Linking morphology with activity through the lifetime of pretreated PtNi nanostructured thin film catalysts

DOE PAGES

Cullen, David A.; Lopez-Haro, Miguel; Bayle-Guillemaud, Pascale; ...

2015-04-10

In this study, the nanoscale morphology of highly active Pt 3Ni 7 nanostructured thin film fuel cell catalysts is linked with catalyst surface area and activity following catalyst pretreatments, conditioning and potential cycling. The significant role of fuel cell conditioning on the structure and composition of these extended surface catalysts is demonstrated by high resolution imaging, elemental mapping and tomography. The dissolution of Ni during fuel cell conditioning leads to highly complex, porous structures which were visualized in 3D by electron tomography. Quantification of the rendered surfaces following catalyst pretreatment, conditioning, and cycling shows the important role pore structure playsmore » in surface area, activity, and durability.« less

[Peculiarities of mitosis and nucleolar characteristics of the birch plantlets under antropogenous pollution].

PubMed

Butorina, A K; Kalaev, V N; Karpova, S S

2002-01-01

A study was made of some cytogenetic characteristics (mitotic activity, the level and spectrum of pathological mitosis, nucleolar features in root tip cells) in birch plantlets. The seeds were collected in four districts of Voronezh and in the ecologically clean territory. The index of mitotic activity has a considerable resistance to anthropogenous pollution. In the experimental areas, the level and spectrum of pathological mitosis increase. In contaminated areas we observed changes of nucleolar characteristics (the increased surface area of nucleoli and their higher number in cells, the increased number of cells with highly active types of nucleoli, the appearance of residual nucleoli). These changes can be considered as possible mechanisms of adaptation to stress due to antropogenous pollution. It is suggested that the use of such indices as single nucleolar surface area or the level of pathological mitosis may be perspective for cytogenetic monitoring of the environment, and for prognostification of environmental conditions suitable or unsuitable for the human health.

Quantitative structure-cytotoxicity relationship of phenylpropanoid amides.

PubMed

Shimada, Chiyako; Uesawa, Yoshihiro; Ishihara, Mariko; Kagaya, Hajime; Kanamoto, Taisei; Terakubo, Shigemi; Nakashima, Hideki; Takao, Koichi; Saito, Takayuki; Sugita, Yoshiaki; Sakagami, Hiroshi

2014-07-01

A total of 12 phenylpropanoid amides were subjected to quantitative structure-activity relationship (QSAR) analysis, based on their cytotoxicity, tumor selectivity and anti-HIV activity, in order to investigate on their biological activities. Cytotoxicity against four human oral squamous cell carcinoma (OSCC) cell lines and three human oral normal cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Tumor selectivity was evaluated by the ratio of the mean CC50 (50% cytotoxic concentration) against normal oral cells to that against OSCC cell lines. Anti-HIV activity was evaluated by the ratio of CC50 to EC50 (50% cytoprotective concentration from HIV infection). Physicochemical, structural, and quantum-chemical parameters were calculated based on the conformations optimized by the LowModeMD method followed by density functional theory (DFT) method. Twelve phenylpropanoid amides showed moderate cytotoxicity against both normal and OSCC cell lines. N-Caffeoyl derivatives coupled with vanillylamine and tyramine exhibited relatively higher tumor selectivity. Cytotoxicity against normal cells was correlated with descriptors related to electrostatic interaction such as polar surface area and chemical hardness, whereas cytotoxicity against tumor cells correlated with free energy, surface area and ellipticity. The tumor-selective cytotoxicity correlated with molecular size (surface area) and electrostatic interaction (the maximum electrostatic potential). The molecular size, shape and ability for electrostatic interaction are useful parameters for estimating the tumor selectivity of phenylpropanoid amides. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Digital signaling decouples activation probability and population heterogeneity.

PubMed

Kellogg, Ryan A; Tian, Chengzhe; Lipniacki, Tomasz; Quake, Stephen R; Tay, Savaş

2015-10-21

Digital signaling enhances robustness of cellular decisions in noisy environments, but it is unclear how digital systems transmit temporal information about a stimulus. To understand how temporal input information is encoded and decoded by the NF-κB system, we studied transcription factor dynamics and gene regulation under dose- and duration-modulated inflammatory inputs. Mathematical modeling predicted and microfluidic single-cell experiments confirmed that integral of the stimulus (or area, concentration × duration) controls the fraction of cells that activate NF-κB in the population. However, stimulus temporal profile determined NF-κB dynamics, cell-to-cell variability, and gene expression phenotype. A sustained, weak stimulation lead to heterogeneous activation and delayed timing that is transmitted to gene expression. In contrast, a transient, strong stimulus with the same area caused rapid and uniform dynamics. These results show that digital NF-κB signaling enables multidimensional control of cellular phenotype via input profile, allowing parallel and independent control of single-cell activation probability and population heterogeneity.

The development of primary and secondary lymphoid tissues in the nurse shark Ginglymostoma cirratum: B-cell zones precede dendritic cell immigration and T-cell zone formation during ontogeny of the spleen.

PubMed

Rumfelt, L L; McKinney, E C; Taylor, E; Flajnik, M F

2002-08-01

Secondary lymphoid tissue and immunoglobulin (Ig) production in mammals is not fully developed at birth, requiring time postnatally to attain all features required for adaptive immune responses. The immune system of newborn sharks - the oldest vertebrate group having adaptive immunity - also displays immature characteristics such as low serum IgM concentration and high levels of IgM1gj, an innate-like Ig. Primary and secondary lymphoid tissues in sharks and other cartilaginous fish were identified previously, but their cellular organization was not examined in detail. In this study of nurse shark lymphoid tissue, we demonstrate that the adult spleen contains well-defined, highly vascularized white pulp (WP) areas, composed of a central T-cell zone containing a major histocompatibility complex (MHC) class II+ dendritic cell (DC) network and a small number of Ig+ secretory cells, surrounded by smaller zones of surface Ig+ (sIg+) B cells. In neonates, splenic WPs are exclusively B-cell zones containing sIgM+-MHC class IIlow B cells; thus compartmentalized areas with T cells and DCs, as well as surface Ig novel antigen receptor (sIgNAR)-expressing B cells are absent at birth. Not until the pups are 5 months old do these WP areas become adult-like; concomitantly, sIgNAR+ B cells are readily detectable, indicating that this Ig class requires a 'mature immune-responsive environment'. The epigonal organ is the major site of neonatal B lymphopoiesis, based on the presence of developing B cells and recombination-activating gene 1 (RAG1)/terminal deoxynucleotidyl transferase (TdT) expression, indicative of antigen receptor rearrangement; such expression persists into adult life, whereas the spleen has negligible lymphopoietic activity. In adults but not neonates, many secretory B cells reside in the epigonal organ, suggesting, like in mammals, that B cells home to this primary lymphoid tissue after activation in other areas of the body.

Phosphoric acid electric utility fuel cell technology development

NASA Astrophysics Data System (ADS)

Breault, R. D.; Briggs, T. A.; Congdon, J. V.; Demarche, T. E.; Gelting, R. L.; Goller, G. J.; Luoma, W. L.; McCloskey, M. W.; Mientek, A. P.; Obrien, J. J.

1991-04-01

The major objective of this effort was the advancement of cell and stack technology required to meet performance and cost criteria for fabrication and operation of a prototype large area, full height phosphoric acid fuel cell stack. The performance goal for the cell stack corresponded to a power density of 150 wsf, and the manufactured cost goal was a 510 $/kW reduction (in 1981 dollars) compared to existing 3.7 ft.(exp 2) active area cell stacks.

Responses of Cells in the Midbrain Near-Response Area in Monkeys with Strabismus

PubMed Central

Das, Vallabh E.

2012-01-01

Purpose. To investigate whether neuronal activity within the supraoculomotor area (SOA—monosynaptically connected to medial rectus motoneurons and encode vergence angle) of strabismic monkeys was correlated with the angle of horizontal misalignment and therefore helps to define the state of strabismus. Methods. Single-cell neural activity was recorded from SOA neurons in two monkeys with exotropia as they performed eye movement tasks during monocular viewing. Results. Horizontal strabismus angle varied depending on eye of fixation (dissociated horizontal deviation) and the activity of SOA cells (n = 35) varied in correlation with the angle of strabismus. Both near-response (cells that showed larger firing rates for smaller angles of exotropia) and far-response (cells that showed lower firing rates for smaller angles of exotropia) cells were identified. SOA cells showed no modulation of activity with changes in conjugate eye position as tested during smooth-pursuit, thereby verifying that the responses were related to binocular misalignment. SOA cell activity was also not correlated with change in horizontal misalignment due to A-patterns of strabismus. Comparison of SOA population activity in strabismic animals and normal monkeys (described in the literature) show that both neural thresholds and neural sensitivities are altered in the strabismic animals compared with the normal animals. Conclusions. SOA cell activity is important in determining the state of horizontal strabismus, possibly by altering vergence tone in extraocular muscle. The lack of correlated SOA activity with changes in misalignment due to A/V patterns suggest that circuits mediating horizontal strabismus angle and those that mediate A/V patterns are different. PMID:22562519

Orphan nuclear receptor TLX activates Wnt/β-catenin signalling to stimulate neural stem cell proliferation and self-renewal

PubMed Central

Qu, Qiuhao; Sun, Guoqiang; Li, Wenwu; Yang, Su; Ye, Peng; Zhao, Chunnian; Yu, Ruth T.; Gage, Fred H.; Evans, Ronald M.; Shi, Yanhong

2010-01-01

The nuclear receptor TLX (also known as NR2E1) is essential for adult neural stem cell self-renewal; however, the molecular mechanisms involved remain elusive. Here we show that TLX activates the canonical Wnt/β-catenin pathway in adult mouse neural stem cells. Furthermore, we demonstrate that Wnt/β-catenin signalling is important in the proliferation and self-renewal of adult neural stem cells in the presence of epidermal growth factor and fibroblast growth factor. Wnt7a and active β-catenin promote neural stem cell self-renewal, whereas the deletion of Wnt7a or the lentiviral transduction of axin, a β-catenin inhibitor, led to decreased cell proliferation in adult neurogenic areas. Lentiviral transduction of active β-catenin led to increased numbers of type B neural stem cells in the subventricular zone of adult brains, whereas deletion of Wnt7a or TLX resulted in decreased numbers of neural stem cells retaining bromodeoxyuridine label in the adult brain. Both Wnt7a and active β-catenin significantly rescued a TLX (also known as Nr2e1) short interfering RNA-induced deficiency in neural stem cell proliferation. Lentiviral transduction of an active β-catenin increased cell proliferation in neurogenic areas of TLX-null adult brains markedly. These results strongly support the hypothesis that TLX acts through the Wnt/β-catenin pathway to regulate neural stem cell proliferation and self-renewal. Moreover, this study suggests that neural stem cells can promote their own self-renewal by secreting signalling molecules that act in an autocrine/paracrine mode. PMID:20010817

Orphan nuclear receptor TLX activates Wnt/beta-catenin signalling to stimulate neural stem cell proliferation and self-renewal.

PubMed

Qu, Qiuhao; Sun, Guoqiang; Li, Wenwu; Yang, Su; Ye, Peng; Zhao, Chunnian; Yu, Ruth T; Gage, Fred H; Evans, Ronald M; Shi, Yanhong

2010-01-01

The nuclear receptor TLX (also known as NR2E1) is essential for adult neural stem cell self-renewal; however, the molecular mechanisms involved remain elusive. Here we show that TLX activates the canonical Wnt/beta-catenin pathway in adult mouse neural stem cells. Furthermore, we demonstrate that Wnt/beta-catenin signalling is important in the proliferation and self-renewal of adult neural stem cells in the presence of epidermal growth factor and fibroblast growth factor. Wnt7a and active beta-catenin promote neural stem cell self-renewal, whereas the deletion of Wnt7a or the lentiviral transduction of axin, a beta-catenin inhibitor, led to decreased cell proliferation in adult neurogenic areas. Lentiviral transduction of active beta-catenin led to increased numbers of type B neural stem cells in the subventricular zone of adult brains, whereas deletion of Wnt7a or TLX resulted in decreased numbers of neural stem cells retaining bromodeoxyuridine label in the adult brain. Both Wnt7a and active beta-catenin significantly rescued a TLX (also known as Nr2e1) short interfering RNA-induced deficiency in neural stem cell proliferation. Lentiviral transduction of an active beta-catenin increased cell proliferation in neurogenic areas of TLX-null adult brains markedly. These results strongly support the hypothesis that TLX acts through the Wnt/beta-catenin pathway to regulate neural stem cell proliferation and self-renewal. Moreover, this study suggests that neural stem cells can promote their own self-renewal by secreting signalling molecules that act in an autocrine/paracrine mode.

Cell Mergers and Their Impact on Cloud-to-Ground Lightning Over the Houston Area

NASA Technical Reports Server (NTRS)

Gauthier, Michael L.; Petersen, Walter A.; Carey, Lawrence D.

2009-01-01

A previous hypothesis advanced from observational studies such as METROMEX suggests that the intensity, frequency, and organization of cumulus convection may be impacted by the forcing of enhanced merger activity downstream of urban zones. A resulting corollary is that cities may exert an indirect anthropogenic forcing of parameters related to convection and associated phenomena such as lightning and precipitation. This paper investigates the urban merger hypothesis by examining the role of convective cell mergers on the existence and persistence of the Houston lightning "anomaly", a local maximum in cloud-to-ground (CG) lightning activity documented to exist over and east of Houston. Using eight summer seasons of peak columnar radar reflectivity, CG lightning data and a cell-tracking algorithm, a two-dimensional cell merger climatology is created for portions of eastern Texas and Louisiana. Results from the tracking and analysis of over 3.8 million cells indicate that merger-driven enhancements in convection induce a positive response (O 46%) in ground-flash densities throughout the domain, with areas of enhanced lightning typically being co-located with areas of enhanced merger activity. However, while mergers over the Houston area (relative to elsewhere in the domain) do result in more vigorous convective cells that produce larger CG flash densities, we find that CG lightning contributions due to mergers are distributed similarly throughout the domain. Hence while we demonstrate that cell mergers do greatly impact the production of lightning, the urban cell merger hypothesis does not uniquely explain the presence of a local lightning maximum near and downstream of Houston.

Overview of processing activities aimed at higher efficiencies and economical production

NASA Technical Reports Server (NTRS)

Bickler, D. B.

1985-01-01

An overview of processing activities aimed at higher efficiencies and economical production were presented. Present focus is on low-cost process technology for higher-efficiency cells of up to 18% or higher. Process development concerns center on the use of less than optimum silicon sheet, the control of production yields, and making uniformly efficient large-area cells. High-efficiency cell factors that require process development are bulk material perfection, very shallow junction formation, front-surface passivation, and finely detailed metallization. Better bulk properties of the silicon sheet and the keeping of those qualities throughout large areas during cell processing are required so that minority carrier lifetimes are maintained and cell performance is not degraded by high doping levels. When very shallow junctions are formed, the process must be sensitive to metallizatin punch-through, series resisitance in the cell, and control of dopant leaching during surface passivation. There is a need to determine the sensitivity to processing by mathematical modeling and experimental activities.

Research, development, and demonstration of lead-acid batteries for electric vehicle propulsion

NASA Astrophysics Data System (ADS)

1984-06-01

Research on electric motor vehicles is reported in the areas of active material utilization and active material integrity; design and fabrication of components, advanced cells, and modules; cell testing; and battery thermal management and electrolyte circulation subsystems.

Terminal Field and Firing Selectivity of Cholecystokinin-Expressing Interneurons in the Hippocampal CA3 Area

PubMed Central

Lasztóczi, Bálint; Tukker, John J.; Somogyi, Peter; Klausberger, Thomas

2015-01-01

Hippocampal oscillations reflect coordinated neuronal activity on many timescales. Distinct types of GABAergic interneuron participate in the coordination of pyramidal cells over different oscillatory cycle phases. In the CA3 area, which generates sharp waves and gamma oscillations, the contribution of identified GABAergic neurons remains to be defined. We have examined the firing of a family of cholecystokinin-expressing interneurons during network oscillations in urethane-anesthetized rats and compared them with firing of CA3 pyramidal cells. The position of the terminals of individual visualized interneurons was highly diverse, selective, and often spatially coaligned with either the entorhinal or the associational inputs to area CA3. The spike timing in relation to theta and gamma oscillations and sharp waves was correlated with the innervated pyramidal cell domain. Basket and dendritic-layer-innervating interneurons receive entorhinal and associational inputs and preferentially fire on the ascending theta phase, when pyramidal cell assemblies emerge. Perforant-path-associated cells, driven by recurrent collaterals of pyramidal cells fire on theta troughs, when established pyramidal cell assemblies are most active. In the CA3 area, slow and fast gamma oscillations occurred on opposite theta oscillation phases. Perforant-path-associated and some COUP-TFII-positive interneurons are strongly coupled to both fast and slow gamma oscillations, but basket and dendritic-layer-innervating cells are weakly coupled to fast gamma oscillations only. During sharp waves, different interneuron types are activated, inhibited, or remain unaffected. We suggest that specialization in pyramidal cell domain and glutamatergic input-specific operations, reflected in the position of GABAergic terminals, is the evolutionary drive underlying the diversity of cholecystokinin-expressing interneurons. PMID:22159120

CD81 Controls Sustained T Cell Activation Signaling and Defines the Maturation Stages of Cognate Immunological Synapses

PubMed Central

Rocha-Perugini, V.; Zamai, M.; González-Granado, J. M.; Barreiro, O.; Tejera, E.; Yañez-Mó, M.; Caiolfa, V. R.

2013-01-01

In this study, we investigated the dynamics of the molecular interactions of tetraspanin CD81 in T lymphocytes, and we show that CD81 controls the organization of the immune synapse (IS) and T cell activation. Using quantitative microscopy, including fluorescence recovery after photobleaching (FRAP), phasor fluorescence lifetime imaging microscopy-Föster resonance energy transfer (phasorFLIM-FRET), and total internal reflection fluorescence microscopy (TIRFM), we demonstrate that CD81 interacts with ICAM-1 and CD3 during conjugation between T cells and antigen-presenting cells (APCs). CD81 and ICAM-1 exhibit distinct mobilities in central and peripheral areas of early and late T cell-APC contacts. Moreover, CD81–ICAM-1 and CD81-CD3 dynamic interactions increase over the time course of IS formation, as these molecules redistribute throughout the contact area. Therefore, CD81 associations unexpectedly define novel sequential steps of IS maturation. Our results indicate that CD81 controls the temporal progression of the IS and the permanence of CD3 in the membrane contact area, contributing to sustained T cell receptor (TCR)-CD3-mediated signaling. Accordingly, we find that CD81 is required for proper T cell activation, regulating CD3ζ, ZAP-70, LAT, and extracellular signal-regulated kinase (ERK) phosphorylation; CD69 surface expression; and interleukin-2 (IL-2) secretion. Our data demonstrate the important role of CD81 in the molecular organization and dynamics of the IS architecture that sets the signaling threshold in T cell activation. PMID:23858057

Cold plasma selectivity in the interaction with various types of the cells

NASA Astrophysics Data System (ADS)

Volotskova, Olga; Stepp, Mary Ann; Keidar, Michael

2011-10-01

Present research in the area of cold atmospheric plasma (CAP) demonstrates great potential in various areas including medicine and biology. Depending on their configuration they can be used for wound healing, sterilization, targeted cell/tissue removal, and cancer treatments. Here we explore potential mechanisms by which CAP alters cell migration and influences cell adhesion. The migration studies are focused on the CAP interaction with fibroblasts and corneal epithelial cells. Data show that various types of cells have different thresholds (treatment times) required to achieve maximum inhibition of cell migration which is around ~30-40%. Studies to assess the impact of CAP treatment on the activation state of integrins and focal adhesion size by immunofluorescence showed more active b1 integrin on the cell surface and large focal adhesions after CAP treatment. Based on these data, a thermodynamic model is presented to explain how CAP leads to integrin activation and focal adhesion assembly. Also responses of the various types of the cells to the cold plasma treatment on the example of the epithelial keratinocytes, papilloma and carcinoma cells are studied. Cell cycle, migration and cell vitality analysis were performed. The goal of this study is to understand the mechanism by which the CAP jet alters cell migration, influences adhesion and cell survival.

Rhythmically Active Enkephalin-Expressing GABAergic Cells in the CA1 Area of the Hippocampus Project to the Subiculum and Preferentially Innervate Interneurons

PubMed Central

Fuentealba, Pablo; Tomioka, Ryohei; Dalezios, Yannis; Márton, László F.; Studer, Michele; Rockland, Kathleen; Klausberger, Thomas; Somogyi, Peter

2015-01-01

Enkephalins (ENKs) are endogenous opioids that regulate synaptic excitability of GABAergic networks in the cerebral cortex. Using retrograde tracer injections in the subiculum, we identified a hippocampal population of ENK-expressing projection neurons. In situ hybridization for GAD shows that ENK-expressing cells are a small GABAergic subpopulation. Furthermore, by extracellular recording and juxtacellular labeling in vivo, we identified an ENK-expressing cell in stratum radiatum of the CA1 area by its complete axodendritic arborization and characteristic spike timing during network oscillations. The somatodendritic membrane was immunopositive for mGluR1α, and there was both a rich local axon in CA1 and subicular-projecting branches. The boutons showed cell-type- and layer-specific innervation, i.e., interneurons were the main targets in the alveus, both interneurons and pyramidal cell dendrites were innervated in the other layers, and interneurons were exclusive targets in the subiculum. Parvalbumin-, but not somatostatin-, calbindin-, or cholecystokinin-expressing interneurons were preferred synaptic targets. During network activity, the juxtacellularly labeled ENK-expressing cell was phase modulated throughout theta oscillations, but silenced during sharp-wave/ripple episodes. After these episodes the interneuron exhibited rebound activity of high-frequency spike bursts, presumably causing peptide release. The ENK-expressing interneurons innervating parvalbumin-positive interneurons might contribute to the organization of the sharp-wave/ripple episodes by decreased firing during and rebound activity after the ripple episodes, as well as to the coordination of activity between the CA1 and subicular areas during network oscillations. PMID:18829959

Apoptotic microtubules delimit an active caspase free area in the cellular cortex during the execution phase of apoptosis.

PubMed

Oropesa-Ávila, M; Fernández-Vega, A; de la Mata, M; Maraver, J G; Cordero, M D; Cotán, D; de Miguel, M; Calero, C P; Paz, M V; Pavón, A D; Sánchez, M A; Zaderenko, A P; Ybot-González, P; Sánchez-Alcázar, J A

2013-03-07

Apoptotic microtubule network (AMN) is organized during apoptosis, forming a cortical structure beneath plasma membrane, which has an important role in preserving cell morphology and plasma membrane permeability. The aim of this study was to examine the role of AMN in maintaining plasma membrane integrity during the execution phase of apoptosis. We demonstrated in camptothecin-induced apoptosis in H460 cells that AMN delimits an active caspase free area beneath plasma membrane that permits the preservation of cellular cortex and transmembrane proteins. AMN depolymerization in apoptotic cells by a short exposure to colchicine allowed active caspases to reach the cellular cortex and cleave many key proteins involved in plasma membrane structural support, cell adhesion and ionic homeostasis. Cleavage of cellular cortex and plasma membrane proteins, such as α-spectrin, paxilin, focal adhesion kinase (FAK), E-cadherin and integrin subunit β4 was associated with cell collapse and cell detachment. Otherwise, cleavage-mediated inactivation of calcium ATPase pump (PMCA-4) and Na(+)/Ca(2+) exchanger (NCX) involved in cell calcium extrusion resulted in calcium overload. Furthermore, cleavage of Na(+)/K(+) pump subunit β was associated with altered sodium homeostasis. Cleavage of cell cortex and plasma membrane proteins in apoptotic cells after AMN depolymerization increased plasma permeability, ionic imbalance and bioenergetic collapse, leading apoptotic cells to secondary necrosis. The essential role of caspase-mediated cleavage in this process was demonstrated because the concomitant addition of colchicine that induces AMN depolymerization and the pan-caspase inhibitor z-VAD avoided the cleavage of cortical and plasma membrane proteins and prevented apoptotic cells to undergo secondary necrosis. Furthermore, the presence of AMN was also critical for proper phosphatidylserine externalization and apoptotic cell clearance by macrophages. These results indicate that AMN is essential to preserve an active caspase free area in the cellular cortex of apoptotic cells that allows plasma membrane integrity during the execution phase of apoptosis.

Apoptotic microtubules delimit an active caspase free area in the cellular cortex during the execution phase of apoptosis

PubMed Central

Oropesa-Ávila, M; Fernández-Vega, A; de la Mata, M; Maraver, J G; Cordero, M D; Cotán, D; de Miguel, M; Calero, C P; Paz, M V; Pavón, A D; Sánchez, M A; Zaderenko, A P; Ybot-González, P; Sánchez-Alcázar, J A

2013-01-01

Apoptotic microtubule network (AMN) is organized during apoptosis, forming a cortical structure beneath plasma membrane, which has an important role in preserving cell morphology and plasma membrane permeability. The aim of this study was to examine the role of AMN in maintaining plasma membrane integrity during the execution phase of apoptosis. We demonstrated in camptothecin-induced apoptosis in H460 cells that AMN delimits an active caspase free area beneath plasma membrane that permits the preservation of cellular cortex and transmembrane proteins. AMN depolymerization in apoptotic cells by a short exposure to colchicine allowed active caspases to reach the cellular cortex and cleave many key proteins involved in plasma membrane structural support, cell adhesion and ionic homeostasis. Cleavage of cellular cortex and plasma membrane proteins, such as α-spectrin, paxilin, focal adhesion kinase (FAK), E-cadherin and integrin subunit β4 was associated with cell collapse and cell detachment. Otherwise, cleavage-mediated inactivation of calcium ATPase pump (PMCA-4) and Na+/Ca2+ exchanger (NCX) involved in cell calcium extrusion resulted in calcium overload. Furthermore, cleavage of Na+/K+ pump subunit β was associated with altered sodium homeostasis. Cleavage of cell cortex and plasma membrane proteins in apoptotic cells after AMN depolymerization increased plasma permeability, ionic imbalance and bioenergetic collapse, leading apoptotic cells to secondary necrosis. The essential role of caspase-mediated cleavage in this process was demonstrated because the concomitant addition of colchicine that induces AMN depolymerization and the pan-caspase inhibitor z-VAD avoided the cleavage of cortical and plasma membrane proteins and prevented apoptotic cells to undergo secondary necrosis. Furthermore, the presence of AMN was also critical for proper phosphatidylserine externalization and apoptotic cell clearance by macrophages. These results indicate that AMN is essential to preserve an active caspase free area in the cellular cortex of apoptotic cells that allows plasma membrane integrity during the execution phase of apoptosis. PMID:23470534

Alternative interpretation for the active zones of Cuba

NASA Astrophysics Data System (ADS)

Rodríguez, Mario Octavio Cotilla

2014-11-01

An alternative explanation to the seismoactivity of Cuban faults is presented. The model is a consequence of the interaction between Caribbean and North American plates. It is made with 12 geodynamic cells form by a set of 13 active faults and their 14 areas of intersection. These cells are recognized morpho-structural blocks. The area between Eastern Matanzas and Western Cauto-Nipe is excluded because of the low level of seismic information. Cuba has two types of seismogenetic structures: faults and intersection of faults.

Organization of hyperactive microglial cells in trigeminal spinal subnucleus caudalis and upper cervical spinal cord associated with orofacial neuropathic pain.

PubMed

Shibuta, Kazuo; Suzuki, Ikuko; Shinoda, Masamichi; Tsuboi, Yoshiyuki; Honda, Kuniya; Shimizu, Noriyoshi; Sessle, Barry J; Iwata, Koichi

2012-04-27

The aim of this study was to evaluate spatial organization of hyperactive microglial cells in trigeminal spinal subnucleus caudalis (Vc) and upper cervical spinal cord (C1), and to clarify the involvement in mechanisms underlying orofacial secondary hyperalgesia following infraorbital nerve injury. We found that the head-withdrawal threshold to non-noxious mechanical stimulation of the maxillary whisker pad skin was significantly reduced in chronic constriction injury of the infraorbital nerve (ION-CCI) rats from day 1 to day 14 after ION-CCI. On day 3 after ION-CCI, mechanical allodynia was obvious in the orofacial skin areas innervated by the 1st and 3rd branches of the trigeminal nerve as well as the 2nd branch area. Hyperactive microglial cells in Vc and C1 were observed on days 3 and 7 after ION-CCI. On day 3 after ION-CCI, a large number of phosphorylated extracellular signal-regulated kinase (pERK)-immunoreactive (IR) cells were observed in Vc and C1. Many hyperactive microglial cells were also distributed over a wide area of Vc and C1 innervated by the trigeminal nerve. The intraperitoneal administration of minocycline significantly reduced the activation of microglial cells and the number of pERK-IR cells in Vc and C1, and also significantly attenuated the development of mechanical allodynia. Furthermore, enhanced background activity and mechanical evoked responses of Vc wide dynamic range neurons in ION-CCI rats were significantly reversed following minocycline administration. These findings suggest that activation of microglial cells over a wide area of Vc and C1 is involved in the enhancement of Vc and C1 neuronal excitability in the early period after ION-CCI, resulting in the neuropathic pain in orofacial areas innervated by the injured as well as uninjured nerves. Copyright © 2012 Elsevier B.V. All rights reserved.

Cost effective flat plate photovoltaic modules using light trapping

NASA Technical Reports Server (NTRS)

Bain, C. N.; Gordon, B. A.; Knasel, T. M.; Malinowski, R. L.

1981-01-01

Work in optical trapping in 'thick films' is described to form a design guide for photovoltaic engineers. A thick optical film can trap light by diffusive reflection and total internal reflection. Light can be propagated reasonably long distances compared with layer thicknesses by this technique. This makes it possible to conduct light from inter-cell and intra-cell areas now not used in photovoltaic modules onto active cell areas.

Correlation of lung surface area to apoptosis and proliferation in human emphysema.

PubMed

Imai, K; Mercer, B A; Schulman, L L; Sonett, J R; D'Armiento, J M

2005-02-01

Pulmonary emphysema is associated with alterations in matrix proteins and protease activity. These alterations may be linked to programmed cell death by apoptosis, potentially influencing lung architecture and lung function. To evaluate apoptosis in emphysema, lung tissue was analysed from 10 emphysema patients and six individuals without emphysema (normal). Morphological analysis revealed alveolar cells in emphysematous lungs with convoluted nuclei characteristic of apoptosis. DNA fragmentation was detected using terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL) and gel electrophoresis. TUNEL revealed higher apoptosis in emphysematous than normal lungs. Markers of apoptosis, including active caspase-3, proteolytic fragment of poly (ADP-ribose) polymerase, Bax and Bad, were detected in emphysematous lungs. Linear regression showed that apoptosis was inversely correlated with surface area. Emphysematous lungs demonstrated lower surface areas and increased cell proliferation. There was no correlation between apoptosis and proliferation, suggesting that, although both events increase during emphysema, they are not in equilibrium, potentially contributing to reduced lung surface area. In summary, cell-based mechanisms associated with emphysematous parenchymal damage include increased apoptosis and cell proliferation. Apoptosis correlated with airspace enlargement, supporting epidemiological evidence of the progressive nature of emphysema. These data extend the understanding of cell dynamics and structural changes within the lung during emphysema pathogenesis.

Program for fundamental and applied research of fuel cells in VNIIEF

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

Anisin, A.V.; Borisseonock, V.A.; Novitskii, Y.Z.

1996-04-01

According to VNIIEF the integral part of development of fuel cell power plants is fundamental and applied research. This paper describes areas of research on molten carbonate fuel cells. Topics include the development of mathematical models for porous electrodes, thin film electrolytes, the possibility of solid nickel anodes, model of activation polarization of anode, electrolyte with high solubility of oxygen. Other areas include research on a stationary mode of stack operation, anticorrosion coatings, impedance diagnostic methods, ultrasound diagnostics, radiation treatments, an air aluminium cell, and alternative catalysts for low temperature fuel cells.

A comparison of binocular depth mechanisms in areas 17 and 18 of the cat visual cortex

PubMed Central

Ferster, David

1981-01-01

1. The retinal disparity sensitivity of neurones in areas 17 and 18 of the cat visual cortex was examined. The response of each cell to an optimally oriented slit was measured as disparity was varied orthogonally to the receptive field orientation. Eye movements were monitored with a binocular reference cell simultaneously recorded in area 17 (Hubel & Wiesel, 1970). 2. Two types of disparity-sensitive cells were found, similar to those observed in the monkey by Poggio & Fischer (1977). The first type, tuned excitatory cells, were usually binocular and had a sharp peak in their disparity—response curve. They responded maximally at the disparity that brought their receptive fields into superposition on the tangent screen. This disparity closely coincided with the disparity at which the reference cell's receptive fields were also superimposed. By analogy with the monkey this point was taken to be the fixation point, or 0°. The second type, near and far cells, were most often monocular. They gave their weakest response (which was usually no response at all) at 0°. On one side of 0° the response grew linearly for up to 4° and then remained at the maximum. On the other side of zero, it remained at the minimum for up to several degrees before rising towards the maximum. 3. The receptive field organization of several disparity-sensitive cells was examined using the activity profile method of Henry, Bishop & Coombs (1969). The size and strength of the discrete excitatory and inhibitory regions of the receptive fields of a cell could quantitatively account for the shape of its disparity—response curve. 4. The laminar distribution of disparity sensitivity as well as of several other receptive field properties in areas 17 and 18 was studied. The organization of the two areas was remarkably similar in many respects. There was a difference, however, in the proportions of the two types of disparity-sensitive cells in the two areas. Area 17 contained many more tuned excitatory cells than near and far cells, while area 18 had the reverse distribution. In addition, the cells in area 18 were sensitive to a much broader range of disparities. While both areas contain disparity-sensitive neurones, these differences suggest that they play different roles in depth vision. 5. Recent psychophysical and neurophysiological evidence has led to a new model of stereopsis in which depth is signalled by the pooled activity of large groups of cells (Richards, 1971). The current results are consistent with this model. PMID:7264985

Lightweight fuel cell powerplant components program

NASA Technical Reports Server (NTRS)

Martin, R. E.

1980-01-01

A lightweight hydrogen-oxygen alkaline fuel cell incorporated into the design of a lightweight fuel cell powerplant (LFCP) was analytically and experimentally developed. The powerplant operates with passive water removal which contributes to a lower system weight and extended operating life. A preliminary LFCP specification and design table were developed along with a lightweight power section for the LFCP design, consisting of repeating two-cell modules was designed. Two, four-cell modules were designed incorporating 0.508 sq ft active area space shuttle technology fuel cells. Over 1,200 hours of single-cell and over 8,800 hours of two-cell module testing was completed. The 0.25 sq ft active area lightweight cell design was shown to be capable of operating on propellant purity reactants out to a current density of 600ASF. Endurance testing of the two-cell module configuration exceeded the 2,500-hour LFCP voltage requirements out to 3700-hours. A two-cell module capable of operating at increased reactant pressure completed 1000 hours of operation at a 30 psia reactant pressure. A lightweight power section consisting of fifteen, two-cell modules connected electrically in series was fabricated.

Microglia in mouse retina contralateral to experimental glaucoma exhibit multiple signs of activation in all retinal layers

PubMed Central

2014-01-01

Background Glaucomatous optic neuropathy, a leading cause of blindness, can progress despite control of intraocular pressure - currently the main risk factor and target for treatment. Glaucoma progression shares mechanisms with neurodegenerative disease, including microglia activation. In the present model of ocular hypertension (OHT), we have recently described morphological signs of retinal microglia activation and MHC-II upregulation in both the untreated contralateral eyes and OHT eyes. By using immunostaining, we sought to analyze and quantify additional signs of microglia activation and differences depending on the retinal layer. Methods Two groups of adult Swiss mice were used: age-matched control (naïve, n = 12), and lasered (n = 12). In the lasered animals, both OHT eyes and contralateral eyes were analyzed. Retinal whole-mounts were immunostained with antibodies against Iba-1, MHC-II, CD68, CD86, and Ym1. The Iba-1+ cell number in the plexiform layers (PL) and the photoreceptor outer segment (OS), Iba-1+ arbor area in the PL, and area of the retina occupied by Iba-1+ cells in the nerve fiber layer-ganglion cell layer (NFL-GCL) were quantified. Results The main findings in contralateral eyes and OHT eyes were: i) ameboid microglia in the NFL-GCL and OS; ii) the retraction of processes in all retinal layers; iii) a higher level of branching in PL and in the OS; iv) soma displacement to the nearest cell layers in the PL and OS; v) the reorientation of processes in the OS; vi) MHC-II upregulation in all retinal layers; vii) increased CD68 immunostaining; and viii) CD86 immunolabeling in ameboid cells. In comparison with the control group, a significant increase in the microglial number in the PL, OS, and in the area occupied by Iba-1+ cells in the NFL-GCL, and significant reduction of the arbor area in the PL. In addition, rounded Iba-1+ CD86+ cells in the NFL-GCL, OS and Ym1+ cells, and rod-like microglia in the NFL-GCL were restricted to OHT eyes. Conclusions Several quantitative and qualitative signs of microglia activation are detected both in the contralateral and OHT eyes. Such activation extended beyond the GCL, involving all retinal layers. Differences between the two eyes could help to elucidate glaucoma pathophysiology. PMID:25064005

Profile of cell proliferation and apoptosis activated by the intrinsic and extrinsic pathways in the prostate of aging rats.

PubMed

Gonzaga, Amanda C R; Campolina-Silva, Gabriel H; Werneck-Gomes, Hipácia; Moura-Cordeiro, Júnia D; Santos, Letícia C; Mahecha, Germán A B; Morais-Santos, Mônica; Oliveira, Cleida A

2017-06-01

Estrogens acting through the receptors ERα and ERβ participate in prostate normal growth and cancer. ERβ is highly expressed in the prostate epithelium, playing pro-apoptotic, anti-proliferative, and pro-differentiation roles. Apoptosis is activated by the intrinsic pathway after castration and by the extrinsic pathway after ERβ agonist treatment. This differential activation of apoptotic pathways is important since a major problem in the treatment of prostate cancer is the recurrence of tumors after androgen withdrawal. However, a comprehensive study about the pattern of apoptosis in the aging prostate is lacking, a knowledge gap that we aimed to address herein. Cellular age-related proliferative and apoptotic profiles of prostate tissue obtained from aging Wistar rats were evaluated. Cell death (caspase-3, -8, -9, TNFα) was assessed by immunohistochemistry, immunofluorescence, and TUNEL. Cell proliferation (MCM7) and cell survival factors (ERK1/2, p-ERK1/2, p-Akt, and NF-κB) were determined by immunohistochemistry. As the rats aged, the number of proliferating cells gradually reduced in the normal epithelium of all prostate lobes, while increasing in focal areas of intraepithelial proliferation. Interestingly, in areas of intraepithelial proliferation, we observed a reduction in the number of cells positive for caspase-3, -8, and -9. Regardless the animal's age, few prostate epithelial cells were positive for caspase-3, caspase-9, and TUNEL. In contrast, a progressive increase was seen in the positivity for caspase-8, especially in the atrophic epithelium of ventral prostate, which coincided with a reduction in TNFα immunoreaction. However, morphology of most caspase-8 positive cells suggests that they were not apoptotic. We also found reduced ERβ expression in the same areas. Possibly, low levels of the pro-apoptotic inductors TNFα and ERβ direct caspase-8 activity to an alternative pro-survival role in the atrophic epithelium. This hypothesis is supported by the increased expression of the key survival factors (ERK1/2, p-ERK1/2, p-Akt, and NF-κB) in these areas. Our findings reveal that, as the animals age, there is an increase of proliferation in restricted areas of the prostate epithelium, and a concomitant reduction of the apoptosis rate with an increase in cell survival induced by caspase-8, indicating a focused and spontaneous disruption of tissue homeostasis. © 2017 Wiley Periodicals, Inc.

Neural Mechanisms of Cortical Motion Computation Based on a Neuromorphic Sensory System

PubMed Central

Abdul-Kreem, Luma Issa; Neumann, Heiko

2015-01-01

The visual cortex analyzes motion information along hierarchically arranged visual areas that interact through bidirectional interconnections. This work suggests a bio-inspired visual model focusing on the interactions of the cortical areas in which a new mechanism of feedforward and feedback processing are introduced. The model uses a neuromorphic vision sensor (silicon retina) that simulates the spike-generation functionality of the biological retina. Our model takes into account two main model visual areas, namely V1 and MT, with different feature selectivities. The initial motion is estimated in model area V1 using spatiotemporal filters to locally detect the direction of motion. Here, we adapt the filtering scheme originally suggested by Adelson and Bergen to make it consistent with the spike representation of the DVS. The responses of area V1 are weighted and pooled by area MT cells which are selective to different velocities, i.e. direction and speed. Such feature selectivity is here derived from compositions of activities in the spatio-temporal domain and integrating over larger space-time regions (receptive fields). In order to account for the bidirectional coupling of cortical areas we match properties of the feature selectivity in both areas for feedback processing. For such linkage we integrate the responses over different speeds along a particular preferred direction. Normalization of activities is carried out over the spatial as well as the feature domains to balance the activities of individual neurons in model areas V1 and MT. Our model was tested using different stimuli that moved in different directions. The results reveal that the error margin between the estimated motion and synthetic ground truth is decreased in area MT comparing with the initial estimation of area V1. In addition, the modulated V1 cell activations shows an enhancement of the initial motion estimation that is steered by feedback signals from MT cells. PMID:26554589

Enhancing Performance of Large-Area Organic Solar Cells with Thick Film via Ternary Strategy.

PubMed

Zhang, Jianqi; Zhao, Yifan; Fang, Jin; Yuan, Liu; Xia, Benzheng; Wang, Guodong; Wang, Zaiyu; Zhang, Yajie; Ma, Wei; Yan, Wei; Su, Wenming; Wei, Zhixiang

2017-06-01

Large-scale fabrication of organic solar cells requires an active layer with high thickness tolerability and the use of environment-friendly solvents. Thick films with high-performance can be achieved via a ternary strategy studied herein. The ternary system consists of one polymer donor, one small molecule donor, and one fullerene acceptor. The small molecule enhances the crystallinity and face-on orientation of the active layer, leading to improved thickness tolerability compared with that of a polymer-fullerene binary system. An active layer with 270 nm thickness exhibits an average power conversion efficiency (PCE) of 10.78%, while the PCE is less than 8% with such thick film for binary system. Furthermore, large-area devices are successfully fabricated using polyethylene terephthalate (PET)/Silver gride or indium tin oxide (ITO)-based transparent flexible substrates. The product shows a high PCE of 8.28% with an area of 1.25 cm 2 for a single cell and 5.18% for a 20 cm 2 module. This study demonstrates that ternary organic solar cells exhibit great potential for large-scale fabrication and future applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Scanning electron microscopic study of Piper betle L. leaves extract effect against Streptococcus mutans ATCC 25175.

PubMed

Rahim, Zubaidah Haji Abdul; Thurairajah, Nalina

2011-04-01

Previous studies have shown that Piper betle L. leaves extract inhibits the adherence of Streptococcus mutans to glass surface, suggesting its potential role in controlling dental plaque development. In this study, the effect of the Piper betle L. extract towards S. mutans (with/without sucrose) using scanning electron microscopy (SEM) and on partially purified cell-associated glucosyltransferase activity were determined. S. mutans were allowed to adhere to glass beads suspended in 6 different Brain Heart Infusion broths [without sucrose; with sucrose; without sucrose containing the extract (2 mg mL(-1) and 4 mg mL(-1)); with sucrose containing the extract (2 mg mL(-1) and 4 mg mL(-1))]. Positive control was 0.12% chlorhexidine. The glass beads were later processed for SEM viewing. Cell surface area and appearance and, cell population of S. mutans adhering to the glass beads were determined upon viewing using the SEM. The glucosyltransferase activity (with/without extract) was also determined. One- and two-way ANOVA were used accordingly. It was found that sucrose increased adherence and cell surface area of S. mutans (p<0.001). S. mutans adhering to 100 µm² glass surfaces (with/without sucrose) exhibited reduced cell surface area, fluffy extracellular appearance and cell population in the presence of the Piper betle L. leaves extract. It was also found that the extract inhibited glucosyltransferase activity and its inhibition at 2.5 mg mL(-1) corresponded to that of 0.12% chlorhexidine. At 4 mg mL(-1) of the extract, the glucosyltransferase activity was undetectable and despite that, bacterial cells still demonstrated adherence capacity. The SEM analysis confirmed the inhibitory effects of the Piper betle L. leaves extract towards cell adherence, cell growth and extracellular polysaccharide formation of S. mutans visually. In bacterial cell adherence, other factors besides glucosyltransferase are involved.

Scanning Electron Microscopic study of Piper betle L. leaves extract effect against Streptococcus mutans ATCC 25175

PubMed Central

RAHIM, Zubaidah Haji Abdul; THURAIRAJAH, Nalina

2011-01-01

Introduction Previous studies have shown that Piper betle L. leaves extract inhibits the adherence of Streptococcus mutans to glass surface, suggesting its potential role in controlling dental plaque development. Objectives: In this study, the effect of the Piper betle L. extract towards S. mutans (with/without sucrose) using scanning electron microscopy (SEM) and on partially purified cell-associated glucosyltransferase activity were determined. Material and Methods S. mutans were allowed to adhere to glass beads suspended in 6 different Brain Heart Infusion broths [without sucrose; with sucrose; without sucrose containing the extract (2 mg mL-1 and 4 mg mL-1); with sucrose containing the extract (2 mg mL-1 and 4 mg mL-1)]. Positive control was 0.12% chlorhexidine. The glass beads were later processed for SEM viewing. Cell surface area and appearance and, cell population of S. mutans adhering to the glass beads were determined upon viewing using the SEM. The glucosyltransferase activity (with/without extract) was also determined. One- and two-way ANOVA were used accordingly. Results It was found that sucrose increased adherence and cell surface area of S. mutans (p<0.001). S. mutans adhering to 100 µm2 glass surfaces (with/without sucrose) exhibited reduced cell surface area, fluffy extracellular appearance and cell population in the presence of the Piper betle L. leaves extract. It was also found that the extract inhibited glucosyltransferase activity and its inhibition at 2.5 mg mL-1 corresponded to that of 0.12% chlorhexidine. At 4 mg mL-1 of the extract, the glucosyltransferase activity was undetectable and despite that, bacterial cells still demonstrated adherence capacity. Conclusion The SEM analysis confirmed the inhibitory effects of the Piper betle L. leaves extract towards cell adherence, cell growth and extracellular polysaccharide formation of S. mutans visually. In bacterial cell adherence, other factors besides glucosyltransferase are involved. PMID:21552715

Singing-related neural activity distinguishes two putative pallidal cell types in the songbird basal ganglia: comparison to the primate internal and external pallidal segments

PubMed Central

Goldberg, Jesse H.; Adler, Avital; Bergman, Hagai; Fee, Michale S.

2010-01-01

The songbird area X is a basal ganglia homologue that contains two pallidal cell types—local neurons that project within the basal ganglia and output neurons that project to the thalamus. Based on these projections, it has been proposed that these classes are structurally homologous to the primate external (GPe) and internal (GPi) pallidal segments. To test the hypothesis that the two area X pallidal types are functionally homologous to GPe and GPi neurons, we recorded from neurons in area X of singing juvenile male zebra finches, and directly compare their firing patterns to neurons recorded in the primate pallidus. In area X, we find two cell classes that exhibited high firing (HF) rates (>60Hz) characteristic of pallidal neurons. HF-1 neurons, like most GPe neurons we examined, exhibited large firing rate modulations, including bursts and long pauses. In contrast, HF-2 neurons, like GPi neurons, discharged continuously without bursts or long pauses. To test if HF-2 neurons were the output neurons that project to the thalamus, we next recorded directly from pallidal axon terminals in thalamic nucleus DLM, and found that all terminals exhibited singing-related firing patterns indistinguishable from HF-2 neurons. Our data show that singing-related neural activity distinguishes two putative pallidal cell types in area X: thalamus-projecting neurons that exhibit activity similar to the primate GPi, and non-thalamus-projecting neurons that exhibit activity similar to the primate GPe. These results suggest that song learning in birds and motor learning in mammals employ conserved basal ganglia signaling strategies. PMID:20484651

In-plane structuring of proton exchange membrane fuel cell cathodes: Effect of ionomer equivalent weight structuring on performance and current density distribution

NASA Astrophysics Data System (ADS)

Herden, Susanne; Riewald, Felix; Hirschfeld, Julian A.; Perchthaler, Markus

2017-07-01

Within the active area of a fuel cell inhomogeneous operating conditions occur, however, state of the art electrodes are homogenous over the complete active area. This study uses current density distribution measurements to analyze which ionomer equivalent weight (EW) shows locally the highest current densities. With this information a segmented cathode electrode is manufactured by decal transfer. The segmented electrode shows better performance especially at high current densities compared to homogenous electrodes. Furthermore this segmented catalyst coated membrane (CCM) performs optimal in wet as well as dry conditions, both operating conditions arise in automotive fuel cell applications. Thus, cathode electrodes with an optimized ionomer EW distribution might have a significant impact on future automotive fuel cell development.

Somatic sensory cortex (SmI) of the prosimian primate Galago crassicaudatus: organization of mechanoreceptive input from the hand in relation to cytoarchitecture.

PubMed

Carlson, M; Welt, C

1980-01-15

Mechanoreceptive input from the hand to the somatic sensory cortex (SmI) of the prosimian primate Galago crassicaudatus was examined with microelectrode mapping methods. In anesthetized animals, low threshold cutaneous input from the hand projects to SmI cortex in a single, complete, somatotopically organized pattern. Within this single pattern, cells with receptive fields on the glabrous skin of the palm, digits and digit tips are located in the rostral half, and cells with RFs on the hairy skin of the dorsal hand and digits are located in the caudal half of the hand areas. The cutaneous hand area is coextensive with the densely granular architectonic region of SmI. Studies of single cells in this region of awake galagos reveal the same pattern of cutaneous input and, in addition, demonstrate the presence of cells responding to joint movement not detected in anesthetized animals. Cells responsive to joint movement are arranged in vertically oriented columns located adjacent to cutaneous columns with receptive fields on the same part of the hand. In anesthetized animals, cells rostral to the granular region, in an area typified by increasing numbers of pyramidal cells in layer V and decreasing numbers of granular cells in upper layers, respond to high threshold stimulation of large areas of the hand. The few cells isolated in this area in awake animals respond to either active or passive hand movements. In such animals, cells caudal to the granular region, in an area characterized as agranular and alaminar cortex, respond to either passive stimulation of single or multiple joints or to active hand movements. These results, together with similar findings in a related prosimian, Nycticebus coucang, emphasize the generality of a single cutaneous hand area in SmI of prosimian species. The demonstration of multiple hand areas corresponding to multiple cytoarchitectonic subdivisions in SmI of Old and New World simians illustrates the increased degree of SmI differentiation from the prosimian to the simian grade of organization. The present results further suggest that determination of the homologues of multiple areas or subdivisions within and surrounding SmI in primates will require comparisons of somatotopy, submodality, sulcal patterns, cytoarchitecture, and connectivity in representative members of prosimian and simian families.

Amorphous silicon research. Final technical progress report, 1 August 1994--28 February 1998

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

Guha, S

1998-05-01

This report describes the status and accomplishments of work performed under this subcontract by United Solar Systems. United Solar researchers explored several new deposition regimes/conditions to investigate their effect on material/device performance. To facilitate optimum ion bombardment during growth, a large parameter space involving chamber pressure, rf power, and hydrogen dilution were investigated. United Solar carried out a series of experiments using discharge modulation at various pulsed-plasma intervals to study the effect of Si-particle incorporation on solar cell performance. Hydrogen dilution during deposition is found to improve both the initial and stable performance of a-Si and a-SiGe alloy cells. Researchersmore » conducted a series of temperature-ramping experiments on samples prepared with high and low hydrogen dilutions to study the effect of hydrogen effusion on solar cell performance. Using an internal photoemission method, the electrical bandgap of a microcrystalline p layer used in high-efficiency solar cells was measured to be 1.6 eV. New measurement techniques were developed to evaluate the interface and bulk contributions of losses to solar cell performance. Researchers replaced hydrogen with deuterium and found deuterated amorphous silicon alloy solar cells exhibit reduced light-induced degradation. The incorporation of a microcrystalline n layer in a multijunction cell is seen to improve cell performance. United Solar achieved a world-record single-junction a-Si alloy stable cell efficiency of 9.2% with an active area of 0.25 cm{sup 2} grown with high hydrogen dilution. They also achieved a world-record triple-junction, stable, active-area cell efficiency of 13.0% with an active area of 0.25 cm{sup 2}.« less

[Tyrosine hydroxylase in telencephalon and diencephalon of Rhodeus sericeus (Cyprinidae)].

PubMed

Pushchina, E V

2009-01-01

Immunohistochemical labeling of tyrosine hydroxylase was used to demonstrate catecholaminergic neuronal populations in the telencephalon and diencephalonof adult cypryniform fish Rhodeus sericeus. Various immunoreactive cell populations have been found in the telencephalon (ventral, central and lateral nuclei of ventral telencephalic area). Immunoreactive cells and fibers were discovered in dorsal nucleus of ventral telencephalic area and supracomissural nucleus in the caudal part of the telencephalon. In the diencephalon, periventricular nuclei (preoptic, periventricular nucleus of posterior tuberculum and periventricular organ) contained considerable TH-ergic cells. High activity of tyrosine hydroxylase was revealed in the pretectal, ventro-medial, ventro-lateral and suprachiasmatic nuclei. Periventricular hypothalamic nuclei also displayed high activity of tyrosine hydroxylase. Pseudounipolar neurons prevailed in all TH-immunereactive structures of the telencephalon and diencephalon: numerous bipolar liquor-contacting cells were discovered in the periventricular nuclei. Large pear-shaped cells and bipolar TH-ergic cells were found in posterior tuberculum. These cells may be functionally related to the dopamine-acquiring system.

Discrete regenerative fuel cell reduces hysteresis for sustainable cycling of water

PubMed Central

Park, Kiwon; Lee, Jungkoo; Kim, Hyung-Man; Choi, Kap-Seung; Hwang, Gunyong

2014-01-01

The discrete regenerative fuel cell is being developed as a residential power control that synchronizes with a renewables load which fluctuates significantly with the time and weather. The power of proton exchange membrane fuel cells can be scaled-up adjustably to meet the residential power demand. As a result, scale-ups from a basic unit cell with a 25 cm2 active area create a serpentine flow-field on an active area of 100 cm2 and take into account the excessive current and the remaining power obtained by stacking single cells. Operating a fuel cell utilising oxygen produced by the electrolyser instead of air improves the electrochemical reaction and the water balance. Furthermore, the performance test results with oxygen instead of air show almost no hysteresis, which results in the very stable operation of the proton exchange membrane fuel cell as well as the sustainable cycle of water by hydrogen and oxygen mediums. PMID:24699531

Electrospinning Nanofiber Based Organic Solar Cell

NASA Astrophysics Data System (ADS)

Yang, Zhenhua; Liu, Ying; Moffa, Maria; Nam, Chang-Yong; Pisignano, Dario; Rafailovich, Miriam

Bulk heterojunction (BHJ) polymer solar cells are an area of intense interest due to their potential to result in printable, inexpensive solar cells which can be processed onto flexible substrates. The active layer is typically spin coated from the solution of polythiophene derivatives (donor) and fullerenes (acceptor) and interconnected domains are formed because of phase separation. However, the power conversion efficiency (PCE) of BHJ solar cell is restricted by the presence of unfavorable morphological features, including dead ends or isolated domains. Here we MEH-PPV:PVP:PCBM electrospun nanofiber into BHJ solar cell for the active layer morphology optimization. Larger interfacial area between donor and acceptor is abtained with electrospinning method and the high aspect ratio of the MEH-PPV:PVP:PCBM nanofibers allow them to easily form a continuous pathway. The surface morphology is investigated with atomic force microscopy (AFM) and scanning electron microscopy (SEM). Electrospun nanofibers are discussed as a favorable structure for application in bulk-heterojunction organic solar cells. Electrospinning Nanofiber Based Bulk Heterojunction Organic Solar Cell.

Quantifying substrate uptake by individual cells of marine bacterioplankton by catalyzed reporter deposition fluorescence in situ hybridization combined with microautoradiography.

PubMed

Sintes, Eva; Herndl, Gerhard J

2006-11-01

Catalyzed reporter deposition fluorescence in situ hybridization combined with microautoradiography (MICRO-CARD-FISH) is increasingly being used to obtain qualitative information on substrate uptake by individual members of specific prokaryotic communities. Here we evaluated the potential for using this approach quantitatively by relating the measured silver grain area around cells taking up (3)H-labeled leucine to bulk leucine uptake measurements. The increase in the silver grain area over time around leucine-assimilating cells of coastal bacterial assemblages was linear during 4 to 6 h of incubation. By establishing standardized conditions for specific activity levels and concomitantly performing uptake measurements with the bulk community, MICRO-CARD-FISH can be used quantitatively to determine uptake rates on a single-cell level. Therefore, this approach allows comparisons of single-cell activities for bacterial communities obtained from different sites or growing under different ecological conditions.

Quantifying Substrate Uptake by Individual Cells of Marine Bacterioplankton by Catalyzed Reporter Deposition Fluorescence In Situ Hybridization Combined with Microautoradiography▿

PubMed Central

Sintes, Eva; Herndl, Gerhard J.

2006-01-01

Catalyzed reporter deposition fluorescence in situ hybridization combined with microautoradiography (MICRO-CARD-FISH) is increasingly being used to obtain qualitative information on substrate uptake by individual members of specific prokaryotic communities. Here we evaluated the potential for using this approach quantitatively by relating the measured silver grain area around cells taking up 3H-labeled leucine to bulk leucine uptake measurements. The increase in the silver grain area over time around leucine-assimilating cells of coastal bacterial assemblages was linear during 4 to 6 h of incubation. By establishing standardized conditions for specific activity levels and concomitantly performing uptake measurements with the bulk community, MICRO-CARD-FISH can be used quantitatively to determine uptake rates on a single-cell level. Therefore, this approach allows comparisons of single-cell activities for bacterial communities obtained from different sites or growing under different ecological conditions. PMID:16950912

Characterization of blood dendritic and regulatory T cells in asymptomatic adults with sub-microscopic Plasmodium falciparum or Plasmodium vivax infection.

PubMed

Kho, Steven; Marfurt, Jutta; Handayuni, Irene; Pava, Zuleima; Noviyanti, Rintis; Kusuma, Andreas; Piera, Kim A; Burdam, Faustina H; Kenangalem, Enny; Lampah, Daniel A; Engwerda, Christian R; Poespoprodjo, Jeanne R; Price, Ric N; Anstey, Nicholas M; Minigo, Gabriela; Woodberry, Tonia

2016-06-21

Plasmodium falciparum and Plasmodium vivax infections compromise dendritic cell (DC) function and expand regulatory T (Treg) cells in both clinical disease (malaria) and experimental human sub-microscopic infection. Conversely, in asymptomatic microscopy-positive (patent) P. falciparum or P. vivax infection in endemic areas, blood DC increase or retain HLA-DR expression and Treg cells exhibit reduced activation, suggesting that DC and Treg cells contribute to the control of patent asymptomatic infection. The effect of sub-microscopic (sub-patent) asymptomatic Plasmodium infection on DC and Treg cells in malaria-endemic area residents remains unclear. In a cross-sectional household survey conducted in Papua, Indonesia, 162 asymptomatic adults were prospectively evaluated for DC and Treg cells using field-based flow cytometry. Of these, 161 individuals (99 %) were assessed retrospectively by polymerase chain reaction (PCR), 19 of whom had sub-microscopic infection with P. falciparum and 15 with sub-microscopic P. vivax infection. Flow cytometric data were re-analysed after re-grouping asymptomatic individuals according to PCR results into negative controls, sub-microscopic and microscopic parasitaemia to examine DC and Treg cell phenotype in sub-microscopic infection. Asymptomatic adults with sub-microscopic P. falciparum or P. vivax infection had DC HLA-DR expression and Treg cell activation comparable to PCR-negative controls. Sub-microscopic P. falciparum infection was associated with lower peripheral CD4(+) T cells and lymphocytes, however sub-microscopic Plasmodium infection had no apparent effect on DC sub-set number or Treg cell frequency. In contrast to the impairment of DC maturation/function and the activation of Treg cells seen with sub-microscopic parasitaemia in primary experimental human Plasmodium infection, no phenotypic evidence of dysregulation of DC and Treg cells was observed in asymptomatic sub-microscopic Plasmodium infection in Indonesian adults. This is consistent with DC and Treg cells retaining their functional capacity in sub-microscopic asymptomatic infection with P. falciparum or P. vivax in malaria-endemic areas.

Heterogeneity of cellular proliferation within transitional cell carcinoma: correlation of protein kinase C alpha/betaI expression and activity.

PubMed

Aaltonen, Vesa; Koivunen, Jussi; Laato, Matti; Peltonen, Juha

2006-07-01

A total of 18 histological samples containing both transitional cell carcinoma (TCC) and normal urothelial epithelium were analyzed for protein kinase C (PKC)-alpha and -betaI expression, and for their phosphorylated substrates. The results showed an increased expression of PKC-alpha in 13 out of 18 samples and -betaI in 11 out of 18 TCC samples when compared with normal urothelium. In addition, 11 out of 18 of the TCC tumors displayed heterogeneous expression of the PKC isoenzymes, with different levels of immunosignal in different areas of the tumor. Within the same sample, areas of highest PKC isoenzyme expression also showed highest classical PKC activity, as estimated by immunodetection of phosphorylated forms of PKC substrates. The areas of highest expression of PKC-alpha and/or -betaI isoenzymes showed also the highest number of cells positive for Ki67, an indicator of proliferation. Immunofluorescence and Western blotting demonstrated that in cultured TCC cells, PKC-alpha was located in the cytoplasm, whereas PKC-betaI was located primarily in the nucleus as a 65-kDa fragment and in the cytoplasm as a full-size 79-kDa protein. Our results indicate that increased expression of PKC-alpha and -betaI leads to increased total classical PKC kinase activity and suggest that increased activity of the isoenzymes plays a role in accelerated growth of TCC. Furthermore, these results suggest that even in carcinoma tissue, PKC expression and activity are under strict control.

Ternary blend polymer solar cells with self-assembled structure for enhancing power conversion efficiency

NASA Astrophysics Data System (ADS)

Yang, Zhenhua; Li, Hongfei; Nam, Chang-Yong; Kisslinger, Kim; Satija, Sushil; Rafailovich, Miriam

Bulk heterojunction (BHJ) polymer solar cells are an area of intense interest due to their advantages such as mechanical flexibility. The active layer is typically spin coated from the solution of polythiophene derivatives (donor) and fullerenes (acceptor) and interconnected domains are formed because of phase separation. However, the power conversion efficiency (PCE) of BHJ solar cell is restricted by the disordered inner structures in the active layer, donor or acceptor domains isolated from electrodes. Here we report a self-assembled columnar structure formed by phase separation between (PCDTBT) and polystyrene (PS) for the active layer morphology optimization. The BHJ solar cell device based on this structure is promising for exhibiting higher performance due to the shorter carrier transportation pathway and larger interfacial area between donor and acceptor. The surface morphology is investigated with atomic force microscopy (AFM) and the columnar structure is studied by investigation of cross-section of the blend thin film of PCDTBT and PS under the transmission electron microscopy (TEM). The different morphological structures formed via phase segregation are correlated with the performance of the BHJ solar cells.

Automated array assembly, phase 2

NASA Technical Reports Server (NTRS)

Carbajal, B. G.

1979-01-01

Tasks of scaling up the tandem junction cell (TJC) from 2 cm x 2 cm to 6.2 cm and the assembly of several modules using these large area TJC's are described. The scale-up of the TJC was based on using the existing process and doing the necessary design activities to increase the cell area to an acceptably large area. The design was carried out using available device models. The design was verified and sample large area TJCs were fabricated. Mechanical and process problems occurred causing a schedule slippage that resulted in contract expiration before enough large-area TJCs were fabricated to populate the sample tandem junction modules (TJM). A TJM design was carried out in which the module interconnects served to augment the current collecting buses on the cell. No sample TJMs were assembled due to a shortage of large-area TJCs.

Spatio-temporal specialization of GABAergic septo-hippocampal neurons for rhythmic network activity.

PubMed

Unal, Gunes; Crump, Michael G; Viney, Tim J; Éltes, Tímea; Katona, Linda; Klausberger, Thomas; Somogyi, Peter

2018-03-03

Medial septal GABAergic neurons of the basal forebrain innervate the hippocampus and related cortical areas, contributing to the coordination of network activity, such as theta oscillations and sharp wave-ripple events, via a preferential innervation of GABAergic interneurons. Individual medial septal neurons display diverse activity patterns, which may be related to their termination in different cortical areas and/or to the different types of innervated interneurons. To test these hypotheses, we extracellularly recorded and juxtacellularly labeled single medial septal neurons in anesthetized rats in vivo during hippocampal theta and ripple oscillations, traced their axons to distant cortical target areas, and analyzed their postsynaptic interneurons. Medial septal GABAergic neurons exhibiting different hippocampal theta phase preferences and/or sharp wave-ripple related activity terminated in restricted hippocampal regions, and selectively targeted a limited number of interneuron types, as established on the basis of molecular markers. We demonstrate the preferential innervation of bistratified cells in CA1 and of basket cells in CA3 by individual axons. One group of septal neurons was suppressed during sharp wave-ripples, maintained their firing rate across theta and non-theta network states and mainly fired along the descending phase of CA1 theta oscillations. In contrast, neurons that were active during sharp wave-ripples increased their firing significantly during "theta" compared to "non-theta" states, with most firing during the ascending phase of theta oscillations. These results demonstrate that specialized septal GABAergic neurons contribute to the coordination of network activity through parallel, target area- and cell type-selective projections to the hippocampus.

The infiltration of experimentally induced lung metastases of colon carcinoma CC531 by adoptively transferred interleukin-2-activated natural killer cells in Wag rats.

PubMed

Kuppen, P J; Basse, P H; Goldfarb, R H; Van De Velde, C J; Fleuren, G J; Eggermont, A M

1994-02-15

The number of IL-2-activated natural killer (A-NK) cells reaching the tumor site in vivo may be crucial for their anti-tumor effect following adoptive immunotherapy. We investigated in a syngeneic rat model the infiltration of established lung metastases by adoptively transferred A-NK cells. The Wag rat colon carcinoma CC531 was injected via a tail vein to induce pulmonary metastases. Syngeneic A-NK cells were labeled with the fluorescent dye rhodamine (TRITC) and next injected via a tail vein in rats bearing day-12 lung tumors. The number of A-NK cells in tumor and in normal tissue per rat was counted in sections after administration of A-NK cells. At all time points tested, a significant linear relationship between the cross-section area of the tumor and the number of infiltrating cells was observed, but small tumor areas became fully infiltrated earlier than larger areas. At 24 hr after injection, approximately 10% of the injected cells were found in the tumor tissue and the average A-NK-cell-to-tumor-cell ratio was estimated to be 1:3. A-NK cells were found in the liver too, although the number of cells per mm2 tissue was low compared with the pulmonary tumor tissue. Very low numbers of A-NK cells were found in kidney, adrenal gland, spleen, and blood. We conclude that, in this syngeneic rat model, adoptively transferred A-NK cells are able to find and specifically infiltrate pulmonary metastases in a time-dependent fashion.

Persistent neural activity in head direction cells

NASA Technical Reports Server (NTRS)

Taube, Jeffrey S.; Bassett, Joshua P.; Oman, C. M. (Principal Investigator)

2003-01-01

Many neurons throughout the rat limbic system discharge in relation to the animal's directional heading with respect to its environment. These so-called head direction (HD) cells exhibit characteristics of persistent neural activity. This article summarizes where HD cells are found, their major properties, and some of the important experiments that have been conducted to elucidate how this signal is generated. The number of HD and angular head velocity cells was estimated for several brain areas involved in the generation of the HD signal, including the postsubiculum, anterior dorsal thalamus, lateral mammillary nuclei and dorsal tegmental nucleus. The HD cell signal has many features in common with what is known about how neural integration is accomplished in the oculomotor system. The nature of the HD cell signal makes it an attractive candidate for using neural network models to elucidate the signal's underlying mechanisms. The conditions that any network model must satisfy in order to accurately represent how the nervous system generates this signal are highlighted and areas where key information is missing are discussed.

Towards high resolution analysis of metabolic flux in cells and tissues.

PubMed

Sims, James K; Manteiga, Sara; Lee, Kyongbum

2013-10-01

Metabolism extracts chemical energy from nutrients, uses this energy to form building blocks for biosynthesis, and interconverts between various small molecules that coordinate the activities of cellular pathways. The metabolic state of a cell is increasingly recognized to determine the phenotype of not only metabolically active cell types such as liver, muscle, and adipose, but also other specialized cell types such as neurons and immune cells. This review focuses on methods to quantify intracellular reaction flux as a measure of cellular metabolic activity, with emphasis on studies involving cells of mammalian tissue. Two key areas are highlighted for future development, single cell metabolomics and noninvasive imaging, which could enable spatiotemporally resolved analysis and thereby overcome issues of heterogeneity, a distinctive feature of tissue metabolism. Copyright © 2013 Elsevier Ltd. All rights reserved.

Towards High Resolution Analysis of Metabolic Flux in Cells and Tissues

PubMed Central

Sims, James K; Manteiga, Sara; Lee, Kyongbum

2013-01-01

Metabolism extracts chemical energy from nutrients, uses this energy to form building blocks for biosynthesis, and interconverts between various small molecules that coordinate the activities of cellular pathways. The metabolic state of a cell is increasingly recognized to determine the phenotype of not only metabolically active cell types such as liver, muscle, and adipose, but also other specialized cell types such as neurons and immune cells. This review focuses on methods to quantify intracellular reaction flux as a measure of cellular metabolic activity, with emphasis on studies involving cells of mammalian tissue. Two key areas are highlighted for future development, single cell metabolomics and noninvasive imaging, which could enable spatiotemporally resolved analysis and thereby overcome issues of heterogeneity, a distinctive feature of tissue metabolism. PMID:23906926

Involvement of Mossy Cells in Sharp Wave-Ripple Activity In Vitro.

PubMed

Swaminathan, Aarti; Wichert, Ines; Schmitz, Dietmar; Maier, Nikolaus

2018-05-29

The role of mossy cells (MCs) of the hippocampal dentate area has long remained mysterious. Recent research has begun to unveil their significance in spatial computation of the hippocampus. Here, we used an in vitro model of sharp wave-ripple complexes (SWRs), which contribute to hippocampal memory formation, to investigate MC involvement in this fundamental population activity. We find that a significant fraction of MCs (∼47%) is recruited into the active neuronal network during SWRs in the CA3 area. Moreover, MCs receive pronounced, ripple-coherent, excitatory and inhibitory synaptic input. Finally, we find evidence for SWR-related synaptic activity in granule cells that is mediated by MCs. Given the widespread connectivity of MCs within and between hippocampi, our data suggest a role for MCs as a hub functionally coupling the CA3 and the DG during ripple-associated computations. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Zone-specific cell biosynthetic activity in mature bovine articular cartilage: a new method using confocal microscopic stereology and quantitative autoradiography.

PubMed

Wong, M; Wuethrich, P; Eggli, P; Hunziker, E

1996-05-01

A new methodology was developed to measure spatial variations in chondrocyte/matrix structural parameters and chondrocyte biosynthetic activity in articular cartilage. This technique is based on the use of a laser scanning confocal microscope that can "optically" section chemically fixed, unembedded tissue. The confocal images are used for morphometric measurement of stereologic parameters such as cell density (cells/mm3), cell volume fraction (%), surface density (l/cm), mean cell volume (micron3), and mean cell surface area (micron2). Adjacent pieces of tissue are simultaneously processed for conventional liquid emulsion autoradiography, and a semiautomated grain counting program is used to measure the silver grain density at regions corresponding to the same sites used for structural measurements. An estimate of chondrocyte biosynthetic activity in terms of grains per cell is obtained by dividing the value for grain density by that for cell density. In this paper, the newly developed methodology was applied to characterize the zone-specific behavior of adult articular cartilage in the free-swelling state. Cylinders of young adult bovine articular cartilage were labelled with either [3H]proline or [35S]sulfate, and chondrocyte biosynthesis and structural parameters were measured from the articular surface to the tidemark. The results showed that chondrocytes of the radial zone occupied twice the volume and surface area of the chondrocytes of the superficial zone but were 10 times more synthetically active. This efficient and unbiased technique may prove useful in studying the correlation between mechanically induced changes in cell form and biosynthetic activity within inhomogeneous tissue as well as metabolic changes in cartilage due to ageing and disease.

A Novel Plasma Membrane-Anchored Protein Regulates Xylem Cell-Wall Deposition through Microtubule-Dependent Lateral Inhibition of Rho GTPase Domains.

PubMed

Sugiyama, Yuki; Wakazaki, Mayumi; Toyooka, Kiminori; Fukuda, Hiroo; Oda, Yoshihisa

2017-08-21

Spatial control of cell-wall deposition is essential for determining plant cell shape [1]. Rho-type GTPases, together with the cortical cytoskeleton, play central roles in regulating cell-wall patterning [2]. In metaxylem vessel cells, which are the major components of xylem tissues, active ROP11 Rho GTPases form oval plasma membrane domains that locally disrupt cortical microtubules, thereby directing the formation of oval pits in secondary cell walls [3-5]. However, the regulatory mechanism that determines the planar shape of active Rho of Plants (ROP) domains is still unknown. Here we show that IQD13 associates with cortical microtubules and the plasma membrane to laterally restrict the localization of ROP GTPase domains, thereby directing the formation of oval secondary cell-wall pits. Loss and overexpression of IQD13 led to the formation of abnormally round and narrow secondary cell-wall pits, respectively. Ectopically expressed IQD13 increased the presence of parallel cortical microtubules by promoting microtubule rescue. A reconstructive approach revealed that IQD13 confines the area of active ROP domains within the lattice of the cortical microtubules, causing narrow ROP domains to form. This activity required the interaction of IQD13 with the plasma membrane. These findings suggest that IQD13 positively regulates microtubule dynamics as well as their linkage to the plasma membrane, which synergistically confines the area of active ROP domains, leading to the formation of oval secondary cell-wall pits. This finding sheds light on the role of microtubule-plasma membrane linkage as a lateral fence that determines the planar shape of Rho GTPase domains. Copyright © 2017 Elsevier Ltd. All rights reserved.

Human germinal center CD4+CD57+ T cells act differently on B cells than do classical T-helper cells.

PubMed

Bouzahzah, F; Bosseloir, A; Heinen, E; Simar, L J

1995-01-01

We have isolated two subtypes of helper T cells from human tonsils: CD4+CD57+ cells, mostly located in the germinal center (GC), and CD4+CD57- cells, distributed through the interfollicular areas but also present in the GC. In a functional study, we have compared the capacities of these T-cell subtypes to stimulate B cells in cocultures. In order to block T-cell proliferation while maintaining their activation level, we pretreated isolated T cells with mitomycin C prior to culture in the presence of B cells and added polyclonal activators such as PHA and Con A, combined or not with IL-2. Contrary to CD4+ CD57- cells, CD4+CD57+ cells did not markedly enhance B-cell proliferation. Even when sIgD.B cells typical of germinal center cells were tested, the CD4+CD57+ cells had no significant effect. This is in accordance with the location of these cells: They mainly occupy the light zones of the GC where few B cells divide. Even when added to preactivated, actively proliferating cells, CD4+CD57 cells failed to modulate B-cell multiplication. On the supernatants of B-cell-T-cell cocultures, we examined by the ELISA technique the effect of T cells on Ig synthesis. Contrary to CD57+ T cells, whose effect was strong, CD57- T cells weakly stimulated Ig synthesis. More IgM than IgG was generally found. Because CD57 antigen is a typical marker of natural killer cells, we tested the cytolytic activity of tonsillar CD4+CD57+ cells on K562 target cells. Unlike NK cells, neither CD4+CD57+ nor CD4+CD57- cells exhibit any cytotoxicity. Thus, germinal center CD4+CD57+ cells are not cytolytic and do not strongly stimulate either B-cell proliferation or Ig secretion. CD4+CD57- cells, however, enhance B-cell proliferation and differentiation, thus acting like the classical helper cells of the T-dependent areas.

Pathological proof of cellular death in radiofrequency ablation therapy and correlation with flash echo imaging--an experiment study.

PubMed

Fujiki, Kei

2004-01-01

The aims of this study were to clarify the geographic distribution of complete cell death in the radiofrequency ablated area in a porcine liver experiment, and to evaluate the efficacy of ultrasonography using contrast media in detecting the area of Radiofrequency-induced cell death. Radiofrequency ablation was performed at 3 sites in each liver in seven swine with a RF2000TM radiofrequency generator using an expandable type needle electrode. The ablation area was investigated histologically by Hematoxylin-Eosin staining and NADH staining. The area of radiofrequency-induced cell death was correlated to the ultrasonographic findings using contrast media, by means of contrast harmonic imaging, flash echo imaging-subtraction and flash echo imaging-power Doppler. The ablation area showed three distinct regions. Although the HE staining did not indicate necrosis, the NADH staining showed a complete loss of cellular activity in the inner and middle layers of the ablation area. However, in the outer layer cells displaying cellular integrity were intermingled with the necrotic cells, indicating that some of the cells in this layer had a chance to survive. Further, in some cases the outer layer of the ablated area had irregular margins. The flash-echo power-doppler images were accurately correlated in size and shape to the pathologically proved region of complete cell death in the radiofrequency-induced lesions. In the marginal part of the radiofrequency ablation area, cell death was incomplete. Flash echo imaging-power doppler was a useful and sensitive real time imaging technique for accurate evaluation of the region of complete cell death.

High-surface-area, dual-function oxygen electrocatalysts for space power applications

NASA Technical Reports Server (NTRS)

Ham, David O.; Moniz, Gary; Taylor, E. Jennings

1987-01-01

The processes of hydration/dehydration and carbonation/decarbonation are investigated as an approach to provide higher surface area mixed metal oxides that are more active electrochemically. These materials are candidates for use as electrocatalysts and electrocatalyst supports for alkaline electrolyzers and fuel cells. For the case of the perovskite, LaCoO3 , higher surface areas were achieved with no change in structure and a more active oxygen electrocatalyst.

Effects of deuterium oxide and galvanic vestibular stimulation on visual cortical cell function

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

Reinis, S.; Landolt, J.P.; Weiss, D.S.

1984-03-01

The spontaneous and evoked unit activities of complex visual cortical cells were recorded from Brodmann's area 18 in immobilized, unanesthetized cats before, during, and after stimulation of the vestibular system. The vestibular system was stimulated by intravenous injection of deuterium oxide (D2O)--a noted nystagmogenic agent--or by direct galvanic stimulation of the labyrinth. Measures of the receptive-field areas, poststimulus time histograms, directional preferences, and the optimal speed of the light bar stimulating the cell were obtained before and after the application of D2O. Directional preferences were determined in a novel manner, using a method derived from a hierarchical clustering technique. Datamore » were collected and analyzed from a) visual cortical cells in cats with intact labyrinths, b) visual cortical cells in cats following bilateral labrinthectomies, and c) nonvisual cortical cells in cats with intact labyrinths. The other cellular characteristics were also altered by the D2O. Galvanic stimulation of the labyrinth resembles, in its effects, the injection of D2O. In labyrinth-intact cats, the time course of area 18 spontaneous activity dramatically increased 30 min or more after D2O was administered. It peaked 2-3 h later and still had not returned to preinjection levels even 7 h after the D2O administration. In bilaterally labyrinthectomized cats, the spontaneous activity of the visual cells did not change following D2O administration. In nonvisual cells from labyrinth-intact cats, the spontaneous activity demonstrated a slight but significant decrease over time after D2O injection. In pilot studies, the cats were injected with D2O. Within 8-10 min afterward, signs of positional nystagmus commenced; and within 30 min, problems in maintaining balance were noted. This continued for 7-8 h before disappearing. In the labyrinthectomized animals, such effects were not observed.« less

Postnatal somatic cell proliferation and seminiferous tubule maturation in pigs: A non-random event

PubMed Central

Avelar, Gleide F.; Oliveira, Carolina F.A.; Soares, Jaqueline M.; Silva, Israel J.; Dobrinski, Ina; Hess, Rex A.; França, Luiz R.

