crystal dissolution, assessed by total internal reflection fluorescence microscopy, were unchanged or enhanced in ZnT8−/− islets. Insulin processing was normal. Molecular modeling revealed that residue-325 was located at the interface between ZnT8 monomers. Correspondingly, the R325 variant displayed lower apparent Zn2+ transport activity than W325 ZnT8 by fluorescence-based assay. CONCLUSIONS ZnT8 is required for normal insulin crystallization and insulin release in vivo but not, remarkably, in vitro. Defects in the former processes in carriers of the R allele may increase type 2 diabetes risks. PMID:19542200

Molecular, mesoscopic and microscopic structure evolution during amylase digestion of maize starch granules.

PubMed

Shrestha, Ashok K; Blazek, Jaroslav; Flanagan, Bernadine M; Dhital, Sushil; Larroque, Oscar; Morell, Matthew K; Gilbert, Elliot P; Gidley, Michael J

2012-09-01

Cereal starch granules with high (>50%) amylose content are a promising source of nutritionally desirable resistant starch, i.e. starch that escapes digestion in the small intestine, but the structural features responsible are not fully understood. We report the effects of partial enzyme digestion of maize starch granules on amylopectin branch length profiles, double and single helix contents, gelatinisation properties, crystallinity and lamellar periodicity. Comparing results for three maize starches (27, 57, and 84% amylose) that differ in both structural features and amylase-sensitivity allows conclusions to be drawn concerning the rate-determining features operating under the digestion conditions used. All starches are found to be digested by a side-by-side mechanism in which there is no major preference during enzyme attack for amylopectin branch lengths, helix form, crystallinity or lamellar organisation. We conclude that the major factor controlling enzyme susceptibility is granule architecture, with shorter length scales not playing a major role as inferred from the largely invariant nature of numerous structural measures during the digestion process (XRD, NMR, SAXS, DSC, FACE). Results are consistent with digestion rates being controlled by restricted diffusion of enzymes within densely packed granular structures, with an effective surface area for enzyme attack determined by external dimensions (57 or 84% amylose - relatively slow) or internal channels and pores (27% amylose - relatively fast). Although the process of granule digestion is to a first approximation non-discriminatory with respect to structure at molecular and mesoscopic length scales, secondary effects noted include (i) partial crystallisation of V-type helices during digestion of 27% amylose starch, (ii) preferential hydrolysis of long amylopectin branches during the early stage hydrolysis of 27% and 57% but not 84% amylose starches, linked with disruption of lamellar repeating structure and (iii) partial B-type recrystallisation after prolonged enzyme incubation for 57% and 84% amylose starches but not 27% amylose starch. Copyright © 2012 Elsevier Ltd. All rights reserved.

Suggestive evidence of a vesicle-mediated mode of cell degranulation in chromaffin cells. A high-resolution scanning electron microscopy investigation

PubMed Central

Crivellato, Enrico; Solinas, Paola; Isola, Raffaella; Ribatti, Domenico; Riva, Alessandro

2010-01-01

In this study we used a modified osmium maceration method for high-resolution scanning electron microscopy to study some ultrastructural details fitting the schema of piecemeal degranulation in chromaffin cells. Piecemeal degranulation refers to a particulate pattern of cell secretion that is accomplished by vesicle-mediated extracellular transport of granule-stored material. We investigated adrenal samples from control and angiotensin II-treated rats, and identified a variable proportion of smooth, 30–60-nm-diameter vesicles in the cytoplasm of chromaffin cells. A percentage of these vesicles were interspersed in the cytosol among chromaffin granules but the majority appeared to be attached to granules. Remarkably, the number of unattached cytoplasmic vesicles was greatly increased in chromaffin cells from angiotensin II-treated animals. Vesicles of the same structure and dimension were detected close to or attached to the cytoplasmic face of the plasma membrane; these, too, were increased in number in chromaffin cells from rats stimulated with angiotensin II. In specimens shaken with a rotating agitator during maceration, the cytoplasmic organelles could be partially removed and the fine structure of the vesicular interaction with the inner side of the plasma membrane emerged most clearly. A proportion of chromaffin granules showed protrusions that we interpreted as vesicular structures budding from the granular envelope. In some instances, the transection plane intersected granules with putative vesicles emerging from the surfaces. In these cases, the protrusions of budding vesicles could be observed from the internal side. This study provides high-resolution scanning electron microscopy images compatible with a vesicle-mediated degranulation mode of cell secretion in adrenal chromaffin cells. The data indicating an increase in the number of vesicles observed in chromaffin cells after stimulation with the chromaffin cell secretagogue angiotensin II suggests that this secretory process may be susceptible to fine regulation. PMID:20136671

Lithium granule ablation and penetration during ELM pacing experiments at DIII-D

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lunsford, R.; Bortolon, A.; Roquemore, A. L.

At DIII-D, lithium granules were radially injected into the plasma at the outer midplane to trigger and pace edge localized modes (ELMs). Granules ranging in size from 300 to 1000 microns were horizontally launched into H-mode discharges with velocities near 100 m/s, and granule to granule injection frequencies less than 500 Hz. While the smaller granules were only successful in triggering ELMs approximately 20% of the time, the larger granules regularly demonstrated ELM triggering efficiencies of greater than 80%. A fast visible camera looking along the axis of injection observed the ablation of the lithium granules. We used the durationmore » of ablation as a benchmark for a neutral gas shielding calculation, and approximated the ablation rate and mass deposition location for the various size granules, using measured edge plasma profiles as inputs. In conclusion, this calculation suggests that the low triggering efficiency of the smaller granules is due to the inability of these granules to traverse the steep edge pressure gradient region and reach the top of the pedestal prior to full ablation.« less

Lithium granule ablation and penetration during ELM pacing experiments at DIII-D

DOE PAGES

Lunsford, R.; Bortolon, A.; Roquemore, A. L.; ...

2016-05-25

At DIII-D, lithium granules were radially injected into the plasma at the outer midplane to trigger and pace edge localized modes (ELMs). Granules ranging in size from 300 to 1000 microns were horizontally launched into H-mode discharges with velocities near 100 m/s, and granule to granule injection frequencies less than 500 Hz. While the smaller granules were only successful in triggering ELMs approximately 20% of the time, the larger granules regularly demonstrated ELM triggering efficiencies of greater than 80%. A fast visible camera looking along the axis of injection observed the ablation of the lithium granules. We used the durationmore » of ablation as a benchmark for a neutral gas shielding calculation, and approximated the ablation rate and mass deposition location for the various size granules, using measured edge plasma profiles as inputs. In conclusion, this calculation suggests that the low triggering efficiency of the smaller granules is due to the inability of these granules to traverse the steep edge pressure gradient region and reach the top of the pedestal prior to full ablation.« less

Foot-and-Mouth Disease Virus Counteracts on Internal Ribosome Entry Site Suppression by G3BP1 and Inhibits G3BP1-Mediated Stress Granule Assembly via Post-Translational Mechanisms

PubMed Central

Ye, Xu; Pan, Ting; Wang, Dang; Fang, Liurong; Ma, Jun; Zhu, Xinyu; Shi, Yanling; Zhang, Keshan; Zheng, Haixue; Chen, Huanchun; Li, Kui; Xiao, Shaobo

2018-01-01

Foot-and-mouth disease (FMD) is a highly contagious, severe viral illness notifiable to the World Organization for Animal Health. The causative agent, FMD virus (FMDV), replicates rapidly and efficiently inhibits host translation and the innate immune response for it has developed multiple tactics to evade host defenses and takes over gene expression machinery in the host cell. Here, we report a systemic analysis of the proteome and phosphoproteome of FMDV-infected cells. Bioinformatics analysis suggested that FMDV infection shuts off host cap-dependent translation, but leaves intact internal ribosome entry site (IRES)-mediated translation for viral proteins. Interestingly, several FMDV IRES-transacting factors, including G3BP stress granule assembly factor 1 (G3BP1), were dephosphorylated during FMDV infection. Ectopic expression of G3BP1 inhibited FMDV IRES activity, promoted assembly of stress granules, and activated innate immune responses, collectively suppressing FMDV replication. To counteract these host protective responses, FMDV-induced dephosphorylation of G3BP1, compromising its inhibitory effect on viral IRES. In addition, FMDV also proteolytically cleaved G3BP1 by its 3C protease (3Cpro). G3BP1 was cleaved at glutamic acid-284 (E284) by FMDV 3Cpro, and this cleavage completely lost the abilities of G3BP1 to activate innate immunity and to inhibit FMDV replication. Together, these data provide new insights into the post-translational mechanisms by which FMDV limits host stress and antiviral responses and indicate that G3BP1 dephosphorylation and its proteolysis by viral protease are important factors in the failure of host defense against FMDV infection.

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

PubMed

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

2014-04-01

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

Formulation of a poorly water-soluble drug in sustained-release hollow granules with a high viscosity water-soluble polymer using a fluidized bed rotor granulator.

PubMed

Asada, Takumi; Yoshihara, Naoki; Ochiai, Yasushi; Kimura, Shin-Ichiro; Iwao, Yasunori; Itai, Shigeru

2018-04-25

Water-soluble polymers with high viscosity are frequently used in the design of sustained-release formulations of poorly water-soluble drugs to enable complete release of the drug in the gastrointestinal tract. Tablets containing matrix granules with a water-soluble polymer are preferred because tablets are easier to handle and the multiple drug-release units of the matrix granules decreases the influences of the physiological environment on the drug. However, matrix granules with a particle size of over 800 μm sometimes cause a content uniformity problem in the tableting process because of the large particle size. An effective method of manufacturing controlled-release matrix granules with a smaller particle size is desired. The aim of this study was to develop tablets containing matrix granules with a smaller size and good controlled-release properties, using phenytoin as a model poorly water-soluble drug. We adapted the recently developed hollow spherical granule granulation technology, using water-soluble polymers with different viscosities. The prepared granules had an average particle size of 300 μm and sharp particle size distribution (relative width: 0.52-0.64). The values for the particle strength of the granules were 1.86-1.97 N/mm 2 , and the dissolution profiles of the granules were not affected by the tableting process. The dissolution profiles and the blood concentration levels of drug released from the granules depended on the viscosity of the polymer contained in the granules. We succeeded in developing the desired controlled-release granules, and this study should be valuable in the development of sustained-release formulations of poorly water-soluble drugs. Copyright © 2018 Elsevier B.V. All rights reserved.

Physical, electrochemical, and thermal properties of granulated natural graphite as anodes for Li-ion batteries.

PubMed

Jo, Yong Nam; Park, Min-Sik; Kim, Jae-Hun; Kim, Young-Jun

2013-05-01

Two different types of granulated graphites were synthesized by blending and kneading of natural graphite with pitch followed by sintering methods. The electrochemical performances of granulated graphites were investigated as anode materials for use in Li-ion batteries. The blending type granulated graphite possesses a large amount of cavities and voids, while the kneading type granulated graphite has a relatively compact microstructure, which is responsible for a high tap density. Both granulated graphites show improved the initial coulombic efficiencies as a result of decrease of surface area by the granulations. In particular, the kneading type granulated graphite exhibits an excellent rate-capability without significant capacity loss. In addition, the thermal stabilities of both granulated graphites were also improved, which could be attributed to the decrease of active surface area due to pitch coating.

New Insights into PhaM-PhaC-Mediated Localization of Polyhydroxybutyrate Granules in Ralstonia eutropha H16

PubMed Central

Bresan, Stephanie

2017-01-01

ABSTRACT The formation and localization of polyhydroxybutyrate (PHB) granules in Ralstonia eutropha are controlled by PhaM, which interacts both with the PHB synthase (PhaC) and with the bacterial nucleoid. Here, we studied the importance of proline and lysine residues of two C-terminal PAKKA motifs in PhaM for their importance in attaching PHB granules to DNA by in vitro and in vivo methods. Substitution of the lysine residues but not of the proline residues resulted in detachment of formed PHB granules from the nucleoid. Instead, formation of PHB granule clusters at polar regions of the rod-shaped cells and an unequal distribution of PHB granules to daughter cells were observed. The formation of PHB granules was studied by the expression of chromosomally anchored gene fusions of fluorescent proteins with PhaM and PhaC in different backgrounds. PhaM and PhaC fusions showed a distinct colocalization at formed PHB granules in the nucleoid region of the wild type. In a ΔphaC background, PhaM and the catalytically inactive PhaCC319A protein were not able to form fluorescent foci, indicating that correct positioning requires the formation of PHB. Furthermore, time-lapse experiments revealed that PhaC and PhaM proteins detach from formed PHB granules at later stages, resulting in a nonhomogeneous population of PHB granules. This could explain why growth of individual PHB granules stops under PHB-permissive conditions at a certain size. IMPORTANCE PHB granules are storage compounds for carbon and energy in many prokaryotes. Equal distribution of accumulated PHB granules during cell division is therefore important for optimal fitness of the daughter cells. In R. eutropha, PhaM is responsible for maximal activity of PHB synthase, for initiation of PHB granule formation at discrete regions in the cells, and for association of formed PHB granules with the nucleoid. Here we found that four lysine residues of C-terminal PhaM sequence motifs are essential for association of PHB granules with the nucleoid. Furthermore, we followed PHB granule formation by time-lapse microscopy and provide evidence for aging of PHB granules that is manifested by detachment of previously PHB granule-associated PhaM and PHB synthase. PMID:28389545

Formation of artificial granules for proving gelation as the main mechanism of aerobic granulation in biological wastewater treatment.

PubMed

Li, Yun; Yang, Shu-Fang; Zhang, Jian-Jun; Li, Xiao-Yan

2014-01-01

In this study, gelation-facilitated biofilm formation as a new mechanism is proposed for the phenomenon of aerobic granulation in biological wastewater treatment. To obtain an experimental proof for the gelation-based theory, the granulation process was simulated in a chemical system using latex particles for bacterial cells and organic polymers (alginate and peptone) for extracellular polymeric substances (EPS) in a solution with the addition of cations (Ca²⁺, Mg²⁺ and Fe³⁺). The results showed that at a low alginate content (70 mg g⁻¹ mixed liquid suspended solids (MLSS)) flocculation was observed in the suspension with loose flocs. At a higher alginate content (180 mg g⁻¹ MLSS), together with discharge of small flocs, formation of artificial gel granules was successfully achieved leading to granulation. The artificial granules show a morphological property similar to that of actual microbial granules. However, if the protein content increased, granulation became difficult with little gel formation. The experimental work demonstrates the importance of the bonding interactions between EPS functional groups and cations in gel formation and granulation. The laboratory results on the formation of artificial granules provide a sound proof for the theory of gelation-facilitated biofilm formation as the main mechanism for aerobic granulation in sludge suspensions.

Granule Formation Mechanisms within an Aerobic Wastewater System for Phosphorus Removal▿ †

PubMed Central

Barr, Jeremy J.; Cook, Andrew E.; Bond, Phillip L.

2010-01-01

Granular sludge is a novel alternative for the treatment of wastewater and offers numerous operational and economic advantages over conventional floccular-sludge systems. The majority of research on granular sludge has focused on optimization of engineering aspects relating to reactor operation with little emphasis on the fundamental microbiology. In this study, we hypothesize two novel mechanisms for granule formation as observed in three laboratory scale sequencing batch reactors operating for biological phosphorus removal and treating two different types of wastewater. During the initial stages of granulation, two distinct granule types (white and yellow) were distinguished within the mixed microbial population. White granules appeared as compact, smooth, dense aggregates dominated by 97.5% “Candidatus Accumulibacter phosphatis,” and yellow granules appeared as loose, rough, irregular aggregates with a mixed microbial population of 12.3% “Candidatus Accumulibacter phosphatis” and 57.9% “Candidatus Competibacter phosphatis,” among other bacteria. Microscopy showed white granules as homogeneous microbial aggregates and yellow granules as segregated, microcolony-like aggregates, with phylogenetic analysis suggesting that the granule types are likely not a result of strain-associated differences. The microbial community composition and arrangement suggest different formation mechanisms occur for each granule type. White granules are hypothesized to form by outgrowth from a single microcolony into a granule dominated by one bacterial type, while yellow granules are hypothesized to form via multiple microcolony aggregation into a microcolony-segregated granule with a mixed microbial population. Further understanding and application of these mechanisms and the associated microbial ecology may provide conceptual information benefiting start-up procedures for full-scale granular-sludge reactors. PMID:20851963

Development of a discriminative biphasic in vitro dissolution test and correlation with in vivo pharmacokinetic studies for differently formulated racecadotril granules.

PubMed

Deng, Jia; Staufenbiel, Sven; Hao, Shilei; Wang, Bochu; Dashevskiy, Andriy; Bodmeier, Roland

2017-06-10

The purpose of this study was to discriminate the release behavior from three differently formulated racecadotril (BCS II) granules and to establish an in vitro-in vivo correlation. Three granule formulations of the lipophilic drug were prepared with equivalent composition but prepared with different manufacturing processes (dry granulation, wet granulation with or without binder). In vitro release of the three granules was investigated using a biphasic dissolution system (phosphate buffer pH6.8 and octanol) and compared to the conventional single phase USP II dissolution test performed under sink and non-sink conditions. In vivo studies with each granule formulation were performed in rats. Interestingly, the granule formulations exhibited pronouncedly different behavior in the different dissolution systems depending on different wetting and dissolution conditions. Single phase USP II dissolution tests lacked discrimination. In contrast, remarkable discrimination between the granule formulations was observed in the octanol phase of biphasic dissolution system with a rank order of release from granules prepared by wet granulation with binder>wet granulation without binder>dry granulation. This release order correlated well with the wettability of these granules. An excellent correlation was also established between in vitro release in the octanol phase of the biphasic test and in vivo data (R 2 =0.999). Compared to conventional dissolution methods, the biphasic method provides great potential to discriminate between only minor formulation and process changes within the same dosage form for poorly soluble drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Modification of drug release from acetaminophen granules by melt granulation technique - consideration of release kinetics.

PubMed

Uhumwangho, M U; Okor, R S

2006-01-01

Acetaminophen granules have been formed by a melt granulation process with the objective of retarding drug release for prolonged action formulations. The waxes used were goat wax, carnuba wax and glyceryl monostearate. In the melt granulation procedure, acetaminophen powder was triturated with the melted waxes and passed through a sieve of mesh 10 (aperture size 710 microm). The content of wax in resulting granules ranged from 10 to 40%w/w. Acetaminophen granules were also formed by the convectional method of wet granulation with starch mucilage (20%w/w). The granules were subjected to in-vitro drug release tests. The release data were subjected to analysis by three different well-established mathematical models (release kinetics) namely, - zero order flux, first order, and the Higuchi square root of time relationship. The convectional granules exhibited an initial zero order flux (first 55%) followed by a first order release profile (the remaining 45%). The pattern of drug release from the melt granulations was consistent with the first order kinetic and the Higuchi square root of time relationship, indicating a diffusion-controlled release mechanism. The first order release rate constant of the convectional granules was 1.95 +/- 0.02 h(-1). After melt granulation (wax content, 20%w/w) the rate constants dropped drastically to 0.130+/-0.001 h(-1) (goat wax), 0.120+/-0.003 h(-1) (carnuba wax), and 0.130+/-0.002 h(-1) (glyceryl monosterate) indicating that all three waxes were equivalent in retarding drug release from the melt granulations.

State of the art of aerobic granulation in continuous flow bioreactors.

PubMed

Kent, Timothy R; Bott, Charles B; Wang, Zhi-Wu

In the wake of the success of aerobic granulation in sequential batch reactors (SBRs) for treating wastewater, attention is beginning to turn to continuous flow applications. This is a necessary step given the advantages of continuous flow treatment processes and the fact that the majority of full-scale wastewater treatment plants across the world are operated with aeration tanks and clarifiers in a continuous flow mode. As in SBRs, applying a selection pressure, based on differences in either settling velocity or the size of the biomass, is essential for successful granulation in continuous flow reactors (CFRs). CFRs employed for aerobic granulation come in multiple configurations, each with their own means of achieving such a selection pressure. Other factors, such as bioaugmentation and hydraulic shear force, also contribute to aerobic granulation to some extent. Besides the formation of aerobic granules, long-term stability of aerobic granules is also a critical issue to be addressed. Inorganic precipitation, special inocula, and various operational optimization strategies have been used to improve granule long-term structural integrity. Accumulated studies reviewed in this work demonstrate that aerobic granulation in CFRs is capable of removing a wide spectrum of contaminants and achieving properties generally comparable to those in SBRs. Despite the notable research progress made toward successful aerobic granulation in lab-scale CFRs, to the best of our knowledge, there are only three full-scale tests of the technique, two being seeded with anammox-supported aerobic granules and the other with conventional aerobic granules; two other process alternatives are currently in development. Application of settling- or size-based selection pressures and feast/famine conditions are especially difficult to implement to these and similar mainstream systems. Future research efforts needs to be focused on the optimization of the granule-to-floc ratio, enhancement of granule activity, improvement of long-term granule stability, and a better understanding of aerobic granulation mechanisms in CFRs, especially in full-scale applications. Copyright © 2018 Elsevier Inc. All rights reserved.

Structural micro-porous carbon anode for rechargeable lithium-ion batteries

DOEpatents

Delnick, F.M.; Even, W.R. Jr.; Sylwester, A.P.; Wang, J.C.F.; Zifer, T.

1995-06-20

A secondary battery having a rechargeable lithium-containing anode, a cathode and a separator positioned between the cathode and anode with an organic electrolyte solution absorbed therein is provided. The anode comprises three-dimensional microporous carbon structures synthesized from polymeric high internal phase emulsions or materials derived from this emulsion source, i.e., granules, powders, etc. 6 figs.

Granulation of fine powder

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 formmore » a dense compact with a higher density and more uniform pore size distribution.« less

The effect of the chopper on granules from wet high-shear granulation using a PMA-1 granulator.

PubMed

Briens, Lauren; Logan, Ryan

2011-12-01

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 perimeter obscured the effect of the chopper on the flow pattern. Differences in the granule flowability were minimal. However, it was concluded that the largest fraction of optimal granules would be obtained at an impeller speed of 700 rpm with the chopper at 1,000 rpm allowing balances between flow establishment, segregation, and centrifugal forces.

Characteristics of aerobic granules grown on glucose and acetate in sequential aerobic sludge blanket reactors.

PubMed

Tay, J H; Liu, Q S; Liu, Y

2002-08-01

Aerobic granules were cultivated in two column-type sequential aerobic sludge blanket reactors fed with glucose and acetate, respectively. The characteristics of aerobic granules were investigated. Results indicated that the glucose- and acetate-fed granules have comparable characteristics in terms of settling velocity, size, shape, biomass density, hydrophobicity, physical strength, microbial activity and storage stability. Substrate component does not seem to be a key factor on the formation of aerobic granules. However, microbial diversity of the granules is closely associated with the carbon sources supplied to the reactors. Compared with the conventional activated sludge flocs, aerobic granules exhibit excellent physical characteristics that would be essential for industrial application. This research provides a complete set of characteristics data of aerobic granules grown on glucose and acetate, which would be useful for further development of aerobic granules-based compact bioreactor for handling high strength organic wastewater.

Starch-Branching Enzymes Preferentially Associated with A-Type Starch Granules in Wheat Endosperm1

PubMed Central

Peng, Mingsheng; Gao, Ming; Båga, Monica; Hucl, Pierre; Chibbar, Ravindra N.

2000-01-01

Two starch granule-bound proteins (SGP), SGP-140 and SGP-145, were preferentially associated with A-type starch granules (>10 μm) in developing and mature wheat (Triticum aestivum) kernels. Immunoblotting and N-terminal sequencing suggested that the two proteins were different variants of SBEIc, a 152-kD isoform of wheat starch-branching enzyme. Both SGP-140 and SGP-145 were localized to the endosperm starch granules but were not found in the endosperm soluble fraction or pericarp starch granules younger than 15 d post anthesis (DPA). Small-size starch granules (<10 μm) initiated before 15 DPA incorporated SGP-140 and SGP-145 throughout endosperm development and grew into full-size A-type starch granules (>10 μm). In contrast, small-size starch granules harvested after 15 DPA contained only low amounts of SGP-140 and SGP-145 and developed mainly into B-type starch granules (<10 μm). Polypeptides of similar mass and immunologically related to SGP-140 and/or SGP-145 were also preferentially incorporated into A-type starch granules of barley (Hordeum vulgare), rye (Secale cereale), and triticale (× Triticosecale Wittmack) endosperm, which like wheat endosperm have a bimodal starch granule size distribution. PMID:10982441

Novel insights into RNP granules by employing the trypanosome's microtubule skeleton as a molecular sieve.

PubMed

Fritz, Melanie; Vanselow, Jens; Sauer, Nadja; Lamer, Stephanie; Goos, Carina; Siegel, T Nicolai; Subota, Ines; Schlosser, Andreas; Carrington, Mark; Kramer, Susanne

2015-09-18

RNP granules are ribonucleoprotein assemblies that regulate the post-transcriptional fate of mRNAs in all eukaryotes. Their exact function remains poorly understood, one reason for this is that RNP granule purification has not yet been achieved. We have exploited a unique feature of trypanosomes to prepare a cellular fraction highly enriched in starvation stress granules. First, granules remain trapped within the cage-like, subpellicular microtubule array of the trypanosome cytoskeleton while soluble proteins are washed away. Second, the microtubules are depolymerized and the granules are released. RNA sequencing combined with single molecule mRNA FISH identified the short and highly abundant mRNAs encoding ribosomal mRNAs as being excluded from granules. By mass spectrometry we have identified 463 stress granule candidate proteins. For 17/49 proteins tested by eYFP tagging we have confirmed the localization to granules, including one phosphatase, one methyltransferase and two proteins with a function in trypanosome life-cycle regulation. The novel method presented here enables the unbiased identification of novel RNP granule components, paving the way towards an understanding of RNP granule function. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

A theory of cerebellar cortex and adaptive motor control based on two types of universal function approximation capability.

PubMed

Fujita, Masahiko

2016-03-01

Lesions of the cerebellum result in large errors in movements. The cerebellum adaptively controls the strength and timing of motor command signals depending on the internal and external environments of movements. The present theory describes how the cerebellar cortex can control signals for accurate and timed movements. A model network of the cerebellar Golgi and granule cells is shown to be equivalent to a multiple-input (from mossy fibers) hierarchical neural network with a single hidden layer of threshold units (granule cells) that receive a common recurrent inhibition (from a Golgi cell). The weighted sum of the hidden unit signals (Purkinje cell output) is theoretically analyzed regarding the capability of the network to perform two types of universal function approximation. The hidden units begin firing as the excitatory inputs exceed the recurrent inhibition. This simple threshold feature leads to the first approximation theory, and the network final output can be any continuous function of the multiple inputs. When the input is constant, this output becomes stationary. However, when the recurrent unit activity is triggered to decrease or the recurrent inhibition is triggered to increase through a certain mechanism (metabotropic modulation or extrasynaptic spillover), the network can generate any continuous signals for a prolonged period of change in the activity of recurrent signals, as the second approximation theory shows. By incorporating the cerebellar capability of two such types of approximations to a motor system, in which learning proceeds through repeated movement trials with accompanying corrections, accurate and timed responses for reaching the target can be adaptively acquired. Simple models of motor control can solve the motor error vs. sensory error problem, as well as the structural aspects of credit (or error) assignment problem. Two physiological experiments are proposed for examining the delay and trace conditioning of eyelid responses, as well as saccade adaptation, to investigate this novel idea of cerebellar processing. Copyright © 2015 Elsevier Ltd. All rights reserved.

Height-dependent Velocity Structure of Photospheric Convection in Granules and Intergranular Lanes with Hinode /SOT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oba, T.; Iida, Y.; Shimizu, T., E-mail: oba.takayoshi@ac.jaxa.jp

The solar photosphere is the visible surface of the Sun, where many bright granules, surrounded by narrow dark intergranular lanes, are observed everywhere. The granular pattern is a manifestation of convective motion at the photospheric level, but its velocity structure in the height direction is poorly understood observationally. Applying bisector analysis to a photospheric spectral line recorded by the Hinode Solar Optical Telescope, we derived the velocity structure of the convective motion in granular regions and intergranular lanes separately. The amplitude of motion of the convective material decreases from 0.65 to 0.40 km s{sup −1} as the material rises inmore » granules, whereas the amplitude of motion increases from 0.30 to 0.50 km s{sup −1} as it descends in intergranular lanes. These values are significantly larger than those obtained in previous studies using bisector analysis. The acceleration of descending materials with depth is not predicted from the convectively stable condition in a stratified atmosphere. Such convective instability can be developed more efficiently by radiative cooling and/or a gas pressure gradient, which can control the dynamical behavior of convective material in intergranular lanes. Our analysis demonstrated that bisector analysis is a useful method for investigating the long-term dynamic behavior of convective material when a large number of pixels is available. In addition, one example is the temporal evolution of granular fragmentation, in which downflowing material develops gradually from a higher layer downward.« less

Embryo and endosperm development in wheat (Triticum aestivum L.) kernels subjected to drought stress.

PubMed

Fábián, Attila; Jäger, Katalin; Rakszegi, Mariann; Barnabás, Beáta

2011-04-01

The aim of the present work was to reveal the histological alterations triggered in developing wheat kernels by soil drought stress during early seed development resulting in yield losses at harvest. For this purpose, observations were made on the effect of drought stress, applied in a controlled environment from the 5th to the 9th day after pollination, on the kernel morphology, starch content and grain yield of the drought-sensitive Cappelle Desprez and drought-tolerant Plainsman V winter wheat (Triticum aestivum L.) varieties. As a consequence of water withdrawal, there was a decrease in the size of the embryos and the number of A-type starch granules deposited in the endosperm, while the development of aleurone cells and the degradation of the cell layers surrounding the ovule were significantly accelerated in both genotypes. In addition, the number of B-type starch granules per cell was significantly reduced. Drought stress affected the rate of grain filling shortened the grain-filling and ripening period and severely reduced the yield. With respect to the recovery of vegetative tissues, seed set and yield, the drought-tolerant Plainsman V responded significantly better to drought stress than Cappelle Desprez. The reduction in the size of the mature embryos was significantly greater in the sensitive genotype. Compared to Plainsman V, the endosperm cells of Cappelle Desprez accumulated significantly fewer B-type starch granules. In stressed kernels of the tolerant genotype, the accumulation of protein bodies occurred significantly earlier than in the sensitive variety.