2015-01-01

Although seminiferous tubule maturation in horses begins in the central area of the testis, this process is thought to occur randomly throughout the testis in most mammals. Studies in our laboratory revealed that the establishment of spermatogenesis may not be a synchronous event in the testicular parenchyma of pigs. The objectives of the present study were to evaluate the pattern of seminiferous cord/tubule maturation and the morphological and functional characteristics of testicular somatic cells during postnatal development in three regions of the pig testis: a) near the tunica albuginea (TA); b) in the transitional area between the seminiferous tubules and mediastinum (TR); and c) in the intermediate area (ID) between the TA and TR. Based on the diameter of seminiferous cords/tubules, nucleus size of Sertoli cells and fluid secretion, mainly at 90 and 120 d of age, seminiferous tubule maturation was more advanced in the ID and TR. The mitotic activity of Sertoli cells was higher (P < 0.05) in the TR than the ID and TA at 7 and 120 d. Except for the mitotic index of the Leydig cells, which was lower (P < 0.05) in the ID at 7, 30, and 180 d than in the TA and TR, other Leydig cell ebd points, e.g., individual cell size, nuclear volume, and cytoplasmic volume, were consistently higher (P < 0.05) in the ID, suggesting that steroidogenesis was more active in this region during the period investigated. Overall, we inferred that Leydig cells in the ID may play a pivotal role in postnatal testis development in pigs and this type of cell is likely related to asynchronous testicular parenchyma development, with the transitional area providing the primary zone for growth of seminiferous tubules. PMID:20189235

Direct hydrothermal growth of GDC nanorods for low temperature solid oxide fuel cells

NASA Astrophysics Data System (ADS)

Hong, Soonwook; Lee, Dohaeng; Yang, Hwichul; Kim, Young-Beom

2018-06-01

We report a novel synthesis technique of gadolinia-doped ceria (GDC) nano-rod (NRs) via direct hydrothermal process to enhance performance of low temperature solid oxide fuel cell by increasing active reaction area and ionic conductivity at interface between cathode and electrolyte. The cerium nitrate hexahydrate, gadolinium nitrate hexahydrate and urea were used to synthesis GDC NRs for growth on diverse substrate. The directly grown GDC NRs on substrate had a width from 819 to 490 nm and height about 2200 nm with a varied urea concentration. Under the optimized urea concentration of 40 mMol, we confirmed that GDC NRs able to fully cover the substrate by enlarging active reaction area. To maximize ionic conductivity of GDC NRs, we synthesis varied GDC NRs with different ratio of gadolinium and cerium precursor. Electrochemical analysis revealed a significant enhanced performance of fuel cells applying synthesized GDC NRs with a ratio of 2:8 gadolinium and cerium precursor by reducing polarization resistance, which was chiefly attributed to the enlarged active reaction area and enhanced ionic conductivity of GDC NRs. This method of direct hydrothermal growth of GDC NRs enhancing fuel cell performance was considered to apply other types of catalyzing application using nano-structure such as gas sensing and electrolysis fields.

Monitoring geo-biodiversity interactions of a restored inland drift-sand cell in Nieuw Bergen (Li)

NASA Astrophysics Data System (ADS)

Jungerius, Pieter Dirk; van den Ancker, Hanneke; Arts, Andries; Borkent, Ido; Ketner-Oostra, Rita; Ketner, Pieter

2013-04-01

In 2002, a research was carried out by Jungerius, van den Ancker, Ketner-Oostra and Evers to see if it was possible to restore active inland drift-sand areas in National Park De Maasduinen in Nieuw Bergen, Limburg. The active drift-sand had completely disappeared from the area by nitrogen-rich precipitation. It was decided to try and restore the activity depicted on the first aerial photographs in 1933, if soil profile development and Natura 2000 species allowed this. The areas stabilized since then were overgrown, dominantly by the invasive moss Campylopus introflexus, a species introduced to the Netherlands by tanks during World War II. Areas colonized by Natura 2000 lichens were spared as centres for re-colonization. The research gave insight in the elongated geomorphological cell-structure of the original drift-sands and the rate of soil development after stabilisation. In 2005, the first active drift-sand cell was restored by increasing the erodibility of the terrain, by mechanically removing the sod and up to 5 cm thick soil formed since 1933, and increasing the erosivity of the wind by removing trees, mainly in the upwind direction. In 2008 a second cell was restored, and a third one in 2011. A monitoring programme was set up for the first cell to improve our understanding of stabilization and geodiversity-biodiversity interactions in drift-sand areas. Lines of erosion pins were monitored at regular intervals for a five year period. Aerial photographs made in 2005 and 2008 showed the pattern of stabilization of the moving sand. The poster will present the results of these experiments. In 2012, five years after the restoration, the active drift-sand cell was stable again and had turned into an open dry grassland, almost completely dominated by the Natura 2000 species Corynephorus canescens. Unfortunately several of the areas that were spared as centres for re-colonization of Natura 2000 lichens lay in the sand transport zone and had acted as sandtraps, and most Natura-2000 species had disappeared from these areas. Discussion and recommendations From the Natura-2000 viewpoint the restoration measures were very successful as the terrain now classifies as habitat type 2330. Different views exist on how to further manage the terrain. One view is to try and create a steady-state situation by regularly removing part of the Corynephorus canescens vegetation and having an active erosion- and transport-zone while further increasing the erosivity of the wind by removing more trees. Another view is to let succession have its way, and see which species appear in the course of succession. As cells in successive stages are now available, we propose to test the different views and proceed with the monitoring of the terrains. Reference Ancker, J.A.M. van den, Everts, H., Jungerius, P.D. & Ketner-Oostra, R., 2002. Vooronderzoek herstel stuifzanden gemeente Bergen (Limburg). Rapport Stichting G&L, Ede, i.s.m. Rita Ketner en Ecologisch Advies & Onderzoeksbureau Everts & de Vries, i.o.v. de gemeente Bergen (Li).

Distribution of bacterioplankton with active metabolism in waters of the St. Anna Trough, Kara Sea, in autumn 2011

NASA Astrophysics Data System (ADS)

Mosharova, I. V.; Mosharov, S. A.; Ilinskiy, V. V.

2017-01-01

The distribution of bacterioplankton with active electron transport chains, as well as bacteria with intact cell membranes, was investigated for the first time in the region of St. Anna Trough in the Kara Sea. The average number of bacteria with active electron transport chains in the waters of the St. Anna Trough was 15.55 × 103 cells mL-1 (the limits of variation were 1.06-92.17 × 103 cells mL-1). The average number of bacteria with intact membranes was 33.46 × 103 cells mL-1 (the limits of variation were 6.78 to 103.18 × 103 cells mL-1). Almost all bacterioplankton microorganisms in the studied area were potentially viable, and the average share of bacteria with intact membranes was 92.1% of the total number of bacterioplankton (TNB) (the limits of variation were 76.2 to 98.4%). The share of bacteria with active metabolisms was 38.2% of the TNB (the limits of variation were 5.6-93.4%). The shares of the bacteria with active metabolisms were maximum in areas with the most stable environmental conditions (on the shelf and in deep water), whereas on the slope, where the gradients of water temperature and salinity were maximum, these values were lower.

High-surface-area architectures for improved charge transfer kinetics at the dark electrode in dye-sensitized solar cells.

PubMed

Hoffeditz, William L; Katz, Michael J; Deria, Pravas; Martinson, Alex B F; Pellin, Michael J; Farha, Omar K; Hupp, Joseph T

2014-06-11

Dye-sensitized solar cell (DSC) redox shuttles other than triiodide/iodide have exhibited significantly higher charge transfer resistances at the dark electrode. This often results in poor fill factor, a severe detriment to device performance. Rather than moving to dark electrodes of untested materials that may have higher catalytic activity for specific shuttles, the surface area of platinum dark electrodes could be increased, improving the catalytic activity by simply presenting more catalyst to the shuttle solution. A new copper-based redox shuttle that experiences extremely high charge-transfer resistance at conventional Pt dark electrodes yields cells having fill-factors of less than 0.3. By replacing the standard Pt dark electrode with an inverse opal Pt electrode fabricated via atomic layer deposition, the dark electrode surface area is boosted by ca. 50-fold. The resulting increase in interfacial electron transfer rate (decrease in charge-transfer resistance) nearly doubles the fill factor and therefore the overall energy conversion efficiency, illustrating the utility of this high-area electrode for DSCs.

The Repeated Replacement Method: A Pure Lagrangian Meshfree Method for Computational Fluid Dynamics

PubMed Central

Walker, Wade A.

2012-01-01

In this paper we describe the repeated replacement method (RRM), a new meshfree method for computational fluid dynamics (CFD). RRM simulates fluid flow by modeling compressible fluids’ tendency to evolve towards a state of constant density, velocity, and pressure. To evolve a fluid flow simulation forward in time, RRM repeatedly “chops out” fluid from active areas and replaces it with new “flattened” fluid cells with the same mass, momentum, and energy. We call the new cells “flattened” because we give them constant density, velocity, and pressure, even though the chopped-out fluid may have had gradients in these primitive variables. RRM adaptively chooses the sizes and locations of the areas it chops out and replaces. It creates more and smaller new cells in areas of high gradient, and fewer and larger new cells in areas of lower gradient. This naturally leads to an adaptive level of accuracy, where more computational effort is spent on active areas of the fluid, and less effort is spent on inactive areas. We show that for common test problems, RRM produces results similar to other high-resolution CFD methods, while using a very different mathematical framework. RRM does not use Riemann solvers, flux or slope limiters, a mesh, or a stencil, and it operates in a purely Lagrangian mode. RRM also does not evaluate numerical derivatives, does not integrate equations of motion, and does not solve systems of equations. PMID:22866175

Effects of voluntary wheel running on satellite cells in the rat plantaris muscle.

PubMed

Kurosaka, Mitsutoshi; Naito, Hisashi; Ogura, Yuji; Kojima, Atsushi; Goto, Katsumasa; Katamoto, Shizuo

2009-01-01

This study investigated the effects of voluntary wheel running on satellite cells in the rat plantaris muscle. Seventeen 5-week-old male Wistar rats were assigned to a control (n = 5) or training (n = 12) group. Each rat in the training group ran voluntarily in a running-wheel cage for 8 weeks. After the training period, the animals were anesthetized, and the plantaris muscles were removed, weighed, and analyzed immunohistochemically and biochemically. Although there were no significant differences in muscle weight or fiber area between the groups, the numbers of satellite cells and myonuclei per muscle fiber, percentage of satellite cells, and citrate synthase activity were significantly higher in the training group compared with the control group (p < 0.05). The percentage of satellite cells was also positively correlated with distance run in the training group (r = 0.61, p < 0.05). Voluntary running can induce an increase in the number of satellite cells without changing the mean fiber area in the rat plantaris muscle; this increase in satellite cell content is a function of distance run. Key pointsThere is no study about the effect of voluntary running on satellite cells in the rat plantaris muscle.Voluntary running training causes an increase of citrate synthase activity in the rat plantaris muscle but does not affect muscle weight and mean fiber area in the rat plantaris muscle.Voluntary running can induce an increase in the number of satellite cells without hypertrophy of the rat plantaris muscle.

Design and fabrication of segmented-in-series solid oxide fuel cells

NASA Astrophysics Data System (ADS)

Lai, Tammy S.

Segmented-in-series solid oxide fuel cells (SS-SOFC) consist of several thick film cells deposited onto a porous, flattened tubular substrate. SS-SOFCs have a reduced need for gas-tight seals relative to planar SOFCs and can have a short current path compared to tubular SOFCs, limiting electrode ohmic resistance. Like tubular SOFCs, SS-SOFCs are suitable for stationary power generation. Their potentially small cell size makes them candidates for portable applications as well. The goals of this thesis project were to develop SS-SOFCs with 1-2 mm cell lengths and to analyze the effects of cell geometry and support current shunting on performance. Standard SOFC materials were chosen for the active components: yttria stabilized zirconia (YSZ) electrolyte; Ni-YSZ cermet anode; and (La,Sr)MnO 3-based cathode. A Pt-YSZ cermet was used as the interconnect material. Screen printing was the deposition method for all layers due to its low cost and patterning ability. A power density of >900 mW/cm2 was achieved with a cathode sheet resistance of ≈3 O/□ (≈90 mum LSM thickness). A D-optimal study was conducted to find processing conditions yielding substrates with ≥30 vol% porosity and high strength. Uniaxially pressed partially stabilized zirconia (PSZ) with 15 wt% starch pore former met the requirements, though 20 wt% graphite pore former was later found to give a smoother surface that improved screen printed layer quality. Calculations presented in this thesis take into account losses due to cell resistances, electrode ohmic resistances, interconnect resistance, and shunting by a weakly-conductive support material. Power density was maximized at an optimal cell length---it decreased at larger cell lengths due to electrode lateral resistance loss and at smaller cell lengths due to a decreasing fraction of cell active area. Assuming dimensions expected for screen printing and typical area specific resistances (RAS), optimal cell lengths typically ranged from 1 to 3 mm. The calculated and experimental values for the array RAS (active and inactive areas) showed similar dependences on cathode sheet resistance. The impact of shunting current increased with decreasing cell lengths. Shunting current was predicted to decrease array current by ˜10% for a 1.5 mm active cell length, though experimental measurements suggest that the calculation may overestimate the shunting effect.

Fc-receptor induced cell spreading during frustrated phagocytosis in J774A.1 macrophages

NASA Astrophysics Data System (ADS)

Kovari, Daniel; Curtis, Jennifer; Wei, Wenbin

2014-03-01

Phagocytosis is the process where by cells engulf foreign particles. It is the primary mechanism through which macrophages and neutrophils (white blood cells) eliminate pathogens and debris from the body. The behavior is the result of a cascade of chemical and mechanical cues, which result in the actin-driven expansion of the cell's membrane around its target. For macrophages undergoing Fc-mediated phagocytosis, we show that above a minimum threshold the spreading rate and maximum cell-target contact area are independent of the target's opsonin density. Qualitatively, macrophage phagocytic spreading is similar to the spreading of other cell types (e.g. fibroblasts, lymphocytes, and Dict.d.). Early spreading is most likely the result of ``passive'' alignment of the cell to the target surface. This is followed by an active expansion period driven by actin. Finally upon reaching a maximum contact area, typically 2-3 times the size of ``non-activated'' cells, macrophages often undergo a period of rapid contraction not reported in other cell types. We hypothesize that this, as yet unexplained, transition may be specific to the chemical and mechanical machinery associated with phagocytosis. This work was funded by NSF grant PHYS 0848797 and NSF grant DMR 0820382.

Liquid-permeable electrode

DOEpatents

Folser, George R.

1980-01-01

Electrodes for use in an electrolytic cell, which are liquid-permeable and have low electrical resistance and high internal surface area are provided of a rigid, porous, carbonaceous matrix having activated carbon uniformly embedded throughout. The activated carbon may be catalyzed with platinum for improved electron transfer between electrode and electrolyte. Activated carbon is mixed with a powdered thermosetting phenolic resin and compacted to the desired shape in a heated mold to melt the resin and form the green electrode. The compact is then heated to a pyrolyzing temperature to carbonize and volatilize the resin, forming a rigid, porous structure. The permeable structure and high internal surface area are useful in electrolytic cells where it is necessary to continuously remove the products of the electrochemical reaction.

Analysis of Invasive Activity of CAF Spheroids into Three Dimensional (3D) Collagen Matrices.

PubMed

Villaronga, María Ángeles; Teijeiro, Saúl Álvarez; Hermida-Prado, Francisco; Garzón-Arango, Marta; Sanz-Moreno, Victoria; García-Pedrero, Juana María

2018-01-01

Tumor growth and progression is the result of a complex process controlled not only by malignant cancer cells but also by the surrounding tumor microenvironment (TME). Cancer associated fibroblasts (CAFs), the most abundant cellular component of TME, play an active role in tumor invasion and metastasis by promoting cancer cell invasion through cell-cell interactions and secretion of pro-invasive factors such as extracellular matrix (ECM)-degrading proteases. Due to their tumor-promoting activities, there is an emerging interest in investigating CAFs biology and its potential as drug targets for cancer therapies. Here we describe an easy and highly reproducible quantitative method to analyze CAF invasive activity by forming multicellular spheroids embedded into a three-dimensional (3D) matrix that mimics in vivo ECM. Subsequently, invasion is monitored over time using a time-lapse microscope. We also provide an automated image analysis system that enables the rapid quantification of the spheroid area increase (invasive area) over time. The use of a 96-well plate format with one CAF spheroid per well and the automated analysis provides a method suitable for drug screening test, such as protease inhibitors.

Capacitance measurements of regulated exocytosis in mouse taste cells.

PubMed

Vandenbeuch, Aurelie; Zorec, Robert; Kinnamon, Sue C

2010-11-03

Exocytosis, consisting of the merger of vesicle and plasma membrane, is a common mechanism used by different types of nucleated cells to release their vesicular contents. Taste cells possess vesicles containing various neurotransmitters to communicate with adjacent taste cells and afferent nerve fibers. However, whether these vesicles engage in exocytosis on a stimulus is not known. Since vesicle membrane merger with the plasma membrane is reflected in plasma membrane area fluctuations, we measured membrane capacitance (C(m)), a parameter linearly related to membrane surface area. To investigate whether taste cells undergo regulated exocytosis, we used the compensated tight-seal whole-cell recording technique to monitor depolarization-induced changes in C(m) in the different types of taste cells. To identify taste cell types, mice expressing green fluorescent protein from the TRPM5 promoter or from the GAD67 promoter were used to discriminate type II and type III taste cells, respectively. Moreover, the cell types were also identified by monitoring their voltage-current properties. The results demonstrate that only type III taste cells show significant depolarization-induced increases in C(m), which were correlated to the voltage-activated calcium currents. The results suggest that type III, but neither type II nor type I cells exhibit depolarization-induced regulated exocytosis to release transmitter and activate gustatory afferent nerve fibers.

Sampling alien species inside and outside protected areas: Does it matter?

NASA Astrophysics Data System (ADS)

Moustakas, Aristides; Voutsela, Anneta; Katsanevakis, Stelios

2018-06-01

Data of alien species presences are generally more readily available in protected than non-protected areas due to higher sampling efforts inside protected areas. Are the results and conclusions based on analyses of data collected in protected areas representative of wider non-protected regions? We address this question by analysing some recently published data of alien plants in Greece. Mixed effects models were used with alien species presences in 8.25 x 8.25 km cells as dependent variable and the percentage of protected area, as well as the agricultural and artificial land cover types richness (as indicators of human presence) as independent variables. In addition, the spatial cross-correlation between the percentage of protected area and alien species richness was examined across scales. Results indicated that the percentage of protected area per cell is a poor predictor of alien species richness. Spatial analysis indicated that cells with higher percentage of protected areas have slightly less alien species than cells with lower percentage of protected areas. This result is likely to be driven by the overall negative correlation between habitat protection and anthropogenic activities. Thus, the conclusions deduced by data deriving from protected areas are likely to hold true for patterns of alien species in non-protected areas when the human pressures are accounted for.

Cytological Study of Breast Carcinoma Before and After Oncotherapy with Special Reference to Morphometry and Proliferative Activity.

PubMed

Koley, Sananda; Chakrabarti, Srabani; Pathak, Swapan; Manna, Asim Kumar; Basu, Siddhartha

2015-12-01

Our study was done to assess the cytological changes due to oncotherapy in breast carcinoma especially on morphometry and proliferative activity. Cytological aspirates were collected from a total of 32 cases of invasive ductal carcinoma both before and after oncotherapy. Morphometry was done on the stained cytological smears to assess the different morphological parameters of cell dimension by using the ocular morphometer and the software AutoCAD 2007. Staining was done with Ki-67 and proliferating cell nuclear antigen (PCNA) as proliferative markers. Different morphological parameters were compared before and after oncotherapy by unpaired Student's t test. Statistically significant differences were found in morphometric parameters, e.g., mean nuclear diameter, mean nuclear area, mean cell diameter, and mean cell area, and in the expression of proliferative markers (Ki-67 and PCNA). Statistical analysis was done by obtaining p values. There are statistically significant differences between morphological parameter of breast carcinoma cells before and after oncotherapy.

Automated image-based assay for evaluation of HIV neutralization and cell-to-cell fusion inhibition.

PubMed

Sheik-Khalil, Enas; Bray, Mark-Anthony; Özkaya Şahin, Gülsen; Scarlatti, Gabriella; Jansson, Marianne; Carpenter, Anne E; Fenyö, Eva Maria

2014-08-30

Standardized techniques to detect HIV-neutralizing antibody responses are of great importance in the search for an HIV vaccine. Here, we present a high-throughput, high-content automated plaque reduction (APR) assay based on automated microscopy and image analysis that allows evaluation of neutralization and inhibition of cell-cell fusion within the same assay. Neutralization of virus particles is measured as a reduction in the number of fluorescent plaques, and inhibition of cell-cell fusion as a reduction in plaque area. We found neutralization strength to be a significant factor in the ability of virus to form syncytia. Further, we introduce the inhibitory concentration of plaque area reduction (ICpar) as an additional measure of antiviral activity, i.e. fusion inhibition. We present an automated image based high-throughput, high-content HIV plaque reduction assay. This allows, for the first time, simultaneous evaluation of neutralization and inhibition of cell-cell fusion within the same assay, by quantifying the reduction in number of plaques and mean plaque area, respectively. Inhibition of cell-to-cell fusion requires higher quantities of inhibitory reagent than inhibition of virus neutralization.

Development status on a TPV cylinder for combined heat and electric power for the home

NASA Astrophysics Data System (ADS)

Fraas, Lewis; Samaras, John; Huang, Han-Xiang; Seal, Michael; West, Edward

1999-03-01

Several first-generation water-cooled TPV cylinders have been built and tested. The existing units contain 380 GaSb cells mounted on 20 circuits; the design and test results on these photovoltaic converter arrays are presented here. Tested with a 1600 °C glowbar, one of these cylinders generated 990 Watts from a cell active area of 396 cm2, which is an electric power density of 2.5 Watts per cm2. A second-generation design is presented, using a new shingled circuit assembly. These shingled circuits allow for a slightly larger cylinder design with nearly double the cell active area. Using a SiC emitter operating at 1425 °C, this second-generation cylinder should produce over 1.5 kW of power with improved efficiency.

Polymer based organic solar cells using ink-jet printed active layers

NASA Astrophysics Data System (ADS)

Aernouts, T.; Aleksandrov, T.; Girotto, C.; Genoe, J.; Poortmans, J.

2008-01-01

Ink-jet printing is used to deposit polymer:fullerene blends suitable as active layer for organic solar cells. We show that merging of separately deposited ink droplets into a continuous, pinhole-free organic thin film results from a balance between ink viscosity and surface wetting, whereas for certain of the studied solutions clear coffee drop effect occurs for single droplets; this can be minimized for larger printed areas, yielding smooth layers with minimal surface roughness. Resulting organic films are used as active layer for solar cells with power conversion efficiency of 1.4% under simulated AM1.5 solar illumination.

Leucine incorporation by aerobic anoxygenic phototrophic bacteria in the Delaware estuary

PubMed Central

Stegman, Monica R; Cottrell, Matthew T; Kirchman, David L

2014-01-01

Aerobic anoxygenic phototrophic (AAP) bacteria are well known to be abundant in estuaries, coastal regions and in the open ocean, but little is known about their activity in any aquatic ecosystem. To explore the activity of AAP bacteria in the Delaware estuary and coastal waters, single-cell 3H-leucine incorporation by these bacteria was examined with a new approach that combines infrared epifluorescence microscopy and microautoradiography. The approach was used on samples from the Delaware coast from August through December and on transects through the Delaware estuary in August and November 2011. The percent of active AAP bacteria was up to twofold higher than the percentage of active cells in the rest of the bacterial community in the estuary. Likewise, the silver grain area around active AAP bacteria in microautoradiography preparations was larger than the area around cells in the rest of the bacterial community, indicating higher rates of leucine consumption by AAP bacteria. The cell size of AAP bacteria was 50% bigger than the size of other bacteria, about the same difference on average as measured for activity. The abundance of AAP bacteria was negatively correlated and their activity positively correlated with light availability in the water column, although light did not affect 3H-leucine incorporation in light–dark experiments. Our results suggest that AAP bacteria are bigger and more active than other bacteria, and likely contribute more to organic carbon fluxes than indicated by their abundance. PMID:24824666

Leucine incorporation by aerobic anoxygenic phototrophic bacteria in the Delaware estuary.

PubMed

Stegman, Monica R; Cottrell, Matthew T; Kirchman, David L

2014-11-01

Aerobic anoxygenic phototrophic (AAP) bacteria are well known to be abundant in estuaries, coastal regions and in the open ocean, but little is known about their activity in any aquatic ecosystem. To explore the activity of AAP bacteria in the Delaware estuary and coastal waters, single-cell (3)H-leucine incorporation by these bacteria was examined with a new approach that combines infrared epifluorescence microscopy and microautoradiography. The approach was used on samples from the Delaware coast from August through December and on transects through the Delaware estuary in August and November 2011. The percent of active AAP bacteria was up to twofold higher than the percentage of active cells in the rest of the bacterial community in the estuary. Likewise, the silver grain area around active AAP bacteria in microautoradiography preparations was larger than the area around cells in the rest of the bacterial community, indicating higher rates of leucine consumption by AAP bacteria. The cell size of AAP bacteria was 50% bigger than the size of other bacteria, about the same difference on average as measured for activity. The abundance of AAP bacteria was negatively correlated and their activity positively correlated with light availability in the water column, although light did not affect (3)H-leucine incorporation in light-dark experiments. Our results suggest that AAP bacteria are bigger and more active than other bacteria, and likely contribute more to organic carbon fluxes than indicated by their abundance.

STATs: An Old Story, Yet Mesmerizing.

PubMed

Abroun, Saeid; Saki, Najmaldin; Ahmadvand, Mohammad; Asghari, Farahnaz; Salari, Fatemeh; Rahim, Fakher

2015-01-01

Signal transducers and activators of transcription (STATs) are cytoplasmic transcription factors that have a key role in cell fate. STATs, a protein family comprised of seven members, are proteins which are latent cytoplasmic transcription factors that convey signals from the cell surface to the nucleus through activation by cytokines and growth factors. The signaling pathways have diverse biological functions that include roles in cell differentiation, proliferation, development, apoptosis, and inflammation which place them at the center of a very active area of research. In this review we explain Janus kinase (JAK)/STAT signaling and focus on STAT3, which is transient from cytoplasm to nucleus after phosphorylation. This procedure controls fundamental biological processes by regulating nuclear genes controlling cell proliferation, survival, and development. In some hematopoietic disorders and cancers, overexpression and activation of STAT3 result in high proliferation, suppression of cell differentiation and inhibition of cell maturation. This article focuses on STAT3 and its role in malignancy, in addition to the role of microRNAs (miRNAs) on STAT3 activation in certain cancers.

Tanshinone IIA Pretreatment Renders Free Flaps against Hypoxic Injury through Activating Wnt Signaling and Upregulating Stem Cell-Related Biomarkers

PubMed Central

Xu, Zihan; Zhang, Zhenxin; Wu, Lijun; Sun, Yaowen; Guo, Yadong; Qin, Gaoping; Mu, Shengzhi; Fan, Ronghui; Wang, Benfeng; Gao, Wenjie

2014-01-01

Partial or total flap necrosis after flap transplantation is sometimes clinically encountered in reconstructive surgery, often as a result of a period of hypoxia that exceeds the tolerance of the flap tissue. In this study, we determine whether tanshinone IIA (TSA) pretreatment can protect flap tissue against hypoxic injury and improve its viability. Primary epithelial cells isolated from the dorsal skin of mice were pretreated with TSA for two weeks. Cell counting kit-8 and Trypan Blue assays were carried out to examine the proliferation of TSA-pretreated cells after exposure to cobalt chloride. Then, Polymerase chain reaction and Western blot analysis were used to determine the expression of β-catenin, GSK-3β, SOX2, and OCT4 in TSA-treated cells. In vivo, after mice were pretreated with TSA for two weeks, a reproducible ischemic flap model was implemented, and the area of surviving tissue in the transplanted flaps was measured. Immunohistochemistry was also conducted to examine the related biomarkers mentioned above. Results show that epidermal cells, pretreated with TSA, showed enhanced resistance to hypoxia. Activation of the Wnt signaling pathway in TSA-pretreated cells was characterized by the upregulation of β-catenin and the downregulation of GSK-3β. The expression of SOX2 and OCT4 controlled by Wnt signaling were also found higher in TSA pretreated epithelial cells. In the reproducible ischaemic flap model, pretreatment with TSA enhanced resistance to hypoxia and increased the area of surviving tissue in transplanted flaps. The expression of Wnt signaling pathway components, stem-cell related biomarkers, and CD34, which are involved in the regeneration of blood vessels, was also upregulated in TSA-pretreated flap tissue. The results show that TSA pretreatment protects free flaps against hypoxic injury and increases the area of surviving tissue by activating Wnt signaling and upregulating stem cell-related biomarkers. PMID:25302618

Immunohistochemical characterisation of the hepatic stem cell niche in feline hepatic lipidosis: a preliminary morphological study.

PubMed

Valtolina, Chiara; Robben, Joris H; Favier, Robert P; Rothuizen, Jan; Grinwis, Guy Cm; Schotanus, Baukje A; Penning, Louis C

2018-05-01

Objectives The aim of this study was to describe the cellular and stromal components of the hepatic progenitor cell niche in feline hepatic lipidosis (FHL). Methods Immunohistochemical staining for the progenitor/bile duct marker (K19), activated Kupffer cells (MAC387), myofibroblasts (alpha-smooth muscle actin [α-SMA]) and the extracellular matrix component laminin were used on seven liver biopsies of cats with FHL and three healthy cats. Double immunofluorescence stainings were performed to investigate co-localisation of different cell types in the hepatic progenitor cell (HPC) niche. Results HPCs, Kupffer cells, myofibroblasts and laminin deposition were observed in the liver samples of FHL, although with variability in the expression and positivity of the different immunostainings between different samples. When compared with the unaffected cats where K19 positivity and minimal α-SMA and laminin positivity were seen mainly in the portal area, in the majority of FHL samples K19 and α-SMA-positive cells and laminin positivity were seen also in the periportal and parenchymatous area. MAC387-positive cells were present throughout the parenchyma. Conclusions and relevance This is a preliminary morphological study to describe the activation and co-localisation of components of the HPC niche in FHL. Although the HPC niche in FHL resembles that described in hepatopathies in dogs and in feline lymphocytic cholangitis, the expression of K19, α-SMA, MAC387 and lamin is more variable in FHL, and a common pattern of activation could not be established. Nevertheless, when HPCs were activated, a spatial association between HPCs and their niche could be demonstrated.

One-pot synthesis of transition metal ion-chelating ordered mesoporous carbon/carbon nanotube composites for active and durable fuel cell catalysts

NASA Astrophysics Data System (ADS)

Dombrovskis, Johanna K.; Palmqvist, Anders E. C.

2017-07-01

Development of non-precious metal catalysts for the oxygen reduction reaction (ORR) in proton exchange membrane (PEM) fuel cells with high activity and durability and with optimal water management properties is of outmost technological importance and highly challenging. Here we study the possibilities offered through judicious selection of small molecular precursors used for the formation of ordered mesoporous carbon-based non-precious metal ORR catalysts. By combining two complementary precursors, we present a one-pot synthesis that leads to a composite material consisting of transition metal ion-chelating ordered mesoporous carbon and multi-walled carbon nanotubes (TM-OMC/CNT). The resulting composite materials show high specific surface areas and a carbon structure that exhibits graphitic signatures. The synthesis procedure allows for tuning of the carbon structure, the surface area, the pore volume and the ratio of the two components of the composite. The TM-OMC/CNT composites were processed into membrane electrode assemblies and evaluated in single cell fuel cell measurements where they showed a combination of good ORR activity and very high durability.

High-content analysis of single cells directly assembled on CMOS sensor based on color imaging.

PubMed

Tanaka, Tsuyoshi; Saeki, Tatsuya; Sunaga, Yoshihiko; Matsunaga, Tadashi

2010-12-15

A complementary metal oxide semiconductor (CMOS) image sensor was applied to high-content analysis of single cells which were assembled closely or directly onto the CMOS sensor surface. The direct assembling of cell groups on CMOS sensor surface allows large-field (6.66 mm×5.32 mm in entire active area of CMOS sensor) imaging within a second. Trypan blue-stained and non-stained cells in the same field area on the CMOS sensor were successfully distinguished as white- and blue-colored images under white LED light irradiation. Furthermore, the chemiluminescent signals of each cell were successfully visualized as blue-colored images on CMOS sensor only when HeLa cells were placed directly on the micro-lens array of the CMOS sensor. Our proposed approach will be a promising technique for real-time and high-content analysis of single cells in a large-field area based on color imaging. Copyright © 2010 Elsevier B.V. All rights reserved.

Interim Closure Activities at Corrective Action Unit 114: Area 25 EMAD Facility, Nevada National Security Site, Nevada

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

Boehlecke, R. F.

This letter report documents interim activities that have been completed at CAU 114 to support ongoing access and generate information necessary to plan future closure activities. General housekeeping and cleanup of debris was conducted in the EMAD yard, cold bays, support areas of Building 3900, and postmortem cell tunnel area of the hot bay. All non-asbestos ceiling tiles and loose and broken non-friable asbestos floor tiles were removed from support galleries and office areas. Non-radiologically contaminated piping and equipment in the cold areas of the building and in the two 120-ton locomotives in the yard were tapped, characterized, drained, andmore » verified free of contents.« less

Automated Array Assembly, Phase 2

NASA Technical Reports Server (NTRS)

Carbajal, B. G.

1979-01-01

The Automated Array Assembly Task, Phase 2 of the Low Cost Silicon Solar Array Project is a process development task. The contract provides for the fabrication of modules from large area tandem junction cells (TJC). During this quarter, effort was focused on the design of a large area, approximately 36 sq cm, TJC and process verification runs. The large area TJC design was optimized for minimum I squared R power losses. In the TJM activity, the cell-module interfaces were defined, module substrates were formed and heat treated and clad metal interconnect strips were fabricated.

Activity targets for nanostructured platinum-group-metal-free catalysts in hydroxide exchange membrane fuel cells.

PubMed

Setzler, Brian P; Zhuang, Zhongbin; Wittkopf, Jarrid A; Yan, Yushan

2016-12-06

Fuel cells are the zero-emission automotive power source that best preserves the advantages of gasoline automobiles: low upfront cost, long driving range and fast refuelling. To make fuel-cell cars a reality, the US Department of Energy has set a fuel cell system cost target of US$30 kW -1 in the long-term, which equates to US$2,400 per vehicle, excluding several major powertrain components (in comparison, a basic, but complete, internal combustion engine system costs approximately US$3,000). To date, most research for automotive applications has focused on proton exchange membrane fuel cells (PEMFCs), because these systems have demonstrated the highest power density. Recently, however, an alternative technology, hydroxide exchange membrane fuel cells (HEMFCs), has gained significant attention, because of the possibility to use stable platinum-group-metal-free catalysts, with inherent, long-term cost advantages. In this Perspective, we discuss the cost profile of PEMFCs and the advantages offered by HEMFCs. In particular, we discuss catalyst development needs for HEMFCs and set catalyst activity targets to achieve performance parity with state-of-the-art automotive PEMFCs. Meeting these targets requires careful optimization of nanostructures to pack high surface areas into a small volume, while maintaining high area-specific activity and favourable pore-transport properties.

Activity targets for nanostructured platinum-group-metal-free catalysts in hydroxide exchange membrane fuel cells

NASA Astrophysics Data System (ADS)

Setzler, Brian P.; Zhuang, Zhongbin; Wittkopf, Jarrid A.; Yan, Yushan

2016-12-01

Fuel cells are the zero-emission automotive power source that best preserves the advantages of gasoline automobiles: low upfront cost, long driving range and fast refuelling. To make fuel-cell cars a reality, the US Department of Energy has set a fuel cell system cost target of US$30 kW-1 in the long-term, which equates to US$2,400 per vehicle, excluding several major powertrain components (in comparison, a basic, but complete, internal combustion engine system costs approximately US$3,000). To date, most research for automotive applications has focused on proton exchange membrane fuel cells (PEMFCs), because these systems have demonstrated the highest power density. Recently, however, an alternative technology, hydroxide exchange membrane fuel cells (HEMFCs), has gained significant attention, because of the possibility to use stable platinum-group-metal-free catalysts, with inherent, long-term cost advantages. In this Perspective, we discuss the cost profile of PEMFCs and the advantages offered by HEMFCs. In particular, we discuss catalyst development needs for HEMFCs and set catalyst activity targets to achieve performance parity with state-of-the-art automotive PEMFCs. Meeting these targets requires careful optimization of nanostructures to pack high surface areas into a small volume, while maintaining high area-specific activity and favourable pore-transport properties.

Continuous-feed electrochemical cell with nonpacking particulate electrode

DOEpatents

Cooper, John F.

1995-01-01

An electrochemical cell providing full consumption of electrochemically active particles in a nonpacking, electrolyte-permeable bed has a tapered cell cavity bounded by two nonparallel surfaces separated by a distance that promotes bridging of particles across the cavity. The gap/particle size ratio is maintained as the particles are consumed, decrease in size, and travel from the point of entry to the narrower end of the cell. A cell of this configuration supports a bed of low packing density maintained in a dynamic steady state by alternate formation and collapse of particle bridges across the gap and associated voids over the entire active area of the cell. The cell design can be applied to refuelable zinc/air cells and zinc/ferrocyanide storage batteries.

Continuous-feed electrochemical cell with nonpacking particulate electrode

DOEpatents

Cooper, J.F.

1995-07-18

An electrochemical cell providing full consumption of electrochemically active particles in a nonpacking, electrolyte-permeable bed has a tapered cell cavity bounded by two nonparallel surfaces separated by a distance that promotes bridging of particles across the cavity. The gap/particle size ratio is maintained as the particles are consumed, decrease in size, and travel from the point of entry to the narrower end of the cell. A cell of this configuration supports a bed of low packing density maintained in a dynamic steady state by alternate formation and collapse of particle bridges across the gap and associated voids over the entire active area of the cell. The cell design can be applied to refuelable zinc/air cells and zinc/ferrocyanide storage batteries. 6 figs.

Role of natural killer cells in antibacterial immunity.

PubMed

Schmidt, Stanislaw; Ullrich, Evelyn; Bochennek, Konrad; Zimmermann, Stefanie-Yvonne; Lehrnbecher, Thomas

2016-12-01

Bacteria are a significant cause of infectious complications, in particular in immunocompromised patients. There is an increasing understanding that Natural Killer (NK) cells not only exhibit direct activity against bacteria, but also exert indirect antibacterial activity through interaction with other immune cells via cytokines and interferons. Areas covered: This review seeks to give a global overview of in vitro and in vivo data how NK cells interact with bacteria. In this regard, the review describes how NK cells directly damage and kill bacteria by soluble factors such as perforin, the impact of NK cells on other arms of the immune system, as well as how bacteria may inhibit NK cell activities. Expert commentary: A better characterization of the antibacterial effects of NK cells is urgently needed. With a better understanding of the interaction of NK cells and bacteria, NK cells may become a promising tool to prevent or to combat bacterial infections, e.g. by adoptively transferring NK cells to immunocompromised patients.

All-solution-processed PbS quantum dot solar modules

NASA Astrophysics Data System (ADS)

Jang, Jihoon; Shim, Hyung Cheoul; Ju, Yeonkyeong; Song, Jung Hoon; An, Hyejin; Yu, Jong-Su; Kwak, Sun-Woo; Lee, Taik-Min; Kim, Inyoung; Jeong, Sohee

2015-05-01

A rapid increase in power conversion efficiencies in colloidal quantum dot (QD) solar cells has been achieved recently with lead sulphide (PbS) QDs by adapting a heterojunction architecture, which consists of small-area devices associated with a vacuum-deposited buffer layer with metal electrodes. The preparation of QD solar modules by low-cost solution processes is required to further increase the power-to-cost ratio. Herein we demonstrate all-solution-processed flexible PbS QD solar modules with a layer-by-layer architecture comprising polyethylene terephthalate (PET) substrate/indium tin oxide (ITO)/titanium oxide (TiO2)/PbS QD/poly(3-hexylthiophene) (P3HT)/poly(3,4-ethylenedioxythiophene) : poly(styrene sulfonate) (PEDOT : PSS)/Ag, with an active area of up to 30 cm2, exhibiting a power conversion efficiency (PCE) of 1.3% under AM 1.5 conditions (PCE of 2.2% for a 1 cm2 unit cell). Our approach affords trade-offs between power and the active area of the photovoltaic devices, which results in a low-cost power source, and which is scalable to larger areas.A rapid increase in power conversion efficiencies in colloidal quantum dot (QD) solar cells has been achieved recently with lead sulphide (PbS) QDs by adapting a heterojunction architecture, which consists of small-area devices associated with a vacuum-deposited buffer layer with metal electrodes. The preparation of QD solar modules by low-cost solution processes is required to further increase the power-to-cost ratio. Herein we demonstrate all-solution-processed flexible PbS QD solar modules with a layer-by-layer architecture comprising polyethylene terephthalate (PET) substrate/indium tin oxide (ITO)/titanium oxide (TiO2)/PbS QD/poly(3-hexylthiophene) (P3HT)/poly(3,4-ethylenedioxythiophene) : poly(styrene sulfonate) (PEDOT : PSS)/Ag, with an active area of up to 30 cm2, exhibiting a power conversion efficiency (PCE) of 1.3% under AM 1.5 conditions (PCE of 2.2% for a 1 cm2 unit cell). Our approach affords trade-offs between power and the active area of the photovoltaic devices, which results in a low-cost power source, and which is scalable to larger areas. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr01508a

2015 Annual Progress Report: DOE Hydrogen and Fuel Cells Program

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

None, None

The 2015 Annual Progress Report summarizes fiscal year 2015 activities and accomplishments by projects funded by the DOE Hydrogen and Fuel Cells Program. It covers the program areas of hydrogen production; hydrogen delivery; hydrogen storage; fuel cells; manufacturing R&D; technology validation; safety, codes and standards; systems analysis; and market transformation.

Specific role of LeMAN2 in the control of seed germination exposed by overexpression of the LeMAN3 gene in tomato plants.

PubMed

Belotserkovsky, Harel; Berger, Yael; Shahar, Ron; Wolf, Shmuel

2007-12-01

Endo-beta-mannanase is one of the key enzymes involved in the hydrolysis of the mannan-rich cell walls of tomato (Solanum lycopersicon) seeds. Two isoforms of endo-beta-mannanase have been characterized in tomato seeds: LeMAN2 is active in the micropylar area prior to germination and LeMAN1 is active after germination in all endosperm cells surrounding the cotyledons. To explore whether general mannanase activity in the endosperm cap is sufficient to promote germination, the gene encoding LeMAN3 was inserted into transgenic tomato plants under the control of a CaMV-35S promoter. Expression of LeMAN3 was evident in the endosperm cap and in the lateral endosperm of the transgenic seeds 10 min after imbibition. An activity test indicated increased activity of endo-beta-mannanase in the transgenic lines relative to the control line in all seed parts, during the first 20 h of imbibition. However, overexpression of LeMAN3 in transgenic seeds inhibited seed germination at both optimal and suboptimal temperatures. Detailed RT-PCR analyses revealed the transcription patterns of the genes encoding the various mannanase isoforms, and indicated a delay in LeMAN2 transcription in the endosperm cap of the transgenic seeds. Interestingly, tissue-print assays indicated similar mannanase activity in the micropylar areas for both transgenic and control seeds. These results indicate that overexpression of active endo-beta-mannanase in the endosperm cap is not sufficient to enable hydrolysis of the cell walls or to promote germination of tomato seeds. Cell-wall hydrolysis in these endosperm cells is under tight control and requires the specific activity of LeMAN2.

Ultrastructural Changes and Corneal Wound Healing After SMILE and PRK Procedures.

PubMed

Wei, Shengsheng; Wang, Yan; Wu, Di; Zu, PeiPei; Zhang, Hui; Su, Xiaolian

2016-10-01

To compare keratocyte activation, cellular morphologic changes and wound healing after SMILE and PRK procedures using transmission electron microscope (TEM). In this study, 22 New Zealand white rabbits (10- to 15-week old) were used. The right eyes of all animals underwent SMILE procedure and the left eyes underwent PRK procedure. Cornea samples taken 1 day and 1 week postoperatively were examined using TEM. Using TEM 1 day after SMILE procedure, the organization of collagen fibers seemed to have been preserved without thermal alterations. Keratocyte activation was observed in the anterior stroma. Disrupted collagen arrangement and debris of cells are visible in the area of damage, and some phagocytic cells and a large number of secondary lysosomes are visible in those cells. At the perimeter zone of the interface, many coenocytes and collagen fragments could be found within the phagocytic cell. One week after SMILE procedure, potential lacuna could be discerned. A large part of the interface of the lenticule extracted had an appearance of clearly being adhered to some mucus secretions. One day after PRK procedure, an irregular epithelial surface was visible using TEM. Keratocytes had been activated and the rough endoplasmic reticulum in those cells had expanded. One week after PRK procedure, the epithelial surface still was irregular and keratinization of the epithelium was still visible in some areas. Corneal endothelium cells were mildly damaged and some vacuoles within the cytoplasm could be discerned. In the anterior stroma, some unhealthy activated keratocytes could still be observed. New collagen fibrils were found present near the activated keratocytes. Using TEM, keratocyte activation could still be observed after SMILE compared to after PRK procedure. Fewer cellular ultrastructural changes were seen after SMILE procedure. Unlike in PRK procedure, no damaged epithelium and endothelium were found after SMILE.

Plastic Schottky-barrier solar cells

DOEpatents

Waldrop, J.R.; Cohen, M.J.

1981-12-30

A photovoltaic cell structure is fabricated from an active medium including an undoped polyacetylene, organic semiconductor. When a film of such material is in rectifying contact with a metallic area electrode, a Schottky-barrier junction is obtained within the body of the cell structure. Also, a gold overlayer passivates a magnesium layer on the undoped polyacetylene film. With the proper selection and location of elements a photovoltaic cell structure and solar cell are obtained.

Mouse neuroblastoma cell based model and the effect of epileptic events on calcium oscillations and neural spikes

NASA Astrophysics Data System (ADS)

Kim, Suhwan; Baek, Juyeong; Jung, Unsang; Lee, Sangwon; Jung, Woonggyu; Kim, Jeehyun; Kang, Shinwon

2013-05-01

Recently, Mouse neuroblastoma cells are considered as an attractive model for the study of human neurological and prion diseases, and intensively used as a model system in different areas. Among those areas, differentiation of neuro2a (N2A) cells, receptor mediated ion current, and glutamate induced physiological response are actively investigated. The reason for the interest to mouse neuroblastoma N2A cells is that they have a fast growing rate than other cells in neural origin with a few another advantages. This study evaluated the calcium oscillations and neural spikes recording of mouse neuroblastoma N2A cells in an epileptic condition. Based on our observation of neural spikes in mouse N2A cell with our proposed imaging modality, we report that mouse neuroblastoma N2A cells can be an important model related to epileptic activity studies. It is concluded that the mouse neuroblastoma N2A cells produce the epileptic spikes in vitro in the same way as produced by the neurons or the astrocytes. This evidence advocates the increased and strong level of neurotransmitters release by enhancement in free calcium using the 4-aminopyridine which causes the mouse neuroblastoma N2A cells to produce the epileptic spikes and calcium oscillation.

Heme-mediated cell activation: the inflammatory puzzle of sickle cell anemia.

PubMed

Guarda, Caroline Conceição da; Santiago, Rayra Pereira; Fiuza, Luciana Magalhães; Aleluia, Milena Magalhães; Ferreira, Júnia Raquel Dutra; Figueiredo, Camylla Vilas Boas; Yahouedehou, Setondji Cocou Modeste Alexandre; Oliveira, Rodrigo Mota de; Lyra, Isa Menezes; Gonçalves, Marilda de Souza

2017-06-01

Hemolysis triggers the onset of several clinical manifestations of sickle cell anemia (SCA). During hemolysis, heme, which is derived from hemoglobin (Hb), accumulates due to the inability of detoxification systems to scavenge sufficiently. Heme exerts multiple harmful effects, including leukocyte activation and migration, enhanced adhesion molecule expression by endothelial cells and the production of pro-oxidant molecules. Area covered: In this review, we describe the effects of heme on leukocytes and endothelial cells, as well as the features of vascular endothelial cells related to vaso-occlusion in SCA. Expert commentary: Free Hb, heme and iron, potent cytotoxic intravascular molecules released during hemolysis, can exacerbate, modulate and maintain the inflammatory response, a main feature of SCA. Endothelial cells in the vascular environment, as well as leukocytes, can become activated via the molecular signaling effects of heme. Due to the hemolytic nature of SCA, hemolysis represents an interesting therapeutic target for heme-scavenging purposes.

Subcellular localization based comparative study on radioresistant bacteria: A novel approach to mine proteins involve in radioresistance.

PubMed

Vishambra, Divya; Srivastava, Malay; Dev, Kamal; Jaiswal, Varun

2017-08-01

Radioresistant bacteria (RRB) are among the most radioresistant organisms and has a unique role in evolution. Along with the evolutionary role, radioresistant organisms play important role in paper industries, bioremediation, vaccine development and possibility in anti-aging and anti-cancer treatment. The study of radiation resistance in RRB was mainly focused on cytosolic mechanisms such as DNA repair mechanism, cell cleansing activity and high antioxidant activity. Although it was known that protein localized on outer areas of cell play role in resistance towards extreme condition but the mechanisms/proteins localized on the outer area of cells are not studied for radioresistance. Considering the fact that outer part of cell is more exposed to radiations and proteins present in outer area of the cell may have role in radioresistance. Localization based comparative study of proteome from RRB and non-radio resistant bacteria was carried out. In RRB 20 unique proteins have been identified. Further domain, structural, and pathway analysis of selected proteins were carried out. Out of 20 proteins, 8 proteins were direct involvement in radioresistance and literature study strengthens this, however, 1 proteins had assumed relation in radioresistance. Selected radioresistant proteins may be helpful for optimal use of RRB in industry and health care. Copyright © 2017 Elsevier Ltd. All rights reserved.

Insecticide exposure affects DNA and antioxidant enzymes activity in honey bee species Apis florea and A. dorsata: Evidence from Punjab, Pakistan.

PubMed

Hayat, Khizar; Afzal, Muhammad; Aqueel, Muhammad Anjum; Ali, Sajjad; Saeed, Muhammad Farhan; Khan, Qaiser M; Ashfaq, Muhammad; Damalas, Christos A

2018-09-01

Insecticide exposure can affect honey bees in agro-ecosystems, posing behavioral stresses that can lead to population decline. In this study, insecticide incidence, DNA damage, and antioxidant enzyme activity were studied in Apis florea and A. dorsata honey bee samples collected from insecticide-treated and insecticide-free areas of Punjab, Pakistan. Seven insecticides: chlorpyrifos, dimethoate, imidacloprid, phorate, emamectin, chlorfenapyr, and acetamiprid were detected in seven samples of A. florea and five samples of A. dorsata. In total, 12 samples (22.2%) of honey bees were found positive to insecticide presence out of 54 samples. The most frequently detected insecticide was chlorpyrifos, which was found in four samples (7.4%), with a concentration ranging from 0.01 to 0.05 μg/g and an average concentration 0.03 μg/g. The comet assay or single cell gel electrophoresis assay, a simple way to measure DNA strand breaks in eukaryotic cells, was used to microscopically find damage of DNA at the level of a single cell. Comet tail lengths of DNA in A. florea and A. dorsata samples from insecticide-treated areas were significantly higher (P < 0.05) than samples from insecticide-free areas. The highest comet tail length (19.28 ± 2.67 μm) was observed in DNA of A. dorsata from insecticide-treated areas, while the minimum one (3.18 ± 1.46 μm) was noted in A. dorsata from insecticide-free areas. Catalase (CAT) activity did not vary significantly between honey bee samples from insecticide-treated and insecticide-free areas, while glutathione S-transferase (GST) activity showed a significant reduction in response to insecticide exposure. Significant positive correlations were detected between enzyme activity and insecticide concentration in honey bee species from insecticide-treated areas compared with control groups. Toxicity from pesticide exposure at sub-lethal levels after application or from exposure to pesticide residues should not be underestimated in honey bees, as it may induce physiological impairment that can decline honey bees' health. Copyright © 2018 Elsevier B.V. All rights reserved.

Synergistic antitumor effect of combining metronomic chemotherapy with adoptive cell immunotherapy in nude mice.

PubMed

Shi, Shujing; Tao, Leilei; Song, Haizhu; Chen, Longbang; Huang, Guichun

2014-05-01

Adoptive cell immunotherapy with cytokine-induced killer cell (CIK cell) represents a promising non-toxic anticancer therapy. However, the clinical efficacy of CIK cells is limited because of abnormal tumor vasculature. Metronomic chemotherapy shows promising anticancer activity by its potential antiangiogenic effect and reduced toxicity. We hypothesized that metronomic chemotherapy with paclitaxel could improve the antitumor effect of adoptive CIK cell immunotherapy. Mice health status was analyzed by measuring mice weight and observing mice behavior. Immunohistochemistry was used to investigate the recruitment of CIK cells, the expression of endothelial cell molecules, as well as the hypoxic tumor area. Metronomic paclitaxel synergized with adoptive CIK cell immunotherapy to inhibit the growth of non-small cell lung cancer (NSCLC). Metronomic paclitaxel reduced hypoxic tumor area and increased CIK cell infiltration. Hypoxia impeded the adhesion of CIK cells and reduced the expression of endothelial cell adhesion molecules. In vivo studies demonstrated that more CIK cells were found in endothelial cell adhesion molecules high expressed area. Our study provides a new rationale for combining metronomic chemotherapy with adoptive cell immunotherapy in the treatment of xenograft NSCLC tumors in immunodeficient mice. Further clinical trials integrating translational research are necessary to better evaluate the clinical benefit of this promising approach. © 2014 APMIS. Published by John Wiley & Sons Ltd.

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

Vanderlaan, M.; Fong, S.; King, E.B.

To improve identification of preneoplastic bladder cancer cells, we have studied two enzyme histochemical changes in bladder tumors induced in male Fisher 344 rats by the carcinogen N-butyl-N-(4-hydroxybutyl)-nitrosamine. In early areas of focal nodular hyperplasia there was a dramatic increase in staining for NADH:menadione oxidoreductase (diaphorase) activity. In nonfocal areas as well, there were many individual cells with intense staining, while the controls were of uniform moderate staining. Large papillomas and carcinomas often showed heterogeneous staining, ..gamma..-Glutamyltranspeptidase (GGT) was absent from normal urothelium and from all tumors except the most advanced carcinomas and large papillomas. In old, carcinogen-exposed animals, GGTmore » activity was seen in the luminal surface of tumors and in the interlesion urothelium. In newborn rats and in rats with regenerative hyperplasia following wounding of the urothelium, the diaphorase staining was less than that in the untreated adult. Our findings suggest that increased diaphorase activity may serve to identify early islands of carcinogen-induced, enzymatically altered bladder cells, while GGT will not.« less

Quercetin as an Emerging Anti-Melanoma Agent: A Four-Focus Area Therapeutic Development Strategy.

PubMed

Harris, Zoey; Donovan, Micah G; Branco, Gisele Morais; Limesand, Kirsten H; Burd, Randy

2016-01-01

Replacing current refractory treatments for melanoma with new prevention and therapeutic approaches is crucial in order to successfully treat this aggressive cancer form. Melanoma develops from neural crest cells, which express tyrosinase - a key enzyme in the pigmentation pathway. The tyrosinase enzyme is highly active in melanoma cells and metabolizes polyphenolic compounds; tyrosinase expression thus makes feasible a target for polyphenol-based therapies. For example, quercetin (3,3',4',5,7-pentahydroxyflavone) is a highly ubiquitous and well-classified dietary polyphenol found in various fruits, vegetables, and other plant products including onions, broccoli, kale, oranges, blueberries, apples, and tea. Quercetin has demonstrated antiproliferative and proapoptotic activity in various cancer cell types. Quercetin is readily metabolized by tyrosinase into various compounds that promote anticancer activity; additionally, given that tyrosinase expression increases during tumorigenesis, and its activity is associated with pigmentation changes in both early- and late-stage melanocytic lesions, it suggests that quercetin can be used to target melanoma. In this review, we explore the potential of quercetin as an anti-melanoma agent utilizing and extrapolating on evidence from previous in vitro studies in various human malignant cell lines and propose a "four-focus area strategy" to develop quercetin as a targeted anti-melanoma compound for use as either a preventative or therapeutic agent. The four areas of focus include utilizing quercetin to (i) modulate cellular bioreduction potential and associated signaling cascades, (ii) affect transcription of relevant genes, (iii) regulate epigenetic processes, and (iv) develop effective combination therapies and delivery modalities/protocols. In general, quercetin could be used to exploit tyrosinase activity to prevent, and/or treat, melanoma with minimal additional side effects.

Lipid peroxidation and apoptotic response in rat brain areas induced by long-term administration of nandrolone: the mutual crosstalk between ROS and NF-kB.

PubMed

Turillazzi, Emanuela; Neri, Margherita; Cerretani, Daniela; Cantatore, Santina; Frati, Paola; Moltoni, Laura; Busardò, Francesco Paolo; Pomara, Cristoforo; Riezzo, Irene; Fineschi, Vittorio

2016-04-01

The aim of this study was to evaluate the played by oxidative stress in the apoptotic response in different brain areas of rats chronically treated with supra-physiological doses of nandrolone decanoate (ND). Immunohistochemical study and Western blot analysis were performed to evaluate cells' apoptosis and to measure the effects of expression of specific mediators, such as NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), Bcl-2 (B-cell lymphoma 2), SMAC/DIABLO (second mitochondria-derived activator of caspases/direct IAP-binding protein with low PI) and VMAT2 (vesicular monoamine transporter 2) on apoptosis. The results of the present study indicate that a long-term administration of ND promotes oxidative injury in rat brain specific areas. A link between oxidative stress and NF-κB signalling pathways is supported by our results. In addition to high levels of oxidative stress, we consistently observed a strong immunopositivity to NF-κB. It has been argued that one of the pathways leading to the activation of NF-κB could be under reactive oxygen species (ROS)-mediated control. In fact, growing evidence suggests that although in limited doses, endogenous ROS may play an activating role in NF-κB signalling, while above a certain threshold, they may negatively impact upon this signalling. However, a mutual crosstalk between ROS and NF-κB exists and recent studies have shown that ROS activity is subject to negative feedback regulation by NF-κB, and that this negative regulation of ROS is the means through which NF-κB counters programmed cells. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Cellular immunotherapy for malignant gliomas

PubMed Central

Lin, Yi

2016-01-01

Introduction Cancer immunotherapy has made much progress in recent years. Clinical trials evaluating a variety of immunotherapeutic approaches are underway in patients with malignant gliomas. Thanks to recent advancements in cell engineering technologies, infusion of ex vivo prepared immune cells have emerged as promising strategies of cancer immunotherapy. Areas covered Herein, the authors review recent and current studies using cellular immunotherapies for malignant gliomas. Specifically, they cover the following areas: a) cellular vaccine approaches using tumor cell-based or dendritic cell (DC)-based vaccines, and b) adoptive cell transfer (ACT) approaches, including lymphokine-activated killer (LAK) cells, γδ T cells, tumor-infiltrating lymphocytes (TIL), chimeric antigen receptor (CAR)-T cells and T-cell receptor (TCR) transduced T cells. Expert opinion While some of the recent studies have shown promising results, the ultimate success of cellular immunotherapy in brain tumor patients would require improvements in the following areas: 1) feasibility in producing cellular therapeutics; 2) identification and characterization of targetable antigens given the paucity and heterogeneity of tumor specific antigens; 3) the development of strategies to promote effector T-cell trafficking; 4) overcoming local and systemic immune suppression, and 5) proper interpretation of imaging data for brain tumor patients receiving immunotherapy. PMID:27434205

High-Temperature-Short-Time Annealing Process for High-Performance Large-Area Perovskite Solar Cells.

PubMed

Kim, Minjin; Kim, Gi-Hwan; Oh, Kyoung Suk; Jo, Yimhyun; Yoon, Hyun; Kim, Ka-Hyun; Lee, Heon; Kim, Jin Young; Kim, Dong Suk

2017-06-27

Organic-inorganic hybrid metal halide perovskite solar cells (PSCs) are attracting tremendous research interest due to their high solar-to-electric power conversion efficiency with a high possibility of cost-effective fabrication and certified power conversion efficiency now exceeding 22%. Although many effective methods for their application have been developed over the past decade, their practical transition to large-size devices has been restricted by difficulties in achieving high performance. Here we report on the development of a simple and cost-effective production method with high-temperature and short-time annealing processing to obtain uniform, smooth, and large-size grain domains of perovskite films over large areas. With high-temperature short-time annealing at 400 °C for 4 s, the perovskite film with an average domain size of 1 μm was obtained, which resulted in fast solvent evaporation. Solar cells fabricated using this processing technique had a maximum power conversion efficiency exceeding 20% over a 0.1 cm 2 active area and 18% over a 1 cm 2 active area. We believe our approach will enable the realization of highly efficient large-area PCSs for practical development with a very simple and short-time procedure. This simple method should lead the field toward the fabrication of uniform large-scale perovskite films, which are necessary for the production of high-efficiency solar cells that may also be applicable to several other material systems for more widespread practical deployment.

Integrin activation by a cold atmospheric plasma jet

NASA Astrophysics Data System (ADS)

Volotskova, Olga; Stepp, Mary Ann; Keidar, Michael

2012-05-01

Current breakthrough research on cold atmospheric plasma (CAP) demonstrates that CAP has great potential in various areas, including medicine and biology, thus providing a new tool for living tissue treatment. In this paper, we explore potential mechanisms by which CAP alters cell migration and influences cell adhesion. We focus on the study of CAP interaction with fibroblasts and corneal epithelial cells. The data show that fibroblasts and corneal epithelial cells have different thresholds (treatment times) required to achieve maximum inhibition of cell migration. Both cell types reduced their migration rates by ˜30-40% after CAP compared to control cells. Also, the impact of CAP treatment on cell migration and persistence of fibroblasts after integrin activation by MnCl2, serum starvation or replating cells onto surfaces coated with integrin ligands is assessed; the results show that activation by MnCl2 or starvation attenuates cells’ responses to plasma. Studies carried out to assess the impact of CAP treatment on the activation state of β1 integrin and focal adhesion size by using immunofluorescence show that fibroblasts have more active β1 integrin on their surface and large focal adhesions after CAP treatment. Based on these data, a thermodynamic model is presented to explain how CAP leads to integrin activation and focal adhesion assembly.

Clustering T cell GM1 Lipid Rafts Increases Cellular Resistance to Shear on Fibronectin through Changes in Integrin Affinity and Cytoskeletal Dynamics

PubMed Central

Mitchell, Jason S.; Brown, Wells S.; Woodside, Darren G.; Vanderslice, Peter; McIntyre, Bradley W.

2008-01-01

Lipid rafts are small laterally mobile microdomains that are highly enriched in lymphocyte signaling molecules. GM1 gangliosides are a common lipid raft component and have been shown to be important in many T cell functions. The aggregation of specific GM1 lipid rafts can control many T cell activation events, including their novel association with T cell integrins. We found that clustering GM1 lipid rafts can regulate β1 integrin function. This was apparent through increased resistance to shear flow dependent detachment of T cells adherent to the α4β1 and α5β1 integrin ligand fibronectin (FN). Adhesion strengthening as a result of clustering GM1 enriched lipid rafts correlated with increased cellular rigidity and morphology through the localization of cortical F-actin, the resistance to shear induced cell stretching, and an increase in the surface area and symmetry of the contact area between the cell surface and adhesive substrate. Furthermore, clustering GM1 lipid rafts could initiate integrin “inside-out” signaling mechanisms. This was seen through increased integrin-cytoskeleton associations and enhanced soluble binding of FN and VCAM-1 suggesting the induction of high affinity integrin conformations. The activation of these adhesion strengthening characteristics appear to be specific for the aggregation of GM1 lipid rafts as the aggregation of the heterogeneous raft associated molecule CD59 failed to activate these functions. These findings indicate a novel mechanism to signal to β1 integrins and to activate adhesion strengthening processes. PMID:19139760

N-acetyl-L-cysteine increases MnSOD activity and enhances the recruitment of quiescent human fibroblasts to the proliferation cycle during wound healing.

PubMed

Mao, Gaowei; Goswami, Monali; Kalen, Amanda L; Goswami, Prabhat C; Sarsour, Ehab H

2016-01-01

The rebuilding of the connective tissue during wound healing requires the recruitment of fibroblasts to the wound area as well as reentry of quiescent fibroblasts to the proliferative cycle. Whether this process can be modulated by a small molecular weight thiol antioxidant N-acetyl-L-cysteine (NAC) was tested in normal human skin fibroblasts (NHFs) using a uni-directional wound healing assay. NAC treated cells demonstrated a decreased migration rate but increased number of proliferating cells recruited into the wound area post wounding. Fifteen day quiescent control and NAC treated NHFs were re-plated at a lower density and cell numbers counted at different days post-plating. Interestingly, NAC treated cells exhibited increased cellular proliferation indicated by both decreased cell population doubling time and increased S phase cells. NAC treated cells demonstrated decreased steady state levels of reactive oxygen species as well as increased protein and activity levels of manganese superoxide dismutase (MnSOD). NAC treatment failed to induce proliferation in quiescent cells lacking MnSOD expression. These results demonstrate that NAC enhanced the recruitment of quiescent NHFs into proliferation cycle during wound healing. Our results also suggest that the wound healing properties of NAC might be due to its ability to induce and enhance MnSOD expression and activity. Altogether, these findings suggest NAC might be potentially developed as a dietary intervention to improve tissue injury in animals and humans.

CAR T-cell therapy for glioblastoma: ready for the next round of clinical testing?

PubMed

Prinzing, Brooke L; Gottschalk, Stephen M; Krenciute, Giedre

2018-05-01

The outcome for patients with glioblastoma (GBM) remains poor, and there is an urgent need to develop novel therapeutic approaches. T cells genetically modified with chimeric antigen receptors (CARs) hold the promise to improve outcomes since they recognize and kill cells through different mechanisms than conventional therapeutics. Areas covered: This article reviews CAR design, tumor associated antigens expressed by GBMs that can be targeted with CAR T cells, preclinical and clinical studies conducted with CAR T cells, and genetic approaches to enhance their effector function. Expert commentary: While preclinical studies have highlighted the potent anti-GBM activity of CAR T cells, the initial foray of CAR T-cell therapies into the clinic resulted only in limited benefits for GBM patients. Additional genetic modification of CAR T cells has resulted in a significant increase in their anti-GBM activity in preclinical models. We are optimistic that clinical testing of these enhanced CAR T cells will be safe and result in improved anti-glioma activity in GBM patients.

Colocalization of Mating-Induced Fos and D2-Like Dopamine Receptors in the Medial Preoptic Area: Influence of Sexual Experience.

PubMed

Nutsch, Victoria L; Will, Ryan G; Robison, Christopher L; Martz, Julia R; Tobiansky, Daniel J; Dominguez, Juan M

2016-01-01

Dopamine in the medial preoptic area (mPOA) stimulates sexual activity in males. This is evidenced by microdialysis and microinjection experiments revealing that dopamine receptor antagonists in the mPOA inhibit sexual activity, whereas agonists facilitate behavior. Microdialysis experiments similarly show a facilitative role for dopamine, as levels of dopamine in the mPOA increase with mating. While the majority of evidence suggests an important role for dopamine receptors in the mPOA in the regulation of male sexual behaviors, whether sexual activity or sexual experience influence dopamine receptor function in the mPOA has not been previously shown. Here we used immunohistochemical assays to determine whether varying levels of sexual activity or experience influence the number of cells containing Fos or D2 receptor immunoreactivity. Results show that sexual experience facilitated subsequent behavior, namely experience decreased latencies. Moreover, the number of cells with immunoreactivity for Fos or D2 correlated with levels of sexual experience and sexual activity. Sexual activity increased Fos immunoreactivity. Sexually experienced animals also had significantly more D2-positive cells. Sexually inexperienced animals copulating for the first time had a larger percentage of D2-positive cells containing Fos, when compared to sexually experienced animals. Finally, regardless of experience, animals that had sex prior to sacrifice had significantly more D2-positive cells that contained Fos, vs. animals that did not copulate. These findings are noteworthy because sexually experienced animals display increased sexual efficiency. The differences in activation of D2 and changes in receptor density may play a role in this efficiency and other behavioral changes across sexual experience.

2016 Annual Progress Report: DOE Hydrogen and Fuel Cells Program

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

None, None

The 2016 Annual Progress Report summarizes fiscal year 2016 activities and accomplishments by projects funded by the DOE Hydrogen and Fuel Cells Program. It covers the program areas of hydrogen production; hydrogen delivery; hydrogen storage; fuel cells; manufacturing R&D; technology validation; safety, codes and standards; systems analysis; market transformation; and Small Business Innovation Research projects.

NREL and Fraunhofer ISE to Collaborate on Hydrogen and Fuel Cell Research |

Science.gov Websites

(R&D) activities to accelerate progress in these fields. NREL's long-term research and accelerate progress toward shared R&D goals and to ensure sustainable use of hydrogen and fuel cell Fraunhofer ISE in the following areas: Electrolysis, including cell, stack, and system R&D and

Modelling the Immune Response to Cancer: An Individual-Based Approach Accounting for the Difference in Movement Between Inactive and Activated T Cells.

PubMed

Macfarlane, Fiona R; Lorenzi, Tommaso; Chaplain, Mark A J

2018-06-01

A growing body of experimental evidence indicates that immune cells move in an unrestricted search pattern if they are in the pre-activated state, whilst they tend to stay within a more restricted area upon activation induced by the presence of tumour antigens. This change in movement is not often considered in the existing mathematical models of the interactions between immune cells and cancer cells. With the aim to fill such a gap in the existing literature, in this work we present a spatially structured individual-based model of tumour-immune competition that takes explicitly into account the difference in movement between inactive and activated immune cells. In our model, a Lévy walk is used to capture the movement of inactive immune cells, whereas Brownian motion is used to describe the movement of antigen-activated immune cells. The effects of activation of immune cells, the proliferation of cancer cells and the immune destruction of cancer cells are also modelled. We illustrate the ability of our model to reproduce qualitatively the spatial trajectories of immune cells observed in experimental data of single-cell tracking. Computational simulations of our model further clarify the conditions for the onset of a successful immune action against cancer cells and may suggest possible targets to improve the efficacy of cancer immunotherapy. Overall, our theoretical work highlights the importance of taking into account spatial interactions when modelling the immune response to cancer cells.

Electrophysiology of glioma: a Rho GTPase-activating protein reduces tumor growth and spares neuron structure and function.

PubMed

Vannini, Eleonora; Olimpico, Francesco; Middei, Silvia; Ammassari-Teule, Martine; de Graaf, Erik L; McDonnell, Liam; Schmidt, Gudula; Fabbri, Alessia; Fiorentini, Carla; Baroncelli, Laura; Costa, Mario; Caleo, Matteo

2016-12-01

Glioblastomas are the most aggressive type of brain tumor. A successful treatment should aim at halting tumor growth and protecting neuronal cells to prevent functional deficits and cognitive deterioration. Here, we exploited a Rho GTPase-activating bacterial protein toxin, cytotoxic necrotizing factor 1 (CNF1), to interfere with glioma cell growth in vitro and vivo. We also investigated whether this toxin spares neuron structure and function in peritumoral areas. We performed a microarray transcriptomic and in-depth proteomic analysis to characterize the molecular changes triggered by CNF1 in glioma cells. We also examined tumor cell senescence and growth in vehicle- and CNF1-treated glioma-bearing mice. Electrophysiological and morphological techniques were used to investigate neuronal alterations in peritumoral cortical areas. Administration of CNF1 triggered molecular and morphological hallmarks of senescence in mouse and human glioma cells in vitro. CNF1 treatment in vivo induced glioma cell senescence and potently reduced tumor volumes. In peritumoral areas of glioma-bearing mice, neurons showed a shrunken dendritic arbor and severe functional alterations such as increased spontaneous activity and reduced visual responsiveness. CNF1 treatment enhanced dendritic length and improved several physiological properties of pyramidal neurons, demonstrating functional preservation of the cortical network. Our findings demonstrate that CNF1 reduces glioma volume while at the same time maintaining the physiological and structural properties of peritumoral neurons. These data indicate a promising strategy for the development of more effective antiglioma therapies. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Type I interferon dependence of plasmacytoid dendritic cell activation and migration

PubMed Central

Asselin-Paturel, Carine; Brizard, Géraldine; Chemin, Karine; Boonstra, Andre; O'Garra, Anne; Vicari, Alain; Trinchieri, Giorgio

2005-01-01

Differential expression of Toll-like receptor (TLR) by conventional dendritic cells (cDCs) and plasmacytoid DC (pDCs) has been suggested to influence the type of immune response induced by microbial pathogens. In this study we show that, in vivo, cDCs and pDCs are equally activated by TLR4, -7, and -9 ligands. Type I interferon (IFN) was important for pDC activation in vivo in response to all three TLR ligands, whereas cDCs required type I IFN signaling only for TLR9- and partially for TLR7-mediated activation. Although TLR ligands induced in situ migration of spleen cDC into the T cell area, spleen pDCs formed clusters in the marginal zone and in the outer T cell area 6 h after injection of TLR9 and TLR7 ligands, respectively. In vivo treatment with TLR9 ligands decreased pDC ability to migrate ex vivo in response to IFN-induced CXCR3 ligands and increased their response to CCR7 ligands. Unlike cDCs, the migration pattern of pDCs required type I IFN for induction of CXCR3 ligands and responsiveness to CCR7 ligands. These data demonstrate that mouse pDCs differ from cDCs in the in vivo response to TLR ligands, in terms of pattern and type I IFN requirement for activation and migration. PMID:15795237

Hypoxia-mediated alterations and their role in the HER-2/neuregulated CREB status and localization

PubMed Central

Steven, André; Leisz, Sandra; Sychra, Katharina; Hiebl, Bernhard; Wickenhauser, Claudia; Mougiakakos, Dimitrios; Kiessling, Rolf; Denkert, Carsten; Seliger, Barbara

2016-01-01

The cAMP-responsive element-binding protein (CREB) is involved in the tumorigenicity of HER-2/neu-overexpressing murine and human tumor cells, but a link between the HER-2/neu-mediated CREB activation, its posttranslational modification and localization and changes in the cellular metabolism, due to an altered (tumor) microenvironment remains to be established. The present study demonstrated that shRNA-mediated silencing of CREB in HER-2/neu-transformed cells resulted in decreased tumor formation, which was associated with reduced angiogenesis, but increased necrotic and hypoxic areas in the tumor. Hypoxia induced pCREBSer133, but not pCREBSer121 expression in HER-2/neu-transformed cells. This was accompanied by upregulation of the hypoxia-inducible genes GLUT1 and VEGF, increased cell migration and matrix metalloproteinase-mediated invasion. Treatment of HER-2/neu+ cells with signal transduction inhibitors targeting in particular HER-2/neu was able to revert hypoxia-controlled CREB activation. In addition to changes in the phosphorylation, hypoxic response of HER-2/neu+ cells caused a transient ubiquitination and SUMOylation as well as a co-localization of nuclear CREB to the mitochondrial matrix. A mitochondrial localization of CREB was also demonstrated in hypoxic areas of HER-2/neu+ mammary carcinoma lesions. This was accompanied by an altered gene expression pattern, activity and metabolism of mitochondria leading to an increased respiratory rate, oxidative phosphorylation and mitochondrial membrane potential and consequently to an enhanced apoptosis and reduced cell viability. These data suggest that the HER-2/neu-mediated CREB activation caused by a hypoxic tumor microenvironment contributes to the neoplastic phenotype of HER-2/neu+ cells at various levels. PMID:27409833

Optoelectronic tweezers integrated with lensfree holographic microscopy for wide-field interactive cell and particle manipulation on a chip.

PubMed

Huang, Kuo-Wei; Su, Ting-Wei; Ozcan, Aydogan; Chiou, Pei-Yu

2013-06-21

We demonstrate an optoelectronic tweezer (OET) coupled to a lensfree holographic microscope for real-time interactive manipulation of cells and micro-particles over a large field-of-view (FOV). This integrated platform can record the holographic images of cells and particles over the entire active area of a CCD sensor array, perform digital image reconstruction to identify target cells, dynamically track the positions of cells and particles, and project light beams to trigger light-induced dielectrophoretic forces to pattern and sort cells on a chip. OET technology has been previously shown to be capable of performing parallel single cell manipulation over a large area. However, its throughput has been bottlenecked by the number of cells that can be imaged within the limited FOV of a conventional microscope objective lens. Integrating lensfree holographic imaging with OET solves this fundamental FOV barrier, while also creating a compact on-chip cell/particle manipulation platform. Using this unique platform, we have successfully demonstrated real-time interactive manipulation of thousands of single cells and micro-particles over an ultra-large area of e.g., 240 mm(2) (i.e. 17.96 mm × 13.52 mm).

Fundamental research in the area of high temperature fuel cells in Russia

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

Dyomin, A.K.

1996-04-01

Research in the area of molten carbonate and solid oxide fuel cells has been conducted in Russia since the late 60`s. Institute of High Temperature Electrochemistry is the lead organisation in this area. Research in the area of materials used in fuel cells has allowed us to identify compositions of electrolytes, electrodes, current paths and transmitting, sealing and structural materials appropriate for long-term fuel cell applications. Studies of electrode processes resulted in better understanding of basic patterns of electrode reactions and in the development of a foundation for electrode structure optimization. We have developed methods to increase electrode activity levelsmore » that allowed us to reach current density levels of up to 1 amper/cm{sup 2}. Development of mathematical models of processes in high temperature fuel cells has allowed us to optimize their structure. The results of fundamental studies have been tested on laboratory mockups. MCFC mockups with up to 100 W capacity and SOFC mockups with up to 1 kW capacity have been manufactured and tested at IHTE. There are three SOFC structural options: tube, plate and modular.« less

A comparison of epithalamic, hypothalamic and spinal neurosecretory terminals.

PubMed

Vigh-Teichmann, I; Vigh, B

1979-01-01

Nerve endings of epithalamic, hypothalamic and spinal neurosecretory areas were studied by light and electron microscopy in various vertebrates (from fishes up to mammals) including the lancelet. Areas investigated were the pineal organ, the pulvinar corporis pinealis, the neurohypophysis, the median eminence, the urophysis, the terminal filum and the medullo-spinal neurosecretory zones. We found that in all these areas the neurosecretory endings have common structures, which we call synaptic hemidesmosomes or neurohormonal terminals. These are characterized by accumulation of vesicles, and dense projections in a terminal on the basal lamina of the surface of the nervous tissue. A critical review of the literature suggests that a considerble neuroendocrine activity is associated with synaptic hemidesmosomes as special neurohormonal effector structures of the nerve cells. The cell-to-cell synapses formed by neurosecretory cells are discussed in connection with the dual capacity of these cells to function as both endocrine and "ordinary# neuronal elements. The importance of the external cerebrospinal fluid (CSF) space for the transport of materials released in the so-called neurohemal areas, is stressed.

Tandem concentrator photovoltaic array applied to Space Station Freedom evolutionary power requirements

NASA Technical Reports Server (NTRS)

Fisher, Edward M., Jr.

1991-01-01

Additional power is required to support Space Station Freedom (SSF) evolution. Boeing Defense and Space Group, LeRC, and Entech Corporation have participated in the development of efficiency gallium arsenide and gallium antimonide solar cells make up the solar array tandem cell stacks. Entech's Mini-Dome Fresnel Lens Concentrators focus solar energy onto the active area of the solar cells at 50 times one solar energy flux. Development testing for a flight array, to be launched in Nov. 1992 is under way with support from LeRC. The tandem cells, interconnect wiring, concentrator lenses, and structure were integrated into arrays subjected to environmental testing. A tandem concentrator array can provide high mass and area specific power and can provide equal power with significantly less array area and weight than the baseline array design. Alternatively, for SSF growth, an array of twice the baseline power can be designed which still has a smaller drag area than the baseline.

A novel three-dimensional heterotypic spheroid model for the assessment of the activity of cancer immunotherapy agents.

PubMed

Herter, Sylvia; Morra, Laura; Schlenker, Ramona; Sulcova, Jitka; Fahrni, Linda; Waldhauer, Inja; Lehmann, Steffi; Reisländer, Timo; Agarkova, Irina; Kelm, Jens M; Klein, Christian; Umana, Pablo; Bacac, Marina

2017-01-01

The complexity of the tumor microenvironment is difficult to mimic in vitro, particularly regarding tumor-host interactions. To enable better assessment of cancer immunotherapy agents in vitro, we developed a three-dimensional (3D) heterotypic spheroid model composed of tumor cells, fibroblasts, and immune cells. Drug targeting, efficient stimulation of immune cell infiltration, and specific elimination of tumor or fibroblast spheroid areas were demonstrated following treatment with a novel immunocytokine (interleukin-2 variant; IgG-IL2v) and tumor- or fibroblast-targeted T cell bispecific antibody (TCB). Following treatment with IgG-IL2v, activation of T cells, NK cells, and NKT cells was demonstrated by increased expression of the activation marker CD69 and enhanced cytokine secretion. The combination of TCBs with IgG-IL2v molecules was more effective than monotherapy, as shown by enhanced effects on immune cell infiltration; activation; increased cytokine secretion; and faster, more efficient elimination of targeted cells. This study demonstrates that the 3D heterotypic spheroid model provides a novel and versatile tool for in vitro evaluation of cancer immunotherapy agents and allows for assessment of additional aspects of the activity of cancer immunotherapy agents, including analysis of immune cell infiltration and drug targeting.