Enhanced Column Filtration for Arsenic Removal from Water: Polymer-Templated Iron Oxide Nanoparticles Immobilized on Sand via Layer-by-Layer Deposition

NASA Astrophysics Data System (ADS)

Cheng, Calvin Chia-Hung

Arsenic is ubiquitous in water sources around the world and is highly toxic. While precipitation and membrane filtration techniques are successfully implemented in developed cities, they are unsuitable for rural and low-resource settings lacking centralized facilities. This thesis presents the use of ultra-small iron oxide (Fe2O3) nanoparticles functionalized on sand granules for use as a house-hold scale adsorption filter. Water-stable alpha-Fe2O3 (hematite) nanoparticles (<10 nm) were synthesized via a collapsed-polymer approach using poly(acrylic acid) and Fe3+ ions. The nanoparticles exhibited high arsenic adsorption, with 147 +/- 2 mg As(III) per g Fe2O3 and 91 +/- 10 mg As(V) per g Fe2O3. The platform was also used to synthesize iron-based composites, including magnetite (Fe 3O4) and Fe-Cu oxide nanoparticles. For use as a column filter, Fe2O3-PAA nanoparticles were functionalized on sand granules using a layer-by-layer deposition method, with the nanoparticles embedded in the negative layer. The removal of As(III) by the Fe2O 3-PAA functionalized column was described by reversible 1st order kinetics where the forward and reverse rate constants were 0.31 hr -1 and 0.097 hr-1, respectively. Implemented as a passive water filter with 30 x 30 x 50 cm3 dimensions, the filter has an expected lifetime in the order of many years. By controlling the flow rate of the column depending on contamination levels, the filter effectively removes arsenic down to the safety limit of 0.01 mg/L. In a parallel project, the layer-by-layer deposition of Poly(diallydimethyl ammonium chloride) (PDDA) and poly(sodium 5-styrenesulfonate) (PSS) was exploited for a highly practical synthesis of discrete gradient surfaces. By independently controlling the concentration of NaCl in PDDA and PSS deposition solutions, a 2-dimensional matrix of surfaces was created in 96-well microtiter plates. Distinct non-monotonic dye adsorption patterns on the gradient surfaces was observed. Practical knowledge from this project was also used to enhance the nanoparticle surface functionalization described above. In all, a practical, no expertise-needed passive water filtration unit was described in this thesis. The unit makes use of hardware available in existing sand-based water filters, and is designed to address the unmet need of arsenic removal from drinking water in low-resource or rural settings.

The role of two isoenzymes of alpha-amylase of Araucaria araucana (Araucariaceae) on the digestion of starch granules during germination.

PubMed

Waghorn, Juana J; del Pozo, Talía; Acevedo, Elba A; Cardemil, Liliana A

2003-03-01

Starch is the principal reserve of Araucaria araucana seeds, and it is hydrolysed during germination mainly by alpha-amylase. There are several alpha-amylase isoenzymes whose patterns change in the embryo and in the megagametophyte from the one observed in quiescent seeds (T(0)) to a different one observed 90 h after imbibition (T(90)). The objective of this research was to study the roles of two purified alpha-amylase isoenzymes by in vitro digestion of starch granules extracted from the tissues at two times of imbibition: one is abundant in quiescent seeds and the other is abundant after 90 h of imbibition. The isoenzymes digested the starch granules of their own stage of germination better, since the isoenzyme T(0) digested starch granules mainly from quiescent seeds, while the isoenzyme T(90) digested starch mainly at 90 h of imbibition. The sizes of the starch granule and the tissue from which these granules originated make a difference to digestion by the isoenzymes. Embryonic isoenzyme T(0) digested large embryonic starch granules better than small and medium-sized granules, and better than those isolated from megagametophytes. Similarly isoenzyme T(90) digested small embryonic starch granules better than medium-sized and large granules, and better than those isolated from megagametophytes. However, a mixture of partially purified megagametophytic isoenzymes T(0) and T(90) digested the megagametophytic granules better than those isolated from embryos. Studies of in vitro sequential digestion of starch granules with these isoenzymes corroborated their specificity. The isoenzyme T(90) digested starch granules previously digested by the isoenzyme T(0). This suggests that in vivo these two isoenzymes may act sequentially in starch granule digestion.

Reducing the startup time of aerobic granular sludge reactors through seeding floccular sludge with crushed aerobic granules.

PubMed

Pijuan, Maite; Werner, Ursula; Yuan, Zhiguo

2011-10-15

One of the main challenging issues for the aerobic granular sludge technology is the long startup time when dealing with real wastewaters. This study presents a novel strategy to reduce the time required for granulation while ensuring a high level of nutrient removal. This new approach consists of seeding the reactor with a mixture of crushed aerobic granules and floccular sludge. The effectiveness of the strategy was demonstrated using abattoir wastewater, containing nitrogen and phosphorus at approximately 250 mgN/L and 30 mgP/L, respectively. Seven different mixtures of crushed granules and floccular sludge at granular sludge fractions (w/w in dry mass) of 0%, 5%, 10%, 15%, 25%, 30% and 50% were used to start eight granulation processes. The granulation time (defined as the time when the 10th percentile bacterial aggregate size is larger than 200 μm) displayed a strong dependency on the fraction of granular sludge. The shortest granulation time of 18 days was obtained with 50% crushed granules, in comparison with 133 days with 5% crushed granules. Full granulation was not achieved in the two trials without seeding with crushed granules. In contrast to the 100% floccular sludge cases, where a substantial loss of biomass occurred during granulation, the biomass concentration in all other trails did not decrease during granulation. This allowed that good nitrogen removal was maintained in all the reactors during the granulation process. However, enhanced biological phosphorus removal was achieved in only one of the eight trials. This was likely due to the temporary accumulation of nitrite, a strong inhibitor of polyphosphate accumulating organisms. Copyright © 2011 Elsevier Ltd. All rights reserved.

High-rate hydrogenotrophic methanogenesis for biogas upgrading: the role of anaerobic granules.

PubMed

Xu, Heng; Gong, Shufen; Sun, Yuanzi; Ma, Hailing; Zheng, Mingyue; Wang, Kaijun

2015-01-01

Hydrogenotrophic methanogenesis has been proved to be a feasible biological method for biogas upgrading. To improve its performance, the feasibility of typical anaerobic granules as the inoculum was investigated in both batch and continuous experiments. The results from batch experiments showed that glucose-acclimated granules seemed to perform better than granules acclimated to acidified products (AP, i.e. acetate, propionate and ethanol) in in situ biogas upgrading systems and a slightly higher H2 consumption rate (1.5 mmol H2 g VSS(-1) h(-1)) was obtained for glucose-acclimated granules. For AP-acclimated granules, the inhibition on anaerobic digestion and pH increase (up to 9.55±0.16) took place, and the upgrading performance was adversely affected. In contrast, better performance for AP-acclimated granules was observed in ex situ systems, possibly due to their higher hydrogenotrophic methanogenic activities (HMA). Moreover, when gas-liquid mass transfer limitations were alleviated, the upgrading performance was significantly improved (three-fold) for both glucose-acclimated and AP-acclimated granules. The HMA of anaerobic granules could be further enhanced to improve biogas upgrading performance via continuous cultivation with H2/CO2 as the sole substrate. During the three months' cultivation, secondary granulation and microbial population shift were observed, but anaerobic granules still remained intact and their HMA increased from 0.2 to 0.6 g COD g VSS(-1) d(-1). It indicated that the formation of hydrogenotrophic methanogenic granules, a new type of anaerobic granules specialized for high-rate hydrogenotrophic methanogenesis and biogas upgrading, might be possible. Conclusively, anaerobic granules showed great potential for biogas upgrading.

Homologs of PROTEIN TARGETING TO STARCH Control Starch Granule Initiation in Arabidopsis Leaves[OPEN

PubMed Central

David, Laure C.; Abt, Melanie; Lu, Kuan-Jen

2017-01-01

The molecular mechanism that initiates the synthesis of starch granules is poorly understood. Here, we discovered two plastidial proteins involved in granule initiation in Arabidopsis thaliana leaves. Both contain coiled coils and a family-48 carbohydrate binding module (CBM48) and are homologs of the PROTEIN TARGETING TO STARCH (PTST) protein; thus, we named them PTST2 and PTST3. Chloroplasts in mesophyll cells typically contain five to seven granules, but remarkably, most chloroplasts in ptst2 mutants contained zero or one large granule. Chloroplasts in ptst3 had a slight reduction in granule number compared with the wild type, while those of the ptst2 ptst3 double mutant contained even fewer granules than ptst2. The ptst2 granules were larger but similar in morphology to wild-type granules, but those of the double mutant had an aberrant morphology. Immunoprecipitation showed that PTST2 interacts with STARCH SYNTHASE4 (SS4), which influences granule initiation and morphology. Overexpression of PTST2 resulted in chloroplasts containing many small granules, an effect that was dependent on the presence of SS4. Furthermore, isothermal titration calorimetry revealed that the CBM48 domain of PTST2, which is essential for its function, interacts with long maltooligosaccharides. We propose that PTST2 and PTST3 are critical during granule initiation, as they bind and deliver suitable maltooligosaccharide primers to SS4. PMID:28684429

Injected mass deposition thresholds for lithium granule instigated triggering of edge localized modes on EAST

NASA Astrophysics Data System (ADS)

Lunsford, R.; Sun, Z.; Maingi, R.; Hu, J. S.; Mansfield, D.; Xu, W.; Zuo, G. Z.; Diallo, A.; Osborne, T.; Tritz, K.; Canik, J.; Huang, M.; Meng, X. C.; Gong, X. Z.; Wan, B. N.; Li, J. G.; the EAST Team

2018-03-01

The ability of an injected lithium granule to promptly trigger an edge localized mode (ELM) has been established in multiple experiments. By horizontally injecting granules ranging in diameter from 200 microns to 1 mm in diameter into the low field side of EAST H-mode discharges we have determined that granules with diameter  >600 microns are successful in triggering ELMs more than 95% of the time. It was also demonstrated that below 600 microns the triggering efficiency decreased roughly with granule size. Granules were radially injected from the outer midplane with velocities ~80 m s-1 into EAST upper single null discharges with an ITER like tungsten monoblock divertor. These granules were individually tracked throughout their injection cycle in order to determine their efficacy at triggering an ELM. For those granules of sufficient size, ELM triggering was a prompt response to granule injection. By simulating the granule injection with an experimentally benchmarked neutral gas shielding (NGS) model, the ablatant mass deposition required to promptly trigger an ELM is calculated and the fractional mass deposition is determined.

Compressibility and compactibility of granules produced by wet and dry granulation.

PubMed

Bacher, C; Olsen, P M; Bertelsen, P; Sonnergaard, J M

2008-06-24

The bulk properties, compactibility and compressibility of granules produced by wet and dry granulation were compared applying a rotary tablet press, three different morphological forms of calcium carbonate and two particle sizes of sorbitol. Granules from both granulation methods possessed acceptable flow properties; however, the ground (Mikhart) and cubic (Scoralite) calcium carbonate demonstrated better die-filling abilities in the tablet press than the scalenhedral calcium carbonate (Sturcal). The wet processed granules showed in general larger compression properties. This was explained as these granules were mechanical stronger and had a higher initial porosity. In some cases, a large particle surface area of calcium carbonate and sorbitol resulted in a small, insignificant improvement of the consolidation characteristics. A correlation between the compression and compaction characteristics was demonstrated.

Socket Preservation using Enzyme-treated Equine Bone Granules and an Equine Collagen Matrix: A Case Report with Histological and Histomorphometrical Assessment.

PubMed

Leonida, Alessandro; Todeschini, Giovanni; Lomartire, Giovanni; Cinci, Lorenzo; Pieri, Laura

2016-11-01

To histologically assess the effectiveness of a socket-preservation technique using enzyme-treated equine bone granules as a bone-graft material in combination with an equine collagen matrix as a scaffold for soft-tissue regeneration. Enzyme-treated equine bone granules and equine collagen matrix recently have been developed to help overcome alveolar bone deficiencies that develop in the wake of edentulism. The patient had one mandibular molar extracted and the socket grafted with equine bone granules. The graft was covered with the equine collagen matrix, placed in a double layer. No flap was prepared, and the gingival margins were stabilized with a single stitch, leaving the matrix partially exposed and the site to heal by secondary intention. The adjacent molar was extracted 1 month later, and that socket was left to heal by secondary intention without any further treatment. Three months after each surgery, an implant was placed and a biopsy was collected. The two biopsies underwent histological processing and qualitative evaluation. Histomorphometric analysis was also performed to calculate the percentage of newly formed bone (NFB) in the two cores. Healing at both sites was uneventful, and no inflammation or other adverse reactions were observed in the samples. Soft-tissue healing by secondary intention appeared to occur faster at the grafted site. The corresponding core showed a marked separation between soft and hard tissue that was not observed in the core from the nongrafted site, where soft-tissue hypertrophy could be observed. Newly formed bone at the grafted and nongrafted sites was not significantly different (27.2 ± 7.1 and 29.4 ± 6.2% respectively, p = 0.45). The surgical technique employed in this case appeared to facilitate postextraction soft-tissue healing by second intention and simplify soft-tissue management. Using a collagen-based matrix to cover a postextraction grafted site may facilitate second intention soft-tissue healing and proper soft-tissue growth.

Fundus Autofluorescence in the Abca4−/− Mouse Model of Stargardt Disease—Correlation With Accumulation of A2E, Retinal Function, and Histology

PubMed Central

Charbel Issa, Peter; Barnard, Alun R.; Singh, Mandeep S.; Carter, Emma; Jiang, Zhichun; Radu, Roxana A.; Schraermeyer, Ulrich; MacLaren, Robert E.

2013-01-01

Purpose. To investigate fundus autofluorescence (AF) characteristics in the Abca4−/− mouse, an animal model for AMD and Stargardt disease, and to correlate findings with functional, structural, and biochemical assessments. Methods. Blue (488 nm) and near-infrared (790 nm) fundus AF images were quantitatively and qualitatively analyzed in pigmented Abca4−/− mice and wild type (WT) controls in vivo. Functional, structural, and biochemical assessments included electroretinography (ERG), light and electron microscopic analysis, and A2E quantification. All assessments were performed across age groups. Results. In Abca4−/− mice, lipofuscin-related 488 nm AF increased early in life with a ceiling effect after 6 months. This increase was first paralleled by an accumulation of typical lipofuscin granules in the retinal pigment epithelium (RPE). Later, lipofuscin and melanin granules decreased in number, whereas melanolipofuscin granules increased. This increase in melanolipofuscin granules paralleled an increase in melanin-related 790 nm AF. Old Abca4−/− mice revealed a flecked fundus AF pattern at both excitation wavelengths. The amount of A2E, a major lipofuscin component, increased 10- to 12-fold in 6- to 9-month-old Abca4−/− mice compared with controls, while 488 nm AF intensity only increased 2-fold. Despite pronounced lipofuscin accumulation in the RPE of Abca4−/− mice, ERG and histology showed a slow age-related thinning of the photoreceptor layer similar to WT controls up to 12 months. Conclusions. Fundus AF can be used to monitor lipofuscin accumulation and melanin-related changes in vivo in mouse models of retinal disease. High RPE lipofuscin may not adversely affect retinal structure or function over prolonged time intervals, and melanin-related changes (melanolipofuscin formation) may occur before the decline in retinal function. PMID:23761084

Soft and Hard Textured Wheat Differ in Starch Properties as Indicated by Trimodal Distribution, Morphology, Thermal and Crystalline Properties

PubMed Central

Kumar, Rohit; Kumar, Aman; Sharma, Nand Kishor; Kaur, Navneet; Chunduri, Venkatesh; Chawla, Meenakshi; Sharma, Saloni; Singh, Kashmir; Garg, Monika

2016-01-01

Starch and proteins are major components in the wheat endosperm that affect its end product quality. Between the two textural classes of wheat i.e. hard and soft, starch granules are loosely bound with the lipids and proteins in soft wheat due to higher expression of interfering grain softness proteins. It might have impact on starch granules properties. In this work for the first time the physiochemical and structural properties of different sized starch granules (A-, B- and C-granules) were studied to understand the differences in starches with respect to soft and hard wheat. A-, B- and C-type granules were separated with >95% purity. Average number and proportion of A-, B-, and C-type granules was 18%, 56%, 26% and 76%, 19%, 5% respectively. All had symmetrical birefringence pattern with varied intensity. All displayed typical A-type crystallites. A-type granules also showed V-type crystallinity that is indicative of starch complexes with lipids and proteins. Granules differing in gelatinization temperature (ΔH) and transition temperature (ΔT), showed different enthalpy changes during heating. Substitution analysis indicated differences in relative substitution pattern of different starch granules. Birefringence, percentage crystallinity, transmittance, gelatinization enthalpy and substitution decreased in order of A>B>C being higher in hard wheat than soft wheat. Amylose content decreased in order of A>B>C being higher in soft wheat than hard wheat. Reconstitution experiment showed that starch properties could be manipulated by changing the composition of starch granules. Addition of A-granules to total starch significantly affected its thermal properties. Effect of A-granule addition was higher than B- and C-granules. Transmittance of the starch granules paste showed that starch granules of hard wheat formed clear paste. These results suggested that in addition to differences in protein concentration, hard and soft wheat lines have differences in starch composition also. PMID:26824830

Soft and Hard Textured Wheat Differ in Starch Properties as Indicated by Trimodal Distribution, Morphology, Thermal and Crystalline Properties.

PubMed

Kumar, Rohit; Kumar, Aman; Sharma, Nand Kishor; Kaur, Navneet; Chunduri, Venkatesh; Chawla, Meenakshi; Sharma, Saloni; Singh, Kashmir; Garg, Monika

2016-01-01

Starch and proteins are major components in the wheat endosperm that affect its end product quality. Between the two textural classes of wheat i.e. hard and soft, starch granules are loosely bound with the lipids and proteins in soft wheat due to higher expression of interfering grain softness proteins. It might have impact on starch granules properties. In this work for the first time the physiochemical and structural properties of different sized starch granules (A-, B- and C-granules) were studied to understand the differences in starches with respect to soft and hard wheat. A-, B- and C-type granules were separated with >95% purity. Average number and proportion of A-, B-, and C-type granules was 18%, 56%, 26% and 76%, 19%, 5% respectively. All had symmetrical birefringence pattern with varied intensity. All displayed typical A-type crystallites. A-type granules also showed V-type crystallinity that is indicative of starch complexes with lipids and proteins. Granules differing in gelatinization temperature (ΔH) and transition temperature (ΔT), showed different enthalpy changes during heating. Substitution analysis indicated differences in relative substitution pattern of different starch granules. Birefringence, percentage crystallinity, transmittance, gelatinization enthalpy and substitution decreased in order of A>B>C being higher in hard wheat than soft wheat. Amylose content decreased in order of A>B>C being higher in soft wheat than hard wheat. Reconstitution experiment showed that starch properties could be manipulated by changing the composition of starch granules. Addition of A-granules to total starch significantly affected its thermal properties. Effect of A-granule addition was higher than B- and C-granules. Transmittance of the starch granules paste showed that starch granules of hard wheat formed clear paste. These results suggested that in addition to differences in protein concentration, hard and soft wheat lines have differences in starch composition also.

Bioinspired Synthesis of Monolithic and Layered Aerogels.

PubMed

Han, Xiao; Hassan, Khalil T; Harvey, Alan; Kulijer, Dejan; Oila, Adrian; Hunt, Michael R C; Šiller, Lidija

2018-06-01

Aerogels are the least dense and most porous materials known to man, with potential applications from lightweight superinsulators to smart energy materials. To date their use has been seriously hampered by their synthesis methods, which are laborious and expensive. Taking inspiration from the life cycle of the damselfly, a novel ambient pressure-drying approach is demonstrated in which instead of employing low-surface-tension organic solvents to prevent pore collapse during drying, sodium bicarbonate solution is used to generate pore-supporting carbon dioxide in situ, significantly reducing energy, time, and cost in aerogel production. The generic applicability of this readily scalable new approach is demonstrated through the production of granules, monoliths, and layered solids with a number of precursor materials. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Morphological and Structural Aspects of the Extremely Halophilic Archaeon Haloquadratum walsbyi

PubMed Central

Sublimi Saponetti, Matilde; Bobba, Fabrizio; Salerno, Grazia; Scarfato, Alessandro; Corcelli, Angela; Cucolo, Annamaria

2011-01-01

Ultrathin square cell Haloquadratum walsbyi from the Archaea domain are the most abundant microorganisms in the hypersaline water of coastal salterns and continental salt lakes. In this work, we explore the cell surface of these microorganisms using amplitude-modulation atomic-force microscopy in nearly physiological conditions. We demonstrate the presence of a regular corrugation with a periodicity of 16–20 nm attributed to the surface layer (S-layer) protein lattice, striped domains asymmetrically distributed on the cell faces and peculiar bulges correlated with the presence of intracellular granules. Besides, subsequent images of cell evolution during the drying process indicate the presence of an external capsule that might correspond to the giant protein halomucin, predicted by the genome but never before observed by other microscopy studies. PMID:21559517

Morphological and structural aspects of the extremely halophilic archaeon Haloquadratum walsbyi.

PubMed

Sublimi Saponetti, Matilde; Bobba, Fabrizio; Salerno, Grazia; Scarfato, Alessandro; Corcelli, Angela; Cucolo, Annamaria

2011-04-29

Ultrathin square cell Haloquadratum walsbyi from the Archaea domain are the most abundant microorganisms in the hypersaline water of coastal salterns and continental salt lakes. In this work, we explore the cell surface of these microorganisms using amplitude-modulation atomic-force microscopy in nearly physiological conditions. We demonstrate the presence of a regular corrugation with a periodicity of 16-20 nm attributed to the surface layer (S-layer) protein lattice, striped domains asymmetrically distributed on the cell faces and peculiar bulges correlated with the presence of intracellular granules. Besides, subsequent images of cell evolution during the drying process indicate the presence of an external capsule that might correspond to the giant protein halomucin, predicted by the genome but never before observed by other microscopy studies.

Surface characterization of Nb samples electropolished together with real superconducting rf accelerator cavities

DOE PAGES

Xin Zhao; Geng, Rong -Li; Tyagi, P. V.; ...

2010-12-30

Here, we report the results of surface characterizations of niobium (Nb) samples electropolished together with a single cell superconducting radio-frequency accelerator cavity. These witness samples were located in three regions of the cavity, namely at the equator, the iris and the beam-pipe. Auger electron spectroscopy (AES) was utilized to probe the chemical composition of the topmost four atomic layers. Scanning electron microscopy with energy dispersive X-ray for elemental analysis (SEM/EDX) was used to observe the surface topography and chemical composition at the micrometer scale. A few atomic layers of sulfur (S) were found covering the samples non-uniformly. Niobium oxide granulesmore » with a sharp geometry were observed on every sample. Some Nb-O granules appeared to also contain sulfur.« less

Structure of the starch granule--a curved crystal.

PubMed

Larsson, K

1991-09-01

A structure model of the molecular arrangement in native starch proposed earlier is further considered, with special regard to the lateral packing of cluster units. The amylopectin molecules are radially distributed, with branches concentrated in clusters. Within each cluster the polyglucan chains form double helices which are hexagonally packed. The clusters form spherically concentric crystalline layers with amylose in an amorphous form acting as a space-filler. A translational mechanism for the change of helical direction at boundaries between clusters is proposed which can account for variations in the curvature of the concentric layers. The model is related to X-ray diffraction data and optical birefringence, considering dissembly at gelatinization. The structure is also discussed in relation to biosynthesis. Some aspects of gelatinization, such as the recent glass-transition approach, are then considered.

Characterization and taste-masking evaluation of acetaminophen granules: comparison between different preparation methods in a high-shear mixer.

PubMed

Albertini, Beatrice; Cavallari, Cristina; Passerini, Nadia; Voinovich, Dario; González-Rodríguez, Marisa L; Magarotto, Lorenzo; Rodriguez, Lorenzo

2004-02-01

The aim of this study was to prepare and to investigate acetaminophen taste-masked granules obtained in a high-shear mixer using three different wet granulation methods (method A: water granulation, method B: granulation with a polyvinylpyrrolidone (PVP) binding solution and method C: steam granulation). The studied formulation was: acetaminophen 15%, alpha-lactose monohydrate 30%, cornstarch 45%, polyvinylpyrrolidone K30 5% and orange flavour 5% (w/w). In vitro dissolution studies, performed at pH 6.8, showed that steam granules enabled the lower dissolution rate in comparison to the water and binding solution granules; these results were then confirmed by their lower surface reactivity (D(R)) during the dissolution process. Moreover, the results of the gustatory sensation test performed by six volunteers confirmed the taste-masking effects of the granules, especially steam granules (P<0.001). Morphological, fractal and porosity analysis were then performed to explain the dissolution profiles and the results of the gustatory sensation test. Scanning electron microscopy (SEM) analysis revealed the smoother and the more regular surface of steam granules with respect to the samples obtained using methods A and B; these results were also confirmed by their lower fractal dimension (D(s)) and porosity values. Finally, differential scanning calorimetry (DSC) results showed a shift of the melting point of the drug, which was due to the simple mixing of the components and not to the granulation processes. In conclusion, the steam granulation technique resulted a suitable method to comply the purpose of this work, without modifying the availability of the drug.

Continuous twin screw granulation of controlled release formulations with various HPMC grades.

PubMed

Vanhoorne, V; Janssens, L; Vercruysse, J; De Beer, T; Remon, J P; Vervaet, C

2016-09-25

HPMC is a popular matrix former to formulate tablets with extended drug release. Tablets with HPMC are preferentially produced by direct compression. However, granulation is often required prior to tableting to overcome poor flowability of the formulation. While continuous twin screw granulation has been extensively evaluated for granulation of immediate release formulations, twin screw granulation of controlled release formulations including the dissolution behavior of the formulations received little attention. Therefore, the influence of the HPMC grade (viscosity and substitution degree) and the particle size of theophylline on critical quality attributes of granules (continuously produced via twin screw granulation) and tablets was investigated in the current study. Formulations with 20 or 40% HPMC, 20% theophylline and lactose were granulated with water at fixed process parameters via twin screw granulation. The torque was influenced by the viscosity and substitution degree of HPMC, but was not a limiting factor for the granulation process. An optimal L/S ratio was selected for each formulation based on the granule size distribution. The granule size distributions were influenced by the substitution degree and concentration of HPMC and the particle size of theophylline. Raman and UV spectroscopic analysis on 8 sieve fractions of granules indicated an inhomogeneous distribution of theophylline over the size fractions. However, this phenomenon was not correlated with the hydration rate or viscosity of HPMC. Controlled release of theophylline could be obtained over 24h with release profiles close to zero-order. The release of theophylline could be tailored via selection of the substitution degree and viscosity of HPMC. Copyright © 2016 Elsevier B.V. All rights reserved.

Stochastic Seeding Coupled with mRNA Self-Recruitment Generates Heterogeneous Drosophila Germ Granules.

PubMed

Niepielko, Matthew G; Eagle, Whitby V I; Gavis, Elizabeth R

2018-06-18

The formation of ribonucleoprotein assemblies called germ granules is a conserved feature of germline development. In Drosophila, germ granules form at the posterior of the oocyte in a specialized cytoplasm called the germ plasm, which specifies germline fate during embryogenesis. mRNAs, including nanos (nos) and polar granule component (pgc), that function in germline development are localized to the germ plasm through their incorporation into germ granules, which deliver them to the primordial germ cells. Germ granules are nucleated by Oskar (Osk) protein and contain varying combinations and quantities of their constituent mRNAs, which are organized as spatially distinct, multi-copy homotypic clusters. The process that gives rise to such heterogeneous yet organized granules remains unknown. Here, we show that individual nos and pgc transcripts can populate the same nascent granule, and these first transcripts then act as seeds, recruiting additional like transcripts to form homotypic clusters. Within a granule, homotypic clusters grow independently of each other but depend on the simultaneous acquisition of additional Osk. Although granules can contain multiple clusters of a particular mRNA, granule mRNA content is dominated by cluster size. These results suggest that the accumulation of mRNAs in the germ plasm is controlled by the mRNAs themselves through their ability to form homotypic clusters; thus, RNA self-association drives germ granule mRNA localization. We propose that a stochastic seeding and self-recruitment mechanism enables granules to simultaneously incorporate many different mRNAs while ensuring that each becomes enriched to a functional threshold. Copyright © 2018 Elsevier Ltd. All rights reserved.

Extended-release mesalamine granules for ulcerative colitis.

PubMed

Love, Bryan L; Miller, April D

2012-11-01

To evaluate the efficacy and safety of extended-release mesalamine granules in the maintenance of remission in ulcerative colitis (UC). Literature was obtained through searches of MEDLINE (1990-June 2012) using the terms mesalamine granules, ulcerative colitis, Apriso, and Salofalk. Bibliographies from retrieved articles were searched for additional citations. All English-language articles reporting on use of extended-release mesalamine granules in humans identified through the search were evaluated and included. The preferred initial treatment for induction and maintenance of remission in mild to moderate UC is agents from the 5-aminosalicylate class (balsalazide, mesalamine, olsalazine, sulfasalazine). Mesalamine granules are available as an encapsulated product in the US and as a nonencapsulated formulation in Europe. Data evaluating encapsulated mesalamine granules for induction of remission are lacking; however, the European mesalamine granule formulation has been evaluated for induction of remission. Patients receiving mesalamine granules for induction achieved clinical and endoscopic remission more frequently than those receiving placebo. Two pivotal, randomized, double-blind, placebo-controlled, multicenter studies have evaluated encapsulated mesalamine granules for maintenance in 562 adults in remission from UC. In both studies, the proportion of patients who remained relapse-free at 6 months was higher for those receiving encapsulated mesalamine granules than placebo. Mesalamine granules are well tolerated, with headache, nausea, and upper respiratory infections being the most frequently reported adverse effects. Current evidence supports the use of extended-release mesalamine granules for maintenance of remission in mild to moderate UC. Further studies are necessary to examine the ideal dose and regimen of encapsulated mesalamine granules for induction of remission in UC.

The morphology of solar granulations and dark networks

NASA Astrophysics Data System (ADS)

Graves, J. Elon; Pierce, A. Keith

1986-08-01

Solar granules are classified into four groups based on shape and splitting by sharp rifts crossing them. Grains are classified as: single granules varying in size from 1/8 to 3 in., single granules embayed by a broad dark area or possessing a central darkening, single granules split by very narrow rifts which are significantly narrower than the intergranular lanes, and complexes of granules displaying a daisy pattern. The formation and growth of 'white-light dark networks' are also discussed

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

NASA Technical Reports Server (NTRS)

Title, A. M.; Tarbell, T. D.; Topka, K. P.; Ferguson, S. H.; Shine, R. A.