Notch1 engagement by Delta-like-1 promotes differentiation of B lymphocytes to antibody-secreting cells

PubMed Central

Santos, Margarida Almeida; Sarmento, Leonor Morais; Rebelo, Manuel; Doce, Ana Agua; Maillard, Ivan; Dumortier, Alexis; Neves, Helia; Radtke, Freddy; Pear, Warren S.; Parreira, Leonor; Demengeot, Jocelyne

2007-01-01

Notch signaling regulates B and T lymphocyte development and T cell effector class decision. In this work, we tested whether Notch activity affects mature B cell activation and differentiation to antibody-secreting cells (ASC). We show increased frequency of ASC in cultures of splenic B cells activated with LPS or anti-CD40 when provided exogenous Notch ligand Delta-like-1 (Dll1). Our results indicate that Notch–Dll1 interaction releases a default pathway that otherwise inhibits Ig secretion upon B cell activation. Thus, Dll1 enhanced spontaneous Ig secretion by naturally activated marginal zone B and B1 cells and reversed the inhibition of ASC differentiation mediated by B cell receptor crosslinking during LPS. Moreover, suppression of Notch signaling in B cell expression of either a dominant-negative mutant form of Mastermind-like 1 or a null mutation of Notch1 not only prevented Dll1-mediated enhancement of ASC differentiation but also reduced dramatically LPS-induced Ig secretion. Finally, we show that Dll1 and Jagged-1 are differentially expressed in discrete areas of the spleen, and that the effect of Notch engagement on Ig secretion is ligand-specific. These results indicate that Notch ligands participate in the definition of the mature B cell microenvironment that influences their terminal differentiation. PMID:17878313

The dormant cells of Mycobacterium tuberculosis may be resuscitated by targeting-expression system of recombinant mycobacteriophage-Rpf: implication of shorter course of TB chemotherapy in the future.

PubMed

Gan, Yiling; Yao, Yiyong; Guo, Shuliang

2015-05-01

Here we hypothesized that dormant cells of Mycobacterium tuberculosis (M. tuberculosis) may be resuscitated by a new expression system of recombinant mycobacteriophage-resuscitation-promoting factor (Rpf). In this system, gene of targeted Rpf was cloned into mycobacteriophage genome, since mycobacteriophages possess several characteristics, including automatic identification and specific infection of M. tuberculosis. Thus the targeted delivery and endogenous expression of Rpf to the infected area of M. tuberculosis can be realized, followed by resuscitating the dormant cells of M. tuberculosis. Finally, these resuscitated M. tuberculosis can be thoroughly killed by a strong short-term subsequent chemotherapy, which makes the course of TB chemotherapy much shorter in the future compared to simple chemotherapy. Early studies have confirmed that dormant cells of M. tuberculosis can be resuscitated by Rpf in vitro, but so far, there is no report that Rpf can succeed in resuscitating dormant cells of M. tuberculosis in vivo, the reason may be that it is difficult for purified Rpf to remain active in vivo, especially to achieve targeted delivery of exogenous Rpf to the infected area of dormant cells of M. tuberculosis. Mycobacteriophage is a virus, capable of specifically identifying and infecting mycobacterium, such as M. tuberculosis. Several studies show that motif 3-containing proteins have peptidoglycan-hydrolysing activity and that while this activity is not required for mycobacteriophage viability, it facilitates efficient infection and DNA injection of mycobacteriophage (including motif 3 protein) into stationary phase cells. Thus this expression system can achieve targeted delivery and endogenous expression of Rpf to infected area of dormant cells of M. tuberculosis. Finally, we discuss the implication of this recombinant expression system for shortening the course of TB chemotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Controlling Mast Cell Activation and Homeostasis: Work Influenced by Bill Paul That Continues Today.

PubMed

Caslin, Heather L; Kiwanuka, Kasalina N; Haque, Tamara T; Taruselli, Marcela T; MacKnight, H Patrick; Paranjape, Anuya; Ryan, John J

2018-01-01

Mast cells are tissue resident, innate immune cells with heterogenous phenotypes tuned by cytokines and other microenvironmental stimuli. Playing a protective role in parasitic, bacterial, and viral infections, mast cells are also known for their role in the pathogenesis of allergy, asthma, and autoimmune diseases. Here, we review factors controlling mast cell activation, with a focus on receptor signaling and potential therapies for allergic disease. Specifically, we will discuss our work with FcεRI and FγR signaling, IL-4, IL-10, and TGF-β1 treatment, and Stat5. We conclude with potential therapeutics for allergic disease. Much of these efforts have been influenced by the work of Bill Paul. With many mechanistic targets for mast cell activation and different classes of therapeutics being studied, there is reason to be hopeful for continued clinical progress in this area.

STATs: An Old Story, Yet Mesmerizing

PubMed Central

Abroun, Saeid; Saki, Najmaldin; Ahmadvand, Mohammad; Asghari, Farahnaz; Salari, Fatemeh; Rahim, Fakher

2015-01-01

Signal transducers and activators of transcription (STATs) are cytoplasmic transcription factors that have a key role in cell fate. STATs, a protein family comprised of seven members, are proteins which are latent cytoplasmic transcription factors that convey signals from the cell surface to the nucleus through activation by cytokines and growth factors. The signaling pathways have diverse biological functions that include roles in cell differentiation, proliferation, development, apoptosis, and inflammation which place them at the center of a very active area of research. In this review we explain Janus kinase (JAK)/STAT signaling and focus on STAT3, which is transient from cytoplasm to nucleus after phosphorylation. This procedure controls fundamental biological processes by regulating nuclear genes controlling cell proliferation, survival, and development. In some hematopoietic disorders and cancers, overexpression and activation of STAT3 result in high proliferation, suppression of cell differentiation and inhibition of cell maturation. This article focuses on STAT3 and its role in malignancy, in addition to the role of microRNAs (miRNAs) on STAT3 activation in certain cancers. PMID:26464811

Elevated lead levels and adverse effects on natural killer cells in children from an electronic waste recycling area.

PubMed

Zhang, Yu; Huo, Xia; Cao, Junjun; Yang, Tian; Xu, Long; Xu, Xijin

2016-06-01

Lead (Pb) has been proved to exert immunotoxicity to influence immune homeostasis in humans. To monitor the internal Pb level and evaluate its effect on natural killer (NK) cells and cytokine/chemokine concentrations, we recruited 285 preschool children from Guiyu, one of the largest electronic waste (e-waste) destinations and recycling areas in the world, and known to have high concentrations of Pb in the air, soil, water, sediment and plants. A total of 126 preschool children were selected from Haojiang as a reference group. Results showed that children in Guiyu, the exposed area, had higher blood Pb levels and lower percentages of NK cells than children from the reference area. A significantly negative association was found between the percentage of NK cells and increasing Pb levels. Moreover, children in Guiyu area had higher platelet counts and IL-1β concentrations, and lower levels of IL-2, IL-27, MIP-1α and MIP-1β were observed in the exposed children. These changes might not be conducive to the development and differentiation of NK cells. Taken together, the elevated Pb levels result in the lower percentages of NK cells, but also alter the levels of platelets, IL-1β and IL-27, which might be unconducive to the activity and function of NK cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

Education of Advanced Biotechnologists of Kitakyushu National College of Technology

NASA Astrophysics Data System (ADS)

Kawahara, Hiroharu

The Cell Engineering Center was established in October, 2003 to research and develop manufacturing technologies and cell engineering technologies with human cell lines, which boost their uniqueness. The center serves as a base for advancing industrial development and creating new industries in Kitakyushu City area. One of the features in this center's activities is to promote technology exchanges between the students and researchers in private firms and to facilitate developed biotechnologies transferred to the private sectors. The Cell Engineering Center aims to train the advanced biotechnologists who have abilities for applying for patents, international communications, and leaderships. In this work, the educational and research activities in the Cell Engineering Center will be reported.

Cholinesterases and cell proliferation in "nonstratified" and "stratified" cell aggregates from chicken retina and tectum.

PubMed

Vollmer, G; Layer, P G

1987-12-01

Dissociated single cells from chicken retina or tectum kept in rotation-mediated cell culture aggregate, proliferate and establish a certain degree of histotypical cell-to-cell relationships ("sorting out"), but these systems never form highly laminated aggregates ("nonstratified" R- and T-aggregates). In contrast, a mixture of retinal plus pigment epithelial cells forms highly "stratified" aggregates ("RPE-aggregates", see Vollmer et al. 1984). The present comparative study of "stratified" and "nonstratified" aggregates enables us to investigate the process of cell proliferation uncoupled from that of tissue stratification. Here we try to relate these two basic neurogenetic processes with patterns of expression of cholinesterases (AChE, BChE) during formation of both types of aggregates. During early aggregate formation, in both "stratified" and "nonstratified" aggregates an increased butyrylcholinesterase activity is observed close to mitotically active cells. Quantitatively both phenomena show their maxima after 2-3 days in culture. In contrast, AChE-expression in all systems increases with incubation time. In nonproliferative areas, in the center of RPE-aggregates, the formation of plexiform layers is characterized initially by weak BChE- and then strong AChE-activity. These areas correspond with the inner (IPL) and outer (OPL) plexiform layers of the retina in vivo. Although by sucrose gradient centrifugation we find that the 6S- and the fiber-associated 11S-molecules of AChE are present in all types of aggregates, during the culture period the ratio of 11S/6S-forms increases only in RPE-aggregates, which again indicates the advanced degree of differentiation within these aggregates.(ABSTRACT TRUNCATED AT 250 WORDS)

Changing Paradigms in Cranio-Facial Regeneration: Current and New Strategies for the Activation of Endogenous Stem Cells

PubMed Central

Mele, Luigi; Vitiello, Pietro Paolo; Tirino, Virginia; Paino, Francesca; De Rosa, Alfredo; Liccardo, Davide; Papaccio, Gianpaolo; Desiderio, Vincenzo

2016-01-01

Craniofacial area represent a unique district of human body characterized by a very high complexity of tissues, innervation and vascularization, and being deputed to many fundamental function such as eating, speech, expression of emotions, delivery of sensations such as taste, sight, and earing. For this reasons, tissue loss in this area following trauma or for example oncologic resection, have a tremendous impact on patients' quality of life. In the last 20 years regenerative medicine has emerged as one of the most promising approach to solve problem related to trauma, tissue loss, organ failure etc. One of the most powerful tools to be used for tissue regeneration is represented by stem cells, which have been successfully implanted in different tissue/organs with exciting results. Nevertheless, both autologous and allogeneic stem cell transplantation raise many practical and ethical concerns that make this approach very difficult to apply in clinical practice. For this reason different cell free approaches have been developed aiming to the mobilization, recruitment, and activation of endogenous stem cells into the injury site avoiding exogenous cells implant but instead stimulating patients' own stem cells to repair the lesion. To this aim many strategies have been used including functionalized bioscaffold, controlled release of stem cell chemoattractants, growth factors, BMPs, Platelet–Rich-Plasma, and other new strategies such as ultrasound wave and laser are just being proposed. Here we review all the current and new strategies used for activation and mobilization of endogenous stem cells in the regeneration of craniofacial tissue. PMID:26941656

Behavior-Dependent Activity and Synaptic Organization of Septo-hippocampal GABAergic Neurons Selectively Targeting the Hippocampal CA3 Area.

PubMed

Joshi, Abhilasha; Salib, Minas; Viney, Tim James; Dupret, David; Somogyi, Peter

2017-12-20

Rhythmic medial septal (MS) GABAergic input coordinates cortical theta oscillations. However, the rules of innervation of cortical cells and regions by diverse septal neurons are unknown. We report a specialized population of septal GABAergic neurons, the Teevra cells, selectively innervating the hippocampal CA3 area bypassing CA1, CA2, and the dentate gyrus. Parvalbumin-immunopositive Teevra cells show the highest rhythmicity among MS neurons and fire with short burst duration (median, 38 ms) preferentially at the trough of both CA1 theta and slow irregular oscillations, coincident with highest hippocampal excitability. Teevra cells synaptically target GABAergic axo-axonic and some CCK interneurons in restricted septo-temporal CA3 segments. The rhythmicity of their firing decreases from septal to temporal termination of individual axons. We hypothesize that Teevra neurons coordinate oscillatory activity across the septo-temporal axis, phasing the firing of specific CA3 interneurons, thereby contributing to the selection of pyramidal cell assemblies at the theta trough via disinhibition. VIDEO ABSTRACT. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Bone marrow adipocytes: a neglected target tissue for growth hormone.

PubMed

Gevers, Evelien F; Loveridge, Nigel; Robinson, Iain C A F

2002-10-01

Bone marrow (BM) contains numerous adipocytes. These share a common precursor with osteoblasts and chondrocytes, but their function is unknown. It is unclear what regulates the differentiation of these three different cell types, though their subsequent metabolic activity is under hormonal regulation. GH and estrogen stimulate bone growth and mineralization, by direct effects on chondrocytes and osteoblasts. GH also stimulates lipolysis in subcutaneous and visceral adipocytes. However, adipocytes in BM have largely been ignored as potential targets for GH or estrogen action. We have addressed this by measuring BM adipocyte number, perimeter and area as well as bone area and osteoblast activity in GH-deficient dwarf (dw/dw), normal, or ovariectomized (Ovx) rats, with or without GH, IGF-1, PTH, or estrogen treatment or high fat feeding. Marrow adipocyte numbers were increased 5-fold (P < 0.001) in dw/dw rats, and cell size was also increased by 20%. These values returned toward normal in dw/dw rats given GH but not when given IGF-1. Cancellous bone area and osteoblast number were significantly (P < 0.005) lower in dw/dw rats, though alkaline phosphatase (ALP) activity in individual osteoblasts was unchanged. GH treatment increased % osteoblast covered bone surface without affecting individual cell ALP activity. Ovariectomy in normal or dw/dw rats had no affect on marrow adipocyte number nor size, although estrogen treatment in ovariectomized (Ovx) normal rats did increase adipocyte number. Ovx decreased tibial cancellous bone area in normal rats (64%; P < 0.05) and decreased osteoblast ALP-activity (P < 0.01) but did not affect the percentage of osteoblast-covered bone surface. Estrogen replacement reversed these changes. While treatment with PTH by continuous sc infusion decreased cancellous bone (P < 0.05) and high fat feeding increased the size of BM adipocytes (P < 0.01), they did not affect BM adipocyte number. These results suggest that GH has a specific action on BM adipocytes that is not simply due to altered bone or fat metabolism. We conclude that the marrow adipocyte lineage is an important and specific target for GH action. The inverse relationship between adipocyte number and osteoblast covered bone surface, together with the well-known effects of GH on epiphysial chondrocytes leads us to propose that GH plays two important roles on cells of all three lineages. During differentiation, it regulates the numbers of each cell type that are maintained from the common precursor lineage. Subsequently it has cell-specific effects on the metabolic activities of the differentiated cells. In the case of marrow adipocytes, GH-dependent lipolysis could provide an important hormonally regulated local high energy source in bone.

In vitro effects of cisplatin-functionalized silica nanoparticles on chondrocytes

NASA Astrophysics Data System (ADS)

Bhowmick, Tridib Kumar; Yoon, Diana; Patel, Minal; Fisher, John; Ehrman, Sheryl

2010-10-01

In this study, we evaluated the combined effect of a known toxic molecule, cisplatin, in combination with relatively nontoxic nanoparticles, amorphous fumed silica, on chondrocyte cells. Cisplatin was attached to silica nanoparticles using aminopropyltriethoxy silane as a linker molecule, and characterized in terms of size, shape, specific surface area, as well as the dissolution of cisplatin from the silica surface. The primary particle diameter of the as-received silica nanoparticles ranged from 7.1 to 61 nm, estimated from measurements of specific surface area, and the primary particles were aggregated. The effects of cisplatin-functionalized silica particles with different specific surface areas (41, 85, 202, 237, and 297 m2/g) were compared in vitro on chondrocytes, the parenchymal cell of hyaline cartilage. The results show that adverse effects on cell function, as evidenced by reduced metabolic activity measured by the MTT assay and increased membrane permeability observed using the Live/Dead stain, can be correlated with specific surface area of the silica. Cisplatin-functionalized silica nanoparticles with the highest specific surface area incited the greatest response, which was almost equivalent to that induced by free cisplatin. This result suggests the importance of particle specific surface area in interactions between cells and surface-functionalized nanomaterials.

Attentional modulation of cell-class specific gamma-band synchronization in awake monkey area V4

PubMed Central

Vinck, Martin; Womelsdorf, Thilo; Buffalo, Elizabeth A.; Desimone, Robert; Fries, Pascal

2013-01-01

Summary Selective visual attention is subserved by selective neuronal synchronization, entailing precise orchestration among excitatory and inhibitory cells. We tentatively identified these as broad (BS) and narrow spiking (NS) cells and analyzed their synchronization to the local field potential in two macaque monkeys performing a selective visual attention task. Across cells, gamma phases scattered widely but were unaffected by stimulation or attention. During stimulation, NS cells lagged BS cells on average by ~60° and gamma synchronized twice as strongly. Attention enhanced and reduced the gamma locking of strongly and weakly activated cells, respectively. During a pre-stimulus attentional cue period, BS cells showed weak gamma synchronization, while NS cells gamma synchronized as strongly as with visual stimulation. These analyses reveal the cell-type specific dynamics of the gamma cycle in macaque visual cortex and suggest that attention affects neurons differentially depending on cell type and activation level. PMID:24267656

6-Shogaol, a natural product, reduces cell death and restores motor function in rat spinal cord injury.

PubMed

Kyung, Kang Soo; Gon, Jeon Hyo; Geun, Kim Yong; Sup, Jung Jin; Suk, Woo Jae; Ho, Kim Jae

2006-08-01

Spinal cord injury (SCI) results in progressive waves of secondary injuries, which via the activation of a barrage of noxious pathological mechanisms exacerbate the injury to the spinal cord. Secondary injuries are associated with edema, inflammation, excitotoxicity, excessive cytokine release, caspase activation and cell apoptosis. This study was aimed at investigating the possible neuroprotective effects of 6-shogaol purified from Zingiber officinale by comparing an experimental SCI rat group with SCI control rats. Shogaol attenuated apoptotic cell death, including poly(ADP-ribose) polymerase activity, and reduced astrogliosis and hypomyelination which occurs in areas of active cell death in the spinal cords of SCI rats. The foremost protective effect of shogaol in SCI would therefore be manifested in the suppression of the acute secondary apoptotic cell death. However, it does not attenuate active microglia and macrophage infiltration. This finding is supported by a lack of histopathological changes in the areas of the lesion in the shogaol-treated SCI rats. Moreover, shogaol-mediated neuroprotection has been linked with shogaol's attenuation of p38 mitogen-activated protein kinase, p-SAPK/JNK and signal transducer, and with transcription-3 activation. Our results demonstrate that shogaol administrated immediately after SCI significantly diminishes functional deficits. The shogaol-treated group recovered hindlimb reflexes more rapidly and a higher percentage of these rats regained responses compared with the untreated injured rats. The overall hindlimb functional improvement of hindlimbs, as measured by the Basso, Beattie and Bresnahan scale, was significantly enhanced in the shogaol-treated group relative to the SCI control rats. Our data show that the therapeutic outcome of shogaol probably results from its comprehensive effects of blocking apoptotic cell death, resulting in the protection of white matter, oligodendrocytes and neurons, and inhibiting astrogliosis. Our finding that the administration of shogaol prevents secondary pathological events in traumatic SCIs and promotes recovery of motor functions in an animal model raises the issue of whether shogaol could be used therapeutically in humans after SCI.

The dog mite, Demodex canis: prevalence, fungal co-infection, reactions to light, and hair follicle apoptosis.

PubMed

Tsai, Yu-Jen; Chung, Wen-Cheng; Wang, Lian-Chen; Ju, Yu-Ten; Hong, Chin-Lin; Tsai, Yu-Yang; Li, Yi-Hung; Wu, Ying-Ling

2011-01-01

Infection rate, reaction to light, and hair follicle apoptosis are examined in the dogmite, Demodex canis Leydig (Prostigmata: Demodicidae), in dogs from the northern area of Taiwan. An analysis of relevant samples revealed 7.2% (73/1013) prevalence of D. canis infection. Infection during the investigation peaked each winter, with an average prevalence of 12.5% (32/255). The infection rates significantly varied in accordance with month, sex, age, and breed (p < 0.05). Most of the lesions were discovered on the backs of the infected animals, where the infection rate was 52.1% (38/73) (P < 0.05). The epidemiologic analysis of infection based on landscape area factor, found that employing a map-overlapping method showed a higher infection rate in the eastern distribution of Taiwan's northern area than other areas. Isolation tests for Microsporum canis Bodin (Onygenales: Arthrodermataceae) and Trichophyton mentagrophyte Robin (Blanchard) on the D. canis infected dogs revealed prevalence rates of 4.4% (2/45) and 2.2% (1/45), respectively. Observations demonstrated that D. canis slowly moved from a light area to a dark area. Skin samples were examined for cellular apoptosis by activated caspase3 immunohistochemical staining. Cells that surrounded the infected hair follicles were activated caspase3-positive, revealing cell apoptosis in infected follicles via the activation of caspase3.

Fgf receptor 3 activation promotes selective growth and expansion of occipitotemporal cortex

PubMed Central

Thomson, Rachel E; Kind, Peter C; Graham, Nicholas A; Etherson, Michelle L; Kennedy, John; Fernandes, Ana C; Marques, Catia S; Hevner, Robert F; Iwata, Tomoko

2009-01-01

Background Fibroblast growth factors (Fgfs) are important regulators of cerebral cortex development. Fgf2, Fgf8 and Fgf17 promote growth and specification of rostromedial (frontoparietal) cortical areas. Recently, the function of Fgf15 in antagonizing Fgf8 in the rostral signaling center was also reported. However, regulation of caudal area formation by Fgf signaling remains unknown. Results In mutant mice with constitutive activation of Fgf receptor 3 (Fgfr3) in the forebrain, surface area of the caudolateral cortex was markedly expanded at early postnatal stage, while rostromedial surface area remained normal. Cortical thickness was also increased in caudal regions. The expression domain and levels of Fgf8, as well as overall patterning, were unchanged. In contrast, the changes in caudolateral surface area were associated with accelerated cell cycle in early stages of neurogenesis without an alteration of cell cycle exit. Moreover, a marked overproduction of intermediate neuronal progenitors was observed in later stages, indicating prolongation of neurogenesis. Conclusion Activation of Fgfr3 selectively promotes growth of caudolateral (occipitotemporal) cortex. These observations support the 'radial unit' and 'radial amplification' hypotheses and may explain premature sulcation of the occipitotemporal cortex in thanatophoric dysplasia, a human FGFR3 disorder. Together with previous work, this study suggests that formation of rostral and caudal areas are differentially regulated by Fgf signaling in the cerebral cortex. PMID:19192266

The Dog Mite, Demodex canis: Prevalence, Fungal Co-Infection, Reactions to Light, and Hair Follicle Apoptosis

PubMed Central

Tsai, Yu-Jen; Chung, Wen-Cheng; Wang, Lian-Chen; Ju, Yu-Ten; Hong, Chin-Lin; Tsai, Yu-Yang; Li, Yi-Hung; Wu, Ying-Ling

2011-01-01

Infection rate, reaction to light, and hair follicle apoptosis are examined in the dogmite, Demodex canis Leydig (Prostigmata: Demodicidae), in dogs from the northern area of Taiwan. An analysis of relevant samples revealed 7.2% (73/1013) prevalence of D. canis infection. Infection during the investigation peaked each winter, with an average prevalence of 12.5% (32/255). The infection rates significantly varied in accordance with month, sex, age, and breed (p < 0.05). Most of the lesions were discovered on the backs of the infected animals, where the infection rate was 52.1% (38/73) (P < 0.05). The epidemiologic analysis of infection based on landscape area factor, found that employing a map-overlapping method showed a higher infection rate in the eastern distribution of Taiwan's northern area than other areas. Isolation tests for Microsporum canis Bodin (Onygenales: Arthrodermataceae) and Trichophyton mentagrophyte Robin (Blanchard) on the D. canis infected dogs revealed prevalence rates of 4.4% (2/45) and 2.2% (1/45), respectively. Observations demonstrated that D. canis slowly moved from a light area to a dark area. Skin samples were examined for cellular apoptosis by activated caspase3 immunohistochemical staining. Cells that surrounded the infected hair follicles were activated caspase3-positive, revealing cell apoptosis in infected follicles via the activation of caspase3. PMID:21867442

Special section guest editorial: Hybrid organic-inorganic solar cells

DOE PAGES

Nogueira, Ana Flavia; Rumbles, Garry

2015-04-06

In this special section of the Journal of Photonics for Energy, there is a focus on some of the science and technology of a range of different hybrid organic-inorganic solar cells. Prior to 1991 there were many significant scientific research reports of hybrid organic-inorganic solar cells; finally, however, it wasn’t until the dye-sensitized solar cell entered the league table of certified research cell efficiencies that this area experienced an explosion of research activity.

Network dynamics underlying the formation of sparse, informative representations in the hippocampus.

PubMed

Karlsson, Mattias P; Frank, Loren M

2008-12-24

During development, activity-dependent processes increase the specificity of neural responses to stimuli, but the role that this type of process plays in adult plasticity is unclear. We examined the dynamics of hippocampal activity as animals learned about new environments to understand how neural selectivity changes with experience. Hippocampal principal neurons fire when the animal is located in a particular subregion of its environment, and in any given environment the hippocampal representation is sparse: less than half of the neurons in areas CA1 and CA3 are active whereas the rest are essentially silent. Here we show that different dynamics govern the evolution of this sparsity in CA1 and upstream area CA3. CA1, but not CA3, produces twice as many spikes in novel compared with familiar environments. This high rate firing continues during sharp wave ripple events in a subsequent rest period. The overall CA1 population rate declines and the number of active cells decreases as the environment becomes familiar and task performance improves, but the decline in rate is not uniform across neurons. Instead, the activity of cells with initial peak spatial rates above approximately 12 Hz is enhanced, whereas the activity of cells with lower initial peak rates is suppressed. The result of these changes is that the active CA1 population comes to consist of a relatively small group of cells with strong spatial tuning. This process is not evident in CA3, indicating that a region-specific and long timescale process operates in CA1 to create a sparse, spatially informative population of neurons.

Broadband integrated mid infrared light sources as enabling technology for point of care mid-infrared spectroscopy

DTIC Science & Technology

2017-08-20

liquid crystal cell was successfully employed as an active q-switching element in the same type of chip lasers. The short laser pulses that were...switched mode-locked (QML) operation of those chip lasers. Further, a novel nematic liquid crystal cell was successfully employed as an active q... gas spectroscopy and environmental monitoring, areas that hold immense significance and importance. However, laser source development at these

2009 Annual Progress Report: DOE Hydrogen Program, November 2009 (Book)

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

Not Available

2009-11-01

This report summarizes the hydrogen and fuel cell R&D activities and accomplishments of the DOE Hydrogen Program for FY2009. It covers the program areas of hydrogen production and delivery; fuel cells; manufacturing; technology validation; safety, codes and standards; education; and systems analysis.

Chronic exposure to volcanic air pollution and DNA damage in Furnas Volcano (São Miguel Island, Azores, Portugal) inhabitants

NASA Astrophysics Data System (ADS)

Linhares, Diana; Garcia, Patricia; Silva, Catarina; Ferreira, Teresa; Barroso, Joana; Camarinho, Ricardo; Rodrigues, Armindo

2015-04-01

Many studies in volcanic air pollution only have in consideration the acute toxic effects of gas or ash releases however the impact of chronic exposure to ground gas emissions in human health is yet poorly known. In the Azores archipelago (Portugal), São Miguel island has one of the most active and dangerous volcanoes: Furnas Volcano. Highly active fumarolic fields, hot springs and soil diffuse degassing phenomena are the main secondary volcanic phenomena that can be seen at the volcano surroundings. One of the main gases released in these diffuse degassing areas is radon (222Rn), which decay results in solid particles that readily settle within the airways. These decay particles emit alpha radiation that is capable of causing severe DNA damage that cumulatively can eventually cause cancer. Previous studies have established that chronic exposure to chromosome-damaging agents can lead to the formation of nuclear anomalies, such as micronuclei that is used for monitoring DNA damage in human populations. The present study was designed to evaluate whether chronic exposure to volcanic air pollution, associated to 222Rn, might result in DNA damage in human oral epithelial cells. A cross sectional study was performed in a study group of 142 individuals inhabiting an area where volcanic activity is marked by active fumarolic fields and soil degassing (hydrothermal area), and a reference group of 368 individuals inhabiting an area without these secondary manifestations of volcanism (non-hydrothermal area). For each individual, 1000 buccal epithelial cells were analyzed for the frequency of micronucleated cells (MNc) and the frequency of cells with other nuclear anomalies (ONA: pyknosis, karyolysis and karyorrhexis), by using the micronucleus assay. Information on lifestyle factors and an informed consent were obtained from each participant. Assessment of indoor radon was performed with the use of radon detectors. Data were analyzed with logistic regression models, adjusted for confounding factors (age, gender, smoking and drinking status, and number of cigarettes smoked per day). Results demonstrated that levels of radon in the environment were significantly different in study and reference groups (115 Bq/m3 vs. 47 Bq/m3, respectively; p<0.001); in winter, radon measurements reached the highest values both in the study and the reference groups (809 Bq/m3 vs. 56 Bq/m3, respectively). The frequency of MNc in the study group was significantly higher than in the reference group (2.93‰ vs. 2.58‰, respectively; p=0.002). The OR for formation of MNc in the hydrothermal area was 1.5 (95% CI 1.07-2.02). A moderate and positive correlation was found between the frequency of MNc and 222Rn (rs = 0.459, p<0.001). To our knowledge this is the first study that clearly associates the exposure of volcanogenic indoor radon in inhabitants of hydrothermal areas and the DNA damage in human oral epithelial cells, evidencing that volcanic air pollution is a risk factor of carcinogenesis. Although the present findings require confirmation in larger studies, bio-monitoring for DNA damage is recommended for inhabitants of localities with active volcanism and mitigation measures such as restriction of building in certain areas should be taken into consideration in these volcanically active areas.

Human CD34+ cells engineered to express membrane-bound tumor necrosis factor-related apoptosis-inducing ligand target both tumor cells and tumor vasculature.

PubMed

Lavazza, Cristiana; Carlo-Stella, Carmelo; Giacomini, Arianna; Cleris, Loredana; Righi, Marco; Sia, Daniela; Di Nicola, Massimo; Magni, Michele; Longoni, Paolo; Milanesi, Marco; Francolini, Maura; Gloghini, Annunziata; Carbone, Antonino; Formelli, Franca; Gianni, Alessandro M

2010-03-18

Adenovirus-transduced CD34+ cells expressing membrane-bound tumor necrosis factor-related apoptosis-inducing ligand (CD34-TRAIL+ cells) exert potent antitumor activity. To further investigate the mechanism(s) of action of CD34-TRAIL+ cells, we analyzed their homing properties as well as antitumor and antivascular effects using a subcutaneous myeloma model in immunodeficient mice. After intravenous injection, transduced cells homed in the tumor peaking at 48 hours when 188 plus or minus 25 CD45+ cells per 10(5) tumor cells were detected. Inhibition experiments showed that tumor homing of CD34-TRAIL+ cells was largely mediated by vascular cell adhesion molecule-1 and stromal cell-derived factor-1. Both CD34-TRAIL+ cells and soluble (s)TRAIL significantly reduced tumor volume by 40% and 29%, respectively. Computer-aided analysis of TdT-mediated dUTP nick end-labeling-stained tumor sections demonstrated significantly greater effectiveness for CD34-TRAIL+ cells in increasing tumor cell apoptosis and necrosis over sTRAIL. Proteome array analysis indicated that CD34-TRAIL+ cells and sTRAIL activate similar apoptotic machinery. In vivo staining of tumor vasculature with sulfosuccinimidyl-6-(biotinamido) hexanoate-biotin revealed that CD34-TRAIL+ cells but not sTRAIL significantly damaged tumor vasculature, as shown by TdT-mediated dUTP nick end-labeling+ endothelial cells, appearance of hemorrhagic areas, and marked reduction of endothelial area. These results demonstrate that tumor homing of CD34-TRAIL+ cells induces early vascular disruption, resulting in hemorrhagic necrosis and tumor destruction.

Corrective action investigation plan for CAU Number 453: Area 9 Landfill, Tonopah Test Range

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

NONE

This Corrective Action Investigation Plan (CAIP) contains the environmental sample collection objectives and criteria for conducting site investigation activities at the Area 9 Landfill, Corrective Action Unit (CAU) 453/Corrective Action (CAS) 09-55-001-0952, which is located at the Tonopah Test Range (TTR). The TTR, included in the Nellis Air Force Range, is approximately 255 kilometers (140 miles) northwest of Las Vegas, Nevada. The Area 9 Landfill is located northwest of Area 9 on the TTR. The landfill cells associated with CAU 453 were excavated to receive waste generated from the daily operations conducted at Area 9 and from range cleanup whichmore » occurred after test activities.« less

IRF4 controls the positioning of mature B cells in the lymphoid microenvironments by regulating NOTCH2 expression and activity

PubMed Central

Simonetti, Giorgia; Carette, Amanda; Silva, Kathryn; Wang, Haowei; De Silva, Nilushi S.; Heise, Nicole; Siebel, Christian W.; Shlomchik, Mark J.

2013-01-01

The transcription factor interferon regulatory factor-4 (IRF4) is expressed in B cells at most developmental stages. In antigen-activated B cells, IRF4 controls germinal center formation, class-switch recombination, and the generation of plasma cells. Here we describe a novel function for IRF4 in the homeostasis of mature B cells. Inducible deletion of irf4 specifically in B cells in vivo led to the aberrant accumulation of irf4-deleted follicular B cells in the marginal zone (MZ) area. IRF4-deficient B cells showed elevated protein expression and activation of NOTCH2, a transmembrane receptor and transcriptional regulator known to be required for MZ B cell development. Administration of a NOTCH2-inhibitory antibody abolished nuclear translocation of NOTCH2 in B cells within 12 h and caused a rapid and progressive disintegration of the MZ that was virtually complete 48 h after injection. The disappearance of the MZ was accompanied by a transient increase of MZ-like B cells in the blood rather than increased B cell apoptosis, demonstrating that continued NOTCH2 activation is critical for the retention of B cells in the MZ. Our results suggest that IRF4 controls the positioning of mature B cells in the lymphoid microenvironments by regulating NOTCH2 expression. These findings may have implications for the understanding of B cell malignancies with dysregulated IRF4 and NOTCH2 activity. PMID:24323359

Activation patterns of cells in selected brain stem nuclei of more and less stress responsive rats in two animal models of PTSD - predator exposure and submersion stress.

PubMed

Adamec, Robert; Toth, Mate; Haller, Jozsef; Halasz, Jozsef; Blundell, Jacqueline

2012-02-01

This study had two purposes. First: compare predator and water submersion stress cFos activation patterns in dorsal raphe (DR), locus coeruleus (LC) and periaqueductal gray (PAG). Second: identify markers of vulnerability to stressors within these areas. Rats were either predator or submersion stressed and tested 1.75 h later for anxiety-like behavior. Immediately thereafter, rats were sacrificed and cFos expression examined. In DR, serotonergic cells expressing or not expressing cFos were also counted. Predator and submersion stress increased anxiety-like behavior (in the elevated plus maze- EPM) equally over controls. Moreover, stressed rats spent equally less time in the center of the hole board than handled controls, another indication of increased anxiety-like behavior. To examine vulnerability, rats which were less anxious (LA) and more (highly) anxious (MA) in the EPM were selected from among handled control and stressed animals. LA rats in the stressed groups were considered stress non-responsive and MA stressed rats were considered stress responsive. LA and MA rats did not differ in cFos expression in any brain area, though stressors did increase cFos cell counts in all areas over controls. Intriguingly, the number of serotonergic DR neurons not activated by stress predicted degree of anxiety response to submersion stress only. LA submersion stressed rats had more serotonergic cells than all other groups, and MA submersion stressed rats had fewer serotonergic cells than all other groups, which did not differ. Moreover, these cell counts correlated with EPM anxiety. We conclude that a surplus of such cells protects against anxiogenic effects of submersion, while a paucity of such cells enhances vulnerability to submersion stress. Other data suggest serotonergic cells may exert their effects via inhibition of dorsolateral PAG cells during submersion stress. Findings are discussed with respect to serotonergic transmission in vulnerability to predator stress and relevance of findings for post traumatic stress disorder (PTSD). This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. Copyright © 2010 Elsevier Ltd. All rights reserved.

Research on major antitumor active components in Zi-Cao-Cheng-Qi decoction based on hollow fiber cell fishing with high performance liquid chromatography.

PubMed

Li, Miaomiao; Hu, Shuang; Chen, Xuan; Wang, Runqin; Bai, Xiaohong

2018-02-05

Hollow fiber cell fishing (HFCF) based on hepatoma HepG-2 cells, human renal tubular ACHN cells or human cervical carcinoma HeLa cells, coupled with high-performance liquid chromatography (HPLC), was developed and employed to research the major active components in Zi-Cao-Cheng-Qi decoction both in vitro and in vivo. The research showed that the active components, such as hesperidin, magnolol, honokiol, shikonin, emodin and β,β'-dimethylacrylshikonin were screened out by HFCF based on the cancer cells in vitro, furthermore they can be absorbed into blood and reach in the target organ, and some of the active components can be fished by the cells and maintain effective concentrations. Before application of HFCF with HPLC, cell growth state, cell survival rate, positive effect on screening results binding between active centers on the fiber and target components, repeatability of retention times and relative peak areas of the target analytes were analysed and investigated. In short, HFCF with HPLC is a simple, inexpensive, effective, and reliable method that can be used in researching active components from traditional Chinese medicine (TCM) and its formula both in vitro and in vivo, elucidating preliminarily the TCM characteristics of multiple components and multiple targets, laying a foundation for expounding the antitumor efficacy material basis in TCM. Copyright © 2017 Elsevier B.V. All rights reserved.

Are neural correlates of visual consciousness retinotopic?

PubMed

ffytche, Dominic H; Pins, Delphine

2003-11-14

Some visual neurons code what we see, their defining characteristic being a response profile which mirrors conscious percepts rather than veridical sensory attributes. One issue yet to be resolved is whether, within a given cortical area, conscious visual perception relates to diffuse activity across the entire population of such cells or focal activity within the sub-population mapping the location of the perceived stimulus. Here we investigate the issue in the human brain with fMRI, using a threshold stimulation technique to dissociate perceptual from non-perceptual activity. Our results point to a retinotopic organisation of perceptual activity in early visual areas, with independent perceptual activations for different regions of visual space.

Constitutive properties of adult mammalian cardiac muscle cells

NASA Technical Reports Server (NTRS)

Zile, M. R.; Richardson, K.; Cowles, M. K.; Buckley, J. M.; Koide, M.; Cowles, B. A.; Gharpuray, V.; Cooper, G. 4th

1998-01-01

BACKGROUND: The purpose of this study was to determine whether changes in the constitutive properties of the cardiac muscle cell play a causative role in the development of diastolic dysfunction. METHODS AND RESULTS: Cardiocytes from normal and pressure-hypertrophied cats were embedded in an agarose gel, placed on a stretching device, and subjected to a change in stress (sigma), and resultant changes in cell strain (epsilon) were measured. These measurements were used to examine the passive elastic spring, viscous damping, and myofilament activation. The passive elastic spring was assessed in protocol A by increasing the sigma on the agarose gel at a constant rate to define the cardiocyte sigma-versus-epsilon relationship. Viscous damping was assessed in protocol B from the loop area between the cardiocyte sigma-versus-epsilon relationship during an increase and then a decrease in sigma. In both protocols, myofilament activation was minimized by a reduction in [Ca2+]i. Myofilament activation effects were assessed in protocol C by defining cardiocyte sigma versus epsilon during an increase in sigma with physiological [Ca2+]i. In protocol A, the cardiocyte sigma-versus-epsilon relationship was similar in normal and hypertrophied cells. In protocol B, the loop area was greater in hypertrophied than normal cardiocytes. In protocol C, the sigma-versus-epsilon relation in hypertrophied cardiocytes was shifted to the left compared with normal cells. CONCLUSIONS: Changes in viscous damping and myofilament activation in combination may cause pressure-hypertrophied cardiocytes to resist changes in shape during diastole and contribute to diastolic dysfunction.

Cell-based therapy technology classifications and translational challenges

PubMed Central

Mount, Natalie M.; Ward, Stephen J.; Kefalas, Panos; Hyllner, Johan

2015-01-01

Cell therapies offer the promise of treating and altering the course of diseases which cannot be addressed adequately by existing pharmaceuticals. Cell therapies are a diverse group across cell types and therapeutic indications and have been an active area of research for many years but are now strongly emerging through translation and towards successful commercial development and patient access. In this article, we present a description of a classification of cell therapies on the basis of their underlying technologies rather than the more commonly used classification by cell type because the regulatory path and manufacturing solutions are often similar within a technology area due to the nature of the methods used. We analyse the progress of new cell therapies towards clinical translation, examine how they are addressing the clinical, regulatory, manufacturing and reimbursement requirements, describe some of the remaining challenges and provide perspectives on how the field may progress for the future. PMID:26416686

A Moore's cellular automaton model to get probabilistic seismic hazard maps for different magnitude releases: A case study for Greece

NASA Astrophysics Data System (ADS)

Jiménez, A.; Posadas, A. M.

2006-09-01

Cellular automata are simple mathematical idealizations of natural systems and they supply useful models for many investigations in natural science. Examples include sandpile models, forest fire models, and slider block models used in seismology. In the present paper, they have been used for establishing temporal relations between the energy releases of the seismic events that occurred in neighboring parts of the crust. The catalogue is divided into time intervals, and the region is divided into cells which are declared active or inactive by means of a threshold energy release criterion. Thus, a pattern of active and inactive cells which evolves over time is determined. A stochastic cellular automaton is constructed starting with these patterns, in order to simulate their spatio-temporal evolution, by supposing a Moore's neighborhood interaction between the cells. The best model is chosen by maximizing the mutual information between the past and the future states. Finally, a Probabilistic Seismic Hazard Map is given for the different energy releases considered. The method has been applied to the Greece catalogue from 1900 to 1999. The Probabilistic Seismic Hazard Maps for energies corresponding to m = 4 and m = 5 are close to the real seismicity after the data in that area, and they correspond to a background seismicity in the whole area. This background seismicity seems to cover the whole area in periods of around 25-50 years. The optimum cell size is in agreement with other studies; for m > 6 the optimum area increases according to the threshold of clear spatial resolution, and the active cells are not so clustered. The results are coherent with other hazard studies in the zone and with the seismicity recorded after the data set, as well as provide an interaction model which points out the large scale nature of the earthquake occurrence.

Investigation of rough surfaces on Cu2ZnSn(SxSe1-x)4 monograin layers using light beam induced current measurements

NASA Astrophysics Data System (ADS)

Neubauer, Christian; Babatas, Ertug; Meissner, Dieter

2017-11-01

Monograin technology has proven to be a successful way of manufacturing low cost photovoltaic applications using the pentanary Cu2ZnSn(SxSe1-x)4 (CZTSSe) as an absorber material in an industrial roll-to-roll process. For high efficient CZTSSe monograin device fabrication a thorough understanding of the impacts of the device characteristics and surface structure is important. A new evaluation method of Light Beam Induced Current (LBIC) images had to be developed to distinguish between different effects resulting from different surface orientations, grain sizes, packing densities and contacting areas. In this work we will show that with LBIC measurements it is possible to evaluate the quality and differences in produced CZTSSe monograin cells in a post-production and non-destructive step. The high spatial resolution evaluation allows investigating the homogeneity of single crystalline grains as well as certain areas of a CZTSSe device. By introducing a statistical method the active area as a major factor for the current density of a device will be calculated and evaluated. The results show that with LBIC measurements the active area can be quantified, which differs for the investigated cells up to 9%. Additionally, the homogeneity of short circuit current densities of the monograins and also of certain areas of a cell can be detected and quantified.

Area 21a of cat visual cortex strongly modulates neuronal activities in the superior colliculus

PubMed Central

Hashemi-Nezhad, M; Wang, C; Burke, W; Dreher, B

2003-01-01

We have examined the influence of cortico-tectal projections from one of the pattern-processing extrastriate visual cortical areas, area 21a, on the responses to visual stimuli of single neurones in the superior colliculi of adult cats. For this purpose area 21a was briefly inactivated by cooling to 10 °C using a Peltier device. Responses to visual stimuli before and during cooling as well as after rewarming ipsilateral area 21a were compared. In addition, in a subpopulation of collicular neurones we have studied the effects of reversible inactivation of ipsilateral striate cortex (area 17, area V1). When area 21a was cooled, the temperature of area 17 was kept at 36 °C and vice versa. In the majority of cases (41/65; 63 %), irrespective of the velocity response profiles of collicular neurones, inactivation of area 21a resulted in a significant decrease in magnitude of responses of neurones in the ipsilateral colliculus and only in a small proportion of cells (2/65; 3.1 %) was there a significant increase in the magnitude of responses. Inactivation of area 21a resulted in significant changes in the magnitude of responses of collicular cells located not only in the retino-recipient layers but also in the stratum griseum intermediale. In most cases, reversible inactivation of area 17 resulted in a greater reduction in the magnitude of responses of collicular cells than inactivation of area 21a. Reversible inactivation of area 21a also affected the direction selectivity indices and length tuning of most collicular cells tested. PMID:12794178

A blessing and a curse: is high NK cell activity good for health and bad for reproduction?

PubMed

Templer, Sophie; Sacks, Gavin

2016-09-01

Few topics in recent reproductive medicine have been the subject of as much controversy, media attention and passionate debate as natural killer (NK) cells and their role in reproductive failure. The question of whether elevated NK cell levels are a cause of infertility and pregnancy loss, and whether they provide a potential target for therapy to improve reproductive outcomes, lacks a definitive answer. It is clear, however, that a significant number of women with reproductive failure have abnormal NK cell parameters reflecting high immunological activity. Amongst all the debate, the wider implications of NK cell overactivity - and attempts to suppress it - have not yet been considered. The literature suggests that although elevated NK cell activity may not be conducive to reproduction, it could in fact be beneficial in other areas of health and disease such as cancer and infection. Further research is needed to determine whether this hypothesis holds true in women with NK cell-related reproductive failure.

N-acetyl-L-cysteine increases MnSOD activity and enhances the recruitment of quiescent human fibroblasts to the proliferation cycle during wound healing

PubMed Central

Mao, Gaowei; Goswami, Monali; Kalen, Amanda L.; Goswami, Prabhat C.; Sarsour, Ehab H.

2016-01-01

Background The rebuilding of the connective tissue during wound healing requires the recruitment of fibroblasts to the wound area as well as reentry of quiescent fibroblasts to the proliferative cycle. Whether this process can be modulated by a small molecular weight thiol antioxidant N-acetyl-L-cysteine (NAC) was tested in normal human skin fibroblasts (NHFs) in this study. Methods and Results By using a uni-directional wound healing assay, NAC treated cells demonstrated a decreased migration rate but increased number of proliferating cells recruited into the wound area post wounding. Fifteen day quiescent control and NAC treated NHFs were re-plated at a lower density and cell numbers counted at different days post-plating. Interestingly, NAC treated cells exhibited increased cellular proliferation indicated by both decreased cell population doubling time and increased S phase cells. NAC treated cells demonstrated decreased steady state levels of reactive oxygen species as well as increased protein and activity levels of manganese superoxide dismutase (MnSOD). NAC treatment failed to induce proliferation in quiescent cells lacking MnSOD expression. Conclusions These results demonstrate that NAC enhanced the recruitment of quiescent NHFs into proliferation cycle during wound healing. Our results also suggest that the wound healing properties of NAC might be due to its ability to induce and enhance MnSOD expression and activity. Altogether, these findings suggest NAC might be potentially developed as a dietary intervention to improve tissue injury in animals and humans. PMID:26671656

Traction force dynamics predict gap formation in activated endothelium

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

Valent, Erik T.; Nieuw Amerongen, Geerten P. van; Hinsbergh, Victor W.M. van

In many pathological conditions the endothelium becomes activated and dysfunctional, resulting in hyperpermeability and plasma leakage. No specific therapies are available yet to control endothelial barrier function, which is regulated by inter-endothelial junctions and the generation of acto-myosin-based contractile forces in the context of cell-cell and cell-matrix interactions. However, the spatiotemporal distribution and stimulus-induced reorganization of these integral forces remain largely unknown. Traction force microscopy of human endothelial monolayers was used to visualize contractile forces in resting cells and during thrombin-induced hyperpermeability. Simultaneously, information about endothelial monolayer integrity, adherens junctions and cytoskeletal proteins (F-actin) were captured. This revealed a heterogeneousmore » distribution of traction forces, with nuclear areas showing lower and cell-cell junctions higher traction forces than the whole-monolayer average. Moreover, junctional forces were asymmetrically distributed among neighboring cells. Force vector orientation analysis showed a good correlation with the alignment of F-actin and revealed contractile forces in newly formed filopodia and lamellipodia-like protrusions within the monolayer. Finally, unstable areas, showing high force fluctuations within the monolayer were prone to form inter-endothelial gaps upon stimulation with thrombin. To conclude, contractile traction forces are heterogeneously distributed within endothelial monolayers and force instability, rather than force magnitude, predicts the stimulus-induced formation of intercellular gaps. - Highlights: • Endothelial monolayers exert dynamic- and heterogeneous traction forces. • High traction forces correlate with junctional areas and the F-actin cytoskeleton. • Newly formed inter-endothelial gaps are characterized by opposing traction forces. • Force stability is a key feature controlling endothelial permeability.« less

The distribution of immunomodulatory cells in the lungs of patients with idiopathic pulmonary fibrosis

PubMed Central

Nuovo, Gerard J.; Hagood, James S.; Magro, Cynthia M.; Chin, Nena; Kapil, Rubina; Davis, Luke; Marsh, Clay B.; Folcik, Virginia A.

2011-01-01

We have characterized the immune system involvement in the disease processes of idiopathic pulmonary fibrosis in novel ways. To do so, we analyzed lung tissue from 21 cases of idiopathic pulmonary fibrosis and 21 (non-fibrotic, non-cancerous) controls for immune cell and inflammation-related markers. The immunohistochemical analysis of the tissue was grouped by patterns of severity in disease pathology. There were significantly greater numbers of CD68+ and CD80+ cells, and significantly fewer CD3+, CD4+, and CD45RO+ cells in areas of relatively (histologically) normal lung in biopsies from idiopathic pulmonary fibrosis patients compared to controls. In zones of active disease, characterized by epithelial cell regeneration and fibrosis, there were significantly more cells expressing CD4, CD8, CD20, CD68, CD80, CCR6, S100, IL-17, tumor necrosis factor-α, and retinoic acid-related orphan receptors compared to histologically normal lung areas from idiopathic pulmonary fibrosis patients. Inflammation was implicated in these active regions by the cells that expressed retinoid orphan receptor-α, -β, and -γ, CCR6, and IL-17. The regenerating epithelial cells predominantly expressed these pro-inflammatory molecules, as evidenced by co-expression analyses with epithelial cytokeratins. Macrophages in pseudo-alveoli and CD3+ T cells in the fibrotic interstitium also expressed IL-17. Co-expression of IL-17 with retinoid orphan receptors, and epithelial cytoskeletal proteins, CD68, and CD3 in epithelial cells, macrophages, and T-cells, respectively, confirmed the production of IL-17 by these cell types. There was little staining for Foxp3, CD56, or CD34 in any idiopathic pulmonary fibrosis lung regions. The fibrotic regions had fewer immune cells overall. In summary, our study shows participation of innate and adaptive mononuclear cells in active-disease regions of idiopathic pulmonary fibrosis lung, where the regenerating epithelial cells appear to propagate inflammation. The regenerative mechanisms become skewed to ultimately result in lethal, fibrotic restriction of lung function. PMID:22037258

2014 Annual Progress Report: DOE Hydrogen and Fuel Cells Program

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

none,

2014-11-01

The 2014 Annual Progress Report summarizes fiscal year 2014 activities and accomplishments by projects funded by the DOE Hydrogen Program. It covers the program areas of hydrogen production and delivery; hydrogen storage; fuel cells; manufacturing; technology validation; safety, codes and standards; market transformation; and systems analysis.

Get Up and Move with Nonfiction

ERIC Educational Resources Information Center

Polette, Nancy

2008-01-01

Using an approach based on a Harvard study that found "when the whole body is involved, the number of brain cells brought to the learning activity doubles," the author offers over one hundred kinesthetic activities for classroom use. Activities are organized by content area, include directions for number of players, objective, and procedure, and…

Distributed solar radiation fast dynamic measurement for PV cells

NASA Astrophysics Data System (ADS)

Wan, Xuefen; Yang, Yi; Cui, Jian; Du, Xingjing; Zheng, Tao; Sardar, Muhammad Sohail

2017-10-01

To study the operating characteristics about PV cells, attention must be given to the dynamic behavior of the solar radiation. The dynamic behaviors of annual, monthly, daily and hourly averages of solar radiation have been studied in detail. But faster dynamic behaviors of solar radiation need more researches. The solar radiation random fluctuations in minute-long or second-long range, which lead to alternating radiation and cool down/warm up PV cell frequently, decrease conversion efficiency. Fast dynamic processes of solar radiation are mainly relevant to stochastic moving of clouds. Even in clear sky condition, the solar irradiations show a certain degree of fast variation. To evaluate operating characteristics of PV cells under fast dynamic irradiation, a solar radiation measuring array (SRMA) based on large active area photodiode, LoRa spread spectrum communication and nanoWatt MCU is proposed. This cross photodiodes structure tracks fast stochastic moving of clouds. To compensate response time of pyranometer and reduce system cost, the terminal nodes with low-cost fast-responded large active area photodiode are placed besides positions of tested PV cells. A central node, consists with pyranometer, large active area photodiode, wind detector and host computer, is placed in the center of the central topologies coordinate to scale temporal envelope of solar irradiation and get calibration information between pyranometer and large active area photodiodes. In our SRMA system, the terminal nodes are designed based on Microchip's nanoWatt XLP PIC16F1947. FDS-100 is adopted for large active area photodiode in terminal nodes and host computer. The output current and voltage of each PV cell are monitored by I/V measurement. AS62-T27/SX1278 LoRa communication modules are used for communicating between terminal nodes and host computer. Because the LoRa LPWAN (Low Power Wide Area Network) specification provides seamless interoperability among Smart Things without the need of complex local installations, configuring of our SRMA system is very easy. Lora also provides SRMA a means to overcome the short communication distance and weather signal propagation decline such as in ZigBee and WiFi. The host computer in SRMA system uses the low power single-board PC EMB-3870 which was produced by NORCO. Wind direction sensor SM5386B and wind-force sensor SM5387B are installed to host computer through RS-485 bus for wind reference data collection. And Davis 6450 solar radiation sensor, which is a precision instrument that detects radiation at wavelengths of 300 to 1100 nanometers, allow host computer to follow real-time solar radiation. A LoRa polling scheme is adopt for the communication between host computer and terminal nodes in SRMA. An experimental SRMA has been established. This system was tested in Ganyu, Jiangshu province from May to August, 2016. In the test, the distances between the nodes and the host computer were between 100m and 1900m. At work, SRMA system showed higher reliability. Terminal nodes could follow the instructions from host computer and collect solar radiation data of distributed PV cells effectively. And the host computer managed the SRAM and achieves reference parameters well. Communications between the host computer and terminal nodes were almost unaffected by the weather. In conclusion, the testing results show that SRMA could be a capable method for fast dynamic measuring about solar radiation and related PV cell operating characteristics.

Ventral Tegmental Area Dopamine Cell Activation during Male Rat Sexual Behavior Regulates Neuroplasticity and d-Amphetamine Cross-Sensitization following Sex Abstinence.

PubMed

Beloate, Lauren N; Omrani, Azar; Adan, Roger A; Webb, Ian C; Coolen, Lique M

2016-09-21

Experience with sexual behavior causes cross-sensitization of amphetamine reward, an effect dependent on a period of sexual reward abstinence. We previously showed that ΔFosB in the nucleus accumbens (NAc) is a key mediator of this cross-sensitization, potentially via dopamine receptor activation. However, the role of mesolimbic dopamine for sexual behavior or cross-sensitization between natural and drug reward is unknown. This was tested using inhibitory designer receptors exclusively activated by designer drugs in ventral tegmental area (VTA) dopamine cells. rAAV5/hSvn-DIO-hm4D-mCherry was injected into the VTA of TH::Cre adult male rats. Males received clozapine N-oxide (CNO) or vehicle injections before each of 5 consecutive days of mating or handling. Following an abstinence period of 7 d, males were tested for amphetamine conditioned place preference (CPP). Next, males were injected with CNO or vehicle before mating or handling for analysis of mating-induced cFos, sex experience-induced ΔFosB, and reduction of VTA dopamine soma size. Results showed that CNO did not affect mating behavior. Instead, CNO prevented sexual experience-induced cross-sensitization of amphetamine CPP, ΔFosB in the NAc and medial prefrontal cortex, and decreases in VTA dopamine soma size. Expression of hm4D-mCherry was specific to VTA dopamine cells and CNO blocked excitation and mating-induced cFos expression in VTA dopamine cells. These findings provide direct evidence that VTA dopamine activation is not required for initiation or performance of sexual behavior. Instead, VTA dopamine directly contributes to increased vulnerability for drug use following loss of natural reward by causing neuroplasticity in the mesolimbic pathway during the natural reward experience. Drugs of abuse act on the neural pathways that mediate natural reward learning and memory. Exposure to natural reward behaviors can alter subsequent drug-related reward. Specifically, experience with sexual behavior, followed by a period of abstinence from sexual behavior, causes increased reward for amphetamine in male rats. This study demonstrates that activation of ventral tegmental area dopamine neurons during sexual experience regulates cross-sensitization of amphetamine reward. Finally, ventral tegmental area dopamine cell activation is essential for experience-induced neural adaptations in the nucleus accumbens, prefrontal cortex, and ventral tegmental area. These findings demonstrate a role of mesolimbic dopamine in the interaction between natural and drug rewards, and identify mesolimbic dopamine as a key mediator of changes in vulnerability for drug use after loss of natural reward. Copyright © 2016 the authors 0270-6474/16/369949-13$15.00/0.

Shared target antigens on cancer cells and tissue stem cells: go or no-go for CAR T cells?

PubMed

Hombach, Andreas A; Abken, Hinrich

2017-02-01

Adoptive therapy with chimeric antigen receptor (CAR) T cells redirected towards CD19 produces remissions of B cell malignancies, however, it also eradicates healthy B cells sharing the target antigen. Such 'on-target off-tumor' toxicity raises serious safety concerns when the target antigen is also expressed by tissue stem cells, with the risk of lasting tissue destruction. Areas covered: We discuss CAR T cell targeting of activation antigens versus lineage associated antigens on the basis of recent experimental and animal data and the literature in the field. Expert commentary: Targeting an activation associated antigen which is transiently expressed by stem cells seems to be safe, like CAR T cells targeting CD30 spare CD30 + hematopoietic stem and progenitor cells while eliminating CD30 + lymphoma cells, whereas targeting lineage associated antigens which increase in expression during cell maturation, like folate receptor-β and CD123, is of risk to destruct tissue stem cells.

Generation of effector CD8+ T cells and their conversion to memory T cells

PubMed Central

Cui, Weiguo; Kaech, Susan M.

2015-01-01

Summary Immunological memory is a cardinal feature of adaptive immunity. We are now beginning to elucidate the mechanisms that govern the formation of memory T cells and their ability to acquire longevity, survive the effector-to-memory transition, and mature into multipotent, functional memory T cells that self-renew. Here, we discuss the recent findings in this area and highlight extrinsic and intrinsic factors that regulate the cellular fate of activated CD8+ T cells. PMID:20636815

Improved Reproducibility for Perovskite Solar Cells with 1 cm2 Active Area by a Modified Two-Step Process.

PubMed

Shen, Heping; Wu, Yiliang; Peng, Jun; Duong, The; Fu, Xiao; Barugkin, Chog; White, Thomas P; Weber, Klaus; Catchpole, Kylie R

2017-02-22

With rapid progress in recent years, organohalide perovskite solar cells (PSC) are promising candidates for a new generation of highly efficient thin-film photovoltaic technologies, for which up-scaling is an essential step toward commercialization. In this work, we propose a modified two-step method to deposit the CH 3 NH 3 PbI 3 (MAPbI 3 ) perovskite film that improves the uniformity, photovoltaic performance, and repeatability of large-area perovskite solar cells. This method is based on the commonly used two-step method, with one additional process involving treating the perovskite film with concentrated methylammonium iodide (MAI) solution. This additional treatment is proved to be helpful for tailoring the residual PbI 2 level to an optimal range that is favorable for both optical absorption and inhibition of recombination. Scanning electron microscopy and photoluminescence image analysis further reveal that, compared to the standard two-step and one-step methods, this method is very robust for achieving uniform and pinhole-free large-area films. This is validated by the photovoltaic performance of the prototype devices with an active area of 1 cm 2 , where we achieved the champion efficiency of ∼14.5% and an average efficiency of ∼13.5%, with excellent reproducibility.

Corrective Action Management Unit Report of Post-Closure Care Activities Calendar Year 2016.

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

Ziock, Robert; Little, Bonnie Colleen

The Corrective Action Management Unit (CAMU) at Sandia National Laboratories, New Mexico (SNL/NM) consisted of a containment cell, two treatment systems, four associated waste staging and storage areas, and support areas; all were used for management of remediation wastes between 1997 and 2003.

HURTLE CELLS IMMUNOHISTOCHEMICAL ACTIVITIES IN HASHIMOTO THYROIDITIS PARENCHYMA.

PubMed

Tsagareli, Z; Kvachadze, T; Melikadze, E; Metreveli, L; Nikobadze, E; Gogiashvili, L

2016-11-01

The present study was designed to evaluate the participation and utility of Hǘrtle cells morphological requirment and transformation under Hashimoto autoimmune thyroiditis versus Riedel´s struma. Several markers have been evaluated to detect induced activities of Hǘrtle cells. Study subject - specimens (tissue fragments) collected from TG surgery (thyroidectomy) for mollecular (receptor) diagnosis of Hǘrtle cells activities using routine histological and immunohistochemical samples. 89 cases were selected in Hashimoto thyroiditis diagnosis with Hǘrtle cells history (adenoma and adenomatous grouth of oncocytes). Markers as: TSH receptors, TTF-1, S-100 protein, also anti-TPO and anti-TG levels in blood plasm were detected. It was shown that solid cell claster-nests like agregation of oncocytes and adenomatous growth foci in parafollicular areas with anti-TPO and anti-TG antibodies levels arising while Riedel´s struma shown only large intra- and extra glandular inflammatory proliferative fibrosing process. Large positive expression of TTF-1 and S-100 protein and the negative reaction of TSH receptor factor suggest that Thyroid parenchyma disorganization and mollecular biological atypia with Hǘrtle cells are proceses due to hypothyreoidismus, as well as neuroectodermal cells prominent activities in 70% of Hashimoto cases.

Pyridoindole antioxidant-induced preservation of rat hippocampal pyramidal cell number linked with reduction of oxidative stress yet without influence on cognitive deterioration in Alzheimer-like neurodegeneration.

PubMed

Gasparova, Zdenka; Stara, Veronika; Janega, Pavol; Navarova, Jana; Sedlackova, Natalia; Mach, Mojmir; Ujhazy, Eduard

2014-01-01

The idea of antioxidant therapy attenuating Alzheimer disease (AD) neuropathology starts to be attractive. Animal models are often used in these studies. An AD-like model of trimethyltin (TMT)-induced neurodegeneration, targeting the hippocampus, involves neuronal cell death and cognitive impairment. Effect of the pyridoindole SMe1EC2 (3×50 mg/kg) and vitamin C (3×50mg/kg) was analyzed in the model of TMT-induced (8 mg/kg) neurodegeneration. The study was focused on the effect of the antioxidants tested on learning performance in the Morris water maze (MWM) on days 21-25 after TMT administration, on biochemical variables - malondyaldehyde (MDA) and lysosomal enzyme NAGA in brain cortex and blood serum, and on pyramidal cell number in the CA1 area of the hippocampus on day 31 after TMT administration in adult male Wistar rats (n=32). Critical deterioration of learning performance was observed due to the TMT administration in the MWM. Further, apparent reduction of pyramidal cell number to 21% in the CA1 area of the hippocampus, increased MDA and NAGA activity in serum and increased NAGA activity in the cortex were determined contrary to controls. In serum, an increase of MDA level was prevented by both antioxidants tested without any effect on NAGA activity. SMe1EC2 apparently preserved pyramidal cell viability in the CA1 area. Both substances tested failed to ameliorate the detrimental effect of TMT on spatial memory. The biochemical and morphometrical findings suggest that reduction of oxidative stress may play a role in AD-like neurodegeneration. Different doses and timing of SMe1EC2 administration might bring improvement in next learning performance.

Role of adrenal hormones in regulating distal nephron structure and ion transport.

PubMed

Stanton, B A

1985-08-01

Mineralocorticoid levels are an important determinant of membrane area and ion transport in the renal initial (ICT) and cortical (CCT) collecting tubules. Adrenalectomy leads to a dramatic and specific decrease in basolateral membrane area of principal (P) cells and depresses sodium reabsorption and potassium secretion. Although aldosterone replacement for 10 days restores basolateral membrane area and ATPase activity to control levels and dramatically elevates ion transport, glucocorticoids have no effect on basolateral membrane area, ion transport, or ATPase. It is suggested that the aldosterone-induced amplification of membrane area occurs as a mechanism whereby cells increase the number of ATPase pumps in the basolateral membrane. An acute (of 2-3 h) increase in aldosterone, but not dexamethasone, also stimulates potassium transport by the ICT. Future studies will have to establish whether the acute stimulation of transport by aldosterone involves a change in basolateral membrane area. It is concluded that mineralocorticoids, but not glucocorticoids, regulate sodium and potassium transport by P cells of the ICT and CCT, in part, by determining the number of ATPase pumps available for transport.

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

Guha, S.

This report describes the research program intended to expand, enhance, and accelerate knowledge and capabilities for developing high-performance, two-terminal multijunction amorphous silicon (a-Si) alloy cells, and modules with low manufacturing cost and high reliability. United Solar uses a spectrum-splitting, triple-junction cell structure. The top cell uses an amorphous silicon alloy of {approx}1.8-eV bandgap to absorb blue photons. The middle cell uses an amorphous silicon germanium alloy ({approx}20% germanium) of {approx}1.6-eV bandgap to capture green photons. The bottom cell has {approx}40% germanium to reduce the bandgap to {approx}1.4-eV to capture red photons. The cells are deposited on a stainless-steel substrate withmore » a predeposited silver/zinc oxide back reflector to facilitate light-trapping. A thin layer of antireflection coating is applied to the top of the cell to reduce reflection loss. The major research activities conducted under this program were: (1) Fundamental studies to improve our understanding of materials and devices; the work included developing and analyzing a-Si alloy and a-SiGe alloy materials prepared near the threshold of amorphous-to-microcrystalline transition and studying solar cells fabricated using these materials. (2) Deposition of small-area cells using a radio-frequency technique to obtain higher deposition rates. (3) Deposition of small-area cells using a modified very high frequency technique to obtain higher deposition rates. (4) Large-area cell research to obtain the highest module efficiency. (5) Optimization of solar cells and modules fabricated using production parameters in a large-area reactor.« less

Nonlocal origin of response suppression from stimulation outside the classic receptive field in area 17 of the cat.

PubMed

Brown, H A; Allison, J D; Samonds, J M; Bonds, A B

2003-01-01

A stimulus located outside the classic receptive field (CRF) of a striate cortical neuron can markedly influence its behavior. To study this phenomenon, we recorded from two cortical sites, recorded and peripheral, with separate electrodes in cats anesthetized with Propofol and nitrous oxide. The receptive fields of each site were discrete (2-7.3 deg between centers). A control orientation tuning (OT) curve was measured for a single recorded cell with a drifting grating. The OT curve was then remeasured while stimulating simultaneously the cell's CRF as well as the peripheral site with a stimulus optimized for that location. For 22/60 cells, the peripheral stimulus suppressed the peak response and/or shifted the center of mass of the OT curve. For 19 of these 22 cells, we then reversibly blocked stimulus-driven activity at the peripheral site by iontophoretic application of GABA (0.5 M). For 6/19 cells, the response returned to control levels, implying that for these cells the inhibitory influence arose from the blocked site. The responses of nine cells remained reduced during inactivation of the peripheral site, suggesting that influence was generated outside the region of local block in area 17. This is consistent with earlier findings suggesting that modulatory influences can originate from higher cortical areas. Three cells had mixed results, suggesting multiple origins of influence. The response of each cell returned to suppressed levels after dissipation of the GABA and returned to baseline values when the peripheral stimulus was removed. These findings support a cortical model in which a cell's response is modulated by an inhibitory network originating from beyond the receptive field that supplants convergence of excitatory lateral geniculate neurons. The existence of cells that exhibit no change in peripherally inhibited responses during the GABA application suggests that peripheral influences may arise from outside area 17, presumably from other cortical areas (e.g. area 18).

Chemical Activation of the Hypoxia-Inducible Factor Reversibly Reduces Tendon Stem Cell Proliferation, Inhibits Their Differentiation, and Maintains Cell Undifferentiation.

PubMed

Menon, Alessandra; Creo, Pasquale; Piccoli, Marco; Bergante, Sonia; Conforti, Erika; Banfi, Giuseppe; Randelli, Pietro; Anastasia, Luigi

2018-01-01

Adult stem cell-based therapeutic approaches for tissue regeneration have been proposed for several years. However, adult stem cells are usually limited in number and difficult to be expanded in vitro, and they usually tend to quickly lose their potency with passages, as they differentiate and become senescent. Culturing stem cells under reduced oxygen tensions (below 21%) has been proposed as a tool to increase cell proliferation, but many studies reported opposite effects. In particular, cell response to hypoxia seems to be very stem cell type specific. Nonetheless, it is clear that a major role in this process is played by the hypoxia inducible factor (HIF), the master regulator of cell response to oxygen deprivation, which affects cell metabolism and differentiation. Herein, we report that a chemical activation of HIF in human tendon stem cells reduces their proliferation and inhibits their differentiation in a reversible and dose-dependent manner. These results support the notion that hypoxia, by activating HIF, plays a crucial role in preserving stem cells in an undifferentiated state in the "hypoxic niches" present in the tissue in which they reside before migrating in more oxygenated areas to heal a damaged tissue.

Reduction of In-Stent Restenosis by Cholesteryl Ester Transfer Protein Inhibition.

PubMed

Wu, Ben J; Li, Yue; Ong, Kwok L; Sun, Yidan; Shrestha, Sudichhya; Hou, Liming; Johns, Douglas; Barter, Philip J; Rye, Kerry-Anne

2017-12-01

Angioplasty and stent implantation, the most common treatment for atherosclerotic lesions, have a significant failure rate because of restenosis. This study asks whether increasing plasma high-density lipoprotein (HDL) levels by inhibiting cholesteryl ester transfer protein activity with the anacetrapib analog, des-fluoro-anacetrapib, prevents stent-induced neointimal hyperplasia. New Zealand White rabbits received normal chow or chow supplemented with 0.14% (wt/wt) des-fluoro-anacetrapib for 6 weeks. Iliac artery endothelial denudation and bare metal steel stent deployment were performed after 2 weeks of des-fluoro-anacetrapib treatment. The animals were euthanized 4 weeks poststent deployment. Relative to control, dietary supplementation with des-fluoro-anacetrapib reduced plasma cholesteryl ester transfer protein activity and increased plasma apolipoprotein A-I and HDL cholesterol levels by 53±6.3% and 120±19%, respectively. Non-HDL cholesterol levels were unaffected. Des-fluoro-anacetrapib treatment reduced the intimal area of the stented arteries by 43±5.6% ( P <0.001), the media area was unchanged, and the arterial lumen area increased by 12±2.4% ( P <0.05). Des-fluoro-anacetrapib treatment inhibited vascular smooth muscle cell proliferation by 41±4.5% ( P <0.001). Incubation of isolated HDLs from des-fluoro-anacetrapib-treated animals with human aortic smooth muscle cells at apolipoprotein A-I concentrations comparable to their plasma levels inhibited cell proliferation and migration. These effects were dependent on scavenger receptor-B1, the adaptor protein PDZ domain-containing protein 1, and phosphatidylinositol-3-kinase/Akt activation. HDLs from des-fluoro-anacetrapib-treated animals also inhibited proinflammatory cytokine-induced human aortic smooth muscle cell proliferation and stent-induced vascular inflammation. Inhibiting cholesteryl ester transfer protein activity in New Zealand White rabbits with iliac artery balloon injury and stent deployment increases HDL levels, inhibits vascular smooth muscle cell proliferation, and reduces neointimal hyperplasia in an scavenger receptor-B1, PDZ domain-containing protein 1- and phosphatidylinositol-3-kinase/Akt-dependent manner. © 2017 American Heart Association, Inc.

Safety and pharmacodynamics of dalazatide, a Kv1.3 channel inhibitor, in the treatment of plaque psoriasis: A randomized phase 1b trial

PubMed Central

Tarcha, Eric J.; Probst, Peter; Peckham, David; Muñoz-Elías, Ernesto J.; Kruger, James G.; Iadonato, Shawn P.

2017-01-01

Background Dalazatide is a specific inhibitor of the Kv1.3 potassium channel. The expression and function of Kv1.3 channels are required for the function of chronically activated memory T cells, which have been shown to be key mediators of autoimmune diseases, including psoriasis. Objective The primary objective was to evaluate the safety of repeat doses of dalazatide in adult patients with mild-to-moderate plaque psoriasis. Secondary objectives were to evaluate clinical proof of concept and the effects of dalazatide on mediators of inflammation in the blood and on chronically activated memory T cell populations. Methods Patients (n = 24) were randomized 5:5:2 to receive dalazatide at 30 mcg/dose, 60 mcg/dose, or placebo twice weekly by subcutaneous injection (9 doses total). Safety was assessed on the basis of physical and neurological examination and laboratory testing. Clinical assessments included body-surface area affected, Psoriasis Area and Severity Index (PASI), and investigator and patient questionnaires. Results The most common adverse events were temporary mild (Grade 1) hypoesthesia (n = 20; 75% placebo, 85% dalazatide) and paresthesia (n = 15; 25% placebo, 70% dalazatide) involving the hands, feet, or perioral area. Nine of 10 patients in the 60 mcg/dose group had a reduction in their PASI score between baseline and Day 32, and the mean reduction in PASI score was significant in this group (P < 0.01). Dalazatide treatment reduced the plasma levels of multiple inflammation markers and reduced the expression of T cell activation markers on peripheral blood memory T cells. Limitations The study was small and drug treatment was for a short duration (4 weeks). Conclusion This study indicates that dalazatide is generally well tolerated and can improve psoriatic skin lesions by modulating T cell surface and activation marker expression and inhibiting mediators of inflammation in the blood. Larger studies of longer duration are warranted. PMID:28723914

Fabrication of Highly Stable and Efficient PtCu Alloy Nanoparticles on Highly Porous Carbon for Direct Methanol Fuel Cells.

PubMed

Khan, Inayat Ali; Qian, Yuhong; Badshah, Amin; Zhao, Dan; Nadeem, Muhammad Arif

2016-08-17

Boosting the durability of Pt nanoparticles by controlling the composition and morphology is extremely important for fuel cells commercialization. We deposit the Pt-Cu alloy nanoparticles over high surface area carbon in different metallic molar ratios and optimize the conditions to achieve desired material. The novel bimetallic electro-catalyst {Pt-Cu/PC-950 (15:15%)} offers exceptional electrocatalytic activity when tested for both oxygen reduction reaction and methanol oxidation reactions. A high mass activity of 0.043 mA/μgPt (based on Pt mass) is recorded for ORR. An outstanding longevity of this electro-catalyst is noticed when compared to 20 wt % Pt loaded either on PC-950 or commercial carbon. The high surface area carbon support offers enhanced activity and prevents the nanoparticles from agglomeration, migration, and dissolution as evident by TEM analysis.

The human urothelium consists of multiple clonal units, each maintained by a stem cell.

PubMed

Gaisa, Nadine T; Graham, Trevor A; McDonald, Stuart A C; Cañadillas-Lopez, Sagrario; Poulsom, Richard; Heidenreich, Axel; Jakse, Gerhard; Tadrous, Paul J; Knuechel, Ruth; Wright, Nicholas A

2011-10-01

Little is known about the clonal architecture of human urothelium. It is likely that urothelial stem cells reside within the basal epithelial layer, yet lineage tracing from a single stem cell as a means to show the presence of a urothelial stem cell has never been performed. Here, we identify clonally related cell areas within human bladder mucosa in order to visualize epithelial fields maintained by a single founder/stem cell. Sixteen frozen cystectomy specimens were serially sectioned. Patches of cells deficient for the mitochondrially encoded enzyme cytochrome c oxidase (CCO) were identified using dual-colour enzyme histochemistry. To show that these patches represent clonal proliferations, small CCO-proficient and -deficient areas were individually laser-capture microdissected and the entire mitochondrial genome (mtDNA) in each area was PCR amplified and sequenced to identify mtDNA mutations. Immunohistochemistry was performed for the different cell layers of the urothelium and adjacent mesenchyme. CCO-deficient patches could be observed in normal urothelium of all cystectomy specimens. The two-dimensional length of these negative patches varied from 2-3 cells (about 30 µm) to 4.7 mm. Each cell area within a CCO-deficient patch contained an identical somatic mtDNA mutation, indicating that the patch was a clonal unit. Patches contained all the mature cell differentiation stages present in the urothelium, suggesting the presence of a stem cell. Our results demonstrate that the normal mucosa of human bladder contains stem cell-derived clonal units that actively replenish the urothelium during ageing. The size of the clonal unit attributable to each stem cell was broadly distributed, suggesting replacement of one stem cell clone by another. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Sch proteins are localized on endoplasmic reticulum membranes and are redistributed after tyrosine kinase receptor activation.

PubMed Central

Lotti, L V; Lanfrancone, L; Migliaccio, E; Zompetta, C; Pelicci, G; Salcini, A E; Falini, B; Pelicci, P G; Torrisi, M R

1996-01-01

The intracellular localization of Shc proteins was analyzed by immunofluorescence and immunoelectron microscopy in normal cells and cells expressing the epidermal growth factor receptor or the EGFR/erbB2 chimera. In unstimulated cells, the immunolabeling was localized in the central perinuclear area of the cell and mostly associated with the cytosolic side of rough endoplasmic reticulum membranes. Upon epidermal growth factor treatment and receptor tyrosine kinase activation, the immunolabeling became peripheral and was found to be associated with the cytosolic surface of the plasma membrane and endocytic structures, such as coated pits and endosomes, and with the peripheral cytosol. Receptor activation in cells expressing phosphorylation-defective mutants of Shc and erbB-2 kinase showed that receptor autophosphorylation, but not Shc phosphorylation, is required for redistribution of Shc proteins. The rough endoplasmic reticulum localization of Shc proteins in unstimulated cells and their massive recruitment to the plasma membrane, endocytic structures, and peripheral cytosol following receptor tyrosine kinase activation could account for multiple putative functions of the adaptor protein. PMID:8628261

Assessment of rockfall susceptibility by integrating statistical and physically-based approaches

NASA Astrophysics Data System (ADS)

Frattini, Paolo; Crosta, Giovanni; Carrara, Alberto; Agliardi, Federico

In Val di Fassa (Dolomites, Eastern Italian Alps) rockfalls constitute the most significant gravity-induced natural disaster that threatens both the inhabitants of the valley, who are few, and the thousands of tourists who populate the area in summer and winter. To assess rockfall susceptibility, we developed an integrated statistical and physically-based approach that aimed to predict both the susceptibility to onset and the probability that rockfalls will attain specific reaches. Through field checks and multi-temporal aerial photo-interpretation, we prepared a detailed inventory of both rockfall source areas and associated scree-slope deposits. Using an innovative technique based on GIS tools and a 3D rockfall simulation code, grid cells pertaining to the rockfall source-area polygons were classified as active or inactive, based on the state of activity of the associated scree-slope deposits. The simulation code allows one to link each source grid cell with scree deposit polygons by calculating the trajectory of each simulated launch of blocks. By means of discriminant analysis, we then identified the mix of environmental variables that best identifies grid cells with low or high susceptibility to rockfalls. Among these variables, structural setting, land use, and morphology were the most important factors that led to the initiation of rockfalls. We developed 3D simulation models of the runout distance, intensity and frequency of rockfalls, whose source grid cells corresponded either to the geomorphologically-defined source polygons ( geomorphological scenario) or to study area grid cells with slope angle greater than an empirically-defined value of 37° ( empirical scenario). For each scenario, we assigned to the source grid cells an either fixed or variable onset susceptibility; the latter was derived from the discriminant model group (active/inactive) membership probabilities. Comparison of these four models indicates that the geomorphological scenario with variable onset susceptibility appears to be the most realistic model. Nevertheless, political and legal issues seem to guide local administrators, who tend to select the more conservative empirically-based scenario as a land-planning tool.

Cortical cell and neuron density estimates in one chimpanzee hemisphere.

PubMed

Collins, Christine E; Turner, Emily C; Sawyer, Eva Kille; Reed, Jamie L; Young, Nicole A; Flaherty, David K; Kaas, Jon H

2016-01-19

The density of cells and neurons in the neocortex of many mammals varies across cortical areas and regions. This variability is, perhaps, most pronounced in primates. Nonuniformity in the composition of cortex suggests regions of the cortex have different specializations. Specifically, regions with densely packed neurons contain smaller neurons that are activated by relatively few inputs, thereby preserving information, whereas regions that are less densely packed have larger neurons that have more integrative functions. Here we present the numbers of cells and neurons for 742 discrete locations across the neocortex in a chimpanzee. Using isotropic fractionation and flow fractionation methods for cell and neuron counts, we estimate that neocortex of one hemisphere contains 9.5 billion cells and 3.7 billion neurons. Primary visual cortex occupies 35 cm(2) of surface, 10% of the total, and contains 737 million densely packed neurons, 20% of the total neurons contained within the hemisphere. Other areas of high neuron packing include secondary visual areas, somatosensory cortex, and prefrontal granular cortex. Areas of low levels of neuron packing density include motor and premotor cortex. These values reflect those obtained from more limited samples of cortex in humans and other primates.

Natural Killer Cells and Helicobacter pylori Infection: Bacterial Antigens and Interleukin-12 Act Synergistically To Induce Gamma Interferon Production

PubMed Central

Yun, Cheol H.; Lundgren, Anna; Azem, Josef; Sjöling, Åsa; Holmgren, Jan; Svennerholm, Ann-Mari; Lundin, B. Samuel

2005-01-01

Helicobacter pylori is known to induce a local immune response, which is characterized by activation of lymphocytes and the production of IFN-γ in the stomach mucosa. Since not only T cells, but also natural killer (NK) cells, are potent producers of gamma interferon (IFN-γ), we investigated whether NK cells play a role in the immune response to H. pylori infection. Our results showed that NK cells were present in both the gastric and duodenal mucosae but that H. pylori infection did not affect the infiltration of NK cells into the gastrointestinal area. Furthermore, we could show that NK cells could be activated directly by H. pylori antigens, as H. pylori bacteria, as well as lysate from H. pylori, induced the secretion of IFN-γ by NK cells. NK cells were also activated without direct contact when separated from the bacteria by an epithelial cell layer, indicating that the activation of NK cells by H. pylori can also occur in vivo, in the infected stomach mucosa. Moreover, the production of IFN-γ by NK cells was greatly enhanced when a small amount of interleukin-12 (IL-12) was added, and this synergistic effect was associated with increased expression of the IL-12 receptor β2. It was further evident that bacterial lysate alone was sufficient to induce the activation of cytotoxicity-related molecules. In conclusion, we demonstrated that NK cells are present in the gastroduodenal mucosa of humans and that NK cells produce high levels of IFN-γ when stimulated with a combination of H. pylori antigen and IL-12. We propose that NK cells play an active role in the local immune response to H. pylori infection. PMID:15731046

Tissue-based standoff biosensors for detecting chemical warfare agents

DOEpatents

Greenbaum, Elias; Sanders, Charlene A.

2003-11-18

A tissue-based, deployable, standoff air quality sensor for detecting the presence of at least one chemical or biological warfare agent, includes: a cell containing entrapped photosynthetic tissue, the cell adapted for analyzing photosynthetic activity of the entrapped photosynthetic tissue; means for introducing an air sample into the cell and contacting the air sample with the entrapped photosynthetic tissue; a fluorometer in operable relationship with the cell for measuring photosynthetic activity of the entrapped photosynthetic tissue; and transmitting means for transmitting analytical data generated by the fluorometer relating to the presence of at least one chemical or biological warfare agent in the air sample, the sensor adapted for deployment into a selected area.

Mammalian Cell-Based Sensor System

NASA Astrophysics Data System (ADS)

Banerjee, Pratik; Franz, Briana; Bhunia, Arun K.

Use of living cells or cellular components in biosensors is receiving increased attention and opens a whole new area of functional diagnostics. The term "mammalian cell-based biosensor" is designated to biosensors utilizing mammalian cells as the biorecognition element. Cell-based assays, such as high-throughput screening (HTS) or cytotoxicity testing, have already emerged as dependable and promising approaches to measure the functionality or toxicity of a compound (in case of HTS); or to probe the presence of pathogenic or toxigenic entities in clinical, environmental, or food samples. External stimuli or changes in cellular microenvironment sometimes perturb the "normal" physiological activities of mammalian cells, thus allowing CBBs to screen, monitor, and measure the analyte-induced changes. The advantage of CBBs is that they can report the presence or absence of active components, such as live pathogens or active toxins. In some cases, mammalian cells or plasma membranes are used as electrical capacitors and cell-cell and cell-substrate contact is measured via conductivity or electrical impedance. In addition, cytopathogenicity or cytotoxicity induced by pathogens or toxins resulting in apoptosis or necrosis could be measured via optical devices using fluorescence or luminescence. This chapter focuses mainly on the type and applications of different mammalian cell-based sensor systems.

Stem/Progenitor Cell Proteoglycans Decorated with 7-D-4, 4-C-3 and 3-B-3(-) Chondroitin Sulphate Motifs Are Morphogenetic Markers Of Tissue Development.

PubMed

Hayes, Anthony J; Smith, Susan M; Caterson, Bruce; Melrose, James

2018-06-11

This study reviewed the occurrence of chondroitin sulphate (CS) motifs 4-C-3, 7-D-4 and 3-B-3(-) which are expressed by progenitor cells in tissues undergoing morphogenesis. These motifs have a transient early expression pattern during tissue development and also appear in mature tissues during pathological remodeling and attempted repair processes by activated adult stem cells. The CS motifs are information and recognition modules, which may regulate cellular behavior and delineate stem cell niches in developmental tissues. One of the difficulties in determining the precise role of stem cells in tissue development and repair processes is their short engraftment period and the lack of specific markers, which differentiate the activated stem cell lineages from the resident cells. The CS sulphation motifs 7-D-4, 4-C-3 and 3-B-3 (-) decorate cell surface proteoglycans on activated stem/progenitor cells and appear to identify these cells in transitional areas of tissue development and in tissue repair and may be applicable to determining a more precise role for stem cells in tissue morphogenesis. This article is protected by copyright. All rights reserved. © 2018 AlphaMed Press.

Application of speckle image correlation for real-time assessment of metabolic activity in herpes virus-infected cells

NASA Astrophysics Data System (ADS)

Vladimirov, A. P.; Malygin, A. S.; Mikhailova, J. A.; Borodin, E. M.; Bakharev, A. A.; Poryvayeva, A. P.

2014-09-01

Earlier we reported developing a speckle interferometry technique and a device designed to assess the metabolic activity of a cell monolayer cultivated on a glass substrate. This paper aimed at upgrading the technique and studying its potential for real-time assessment of herpes virus development process. Speckle dynamics was recorded in the image plane of intact and virus-infected cell monolayer. HLE-3, L-41 and Vero cells were chosen as research targets. Herpes simplex virus-1-(HSV-1)- infected cell cultures were studied. For 24 h we recorded the digital value of optical signal I in one pixel and parameter η characterizing change in the distribution of the optical signal on 10 × 10-pixel areas. The coefficient of multiple determination calculated by η time dependences for three intact cell cultures equals 0.94. It was demonstrated that the activity parameters are significantly different for intact and virus-infected cells. The difference of η value for intact and HSV-1-infected cells is detectable 10 minutes from the experiment start.

In situ modification of cell-culture scaffolds by photocatalysis of visible-light-responsive TiO2 film

NASA Astrophysics Data System (ADS)

Kono, Sho; Furusawa, Kohei; Kurotobi, Atsushi; Hattori, Kohei; Yamamoto, Hideaki; Hirano-Iwata, Ayumi; Tanii, Takashi

2018-02-01

We propose a novel process to modify the cell affinity of scaffolds in a cell-culture environment using the photocatalytic activity of visible-light (VL)-responsive TiO2. The proposed process is the improved version of our previous demonstration in which ultraviolet (UV)-responsive TiO2 was utilized. In that demonstration, we showed that cell-repellent molecules on TiO2 were decomposed and replaced with cell-permissive molecules upon UV exposure in the medium where cells are being cultured. However, UV irradiation involves taking the risk of inducing damage to the cells. In this work, a TiO2 film was sputter-deposited on a quartz coverslip at 640 °C without O2 gas injection to create a rutile structure containing oxygen defects, which is known to exhibit photocatalytic activity upon VL exposure. We show that the cell adhesion site and migration area can be controlled with the photocatalytic activity of the VL-responsive TiO2 film, while the cellular oxidative stress is reduced markedly by the substitution of VL for UV.

Anticancer and enhanced antimicrobial activity of biosynthesizd silver nanoparticles against clinical pathogens

NASA Astrophysics Data System (ADS)

Rajeshkumar, Shanmugam; Malarkodi, Chelladurai; Vanaja, Mahendran; Annadurai, Gurusamy

2016-07-01

The present investigation shows the biosynthesis of eco-friendly silver nanoparticles using culture supernatant of Enterococcus sp. and study the effect of enhanced antimicrobial activity, anticancer activity against pathogenic bacteria, fungi and cancer cell lines. Silver nanoparticles was synthesized by adding 1 mM silver nitrate into the 100 ml of 24 h freshly prepared culture supernatant of Enterococcus sp. and were characterized by UV-vis spectroscopy, X-ray diffraction (XRD), Transmission Electron Microscope (TEM), Selected Area Diffraction X-Ray (SAED), Energy Dispersive X Ray (EDX) and Fourier Transform Infra red Spectroscopy (FT-IR). The synthesized silver nanoparticles were impregnated with commercial antibiotics for evaluation of enhanced antimicrobial activity. Further these synthesized silver nanoparticles were assessed for its anticancer activity against cancer cell lines. In this study crystalline structured nanoparticles with spherical in the size ranges from 10 to 80 nm and it shows excellent enhanced antimicrobial activity than the commercial antibiotics. The in vitro assay of silver nanoparticles on anticancer have great potential to inhibit the cell viability. Amide linkages and carboxylate groups of proteins from Enterococcus sp. may bind with silver ions and convert into nanoparticles. The activities of commercial antibiotics were enhanced by coating silver nanoparticles shows significant improved antimicrobial activity. Silver nanoparticles have the great potential to inhibit the cell viability of liver cancer cells lines (HepG2) and lung cancer cell lines (A549).

Chemical chaperones reduce ionizing radiation-induced endoplasmic reticulum stress and cell death in IEC-6 cells

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

Lee, Eun Sang; Lee, Hae-June; Lee, Yoon-Jin

Highlights: • UPR activation precedes caspase activation in irradiated IEC-6 cells. • Chemical ER stress inducers radiosensitize IEC-6 cells. • siRNAs that targeted ER stress responses ameliorate IR-induced cell death. • Chemical chaperons prevent cell death in irradiated IEC-6 cells. - Abstract: Radiotherapy, which is one of the most effective approaches to the treatment of various cancers, plays an important role in malignant cell eradication in the pelvic area and abdomen. However, it also generates some degree of intestinal injury. Apoptosis in the intestinal epithelium is the primary pathological factor that initiates radiation-induced intestinal injury, but the mechanism by whichmore » ionizing radiation (IR) induces apoptosis in the intestinal epithelium is not clearly understood. Recently, IR has been shown to induce endoplasmic reticulum (ER) stress, thereby activating the unfolded protein response (UPR) signaling pathway in intestinal epithelial cells. However, the consequences of the IR-induced activation of the UPR signaling pathway on radiosensitivity in intestinal epithelial cells remain to be determined. In this study, we investigated the role of ER stress responses in IR-induced intestinal epithelial cell death. We show that chemical ER stress inducers, such as tunicamycin or thapsigargin, enhanced IR-induced caspase 3 activation and DNA fragmentation in intestinal epithelial cells. Knockdown of Xbp1 or Atf6 with small interfering RNA inhibited IR-induced caspase 3 activation. Treatment with chemical chaperones prevented ER stress and subsequent apoptosis in IR-exposed intestinal epithelial cells. Our results suggest a pro-apoptotic role of ER stress in IR-exposed intestinal epithelial cells. Furthermore, inhibiting ER stress may be an effective strategy to prevent IR-induced intestinal injury.« less

Spatial modeling of the membrane-cytosolic interface in protein kinase signal transduction

PubMed Central

Schröder, Andreas

2018-01-01

The spatial architecture of signaling pathways and the interaction with cell size and morphology are complex, but little understood. With the advances of single cell imaging and single cell biology, it becomes crucial to understand intracellular processes in time and space. Activation of cell surface receptors often triggers a signaling cascade including the activation of membrane-attached and cytosolic signaling components, which eventually transmit the signal to the cell nucleus. Signaling proteins can form steep gradients in the cytosol, which cause strong cell size dependence. We show that the kinetics at the membrane-cytosolic interface and the ratio of cell membrane area to the enclosed cytosolic volume change the behavior of signaling cascades significantly. We suggest an estimate of average concentration for arbitrary cell shapes depending on the cell volume and cell surface area. The normalized variance, known from image analysis, is suggested as an alternative measure to quantify the deviation from the average concentration. A mathematical analysis of signal transduction in time and space is presented, providing analytical solutions for different spatial arrangements of linear signaling cascades. Quantification of signaling time scales reveals that signal propagation is faster at the membrane than at the nucleus, while this time difference decreases with the number of signaling components in the cytosol. Our investigations are complemented by numerical simulations of non-linear cascades with feedback and asymmetric cell shapes. We conclude that intracellular signal propagation is highly dependent on cell geometry and, thereby, conveys information on cell size and shape to the nucleus. PMID:29630597

Opto-acoustic microscopy reveals adhesion mechanics of single cells

NASA Astrophysics Data System (ADS)

Abi Ghanem, Maroun; Dehoux, Thomas; Liu, Liwang; Le Saux, Guillaume; Plawinski, Laurent; Durrieu, Marie-Christine; Audoin, Bertrand

2018-01-01

Laser-generated GHz-ultrasonic-based technologies have shown the ability to image single cell adhesion and stiffness simultaneously. Using this new modality, we here demonstrate quantitative indicators to investigate contact mechanics and adhesion processes of the cell. We cultured human cells on a rigid substrate, and we used an inverted pulsed opto-acoustic microscope to generate acoustic pulses containing frequencies up to 100 GHz in the substrate. We map the reflection of the acoustic pulses at the cell-substrate interface to obtain images of the acoustic impedance of the cell, Zc, as well as of the stiffness of the interface, K, with 1 μm lateral resolution. Our results show that the standard deviation ΔZc reveals differences between different cell types arising from the multiplicity of local conformations within the nucleus. From the distribution of K-values within the nuclear region, we extract a mean interfacial stiffness, Km, that quantifies the average contact force in areas of the cell displaying weak bonding. By analogy with classical contact mechanics, we also define the ratio of the real to nominal contact areas, Sr/St. We show that Km can be interpreted as a quantitative indicator of passive contact at metal-cell interfaces, while Sr/St is sensitive to active adhesive processes in the nuclear region. The ability to separate the contributions of passive and active adhesion processes should allow gaining insight into cell-substrate interactions, with important applications in tissue engineering.

Opto-acoustic microscopy reveals adhesion mechanics of single cells.

PubMed

Abi Ghanem, Maroun; Dehoux, Thomas; Liu, Liwang; Le Saux, Guillaume; Plawinski, Laurent; Durrieu, Marie-Christine; Audoin, Bertrand

2018-01-01

Laser-generated GHz-ultrasonic-based technologies have shown the ability to image single cell adhesion and stiffness simultaneously. Using this new modality, we here demonstrate quantitative indicators to investigate contact mechanics and adhesion processes of the cell. We cultured human cells on a rigid substrate, and we used an inverted pulsed opto-acoustic microscope to generate acoustic pulses containing frequencies up to 100 GHz in the substrate. We map the reflection of the acoustic pulses at the cell-substrate interface to obtain images of the acoustic impedance of the cell, Z c , as well as of the stiffness of the interface, K, with 1 μm lateral resolution. Our results show that the standard deviation ΔZ c reveals differences between different cell types arising from the multiplicity of local conformations within the nucleus. From the distribution of K-values within the nuclear region, we extract a mean interfacial stiffness, K m , that quantifies the average contact force in areas of the cell displaying weak bonding. By analogy with classical contact mechanics, we also define the ratio of the real to nominal contact areas, S r /S t . We show that K m can be interpreted as a quantitative indicator of passive contact at metal-cell interfaces, while S r /S t is sensitive to active adhesive processes in the nuclear region. The ability to separate the contributions of passive and active adhesion processes should allow gaining insight into cell-substrate interactions, with important applications in tissue engineering.

Activation of DNA Damage Response Induced by the Kaposi’s Sarcoma-Associated Herpes Virus

PubMed Central

Di Domenico, Enea Gino; Toma, Luigi; Bordignon, Valentina; Trento, Elisabetta; D’Agosto, Giovanna; Cordiali-Fei, Paola; Ensoli, Fabrizio

2016-01-01

The human herpes virus 8 (HHV-8), also known as Kaposi sarcoma-associated herpes virus (KSHV), can infect endothelial cells often leading to cell transformation and to the development of tumors, namely Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL), and the plasmablastic variant of multicentric Castleman’s disease. KSHV is prevalent in areas such as sub-Saharan Africa and the Mediterranean region presenting distinct genotypes, which appear to be associated with differences in disease manifestation, according to geographical areas. In infected cells, KSHV persists in a latent episomal form. However, in a limited number of cells, it undergoes spontaneous lytic reactivation to ensure the production of new virions. During both the latent and the lytic cycle, KSHV is programmed to express genes which selectively modulate the DNA damage response (DDR) through the activation of the ataxia telangiectasia mutated (ATM) pathway and by phosphorylating factors associated with the DDR, including the major tumor suppressor protein p53 tumor suppressor p53. This review will focus on the interplay between the KSHV and the DDR response pathway throughout the viral lifecycle, exploring the putative molecular mechanism/s that may contribute to malignant transformation of host cells. PMID:27258263

Reciprocal Activation of Transcription Factors Underlies the Dichotomy between Proliferation and Invasion of Glioma Cells

PubMed Central

Dhruv, Harshil D.; McDonough Winslow, Wendy S.; Armstrong, Brock; Tuncali, Serdar; Eschbacher, Jenny; Kislin, Kerri; Loftus, Joseph C.; Tran, Nhan L.; Berens, Michael E.

2013-01-01

Histology of malignant glioma depicts dense proliferative areas rich in angiogenesis as well as dissemination of neoplastic cells into adjacent brain tissue. Although the mechanisms that trigger transition from proliferative to invasive phenotypes are complex, the dichotomy of cell proliferation and migration, the “Go or Grow” hypothesis, argues for specific and coordinated regulation of these phenotypes. We investigated transcriptional elements that accompany the phenotypes of migration and proliferation, and consider the therapeutic significance of the “Go or Grow” hypothesis. Interrogation of matched core and rim regions from human glioblastoma biopsy specimens in situ (n = 44) revealed higher proliferation (Ki67 labeling index) in cells residing at the core compared to the rim. Profiling activated transcription factors in a panel of migration-activated versus migration-restricted GBM cells portrayed strong NF-κB activity in the migratory cell population. In contrast, increased c-Myc activity was found in migration-restricted proliferative cells. Validation of transcriptional activity by NF-κB- or c-Myc-driven GFP or RFP, respectively, showed an increased NF-κB activity in the active migrating cells, whereas the proliferative, migration restricted cells displayed increased c-Myc activity. Immunohistochemistry on clinical specimens validated a robust phosphorylated c-Myc staining in tumor cells at the core, whereas increased phosphorylated NF-κB staining was detected in the invasive tumor cells at the rim. Functional genomics revealed that depletion of c-Myc expression by siRNA oligonucleotides reduced cell proliferation in vitro, but surprisingly, cell migration was enhanced significantly. Conversely, inhibition of NF-κB by pharmacological inhibitors, SN50 or BAY-11, decreased both cell migration in vitro and invasion ex vivo. Notably, inhibition of NF-κB was found to have no effect on the proliferation rate of glioma cells. These findings suggest that the reciprocal and coordinated suppression/activation of transcription factors, such as c-Myc and NF-κB may underlie the shift of glioma cells from a “growing-to-going” phenotype. PMID:23967279

Leptin-mediated ion channel regulation: PI3K pathways, physiological role, and therapeutic potential.

PubMed

Gavello, Daniela; Carbone, Emilio; Carabelli, Valentina

2016-07-03

Leptin is produced by adipose tissue and identified as a "satiety signal," informing the brain when the body has consumed enough food. Specific areas of the hypothalamus express leptin receptors (LEPRs) and are the primary site of leptin action for body weight regulation. In response to leptin, appetite is suppressed and energy expenditure allowed. Beside this hypothalamic action, leptin targets other brain areas in addition to neuroendocrine cells. LEPRs are expressed also in the hippocampus, neocortex, cerebellum, substantia nigra, pancreatic β-cells, and chromaffin cells of the adrenal gland. It is intriguing how leptin is able to activate different ionic conductances, thus affecting excitability, synaptic plasticity and neurotransmitter release, depending on the target cell. Most of the intracellular pathways activated by leptin and directed to ion channels involve PI3K, which in turn phosphorylates different downstream substrates, although parallel pathways involve AMPK and MAPK. In this review we will describe the effects of leptin on BK, KATP, KV, CaV, TRPC, NMDAR and AMPAR channels and clarify the landscape of pathways involved. Given the ability of leptin to influence neuronal excitability and synaptic plasticity by modulating ion channels activity, we also provide a short overview of the growing potentiality of leptin as therapeutic agent for treating neurological disorders.

Identification of preoptic sleep neurons using retrograde labelling and gene profiling.

PubMed

Chung, Shinjae; Weber, Franz; Zhong, Peng; Tan, Chan Lek; Nguyen, Thuc Nghi; Beier, Kevin T; Hörmann, Nikolai; Chang, Wei-Cheng; Zhang, Zhe; Do, Johnny Phong; Yao, Shenqin; Krashes, Michael J; Tasic, Bosiljka; Cetin, Ali; Zeng, Hongkui; Knight, Zachary A; Luo, Liqun; Dan, Yang

2017-05-25

In humans and other mammalian species, lesions in the preoptic area of the hypothalamus cause profound sleep impairment, indicating a crucial role of the preoptic area in sleep generation. However, the underlying circuit mechanism remains poorly understood. Electrophysiological recordings and c-Fos immunohistochemistry have shown the existence of sleep-active neurons in the preoptic area, especially in the ventrolateral preoptic area and median preoptic nucleus. Pharmacogenetic activation of c-Fos-labelled sleep-active neurons has been shown to induce sleep. However, the sleep-active neurons are spatially intermingled with wake-active neurons, making it difficult to target the sleep neurons specifically for circuit analysis. Here we identify a population of preoptic area sleep neurons on the basis of their projection target and discover their molecular markers. Using a lentivirus expressing channelrhodopsin-2 or a light-activated chloride channel for retrograde labelling, bidirectional optogenetic manipulation, and optrode recording, we show that the preoptic area GABAergic neurons projecting to the tuberomammillary nucleus are both sleep active and sleep promoting. Furthermore, translating ribosome affinity purification and single-cell RNA sequencing identify candidate markers for these neurons, and optogenetic and pharmacogenetic manipulations demonstrate that several peptide markers (cholecystokinin, corticotropin-releasing hormone, and tachykinin 1) label sleep-promoting neurons. Together, these findings provide easy genetic access to sleep-promoting preoptic area neurons and a valuable entry point for dissecting the sleep control circuit.

Synaptic Targets of Medial Septal Projections in the Hippocampus and Extrahippocampal Cortices of the Mouse

PubMed Central

Joshi, Abhilasha; Viney, Tim J.; Kis, Viktor

2015-01-01

Temporal coordination of neuronal assemblies among cortical areas is essential for behavioral performance. GABAergic projections from the medial septum and diagonal band complex exclusively innervate GABAergic interneurons in the rat hippocampus, contributing to the coordination of neuronal activity, including the generation of theta oscillations. Much less is known about the synaptic target neurons outside the hippocampus. To reveal the contribution of synaptic circuits involving the medial septum of mice, we have identified postsynaptic cortical neurons in wild-type and parvalbumin-Cre knock-in mice. Anterograde axonal tracing from the septum revealed extensive innervation of the hippocampus as well as the subiculum, presubiculum, parasubiculum, the medial and lateral entorhinal cortices, and the retrosplenial cortex. In all examined cortical regions, many septal GABAergic boutons were in close apposition to somata or dendrites immunopositive for interneuron cell-type molecular markers, such as parvalbumin, calbindin, calretinin, N-terminal EF-hand calcium-binding protein 1, cholecystokinin, reelin, or a combination of these molecules. Electron microscopic observations revealed septal boutons forming axosomatic or axodendritic type II synapses. In the CA1 region of hippocampus, septal GABAergic projections exclusively targeted interneurons. In the retrosplenial cortex, 93% of identified postsynaptic targets belonged to interneurons and the rest to pyramidal cells. These results suggest that the GABAergic innervation from the medial septum and diagonal band complex contributes to temporal coordination of neuronal activity via several types of cortical GABAergic interneurons in both hippocampal and extrahippocampal cortices. Oscillatory septal neuronal firing at delta, theta, and gamma frequencies may phase interneuron activity. SIGNIFICANCE STATEMENT Diverse types of GABAergic interneurons coordinate the firing of cortical principal cells required for memory processes. During wakefulness and rapid eye movement sleep, the rhythmic firing of cortical GABAergic neurons plays a key role in governing network activity. We investigated subcortical GABAergic projections in the mouse that extend from the medial septum/diagonal band nuclei to GABAergic neurons in the hippocampus and related extrahippocampal cortical areas, including the medial entorhinal cortex. These areas contribute to navigation and show theta rhythmic activity. We found selective GABAergic targeting of different groups of cortical GABAergic neurons, immunoreactive for combinations of cell-type markers. As septal GABAergic neurons also fire rhythmically, their selective innervation of cortical GABAergic neurons suggests an oscillatory synchronization of neuronal activity across functionally related areas. PMID:26631464

A novel population of α-smooth muscle actin-positive cells activated in a rat model of stroke: an analysis of the spatio-temporal distribution in response to ischemia.

PubMed

Sharma, Varun; Ling, Tina W; Rewell, Sarah S; Hare, David L; Howells, David W; Kourakis, Angela; Wookey, Peter J

2012-11-01

In a rat model of stroke, the spatio-temporal distribution of α-smooth muscle actin-positive, (αSMA+) cells was investigated in the infarcted hemisphere (ipsilateral) and compared with the contralateral hemisphere. At day 3 postischemia, αSMA+ cells were concentrated in two main loci within the ipsilateral hemisphere (Area A) in the medial corpus callosum and (Area B) midway through the striatum adjacent to the lateral ventricle. By day 7 and further by day 14, fewer αSMA+ cells remained in Areas A and B but a steady increase in the peri-infarct was observed. αSMA+ cells also expressed glial acidic fibrillary protein [GFAP: αSMA+/GFAP+ (29%); αSMA+/GFAP- (71%) phenotypes] and feline leukemia virus C receptor 2 (FLVCR2), but not ED1(microglia) and established markers of pericytes normally located in vascular wall. αSMA+ cells were also located close to the subventricular zones (SVZ) adjacent to Areas A and B. In conclusion, αSMA+ cells have been identified in a spatial and temporal sequence from the SVZ, at intermediate loci and in the vicinity of the peri-infarct. It is hypothesized that novel populations of αSMA+ precursors of pericytes are born on the SVZ, migrate into the peri-infarct region and are incorporated into new vessels of the peri-infarct regions.

SU-E-CAMPUS-I-01: Nanometric Organic Photovoltaic Thin Film X-Ray Detectors for Clinical KVp Beams

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

Elshahat, Bassem; Gill, Hardeep; Kumar, Jayant

2014-06-15

Purpose: To fabricate and test nanometric organic photovoltaic (OPV) cells made of various active-layer/electrode thicknesses and sizes; to determine the optimal material combinations and geometries suitable for dose measurements in clinical kilovoltage x-ray beams. Methods: The OPV consisted of P3HT:PCBM photoactive materials sandwiched between aluminum and Indium Tin Oxide (ITO) electrodes. Direct conversion of xrays in the active layer composed of donor and acceptor semiconducting organic materials generated signal in photovoltaic mode (without external voltage bias). OPV cells were fabricated with different active layer thicknesses (150, 270, 370 nm) and electrode areas (0.4, 0.7, 0.9, 1.4, 2.6 cm{sup 2}). Amore » series of experiments were preformed in the energy range of 60–150 kVp. The net current per unit area (nA/cm{sup 2}) was measured using 200 mAs time-integrated beam current. Results: The net OPV current as function of beam energy (kVp) was proportional to ∼E{sup 0,4} {sup 5} when adjusted for beam output. The best combination of parameters for these cells was 270 nm active layer thicknesses for 0.7 cm{sup 2} electrode area. The measured current ranged from 0.69 to 2.43 nA/cm{sup 2} as a function of x-ray energy between 60 and 150 kVp, corresponding to 0.09 – 0.06 nA/cm{sup 2}/mGy, respectively, when adjusted for the beam output. Conclusion: The experiments indicate that OPV detectors possessing 270 nm active layer and 0.7 cm{sup 2} Al electrode areas have sensitivity by a factor of 2.5 greater than commercial aSi thin film PV. Because OPV can be made flexible and they do not require highvoltage bias supply, they open the possibility for using as in-vivo detectors in radiation safety in x-ray imaging beams.« less

Biflorin: an o-naphthoquinone of clinical significance.

PubMed

Wisintainer, Gabrielle G N S; Simões, Evelyne R B; Lemos, Telma L G; Moura, Sidnei; Souza, Luciana G S; Fonseca, Aluisio M; Moraes, Manoel Odorico; Pessoa, Claudia; Roesch-Ely, Mariana; Henriques, João A P

2014-12-01

Biflorin is an o-naphthoquinone with proven cytotoxic effects on tumor cells showing antimicrobial, antitumor and antimutagenic activities. Biflorin is an isolated compound taken from the roots of the plant Capraria biflora L. (Schrophulariaceae), indigenous of the West Indies and South America, which is located in temperate or tropical areas. This compound has shown to be strongly active against grampositive and alcohol-acid-resistant bacteria. It has been efficient in inhibiting the proliferation tumor cell lines CEM, HL-60, B16, HCT-8 and MCF-7. Recently, SK-Br3 cell line was treated with biflorin showing important cytotoxic effects. In this article, information related to the first structural characterization studies are presented, as well as the latest reports concerning the biological activity of this molecule.

Biflorin: an o-naphthoquinone of clinical significance.

PubMed

Wisintainer, Gabrielle G N S; Simões, Evelyne R B; Lemos, Telma L G; Moura, Sidnei; Souza, Luciana G S; Fonseca, Aluisio M; Moraes, Manoel Odorico; Pessoa, Claudia; Roesch-Ely, Mariana; Henriques, João A P

2014-10-14

Biflorin is an o-naphthoquinone with proven cytotoxic effects on tumor cells showing antimicrobial, antitumor and antimutagenic activities. Biflorin is an isolated compound taken from the roots of the plant Capraria biflora L. (Schrophulariaceae), indigenous of the West Indies and South America, which is located in temperate or tropical areas. This compound has shown to be strongly active against grampositive and alcohol-acid-resistant bacteria. It has been efficient in inhibiting the proliferation tumor cell lines CEM, HL-60, B16, HCT-8 and MCF-7. Recently, SK-Br3 cell line was treated with biflorin showing important cytotoxic effects. In this article, information related to the first structural characterization studies are presented, as well as the latest reports concerning the biological activity of this molecule.

Micro-Biocidal Activity of Yeast Cells by Needle Plasma Irradiation at Atmospheric Pressure

NASA Astrophysics Data System (ADS)

Kurumi, Satoshi; Takahashi, Hideyuki; Taima, Tomohito; Suzuki, Kaoru; Hirose, Hideharu; Masutani, Shigeyuki

In this study, we report on the biocidal activity technique by needle helium plasma irradiation at atmospheric pressure using borosilicate capillary nozzle to apply for the oral surgery. The diameter of needle plasma was less than 50 µm, and temperature of plasma irradiated area was less than body temperature. Needle plasma showed emission due to OH and O radical. Raman spectra and methylene blue stain showed yeast cells were inactivated by needle plasma irradiation.

Novel microneutralization assay for HCMV using automated data collection and analysis.

PubMed

Abai, Anna Maria; Smith, Larry R; Wloch, Mary K

2007-04-30

In addition to being sensitive and specific, an assay for the assessment of neutralizing antibody activity from clinical trial samples must be amenable to automation for use in high-volume screening. To that effect, we developed a 96-well microplate assay for the measurement of HCMV-neutralizing activity in human sera using the HCMV-permissive human cell line HEL-299 and the laboratory strain of HCMV AD169. The degree to which neutralizing antibodies diminish HCMV infection of cells in the assay is determined by quantifying the nuclei of infected cells based on expression of the 72 kDa IE1 viral protein. Nuclear IE1 is visualized using a highly sensitive immunoperoxidase staining and the stained nuclei are counted using an automated ELISPOT analyzer. The use of Half Area 96-well microplates, with wells in which the surface area of the well bottom is half the area of a standard 96-well microplate plate, improves signal detection compared with standard microplates and economizes on the usage of indicator cells, virus, and reagents. The staining process was also streamlined by using a microplate washer and data analysis was simplified and accelerated by employing a software program that automatically plots neutralization curves and determines NT(50) values using 4-PL curve fitting. The optimized assay is not only fast and convenient, but also specific, sensitive, precise and reproducible and thus has the characteristics necessary for use in measuring HCMV-neutralizing activity in the sera of vaccine trial subjects such as the recipients of Vical's HCMV pDNA vaccine candidates.

Chemosensitivity testing of human tumors using a microplate adenosine triphosphate luminescence assay: clinical correlation for cisplatin resistance of ovarian carcinoma.

PubMed

Andreotti, P E; Cree, I A; Kurbacher, C M; Hartmann, D M; Linder, D; Harel, G; Gleiberman, I; Caruso, P A; Ricks, S H; Untch, M

1995-11-15

An ATP luminescence assay (TCA 100) was used to measure chemotherapeutic drug sensitivity and resistance of dissociated tumor cells cultured for 6 days in serum-free medium and 96-well polypropylene microplates. Studies were performed with surgical, needle biopsy, pleural, or ascitic fluid specimens using 10,000-20,000 cells/well. ATP measurements were used to determine tumor growth inhibition. Single agent and drug combinations were evaluated using the area under the curve and 50% inhibitory concentration (IC50) results for a series of test drug concentrations. The ATP luminometry method had high sensitivity, linearity, and precision for measuring the activity of single agents and drug combinations. Assay reproducibility was high with intraassay and interassay coefficients of variation of 10-15% for percentage of tumor growth inhibition, 5-10% for area under curve, and 15-20% for IC50 results. Good correlation (r = 0.93) between the area under the curve, and IC50 results was observed. Cytological studies with 124 specimens demonstrated selective growth of malignant cells in the serum-free culture system. Studies with malignant and benign specimens also showed selective growth of malignant cells in the serum-free medium used for assay. The assay had a success rate of 87% based on criteria for specimen histopathology, magnitude of cell growth, and dose-response drug activity. Cisplatin results for ovarian carcinoma are presented for 81 specimens from 70 untreated patients and 33 specimens from 30 refractory patients. A model for interpretation of these results based on the correlation of clinical response with the area under the curve and IC50 results indicates that the assay has > 90% accuracy for cisplatin resistance of ovarian carcinoma. Additional studies are in progress to evaluate the clinical efficacy of this assay.

Information processing in the hemisphere of the cerebellar cortex for control of wrist movement

PubMed Central

Tomatsu, Saeka; Ishikawa, Takahiro; Tsunoda, Yoshiaki; Lee, Jongho; Hoffman, Donna S.

2015-01-01

A region of cerebellar lobules V and VI makes strong loop connections with the primary motor (M1) and premotor (PM) cortical areas and is assumed to play essential roles in limb motor control. To examine its functional role, we compared the activities of its input, intermediate, and output elements, i.e., mossy fibers (MFs), Golgi cells (GoCs), and Purkinje cells (PCs), in three monkeys performing wrist movements in two different forearm postures. The results revealed distinct steps of information processing. First, MF activities displayed temporal and directional properties that were remarkably similar to those of M1/PM neurons, suggesting that MFs relay near copies of outputs from these motor areas. Second, all GoCs had a stereotyped pattern of activity independent of movement direction or forearm posture. Instead, GoC activity resembled an average of all MF activities. Therefore, inhibitory GoCs appear to provide a filtering function that passes only prominently modulated MF inputs to granule cells. Third, PCs displayed highly complex spatiotemporal patterns of activity, with coordinate frames distinct from those of MF inputs and directional tuning that changed abruptly before movement onset. The complexity of PC activities may reflect rapidly changing properties of the peripheral motor apparatus during movement. Overall, the cerebellar cortex appears to transform a representation of outputs from M1/PM into different movement representations in a posture-dependent manner and could work as part of a forward model that predicts the state of the peripheral motor apparatus. PMID:26467515

Network Oscillations Drive Correlated Spiking of ON and OFF Ganglion Cells in the rd1 Mouse Model of Retinal Degeneration

PubMed Central

Margolis, David J.; Gartland, Andrew J.; Singer, Joshua H.; Detwiler, Peter B.

2014-01-01

Following photoreceptor degeneration, ON and OFF retinal ganglion cells (RGCs) in the rd-1/rd-1 mouse receive rhythmic synaptic input that elicits bursts of action potentials at ∼10 Hz. To characterize the properties of this activity, RGCs were targeted for paired recording and morphological classification as either ON alpha, OFF alpha or non-alpha RGCs using two-photon imaging. Identified cell types exhibited rhythmic spike activity. Cross-correlation of spike trains recorded simultaneously from pairs of RGCs revealed that activity was correlated more strongly between alpha RGCs than between alpha and non-alpha cell pairs. Bursts of action potentials in alpha RGC pairs of the same type, i.e. two ON or two OFF cells, were in phase, while bursts in dissimilar alpha cell types, i.e. an ON and an OFF RGC, were 180 degrees out of phase. This result is consistent with RGC activity being driven by an input that provides correlated excitation to ON cells and inhibition to OFF cells. A2 amacrine cells were investigated as a candidate cellular mechanism and found to display 10 Hz oscillations in membrane voltage and current that persisted in the presence of antagonists of fast synaptic transmission and were eliminated by tetrodotoxin. Results support the conclusion that the rhythmic RGC activity originates in a presynaptic network of electrically coupled cells including A2s via a Na+-channel dependent mechanism. Network activity drives out of phase oscillations in ON and OFF cone bipolar cells, entraining similar frequency fluctuations in RGC spike activity over an area of retina that migrates with changes in the spatial locus of the cellular oscillator. PMID:24489706

Pituitary adenylate cyclase-activating peptide in the rat central nervous system: an immunohistochemical and in situ hybridization study.

PubMed

Hannibal, Jens

2002-11-25

In the present study the localization of pituitary adenylate cyclase-activating peptide (PACAP)-expressing cell bodies and PACAP projections were mapped in the adult rat brain and spinal cord by using immunohistochemistry and in situ hybridization histochemistry. A widespread occurrence of PACAP-containing cell bodies was found, with the greatest accumulation in several hypothalamic nuclei and in several brainstem nuclei, especially the habenular nuclei, the pontine nucleus, the lateral parabrachial nucleus (LPB), and the vagal complex. PACAP was also present in cell bodies in the olfactory areas, in neocortical areas, in the hippocampus, in the vestibulo- and cochlear nuclei, in cell bodies of the intermediolateral cell column of the spinal cord and in Purkinje cells of the cerebellum, in the subfornical organ, and in the organum vasculosum of the lamina terminalis. An intense accumulation of PACAP-immunoreactive (-IR) nerve fibers was observed throughout the hypothalamus, in the amydaloid and extended amygdaloid complex, in the anterior and paraventricular thalamic nuclei, in the intergeniculate leaflet, in the pretectum, and in several brainstem nuclei, such as the parabrachial nucleus, the sensory trigeminal nucleus, and the nucleus of the solitary tract. PACAP-IR nerve fibers were also found in the area postrema, the posterior pituitary and the choroid plexus, and the dorsal and ventral horn of the spinal cord. The widespread distribution of PACAP in the brain and spinal cord suggests that PACAP is involved in the control of many autonomic and sensory functions as well as higher cortical processes. Copyright 2002 Wiley-Liss, Inc.

Nanofluidic fuel cell

NASA Astrophysics Data System (ADS)

Lee, Jin Wook; Kjeang, Erik

2013-11-01

Fuel cells are gaining momentum as a critical component in the renewable energy mix for stationary, transportation, and portable power applications. State-of-the-art fuel cell technology benefits greatly from nanotechnology applied to nanostructured membranes, catalysts, and electrodes. However, the potential of utilizing nanofluidics for fuel cells has not yet been explored, despite the significant opportunity of harnessing rapid nanoscale reactant transport in close proximity to the reactive sites. In the present article, a nanofluidic fuel cell that utilizes fluid flow through nanoporous media is conceptualized and demonstrated for the first time. This transformative concept captures the advantages of recently developed membraneless and catalyst-free fuel cell architectures paired with the enhanced interfacial contact area enabled by nanofluidics. When compared to previously reported microfluidic fuel cells, the prototype nanofluidic fuel cell demonstrates increased surface area, reduced activation overpotential, superior kinetic characteristics, and moderately enhanced fuel cell performance in the high cell voltage regime with up to 14% higher power density. However, the expected mass transport benefits in the high current density regime were constrained by high ohmic cell resistance, which could likely be resolved through future optimization studies.

All-solution-processed PbS quantum dot solar modules.

PubMed

Jang, Jihoon; Shim, Hyung Cheoul; Ju, Yeonkyeong; Song, Jung Hoon; An, Hyejin; Yu, Jong-Su; Kwak, Sun-Woo; Lee, Taik-Min; Kim, Inyoung; Jeong, Sohee

2015-05-21

A rapid increase in power conversion efficiencies in colloidal quantum dot (QD) solar cells has been achieved recently with lead sulphide (PbS) QDs by adapting a heterojunction architecture, which consists of small-area devices associated with a vacuum-deposited buffer layer with metal electrodes. The preparation of QD solar modules by low-cost solution processes is required to further increase the power-to-cost ratio. Herein we demonstrate all-solution-processed flexible PbS QD solar modules with a layer-by-layer architecture comprising polyethylene terephthalate (PET) substrate/indium tin oxide (ITO)/titanium oxide (TiO2)/PbS QD/poly(3-hexylthiophene) (P3HT)/poly(3,4-ethylenedioxythiophene) : poly(styrene sulfonate) (PEDOT : PSS)/Ag, with an active area of up to 30 cm(2), exhibiting a power conversion efficiency (PCE) of 1.3% under AM 1.5 conditions (PCE of 2.2% for a 1 cm(2) unit cell). Our approach affords trade-offs between power and the active area of the photovoltaic devices, which results in a low-cost power source, and which is scalable to larger areas.

High surface area bio-waste based carbon as a superior electrode for vanadium redox flow battery

NASA Astrophysics Data System (ADS)

Maharjan, Makhan; Bhattarai, Arjun; Ulaganathan, Mani; Wai, Nyunt; Oo, Moe Ohnmar; Wang, Jing-Yuan; Lim, Tuti Mariana

2017-09-01

Activated carbon (AC) with high surface area (1901 m2 g-1) is synthesized from low cost bio-waste orange (Citrus sinensis) peel for vanadium redox flow battery (VRB). The composition, structure and electrochemical properties of orange peel derived AC (OP-AC) are characterized by elemental analyzer, field emission-scanning electron microscopy, X-ray diffraction, Raman spectroscopy, X-ray photoelectron spectroscopy, cyclic voltammetry (CV), and electrochemical impedance spectroscopy. CV results show that OP-AC coated bipolar plate demonstrates improved electro-catalytic activity in both positive and negative side redox couples than the pristine bipolar plate electrode and this is ascribed to the high surface area of OP-AC which provides effective electrode area and better contact between the porous electrode and bipolar plate. Consequently, the performance of VRB in a static cell shows higher energy efficiency for OP-AC electrode than the pristine electrode at all current densities tested. The results suggest the OP-AC to be a promising electrode for VRB applications and can be incorporated into making conducting plastics electrode to lower the VRB cell stack weight and cost.

A series of low-altitude aerial radiological surveys of selected regions within Areas 3, 5, 8, 9, 11, 18, and 25 at the Nevada Test Site

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

Colton, D.P.

1999-12-01

A series of low-altitude, aerial radiological surveys of selected regions within Areas 3, 5, 8, 9, 11, 18,and 25 of the Nevada Test Site was conducted from December 1996 through June 1999. The surveys were conducted for the US Department of Energy by the Remote Sensing Laboratory, located in Las Vegas, Nevada, and maintained and operated by Bechtel Nevada. The flights were conducted at a nominal altitude of 15 meters above ground level along a set of parallel flight lines spaced 23 meters apart. The purpose of these low-altitude surveys was to measure, map, and define the areas of americium-241more » activity. The americium contamination will be used to determine the areas of plutonium contamination. Americium-241 activity was detected within 8 of the 11 regions. The three regions where americium-241 was not detected were in the inactive Nuclear Rocket Development Station complex in Area 25, which encompassed the Test Cell A and Test Cell C reactor test stands and the Reactor Maintenance Assembly and Disassembly facility.« less

Low track height standard-cells enable high-placement density and low-BEOL cost (Conference Presentation)

NASA Astrophysics Data System (ADS)

Debacker, Peter; Matti, Luca; Sherazi, Syed M. Y.; Baert, Rogier; Gerousis, Vassilios; Nauts, Claire; Raghavan, Praveen; Ryckaert, Julien; Kim, Ryoung-Han; Verkest, Diederik

2017-04-01

Making standards cells smaller by lowering the cell height from 7.5 tracks to 6 tracks for the same set of ground rules is an efficient way to reduce area for high density digital IP blocks without increasing wafer cost. Denser cells however also imply a higher pin density and possible more routing congestion because of that. In Place and Route phase, this limits the cell density (a.k.a. utilization) that can be reached without design rule violations. This study shows that 6-track cells (192nm high) and smart routing results in up to 60% lower area than 7.5-track cells in N5 technology. Standard cells have been created for 7.5T and 6T cells in N5 technology (poly pitch 42nm, metal pitch 32nm). The cells use a first horizontal routing layer (Mint) and vertical M1 for 1D intra-cell routing as much as possible. Place and route was performed on an opencores LDPC decoder. Various cell architectures and place and route optimizations are used to scale down the cell area and improve density. Most are not process optimizations, but optimized cell architectures and routing methods: • Open M1: M1 is removed as much as possible. This allows the router to use M1 for inter-cell routing in dense areas. • Routing in Mint: With open M1 the router can also use Mint to extend pins to access nearby free M1 tracks in congested areas. • Outbound rail: The 7.5T cells have inbound VDD/VSS rails in Mint for easy supply tapping. Moving the Mint rail outbound and shared between cells is required to enable lower track height cells. • Vertical Power distribution network (PDN): in 6T cells too many horizontal tracks would be consumed by the wide M2 rail. Mint is used instead combined with a vertical PDN in M1. • Self-Aligned Gate Contact allows to contact the gate on top of active fins. Any Mint track then can contact a gate, reducing cell area considerably. • Partially landing Mint Via trench: In 6T cells, a continuous Via trench underneath the Mint rail is used. This via partially lands on M0A to relax tip-to-tip requirements. • Relaxed M2 pitch: When pin access is handled in Mint and M1, this allows for a relaxed M2 pitch (48nm) with cheaper double patterning. To avoid horizontal routing layer congestion with the smaller cells, the 6T cells depend on the vertical PDN and open M1 to improve routability and pin access. Already in 7.5T cells, open M1 and vertical PDN help to improve routable utilization from 50% with closed M1 to 85% maximum. Moving to 6T cells, the combination of reduced cell area and high 85% utilization of result in a 60% area reduction vs the original 7.5T cells. We have shown that combining 6-track cells and smart routing results in up to 60% lower area than 7.5-track cells in N5 technology. Open M1 and vertical PDN are main area boosters for any cell architecture, boosting utilization from 50% to 85% already for the 7.5T cells.

A study on the cytotoxicity of carbon-based materials

DOE PAGES

Saha, Dipendu; Heldt, Caryn L.; Gencoglu, Maria F.; ...

2016-05-25

With an aim to understand the origin and key contributing factors towards carboninduced cytotoxicity, we have studied five different carbon samples with diverse surface area, pore width, shape and size, conductivity and surface functionality. All the carbon materials were characterized with surface area and pore size distribution, x-ray photoelectron spectroscopy (XPS) and electron microscopic imaging. We performed cytotoxicity study in Caco-2 cells by colorimetric assay, oxidative stress analysis by reactive oxygen species (ROX) detection, cellular metabolic activity measurement by adenosine triphosphate (ATP) depletion and visualization of cellular internalization by TEM imaging. The carbon materials demonstrated a varying degree of cytotoxicitymore » in contact with Caco-2 cells. The lowest cell survival rate was observed for nanographene, which possessed the minimal size amongst all the carbon samples under study. None of the carbons induced oxidative stress to the cells as indicated by the ROX generation results. Cellular metabolic activity study revealed that the carbon materials caused ATP depletion in cells and nanographene caused the highest depletion. Visual observation by TEM imaging indicated the cellular internalization of nanographene. This study confirmed that the size is the key cause of carbon-induced cytotoxicity and it is probably caused by the ATP depletion within the cell.« less

Immunohistochemical profile of neurotrophins in human cranial dura mater and meningiomas.

PubMed

Artico, Marco; Bronzetti, Elena; Pompili, Elena; Ionta, Brunella; Alicino, Valentina; D'Ambrosio, Anna; Santoro, Antonio; Pastore, Francesco S; Elenkov, Ilia; Fumagalli, Lorenzo

2009-06-01

The immunohistochemical profile of neurotrophins and their receptors in the human cranial dura mater was studied by examining certain dural zones in specimens harvested from different regions (frontal, temporal, parietal and occipital). Dural specimens were obtained during neurosurgical operations performed in ten patients for surgical treatment of intracranial lesions (meningiomas, traumas, gliomas, vascular malformations). The dural fragments were taken from the area of the craniotomy at least 8 cm from the lesion as well as from the area in which the meningioma had its dural attachment. Immunohistochemical characterization and distribution of neurotrophins, with their receptors, were analyzed. The concrete role played by these neurotrophic factors in general regulation, vascular permeability, algic responsivity and release of locally active substances in the human dura mater is still controversial. Our study revealed a general structural alteration of dural tissue due to the invasivity of meningiomatous lesions, together with an improved expression of brain derived neurotrophic factor (BDNF) in highly proliferating neoplastic cells and an evident production of nerve growth factor (NGF) in inflammatory cells, suggesting that BDNF has a role in supporting the proliferation rate of neoplastic cells, while NGF is involved in the activation of a chronic inflammatory response in neoplastic areas.

Electrodeposition of Highly Porous Pt Nanoparticles Studied by Quantitative 3D Electron Tomography: Influence of Growth Mechanisms and Potential Cycling on the Active Surface Area.

PubMed

Ustarroz, Jon; Geboes, Bart; Vanrompay, Hans; Sentosun, Kadir; Bals, Sara; Breugelmans, Tom; Hubin, Annick

2017-05-17

Nanoporous Pt nanoparticles (NPs) are promising fuel cell catalysts due to their large surface area and increased electrocatalytic activity toward the oxygen reduction reaction (ORR). Herein, we report on the influence of the growth mechanisms on the surface properties of electrodeposited Pt dendritic NPs with large surface areas. The electrochemically active surface was studied by hydrogen underpotential deposition (H UPD) and compared for the first time to high-angle annular dark field scanning transmission electron microscopy (HAADF-STEM) quantitative 3D electron tomography of individual nanoparticles. Large nucleation overpotential leads to a large surface coverage of roughened spheroids, which provide a large roughness factor (R f ) but low mass-specific electrochemically active surface area (EASA). Lowering the nucleation overpotential leads to highly porous Pt NPs with pores stretching to the center of the structure. At the expense of smaller R f , the obtained EASA values of these structures are in the range of those of large surface area supported fuel cell catalysts. The active surface area of the Pt dendritic NPs was measured by electron tomography, and it was found that the potential cycling in the H adsorption/desorption and Pt oxidation/reduction region, which is generally performed to determine the EASA, leads to a significant reduction of that surface area due to a partial collapse of their dendritic and porous morphology. Interestingly, the extrapolation of the microscopic tomography results in macroscopic electrochemical parameters indicates that the surface properties measured by H UPD are comparable to the values measured on individual NPs by electron tomography after the degradation caused by the H UPD measurement. These results highlight that the combination of electrochemical and quantitative 3D surface analysis techniques is essential to provide insights into the surface properties, the electrochemical stability, and, hence, the applicability of these materials. Moreover, it indicates that care must be taken with widely used electrochemical methods of surface area determination, especially in the case of large surface area and possibly unstable nanostructures, since the measured surface can be strongly affected by the measurement itself.

Visual area of the lateral suprasylvian gyrus (Clare—Bishop area) of the cat

PubMed Central

Hubel, David H.; Wiesel, Torsten N.

1969-01-01

On anatomical and physiological grounds a zone of cat cortex deep in the medial bank of the suprasylvian sulcus (the Clare—Bishop area) is known to receive strong visual projections both from the lateral geniculate body and area 17. We have mapped receptive fields of single cells in this area in eight cats. Active responses to visual stimuli were found over most of the medial bank of the suprasylvian sulcus extending to the depths and over to the lowest part of the lateral bank. The area is clearly topographically arranged. The first responsive cells, recorded over the lateral convexity and 2-3 mm down the medial bank, had receptive fields in the far periphery of the contralateral visual fields. The receptive fields tended to be large, but showed considerable variation in size and scatter in their positions. As the electrode advanced down the bank, fields of successively recorded cells gradually tended to move inwards, so that in the depths of the sulcus the inner borders of many of the fields reached the vertical mid line. Here the fields were smaller, though they still varied very much in size. Receptive fields were larger than in 17, 18, or 19, but otherwise were not obviously different from the complex and lower-order hypercomplex fields in those areas. No simple fields, or concentric fields of the retino-geniculate type, were seen. Cells with common receptive-field orientation were grouped together, but whether or not the grouping occurs in columns was not established. Most cells were driven independently by the two eyes. Fields in the two eyes seemed to be identical in organization. Cells dominated by the contralateral eye were much more common than ipsilaterally dominated ones, but when cells with parafoveal and peripheral fields were considered separately, the asymmetry was seen to apply mainly to cells with peripheral fields. PMID:5770897

Comparison of inducible nitric oxide synthase expression in the brains of Listeria monocytogenes-infected cattle, sheep, and goats and in macrophages stimulated in vitro.

PubMed

Jungi, T W; Pfister, H; Sager, H; Fatzer, R; Vandevelde, M; Zurbriggen, A

1997-12-01

The expression of inducible nitric oxide synthase (iNOS) was studied in the brains of cattle, sheep, and goat that succumbed to a natural infection with Listeria monocytogenes. The lesions in infected brains are characterized by microabscesses, perivascular cuffs, gliosis, glial nodules, and large areas of malacia. Using immunocytochemistry, we detected bacteria in microabscesses, particularly in sheep and goats, and in areas without signs of inflammation, but not in perivascular infiltrates. iNOS was expressed by macrophage (Mphi)-type cells of microabscesses and glial nodules but rarely by Mphi in areas of malacia, as determined by immunohistochemistry with iNOS-specific antibodies. iNOS was not detected in perivascular cuffs. Major histocompatibility complex class II molecules (MHC-II), another marker of cell activation, showed a different pattern of distribution. Perivascular cuffs contained high numbers of MHC-II-positive cells, including some with Mphi characteristics. Microabscesses in sheep and goats showed low expression of MHC-II, particularly in iNOS-expressing cells. In cattle, the expression of markers for activated or recruited phagocytes, the calcium-binding proteins S100A8 and S100A9 (formerly called MRP-8 and MRP-14, respectively), was largely restricted to cells showing weak or undetectable iNOS expression; iNOS-positive Mphi showed a low expression of S100A8 and S100A9. Thus, iNOS is expressed by a restricted subset of Mphi in listeric encephalitis. In cultured sheep and goat Mphi, a low proportion of cells expressed iNOS upon activation by L. monocytogenes and gamma interferon, resulting in nitrite generation at least 1 order of magnitude lower than that in similarly treated cattle Mphi. Since these species differences were much less obvious in vivo, it appears that the well-known species variation in iNOS expression by Mphi could reflect an in vitro phenomenon.

The cellular mastermind(?) – Mechanotransduction and the nucleus

PubMed Central

Kaminski, Ashley; Fedorchak, Gregory R.; Lammerding, Jan

2015-01-01

Cells respond to mechanical stimulation by activation of specific signaling pathways and genes that allow the cell to adapt to its dynamic physical environment. How cells sense the various mechanical inputs and translate them into biochemical signals remains an area of active investigation. Recent reports suggest that the cell nucleus may be directly implicated in this cellular mechanotransduction process. In this chapter, we discuss how forces applied to the cell surface and cytoplasm induce changes in nuclear structure and organization, which could directly affect gene expression, while also highlighting the complex interplay between nuclear structural proteins and transcriptional regulators that may further modulate mechanotransduction signaling. Taken together, these findings paint a picture of the nucleus as a central hub in cellular mechanotransduction—both structurally and biochemically—with important implications in physiology and disease. PMID:25081618

Temporal redistribution of inhibition over neuronal subcellular domains underlies state-dependent rhythmic change of excitability in the hippocampus

PubMed Central

Somogyi, Peter; Katona, Linda; Klausberger, Thomas; Lasztóczi, Bálint; Viney, Tim J.

2014-01-01

The behaviour-contingent rhythmic synchronization of neuronal activity is reported by local field potential oscillations in the theta, gamma and sharp wave-related ripple (SWR) frequency ranges. In the hippocampus, pyramidal cell assemblies representing temporal sequences are coordinated by GABAergic interneurons selectively innervating specific postsynaptic domains, and discharging phase locked to network oscillations. We compare the cellular network dynamics in the CA1 and CA3 areas recorded with or without anaesthesia. All parts of pyramidal cells, except the axon initial segment, receive GABA from multiple interneuron types, each with distinct firing dynamics. The axon initial segment is exclusively innervated by axo-axonic cells, preferentially firing after the peak of the pyramidal layer theta cycle, when pyramidal cells are least active. Axo-axonic cells are inhibited during SWRs, when many pyramidal cells fire synchronously. This dual inverse correlation demonstrates the key inhibitory role of axo-axonic cells. Parvalbumin-expressing basket cells fire phase locked to field gamma activity in both CA1 and CA3, and also strongly increase firing during SWRs, together with dendrite-innervating bistratified cells, phasing pyramidal cell discharge. Subcellular domain-specific GABAergic innervation probably developed for the coordination of multiple glutamatergic inputs on different parts of pyramidal cells through the temporally distinct activity of GABAergic interneurons, which differentially change their firing during different network states. PMID:24366131

Self-Assembled ZnO Nanosheet-Based Spherical Structure as Photoanode in Dye-Sensitized Solar Cells

NASA Astrophysics Data System (ADS)

Ameri, Mohsen; Raoufi, Meysam; Zamani-Meymian, M.-R.; Samavat, Feridoun; Fathollahi, M.-R.; Mohajerani, Ezeddin

2018-03-01

High surface area and enhanced light scattering of ZnO nanosheet aggregates have made them a promising active layer candidate material for fabrication of nanostructure dye-sensitized solar cells. Here, we propose a facile preparation method of such ZnO nanosheet structures, and in order to verify their applicability as photoanode material for dye-sensitized solar cells, we employ morphological, optical, structural and electrical measurements. The results reveal the high surface area available for dye molecules for enhancing adsorption, high light scattering and competitive power conversion efficiencies compared to the works in literature. Finally, the device is optimized with respect to the photoanode thickness. The favorable features shown here can extend the application of the structure to other types of sensitization-based perovskite and quantum dot solar cells.

Copper(ii) oxide nanoparticles penetrate into HepG2 cells, exert cytotoxicity via oxidative stress and induce pro-inflammatory response

NASA Astrophysics Data System (ADS)

Piret, Jean-Pascal; Jacques, Diane; Audinot, Jean-Nicolas; Mejia, Jorge; Boilan, Emmanuelle; Noël, Florence; Fransolet, Maude; Demazy, Catherine; Lucas, Stéphane; Saout, Christelle; Toussaint, Olivier

2012-10-01

The potential toxic effects of two types of copper(ii) oxide (CuO) nanoparticles (NPs) with different specific surface areas, different shapes (rod or spheric), different sizes as raw materials and similar hydrodynamic diameter in suspension were studied on human hepatocarcinoma HepG2 cells. Both CuO NPs were shown to be able to enter into HepG2 cells and induce cellular toxicity by generating reactive oxygen species. CuO NPs increased the abundance of several transcripts coding for pro-inflammatory interleukins and chemokines. Transcriptomic data, siRNA knockdown and DNA binding activities suggested that Nrf2, NF-κB and AP-1 were implicated in the response of HepG2 cells to CuO NPs. CuO NP incubation also induced activation of MAPK pathways, ERKs and JNK/SAPK, playing a major role in the activation of AP-1. In addition, cytotoxicity, inflammatory and antioxidative responses and activation of intracellular transduction pathways induced by rod-shaped CuO NPs were more important than spherical CuO NPs. Measurement of Cu2+ released in cell culture medium suggested that Cu2+ cations released from CuO NPs were involved only to a small extent in the toxicity induced by these NPs on HepG2 cells.The potential toxic effects of two types of copper(ii) oxide (CuO) nanoparticles (NPs) with different specific surface areas, different shapes (rod or spheric), different sizes as raw materials and similar hydrodynamic diameter in suspension were studied on human hepatocarcinoma HepG2 cells. Both CuO NPs were shown to be able to enter into HepG2 cells and induce cellular toxicity by generating reactive oxygen species. CuO NPs increased the abundance of several transcripts coding for pro-inflammatory interleukins and chemokines. Transcriptomic data, siRNA knockdown and DNA binding activities suggested that Nrf2, NF-κB and AP-1 were implicated in the response of HepG2 cells to CuO NPs. CuO NP incubation also induced activation of MAPK pathways, ERKs and JNK/SAPK, playing a major role in the activation of AP-1. In addition, cytotoxicity, inflammatory and antioxidative responses and activation of intracellular transduction pathways induced by rod-shaped CuO NPs were more important than spherical CuO NPs. Measurement of Cu2+ released in cell culture medium suggested that Cu2+ cations released from CuO NPs were involved only to a small extent in the toxicity induced by these NPs on HepG2 cells. Electronic supplementary information (ESI) available: Additional tables and figures supporting the information presented in the manuscript. See DOI: 10.1039/c2nr31785k

Cost-driven materials selection criteria for redox flow battery electrolytes

NASA Astrophysics Data System (ADS)

Dmello, Rylan; Milshtein, Jarrod D.; Brushett, Fikile R.; Smith, Kyle C.

2016-10-01

Redox flow batteries show promise for grid-scale energy storage applications but are presently too expensive for widespread adoption. Electrolyte material costs constitute a sizeable fraction of the redox flow battery price. As such, this work develops a techno-economic model for redox flow batteries that accounts for redox-active material, salt, and solvent contributions to the electrolyte cost. Benchmark values for electrolyte constituent costs guide identification of design constraints. Nonaqueous battery design is sensitive to all electrolyte component costs, cell voltage, and area-specific resistance. Design challenges for nonaqueous batteries include minimizing salt content and dropping redox-active species concentration requirements. Aqueous battery design is sensitive to only redox-active material cost and cell voltage, due to low area-specific resistance and supporting electrolyte costs. Increasing cell voltage and decreasing redox-active material cost present major materials selection challenges for aqueous batteries. This work minimizes cost-constraining variables by mapping the battery design space with the techno-economic model, through which we highlight pathways towards low price and moderate concentration. Furthermore, the techno-economic model calculates quantitative iterations of battery designs to achieve the Department of Energy battery price target of 100 per kWh and highlights cost cutting strategies to drive battery prices down further.

Roll-to-Roll printed large-area all-polymer solar cells with 5% efficiency based on a low crystallinity conjugated polymer blend

NASA Astrophysics Data System (ADS)

Gu, Xiaodan; Zhou, Yan; Gu, Kevin; Kurosawa, Tadanori; Yan, Hongping; Wang, Cheng; Toney, Micheal; Bao, Zhenan

The challenge of continuous printing in high efficiency large-area organic solar cells is a key limiting factor for their widespread adoption. We present a materials design concept for achieving large-area, solution coated all-polymer bulk heterojunction (BHJ) solar cells with stable phase separation morphology between the donor and acceptor. The key concept lies in inhibiting strong crystallization of donor and acceptor polymers, thus forming intermixed, low crystallinity and mostly amorphous blends. Based on experiments using donors and acceptors with different degree of crystallinity, our results showed that microphase separated donor and acceptor domain sizes are inversely proportional to the crystallinity of the conjugated polymers. This methodology of using low crystallinity donors and acceptors has the added benefit of forming a consistent and robust morphology that is insensitive to different processing conditions, allowing one to easily scale up the printing process from a small scale solution shearing coater to a large-scale continuous roll-to-roll (R2R) printer. We were able to continuously roll-to-roll slot die print large area all-polymer solar cells with power conversion efficiencies of 5%, with combined cell area up to 10 cm2. This is among the highest efficiencies realized with R2R coated active layer organic materials on flexible substrate. DOE BRIDGE sunshot program. Office of Naval Research.

Roll-to-Roll Printed Large-Area All-Polymer Solar Cells with 5% Efficiency Based on a Low Crystallinity Conjugated Polymer Blend

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

Gu, Xiaodan; Zhou, Yan; Gu, Kevin

The challenge of continuous printing in high-efficiency large-area organic solar cells is a key limiting factor for their widespread adoption. We present a materials design concept for achieving large-area, solution-coated all-polymer bulk heterojunction solar cells with stable phase separation morphology between the donor and acceptor. The key concept lies in inhibiting strong crystallization of donor and acceptor polymers, thus forming intermixed, low crystallinity, and mostly amorphous blends. Based on experiments using donors and acceptors with different degree of crystallinity, the results show that microphase separated donor and acceptor domain sizes are inversely proportional to the crystallinity of the conjugated polymers.more » This particular methodology of using low crystallinity donors and acceptors has the added benefit of forming a consistent and robust morphology that is insensitive to different processing conditions, allowing one to easily scale up the printing process from a small-scale solution shearing coater to a large-scale continuous roll-to-roll (R2R) printer. Large-area all-polymer solar cells are continuously roll-to-roll slot die printed with power conversion efficiencies of 5%, with combined cell area up to 10 cm 2. This is among the highest efficiencies realized with R2R-coated active layer organic materials on flexible substrate.« less

Roll-to-Roll Printed Large-Area All-Polymer Solar Cells with 5% Efficiency Based on a Low Crystallinity Conjugated Polymer Blend

DOE PAGES

Gu, Xiaodan; Zhou, Yan; Gu, Kevin; ...

2017-03-07

The challenge of continuous printing in high-efficiency large-area organic solar cells is a key limiting factor for their widespread adoption. We present a materials design concept for achieving large-area, solution-coated all-polymer bulk heterojunction solar cells with stable phase separation morphology between the donor and acceptor. The key concept lies in inhibiting strong crystallization of donor and acceptor polymers, thus forming intermixed, low crystallinity, and mostly amorphous blends. Based on experiments using donors and acceptors with different degree of crystallinity, the results show that microphase separated donor and acceptor domain sizes are inversely proportional to the crystallinity of the conjugated polymers.more » This particular methodology of using low crystallinity donors and acceptors has the added benefit of forming a consistent and robust morphology that is insensitive to different processing conditions, allowing one to easily scale up the printing process from a small-scale solution shearing coater to a large-scale continuous roll-to-roll (R2R) printer. Large-area all-polymer solar cells are continuously roll-to-roll slot die printed with power conversion efficiencies of 5%, with combined cell area up to 10 cm 2. This is among the highest efficiencies realized with R2R-coated active layer organic materials on flexible substrate.« less

Current density and catalyst-coated membrane resistance distribution of hydro-formed metallic bipolar plate fuel cell short stack with 250 cm2 active area

NASA Astrophysics Data System (ADS)

Haase, S.; Moser, M.; Hirschfeld, J. A.; Jozwiak, K.

2016-01-01

An automotive fuel cell with an active area of 250 cm2 is investigated in a 4-cell short stack with a current and temperature distribution device next to the bipolar plate with 560 current and 140 temperature segments. The electrical conductivities of the bipolar plate and gas diffusion layer assembly are determined ex-situ with this current scan shunt module. The applied fuel cell consists of bipolar plates constructed of 75-μm-thick, welded stainless-steel foils and a graphitic coating. The electrical conductivities of the bipolar plate and gas diffusion layer assembly are determined ex-situ with this module with a 6% deviation in in-plane conductivity. The current density distribution is evaluated up to 2.4 A cm-2. The entire cell's investigated volumetric power density is 4.7 kW l-1, and its gravimetric power density is 4.3 kW kg-1 at an average cell voltage of 0.5 V. The current density distribution is determined without influencing the operating cell. In addition, the current density distribution in the catalyst-coated membrane and its effective resistivity distribution with a finite volume discretisation of Ohm's law are evaluated. The deviation between the current density distributions in the catalyst-coated membrane and the bipolar plate is determined.

Homocysteine Test

MedlinePlus

... Time and International Normalized Ratio (PT/INR) PSEN1 Quantitative Immunoglobulins Red Blood Cell (RBC) Antibody Identification Red ... and heart disease remains an active area of research. At present, however, the use of homocysteine levels ...

Localized cyclic AMP-dependent protein kinase activity is required for myogenic cell fusion

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

Mukai, Atsushi; Hashimoto, Naohiro

2008-01-15

Multinucleated myotubes are formed by fusion of mononucleated myogenic progenitor cells (myoblasts) during terminal skeletal muscle differentiation. In addition, myoblasts fuse with myotubes, but terminally differentiated myotubes have not been shown to fuse with each other. We show here that an adenylate cyclase activator, forskolin, and other reagents that elevate intracellular cyclic AMP (cAMP) levels induced cell fusion between small bipolar myotubes in vitro. Then an extra-large myotube, designated a 'myosheet,' was produced by both primary and established mouse myogenic cells. Myotube-to-myotube fusion always occurred between the leading edge of lamellipodia at the polar end of one myotube and themore » lateral plasma membrane of the other. Forskolin enhanced the formation of lamellipodia where cAMP-dependent protein kinase (PKA) was accumulated. Blocking enzymatic activity or anchoring of PKA suppressed forskolin-enhanced lamellipodium formation and prevented fusion of multinucleated myotubes. Localized PKA activity was also required for fusion of mononucleated myoblasts. The present results suggest that localized PKA plays a pivotal role in the early steps of myogenic cell fusion, such as cell-to-cell contact/recognition through lamellipodium formation. Furthermore, the localized cAMP-PKA pathway might be involved in the specification of the fusion-competent areas of the plasma membrane in lamellipodia of myogenic cells.« less

Activated c-Kit receptor in the heart promotes cardiac repair and regeneration after injury

PubMed Central

Di Siena, S; Gimmelli, R; Nori, S L; Barbagallo, F; Campolo, F; Dolci, S; Rossi, P; Venneri, M A; Giannetta, E; Gianfrilli, D; Feigenbaum, L; Lenzi, A; Naro, F; Cianflone, E; Mancuso, T; Torella, D; Isidori, A M; Pellegrini, M

2016-01-01

The role of endogenous c-Kit receptor activation on cardiac cell homeostasis and repair remains largely unexplored. Transgenic mice carrying an activating point mutation (TgD814Y) in the kinase domain of the c-Kit gene were generated. c-KitTgD814Y receptor was expressed in the heart during embryonic development and postnatal life, in a similar timing and expression pattern to that of the endogenous gene, but not in the hematopoietic compartment allowing the study of a cardiac-specific phenotype. c-KitTgD814Y mutation produced a constitutive active c-Kit receptor in cardiac tissue and cells from transgenic mice as demonstrated by the increased phosphorylation of ERK1/2 and AKT, which are the main downstream molecular effectors of c-Kit receptor signaling. In adult transgenic hearts, cardiac morphology, size and total c-Kit+ cardiac cell number was not different compared with wt mice. However, when c-KitTgD814Y mice were subjected to transmural necrotic heart damage by cryoinjury (CI), all transgenic survived, compared with half of wt mice. In the sub-acute phase after CI, transgenic and wt mice showed similar heart damage. However, 9 days after CI, transgenic mice exhibited an increased number of c-Kit+CD31+ endothelial progenitor cells surrounding the necrotic area. At later follow-up, a consistent reduction of fibrotic area, increased capillary density and increased cardiomyocyte replenishment rate (as established by BrdU incorporation) were observed in transgenic compared with wt mice. Consistently, CD45−c-Kit+ cardiac stem cells isolated from transgenic c-KitTgD814Y mice showed an enhanced endothelial and cardiomyocyte differentiation potential compared with cells isolated from the wt. Constitutive activation of c-Kit receptor in mice is associated with an increased cardiac myogenic and vasculogenic reparative potential after injury, with a significant improvement of survival. PMID:27468693

Metabolic and morphological differences between rapidly proliferating cancerous and normal breast epithelial cells.

PubMed

Meadows, Adam L; Kong, Becky; Berdichevsky, Marina; Roy, Siddhartha; Rosiva, Rosiva; Blanch, Harvey W; Clark, Douglas S

2008-01-01

The metabolic and morphological characteristics of two human epithelial breast cell populations--MCF7 cells, a cancerous cell line, and 48R human mammary epithelial cells (48R HMECs), a noncancerous, finite lifespan cell strain--were compared at identical growth rates. Both cell types were induced to grow rapidly in nutrient-rich media containing 13C-labeled glucose, and the isotopic enrichment of cellular metabolites was quantified to calculate metabolic fluxes in key pathways. Despite their similar growth rates, the cells exhibited distinctly different metabolic and morphological profiles. MCF7 cells have an 80% smaller exposed surface area and contain 26% less protein per cell than the 48R cells. Surprisingly, rapidly proliferating 48R cells exhibited a 225% higher per-cell glucose consumption rate, a 250% higher per-cell lactate production rate, and a nearly identical per-cell glutamine consumption rate relative to the cancer cell line. However, when fluxes were considered on the basis of exposed area, the cancer cells were observed to have higher glucose, lactate, and glutamine fluxes, demonstrating superior transport capabilities per unit area of cell membrane. MCF7 cells also consumed amino acids at rates much higher than are generally required for protein synthesis, whereas 48R cells generally did not. Pentose phosphate pathway activity was higher in MCF7 cells, and the flux of glutamine to glutamate was less reversible. Energy efficiency was significantly higher in MCF7 cells, as a result of a combination of their smaller size and greater reliance on the TCA cycle than the 48R cells. These observations support evolutionary models of cancer cell metabolism and suggest targets for metabolic drugs in metastatic breast cancers.

Fluence Rate Differences in Photodynamic Therapy Efficacy and Activation of Epidermal Growth Factor Receptor after Treatment of the Tumor-Involved Murine Thoracic Cavity

PubMed Central

Grossman, Craig E.; Carter, Shirron L.; Czupryna, Julie; Wang, Le; Putt, Mary E.; Busch, Theresa M.

2016-01-01

Photodynamic therapy (PDT) of the thoracic cavity can be performed in conjunction with surgery to treat cancers of the lung and its pleura. However, illumination of the cavity results in tissue exposure to a broad range of fluence rates. In a murine model of intrathoracic PDT, we studied the efficacy of 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH; Photochlor®)-mediated PDT in reducing the burden of non-small cell lung cancer for treatments performed at different incident fluence rates (75 versus 150 mW/cm). To better understand a role for growth factor signaling in disease progression after intrathoracic PDT, the expression and activation of epidermal growth factor receptor (EGFR) was evaluated in areas of post-treatment proliferation. The low fluence rate of 75 mW/cm produced the largest reductions in tumor burden. Bioluminescent imaging and histological staining for cell proliferation (anti-Ki-67) identified areas of disease progression at both fluence rates after PDT. However, increased EGFR activation in proliferative areas was detected only after treatment at the higher fluence rate of 150 mW/cm. These data suggest that fluence rate may affect the activation of survival factors, such as EGFR, and weaker activation at lower fluence rate could contribute to a smaller tumor burden after PDT at 75 mW/cm. PMID:26784170

Fluence Rate Differences in Photodynamic Therapy Efficacy and Activation of Epidermal Growth Factor Receptor after Treatment of the Tumor-Involved Murine Thoracic Cavity.

PubMed

Grossman, Craig E; Carter, Shirron L; Czupryna, Julie; Wang, Le; Putt, Mary E; Busch, Theresa M

2016-01-14

Photodynamic therapy (PDT) of the thoracic cavity can be performed in conjunction with surgery to treat cancers of the lung and its pleura. However, illumination of the cavity results in tissue exposure to a broad range of fluence rates. In a murine model of intrathoracic PDT, we studied the efficacy of 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH; Photochlor(®))-mediated PDT in reducing the burden of non-small cell lung cancer for treatments performed at different incident fluence rates (75 versus 150 mW/cm). To better understand a role for growth factor signaling in disease progression after intrathoracic PDT, the expression and activation of epidermal growth factor receptor (EGFR) was evaluated in areas of post-treatment proliferation. The low fluence rate of 75 mW/cm produced the largest reductions in tumor burden. Bioluminescent imaging and histological staining for cell proliferation (anti-Ki-67) identified areas of disease progression at both fluence rates after PDT. However, increased EGFR activation in proliferative areas was detected only after treatment at the higher fluence rate of 150 mW/cm. These data suggest that fluence rate may affect the activation of survival factors, such as EGFR, and weaker activation at lower fluence rate could contribute to a smaller tumor burden after PDT at 75 mW/cm.

Opinion: Interactions of innate and adaptive lymphocytes

PubMed Central

Gasteiger, Georg; Rudensky, Alexander Y.

2015-01-01

Innate lymphocytes, including natural killer (NK) cells and the recently discovered innate lymphoid cells (ILCs) have crucial roles during infection, tissue injury and inflammation. Innate signals regulate the activation and homeostasis of innate lymphocytes. Less well understood is the contribution of the adaptive immune system to the orchestration of innate lymphocyte responses. We review our current understanding of the interactions between adaptive and innate lymphocytes, and propose a model in which adaptive T cells function as antigen-specific sensors for the activation of innate lymphocytes to amplify and instruct local immune responses. We highlight the potential role of regulatory and helper T cells in these processes and discuss major questions in the emerging area of crosstalk between adaptive and innate lymphocytes. PMID:25132095

Design and assembly considerations for Redox cells and stacks

NASA Technical Reports Server (NTRS)

Stalnaker, D. K.; Lieberman, A.

1981-01-01

Individual redox flow cells are arranged electrically in series and hydraulically in parallel to form a single assembly called a stack. The hardware currently being tested in the laboratory has an active electrode area of either 310 sq cm or 929 sq cm. Four 310 sq cm stacks, each consisting of 39 active cells, were incorporated into a 1.0 kW preprototype system. The physical design of the stack is very critical to the performance and efficiency of the redox storage sytem. This report will discuss the mechanical aspects of the cell and stack design for the current Redox hardware, with regard to sealing the stack internally as well as externally, minimizing shunt currents and minimizing the electrical resistance of the stack.

Cooperative synchronized assemblies enhance orientation discrimination.

PubMed

Samonds, Jason M; Allison, John D; Brown, Heather A; Bonds, A B

2004-04-27

There is no clear link between the broad tuning of single neurons and the fine behavioral capabilities of orientation discrimination. We recorded from populations of cells in the cat visual cortex (area 17) to examine whether the joint activity of cells can support finer discrimination than found in individual responses. Analysis of joint firing yields a substantial advantage (i.e., cooperation) in fine-angle discrimination. This cooperation increases to more considerable levels as the population of an assembly is increased. The cooperation in a population of six cells provides encoding of orientation with an information advantage that is at least 2-fold in terms of requiring either fewer cells or less time than independent coding. This cooperation suggests that correlated or synchronized activity can increase information.

Regulation of the muscle fiber microenvironment by activated satellite cells during hypertrophy

PubMed Central

Fry, Christopher S.; Lee, Jonah D.; Jackson, Janna R.; Kirby, Tyler J.; Stasko, Shawn A.; Liu, Honglu; Dupont-Versteegden, Esther E.; McCarthy, John J.; Peterson, Charlotte A.