1989-01-01

Computer algorithms and statistical techniques were used to identify, measure, and quantify the properties of solar granulation derived from movies collected by the Solar Optical Universal Polarimeter on Spacelab 2. The results show that there is neither a typical solar granule nor a typical granule evolution. A granule's evolution is dependent on local magnetic flux density, its position with respect to the active region plage, its position in the mesogranulation pattern, and the evolution of granules in its immediate neighborhood.

Effect of suspension property on granule morphology and compaction behavior

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hae-Weon Lee, Guesup Song, In-Sik Suk

1995-12-31

Granule morphology is an important factor during dry pressing, since it has great influences on die flowability, compaction ratio, and resulting green microstructure. Granule morphology and packing structure of ultrafine Si{sub 3}N{sub 4} particles in the granule were optimized during spray drying by adjusting the suspension structure. The particle packing structure of spray-dried granule was investigated with suspension structure. The effects of granule morphology and its particle packing structure on compaction and resultant sintering behavior were evaluated.

Simultaneous Comparison of Two Roller Compaction Techniques and Two Particle Size Analysis Methods.

PubMed

Saarinen, Tuomas; Antikainen, Osmo; Yliruusi, Jouko

2017-11-01

A new dry granulation technique, gas-assisted roller compaction (GARC), was compared with conventional roller compaction (CRC) by manufacturing 34 granulation batches. The process variables studied were roll pressure, roll speed, and sieve size of the conical mill. The main quality attributes measured were granule size and flow characteristics. Within granulations also the real applicability of two particle size analysis techniques, sieve analysis (SA) and fast imaging technique (Flashsizer, FS), was tested. All granules obtained were acceptable. In general, the particle size of GARC granules was slightly larger than that of CRC granules. In addition, the GARC granules had better flowability. For example, the tablet weight variation of GARC granules was close to 2%, indicating good flowing and packing characteristics. The comparison of the two particle size analysis techniques showed that SA was more accurate in determining wide and bimodal size distributions while FS showed narrower and mono-modal distributions. However, both techniques gave good estimates for mean granule sizes. Overall, SA was a time-consuming but accurate technique that provided reliable information for the entire granule size distribution. By contrast, FS oversimplified the shape of the size distribution, but nevertheless yielded acceptable estimates for mean particle size. In general, FS was two to three orders of magnitude faster than SA.

Studies on the compressibility of wax matrix granules of acetaminophen and their admixtures with various tableting bases.

PubMed

Uhumwangho, M U; Okor, R S

2006-04-01

Matrix granules of acetaminophen have been formed by a melt granulation process whereby the acetaminophen powder was triturated with the melted wax--goat wax, glyceryl monostearate or carnuba wax. The compressibility of the matrix granules and their admixture, with diluent granules (lactose, alpha-cellulose or microcrystalline cellulose) was investigated. The granules were compressed to tablets at a constant load (30 arbitrary units on the load scale) of a manesty single punch machine. Resulting tablets were evaluated for tensile strength (T) and disintegration times (DT). Granule flow was determined by measuring their angle of repose when allowed to fall freely on a level surface. Matrix granules prepared by melt granulation with goat wax or glyceryl monostearate were too sticky and therefore did not flow at all. They were also poorly compressible (T values = 0.20MN/m2). Inclusion of the diluent remarkably improved granule flow property and compressibility. The T values of the tablets (measure of compressibility) increased from about 0.24 to 0.65 MN/m2 during increase in diluent (lactose) content from 20 to 80 %w/w. Microcrystalline cellulose and alpha-cellulose were more effective than lactose in promoting compressibility of the granules. By contrast the matrix granules formed with carnuba wax were free flowing (angle of repose, 18.60). Addition of the diluent further improved flowability slightly. The matrix granules (without a diluent) were readily compressible (T value, 1.79MN/m2). Addition of the diluent (80%w/w) reduced T values (MN/m2) slightly to 1.32 (lactose), 1.48 (alpha-cellulose) and 1.74 (microcrystalline cellulose). Tablets of the matrix granules only, disintegrated rapidly within 3 minutes. DT was further reduced to <30 s by addition of any of the diluents. The indication is that the inclusion of the diluents studied can be used to improve the compressibility of the otherwise poorly compressible matrix granules. Based on the flowability, compressibility, and disintegration data, carnuba wax proved most promising in the melt granulation of the test drug for sustained release applications.

Improved tabletability after a polymorphic transition of delta-mannitol during twin screw granulation.

PubMed

Vanhoorne, V; Bekaert, B; Peeters, E; De Beer, T; Remon, J-P; Vervaet, C

2016-06-15

In most formulations processed via continuous twin screw granulation microcrystalline cellulose (MCC) and/or lactose are used as excipients, but mannitol is also a preferred excipient for wet granulation and tableting due to its non-hygroscopicity and inertness. Therefore, the aim of the current study was to investigate the influence of process parameters on critical quality attributes of granules (moisture content, solid state, morphology, size distribution, specific surface area, friability, flowability and hygroscopicity) and tablets (tensile strength and friability) after twin screw granulation of δ-mannitol. The δ-polymorph was selected since a moisture-induced transformation to β-mannitol was observed during batch wet granulation, which exhibited a unique morphology with a large surface area and improved tabletability. A full factorial experimental design was performed, varying screw speed (400-900rpm), granulation temperature (25-40°C), number of kneading elements (6 or 12) and liquid-to-solid (L/S) ratio, on the granulation unit of a ConsiGma™-25 line (a continuous powder-to-tablet manufacturing system). After tray drying the granules were milled and tableted. The results showed that the polymorphic transition from δ- to β-mannitol also occurred during twin screw granulation, although the residence time and L/S ratios were much lower in continuous twin screw granulation compared to batch processing. However, the polymorphic transition was not complete in all experiments and depended on the L/S ratio, screw speed and number of kneading elements. Nevertheless all granules exhibited the unique morphology linked to the polymorphic transition and had a superior tabletability compared to granules produced with β-mannitol as starting material. This was attributed to enhanced plastic deformation of the granules manufactured using δ-mannitol as starting material. In addition, it was concluded that mannitol was granulated via a different mechanism than other, less-soluble, excipients (e.g. lactose, microcrystalline cellulose) due to its high solubility and dissolution rate as the influence of process parameters on the mannitol granule characteristics was different. Copyright © 2016 Elsevier B.V. All rights reserved.

Elucidation of solution state complexation in wet-granulated oven-dried ibuprofen and beta-cyclodextrin: FT-IR and 1H-NMR studies.

PubMed

Ghorab, M K; Adeyeye, M C

2001-08-01

The effect of oven-dried wet granulation on the complexation of beta-cyclodextrin with ibuprofen (IBU) in solution was investigated using Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (1H NMR), and molecular modeling. Granulation was carried out using 5 mL of three different granulating solvents; water, ethanol (95% v/v), and isopropanol and the granules were oven-dried at 60 degrees C for 2 h. The granules were compared to oven-dried physical mixture and conventionally prepared complex. Phase solubility study was performed to investigate the stability of the granulation-formed complexes in solution. FT-IR was used to examine the complexation in the granules while 1H NMR, and molecular modeling studies were carried out to determine the mechanism of complexation in the water-prepared granules. The solubility studies suggested a 1:1 complex between IBU and betaCD. It also showed that the stability of the complex in solution was in the following order with respect to the granulating solvents: ethanol > water > isopropanol. The FT-IR study revealed a shift in the carboxylic acid stretching band and decrease in the intensities of the C-H bending bands of the isopropyl group and the out-of-plane aromatic ring, of IBU, in granules compared to the oven-dried physical mixture. This indicated that granules might have some extent of solid state complexation that could further enhance dissolution and the IBU-betaCD solution state complexation. 1H NMR showed that water prepared oven-dried granules had a different 1H NMR spectrum compared to similarly made oven-dried physical mixture, indicative of complexation in the former. The 1H NMR and the molecular modeling studies together revealed that solution state complexation from the granules occurred by inclusion of the isopropyl group together with part of the aromatic ring of IBU into the betaCD cavity probably through its wider side. These results indicate that granulation process induced faster complexation in solution which enhances the solubility and the dissolution rate of poorly soluble drugs. The extent of complexation in the granules was dependent on the type of solvent used.

Fast formation of aerobic granules by combining strong hydraulic selection pressure with overstressed organic loading rate.

PubMed

Liu, Yong-Qiang; Tay, Joo-Hwa

2015-09-01

The combined strong hydraulic selection pressure (HSP) with overstressed organic loading rate (OLR) as a fast granulation strategy was used to enhance aerobic granulation. To investigate the wide applicability of this strategy to different scenarios and its relevant mechanism, different settling times, different inoculums, different exchange ratios, different reactor configurations, and different shear force were used in this study. It was found that clear granules were formed within 24 h and steady state reached within three days when the fast granulation strategy was used in a lab-scale reactor seeded with well settled activated sludge (Reactor 2). However, granules appeared after 2-week operation and reached steady state after one month at the traditional step-wise decreased settling time from 20 to 2 min with OLR of 6 g COD/L·d (Reactor 1). With the fast granulation strategy, granules appeared within 24 h even with bulking sludge as seed to start up Reactor 3, but 6-day lag phase was observed compared with Reactor 2. Both Reactor 2 and Reactor 3 experienced sigmoidal growth curve in terms of biomass accumulation and granule size increase after granulation. In addition, the reproducible results in pilot-scale reactors (Reactor 5 and Reactor 6) with diameter of 20 cm and height/diameter ratio (H/D) of 4 further proved that reactor configuration and fluid flow pattern had no effect on the aerobic granulation when the fast granulation strategy was employed, but biomass accumulation experienced a short lag phase too in Reactor 5 and Reactor 6. Although overstressed OLR was favorable for fast granulation, it also led to the fluffy granules after around two-week operation. However, the stable 6-month operation of Reactor 3 demonstrated that the rapidly formed granules were able to maintain long-term stability by reducing OLR from 12 g COD/L·d to 6 g COD/L·d. A mechanism of fast granulation with the strategy of combined strong HSP and OLR was proposed to explain results and guide the operation with this fast strategy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modeling of lithium granule injection in NSTX using M3D-C1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fil, A.; Kolemen, E.; Ferraro, N.

In this paper, we present simulations of pedestal control by lithium granule injection (LGI) in NSTX. A model for small granule ablation has been implemented in the M3D-C1 code (Jardin et al 2012 Comput. Sci. Discovery 5 014002), allowing the simulation of realistic lithium granule injections. 2D and 3D simulations of Li injections in NSTX H-mode plasmas are performed and the effect of granule size, injection angle and velocity on the pedestal gradient increase is studied. The amplitude of the local pressure perturbation caused by the granules is found to be highly dependent on the solid granule size. Adjusting themore » granule injection velocity allows one to inject more particles at the pedestal top. 3D simulations show the destabilization of high order MHD modes whose amplitude is directly linked to the localized pressure perturbation, which is found to depend on the toroidal localization of the granule density source.« less

Autophagy meets fused in sarcoma-positive stress granules.

PubMed

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

2014-12-01

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

New Class of Cargo Protein in Tetrahymena thermophila Dense Core Secretory Granules

PubMed Central

Haddad, Alex; Bowman, Grant R.; Turkewitz, Aaron P.

2002-01-01

Regulated exocytosis of dense core secretory granules releases biologically active proteins in a stimulus-dependent fashion. The packaging of the cargo within newly forming granules involves a transition: soluble polypeptides condense to form water-insoluble aggregates that constitute the granule cores. Following exocytosis, the cores generally disassemble to diffuse in the cell environment. The ciliates Tetrahymena thermophila and Paramecium tetraurelia have been advanced as genetically manipulatable systems for studying exocytosis via dense core granules. However, all of the known granule proteins in these organisms condense to form the architectural units of lattices that are insoluble both before and after exocytosis. Using an approach designed to detect new granule proteins, we have now identified Igr1p (induced during granule regeneration). By structural criteria, it is unrelated to the previously characterized lattice-forming proteins. It is distinct in that it is capable of dissociating from the insoluble lattice following secretion and therefore represents the first diffusible protein identified in ciliate granules. PMID:12456006

Modeling of lithium granule injection in NSTX using M3D-C1

DOE PAGES

Fil, A.; Kolemen, E.; Ferraro, N.; ...

2017-04-06

In this paper, we present simulations of pedestal control by lithium granule injection (LGI) in NSTX. A model for small granule ablation has been implemented in the M3D-C1 code (Jardin et al 2012 Comput. Sci. Discovery 5 014002), allowing the simulation of realistic lithium granule injections. 2D and 3D simulations of Li injections in NSTX H-mode plasmas are performed and the effect of granule size, injection angle and velocity on the pedestal gradient increase is studied. The amplitude of the local pressure perturbation caused by the granules is found to be highly dependent on the solid granule size. Adjusting themore » granule injection velocity allows one to inject more particles at the pedestal top. 3D simulations show the destabilization of high order MHD modes whose amplitude is directly linked to the localized pressure perturbation, which is found to depend on the toroidal localization of the granule density source.« less

Biomineralisation by earthworms - an investigation into the stability and distribution of amorphous calcium carbonate.

PubMed

Hodson, Mark E; Benning, Liane G; Demarchi, Bea; Penkman, Kirsty E H; Rodriguez-Blanco, Juan D; Schofield, Paul F; Versteegh, Emma A A

Many biominerals form from amorphous calcium carbonate (ACC), but this phase is highly unstable when synthesised in its pure form inorganically. Several species of earthworm secrete calcium carbonate granules which contain highly stable ACC. We analysed the milky fluid from which granules form and solid granules for amino acid (by liquid chromatography) and functional group (by Fourier transform infrared (FTIR) spectroscopy) compositions. Granule elemental composition was determined using inductively coupled plasma-optical emission spectroscopy (ICP-OES) and electron microprobe analysis (EMPA). Mass of ACC present in solid granules was quantified using FTIR and compared to granule elemental and amino acid compositions. Bulk analysis of granules was of powdered bulk material. Spatially resolved analysis was of thin sections of granules using synchrotron-based μ-FTIR and EMPA electron microprobe analysis. The milky fluid from which granules form is amino acid-rich (≤ 136 ± 3 nmol mg -1 (n = 3; ± std dev) per individual amino acid); the CaCO 3 phase present is ACC. Even four years after production, granules contain ACC. No correlation exists between mass of ACC present and granule elemental composition. Granule amino acid concentrations correlate well with ACC content (r ≥ 0.7, p ≤ 0.05) consistent with a role for amino acids (or the proteins they make up) in ACC stabilisation. Intra-granule variation in ACC (RSD = 16%) and amino acid concentration (RSD = 22-35%) was high for granules produced by the same earthworm. Maps of ACC distribution produced using synchrotron-based μ-FTIR mapping of granule thin sections and the relative intensity of the ν 2 : ν 4 peak ratio, cluster analysis and component regression using ACC and calcite standards showed similar spatial distributions of likely ACC-rich and calcite-rich areas. We could not identify organic peaks in the μ-FTIR spectra and thus could not determine whether ACC-rich domains also had relatively high amino acid concentrations. No correlation exists between ACC distribution and elemental concentrations determined by EMPA. ACC present in earthworm CaCO 3 granules is highly stable. Our results suggest a role for amino acids (or proteins) in this stability. We see no evidence for stabilisation of ACC by incorporation of inorganic components. Graphical abstractSynchrotron-based μ-FTIR mapping was used to determine the spatial distribution of amorphous calcium carbonate in earthworm-produced CaCO 3 granules.

High organic loading influences the physical characteristics of aerobic sludge granules.

PubMed

Moy, B Y-P; Tay, J-H; Toh, S-K; Liu, Y; Tay, S T-L

2002-01-01

The effect of high organic loading rate (OLR) on the physical characteristics of aerobic granules was studied. Two column-type sequential aerobic sludge blanket reactors were fed with either glucose or acetate as the main carbon source, and the OLR was gradually raised from 6 to 9, 12 and 15 kg chemical oxygen demand (COD) m(-3) d(-1). Glucose-fed granules could sustain the maximum OLR tested. At a low OLR, these granules exhibited a loose fluffy morphology dominated by filamentous bacteria. At higher OLRs, these granules became irregularly shaped, with folds, crevices and depressions. In contrast, acetate-fed granules had a compact spherical morphology at OLRs of 6 and 9 kg COD m(-3) d(-1), with better settling and strength characteristics than glucose-fed granules at similar OLRs. However, acetate-fed granules could not sustain high OLRs and disintegrated when the OLR reached 9 kg COD m(-3) d(-1). The compact regular microstructure of the acetate-fed granules appeared to limit mass transfer of nutrients at an OLR of 9 kg COD m(-3) d(-1). The looser filamentous microstructure of the glucose-fed granules and the subsequent irregular morphology delayed the onset of diffusion limitation and allowed significantly higher OLRs to be attained. SIGNIFICNACE AND IMPACT OF THE STUDY: High organic loading rates are possible with aerobic granules. This research would be helpful in the development of aerobic granule-based systems for high-strength wastewaters.

Granulation of snow: From tumbler experiments to discrete element simulations

NASA Astrophysics Data System (ADS)

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

2015-06-01

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

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

NASA Astrophysics Data System (ADS)

Topka, K.; Title, A.; Tarbell, T.; Ferguson, S.; Shine, R.

1988-11-01

The Solar Optical Universal Polarimeter (SOUP) on Spacelab 2 collected movies of solar granulation completely free from atmospheric blurring, and are not degraded by pointint jitter (the pointing stability was 0.003 sec root mean square). The movies illustrate that the solar five minute oscillation has a major role in the appearance of solar granulation and that exploding granules are a common feature of the granule evolution. Using 3-D Fourier filtering techniques the oscillations were removed and it was demonstrated that the autocorrelation lifetime of granulation is a factor of two greater in magnetic field regions than in field-free quiet sun. Horizontal velocities were measured and flow patterns were observed on the scale of meso- and super granulation. In quiet regions the mean flow velocity is 370 m/s while in the magnetic regions it is about 125 m/s. It was also found that the root mean square (RMS) fluctuating horizonal velocity field is substantially greater in quiet sun than in strong magnetic field regions. By superimposing the location of exploding granules on the average flow maps it was found that they appear almost exclusively in the center of mesogranulation size flow cells. Because of the nonuniformity of the distribution of exploding granules, the evolution of the granulation pattern in mesogranule cell centers and boundaries differs fundamentally. It is clear from this study there is neither a typical granule nor a typical granule evolution.

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

NASA Technical Reports Server (NTRS)

Topka, K.; Title, A.; Tarbell, T.; Ferguson, S.; Shine, R.

1988-01-01

The Solar Optical Universal Polarimeter (SOUP) on Spacelab 2 collected movies of solar granulation completely free from atmospheric blurring, and are not degraded by pointint jitter (the pointing stability was 0.003 sec root mean square). The movies illustrate that the solar five minute oscillation has a major role in the appearance of solar granulation and that exploding granules are a common feature of the granule evolution. Using 3-D Fourier filtering techniques the oscillations were removed and it was demonstrated that the autocorrelation lifetime of granulation is a factor of two greater in magnetic field regions than in field-free quiet sun. Horizontal velocities were measured and flow patterns were observed on the scale of meso- and super granulation. In quiet regions the mean flow velocity is 370 m/s while in the magnetic regions it is about 125 m/s. It was also found that the root mean square (RMS) fluctuating horizonal velocity field is substantially greater in quiet sun than in strong magnetic field regions. By superimposing the location of exploding granules on the average flow maps it was found that they appear almost exclusively in the center of mesogranulation size flow cells. Because of the nonuniformity of the distribution of exploding granules, the evolution of the granulation pattern in mesogranule cell centers and boundaries differs fundamentally. It is clear from this study there is neither a typical granule nor a typical granule evolution.

Investigation on the pitting of potato starch granules during high frequency ultrasound treatment.

PubMed

Bai, Wenzhe; Hébraud, Pascal; Ashokkumar, Muthupandian; Hemar, Yacine

2017-03-01

In this paper, the pitting of potato starch granules in aqueous suspensions (1%) by high-frequency high-power ultrasound (850kHz at a power of 0.2W, 2W or 3.7W; and also 500kHz and 1MHz at a power of 2W) is reported. The number of pits per starch granules was found to be independent of the amylose content of starches, and the surface properties of starch granules as modified through SDS and ethanol washing. At 850kHz, the maximum number of pits per starch granule, for both normal and waxy starches, did not exceed 11. However, a close inspection of fractionated starch granules based on their sizes showed that there is an optimum granule size for which a maximum pit number is obtained. For example, starch granules with diameter size range of ∼15 to ∼30μm had a maximum pit number (between 10 and 20 pits per granule) when sonicated (2W, 850kHz and 30min); while sonication of small (<10μm) and very large (>45μm) granules resulted in a smaller number of pits per granule (∼5). Further, the maximum number of pits per granules is also found to be proportional to the ultrasound frequency, with values of approximately 7, 10 and 11 at 0.50, 0.85, and 1MHz, respectively. FTIR measurements did not show any breakup of starch molecules. Copyright © 2016 Elsevier B.V. All rights reserved.

Correlative microscopy of detergent granules.

PubMed

van Dalen, G; Nootenboom, P; Heussen, P C M

2011-03-01

The microstructure of detergent products for textile cleaning determines to a large extent the physical properties of these products. Correlative microscopy was used to reveal the microstructure by reconciling images obtained by scanning electron microscopy with energy dispersive X-ray analysis, X-ray microtomography and Fourier transform infrared microscopy. These techniques were applied on the same location of a subsample of a spray-dried detergent base powder embedded in polyacrylate. In this way, the three-dimensional internal and external structure of detergent granules could be investigated from milli to nano scale with detailed spatial information about the components present. This will generate knowledge how to design optimal microstructures for laundry products to obtain product properties demanded by the market. This method is also very useful for other powder systems used in a large variety of industries (e.g. for pharmaceutical, food, ceramic and metal industries). © 2010 The Authors Journal of Microscopy © 2010 The Royal Microscopical Society.

International review of cytology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bourne, G.H.; Jeon, K.W.; Friedlander, M.

1988-01-01

This book contains the following chapters: Transferrin and the growth-promoting effect of nerves; Nuclear functions and organization: The potential of immunochemical approaches; On the character of the secretory granules in juxtaglomerular eptihelioid cells; Protein secretions of sertoili cells; Problems of immune surveillance over the cytodifferentiation state and some cellular mechanisms of natural antitumor resistance; and Potassium estimation, uptake, and its role in the physiology and metabolism of flowering plants.

In vitro and in vivo evaluation of medicinal carbon granules and tablet on the adsorption of acetaminophen.

PubMed

Yamamoto, Kenta; Onishi, Hiraku; Ito, Akihiko; Machida, Yoshiharu

2007-01-10

Medicinal carbon (MC) granules were prepared by wet granulation using maltitol (MT), and the MC tablet was produced by compression of the granules. The physical properties and the in vitro adsorption capacity for AA of the formulations were examined. Further, the effects of MC alone and the granules on gastrointestinal absorption of AA were examined in rats when they were administered intragastrically at 15 or 45 min after the intragastrical administration of AA. AA was rapidly adsorbed by MC, and the maximum adsorption capacity of MC was 0.329g AA per gram MC. The granules and tablet exhibited adequate strength, and the tablet disintegrated rapidly. The granules and tablet showed similar adsorption profiles, but somewhat lower adsorption capacity than MC alone. MC alone and granules administered at 15 min reduced the AUC(0-infinity) significantly against the control (no treatment); however, the suppression effect on the plasma concentration was lower with the granules than with MC alone. Thus, granules and tablet are useful as a compact dosage form of MC; though the reduced adsorption capacity must be taken into account in order to expect efficacy equivalent to that of MC alone.

Investigation of the effect of impeller speed on granules formed using a PMA-1 high shear granulator.

PubMed

Logan, R; Briens, L

2012-11-01

Impeller speed was varied from 300 to 1500 rpm during the wet high shear granulation of a placebo formulation using a new vertical shaft PharmaMATRIX-1 granulator. The resulting granules were extensively analysed for differences caused by the varying impeller speed with emphasis on flowability. Microscopy showed that initial granules were formed primarily from microcrystalline cellulose at all tested impeller speeds. At low impeller speed of 300 rpm in the "bumpy" flow regime, forces from the impeller were insufficient to incorporate all the components of the formulation into the granules and to promote granule growth to a size that significantly improved flowability. The "roping" flow regime at higher impeller speeds promoted granule growth to a median particle size of at least 100 µm that improved the flowability of the mixture. Particle size distribution measurements and advanced indicators based on avalanching behavior, however, showed that an impeller speed of 700 rpm produced the largest fraction of optimal granules with the best flowability potential. This impeller speed allowed good development of "roping" flow for sufficient mixing, collision rates and kinetic energy for collisions while minimizing excessive centrifugal forces that promote buildup around the bowl perimeter.

Starch synthase 4 is essential for coordination of starch granule formation with chloroplast division during Arabidopsis leaf expansion

PubMed Central

Crumpton-Taylor, Matilda; Pike, Marilyn; Lu, Kuan-Jen; Hylton, Christopher M; Feil, Regina; Eicke, Simona; Lunn, John E; Zeeman, Samuel C; Smith, Alison M

2013-01-01

Arabidopsis thaliana mutants lacking the SS4 isoform of starch synthase have strongly reduced numbers of starch granules per chloroplast, suggesting that SS4 is necessary for the normal generation of starch granules. To establish whether it plays a direct role in this process, we investigated the circumstances in which granules are formed in ss4 mutants. Starch granule numbers and distribution and the accumulation of starch synthase substrates and products were investigated during ss4 leaf development, and in ss4 mutants carrying mutations or transgenes that affect starch turnover or chloroplast volume. We found that immature ss4 leaves have no starch granules, but accumulate high concentrations of the starch synthase substrate ADPglucose. Granule numbers are partially restored by elevating the capacity for glucan synthesis (via expression of bacterial glycogen synthase) or by increasing the volumes of individual chloroplasts (via introduction of arc mutations). However, these granules are abnormal in distribution, size and shape. SS4 is an essential component of a mechanism that coordinates granule formation with chloroplast division during leaf expansion and determines the abundance and the flattened, discoid shape of leaf starch granules. PMID:23952675

Comparison of low-shear and high-shear granulation processes: effect on implantable calcium phosphate granule properties.

PubMed

Chevalier, E; Viana, M; Cazalbou, S; Chulia, D

2009-10-01

Calcium phosphate porous ceramics present a great interest not only as complex bone defect fillers but also as drug delivery systems. Most of the methods described in the literature to fabricate pellets are based on compaction, casting into spherical molds, or on processes such as liquid immiscibility or foaming. Despite wet granulation is used in a wide range of applications in pharmaceuticals, food, detergents, fertilizers, and minerals, it is not applied in the biomaterial field to produce granules. In this study physicochemical and in vitro drug delivery properties of implantable calcium phosphate granules, produced by two wet agglomeration processes, were compared. Pellets obtained by high shear granulation (granulation in a Mi-Pro apparatus) were shown to be more spherical and less friable than granules elaborated by low shear process (granulation in a Kenwood apparatus). Although Mi-Pro pellets had a slightly lower porosity compared to Kenwood granules, ibuprofen loading efficiency and dissolution profiles were not statistically different and the release mechanism was mainly controlled by diffusion, in both cases. Mi-Pro pellets appeared to be better candidates as bone defect fillers and local drug delivery systems as far as they were more spherical and less friable than Kenwood agglomerates.

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

PubMed

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

2009-07-30

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

Stimulation of microtubule-based transport by nucleation of microtubules on pigment granules

PubMed Central

Semenova, Irina; Gupta, Dipika; Usui, Takeo; Hayakawa, Ichiro; Cowan, Ann; Rodionov, Vladimir

2017-01-01

Microtubule (MT)-based transport can be regulated through changes in organization of MT transport tracks, but the mechanisms that regulate these changes are poorly understood. In Xenopus melanophores, aggregation of pigment granules in the cell center involves their capture by the tips of MTs growing toward the cell periphery, and granule aggregation signals facilitate capture by increasing the number of growing MT tips. This increase could be explained by stimulation of MT nucleation either on the centrosome or on the aggregate of pigment granules that gradually forms in the cell center. We blocked movement of pigment granules to the cell center and compared the MT-nucleation activity of the centrosome in the same cells in two signaling states. We found that granule aggregation signals did not stimulate MT nucleation on the centrosome but did increase MT nucleation activity of pigment granules. Elevation of MT-nucleation activity correlated with the recruitment to pigment granules of a major component of MT-nucleation templates, γ-tubulin, and was suppressed by γ-tubulin inhibitors. We conclude that generation of new MT transport tracks by concentration of the leading pigment granules provides a positive feedback loop that enhances delivery of trailing granules to the cell center. PMID:28381426

To Evaluate the Effect of Solvents and Different Relative Humidity Conditions on Thermal and Rheological Properties of Microcrystalline Cellulose 101 Using METHOCEL™ E15LV as a Binder.

PubMed

Jagia, Moksh; Trivedi, Maitri; Dave, Rutesh H

2016-08-01

The solvent used for preparing the binder solution in wet granulation can affect the granulation end point and also impact the thermal, rheological, and flow properties of the granules. The present study investigates the effect of solvents and percentage relative humidity (RH) on the granules of microcrystalline cellulose (MCC) with hydroxypropyl methyl cellulose (HPMC) as the binder. MCC was granulated using 2.5% w/w binder solution in water and ethanol/water mixture (80:20 v/v). Prepared granules were dried until constant percentage loss on drying, sieved, and further analyzed. Dried granules were exposed to different percentage RH for 48 h at room temperature. Powder rheometer was used for the rheological and flow characterization, while thermal effusivity and differential scanning calorimeter were used for thermal analysis. The thermal effusivity values for the wet granules showed a sharp increase beginning 50% w/w binder solution in both cases, which reflected the over-wetting of granules. Ethanol/water solvent batches showed greater resistance to flow as compared to the water solvent batches in the wet granule stage, while the reverse was true for the dried granule stage, as evident from the basic flowability energy values. Although the solvents used affected the equilibration kinetics of moisture content, the RH-exposed granules remained unaffected in their flow properties in both cases. This study indicates that the solvents play a vital role on the rheology and flow properties of MCC granules, while the different RH conditions have little or no effect on them for the above combination of solvent and binder.

CERES Search and Subset Tool

Atmospheric Science Data Center

2016-06-24

... data granules using a high resolution spatial metadata database and directly accessing the archived data granules. Subset results are ... data granules using a high resolution spatial metadata database and directly accessing the archived data granules. Subset results are ...

Lymphatic involvement in the histopathogenesis of mucous retention cyst.

PubMed

Kundu, Sukalyan; Cheng, Jun; Maruyama, Satoshi; Suzuki, Makoto; Kawashima, Hiroyuki; Saku, Takashi

2007-01-01

Mucous retention cyst results from extravasation of saliva. Our intent was to study the role of lymphatics in its pathogenesis. Twenty-three surgical specimens of mucous retention cyst of the lip were examined for involvement of lymphatic vessels by a comparative immunohistochemical demonstration of lymphatic and blood vascular endothelial cells, as well as lymphatic and salivary contents. Mucous retention cysts were histopathologically classified into three stages: early, intermediate, and advanced. In the early stage, there was diffuse extravasation of mucous material in the interstitium of the lamina propria or the submucosal layer of the oral mucosa. In the intermediate stage, lymphatics, which were clearly revealed and immunohistochemically distinguished from blood vessels by monoclonal antibody D2-40, were dilated and finally ruptured, leaving fragments of lymphatic walls in the periphery of mucous pools. In the advanced stage, thick cyst walls of granulation tissue were formed around mucous retention. Lymphatics were no longer involved in the granulation tissue wall, which was actively driven by blood vessel formation. The results suggest that the lymphatic rupture seems to contribute to the enlargement in the pathogenesis of mucous retention cyst.

THE FINE STRUCTURE OF THE NUCLEOLUS DURING MITOSIS IN THE GRASSHOPPER NEUROBLAST CELL

PubMed Central

Stevens, Barbara J.

1965-01-01

The behavior of the nucleolus during mitosis was studied by electron microscopy in neuroblast cells of the grasshopper embryo, Chortophaga viridifasciata. Living neuroblast cells were observed in the light microscope, and their mitotic stages were identified and recorded. The cells were fixed and embedded; alternate thick and thin sections were made for light and electron microscopy. The interphase nucleolus consists of two fine structural components arranged in separate zones. Concentrations of 150 A granules form a dense peripheral zone, while the central regions are composed of a homogeneous background substance. Observations show that nucleolar dissolution in prophase occurs in two steps with a preliminary loss of the background substance followed by a dispersal of the granules. Nucleolar material reappears at anaphase as small clumps or layers at the chromosome surfaces. These later form into definite bodies, which disappear as the nucleolus grows in telophase. Evidence suggests both a collecting and a synthesizing role for the nucleolus-associated chromatin. The final, mature nucleolar form is produced by a rearrangement of the fine structural components and an increase in their mass. PMID:14326121

31-mode piezoelectric micromachined ultrasonic transducer with PZT thick film by granule spraying in vacuum process

NASA Astrophysics Data System (ADS)

Jung, Joontaek; Annapureddy, Venkateswarlu; Hwang, Geon-Tae; Song, Youngsup; Lee, Wonjun; Kang, Woojin; Ryu, Jungho; Choi, Hongsoo

2017-05-01

A piezoelectric micromachined ultrasonic transducer (pMUT) is an ideal device for portable medical diagnosis systems, intravascular ultrasound systems, and ultrasonic cameras because of its favorable characteristics including small size, acoustic impedance matching with the body, low power consumption, and simple integration with the systems. Despite these advantages, practical applications are limited because of insufficient acoustic pressure of the pMUT caused by the thin active piezoelectric layer. Here, we report the fabrication of a thick piezoelectric Pb(Zr,Ti)O3 (PZT) film-based pMUT device having high deflection at low driving voltage using the granule spraying in vacuum (GSV) process. Pre-patterned high-density thick (exceeding 8 μm) PZT films were grown on 6-inch-diameter Si/SiO2/Ti/Pt silicon-on-insulator wafers at room temperature at a high deposition rate of ˜5 μm min-1. The fabrication process using the proposed GSV process was simple and fast, and the deflection of the pMUT exhibited a high value of 0.8 μm.

A new species of Eimeria (Apicomplexa: Eimeriidae) from tri-colored bats, Perimyotis subflavus (Chiroptera: Vespertilionidae), from the Ouachitas of Arkansas.

PubMed

McAllister, Chris T; Seville, R Scott; Arlen, Robert; Connior, Matthew B

2014-10-01

Between February 2013 and October 2013, eleven tri-colored bats, Perimyotis subflavus were collected from Marion, Polk, and Searcy counties, Arkansas, and their faeces examined for coccidian parasites. Two of eleven (18%) harboured an eimerian that we describe here as new. Oocysts of Eimeria mcdanieli sp. n. were ellipsoidal to elongate with a bi-layered wall and measured (length × width, L × W) 28.3 × 17.9 μm, with an L/W ratio of 1.6. A micropyle and oocyst residuum were absent but a single polar granule was present. Sporocysts were ovoidal, 12.6 × 8.3 μm, with an L/W ratio of 1.5. A pronounced, nipple-like Stieda body was present as well as a substieda body. A sporocyst residuum was present as dispersed bubble-like granules. This is the third coccidian described from tri-colored bats and the sixth species reported from Arkansas chiropterans. In addition, both infected bats harbored a concurrent infection of Eimeria heidti McAllister, Burt, Seville, and Robison, 2011.

Energy metabolism of synaptosomes from different neuronal systems of rat cerebellum during aging: a functional proteomic characterization.

PubMed

Ferrari, Federica; Gorini, Antonella; Villa, Roberto Federico

2015-01-01

Functional proteomics was used to characterize age-related changes in energy metabolism of different neuronal pathways within the cerebellar cortex of Wistar rats aged 2, 6, 12, 18, and 24 months. The "large" synaptosomes, derived from the glutamatergic mossy fibre endings which make synaptic contact with the granule cells of the granular layer, and the "small" synaptosomes, derived from the pre-synaptic terminals of granule cells making synaptic contact with the dendrites of Purkinje cells, were isolated by a combined differential/gradient centrifugation technique. Because most brain disorders are associated with bioenergetic changes, the maximum rate (Vmax) of selected enzymes of glycolysis, Krebs' cycle, glutamate and amino acids metabolism, and acetylcholine catabolism were evaluated. The results show that "large" and "small" synaptosomes possess specific and independent metabolic features. This study represents a reliable model to study in vivo (1) the physiopathological molecular mechanisms of some brain diseases dependent on energy metabolism, (2) the responsiveness to noxious stimuli, and (3) the effects of drugs, discriminating their action sites at subcellular level on specific neuronal pathways.

Synthesis of high-performance Li4Ti5O12 and its application to the asymmetric hybrid capacitor

NASA Astrophysics Data System (ADS)

Lee, Byunggwan; Yoon, Jung Rag

2013-11-01

In this work, granule Li4Ti5O12 was successfully synthesized by spray drying a precursor slurry, followed by the solid-state reaction method. The precursor slurry was prepared from a solution of lithium carbonate (Li2CO3) and titanium dioxide (TiO2) in deionized water. A hybrid capacitor was fabricated which comprised a granule Li4Ti5O12 anode and activated carbon cathode. For comparison, an electrical double-layer capacitor (EDLC) cell was fabricated by using activated carbon electrodes in the same way. The electrochemical performance of the hybrid capacitor and the EDLC was characterized by constant current charge/discharge curves and cycle performance testing. The electrochemical testing results showed that the capacitance of the hybrid capacitor is approximately 2.5 times higher than that of the EDLC. Furthermore, the capacitance of the EDLC and the hybrid capacitor barely decreased after 1,000 cycles. The results of this study demonstrate that the hybrid capacitor has the advantages of the high rate capability of a supercapacitor (EDLC) and high battery capacity.

A new species of Eimeria Schneider, 1875 (Apicomplexa: Eimeriidae) from the Solomon ground skink, Sphenomorphus solomonis (Boulenger) (Sauria: Scincidae) from Papua New Guinea

USGS Publications Warehouse

McAllister, Chris T.; Duszynski, Donald W.; Fisher, Robert N.; Austin, Christopher C.

2014-01-01

Between September 1990 and November 1991, 19 Sphenomorphus spp. skinks, including nine S. jobiense, three S. simus, and seven Solomon ground skinks, S. solomonis (Boulenger), were collected from Madang and Morobe Provinces, Papua New Guinea (PNG), and examined for coccidia. A single S. solomonis was found to be infected with a new species of Eimeria Schneider, 1875. Oöcysts of Eimeria perkinsae n. sp. are ellipsoidal with a smooth, colourless, bi-layered wall, measure 18.6 × 14.7 μm, and have a length/width (L/W) ratio of 1.3; both micropyle and oöcyst residuum are absent, but a fragmented polar granule is present. Sporocysts are ovoidal, 8.9 × 6.4 μm, L/W 1.4; neither Stieda, sub-Stieda or para-Stieda bodies are present; a sporocyst residuum consisted of a loose cluster of granules dispersed between sporozoites. Sporozoites are comma-shaped with spheroidal anterior and posterior refractile bodies. This represents the first report of coccidia from this skink genus.

Evidence of photospheric vortex flows at supergranular junctions observed by FG/SOT (Hinode)

NASA Astrophysics Data System (ADS)

Attie, R.; Innes, D. E.; Potts, H. E.

2009-01-01

Context: Twisting motions of different sorts are observed in several layers of the solar atmosphere. Chromospheric sunspot whorls and rotation of sunspots or even higher up in the lower corona sigmoids are examples of the large-scale twisted topology of many solar features. Nevertheless, their occurrence on a large scale in the quiet photosphere has not been investigated yet. Aims: The present study reveals the existence of vortex flows located at the supergranular junctions of the quiet Sun. Methods: We used a 1-h and a 5-h time series of the granulation in blue continuum and G-band images from FG/SOT to derive the photospheric flows. A feature-tracking technique called balltracking was performed to track the granules and reveal the underlying flow fields. Results: In both time series, we identify long lasting vortex flow located at supergranular junctions. The first vortex flow lasts at least 1 h and is ~20´´ wide (~15.5 Mm). The second vortex flow lasts more than 2 h and is ~27´´ wide (~21 Mm).

Nonequilibrium electrophoresis of an ion-selective microgranule for weak and moderate external electric fields

NASA Astrophysics Data System (ADS)

Frants, E. A.; Ganchenko, G. S.; Shelistov, V. S.; Amiroudine, S.; Demekhin, E. A.

2018-02-01

Electrokinetics and the movement of charge-selective micro-granules in an electrolyte solution under the influence of an external electric field are investigated theoretically. Straightforward perturbation analysis is applied to a thin electric double layer and a weak external field, while a numerical solution is used for moderate electric fields. The asymptotic solution enables the determination of the salt concentration, electric charge distribution, and electro-osmotic velocity fields. It may also be used to obtain a simple analytical formula for the electrophoretic velocity in the case of quasi-equilibrium electrophoresis (electrophoresis of the first kind). This formula differs from the famous Helmholtz-Smoluchowski relation, which applies to dielectric microparticles, but not to ion-selective granules. Numerical calculations are used to validate the derived formula for weak external electric fields, but for moderate fields, nonlinear effects lead to a significant increase in electrophoretic mobility and to a transition from quasi-equilibrium electrophoresis of the first kind to nonequilibrium electrophoresis of the second kind. Theoretical results are successfully compared with experimental data.

Aliphatic Chains of Esterified Lipids in Isolated Eyespots of Euglena gracilis var. bacillaris1

PubMed Central

Hilenski, Lula L.; Walne, Patricia L.; Snyder, Fred

1976-01-01

Isolated eyespot granules of Euglena gracilis Klebs var. bacillaris Pringsheim contained approximately 6% lipids (based on protein). Separation of the lipid extracts by thin layer chromatography revealed four major fractions: wax esters, triacylglycerols, free fatty acids, and phospholipids. Methanolysis of each fraction yielded between 27 and 29 different fatty acids ranging from 12:0 to 22:6. Acetates of the fatty alcohols of the wax fraction consisted of 11:0 to 18:0 carbon chains, with 14:0 being the major component; unsaturated alcohols were not detected. PMID:16659543

Light-toned Rock Outcrop in Aureum Chaos

NASA Technical Reports Server (NTRS)

2006-01-01

30 October 2006 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows an outcrop of light-toned, layered, sedimentary rock in Aureum Chaos. The darker material, which includes ripples, is composed of windblown sand and granules. This scene is located near 3.8oS, 26.2oW, and covers an area roughly 7.7 km by 3 km (4.8 by 1.9 mi) wide. Sunlight illuminates the terrain from the top/upper right. This southern autumn image was acquired on 14 July 2006.

Initial Results from the MER Athena Science Investigation at Gusev Crater and Meridiani Planum

NASA Astrophysics Data System (ADS)

Squyres, S.

2004-05-01

The Mars Exploration Rover Spirit landed in Gusev Crater on January 4 (UTC), 2004. It was followed 21 days later by the rover Opportunity, which landed on Meridiani Planum. The landing site at Gusev crater lies on a flat, rock-strewn plain. The rock at Gusev that has been studied best to date has been named Adirondack. In its surface texture, Adirondack appears to be dense, fine-grained and sand-blasted. Three sets of measurements have been made on Adirondack with the full set of payload instruments: one of the natural rock surface, one of the same location after being brushed by the RAT, and one of the same location after removal of 2-3 mm of rock by the RAT. The concentration of presumably dust-borne elements like sulfur and chlorine diminished significantly with brushing, and diminished dramatically with grinding. All of the observations of Adirondack are consistent with it being an essentially unweathered olivine and magnetite-bearing, low-silica basalt. The only soil at Gusev that has been investigated in detail so far is one dominated by fairly coarse (100-300 micron) grains that have the appearance and behavior of well-cemented agglomerates. APXS spectra of this soil are similar to those of soils found at the Viking and Pathfinder sites. Mössbauer spectra show two ferrous doublets and a ferric doublet, with the stronger ferrous doublet assigned to olivine. Mini-TES spectra have been acquired for soils surrounding the the Spirit landing site, and show spectra nearly identical to globally averaged soil viewed by the TES instrument on Mars Global Surveyor. This includes identification of a small amount (a few percent) of carbonate. The landing site at Meridiani Planum lies inside an impact crater that is roughly 20 meters in diameter. The lander came to rest on soil that fills most of the crater. An outcrop of layered bedrock is exposed on the crater wall. The landing site was selected partly because coarse gray hematite was expected to be present on the basis of orbital data. Mini-TES data have confirmed the presence of this hematite in the soil. The soil within the crater has several components. Microscopic images of undisturbed surface soil show that one component is fine (~100 micron) sand. Mössbauer spectra of the sand show two ferrous doublets (one of them due to olivine), a ferric doublet, and a weak magnetic sextet. APXS and Mini-TES data on this sand are consistent with a composition dominated by basalt. Another component of the soil consists of coarse (several mm) granules. These range in shape from subangular to rounded to remarkably spherical. In some locations, granules have been pressed down into the soil by the impact of the landers airbags. At those locations the concentration of hematite as determined by Mini-TES is sharply reduced, suggesting that at least some of the granules are hematite-bearing. The bedrock outcrop is finely laminated, with typical layer thicknesses of only a few mm. The texture of the outcrop as viewed in miroscopic images suggests that it is fine-grained, with well-expressed structure that is revealed by varying degrees of mechanical abrasion of layers of varying induration. Initial APXS results on this fine-grained matrix indicate sulfur concentrations significantly higher than any observed elsewhere on Mars. Embedded within the outcrop and weathering out of it are highly spherical granules with diameters of several mm. The visible to near-IR spectral properties of these embedded spherical granules, as determined by Pancam, are distinctly different from those of the matrix in which they are embedded.

Lack of the central nervous system- and neural crest-expressed forkhead gene Foxs1 affects motor function and body weight.

PubMed

Heglind, Mikael; Cederberg, Anna; Aquino, Jorge; Lucas, Guilherme; Ernfors, Patrik; Enerbäck, Sven

2005-07-01

To gain insight into the expression pattern and functional importance of the forkhead transcription factor Foxs1, we constructed a Foxs1-beta-galactosidase reporter gene "knock-in" (Foxs1beta-gal/beta-gal) mouse, in which the wild-type (wt) Foxs1 allele has been inactivated and replaced by a beta-galactosidase reporter gene. Staining for beta-galactosidase activity reveals an expression pattern encompassing neural crest-derived cells, e.g., cranial and dorsal root ganglia as well as several other cell populations in the central nervous system (CNS), most prominently the internal granule layer of cerebellum. Other sites of expression include the lachrymal gland, outer nuclear layer of retina, enteric ganglion neurons, and a subset of thalamic and hypothalamic nuclei. In the CNS, blood vessel-associated smooth muscle cells and pericytes stain positive for Foxs1. Foxs1beta-gal/beta-gal mice perform significantly better (P < 0.01) on a rotating rod than do wt littermates. We have also noted a lower body weight gain (P < 0.05) in Foxs1beta-gal/lbeta-gal males on a high-fat diet, and we speculate that dorsomedial hypothalamic neurons, expressing Foxs1, could play a role in regulating body weight via regulation of sympathetic outflow. In support of this, we observed increased levels of uncoupling protein 1 mRNA in Foxs1beta-gal/beta-gal mice. This points toward a role for Foxs1 in the integration and processing of neuronal signals of importance for energy turnover and motor function.

Injected mass deposition thresholds for lithium granule instigated triggering of edge localized modes on EAST

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lunsford, R.; Sun, Zhen; Maingi, Rajesh

The ability of an injected lithium granule to promptly trigger an edge localized mode (ELM) has been established in multiple experiments. By horizontally injecting granules ranging in diameter from 200 microns to 1mm in diameter into the low field side of EAST H-mode discharges we have determined that granules with diameter > 600 microns are successful in triggering ELMs more than 95% of the time. Granules were radially injected from the outer midplane with velocities ~ 80 m/s into EAST upper-single null discharges with an ITER like tungsten monoblock divertor. ELM triggering was a prompt response to granule injection, andmore » for granules of a sufficient size there was no evidence of a "trigger lag" phenomenon as observed in full metal machines. We also demonstrated that the triggering efficiency decreased with granule size during dynamic size scans. These granules were individually tracked throughout their injection cycle in order to determine their efficacy at triggering an ELM. Furthermore, by simulating the granule injection with an experimentally benchmarked neutral gas shielding (NGS) model, the ablatant mass deposition required to promptly trigger an ELM is calculated and the fractional mass deposition is determined. Simulated 900 micron granules capable of triggering an ELM show a peaked mass deposition of 3.9 x 10 17 atoms per mm of penetration at a depth of approximately 5 cm past the separatrix.« less

The importance of binder moisture content in Metformin HCL high-dose formulations prepared by moist aqueous granulation (MAG).

PubMed

Takasaki, Hiroshi; Yonemochi, Etsuo; Ito, Masanori; Wada, Koichi; Terada, Katsuhide

2015-01-01

The aim of this study was to evaluate binders to improve the flowability of granulates and compactibility of Metformin HCL (Met) using the moist aqueous granulation (MAG) process. The effect of the binder moisture content on granulate and tablet quality was also evaluated. Vinylpyrrolidone-vinyl acetate copolymer (Kollidon VA64 fine: VA64), polyvidone (Povidone K12: PVP), hydroxypropyl cellulose (HPC SSL SF: HPC) and hydroxypropyl methylcellulose (Methocel E5 LV: HPMC) were evaluated as binders. These granulates, except for HPMC, had a lower yield pressure than Met active pharmaceutical ingredient (API). HPMC Met was not sufficiently granulated with low water volume. No problems were observed with the VA64 Met granulates during the tableting process. However, HPC Met granulates had a bowl-forming tendency, and PVP Met granulates had the tendency to stick during the tableting process. These bowl-forming and sticking tendencies may have been due to the low moisture absorbency of HPC and the high volume of bound water of PVP, respectively. VA64 Met granulates had the highest ambient moisture content (bulk water, bound water) and moisture absorbency. It was concluded that the type of binder used for the Met MAG process has an impact on granulate flow and compactibility, as well as moisture absorbency and maintenance of moisture balance.

The importance of binder moisture content in Metformin HCL high-dose formulations prepared by moist aqueous granulation (MAG)

PubMed Central

Takasaki, Hiroshi; Yonemochi, Etsuo; Ito, Masanori; Wada, Koichi; Terada, Katsuhide

2015-01-01

The aim of this study was to evaluate binders to improve the flowability of granulates and compactibility of Metformin HCL (Met) using the moist aqueous granulation (MAG) process. The effect of the binder moisture content on granulate and tablet quality was also evaluated. Vinylpyrrolidone–vinyl acetate copolymer (Kollidon VA64 fine: VA64), polyvidone (Povidone K12: PVP), hydroxypropyl cellulose (HPC SSL SF: HPC) and hydroxypropyl methylcellulose (Methocel E5 LV: HPMC) were evaluated as binders. These granulates, except for HPMC, had a lower yield pressure than Met active pharmaceutical ingredient (API). HPMC Met was not sufficiently granulated with low water volume. No problems were observed with the VA64 Met granulates during the tableting process. However, HPC Met granulates had a bowl-forming tendency, and PVP Met granulates had the tendency to stick during the tableting process. These bowl-forming and sticking tendencies may have been due to the low moisture absorbency of HPC and the high volume of bound water of PVP, respectively. VA64 Met granulates had the highest ambient moisture content (bulk water, bound water) and moisture absorbency. It was concluded that the type of binder used for the Met MAG process has an impact on granulate flow and compactibility, as well as moisture absorbency and maintenance of moisture balance. PMID:26779418

Impact of functionalized particle structure on roll compaction/dry granulation and tableting of calcium carbonate.

PubMed

Grote, Simon; Kleinebudde, Peter

2018-06-10

The influence of a functionalized raw material particle structure on the granulation behavior and tabletabilty of calcium carbonate (CaCO 3 ) was investigated. Therefore, a milled grade of CaCO 3 was compared to different binary mixtures of milled and functionalized CaCO 3 . Relevant properties of raw materials, ribbons and granules were measured. The starting materials and two fractions of dry granules were compressed to tablets. The tabletability of granules was compared to that of the powders and the influence of specific compaction force and granule size on tablet tensile strength was evaluated. Adding functionalized particles drastically influenced the granulation and tableting behavior of CaCO 3 . Increasing proportions increased the ribbon porosity and granule size. Tensile strength of tablets from powder mixtures and granules was increased as well. Nevertheless, adding functionalized CaCO 3 led to a loss in tabletability induced by a previous compaction step to an extent depending on its proportion in the formulation. A clear influence of the particle morphology on granulation and tableting behavior was demonstrated by the study. The functionalized structure showed aspects of a more plastic deformation behavior. Adding functionalized CaCO 3 to a mixture, even in small amounts, seemed to be beneficial to increase granule size and tablet strength. Copyright © 2018 Elsevier B.V. All rights reserved.

Injected mass deposition thresholds for lithium granule instigated triggering of edge localized modes on EAST

DOE PAGES

Lunsford, R.; Sun, Zhen; Maingi, Rajesh; ...

2017-12-19

The ability of an injected lithium granule to promptly trigger an edge localized mode (ELM) has been established in multiple experiments. By horizontally injecting granules ranging in diameter from 200 microns to 1mm in diameter into the low field side of EAST H-mode discharges we have determined that granules with diameter > 600 microns are successful in triggering ELMs more than 95% of the time. Granules were radially injected from the outer midplane with velocities ~ 80 m/s into EAST upper-single null discharges with an ITER like tungsten monoblock divertor. ELM triggering was a prompt response to granule injection, andmore » for granules of a sufficient size there was no evidence of a "trigger lag" phenomenon as observed in full metal machines. We also demonstrated that the triggering efficiency decreased with granule size during dynamic size scans. These granules were individually tracked throughout their injection cycle in order to determine their efficacy at triggering an ELM. Furthermore, by simulating the granule injection with an experimentally benchmarked neutral gas shielding (NGS) model, the ablatant mass deposition required to promptly trigger an ELM is calculated and the fractional mass deposition is determined. Simulated 900 micron granules capable of triggering an ELM show a peaked mass deposition of 3.9 x 10 17 atoms per mm of penetration at a depth of approximately 5 cm past the separatrix.« less

The influence of granulation on super disintegrant performance.

PubMed

Zhao, Na; Augsburger, Larry L

2006-02-01

The purpose of this study is to identify the causes of efficiency loss of super disintegrants following granulation or reworking. Two processes, precompression and prewetting, were proposed to simulate the processes during dry and wet granulation, respectively. The disintegration efficiency of the resulting disintegrant granules was tested in model formulations composed of dicalcium phosphate and lactose with the unprocessed disintegrants as controls. No significant difference was shown in the intrinsic swelling and the water uptake abilities of all super disintegrants following dry granulation. However, a significant decrease was observed for both Primojel and Polyplasdone XL10 in the rate of water being absorbed into the tablet matrix following wet granulation, but not for Ac-Di-Sol. United States Pharmacopeia (USP) disintegration testing without disc revealed a significant increase in disintegration time for tablets formulated with dry granulated Primojel and Polyplasdone XL10 and all wet granulated disintegrants. The increase in particle size following granulation appears to be the cause of the loss in disintegration efficiency. In conclusion, Ac-Di-Sol is less affected by both precompression and prewetting. The efficiency of Primojel and Polyplasdone XL10 is highly dependent on their particle size. Descreasing the particle size tends to increase their efficiency. Due to the size increase following granulation, a higher addition level of super disintegrant is required to ensure fast and uniform disintegration of tablets prepared by granulation.

Aspergillus oryzae AoSO is a novel component of stress granules upon heat stress in filamentous fungi.

PubMed

Huang, Hsiang-Ting; Maruyama, Jun-ichi; Kitamoto, Katsuhiko

2013-01-01

Stress granules are a type of cytoplasmic messenger ribonucleoprotein (mRNP) granule formed in response to the inhibition of translation initiation, which typically occurs when cells are exposed to stress. Stress granules are conserved in eukaryotes; however, in filamentous fungi, including Aspergillus oryzae, stress granules have not yet been defined. For this reason, here we investigated the formation and localization of stress granules in A. oryzae cells exposed to various stresses using an EGFP fusion protein of AoPab1, a homolog of Saccharomyces cerevisiae Pab1p, as a stress granule marker. Localization analysis showed that AoPab1 was evenly distributed throughout the cytoplasm under normal growth conditions, and accumulated as cytoplasmic foci mainly at the hyphal tip in response to stress. AoSO, a homolog of Neurospora crassa SO, which is necessary for hyphal fusion, colocalized with stress granules in cells exposed to heat stress. The formation of cytoplasmic foci of AoSO was blocked by treatment with cycloheximide, a known inhibitor of stress granule formation. Deletion of the Aoso gene had effects on the formation and localization of stress granules in response to heat stress. Our results suggest that AoSO is a novel component of stress granules specific to filamentous fungi. The authors would specially like to thank Hiroyuki Nakano and Kei Saeki for generously providing experimental and insightful opinions.

Behavior of hollow balls containing granules bouncing repeatedly off the ground

NASA Astrophysics Data System (ADS)

Hu, Min; Mu, Qing-song; Luo, Ning; Li, Gang; Peng, Ning-bo

2013-07-01

An experimental study of the behavior of hollow balls filled with some granules (mung beans or millets) bouncing repeatedly off a static flat horizontal surface is presented. We observed that the bounce number of the ball is limited and decreases regularly with an increasing number of granules. Moreover, for two balls containing a different kind of granules, their bounce numbers are basically equal when the two balls have the same mass of granules. While there is no clear relationship between the first rebound height of one ball and the number of granules, there appears an exponential decay of the second rebound height with an increase of the granule number. Furthermore, a two-dimensional numerical model has been created to find out the law of the ball's rebound height and the dissipation law of the granule nested system. A generalized prediction equation to reasonably explain the law of the bounce number has also been proposed.

An investigation of the influence of process and formulation variables on mechanical properties of high shear granules using design of experiment.

PubMed

Mangwandi, Chirangano; Adams, Michael J; Hounslow, Michael J; Salman, Agba D

2012-05-10

Being able to predict the properties of granules from the knowledge of the process and formulation variables is what most industries are striving for. This research uses experimental design to investigate the effect of process variables and formulation variables on mechanical properties of pharmaceutical granules manufactured from a classical blend of lactose and starch using hydroxypropyl cellulose (HPC) as the binder. The process parameters investigated were granulation time and impeller speed whilst the formulation variables were starch-to-lactose ratio and HPC concentration. The granule properties investigated include granule packing coefficient and granule strength. The effect of some components of the formulation on mechanical properties would also depend on the process variables used in granulation process. This implies that by subjecting the same formulation to different process conditions results in products with different properties. Copyright © 2012 Elsevier B.V. All rights reserved.

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

PubMed

Fonteyne, Margot; Fussell, Andrew Luke; Vercruysse, Jurgen; Vervaet, Chris; Remon, Jean Paul; Strachan, Clare; Rades, Thomas; De Beer, Thomas

2014-02-28

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-granular distribution of PVP was evaluated by means of hyperspectral coherent anti-Stokes Raman scattering (CARS) microscopy. For the evaluated formulation, no PVP rich zones were detected when applying a lateral spatial resolution of 0.5 μm, indicating that PVP is homogenously distributed within the granules. Copyright © 2013 Elsevier B.V. All rights reserved.

Neuronal RNA granules: a link between RNA localization and stimulation-dependent translation

NASA Technical Reports Server (NTRS)

Krichevsky, A. M.; Kosik, K. S.

2001-01-01

RNA granules are a macromolecular structure observed in neurons, where they serve as motile units that translocate mRNAs. Isolated RNA granules are highly enriched in Staufen protein and ultrastructurally contain densely packed clusters of ribosomes. With depolarization, many mRNAs, including those involved in plasticity, rapidly shift from the RNA granule fraction to polysomes. Depolarization reorganizes granules and induces a less compact organization of their ribosomes. RNA granules are not translationally competent, as indicated by the failure to incorporate radioactive amino acids and the absence of eIF4E, 4G, and tRNAs. We concluded that RNA granules are a local storage compartment for mRNAs under translational arrest but are poised for release to actively translated pools. Local release of mRNAs and ribosomes from granules may serve as a macromolecular mechanism linking RNA localization to translation and synaptic plasticity.

The converse magnetoelectric coupling in asymmetric granule/matrix composite film with Ni/PZT component

NASA Astrophysics Data System (ADS)

Chen, Bo; Su, Ning-Ning; Cui, Wen-Li; Yan, Shi-Nong

2018-04-01

In this work, a type of asymmetric granule/matrix composite film is designed, where the Ni granule is dispersed in PZT matrix, meanwhile the top and bottom electrode is constituted by Au and SRO respectively. Predicted through the electrostatic screening model and mean field approximation, considerable electrostatic charge is induced on Ni granule surface by ferroelectric PZT polarization. Predicted through the spin splitting model and spherical shell approximation, both the magnetization and magnetic anisotropy of Ni granule are modulated by ferroelectric PZT polarization. As the volume fraction of Ni granule is increased, the electric modulation of magnetization and magnetic anisotropy is reduced and enhanced respectively. As the dimension of granule/matrix composite is varied, such modulation is retained. Due to the large area-volume ratio of nano-granule, this work benefits to realize the converse magnetoelectric coupling in nanoscale.