2014-01-01

Our aim in the current study was to determine the necessity of satellite cells for long-term muscle growth and maintenance. We utilized a transgenic Pax7-DTA mouse model, allowing for the conditional depletion of > 90% of satellite cells with tamoxifen treatment. Synergist ablation surgery, where removal of synergist muscles places functional overload on the plantaris, was used to stimulate robust hypertrophy. Following 8 wk of overload, satellite cell-depleted muscle demonstrated an accumulation of extracellular matrix (ECM) and fibroblast expansion that resulted in reduced specific force of the plantaris. Although the early growth response was normal, an attenuation of hypertrophy measured by both muscle wet weight and fiber cross-sectional area occurred in satellite cell-depleted muscle. Isolated primary myogenic progenitor cells (MPCs) negatively regulated fibroblast ECM mRNA expression in vitro, suggesting a novel role for activated satellite cells/MPCs in muscle adaptation. These results provide evidence that satellite cells regulate the muscle environment during growth.—Fry, C. S., Lee, J. D., Jackson, J. R., Kirby, T. J., Stasko, S. A., Liu, H., Dupont-Versteegden, E. E., McCarthy, J. J., Peterson, C. A. Regulation of the muscle fiber microenvironment by activated satellite cells during hypertrophy. PMID:24376025

T Lymphocyte Activation Threshold is Increased in Reduced Gravity

NASA Technical Reports Server (NTRS)

Adams, Charley L.; Gonzalez, M.; Sams, C. F.

2000-01-01

There have been substantial advances in molecular and cellular biology that have provided new insight into the biochemical and genetic basis of lymphocyte recognition, activation and expression of distinct functional phenotypes. It has now become evident that for both T and B cells, stimuli delivered through their receptors can result in either clonal expansion or apoptosis. In the case of T cells, clonal expansion of helper cells is accompanied by differentiation into two major functional subsets which regulate the immune response. The pathways between the membrane and the nucleus and their molecular components are an area of very active investigation. This meeting will draw together scientists working on diverse aspects of this problem, including receptor ligand interactions, intracellular pathways that transmit receptor mediated signals and the effect of such signal transduction pathways on gene regulation. The aim of this meeting is to integrate the information from these various experimental approaches into a new synthesis and molecular explanation of T cell activation, differentiation and death.

CMOS SiPM with integrated amplifier

NASA Astrophysics Data System (ADS)

Schwinger, Alexander; Brockherde, Werner; Hosticka, Bedrich J.; Vogt, Holger

2017-02-01

The integration of silicon photomultiplier (SiPM) and frontend electronics in a suitable optoelectronic CMOS process is a promising approach to increase the versatility of single-photon avalanche diode (SPAD)-based singlephoton detectors. By integrating readout amplifiers, the device output capacitance can be reduced to minimize the waveform tail, which is especially important for large area detectors (>10 × 10mm2). Possible architectures include a single readout amplifier for the whole detector, which reduces the output capacitance to 1:1 pF at minimal reduction in detector active area. On the other hand, including a readout amplifier in every SiPM cell would greatly improve the total output capacitance by minimizing the influence of metal routing parasitic capacitance, but requiring a prohibitive amount of detector area. As tradeoff, the proposed detector features one readout amplifier for each column of the detector matrix to allow for a moderate reduction in output capacitance while allowing the electronics to be placed in the periphery of the active detector area. The presented detector with a total size of 1.7 ♢ 1.0mm2 features 400 cells with a 50 μm pitch, where the signal of each column of 20 SiPM cells is summed in a readout channel. The 20 readout channels are subsequently summed into one output channel, to allow the device to be used as a drop-in replacement for commonly used analog SiPMs.

Activation requirements and responses to TLR ligands in human CD4+ T cells: comparison of two T cell isolation techniques.

PubMed

Lancioni, Christina L; Thomas, Jeremy J; Rojas, Roxana E

2009-05-15

Direct regulation of T cell function by microbial ligands through Toll-like receptors (TLR) is an emerging area of T cell biology. Currently either immunomagnetic cell sorting (IMACS) or fluorescence-activated cell sorting (FACS), are utilized to isolate T-cell subsets for such studies. However, it is unknown to what extent differences in T cell purity between these isolation techniques influence T cell functional assays. We compared the purity, response to mitogen, activation requirements, and response to TLR ligands between human CD4(+) T cells isolated either by IMACS (IMACS-CD4(+)) or by IMACS followed by FACS (IMACS/FACS-CD4(+)). As expected, IMACS-CD4(+) were less pure than IMACS/FACS-CD4(+) (92.5%+/-1.4% versus 99.7%+/-0.2%, respectively). Consequently, IMACS-CD4(+) proliferated and produced cytokines in response to mitogen alone and had lower activation requirements compared to IMACS/FACS-CD4(+). In addition IMACS-CD4(+) but not IMACS/FACS-CD4(+) responses were upregulated by the TLR-4 ligand lipopolysaccharide (LPS). On the other hand, TLR-2 and TLR-5 engagement induced costimulation in both IMACS-CD4(+) and highly purified IMACS-/FACS-CD4(+). Altogether these results indicate that small differences in cell purity can significantly alter T cell responses to TLR ligands. This study stresses the importance of a stringent purification method when investigating the role of microbial ligands in T cell function.

Early stellate cell activation and veno-occlusive-disease (VOD)-like hepatotoxicity in dogs treated with AR-H047108, an imidazopyridine proton pump inhibitor.

PubMed

Berg, Anna-Lena; Böttcher, Gerhard; Andersson, Kjell; Carlsson, Enar; Lindström, Anna-Karin; Huby, Russell; Håkansson, Helen; Skånberg-Wilhelmsson, Inger; Hellmold, Heike

2008-07-01

Dogs treated with AR-H047108, an imidazopyridine potassium competitive acid blocker (P-CAB), developed clinical signs of hepatic dysfunction as well as morphologically manifest hepatotoxicity in repeat-dose toxicity studies. An investigative one-month study was performed, with interim euthanasia after one and two weeks. A detailed histopathological and immunohistochemical characterization of the liver lesions was conducted, including markers for fibrosis, Kupffer cell activation, apoptosis, and endothelial injury. In addition, hepatic retinoid and procollagen 1alpha2 mRNA levels in livers of dogs treated with AR-H047108 were analyzed. The results showed an early inflammatory process in central veins and centrilobular areas, present after one week of treatment. This inflammatory reaction was paralleled by activation of stellate/Ito cells to myofibroblasts and was associated with sinusoidal and centrivenular fibrosis. The early activation of stellate cells coincided with a significant decrease in retinyl ester levels, and a significant increase in procollagen 1alpha2 mRNA levels, in the liver. At later time points (three and six months), there was marked sinusoidal fibrosis in centrilobular areas, as well as occlusion of central veins resulting from a combination of fibrosis and increased thickness of smooth muscle bundles in the vessel wall. The pattern of lesions suggests a veno-occlusive-disease (VOD)-like scenario, possibly linked to the imidazopyridine chemical structure of the compound facilitated by specific morphological features of the dog liver.

Aluminum-induced cell death of barley-root border cells is correlated with peroxidase- and oxalate oxidase-mediated hydrogen peroxide production.

PubMed

Tamás, L; Budíková, S; Huttová, J; Mistrík, I; Simonovicová, M; Siroká, B

2005-06-01

The function of root border cells (RBC) during aluminum (Al) stress and the involvement of oxalate oxidase, peroxidase and H(2)O(2) generation in Al toxicity were studied in barley roots. Our results suggest that RBC effectively protect the barley root tip from Al relative to the situation in roots cultivated in hydroponics where RBC are not sustained in the area surrounding the root tip. The removal of RBC from Al-treated roots increased root growth inhibition, Al and Evans blue uptake, inhibition of RBC production, the level of dead RBC, peroxidase and oxalate oxidase activity and the production of H(2)O(2). Our results suggest that even though RBC actively produce active oxygen species during Al stress, their role in the protection of root tips against Al toxicity is to chelate Al in their dead cell body.

Development of a Micro-Fiber Nickel Electrode for Nickel-Hydrogen Cell

NASA Technical Reports Server (NTRS)

Britton, Doris L.

1996-01-01

The development of a high specific energy battery is one of the objectives of the lightweight nickel-hydrogen (NiH2) program at the NASA Lewis Research Center. The approach has been to improve the nickel electrode by continuing combined in-house and contract efforts to develop a more efficient and lighter weight electrode for the nickel-hydrogen fuel cell. Small fiber diameter nickel plaques are used as conductive supports for the nickel hydroxide active material. These plaques are commercial products and have an advantage of increased surface area available for the deposition of active materials. Initial tests include activation and capacity measurements at different discharge levels followed by half-cell cycle testing at 80 percent depth-of-discharge in a low Earth orbit regime. The electrodes that pass the initial tests are life cycle tested in a boiler plate nickel-hydrogen cell before flightweight designs are built and tested.

Development of a micro-fiber nickel electrode for nickel-hydrogen cell

NASA Technical Reports Server (NTRS)

Britton, Doris L.

1995-01-01

Development of a high specific energy nickel electrode is the main goal of the lightweight nickel electrode program at the NASA Lewis Research Center. The approach has been to improve the nickel electrode by continuing combined in-house and contract efforts to develop a more efficient and lighter weight electrode for the nickel-hydrogen cell. Small fiber diameter nickel plaques are used as conductive supports for the nickel hydroxide active material. These plaques are commercial products and have an advantage of increased surface area available for the deposition of active material. Initial tests include activation and capacity measurements at different discharge levels followed by half-cell cycle testing at 80 percent depth-of-discharge in a low-Earth-orbit regime. The electrodes that pass the initial tests are life cycle-tested in a boiler plate nickel-hydrogen cell before flightweight designs are built and tested.

A Location-Based Duplex Scheme for Cost Effective Rural Broadband Connectivity Using IEEE 802.22 Cognitive Radio Based Wireless Regional Area Networks

NASA Astrophysics Data System (ADS)

Kalidoss, R.; Bhagyaveni, M. A.; Vishvaksenan, K. S.

2014-08-01

The search for a method of utilizing the scarce spectrum in an efficient manner is an active area of research in both academic and industrial communities. IEEE 802.22 is a standard for wireless regional area network (WRAN) based on cognitive radio (CR) that operates over underutilized portions of TV bands (54-862 MHz). Time division duplex (TDD)-based WRAN cells have such advantages as dynamic traffic allocation, traffic asymmetry to users and ease of spectrum allocation. However, these cells suffer from severe cross time slot (CTS) interference when the frames of the cells are not synchronized with adjacent WRAN cells. In this paper, we evaluate the location-based duplex (LBD) scheme for eliminating the CTS interference. The proposed LBD system is much more flexible and efficient in providing asymmetric data service and eliminating CTS interference by exploiting the advantages of both TDD and frequency division duplex (FDD) schemes. We also compare the performance of LBD systems with virtual cell concepts. Furthermore, our simulation results reveal that LBD-based systems outperform the virtual cell approach in terms of the low signal-to-interference (SIR) ratio requirement by mitigating the effects of CTS.

Chemical Activation of the Hypoxia-Inducible Factor Reversibly Reduces Tendon Stem Cell Proliferation, Inhibits Their Differentiation, and Maintains Cell Undifferentiation

PubMed Central

Creo, Pasquale; Bergante, Sonia; Conforti, Erika; Banfi, Giuseppe

2018-01-01

Adult stem cell-based therapeutic approaches for tissue regeneration have been proposed for several years. However, adult stem cells are usually limited in number and difficult to be expanded in vitro, and they usually tend to quickly lose their potency with passages, as they differentiate and become senescent. Culturing stem cells under reduced oxygen tensions (below 21%) has been proposed as a tool to increase cell proliferation, but many studies reported opposite effects. In particular, cell response to hypoxia seems to be very stem cell type specific. Nonetheless, it is clear that a major role in this process is played by the hypoxia inducible factor (HIF), the master regulator of cell response to oxygen deprivation, which affects cell metabolism and differentiation. Herein, we report that a chemical activation of HIF in human tendon stem cells reduces their proliferation and inhibits their differentiation in a reversible and dose-dependent manner. These results support the notion that hypoxia, by activating HIF, plays a crucial role in preserving stem cells in an undifferentiated state in the “hypoxic niches” present in the tissue in which they reside before migrating in more oxygenated areas to heal a damaged tissue. PMID:29713352

Status and applicability of solid polymer electrolyte technology to electrolytic hydrogen and oxygen production

NASA Technical Reports Server (NTRS)

Titterington, W. A.

1973-01-01

The solid polymer electrolyte (SPE) water electrolysis technology is presented as a potential energy conversion method for wind driven generator systems. Electrolysis life and performance data are presented from laboratory sized single cells (7.2 sq in active area) with high cell current density selected (1000 ASF) for normal operation.

Single unit activity in the medial prefrontal cortex during Pavlovian heart rate conditioning: Effects of peripheral autonomic blockade.

PubMed

Powell, D A; Ginsberg, Jay P

2005-11-01

Electrical activity was recorded from single neurons in the medial prefrontal cortex of rabbits during differential Pavlovian heart rate (HR) conditioning. A heterogeneous population of cells were found, some of which showed CS-evoked increases and others CS-evoked decreases in discharge, while some cells were biphasic. A subset of cells also showed trial-related changes in discharge that were related to acquisition of the HR discrimination between the reinforced CS+ and non-reinforced CS-. Administration of the peripheral cholinergic antagonist, methylscopolamine, and the andrenergic antagonist, atenolol, either increased or decreased maintained baseline activity of many cells, but had little or no effect on the CS-evoked activity of these cells. Waveform changes also did not result from administration of these drugs. This finding suggests that CS-evoked mPFC activity is not being driven by cardiac afferent input to CNS cardiac control centers. Previous studies have shown that ibotenic acid lesions of this area greatly decreases the magnitude of decelerative heart rate conditioned responses; the latter finding, plus the results of the present study, suggest that processing of CS/US contingencies by the prefrontal cortex contributes to the acquisition of autonomic changes during Pavlovian conditioning.

Biochar and lignite affect H+-ATPase and H+-PPase activities in root tonoplast and nutrient contents of mung bean under salt stress.

PubMed

Torabian, Shahram; Farhangi-Abriz, Salar; Rathjen, Judith

2018-05-31

This research was conducted to evaluate effects of biochar (50 and 100 g kg -1 soil) and lignite (50 and 100 g kg -1 soil) treatments on H + -ATPase and H + -PPase activity of root tonoplast, nutrient content, and performance of mung bean under salt stress. High saline conditions increased H + -ATPase and H + -PPase activities in root tonoplast, sodium (Na) content, reactive oxygen species (H 2 O 2 and O 2 - ) generation, relative electrolyte leakage (REL) and 2,2-Diphenyl-1-picrylhydrazyl (DPPH) activity in root and leaf, but decreased relative water content (RWC), chlorophyll content index, leaf area, potassium (K), calcium (Ca), magnesium (Mg), zinc (Zn) and iron (Fe) content of plant tissues, root and shoot dry weight of mung bean. Lignite and biochar treatments decreased the H + -ATPase and H + -PPase activities of root tonoplast under salt stress. Moreover, these treatments increased the cation exchange capacity of soil and nutrient values in plant tissues. Biochar and lignite diminished the generation of reactive oxygen species and DPPH activity in root and leaf cells, and these superior effects improved chlorophyll content index, leaf area and growth of mung bean under both conditions. In general, the results of this study demonstrated that biochar and lignite decreased the entry of Na ion into the cells, enriched plant cells with nutrients, and consequently improved mung bean performance under salt toxicity. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Activation and Inhibition of The Wnt3A Signaling Pathway in Buffalo (Bubalus bubalis) Embryonic Stem Cells: Effects of WNT3A, Bio and Dkk1.

PubMed

Zandi, Mohammad; Shah, Syed Mohamad; Muzaffar, Musharifa; Kumar Singh, Manoj; Palta, Prabhat; Kumar Singla, Suresh; Sham Manik, Radhey; Chauhan, Manmohan Singh

2015-01-01

This research studies the effects of activation and inhibition of Wnt3A signaling pathway in buffalo (Bubalus bubalis) embryonic stem (ES) cell-like cells. To carry on this experimental study, the effects of activation and inhibition of Wnt3A signaling in buffalo ES cell-like cells were examined using Bio (0.5 mM) combined with WNT3A (200 ng/ml), as an activator, and Dickkopf-1 (Dkk1, 250 ng/ml), as an inhibitor, of the pathway. ES cells were cultured up to three weeks in ES cell medium without fibroblast growth factor-2 (FGF-2) and leukemia inhibitory factor (LIF), but in the presence of Bio, WNT3A, Bio+WNT3A and Dkk1. The effects of these supplements were measured on the mean area of ES cell colonies and on the expression levels of a number of important genes related to pluripotency (Oct4, Nanog, Sox2 and c-Myc) and the Wnt pathway (β-catenin). ES cell colonies cultured in ES cell medium that contained optimized quantities of LIF and FGF-2 were used as the control. Data were collected for week-1 and week-3 treated cultures. In addition, WNT3A-transfected ES cells were compared with the respective mock-transfected colonies, either alone or in combination with Dkk1 for expression of β-catenin and the pluripotency-related genes. Data were analyzed by ANOVA, and statistical significance was accepted at P<0.05. Among various examined concentrations of Bio (0.5-5 mM), the optimum effect was observed at the 0.5 mM dose as indicated by colony area and expressions of pluripotency-related genes at both weeks-1 and -3 culture periods. At this concentration,the expressions of Nanog, Oct3/4, Sox2, c-Myc and β-catenin genes were nonsignificantly higher compared to the controls. Expressions of these genes were highest in the Bio+WNT3A treated group, followed by the WNT3A and Bio-supplemented groups, and lowest in the Dkk1-treated group. The WNT-transfected colonies showed higher expressions compared to both mock and Dkk1-treated mock transfected colonies. WNT3A functions to maintain the pluripotency of ES cell-like cells both as an exogenous growth factor as well as an endogenously expressed gene. It complements the absence of FGF-2 and LIF, otherwise propounded essential for buffalo ES cell culture. WNT3A antagonizes the inhibitory effects of Dkk1 and acts in combination with its activator, Bio, to activate the Wnt signaling pathway.

Functional Na+ Channels in Cell Adhesion probed by Transistor Recording

PubMed Central

Schmidtner, Markus; Fromherz, Peter

2006-01-01

Cell membranes in a tissue are in close contact to each other, embedded in the extracellular matrix. Standard electrophysiological methods are not able to characterize ion channels under these conditions. Here we consider the area of cell adhesion on a solid substrate as a model system. We used HEK 293 cells cultured on fibronectin and studied the activation of NaV1.4 sodium channels in the adherent membrane with field-effect transistors in a silicon substrate. Under voltage clamp, we compared the transistor response with the whole-cell current. We observed that the extracellular voltage in the cell-chip contact was proportional to the total membrane current. The relation was calibrated by alternating-current stimulation. We found that Na+ channels are present in the area of cell adhesion on fibronectin with a functionality and a density that is indistinguishable from the free membrane. The experiment provides a basis for studying selective accumulation and depletion of ion channels in cell adhesion and also for a development of cell-based biosensoric devices and neuroelectronic systems. PMID:16227504

Electric utility acid fuel cell stack technology advancement

NASA Astrophysics Data System (ADS)

Congdon, J. V.; Goller, G. J.; Greising, G. J.; Obrien, J. J.; Randall, S. A.; Sandelli, G. J.; Breault, R. D.; Austin, G. W.; Bopse, S.; Coykendall, R. D.

1984-11-01

The principal effort under this program was directed at the fuel cell stack technology required to accomplish the initial feasibility demonstrations of increased cell stack operating pressures and temperatures, increased cell active area, incorporation of the ribbed substrate cell configuration at the bove conditions, and the introduction of higher performance electrocatalysts. The program results were successful with the primary accomplishments being: (1) fabrication of 10 sq ft ribbed substrate, cell components including higher performing electrocatalysts; (2) assembly of a 10 sq ft, 30-cell short stack; and (3) initial test of this stack at 120 psia and 405 F. These accomplishments demonstrate the feasibility of fabricating and handling large area cells using materials and processes that are oriented to low cost manufacture. An additional accomplishment under the program was the testing of two 3.7 sq ft short stacks at 12 psia/405 F to 5400 and 4500 hours respectively. These tests demonstrate the durability of the components and the cell stack configuration to a nominal 5000 hours at the higher pressure and temperature condition planned for the next electric utility power plant.

Electric utility acid fuel cell stack technology advancement

NASA Technical Reports Server (NTRS)

Congdon, J. V.; Goller, G. J.; Greising, G. J.; Obrien, J. J.; Randall, S. A.; Sandelli, G. J.; Breault, R. D.; Austin, G. W.; Bopse, S.; Coykendall, R. D.

1984-01-01

The principal effort under this program was directed at the fuel cell stack technology required to accomplish the initial feasibility demonstrations of increased cell stack operating pressures and temperatures, increased cell active area, incorporation of the ribbed substrate cell configuration at the bove conditions, and the introduction of higher performance electrocatalysts. The program results were successful with the primary accomplishments being: (1) fabrication of 10 sq ft ribbed substrate, cell components including higher performing electrocatalysts; (2) assembly of a 10 sq ft, 30-cell short stack; and (3) initial test of this stack at 120 psia and 405 F. These accomplishments demonstrate the feasibility of fabricating and handling large area cells using materials and processes that are oriented to low cost manufacture. An additional accomplishment under the program was the testing of two 3.7 sq ft short stacks at 12 psia/405 F to 5400 and 4500 hours respectively. These tests demonstrate the durability of the components and the cell stack configuration to a nominal 5000 hours at the higher pressure and temperature condition planned for the next electric utility power plant.

Assessment of Climate Driven Dynamics of Active Layer, Hydrological and Vegetation Status at the Qinghai-Tibet Plateau Using Dynamic Global Vegetation Model

NASA Astrophysics Data System (ADS)

Yang, Y.

2014-12-01

Extensive permafrost degradation starting from 1970s is observed at the Qinghai-Tibet Plateau , China. Degradation is attributed to an increase in mean annual ground temperature 0.1◦-0.5◦ C with mainly winter warming. The construction of Qinghai-Tibet Railway also influenced a state of permafrost in the area Permafrost degradation caused negative environmental consequences in the area. The areas covered by sand are expanding steadily making large concern of accelerating desertification. The general pathway of future joint dynamics of permafrost, vegetation and hydrological status at the Qinghai-Tibet Plateau is still poorly understood and foreseeable. Hydrology in the area is determined by heat-moisture dynamics of active layer. This dynamics is highly non-linear and depends as on external climatic variables temperature and precipitation, so on soil and rock properties (amount of sand against aeolian deposits in the Plateau) as well as vegetation cover, which determine thaw and freeze processes in the active layer and evaporation and run-off. SEVER DGVM was modified to include heat-moisture dynamics of active layer in the Qinghai-Tibet Plateau. SEVER DGVM imitates processes in 10 plant functional types at coarse resolution of 0.5 degrees. This model imitates behavior of average individual of each plant type in each grid cell through simulation years. Each of those grid cells processed independently. First, this model starts from "bare soil", placing a bit of each plant type and giving them some time to grow and achieve equilibrium. Then, including active layer thickness and soil moisture dynamics into this layer, it allows assessment of potential environmental dynamics in this area. Simulations demonstrate further degradation of pastureland and accelerating desertification processes in this vitally important water feed area for many Asian rivers. Negative environmental problems related to operation of Qinghai-Tibet are also assessed.

Active Tension Network model reveals an exotic mechanical state realized in epithelial tissues

NASA Astrophysics Data System (ADS)

Noll, Nicholas; Mani, Madhav; Heemskerk, Idse; Streicha, Sebastian; Shraiman, Boris

Mechanical interactions play a crucial role in epithelial morphogenesis, yet understanding the complex mechanisms through which stress and deformation affect cell behavior remains an open problem. Here we formulate and analyze the Active Tension Network (ATN) model, which assumes that mechanical balance of cells is dominated by cortical tension and introduces tension dependent active remodeling of the cortex. We find that ATNs exhibit unusual mechanical properties: i) ATN behaves as a fluid at short times, but at long times it supports external tension, like a solid; ii) its mechanical equilibrium state has extensive degeneracy associated with a discrete conformal - ''isogonal'' - deformation of cells. ATN model predicts a constraint on equilibrium cell geometry, which we demonstrate to hold in certain epithelial tissues. We further show that isogonal modes are observed in a fruit fly embryo, accounting for the striking variability of apical area of ventral cells and helping understand the early phase of gastrulation. Living matter realizes new and exotic mechanical states, understanding which helps understand biological phenomena.

Induction of apoptosis and cell cycle arrest in human colon carcinoma cells by Corema album leaves.

PubMed

León-González, Antonio J; Manson, Margaret M; López-Lizaro, Miguel; Navarro, Inmaculada; Martín-Cordero, Carmen

2014-01-01

The leaves of Corema album (Ericaceae), an endemic shrub which grows in Atlantic coastal areas of the Iberian Peninsula, are rich in flavonoids and other secondary metabolites. Silica gel column chromatography of the ethyl acetate extract from dried leaves was performed and a flavonic active fraction was obtained. The cytotoxic activity of this fraction was assessed using the colon cancer cell lines HCT116 and HT29. After 48 hours of treatment, cell viability was determined with luminescence-based ATPLite assay, showing IC50 values of 7.2 +/- 0.7 and 6.8 +/- 1.2 microg/mL, respectively. The study by flow cytometry revealed that the cytotoxicity of this fraction was mediated, at least in part, by induction of apoptosis and G2/M cell cycle arrest. The active fraction was then subjected to Sephadex LH-20 chromatography and two flavonoids were separated and identified as the flavanone pinocembrin and 2',4'-dihydroxychalcone after UV, MS and NMR analysis.

Weakening effect of cell permeabilizers on gram-negative bacteria causing biodeterioration.

PubMed

Alakomi, H-L; Paananen, A; Suihko, M-L; Helander, I M; Saarela, M

2006-07-01

Gram-negative bacteria play an important role in the formation and stabilization of biofilm structures on stone surfaces. Therefore, the control of growth of gram-negative bacteria offers a way to diminish biodeterioration of stone materials. The effect of potential permeabilizers on the outer membrane (OM) properties of gram-negative bacteria was investigated and further characterized. In addition, efficacy of the agents in enhancing the activity of a biocide (benzalkonium chloride) was assessed. EDTA, polyethylenimine (PEI), and succimer (meso-2,3-dimercaptosuccinic) were shown to be efficient permeabilizers of the members of Pseudomonas and Stenotrophomonas genera, as indicated by an increase in the uptake of a hydrophobic probe (1-N-phenylnaphthylamine) and sensitization to hydrophobic antibiotics. Visualization of Pseudomonas cells treated with EDTA or PEI by atomic force microscopy revealed damage in the outer membrane structure. PEI especially increased the surface area and bulges of the cells. Topographic images of EDTA-treated cells were compatible with events assigned for the effect of EDTA on outer membranes, i.e., release of lipopolysaccharide and disintegration of OM structure. In addition, the effect of EDTA treatment was visualized in phase-contrast images as large areas with varying hydrophilicity on cell surfaces. In liquid culture tests, EDTA and PEI supplementation enhanced the activity of benzalkonium chloride toward the target strains. Use of permeabilizers in biocide formulations would enable the use of decreased concentrations of the active biocide ingredient, thereby providing environmentally friendlier products.

[Algicidal activity against red-tide algaes by marine bacterial strain N3 isolated from a HABs area, southern China].

PubMed

Shi, Rong-jun; Huang, Hong-hui; Qi, Zhan-hui; Hu, Wei-an; Tian, Zi-yang; Dai, Ming

2013-05-01

A marine algicidal bacterium N3 was isolated from a HABs area in Mirs Bay, a subtropical bay, in southern China. Algicidal activity and algicidal mode against Phaeodactylum tricornutum, Scrippsiella trochoidea, Prorocentrum micans and Skeletonema costatum were observed by the liquid infection method. The results showed that there were no algicidal activities against P. tricornutum and S. costatum. However, when the bacterial volume fractions were 2% and 10% , S. trochoidea and P. micans could be killed, respectively. S. trochoidea cells which were exposed to strain N3 became irregular in shape and the cellular components lost their integrity and were decomposed. While, the P. micans cells became inflated and the cellular components aggregated, followed by cell lysis. Strain N3 killed S. trochoidea and P. micans directly, and the algicidal activities of the bacterial strain N3 was concentration-dependent. To S. trochoidea, 2% (V/V) of bacteria in algae showed the strongest algicidal activity, all of the S. trochoidea cells were killed within 120 h. But the growth rates of cells, in the 1% and 0. 1% treatment groups, were only slightly lower than that in the control group. In all treatment groups, the densities of strain N3 were in declining trends. While, to P. micans, 10% and 5% of bacteria in algae showed strong algicidal activities, 78% and 70% of the S. trochoidea were killed within 120 h, respectively. However, the number of S. trochoidea after exposure to 1% of bacterial cultures still increased up to 5 incubation days. And in the three treatment groups, the densities of strain N3 experienced a decrease process. The isolated strain N3 was identified as Bacillus sp. by morphological observation, physiological and biochemical characterization, and homology comparisons based on 16S rRNA sequences.

Turbulent Dynamics of Epithelial Cell Cultures

NASA Astrophysics Data System (ADS)

Blanch-Mercader, C.; Yashunsky, V.; Garcia, S.; Duclos, G.; Giomi, L.; Silberzan, P.

2018-05-01

We investigate the large length and long time scales collective flows and structural rearrangements within in vitro human bronchial epithelial cell (HBEC) cultures. Activity-driven collective flows result in ensembles of vortices randomly positioned in space. By analyzing a large population of vortices, we show that their area follows an exponential law with a constant mean value and their rotational frequency is size independent, both being characteristic features of the chaotic dynamics of active nematic suspensions. Indeed, we find that HBECs self-organize in nematic domains of several cell lengths. Nematic defects are found at the interface between domains with a total number that remains constant due to the dynamical balance of nucleation and annihilation events. The mean velocity fields in the vicinity of defects are well described by a hydrodynamic theory of extensile active nematics.

Synchronous activity in cat visual cortex encodes collinear and cocircular contours.

PubMed

Samonds, Jason M; Zhou, Zhiyi; Bernard, Melanie R; Bonds, A B

2006-04-01

We explored how contour information in primary visual cortex might be embedded in the simultaneous activity of multiple cells recorded with a 100-electrode array. Synchronous activity in cat visual cortex was more selective and predictable in discriminating between drifting grating and concentric ring stimuli than changes in firing rate. Synchrony was found even between cells with wholly different orientation preferences when their receptive fields were circularly aligned, and membership in synchronous groups was orientation and curvature dependent. The existence of synchrony between cocircular cells reinforces its role as a general mechanism for contour integration and shape detection as predicted by association field concepts. Our data suggest that cortical synchrony results from common and synchronous input from earlier visual areas and that it could serve to shape extrastriate response selectivity.

Thrombin and factor Xa link the coagulation system with liver fibrosis.

PubMed

Dhar, Ameet; Sadiq, Fouzia; Anstee, Quentin M; Levene, Adam P; Goldin, Robert D; Thursz, Mark R

2018-05-08

Thrombin activates hepatic stellate cells via protease-activated receptor-1. The role of Factor Xa (FXa) in hepatic fibrosis has not been elucidated. We aimed to evaluate the impact of FXa and thrombin in vitro on stellate cells and their respective inhibition in vivo using a rodent model of hepatic fibrosis. HSC-LX2 cells were incubated with FXa and/or thrombin in cell culture, stained for αSMA and relative gene expression and gel contraction calculated. C57BL/6 J mice were administered thioacetamide (TAA) for 8 weeks with Rivaroxaban (n = 15) or Dabigatran (n = 15). Control animals received TAA alone (n = 15). Fibrosis was scored and quantified using digital image analysis and hepatic tissue hydroxyproline estimated. Stellate cells treated with FXa and thrombin demonstrated upregulation of procollagen, TGF-beta, αSMA and significant cell contraction (43.48%+/- 4.12) compared to culturing with FXa or thrombin alone (26.90%+/- 8.90, p = 0.02; 13.1%+/- 9.84, p < 0.001). Mean fibrosis score, percentage area of fibrosis and hepatic hydroxyproline content (2.46 vs 4.08, p = 0.008; 2.02% vs 3.76%, p = 0.012; 276.0 vs 651.3, p = 0.0001) were significantly reduced in mice treated with the FXa inhibitor compared to control mice. FXa inhibition was significantly more effective than thrombin inhibition in reducing percentage area of fibrosis and hepatic hydroxyproline content (2.02% vs 3.70%,p = 0.031; 276.0 vs 413.1,p = 0.001). FXa promotes stellate cell contractility and activation. Early inhibition of coagulation using a FXa inhibitor significantly reduces TAA induced murine liver fibrosis and may be a viable treatment for liver fibrosis in patients.

Hypoxia-inducible factor-1 signalling promotes goblet cell hyperplasia in airway epithelium

PubMed Central

Polosukhin, Vasiliy V; Cates, Justin M; Lawson, William E; Milstone, Aaron P; Matafonov, Anton G; Massion, Pierre P; Lee, Jae Woo; Randell, Scott H; Blackwell, Timothy S

2018-01-01

Goblet cell hyperplasia is a common feature of chronic obstructive pulmonary disease (COPD) airways, but the mechanisms that underlie this epithelial remodelling in COPD are not understood. Based on our previous finding of hypoxia-inducible factor-1α (HIF-1α) nuclear localization in large airways from patients with COPD, we investigated whether hypoxia-inducible signalling could influence the development of goblet cell hyperplasia. We evaluated large airway samples obtained from 18 lifelong non-smokers and 13 former smokers without COPD, and 45 former smokers with COPD. In these specimens, HIF-1α nuclear staining occurred almost exclusively in COPD patients in areas of airway remodelling. In COPD patients, 93.2 ± 3.9% (range 65 – 100%) of goblet cells were HIF-1α positive in areas of goblet cell hyperplasia, whereas nuclear HIF-1α was not detected in individuals without COPD or in normal-appearing pseudostratified epithelium from COPD patients. To determine the direct effects of hypoxia-inducible signalling on epithelial cell differentiation in vitro, human bronchial epithelial cells (HBECs) were grown in air-liquid interface cultures under hypoxia (1% O2) or following treatment with a selective HIF-1α stabilizer, (2R)-[(4-biphenylylsulphonyl)amino]-N-hydroxy-3-phenyl-propionamide (BiPS). HBECs grown in hypoxia or with BiPS treatment were characterized by HIF-1α activation, carbonic anhydrase IX expression, mucus-producing cell hyperplasia and increased expression of MUC5AC. Analysis of signal transduction pathways in cells with HIF-1α activation showed increased ERK1/2 phosphorylation without activation of epidermal growth factor receptor, Ras, PI3K-Akt or STAT6. These data indicate an important effect of hypoxia-inducible signalling on airway epithelial cell differentiation and identify a new potential target to limit mucus production in COPD. PMID:21557221

Decreased expression of CD69 in chronic fatigue syndrome in relation to inflammatory markers: evidence for a severe disorder in the early activation of T lymphocytes and natural killer cells.

PubMed

Mihaylova, Ivana; DeRuyter, Marcel; Rummens, Jean-Luc; Bosmans, Eugene; Maes, Michael

2007-08-01

There is some evidence that patients with chronic fatigue syndrome (CFS) suffer from immune abnormalities, such as immune activation and decreased immune cell responsivity upon polyclonal stimili. This study was designed to evaluate lymphocyte activation in CFS by using a CD69 expression assay. CD69 acts as a costimulatory molecule for T- and natural killer (NK) cell activation. We collected whole blood from CFS patients, who met CDC criteria, and healthy volunteers. The blood samples were stimulated with mitogens during 18 h and the levels of activated T and NK cells expressing CD69 were measured on a Coulter Epics flow cytometer using a three color immunofluorescence staining protocol. The expression of the CD69 activation marker on T cells (CD3+, CD3+CD4+, and CD3+CD8+) and on NK cells (CD45+CD56+) was significantly lower in CFS patients than in healthy subjects. These differences were significant to the extent that a significant diagnostic performance was obtained, i.e. the area under the ROC curve was around 89%. No differences either in the number of leukocytes or in the number or percentage of lymphocytes, i.e. CD3, CD4, CD8 and CD19, could be found between CFS patients and the controls. Patients with CFS show defects in T- and NK cell activation. Since induction of CD69 surface expression is dependent on the activation of the protein kinase C (PKC) activation pathway, it is suggested that in CFS there is a disorder in the early activation of the immune system involving PKC.

PAS kinase as a nutrient sensor in neuroblastoma and hypothalamic cells required for the normal expression and activity of other cellular nutrient and energy sensors.

PubMed

Hurtado-Carneiro, Verónica; Roncero, Isabel; Blazquez, Enrique; Alvarez, Elvira; Sanz, Carmen

2013-12-01

PAS kinase (PASK) is a nutrient sensor that is highly conserved throughout evolution. PASK-deficient mice reveal a metabolic phenotype similar to that described in S6 kinase-1 S6K1-deficient mice that are protected against obesity. Hypothalamic metabolic sensors, such as AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR), play an important role in feeding behavior, the homeostasis of body weight, and energy balance. These sensors respond to changes in nutrient levels in the hypothalamic areas involved in feeding behavior and in neuroblastoma N2A cells, and we have recently reported that those effects are modulated by the anorexigenic peptide glucagon-like peptide-1 (GLP-1). Here, we identified PASK in both N2A cells and rat VMH and LH areas and found that its expression is regulated by glucose and GLP-1. High levels of glucose decreased Pask gene expression. Furthermore, PASK-silenced N2A cells record an impaired response by the AMPK and mTOR/S6K1 pathways to changes in glucose levels. Likewise, GLP-1 effect on the activity of AMPK, S6K1, and other intermediaries of both pathways and the regulatory role at the level of gene expression were also blocked in PASK-silenced cells. The absence of response to low glucose concentrations in PASK-silenced cells correlates with increased ATP content, low expression of mRNA coding for AMPK upstream kinase LKB1, and enhanced activation of S6K1. Our findings indicate that, at least in N2A cells, PASK is a key kinase in GLP-1 actions and exerts a coordinated response with the other metabolic sensors, suggesting that PASK might play an important role in feeding behavior.

Cytochemical analysis of alkaline phosphatase and esterase activities and of lectin-binding and anionic sites in rat and mouse Peyer's patch M cells.

PubMed

Owen, R L; Bhalla, D K

1983-10-01

M cells in Peyer's patch follicle epithelium endocytose and transport luminal materials to intraepithelial lymphocytes. We examined (1) enzymatic characteristics of the epithelium covering mouse and rat Peyer's patches by using cytochemical techniques, (2) distribution of lectin-binding sites by peroxidase-labeled lectins, and (3) anionic site distribution by using cationized ferritin to develop a profile of M cell surface properties. Alkaline phosphatase activity resulted in deposits of dense reaction product over follicle surfaces but was markedly reduced over M cells, unlike esterase which formed equivalent or greater product over M cells. Concanavalin A, ricinus communis agglutinin, wheat germ agglutinin and peanut agglutinin reacted equally with M cells and with surrounding enterocytes over follicle surfaces. Cationized ferritin distributed in a random fashion along microvillus membranes of both M cells and enterocytes, indicating equivalent anionic site distribution. Staining for alkaline phosphatase activity provides a new approach for distinguishing M cells from enterocytes at the light microscopic level. Identical binding of lectins indicates that M cells and enterocytes share common glycoconjugates even though molecular groupings may differ. Lectin binding and anionic charge similarities of M cells and enterocytes may facilitate antigen sampling by M cells of particles and compounds that adhere to intestinal surfaces in non-Peyer's patch areas.

The intratumoral distribution of radiolabeled 177Lu-BR96 monoclonal antibodies changes in relation to tumor histology over time in a syngeneic rat colon carcinoma model.

PubMed

Örbom, Anders; Eriksson, Sophie E; Elgström, Erika; Ohlsson, Tomas; Nilsson, Rune; Tennvall, Jan; Strand, Sven-Erik

2013-08-01

The therapeutic effect of radioimmunotherapy depends on the distribution of the absorbed dose in relation to viable cancer cells within the tumor, which in turn is a function of the activity distribution. The aim of this study was to investigate the distribution of (177)Lu-DOTA-BR96 monoclonal antibodies targeting the Lewis Y antigen over 7 d using a syngeneic rat model of colon carcinoma. Thirty-eight tumor-bearing rats were intravenously given 25 or 50 MBq of (177)Lu-DOTA-BR96 per kilogram of body weight and were sacrificed 2, 8, 24, 48, 72, 96, 120, or 168 h after injection, with activity measured in blood and tumor samples. Adjacent cryosections of each tumor were analyzed in 3 ways: imaging using a silicon-strip detector for digital autoradiography, staining for histologic characterization, or staining to determine the distribution of the antigen, vasculature, and proliferating cells using immunohistochemistry. Absorbed-dose rate distribution images at the moment of sacrifice were calculated using the activity distribution and a point-dose kernel. The correlations between antigen expression and both activity uptake and absorbed-dose rate were calculated for several regions of interest in each tumor. Nine additional animals with tumors were given unlabeled antibody to evaluate possible immunologic effects. At 2-8 h after injection, activity was found in the tumor margins; at 24 h, in viable antigen-expressing areas within the tumor; and at 48 h and later, increasingly in antigen-negative areas of granulation tissue. The correlation between antigen expression and both the mean activity and the absorbed-dose rate in regions of interest changed from positive to negative after 24 h after injection. Antigen-negative areas also increased over time in animals injected with unlabeled BR96, compared with untreated tumors. The results indicate that viable Lewis Y-expressing tumor cells are most efficiently treated during the initial uptake period. The activity then seems to remain in these initial uptake regions after the elimination of tumor cells and formation of granulation tissue. Further studies using these techniques could aid in determining the effects of the intratumoral activity distribution on overall therapeutic efficacy.

Phenothiaziniums as putative photobactericidal agents for red blood cell concentrates.

PubMed

Wainwright, M; Phoenix, D A; Smillie, T E; Wareing, D R

2001-10-01

The antibacterial activities of Methylene Blue and several of its congeners were measured against Yersinia enterocolitica, a gram-negative pathogen known to exhibit significant growth at 4 degrees C and thus constituting a threat to red blood cell concentrates which are stored at this temperature. None of the derivatives was highly active in dark conditions, as expected, but on illumination using a lamp emitting light in the waveband 615-645 nm, considerable bactericidal activity was noted using similar photosensitizer concentrations to those used elsewhere to inactivate blood-borne viruses. Two novel compounds in this area, the phenothiazinium New Methylene Blue N and the phenoxazinium Brilliant Cresyl Blue, exhibited bactericidal activity at lower concentrations than both of the established phenothiaziniums, Methylene Blue and Toluidine Blue O and the recently published blood photovirucidal agent 1,9-Dimethyl Methylene Blue. The photoactivity of these compounds was undiminished in the presence of red blood cells.

Spontaneous calcium transients in the immature adult-born neurons of the olfactory bulb.

PubMed

Maslyukov, Anatoliy; Li, Kaizhen; Su, Xin; Kovalchuk, Yury; Garaschuk, Olga

2018-06-06

Spontaneous neuronal activity and concomitant intracellular Ca 2+ signaling are abundant during early perinatal development and are well known for their key role in neuronal proliferation, migration, differentiation and wiring. However, much less is known about the in vivo patterns of spontaneous Ca 2+ signaling in immature adult-born cells. Here, by using two-photon Ca 2+ imaging, we analyzed spontaneous in vivo Ca 2+ signaling in adult-born juxtaglomerular cells of the mouse olfactory bulb over the time period of 5 weeks, from the day of their arrival in the glomerular layer till their stable integration into the preexisting neural network. We show that spontaneous Ca 2+ transients are ubiquitously present in adult-born cells right after their arrival, require activation of voltage-gated Na + channels and are little sensitive to isoflurane anesthesia. Interestingly, several parameters of this spontaneous activity, such as the area under the curve, the time spent in the active state as well as the fraction of continuously active cells show a bell-shaped dependence on cell's age, all peaking in 3-4 weeks old cells. This data firmly document the in vivo presence of spontaneous Ca 2+ signaling during the layer-specific maturation of adult-born neurons in the olfactory bulb and motivate further analyses of the functional role(s) of this activity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Area efficient layout design of CMOS circuit for high-density ICs

NASA Astrophysics Data System (ADS)

Mishra, Vimal Kumar; Chauhan, R. K.

2018-01-01

Efficient layouts have been an active area of research to accommodate the greater number of devices fabricated on a given chip area. In this work a new layout of CMOS circuit is proposed, with an aim to improve its electrical performance and reduce the chip area consumed. The study shows that the design of CMOS circuit and SRAM cells comprising tapered body reduced source fully depleted silicon on insulator (TBRS FD-SOI)-based n- and p-type MOS devices. The proposed TBRS FD-SOI n- and p-MOSFET exhibits lower sub-threshold slope and higher Ion to Ioff ratio when compared with FD-SOI MOSFET and FinFET technology. Other parameters like power dissipation, delay time and signal-to-noise margin of CMOS inverter circuits show improvement when compared with available inverter designs. The above device design is used in 6-T SRAM cell so as to see the effect of proposed layout on high density integrated circuits (ICs). The SNM obtained from the proposed SRAM cell is 565 mV which is much better than any other SRAM cell designed at 50 nm gate length MOS device. The Sentaurus TCAD device simulator is used to design the proposed MOS structure.

Novel optical methodologies in studying mechanical signal transduction in mammalian cells

NASA Technical Reports Server (NTRS)

Stamatas, G. N.; McIntire, L. V.

1999-01-01

For the last 3 decades evidence has been accumulating that some types of mammalian cells respond to their mechanically active environment by altering their morphology, growth rate, and metabolism. The study of such responses is very important in understanding, physiological and pathological conditions ranging from bone formation to atherosclerosis. Obtaining this knowledge has been the goal for an active research area in bioengineering termed cell mechanotransduction. The advancement of optical methodologies used in cell biology research has given the tools to elucidate cellular mechanisms that would otherwise be impossible to visualize. Combined with molecular biology techniques, they give engineers invaluable tools in understanding the chemical pathways involved in mechanotransduction. Herein we briefly review the current knowledge on mechanical signal transduction in mammalian cells, focusing on the application of novel optical techniques in the ongoing research.

An Automatic Segmentation Method Combining an Active Contour Model and a Classification Technique for Detecting Polycomb-group Proteinsin High-Throughput Microscopy Images.

PubMed

Gregoretti, Francesco; Cesarini, Elisa; Lanzuolo, Chiara; Oliva, Gennaro; Antonelli, Laura

2016-01-01

The large amount of data generated in biological experiments that rely on advanced microscopy can be handled only with automated image analysis. Most analyses require a reliable cell image segmentation eventually capable of detecting subcellular structures.We present an automatic segmentation method to detect Polycomb group (PcG) proteins areas isolated from nuclei regions in high-resolution fluorescent cell image stacks. It combines two segmentation algorithms that use an active contour model and a classification technique serving as a tool to better understand the subcellular three-dimensional distribution of PcG proteins in live cell image sequences. We obtained accurate results throughout several cell image datasets, coming from different cell types and corresponding to different fluorescent labels, without requiring elaborate adjustments to each dataset.

Adenosinergic Immunosuppression by Human Mesenchymal Stromal Cells Requires Co-Operation with T cells.

PubMed

Kerkelä, Erja; Laitinen, Anita; Räbinä, Jarkko; Valkonen, Sami; Takatalo, Maarit; Larjo, Antti; Veijola, Johanna; Lampinen, Milla; Siljander, Pia; Lehenkari, Petri; Alfthan, Kaija; Laitinen, Saara

2016-03-01

Mesenchymal stem/stromal cells (MSCs) have the capacity to counteract excessive inflammatory responses. MSCs possess a range of immunomodulatory mechanisms, which can be deployed in response to signals in a particular environment and in concert with other immune cells. One immunosuppressive mechanism, not so well-known in MSCs, is mediated via adenosinergic pathway by ectonucleotidases CD73 and CD39. In this study, we demonstrate that adenosine is actively produced from adenosine 5'-monophosphate (AMP) by CD73 on MSCs and MSC-derived extracellular vesicles (EVs). Our results indicate that although MSCs express CD39 at low level and it colocalizes with CD73 in bulge areas of membranes, the most efficient adenosine production from adenosine 5'-triphosphate (ATP) requires co-operation of MSCs and activated T cells. Highly CD39 expressing activated T cells produce AMP from ATP and MSCs produce adenosine from AMP via CD73 activity. Furthermore, adenosinergic signaling plays a role in suppression of T cell proliferation in vitro. In conclusion, this study shows that adenosinergic signaling is an important immunoregulatory mechanism of MSCs, especially in situations where ATP is present in the extracellular environment, like in tissue injury. An efficient production of immunosuppressive adenosine is dependent on the concerted action of CD39-positive immune cells with CD73-positive cells such as MSCs or their EVs. © 2016 AlphaMed Press.

Fibroblast growth factor-2 regulates the cell function of human dental pulp cells.

PubMed

Shimabukuro, Yoshio; Ueda, Maki; Ozasa, Masao; Anzai, Jun; Takedachi, Masahide; Yanagita, Manabu; Ito, Masako; Hashikawa, Tomoko; Yamada, Satoru; Murakami, Shinya

2009-11-01

Homeostasis and tissue repair of dentin-pulp complex are attributed to dental pulp tissue and several growth factors. Dental pulp cells play a pivotal role in homeostasis of dentin-pulp complex and tissue responses after tooth injury. Among these cytokines, fibroblast growth factor (FGF)-2 has multifunctional biologic activity and is known as a signaling molecule that induces tissue regeneration. In this study, we examined the effects of FGF-2 on growth, migration, and differentiation of human dental pulp cells (HDPC). HDPC were isolated from healthy dental pulp. Cellular response was investigated by [(3)H]-thymidine incorporation into DNA. Cytodifferentiation was examined by alkaline phosphatase (ALPase) assay and cytochemical staining of calcium by using alizarin red. Migratory activity was determined by counting the cells migrating into cleared area that had introduced with silicon block. FGF-2 activated HDPC growth and migration but suppressed ALPase activity and calcified nodule formation. Interestingly, HDPC, which had been pretreated with FGF-2, showed increased ALPase activity and calcified nodule formation when subsequently cultured without FGF-2. These results suggest that FGF-2 potentiates cell growth and accumulation of HDPC that notably did not disturb cytodifferentiation of the cells later. Thus, FGF-2 is a favorable candidate for pulp capping agent. These results provide new evidence for the possible involvement of FGF-2 not only in homeostasis but also in regeneration of dentin-pulp complex.

Running increases neurogenesis without retinoic acid receptor activation in the adult mouse dentate gyrus.

PubMed

Aberg, Elin; Perlmann, Thomas; Olson, Lars; Brené, Stefan

2008-01-01

Both vitamin A deficiency and high doses of retinoids can result in learning and memory impairments, depression as well as decreases in cell proliferation, neurogenesis and cell survival. Physical activity enhances hippocampal neurogenesis and can also exert an antidepressant effect. Here we elucidate a putative link between running, retinoid signaling, and neurogenesis in hippocampus. Adult transgenic reporter mice designed to detect ligand-activated retinoic acid receptors (RAR) or retinoid X receptors (RXR) were used to localize the distribution of activated RAR or RXR at the single-cell level in the brain. Two months of voluntary wheel-running induced an increase in hippocampal neurogenesis as indicated by an almost two-fold increase in doublecortin-immunoreactive cells. Running activity was correlated with neurogenesis. Under basal conditions a distinct pattern of RAR-activated cells was detected in the granule cell layer of the dentate gyrus (DG), thalamus, and cerebral cortex layers 3-4 and to a lesser extent in hippocampal pyramidal cell layers CA1-CA3. Running did not change the number of RAR-activated cells in the DG. There was no correlation between running and RAR activation or between RAR activation and neurogenesis in the DG of hippocampus. Only a few scattered activated retinoid X receptors were found in the DG under basal conditions and after wheel-running, but RXR was detected in other areas such as in the hilus region of hippocampus and in layer VI of cortex cerebri. RAR agonists affect mood in humans and reduce neurogenesis, learning and memory in animal models. In our study, long-term running increased neurogenesis but did not alter RAR ligand activation in the DG in individually housed mice. Thus, our data suggest that the effects of exercise on neurogenesis and other plasticity changes in the hippocampal formation are mediated by mechanisms that do not involve retinoid receptor activation. (c) 2008 Wiley-Liss, Inc.

Immunolocalization of receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) in Meckel's cartilage compared with developing endochondral bones in mice

PubMed Central

Sakakura, Yasunori; Tsuruga, Eichi; Irie, Kazuharu; Hosokawa, Yoichiro; Nakamura, Hiroaki; Yajima, Toshiniko

2005-01-01

We examined the immunolocalization of receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) in areas of resorption caused by osteoclasts/chondroclasts on embryonic days 14–16 (E14–16) in Meckel's cartilage, and compared the results with those in endochondral bones in mice. Intense RANKL and OPG immunoreactivity was detected in the chondrocytes in Meckel's cartilage. On E15, when the incisor teeth were closest to the middle portion of Meckel's cartilage, tartrate-resistant acid phosphatase (TRAP)-positive cells appeared on the lateral side of the cartilage. Furthermore, the dental follicle showed moderate immunoreactivity for RANKL and OPG, whereas osteoblasts derived from perichondral cells were immunonegative for RANKL and OPG in that area. On E16, cartilage resorption by TRAP-positive cells had progressed at the differential position, and intensely immunoreactive products of RANKL were overlapped on and found to exist next to TRAP-positive cells in the resorption area. In developing metatarsal tissue, OPG immunoreactivity was intense in periosteal osteoblasts, whereas RANKL was only faintly seen in some of the periosteal cells. In epiphyseal chondrocytes of the developing femur, RANKL immunoreactivity was moderate, and OPG scarcely detected. These results indicate a peculiarity of RANKL and OPG immunolocalization in resorption of Meckel's cartilage. Growth of the incisor teeth may be involved in the time- and position-specific resorption of Meckel's cartilage through local regulation of the RANKL/OPG system in dental follicular cells and periosteal osteoblasts, whereas RANKL and OPG in chondrocytes seem to contribute to resorption through regulation of the chondroclast function. PMID:16191162

Comparative analysis of Met-enkephalin, galanin and GABA immunoreactivity in the developing trout preoptic-hypophyseal system.

PubMed

Rodríguez Díaz, M A; Candal, E; Santos-Durán, G N; Adrio, F; Rodríguez-Moldes, I

2011-08-01

We studied the organization of Met-enkephalin-containing cells and fibers in the developing preoptic-hypophyseal system of the brown trout (Salmo trutta fario) by immunohistochemistry and determined the relationship of these cells and fibers to the galaninergic and GABAergic systems. Met-enkephalin immunoreactivity was observed in cells in the preoptic area, the hypothalamus and the pituitary of late larvae. In the hypophysis, a few Met-enkephalin-containing cells were present in all divisions of the adenohypophysis, and some immunoreactive fibers were present in the interdigitations of the neural lobe with the proximal pars distalis. Concurrently, GABAergic fibers innervated the anterior and posterior neural lobe. Galanin cells coexisted with Met-enkephalin cells in neuronal groups of the preoptic-hypophyseal system. Galaninergic and GABAergic fibers innervated the preoptic and hypothalamic areas, but GABAergic fibers containing galanin were not observed. These results indicate that Met-enkephalin, galanin and GABA may modulate neuroendocrine activities in the preoptic area, hypothalamus and pituitary during the transition from larval to juvenile period. To better know how the development of the trout preoptic-hypophyseal system takes place, we studied the patterns of cell proliferation and expression of Pax6, a conserved transcription factor involved in the hypophysis development. Pax6 expressing cells and proliferating cells were present in the Rathke's pouch, the hypothalamus and the hypophysis of early larvae. In late larvae, Pax6 expression was no longer observed in these areas, and the density of proliferating cells largely decreased throughout development, although they remained in the hypophysis of late larvae and juveniles, suggesting that Pax6 might play an important role in the early regionalization of the pituitary in the trout. Copyright © 2011 Elsevier Inc. All rights reserved.

Triggered by asphyxia neurogenesis seems not to be an endogenous repair mechanism, gliogenesis more like it.

PubMed

Keilhoff, G; John, R; Langnaese, K; Schweizer, H; Ebmeyer, U

2010-12-15

We analyzed the long-term consequences of asphyxial cardiac arrest for hippocampal cell proliferation in rats to evaluate if the ischaemia-induced degenerated CA1 region may be repopulated by endogenous (stem) cells. Studies were performed in an asphyxial cardiac arrest model with 5 minutes of asphyxiation and three different survival times: 7, 21, and 90 days. Sham-operated non-asphyxiated rats served as control. Cell proliferation was studied by labeling dividing cells with 5-bromo-2'-deoxy-uridine (BrdU). The neurodegenerative/regenerative pattern at single cell levels was monitored by immunohistochemistry. Alterations of gene expression were analyzed by real-time quantitative RT-PCR. Analysis of BrdU-incorporation demonstrated an increase at 7, 21 as well as 90 days after global ischaemia in the hippocampal CA1 pyramidal cell layer. Similar results were found in the dentate gyrus. Differentiation of BrdU-positive cells, investigated by cell phenotype-specific double fluorescent labeling, showed increased neurogenesis only in the dentate gyrus of animals surviving the cardiac arrest for 7 days. The majority of newcomers, especially in the damaged CA1 region, consisted of glial cells. Moreover, asphyxia seemed to be able to induce the migration of microglia and astroglia from adjacent areas into the damaged area and/or the activation of resident cells. In addition, we show microglia proliferation/activation even 90 days after cardiac arrest. This morphological finding was confirmed by PCR analysis. The results indicate that asphyxia triggers cell proliferation in general and gliogenesis in particular - a possible pro-reparative event. Furthermore, from the finding of microglia proliferation up to 90 days after insult we conclude that delayed cell death processes take place which should be considered for further therapy strategies. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

fMRI evidence for areas that process surface gloss in the human visual cortex

PubMed Central

Sun, Hua-Chun; Ban, Hiroshi; Di Luca, Massimiliano; Welchman, Andrew E.

2015-01-01

Surface gloss is an important cue to the material properties of objects. Recent progress in the study of macaque’s brain has increased our understating of the areas involved in processing information about gloss, however the homologies with the human brain are not yet fully understood. Here we used human functional magnetic resonance imaging (fMRI) measurements to localize brain areas preferentially responding to glossy objects. We measured cortical activity for thirty-two rendered three-dimensional objects that had either Lambertian or specular surface properties. To control for differences in image structure, we overlaid a grid on the images and scrambled its cells. We found activations related to gloss in the posterior fusiform sulcus (pFs) and in area V3B/KO. Subsequent analysis with Granger causality mapping indicated that V3B/KO processes gloss information differently than pFs. Our results identify a small network of mid-level visual areas whose activity may be important in supporting the perception of surface gloss. PMID:25490434

Acidic and alkaline pretreatments of activated carbon and their effects on the performance of air-cathodes in microbial fuel cells.

PubMed

Wang, Xin; Gao, Ningshengjie; Zhou, Qixing; Dong, Heng; Yu, Hongbing; Feng, Yujie

2013-09-01

Activated carbon (AC) is a high performing and cost effective catalyst for oxygen reduction reactions (ORRs) of air-cathodes in microbial fuel cells (MFCs). Acidic (HNO3) and alkaline (KOH) pretreatments on AC at low temperature (85°C) are conducted to enhance the performance of MFCs. The alkaline pretreatment increased the power density by 16% from 804±70 to 957±31 mW m(-2), possibly due to the decrease of ohmic resistance (from 20.58 to 19.20 Ω) and the increase of ORR activities provided by the adsorbed hydroxide ion and extra micropore area/volume after alkaline pretreatment. However, acidic pretreatment decreased the power output to 537±36 mW m(-2), which can be mainly attributed to the corrosion by adsorbed proton at the interface of AC powder and stainless steel mesh and the decreased pore area. Copyright © 2013 Elsevier Ltd. All rights reserved.

Role of Bruton’s tyrosine kinase in myeloma cell migration and induction of bone disease

PubMed Central

Bam, Rakesh; Ling, Wen; Khan, Sharmin; Pennisi, Angela; Venkateshaiah, Sathisha Upparahalli; Li, Xin; van Rhee, Frits; Usmani, Saad; Barlogie, Bart; Shaughnessy, John; Epstein, Joshua; Yaccoby, Shmuel

2014-01-01

Myeloma cells typically grow in bone, recruit osteoclast precursors and induce their differentiation and activity in areas adjacent to tumor foci. Bruton’s tyrosine kinase (BTK), of the TEC family, is expressed in hematopoietic cells and is particularly involved in B-lymphocyte function and osteoclastogenesis. We demonstrated BTK expression in clinical myeloma plasma cells, interleukin (IL) –6– or stroma–dependent cell lines and osteoclasts. SDF-1 induced BTK activation in myeloma cells and BTK inhibition by small hairpin RNA or the small molecule inhibitor, LFM-A13, reduced their migration toward stromal cell-derived factor-1 (SDF-1). Pretreatment with LFM-A13 also reduced in vivo homing of myeloma cells to bone using bioluminescence imaging in the SCID-rab model. Enforced expression of BTK in myeloma cell line enhanced cell migration toward SDF-1 but had no effect on short-term growth. BTK expression was correlated with cell-surface CXCR4 expression in myeloma cells (n = 33, r = 0.81, P < 0.0001), and BTK gene and protein expression was more profound in cell-surface CXCR4-expressing myeloma cells. BTK was not upregulated by IL-6 while its inhibition had no effect on IL-6 signaling in myeloma cells. Human osteoclast precursors also expressed BTK and cell-surface CXCR4 and migrated toward SDF-1. LFM-A13 suppressed migration and differentiation of osteoclast precursors as well as bone-resorbing activity of mature osteoclasts. In primary myeloma-bearing SCID-rab mice, LFM-A13 inhibited osteoclast activity, prevented myeloma-induced bone resorption and moderately suppressed myeloma growth. These data demonstrate BTK and cell-surface CXCR4 association in myeloma cells and that BTK plays a role in myeloma cell homing to bone and myeloma-induced bone disease. PMID:23456977

Simultaneous recording of mouse retinal ganglion cells during epiretinal or subretinal stimulation

PubMed Central

Sim, S.L.; Szalewski, R.J.; Johnson, L.J.; Akah, L.E.; Shoemaker, L.E.; Thoreson, W.B.; Margalit, E.

2015-01-01

We compared response patterns and electrical receptive fields (ERF) of retinal ganglion cells (RGCs) during epiretinal and subretinal electrical stimulation of isolated mouse retina. Retinas were stimulated with an array of 3200 independently controllable electrodes. Four response patterns were observed: a burst of activity immediately after stimulation (Type I cells, Vision Research (2008), 48, 1562–1568), delayed bursts beginning >25 ms after stimulation (Type II), a combination of both (Type III), and inhibition of ongoing spike activity. Type I responses were produced more often by epiretinal than subretinal stimulation whereas delayed and inhibitory responses were evoked more frequently by subretinal stimulation. Response latencies were significantly shorter with epiretinal than subretinal stimulation. These data suggest that subretinal stimulation is more effective at activating intraretinal circuits than epiretinal stimulation. There was no significant difference in charge threshold between subretinal and epiretinal configurations. ERFs were defined by the stimulating array surface area that successfully stimulated spikes in an RGC. ERFs were complex in shape, similar to receptive fields mapped with light. ERF areas were significantly smaller with subretinal than epiretinal stimulation. This may reflect the greater distance between stimulating electrodes and RGCs in the subretinal configuration. ERFs for immediate and delayed responses mapped within the same Type III cells differed in shape and size, consistent with different sites and mechanisms for generating these two response types. PMID:24863584

Antiviral Activity of Intranasally Applied Human Leukocyte Interferon

PubMed Central

Greenberg, Stephen B.; Harmon, Maurice W.; Johnson, Paul E.; Couch, Robert B.

1978-01-01

Previous studies in our laboratory have demonstrated that the development of antiviral activity of human leukocyte interferon (IF) in nasal epithelial cells is time and concentration dependent and that the loss of intranasally applied human leukocyte IF is rapid. The present studies compared the activity of IF applied intranasally either by nasal drops or by a saturated cotton pledget. Adult volunteers had IF applied to an area of nasal mucosa (2 by 2 cm2) either by repeated nose drops or by a saturated cotton pledget that was applied to the nasal mucosa and left in place for 1 h. Nasal epithelial cells scraped from the area of application, as well as the control, untreated side of the same volunteers, were challenged with vesicular stomatitis virus. No significant reduction in mean virus yield was found in volunteers who received 80,000 U by nose drops. Significant reduction (P < 0.025) in mean virus yield was found in cells obtained 4 h after 80,000, 50,000, or 20,000 U was applied by cotton pledget or in volunteers pretreated with oral antihistamines prior to receiving 80,000 U by nose drops. These experiments indicate that nasal epithelial cells can be made antiviral in vivo by application of human leukocyte IF. However, practical usefulness of human leukocyte IF for prophylaxis against respiratory viral infections may depend on the method of local application. PMID:214028

Ultra-fine Pt nanoparticles on graphene aerogel as a porous electrode with high stability for microfluidic methanol fuel cell

NASA Astrophysics Data System (ADS)

Kwok, Y. H.; Tsang, Alpha C. H.; Wang, Yifei; Leung, Dennis Y. C.

2017-05-01

Platinum-decorated graphene aerogel as a porous electrode for flow-through direct methanol microfluidic fuel cell is introduced. Ultra-fine platinum nanoparticles with size ranged from diameter 1.5 nm-3 nm are evenly anchored on the graphene nanosheets without agglomeration. The electrode is characterized by scanning electron microscopy, transmission electron microscopy and energy-dispersive X-ray spectroscopy. Catalytic activity is confirmed by cyclic voltammetry. The electroactive surface area and catalytic activity of platinum on graphene oxide (Pt/GO) are much larger than commercial platinum on carbon black (Pt/C). A counterflow microfluidic fuel cell is designed for contrasting the cell performance between flow-over type and flow-through type electrodes using Pt/C on carbon paper and Pt/GO, respectively. The Pt/GO electrode shows 358% increment in specific power compared with Pt/C anode. Apart from catalytic activity, the effect of porous electrode conductivity to cell performance is also studied. The conductivity of the porous electrode should be further enhanced to achieve higher cell performance.

Synaptic connectivity and spatial memory: a topological approach

NASA Astrophysics Data System (ADS)

Milton, Russell; Babichev, Andrey; Dabaghian, Yuri

2015-03-01

In the hippocampus, a network of place cells generates a cognitive map of space, in which each cell is responsive to a particular area of the environment - its place field. The peak response of each cell and the size of each place field have considerable variability. Experimental evidence suggests that place cells encode a topological map of space that serves as a basis of spatial memory and spatial awareness. Using a computational model based on Persistent Homology Theory we demonstrate that if the parameters of the place cells spiking activity fall inside of the physiological range, the network correctly encodes the topological features of the environment. We next introduce parameters of synaptic connectivity into the model and demonstrate that failures in synapses that detect coincident neuronal activity lead to spatial learning deficiencies similar to the ones that are observed in rodent models of neurodegenerative diseases. Moreover, we show that these learning deficiencies may be mitigated by increasing the number of active cells and/or by increasing their firing rate, suggesting the existence of a compensatory mechanism inherent to the cognitive map.

Differences in cytokinin control on cellular dynamics of zucchini cotyledons cultivated in two experimental systems.

PubMed

Stoynova-Bakalova, E; Petrov, P; Gigova, L; Ivanova, N

2011-01-01

The effect of endogenous cytokinins on the pattern of palisade cell division post-germination does not depend on the conditions of cotyledon development -in planta (attached to seedlings) or in vitro (isolated from dry zucchini seeds and cultured on water). In cotyledons originating from 4-day-old seedlings (experimental system 1), exogenous cytokinin temporarily (in the first 2 day of cultivation) enhanced post-mitotic cell enlargement of palisade cells, mainly due to enhanced water uptake and use of cell storage compounds, all of which lead to cotyledon senescence. Cytokinin is not able to resume the completed palisade cell division on day 5. As a result, the number of cells and the final areas of treated and control cotyledons are quite similar. By contrast, the effects of cytokinin on cotyledons isolated from dry seeds (experimental system 2) are better expressed, promoting an increase in number of palisade cells accompanied by additional cotyledon area enlargement. However, the prolonged post-mitotic cell expansion in control cotyledons compensates for the reduced speed of cell growth and division activity and decreases differences in final cotyledon area between treatments. The results define cell division as the primary target of cytokinin stimulation in cotyledon tissues competent for division, and determine the temporal patterns of palisade cell cycling related to cotyledon age. This knowledge permits a better choice of experimental system to study effects on cell proliferation and cell growth, as well as cell enlargement and senescence-related events using physiologically homogeneous material. © 2010 German Botanical Society and The Royal Botanical Society of the Netherlands.

Recent advances in nontoxic Escherichia coli heat-labile toxin and its derivative adjuvants.

PubMed

Ma, Yongping

2016-11-01

The nontoxic heat-labile enterotoxin (LT) of Escherichia coli and the B subunit of LT (LTB) have been extensively studied as potent vaccine adjuvants. Areas covered: This review covers the area of enterotoxin based vaccine adjuvant and summarizes the development of nontoxic LT mutant (mLT) and LTB and their potency as oral, parenteral and injection adjuvants. Recent evidences indicated that the mechanism of LTB adjuvanticity was to enhance the turnover of dendritic cells (DCs) in spleen and increase DCs capacity to perform as antigen presentation cells (APCs) encountered with T cells. LTB also induces B and T cells clustering and delay/arrest in T-cell division following endocytosis or B-cell receptor (BCR) uptaking of antigen in a ganglioside-mediated manner. Expert commentary: It is pointed out that the immunogenicity of LTB (or LT) is more important than the receptor binding property (or ADP-ribosylation activity) for the adjuvanticity of LT toxoid. The immunogenicity of LTB (or LT) might confer unknown characteristics to maintain LT toxoid adjuvanticity.

Global Population Distribution (1990),Terrestrial Area and Country Name Information on a One by One Degree Grid Cell Basis

DOE Data Explorer

Li, Yi-Fan [Canadian Global Emissions Inventory Centre, Downsview, Ontario (Canada); Brenkert, A. L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

1996-01-01

This data base contains gridded (one degree by one degree) information on the world-wide distribution of the population for 1990 and country-specific information on the percentage of the country's population present in each grid cell (Li, 1996a). Secondly, the data base contains the percentage of a country's total area in a grid cell and the country's percentage of the grid cell that is terrestrial (Li, 1996b). Li (1996b) also developed an indicator signifying how many countries are represented in a grid cell and if a grid cell is part of the sea; this indicator is only relevant for the land, countries, and sea-partitioning information of the grid cell. Thirdly, the data base includes the latitude and longitude coordinates of each grid cell; a grid code number, which is a translation of the latitude/longitude value and is used in the Global Emission Inventory Activity (GEIA) data bases; the country or region's name; and the United Nations three-digit country code that represents that name.

Polymer-based solar cells having an active area of 1.6 cm{sup 2} fabricated via spray coating

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

Scarratt, N. W.; Griffin, J.; Zhang, Y.

We demonstrate the fabrication of polymer solar cells in which both a PEDOT:PSS hole transport and a PCDTBT:PC{sub 71}BM photoactive layer are deposited by spray-casting. Two device geometries are explored, with devices having a pixel area of 165 mm{sup 2} attaining a power conversion efficiency of 3.7%. Surface metrology indicates that the PEDOT:PSS and PCDTBT:PC{sub 71}BM layers have a roughness of 2.57 nm and 1.18 nm over an area of 100 μm{sup 2}. Light beam induced current mapping reveals fluctuations in current generation efficiency over length-scales of ∼2 mm, with the average photocurrent being 75% of its maximum value.

Fabricating solid carbon porous electrodes from powders

DOEpatents

Kaschmitter, James L.; Tran, Tri D.; Feikert, John H.; Mayer, Steven T.

1997-01-01

Fabrication of conductive solid porous carbon electrodes for use in batteries, double layer capacitors, fuel cells, capacitive dionization, and waste treatment. Electrodes fabricated from low surface area (<50 m.sup.2 /gm) graphite and cokes exhibit excellent reversible lithium intercalation characteristics, making them ideal for use as anodes in high voltage lithium insertion (lithium-ion) batteries. Electrodes having a higher surface area, fabricated from powdered carbon blacks, such as carbon aerogel powder, carbon aerogel microspheres, activated carbons, etc. yield high conductivity carbon compositives with excellent double layer capacity, and can be used in double layer capacitors, or for capacitive deionization and/or waste treatment of liquid streams. By adding metallic catalysts to be high surface area carbons, fuel cell electrodes can be produced.

Fabricating solid carbon porous electrodes from powders

DOEpatents

Kaschmitter, J.L.; Tran, T.D.; Feikert, J.H.; Mayer, S.T.

1997-06-10

Fabrication is described for conductive solid porous carbon electrodes for use in batteries, double layer capacitors, fuel cells, capacitive deionization, and waste treatment. Electrodes fabricated from low surface area (<50 m{sup 2}/gm) graphite and cokes exhibit excellent reversible lithium intercalation characteristics, making them ideal for use as anodes in high voltage lithium insertion (lithium-ion) batteries. Electrodes having a higher surface area, fabricated from powdered carbon blacks, such as carbon aerogel powder, carbon aerogel microspheres, activated carbons, etc. yield high conductivity carbon composites with excellent double layer capacity, and can be used in double layer capacitors, or for capacitive deionization and/or waste treatment of liquid streams. By adding metallic catalysts to high surface area carbons, fuel cell electrodes can be produced. 1 fig.

Hydrogen Research for Spaceport and Space-Based Applications: Fuel Cell Projects

NASA Technical Reports Server (NTRS)

Anderson, Tim; Balaban, Canan

2008-01-01

The activities presented are a broad based approach to advancing key hydrogen related technologies in areas such as fuel cells, hydrogen production, and distributed sensors for hydrogen-leak detection, laser instrumentation for hydrogen-leak detection, and cryogenic transport and storage. Presented are the results from research projects, education and outreach activities, system and trade studies. The work will aid in advancing the state-of-the-art for several critical technologies related to the implementation of a hydrogen infrastructure. Activities conducted are relevant to a number of propulsion and power systems for terrestrial, aeronautics and aerospace applications. Fuel cell research focused on proton exchange membranes (PEM), solid oxide fuel cells (SOFC). Specific technologies included aircraft fuel cell reformers, new and improved electrodes, electrolytes, interconnect, and seals, modeling of fuel cells including CFD coupled with impedance spectroscopy. Research was conducted on new materials and designs for fuel cells, along with using embedded sensors with power management electronics to improve the power density delivered by fuel cells. Fuel cell applications considered were in-space operations, aviation, and ground-based fuel cells such as; powering auxiliary power units (APUs) in aircraft; high power density, long duration power supplies for interplanetary missions (space science probes and planetary rovers); regenerative capabilities for high altitude aircraft; and power supplies for reusable launch vehicles.

Natural Killer Cells for Therapy of Leukemia

PubMed Central

Suck, Garnet; Linn, Yeh Ching; Tonn, Torsten

2016-01-01

Summary Clinical application of natural killer (NK) cells against leukemia is an area of intense investigation. In human leukocyte antigen-mismatched allogeneic hematopoietic stem cell transplantations (HSCT), alloreactive NK cells exert powerful anti-leukemic activity in preventing relapse in the absence of graft-versus-host disease, particularly in acute myeloid leukemia patients. Adoptive transfer of donor NK cells post-HSCT or in non-transplant scenarios may be superior to the currently widely used unmanipulated donor lymphocyte infusion. This concept could be further improved through transfusion of activated NK cells. Significant progress has been made in good manufacturing practice (GMP)-compliant large-scale production of stimulated effectors. However, inherent limitations remain. These include differing yields and compositions of the end-product due to donor variability and inefficient means for cryopreservation. Moreover, the impact of the various novel activation strategies on NK cell biology and in vivo behavior are barely understood. In contrast, reproduction of the third-party NK-92 drug from a cryostored GMP-compliant master cell bank is straightforward and efficient. Safety for the application of this highly cytotoxic cell line was demonstrated in first clinical trials. This novel ‘off-the-shelf’ product could become a treatment option for a broad patient population. For specific tumor targeting chimeric-antigen-receptor-engineered NK-92 cells have been designed. PMID:27226791

Advances in Studies of Electrode Kinetics and Mass Transport in AMTEC Cells (abstract)

NASA Technical Reports Server (NTRS)

Williams, R. M.; Jeffries-Nakamura, B.; Ryan, M. A.; Underwood, M. L.; Kisor, A.; O'Connor, D.; Kikkert, S.

1993-01-01

Previous work reported from JPL has included characterization of electrode kinetics and alkali atom transport from electrodes including Mo, W, WRh(sub x), WPt(sub x)(Mn), in sodium AMTEC cells and vapor exposure cells, and Mo in potassium vapor exposure cells. These studies were generally performed in cells with small area electrodes (about 1 to 5 cm(sup 2)), and device geometry had little effect on transport. Alkali diffusion coefficients through these electrodes have been characterized, and approximate surface diffusion coefficients derived in cases of activated transport. A basic model of electrode kinetic at the alkali metal vapor/porous metal electrode/alkali beta'-alumina solid electrolyte three phase boundary has been proposed which accounts for electrochemical reaction rates with a collision frequency near the three phase boundary and tunneling from the porous electrode partially covered with adsorbed alkali metal atoms. The small electrode effect in AMTEC cells has been discussed in several papers, but quantitative investigations have described only the overall effect and the important contribution of electrolyte resistance. The quantitative characterization of transport losses in cells with large area electrodes has been limited to simulations of large area electrode effects, or characterization of transport losses from large area electrodes with significant longitudinal temperature gradients. This paper describes new investigations of electrochemical kinetics and transport, particularily with WPt(sub 3.5) electrodes, including the influence of electrode size on the mass transport loss in the AMTEC cell. These electrodes possess excellent sodium transport properties making verification of device limitations on transport much more readily attained.

Cellular immunotherapy for malignant gliomas.

PubMed

Lin, Yi; Okada, Hideho

2016-10-01

Cancer immunotherapy has made much progress in recent years. Clinical trials evaluating a variety of immunotherapeutic approaches are underway in patients with malignant gliomas. Thanks to recent advancements in cell engineering technologies, infusion of ex vivo prepared immune cells have emerged as promising strategies of cancer immunotherapy. Herein, the authors review recent and current studies using cellular immunotherapies for malignant gliomas. Specifically, they cover the following areas: a) cellular vaccine approaches using tumor cell-based or dendritic cell (DC)-based vaccines, and b) adoptive cell transfer (ACT) approaches, including lymphokine-activated killer (LAK) cells, γδ T cells, tumor-infiltrating lymphocytes (TIL), chimeric antigen receptor (CAR)-T cells and T-cell receptor (TCR) transduced T cells. While some of the recent studies have shown promising results, the ultimate success of cellular immunotherapy in brain tumor patients would require improvements in the following areas: 1) feasibility in producing cellular therapeutics; 2) identification and characterization of targetable antigens given the paucity and heterogeneity of tumor specific antigens; 3) the development of strategies to promote effector T-cell trafficking; 4) overcoming local and systemic immune suppression, and 5) proper interpretation of imaging data for brain tumor patients receiving immunotherapy.

Quiescence and activation of stem and precursor cell populations in the subependymal zone of the mammalian brain are associated with distinct cellular and extracellular matrix signals

USDA-ARS?s Scientific Manuscript database

The subependymal zone (SEZ) of the lateral ventricles is one of the areas of the adult brain where new neurons are continuously generated from neural stem cells (NSCs), via rapidly dividing precursors. This neurogenic niche is a complex cellular and extracellular microenvironment, highly vascularize...

Internal and External Temperature Monitoring of a Li-Ion Battery with Fiber Bragg Grating Sensors

PubMed Central

Novais, Susana; Nascimento, Micael; Grande, Lorenzo; Domingues, Maria Fátima; Antunes, Paulo; Alberto, Nélia; Leitão, Cátia; Oliveira, Ricardo; Koch, Stephan; Kim, Guk Tae; Passerini, Stefano; Pinto, João

2016-01-01

The integration of fiber Bragg grating (FBG) sensors in lithium-ion cells for in-situ and in-operando temperature monitoring is presented herein. The measuring of internal and external temperature variations was performed through four FBG sensors during galvanostatic cycling at C-rates ranging from 1C to 8C. The FBG sensors were placed both outside and inside the cell, located in the center of the electrochemically active area and at the tab-electrode connection. The internal sensors recorded temperature variations of 4.0 ± 0.1 °C at 5C and 4.7 ± 0.1 °C at 8C at the center of the active area, and 3.9 ± 0.1 °C at 5C and 4.0 ± 0.1 °C at 8C at the tab-electrode connection, respectively. This study is intended to contribute to detection of a temperature gradient in real time inside a cell, which can determine possible damage in the battery performance when it operates under normal and abnormal operating conditions, as well as to demonstrate the technical feasibility of the integration of in-operando microsensors inside Li-ion cells. PMID:27589749

Clinical status of benzoporphyrin derivative

NASA Astrophysics Data System (ADS)

Levy, Julia G.; Chan, Agnes H.; Strong, H. Andrew

1996-01-01

Benzoporphyrin derivative monoacid ring A (BPD) is currently in Phase II clinical trials for the treatment of cutaneous malignancies (basal cell carcinoma and cutaneous metastases) and psoriasis. Results to date suggest that this photosensitizer has potential in both of these areas. Recently, a clinical trial with BPD was initiated for the treatment of age related macular degeneration, a neovascular condition in the eye which leads to blindness. BPD is a lipophilic photosensitizer which is rapidly taken up by activated cells and the vascular endothelium of neovasculature. The PDT effects seen with BPD appear to be a combination of vascular occlusion and direct killing of target cells. Since many diseases involve either activated cells and/or neovasculature, PDT with photosensitizer with characteristics like those of BPD, has applications far wider than oncology. A new area of interest involving photosensitizers is that of immune modulation. A number of photosensitizers have been shown to effect immune modulation in animal models of immune dysfunction including autoimmunity (rheumatoid arthritis, lupus), cutaneous hypersensitivity and allografts. BPD and PHOTOFRINR have both been shown to be effective in ameliorating arthritic symptoms in a number of animal models. The mechanisms by which immune modulation is affected in these studies still remains to be resolved.