Clarithromycin highly-loaded gastro-floating fine granules prepared by high-shear melt granulation can enhance the efficacy of Helicobacter pylori eradication.

PubMed

Aoki, Hajime; Iwao, Yasunori; Mizoguchi, Midori; Noguchi, Shuji; Itai, Shigeru

2015-05-01

In an effort to develop a new gastro-retentive drug delivery system (GRDDS) without a large amount of additives, 75% clarithromycin (CAM) loaded fine granules were prepared with three different hydrophobic binders by high-shear melt granulation and their properties were evaluated. Granules containing the higher hydrophobic binder showed sustained drug release and were able to float over 24h. The synchrotron X-ray CT measurement indicated that both the high hydrophobicity of the binder and the void space inside the granules might be involved in their buoyancy. In an in vivo experiment, the floating granules more effectively eradicated Helicobacter pylori than a CAM suspension by remaining in the stomach for a longer period. In short, CAM highly-loaded gastro-floating fine granules can enhance the eradication efficiency of H. pylori compared with CAM alone. Copyright © 2015 Elsevier B.V. All rights reserved.

Tang Wang Ming Mu Granule Attenuates Diabetic Retinopathy in Type 2 Diabetes Rats.

PubMed

Chen, Mingxia; Lv, Haibo; Gan, Jiakuan; Ren, Junguo; Liu, Jianxun

2017-01-01

Aims: This study aimed to determine the influence of Tang Wang Ming Mu granule (TWMM) on the diabetic retinopathy of diabetic rats. Methods: Male Wistar rats were divided into seven groups: normal control, diabetes model(DM), diabetes with TWMM (3.6, 7.2, and 14.4 g/kg) treatment, the positive control treatment groups of Qi Ming granules and Calcium dobesilate capsules. All rats were treated for 8 weeks. The levels of body weight, fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) in blood were measured to evaluate the antihyperglycemic activity of TWMM. Furthermore, malondialdehyde (MDA), intracellular adhesion molecule-1 (ICAM-1) and vascular endothelial growth factor (VEGF) in serum were measured to study effects of TWMM on oxidative stress and inflammatory in DM2 rats. VEGF, JAK/STAT signaling pathway and SOCS3 in retina was detected by immunohistochemistry. Results: TWMM and the positive control drugs Qi Ming and Calcium dobesilate showed a remarkable suppression of retinal neovascularization and amelioration of retinal internal limiting membrane morphology. Moreover, TWMM significantly decreased HbA1c, MDA, ICAM-1, and VEGF levels in serum of diabetic rats. However, Qi Ming granules showed significantly reduced MDA and VEGF levels ( P < 0.01, and P < 0.05, respectively), Calcium dobesilate showed significantly reduced MDA and ICAM-1levels ( P < 0.01 and P < 0.05, respectively) in serum. All drug- treated DM2 rats showed significantly lower levels of VEGF, JAK2, P-JAK2, STAT3, and P-STAT3 in retina than DM group, while TWMM and Calcium dobesilate significantly increased SOCS3 in retina. Conclusion: Our data suggest that the diabetic retina protective effect of TWMM might be related to antiinflammatory, antioxidative, upregulation of SOCS3 expression, inhibition of the JAK/STAT/VEGF signaling pathway.

Real-time monitoring of the mechanism of ibuprofen-cationic dextran crystanule formation using crystallization process informatics system (CryPRINS).

PubMed

Abioye, Amos Olusegun; Chi, George Tangyie; Simone, Elena; Nagy, Zoltan

2016-07-25

One step aqueous melt-crystallization and in situ granulation was utilized to produce ibuprofen-cationic dextran [diethylaminoethyl dextran (Ddex)] conjugate crystanules without the use of surfactants or organic solvents. This study investigates the mechanism of in situ granulation-induced crystanule formation using ibuprofen (Ibu) and Ddex. Laboratory scale batch aqueous crystallization system containing in situ monitoring probes for particle vision measurement (PVM), UV-vis measurement and focused beam reflectance measurements (FBRM) was adapted using pre-defined formulation and process parameters. Pure ibuprofen showed nucleation domain between 25 and 64°C, producing minicrystals with onset of melting at 76°C and enthalpy of fusion (ΔH) of 26.22kJ/mol. On the other hand Ibu-Ddex crystanules showed heterogeneous nucleation which produced spherical core-shell structure. PVM images suggest that internalization of ibuprofen in Ddex corona occurred during the melting phase (before nucleation) which inhibited crystal growth inside the Ddex corona. The remarkable decrease in ΔH of the crystanules from 26.22 to 11.96kJ/mol and the presence of broad overlapping DSC thermogram suggests formation of ibuprofen-Ddex complex and crystalline-amorphous transformation. However Raman and FTIR spectra did not show any significant chemical interaction between ibuprofen and Ddex. A significant increase in dissolution efficiency from 45 to 81% within 24h and reduced burst release provide evidence for potential application of crystanules in controlled drug delivery systems. It was evident that in situ granulation of ibuprofen inhibited the aqueous crystallization process. It was concluded that in situ granulation-aqueous crystallization technique is a novel unit operation with potential application in continuous pharmaceutical processing. Copyright © 2016 Elsevier B.V. All rights reserved.

Differential gene expression in dentate granule cells in mesial temporal lobe epilepsy with and without hippocampal sclerosis.

PubMed

Griffin, Nicole G; Wang, Yu; Hulette, Christine M; Halvorsen, Matt; Cronin, Kenneth D; Walley, Nicole M; Haglund, Michael M; Radtke, Rodney A; Skene, J H Pate; Sinha, Saurabh R; Heinzen, Erin L

2016-03-01

Hippocampal sclerosis is the most common neuropathologic finding in cases of medically intractable mesial temporal lobe epilepsy. In this study, we analyzed the gene expression profiles of dentate granule cells of patients with mesial temporal lobe epilepsy with and without hippocampal sclerosis to show that next-generation sequencing methods can produce interpretable genomic data from RNA collected from small homogenous cell populations, and to shed light on the transcriptional changes associated with hippocampal sclerosis. RNA was extracted, and complementary DNA (cDNA) was prepared and amplified from dentate granule cells that had been harvested by laser capture microdissection from surgically resected hippocampi from patients with mesial temporal lobe epilepsy with and without hippocampal sclerosis. Sequencing libraries were sequenced, and the resulting sequencing reads were aligned to the reference genome. Differential expression analysis was used to ascertain expression differences between patients with and without hippocampal sclerosis. Greater than 90% of the RNA-Seq reads aligned to the reference. There was high concordance between transcriptional profiles obtained for duplicate samples. Principal component analysis revealed that the presence or absence of hippocampal sclerosis was the main determinant of the variance within the data. Among the genes up-regulated in the hippocampal sclerosis samples, there was significant enrichment for genes involved in oxidative phosphorylation. By analyzing the gene expression profiles of dentate granule cells from surgically resected hippocampal specimens from patients with mesial temporal lobe epilepsy with and without hippocampal sclerosis, we have demonstrated the utility of next-generation sequencing methods for producing biologically relevant results from small populations of homogeneous cells, and have provided insight on the transcriptional changes associated with this pathology. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

GENE EXPRESSION CHANGES AFTER SEIZURE PRECONDITIONING IN THE THREE MAJOR HIPPOCAMPAL CELL LAYERS

PubMed Central

Borges, Karin; Shaw, Renee; Dingledine, Raymond

2008-01-01

Rodents experience hippocampal damage after status epilepticus (SE) mainly in pyramidal cells while sparing the dentate granule cell layer (DGCL). Hippocampal damage was prevented in rats that had been preconditioned by brief seizures on two consecutive days before SE. To identify neuroprotective genes and biochemical pathways changed after preconditioning we compared the effect of preconditioning on gene expression in the CA1 and CA3 pyramidal and DGCLs, harvested by laser capture microscopy. In the DGCL the expression of 632 genes was altered, compared to only 151 and 58 genes in CA1 and CA3 pyramidal cell layers. Most of the differentially expressed genes regulate tissue structure and intra- and extracellular signaling, including neurotransmission. A selective upregulation of energy metabolism transcripts occurred in CA1 pyramidal cells relative to the DGCL. These results reveal a broad transcriptional response of the DGCL to preconditioning, and suggest several mechanisms underlying the neuroprotective effect of preconditioning seizures. PMID:17239605

Conductive, magnetic and structural properties of multilayer films

NASA Astrophysics Data System (ADS)

Kotov, L. N.; Turkov, V. K.; Vlasov, V. S.; Lasek, M. P.; Kalinin, Yu E.; Sitnikov, A. V.

2013-12-01

Composite-semiconductor and composite-dielectric multilayer films were obtained by the ion beam sputtering method in the argon and hydrogen atmospheres with compositions: {[(Co45-Fe45-Zr10)x(Al2O3)y]-[α-Si]}120, {[(Co45-Ta45-Nb10)x(SiO2)y]-[SiO2]}56, {[(Co45-Fe45-Zr10)x(Al2O3)y]-[α-Si:H]}120. The images of surface relief and distribution of the dc current on composite layer surface were obtained with using of atomic force microscopy (AFM). The dependencies of specific electric resistance, ferromagnetic resonance (FMR) fields and width of line on metal (magnetic) phase concentration x and nanolayers thickness of multilayer films were obtained. The characteristics of FMR depend on magnetic interaction among magnetic granules in the composite layers and between the layers. These characteristics depend on the thickness of composite and dielectric or semiconductor nanolayers. The dependences of electric microwave losses on the x and alternating field frequency were investigated.

Impact of screw configuration on the particle size distribution of granules produced by twin screw granulation.

PubMed

Vercruysse, J; Burggraeve, A; Fonteyne, M; Cappuyns, P; Delaet, U; Van Assche, I; De Beer, T; Remon, J P; Vervaet, C

2015-02-01

Twin screw granulation (TSG) has been reported by different research groups as an attractive technology for continuous wet granulation. However, in contrast to fluidized bed granulation, granules produced via this technique typically have a wide and multimodal particle size distribution (PSD), resulting in suboptimal flow properties. The aim of the current study was to evaluate the impact of granulator screw configuration on the PSD of granules produced by TSG. Experiments were performed using a 25 mm co-rotating twin screw granulator, being part of the ConsiGma™-25 system (a fully continuous from-powder-to-tablet manufacturing line from GEA Pharma Systems). Besides the screw elements conventionally used for TSG (conveying and kneading elements), alternative designs of screw elements (tooth-mixing-elements (TME), screw mixing elements (SME) and cutters) were investigated using an α-lactose monohydrate formulation granulated with distilled water. Granulation with only conveying elements resulted in wide and multimodal PSD. Using kneading elements, the width of the PSD could be partially narrowed and the liquid distribution was more homogeneous. However, still a significant fraction of oversized agglomerates was obtained. Implementing additional kneading elements or cutters in the final section of the screw configuration was not beneficial. Furthermore, granulation with only TME or SME had limited impact on the width of the PSD. Promising results were obtained by combining kneading elements with SME, as for these configurations the PSD was narrower and shifted to the size fractions suitable for tableting. Copyright © 2015 Elsevier B.V. All rights reserved.

Differential compaction behaviour of roller compacted granules of clopidogrel bisulphate polymorphs.

PubMed

Khomane, Kailas S; Bansal, Arvind K

2014-09-10

In the present work, in-die and out-of-die compaction behaviour of dry-granulated powders of clopidogrel bisulphate (CLP) polymorphs, form I and form II, was investigated using a fully instrumented rotary tablet press. Each polymorph was compacted at three different roller pressures [70.3 (S1), 105.5 (S2) and 140.6 (S3)kgf/cm(2)], and obtained granules were characterized for their physico-mechanical properties. Compaction data were analyzed for out-of-die compressibility, tabletability and compactibility profiles, and in-die Heckel, Kawakita and Walker analysis. The roller compacted granules of both forms showed markedly different tabletting behaviour. Roller pressure exhibited a trend on compaction behaviour of form I granules, whereas, in case of form II, the effect was insignificant. Tabletability of the six granule batches follows the order; I_S1>I_S2>I_S3>II_S1≈II_S2≈II_S3. In case of form I, the reduced tabletability of the granules compacted at higher roller pressure was attributed to the decreased compressibility and plastic deformation. This was confirmed by compressibility plot and various mathematical parameters derived from Heckel (Py), Kawakita (1/b) and Walker (W) equations. The reduced tabletability of form I granules was due to 'granule hardening' during roller compaction. On the other hand, insignificant effect of roller compaction on tabletting behaviour of form II granules was attributed to brittle fragmentation. The extensive fragmentation of granules offered new 'clean' surfaces and higher contact points that negated the effect of granule hardening. Copyright © 2014 Elsevier B.V. All rights reserved.

A Quasi-Periodic Linear Feeder for the Impurity Granular Injection on DIII-D

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nagy, Alex; Bortolon, A.; Brown, W.

Injection of solid nonfuel pellets has been actively used as a tool for pacing and mitigation of edge localized modes (ELMs). In DIII-D, effective ELM pacing has been demonstrated by the high-frequency injection of lithium and carbon submillimeter spheres, using the impurity granule injector (IGI). This device injects granules into the plasma at speeds up to 150 m/s, through impact with a rotating impeller. In the IGI, high-frequency granule delivery was accomplished through a vibrational granule dropper, in which high time-average rates are obtained at the cost of lack of period control. Here, we present a new in-line granule feeder,more » capable of delivering granules of size 0.2-2 mm with no restriction of material properties, at quasi-periodic rates of up to 150 Hz, for 0.7-mm diameter lithium granules (600 Hz using 0.3-mm granules). The new dropper mechanism combines two piezo-in-line units; one which feeds the impeller and one which circulates granules that are filtered out of the feeder path. A remotely adjustable filter eliminates granules that are stacked, oversized, or side by side allowing the formation of a single moving granule injection line. The granules fall off the in-line feeder exit one at a time, achieving a quasi-periodic delivery rate proportional to the exit speed. At higher rates, the periodicity deteriorates. This behavior was studied using high-speed cameras and electrostatic measurements, and it was found that at drop rates <60 Hz, the granule delivery period has a variation of ±25% which appears to be caused by gaps which develop in the last centimeter of the injection line, as granules exit off the moving track. The linear feeder concept is robust against bridge instabilities and clogging issues, thanks to the simple diverter filter and constant recirculation of granules. Furthermore, the open-top design of the device facilitates refilling the device from separate reservoirs and has easy access for directly monitoring operation and adjustment. This paper describes the details of the in-line feeder design, along with several design iterations. The goal is a robust in-vacuum mechanism that can deliver granule flow ranging from a single particle to a line of particles at 150 per second, using different sizes and materials from the same apparatus.« less

A Quasi-Periodic Linear Feeder for the Impurity Granular Injection on DIII-D

DOE PAGES

Nagy, Alex; Bortolon, A.; Brown, W.; ...

2018-04-10

Injection of solid nonfuel pellets has been actively used as a tool for pacing and mitigation of edge localized modes (ELMs). In DIII-D, effective ELM pacing has been demonstrated by the high-frequency injection of lithium and carbon submillimeter spheres, using the impurity granule injector (IGI). This device injects granules into the plasma at speeds up to 150 m/s, through impact with a rotating impeller. In the IGI, high-frequency granule delivery was accomplished through a vibrational granule dropper, in which high time-average rates are obtained at the cost of lack of period control. Here, we present a new in-line granule feeder,more » capable of delivering granules of size 0.2-2 mm with no restriction of material properties, at quasi-periodic rates of up to 150 Hz, for 0.7-mm diameter lithium granules (600 Hz using 0.3-mm granules). The new dropper mechanism combines two piezo-in-line units; one which feeds the impeller and one which circulates granules that are filtered out of the feeder path. A remotely adjustable filter eliminates granules that are stacked, oversized, or side by side allowing the formation of a single moving granule injection line. The granules fall off the in-line feeder exit one at a time, achieving a quasi-periodic delivery rate proportional to the exit speed. At higher rates, the periodicity deteriorates. This behavior was studied using high-speed cameras and electrostatic measurements, and it was found that at drop rates <60 Hz, the granule delivery period has a variation of ±25% which appears to be caused by gaps which develop in the last centimeter of the injection line, as granules exit off the moving track. The linear feeder concept is robust against bridge instabilities and clogging issues, thanks to the simple diverter filter and constant recirculation of granules. Furthermore, the open-top design of the device facilitates refilling the device from separate reservoirs and has easy access for directly monitoring operation and adjustment. This paper describes the details of the in-line feeder design, along with several design iterations. The goal is a robust in-vacuum mechanism that can deliver granule flow ranging from a single particle to a line of particles at 150 per second, using different sizes and materials from the same apparatus.« less

Promiscuous interactions and protein disaggregases determine the material state of stress-inducible RNP granules

PubMed Central

Kroschwald, Sonja; Maharana, Shovamayee; Mateju, Daniel; Malinovska, Liliana; Nüske, Elisabeth; Poser, Ina; Richter, Doris; Alberti, Simon

2015-01-01

RNA-protein (RNP) granules have been proposed to assemble by forming solid RNA/protein aggregates or through phase separation into a liquid RNA/protein phase. Which model describes RNP granules in living cells is still unclear. In this study, we analyze P bodies in budding yeast and find that they have liquid-like properties. Surprisingly, yeast stress granules adopt a different material state, which is reminiscent of solid protein aggregates and controlled by protein disaggregases. By using an assay to ectopically nucleate RNP granules, we further establish that RNP granule formation does not depend on amyloid-like aggregation but rather involves many promiscuous interactions. Finally, we show that stress granules have different properties in mammalian cells, where they show liquid-like behavior. Thus, we propose that the material state of RNP granules is flexible and that the solid state of yeast stress granules is an adaptation to extreme environments, made possible by the presence of a powerful disaggregation machine. DOI: http://dx.doi.org/10.7554/eLife.06807.001 PMID:26238190

The design of free structure granular mappings: the use of the principle of justifiable granularity.

PubMed

Pedrycz, Witold; Al-Hmouz, Rami; Morfeq, Ali; Balamash, Abdullah

2013-12-01

The study introduces a concept of mappings realized in presence of information granules and offers a design framework supporting the formation of such mappings. Information granules are conceptually meaningful entities formed on a basis of a large number of experimental input–output numeric data available for the construction of the model. We develop a conceptually and algorithmically sound way of forming information granules. Considering the directional nature of the mapping to be formed, this directionality aspect needs to be taken into account when developing information granules. The property of directionality implies that while the information granules in the input space could be constructed with a great deal of flexibility, the information granules formed in the output space have to inherently relate to those built in the input space. The input space is granulated by running a clustering algorithm; for illustrative purposes, the focus here is on fuzzy clustering realized with the aid of the fuzzy C-means algorithm. The information granules in the output space are constructed with the aid of the principle of justifiable granularity (being one of the underlying fundamental conceptual pursuits of Granular Computing). The construct exhibits two important features. First, the constructed information granules are formed in the presence of information granules already constructed in the input space (and this realization is reflective of the direction of the mapping from the input to the output space). Second, the principle of justifiable granularity does not confine the realization of information granules to a single formalism such as fuzzy sets but helps form the granules expressed any required formalism of information granulation. The quality of the granular mapping (viz. the mapping realized for the information granules formed in the input and output spaces) is expressed in terms of the coverage criterion (articulating how well the experimental data are “covered” by information granules produced by the granular mapping for any input experimental data). Some parametric studies are reported by quantifying the performance of the granular mapping (expressed in terms of the coverage and specificity criteria) versus the values of a certain parameters utilized in the construction of output information granules through the principle of justifiable granularity. The plots of coverage–specificity dependency help determine a knee point and reach a sound compromise between these two conflicting requirements imposed on the quality of the granular mapping. Furthermore, quantified is the quality of the mapping with regard to the number of information granules (implying a certain granularity of the mapping). A series of experiments is reported as well.

TDP-43 is directed to stress granules by sorbitol, a novel physiological osmotic and oxidative stressor.

PubMed

Dewey, Colleen M; Cenik, Basar; Sephton, Chantelle F; Dries, Daniel R; Mayer, Paul; Good, Shannon K; Johnson, Brett A; Herz, Joachim; Yu, Gang

2011-03-01

TDP-43, or TAR DNA-binding protein 43, is a pathological marker of a spectrum of neurodegenerative disorders, including amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin-positive inclusions. TDP-43 is an RNA/DNA-binding protein implicated in transcriptional and posttranscriptional regulation. Recent work also suggests that TDP-43 associates with cytoplasmic stress granules, which are transient structures that form in response to stress. In this study, we establish sorbitol as a novel physiological stressor that directs TDP-43 to stress granules in Hek293T cells and primary cultured glia. We quantify the association of TDP-43 with stress granules over time and show that stress granule association and size are dependent on the glycine-rich region of TDP-43, which harbors the majority of pathogenic mutations. Moreover, we establish that cells harboring wild-type and mutant TDP-43 have distinct stress responses: mutant TDP-43 forms significantly larger stress granules, and is incorporated into stress granules earlier, than wild-type TDP-43; in striking contrast, wild-type TDP-43 forms more stress granules over time, but the granule size remains relatively unchanged. We propose that mutant TDP-43 alters stress granule dynamics, which may contribute to the progression of TDP-43 proteinopathies.

Distribution of a viscous binder during high shear granulation--sensitivity to the method of delivery and its impact on product properties.

PubMed

Tan, Bernice Mei Jin; Loh, Zhi Hui; Soh, Josephine Lay Peng; Liew, Celine Valeria; Heng, Paul Wan Sia

2014-01-02

Binder distribution in the powder mass during high shear granulation is especially critical with the use of viscous liquid binders and with short processing times. A viscous liquid binder was delivered into the powder mass at two flow rates using three methods: pouring, pumping and spraying from a pressure pot. Binder content analyses at the scale of individual granules were conducted to investigate the impact of different delivery conditions on the homogeneity of binder distribution. There was clear evidence of non-uniformity of binder content among individual granules across all delivery conditions, particularly for the fast rates of delivery. Poorer reproducibility values of tablet thickness and disintegration time were observed when binder was poured but this may be overcome by pumping or spraying from the pressure pot. Greater homogeneity of binder distribution occurred with the slow rates of delivery and led to the earlier onset of granule growth and a consequent increase in granule size. Larger granule size and lower proportion of fines were in turn associated with increased granule bulk density and improvement of granule flow. In conclusion, delivery of a viscous binder at a slow rate either by pumping or via a pressure pot was most desirable during granulation. Copyright © 2013 Elsevier B.V. All rights reserved.

Common spectrum of polypeptides occurs in secretion granule membranes of different exocrine glands

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cameron, R.S.; Cameron, P.L.; Castle, J.D.

1986-10-01

A highly purified membrane preparation from rat parotid secretion granules has been used as a comparative probe to examine the extent of compositional overlap in granule membranes of three other exocrine secretory tissues - pancreatic, lacrimal, and submandibular - from several standpoints. First, indirect immunofluorescent studies using a polyclonal polyspecific anti-parotid granule membrane antiserum has indicated a selective staining of granule membrane profiles in all acinar cells of all tissues. Second, highly purified granule membrane subfractions have been isolated from each exocrine tissue; comparative two-dimensional (isoelectric focusing; SDS) PAGE of radioiodinated granule membranes has identified 10-15 polypeptides of identical pImore » and apparent molecular mass. These species are likely to be integral membrane components since they are not extracted by either saponin-sodium sulfate or sodium carbonate (pH 11.5) treatments, and they do not have counterparts in the granule content. Finally, the identity among selected parotid and pancreatic radioiodinated granule membrane polypeptides has been documented using two-dimensional peptide mapping of chymotryptic and tryptic digests. These findings clearly indicate that exocrine secretory granules, irrespective of the nature of stored secretion, comprise a type of vesicular carrier with a common (and probably refined) membrane composition. Conceivably, the polypeptides identified carry out general functions related to exocrine secretion.« less

A comparative study of the influence of alpha-lactose monohydrate particle morphology on granule and tablet properties after roll compaction/dry granulation.

PubMed

Grote, Simon; Kleinebudde, Peter

2018-05-29

The influence of particle morphology and size of alpha-lactose monohydrate on dry granules and tablets was studied. Four different morphologies were investigated: Two grades of primary crystals, which differed in their particle size and structure (compact crystals vs. agglomerates). The materials were roll compacted at different specific compaction forces and changes in the particle size distribution and the specific surface area were measured. Afterwards, two fractions of granules were pressed to tablets and the tensile strength was compared to that from tablets compressed from the raw materials. The specific surface area was increased induced by roll compaction/dry granulation for all materials. At increased specific compaction forces, the materials showed sufficient size enlargement. The morphology of lactose determined the strength of direct compressed tablets. In contrast, the strength of granule tablets was leveled by the previous compression step during roll compaction/dry granulation. Thus, the tensile strength of tablets compressed directly from the powder mixtures determined whether materials exhibited a loss in tabletability after roll compaction/dry granulation or not. The granule size had only a slight influence on the strength of produced tablets. In some cases, the fraction of smaller granules showed a higher tensile strength compared to the larger fraction.

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

PubMed

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

2018-05-02

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

Denitrifying capability and community dynamics of glycogen accumulating organisms during sludge granulation in an anaerobic-aerobic sequencing batch reactor

PubMed Central

Bin, Zhang; Bin, Xue; Zhigang, Qiu; Zhiqiang, Chen; Junwen, Li; Taishi, Gong; Wenci, Zou; Jingfeng, Wang

2015-01-01

Denitrifying capability of glycogen accumulating organisms (GAOs) has received great attention in environmental science and microbial ecology. Combining this ability with granule processes would be an interesting attempt. Here, a laboratory-scale sequencing batch reactor (SBR) was operated to enrich GAOs and enable sludge granulation. The results showed that the GAO granules were cultivated successfully and the granules had denitrifying capability. The batch experiments demonstrated that all NO3−-N could be removed or reduced, some amount of NO2−-N were accumulated in the reactor, and N2 was the main gaseous product. SEM analysis suggested that the granules were tightly packed with a large amount of tetrad-forming organisms (TFOs); filamentous bacteria served as the supporting structures for the granules. The microbial community structure of GAO granules was differed substantially from the inoculant conventional activated sludge. Most of the bacteria in the seed sludge grouped with members of Proteobacterium. FISH analysis confirmed that GAOs were the predominant members in the granules and were distributed evenly throughout the granular space. In contrast, PAOs were severely inhibited. Overall, cultivation of the GAO granules and utilizing their denitrifying capability can provide us with a new approach of nitrogen removal and saving more energy. PMID:26257096

Denitrifying capability and community dynamics of glycogen accumulating organisms during sludge granulation in an anaerobic-aerobic sequencing batch reactor.

PubMed

Bin, Zhang; Bin, Xue; Zhigang, Qiu; Zhiqiang, Chen; Junwen, Li; Taishi, Gong; Wenci, Zou; Jingfeng, Wang

2015-08-10

Denitrifying capability of glycogen accumulating organisms (GAOs) has received great attention in environmental science and microbial ecology. Combining this ability with granule processes would be an interesting attempt. Here, a laboratory-scale sequencing batch reactor (SBR) was operated to enrich GAOs and enable sludge granulation. The results showed that the GAO granules were cultivated successfully and the granules had denitrifying capability. The batch experiments demonstrated that all NO3(-)-N could be removed or reduced, some amount of NO2(-)-N were accumulated in the reactor, and N2 was the main gaseous product. SEM analysis suggested that the granules were tightly packed with a large amount of tetrad-forming organisms (TFOs); filamentous bacteria served as the supporting structures for the granules. The microbial community structure of GAO granules was differed substantially from the inoculant conventional activated sludge. Most of the bacteria in the seed sludge grouped with members of Proteobacterium. FISH analysis confirmed that GAOs were the predominant members in the granules and were distributed evenly throughout the granular space. In contrast, PAOs were severely inhibited. Overall, cultivation of the GAO granules and utilizing their denitrifying capability can provide us with a new approach of nitrogen removal and saving more energy.

Spatial patterning of P granules by RNA-induced phase separation of the intrinsically-disordered protein MEG-3

PubMed Central

Smith, Jarrett; Calidas, Deepika; Schmidt, Helen; Lu, Tu; Rasoloson, Dominique; Seydoux, Geraldine

2016-01-01

RNA granules are non-membrane bound cellular compartments that contain RNA and RNA binding proteins. The molecular mechanisms that regulate the spatial distribution of RNA granules in cells are poorly understood. During polarization of the C. elegans zygote, germline RNA granules, called P granules, assemble preferentially in the posterior cytoplasm. We present evidence that P granule asymmetry depends on RNA-induced phase separation of the granule scaffold MEG-3. MEG-3 is an intrinsically disordered protein that binds and phase separates with RNA in vitro. In vivo, MEG-3 forms a posterior-rich concentration gradient that is anti-correlated with a gradient in the RNA-binding protein MEX-5. MEX-5 is necessary and sufficient to suppress MEG-3 granule formation in vivo, and suppresses RNA-induced MEG-3 phase separation in vitro. Our findings suggest that MEX-5 interferes with MEG-3’s access to RNA, thus locally suppressing MEG-3 phase separation to drive P granule asymmetry. Regulated access to RNA, combined with RNA-induced phase separation of key scaffolding proteins, may be a general mechanism for controlling the formation of RNA granules in space and time. DOI: http://dx.doi.org/10.7554/eLife.21337.001 PMID:27914198

Denitrifying capability and community dynamics of glycogen accumulating organisms during sludge granulation in an anaerobic-aerobic sequencing batch reactor

NASA Astrophysics Data System (ADS)

Bin, Zhang; Bin, Xue; Zhigang, Qiu; Zhiqiang, Chen; Junwen, Li; Taishi, Gong; Wenci, Zou; Jingfeng, Wang

2015-08-01

Denitrifying capability of glycogen accumulating organisms (GAOs) has received great attention in environmental science and microbial ecology. Combining this ability with granule processes would be an interesting attempt. Here, a laboratory-scale sequencing batch reactor (SBR) was operated to enrich GAOs and enable sludge granulation. The results showed that the GAO granules were cultivated successfully and the granules had denitrifying capability. The batch experiments demonstrated that all NO3--N could be removed or reduced, some amount of NO2--N were accumulated in the reactor, and N2 was the main gaseous product. SEM analysis suggested that the granules were tightly packed with a large amount of tetrad-forming organisms (TFOs); filamentous bacteria served as the supporting structures for the granules. The microbial community structure of GAO granules was differed substantially from the inoculant conventional activated sludge. Most of the bacteria in the seed sludge grouped with members of Proteobacterium. FISH analysis confirmed that GAOs were the predominant members in the granules and were distributed evenly throughout the granular space. In contrast, PAOs were severely inhibited. Overall, cultivation of the GAO granules and utilizing their denitrifying capability can provide us with a new approach of nitrogen removal and saving more energy.

RNA in development: how ribonucleoprotein granules regulate the life cycles of pathogenic protozoa.

PubMed

Kramer, Susanne

2014-01-01

Ribonucleoprotein (RNP) granules are important posttranscriptional regulators of messenger RNA (mRNA) fate. Several types of RNP granules specifically regulate gene expression during development of multicellular organisms and are commonly referred to as germ granules. The function of germ granules is not entirely understood and probably diverse, but it is generally agreed that one main function is posttranscriptional regulation of gene expression during early development, when transcription is silent. One example is the translational repression of maternally derived mRNAs in oocytes. Here, I hope to show that the need for regulation of gene expression by RNP granules is not restricted to animal development, but plays an equally important role during the development of pathogenic protozoa. Apicomplexa and Trypanosomatidae have complex life cycles with frequent host changes. The need to quickly adapt gene expression to a new environment as well as the ability to suppress translation to survive latencies is critical for successful completion of life cycles. Posttranscriptional gene regulation is not necessarily simpler in protozoa. Apicomplexa surprise with the presence of micro RNA (miRNAs) and upstream open reading frames (µORFs). Trypanosomes have an unusually large repertoire of different RNP granule types. A better understanding of RNP granules in protozoa may help to gain insight into the evolutionary origin of RNP granules: Trypanosomes for example have two types of granules with interesting similarities to animal germ granules. © 2013 John Wiley & Sons, Ltd.

Formation of tRNA granules in the nucleus of heat-induced human cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miyagawa, Ryu; Department of Biological Science, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8654; Mizuno, Rie

Highlights: Black-Right-Pointing-Pointer tRNAs are tranlocated into the nucleus in heat-induced HeLa cells. Black-Right-Pointing-Pointer tRNAs form the unique granules in the nucleus. Black-Right-Pointing-Pointer tRNA ganules overlap with nuclear stress granules. -- Abstract: The stress response, which can trigger various physiological phenomena, is important for living organisms. For instance, a number of stress-induced granules such as P-body and stress granule have been identified. These granules are formed in the cytoplasm under stress conditions and are associated with translational inhibition and mRNA decay. In the nucleus, there is a focus named nuclear stress body (nSB) that distinguishes these structures from cytoplasmic stress granules.more » Many splicing factors and long non-coding RNA species localize in nSBs as a result of stress. Indeed, tRNAs respond to several kinds of stress such as heat, oxidation or starvation. Although nuclear accumulation of tRNAs occurs in starved Saccharomyces cerevisiae, this phenomenon is not found in mammalian cells. We observed that initiator tRNA{sup Met} (Meti) is actively translocated into the nucleus of human cells under heat stress. During this study, we identified unique granules of Meti that overlapped with nSBs. Similarly, elongator tRNA{sup Met} was translocated into the nucleus and formed granules during heat stress. Formation of tRNA granules is closely related to the translocation ratio. Then, all tRNAs may form the specific granules.« less

Proteome Profile of Starch Granules Purified from Rice (Oryza sativa) Endosperm.

PubMed

Xing, Shihai; Meng, Xiaoxi; Zhou, Lihui; Mujahid, Hana; Zhao, Chunfang; Zhang, Yadong; Wang, Cailin; Peng, Zhaohua

2016-01-01

Starch is the most important food energy source in cereals. Many of the known enzymes involved in starch biosynthesis are partially or entirely granule-associated in the endosperm. Studying the proteome of rice starch granules is critical for us to further understand the mechanisms underlying starch biosynthesis and packaging of starch granules in rice amyloplasts, consequently for the improvement of rice grain quality. In this article, we developed a protocol to purify starch granules from mature rice endosperm and verified the quality of purified starch granules by microscopy observations, I2 staining, and Western blot analyses. In addition, we found the phenol extraction method was superior to Tris-HCl buffer extraction method with respect to the efficiency in recovery of starch granule associated proteins. LC-MS/MS analysis showed identification of already known starch granule associated proteins with high confidence. Several proteins reported to be involved in starch synthesis in prior genetic studies in plants were also shown to be enriched with starch granules, either directly or indirectly, in our studies. In addition, our results suggested that a few additional candidate proteins may also be involved in starch synthesis. Furthermore, our results indicated that some starch synthesis pathway proteins are subject to protein acetylation modification. GO analysis and KEGG pathway enrichment analysis showed that the identified proteins were mainly located in plastids and involved in carbohydrate metabolism. This study substantially advances the understanding of the starch granule associated proteome in rice and post translational regulation of some starch granule associated proteins.

Gastroretentive extended-release floating granules prepared using a novel fluidized hot melt granulation (FHMG) technique.

PubMed

Zhai, H; Jones, D S; McCoy, C P; Madi, A M; Tian, Y; Andrews, G P

2014-10-06

The objective of this work was to investigate the feasibility of using a novel granulation technique, namely, fluidized hot melt granulation (FHMG), to prepare gastroretentive extended-release floating granules. In this study we have utilized FHMG, a solvent free process in which granulation is achieved with the aid of low melting point materials, using Compritol 888 ATO and Gelucire 50/13 as meltable binders, in place of conventional liquid binders. The physicochemical properties, morphology, floating properties, and drug release of the manufactured granules were investigated. Granules prepared by this method were spherical in shape and showed good flowability. The floating granules exhibited sustained release exceeding 10 h. Granule buoyancy (floating time and strength) and drug release properties were significantly influenced by formulation variables such as excipient type and concentration, and the physical characteristics (particle size, hydrophilicity) of the excipients. Drug release rate was increased by increasing the concentration of hydroxypropyl cellulose (HPC) and Gelucire 50/13, or by decreasing the particle size of HPC. Floating strength was improved through the incorporation of sodium bicarbonate and citric acid. Furthermore, floating strength was influenced by the concentration of HPC within the formulation. Granules prepared in this way show good physical characteristics, floating ability, and drug release properties when placed in simulated gastric fluid. Moreover, the drug release and floating properties can be controlled by modification of the ratio or physical characteristics of the excipients used in the formulation.

High shear mixing granulation of ibuprofen and beta-cyclodextrin: effects of process variables on ibuprofen dissolution.

PubMed

Ghorab, Mohamed K; Adeyeye, Moji Christianah

2007-10-19

The aims of the study were to evaluate the effect of high shear mixer (HSM) granulation process parameters and scale-up on wet mass consistency and granulation characteristics. A mixer torque rheometer (MTR) was employed to evaluate the granulating solvents used (water, isopropanol, and 1:1 vol/vol mixture of both) based on the wet mass consistency. Gral 25 and mini-HSM were used for the granulation. The MTR study showed that the water significantly enhanced the beta-cyclodextrin (beta CD) binding tendency and the strength of liquid bridges formed between the particles, whereas the isopropanol/water mixture yielded more suitable agglomerates. Mini-HSM granulation with the isopropanol/water mixture (1:1 vol/vol) showed a reduction in the extent of torque value rise by increasing the impeller speed as a result of more breakdown of agglomerates than coalescence. In contrast, increasing the impeller speed of the Gral 25 resulted in higher torque readings, larger granule size, and consequently, slower dissolution. This was due to a remarkable rise in temperature during Gral granulation that reduced the isopropanol/water ratio in the granulating solvent as a result of evaporation and consequently increased the beta CD binding strength. In general, the HSM granulation retarded ibuprofen dissolution compared with the physical mixture because of densification and agglomeration. However, a successful HSM granulation scale-up was not achieved due to the difference in the solvent mixture's effect from 1 scale to the other.

Second Harmonic Generation Mediated by Aligned Water in Starch Granules.

PubMed

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

2014-12-26

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.

[Study on spray-drier preparation technology of weitai granules using orthogonal experiments].

PubMed

Qu, Cai-Hong; Yang, Li; Chen, Zhi-Liang

2006-04-01

To screen preparation technique in order to raise the end-product and economical efficiency of spray-drier preparation technology of weitai granules. Newly Fluid-bed-spray-drier-granulation technique was adoped and taken extracting technique, temperature of exit and entry and the matching of accessories as inspecting factors, two levels of each factors, end-product and the water content of semi-finished weitai granules as inspecting marker, the best preparation technique of weitai granules was screened by orthogonal desing. Among the 3 factors, the matching of accessories was most notalbe (P < 0.01), next was the temperature of exit and entry (P < 0.05). However, the extracting technique was of little importance (P > 0.05). The optimum spray-drier granulation technique of weitai granules is A3B1C3.

The Neuronal Organization of a Unique Cerebellar Specialization: The Valvula Cerebelli of a Mormyrid Fish

PubMed Central

Shi, Zhigang; Zhang, Yueping; Meek, Johannes; Qiao, Jiantian; Han, Victor Z.

2018-01-01

The distal valvula cerebelli is the most prominent part of the mormyrid cerebellum. It is organized in ridges of ganglionic and molecular layers, oriented perpendicular to the granular layer. We have combined intracellular recording and labelling techniques to reveal the cellular morphology of the valvula ridges in slice preparations. We have also locally ejected tracer in slices and in intact animals to examine its input fibers. The palisade dendrites and fine axon arbors of Purkinje cells are oriented in the horizontal plane of the ridge. The dendrites of basal efferent cells and large central cells are confined to the molecular layer, but are not planer. Basal efferent cell axons are thick, and join the basal bundle leaving the cerebellum. Large central cell axons are also thick, and traverse long distances in the transverse plane, with local collaterals in the ganglionic layer. Vertical cells and small central cells also have thick axons with local collaterals. The dendrites of Golgi cells are confined to the molecular layer, but their axon arbors are either confined to the granular layer or proliferate in both the granular and ganglionic layers. Dendrites of deep stellate cells are distributed in the molecular layer, with fine axon arbors in the ganglionic layer. Granule cell axons enter the molecular layer as parallel fibers without bifurcating. Climbing fibers run in the horizontal plane and terminate exclusively in the ganglionic layer. Our results confirm and extend previous studies and suggest a new concept of the circuitry of the mormyrid valvula cerebelli. PMID:18537139

New gentle-wing high-shear granulator: impact of processing variables on granules and tablets characteristics of high-drug loading formulation using design of experiment approach.

PubMed

Fayed, Mohamed H; Abdel-Rahman, Sayed I; Alanazi, Fars K; Ahmed, Mahrous O; Tawfeek, Hesham M; Al-Shdefat, Ramadan I

2017-10-01

The aim of this work was to study the application of design of experiment (DoE) approach in defining design space for granulation and tableting processes using a novel gentle-wing high-shear granulator. According to quality-by-design (QbD) prospective, critical attributes of granules, and tablets should be ensured by manufacturing process design. A face-centered central composite design has been employed in order to investigate the effect of water amount (X 1 ), impeller speed (X 2 ), wet massing time (X 3 ), and water addition rate (X 4 ) as independent process variables on granules and tablets characteristics. Acetaminophen was used as a model drug and granulation experiments were carried out using dry addition of povidone k30. The dried granules have been analyzed for their size distribution, density, and flow pattern. Additionally, the produced tablets have been investigated for; weight uniformity, breaking force, friability and percent capping, disintegration time, and drug dissolution. Results of regression analysis showed that water amount, impeller speed and wet massing time have significant (p < .05) effect on granules and tablets characteristics. However, the water amount had the most pronounced effect as indicated by its higher parameter estimate. On the other hand, water addition rate showed a minimal impact on granules and tablets properties. In conclusion, water amount, impeller speed, and wet massing time could be considered as critical process variables. Thus, understanding the relationship between these variables and quality attributes of granules and corresponding tablets provides the basis for adjusting granulation variables in order to optimize product performance.

Assessment of bacterial and structural dynamics in aerobic granular biofilms

PubMed Central

Weissbrodt, David G.; Neu, Thomas R.; Kuhlicke, Ute; Rappaz, Yoan; Holliger, Christof

2013-01-01

Aerobic granular sludge (AGS) is based on self-granulated flocs forming mobile biofilms with a gel-like consistence. Bacterial and structural dynamics from flocs to granules were followed in anaerobic-aerobic sequencing batch reactors (SBR) fed with synthetic wastewater, namely a bubble column (BC-SBR) operated under wash-out conditions for fast granulation, and two stirred-tank enrichments of Accumulibacter (PAO-SBR) and Competibacter (GAO-SBR) operated at steady-state. In the BC-SBR, granules formed within 2 weeks by swelling of Zoogloea colonies around flocs, developing subsequently smooth zoogloeal biofilms. However, Zoogloea predominance (37–79%) led to deteriorated nutrient removal during the first months of reactor operation. Upon maturation, improved nitrification (80–100%), nitrogen removal (43–83%), and high but unstable dephosphatation (75–100%) were obtained. Proliferation of dense clusters of nitrifiers, Accumulibacter, and Competibacter from granule cores outwards resulted in heterogeneous bioaggregates, inside which only low abundance Zoogloea (<5%) were detected in biofilm interstices. The presence of different extracellular glycoconjugates detected by fluorescence lectin-binding analysis showed the complex nature of the intracellular matrix of these granules. In the PAO-SBR, granulation occurred within two months with abundant and active Accumulibacter populations (56 ± 10%) that were selected under full anaerobic uptake of volatile fatty acids and that aggregated as dense clusters within heterogeneous granules. Flocs self-granulated in the GAO-SBR after 480 days during a period of over-aeration caused by biofilm growth on the oxygen sensor. Granules were dominated by heterogeneous clusters of Competibacter (37 ± 11%). Zoogloea were never abundant in biomass of both PAO- and GAO-SBRs. This study showed that Zoogloea, Accumulibacter, and Competibacter affiliates can form granules, and that the granulation mechanisms rely on the dominant population involved. PMID:23847600

Investigation of Dissolution Behavior HPMC/Eudragit®/Magnesium Aluminometasilicate Oral Matrices Based on NMR Solid-State Spectroscopy and Dynamic Characteristics of Gel Layer.

PubMed

Naiserová, M; Kubová, K; Vysloužil, J; Pavloková, S; Vetchý, D; Urbanová, M; Brus, J; Vysloužil, J; Kulich, P

2018-02-01

Burst drug release is often considered a negative phenomenon resulting in unexpected toxicity or tissue irritation. Optimal release of a highly soluble active pharmaceutical ingredient (API) from hypromellose (HPMC) matrices is technologically impossible; therefore, a combination of polymers is required for burst effect reduction. Promising variant could be seen in combination of HPMC and insoluble Eudragits ® as water dispersions. These can be applied only on API/insoluble filler mixture as over-wetting prevention. The main hurdle is a limited water absorption capacity (WAC) of filler. Therefore, the object of this study was to investigate the dissolution behavior of levetiracetam from HPMC/Eudragit ® NE matrices using magnesium aluminometasilicate (Neusilin ® US2) as filler with excellent WAC. Part of this study was also to assess influence of thermal treatment on quality parameters of matrices. The use of Neusilin ® allowed the application of Eudragit ® dispersion to API/Neusilin ® mixture in one step during high-shear wet granulation. HPMC was added extragranularly. Obtained matrices were investigated for qualitative characteristics, NMR solid-state spectroscopy (ssNMR), gel layer dynamic parameters, SEM, and principal component analysis (PCA). Decrease in burst effect (max. of 33.6%) and dissolution rate, increase in fitting to zero-order kinetics, and paradoxical reduction in gel layer thickness were observed with rising Eudragit ® NE concentration. The explanation was done by ssNMR, which clearly showed a significant reduction of the API particle size (150-500 nm) in granules as effect of surfactant present in dispersion in dependence on Eudragit ® NE amount. This change in API particle size resulted in a significantly larger interface between these two entities. Based on ANOVA and PCA, thermal treatment was not revealed as a useful procedure for this system.

Oxytocin depolarizes fast-spiking hilar interneurons and induces GABA release onto mossy cells of the rat dentate gyrus.

PubMed

Harden, Scott W; Frazier, Charles J

2016-09-01

Delivery of exogenous oxytocin (OXT) to central oxytocin receptors (OXT-Rs) is currently being investigated as a potential treatment for conditions such as post-traumatic stress disorder (PTSD), depression, social anxiety, and autism spectrum disorder (ASD). Despite significant research implicating central OXT signaling in modulation of mood, affect, social behavior, and stress response, relatively little is known about the cellular and synaptic mechanisms underlying these complex actions, particularly in brain regions which express the OXT-R but lie outside of the hypothalamus (where OXT-synthesizing neurons reside). We report that bath application of low concentrations of the selective OXT-R agonist Thr4,Gly7-OXT (TGOT) reliably and robustly drives GABA release in the dentate gyrus in an action potential dependent manner. Additional experiments led to identification of a small subset of small hilar interneurons that are directly depolarized by acute application of TGOT. From a physiological perspective, TGOT-responsive hilar interneurons have high input resistance, rapid repolarization velocity during an action potential, and a robust afterhyperpolarization. Further, they fire irregularly (or stutter) in response to moderate depolarization, and fire quickly with minimal spike frequency accommodation in response to large current injections. From an anatomical perspective, TGOT responsive hilar interneurons have dense axonal arborizations in the hilus that were found in close proximity with mossy cell somata and/or proximal dendrites, and also invade the granule cell layer. Further, they have primary dendrites that always extend into the granule cell layer, and sometimes have clear arborizations in the molecular layer. Overall, these data reveal a novel site of action for OXT in an important limbic circuit, and represent a significant step towards better understanding how endogenous OXT may modulate flow of information in hippocampal networks. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Detection and Analysis of the Quality of Ibuprofen Granules

NASA Astrophysics Data System (ADS)

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

2017-12-01

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

Carbon, nitrogen and phosphorus removal mechanisms of aerobic granules.

PubMed

Sarma, Saurabh Jyoti; Tay, Joo-Hwa

2018-04-10

Aerobic granules are the potential tools to develop modern wastewater treatment technologies with improved nutrient removal efficiency. These granules have several promising advantages over conventional activated sludge-based wastewater treatment processes. This technology has the potential of reducing the infrastructure and operation costs of wastewater treatment by 25%, energy requirement by 30%, and space requirement by 75%. The nutrient removal mechanisms of aerobic granules are slightly different from that of the activated sludge. For instance, unlike activated sludge process, according to some reports, as high as 70% of the total phosphorus removed by aerobic granules were attributed to precipitation within the granules. Similarly, aerobic granule-based technology reduces the total amount of sludge produced during wastewater treatment. However, the reason behind this observation is unknown and it needs further explanations based on carbon and nitrogen removal mechanisms. Thus, as a part of the present review, a set of new hypotheses have been proposed to explain the peculiar nutrient removal mechanisms of the aerobic granules.

Native granule associated short chain length polyhydroxyalkanoate synthase from a marine derived Bacillus sp. NQ-11/A2.

PubMed

Prabhu, Nimali N; Santimano, Maria Celisa; Mavinkurve, Suneela; Bhosle, Saroj N; Garg, Sandeep

2010-01-01

A rapidly growing marine derived Bacillus sp. strain NQ-11/A2, identified as Bacillus megaterium, accumulated 61% polyhydroxyalkanoate by weight. Diverse carbon sources served as substrates for the accumulation of short chain length polyhydroxyalkanoate. Three to nine granules either single or attached as buds could be isolated intact from each cell. Maximum activity of polyhydroxyalkanoate synthase was associated with the granules. Granule-bound polyhydroxyalkanoate synthase had a K(m) of 7.1 x 10(-5) M for DL-beta-hydroxybutyryl-CoA. Temperature and pH optima for maximum activity were 30 degrees C and 7.0, respectively. Sodium ions were required for granule-bound polyhydroxyalkanoate synthase activity and inhibited by potassium. Granule-bound polyhydroxyalkanoate synthase was apparently covalently bound to the polyhydroxyalkanoate-core of the granules and affected by the chaotropic reagent urea. Detergents inhibited the granule-bound polyhydroxyalkanoate synthase drastically whilst glycerol and bovine serum albumin stabilized the synthase.

Artificial Intelligence Tools for Scaling Up of High Shear Wet Granulation Process.

PubMed

Landin, Mariana

2017-01-01

The results presented in this article demonstrate the potential of artificial intelligence tools for predicting the endpoint of the granulation process in high-speed mixer granulators of different scales from 25L to 600L. The combination of neurofuzzy logic and gene expression programing technologies allowed the modeling of the impeller power as a function of operation conditions and wet granule properties, establishing the critical variables that affect the response and obtaining a unique experimental polynomial equation (transparent model) of high predictability (R 2 > 86.78%) for all size equipment. Gene expression programing allowed the modeling of the granulation process for granulators of similar and dissimilar geometries and can be improved by implementing additional characteristics of the process, as composition variables or operation parameters (e.g., batch size, chopper speed). The principles and the methodology proposed here can be applied to understand and control manufacturing process, using any other granulation equipment, including continuous granulation processes. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Sustained-release progesterone vaginal suppositories 1--development of sustained-release granule--.

PubMed

Nakayama, Ayako; Sunada, Hisakazu; Okamoto, Hirokazu; Furuhashi, Kaoru; Ohno, Yukiko; Ito, Mikio

2009-02-01

Progesterone (P) is an important hormone for the establishment of pregnancy, and its administration is useful for luteal insufficiency. Considering the problems of commercially available oral and injection drugs, hospital-formulated vaginal suppositories are clinically used. However, since the half-life of P suppositories is short, it is difficult to maintain its constant blood concentration. To sustain drug efficacy and prevent side-effects, we are attempting to develop sustained-release suppositories by examining the degree of sustained-release of active ingredients. In this study, we examined the combinations of granulation methods and release systems for the preparation of sustained-release granules of P, and produced 13 types of sustained-release granules. We also examined the diameter, content, and dissolution of each type of granules, and confirmed that the sustained-release of all types of granules was satisfactory. Among the sustained-release granules, we selected granules with a content and a degree of sustained-release suitable for sustained-release suppositories.

Amyloid β-Mediated Zn2+ Influx into Dentate Granule Cells Transiently Induces a Short-Term Cognitive Deficit

PubMed Central

Takeda, Atsushi; Nakamura, Masatoshi; Fujii, Hiroaki; Uematsu, Chihiro; Minamino, Tatsuya; Adlard, Paul A.; Bush, Ashley I.; Tamano, Haruna

2014-01-01

We examined an idea that short-term cognition is transiently affected by a state of confusion in Zn2+ transport system due to a local increase in amyloid-β (Aβ) concentration. A single injection of Aβ (25 pmol) into the dentate gyrus affected dentate gyrus long-term potentiation (LTP) 1 h after the injection, but not 4 h after the injection. Simultaneously, 1-h memory of object recognition was affected when the training was performed 1 h after the injection, but not 4 h after the injection. Aβ-mediated impairments of LTP and memory were rescued in the presence of zinc chelators, suggesting that Zn2+ is involved in Aβ action. When Aβ was injected into the dentate gyrus, intracellular Zn2+ levels were increased only in the injected area in the dentate gyrus, suggesting that Aβ induces the influx of Zn2+ into cells in the injected area. When Aβ was added to hippocampal slices, Aβ did not increase intracellular Zn2+ levels in the dentate granule cell layer in ACSF without Zn2+, but in ACSF containing Zn2+. The increase in intracellular Zn2+ levels was inhibited in the presence of CaEDTA, an extracellular zinc chelator, but not in the presence of CNQX, an AMPA receptor antagonist. The present study indicates that Aβ-mediated Zn2+ influx into dentate granule cells, which may occur without AMPA receptor activation, transiently induces a short-term cognitive deficit. Extracellular Zn2+ may play a key role for transiently Aβ-induced cognition deficits. PMID:25536033

Effects of Ethanol on the Cerebellum: Advances and Prospects.

PubMed

Luo, Jia

2015-08-01

Alcohol abuse causes cerebellar dysfunction and cerebellar ataxia is a common feature in alcoholics. Alcohol exposure during development also impacts the cerebellum. Children with fetal alcohol spectrum disorder (FASD) show many symptoms associated specifically with cerebellar deficits. However, the cellular and molecular mechanisms are unclear. This special issue discusses the most recent advances in the study of mechanisms underlying alcoholinduced cerebellar deficits. The alteration in GABAA receptor-dependent neurotransmission is a potential mechanism for ethanol-induced cerebellar dysfunction. Recent advances indicate ethanol-induced increases in GABA release are not only in Purkinje cells (PCs), but also in molecular layer interneurons and granule cells. Ethanol is shown to disrupt the molecular events at the mossy fiber - granule cell - Golgi cell (MGG) synaptic site and granule cell parallel fibers - PCs (GPP) synaptic site, which may be responsible for ethanol-induced cerebellar ataxia. Aging and ethanol may affect the smooth endoplasmic reticulum (SER) of PC dendrites and cause dendritic regression. Ethanol withdrawal causes mitochondrial damage and aberrant gene modifications in the cerebellum. The interaction between these events may result in neuronal degeneration, thereby contributing to motoric deficit. Ethanol activates doublestranded RNA (dsRNA)-activated protein kinase (PKR) and PKR activation is involved ethanolinduced neuroinflammation and neurotoxicity in the developing cerebellum. Ethanol alters the development of cerebellar circuitry following the loss of PCs, which could result in modifications of the structure and function of other brain regions that receive cerebellar inputs. Lastly, choline, an essential nutrient is evaluated for its potential protection against ethanol-induced cerebellar damages. Choline is shown to ameliorate ethanol-induced cerebellar dysfunction when given before ethanol exposure.

A numerical investigation of the interaction between convection and magnetic field in a solar surface layer

NASA Astrophysics Data System (ADS)

Bercik, David John

2002-11-01

Three-dimensional numerical simulations are used to study the dynamic interaction between magnetic fields and convective motions near the solar surface. The magnetic field is found to be transported by convective motions from granules to the intergranular lanes, where it collects and is compressed. A convective instability causes the upper levels of magnetic regions to be evacuated, compressing the field beyond equipartition values, and forming “flux tubes” or “flux sheets”. The degree to which the field is compressed controls how much convective transport is suppressed within the flux structure, and ultimately determines whether the magnetic feature appears brighter or darker than its surroundings. For this reason, the continuum intensity is not a good tracer of the lifetimes of magnetic features, since their bright/dark signature is transient in nature. Larger magnetic structures form at sites where a granule submerges and the surrounding field is pushed into the resulting dark hole. These micropores are devoid of flow in their interior and cool by radiating radially. The convective downflows that collar the micropore heat its edges by lateral radiation, but fail to penetrate far enough into the interior to prevent an overall cooling, and therefore darkening, of the micropore. Magnetic features undergo numerous mergers or splittings during their lifetimes as a result of being pushed and squeezed by the expansion of adjacent granules. Larger structures survive for several convective turnover times, but smaller structures are too weak to resist convective motions, and are destroyed on a convective time scale.

Amyloid β-mediated Zn2+ influx into dentate granule cells transiently induces a short-term cognitive deficit.

PubMed

Takeda, Atsushi; Nakamura, Masatoshi; Fujii, Hiroaki; Uematsu, Chihiro; Minamino, Tatsuya; Adlard, Paul A; Bush, Ashley I; Tamano, Haruna

2014-01-01

We examined an idea that short-term cognition is transiently affected by a state of confusion in Zn2+ transport system due to a local increase in amyloid-β (Aβ) concentration. A single injection of Aβ (25 pmol) into the dentate gyrus affected dentate gyrus long-term potentiation (LTP) 1 h after the injection, but not 4 h after the injection. Simultaneously, 1-h memory of object recognition was affected when the training was performed 1 h after the injection, but not 4 h after the injection. Aβ-mediated impairments of LTP and memory were rescued in the presence of zinc chelators, suggesting that Zn2+ is involved in Aβ action. When Aβ was injected into the dentate gyrus, intracellular Zn2+ levels were increased only in the injected area in the dentate gyrus, suggesting that Aβ induces the influx of Zn2+ into cells in the injected area. When Aβ was added to hippocampal slices, Aβ did not increase intracellular Zn2+ levels in the dentate granule cell layer in ACSF without Zn2+, but in ACSF containing Zn2+. The increase in intracellular Zn2+ levels was inhibited in the presence of CaEDTA, an extracellular zinc chelator, but not in the presence of CNQX, an AMPA receptor antagonist. The present study indicates that Aβ-mediated Zn2+ influx into dentate granule cells, which may occur without AMPA receptor activation, transiently induces a short-term cognitive deficit. Extracellular Zn2+ may play a key role for transiently Aβ-induced cognition deficits.

Resveratrol Restores Nrf2 Level and Prevents Ethanol-Induced Toxic Effects in the Cerebellum of a Rodent Model of Fetal Alcohol Spectrum Disorders

PubMed Central

Kumar, Ambrish; Singh, Chandra K.; LaVoie, Holly A.; DiPette, Donald J.

2011-01-01

In humans, ethanol exposure during pregnancy produces a wide range of abnormalities in infants collectively known as fetal alcohol spectrum disorders (FASD). Neuronal malformations in FASD manifest as postnatal behavioral and functional disturbances. The cerebellum is particularly sensitive to ethanol during development. In a rodent model of FASD, high doses of ethanol (blood ethanol concentration 80 mM) induces neuronal cell death in the cerebellum. However, information on potential agent(s) that may protect the cerebellum against the toxic effects of ethanol is lacking. Growing evidence suggests that a polyphenolic compound, resveratrol, has antioxidant and neuroprotective properties. Here we studied whether resveratrol (3,5,4′-trihydroxy-trans-stilbene), a phytoalexin found in red grapes and blueberries, protects the cerebellar granule neurons against ethanol-induced cell death. In the present study, we showed that administration of resveratrol (100 mg/kg) to postnatal day 7 rat pups prevents ethanol-induced apoptosis by scavenging reactive oxygen species in the external granule layer of the cerebellum and increases the survival of cerebellar granule cells. It restores ethanol-induced changes in the level of transcription factor nuclear factor-erythroid derived 2-like 2 (nfe2l2, also known as Nrf2) in the nucleus. This in turn retains the expression and activity of its downstream gene targets such as NADPH quinine oxidoreductase 1 and superoxide dismutase in cerebellum of ethanol-exposed pups. These studies indicate that resveratrol exhibits neuroprotective effects in cerebellum by acting at redox regulating proteins in a rodent model of FASD. PMID:21697273

Subcellular investigation of photosynthesis-driven carbon assimilation in the symbiotic reef coral Pocillopora damicornis.