Functional μ-Opioid-Galanin Receptor Heteromers in the Ventral Tegmental Area

PubMed Central

Moreno, Estefanía; Quiroz, César; Rea, William; Cai, Ning-Sheng; Cortés, Antoni

2017-01-01

The neuropeptide galanin has been shown to interact with the opioid system. More specifically, galanin counteracts the behavioral effects of the systemic administration of μ-opioid receptor (MOR) agonists. Yet the mechanism responsible for this galanin–opioid interaction has remained elusive. Using biophysical techniques in mammalian transfected cells, we found evidence for selective heteromerization of MOR and the galanin receptor subtype Gal1 (Gal1R). Also in transfected cells, a synthetic peptide selectively disrupted MOR–Gal1R heteromerization as well as specific interactions between MOR and Gal1R ligands: a negative cross talk, by which galanin counteracted MAPK activation induced by the endogenous MOR agonist endomorphin-1, and a cross-antagonism, by which a MOR antagonist counteracted MAPK activation induced by galanin. These specific interactions, which represented biochemical properties of the MOR-Gal1R heteromer, could then be identified in situ in slices of rat ventral tegmental area (VTA) with MAPK activation and two additional cell signaling pathways, AKT and CREB phosphorylation. Furthermore, in vivo microdialysis experiments showed that the disruptive peptide selectively counteracted the ability of galanin to block the dendritic dopamine release in the rat VTA induced by local infusion of endomorphin-1, demonstrating a key role of MOR-Gal1R heteromers localized in the VTA in the direct control of dopamine cell function and their ability to mediate antagonistic interactions between MOR and Gal1R ligands. The results also indicate that MOR-Gal1R heteromers should be viewed as targets for the treatment of opioid use disorders. SIGNIFICANCE STATEMENT The μ-opioid receptor (MOR) localized in the ventral tegmental area (VTA) plays a key role in the reinforcing and addictive properties of opioids. With parallel in vitro experiments in mammalian transfected cells and in situ and in vivo experiments in rat VTA, we demonstrate that a significant population of these MORs form functional heteromers with the galanin receptor subtype Gal1 (Gal1R), which modulate the activity of the VTA dopaminergic neurons. The MOR-Gal1R heteromer can explain previous results showing antagonistic galanin–opioid interactions and offers a new therapeutic target for the treatment of opioid use disorder. PMID:28007761

Ultrastructural study of cytochemical localization of carbonic anhydrase in the inner ear.

PubMed

Hsu, C J

1991-01-01

Vibratome sections were stained for cytochemical localization of carbonic anhydrase (CA) activity in vestibular neuro-epithelium, spiral ligament and spiral limbus. The new finding is the localization of reaction products in the interdental cells of the spiral limbus, Claudius' cells, mesothelial cells of the lower border of spiral ligament, vestibular sensory cells and perilymphatic cells, which have not earlier been proved to have CA activity. The interdental cells showed the products only on the basolateral infoldings. Claudius' cells showed prominent products in the microvilli. In the vestibular sensory cells, the products were present only in the stereocilia and cuticular areas. The perilymphatic fibrocytes under the vestibular sensory epithelium, like the fibrocytes of the spiral ligament, revealed diffuse products throughout the whole cell. In the vestibular supporting cells and transitional cells, the reaction products were localized diffusely in the cytosol, but not in the secretory granules. In the long cell projections of the transitional cells, type II fibrocytes at spiral prominence, mesothelial cells at the uppermost region of the spiral ligament and Borghesan's zone, the localization of the reaction products was the same as that of the basolateral infoldings of the vestibular dark cells and marginal cells of stria vascularis shown previously.

Method of making quasi-grain boundary-free polycrystalline solar cell structure and solar cell structure obtained thereby

DOEpatents

Gonzalez, Franklin N.; Neugroschel, Arnost

1984-02-14

A new solar cell structure is provided which will increase the efficiency of polycrystalline solar cells by suppressing or completely eliminating the recombination losses due to the presence of grain boundaries. This is achieved by avoiding the formation of the p-n junction (or other types of junctions) in the grain boundaries and by eliminating the grain boundaries from the active area of the cell. This basic concept can be applied to any polycrystalline material; however, it will be most beneficial for cost-effective materials having small grains, including thin film materials.

Mitochondrial and Plasma Membrane Pools of Stomatin-Like Protein 2 Coalesce at the Immunological Synapse during T Cell Activation

PubMed Central

Christie, Darah A.; Kirchhof, Mark G.; Vardhana, Santosh; Dustin, Michael L.; Madrenas, Joaquín

2012-01-01

Stomatin-like protein 2 (SLP-2) is a member of the stomatin – prohibitin – flotillin – HflC/K (SPFH) superfamily. Recent evidence indicates that SLP-2 is involved in the organization of cardiolipin-enriched microdomains in mitochondrial membranes and the regulation of mitochondrial biogenesis and function. In T cells, this role translates into enhanced T cell activation. Although the major pool of SLP-2 is associated with mitochondria, we show here that there is an additional pool of SLP-2 associated with the plasma membrane of T cells. Both plasma membrane-associated and mitochondria-associated pools of SLP-2 coalesce at the immunological synapse (IS) upon T cell activation. SLP-2 is not required for formation of IS nor for the re-localization of mitochondria to the IS because SLP-2-deficient T cells showed normal re-localization of these organelles in response to T cell activation. Interestingly, upon T cell activation, we found the surface pool of SLP-2 mostly excluded from the central supramolecular activation complex, and enriched in the peripheral area of the IS where signalling TCR microclusters are located. Based on these results, we propose that SLP-2 facilitates the compartmentalization not only of mitochondrial membranes but also of the plasma membrane into functional microdomains. In this latter location, SLP-2 may facilitate the optimal assembly of TCR signalosome components. Our data also suggest that there may be a net exchange of membrane material between mitochondria and plasma membrane, explaining the presence of some mitochondrial proteins in the plasma membrane. PMID:22623988

Mechanochemical cell biology.

PubMed

Cross, R A; McAinsh, A D; Straube, A

2011-12-01

Eukaryotic systems self-organise by using molecular railways to shuttle specific sets of molecular components to specific locations. In this way, cells are enabled to become larger, more complex and more varied, subtle and effective in their activities. Because of the fundamental importance of molecular railways in eukaryotic systems, understanding how these railways work is an important research goal. Mechanochemical cell biology is a newly circumscribed subject area that concerns itself with the molecular and cell biological mechanisms of motorised directional transport in living systems. Copyright © 2011 Elsevier Ltd. All rights reserved.

Biomimetics in thin film design: Niche-like wrinkles designed for i-cell progenitor cell differentiation.

PubMed

Major, Roman; Lackner, Juergen M; Sanak, Marek; Major, Boguslaw

2017-11-01

The future and development of science are in interdisciplinary areas, such as biomedical engineering. Self-assembled structures, similar to stem cell niches, inhibit rapid cellular division processes and enable the capture of stem cells from blood flow. By modifying the surface topography and stiffness properties, progenitor cells were differentiated towards the formation of endothelial cell monolayers to effectively inhibit the coagulation cascade. Wrinkled material layers in the form of thin polymeric coatings were prepared. An optimized surface topography led to proper cell differentiation and influenced the appropriate formation of endothelial cell monolayers. Blood activation was decelerated by the formed endothelium. Copyright © 2017 Elsevier B.V. All rights reserved.

Technical Note: Nanometric organic photovoltaic thin film detectors for dose monitoring in diagnostic x-ray imaging

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

Elshahat, Bassem; Gill, Hardeep Singh; Kumar, Jayant

2015-07-15

Purpose: To fabricate organic photovoltaic (OPV) cells with nanometric active layers sensitive to ionizing radiation and measure their dosimetric characteristics in clinical x-ray beams in the diagnostic tube potential range of 60–150 kVp. Methods: Experiments were designed to optimize the detector’s x-ray response and find the best parameter combination by changing the active layer thickness and the area of the electrode. The OPV cell consisted of poly (3-hexylthiophene-2,5-diyl): [6,6]-phenyl C{sub 61} butyric acid methyl ester photoactive donor and acceptor semiconducting organic materials sandwiched between an aluminum electrode as an anode and an indium tin oxide electrode as a cathode. Themore » authors measured the radiation-induced electric current at zero bias voltage in all fabricated OPV cells. Results: The net OPV current as a function of beam potential (kVp) was proportional to kVp{sup −0.5} when normalized to x-ray tube output, which varies with kVp. Of the tested configurations, the best combination of parameters was 270 nm active layer thicknesses with 0.7 cm{sup 2} electrode area, which provided the highest signal per electrode area. For this cell, the measured current ranged from approximately 0.7 to 2.4 nA/cm{sup 2} for 60–150 kVp, corresponding to about 0.09 nA–0.06 nA/mGy air kerma, respectively. When compared to commercial amorphous silicon thin film photovoltaic cells irradiated under the same conditions, this represents 2.5 times greater sensitivity. An additional 40% signal enhancement was observed when a 1 mm layer of plastic scintillator was attached to the cells’ beam-facing side. Conclusions: Since both OPVs can be produced as flexible devices and they do not require external bias voltage, they open the possibility for use as thin film in vivo detectors for dose monitoring in diagnostic x-ray imaging.« less

Label-free investigation of the effects of lithium niobate polarization on cell adhesion

NASA Astrophysics Data System (ADS)

Mandracchia, B.; Gennari, O.; Paturzo, M.; Grilli, S.; Ferraro, P.

2017-06-01

The determination of contact area is pivotal to understand how biomaterials properties influence cell adhesion. In particular, the influence of surface charges is well-known but still controversial, especially when new functional materials and methods are introduced. Here, we use for the first time Holographic Total Internal Reflection Microscopy (HoloTIRM) to study the influence of the spontaneous polarization of ferroelectric lithium niobate (LN) on the adhesion properties of fibroblast cells. The selective illumination of a very thin region directly above the substrate, achieved by Total Internal Reflection, provides high-contrast images of the contact regions. Holographic recording, on the other hand, allows for label-free quantitative phase imaging of the contact areas between cells and LN. Phase signal is more sensitive in the first 100nm and, thus more reliable in order to locate focal contacts. This work shows that cells adhering on negatively polarized LN present a significant increase of the contact area in comparison with cells adhering on the positively polarized LN substrate, as well as an intensification of contact vicinity. This confirms the potential of LN as a platform for investigating the role of charges on cellular processes. The similarity of cell adhesion behavior on negatively polarized LN and glass control also confirms the possibility to use LN as an active substrate without impairing cell behavior.

Improved efficiency of a large-area Cu(In,Ga)Se₂ solar cell by a nontoxic hydrogen-assisted solid Se vapor selenization process.

PubMed

Wu, Tsung-Ta; Hu, Fan; Huang, Jyun-Hong; Chang, Chia-ho; Lai, Chih-chung; Yen, Yu-Ting; Huang, Hou-Ying; Hong, Hwen-Fen; Wang, Zhiming M; Shen, Chang-Hong; Shieh, Jia-Min; Chueh, Yu-Lun

2014-04-09

A nontoxic hydrogen-assisted solid Se vapor selenization process (HASVS) technique to achieve a large-area (40 × 30 cm(2)) Cu(In,Ga)Se2 (CIGS) solar panel with enhanced efficiencies from 7.1 to 10.8% (12.0% for active area) was demonstrated. The remarkable improvement of efficiency and fill factor comes from improved open circuit voltage (Voc) and reduced dark current due to (1) decreased interface recombination raised from the formation of a widened buried homojunction with n-type Cd(Cu) participation and (2) enhanced separation of electron and hole carriers resulting from the accumulation of Na atoms on the surface of the CIGS film. The effects of microstructural, compositional, and electrical characteristics with hydrogen-assisted Se vapor selenization, including interdiffusion of atoms and formation of buried homojunction, were examined in detail. This methodology can be also applied to CIS (CuInSe2) thin film solar cells with enhanced efficiencies from 5.3% to 8.5% (9.4% for active area) and provides a facile approach to improve quality of CIGS and stimulate the nontoxic progress in the large scale CIGS PV industry.

Proteolytic Enzymes Clustered in Specialized Plasma-Membrane Domains Drive Endothelial Cells’ Migration

PubMed Central

Salamone, Monica; Carfì Pavia, Francesco

2016-01-01

In vitro cultured endothelial cells forming a continuous monolayer establish stable cell-cell contacts and acquire a “resting” phenotype; on the other hand, when growing in sparse conditions these cells acquire a migratory phenotype and invade the empty area of the culture. Culturing cells in different conditions, we compared expression and clustering of proteolytic enzymes in cells having migratory versus stationary behavior. In order to observe resting and migrating cells in the same microscopic field, a continuous cell monolayer was wounded. Increased expression of proteolytic enzymes was evident in cell membranes of migrating cells especially at sprouting sites and in shed membrane vesicles. Gelatin zymography and western blotting analyses confirmed that in migrating cells, expression of membrane-bound and of vesicle-associated proteolytic enzymes are increased. The enzymes concerned include MMP-2, MMP-9, MT1-MMP, seprase, DPP4 (DiPeptidyl Peptidase 4) and uPA. Shed membrane vesicles were shown to exert degradative activity on ECM components and produce substrates facilitating cell migration. Vesicles shed by migrating cells degraded ECM components at an increased rate; as a result their effect on cell migration was amplified. Inhibiting either Matrix Metallo Proteases (MMPs) or Serine Integral Membrane Peptidases (SIMPs) caused a decrease in the stimulatory effect of vesicles, inhibiting the spontaneous migratory activity of cells; a similar result was also obtained when a monoclonal antibody acting on DPP4 was tested. We conclude that proteolytic enzymes have a synergistic stimulatory effect on cell migration and that their clustering probably facilitates the proteolytic activation cascades needed to produce maximal degradative activity on cell substrates during the angiogenic process. PMID:27152413

Widening of xylem conduits in a conifer tree depends on the longer time of cell expansion downwards along the stem

PubMed Central

Anfodillo, Tommaso; Deslauriers, Annie; Menardi, Roberto; Tedoldi, Laura; Petit, Giai; Rossi, Sergio

2012-01-01

The diameter of vascular conduits increases towards the stem base. It has been suggested that this profile is an efficient anatomical feature for reducing the hydraulic resistance when trees grow taller. However, the mechanism that controls the cell diameter along the plant is not fully understood. The timing of cell differentiation along the stem was investigated. Cambial activity and cell differentiation were investigated in a Picea abies tree (11.5 m in height) collecting microsamples at nine different heights (from 1 to 9 m) along the stem with a 4 d time interval. Wood sections (8–12 μm thick) were stained and observed under a light microscope with polarized light to differentiate the developing xylem cells. Cell wall lignification was detected using cresyl violet acetate. The first enlarging cells appeared almost simultaneously along the tree axis indicating that cambium activation is not height-dependent. A significant increase in the duration of the cell expansion phase was observed towards the tree base: at 9 m from the ground, xylem cells expanded for 7 d, at 6 m for 14 d, and at 3 m for 19 d. The duration of the expansion phase is positively correlated with the lumen area of the tracheids (r2=0.68, P < 0.01) at the same height. By contrast, thickness of the cell wall of the earlywood did not show any trend with height. The lumen area of the conduits down the stem appeared linearly dependent on time during which differentiating cells remained in the expansion phase. However, the inductive signal of such long-distance patterned differentiation remains to be identified. PMID:22016427

Widening of xylem conduits in a conifer tree depends on the longer time of cell expansion downwards along the stem.

PubMed

Anfodillo, Tommaso; Deslauriers, Annie; Menardi, Roberto; Tedoldi, Laura; Petit, Giai; Rossi, Sergio

2012-01-01

The diameter of vascular conduits increases towards the stem base. It has been suggested that this profile is an efficient anatomical feature for reducing the hydraulic resistance when trees grow taller. However, the mechanism that controls the cell diameter along the plant is not fully understood. The timing of cell differentiation along the stem was investigated. Cambial activity and cell differentiation were investigated in a Picea abies tree (11.5 m in height) collecting microsamples at nine different heights (from 1 to 9 m) along the stem with a 4 d time interval. Wood sections (8-12 μm thick) were stained and observed under a light microscope with polarized light to differentiate the developing xylem cells. Cell wall lignification was detected using cresyl violet acetate. The first enlarging cells appeared almost simultaneously along the tree axis indicating that cambium activation is not height-dependent. A significant increase in the duration of the cell expansion phase was observed towards the tree base: at 9 m from the ground, xylem cells expanded for 7 d, at 6 m for 14 d, and at 3 m for 19 d. The duration of the expansion phase is positively correlated with the lumen area of the tracheids (r(2)=0.68, P < 0.01) at the same height. By contrast, thickness of the cell wall of the earlywood did not show any trend with height. The lumen area of the conduits down the stem appeared linearly dependent on time during which differentiating cells remained in the expansion phase. However, the inductive signal of such long-distance patterned differentiation remains to be identified.

CD19+ B cell subsets in the peripheral blood and skin lesions of psoriasis patients and their correlations with disease severity

PubMed Central

Lu, J.; Ding, Y.; Yi, X.; Zheng, J.

2016-01-01

T lymphocytes are important in the pathogenesis of psoriasis, and increasing evidence indicates that B cells also play an important role. The mechanisms of action, however, remain unclear. We evaluated the ratios of CD19+ B cells in peripheral blood mononuclear cells (PBMCs) from 157 patients with psoriasis (65 patients with psoriasis vulgaris, 32 patients with erythrodermic psoriasis, 30 patients with arthropathic psoriasis, and 30 patients with pustular psoriasis) and 35 healthy controls (HCs). Ratios of CD19+ B cells in skin lesions were compared with non-lesions in 7 erythrodermic psoriasis patients. The Psoriasis Area Severity Index (PASI) was used to measure disease severity. CD19+ B cell ratios in PBMCs from psoriasis vulgaris (at both the active and stationary stage) and arthropathic psoriasis patients were higher compared with HCs (P<0.01), but ratios were lower in erythrodermic and pustular psoriasis patients (P<0.01). CD19+ B cell ratios in erythrodermic psoriasis skin lesions were higher than in non-lesion areas (P<0.001). Different subsets of CD19+CD40+, CD19+CD44+, CD19+CD80+, CD19+CD86+, CD19+CD11b+, and CD19+HLA-DR+ B cells in PBMCs were observed in different psoriasis clinical subtypes. PASI scores were positively correlated with CD19+ B cell ratios in psoriasis vulgaris and arthropathic psoriasis cases (r=0.871 and r=0.692, respectively, P<0.01), but were negatively correlated in pustular psoriasis (r=-0.569, P<0.01). The results indicated that similar to T cells, B cells activation may also play important roles in different pathological stages of psoriasis. PMID:27532281

Phosphorylation of basic helix-loop-helix transcription factor Twist in development and disease.

PubMed

Xue, Gongda; Hemmings, Brian A

2012-02-01

The transcription factor Twist plays vital roles during embryonic development through regulating/controlling cell migration. However, postnatally, in normal physiological settings, Twist is either not expressed or inactivated. Increasing evidence shows a strong correlation between Twist reactivation and both cancer progression and malignancy, where the transcriptional activities of Twist support cancer cells to disseminate from primary tumours and subsequently establish a secondary tumour growth in distant organs. However, it is largely unclear how this signalling programme is reactivated or what signalling pathways regulate its activity. The present review discusses recent advances in Twist regulation and activity, with a focus on phosphorylation-dependent Twist activity, potential upstream kinases and the contribution of these factors in transducing biological signals from upstream signalling complexes. The recent advances in these areas have shed new light on how phosphorylation-dependent regulation of the Twist proteins promotes or suppresses Twist activity, leading to differential regulation of Twist transcriptional targets and thereby influencing cell fate.

Improving global fire carbon emissions estimates by combining moderate resolution burned area and active fire observations

NASA Astrophysics Data System (ADS)

Randerson, J. T.; Chen, Y.; Giglio, L.; Rogers, B. M.; van der Werf, G.

2011-12-01

In several important biomes, including croplands and tropical forests, many small fires exist that have sizes that are well below the detection limit for the current generation of burned area products derived from moderate resolution spectroradiometers. These fires likely have important effects on greenhouse gas and aerosol emissions and regional air quality. Here we developed an approach for combining 1km thermal anomalies (active fires; MOD14A2) and 500m burned area observations (MCD64A1) to estimate the prevalence of these fires and their likely contribution to burned area and carbon emissions. We first estimated active fires within and outside of 500m burn scars in 0.5 degree grid cells during 2001-2010 for which MCD64A1 burned area observations were available. For these two sets of active fires we then examined mean fire radiative power (FRP) and changes in enhanced vegetation index (EVI) derived from 16-day intervals immediately before and after each active fire observation. To estimate the burned area associated with sub-500m fires, we first applied burned area to active fire ratios derived solely from within burned area perimeters to active fires outside of burn perimeters. In a second step, we further modified our sub-500m burned area estimates using EVI changes from active fires outside and within of burned areas (after subtracting EVI changes derived from control regions). We found that in northern and southern Africa savanna regions and in Central and South America dry forest regions, the number of active fires outside of MCD64A1 burned areas increased considerably towards the end of the fire season. EVI changes for active fires outside of burn perimeters were, on average, considerably smaller than EVI changes associated with active fires inside burn scars, providing evidence for burn scars that were substantially smaller than the 25 ha area of a single 500m pixel. FRP estimates also were lower for active fires outside of burn perimeters. In our analysis we quantified how including sub-500m burned area influenced global burned area, carbon emissions, and net ecosystem exchange (NEE) in different continental regions using the Global Fire Emissions Database (GFED) biogeochemical model. We conclude by discussing validation needs using higher resolution visible and thermal imagery.

Long pentraxin-3 as an epithelial-stromal fibroblast growth factor-targeting inhibitor in prostate cancer.

PubMed

Ronca, Roberto; Alessi, Patrizia; Coltrini, Daniela; Di Salle, Emanuela; Giacomini, Arianna; Leali, Daria; Corsini, Michela; Belleri, Mirella; Tobia, Chiara; Garlanda, Cecilia; Bonomi, Elisa; Tardanico, Regina; Vermi, William; Presta, Marco

2013-06-01

Fibroblast growth factors (FGFs) exert autocrine/paracrine functions in prostate cancer by stimulating angiogenesis and tumour growth. Here dihydrotestosterone (DHT) up-regulates FGF2 and FGF8b production in murine TRAMP-C2 prostate cancer cells, activating a FGF-dependent autocrine loop of stimulation. The soluble pattern recognition receptor long pentraxin-3 (PTX3) acts as a natural FGF antagonist that binds FGF2 and FGF8b via its N-terminal domain. We demonstrate that recombinant PTX3 protein and the PTX3-derived pentapeptide Ac-ARPCA-NH2 abolish the mitogenic response of murine TRAMP-C2 cells and human LNCaP prostate cancer cells to DHT and FGFs. Also, PTX3 hampers the angiogenic activity of DHT-activated TRAMP-C2 cells on the chick embryo chorioallantoic membrane (CAM). Accordingly, human PTX3 overexpression inhibits the mitogenic activity exerted by DHT or FGFs on hPTX3_TRAMP-C2 cell transfectants and their angiogenic activity. Also, hPTX3_TRAMP-C2 cells show a dramatic decrease of their angiogenic and tumourigenic potential when grafted in syngeneic or immunodeficient athymic male mice. A similar inhibitory effect is observed when TRAMP-C2 cells overexpress only the FGF-binding N-terminal PTX3 domain. In keeping with the anti-tumour activity of PTX3 in experimental prostate cancer, immunohistochemical analysis of prostate needle biopsies from primary prostate adenocarcinoma patients shows that parenchymal PTX3 expression, abundant in basal cells of normal glands, is lost in high-grade prostatic intraepithelial neoplasia and in invasive tumour areas. These results identify PTX3 as a potent FGF antagonist endowed with anti-angiogenic and anti-neoplastic activity in prostate cancer. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

NADH oxidase activity (NOX) and enlargement of HeLa cells oscillate with two different temperature-compensated period lengths of 22 and 24 minutes corresponding to different NOX forms

NASA Technical Reports Server (NTRS)

Wang, S.; Pogue, R.; Morre, D. M.; Morre, D. J.

2001-01-01

NOX proteins are cell surface-associated and growth-related hydroquinone (NADH) oxidases with protein disulfide-thiol interchange activity. A defining characteristic of NOX proteins is that the two enzymatic activities alternate to generate a regular period length of about 24 min. HeLa cells exhibit at least two forms of NOX. One is tumor-associated (tNOX) and is inhibited by putative quinone site inhibitors (e.g., capsaicin or the antitumor sulfonylurea, LY181984). Another is constitutive (CNOX) and refractory to inhibition. The periodic alternation of activities and drug sensitivity of the NADH oxidase activity observed with intact HeLa cells was retained in isolated plasma membranes and with the solubilized and partially purified enzyme. At least two activities were present. One had a period length of 24 min and the other had a period length of 22 min. The lengths of both the 22 and the 24 min periods were temperature compensated (approximately the same when measured at 17, 27 or 37 degrees C) whereas the rate of NADH oxidation approximately doubled with each 10 degrees C rise in temperature. The rate of increase in cell area of HeLa cells when measured by video-enhanced light microscopy also exhibited a complex period of oscillations reflective of both 22 and 24 min period lengths. The findings demonstrate the presence of a novel oscillating NOX activity at the surface of cancer cells with a period length of 22 min in addition to the constitutive NOX of non-cancer cells and tissues with a period length of 24 min.

The hTERT Promoter Enhances the Antitumor Activity of an Oncolytic Adenovirus under a Hypoxic Microenvironment

PubMed Central

Hashimoto, Yuuri; Tazawa, Hiroshi; Teraishi, Fuminori; Kojima, Toru; Watanabe, Yuichi; Uno, Futoshi; Yano, Shuya; Urata, Yasuo; Kagawa, Shunsuke; Fujiwara, Toshiyoshi

2012-01-01

Hypoxia is a microenvironmental factor that contributes to the invasion, progression and metastasis of tumor cells. Hypoxic tumor cells often show more resistance to conventional chemoradiotherapy than normoxic tumor cells, suggesting the requirement of novel antitumor therapies to efficiently eliminate the hypoxic tumor cells. We previously generated a tumor-specific replication-competent oncolytic adenovirus (OBP-301: Telomelysin), in which the human telomerase reverse transcriptase (hTERT) promoter drives viral E1 expression. Since the promoter activity of the hTERT gene has been shown to be upregulated by hypoxia, we hypothesized that, under hypoxic conditions, the antitumor effect of OBP-301 with the hTERT promoter would be more efficient than that of the wild-type adenovirus 5 (Ad5). In this study, we investigated the antitumor effects of OBP-301 and Ad5 against human cancer cells under a normoxic (20% oxygen) or a hypoxic (1% oxygen) condition. Hypoxic condition induced nuclear accumulation of the hypoxia-inducible factor-1α and upregulation of hTERT promoter activity in human cancer cells. The cytopathic activity of OBP-301 was significantly higher than that of Ad5 under hypoxic condition. Consistent with their cytopathic activity, the replication of OBP-301 was significantly higher than that of Ad5 under the hypoxic condition. OBP-301-mediated E1A was expressed within hypoxic areas of human xenograft tumors in mice. These results suggest that the cytopathic activity of OBP-301 against hypoxic tumor cells is mediated through hypoxia-mediated activation of the hTERT promoter. Regulation of oncolytic adenoviruses by the hTERT promoter is a promising antitumor strategy, not only for induction of tumor-specific oncolysis, but also for efficient elimination of hypoxic tumor cells. PMID:22720091

Antiangiogenic therapy improves the antitumor effect of adoptive cell immunotherapy by normalizing tumor vasculature.

PubMed

Shi, Shujing; Chen, Longbang; Huang, Guichun

2013-12-01

Abnormal tumor vasculature and subsequent tumor hypoxia contribute to immune tolerance of tumor cells by impeding the homing of cytotoxic T cells into tumor parenchyma and inhibiting their antitumor efficacy. These obstacles might explain why the promising approach of adoptive cell immunotherapy does not exert significant antitumor activity. Hypoxia contributes to immune suppression by activating hypoxia-inducible factor (HIF-1) and the vascular endothelial growth factor pathway, which plays a determining role in promoting tumor cell growth and survival. Tumor hypoxia creates an immunosuppressive microenvironment via the accumulation and subsequent polarization of inflammatory cells toward immune suppression phenotypes, such as myeloid-derived suppressor cells, tumor-associated macrophages, and dendritic cells. Antiangiogenic therapy could normalize tumor vasculature and decrease hypoxic tumor area and thus may be an effective modality to potentiate immunotherapy. Adoptive cell immunotherapy alone is not efficient enough to decrease tumor growth as its antitumor effect is inhibited by the immunosuppressive hypoxic tumor microenvironment. This review describes that combination of antiangiogenic therapy with adoptive cell immunotherapy can exert synergistic antitumor effect, which will contribute to improve strategies for future anticancer therapies.

Cortical GABAergic excitation contributes to epileptic activities around human glioma

PubMed Central

Pallud, Johan; Varlet, Pascale; Cresto, Noemie; Baulac, Michel; Duyckaerts, Charles; Kourdougli, Nazim; Chazal, Geneviève; Devaux, Bertrand; Rivera, Claudio; Miles, Richard; Capelle, Laurent; Huberfeld, Gilles

2015-01-01

Rationale Diffuse brain gliomas induce seizures in a majority of patients. As in most epileptic disorders, excitatory glutamatergic mechanisms are involved in the generation of epileptic activities in the neocortex surrounding gliomas. However, chloride homeostasis is known to be perturbed in glial tumor cells. Thus the contribution of GABAergic mechanisms which depend on intracellular chloride and which are defective or pro-epileptic in other structural epilepsies merits closer study. Objective We studied in neocortical slices from the peritumoral security margin resected around human brain gliomas, the occurrence, networks, cells and signaling basis of epileptic activities. Results Postoperative glioma tissue from 69% of patients spontaneously generated interictal-like discharges. These events were synchronized, with a high frequency oscillation signature, in superficial layers of neocortex around glioma areas with tumor infiltration. Interictal-like events depended on both glutamatergic transmission and on depolarizing GABAergic signaling. About 65% of pyramidal cells were depolarized by GABA released by interneurons. This effect was related to perturbations in Chloride homeostasis, due to changes in expression of chloride co-transporters: KCC2 was reduced and expression of NKCC1 increased. Ictal-like activities were initiated by convulsant stimuli exclusively in these epileptogenic areas. Conclusions Epileptic activities are sustained by excitatory effects of GABA in the peritumoral human neocortex, as in temporal lobe epilepsies. Glutamate and GABA signaling are involved in oncogenesis and chloride homeostasis is perturbed. These same factors, induce an imbalance between synaptic excitatory and inhibition underly epileptic discharges in tumor patients. PMID:25009229

A study on relationship among apoptosis rates, number of peripheral T cell subtypes and disease activity in rheumatoid arthritis.

PubMed

Ji, Lanlan; Geng, Yan; Zhou, Wei; Zhang, Zhuoli

2016-02-01

Rheumatoid arthritis is characterized by type 17 helper T cell (Th17)/regulatory T cell (Treg) imbalance. The objective of this article is to study whether insufficient apoptosis contributes to the imbalance of Th17/Treg in rheumatoid arthritis. Twenty-one rheumatoid arthritis patients and eight healthy volunteers were involved in this study. The percentage of CD4(+) interleukin (IL)-17(+) T cells and CD4(+) transcription factor-forkhead box protein 3 (Foxp3)(+) T cells were measured by flow cytometry, and active caspase-3 labeling was used to detect early apoptosis. The number of T cell subtypes in peripheral blood between the two groups was compared, as well as the apoptotic ratio. Neither the number of Th17 nor Treg cells was significantly different between rheumatoid arthritis patients and healthy controls. However, the number of regulatory T cells positively correlated with erythrocyte sedimentation rate, Disease Activity Score of 28 joints and rheumatoid factor. For the apoptosis of T cell subtypes, the percentage of apoptotic Th17 cells was higher in peripheral blood of rheumatoid arthritis patients compared to controls. Furthermore, peripheral Th17 cells were more sensitive to apoptosis than Treg cells, but there was no difference between rheumatoid arthritis patients and controls. It seemed that there was no relationship between the number and apoptosis ratio of peripheral Th17/Treg cells. But the number of Treg cells positively correlated with disease activity. Furthermore, Th17 cells are more sensitive to apoptosis after freezing, especially in RA patients. This serendipitous finding may provide new areas for the further study of these two cell populations. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

[Parallel analysis of c-Fos protein and interleukin-2 expression in hypothalamic cells under different influence].

PubMed

Barabanova, S V; Artiukhina, Z E; Ovchinnikova, K T; Abramova, T V; Kazakova, T B; Khavinson, V Kh; Malinin, V V; Korneva, E A

2007-02-01

The objective of this work was to perform a parallel analysis of activation of the rat anterior hypothalamus cells as judged by c-Fos protein expression, and of the expression of interleukin-2 (IL-2) under different influences, i. e., mild stress (handling) and adaptation to it, and intranasal administration of saline and the peptides Vilon (Lys-Glu) and Epithalon (Ala-Glu-Asp-Gly). Changes in the counts of cells positive for c-Fos- and IL-2 proteins were studied in structures of the lateral (LHA) area, anterior (AHN), supraoptic (SO) and paraventricular (PVH) nuclei of Wistar rat hypothalamus. Quantity of the interleukin-2-positive and c-Fos-positive cells was calculated. The findings were: a negative correlation between the activation of cells and the amount of IL-2 in the cells in the hypothalamic structures under study, and the specific patterns of changes in the counts of cells positive for c-Fos and IL-2 under stress and adaptation to stress.

Exosomes and their roles in immune regulation and cancer.

PubMed

Greening, David W; Gopal, Shashi K; Xu, Rong; Simpson, Richard J; Chen, Weisan

2015-04-01

Exosomes, a subset of extracellular vesicles (EVs), function as a mode of intercellular communication and molecular transfer. Exosomes facilitate the direct extracellular transfer of proteins, lipids, and miRNA/mRNA/DNAs between cells in vitro and in vivo. The immunological activities of exosomes affect immunoregulation mechanisms including modulating antigen presentation, immune activation, immune suppression, immune surveillance, and intercellular communication. Besides immune cells, cancer cells secrete immunologically active exosomes that influence both physiological and pathological processes. The observation that exosomes isolated from immune cells such as dendritic cells (DCs) modulate the immune response has enforced the way these membranous vesicles are being considered as potential immunotherapeutic reagents. Indeed, tumour- and immune cell-derived exosomes have been shown to carry tumour antigens and promote immunity, leading to eradication of established tumours by CD8(+) T cells and CD4(+) T cells, as well as directly suppressing tumour growth and resistance to malignant tumour development. Further understanding of these areas of exosome biology, and especially of molecular mechanisms involved in immune cell targeting, interaction and manipulation, is likely to provide significant insights into immunorecognition and therapeutic intervention. Here, we review the emerging roles of exosomes in immune regulation and the therapeutic potential in cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

"Active" drops as phantom models for living cells: a mesoscopic particle-based approach.

PubMed

Dallavalle, Marco; Lugli, Francesca; Rapino, Stefania; Zerbetto, Francesco

2016-04-21

Drops and biological cells share some morphological features and visco-elastic properties. The modelling of drops by mesoscopic non-atomistic models has been carried out to a high degree of success in recent years. We extend such treatment and discuss a simple, drop-like model to describe the interactions of the outer layer of cells with the surfaces of materials. Cells are treated as active mechanical objects that are able to generate adhesion forces. They appear with their true size and are made of "parcels of fluids" or beads. The beads are described by (very) few quantities/parameters related to fundamental chemical forces such as hydrophilicity and lipophilicity that represent an average of the properties of a patch of material or an area of the cell(s) surface. The investigation of adhesion dynamics, motion of individual cells, and the collective behavior of clusters of cells on materials is possible. In the simulations, the drops become active soft matter objects and different from regular droplets they do not fuse when in contact, their trajectories are not Brownian, and they can be forced "to secrete" molecules, to name some of the properties targeted by the modeling. The behavior that emerges from the simulations allows ascribing some cell properties to their mechanics, which are related to their biological features.

Hypoxia-Targeting Drug Evofosfamide (TH-302) Enhances Sunitinib Activity in Neuroblastoma Xenograft Models.

PubMed

Kumar, Sushil; Sun, Jessica D; Zhang, Libo; Mokhtari, Reza Bayat; Wu, Bing; Meng, Fanying; Liu, Qian; Bhupathi, Deepthi; Wang, Yan; Yeger, Herman; Hart, Charles; Baruchel, Sylvain

2018-05-23

Antiangiogenic therapy has shown promising results in preclinical and clinical trials. However, tumor cells acquire resistance to this therapy by gaining ability to survive and proliferate under hypoxia induced by antiangiogenic therapy. Combining antiangiogenic therapy with hypoxia-activated prodrugs can overcome this limitation. Here, we have tested the combination of antiangiogenic drug sunitinib in combination with hypoxia-activated prodrug evofosfamide in neuroblastoma. In vitro, neuroblastoma cell line SK-N-BE(2) was 40-folds sensitive to evofosfamide under hypoxia compared to normoxia. In IV metastatic model, evofosfamide significantly increased mice survival compared to the vehicle (P=.02). In SK-N-BE(2) subcutaneous xenograft model, we tested two different treatment regimens using 30 mg/kg sunitinib and 50 mg/kg evofosfamide. Here, sunitinib therapy when started along with evofosfamide treatment showed higher efficacy compared to single agents in subcutaneous SK-N-BE(2) xenograft model, whereas sunitinib when started 7 days after evofosfamide treatment did not have any advantage compared to treatment with either single agent. Immunofluorescence of tumor sections revealed higher number of apoptotic cells and hypoxic areas compared to either single agent when both treatments were started together. Treatment with 80 mg/kg sunitinib with 50 mg/kg evofosfamide was significantly superior to single agents in both xenograft and metastatic models. This study confirms the preclinical efficacy of sunitinib and evofosfamide in murine models of aggressive neuroblastoma. Sunitinib enhances the efficacy of evofosfamide by increasing hypoxic areas, and evofosfamide targets hypoxic tumor cells. Consequently, each drug enhances the activity of the other. Copyright © 2018. Published by Elsevier Inc.

The effects of ethanol on insulin-like growth factor-I immunoreactive neurons in the central nervous system.

PubMed

Dalcik, Cannur; Yildirim, Guler K; Dalcik, Hakki

2009-08-01

To evaluate the effect of chronically ethanol treatment on insulin-like growth factor-I (IGF-I) synthesis in various adult brain regions using immunocytochemistry. We performed this study at the Faculty of Medicine, Kocaeli University, Kocaeli, Turkey from March 2006 to October 2007. The vascular perfusion was utilized to fix the adult rat brains (10 for each group). After applying the routine histological techniques, the tissues were embedded in the paraffin. The immunohistochemical protocol was applied to the 10 um thick sections and the expression of IGF-I positive cells were observed in the neuro-anatomic areas. The distribution of IGF-I immunoreactive cells differed between the layers of the normal cerebral cortex and in the thalamic areas. In the alcoholic brain, the amount of IGF-I immunoreactive cells were decreased compared to the similar neuro-anatomical areas examined in the normal brains. The presence of IGF-I immunoreactivity in the neurons of the various neuro-anatomic areas demonstrates clearly that, these particular neurons are active in IGF-I synthesis. The decrease in the immunoreactivity of IGF-I in the chronically ethanol treated adult rat brain areas, show clearly that, ethanol effects negatively on the IGF-I synthesis.

The role of tumor necrosis factor-α-related apoptosis-inducing ligand (TRAIL) in mediating autophagy in myositis skeletal muscle: A potential non-immune mechanism of muscle damage

PubMed Central

Alger, Heather M.; Raben, Nina; Pistilli, Emidio; Francia, Dwight; Rawat, Rashmi; Getnet, Derese; Ghimbovschi, Svetlana; Chen, Yi-Wen; Lundberg, Ingrid E.; Nagaraju, Kanneboyina

2011-01-01

Objective Multinucleated cells are relatively resistant to classical apoptosis, and the factors initiating cell-death and damage in myositis are not well defined. We hypothesized that non-immune autophagic cell death may play a role in muscle fiber damage. Recent literature indicates that tumor necrosis factor-alpha-related apoptosis inducing ligand (TRAIL) may induce both NFκB (nuclear factor kappa-light chain enhancer of activated B cells) activation and autophagic cell death in other systems. Here, we have investigated its role in cell death and pathogenesis in vitro and in vivo using myositis (human and mouse) muscle tissues. Methods Gene expression profiling indicated that expression of TRAIL and several autophagy markers was specifically upregulated in myositis muscle tissue; these results were confirmed by immunohistochemistry and immunoblotting. We also analyzed TRAIL-induced cell death (apoptosis and autophagy) and NFκB activation in vitro in cultured cells. Results TRAIL was expressed predominantly in muscle fibers of myositis, but not in biopsies from normal or other dystrophic-diseased muscle. Autophagy markers were upregulated in human and mouse models of myositis. TRAIL expression was restricted to regenerating/atrophic areas of muscle fascicles, blood vessels, and infiltrating lymphocytes. TRAIL induced NFκB activation and IκB degradation in cultured cells that are resistant to TRAIL-induced apoptosis but undergo autophagic cell death. Conclusion Our data demonstrate that TRAIL is expressed in myositis muscle and may mediate both activation of NFκB and autophagic cell death in myositis. Thus, this non-immune pathway may be an attractive target for therapeutic intervention in myositis. PMID:21769834

Macrophage Biochemistry, Activation and Function

DTIC Science & Technology

1981-01-01

vacuolar apparatus become more abundant. Functional capabilities, including phagocytic activity, protein synthesis and surface receptors, also increase...properties of cell components of other tissues has led to the following assignment of marker enzymes to specific macrophage components. This assessment is...subfractions. The surface area of each histogram bar then gives the frac- tional amount of constituent present within each normalized fraction. Distribution

The performances of proto-type Ni/MH secondary batteries using Zr-based hydrogen storage alloys and filamentary type Ni

NASA Astrophysics Data System (ADS)

Lee, Sang-Min; Lee, Ho; Kim, Jin-Ho; Lee, Paul S.; Lee, Jai-Young

2001-04-01

For the purpose of developing a Zr-based Laves phase alloy with higher capacity and better performance for electrochemical application, extensive work has been carried out. After careful alloy design of ZrMn2-based hydrogen storage alloys through varying their stoichiometry by means of substituting or adding alloying elements, the Zr0.9Ti0.1(Mn0.7V0.5Ni1.4)0.92 with high capacity (392 mAh/g at the 0.25C) and improved performance (comparable to that of commercialized AB5 type alloy) was developed. Another endeavor was made to improve the poor activation property and the low rate capability of the developed Zr-based Laves phase alloy for commercialization. The combination method of hot-immersion and slow-charging was introduced. It was found that electrode activation was greatly improved after hot immersion at 80°C for 12h followed by charging at 0.05C. The effects of this method are discussed in comparison with other activation methods. The combination method was successfully applied to the formation process of 80 Ah Ni/MH cells. A series of systematic investigations has been rendered to analyze the inner cell pressure characteristics of a sealed type Ni-MH battery. It was found that the increase of inner cell pressure in the sealed type Ni/MH battery of the above-mentioned Zr-Ti-Mn-V-Ni alloy was mainly due to the accumulation of oxygen gas during charge/discharge cycling. The fact identified that the surface catalytic activity was affected more dominantly by the oxygen recombination reaction than the reaction surface area was also identified. In order to improve the surface catalytic activity of a Zr-Ti-Mn-V-Ni alloy, which is closely related to the inner pressure behavior in a sealed cell, the electrode was fabricated by mixing the alloy with Cu powder and a filamentary type of Ni and replacing 75% of the carbon black with them; thus, the inner cell pressure rarely increases with cycles due to the active gas recombination reaction. Measurements of the surface area of the electrode and the surface catalytic activity showed that the surface catalytic activity for the oxygen recombination reaction was greatly improved by the addition of Cu powder and the filamentary type of Ni. Finally, we have collaborated with Hyundai Motors Company on fabrication of the 80Ah cells for Electric Vehicles and evaluated the cell performance.

Self-assembly Columnar Structure in Active Layer of Bulk Heterojunction Solar Cell

NASA Astrophysics Data System (ADS)

Pan, Cheng; Segui, Jennifer; Yu, Yingjie; Li, Hongfei; Akgun, Bulent; Satijia, Sushil. K.; Gersappe, Dilip; Nam, Chang-Yong; Rafailovich, Miriam

2012-02-01

Bulk Heterojunction (BHJ) polymer solar cells are an area of intense interest due to their flexibility and relatively low cost. However, due to the disordered inner structure in active layer, the power conversion efficiency of BHJ solar cell is relatively low. Our research provides the method to produce ordered self-assembly columnar structure within active layer of bulk heterojunction (BHJ) solar cell by introducing polystyrene (PS) into the active layer. The blend thin film of polystyrene, poly (3-hexylthiophene-2,5-diyl) (P3HT) and [6,6]-phenyl C61 butyric acid methyl ester (PCBM) at different ratio are spin coated on substrate and annealed in vacuum oven for certain time. Atomic force microscopy (AFM) images show uniform phase segregation on the surface of polymer blend thin film and highly ordered columnar structure is then proven by etching the film with ion sputtering. TEM cross-section technology is also used to investigate the column structure. Neutron reflectometry was taken to establish the confinement of PCBM at the interface of PS and P3HT. The different morphological structures formed via phase segregation will be correlated with the performance of the PEV cells to be fabricated at the BNL-CFN.

Introduction to Modern Methods in Light Microscopy.

PubMed

Ryan, Joel; Gerhold, Abby R; Boudreau, Vincent; Smith, Lydia; Maddox, Paul S

2017-01-01

For centuries, light microscopy has been a key method in biological research, from the early work of Robert Hooke describing biological organisms as cells, to the latest in live-cell and single-molecule systems. Here, we introduce some of the key concepts related to the development and implementation of modern microscopy techniques. We briefly discuss the basics of optics in the microscope, super-resolution imaging, quantitative image analysis, live-cell imaging, and provide an outlook on active research areas pertaining to light microscopy.

Immune system alterations in amyotrophic lateral sclerosis.

PubMed

Hovden, H; Frederiksen, J L; Pedersen, S W

2013-11-01

Amyotrophic lateral sclerosis is a disease of which the underlying cause and pathogenesis are unknown. Cumulatative data clearly indicates an active participation by the immune system in the disease. An increasingly recognized theory suggests a non-cell autonomous mechanism, meaning that multiple cells working together are necessary for the pathogenesis of the disease. Observed immune system alterations could indicate an active participation in this mechanism. Damaged motor neurons are able to activate microglia, astrocytes and the complement system, which further can influence each other and contribute to neurodegeneration. Infiltrating peripheral immune cells appears to correlate with disease progression, but their significance and composition is unclear. The deleterious effects of this collaborating system of cells appear to outweigh the protective aspects, and revealing this interplay might give more insight into the disease. Markers from the classical complement pathway are elevated where its initiator C1q appears to derive primarily from motor neurons. Activated microglia and astrocytes are found in close proximity to dying motor neurons. Their activation status and proliferation seemingly increases with disease progression. Infiltrating monocytes, macrophages and T cells are associated with these areas, although with mixed reports regarding T cell composition. This literature review will provide evidence supporting the immune system as an important part of ALS disease mechanism and present a hypothesis to direct the way for further studies. © 2013 John Wiley & Sons A/S.

Tyrosol Suppresses Allergic Inflammation by Inhibiting the Activation of Phosphoinositide 3-Kinase in Mast Cells.

PubMed

Je, In-Gyu; Kim, Duk-Sil; Kim, Sung-Wan; Lee, Soyoung; Lee, Hyun-Shik; Park, Eui Kyun; Khang, Dongwoo; Kim, Sang-Hyun

2015-01-01

Allergic diseases such as atopic dermatitis, rhinitis, asthma, and anaphylaxis are attractive research areas. Tyrosol (2-(4-hydroxyphenyl)ethanol) is a polyphenolic compound with diverse biological activities. In this study, we investigated whether tyrosol has anti-allergic inflammatory effects. Ovalbumin-induced active systemic anaphylaxis and immunoglobulin E-mediated passive cutaneous anaphylaxis models were used for the immediate-type allergic responses. Oral administration of tyrosol reduced the allergic symptoms of hypothermia and pigmentation in both animal models. Mast cells that secrete allergic mediators are key regulators on allergic inflammation. Tyrosol dose-dependently decreased mast cell degranulation and expression of inflammatory cytokines. Intracellular calcium levels and activation of inhibitor of κB kinase (IKK) regulate cytokine expression and degranulation. Tyrosol blocked calcium influx and phosphorylation of the IKK complex. To define the molecular target for tyrosol, various signaling proteins involved in mast cell activation such as Lyn, Syk, phosphoinositide 3-kinase (PI3K), and Akt were examined. Our results showed that PI3K could be a molecular target for tyrosol in mast cells. Taken together, these findings indicated that tyrosol has anti-allergic inflammatory effects by inhibiting the degranulation of mast cells and expression of inflammatory cytokines; these effects are mediated via PI3K. Therefore, we expect tyrosol become a potential therapeutic candidate for allergic inflammatory disorders.

The human uterotubal junction: a scanning electron microscope study during different phases of the menstrual cycle.

PubMed

Fadel, H E; Berns, D; Zaneveld, L J; Wilbanks, G D; Brueschke, E E

1976-10-01

Uterotubal junctions from surgically extirpated human uteri were examined. The specimens were obtained during different phases of the menstrual cycle. The interstitial portions of the tubes together with the cornual areas were dissected, excised, and their luminal surfaces exposed. The specimens were then processed for scanning electron microscopy. The surface epithelium of both the cornual endometrium and interstitial endosalpins. Ciliated cells were more numerous in the endosalpinx. Cyclic changes in ciliated cells were minimal, while cyclic secretory activity was demonstrated, especially in the endometrium. The transitional area between the endometrium and the endosalpinx was characterized by a marked increase in the number of ciliated cells, and a tendency of the secretory cells to assume a flattened, polygonal shape. These morphologic features suggest a possible role in the transport and/or maintenance of spermatozoa and/or ova.

Unexpected severe calcification after transplantation of bone marrow cells in acute myocardial infarction.

PubMed

Yoon, Young-Sup; Park, Jong-Seon; Tkebuchava, Tengiz; Luedeman, Corinne; Losordo, Douglas W

2004-06-29

There has been a rapid increase in the number of clinical trials using unselected bone marrow (BM) cells or the mononuclear fraction of BM cells for treating ischemic heart diseases. Thus far, no significant deleterious effects or complications have been reported in any studies using BM-derived cells for treatment of various cardiac diseases. Seven-week-old female Fisher-344 rats underwent surgery to induce acute myocardial infarction and were randomized into 3 groups of 16 rats, each receiving intramyocardial injection of either 7x10(5) DiI-labeled total BM cells (TBMCs), the same number of DiI-labeled, clonally expanded BM multipotent stem cells, or the same volume of phosphate-buffered saline in the peri-infarct area. Echocardiography 2 weeks after cell transplantation indicated intramyocardial calcification in 4 of 14 surviving rats (28.5%) in the TBMC group. Histological examination with hematoxylin and eosin staining and von Kossa staining confirmed the presence of extensive intramyocardial calcification. Alkaline phosphatase staining revealed strong positivity surrounding the calcified area suggestive of ongoing osteogenic activity. Fluorescent microscopic examination revealed that acellular calcific areas were surrounded by DiI-labeled TBMCs, suggesting the direct involvement of transplanted TBMCs in myocardial calcification. In contrast, in hearts receiving equal volumes of saline or BM multipotent stem cells delivered in the same manner, there was no evidence of calcification. These results demonstrate that direct transplantation of unselected BM cells into the acutely infarcted myocardium may induce significant intramyocardial calcification.

Hypergravity exposure decreases gamma-aminobutyric acid immunoreactivity in axon terminals contacting pyramidal cells in the rat somatosensory cortex: a quantitative immunocytochemical image analysis

NASA Technical Reports Server (NTRS)

D'Amelio, F.; Wu, L. C.; Fox, R. A.; Daunton, N. G.; Corcoran, M. L.; Polyakov, I.

1998-01-01

Quantitative evaluation of gamma-aminobutyric acid immunoreactivity (GABA-IR) in the hindlimb representation of the rat somatosensory cortex after 14 days of exposure to hypergravity (hyper-G) was conducted by using computer-assisted image processing. The area of GABA-IR axosomatic terminals apposed to pyramidal cells of cortical layer V was reduced in rats exposed to hyper-G compared with control rats, which were exposed either to rotation alone or to vivarium conditions. Based on previous immunocytochemical and behavioral studies, we suggest that this reduction is due to changes in sensory feedback information from muscle receptors. Consequently, priorities for muscle recruitment are altered at the cortical level, and a new pattern of muscle activity is thus generated. It is proposed that the reduction observed in GABA-IR of the terminal area around pyramidal neurons is the immunocytochemical expression of changes in the activity of GABAergic cells that participate in reprogramming motor outputs to achieve effective movement control in response to alterations in the afferent information.

Triggering the apoptosis of targeted human renal cancer cells by the vibration of anisotropic magnetic particles attached to the cell membrane.

PubMed

Leulmi, Selma; Chauchet, Xavier; Morcrette, Melissa; Ortiz, Guillermo; Joisten, Hélène; Sabon, Philippe; Livache, Thierry; Hou, Yanxia; Carrière, Marie; Lequien, Stéphane; Dieny, Bernard

2015-10-14

Cancer cells develop resistance to chemotherapy, and the side effects encountered seriously limit the effectiveness of treatments. For these reasons, the search for alternative therapies that target cancer cells without affecting healthy tissues is currently one of the most active areas of research on cancer. The present study focuses on a recently proposed approach for cancer cell destruction based on the targeted triggering of cancer cell spontaneous death through the mechanical vibration of anisotropic magnetic micro/nanoparticles attached to the cell membranes at low frequencies (∼20 Hz) and in weak magnetic fields (∼30 mT). The study was conducted in vitro, on human renal cancer cells with superparamagnetic-like particles. Three types of such particles made of NiFe or magnetite were prepared and characterized (either synthetic antiferromagnetic, vortex or polycrystalline with random grain anisotropy). The triggering of the apoptosis of these cancer cells was demonstrated with NiFe vortex particles and statistically characterized by flow-cytometry studies. The death pathway via apoptosis and not necrosis was identified by the clear observation of caspase activation.

Triggering the apoptosis of targeted human renal cancer cells by the vibration of anisotropic magnetic particles attached to the cell membrane

NASA Astrophysics Data System (ADS)

Leulmi, Selma; Chauchet, Xavier; Morcrette, Melissa; Ortiz, Guillermo; Joisten, Hélène; Sabon, Philippe; Livache, Thierry; Hou, Yanxia; Carrière, Marie; Lequien, Stéphane; Dieny, Bernard

2015-09-01

Cancer cells develop resistance to chemotherapy, and the side effects encountered seriously limit the effectiveness of treatments. For these reasons, the search for alternative therapies that target cancer cells without affecting healthy tissues is currently one of the most active areas of research on cancer. The present study focuses on a recently proposed approach for cancer cell destruction based on the targeted triggering of cancer cell spontaneous death through the mechanical vibration of anisotropic magnetic micro/nanoparticles attached to the cell membranes at low frequencies (~20 Hz) and in weak magnetic fields (~30 mT). The study was conducted in vitro, on human renal cancer cells with superparamagnetic-like particles. Three types of such particles made of NiFe or magnetite were prepared and characterized (either synthetic antiferromagnetic, vortex or polycrystalline with random grain anisotropy). The triggering of the apoptosis of these cancer cells was demonstrated with NiFe vortex particles and statistically characterized by flow-cytometry studies. The death pathway via apoptosis and not necrosis was identified by the clear observation of caspase activation.

New Strategies in Targeted Interventions for Posttraumatic Osteoarthritis (PT-OA)

DTIC Science & Technology

2016-08-01

changes No changes Fisher, M., Sonokawa, M., Conroy, S., Shepard , J., Dealy, N. Reducing EGFR signal activity slows progression of post-traumatic...Quantification for Stem Cell Based Tissue Engineered Cartilage, Stem Cell and Regenerative Medicine, Sept, 2013, University of Illinois at Chicago ...UIC), Chicago , IL. 18. Nukavarapu, S.P.* Tissue Engineered Matrices for Large Area Bone Regeneration, Gordon Research Conference on Musculoskeletal

Visualization of self-heating of an all climate battery by infrared thermography

NASA Astrophysics Data System (ADS)

Zhang, Guangsheng; Tian, Hua; Ge, Shanhai; Marple, Dan; Sun, Fengchun; Wang, Chao-Yang

2018-02-01

Self-heating Li-ion battery (SHLB), a.k.a. all climate battery, has provided a novel and practical solution to the low temperature power loss challenge. During its rapid self-heating, it is critical to keep the heating process and temperature distributions uniform for superior battery performance, durability and safety. Through infrared thermography of an experimental SHLB cell activated from various low ambient temperatures, we find that temperature distribution is uniform over the active electrode area, suggesting uniform heating. We also find that a hot spot exists at the activation terminal during self-heating, which provides diagnostics for improvement of next generation SHLB cells without the hot spot.

IFN-λ: A New Inducer of Local Immunity against Cancer and Infections.

PubMed

Lasfar, Ahmed; Zloza, Andrew; de la Torre, Andrew; Cohen-Solal, Karine A

2016-01-01

IFN-λ is the newly established type III IFN with unique immunomodulatory functions. In contrast to the IFN-α/β family and to some extent IFN-γ, IFN-λ is apparently acting in specific areas of the body to activate resident immune cells and induces a local immunity, instrumental in preventing particular infections and also keeping transformed cells under control. Mucosal areas of lung and gastrointestinal tracts are now under scrutiny to elucidate the immune mechanisms triggered by IFN-λ and leading to viral protection. New evidence also indicates the crucial role of IFN-λ in promoting innate immunity in solid cancer models. Based on its unique biological activities among the IFN system, new immunotherapeutic approaches are now emerging for the treatment of cancer, infection, and autoimmune diseases. In the present review, we highlight the recent advances of IFN-λ immunomodulatory functions. We also discuss the perspectives of IFN-λ as a therapeutic agent.

Mass-produced multi-walled carbon nanotubes as catalyst supports for direct methanol fuel cells.

PubMed

Jang, In Young; Park, Ki Chul; Jung, Yong Chae; Lee, Sun Hyung; Song, Sung Moo; Muramatsu, Hiroyuki; Kim, Yong Jung; Endo, Morinobu

2011-01-01

Commercially mass-produced multi-walled carbon nanotubes, i.e., VGNF (Showa Denko Co.), were applied to support materials for platinum-ruthenium (PtRu) nanoparticles as anode catalysts for direct methanol fuel cells. The original VGNFs are composed of high-crystalline graphitic shells, which hinder the favorable surface deposition of the PtRu nanoparticles that are formed via borohydride reduction. The chemical treatment of VGNFs with potassium hydroxide (KOH), however, enables highly dispersed and dense deposition of PtRu nanoparticles on the VGNF surface. This capability becomes more remarkable depending on the KOH amount. The electrochemical evaluation of the PtRu-deposited VGNF catalysts showed enhanced active surface areas and methanol oxidation, due to the high dispersion and dense deposition of the PtRu nanoparticles. The improvement of the surface deposition states of the PtRu nanoparticles was significantly due to the high surface area and mesorporous surface structure of the KOH-activated VGNFs.

Neural mechanisms underlying auditory feedback control of speech

PubMed Central

Reilly, Kevin J.; Guenther, Frank H.

2013-01-01

The neural substrates underlying auditory feedback control of speech were investigated using a combination of functional magnetic resonance imaging (fMRI) and computational modeling. Neural responses were measured while subjects spoke monosyllabic words under two conditions: (i) normal auditory feedback of their speech, and (ii) auditory feedback in which the first formant frequency of their speech was unexpectedly shifted in real time. Acoustic measurements showed compensation to the shift within approximately 135 ms of onset. Neuroimaging revealed increased activity in bilateral superior temporal cortex during shifted feedback, indicative of neurons coding mismatches between expected and actual auditory signals, as well as right prefrontal and Rolandic cortical activity. Structural equation modeling revealed increased influence of bilateral auditory cortical areas on right frontal areas during shifted speech, indicating that projections from auditory error cells in posterior superior temporal cortex to motor correction cells in right frontal cortex mediate auditory feedback control of speech. PMID:18035557

Changes in immunological profile as a function of urbanization and lifestyle

PubMed Central

Mbow, Moustapha; de Jong, Sanne E; Meurs, Lynn; Mboup, Souleymane; Dieye, Tandakha Ndiaye; Polman, Katja; Yazdanbakhsh, Maria

2014-01-01

Differences in lifestyle and break with natural environment appear to be associated with changes in the immune system resulting in various adverse health effects. Although genetics can have a major impact on the immune system and disease susceptibility, the contribution of environmental factors is thought to be substantial. Here, we investigated the immunological profile of healthy volunteers living in a rural and an urban area of a developing African country (Senegal), and in a European country (the Netherlands). Using flow cytometry, we investigated T helper type 1 (Th1), Th2, Th17, Th22 and regulatory T cells, as well as CD4+ T-cell and B-cell activation markers, and subsets of memory T and B cells in the peripheral blood. Rural Senegalese had significantly higher frequencies of Th1, Th2 and Th22 cells, memory CD4+ T and B cells, as well as activated CD4+ T and B cells compared with urban Senegalese and urban Dutch people. Within the Senegalese population, rural paritcipants displayed significantly higher frequencies of Th2 and Th22 cells, as well as higher pro-inflammatory and T-cell activation and memory profiles compared with the urban population. The greater magnitude of immune activation and the enlarged memory pool, together with Th2 polarization, seen in rural participants from Africa, followed by urban Africans and Europeans suggest that environmental changes may define immunological footprints, which could have consequences for disease patterns in general and vaccine responses in particular. PMID:24924958

Epigallocatechin gallate protects dopaminergic neurons against 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity by inhibiting microglial cell activation.

PubMed

Li, Rui; Peng, Ning; Du, Fang; Li, Xu-ping; Le, Wei-dong

2006-04-01

To observe whether the dopaminergic neuroprotective effect of (-)-epigallocatechin gallate (EGCG) is associated with its inhibition of microglial cell activation in vivo. The effects of EGCG at different doses on dopaminergic neuronal survival were tested in a methyl-4-phenyl-pyridinium (MPP+)-induced dopaminergic neuronal injury model in the primary mesencephalic cell cultures. With unbiased stereological method, tyrosine hydroxylase-immunoreactive (TH-ir) cells were counted in the A8, A9 and A10 regions of the substantia nigra (SN) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated C57BL/6 mice. The effect of EGCG on microglial activation in the SN was also investigated. Pretreatment with EGCG (1 to 100 micromol/L) significantly attenuated MPP+-induced TH-ir cell loss by 22.2% to 80.5% in the mesencephalic cell cultures. In MPTP-treated C57BL/6 mice, EGCG at a low concentration (1 mg/kg) provided significant protection against MPTP-induced TH-ir cell loss by 50.9% in the whole nigral area and by 71.7% in the A9 region. EGCG at 5 mg/kg showed more prominent protective effect than at 1 or 10 mg/kg. EGCG pretreatment significantly inhibited microglial activation and CD11b expression induced by MPTP. EGCG exerts potent dopaminergic neuroprotective activity by means of microglial inhibition, which shed light on the potential use of EGCG in treatment of Parkinson's disease.

Nervus terminalis ganglion of the bonnethead shark (Sphyrna tiburo): evidence for cholinergic and catecholaminergic influence on two cell types distinguished by peptide immunocytochemistry.

PubMed

White, J; Meredith, M

1995-01-16

The nervus terminalis is a ganglionated vertebrate cranial nerve of unknown function that connects the brain and the peripheral nasal structures. To investigate its function, we have studied nervus terminalis ganglion morphology and physiology in the bonnethead shark (Sphyrna tiburo), where the nerve is particularly prominent. Immunocytochemistry for gonadotropin-releasing hormone (GnRH) and Leu-Pro-Leu-Arg-Phe-NH2 (LPLRFamide) revealed two distinct populations of cells. Both were acetylcholinesterase positive, but LPLR-Famide-immunoreactive cells consistently stained more darkly for acetylcholinesterase activity. Tyrosine hydroxylase immunocytochemistry revealed fibers and terminal-like puncta in the ganglion, primarily in areas containing GnRH-immunoreactive cells. Consistent with the anatomy, in vitro electrophysiological recordings provided evidence for cholinergic and catecholaminergic actions. In extracellular recordings, acetylcholine had a variable effect on baseline ganglion cell activity, whereas norepinephrine consistently reduced activity. Electrical stimulation of the nerve trunks suppressed ganglion activity, as did impulses from the brain in vivo. During electrical suppression, acetylcholine consistently increased activity, and norepinephrine decreased activity. Muscarinic and, to a lesser extent, alpha-adrenergic antagonists both increased activity during the electrical suppression, suggesting involvement of both systems. Intracellular recordings revealed two types of ganglion cells that were distinguishable pharmacologically and physiologically. Some cells were hyperpolarized by cholinergic agonists and unaffected by norepinephrine; these cells did not depolarize with peripheral nerve trunk stimulation. Another group of cells did depolarize with peripheral trunk stimulation; a representative of this group was depolarized by carbachol and hyperpolarized by norepinephrine. These and other data suggest that the bonnethead nervus terminalis ganglion contains at least two cell populations that respond differently to acetylcholine and norepinephrine. The bonnethead nervus terminalis ganglion appears to differ fundamentally from sensory and autonomic ganglia but does share some features with the neural circuits of forebrain GnRH systems.

Voluntary wheel running increases satellite cell abundance and improves recovery from disuse in gastrocnemius muscles from mice.

PubMed

Brooks, Matthew J; Hajira, Ameena; Mohamed, Junaith S; Alway, Stephen E

2018-06-01

Reloading of atrophied muscles after hindlimb suspension unloading (HSU) can induce injury and prolong recovery. Low-impact exercise, such as voluntary wheel running, has been identified as a nondamaging rehabilitation therapy in rodents, but its effects on muscle function, morphology, and satellite cell activity after HSU are unclear. This study tested the hypothesis that low-impact wheel running would increase satellite cell proliferation and improve recovery of muscle structure and function after HSU in mice. Young adult male and female C57BL/6 mice ( n = 6/group) were randomly placed into five groups. These included HSU without recovery (HSU), normal ambulatory recovery for 14 days after HSU (HSU+NoWR), and voluntary wheel running recovery for 14 days after HSU (HSU+WR). Two control groups were used: nonsuspended mouse cage controls (Control) and voluntary wheel running controls (ControlWR). Satellite cell activation was evaluated by providing mice 5-bromo-2'-deoxyuridine (BrdU) in their drinking water. As expected, HSU significantly reduced in vivo maximal force, decreased in vivo fatigability, and decreased type I and IIa myosin heavy chain (MHC) abundance in plantarflexor muscles. HSU+WR mice significantly improved plantarflexor fatigue resistance, increased type I and IIa MHC abundance, increased fiber cross-sectional area, and increased the percentage of type I and IIA muscle fibers in the gastrocnemius muscle. HSU+WR mice also had a significantly greater percentage of BrdU-positive and Pax 7-positive nuclei inside muscle fibers and a greater MyoD-to-Pax 7 protein ratio compared with HSU+NoWR mice. The mechanotransduction protein Yes-associated protein (YAP) was elevated with reloading after HSU, but HSU+WR mice had lower levels of the inactive phosphorylated YAP serine127 , which may have contributed to increased satellite cell activation with reloading after HSU. These results indicate that voluntary wheel running increased YAP signaling and satellite cell activity after HSU and this was associated with improved recovery. NEW & NOTEWORTHY Although satellite cell involvement in muscle remodeling has been challenged, the data in this study suggest that voluntary wheel running increased satellite cell activity and suppressed Yes-associated protein (YAP) protein relative to no wheel running and this was associated with improved muscle recovery of force, fatigue resistance, expression of type I myosin heavy chain, and greater fiber cross-sectional area after disuse.

Bio optofluidics cell sorter: cell-BOCS concept and applications

NASA Astrophysics Data System (ADS)

Roth, Tue; Glückstad, Jesper

2012-03-01

The cell-BOCS is a novel microfluidics based cell-sorting instrument utilizing next generation optical trapping technology developed at the Technical University of Denmark. It is targeted emerging bio-medical research and diagnostics markets where it for certain applications offers a number of advantages over conventional fluorescence activated cell-sorting (FACSTM) technology. Advantages include gentle handling of cells, sterile sorting, easy operation, small footprint and lower cost allowing out-of-core-facility use. Application examples are found within sorting of fragile transfected cells, high value samples and primary cell lines, where traditional FACS technology has limited application due to it's droplet-based approach to cell-sorting. In the diagnostics field, in particular applying the cell-BOCS for isolating pure populations of circulating tumor cells is an area that has generated a lot of interest.

The planar multijunction cell - A new solar cell for earth and space

NASA Technical Reports Server (NTRS)

Evans, J. C., Jr.; Chai, A.-T.; Goradia, C.

1980-01-01

A new family of high-voltage solar cells, called the planar multijunction (PMJ) cell is being developed. The new cells combine the attractive features of planar cells with conventional or interdigitated back contacts and the vertical multijunction (VMJ) solar cell. The PMJ solar cell is internally divided into many voltage-generating regions, called unit cells, which are internally connected in series. The key to obtaining reasonable performance from this device was the separation of top surface field regions over each active unit cell area. Using existing solar cell fabricating methods, output voltages in excess of 20 volts per linear centimeter are possible. Analysis of the new device is complex, and numerous geometries are being studied which should provide substantial benefits in both normal sunlight usage as well as with concentrators.

Characterization of the bone marrow adipocyte niche with three-dimensional electron microscopy.

PubMed

Robles, Hero; Park, SungJae; Joens, Matthew S; Fitzpatrick, James A J; Craft, Clarissa S; Scheller, Erica L

2018-01-27

Unlike white and brown adipose tissues, the bone marrow adipocyte (BMA) exists in a microenvironment containing unique populations of hematopoietic and skeletal cells. To study this microenvironment at the sub-cellular level, we performed a three-dimensional analysis of the ultrastructure of the BMA niche with focused ion beam scanning electron microscopy (FIB-SEM). This revealed that BMAs display hallmarks of metabolically active cells including polarized lipid deposits, a dense mitochondrial network, and areas of endoplasmic reticulum. The distinct orientations of the triacylglycerol droplets suggest that fatty acids are taken up and/or released in three key areas - at the endothelial interface, into the hematopoietic milieu, and at the bone surface. Near the sinusoidal vasculature, endothelial cells send finger-like projections into the surface of the BMA which terminate near regions of lipid within the BMA cytoplasm. In some regions, perivascular cells encase the BMA with their flattened cellular projections, limiting contacts with other cells in the niche. In the hematopoietic milieu, BMAT adipocytes of the proximal tibia interact extensively with maturing cells of the myeloid/granulocyte lineage. Associations with erythroblast islands are also prominent. At the bone surface, the BMA extends organelle and lipid-rich cytoplasmic regions toward areas of active osteoblasts. This suggests that the BMA may serve to partition nutrient utilization between diverse cellular compartments, serving as an energy-rich hub of the stromal-reticular network. Lastly, though immuno-EM, we've identified a subset of bone marrow adipocytes that are innervated by the sympathetic nervous system, providing an additional mechanism for regulation of the BMA. In summary, this work reveals that the bone marrow adipocyte is a dynamic cell with substantial capacity for interactions with the diverse components of its surrounding microenvironment. These local interactions likely contribute to its unique regulation relative to peripheral adipose tissues. Copyright © 2018 Elsevier Inc. All rights reserved.

Progress in the Development of Lightweight Nickel Electrode for Nickel-Hydrogen Cell

NASA Technical Reports Server (NTRS)

Britton, Doris L.

1999-01-01

Development of a high specific energy battery is one of the objectives of the lightweight nickel-hydrogen (Ni-H2) program at the NASA Glenn Research Center. The approach has been to improve the nickel electrode by continuing combined in-house and contract efforts to develop a lighter weight electrode for the nickel-hydrogen cell. Small fiber diameter nickel plaques are used as conductive supports for the nickel hydroxide active material. These plaques are commercial products and have an advantage of increased surface area available for the deposition of active material. Initial tests include activation and capacity measurements at five different discharge levels, C/2, 1.0 C, 1.37 C, 2.0 C, and 2.74 C. The electrodes are life cycle tested using a half-cell configuration at 40 and 80% depths-of-discharge (DOD) in a low-Earth-orbit regime. The electrodes that pass the initial tests are life cycle-tested in a boiler plate nickel-hydrogen cell before flight weight design are built and tested.

Anti-tumor activity of staurosporine in the tumor microenvironment of cervical cancer: An in vitro study.

PubMed

Yadav, Suresh Singh; Prasad, Chandra Bhushan; Prasad, Shyam Babu; Pandey, Lakshmi Kant; Singh, Sunita; Pradhan, Satyajit; Narayan, Gopeshwar

2015-07-15

The fundamental events for cancer progression and metastases include loss of cell adhesion, cell proliferation, anchorage-independent cell growth (evading anoikis), cell migration and cell invasion. All these events leading to cancer progression happen in a favorable nurturing tumor microenvironment. This study was designed to explore the anti-tumor activity of staurosporine (a nonspecific protein kinase inhibitor) in the tumor microenvironment of cervical cancer. The anti-tumor activity of staurosporine was investigated by cell adhesion assay, colony formation assay, apoptosis assay and quantitative real-time polymerase chain reaction (PCR) in cervical cancer cell lines. The cell adhesion assay showed that staurosporine induces adhesion of cervical cancer cells to the extracellular matrix (ECM) protein fibronectin. The soft agar colony formation assay showed that staurosporine inhibits both the number and size of colony formation in a dose dependent manner and also induces adherent tendency in the cancer cells. Staurosporine also induces prominent apoptosis in single cell suspensions compared to adherent cells. Stroma cell induced transcription of matrix metalloprotease 1 (MMP1) and matrix metalloprotease 2 (MMP2) in cervical cancer cells was inhibited by staurosporine. Our results indicate that staurosporine induces anti-tumor response in the cervical tumor microenvironment by inhibiting the fundamental events for cancer progression and metastases. The present study represents an attractive area for further research and opens up new avenues towards the understanding of cervical cancer therapeutics. Copyright © 2015 Elsevier Inc. All rights reserved.

Neurons derived from different brain regions are inherently different in vitro: a novel multiregional brain-on-a-chip.

PubMed

Dauth, Stephanie; Maoz, Ben M; Sheehy, Sean P; Hemphill, Matthew A; Murty, Tara; Macedonia, Mary Kate; Greer, Angie M; Budnik, Bogdan; Parker, Kevin Kit

2017-03-01

Brain in vitro models are critically important to developing our understanding of basic nervous system cellular physiology, potential neurotoxic effects of chemicals, and specific cellular mechanisms of many disease states. In this study, we sought to address key shortcomings of current brain in vitro models: the scarcity of comparative data for cells originating from distinct brain regions and the lack of multiregional brain in vitro models. We demonstrated that rat neurons from different brain regions exhibit unique profiles regarding their cell composition, protein expression, metabolism, and electrical activity in vitro. In vivo, the brain is unique in its structural and functional organization, and the interactions and communication between different brain areas are essential components of proper brain function. This fact and the observation that neurons from different areas of the brain exhibit unique behaviors in vitro underline the importance of establishing multiregional brain in vitro models. Therefore, we here developed a multiregional brain-on-a-chip and observed a reduction of overall firing activity, as well as altered amounts of astrocytes and specific neuronal cell types compared with separately cultured neurons. Furthermore, this multiregional model was used to study the effects of phencyclidine, a drug known to induce schizophrenia-like symptoms in vivo, on individual brain areas separately while monitoring downstream effects on interconnected regions. Overall, this work provides a comparison of cells from different brain regions in vitro and introduces a multiregional brain-on-a-chip that enables the development of unique disease models incorporating essential in vivo features. NEW & NOTEWORTHY Due to the scarcity of comparative data for cells from different brain regions in vitro, we demonstrated that neurons isolated from distinct brain areas exhibit unique behaviors in vitro. Moreover, in vivo proper brain function is dependent on the connection and communication of several brain regions, underlining the importance of developing multiregional brain in vitro models. We introduced a novel brain-on-a-chip model, implementing essential in vivo features, such as different brain areas and their functional connections. Copyright © 2017 the American Physiological Society.

Neurons derived from different brain regions are inherently different in vitro: a novel multiregional brain-on-a-chip

PubMed Central

Dauth, Stephanie; Maoz, Ben M.; Sheehy, Sean P.; Hemphill, Matthew A.; Murty, Tara; Macedonia, Mary Kate; Greer, Angie M.; Budnik, Bogdan

2017-01-01

Brain in vitro models are critically important to developing our understanding of basic nervous system cellular physiology, potential neurotoxic effects of chemicals, and specific cellular mechanisms of many disease states. In this study, we sought to address key shortcomings of current brain in vitro models: the scarcity of comparative data for cells originating from distinct brain regions and the lack of multiregional brain in vitro models. We demonstrated that rat neurons from different brain regions exhibit unique profiles regarding their cell composition, protein expression, metabolism, and electrical activity in vitro. In vivo, the brain is unique in its structural and functional organization, and the interactions and communication between different brain areas are essential components of proper brain function. This fact and the observation that neurons from different areas of the brain exhibit unique behaviors in vitro underline the importance of establishing multiregional brain in vitro models. Therefore, we here developed a multiregional brain-on-a-chip and observed a reduction of overall firing activity, as well as altered amounts of astrocytes and specific neuronal cell types compared with separately cultured neurons. Furthermore, this multiregional model was used to study the effects of phencyclidine, a drug known to induce schizophrenia-like symptoms in vivo, on individual brain areas separately while monitoring downstream effects on interconnected regions. Overall, this work provides a comparison of cells from different brain regions in vitro and introduces a multiregional brain-on-a-chip that enables the development of unique disease models incorporating essential in vivo features. NEW & NOTEWORTHY Due to the scarcity of comparative data for cells from different brain regions in vitro, we demonstrated that neurons isolated from distinct brain areas exhibit unique behaviors in vitro. Moreover, in vivo proper brain function is dependent on the connection and communication of several brain regions, underlining the importance of developing multiregional brain in vitro models. We introduced a novel brain-on-a-chip model, implementing essential in vivo features, such as different brain areas and their functional connections. PMID:28031399

Active tension network model suggests an exotic mechanical state realized in epithelial tissues

NASA Astrophysics Data System (ADS)

Noll, Nicholas; Mani, Madhav; Heemskerk, Idse; Streichan, Sebastian J.; Shraiman, Boris I.

2017-12-01

Mechanical interactions play a crucial role in epithelial morphogenesis, yet understanding the complex mechanisms through which stress and deformation affect cell behaviour remains an open problem. Here we formulate and analyse the active tension network (ATN) model, which assumes that the mechanical balance of cells within a tissue is dominated by cortical tension and introduces tension-dependent active remodelling of the cortex. We find that ATNs exhibit unusual mechanical properties. Specifically, an ATN behaves as a fluid at short times, but at long times supports external tension like a solid. Furthermore, an ATN has an extensively degenerate equilibrium mechanical state associated with a discrete conformal--`isogonal'--deformation of cells. The ATN model predicts a constraint on equilibrium cell geometries, which we demonstrate to approximately hold in certain epithelial tissues. We further show that isogonal modes are observed in the fruit fly embryo, accounting for the striking variability of apical areas of ventral cells and helping understand the early phase of gastrulation. Living matter realizes new and exotic mechanical states, the study of which helps to understand biological phenomena.

CA1 cell activity sequences emerge after reorganization of network correlation structure during associative learning

PubMed Central

Modi, Mehrab N; Dhawale, Ashesh K; Bhalla, Upinder S

2014-01-01

Animals can learn causal relationships between pairs of stimuli separated in time and this ability depends on the hippocampus. Such learning is believed to emerge from alterations in network connectivity, but large-scale connectivity is difficult to measure directly, especially during learning. Here, we show that area CA1 cells converge to time-locked firing sequences that bridge the two stimuli paired during training, and this phenomenon is coupled to a reorganization of network correlations. Using two-photon calcium imaging of mouse hippocampal neurons we find that co-time-tuned neurons exhibit enhanced spontaneous activity correlations that increase just prior to learning. While time-tuned cells are not spatially organized, spontaneously correlated cells do fall into distinct spatial clusters that change as a result of learning. We propose that the spatial re-organization of correlation clusters reflects global network connectivity changes that are responsible for the emergence of the sequentially-timed activity of cell-groups underlying the learned behavior. DOI: http://dx.doi.org/10.7554/eLife.01982.001 PMID:24668171

Hydrogen oxidation mechanisms on Ni/yttria stabilized zirconia anodes: Separation of reaction pathways by geometry variation of pattern electrodes

NASA Astrophysics Data System (ADS)

Doppler, M. C.; Fleig, J.; Bram, M.; Opitz, A. K.