PubMed

Kopp, Christophe; Domart-Coulon, Isabelle; Escrig, Stephane; Humbel, Bruno M; Hignette, Michel; Meibom, Anders

2015-02-10

Reef-building corals form essential, mutualistic endosymbiotic associations with photosynthetic Symbiodinium dinoflagellates, providing their animal host partner with photosynthetically derived nutrients that allow the coral to thrive in oligotrophic waters. However, little is known about the dynamics of these nutritional interactions at the (sub)cellular level. Here, we visualize with submicrometer spatial resolution the carbon and nitrogen fluxes in the intact coral-dinoflagellate association from the reef coral Pocillopora damicornis by combining nanoscale secondary ion mass spectrometry (NanoSIMS) and transmission electron microscopy with pulse-chase isotopic labeling using [(13)C]bicarbonate and [(15)N]nitrate. This allows us to observe that (i) through light-driven photosynthesis, dinoflagellates rapidly assimilate inorganic bicarbonate and nitrate, temporarily storing carbon within lipid droplets and starch granules for remobilization in nighttime, along with carbon and nitrogen incorporation into other subcellular compartments for dinoflagellate growth and maintenance, (ii) carbon-containing photosynthates are translocated to all four coral tissue layers, where they accumulate after only 15 min in coral lipid droplets from the oral gastroderm and within 6 h in glycogen granules from the oral epiderm, and (iii) the translocation of nitrogen-containing photosynthates is delayed by 3 h. Our results provide detailed in situ subcellular visualization of the fate of photosynthesis-derived carbon and nitrogen in the coral-dinoflagellate endosymbiosis. We directly demonstrate that lipid droplets and glycogen granules in the coral tissue are sinks for translocated carbon photosynthates by dinoflagellates and confirm their key role in the trophic interactions within the coral-dinoflagellate association. Copyright © 2015 Kopp et al.

Computational Architecture of the Granular Layer of Cerebellum-Like Structures.

PubMed

Bratby, Peter; Sneyd, James; Montgomery, John

2017-02-01

In the adaptive filter model of the cerebellum, the granular layer performs a recoding which expands incoming mossy fibre signals into a temporally diverse set of basis signals. The underlying neural mechanism is not well understood, although various mechanisms have been proposed, including delay lines, spectral timing and echo state networks. Here, we develop a computational simulation based on a network of leaky integrator neurons, and an adaptive filter performance measure, which allows candidate mechanisms to be compared. We demonstrate that increasing the circuit complexity improves adaptive filter performance, and relate this to evolutionary innovations in the cerebellum and cerebellum-like structures in sharks and electric fish. We show how recurrence enables an increase in basis signal duration, which suggest a possible explanation for the explosion in granule cell numbers in the mammalian cerebellum.

Preparation of orally disintegrating tablets with taste-masking function: masking effect in granules prepared with correctives using the dry granulation method and evaluation of tablets prepared using the taste-masked granules.

PubMed

Kawano, Yayoi; Ito, Akihiko; Sasatsu, Masanaho; Machida, Yoshiharu

2010-01-01

We investigated several methods of taste masking in the preparation of orally disintegrating tablets (ODTs), using furosemide (FU) as a model drug. Four types of FU preparations were prepared: granules with maltitol (MA), granules with yogurt powder (YO), a physical mixture of FU and MA, and a physical mixture of FU and YO. All taste-masking granules were prepared using the dry granulation method. The taste of each type of preparation was evaluated. All four preparations markedly improved the taste of the FU tablets, but the mixing ratios of the correctives did not affect the masking effect. No difference in masking effect was found between MA and YO in the physical mixtures, but the masking effect in the granules with YO was superior to that of the granules with MA. Taste-masked FU tablets were prepared using the direct compression method; crystalline cellulose (Avicel PH-302) and mannitol were added as excipients at the mixing ratio of 1/1. All four types of tablets displayed sufficient hardness, but MA-containing tablets were harder than YO-containing tablets. The hardness of the tablets prepared from YO granules increased as the YO content increased. The most rapidly disintegrating tablets were those of YO granules prepared at a mixing ratio of FU/YO=1/1, which disintegrated within 20 s, followed by the tablets of MA granules prepared at a mixing ratio of FU/MA=1/1. The disintegration times of the tablets made from physical mixtures, in contrast, were longer than 200 s. Disintegration time lengthened as the mixing ratio of YO or MA increased. The hardness and disintegration time of these tablets could be controlled by varying the compression pressure. We found that YO is more useful than MA in masking unpleasant tastes and confirmed that orally disintegrating tablets with taste-masking function can be prepared using granules of YO prepared using the dry granulation method as a new corrective.

Morphometry of Hilar Ectopic Granule Cells in the Rat

PubMed Central

Pierce, Joseph P.; McCloskey, Daniel P.; Scharfman, Helen E.

2014-01-01

Granule cell (GC) neurogenesis in the dentate gyrus (DG) does not always proceed normally. After severe seizures (e.g., status epilepticus [SE]) and some other conditions, newborn GCs appear in the hilus. Hilar ectopic GCs (EGCs) can potentially provide insight into the effects of abnormal location and seizures on GC development. Additionally, hilar EGCs that develop after SE may contribute to epileptogenesis and cognitive impairments that follow SE. Thus, it is critical to understand how EGCs differ from normal GCs. Relatively little morphometric information is available on EGCs, especially those restricted to the hilus. This study quantitatively analyzed the structural morphology of hilar EGCs from adult male rats several months after pilocarpineinduced SE, when they are considered to have chronic epilepsy. Hilar EGCs were physiologically identified in slices, intracellularly labeled, processed for light microscopic reconstruction, and compared to GC layer GCs, from both the same post-SE tissue and the NeuroMorpho database (normal GCs). Consistently, hilar EGC and GC layer GCs had similar dendritic lengths and field sizes, and identifiable apical dendrites. However, hilar EGC dendrites were topologically more complex, with more branch points and tortuous dendritic paths. Three-dimensional analysis revealed that, remarkably, hilar EGC dendrites often extended along the longitudinal DG axis, suggesting increased capacity for septotemporal integration. Axonal reconstruction demonstrated that hilar EGCs contributed to mossy fiber sprouting. This combination of preserved and aberrant morphological features, potentially supporting convergent afferent input to EGCs and broad, divergent efferent output, could help explain why the hilar EGC population could impair DG function. PMID:21344409

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yokohira, Masanao; Arnold, Lora L.; Pennington, Karen L.

Arsenic (+ 3 oxidation state) methyltransferase (As3mt) catalyzes reactions which convert inorganic arsenic to methylated metabolites. This study determined whether the As3mt null genotype in the mouse modifies cytotoxic and proliferative effects seen in urinary bladders of wild type mice after exposure to inorganic arsenic. Female wild type C57BL/6 mice and As3mt KO mice were divided into 3 groups each (n = 8) with free access to a diet containing 0, 100 or 150 ppm of arsenic as arsenite (As{sup III}). During the first week of As{sup III} exposure, As3mt KO mice exhibited severe and lethal systemic toxicity. At termination,more » urinary bladders of both As3mt KO and wild type mice showed hyperplasia by light microscopy. As expected, arsenic-containing granules were found in the superficial urothelial layer of wild type mice. In As3mt KO mice these granules were present in all layers of the bladder epithelium and were more abundant and larger than in wild type mice. Scanning electron microscopy of the bladder urothelium of As3mt KO mice treated with 100 ppm As{sup III} showed extensive superficial necrosis and hyperplastic changes. In As3mt KO mice, livers showed severe acute inflammatory changes and spleen size and lymphoid areas were decreased compared with wild type mice. Thus, diminished arsenic methylation in As3mt KO mice exacerbates systemic toxicity and the effects of As{sup III} on the bladder epithelium, showing that altered kinetic and dynamic behavior of arsenic can affect its toxicity.« less

Induction of the UDP-Glucuronosyltransferase 1A1 during the Perinatal Period Can Cause Neurodevelopmental Toxicity.

PubMed

Hirashima, Rika; Michimae, Hirofumi; Takemoto, Hiroaki; Sasaki, Aya; Kobayashi, Yoshinori; Itoh, Tomoo; Tukey, Robert H; Fujiwara, Ryoichi

2016-09-01

Anticonvulsants can increase the risk of developing neurotoxicity in infants; however, the underlying mechanism has not been elucidated to date. Thyroxine [3,5,3',5'-l-tetraiodothyronine (T4)] plays crucial roles in the development of the central nervous system. In this study, we hypothesized that induction of UDP-glucuronosyltransferase 1A1 (UGT1A1)-an enzyme involved in the metabolism of T4-by anticonvulsants would reduce serum T4 levels and cause neurodevelopmental toxicity. Exposure of mice to phenytoin during both the prenatal and postnatal periods significantly induced UGT1A1 and decreased serum T4 levels on postnatal day 14. In the phenytoin-treated mice, the mRNA levels of synaptophysin and synapsin I in the hippocampus were lower than those in the control mice. The thickness of the external granule cell layer was greater in phenytoin-treated mice, indicating that induction of UGT1A1 during the perinatal period caused neurodevelopmental disorders. Exposure to phenytoin during only the postnatal period also caused these neurodevelopmental disorders. A T4 replacement attenuated the increase in thickness of the external granule cell layer, indicating that the reduced T4 was specifically associated with the phenytoin-induced neurodevelopmental disorder. In addition, these neurodevelopmental disorders were also found in the carbamazepine- and pregnenolone-16-α-carbonitrile-treated mice. Our study is the first to indicate that UGT1A1 can control neurodevelopment by regulating serum T4 levels. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Induction of the UDP-Glucuronosyltransferase 1A1 during the Perinatal Period Can Cause Neurodevelopmental Toxicity

PubMed Central

Hirashima, Rika; Michimae, Hirofumi; Takemoto, Hiroaki; Sasaki, Aya; Kobayashi, Yoshinori; Itoh, Tomoo; Tukey, Robert H.

2016-01-01

Anticonvulsants can increase the risk of developing neurotoxicity in infants; however, the underlying mechanism has not been elucidated to date. Thyroxine [3,5,3′,5′-l-tetraiodothyronine (T4)] plays crucial roles in the development of the central nervous system. In this study, we hypothesized that induction of UDP-glucuronosyltransferase 1A1 (UGT1A1)—an enzyme involved in the metabolism of T4—by anticonvulsants would reduce serum T4 levels and cause neurodevelopmental toxicity. Exposure of mice to phenytoin during both the prenatal and postnatal periods significantly induced UGT1A1 and decreased serum T4 levels on postnatal day 14. In the phenytoin-treated mice, the mRNA levels of synaptophysin and synapsin I in the hippocampus were lower than those in the control mice. The thickness of the external granule cell layer was greater in phenytoin-treated mice, indicating that induction of UGT1A1 during the perinatal period caused neurodevelopmental disorders. Exposure to phenytoin during only the postnatal period also caused these neurodevelopmental disorders. A T4 replacement attenuated the increase in thickness of the external granule cell layer, indicating that the reduced T4 was specifically associated with the phenytoin-induced neurodevelopmental disorder. In addition, these neurodevelopmental disorders were also found in the carbamazepine- and pregnenolone-16-α-carbonitrile–treated mice. Our study is the first to indicate that UGT1A1 can control neurodevelopment by regulating serum T4 levels. PMID:27413119

Gestational lead exposure induces developmental abnormalities and up-regulates apoptosis of fetal cerebellar cells in rats.

PubMed

Mousa, Alyaa M; Al-Fadhli, Ameera S; Rao, Muddanna S; Kilarkaje, Narayana

2015-01-01

Lead (Pb), a known environmental toxicant, adversely affects almost all organ systems. In this study, we investigated the effects of maternal lead exposure on fetal rat cerebellum. Female Sprague-Dawley rats were given lead nitrate in drinking water (0, 0.5, and 1%) for two weeks before conception, and during pregnancy. Fetuses were collected by caesarian section on gestational day 21 and observed for developmental abnormalities. The fetal cerebellar sections from control and 1% lead group were stained with cresyl violet. Immunohistochemical expressions of p53, Bax, Bcl-2, and caspase 3 were quantified by AnalySIS image analyzer (Life Science, Germany). Lead exposure induced developmental abnormalities of eyes, ear, limbs, neck and ventral abdominal wall; however, these abnormalities were commonly seen in the 1% lead-treated group. In addition, lead also caused fetal mortality and reduced body growth in both dose groups and reduced brain weight in the 1% lead-treated group. The fetal cerebella from the 1% lead-treated group showed unorganized cerebellar cortical layers, and degenerative changes in granule and Purkinje cells such as the formation of clumps of Nissl granules. An increase in Bax and caspase 3, and a decrease in Bcl-2 (p < 0.05), but not in p53, showed apoptosis of the neurons. In conclusion, gestational lead exposure in rats induces fetal toxicity and developmental abnormalities. The lead exposure also impairs development of cerebellar layers, induces structural changes, and apoptosis in the fetal cerebellar cortex. These results suggest that lead exposure during gestation is extremely toxic to developing cerebellum in rats.

Tactile responses in the granule cell layer of cerebellar folium crus IIa of freely behaving rats

NASA Technical Reports Server (NTRS)

Hartmann, M. J.; Bower, J. M.

2001-01-01

We recorded activity from the granule cell layer (GCL) of cerebellar folium Crus IIa as freely moving rats engaged in a variety of natural behaviors, including grooming, eating, and free tactile exploration. Multiunit responses in the 1000-4500 Hz range were found to be strongly correlated with tactile stimulation of lip and whisker (perioral) regions. These responses occurred regardless of whether the stimulus was externally or self-generated and during both active and passive touch. In contrast, perioral movements that did not tactually stimulate this region of the face (e.g., chewing) produced no detectable increases in GCL activity. In addition, GCL responses were not correlated with movement extremes. When rats used their lips actively for palpation and exploration, the tactile responses in the GCL were not detectably modulated by ongoing jaw movements. However, active palpation and exploratory behaviors did result in the largest and most continuous bursts of GCL activity: responses were on average 10% larger and 50% longer during palpation and exploration than during grooming or passive stimulation. Although activity levels differed between behaviors, the position and spatial extent of the peripheral receptive field was similar over all behaviors that resulted in tactile input. Overall, our data suggest that the 1000-4500 Hz multiunit responses in the Crus IIa GCL of awake rats are correlated with tactile input rather than with movement or any movement parameter and that these responses are likely to be of particular importance during the acquisition of sensory information by perioral structures.

Effects of Deinococcus spp. supplement on egg quality traits in laying hens.

PubMed

Li, I-Chen; Wu, Szu-Yin; Liou, Jenn-Fa; Liu, Hsiao-Hui; Chen, Jiau-Hua; Chen, Chin-Chu

2018-01-01

To counter the ill effects of synthetic dyes, bacterial pigment production as an alternative is now one of the promising and emerging fields of research. This study was conducted to evaluate the applicability of Deinococcus genus on the egg quality traits in laying hens. In study I, 24 single comb White Leghorn layers were fed with various 1 wt % Deinococcus bacterial strains for 10 d. In study II, 84 brown Hendrix layers were fed with one of 4 diets containing 0, 0.2, 1, or 5 wt % Deinococcus sp. GKB-Aid 1995 powder for 12 wk. In study III, 60 White Leghorn laying hens were fed either with or without 1 wt % Deinococcus sp. GKB-Aid 1995 powder, 1 wt % Deinococcus sp. GKB-Aid 1995 granules, or 1 wt % Deinococcus sp. GKB-Aid 1995 oily granules for 10 successive d. In all of the experiments, feeding Deinococcus powder did not affect egg quality traits except for the yolk color. In particular, supplementation with all Deinococcus powder treatments changed the yolk color (P < 0.05) in study I, with the best pigmentation score obtained by D. grandis and Deinococcus sp. GKB-Aid 1995. Moreover, longer supplementation of Deinococcus sp. GKB-Aid 1995 in study II had a significant effect on feed conversion ratio. With these findings under consideration, the present study suggests that the Deinococcus species, especially Deinococcus sp. GKB-Aid 1995, can be an excellent candidate for improving egg yolk color in laying hens. © 2017 Poultry Science Association Inc.

RhoE deficiency alters postnatal subventricular zone development and the number of calbindin-expressing neurons in the olfactory bulb of mouse.

PubMed

Ballester-Lurbe, Begoña; González-Granero, Susana; Mocholí, Enric; Poch, Enric; García-Manzanares, María; Dierssen, Mara; Pérez-Roger, Ignacio; García-Verdugo, José M; Guasch, Rosa M; Terrado, José

2015-11-01

The subventricular zone represents an important reservoir of progenitor cells in the adult brain. Cells from the subventricular zone migrate along the rostral migratory stream and reach the olfactory bulb, where they originate different types of interneurons. In this work, we have analyzed the role of the small GTPase RhoE/Rnd3 in subventricular zone cell development using mice-lacking RhoE expression. Our results show that RhoE null mice display a remarkable postnatal broadening of the subventricular zone and caudal rostral migratory stream. This broadening was caused by an increase in progenitor proliferation, observed in the second postnatal week but not before, and by an altered migration of the cells, which appeared in disorganized cell arrangements that impaired the appropriate contact between cells in the rostral migratory stream. In addition, the thickness of the granule cell layer in the olfactory bulb was reduced, although the density of granule cells did not differ between wild-type and RhoE null mice. Finally, the lack of RhoE expression affected the olfactory glomeruli inducing a severe reduction of calbindin-expressing interneurons in the periglomerular layer. This was already evident in the newborns and even more pronounced 15 days later when RhoE null mice displayed 89% less cells than control mice. Our results indicate that RhoE has pleiotropic functions on subventricular cells because of its role in proliferation and tangential migration, affecting mainly the development of calbindin-expressing cells in the olfactory bulb.

Chronic Fluoxetine Induces the Enlargement of Perforant Path-Granule Cell Synapses in the Mouse Dentate Gyrus

PubMed Central

Kitahara, Yosuke; Ohta, Keisuke; Hasuo, Hiroshi; Shuto, Takahide; Kuroiwa, Mahomi; Sotogaku, Naoki; Togo, Akinobu; Nakamura, Kei-ichiro; Nishi, Akinori

2016-01-01

A selective serotonin reuptake inhibitor is the most commonly prescribed antidepressant for the treatment of major depression. However, the mechanisms underlying the actions of selective serotonin reuptake inhibitors are not fully understood. In the dentate gyrus, chronic fluoxetine treatment induces increased excitability of mature granule cells (GCs) as well as neurogenesis. The major input to the dentate gyrus is the perforant path axons (boutons) from the entorhinal cortex (layer II). Through voltage-sensitive dye imaging, we found that the excitatory neurotransmission of the perforant path synapse onto the GCs in the middle molecular layer of the mouse dentate gyrus (perforant path-GC synapse) is enhanced after chronic fluoxetine treatment (15 mg/kg/day, 14 days). Therefore, we further examined whether chronic fluoxetine treatment affects the morphology of the perforant path-GC synapse, using FIB/SEM (focused ion beam/scanning electron microscopy). A three-dimensional reconstruction of dendritic spines revealed the appearance of extremely large-sized spines after chronic fluoxetine treatment. The large-sized spines had a postsynaptic density with a large volume. However, chronic fluoxetine treatment did not affect spine density. The presynaptic boutons that were in contact with the large-sized spines were large in volume, and the volumes of the mitochondria and synaptic vesicles inside the boutons were correlated with the size of the boutons. Thus, the large-sized perforant path-GC synapse induced by chronic fluoxetine treatment contains synaptic components that correlate with the synapse size and that may be involved in enhanced glutamatergic neurotransmission. PMID:26788851

Isolation of zymogen granules from rat pancreas.

PubMed

Rindler, Michael J

2006-01-01

This unit describes methods for preparing zymogen granules from rat pancreas. Zymogen granules are storage organelles in pancreatic acinar cells containing digestive enzymes that are released into the pancreatic duct. The protocols in this unit take advantage of the large size (up to 1 microm diameter) and high density (>1.20 g/cm(3) on sucrose gradients) of the granules as compared to other cellular organelles. They use a combination of differential sedimentation and density gradient separation to accomplish the purification. Similar procedures can be used to isolate zymogen granules from mouse pancreas and canine pancreas. A protocol for preparing zymogen granules from dog pancreas is also included.

Multi-species impurity granule injection and mass deposition projections in NSTX-U discharges

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lunsford, R.; Bortolon, A.; Roquemore, A. L.

Here, by employing a neutral gas shielding (NGS) model to characterize impurity granule injection, the ablation rates for three different species of granule: lithium, boron, and carbon, are determined. Utilizing the duration of ablation events recorded on experiments performed at DIII-D to calibrate the NGS model, we quantify the ablation rate with respect to the plasma density profile. The species-specific granule shielding constant is then used to model granule ablation within NSTX-U discharges. Simulations of 300, 500 and 700 micron diameter granules injected at 50 m s –1 are presented for NSTX-U L-mode type plasmas, as well as H-mode dischargesmore » with low natural ELM frequency. Additionally, ablation calculations of 500 micron granules of each species are presented at velocities ranging from 50–150 m s –1. In H-mode discharges these simulations show that the majority of the injected granule is ablated within or just past the edge steep gradient region. At this radial position, the perturbation to the background plasma generated by the ablating granule can lead to conditions advantageous for the rapid triggering of ELM crashes.« less

Multi-species impurity granule injection and mass deposition projections in NSTX-U discharges

DOE PAGES

Lunsford, R.; Bortolon, A.; Roquemore, A. L.; ...

2017-05-16

Here, by employing a neutral gas shielding (NGS) model to characterize impurity granule injection, the ablation rates for three different species of granule: lithium, boron, and carbon, are determined. Utilizing the duration of ablation events recorded on experiments performed at DIII-D to calibrate the NGS model, we quantify the ablation rate with respect to the plasma density profile. The species-specific granule shielding constant is then used to model granule ablation within NSTX-U discharges. Simulations of 300, 500 and 700 micron diameter granules injected at 50 m s –1 are presented for NSTX-U L-mode type plasmas, as well as H-mode dischargesmore » with low natural ELM frequency. Additionally, ablation calculations of 500 micron granules of each species are presented at velocities ranging from 50–150 m s –1. In H-mode discharges these simulations show that the majority of the injected granule is ablated within or just past the edge steep gradient region. At this radial position, the perturbation to the background plasma generated by the ablating granule can lead to conditions advantageous for the rapid triggering of ELM crashes.« less

Evaluating scale-up rules of a high-shear wet granulation process.

PubMed

Tao, Jing; Pandey, Preetanshu; Bindra, Dilbir S; Gao, Julia Z; Narang, Ajit S

2015-07-01

This work aimed to evaluate the commonly used scale-up rules for high-shear wet granulation process using a microcrystalline cellulose-lactose-based low drug loading formulation. Granule properties such as particle size, porosity, flow, and tabletability, and tablet dissolution were compared across scales using scale-up rules based on different impeller speed calculations or extended wet massing time. Constant tip speed rule was observed to produce slightly less granulated material at the larger scales. Longer wet massing time can be used to compensate for the lower shear experienced by the granules at the larger scales. Constant Froude number and constant empirical stress rules yielded granules that were more comparable across different scales in terms of compaction performance and tablet dissolution. Granule porosity was shown to correlate well with blend tabletability and tablet dissolution, indicating the importance of monitoring granule densification (porosity) during scale-up. It was shown that different routes can be chosen during scale-up to achieve comparable granule growth and densification by altering one of the three parameters: water amount, impeller speed, and wet massing time. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Pharmaceutical production of tableting granules in an ultra-small-scale high-shear granulator as a pre-formulation study.

PubMed

Ogawa, Tatsuya; Uchino, Tomohiro; Takahashi, Daisuke; Izumi, Tsuyoshi; Otsuka, Makoto

2012-11-01

In some of drug developments, the amount of bulk drug powder to use in early stages is limited and it is not easy to supply a sufficient drug amount for conventional preparation methods. Therefore, an ultra-small-scale high-shear granulator (less than 5 g) (USG) was developed and applied to small-scale granulation as a pre-formulation. The sample powder consisted of 66.5% lactose, 28.5% microcrystalline cellulose and 5.0% hydroxypropylcellulose. The granules were obtained to agitate 5 g of the sample powder with 1.0 mL of water at 300 rpm for 5 min after pre-powder mixing for 3 min by the USG and the manual hand (HM) methods. The granules were evaluated by the 10% and 90% accumulated particle size and the recoveries of the granules and the powder solid. Median particle size for the USG and the HM methods was 159.2 ± 2.3 and 270.9 ± 14.9 µm, respectively. The USG method had a narrower particle size distribution than those by the HM method. The recovery of the granules by USG was significantly larger than that by the HM method. Characteristics of all of the granules indicated that the USG method could produce higher quality granules within a shorter time than the HM methods.

Three novel proteins co-localise with polyhydroxybutyrate (PHB) granules in Rhodospirillum rubrum S1.

PubMed

Narancic, Tanja; Scollica, Elisa; Cagney, Gerard; O'Connor, Kevin E

2018-04-01

Polyhydroxybutyrate (PHB), a biodegradable polymer accumulated by bacteria is deposited intracellularly in the form of inclusion bodies often called granules. The granules are supramolecular complexes harbouring a varied number of proteins on their surface, which have specific but incompletely characterised functions. By comparison with other organisms that produce biodegradable polymers, only two phasins have been described to date for Rhodosprillum rubrum, raising the possibility that more await discovery. Using a comparative proteomics strategy to compare the granules of wild-type R. rubrum with a PHB-negative mutant housing artificial PHB granules, we identified four potential PHB granules' associated proteins. These were: Q2RSI4, an uncharacterised protein; Q2RWU9, annotated as an extracellular solute-binding protein; Q2RQL4, annotated as basic membrane lipoprotein; and Q2RQ51, annotated as glucose-6-phosphate isomerase. In silico analysis revealed that Q2RSI4 harbours a Phasin_2 family domain and shares low identity with a single-strand DNA-binding protein from Sphaerochaeta coccoides. Fluorescence microscopy found that three proteins Q2RSI4, Q2EWU9 and Q2RQL4 co-localised with PHB granules. This work adds three potential new granule associated proteins to the repertoire of factors involved in bacterial storage granule formation, and confirms that proteomics screens are an effective strategy for discovery of novel granule associated proteins.

Deubiquitylases USP5 and USP13 are recruited to and regulate heat-induced stress granules through their deubiquitylating activities.

PubMed

Xie, Xuan; Matsumoto, Shunsuke; Endo, Akinori; Fukushima, Toshiaki; Kawahara, Hiroyuki; Saeki, Yasushi; Komada, Masayuki

2018-04-12

Stress granules are transient cytoplasmic foci induced by various stresses that contain translation-stalled mRNAs and RNA-binding proteins. They are proposed to modulate mRNA translation and stress responses. Here, we show that the deubiquitylases USP5 and USP13 are recruited to heat-induced stress granules. Heat-induced stress granules also contained K48- and K63-linked ubiquitin chains. Depletion of USP5 or USP13 resulted in elevated ubiquitin chain levels and accelerated assembly of heat-induced stress granules, suggesting that these enzymes regulate the stability of the stress granules through their ubiquitin isopeptidase activity. Moreover, disassembly of heat-induced stress granules after returning the cells to normal temperatures was markedly repressed by individual depletion of USP5 or USP13. Finally, overexpression of a ubiquitin mutant lacking the C-terminal diglycine motif caused the accumulation of unanchored ubiquitin chains and the repression of the disassembly of heat-induced stress granules. As unanchored ubiquitin chains are preferred substrates for USP5, we suggest that USP5 regulates the assembly and disassembly of heat-induced stress granules by mediating the hydrolysis of unanchored ubiquitin chains while USP13 regulates stress granules through deubiquitylating protein-conjugated ubiquitin chains.This article has an associated First Person interview with the first author of the paper. © 2018. Published by The Company of Biologists Ltd.

Role of the Caenorhabditis elegans multidrug resistance gene, mrp-4, in gut granule differentiation.

PubMed

Currie, Erin; King, Brian; Lawrenson, Andrea L; Schroeder, Lena K; Kershner, Aaron M; Hermann, Greg J

2007-11-01

Caenorhabditis elegans gut granules are lysosome-related organelles with birefringent contents. mrp-4, which encodes an ATP-binding cassette (ABC) transporter homologous to mammalian multidrug resistance proteins, functions in the formation of gut granule birefringence. mrp-4(-) embryos show a delayed appearance of birefringent material in the gut granule but otherwise appear to form gut granules properly. mrp-4(+) activity is required for the extracellular mislocalization of birefringent material, body-length retraction, and NaCl sensitivity, phenotypes associated with defective gut granule biogenesis exhibited by embryos lacking the activity of GLO-1/Rab38, a putative GLO-1 guanine nucleotide exchange factor GLO-4, and the AP-3 complex. Multidrug resistance protein (MRP)-4 localizes to the gut granule membrane, consistent with it playing a direct role in the transport of molecules that compose and/or facilitate the formation of birefringent crystals within the gut granule. However, MRP-4 is also present in oocytes and early embryos, and our genetic analyses indicate that its site of action in the formation of birefringent material may not be limited to just the gut granule in embryos. In a search for genes that function similarly to mrp-4(+), we identified WHT-2, another ABC transporter that acts in parallel to MRP-4 for the formation of birefringent material in the gut granule.

HIGH-SHEAR GRANULATION PROCESS: INFLUENCE OF PROCESSING PARAMETERS ON CRITICAL QUALITY ATTRIBUTES OF ACETAMINOPHEN GRANULES AND TABLETS USING DESIGN OF EXPERIMENT APPROACH.

PubMed

Fayed, Mohamed H; Abdel-Rahman, Sayed I; Alanazi, Fars K; Ahmed, Mahrous O; Tawfeek, Hesham M; Al-Shedfat, Ramadan I

2017-01-01

Application of quality by design (QbD) in high shear granulation process is critical and need to recognize the correlation between the granulation process parameters and the properties of intermediate (granules) and corresponding final product (tablets). The present work examined the influence of water amount (X,) and wet massing time (X2) as independent process variables on the critical quality attributes of granules and corresponding tablets using design of experiment (DoE) technique. A two factor, three level (32) full factorial design was performed; each of these variables was investigated at three levels to characterize their strength and interaction. The dried granules have been analyzed for their size distribution, density and flow pattern. Additionally, the produced tablets have been investigated for weight uniformity, crushing strength, friability and percent capping, disintegration time and drug dissolution. Statistically significant impact (p < 0.05) of water amount was identified for granule growth, percent fines and distribution width and flow behavior. Granule density and compressibility were found to be significantly influenced (p < 0.05) by the two operating conditions. Also, water amount has significant effect (p < 0.05) on tablet weight unifornity, friability and percent capping. Moreover, tablet disintegration time and drug dissolution appears to be significantly influenced (p < 0.05) by the two process variables. On the other hand, the relationship of process parameters with critical quality attributes of granule and final product tablet was identified and correlated. Ultimately, a judicious selection of process parameters in high shear granulation process will allow providing product of desirable quality.