2018-03-01

Nickel/yttria stabilized zirconia (YSZ) electrodes are affecting the overall performance of solid oxide fuel cells (SOFCs) in general and strongly contribute to the cell resistance in case of novel metal supported SOFCs in particular. The electrochemical fuel conversion mechanisms in these electrodes are, however, still only partly understood. In this study, micro-structured Ni thin film electrodes on YSZ with 15 different geometries are utilized to investigate reaction pathways for the hydrogen electro-oxidation at Ni/YSZ anodes. From electrodes with constant area but varying triple phase boundary (TPB) length a contribution to the electro-catalytic activity is found that does not depend on the TPB length. This additional activity could clearly be attributed to a yet unknown reaction pathway scaling with the electrode area. It is shown that this area related pathway has significantly different electrochemical behavior compared to the TPB pathway regarding its thermal activation, sulfur poisoning behavior, and H2/H2O partial pressure dependence. Moreover, possible reaction mechanisms of this reaction pathway are discussed, identifying either a pathway based on hydrogen diffusion through Ni with water release at the TPB or a path with oxygen diffusion through Ni to be a very likely explanation for the experimental results.

Coherent ongoing subthreshold state of a cortical neural network regulated by slow- and fast-spiking interneurons.

PubMed

Hoshino, Osamu

2006-12-01

Although details of cortical interneurons in anatomy and physiology have been well understood, little is known about how they contribute to ongoing spontaneous neuronal activity that could have a great impact on subsequent neuronal information processing. Simulating a cortical neural network model of an early sensory area, we investigated whether and how two distinct types of inhibitory interneurons, or fast-spiking interneurons with narrow axonal arbors and slow-spiking interneurons with wide axonal arbors, have a spatiotemporal influence on the ongoing activity of principal cells and subsequent cognitive information processing. In the model, dynamic cell assemblies, or population activation of principal cells, expressed information about specific sensory features. Within cell assemblies, fast-spiking interneurons give a feedback inhibitory effect on principal cells. Between cell assemblies, slow-spiking interneurons give a lateral inhibitory effect on principal cells. Here, we show that these interneurons keep the network at a subthreshold level for action potential generation under the ongoing state, by which the reaction time of principal cells to sensory stimulation could be accelerated. We suggest that the best timing of inhibition mediated by fast-spiking interneurons and slow-spiking interneurons allows the network to remain near threshold for rapid responses to input.

Systematic screening of carbon-based anode materials for microbial fuel cells with Shewanella oneidensis MR-1.

PubMed

Kipf, Elena; Koch, Julia; Geiger, Bettina; Erben, Johannes; Richter, Katrin; Gescher, Johannes; Zengerle, Roland; Kerzenmacher, Sven

2013-10-01

We present a systematic screening of carbon-based anode materials for microbial fuel cells with Shewanella oneidensis MR-1. Under anoxic conditions nanoporous activated carbon cloth is a superior anode material in terms of current density normalized to the projected anode area and anode volume (24.0±0.3 μA cm(-2) and 482±7 μA cm(-3) at -0.2 vs. SCE, respectively). The good performance can be attributed to the high specific surface area of the material, which is available for mediated electron transfer through self-secreted flavins. Under aerated conditions no influence of the specific surface area is observed, which we attribute to a shift from primary indirect electron transfer by mediators to direct electron transfer via adherent cells. Furthermore, we show that an aerated initial growth phase enhances the current density under subsequent anoxic conditions fivefold when compared to a similar experiment that was conducted under permanently anoxic conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Spatially restricted electrical activation of retinal ganglion cells in the rabbit retina by hexapolar electrode return configuration

NASA Astrophysics Data System (ADS)

Habib, Amgad G.; Cameron, Morven A.; Suaning, Gregg J.; Lovell, Nigel H.; Morley, John W.

2013-06-01

Objective. Visual prostheses currently in development aim to restore some form of vision to patients suffering from diseases such as age-related macular degeneration and retinitis pigmentosa. Most rely on electrically stimulating inner retinal cells via electrodes implanted on or near the retina, resulting in percepts of light termed ‘phosphenes’. Activation of spatially distinct populations of cells in the retina is key for pattern vision to be produced. To achieve this, the electrical stimulation must be localized, activating cells only in the direct vicinity of the stimulating electrode(s). With this goal in mind, a hexagonal return (hexapolar) configuration has been proposed as an alternative to the traditional monopolar or bipolar return configurations for electrically stimulating the retina. This study investigated the efficacy of the hexapolar configuration in localizing the activation of retinal ganglion cells (RGCs), compared to a monopolar configuration. Approach. Patch-clamp electrophysiology was used to measure the activation thresholds of RGCs in whole-mount rabbit retina to monopolar and hexapolar electrical stimulation, applied subretinally. Main results. Hexapolar activation thresholds for RGCs located outside the hex guard were found to be significantly (>2 fold) higher than those located inside the area of tissue bounded by the hex guard. The hexapolar configuration localized the activation of RGCs more effectively than its monopolar counterpart. Furthermore, no difference in hexapolar thresholds or localization was observed when using cathodic-first versus anodic-first stimulation. Significance. The hexapolar configuration may provide an improved method for electrically stimulating spatially distinct populations of cells in retinal tissue.

Variegation in Arum italicum leaves. A structural-functional study.

PubMed

La Rocca, Nicoletta; Rascio, Nicoletta; Pupillo, Paolo

2011-12-01

The presence of pale-green flecks on leaves (speckling) is a frequent character among herbaceous species from shady places and is usually due to local loosening of palisade tissue (air space type of variegation). In the winter-green Arum italicum L. (Araceae), dark-green areas of variegated leaf blades are ca. 400 μm thick with a chlorophyll content of 1080 mg m⁻² and a palisade parenchyma consisting of a double layer of oblong cells. Pale-green areas are 25% thinner, have 26% less chlorophyll and contain a single, loose layer of short palisade cells. Full-green leaves generally present only one compact layer of cylindrical palisade cells and the same pigment content as dark-green sectors, but the leaf blade is 13% thinner. A spongy parenchyma with extensive air space is present in all leaf types. Green cells of all tissues have normal chloroplasts. Assays of photosynthetic activities by chlorophyll fluorescence imaging and O₂ exchange measurements showed that variegated pale-green and dark-green sectors as well as full-green leaves have comparable photosynthetic activities on a leaf area basis at saturating illumination. However, full-green leaves require a higher saturating light with respect to variegated sectors, and pale-green sectors support relatively higher photosynthesis rates on a chlorophyll basis. We conclude that i) variegation in this species depends on number and organization of palisade cell layers and can be defined as a "variable palisade" type, and ii) the variegated habit has no limiting effects on the photosynthetic energy budget of A. italicum, consistent with the presence of variegated plants side by side to full-green ones in natural populations. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

The pancreatic stellate cell: a star on the rise in pancreatic diseases

PubMed Central

Omary, M. Bishr; Lugea, Aurelia; Lowe, Anson W.; Pandol, Stephen J.

2007-01-01

Pancreatic stellate cells (PaSCs) are myofibroblast-like cells found in the areas of the pancreas that have exocrine function. PaSCs are regulated by autocrine and paracrine stimuli and share many features with their hepatic counterparts, studies of which have helped further our understanding of PaSC biology. Activation of PaSCs induces them to proliferate, to migrate to sites of tissue damage, to contract and possibly phagocytose, and to synthesize ECM components to promote tissue repair. Sustained activation of PaSCs has an increasingly appreciated role in the fibrosis that is associated with chronic pancreatitis and with pancreatic cancer. Therefore, understanding the biology of PaSCs offers potential therapeutic targets for the treatment and prevention of these diseases. PMID:17200706

High-level secretion of tissue factor-rich extracellular vesicles from ovarian cancer cells mediated by filamin-A and protease-activated receptors.

PubMed

Koizume, Shiro; Ito, Shin; Yoshioka, Yusuke; Kanayama, Tomohiko; Nakamura, Yoshiyasu; Yoshihara, Mitsuyo; Yamada, Roppei; Ochiya, Takahiro; Ruf, Wolfram; Miyagi, Etsuko; Hirahara, Fumiki; Miyagi, Yohei

2016-01-01

Thromboembolic events occur frequently in ovarian cancer patients. Tissue factor (TF) is often overexpressed in tumours, including ovarian clear-cell carcinoma (CCC), a subtype with a generally poor prognosis. TF-coagulation factor VII (fVII) complexes on the cell surface activate downstream coagulation mechanisms. Moreover, cancer cells secrete extracellular vesicles (EVs), which act as vehicles for TF. We therefore examined the characteristics of EVs produced by ovarian cancer cells of various histological subtypes. CCC cells secreted high levels of TF within EVs, while the high-TF expressing breast cancer cell line MDA-MB-231 shed fewer TF-positive EVs. We also found that CCC tumours with hypoxic tissue areas synthesised TF and fVII in vivo, rendering the blood of xenograft mice bearing these tumours hypercoagulable compared with mice bearing MDA-MB-231 tumours. Incorporation of TF into EVs and secretion of EVs from CCC cells exposed to hypoxia were both dependent on the actin-binding protein, filamin-A (filA). Furthermore, production of these EVs was dependent on different protease-activated receptors (PARs) on the cell surface. These results show that CCC cells could produce large numbers of TF-positive EVs dependent upon filA and PARs. This phenomenon may be the mechanism underlying the increased incidence of venous thromboembolism in ovarian cancer patients.

Cellulose microfibril deposition: coordinated activity at the plant plasma membrane.

PubMed

Lindeboom, J; Mulder, B M; Vos, J W; Ketelaar, T; Emons, A M C

2008-08-01

Plant cell wall production is a membrane-bound process. Cell walls are composed of cellulose microfibrils, embedded inside a matrix of other polysaccharides and glycoproteins. The cell wall matrix is extruded into the existing cell wall by exocytosis. This same process also inserts the cellulose synthase complexes into the plasma membrane. These complexes, the nanomachines that produce the cellulose microfibrils, move inside the plasma membrane leaving the cellulose microfibrils in their wake. Cellulose microfibril angle is an important determinant of cell development and of tissue properties and as such relevant for the industrial use of plant material. Here, we provide an integrated view of the events taking place in the not more than 100 nm deep area in and around the plasma membrane, correlating recent results provided by the distinct field of plant cell biology. We discuss the coordinated activities of exocytosis, endocytosis, and movement of cellulose synthase complexes while producing cellulose microfibrils and the link of these processes to the cortical microtubules.

Cellular and humoral immune reactions in chronic active liver disease. II. Lymphocyte subsets and viral antigens in liver biopsies of patients with acute and chronic hepatitis B.

PubMed Central

Eggink, H F; Houthoff, H J; Huitema, S; Wolters, G; Poppema, S; Gips, C H

1984-01-01

The characteristics and distribution of the inflammatory infiltrate in liver biopsies of 25 patients with hepatitis B viral (HBV) infection were studied in relation to the distribution and expression of HBV antigens. Mononuclear subsets were characterized with monoclonal (OKT, OKM, Leu) antibodies to surface antigens. For the demonstration of viral antigens directly conjugated antibodies to surface (HBsAg), core (HBcAg) and 'e' (HBeAg) antigen were used. For the study of mutual relations all methods were performed on serial cut tissue sections. In chronic active hepatitis B (CAH-B, n = 12) OKT8+ lymphocytes of T cell origin were the only cell type present in areas with liver cell degeneration and T cell cytotoxicity appears to be the only immune mechanism. In chronic persistent hepatitis B (CPH-B, n = 7) the only conspicuous feature was the presence of many Leu 3+ lymphocytes of the helper/inducer population in the portal tracts. In acute hepatitis B (AHB, n = 6) OKT8+ cells of non-T origin (OKT1-,3-) and Leu 7+ cells of presumed natural killer (NK) potential predominated in the areas with liver cell necrosis, and non-T cell cytotoxicity appears to be the predominant immune mechanism. In none of these disease entities a positive spatial relation could be established between the cytotoxic cells and the demonstrable expression of HBV antigens in hepatocytes. It is concluded that differences in immunological reaction pattern may explain the different course in the three forms of HBV infection studied. Images Fig. 1 Fig. 2 PMID:6713726

Revisiting the liver in human yellow fever: virus-induced apoptosis in hepatocytes associated with TGF-beta, TNF-alpha and NK cells activity.

PubMed

Quaresma, Juarez A S; Barros, Vera L R S; Pagliari, Carla; Fernandes, Elaine R; Guedes, Fernanda; Takakura, Cleusa F H; Andrade, Heitor F; Vasconcelos, Pedro F C; Duarte, Maria I S

2006-02-05

Flavivirus infection as dengue and yellow fever persists as a terrible menace to pandemics, due to Aedes prevalence in the Americas. Yellow fever is characterized by hepatocyte damage, with steatosis, apoptosis and necrosis, mainly in the midzonal region of the liver, but the injury mechanism has not been studied at the light of recent knowledge, such as the advances in cell death mechanisms, inflammatory response and cytokine cell expression tools. We studied 53 human liver paraffin embedded blocks from patients who died with yellow fever, all with histological demonstration of higher prevalence of apoptosis over necrosis and mild disproportionate inflammatory response. Viral antigens were found most frequently in hepatocytes from the midzonal area than other lobule areas, as detected by specific immunohistochemistry. Infiltrating cell subpopulations showed mainly CD4+ T lymphocytes, with small numbers of CD8+ cytotoxic lymphocytes, CD20+ B lymphocytes, NKT+ cells and S100+ dendritic cells in the sites of inflammation, as compared to normal and leptospirosis liver blocks. Some cells expressed TNF-alpha and IFN-gamma, but a much more intense proportion of TGF-beta expressing cells were found, suggesting both a Th1 and Th3 patterns of immune response in yellow fever. Most affected hepatocyte presented apoptosis markers that appear at the cell death main pathway in this infection. Viral antigens, which production could interfere in hepatocyte biology, could induce the activation of apoptosis cascade, but TGF-beta was also an apoptosis promoter. Our finding supports the key effect of the yellow fever virus in hepatocyte injury, resulting in prevalence of apoptosis over necrosis, aside from a TGF-beta action induced by the inflammatory response.

Expression of peroxisome proliferator-activated receptor-gamma in key neuronal subsets regulating glucose metabolism and energy homeostasis.

PubMed

Sarruf, David A; Yu, Fang; Nguyen, Hong T; Williams, Diana L; Printz, Richard L; Niswender, Kevin D; Schwartz, Michael W

2009-02-01

In addition to increasing insulin sensitivity and adipogenesis, peroxisome proliferator-activated receptor (PPAR)-gamma agonists cause weight gain and hyperphagia. Given the central role of the brain in the control of energy homeostasis, we sought to determine whether PPARgamma is expressed in key brain areas involved in metabolic regulation. Using immunohistochemistry, PPARgamma distribution and its colocalization with neuron-specific protein markers were investigated in rat and mouse brain sections spanning the hypothalamus, the ventral tegmental area, and the nucleus tractus solitarius. In several brain areas, nuclear PPARgamma immunoreactivity was detected in cells that costained for neuronal nuclei, a neuronal marker. In the hypothalamus, PPARgamma immunoreactivity was observed in a majority of neurons in the arcuate (including both agouti related protein and alpha-MSH containing cells) and ventromedial hypothalamic nuclei and was also present in the hypothalamic paraventricular nucleus, the lateral hypothalamic area, and tyrosine hydroxylase-containing neurons in the ventral tegmental area but was not expressed in the nucleus tractus solitarius. To validate and extend these histochemical findings, we generated mice with neuron-specific PPARgamma deletion using nestin cre-LoxP technology. Compared with littermate controls, neuron-specific PPARgamma knockout mice exhibited dramatic reductions of both hypothalamic PPARgamma mRNA levels and PPARgamma immunoreactivity but showed no differences in food intake or body weight over a 4-wk study period. We conclude that: 1) PPARgamma mRNA and protein are expressed in the hypothalamus, 2) neurons are the predominant source of PPARgamma in the central nervous system, although it is likely expressed by nonneuronal cell types as well, and 3) arcuate nucleus neurons that control energy homeostasis and glucose metabolism are among those in which PPARgamma is expressed.

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

Satyapal, Sunita

The 2011 Annual Progress Report summarizes fiscal year 2011 activities and accomplishments by projects funded by the DOE Hydrogen Program. It covers the program areas of hydrogen production and delivery; hydrogen storage; fuel cells; manufacturing; technology validation; safety, codes and standards; education; market transformation; and systems analysis.

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

none,

The 2013 Annual Progress Report summarizes fiscal year 2013 activities and accomplishments by projects funded by the DOE Hydrogen Program. It covers the program areas of hydrogen production and delivery; hydrogen storage; fuel cells; manufacturing; technology validation; safety, codes and standards; market transformation; and systems analysis.

Role of 4-hydroxynonenal in chemopreventive activities of sulforaphane

PubMed Central

Sharma, Rajendra; Sharma, Abha; Chaudhary, Pankaj; Sahu, Mukesh; Jaiswal, Shailesh; Awasthi, Sanjay; Awasthi, Yogesh C.

2012-01-01

Chemoprevention of cancer via herbal and dietary supplements is a logical approach to combat cancer and presently it is an attractive area of research investigations. Over the years, the use of isothiocyanates, such as sulforaphane (SFN) found in cruciferous vegetables, has been advocated as chemopreventive agents and their efficacy has been demonstrated in cell lines and animal models. In-vivo studies with SFN suggest that besides protecting normal healthy cells from environmental carcinogens it also exhibits cytotoxicity and apoptotic effects against various cancer cell types. Among several mechanisms for the chemopreventive activity of SFN against chemical carcinogenesis, its effect on drug metabolizing enzymes that causes activation/ neutralization of carcinogenic metabolites is well established. Recent studies suggest that SFN exerts its selective cytotoxicity to cancer cells via reactive oxygen species (ROS)-mediated generation of lipid peroxidation (LPO) products particularly 4-hydroxynonenal (HNE). Against the background of the known biochemical effects of SFN on normal and cancer cells, in this article we have reviewed the underlying molecular mechanisms responsible for the overall chemopreventive effects of SFN focusing on the role of HNE in these mechanisms that may also contribute to its selective cytotoxicity to cancer cells. PMID:22579574

The Role of Immune and Inflammatory Cells in Idiopathic Pulmonary Fibrosis

PubMed Central

Desai, Omkar; Winkler, Julia; Minasyan, Maksym; Herzog, Erica L.

2018-01-01

The contribution of the immune system to idiopathic pulmonary fibrosis (IPF) remains poorly understood. While most sources agree that IPF does not result from a primary immunopathogenic mechanism, evidence gleaned from animal modeling and human studies suggests that innate and adaptive immune processes can orchestrate existing fibrotic responses. This review will synthesize the available data regarding the complex role of professional immune cells in IPF. The role of innate immune populations such as monocytes, macrophages, myeloid suppressor cells, and innate lymphoid cells will be discussed, as will the activation of these cells via pathogen-associated molecular patterns derived from invading or commensural microbes, and danger-associated molecular patterns derived from injured cells and tissues. The contribution of adaptive immune responses driven by T-helper cells and B cells will be reviewed as well. Each form of immune activation will be discussed in the context of its relationship to environmental and genetic factors, disease outcomes, and potential therapies. We conclude with discussion of unanswered questions and opportunities for future study in this area. PMID:29616220

Adipose, Bone Marrow and Synovial Joint-Derived Mesenchymal Stem Cells for Cartilage Repair

PubMed Central

Fellows, Christopher R.; Matta, Csaba; Zakany, Roza; Khan, Ilyas M.; Mobasheri, Ali

2016-01-01

Current cell-based repair strategies have proven unsuccessful for treating cartilage defects and osteoarthritic lesions, consequently advances in innovative therapeutics are required and mesenchymal stem cell-based (MSC) therapies are an expanding area of investigation. MSCs are capable of differentiating into multiple cell lineages and exerting paracrine effects. Due to their easy isolation, expansion, and low immunogenicity, MSCs are an attractive option for regenerative medicine for joint repair. Recent studies have identified several MSC tissue reservoirs including in adipose tissue, bone marrow, cartilage, periosteum, and muscle. MSCs isolated from these discrete tissue niches exhibit distinct biological activities, and have enhanced regenerative potentials for different tissue types. Each MSC type has advantages and disadvantages for cartilage repair and their use in a clinical setting is a balance between expediency and effectiveness. In this review we explore the challenges associated with cartilage repair and regeneration using MSC-based cell therapies and provide an overview of phenotype, biological activities, and functional properties for each MSC population. This paper also specifically explores the therapeutic potential of each type of MSC, particularly focusing on which cells are capable of producing stratified hyaline-like articular cartilage regeneration. Finally we highlight areas for future investigation. Given that patients present with a variety of problems it is unlikely that cartilage regeneration will be a simple “one size fits all,” but more likely an array of solutions that need to be applied systematically to achieve regeneration of a biomechanically competent repair tissue. PMID:28066501

Characterisation of the ex vivo virulence of Leishmania infantum isolates from Phlebotomus perniciosus from an outbreak of human leishmaniosis in Madrid, Spain.

PubMed

Domínguez-Bernal, Gustavo; Jiménez, Maribel; Molina, Ricardo; Ordóñez-Gutiérrez, Lara; Martínez-Rodrigo, Abel; Mas, Alicia; Cutuli, Maria Teresa; Carrión, Javier

2014-11-07

Since mid 2009, an outbreak of human leishmaniosis in Madrid, Spain, has involved more than 560 clinical cases. Many of the cases occurred in people who live in areas around a newly constructed green park (BosqueSur). This periurban park provides a suitable habitat for sand flies (the vectors of Leishmania infantum). Indeed, studies of blood meals from sand flies captured in the area showed a strong association between the insect vector, hares or rabbits, and humans in the area. Interestingly, up to 70% of cases have been found in immunocompetent patients (aged between 46-60 years). This study was designed to evaluate the ex vivo virulence of the L. infantum isolates from Phlebotomus perniciosus captured in this area of Madrid. Murine macrophages and dendritic cells were infected ex vivo with L. infantum strain BCN150, isolate BOS1FL1, or isolate POL2FL7. At different times after infection, the infection indices, cytokine production (IL-12p40 and IL-10), NO release and arginase activities were evaluated. Using an ex vivo model of infection in murine bone marrow-derived cells, we found that infection with isolates BOS1FL1 and POL2FL7 undermined host immune defence mechanisms in multiple ways. The main factors identified were changes in both the balance of iNOS versus arginase activities and the equilibrium between the production of IL-12 and IL-10. Infection with isolates BOS1FL1 and POL2FL7 also resulted in higher infection rates compared to the BCN150 strain. Infection index values at 24 h were as follows: BCN150-infected cells, 110 for infected MØ and 115 for infected DC; BOS1FL1-infected cells, 300 for infected MØ and 247 for infected DC; and POL2FL7-infected cells, 275 for infected MØ and 292 for infected DC. Our data indicate that L. infantum isolates captured from this endemic area exhibited high virulence in terms of infection index, cytokine production and enzymatic activities involved in the pathogenesis of visceral leishmaniosis. Altogether, these data provide a starting point for the study of the virulence behaviour of parasites (BOS1FL1 and POL2FL7) isolated from P. perniciosus during the outbreak of human leishmaniosis in Madrid, Spain, and their involvement in infecting immunocompetent hosts.

Effects of 14 days of spaceflight and nine days of recovery on cell body size and succinate dehydrogenase activity of rat dorsal root ganglion neurons

NASA Technical Reports Server (NTRS)

Ishihara, A.; Ohira, Y.; Roy, R. R.; Nagaoka, S.; Sekiguchi, C.; Hinds, W. E.; Edgerton, V. R.

1997-01-01

The cross-sectional areas and succinate dehydrogenase activities of L5 dorsal root ganglion neurons in rats were determined after 14 days of spaceflight and after nine days of recovery. The mean and distribution of the cross-sectional areas were similar to age-matched, ground-based controls for both the spaceflight and for the spaceflight plus recovery groups. The mean succinate dehydrogenase activity was significantly lower in spaceflight compared to aged-matched control rats, whereas the mean succinate dehydrogenase activity was similar in age-matched control and spaceflight plus recovery rats. The mean succinate dehydrogenase activity of neurons with cross-sectional areas between 1000 and 2000 microns2 was lower (between 7 and 10%) in both the spaceflight and the spaceflight plus recovery groups compared to the appropriate control groups. The reduction in the oxidative capacity of a subpopulation of sensory neurons having relatively large cross-sectional areas immediately following spaceflight and the sustained depression for nine days after returning to 1 g suggest that the 0 g environment induced significant alterations in proprioceptive function.

The antimalarial drug amodiaquine possesses anti-ZIKA virus activities.

PubMed

Han, Yingshan; Mesplède, Thibault; Xu, Hongtao; Quan, Yudong; Wainberg, Mark A

2018-05-01

Zika virus (ZIKV) outbreak has emerged as a global health threat, particularly in tropical areas, over the past few years. No antiviral therapy or vaccine is available at present. For these reasons, repurposing clinically approved drugs against ZIKV infection may provide rapid and cost-effective global health benefits. Here, we explored this strategy and screened eight FDA-approved drugs for antiviral activity against ZIKV using a cell-based assay. Our results show that the antimalarial drug amodiaquine has anti-ZIKV activity with EC 50 at low micromolar concentrations in cell culture. We further characterized amodiaquine antiviral activity against ZIKV and found that it targets early events of the viral replication cycle. Altogether, our results suggest that amodiaquine may be efficacious for the treatment of ZIKV infection. © 2018 Wiley Periodicals, Inc.

Involvement of rho-gtpases in fibroblast adhesion and fibronectine fibrillogenesis under stretch

NASA Astrophysics Data System (ADS)

Guignandon, A.; Lambert, C.; Rattner, A.; Servotte, S.; Lapiere, C.; Nusgens, B.; Vico, L.

The Rho family small GTPases play a crucial role in mediating cellular adaptation to mechanical stimulation (MS), and possibly to microgravity (μg), through effects on the cytoskeleton and cell adhesion which is, in turn, mainly regulated by fibronectin fibrillogenesis (FnF). It remains unclear how mechanical stimulation is transduced to the Rho signaling pathways and how it impacts on fibronectin (fbn) fibrillogenesis (FnF). μg (2 days, mission STS-095) led to de-adhesion of fibroblasts and modification of the underlying extracellular matrix. To determine whether GTPases modulated FnF, we generated stable cell lines expressing high level of activated RhoA and Rac1 (QL) as compared to wild type (WI26-WT). After MS application [8% deformation, 1Hz, 15 min., 3 times/day for 1-2 days], we quantified focal adhesion (vinculin, paxillin, FAKY397), f-actin stress fibers (Sf) and FnF with home-developed softwares. We reported that after MS, Sf are more rapidly (30min) formed under the nucleus in Wi26-WT (+100%) and Rac1 (+200%) than in RhoA (+20%). Vinculin & paxillin were only restricted to the cell edge in static conditions and homogeneously distributed after MS in WT and Rac1. The relative area of contacts (vinculin & paxillin) was more dramatically enhanced by MS in Rac1 (+80%) than in WT (+40%) and RhoA (+25%) indicating that new focal contacts are formed under MS and supported the presence of Sf. MS Activation of FAK (FAKY397) was clear in WT and Rac1 and reduced in RhoA. FnF was restricted to cell-cell contacts zone without any change in the relative area of fbn after a 2-days MS. However we found more numerous spots of fbn at the cell center in Rac1 as compared with RhoA & WT suggesting that these fibrillar contacts will grow upon maturation and modulate FnF. The results indicate that MS induces formation of Sf and focal adhesions and enhances FF. RhoA has been shown to induce the formation of Sf and focal adhesions, and Rac1 activation decreases Rho activity in some cell types. As the sensitivity to MS is Rac1>WI-26>RhoA we speculate (1) that MS increases RhoA activity, and (2) that this effect is more prominent in Rac1 cells due to an induced lower basal level of RhoA activity. This study is a feasibility work for future space missions allowing evaluating the effect of μg on our models.

Oxygen Reduction Reaction Activity of Platinum Thin Films with Different Densities

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

Ergul, Busra; Begum, Mahbuba; Kariuki, Nancy

Platinum thin films with different densities were grown on glassy carbon electrodes by high pressure sputtering deposition and evaluated as oxygen reduction reaction catalysts for polymer electrolyte fuel cells using cyclic voltammetry and rotating disk electrode techniques in aqueous perchloric acid electrolyte. The electrochemically active surface area, ORR mass activity (MA) and specific activity (SA) of the thin film electrodes were obtained. MA and SA were found to be higher for low-density films than for high-density film.

High surface area synthesis, electrochemical activity, and stability of tungsten carbide supported Pt during oxygen reduction in proton exchange membrane fuel cells

NASA Astrophysics Data System (ADS)

Chhina, H.; Campbell, S.; Kesler, O.

The oxidation of carbon catalyst supports to carbon dioxide gas leads to degradation in catalyst performance over time in proton exchange membrane fuel cells (PEMFCs). The electrochemical stability of Pt supported on tungsten carbide has been evaluated on a carbon-based gas diffusion layer (GDL) at 80 °C and compared to that of HiSpec 4000™ Pt/Vulcan XC-72R in 0.5 M H 2SO 4. Due to other electrochemical processes occurring on the GDL, detailed studies were also performed on a gold mesh substrate. The oxygen reduction reaction (ORR) activity was measured both before and after accelerated oxidation cycles between +0.6 V and +1.8 V vs. RHE. Tafel plots show that the ORR activity remained high even after accelerated oxidation tests for Pt/tungsten carbide, while the ORR activity was extremely poor after accelerated oxidation tests for HiSpec 4000™. In order to make high surface area tungsten carbide, three synthesis routes were investigated. Magnetron sputtering of tungsten on carbon was found to be the most promising route, but needs further optimization.

Facile synthesis of bacitracin-templated palladium nanoparticles with superior electrocatalytic activity

NASA Astrophysics Data System (ADS)

Li, Yanji; Wang, Zi; Li, Xiaoling; Yin, Tian; Bian, Kexin; Gao, Faming; Gao, Dawei

2017-02-01

Palladium nanomaterials have attracted great attention on the development of electrocatalysts for fuel cells. Herein, we depicted a novel strategy in the synthesis of palladium nanoparticles with superior electrocatalytic activity. The new approach, based on the self-assembly of bacitracin biotemplate and palladium salt for the preparation of bacitracin-palladium nanoparticles (Bac-PdNPs), was simple, low-cost, and green. The complex, composed by a series of spherical Bac-PdNPs with a diameter of 70 nm, exhibited a chain-liked morphology in TEM and a face-centered cubic crystal structure in X-Ray diffraction and selected area electron diffraction. The palladium nanoparticles were mono-dispersed and stable in aqueous solution as shown in TEM and zeta potential. Most importantly, compared to the commercial palladium on carbon (Pd/C) catalyst (8.02 m2 g-1), the Bac-PdNPs showed a larger electrochemically active surface area (47.57 m2 g-1), which endowed the products an excellent electrocatalytic activity for ethanol oxidation in alkaline medium. The strategy in synthesis of Bac-PdNPs via biotemplate approach might light up new ideas in anode catalysts for direct ethanol fuel cells.

LEACHATE MIGRATION FROM A SOLID WASTE DISPOSAL FACILITY NEAR BISCAYNE NATIONAL PARK, SOUTH FLORIDA.

USGS Publications Warehouse

Waller, Bradley G.; Labowski, James L.

1987-01-01

Leachate from the Dade County Solid Waste Disposal Facility (SWDF) is migrating to the east (seaward) and to the south from the currently active disposal cell. Water levels and ground-water flow directions are strongly influenced by water-management practices. The SWDF is constructed over the salt-intruded part of the highly transmissive Biscayne aquifer and because of this, chloride ion concentrations and specific conductance levels could not be used as indicators of leachate concentrations. Leachate was detected in multi-depth wells located 75 meters to the south and 20 meters to the east of the active cell. Concentrations of water-quality indicators had mean concentrations generally 2 to 10 times higher than baseline conditions. Primary controls over leachate movement in the SWDF are water-management practices in the Black Creek and Gould Canals, configuration and integrity of the liner beneath the active cell, and low hydraulic gradients in the landfill area.

Comparison of Mast Cells Count in Odontogenic Cysts Using Histochemical Staining.

PubMed

Rajabi-Moghaddam, Mahdieh; Abbaszadeh-Bidokhty, Hamid; Bijani, Ali

2015-01-01

Odontogenic cysts are among the most frequent destructive lesions of jaws which their pathogenesis and growth mechanism are not cleared. With respect to different roles of mast cells, they may play a role in the pathogenesis and growth of odontogenic cysts. The aim of present study was to evaluate mast cells in the most common odontogenic cyst. Thirty paraffin-embedded tissue blocks including 10 radicular cysts, 10 dentigerous cysts and 10 odontogenic keratocysts were used and 5 micron sections stained with toluidine blue and observed by light microscope under ×400 magnification to evaluate mast cells within these cysts. For each case, 5 high-power field areas, selected from hot-spot areas, were considered and each area divided into 3 zones: intra-epithelial zone, sub-epithelial zone and deep zone. Most of the studied cyst showed presence of mast cells. There was not any significant difference in mast cell count between studied cysts ( P -values > 0.05).With respect to intra-epithelial, sub-epithelial and deep zones, there was not any significant difference between three studied cysts. There was not any significant difference between sub-epithelial zone and deep zone within each of these cysts. There was only significant difference between intra-epithelial zone and sub-epithelial zone within dentigerous cysts and odontogenic keratocysts ( P -value < 0.05). Prevalence of mast cells in fibrous wall of odontogenic cysts suggests their activity in these cysts. Mast cells may not be directly involved in the pathogenesis of odontogenic keratocysts.

Role of neural stem cell activity in postweaning development of the sexually dimorphic nucleus of the preoptic area in rats.

PubMed

He, Zhen; Ferguson, Sherry A; Cui, Li; Greenfield, L John; Paule, Merle G

2013-01-01

The sexually dimorphic nucleus of the preoptic area (SDN-POA) has received increased attention due to its apparent sensitivity to estrogen-like compounds found in food and food containers. The mechanisms that regulate SDN-POA volume remain unclear as is the extent of postweaning development of the SDN-POA. Here we demonstrate that the female Sprague-Dawley SDN-POA volume increased from weaning to adulthood, although this increase was not statistically significant as it was in males. The number of cells positive for Ki67, a marker of cell proliferation, in both the SDN-POA and the hypothalamus was significantly higher at weaning than at adulthood in male rats. In contrast, the number of Ki67-positive cells was significantly higher in the hypothalamus but not in the SDN-POA (p>0.05) at weaning than at adulthood in female rats. A subset of the Ki67-positive cells in the SDN-POA displayed the morphology of dividing cells. Nestin-immunoreactivity delineated a potential macroscopic neural stem cell niche in the rostral end of the 3rd ventricle. In conclusion, stem cells may partially account for the sexually dimorphic postweaning development of the SDN-POA.

Spirochetal antigens and lymphoid cell surface markers in Lyme synovitis. Comparison with rheumatoid synovium and tonsillar lymphoid tissue.

PubMed

Steere, A C; Duray, P H; Butcher, E C

1988-04-01

Using monoclonal antibodies to spirochetal antigenes and lymphoid cell surface markers, we examined the synovial lesions of 12 patients with Lyme disease, and compared them with rheumatoid synovium and tonsillar lymphoid tissue. The synovial lesions of Lyme disease patients and rheumatoid arthritis patients were similar and often consisted of the elements found in normal organized lymphoid tissue. In both diseases, T cells, predominantly of the helper/inducer subset, were distributed diffusely in subsynovial lining areas, often with nodular aggregates of tightly intermixed T and B cells. IgD-bearing B cells were scattered within the aggregates, and a few follicular dendritic cells and activated germinal center B cells were sometimes present. Outside the aggregates, many plasma cells, high endothelial venules, scattered macrophages, and a few dendritic macrophages were found. HLA-DR and DQ expression was intense throughout the lesions. In 6 of the 12 patients with Lyme arthritis, but in none of those with rheumatoid arthritis, a few spirochetes and globular antigen deposits were seen in and around blood vessels in areas of lymphocytic infiltration. Thus, in Lyme arthritis, a small number of spirochetes are probably the antigenic stimulus for chronic synovial inflammation.

Click-crosslinkable and photodegradable gelatin hydrogels for cytocompatible optical cell manipulation in natural environment

PubMed Central

Tamura, Masato; Yanagawa, Fumiki; Sugiura, Shinji; Takagi, Toshiyuki; Sumaru, Kimio; Kanamori, Toshiyuki

2015-01-01

This paper describes the generation of “click-crosslinkable“ and “photodegaradable“ gelatin hydrogels from the reaction between dibenzocycloctyl-terminated photoclevable tetra-arm polyethylene glycol and azide-modified gelatin. The hydrogels were formed in 30 min through the click-crosslinking reaction. The micropatterned features in the hydrogels were created by micropatterned light irradiation; the minimum resolution of micropatterning was 10-μm widths for line patterns and 20-μm diameters for circle patterns. Cells were successfully encapsulated in the hydrogels without any loss of viability across a wide concentration range of crosslinker. In contrast, an activated-ester-type photocleavable crosslinker, which we previously used to prepare photodegradable gelatin hydrogels, induced a decrease in cell viability at crosslinker concentrations greater than 1.8 mM. We also observed morphology alteration and better growth of cancer cells in the click-crosslinked photodegradable gelatin hydrogels that included matrigel than in the absence of matrigel. We also demonstrated micropatterning of the hydrogels encapsulating cells and optical cell separation. Both of the cells that remained in the non-irradiated area and the cells collected from the irradiated area maintained their viability. PMID:26450015

Protecting enzymatic function through directed packaging into bacterial outer membrane vesicles

PubMed Central

Alves, Nathan J.; Turner, Kendrick B.; Medintz, Igor L.; Walper, Scott A.

2016-01-01

Bacteria possess innate machinery to transport extracellular cargo between cells as well as package virulence factors to infect host cells by secreting outer membrane vesicles (OMVs) that contain small molecules, proteins, and genetic material. These robust proteoliposomes have evolved naturally to be resistant to degradation and provide a supportive environment to extend the activity of encapsulated cargo. In this study, we sought to exploit bacterial OMV formation to package and maintain the activity of an enzyme, phosphotriesterase (PTE), under challenging storage conditions encountered for real world applications. Here we show that OMV packaged PTE maintains activity over free PTE when subjected to elevated temperatures (>100-fold more activity after 14 days at 37 °C), iterative freeze-thaw cycles (3.4-fold post four-cycles), and lyophilization (43-fold). We also demonstrate how lyophilized OMV packaged PTE can be utilized as a cell free reagent for long term environmental remediation of pesticide/chemical warfare contaminated areas. PMID:27117743

Editors' Choice—Electrochemically Active Surface Area Measurement of Aged Pt Alloy Catalysts in PEM Fuel Cells by CO Stripping

DOE PAGES

Garrick, Taylor R.; Moylan, Thomas E.; Carpenter, Michael K.; ...

2016-12-13

The use of hydrogen adsorption/desorption (HAD) is a convenient method to measure the Pt surface area of a catalyst. However, it was shown that electrochemical charges measured by this technique can underestimate the Pt surface area by up to a factor of two for small Pt nanoparticles or Pt alloy nanoparticles. Electrooxidation of CO, so-called CO stripping, has been shown to be more accurate. Yet measurements of CO stripping in MEAs are scarce, especially on high activity alloy catalysts. In this study we investigated CO stripping and the ratio between Pt surface areas measured by CO and by HAD onmore » several Pt and Pt alloy catalysts. The effects on these measurements of temperature and catalyst aging by voltage cycling are discussed.« less

Editors' Choice—Electrochemically Active Surface Area Measurement of Aged Pt Alloy Catalysts in PEM Fuel Cells by CO Stripping

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

Garrick, Taylor R.; Moylan, Thomas E.; Carpenter, Michael K.

The use of hydrogen adsorption/desorption (HAD) is a convenient method to measure the Pt surface area of a catalyst. However, it was shown that electrochemical charges measured by this technique can underestimate the Pt surface area by up to a factor of two for small Pt nanoparticles or Pt alloy nanoparticles. Electrooxidation of CO, so-called CO stripping, has been shown to be more accurate. Yet measurements of CO stripping in MEAs are scarce, especially on high activity alloy catalysts. In this study we investigated CO stripping and the ratio between Pt surface areas measured by CO and by HAD onmore » several Pt and Pt alloy catalysts. The effects on these measurements of temperature and catalyst aging by voltage cycling are discussed.« less

Defined types of cortical interneurone structure space and spike timing in the hippocampus

PubMed Central

Somogyi, Peter; Klausberger, Thomas

2005-01-01

The cerebral cortex encodes, stores and combines information about the internal and external environment in rhythmic activity of multiple frequency ranges. Neurones of the cortex can be defined, recognized and compared on the comprehensive application of the following measures: (i) brain area- and cell domain-specific distribution of input and output synapses, (ii) expression of molecules involved in cell signalling, (iii) membrane and synaptic properties reflecting the expression of membrane proteins, (iv) temporal structure of firing in vivo, resulting from (i)–(iii). Spatial and temporal measures of neurones in the network reflect an indivisible unity of evolutionary design, i.e. neurones do not have separate structure or function. The blueprint of this design is most easily accessible in the CA1 area of the hippocampus, where a relatively uniform population of pyramidal cells and their inputs follow an instantly recognizable laminated pattern and act within stereotyped network activity patterns. Reviewing the cell types and their spatio-temporal interactions, we suggest that CA1 pyramidal cells are supported by at least 16 distinct types of GABAergic neurone. During a given behaviour-contingent network oscillation, interneurones of a given type exhibit similar firing patterns. During different network oscillations representing two distinct brain states, interneurones of the same class show different firing patterns modulating their postsynaptic target-domain in a brain-state-dependent manner. These results suggest roles for specific interneurone types in structuring the activity of pyramidal cells via their respective target domains, and accurately timing and synchronizing pyramidal cell discharge, rather than providing generalized inhibition. Finally, interneurones belonging to different classes may fire preferentially at distinct time points during a given oscillation. As different interneurones innervate distinct domains of the pyramidal cells, the different compartments will receive GABAergic input differentiated in time. Such a dynamic, spatio-temporal, GABAergic control, which evolves distinct patterns during different brain states, is ideally suited to regulating the input integration of individual pyramidal cells contributing to the formation of cell assemblies and representations in the hippocampus and, probably, throughout the cerebral cortex. PMID:15539390

Texas Hydrogen Education Final Scientific/Technical Report

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

Hitchcock, David; Bullock, Dan

2011-06-30

The Texas Hydrogen Education project builds on past interest in hydrogen and fuel cells to help create better informed leaders and stakeholders and thereby improve decision making and planning for inclusion of hydrogen and fuel cell technologies as energy alternatives in Texas. In past years in Texas, there was considerable interest and activities about hydrogen and fuel cells (2000-­2004). During that time, the Houston Advanced Research Center (HARC) created a fuel cell consortium and a fuel cell testing lab. Prior to 2008, interest and activities had declined substantially. In 2008, in cooperation with the Texas H2 Coalition and the Statemore » Energy Conservation Office, HARC conducted a planning process to create the Texas Hydrogen Roadmap. It was apparent from analysis conducted during the course of this process that while Texas has hydrogen and fuel cell advantages, there was little program and project activity as compared with other key states. Outreach and education through the provision of informational materials and organizing meetings was seen as an effective way of reaching decision makers in Texas. Previous hydrogen projects in Texas had identified the five major urban regions for program and project development. This geographic targeting approach was adopted for this project. The project successfully conducted the five proposed workshops in four of the target metropolitan areas: San Antonio, Houston, Austin, and the Dallas-­Ft. Worth area. In addition, eight outreach events were included to further inform state and local government leaders on the basics of hydrogen and fuel cell technologies. The project achieved its primary objectives of developing communication with target audiences and assembling credible and consistent outreach and education materials. The major lessons learned include: (1) DOE’s Clean Cities programs are a key conduit to target transportation audiences, (2) real-­world fuel cell applications (fuel cell buses, fuel cell fork lifts, and hydrogen fueling) are effective for engaging target audiences, and (3) a clear path forward is needed for state and local agencies interested in project implementation (funding, financing, preliminary design, technical assistance, etc.).« less

Palladium Coated Copper Nanowires as a Hydrogen Oxidation Electrocatalyst in Base

DOE PAGES

Alia, Shaun M.; Yan, Yushan

2015-05-09

The palladium (Pd) nanotubes we synthesized by the spontaneous galvanic displacement of copper (Cu) nanowires, are forming extended surface nanostructures highly active for the hydrogen oxidation reaction (HOR) in base. The synthesized catalysts produce specific activities in rotating disk electrode half-cells 20 times greater than Pd nanoparticles and about 80% higher than polycrystalline Pd. Although the surface area of the Pd nanotubes was low compared to conventional catalysts, partial galvanic displacement thrifted the noble metal layer and increased the Pd surface area. Moreover, the use of Pd coated Cu nanowires resulted in a HOR mass exchange current density 7 timesmore » greater than the Pd nanoparticles. The activity of the Pd coated Cu nanowires further nears Pt/C, producing 95% of the mass activity.« less

ELECTROCHEMISTRY AND ON-CELL REFORMATION MODELING FOR SOLID OXIDE FUEL CELL STACKS

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

Recknagle, Kurtis P.; Jarboe, Daniel T.; Johnson, Kenneth I.

2007-01-16

ABSTRACT Providing adequate and efficient cooling schemes for solid-oxide-fuel-cell (SOFC) stacks continues to be a challenge coincident with the development of larger, more powerful stacks. The endothermic steam-methane reformation reaction can provide cooling and improved system efficiency when performed directly on the electrochemically active anode. Rapid kinetics of the endothermic reaction typically causes a localized temperature depression on the anode near the fuel inlet. It is desirable to extend the endothermic effect over more of the cell area and mitigate the associated differences in temperature on the cell to alleviate subsequent thermal stresses. In this study, modeling tools validated formore » the prediction of fuel use, on-cell methane reforming, and the distribution of temperature within SOFC stacks, are employed to provide direction for modifying the catalytic activity of anode materials to control the methane conversion rate. Improvements in thermal management that can be achieved through on-cell reforming is predicted and discussed. Two operating scenarios are considered: one in which the methane fuel is fully pre-reformed, and another in which a substantial percentage of the methane is reformed on-cell. For the latter, a range of catalytic activity is considered and the predicted thermal effects on the cell are presented. Simulations of the cell electrochemical and thermal performance with and without on-cell reforming, including structural analyses, show a substantial decrease in thermal stresses for an on-cell reforming case with slowed methane conversion.« less

Specialized activities and expression differences for Clostridium thermocellum biofilm and planktonic cells

DOE PAGES

Dumitrache, Alexandru; Klingeman, Dawn M.; Natzke, Jace; ...

2017-02-27

Clostridium thermocellum forms biofilms adherent to lignocellulosic feedstock in a typical continuous cell-monolayer to efficiently break down and uptake cellulose hydrolysates. The sessile cells of biofilms may revert to non-adherent planktonic cells through generation of offspring cells or microenvironment constraints such as limited surface area. These interdependent cell populations co-exist and have different contributions to culture activity and growth. Here, we developed a novel bioreactor design to rapidly harvest sessile and planktonic cell populations for omics studies. In RNA-seq analyses, within 3299 protein coding genes, 59% (or 1958 genes) were differentially expressed with a minimum two-fold change between the twomore » cell populations isolated simultaneously at high culture activity. Furthermore, sessile cells had definitive greater expression of genes involved in catabolism of carbohydrates by glycolysis and pyruvate fermentation, ATP generation by proton gradient, the anabolism of proteins and lipids and cellular functions critical for cell division; planktonic cells had notably higher gene expression for flagellar motility and chemotaxis, cellulosomal cellulases and anchoring scaffoldins, and a range of stress induced homeostasis mechanisms such as oxidative stress protection by antioxidants and flavoprotein co-factors, methionine repair, Fe-S cluster assembly and repair in redox proteins, cell growth control through tRNA thiolation, recovery of damaged DNA by nucleotide excision repair and removal of terminal proteins by proteases. Our knowledge of these cellular adaptations will aid the engineering of industrially relevant strains for consolidated bioprocessing of solid lignocellulosic biomass« less

Specialized activities and expression differences for Clostridium thermocellum biofilm and planktonic cells

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

Dumitrache, Alexandru; Klingeman, Dawn M.; Natzke, Jace

Clostridium thermocellum forms biofilms adherent to lignocellulosic feedstock in a typical continuous cell-monolayer to efficiently break down and uptake cellulose hydrolysates. The sessile cells of biofilms may revert to non-adherent planktonic cells through generation of offspring cells or microenvironment constraints such as limited surface area. These interdependent cell populations co-exist and have different contributions to culture activity and growth. Here, we developed a novel bioreactor design to rapidly harvest sessile and planktonic cell populations for omics studies. In RNA-seq analyses, within 3299 protein coding genes, 59% (or 1958 genes) were differentially expressed with a minimum two-fold change between the twomore » cell populations isolated simultaneously at high culture activity. Furthermore, sessile cells had definitive greater expression of genes involved in catabolism of carbohydrates by glycolysis and pyruvate fermentation, ATP generation by proton gradient, the anabolism of proteins and lipids and cellular functions critical for cell division; planktonic cells had notably higher gene expression for flagellar motility and chemotaxis, cellulosomal cellulases and anchoring scaffoldins, and a range of stress induced homeostasis mechanisms such as oxidative stress protection by antioxidants and flavoprotein co-factors, methionine repair, Fe-S cluster assembly and repair in redox proteins, cell growth control through tRNA thiolation, recovery of damaged DNA by nucleotide excision repair and removal of terminal proteins by proteases. Our knowledge of these cellular adaptations will aid the engineering of industrially relevant strains for consolidated bioprocessing of solid lignocellulosic biomass« less

Status of dye solar cell technology as a guideline for further research.

PubMed

Hinsch, Andreas; Veurman, Welmoed; Brandt, Henning; Jensen, Katrine Flarup; Mastroianni, Simone

2014-04-14

Recently, the first commercial dye solar cell (DSC) products based on the mesoscopic principle were successfully launched. Introduction to the market has been accompanied by a strong increase in patent applications in the field during the last four years, which is a good indication of further commercialization activity. Materials and cell concepts have been developed to such extent that easy uptake by industrial manufacturers is possible. The critical phase for broad market acceptance has therefore been reached, which implies focusing on standardization-related research topics. In parallel the number of scientific publications on DSC is growing further (>3500 since 2012), and the range of new or renewed fundamental topics is broadening. A recent example is the introduction of the perovskite mesoscopic cell, for which an efficiency of 14.1% has been certified. Thus, a growing divergence between market introduction and research could be the consequence. Herein, an attempt is made to show that such an unwanted divergence can be prevented, for example, by developing suitable reference-type cell and module concepts as well as manufacturing routes. An in situ cell manufacturing concept that can be applied to mesoscopic-based solar cells in a broader sense is proposed. As a guideline for future module concepts, recent results for large-area, glass-frit-sealed DSC modules from efficiency studies (6.6% active-area efficiency) and outdoor analysis are discussed. Electroluminescence measurements are introduced as a quality tool. Another important point that is addressed is sustainability, which affects both market introduction and the direction of fundamental research. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Strategies to target non-T-cell HIV reservoirs.

PubMed

Sacha, Jonah B; Ndhlovu, Lishomwa C

2016-07-01

A central question for the HIV cure field is to determine new ways to target clinically relevant, latently and actively replicating HIV-infected cells beyond resting memory CD4 T cells, particularly in anatomical areas of low drug penetrability. HIV eradication strategies being positioned for targeting HIV for extinction in the CD4 T-cell compartment may also show promise in non-CD4 T-cells reservoirs. Furthermore, several exciting novel therapeutic approaches specifically focused on HIV clearance from non-CD4 T-cell populations are being developed. Although reservoir validity in these non-CD4 T cells continues to remain debated, this review will highlight recent advances and make an argument as to their clinical relevancy as we progress towards an HIV cure.

Electrical activity controls area-specific expression of neuronal apoptosis in the mouse developing cerebral cortex.

PubMed

Blanquie, Oriane; Yang, Jenq-Wei; Kilb, Werner; Sharopov, Salim; Sinning, Anne; Luhmann, Heiko J

2017-08-21

Programmed cell death widely but heterogeneously affects the developing brain, causing the loss of up to 50% of neurons in rodents. However, whether this heterogeneity originates from neuronal identity and/or network-dependent processes is unknown. Here, we report that the primary motor cortex (M1) and primary somatosensory cortex (S1), two adjacent but functionally distinct areas, display striking differences in density of apoptotic neurons during the early postnatal period. These differences in rate of apoptosis negatively correlate with region-dependent levels of activity. Disrupting this activity either pharmacologically or by electrical stimulation alters the spatial pattern of apoptosis and sensory deprivation leads to exacerbated amounts of apoptotic neurons in the corresponding functional area of the neocortex. Thus, our data demonstrate that spontaneous and periphery-driven activity patterns are important for the structural and functional maturation of the neocortex by refining the final number of cortical neurons in a region-dependent manner.

Mouse neuroblastoma cell-based model and the effect of epileptic events on calcium oscillations and neural spikes

NASA Astrophysics Data System (ADS)

Kim, Suhwan; Jung, Unsang; Baek, Juyoung; Lee, Sangwon; Jung, Woonggyu; Kim, Jeehyun; Kang, Shinwon

2013-01-01

Recently, mouse neuroblastoma cells have been considered as an attractive model for the study of human neurological and prion diseases, and they have been intensively used as a model system in different areas. For example, the differentiation of neuro2a (N2A) cells, receptor-mediated ion current, and glutamate-induced physiological responses have been actively investigated with these cells. These mouse neuroblastoma N2A cells are of interest because they grow faster than other cells of neural origin and have a number of other advantages. The calcium oscillations and neural spikes of mouse neuroblastoma N2A cells in epileptic conditions are evaluated. Based on our observations of neural spikes in these cells with our proposed imaging modality, we reported that they can be an important model in epileptic activity studies. We concluded that mouse neuroblastoma N2A cells produce epileptic spikes in vitro in the same way as those produced by neurons or astrocytes. This evidence suggests that increased levels of neurotransmitter release due to the enhancement of free calcium from 4-aminopyridine causes the mouse neuroblastoma N2A cells to produce epileptic spikes and calcium oscillations.

High-content adhesion assay to address limited cell samples†

PubMed Central

Warrick, Jay W.; Young, Edmond W. K.; Schmuck, Eric G.; Saupe, Kurt W.

2013-01-01

Cell adhesion is a broad topic in cell biology that involves physical interactions between cells and other cells or the surrounding extracellular matrix, and is implicated in major research areas including cancer, development, tissue engineering, and regenerative medicine. While current methods have contributed significantly to our understanding of cell adhesion, these methods are unsuitable for tackling many biological questions requiring intermediate numbers of cells (102–105), including small animal biopsies, clinical samples, and rare cell isolates. To overcome this fundamental limitation, we developed a new assay to quantify the adhesion of ~102–103 cells at a time on engineered substrates, and examined the adhesion strength and population heterogeneity via distribution-based modeling. We validated the platform by testing adhesion strength of cancer cells from three different cancer types (breast, prostate, and multiple myeloma) on both IL-1β activated and non-activated endothelial monolayers, and observed significantly increased adhesion for each cancer cell type upon endothelial activation, while identifying and quantifying distinct subpopulations of cell-substrate interactions. We then applied the assay to characterize adhesion of primary bone marrow stromal cells to different cardiac fibroblast-derived matrix substrates to demonstrate the ability to study limited cell populations in the context of cardiac cell-based therapies. Overall, these results demonstrate the sensitivity and robustness of the assay as well as its ability to enable extraction of high content, functional data from limited and potentially rare primary samples. We anticipate this method will enable a new class of biological studies with potential impact in basic and translational research. PMID:23426645

Activation of cholecystokinin neurons in the dorsal pallium of the telencephalon is indispensable for the acquisition of chick imprinting behavior.

PubMed

Maekawa, Fumihiko; Nakamori, Tomoharu; Uchimura, Motoaki; Fujiwara, Ken; Yada, Toshihiko; Tsukahara, Shinji; Kanamatsu, Tomoyuki; Tanaka, Kohichi; Ohki-Hamazaki, Hiroko

2007-09-01

Chick imprinting behavior is a good model for the study of learning and memory. Imprinting object is recognized and processed in the visual wulst, and the memory is stored in the intermediate medial mesopallium in the dorsal pallium of the telencephalon. We identified chicken cholecystokinin (CCK)-expressing cells localized in these area. The number of CCK mRNA-positive cells increased in chicks underwent imprinting training, and these cells expressed nuclear Fos immunoreactivity at high frequency in these regions. Most of these CCK-positive cells were glutamatergic and negative for parvalbumin immunoreactivity. Semi-quantitative PCR analysis revealed that the CCK mRNA levels were significantly increased in the trained chicks compared with untrained chicks. In contrast, the increase in CCK- and c-Fos-double-positive cells associated with the training was not observed after closure of the critical period. These results indicate that CCK cells in the dorsal pallium are activated acutely by visual training that can elicit imprinting. In addition, the CCK receptor antagonist significantly suppressed the acquisition of memory. These results suggest that the activation of CCK cells in the visual wulst as well as in the intermediate medial mesopallium by visual stimuli is indispensable for the acquisition of visual imprinting.

Simulation of action potential propagation in plants.

PubMed

Sukhov, Vladimir; Nerush, Vladimir; Orlova, Lyubov; Vodeneev, Vladimir

2011-12-21

Action potential is considered to be one of the primary responses of a plant to action of various environmental factors. Understanding plant action potential propagation mechanisms requires experimental investigation and simulation; however, a detailed mathematical model of plant electrical signal transmission is absent. Here, the mathematical model of action potential propagation in plants has been worked out. The model is a two-dimensional system of excitable cells; each of them is electrically coupled with four neighboring ones. Ion diffusion between excitable cell apoplast areas is also taken into account. The action potential generation in a single cell has been described on the basis of our previous model. The model simulates active and passive signal transmission well enough. It has been used to analyze theoretically the influence of cell to cell electrical conductivity and H(+)-ATPase activity on the signal transmission in plants. An increase in cell to cell electrical conductivity has been shown to stimulate an increase in the length constant, the action potential propagation velocity and the temperature threshold, while the membrane potential threshold being weakly changed. The growth of H(+)-ATPase activity has been found to induce the increase of temperature and membrane potential thresholds and the reduction of the length constant and the action potential propagation velocity. Copyright © 2011 Elsevier Ltd. All rights reserved.

Microfluidic Investigation Reveals Distinct Roles for Actin Cytoskeleton and Myosin II Activity in Capillary Leukocyte Trafficking

PubMed Central

Gabriele, Sylvain; Benoliel, Anne-Marie; Bongrand, Pierre; Théodoly, Olivier

2009-01-01

Circulating leukocyte sequestration in pulmonary capillaries is arguably the initiating event of lung injury in acute respiratory distress syndrome. We present a microfluidic investigation of the roles of actin organization and myosin II activity during the different stages of leukocyte trafficking through narrow capillaries (entry, transit and shape relaxation) using specific drugs (latrunculin A, jasplakinolide, and blebbistatin). The deformation rate during entry reveals that cell stiffness depends strongly on F-actin organization and hardly on myosin II activity, supporting a microfilament role in leukocyte sequestration. In the transit stage, cell friction is influenced by stiffness, demonstrating that the actin network is not completely broken after a forced entry into a capillary. Conversely, membrane unfolding was independent of leukocyte stiffness. The surface area of sequestered leukocytes increased by up to 160% in the absence of myosin II activity, showing the major role of molecular motors in microvilli wrinkling and zipping. Finally, cell shape relaxation was largely independent of both actin organization and myosin II activity, whereas a deformed state was required for normal trafficking through capillary segments. PMID:19450501

Microfluidics platform for single-shot dose-response analysis of chloride channel-modulating compounds.

PubMed

Jin, Byung-Ju; Ko, Eun-A; Namkung, Wan; Verkman, A S

2013-10-07

We previously developed cell-based kinetics assays of chloride channel modulators utilizing genetically encoded yellow fluorescent proteins. Fluorescence platereader-based high-throughput screens yielded small-molecule activators and inhibitors of the cAMP-activated chloride channel CFTR and calcium-activated chloride channels, including TMEM16A. Here, we report a microfluidics platform for single-shot determination of concentration-activity relations in which a 1.5 × 1.5 mm square area of adherent cultured cells is exposed for 5-10 min to a pseudo-logarithmic gradient of test compound generated by iterative, two-component channel mixing. Cell fluorescence is imaged following perfusion with an iodide-containing solution to give iodide influx rate at each location in the image field, thus quantifying modulator effects over a wide range of concentrations in a single measurement. IC50 determined for CFTR and TMEM16A activators and inhibitors by single-shot microfluidics were in agreement with conventional plate reader measurements. The microfluidics approach developed here may accelerate the discovery and characterization of chloride channel-targeted drugs.

Lyophilized keratinocyte cell lysates contain multiple mitogenic activities and stimulate closure of meshed skin autograft-covered burn wounds with efficiency similar to that of fresh allogeneic keratinocyte cultures.

PubMed

Duinslaeger, L; Verbeken, G; Reper, P; Delaey, B; Vanhalle, S; Vanderkelen, A

1996-07-01

For several years, grafting with allogeneic keratinocyte cultures has been used successfully as a wound-healing therapy both by us and by many other groups. Since their postgrafting survival time is limited, the effect of these cultures is generally explained by the production of wound repair-stimulating factors that promote proliferation and migration of resident cells. In this study we show that lysates of cultured keratinocytes contain mitogenic activity for keratinocytes, endothelial cells, and fibroblasts. In addition, the lysates inhibit the contraction of collagen gels by human skin fibroblasts. On the basis of these observations and of in vivo data obtained by ourselves and others, we have evaluated the effect of total keratinocyte lysates on the healing of meshed skin autograft-covered burn wounds. Twenty burn wounds were tangentially excised and autografted with one to three meshed conventional skin transplants. An area treated with a gel containing lysated keratinocyte cultures was compared with an area treated with placebo-gel in terms of epithelialization on day 5. In six patients an additional fresh keratinocyte alloculture was applied as a positive control. Results indicate that the newly formed epithelium (difference between percentage of epithelialization on day 5 and on day 0) was 31.1 percent in the treated area compared with 16.5 percent in the placebo area. This result is comparable with the value obtained by treatment with fresh keratinocyte allocultures, namely, 33.8 percent. These figures show a twofold stimulation of epithelialization.

Vγ4 γδ T Cells Provide an Early Source of IL-17A and Accelerate Skin Graft Rejection.

PubMed

Li, Yashu; Huang, Zhenggen; Yan, Rongshuai; Liu, Meixi; Bai, Yang; Liang, Guangping; Zhang, Xiaorong; Hu, Xiaohong; Chen, Jian; Huang, Chibing; Liu, Baoyi; Luo, Gaoxing; Wu, Jun; He, Weifeng

2017-12-01

Activated γδ T cells have been shown to accelerate allograft rejection. However, the precise role of skin-resident γδ T cells and their subsets-Vγ5 (epidermis), Vγ1, and Vγ4 (dermis)-in skin graft rejection have not been identified. Here, using a male to female skin transplantation model, we demonstrated that Vγ4 T cells, rather than Vγ1 or Vγ5 T cells, accelerated skin graft rejection and that IL-17A was essential for Vγ4 T-cell-mediated skin graft rejection. Moreover, we found that Vγ4 T cells were required for early IL-17A production in the transplanted area, both in skin grafts and in the host epidermis around grafts. Additionally, the chemokine (C-C motif) ligand 20-chemokine receptor 6 pathway was essential for recruitment of Vγ4 T cells to the transplantation area, whereas both IL-1β and IL-23 induced IL-17A production from infiltrating cells. Lastly, Vγ4 T-cell-derived IL-17A promoted the accumulation of mature dendritic cells in draining lymph nodes to subsequently regulate αβ T-cell function after skin graft transplantation. Taken together, our data reveal that Vγ4 T cells accelerate skin graft rejection by providing an early source of IL-17A. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Chronic wheel running affects cocaine-induced c-Fos expression in brain reward areas in rats.

PubMed

Zlebnik, Natalie E; Hedges, Valerie L; Carroll, Marilyn E; Meisel, Robert L

2014-03-15

Emerging evidence from human and animal studies suggests that exercise is a highly effective treatment for drug addiction. However, most work has been done in behavioral models, and the effects of exercise on the neurobiological substrates of addiction have not been identified. Specifically, it is unknown whether prior exercise exposure alters neuronal activation of brain reward circuitry in response to drugs of abuse. To investigate this hypothesis, rats were given 21 days of daily access to voluntary wheel running in a locked or unlocked running wheel. Subsequently, they were challenged with a saline or cocaine (15 mg/kg, i.p.) injection and sacrificed for c-Fos immunohistochemistry. The c-Fos transcription factor is a measure of cellular activity and was used to quantify cocaine-induced activation of reward-processing areas of the brain: nucleus accumbens (NAc), caudate putamen (CPu), medial prefrontal cortex (mPFC), and orbitofrontal cortex (OFC). The mean fold change in cocaine-induced c-Fos cell counts relative to saline-induced c-Fos cell counts was significantly higher in exercising compared to control rats in the NAc core, dorsomedial and dorsolateral CPu, the prelimbic area, and the OFC, indicating differential cocaine-specific cellular activation of brain reward circuitry between exercising and control animals. These results suggest neurobiological mechanisms by which voluntary wheel running attenuates cocaine-motivated behaviors and provide support for exercise as a novel treatment for drug addiction. Copyright © 2013 Elsevier B.V. All rights reserved.

Rockfall activity of cliff inferred from deposit and cone method

NASA Astrophysics Data System (ADS)

Jaboyedoff, M.; Baillifard, F.; Rouiller, J.-D.

2003-04-01

Assuming that fresh scree slopes are significant indicators of recent rockfall activity, they can be used as activity indicators for a given rockfall source area. Using simple geometric rules and a DTM (digital elevation model), the propagation zone can be estimated by considering that each potential rockfall source cell (corresponding to the entire cliff) can generate a scree slope within a cone with a slope ranging from 27° to 37°. Thus, the count of pixels representing rockfall deposits that are contained in this cone represents a relative scale of recent rockfall activity. According to Evans and Hungr (1993), the source cell can be chosen at the bottom of the cliff, with lower angles. Choosing the entire cliff or the bottom of the cliff as source area depends on the morphology of the slope situated below the cliff. The cone can also be laterally limited in order to avoid the counting of illogical rock slope trajectories (+-20°). In Switzerland, the vectorized 1:25,000 topographic map (vector25) can provide scree slope and cliff area data sets. Results obtained using this method show good agreement with field observations, although it is evident that the highest topographic reliefs are favored by this method, as verified in the Alps. Compared to the method of Menendéz Duarte and Marquínez (2002), which uses GIS-calculated watersheds as propagation areas, the present method does not take small changes of topography into account. References Evans, S.G. and Hungr, O. The assessment of rockfall hazard at the base of talus slopes. Canadian Geotechnical Journal, 30/4, 620-636, 1993. Menendéz Duarte, R. and Marquínez, J. The influence of environmental and lithologic factors on rockfall at a regional scale: an evaluation using GIS. Geomorphology, 43, 117-136, 2002.

Cellular immune responses and phagocytic activity of fishes exposed to pollution of volcano mud.

PubMed

Risjani, Yenny; Yunianta; Couteau, Jerome; Minier, Christophe

2014-05-01

Since May 29, 2006, a mud volcano in the Brantas Delta of the Sidoarjo district has emitted mud that has inundated nearby villages. Pollution in this area has been implicated in detrimental effects on fish health. In fishes, leukocyte and phagocytic cells play a vital role in body defenses. We report for the first time the effect of "LUSI" volcano mud on the immune systems of fish in the Brantas Delta. The aim of this study was to find biomarkers to allow the evaluation of the effects of volcanic mud and anthropogenic pollution on fish health in the Brantas Delta. The study took places at the Brantas Delta, which was polluted by volcano mud, and at reference sites in Karangkates and Pasuruan. Leukocyte numbers were determined using a Neubauer hemocytometer and a light microscope. Differential leukocyte counts were determined using blood smears stained with May Grunwald-Giemsa, providing neutrophil, lymphocyte and monocyte counts. Macrophages were taken from fish kidney, and their phagocytic activity was measured. In vitro analyses revealed that leukocyte and differential leukocyte counts (DLC) were higher in Channa striata and Chanos chanos caught from the polluted area. Macrophage numbers were higher in Oreochromis mossambicus than in the other species, indicating that this species is more sensitive to pollution. In areas close to volcanic mud eruption, all specimens had lower phagocytic activity. Our results show that immune cells were changed and phagocytic activity was reduced in the polluted area indicating cytotoxicity and alteration of the innate immune system in fishes exposed to LUSI volcano mud and anthropogenic pollution. Copyright © 2014 Elsevier Ltd. All rights reserved.

Long-term plasticity in identified hippocampal GABAergic interneurons in the CA1 area in vivo.

PubMed

Lau, Petrina Yau-Pok; Katona, Linda; Saghy, Peter; Newton, Kathryn; Somogyi, Peter; Lamsa, Karri P

2017-05-01

Long-term plasticity is well documented in synapses between glutamatergic principal cells in the cortex both in vitro and in vivo. Long-term potentiation (LTP) and -depression (LTD) have also been reported in glutamatergic connections to hippocampal GABAergic interneurons expressing parvalbumin (PV+) or nitric oxide synthase (NOS+) in brain slices, but plasticity in these cells has not been tested in vivo. We investigated synaptically-evoked suprathreshold excitation of identified hippocampal neurons in the CA1 area of urethane-anaesthetized rats. Neurons were recorded extracellularly with glass microelectrodes, and labelled with neurobiotin for anatomical analyses. Single-shock electrical stimulation of afferents from the contralateral CA1 elicited postsynaptic action potentials with monosynaptic features showing short delay (9.95 ± 0.41 ms) and small jitter in 13 neurons through the commissural pathway. Theta-burst stimulation (TBS) generated LTP of the synaptically-evoked spike probability in pyramidal cells, and in a bistratified cell and two unidentified fast-spiking interneurons. On the contrary, PV+ basket cells and NOS+ ivy cells exhibited either LTD or LTP. An identified axo-axonic cell failed to show long-term change in its response to stimulation. Discharge of the cells did not explain whether LTP or LTD was generated. For the fast-spiking interneurons, as a group, no correlation was found between plasticity and local field potential oscillations (1-3 or 3-6 Hz components) recorded immediately prior to TBS. The results demonstrate activity-induced long-term plasticity in synaptic excitation of hippocampal PV+ and NOS+ interneurons in vivo. Physiological and pathological activity patterns in vivo may generate similar plasticity in these interneurons.

Automated wholeslide analysis of multiplex-brightfield IHC images for cancer cells and carcinoma-associated fibroblasts

NASA Astrophysics Data System (ADS)

Lorsakul, Auranuch; Andersson, Emilia; Vega Harring, Suzana; Sade, Hadassah; Grimm, Oliver; Bredno, Joerg

2017-03-01

Multiplex-brightfield immunohistochemistry (IHC) staining and quantitative measurement of multiple biomarkers can support therapeutic targeting of carcinoma-associated fibroblasts (CAF). This paper presents an automated digitalpathology solution to simultaneously analyze multiple biomarker expressions within a single tissue section stained with an IHC duplex assay. Our method was verified against ground truth provided by expert pathologists. In the first stage, the automated method quantified epithelial-carcinoma cells expressing cytokeratin (CK) using robust nucleus detection and supervised cell-by-cell classification algorithms with a combination of nucleus and contextual features. Using fibroblast activation protein (FAP) as biomarker for CAFs, the algorithm was trained, based on ground truth obtained from pathologists, to automatically identify tumor-associated stroma using a supervised-generation rule. The algorithm reported distance to nearest neighbor in the populations of tumor cells and activated-stromal fibroblasts as a wholeslide measure of spatial relationships. A total of 45 slides from six indications (breast, pancreatic, colorectal, lung, ovarian, and head-and-neck cancers) were included for training and verification. CK-positive cells detected by the algorithm were verified by a pathologist with good agreement (R2=0.98) to ground-truth count. For the area occupied by FAP-positive cells, the inter-observer agreement between two sets of ground-truth measurements was R2=0.93 whereas the algorithm reproduced the pathologists' areas with R2=0.96. The proposed methodology enables automated image analysis to measure spatial relationships of cells stained in an IHC-multiplex assay. Our proof-of-concept results show an automated algorithm can be trained to reproduce the expert assessment and provide quantitative readouts that potentially support a cutoff determination in hypothesis testing related to CAF-targeting-therapy decisions.

SipA Activation of Caspase-3 Is a Decisive Mediator of Host Cell Survival at Early Stages of Salmonella enterica Serovar Typhimurium Infection

PubMed Central

McIntosh, Anne; Meikle, Lynsey M.; Ormsby, Michael J.; McCormick, Beth A.; Christie, John M.; Brewer, James M.; Roberts, Mark

2017-01-01

ABSTRACT Salmonella invasion protein A (SipA) is a dual-function effector protein that plays roles in both actin polymerization and caspase-3 activation in intestinal epithelial cells. To date its function in other cell types has remained largely unknown despite its expression in multiple cell types and its extracellular secretion during infection. Here we show that in macrophages SipA induces increased caspase-3 activation early in infection. This activation required a threshold level of SipA linked to multiplicity of infection and may be a limiting factor controlling bacterial numbers in infected macrophages. In polymorphonuclear leukocytes, SipA or other Salmonella pathogenicity island 1 effectors had no effect on induction of caspase-3 activation either alone or in the presence of whole bacteria. Tagging of SipA with the small fluorescent phiLOV tag, which can pass through the type three secretion system, allowed visualization and quantification of caspase-3 activation by SipA-phiLOV in macrophages. Additionally, SipA-phiLOV activation of caspase-3 could be tracked in the intestine through multiphoton laser scanning microscopy in an ex vivo intestinal model. This allowed visualization of areas where the intestinal epithelium had been compromised and demonstrated the potential use of this fluorescent tag for in vivo tracking of individual effectors. PMID:28630067

Genotoxicity in child populations exposed to Polycyclic Aromatic Hydrocarbons (PAHs) in the air from Tabasco, Mexico

PubMed Central

Gamboa, Rodríguez T.; Gamboa, Aldeco R.; Bravo, Alvarez H.; Ostrosky, Wegman P.

2008-01-01

The economy of the state of Tabasco is based on oil extraction. However, this imposes major effects to the environment and communities. Examples are the Polycyclic Aromatic Hydrocarbons (PAHs) that may be found in the soil, water and sediment of the region. Their volatility makes them available to living beings and results in genotoxic activity. The purpose of this study was to quantify the levels of PAHs in the air at several points in the state, and to analyze their relationship with possible damage to DNA on local inhabitants. Single Cell Gel Electrophoresis Assay (Comet Assay) was applied to peripheral blood lymphocytes of five groups of children between six and 15 years of age. PAH samples were analyzed following US/EPA TO-13-A method. Results indicated the presence in the air of most of the 16 PAHs considered as high priority by EPA, some of which have been reported with carcinogenic activity. Differences (p<0.05) were found between PAHs concentration in the gaseous component and in the particulate component of air samples, with the greatest values for the gaseous component. Greatest PAH concentrations were detected in areas with high oil extraction activities. Children groups from high oil activity areas presented genotoxic damage labeled from moderate to high according to DNA migration from nuclei (Tail Length: 14.2 – 42.14 μm and Tail/Head: 0.97 – 2.83 μm) compared with control group (12.25 and 0.63 μm, respectively). The group with greatest cell damage was located in the area with the greatest oil activity. We conclude that the presence of PAHs in the air may represent a health risk to populations that are chronically exposed to them at high oil activity regions. PMID:19151429

Alterations in the skin of Labeo rohita exposed to an azo dye, Eriochrome black T: a histopathological and enzyme biochemical investigation.

PubMed

Srivastava, Ayan; Verma, Neeraj; Mistri, Arup; Ranjan, Brijesh; Nigam, Ashwini Kumar; Kumari, Usha; Mittal, Swati; Mittal, Ajay Kumar

2017-03-01

Histopathological changes and alterations in the activity of certain metabolic and antioxidant enzymes were analyzed in the head skin of Labeo rohita, exposed to sublethal test concentrations of the azo dye, Eriochrome black T for 4 days, using 24 h renewal bioassay method. Hypertrophied epithelial cells, increased density of mucous goblet cells, and profuse mucous secretion at the surface were considered to protect the skin from toxic impact of the azo dye. Degenerative changes including vacuolization, shrinkage, decrease in dimension, and density of club cells with simultaneous release of their contents in the intercellular spaces were associated to plug them, preventing indiscriminate entry of foreign matter. On exposure of fish to the dye, significant decline in the activity of enzymes-alkaline phosphatase, acid phosphatase, carboxylesterase, succinate dehydrogenase, catalase, and peroxidase-was associated with the binding of dye to the enzymes. Gradual increase in the activity of lactate dehydrogenase was considered to reflect a shift from aerobic to anaerobic metabolism. On transfer of azo dye exposed fish to freshwater, skin gradually recovers and, by 8 days, density and area of mucous goblet cells, club cells, and activity of the enzymes appear similar to that of controls. Alteration in histopathology and enzyme activity could be considered beneficial tool in monitoring environmental toxicity, valuable in the sustenance of fish populations.

Inhibition of in vitro growth and arrest in the G0/G1 phase of HCT8 line human colon cancer cells by kaempferide triglycoside from Dianthus caryophyllus.

PubMed

Martineti, Valentina; Tognarini, Isabella; Azzari, Chiara; Carbonell Sala, Silvia; Clematis, Francesca; Dolci, Marcello; Lanzotti, Virginia; Tonelli, Francesco; Brandi, Maria Luisa; Curir, Paolo

2010-09-01

The effects of phytoestrogens have been studied in the hypothalamic-pituitary-gonadal axis and in various non-gonadal targets. Epidemiologic and experimental evidence indicates a protective effect of phytoestrogens also in colorectal cancer. The mechanism through which estrogenic molecules control colorectal cancer tumorigenesis could possibly involve estrogen receptor beta, the predominantly expressed estrogen receptor subtype in colon mucosa.To validate this hypothesis, we therefore used an engineered human colon cancer cell line induced to overexpress estrogen receptor beta, beside its native cell line, expressing very low levels of ERbeta and not expressing ERalpha; as a phytoestrogenic molecule, we used kaempferide triglycoside, a glycosylated flavonol from a Dianthus caryophyllus cultivar. The inhibitory properties of this molecule toward vegetal cell growth have been previously demonstrated: however, no data on its activity on animal cell or information about the mechanism of this activity are available. Kaempferide triglycoside proved to inhibit the proliferation of native and estrogen receptor beta overexpressing colon cancer cells through a mechanism not mediated by ligand binding dependent estrogen receptor activation. It affected HCT8 cell cycle progression by increasing the G(0)/G(1) cell fraction and in estrogen receptor beta overexpressing cells increased two antioxidant enzymes. Interestingly, the biological effects of this kaempferide triglycoside were strengthened by the presence of high levels of estrogen receptor beta.Pleiotropic molecular effects of phytoestrogens may explain their protective activity against colorectal cancer and may represent an interesting area for future investigation with potential clinical applications. Copyright 2010 John Wiley & Sons, Ltd.

The identification of specialized pacemaking cells in the anal sphincters.

PubMed

Shafik, Ahmed; El Sibai, Olfat; Ahmed, Ismail

2006-07-01

Interstitial cells of Cajal (ICC) are claimed to generate the electrical activity in the colon and stomach. As the external (EAS) and internal (IAS) anal sphincters exhibit resting electrical activity, we hypothesized the presence of ICC in these sphincters. This hypothesis was investigated in the current study. Specimens from the EAS and IAS were taken from normal areas of the anorectum which had been surgically excised by abdominoperineal operation for rectal cancer of 28 patients (16 men, 12 women, mean age 42.2+/-4.8 years). The specimens were subjected to c-kit immunohistochemistry. Controls for the specificity of the antisera consisted of tissue incubation with normal rabbit serum substituted for the primary antiserum. Fusiform, c-kit positive, ICC-like cells were detected in the anal sphincters; they had dendritic processes. They were clearly distinguishable from the non-branching, c-kit negative smooth and striated muscle cells of the anal sphincters. The specimens contained also c-kit positive mast cells, but they had a rounded body with no dendritic processes. Immunoreactivity was absent in negative controls in which the primary antibody was omitted. We have identified, for the first time, cells in EAS and IAS with morphological and immunological phenotypes similar to ICCs of the gut. These cells appear to be responsible for initiating the slow waves recorded from the anal sphincters and for controlling their activity. A deficiency or absence of these cells may affect the anal motile activity. Studies are needed to explore the role of these cells in anal motility disorders.