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

PubMed

Rehder, Sönke; Christensen, Niels Peter Aae; Rantanen, Jukka; Rades, Thomas; Leopold, Claudia S

2013-11-01

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 influenced by the excipients, since in presence of calcium hydrogenphosphate, the poorly water-soluble salt calcium tartrate monohydrate was formed at high relative humidity. Interestingly, compactability was increased by cocrystal formation compared to that of the reference granules (piracetam and the respective excipients). The drug release was slightly decreased by cocrystal formation, most likely due to the lower solubility of the cocrystal. In the presence of calcium hydrogenphosphate however, no influence of cocrystal formation on either compactability or on drug release were observed, compared with the reference tablets. It was concluded that high-shear wet granulation is a valuable, however complex, manufacturing method for cocrystals. Cocrystal formation may influence compactability and drug release and thus affect drug performance and should be investigated during pre-formulation. Copyright © 2013 Elsevier B.V. All rights reserved.

Proteome Profile of Starch Granules Purified from Rice (Oryza sativa) Endosperm

PubMed Central

Xing, Shihai; Meng, Xiaoxi; Zhou, Lihui; Mujahid, Hana; Zhao, Chunfang; Zhang, Yadong; Wang, Cailin; Peng, Zhaohua

2016-01-01

Starch is the most important food energy source in cereals. Many of the known enzymes involved in starch biosynthesis are partially or entirely granule-associated in the endosperm. Studying the proteome of rice starch granules is critical for us to further understand the mechanisms underlying starch biosynthesis and packaging of starch granules in rice amyloplasts, consequently for the improvement of rice grain quality. In this article, we developed a protocol to purify starch granules from mature rice endosperm and verified the quality of purified starch granules by microscopy observations, I2 staining, and Western blot analyses. In addition, we found the phenol extraction method was superior to Tris-HCl buffer extraction method with respect to the efficiency in recovery of starch granule associated proteins. LC-MS/MS analysis showed identification of already known starch granule associated proteins with high confidence. Several proteins reported to be involved in starch synthesis in prior genetic studies in plants were also shown to be enriched with starch granules, either directly or indirectly, in our studies. In addition, our results suggested that a few additional candidate proteins may also be involved in starch synthesis. Furthermore, our results indicated that some starch synthesis pathway proteins are subject to protein acetylation modification. GO analysis and KEGG pathway enrichment analysis showed that the identified proteins were mainly located in plastids and involved in carbohydrate metabolism. This study substantially advances the understanding of the starch granule associated proteome in rice and post translational regulation of some starch granule associated proteins. PMID:27992503

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

PubMed

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

2013-10-01

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

Dextrose monohydrate as a non-animal sourced alternative diluent in high shear wet granulation tablet formulations.

PubMed

Mitra, Biplob; Wolfe, Chad; Wu, Sy-Juen

2018-05-01

The feasibility of dextrose monohydrate as a non-animal sourced diluent in high shear wet granulation (HSWG) tablet formulations was determined. Impacts of granulation solution amount and addition time, wet massing time, impeller speed, powder and solution binder, and dry milling speed and screen opening size on granule size, friability and density, and tablet solid fraction (SF) and tensile strength (TS) were evaluated. The stability of theophylline tablets TS, disintegration time (DT) and in vitro dissolution were also studied. Following post-granulation drying at 60 °C, dextrose monohydrate lost 9% water and converted into the anhydrate form. Higher granulation solution amounts and faster addition, faster impeller speeds, and solution binder produced larger, denser and stronger (less friable) granules. All granules were compressed into tablets with acceptable TS. Contrary to what is normally observed, denser and larger granules (at ≥21% water level) produced tablets with a higher TS. The TS of the weakest tablets increased the most after storage at both 25 °C/60% RH and 40 °C/75% RH. Tablet DT was higher for stronger granules and after storage. Tablet dissolution profiles for 21% or less water were comparable and did not change on stability. However, the dissolution profile for tablets prepared with 24% water was slower initially and continued to decrease on stability. The results indicate a granulation water amount of not more than 21% is required to achieve acceptable tablet properties. This study clearly demonstrated the utility of dextrose monohydrate as a non-animal sourced diluent in a HSWG tablet formulation.

Degradation of Glucan Primers in the Absence of Starch Synthase 4 Disrupts Starch Granule Initiation in Arabidopsis*

PubMed Central

Lu, Kuan-Jen; Stettler, Michaela; Streb, Sebastian

2016-01-01

Arabidopsis leaf chloroplasts typically contain five to seven semicrystalline starch granules. It is not understood how the synthesis of each granule is initiated or how starch granule number is determined within each chloroplast. An Arabidopsis mutant lacking the glucosyl-transferase, STARCH SYNTHASE 4 (SS4) is impaired in its ability to initiate starch granules; its chloroplasts rarely contain more than one large granule, and the plants have a pale appearance and reduced growth. Here we report that the chloroplastic α-amylase AMY3, a starch-degrading enzyme, interferes with granule initiation in the ss4 mutant background. The amy3 single mutant is similar in phenotype to the wild type under normal growth conditions, with comparable numbers of starch granules per chloroplast. Interestingly, the ss4 mutant displays a pleiotropic reduction in the activity of AMY3. Remarkably, complete abolition of AMY3 (in the amy3 ss4 double mutant) increases the number of starch granules produced in each chloroplast, suppresses the pale phenotype of ss4, and nearly restores normal growth. The amy3 mutation also restores starch synthesis in the ss3 ss4 double mutant, which lacks STARCH SYNTHASE 3 (SS3) in addition to SS4. The ss3 ss4 line is unable to initiate any starch granules and is thus starchless. We suggest that SS4 plays a key role in granule initiation, allowing it to proceed in a way that avoids premature degradation of primers by starch hydrolases, such as AMY3. PMID:27458017

Effects of Manufacturing Methods on Dissolution and Absorption of Ketoconazole in the Presence of Organic Acid as a pH Modifier.

PubMed

Adachi, Masashi; Hinatsu, Yuta; Kusamori, Kosuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Nakatani, Manabu; Wada, Koichi; Yamamoto, Akira

2017-05-01

Poorly water-soluble compounds have a potential risk of low and variable bioavailability caused by incomplete dissolution. Incorporation of organic acids as pH modifiers is effective method for solubility enhancement of basic compounds and requires no special technique and equipment. The purpose of this study was to evaluate the effect of manufacturing method on the extent of drug solubility enhancement. We successfully prepared the granules and tablets containing ketoconazole (KZ), which is weakly basic, as a model compound and citric acid as a pH modifier using conventional wet and dry granulations. KZ solubility under non-sink condition was enhanced with supersaturation using both wet and dry granulations. High-shear granulation was the most effective method in terms of KZ dissolution enhancement, because both an intimate contact and strong bonding between KZ and incorporated acid were achieved. KZ dissolved amount from the granules prepared by high-shear granulation was about eight times higher than that from the granules without the acid. The granulation involved to suppress a diffusion of acid dissolved, leading to the effectively maintained supersaturation state. The bioavailability of KZ after oral administration to rats was improved by applying high-shear granulation with citric acid independent of gastrointestinal pH. The granules prepared by high-shear granulation showed the bioavailability about 1.7-fold higher than that of the physical mixture in rats with and without neutralization of stomach. As a result, both the dissolution and absorption rates of KZ after oral administration were enhanced using conventional manufacturing technology.

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

USDA-ARS?s Scientific Manuscript database

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...

Gating of Long-Term Potentiation by Nicotinic Acetylcholine Receptors at the Cerebellum Input Stage

PubMed Central

Prestori, Francesca; Bonardi, Claudia; Mapelli, Lisa; Lombardo, Paola; Goselink, Rianne; De Stefano, Maria Egle; Gandolfi, Daniela; Mapelli, Jonathan; Bertrand, Daniel; Schonewille, Martijn; De Zeeuw, Chris; D’Angelo, Egidio

2013-01-01

The brain needs mechanisms able to correlate plastic changes with local circuit activity and internal functional states. At the cerebellum input stage, uncontrolled induction of long-term potentiation or depression (LTP or LTD) between mossy fibres and granule cells can saturate synaptic capacity and impair cerebellar functioning, which suggests that neuromodulators are required to gate plasticity processes. Cholinergic systems innervating the cerebellum are thought to enhance procedural learning and memory. Here we show that a specific subtype of acetylcholine receptors, the α7-nAChRs, are distributed both in cerebellar mossy fibre terminals and granule cell dendrites and contribute substantially to synaptic regulation. Selective α7-nAChR activation enhances the postsynaptic calcium increase, allowing weak mossy fibre bursts, which would otherwise cause LTD, to generate robust LTP. The local microperfusion of α7-nAChR agonists could also lead to in vivo switching of LTD to LTP following sensory stimulation of the whisker pad. In the cerebellar flocculus, α7-nAChR pharmacological activation impaired vestibulo-ocular-reflex adaptation, probably because LTP was saturated, preventing the fine adjustment of synaptic weights. These results show that gating mechanisms mediated by specific subtypes of nicotinic receptors are required to control the LTD/LTP balance at the mossy fibre-granule cell relay in order to regulate cerebellar plasticity and behavioural adaptation. PMID:23741401

Alkali-induced changes in functional properties and in vitro digestibility of wheat starch: the role of surface proteins and lipids.

PubMed

Wang, Shujun; Luo, Heyang; Zhang, Jian; Zhang, Yan; He, Zhonghu; Wang, Shuo

2014-04-23

The bread wheat starch was treated with 0.025 and 0.0625 M NaOH solution for 1, 2, and 3 weeks at 30 °C, and the changes in functionality and in vitro digestibility were evaluated. NaOH treatment reduced protein and lipid contents of wheat starch from 0.46 to 0.20% and from 0.59 to 0.25%, respectively. No significant changes were observed in the amylose content, relative crystallinity, and short-range order of double helices, but there was evidence showing that morphology of some starch granules was altered. The swelling power and starch solubility of wheat starch increased from 11.4 to 14.1 g/g and from 10.9 to 22.1%, respectively. The thermal transition temperatures were increased greatly, but the enthalpy change remained largely unchanged. Alkali treatment greatly decreased the pasting temperature, but the pasting viscosities were altered in different ways. The resistant starch (RS) content of wheat starch was decreased significantly from 69.9 to 45.2%, while the starch that is digested slowly (SDS) content was increased greatly from 13.6 to 34.5%. Our results showed that alkali treatment can significantly alter the functionality and in vitro digestibility of wheat starch granules by removing the surface proteins and lipids rather than significantly altering the internal structure of starch granules.

Probing the spatial dependence of the emission spectrum of single human retinal lipofuscin granules using near-field scanning optical microscopy.

PubMed

Haralampus-Grynaviski, N M; Lamb, L E; Simon, J D; Krogmeier, J R; Dunn, R C; Pawlak, A; Rózanowska, M; Sarna, T; Burke, J M

2001-08-01

The emission spectra of single lipofuscin granules are examined using spectrally resolved confocal microscopy and near-field scanning optical microscopy (NSOM). The emission spectrum varies among the granules examined revealing that individual granules are characterized by different distributions of fluorophores. The range of spectra observed is consistent with in vivo spectra of human retinal pigment epithelium cells. NSOM measurements reveal that the shape of the spectrum does not vary with position within the emissive regions of single lipofuscin granules. These results suggest that the relative distribution of fluorophores within the emissive regions of an individual granule is homogeneous on the spatial scale approximately 150 nm.

Aerobic granulation in a modified oxidation ditch with an adjustable volume intraclarifier.

PubMed

Li, Jun; Cai, Ang; Wang, Miao; Ding, Libin; Ni, Yongjiong

2014-04-01

A modified oxidation ditch (MOD) with an adjustable volume intraclarifier was proposed and used to achieve aerobic sludge granulation in continuous flow process. This MOD with working volume of 60L treated onsite wastewater from a town. Excellent aerobic granules with mean diameter of 600μm and sludge volume index (SVI) of 44mL/g were obtained in 120day. Bacterial community analysis revealed that most species from seed sludge were preserved in both MOD and granule SBR (G-SBR) except bacteria (Bacteroidetes) might be easily washed out during granulation. Some different bacterial communities were found in sludges from sequencing batch and continuous flow reactors. Presence of metal ions and inorganics in raw wastewater had positive effect on granule formation, but an adjustable volume intraclarifier for controlling selection pressure and deleting return sludge pump played a key role in aerobic sludge granulation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Preparation and evaluation of gelling granules to improve oral administration.

PubMed

Ito, Ikumi; Ito, Akihiko; Unezaki, Sakae

2015-06-01

We investigated the preparation of oral granules that are solid when stored and that will swell and gel via water absorption, to address problems experienced by patients when taking medication. Important physical properties of gelling granules include elasticity that is normally smooth, quick water absorption and swelling properties that allow easy swallowing. We selected gelatin (GEL), succinylated gelatin (SUC-GEL) and ι-carrageenan (CAR) as matrix polymers that can undergo gelation at room temperature or at cold temperatures. Saccharide and polyethylene glycol (PEG) were added to prepare the experimental granules. The best matrix gelling granule was SUC-GEL. When xylitol (XYL), sorbitol (SOR) and maltitol (MAL) were added, elasticity was improved, and PEG improved the granule's water absorption behavior, which is an important element involved in gelation. The best granules were prepared by selecting SUC-GEL as the matrix and adding a small amount of PEG and XYL in amounts equal to that of SUC-GEL.

Microtubules negatively regulate insulin secretion in pancreatic β cells

PubMed Central

Zhu, Xiaodong; Hu, Ruiying; Brissova, Marcela; Stein, Roland W.; Powers, Alvin C.; Gu, Guoqiang; Kaverina, Irina

2015-01-01

Summary For glucose-stimulated insulin secretion (GSIS) insulin granules have to be localized close to the plasma membrane. The role of microtubule-dependent transport in granule positioning and GSIS has been debated. Here, we report that microtubules, counterintuitively, restrict granule availability for secretion. In β cells, microtubules originate at the Golgi and form a dense non-radial meshwork. Non-directional transport along these microtubules limits granule dwelling at the cell periphery, restricting granule availability for secretion. High glucose destabilizes microtubules, decreasing their density; such local microtubule depolymerization is necessary for GSIS, likely because granule withdrawal from the cell periphery becomes inefficient. Consistently, microtubule depolymerization by nocodazole blocks granule withdrawal, increases their concentration at exocytic sites, and dramatically enhances GSIS in vitro and in mice. Furthermore, glucose-driven MT destabilization is balanced by new microtubule formation, which likely prevents over-secretion. Importantly, microtubule density is greater in dysfunctional β cells of diabetic mice. PMID:26418295

Effects of artemisinin sustained-release granules on mixed alga growth and microcystins production and release.

PubMed

Ni, Lixiao; Li, Danye; Hu, Shuzhen; Wang, Peifang; Li, Shiyin; Li, Yiping; Li, Yong; Acharya, Kumud

2015-12-01

To safely and effectively apply artemisinin sustained-release granules to control and prevent algal water-blooms, the effects of artemisinin and its sustained-release granules on freshwater alga (Scenedesmus obliquus (S. obliquus) and Microcystis aeruginosa (M. aeruginosa)), as well as the production and release of microcystins (MCs) were studied. The results showed that artemisinin sustained-release granules inhibited the growth of M. aeruginosa (above 95% IR) and S. obliquus (about 90% IR), with M. aeruginosa more sensitive. The artemisinin sustained-release granules had a longer inhibition effect on growth of pure algae and algal coexistence than direct artemisinin dosing. The artemisinin sustained-release granules could decrease the production and release of algal toxins due to the continued stress of artemisinin released from artemisinin sustained-release granules. There was no increase in the total amount of MC-LR in the algal cell culture medium.

Low-calorie bread baked with charred cellulose granules and wheat flour to eliminate toxic xanthene food dye in the alimentary canal.

PubMed

Tabara, Aya; Yamane, Chihiro; Seguchi, Masaharu

2012-01-01

We baked low-calorie bread by mixing charred cellulose granules with wheat flour, using the charred cellulose granules to eliminate toxic xanthene food dyes contained in processed foods from the alimentary canal. The size of the charred cellulose granules played an important role in determining good breadmaking properties in respect of the bread height (mm) and specific volume (SV, cm3/g). Charred cellulose granules with a diameter above 270 μm were blended with wheat flour at 10% to obtain bread with a lower caloric content (1020 kcal/gram of bread) than the control bread (1126 kcal) made solely from wheat flour. The charred cellulose granules taken out from the bread adsorbed toxic xanthene food dyes at around pH 6.5, such that toxic food dyes taken into the alimentary canal were excreted in the feces with the non-digestible cellulose granules.

Specific lignin accumulation in granulated juice sacs of Citrus maxima.

PubMed

Wu, Jia-Ling; Pan, Teng-Fei; Guo, Zhi-Xiong; Pan, Dong-Ming

2014-12-17

Juice sac granulation occurring in pummelo fruits [Citrus maxima (Burm.) Merr.] is an undesirable trait, and the underlying mechanism remains unresolved. Previous studies have shown that lignin metabolism is closely associated with the process of juice sac granulation. Here, a method suitable for lignin isolation from pummelo tissues is established. Acetylated lignins from different pummelo tissues and cultivars were analyzed by HSQC NMR. The results showed that lignins in granulated juice sacs were characterized by an extremely high abundance of guaiacyl units (91.13-96.82%), in contrast to lignins from other tissues, including leaves, stems, and segment membranes. The abnormally accumulated lignins in granulated juice sacs were specific and mainly polymerized from coniferyl alcohol. No significant difference was found in lignin types among various cultivars. These findings indicated that the mechanism of juice sac granulation might be similar among various cultivars, although very different degrees of juice sac granulation can be observed.

Application of grey system theory on the influencing parameters of aerobic granulation in SBR.

PubMed

Bindhu, B K; Madhu, G

2017-09-01

Aerobic granulation is a promising technology for wastewater treatment. Four operational parameters were selected as influencing factors for this study. Aerobic granulation was experimented with three different values of organic loading rate (3, 6 and 9 kg COD m -3  d -1 ), superficial upflow air velocity (SUAV) (2, 3 and 4 cm s -1 ), settling time (3, 5 and 10 min) and volume exchange ratio (25%, 50% and 75%) in sequencing batch reactor in nine trials for the optimal performance of aerobic granulation. The influence of compared parameters on five reference parameters (sludge volume index (SVI), time taken for the appearance of granules, size and specific gravity of granules and chemical oxygen demand (COD) removal) was analyzed using grey system theory. The grey relational coefficients and grey entropy relational grade of each parameter were calculated. Hydrodynamic shear force in terms of SUAV was found to have the greatest influence on granule appearance, specific gravity of granules and COD removal efficiency. SVI is greatly affected by settling time. The optimal scopes of all the compared parameters were found.

Rapid aerobic granulation in an SBR treating piggery wastewater by seeding sludge from a municipal WWTP.

PubMed

Liu, Jun; Li, Jun; Wang, Xiaodong; Zhang, Qi; Littleton, Helen

2017-01-01

Aerobic sludge granulation was rapidly obtained in the erlenmeyer bottle and sequencing batch reactor (SBR) using piggery wastewater. Aerobic granulation occurred on day 3 and granules with mean diameter of 0.2mm and SVI 30 of 20.3mL/g formed in SBR on day 18. High concentrations of Ca and Fe in the raw piggery wastewater and operating mode accelerated aerobic granulation, even though the seed sludge was from a municipal wastewater treatment plant (WWTP). Alpha diversity analysis revealed Operational Taxonomic Units, Shannon, ACE and Chao 1 indexes in aerobic granules were 2013, 5.51, 4665.5 and 3734.5, which were obviously lower compared to seed sludge. The percentages of major microbial communities, such as Proteobacteria, Bacteroidetes and Firmicutes were obviously higher in aerobic granules than seed sludge. Chloroflexi, Planctomycetes, Actinobacteria, TM7 and Acidobacteria showed much higher abundances in the inoculum. The main reasons might be the characteristics of raw piggery wastewater and granule structure. Copyright © 2016. Published by Elsevier B.V.

Fabrication of dicalcium phosphate dihydrate-coated β-TCP granules and evaluation of their osteoconductivity using experimental rats.

PubMed

Shariff, Khairul Anuar; Tsuru, Kanji; Ishikawa, Kunio

2017-06-01

β-Tricalcium phosphate (β-TCP) has attracted much attention as an artificial bone substitute owing to its biocompatibility and osteoconductivity. In this study, osteoconductivity of β-TCP bone substitute was enhanced without using growth factors or cells. Dicalcium phosphate dihydrate (DCPD), which is known to possess the highest solubility among calcium phosphates, was coated on β-TCP granules by exposing their surface with acidic calcium phosphate solution. The amount of coated DCPD was regulated by changing the reaction time between β-TCP granules and acidic calcium phosphate solution. Histomorphometry analysis obtained from histological results revealed that the approximately 10mol% DCPD-coated β-TCP granules showed the largest new bone formation compared to DCPD-free β-TCP granules, approximately 2.5mol% DCPD-coated β-TCP granules, or approximately 27mol% DCPD-coated β-TCP granules after 2 and 4weeks of implantation. Based on this finding, we demonstrate that the osteoconductivity of β-TCP granules could be improved by coating their surface with an appropriate amount of DCPD. Copyright © 2017 Elsevier B.V. All rights reserved.

Lysine acetyltransferase NuA4 and acetyl-CoA regulate glucose-deprived stress granule formation in Saccharomyces cerevisiae

PubMed Central

Huard, Sylvain; Morettin, Alan; Fullerton, Morgan D.; Côté, Jocelyn

2017-01-01

Eukaryotic cells form stress granules under a variety of stresses, however the signaling pathways regulating their formation remain largely unknown. We have determined that the Saccharomyces cerevisiae lysine acetyltransferase complex NuA4 is required for stress granule formation upon glucose deprivation but not heat stress. Further, the Tip60 complex, the human homolog of the NuA4 complex, is required for stress granule formation in cancer cell lines. Surprisingly, the impact of NuA4 on glucose-deprived stress granule formation is partially mediated through regulation of acetyl-CoA levels, which are elevated in NuA4 mutants. While elevated acetyl-CoA levels suppress the formation of glucose-deprived stress granules, decreased acetyl-CoA levels enhance stress granule formation upon glucose deprivation. Further our work suggests that NuA4 regulates acetyl-CoA levels through the Acetyl-CoA carboxylase Acc1. Altogether this work establishes both NuA4 and the metabolite acetyl-CoA as critical signaling pathways regulating the formation of glucose-deprived stress granules. PMID:28231279

GABAergic excitation after febrile seizures induces ectopic granule cells and adult epilepsy.

PubMed

Koyama, Ryuta; Tao, Kentaro; Sasaki, Takuya; Ichikawa, Junya; Miyamoto, Daisuke; Muramatsu, Rieko; Matsuki, Norio; Ikegaya, Yuji

2012-08-01

Temporal lobe epilepsy (TLE) is accompanied by an abnormal location of granule cells in the dentate gyrus. Using a rat model of complex febrile seizures, which are thought to be a precipitating insult of TLE later in life, we report that aberrant migration of neonatal-generated granule cells results in granule cell ectopia that persists into adulthood. Febrile seizures induced an upregulation of GABA(A) receptors (GABA(A)-Rs) in neonatally generated granule cells, and hyperactivation of excitatory GABA(A)-Rs caused a reversal in the direction of granule cell migration. This abnormal migration was prevented by RNAi-mediated knockdown of the Na(+)K(+)2Cl(-) co-transporter (NKCC1), which regulates the excitatory action of GABA. NKCC1 inhibition with bumetanide after febrile seizures rescued the granule cell ectopia, susceptibility to limbic seizures and development of epilepsy. Thus, this work identifies a previously unknown pathogenic role of excitatory GABA(A)-R signaling and highlights NKCC1 as a potential therapeutic target for preventing granule cell ectopia and the development of epilepsy after febrile seizures.

Optimization for blast furnace slag dry cooling granulation device

NASA Astrophysics Data System (ADS)

Dazhan, Sheng; Yali, Wang; Ruiyun, Wang; Suping, Cui; Xiaoyu, Ma

2017-03-01

Since the large accumulation amount of blast furnace slag (BFS) with recycling value, it has become a hot topic for recovery utilization. Compared with the existing various BFS granulation process, the dry granulation process can promote the use of blast furnace granulated slag as cement substitute and concrete admixtures. Our research group developed a novel dry cooling granulation experiment device to treat BFS. However, there are still some problems to be solved. The purpose of this research is to improve the cooling and granulation efficiency of the existing dry type cooling equipment. This topic uses the FLUENT simulation software to study the impact of the number of air inlet on the cooling effect of the device. The simulation result is that the device possessing eight air inlets can increase the number of hot and cold gas exchanged, resulting in a better cooling effect. According to the power consumption, LCA analysis was carried out on the cooling granulation process. The results show that the device equipped eight air inlets not only improved the original equipment cooling granulation effect, but also increased resource utilization ratio, realized energy-saving and emission reduction.

Composition of the carbohydrate granules of the cyanobacterium, Cyanothece sp. strain ATCC 51142

NASA Technical Reports Server (NTRS)

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

1997-01-01

Cyanothece sp. strain ATCC 51142 is an aerobic, unicellular, diazotrophic cyanobacterium that temporally separates O2-sensitive N2 fixation from oxygenic photosynthesis. The energy and reducing power needed for N2 fixation appears to be generated by an active respiratory apparatus that utilizes the contents of large interthylakoidal carbohydrate granules. We report here on the carbohydrate and protein composition of the granules of Cyanothece sp. strain ATCC 51142. The carbohydrate component is a glucose homopolymer with branches every nine residues and is chemically identical to glycogen. Granule-associated protein fractions showed temporal changes in the number of proteins and their abundance during the metabolic oscillations observed under diazotrophic conditions. There also were temporal changes in the protein pattern of the granule-depleted supernatant fractions from diazotrophic cultures. None of the granule-associated proteins crossreacted with antisera directed against several glycogen-metabolizing enzymes or nitrogenase, although these proteins were tentatively identified in supernatant fractions. It is suggested that the granule-associated proteins are structural proteins required to maintain a complex granule architecture.

Bioaugmentation of half-matured granular sludge with special microbial culture promoted establishment of 2,4-dichlorophenoxyacetic acid degrading aerobic granules.

PubMed

Quan, Xiangchun; Ma, Jingyun; Xiong, Weicong; Wang, Xinrui

2015-06-01

Aerobic granular sludge degrading recalcitrant compounds are generally hard to be cultivated. This study investigated the feasibility of cultivating 2,4-dichlorophenoxyacetic acid (2,4-D) degrading aerobic granules using half-matured sludge granules pre-grown on glucose as the seeds and bioaugmentation with a 2,4-D degrading strain Achromobacter sp. QXH. Results showed that bioaugmentation promoted the steady transformation of glucose-grown granules to 2,4-D degrading sludge granules and fast establishment of 2,4-D degradation ability. The 2,4-D degradation rate of the bioaugmented granules was enhanced by 36-62 % compared to the control at 2,4-D concentrations of 144-565 mg/L on Day 18. The inoculated strain was incorporated into the half-matured granules successfully and survived till the end of operation (220 days). Sludge granules at a mean size of 420 µm and capable of utilizing 500 mg/L 2,4-D as the sole carbon source were finally obtained. Sludge microbial community shifted slightly during the whole operation and the dominant bacteria species belonged to Proteobacteria.

Glucokinase is an integral component of the insulin granules in glucose-responsive insulin secretory cells and does not translocate during glucose stimulation.

PubMed

Arden, Catherine; Harbottle, Andrew; Baltrusch, Simone; Tiedge, Markus; Agius, Loranne

2004-09-01

The association of glucokinase with insulin secretory granules has been shown by cell microscopy techniques. We used MIN6 insulin-secretory cells and organelle fractionation to determine the effects of glucose on the subcellular distribution of glucokinase. After permeabilization with digitonin, 50% of total glucokinase remained bound intracellularly, while 30% was associated with the 13,000g particulate fraction. After density gradient fractionation of the organelles, immunoreactive glucokinase was distributed approximately equally between dense insulin granules and low-density organelles that cofractionate with mitochondria. Although MIN6 cells show glucose-responsive insulin secretion, glucokinase association with the granules and low-density organelles was not affected by glucose. Subfractionation of the insulin granule components by hypotonic lysis followed by sucrose gradient centrifugation showed that glucokinase colocalized with the granule membrane marker phogrin and not with insulin. PFK2 (6-phosphofructo-2-kinase-2/fructose-2,6-bisphosphatase)/FDPase-2, a glucokinase-binding protein, and glyceraldehyde phosphate dehydrogenase, which has been implicated in granule fusion, also colocalized with glucokinase after hypotonic lysis or detergent extaction of the granules. The results suggest that glucokinase is an integral component of the granule and does not translocate during glucose stimulation.

IoT Big-Data Centred Knowledge Granule Analytic and Cluster Framework for BI Applications: A Case Base Analysis.

PubMed

Chang, Hsien-Tsung; Mishra, Nilamadhab; Lin, Chung-Chih

2015-01-01

The current rapid growth of Internet of Things (IoT) in various commercial and non-commercial sectors has led to the deposition of large-scale IoT data, of which the time-critical analytic and clustering of knowledge granules represent highly thought-provoking application possibilities. The objective of the present work is to inspect the structural analysis and clustering of complex knowledge granules in an IoT big-data environment. In this work, we propose a knowledge granule analytic and clustering (KGAC) framework that explores and assembles knowledge granules from IoT big-data arrays for a business intelligence (BI) application. Our work implements neuro-fuzzy analytic architecture rather than a standard fuzzified approach to discover the complex knowledge granules. Furthermore, we implement an enhanced knowledge granule clustering (e-KGC) mechanism that is more elastic than previous techniques when assembling the tactical and explicit complex knowledge granules from IoT big-data arrays. The analysis and discussion presented here show that the proposed framework and mechanism can be implemented to extract knowledge granules from an IoT big-data array in such a way as to present knowledge of strategic value to executives and enable knowledge users to perform further BI actions.