Alternatively Activated Macrophages Play an Important Role in Vascular Remodeling and Hemorrhaging in Patients with Brain Arteriovenous Malformation.

PubMed

Nakamura, Yukihiko; Sugita, Yasuo; Nakashima, Shinji; Okada, Yousuke; Yoshitomi, Munetake; Kimura, Yoshizou; Miyoshi, Hiroaki; Morioka, Motohiro; Ohshima, Koichi

2016-03-01

Angiogenic and immunoactive lesions in brain arteriovenous malformation (BAVM) contribute to hemorrhagic events and the growth of BAVMs. However, the detailed mechanism is unclear. Our objective is to clarify the relationship between hemorrhagic events of BAVM and alternatively activated macrophages in the perinidal dilated capillary network (PDCN). We examined microsurgical specimens of BVMs (n = 29) and focused on the PDCN area. Ten autopsied brains without intracranial disease were the controls. We performed immunostaining of the inflammatory and endothelial cell markers, macrophage markers (CD163 and CD68), and vascular endothelial growth factor A (VEGF-A). We evaluated each cell's density and the vessel density in the PDCN and analyzed the relationship to hemorrhagic events of BAVM. The PDCN was involved in all the resected arteriovenous malformations, and these vessels showed a high rate of CD105 expression (72.0 ± 10.64%), indicating newly proliferating vessels. Alternatively activated macrophages were found, with a high rate (85.6%) for all macrophages (controls, 56.6%). In the hemorrhagic cases, the cell density was significantly higher than that in the nonhemorrhagic cases and controls (hemorrhagic group, 290 ± 44 cells/mm(2); nonhemorrhagic group, 180 ± 59 cells/mm(2); and control, 19 ± 8 cells/mm(2)). The cell density of alternatively activated macrophages showed a positive correlation with the vessel density of the PDCN. Double immunostaining showed that VEGF-A was secreted by alternatively activated macrophages. Our data suggest that alternatively activated macrophages may have some relationships with angiogenesis of PDCN and hemorrhagic event of BAVM. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

12-Deoxyphorbols Promote Adult Neurogenesis by Inducing Neural Progenitor Cell Proliferation via PKC Activation

PubMed Central

Geribaldi-Doldán, Noelia; Flores-Giubi, Eugenia; Murillo-Carretero, Maribel; García-Bernal, Francisco; Carrasco, Manuel; Macías-Sánchez, Antonio J.; Domínguez-Riscart, Jesús; Verástegui, Cristina; Hernández-Galán, Rosario

2016-01-01

Background: Neuropsychiatric and neurological disorders frequently occur after brain insults associated with neuronal loss. Strategies aimed to facilitate neuronal renewal by promoting neurogenesis constitute a promising therapeutic option to treat neuronal death-associated disorders. In the adult brain, generation of new neurons occurs physiologically throughout the entire life controlled by extracellular molecules coupled to intracellular signaling cascades. Proteins participating in these cascades within neurogenic regions constitute potential pharmacological targets to promote neuronal regeneration of injured areas of the central nervous system. Methodology: We have performed in vitro and in vivo approaches to determine neural progenitor cell proliferation to understand whether activation of kinases of the protein kinase C family facilitates neurogenesis in the adult brain. Results: We have demonstrated that protein kinase C activation by phorbol-12-myristate-13-acetate induces neural progenitor cell proliferation in vitro. We also show that the nontumorogenic protein kinase C activator prostratin exerts a proliferative effect on neural progenitor cells in vitro. This effect can be reverted by addition of the protein kinase C inhibitor G06850, demonstrating that the effect of prostratin is mediated by protein kinase C activation. Additionally, we show that prostratin treatment in vivo induces proliferation of neural progenitor cells within the dentate gyrus of the hippocampus and the subventricular zone. Finally, we describe a library of diterpenes with a 12-deoxyphorbol structure similar to that of prostratin that induces a stronger effect than prostratin on neural progenitor cell proliferation both in vitro and in vivo. Conclusions: This work suggests that protein kinase C activation is a promising strategy to expand the endogenous neural progenitor cell population to promote neurogenesis and highlights the potential of 12-deoxyphorbols as pharmaceutical agents to facilitate neuronal renewal. PMID:26224011

12-Deoxyphorbols Promote Adult Neurogenesis by Inducing Neural Progenitor Cell Proliferation via PKC Activation.

PubMed

Geribaldi-Doldán, Noelia; Flores-Giubi, Eugenia; Murillo-Carretero, Maribel; García-Bernal, Francisco; Carrasco, Manuel; Macías-Sánchez, Antonio J; Domínguez-Riscart, Jesús; Verástegui, Cristina; Hernández-Galán, Rosario; Castro, Carmen

2015-07-29

Neuropsychiatric and neurological disorders frequently occur after brain insults associated with neuronal loss. Strategies aimed to facilitate neuronal renewal by promoting neurogenesis constitute a promising therapeutic option to treat neuronal death-associated disorders. In the adult brain, generation of new neurons occurs physiologically throughout the entire life controlled by extracellular molecules coupled to intracellular signaling cascades. Proteins participating in these cascades within neurogenic regions constitute potential pharmacological targets to promote neuronal regeneration of injured areas of the central nervous system. We have performed in vitro and in vivo approaches to determine neural progenitor cell proliferation to understand whether activation of kinases of the protein kinase C family facilitates neurogenesis in the adult brain. We have demonstrated that protein kinase C activation by phorbol-12-myristate-13-acetate induces neural progenitor cell proliferation in vitro. We also show that the nontumorogenic protein kinase C activator prostratin exerts a proliferative effect on neural progenitor cells in vitro. This effect can be reverted by addition of the protein kinase C inhibitor G06850, demonstrating that the effect of prostratin is mediated by protein kinase C activation. Additionally, we show that prostratin treatment in vivo induces proliferation of neural progenitor cells within the dentate gyrus of the hippocampus and the subventricular zone. Finally, we describe a library of diterpenes with a 12-deoxyphorbol structure similar to that of prostratin that induces a stronger effect than prostratin on neural progenitor cell proliferation both in vitro and in vivo. This work suggests that protein kinase C activation is a promising strategy to expand the endogenous neural progenitor cell population to promote neurogenesis and highlights the potential of 12-deoxyphorbols as pharmaceutical agents to facilitate neuronal renewal. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Human T cell leukaemia virus type 2 tax protein mediates CC-chemokine expression in peripheral blood mononuclear cells via the nuclear factor kappa B canonical pathway.

PubMed

Barrios, C S; Castillo, L; Zhi, H; Giam, C-Z; Beilke, M A

2014-01-01

Retroviral co-infections with human immunodeficiency virus type-1 (HIV-1) and human T cell leukaemia virus type 1 (HTLV-1) or type 2 (HTLV-2) are prevalent in many areas worldwide. It has been observed that HIV-1/HTLV-2 co-infections are associated with slower rates of CD4(+) T cell decline and delayed progression to AIDS. This immunological benefit has been linked to the ability of Tax2, the transcriptional activating protein of HTLV-2, to induce the expression of macrophage inflammatory protein (MIP)-1α/CCL3, MIP-1β/CCL4 and regulated upon activation normal T cell expressed and secreted (RANTES)/CCL5 and to down-regulate the expression of the CCR5 co-receptor in peripheral blood mononuclear cells (PBMCs). This study aimed to assess the role of Tax2-mediated activation of the nuclear factor kappa B (NF-κB) signalling pathway on the production of the anti-viral CC-chemokines MIP-1α, MIP-1β and RANTES. Recombinant Tax1 and Tax2 proteins, or proteins expressed via adenoviral vectors used to infect cells, were tested for their ability to activate the NF-κB pathway in cultured PBMCs in the presence or absence of NF-κB pathway inhibitors. Results showed a significant release of MIP-1α, MIP-1β and RANTES by PBMCs after the activation of p65/RelA and p50. The secretion of these CC-chemokines was significantly reduced (P < 0·05) by canonical NF-κB signalling inhibitors. In conclusion, Tax2 protein may promote innate anti-viral immune responses through the activation of the canonical NF-κB pathway. © 2013 British Society for Immunology.

O-GlcNAc: a novel regulator of immunometabolism.

PubMed

Machacek, Miranda; Slawson, Chad; Fields, Patrick E

2018-06-01

The rapidly expanding field of immunometabolism focuses on how metabolism controls the function of immune cells. CD4 + T cells are essential for the adaptive immune response leading to the eradication of specific pathogens. However, when T cells are inappropriately over-active, they can drive autoimmunity, allergic disease, and chronic inflammation. The mechanisms by which metabolic changes influence function in CD4 + T cells are not fully understood. The post-translational protein modification, O-GlcNAc (O-linked β-N-acetylglucosamine), dynamically cycles on and off of intracellular proteins as cells respond to their environment and flux through metabolic pathways changes. As the rate of O-GlcNAc cycling fluctuates, protein function, stability, and/or localization can be affected. Thus, O-GlcNAc is critically poised at the nexus of cellular metabolism and function. This review highlights the intra- and extracellular metabolic factors that influence CD4 + T cell activation and differentiation and how O-GlcNAc regulates these processes. We also propose areas of future research that may illuminate O-GlcNAc's role in the plasticity and pathogenicity of CD4 + T cells and uncover new potential therapeutic targets.

Current State-of-the-Art 3D Tissue Models and Their Compatibility with Live Cell Imaging.

PubMed

Bardsley, Katie; Deegan, Anthony J; El Haj, Alicia; Yang, Ying

2017-01-01

Mammalian cells grow within a complex three-dimensional (3D) microenvironment where multiple cells are organized and surrounded by extracellular matrix (ECM). The quantity and types of ECM components, alongside cell-to-cell and cell-to-matrix interactions dictate cellular differentiation, proliferation and function in vivo. To mimic natural cellular activities, various 3D tissue culture models have been established to replace conventional two dimensional (2D) culture environments. Allowing for both characterization and visualization of cellular activities within possibly bulky 3D tissue models presents considerable challenges due to the increased thickness and subsequent light scattering features of such 3D models. In this chapter, state-of-the-art methodologies used to establish 3D tissue models are discussed, first with a focus on both scaffold-free and scaffold-based 3D tissue model formation. Following on, multiple 3D live cell imaging systems, mainly optical imaging modalities, are introduced. Their advantages and disadvantages are discussed, with the aim of stimulating more research in this highly demanding research area.

Dynamic Palmitoylation and the Role of DHHC Proteins in T Cell Activation and Anergy

PubMed Central

Ladygina, Nadejda; Martin, Brent R.; Altman, Amnon

2017-01-01

Although protein S-palmitoylation was first characterized >30 years ago, and is implicated in the function, trafficking, and localization of many proteins, little is known about the regulation and physiological implications of this posttranslational modification. Palmitoylation of various signaling proteins required for TCR-induced T cell activation is also necessary for their proper function. LAT (linker for activation of T cells) is an essential scaffolding protein involved in T cell development and activation, and we found that its palmitoylation is selectively impaired in anergic T cells. The recent discovery of the DHHC family of palmitoyl acyl transferases (PATs) and the establishment of sensitive and quantitative proteomics-based methods for global analysis of the palmitoyl proteome led to significant progress in studying the biology and underlying mechanisms of cellular protein palmitoylation. We are using these approaches to explore the palmitoyl proteome in T lymphocytes and, specifically, the mechanistic basis for the impaired palmitoylation of LAT in anergic T cells. This chapter reviews the history of protein palmitoylation and its role in T cell activation, the DHHC family and new methodologies for global analysis of the palmitoyl proteome, and summarizes our recent work in this area. The new methodologies will accelerate the pace of research and provide a greatly improved mechanistic and molecular understanding of the complex process of protein palmitoylation and its regulation, and the substrate specificity of the novel DHHC family. Reversible protein palmitoylation will likely prove to be an important posttranslational mechanism that regulates cellular responses, similar to protein phosphorylation and ubiquitination. PMID:21569911

Lutein facilitates physiological revascularization in a mouse model of retinopathy of prematurity.

PubMed

Fu, Zhongjie; Meng, Steven S; Burnim, Samuel B; Smith, Lois Eh; Lo, Amy Cy

2017-07-01

Retinopathy of prematurity is one of the leading causes of childhood blindness worldwide, with vessel growth cessation and vessel loss in phase I followed by neovascularization in phase II. Ischaemia contributes to its pathogenesis, and lutein protects against ischaemia-induced retinal damages. We aimed to investigate the effects of lutein on a murine model of oxygen-induced retinopathy. Mouse pups were exposed to 75% oxygen for 5 days and returned to room air for another 5 days. Vascular obliteration, neovascularization and blood vessel leakage were examined. Immunohistochemistry for glial cells and microglia were performed. Compared with vehicle controls, mouse pups receiving lutein treatment displayed smaller central vaso-obliterated area and reduced blood vessel leakage. No significant difference in neovascular area was found between lutein and vehicle controls. Lutein promoted endothelial tip cell formation and maintained the astrocytic template in the avascular area in oxygen-induced retinopathy. No significant changes in Müller cell gliosis and microglial activation in the central avascular area were found in lutein-treated pups. Our observations indicated that lutein significantly promoted normal retinal vascular regrowth in the central avascular area, possibly through promoting endothelial tip cell formation and preserving astrocytic template. Our results indicated that lutein might be considered as a supplement for the treatment of proliferative retinopathy of prematurity because of its role in facilitating the revascularization of normal vasculature. © 2016 Royal Australian and New Zealand College of Ophthalmologists.

Spreading of Neutrophils: From Activation to Migration

PubMed Central

Sengupta, Kheya; Aranda-Espinoza, Helim; Smith, Lee; Janmey, Paul; Hammer, Daniel

2006-01-01

Neutrophils rely on rapid changes in morphology to ward off invaders. Time-resolved dynamics of spreading human neutrophils after activation by the chemoattractant fMLF (formyl methionyl leucyl phenylalanine) was observed by RICM (reflection interference contrast microscopy). An image-processing algorithm was developed to identify the changes in the overall cell shape and the zones of close contact with the substrate. We show that in the case of neutrophils, cell spreading immediately after exposure of fMLF is anisotropic and directional. The dependence of spreading area, A, of the cell as a function of time, t, shows several distinct regimes, each of which can be fitted as power laws (A ∼ tb). The different spreading regimes correspond to distinct values of the exponent b and are related to the adhesion state of the cell. Treatment with cytochalasin-B eliminated the anisotropy in the spreading. PMID:17012330

Technical advances power neuroscience

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

Barinaga, M.

New techniques are helping researchers study the development of nerve cells in cell cultures and in vivo. These new methods are offering insights into the brain that were not available even a couple of years ago. Among the new advances discussed are imaging technology for evaluating the thinking human brain. One area in which researchers have made recent progress is the quest for ways to create immortal cell lines from specific types of nerve cells. Other projects using genetically engineered retroviruses and tumor-inducing genes, as well as gene regulation are discussed. Recent advances in neuroscience techniques apply not only tomore » neurons, but also to whole brains as well. One example is a high-resulution electroencephalogram (EEG). Although the EEG cannot pin down the actual sites of activity as precisely as static brain imaging methods, it complements them with real-time recording that can keep up with the very rapid pace of brain activity.« less

Pericytes as a supplementary source of osteoblasts in periosteal osteogenesis.

PubMed

Diaz-Flores, L; Gutierrez, R; Lopez-Alonso, A; Gonzalez, R; Varela, H

1992-02-01

In the adult rat femur, lifting a periosteum strip with microscopic bone flakes on its deep surface, if performed without damaging the surrounding microcirculation, rapidly leads to new bone formation and angiogenesis. Using vascular labeling, the pericytes and endothelial cells (ECs) were labeled with monastral blue (MB) in the preformed, preexisting postcapillary venules of the periosteal microcirculation. MB was detectable by light and electron microscopy and it persisted in some of the daughter cells. Between one and 21 hours, the MB labeling was restricted to the pericytes and ECs of postcapillary venules. Immediately afterward, both pericytes and ECs of these vessels were activated and continued to show MB. The phenomenon of pericyte activation includes enlargement, disruption of their basal lamina, separation from the walls of the preformed vessels, and the presence of mitotic figures. At this stage, activated pericytes with MB in their cytoplasm, fibroblast-like cells, and transitional cell forms between them were seen in interstitial areas. After 27 hours, vascular buds appeared and MB was detected in some ECs and pericytes. Between three and six days, when bone-tissue development was observed, some osteoblasts were MB labeled. Previous findings support the hypothesis that when the periosteum is activated, the process of bone formation from cells already present in the periosteum is augmented by proliferation and differentiation of pericytes, which contribute a supplementary population of osteoprogenitor cells.

Functional μ-Opioid-Galanin Receptor Heteromers in the Ventral Tegmental Area.

PubMed

Moreno, Estefanía; Quiroz, César; Rea, William; Cai, Ning-Sheng; Mallol, Josefa; Cortés, Antoni; Lluís, Carme; Canela, Enric I; Casadó, Vicent; Ferré, Sergi

2017-02-01

The neuropeptide galanin has been shown to interact with the opioid system. More specifically, galanin counteracts the behavioral effects of the systemic administration of μ-opioid receptor (MOR) agonists. Yet the mechanism responsible for this galanin-opioid interaction has remained elusive. Using biophysical techniques in mammalian transfected cells, we found evidence for selective heteromerization of MOR and the galanin receptor subtype Gal1 (Gal1R). Also in transfected cells, a synthetic peptide selectively disrupted MOR-Gal1R heteromerization as well as specific interactions between MOR and Gal1R ligands: a negative cross talk, by which galanin counteracted MAPK activation induced by the endogenous MOR agonist endomorphin-1, and a cross-antagonism, by which a MOR antagonist counteracted MAPK activation induced by galanin. These specific interactions, which represented biochemical properties of the MOR-Gal1R heteromer, could then be identified in situ in slices of rat ventral tegmental area (VTA) with MAPK activation and two additional cell signaling pathways, AKT and CREB phosphorylation. Furthermore, in vivo microdialysis experiments showed that the disruptive peptide selectively counteracted the ability of galanin to block the dendritic dopamine release in the rat VTA induced by local infusion of endomorphin-1, demonstrating a key role of MOR-Gal1R heteromers localized in the VTA in the direct control of dopamine cell function and their ability to mediate antagonistic interactions between MOR and Gal1R ligands. The results also indicate that MOR-Gal1R heteromers should be viewed as targets for the treatment of opioid use disorders. The μ-opioid receptor (MOR) localized in the ventral tegmental area (VTA) plays a key role in the reinforcing and addictive properties of opioids. With parallel in vitro experiments in mammalian transfected cells and in situ and in vivo experiments in rat VTA, we demonstrate that a significant population of these MORs form functional heteromers with the galanin receptor subtype Gal1 (Gal1R), which modulate the activity of the VTA dopaminergic neurons. The MOR-Gal1R heteromer can explain previous results showing antagonistic galanin-opioid interactions and offers a new therapeutic target for the treatment of opioid use disorder. Copyright © 2017 the authors 0270-6474/17/371176-11$15.00/0.

Synthesis and evaluation of (Z)-2,3-diphenylacrylonitrile analogs as anti-cancer and anti-microbial agents.

PubMed

Alam, Mohammad Sayed; Nam, Young-Joo; Lee, Dong-Ung

2013-11-01

In the present study, a series of (Z)-2,3-diphenylacrylonitrile analogs were synthesized and then evaluated in terms of their cytotoxic activities against four human cancer cell lines, e.g. lung cancer (A549), ovarian cancer (SK-OV-3), skin cancer (SK-MEL-2), and colon cancer (HCT15), as well as anti-microbial activities against three microbes, e.g. Staphylococcus aureus, Salmonella typhi, and Aspergillus niger. The title compounds were synthesized by Knoevenagel condensation reaction of benzyl cyanide or p-nitrobenzyl cyanide with substituted benzaldehydes in good yields. Most of the compounds exhibited significant suppressive activities against the growth of all cancer cell lines. Compound 3c was most active in inhibiting the growth of A549, SK-OV-3, SK-MEL-2, and HCT15 cells lines with IC50 values of 0.57, 0.14, 0.65, and 0.34 mg/mL, respectively, followed by compounds 3f, 3i, and 3h. Compound 3c exhibited 2.4 times greater cytotoxic activity against HCT15 cells, whereas it showed similar potency against SK-OV-3 cells to that of the standard anti-cancer agent doxorubicin. Structure-activity relationship study revealed that electron-donating groups at the para-position of phenyl ring B were more favorable for improved cytotoxic activity, whereas the presence of electron-withdrawing groups was unfavorable compare to unsubstituted acrylonitrile. An optimal electron density on phenyl ring A of (Z)-2,3-diphenylacrylonitrile analogs was crucial for their cytotoxic activities against human cancer cell lines used in the present study. Qualitative structure-cytotoxic activity relationships were studied using physicochemical parameters; a good correlation between calculated polar surface area (PSA), a lipophobic parameter, and cytotoxic activity was found. Moreover, all compounds showed significant anti-bacterial activities against S. typhi, whereas compound 3k showed potent inhibition against both S. aureus and S. typhi bacterial strains. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Monitoring the elasticity changes of HeLa cells during mitosis by atomic force microscopy

NASA Astrophysics Data System (ADS)

Jiang, Ningcheng; Wang, Yuhua; Zeng, Jinshu; Ding, Xuemei; Xie, Shusen; Yang, Hongqin

2016-10-01

Cell mitosis plays a crucial role in cell life activity, which is one of the important phases in cell division cycle. During the mitosis, the cytoskeleton micro-structure of the cell changed and the biomechanical properties of the cell may vary depending upon different mitosis stages. In this study, the elasticity property of HeLa cells during mitosis was monitored by atomic force microscopy. Also, the actin filaments in different mitosis stages of the cells were observed by confocal imaging. Our results show that the cell in anaphase is stiffer than that in metaphase and telophase. Furthermore, lots of actin filaments gathered in cells' center area in anaphase, which contributes to the rigidity of the cell in this phase. Our findings demonstrate that the nano-biomechanics of living cells could provide a new index for characterizing cell physiological states.

Responses of neurons to extreme osmomechanical stress.

PubMed

Wan, X; Harris, J A; Morris, C E

1995-05-01

Neurons are often regarded as fragile cells, easily destroyed by mechanical and osmotic insult. The results presented here demonstrate that this perception needs revision. Using extreme osmotic swelling, we show that molluscan neurons are astonishingly robust. In distilled water, a heterogeneous population of Lymnaea stagnalis CNS neurons swelled to several times their initial volume, yet had a ST50 (survival time for 50% of cells) > 60 min. Cells that were initially bigger survived longer. On return to normal medium, survivors were able, over the next 24 hr, to rearborize. Reversible membrane capacitance changes corresponding to about 0.7 muF/cm2 of apparent surface area accompanied neuronal swelling and shrinking in hypo- and hyperosmotic solutions; reversible changes in cell surface area evidently contributed to the neurons' ability to accommodate hydrostatic pressures then recover. The reversible membrane area/capacitance changes were not dependent on extracellular Ca2+. Neurons were monitored for potassium currents during direct mechanical inflation and during osmotically driven inflation. The latter but not the former stimulus routinely elicited small potassium currents, suggesting that tension increases activate the currents only if additional disruption of the cortex has occurred. Under stress in distilled water, a third of the neurons displayed a quite unexpected behavior: prolonged writhing of peripheral regions of the soma. This suggested that a plasma membrane-linked contractile machinery (presumably actomyosin) might contribute to the neurons' mechano-osmotic robustness by restricting water influx. Consistent with this possibility, 1 mM N-ethyl-maleimide, which inhibits myosin ATPase, decreased the ST50 to 18 min, rendered the survival time independent of initial size, and abolished writhing activity. For neurons, active mechanical resistance of the submembranous cortex, along with the mechanical compliance supplied by insertion or eversion of membrane stores may account for the ability to withstand diverse mechanical stresses. Mechanical robustness such as that displayed here could be an asset during neuronal outgrowth or regeneration.

Bacillus cereus strain MCN as a debriding agent

NASA Technical Reports Server (NTRS)

Dalton, H. P.; Haynes, B. W.; Stone, L. L.

1978-01-01

Biologically active means are effective for rapidly removing scar tissue caused by burns or corrosive agents. Specially selected strain of bacteria applied to injury site releases enzymes which are active against eschar. These bacteria tend to locate between eschar and unburned tissue, thus providing optimal cell surface area arrangement for enzyme dispersal. Procedure may prove especially useful in treatment of disaster casualties under relatively primitive conditions.

Planar fuel cell utilizing nail current collectors for increased active surface area

DOEpatents

George, Thomas J.; Meacham, G. B. Kirby

2002-03-26

A plurality of nail current collector members are useful in the gas flow passages of an electrochemical device to optimize the active surfaces of the device and to provide structural support. In addition, the thicknesses of cathode and anode layers within the electrochemical device are varied according to current flow through the device to reduce resistance and increase operating efficiency.

Planar fuel cell utilizing nail current collectors for increased active surface area

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

George, Thomas J.; Meacham, G.B. Kirby

1999-11-26

A plurality of nail current collector members are useful in the gas flow passages of an electrochemical device to optimize the active surfaces of the device and to provide structural support. In addition, the thicknesses of cathode and anode layers within the electrochemical device are varied according to current flow through the device to reduce resistance and increase operating efficiency.

Quarterly Progress Report for the Chemical and Energy Research Section of the Chemical Technology Division: July-September 1999

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

Jubin, R.T.

2001-04-16

This report summarizes the major activities conducted in the Chemical and Energy Research Section of the Chemical Technology Division at Oak Ridge National Laboratory (ORNL) during the period July-September 1999. The section conducts basic and applied research and development in chemical engineering, applied chemistry, and bioprocessing, with an emphasis on energy-driven technologies and advanced chemical separations for nuclear and waste applications. The report describes the various tasks performed within ten major areas of research: Hot Cell Operations, Process Chemistry, Molten Salt Reactor Experiment (MSRE) Remediation Studies, Chemistry Research, Physical Properties Research, Biochemical Engineering, Separations and Materials Synthesis, Fluid Structures andmore » Properties, Biotechnology Research, and Molecular Studies. The name of a technical contact is included with each task described, and readers are encouraged to contact these individuals if they need additional information. Activities conducted within the area of the Cell Operations involved the testing of two continuously stirred tank reactors in series to evaluate the Savannah River-developed process of small-tank tetraphenylborate precipitation to remove cesium, strontium and transuranics from supernatant. Within the area of Process Chemistry, various topics related to solids formation in process solutions from caustic treatment of Hanford sludge were addressed. Saltcake dissolution efforts continued, including the development of a predictive algorithm. New initiatives for the section included modeling activities centered on detection of hydrogen in {sup 233}U storage wells and wax formation in petroleum mixtures, as well as support for the Spallation Neutron Source (investigation of transmutation products formed during operation). Other activities involved in situ grouting and evaluation of options for use (i.e., as castable shapes) of depleted uranium. In a continuation of activities of the preceding quarter, MSRE Remediation Studies focused on recovery of {sup 233}U and its conversion to a stable oxide and radiolysis experiments to permit remediation of MSRE fuel salt. Investigation of options for final disposition of the {sup 233}U inventory represents a new initiative within this area. In the area of Chemistry Research, activities included studies relative to molecular imprinting for use in areas such as selective sorption, chemical sensing, and catalysis, as well as spectroscopic investigation into the fundamental interaction between ionic solvents and solutes in both low- and high-temperature ionic liquids.« less

Herbal medicine Inchin-ko-to (TJ-135) prevents liver fibrosis and enzyme-altered lesions in rat liver cirrhosis induced by a choline-deficient L-amino acid-defined diet.

PubMed

Sakaida, Isao; Tsuchiya, Masako; Kawaguchi, Kotarou; Kimura, Teruaki; Terai, Shuji; Okita, Kiwamu

2003-06-01

The herbal medicine Inchin-ko-to (TJ-135), extract power from three herbs, has recently been reported possessing anti-apoptotic activity. The aim of this study was to investigate whether TJ-135 has any influence on the development of preneoplastic lesions as well as liver fibrosis. The effects of the TJ-135 were examined using the choline-deficient L-amino acid-defined diet-induced liver fibrosis model. In addition, the effect of TJ-135 on mitogen-activated protein (MAP) kinase, type III procollagen mRNA expression and the medium N-terminal procollagen III propeptide (PIIINP) concentration in a hepatic stellate cell line (LI90) were examined. TJ-135 prevented fibrosis in a dose-dependent manner up to 1.5% (w/w). TJ-135 also reduced the expression of type III procollagen mRNA in the liver, as well as the number of activated stellate cells. Furthermore, TJ-135 reduced the area of preneoplastic lesions in the liver. With LI90 cells, TJ-135 reduced MAP kinase (ERK and JNK but not P38) activities resulting in reduced type III procollagen mRNA and PIIINP concentrations in the medium in a dose-dependent manner. These results indicate that although TJ-135 has anti-apoptotic activity, TJ-135 does not increase preneoplastic lesions but significantly reduces liver fibrosis through the inhibition of stellate cell activation without a reduction of hepatocyte cell death.

Memory retrieval-induced activation of adult-born neurons generated in response to damage to the dentate gyrus.

PubMed

Aguilar-Arredondo, Andrea; Zepeda, Angélica

2018-07-01

The dentate gyrus (DG) is a neurogenic structure that exhibits functional and structural reorganization after injury. Neurogenesis and functional recovery occur after brain damage, and the possible relation between both processes is a matter of study. We explored whether neurogenesis and the activation of new neurons correlated with DG recovery over time. We induced a DG lesion in young adult rats through the intrahippocampal injection of kainic acid and analyzed functional recovery and the activation of new neurons after animals performed a contextual fear memory task (CFM) or a control spatial exploratory task. We analyzed the number of BrdU+ cells that co-localized with doublecortin (DCX) or with NeuN within the damaged DG and evaluated the number of cells in each population that were labelled with the activity marker c-fos after either task. At 10 days post-lesion (dpl), a region of the granular cell layer was devoid of cells, evidencing the damaged area, whereas at 30 dpl this region was significantly smaller. At 10 dpl, the number of BrdU+/DCX+/c-fos positive cells was increased compared to the sham-lesion group, but CFM was impaired. At 30 dpl, a significantly greater number of BrdU+/NeuN+/c-fos positive cells was observed than at 10 dpl, and activation correlated with CFM recovery. Performance in the spatial exploratory task induced marginal c-fos immunoreactivity in the BrdU+/NeuN+ population. We demonstrate that neurons born after the DG was damaged survive and are activated in a time- and task-dependent manner and that activation of new neurons occurs along functional recovery.

Partially hydrolyzed guar gum enhances colonic epithelial wound healing via activation of RhoA and ERK1/2.

PubMed

Horii, Yusuke; Uchiyama, Kazuhiko; Toyokawa, Yuki; Hotta, Yuma; Tanaka, Makoto; Yasukawa, Zenta; Tokunaga, Makoto; Okubo, Tsutomu; Mizushima, Katsura; Higashimura, Yasuki; Dohi, Osamu; Okayama, Tetsuya; Yoshida, Naohisa; Katada, Kazuhiro; Kamada, Kazuhiro; Handa, Osamu; Ishikawa, Takeshi; Takagi, Tomohisa; Konishi, Hideyuki; Naito, Yuji; Itoh, Yoshito

2016-07-13

Healing of the intestinal mucosal epithelium was found to be a critical factor in the treatment of inflammatory bowel disease (IBD). In this study, we provide further evidence that partially hydrolyzed dietary fiber (PHGG) enhances colonic epithelial cell wound healing, and partially characterize the mechanism that governs this process. Young adult mouse colonic (YAMC) epithelial cells were scraped with a 10 μl micro-pipette tip to denude a round of the monolayer and were incubated with PHGG. The area of cell migration was measured using Image J software. Meanwhile, Rho activation assays were utilized to monitor Rho activation levels. To assess in vivo effects, C57B6 mice were treated with DSS for 7 days and then provided food supplemented with PHGG for 8 days. YAMC cells treated with PHGG exhibited significantly enhanced wound healing compared to the control cells; however, this enhancement was inhibited by both Y-27632 (RhoA inhibitor) and U0126 (ERK1/2 inhibitor). Likewise, there was a PHGG-dependent increase in F-actin accumulation and Rho kinase activity that was blocked by U0126. Meanwhile, PHGG-dependent ERK1/2 activity was not inhibited by Y-27632. In the DSS-induced mouse colitis model, animals that received food supplemented with PHGG exhibited significant recovery of the colonic mucosa. In this study, we demonstrate that PHGG promotes colonic epithelial cell wound healing via activation of RhoA, which occurs downstream of ERK1/2 activation. These findings indicate that PHGG could be utilized as a therapeutic agent for patients with intestinal mucosal damage such as those with IBD.

Expression of interleukin-8 gene in inflammatory bowel disease is related to the histological grade of active inflammation.

PubMed Central

Mazzucchelli, L.; Hauser, C.; Zgraggen, K.; Wagner, H.; Hess, M.; Laissue, J. A.; Mueller, C.

1994-01-01

Interleukin-8 (IL-8) is a potent cytokine for recruitment and activation of neutrophils. To visualize its distribution in the intestinal mucosa and to understand better its possible role in the induction and promotion of inflammatory bowel disease, expression of the IL-8 gene was analyzed in resected bowel segments of 14 patients with active Crohn's disease or ulcerative colitis. In situ hybridization with IL-8 anti-sense RNA probes revealed strong and specific signals in the histologically affected mucosa. The number of cells expressing IL-8 gene correlated with the histological grade of active inflammation. In accordance with the characteristic histological signs of active disease, IL-8-expressing cells were diffusely distributed over the entire affected mucosa in patients with ulcerative colitis, whereas in patients with Crohn's disease, IL-8-expressing cells showed a focal distribution pattern. Cells expressing IL-8 were mainly located at the base of ulcers, in inflammatory exudates on mucosal surfaces, in crypt abscesses, and at the border of fistulae. Analysis of semi-serial sections pointed to macrophages, neutrophils, and epithelial cells as possible sources of this cytokine in active inflammatory bowel disease. We consistently failed to detect IL-8 messenger RNA in the mucosa of uninvolved bowel segments and in normal-appearing control mucosa of patients with colon cancer. In contrast, tissue specimens from two patients with acute appendicitis displayed IL-8-expressing cells in the mucosa. These results support the notion that IL-8 plays and important but nonspecific role in the pathogenesis of inflammatory bowel disease and that the production of IL-8 messenger RNA is restricted to areas with histological signs of inflammatory activity and mucosal destruction. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8178948

Determination of Optimal Sample Size for Quantification of β-Cell Area, Amyloid Area and β-Cell Apoptosis in Isolated Islets.

PubMed

Meier, Daniel T; Entrup, Leon; Templin, Andrew T; Hogan, Meghan F; Samarasekera, Thanya; Zraika, Sakeneh; Boyko, Edward J; Kahn, Steven E

2015-08-01

Culture of isolated rodent islets is widely used in diabetes research to assess different endpoints, including outcomes requiring histochemical staining. As islet yields during isolation are limited, we determined the number of islets required to obtain reliable data by histology. We found that mean values for insulin-positive β-cell area/islet area, thioflavin S-positive amyloid area/islet area and β-cell apoptosis do not vary markedly when more than 30 islets are examined. Measurement variability declines as more islets are quantified, so that the variability of the coefficient of variation (CV) in human islet amyloid polypeptide (hIAPP) transgenic islets for β-cell area/islet area, amyloid area/islet area and β-cell apoptosis are 13.20% ± 1.52%, 10.03% ± 1.76% and 6.78% ± 1.53%, respectively (non-transgenic: 7.65% ± 1.17% β-cell area/islet area and 8.93% ± 1.56% β-cell apoptosis). Increasing the number of islets beyond 30 had marginal effects on the CV. Using 30 islets, 6 hIAPP-transgenic preparations are required to detect treatment effects of 14% for β-cell area/islet area, 30% for amyloid area/islet area and 23% for β-cell apoptosis (non-transgenic: 9% for β-cell area/islet area and 45% for β-cell apoptosis). This information will be of value in the design of studies using isolated islets to examine β cells and islet amyloid. © The Author(s) 2015.

Mesenchymal stem cells display hepato-protective activity in lymphoma bearing xenografts.

PubMed

Secchiero, Paola; Corallini, Federica; Zavan, Barbara; Tripodo, Claudio; Vindigni, Vincenzo; Zauli, Giorgio

2012-04-01

A disseminated model of non-Hodgkin's lymphoma with prevalent liver metastasis was generated by intraperitoneal (i.p.) injection of EBV(+) B lymphoblastoid SKW6.4 in nude-SCID mice. The survival of SKW6.4 xenografts (median survival = 27 days) was significantly improved when hyaluronan scaffolds embedded with mesenchimal stem cells (MSC) were implanted in the abdominal area 4 days after SKW6.4 injection (median survival = 39.5 days). Mice implanted with MSC showed a significant improvement of hepatic functionality in lymphoma xenografts, as demonstrated by measurement of serum ALT/AST levels. Co-culture of MSC with lymphoma cells enhanced the release of hepatocyte growth factor (HGF) by MSC. These data suggest that hyaluronan-embedded MSC exert anti-lymphoma activity by ameliorating hepatic functionality.

Different regulation of aryl hydrocarbon receptor-regulated genes in response to dioxin in undifferentiated and neuronally differentiated human neuroblastoma SH-SY5Y cells.

PubMed

Imran, Saima; Ferretti, Patrizia; Vrzal, Radim

2015-01-01

Some environmental pollutants derived from industrial processes have been suggested to be responsible for neurological impairment in children, especially in heavily polluted areas. Since these compounds are usually activators of aryl hydrocarbon receptor (AhR), it would be important to better understand the molecular pathways downstream of AhR leading to neural deficits. To this purpose, appropriate in vitro human neural model is much needed. Here we have investigated whether undifferentiated and neuronally differentiated human neuroblastoma cells, SH-SY5Y cells, can provide a suitable model for monitoring AhR activity induced by environmental pollutants, focusing on 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD), a known activator of AhR. Further characterization of differentiated SH-SY5Y showed an increase in AhRR (aryl hydrocarbon receptor repressor), no change in ARNT1 (AhR nuclear translocator 1), and a decrease in ARNT2 expression with differentiation; in contrast, AhR was undetectable in both undifferentiated and differentiated cells. Nonetheless, treatment of parental as well as differentiated SH-SY5Y cells with TCDD resulted in the induction of AhR-regulated genes, CYP1A1 and CYP1B1; AhRR expression was also affected, but to a much smaller extent. These results indicate that undifferentiated SH-SY5Y are less sensitive to TCDD than neuronally differentiated ones, suggesting a higher resistance of the undifferentiated tumor cells to toxic insults. They also suggest that TCDD in these cells may not act via direct activation of AhR that is undetectable in SH-SY5Y as well as in differentiated neurons. Hence, these cells do not provide an appropriate model for studying ligand-mediated activation of AhR.

Inflammation-induced reversible switch of the neuron-specific enolase promoter from Purkinje neurons to Bergmann glia.

PubMed

Sawada, Yusuke; Konno, Ayumu; Nagaoka, Jun; Hirai, Hirokazu

2016-06-13

Neuron-specific enolase (NSE) is a glycolytic isoenzyme found in mature neurons and cells of neuronal origin. Injecting adeno-associated virus serotype 9 (AAV9) vectors carrying the NSE promoter into the cerebellar cortex is likely to cause the specific transduction of neuronal cells, such as Purkinje cells (PCs) and interneurons, but not Bergmann glia (BG). However, we found BG-predominant transduction without PC transduction along a traumatic needle tract for viral injection. The enhancement of neuroinflammation by the co-application of lipopolysaccharide (LPS) with AAV9 significantly expanded the BG-predominant area concurrently with the potentiated microglial activation. The BG-predominant transduction was gradually replaced by the PC-predominant transduction as the neuroinflammation dissipated. Experiments using glioma cell cultures revealed significant activation of the NSE promoter due to glucose deprivation, suggesting that intracellularly stored glycogen is metabolized through the glycolytic pathway for energy. Activation of the glycolytic enzyme promoter in BG concurrently with inactivation in PC may have pathophysiological significance for the production of lactate in activated BG and the utilization of lactate, which is provided by the BG-PC lactate shuttle, as a primary energy resource in injured PCs.

Rac regulates vascular endothelial growth factor stimulated motility.

PubMed

Soga, N; Connolly, J O; Chellaiah, M; Kawamura, J; Hruska, K A

2001-01-01

During angiogenesis endothelial cells migrate towards a chemotactic stimulus. Understanding the mechanism of endothelial cell migration is critical to the therapeutic manipulation of angiogenesis and ultimately cancer prevention. Vascular endothelial growth factor (VEGF) is a potent chemotactic stimulus of endothelial cells during angiogenesis. The endothelial cell signal transduction pathway of VEGF represents a potential target for cancer therapy, but the mechanisms of post-receptor signal transduction including the roles of rho family GTPases in regulating the cytoskeletal effects of VEGF in endothelial cells are not understood. Here we analyze the mechanisms of cell migration in the mouse brain endothelial cell line (bEND3). Stable transfectants containing a tetracycline repressible expression vector were used to induce expression of Rac mutants. Endothelial cell haptotaxis was stimulated by constitutively active V12Rac on collagen and vitronectin coated supports, and chemotaxis was further stimulated by VEGF. Osteopontin coated supports were the most stimulatory to bEND3 haptotaxis, but VEGF was not effective in further increasing migration on osteopontin coated supports. Haptotaxis on support coated with collagen, vitronectin, and to a lesser degree osteopontin was inhibited by N17 Rac. N17 Rac expression blocked stimulation of endothelial cell chemotaxis by VEGF. As part of the chemotactic stimulation, VEGF caused a loss of actin organization at areas of cell-cell contact and increased stress fiber expression in endothelial cells which were directed towards pores in the transwell membrane. N17 Rac prevented the stimulation of cell-cell contact disruption and the stress fiber stimulation by VEGF. These data demonstrate two pathways of regulating endothelial cell motility, one in which Rac is activated by matrix/integrin stimulation and is a crucial modulator of endothelial cell haptotaxis. The other pathway, in the presence of osteopontin, is Rac independent. VEGF stimulated chemotaxis, is critically dependent on Rac activation. Osteopontin was a potent matrix activator of motility, and perhaps one explanation for the absence of a VEGF plus osteopontin effect is that osteopontin stimulated motility was inhibitory to the Rac pathway.

Comparative analysis of the expression of c-Fos and interleukin-2 proteins in hypothalamus cells during various treatments.

PubMed

Barabanova, S V; Artyukhina, Z E; Ovchinnikova, K T; Abramova, T V; Kazakova, T B; Khavinson, V Kh; Malinin, V V; Korneva, E A

2008-03-01

The aim of the present work was to perform a combined analysis of the degree of activation of the anterior hypothalamus of the rat and expression of the interleukin-2 gene during treatments of different types: mild stress ("handling") and adaption to it, as well as intranasal administration of physiological saline and the peptides Vilon (Lys-Glu) and Epitalon (Ala-Glu-Asp-Gly). Changes in the numbers of c-Fos-and IL-2-positive cells in structures of the lateral area (LHA) and anterior (AHN), supraoptic (SON), and paraventricular (PVN) nuclei of the hypothalamus in Wistar rats. Ratios of the quantities of c-Fos-and IL-2-positive cells were determined in intact animals and after activation of brain cells initiated by different treatments; the influences of adaptation to handling on the nature of changes in the expression of these proteins was also studied. Combined analysis of the intensity of expression of these two proteins - c-Fos, a marker of neuron activation and a trans-factor for the IL-2 cytokine gene and other inducible genes, and IL-2 - in intact animals and after various treatments showed that the process of cell activation in most of the hypothalamic structures studied correlated with decreases in the quantity of IL-2-positive cells in these structures; different patterns of changes in the numbers of c-Fos-and IL-2-positive cells were seen in response to different treatments in conditions of stress and adaptation to it.

Ivy and neurogliaform interneurons are a major target of μ opioid receptor modulation

PubMed Central

Krook-Magnuson, Esther; Luu, Lillian; Lee, Sang-Hun; Varga, Csaba; Soltesz, Ivan

2011-01-01

Mu opioid receptors (μORs) are selectively expressed on interneurons in area CA1 of the hippocampus. Fast-spiking, parvalbumin expressing, basket cells express μORs, but circumstantial evidence suggests that another major, unidentified, GABAergic cell class must also be modulated by μORs. Here we report that the abundant, dendritically targeting, neurogliaform family of cells (Ivy and neurogliaform cells) is a previously unrecognized target of direct modulation by μORs. Ivy and neurogliaform cells are not only numerous, but also have unique properties, including promiscuous gap junctions formed with various interneuronal subtypes, volume transmission, and the ability to produce a postsynaptic GABAB response after a single presynaptic spike. Using a mouse line expressing green fluorescent protein under the neuropeptide Y promoter, we find that across all layers of CA1, activation of μORs hyperpolarizes Ivy and neurogliaform cells. Further, paired recordings between synaptically coupled Ivy and pyramidal cells show that Ivy cell terminals are dramatically inhibited by μOR-activation. Effects in Ivy and neurogliaform cells are seen at similar concentrations of agonist as those producing inhibition in fast-spiking PV basket cells. We also report that Ivy cells display the recently described phenomenon of persistent firing, a state of continued firing in the absence of continued input, and that induction of persistent firing is inhibited by μOR-activation. Together these findings identify a major, previously unrecognized, target of μOR-modulation. Given the prominence of this cell type in and beyond CA1, as well as its unique role in microcircuitry, opioid modulation of neurogliaform cells has wide implications. PMID:22016519

Ivy and neurogliaform interneurons are a major target of μ-opioid receptor modulation.

PubMed

Krook-Magnuson, Esther; Luu, Lillian; Lee, Sang-Hun; Varga, Csaba; Soltesz, Ivan

2011-10-19

μ-Opioid receptors (μORs) are selectively expressed on interneurons in area CA1 of the hippocampus. Fast-spiking, parvalbumin-expressing, basket cells express μORs, but circumstantial evidence suggests that another major, unidentified, GABAergic cell class must also be modulated by μORs. Here we report that the abundant, dendritically targeting, neurogliaform family of cells (Ivy and neurogliaform cells) is a previously unrecognized target of direct modulation by μORs. Ivy and neurogliaform cells are not only numerous but also have unique properties, including promiscuous gap junctions formed with various interneuronal subtypes, volume transmission, and the ability to produce a postsynaptic GABA(B) response after a single presynaptic spike. Using a mouse line expressing green fluorescent protein under the neuropeptide Y promoter, we find that, across all layers of CA1, activation of μORs hyperpolarizes Ivy and neurogliaform cells. Furthermore, paired recordings between synaptically coupled Ivy and pyramidal cells show that Ivy cell terminals are dramatically inhibited by μOR activation. Effects in Ivy and neurogliaform cells are seen at similar concentrations of agonist as those producing inhibition in fast-spiking parvalbumin basket cells. We also report that Ivy cells display the recently described phenomenon of persistent firing, a state of continued firing in the absence of continued input, and that induction of persistent firing is inhibited by μOR activation. Together, these findings identify a major, previously unrecognized, target of μOR modulation. Given the prominence of this cell type in and beyond CA1, as well as its unique role in microcircuitry, opioid modulation of neurogliaform cells has wide implications.

Therapeutic Targeting the Diverse Immunologic Functions Expressed by Hepatic NKT cells

PubMed Central

Duwaerts, Caroline C.; Gregory, Stephen H.

2011-01-01

Introduction NKT cells comprise approximately 30% of the hepatic lymphoid population in mice (~50% in humans). Most mouse hepatic NKT cells [invariant (i)NKT cells] express T cell receptors, composed of invariant Vα14Jα18 chains. Unlike conventional T cells, iNKT cells recognize glycolipid molecules presented in association with MHC class Ib (CD1d) molecules. Purportedly, iNKT cells serve a key function in a wide range of immunological events; the precise nature of this function is often unclear. Indeed, the consequences of hepatic iNKT cell activation can be beneficial or detrimental. α-Galactosylceramide, the prototypic glycolipid recognized by the iNKT cell receptor, stimulates the rapid production of both interferon-γ and interleukin-4. The reciprocal suppression exhibited by these cytokines limits the potential therapeutic value of α-galactosylceramide. An extensive research effort is ongoing to develop α-galactosylceramide analogs that modulate iNKT cell activity and selectively promote interferon-γ or interleukin-4. Areas covered This review provides a broad overview of hepatic iNKT cells and their purported role in liver disease. Efforts to develop therapeutic agents that promote their beneficial contributions are detailed. Expert Opinion While a growing body of literature documents the differential effects of α-GalCer analogs on IFN-γ and IL-4 production, the effects of these analogs on other iNKT cell activities, e.g., cytolysis and the production of other cytokines, remain to be determined. Similarly, an exhaustive examination of the effects of these analogs on inflammation and liver injury in animal models remains prior to considering their utility in clinical trials. PMID:21564001

The Basic Helix-Loop-Helix Transcription Factor MYC2 Directly Represses PLETHORA Expression during Jasmonate-Mediated Modulation of the Root Stem Cell Niche in Arabidopsis[W][OA

PubMed Central

Chen, Qian; Sun, Jiaqiang; Zhai, Qingzhe; Zhou, Wenkun; Qi, Linlin; Xu, Li; Wang, Bao; Chen, Rong; Jiang, Hongling; Qi, Jing; Li, Xugang; Palme, Klaus; Li, Chuanyou

2011-01-01

The root stem cell niche, which in the Arabidopsis thaliana root meristem is an area of four mitotically inactive quiescent cells (QCs) and the surrounding mitotically active stem cells, is critical for root development and growth. We report here that during jasmonate-induced inhibition of primary root growth, jasmonate reduces root meristem activity and leads to irregular QC division and columella stem cell differentiation. Consistently, jasmonate reduces the expression levels of the AP2-domain transcription factors PLETHORA1 (PLT1) and PLT2, which form a developmentally instructive protein gradient and mediate auxin-induced regulation of stem cell niche maintenance. Not surprisingly, the effects of jasmonate on root stem cell niche maintenance and PLT expression require the functioning of MYC2/JASMONATE INSENSITIVE1, a basic helix-loop-helix transcription factor that involves versatile aspects of jasmonate-regulated gene expression. Gel shift and chromatin immunoprecipitation experiments reveal that MYC2 directly binds the promoters of PLT1 and PLT2 and represses their expression. We propose that MYC2-mediated repression of PLT expression integrates jasmonate action into the auxin pathway in regulating root meristem activity and stem cell niche maintenance. This study illustrates a molecular framework for jasmonate-induced inhibition of root growth through interaction with the growth regulator auxin. PMID:21954460

Human FGF1 promoter is active in ependymal cells and dopaminergic neurons in the brains of F1B-GFP transgenic mice.

PubMed

Chen, Mei-Shu; Lin, Hua-Kuo; Chiu, Hsun; Lee, Don-Ching; Chung, Yu-Fen; Chiu, Ing-Ming

2015-03-01

FGF1 is involved in multiple biological functions and exhibits the importance in neuroprotective effects. Our previous studies indicated that, in human brain and retina, the FGF1B promoter controlled the expression of FGF1. However, the exact function and regulation of FGF1 in brain is still unclear. Here, we generated F1B-GFP transgenic mice that expressed the GFP reporter gene under the control of human FGF1B promoter (-540 to +31). Using the fresh brain sections of F1B-GFP transgenic mice, we found that the F1B-GFP cells expressed strong fluorescent signals in the ventricular system throughout the brain. The results of immunohistochemistry further showed that two distinct populations of F1B-GFP(+) cells existed in the brains of F1B-GFP transgenic mice. We demonstrated that one population of F1B-GFP(+) cells was ependymal cells, which distributed along the entire ventricles, and the second population of F1B-GFP(+) cells was neuronal cells that projected their long processes into multiple directions in specific areas of the brain. The double labeling of F1B-GFP(+) cells and tyrosine hydroxylase indicated that a subpopulation of F1B-GFP(+) -neuronal cells was dopaminergic neurons. Importantly, these F1B-GFP(+) /TH(+) cells were distributed in the main dopaminergic neuronal groups including hypothalamus, ventral tegmental area, and raphe nuclei. These results suggested that human FGF1B promoter was active in ependymal cells, neurons, and a portion of dopaminergic neurons. Thus, the F1B-GFP transgenic mice provide an animal model not only for studying FGF1 gene expression in vivo but also for understanding the role of FGF1 contribution in neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. © 2014 The Authors Developmental Neurobiology Published by Wiley Periodicals, Inc.

An Automated Method to Monitor Cell Migration.

NASA Astrophysics Data System (ADS)

Giaever, Ivar; Keese, Charles R.

2002-03-01

Electric cell-substrate impedance sensing (ECIS) has been developed as a non-invasive means to follow cell behavior in culture. In this method cells are cultured on small (250 micrometer diameter) gold film electrodes. The impedance of the electrode is measured by an AC current about 1 microampere. When challenged by biochemical or physical stimuli the cells will respond by changing their morphology and motion. These changes are reflected in the measured impedance values. In this study, the basic ECIS system was used in both a non-invasive and invasive mode to carry out an automated wound-healing assay for quantifying cell migration activity. BSC-1, MDCK, and NRK cell lines were grown to confluence in ECIS wells before data was collected. An AC current of approximately 1 milliampere at 40,000 Hz was applied for several seconds, killing the cells in contact with the ECIS electrode and dropping the impedance to that of a cell-free electrode. For the next few hours following this incursion, the neighboring cells migrate into the wounded area replacing the dead cells, and the electrodes return to impedance values of unwounded controls. Data shows that the time required for the completion of this activity is strongly dependent upon cell type, medium composition, and the type of protein adsorbed to the substrate.

Carbon nanotubes might improve neuronal performance by favouring electrical shortcuts.

PubMed

Cellot, Giada; Cilia, Emanuele; Cipollone, Sara; Rancic, Vladimir; Sucapane, Antonella; Giordani, Silvia; Gambazzi, Luca; Markram, Henry; Grandolfo, Micaela; Scaini, Denis; Gelain, Fabrizio; Casalis, Loredana; Prato, Maurizio; Giugliano, Michele; Ballerini, Laura

2009-02-01

Carbon nanotubes have been applied in several areas of nerve tissue engineering to probe and augment cell behaviour, to label and track subcellular components, and to study the growth and organization of neural networks. Recent reports show that nanotubes can sustain and promote neuronal electrical activity in networks of cultured cells, but the ways in which they affect cellular function are still poorly understood. Here, we show, using single-cell electrophysiology techniques, electron microscopy analysis and theoretical modelling, that nanotubes improve the responsiveness of neurons by forming tight contacts with the cell membranes that might favour electrical shortcuts between the proximal and distal compartments of the neuron. We propose the 'electrotonic hypothesis' to explain the physical interactions between the cell and nanotube, and the mechanisms of how carbon nanotubes might affect the collective electrical activity of cultured neuronal networks. These considerations offer a perspective that would allow us to predict or engineer interactions between neurons and carbon nanotubes.

Enhancing the Efficiency of Bulk Heterojunction Solar Cells via Templated Self Assembly

NASA Astrophysics Data System (ADS)

Pan, Cheng; Li, Hongfei; Akgun, Bulent; Satijia, Sushil; Gersappe, Dilip; Zhu, Yimei; Rafailovich, Miriam

2013-03-01

Bulk Heterojunction (BHJ) polymer solar cells are an area of intense interest due to their flexibility and relatively low cost. The mixture of polythiophene derivatives (donor) and fullerenes (acceptor) is spin coated on substrate as the active layer, and are phase-separated into interconnected domains. However, due to the disordered inner structures in the active layer, donor or acceptor domains isolated from electrodes and long path conduction, the power conversion efficiency (PCE) of BHJ solar cell is low. Therefore, morphology control in bulk heterojunction (BHJ) solar cell is considered to be critical for the power conversion efficiency (PCE). Here, we present a novel approach that introduces non-photoactive polymer that organizes the poly(3-hexylthiophene) (P3HT) into columnar phases decorated by [6,6]-phenyl C61-butyric acid methyl ester (PCBM) at the interface. This structure represents a realization of an idealized morphology of an organic solar cell, in which, both exiciton dissociation and the carrier transport are optimized leading to increased power conversion efficiency.

Development of an ultra-safe rechargeable lithium-ion battery

NASA Astrophysics Data System (ADS)

Jacobs, J. K.

1994-11-01

The project activities had an official start on August 15. Based on previous work, a statement of the basic design framework to be used was an important first step. The basic cell is to be a bonded flat-pack containing all active cell components in a sealed envelope. Cell integrity is to be provided by internal bonding, and not through external support. This design approach is fundamentally different from that commonly used in wound and hard-case cells, and has the advantage of ease of scaling for a variety of different form factors. An innovative variant on the fan-fold geometry has been chosen for its manufacturability advantages. Equipment capable of handling the semi-continuous requirements of the fan-fold structure had already been outlined. There are specific advantages in at least three areas: (1) Control of dimensional tolerances; (2) Production rate; (3) Connection of power lead-outs and final assembly. Cell chemistry is viewed to be of less fundamental importance than structural considerations within the bounds of the lithium-ion concept.

Identification and super-resolution imaging of ligand-activated receptor dimers in live cells

NASA Astrophysics Data System (ADS)

Winckler, Pascale; Lartigue, Lydia; Giannone, Gregory; de Giorgi, Francesca; Ichas, François; Sibarita, Jean-Baptiste; Lounis, Brahim; Cognet, Laurent

2013-08-01

Molecular interactions are key to many chemical and biological processes like protein function. In many signaling processes they occur in sub-cellular areas displaying nanoscale organizations and involving molecular assemblies. The nanometric dimensions and the dynamic nature of the interactions make their investigations complex in live cells. While super-resolution fluorescence microscopies offer live-cell molecular imaging with sub-wavelength resolutions, they lack specificity for distinguishing interacting molecule populations. Here we combine super-resolution microscopy and single-molecule Förster Resonance Energy Transfer (FRET) to identify dimers of receptors induced by ligand binding and provide super-resolved images of their membrane distribution in live cells. By developing a two-color universal-Point-Accumulation-In-the-Nanoscale-Topography (uPAINT) method, dimers of epidermal growth factor receptors (EGFR) activated by EGF are studied at ultra-high densities, revealing preferential cell-edge sub-localization. This methodology which is specifically devoted to the study of molecules in interaction, may find other applications in biological systems where understanding of molecular organization is crucial.

In-situ short circuit protection system and method for high-energy electrochemical cells

DOEpatents

Gauthier, Michel; Domroese, Michael K.; Hoffman, Joseph A.; Lindeman, David D.; Noel, Joseph-Robert-Gaetan; Radewald, Vern E.; Rouillard, Jean; Rouillard, Roger; Shiota, Toshimi; Trice, Jennifer L.

2000-01-01

An in-situ thermal management system for an energy storage device. The energy storage device includes a plurality of energy storage cells each being coupled in parallel to common positive and negative connections. Each of the energy storage cells, in accordance with the cell's technology, dimensions, and thermal/electrical properties, is configured to have a ratio of energy content-to-contact surface area such that thermal energy produced by a short-circuit in a particular cell is conducted to a cell adjacent the particular cell so as to prevent the temperature of the particular cell from exceeding a breakdown temperature. In one embodiment, a fuse is coupled in series with each of a number of energy storage cells. The fuses are activated by a current spike capacitively produced by a cell upon occurrence of a short-circuit in the cell, thereby electrically isolating the short-circuited cell from the common positive and negative connections.

In-situ short-circuit protection system and method for high-energy electrochemical cells

DOEpatents

Gauthier, Michel; Domroese, Michael K.; Hoffman, Joseph A.; Lindeman, David D.; Noel, Joseph-Robert-Gaetan; Radewald, Vern E.; Rouillard, Jean; Rouillard, Roger; Shiota, Toshimi; Trice, Jennifer L.

2003-04-15

An in-situ thermal management system for an energy storage device. The energy storage device includes a plurality of energy storage cells each being coupled in parallel to common positive and negative connections. Each of the energy storage cells, in accordance with the cell's technology, dimensions, and thermal/electrical properties, is configured to have a ratio of energy content-to-contact surface area such that thermal energy produced by a short-circuit in a particular cell is conducted to a cell adjacent the particular cell so as to prevent the temperature of the particular cell from exceeding a breakdown temperature. In one embodiment, a fuse is coupled in series with each of a number of energy storage cells. The fuses are activated by a current spike capacitively produced by a cell upon occurrence of a short-circuit in the cell, thereby electrically isolating the short-circuited cell from the common positive and negative connections.

Hypoxic inactivation of glycogen synthase kinase-3β promotes gastric tumor growth and angiogenesis by facilitating hypoxia-inducible factor-1 signaling.

PubMed

Ko, Young San; Cho, Sung Jin; Park, Jinju; Choi, Yiseul; Lee, Jae-Seon; Youn, Hong-Duk; Kim, Woo Ho; Kim, Min A; Park, Jong-Wan; Lee, Byung Lan

2016-09-01

Since the molecular mechanism of hypoxic adaptation in cancer cells is cell-type specific, we investigated whether glycogen synthase kinase-3β (GSK-3β) activation is involved in hypoxia-induced gastric tumor promotion. Stable gastric cancer cell lines (SNU-638, SNU-484, MKN1, and MKN45) were cultured under hypoxic conditions. Cells overexpressing wild-type GSK-3β (WT-GSK-3β) or kinase-dead mutant of GSK-3β (KD-GSK-3β) were generated and used for cell culture and animal studies. In cell culture experiments, hypoxia decreased GSK-3β activation in gastric cancer cells. Cell viability and the expressions of HIF-1α protein and VEGF mRNA in gastric cancer cells were higher in KD-GSK-3β transfectants than in WT-GSK-3β transfectants under hypoxic conditions, but not under normoxic conditions. Gastric cancer xenografts showed that tumor growth, microvessel area, HIF-1α activation, and VEGF expression were higher in KD-GSK-3β tumors than in WT-GSK-3β tumors in vivo. In addition, the expression of hypoxia-induced HIF-1α protein was regulated by GSK-3β at the translational level. Our data suggest that GSK-3β is involved in hypoxic adaptation of gastric cancer cells as an inhibitory upstream regulator of the HIF-1α/VEGF signaling pathway. © 2016 APMIS. Published by John Wiley & Sons Ltd.

High matrix metalloproteinase activity is a hallmark of periapical granulomas.

PubMed

de Paula-Silva, Francisco Wanderley Garcia; D'Silva, Nisha J; da Silva, Léa Assed Bezerra; Kapila, Yvonne Lorraine

2009-09-01

The inability to distinguish periapical cysts from granulomas before performing root canal treatment leads to uncertainty in treatment outcomes because cysts have lower healing rates. Searching for differential expression of molecules within cysts or granulomas could provide information with regard to the identity of the lesion or suggest mechanistic differences that may form the basis for future therapeutic intervention. Thus, we investigated whether granulomas and cysts exhibit differential expression of extracellular matrix (ECM) molecules. Human periapical granulomas, periapical cysts, and healthy periodontal ligament tissues were used to investigate the differential expression of ECM molecules by microarray analysis. Because matrix metalloproteinases (MMP) showed the highest differential expression in the microarray analysis, MMPs were further examined by in situ zymography and immunohistochemistry. Data were analyzed by using one-way analysis of variance followed by the Tukey test. We observed that cysts and granulomas differentially expressed several ECM molecules, especially those from the MMP family. Compared with cysts, granulomas exhibited higher MMP enzymatic activity in areas stained for MMP-9. These areas were composed of polymorphonuclear cells (PMNs) in contrast to cysts. Similarly, MMP-13 was expressed by a greater number of cells in granulomas compared with cysts. Our findings indicate that high enzymatic MMP activity in PMNs together with MMP-9 and MMP-13 stained cells could be a molecular signature of granulomas unlike periapical cysts.

High Matrix Metalloproteinase Activity is a Hallmark of Periapical Granulomas

PubMed Central

de Paula e Silva, Francisco Wanderley Garcia; D'Silva, Nisha J.; da Silva, Léa Assed Bezerra; Kapila, Yvonne Lorraine

2009-01-01

Introduction Inability to distinguish periapical cysts from granulomas prior to performing root canal treatment leads to uncertainty in treatment outcomes, because cysts have lower healing rates. Searching for differential expression of molecules within cysts or granulomas could provide information with regard to the identity of the lesion or suggest mechanistic differences that may form the basis for future therapeutic intervention. Thus, we investigated whether granulomas and cysts exhibit differential expression of extracellular matrix (ECM) molecules. Methods Human periapical granulomas, periapical cysts, and healthy periodontal ligament tissues were used to investigate the differential expression of ECM molecules by microarray analysis. Since matrix metalloproteinases (MMP) showed the highest differential expression in the microarray analysis, MMPs were further examined by in situ zymography and immunohistochemistry. Data were analyzed using one-way ANOVA followed by Tukey test. Results We observed that cysts and granulomas differentially expressed several ECM molecules, especially those from the matrix metalloproteinase (MMP) family. Compared to cysts, granulomas exhibited higher MMP enzymatic activity in areas stained for MMP-9. These areas were composed of polymorphonuclear cells (PMNs), in contrast to cysts. Similarly, MMP-13 was expressed by a greater number of cells in granulomas compared to cysts. Conclusion Our findings indicate that high enzymatic MMP activity in PMNs together with MMP-9 and MMP-13 stained cells could be a molecular signature of granulomas, unlike periapical cysts. PMID:19720222

Beta-Galactosidase Staining in the Nucleus of the Solitary Tract of Fos-Tau-LacZ Mice Is Unaffected by Monosodium Glutamate Taste Stimulation

PubMed Central

Stratford, Jennifer M.; Thompson, John A.

2014-01-01

Fos-Tau-LacZ (FTL) transgenic mice are used to visualize the anatomical connectivity of neurons that express c-Fos, an immediate early gene, in response to activation. In contrast to typical c-Fos protein expression, which is localized to the nucleus of stimulated neurons, activation of the c-Fos gene results in beta galactosidase (β-gal) expression throughout the entire cytoplasm of activated cells in FTL mice; thereby making it possible to discern the morphology of c-Fos expressing cells. This can be an especially important tool in brain areas in which function may be related to cell morphology, such as the primary taste/viscerosensory brainstem nucleus of the solitary tract (nTS). Thus, to further characterize FTL activity in the brain, the current study quantified both β-gal enzymatic activity as well as c-Fos protein expression in the nTS under a variety of experimental conditions (no stimulation, no stimulation with prior overnight food and water restriction, monosodium glutamate taste stimulation, and monosodium glutamate taste stimulation with perfusion 5 h post stimulation). Contrary to previous research, we found that β-gal activity (both labeled cell bodies and overall number of labeled pixels) was unchanged across all experimental conditions. However, traditional c-Fos protein activity (both cell bodies and number of activated pixels) varied significantly across experimental conditions, with the greatest amount of c-Fos protein label found in the group that received monosodium glutamate taste stimulation. Interestingly, although many c-Fos positive cells were also β-gal positive in the taste stimulated group, some c-Fos protein labeled cells were not co-labeled with β-gal. Together, these data suggest that β-gal staining within the nTS reflects a stable population of β-gal- positive neurons whose pattern of expression is unaffected by experimental condition. PMID:25192442

Renewable sustainable biocatalyzed electricity production in a photosynthetic algal microbial fuel cell (PAMFC).

PubMed

Strik, David P B T B; Terlouw, Hilde; Hamelers, Hubertus V M; Buisman, Cees J N

2008-12-01

Electricity production via solar energy capturing by living higher plants and microalgae in combination with microbial fuel cells are attractive because these systems promise to generate useful energy in a renewable, sustainable, and efficient manner. This study describes the proof of principle of a photosynthetic algal microbial fuel cell (PAMFC) based on naturally selected algae and electrochemically active microorganisms in an open system and without addition of instable or toxic mediators. The developed solar-powered PAMFC produced continuously over 100 days renewable biocatalyzed electricity. The sustainable performance of the PAMFC resulted in a maximum current density of 539 mA/m2 projected anode surface area and a maximum power production of 110 mW/m2 surface area photobioreactor. The energy recovery of the PAMFC can be increased by optimization of the photobioreactor, by reducing the competition from non-electrochemically active microorganisms, by increasing the electrode surface and establishment of a further-enriched biofilm. Since the objective is to produce net renewable energy with algae, future research should also focus on the development of low energy input PAMFCs. This is because current algae production systems have energy inputs similar to the energy present in the outcoming valuable products.

Facilitation of the arterial baroreflex by the preoptic area in anaesthetized rats.

PubMed Central

Inui, K; Nomura, J; Murase, S; Nosaka, S

1995-01-01

1. Activation of cell bodies in the ventrolateral part of the midbrain periaqueductal grey matter (PAG) facilitates the arterial baroreflex via the nucleus raphe magnus. The facilitatory effects of stimulation within the hypothalamus on the arterial baroreflex and their relation to the PAG and nucleus raphe magnus were studied in urethane- and chloralose-anaesthetized rats. 2. Systematic mapping experiments revealed that the preoptic area (POA) is the principal location in the hypothalamus of neuronal cell bodies that are responsible for the potentiation of the baroreflex. In addition to provoking hypotension and vagal bradycardia, both electrical and chemical stimulation of the POA produced facilitation of baroreflex vagal bradycardia (BVB) that was evoked by electrical stimulation of the aortic depressor nerve. Baroreflex hypotension was slightly augmented during activation of the POA in vagotomized rats. 3. Selective destruction of cell bodies either in the ventrolateral PAG or in the nucleus raphe magnus reduced facilitation of BVB by the POA. Hypotension and bradycardia due to POA stimulation were also markedly attenuated after such selective destruction. 4. In conclusion, the POA, the ventrolateral PAG and the nucleus raphe magnus constitute a functional complex that produces cardiovascular trophotropic effects including hypotension, vagal bradycardia and baroreflex facilitation. PMID:8568691

Different skeletal effects of the peroxisome proliferator activated receptor (PPAR)α agonist fenofibrate and the PPARγ agonist pioglitazone

PubMed Central

Syversen, Unni; Stunes, Astrid K; Gustafsson, Björn I; Obrant, Karl J; Nordsletten, Lars; Berge, Rolf; Thommesen, Liv; Reseland, Janne E

2009-01-01

Background All the peroxisome proliferator activated receptors (PPARs) are found to be expressed in bone cells. The PPARγ agonist rosiglitazone has been shown to decrease bone mass in mice and thiazolidinediones (TZDs) have recently been found to increase bone loss and fracture risk in humans treated for type 2 diabetes mellitus. The aim of the study was to examine the effect of the PPARα agonist fenofibrate (FENO) and the PPARγ agonist pioglitazone (PIO) on bone in intact female rats. Methods Rats were given methylcellulose (vehicle), fenofibrate or pioglitazone (35 mg/kg body weight/day) by gavage for 4 months. BMC, BMD, and body composition were measured by DXA. Histomorphometry and biomechanical testing of excised femurs were performed. Effects of the compounds on bone cells were studied. Results The FENO group had higher femoral BMD and smaller medullary area at the distal femur; while trabecular bone volume was similar to controls. Whole body BMD, BMC, and trabecular bone volume were lower, while medullary area was increased in PIO rats compared to controls. Ultimate bending moment and energy absorption of the femoral shafts were reduced in the PIO group, while similar to controls in the FENO group. Plasma osteocalcin was higher in the FENO group than in the other groups. FENO stimulated proliferation and differentiation of, and OPG release from, the preosteoblast cell line MC3T3-E1. Conclusion We show opposite skeletal effects of PPARα and γ agonists in intact female rats. FENO resulted in significantly higher femoral BMD and lower medullary area, while PIO induced bone loss and impairment of the mechanical strength. This represents a novel effect of PPARα activation. PMID:19331671

BOLD delay times using group delay in sickle cell disease

NASA Astrophysics Data System (ADS)

Coloigner, Julie; Vu, Chau; Bush, Adam; Borzage, Matt; Rajagopalan, Vidya; Lepore, Natasha; Wood, John

2016-03-01

Sickle cell disease (SCD) is an inherited blood disorder that effects red blood cells, which can lead to vasoocclusion, ischemia and infarct. This disease often results in neurological damage and strokes, leading to morbidity and mortality. Functional Magnetic Resonance Imaging (fMRI) is a non-invasive technique for measuring and mapping the brain activity. Blood Oxygenation Level-Dependent (BOLD) signals contain also information about the neurovascular coupling, vascular reactivity, oxygenation and blood propagation. Temporal relationship between BOLD fluctuations in different parts of the brain provides also a mean to investigate the blood delay information. We used the induced desaturation as a label to profile transit times through different brain areas, reflecting oxygen utilization of tissue. In this study, we aimed to compare blood flow propagation delay times between these patients and healthy subjects in areas vascularized by anterior, middle and posterior cerebral arteries. In a group comparison analysis with control subjects, BOLD changes in these areas were found to be almost simultaneous and shorter in the SCD patients, because of their increased brain blood flow. Secondly, the analysis of a patient with a stenosis on the anterior cerebral artery indicated that signal of the area vascularized by this artery lagged the MCA signal. These findings suggest that sickle cell disease causes blood propagation modifications, and that these changes could be used as a biomarker of vascular damage.

Effects of vegetation management in constructed wetland treatment cells on water quality and mosquito production

USGS Publications Warehouse

Thullen, J.S.; Sartoris, J.J.; Nelson, S.M.

2002-01-01

The impact of three vegetation management strategies on wetland treatment function and mosquito production was assessed in eight free water surface wetland test cells in southern California during 1998–1999. The effectiveness of the strategies to limit bulrush Schoenoplectus californicus culm density within the cells was also investigated. Removing accumulated emergent biomass and physically limiting the area in which vegetation could reestablish, significantly improved the ammonia–nitrogen removal efficiency of the wetland cells, which received an ammonia-dominated municipal wastewater effluent (average loading rate=9.88 kg/ha per day NH4-N). We determined that interspersing open water with emergent vegetation is critical for maintaining the wetland's treatment capability, particularly for systems high in NH4-N. Burning aboveground plant parts and thinning rhizomes only temporarily curtailed vegetation proliferation in shallow zones, whereas creating hummocks surrounded by deeper water successfully restricted the emergent vegetation to the shallower hummock areas. Since the hummock configuration kept open water areas interspersed throughout the stands of emergent vegetation, the strategy was also effective in reducing mosquito production. Decreasing vegetation biomass reduced mosquito refuge areas while increasing mosquito predator habitat. Therefore, the combined goals of water quality improvement and mosquito management were achieved by managing the spatial pattern of emergent vegetation to mimic an early successional growth stage, i.e. actively growing plants interspersed with open water.

Effects of vegetation management in constructed wetland treatment cells on water quality and mosquito production

USGS Publications Warehouse

Thullen, J.S.; Sartoris, J.J.; Walton, W.E.

2002-01-01

The impact of three vegetation management strategies on wetland treatment function and mosquito production was assessed in eight free water surface wetland test cells in southern California during 1998-1999. The effectiveness of the strategies to limit bulrush Schoenoplectus californicus culm density within the cells was also investigated. Removing accumulated emergent biomass and physically limiting the area in which vegetation could reestablish, significantly improved the ammonia - nitrogen removal efficiency of the wetland cells, which received an ammonia-dominated municipal wastewater effluent (average loading rate = 9.88 kg/ha per day NH4-N). We determined that interspersing open water with emergent vegetation is critical for maintaining the wetland's treatment capability, particularly for systems high in NH4-N. Burning aboveground plant parts and thinning rhizomes only temporarily curtailed vegetation proliferation in shallow zones, whereas creating hummocks surrounded by deeper water successfully restricted the emergent vegetation to the shallower hummock areas. Since the hummock configuration kept open water areas interspersed throughout the stands of emergent vegetation, the strategy was also effective in reducing mosquito production. Decreasing vegetation biomass reduced mosquito refuge areas while increasing mosquito predator habitat. Therefore, the combined goals of water quality improvement and mosquito management were achieved by managing the spatial pattern of emergent vegetation to mimic an early successional growth stage, i.e. actively growing plants interspersed with open water. ?? 2002 Elsevier Science B.V. All rights reserved.

An Examination of State and Local Fusion Centers and Data Collection Methods

DTIC Science & Technology

2008-03-01

problems that are active in their area so their skills will remain sharp. He offered prison gangs a one potential area of investigation. Many ... Many documents are prepared and released at the Law Enforcement Sensitive level (LES) while others are prepared and released at the For Official Use ...jihadist terrorists were the result of a domestic cell . These threats come in many forms, such as radicalized prisoners, homegrown jihadists

Mechanisms of Immune Evasion in Leishmaniasis

PubMed Central

Gupta, Gaurav; Oghumu, Steve; Satoskar, Abhay R.

2013-01-01

Diseases caused by Leishmania present a worldwide problem, and current therapeutic approaches are unable to achieve a sterile cure. Leishmania is able to persist in host cells by evading or exploiting host immune mechanisms. A thorough understanding of these mechanisms could lead to better strategies for effective management of Leishmania infections. Current research has focused on parasite modification of host cell signaling pathways, entry into phagocytic cells, and modulation of cytokine and chemokine profiles that alter immune cell activation and trafficking to sites of infection. Immuno-therapeutic approaches that target these mechanisms of immune evasion by Leishmania offer promising areas for preclinical and clinical research. PMID:23415155

Chimeric antigen receptor for adoptive immunotherapy of cancer: latest research and future prospects.

PubMed

Shi, Huan; Sun, Meili; Liu, Lin; Wang, Zhehai

2014-09-21

Chimeric antigen receptors (CARs) are recombinant receptors that combine the specificity of an antigen-specific antibody with the T-cell's activating functions. Initial clinical trials of genetically engineered CAR T cells have significantly raised the profile of T cell therapy, and great efforts have been made to improve this approach. In this review, we provide a structural overview of the development of CAR technology and highlight areas that require further refinement. We also discuss critical issues related to CAR therapy, including the optimization of CAR T cells, the route of administration, CAR toxicity and the blocking of inhibitory molecules.

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.

Non-genomic oestrogen receptor signal in B lymphocytes: An approach towards therapeutic interventions for infection, autoimmunity and cancer.

PubMed

Seto, Karsen; Hoang, Minh; Santos, Thaddeus; Bandyopadhyay, Mausumi; Kindy, Mark S; Dasgupta, Subhajit

2016-07-01

The non-genomic membrane bound oestrogen receptor (mER) regulates intracellular signals through receptor-ligand interactions. The mER, along with G-protein coupled oestrogen receptor GPR 30 (GPER), induces diverse cell signalling pathways in murine lymphocytes. The mER isoform ER-alpha46 has recently been demonstrated in human B and T lymphocytes as an analogue receptor for chemokine CCL18, the signalling events of which are not clearly understood. Ligand-induced mER and GPER signalling events are shared with BCR, CD19 mediated intracellular signalling through phospholipase C, PIP2/IP3/PI3 mediated activation of Akt, MAP kinase, and mTOR. Oestrogen has the ability to induce CD40-mediated activation of B cells. The complete signalling pathways of mER, GPR30 and their interaction with other signals are targeted areas for novel drug development in B cells during infection, autoimmunity and cancer. Therefore, an in depth investigation is critical for determining shared signal outputs during B cell activation. Here, we focus on the mode of action of membrane bound ER in B cells as therapeutic checkpoints. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Induction Effect of Am80 and TSA on ESC Differentiation via Regulation of Stra8 in Chicken.

PubMed

Zhang, Yani; Zuo, Qisheng; Liu, Zhiyong; Li, Dong; Tang, Beibei; Xiao, Tian-Rong; Lian, Chao; Wang, Yingjie; Jin, Kai; Wang, Yilin; Zhang, Wenhui; Li, Bichun

2015-01-01

Stra8 encodes stimulated by retinoic acid gene 8, a protein that is important for initiation of meiosis in mammals and birds. This study was aimed at identifying the active control area of chicken STRA8 gene core promoter, to screen optimum inducers of the STRA8 gene, thus to enhance the differentiation of embryonic stem cells (ESCs) into spermatogonial stem cells. Fragments of chicken STRA8 gene promoter were cloned into fluorescent reporter plasmids and transfected into DF-1 cells. Then Dual-Luciferase® Reporter Assay System was used to identify the activity of the STRA8 gene under different inducers. Our studies showed that the promoter fragment -1055 bp to +54 bp of Suqin chicken Stra8 revealed the strongest activity. The dual-luciferase® reporter showed that Tamibarotene (Am80) and TrichostatinA (TSA) could significantly enhance STRA8 transcription. The in vitro inductive culture of chicken ESCs demonstrated that spermatogonial stem cells (SSC)-like cells appeared and Integrinβ1 protein was expressed on day 10, indicating that Am80 and TSA can promote ESCs differentiation into SSCs via regulation of Stra8.

The Induction Effect of Am80 and TSA on ESC Differentiation via Regulation of Stra8 in Chicken

PubMed Central

Zhang, Yani; Zuo, Qisheng; Liu, Zhiyong; Li, Dong; Tang, Beibei; Xiao, Tian-rong; Lian, Chao; Wang, Yingjie; Jin, Kai; Wang, Yilin; Zhang, Wenhui; Li, Bichun

2015-01-01

Stra8 encodes stimulated by retinoic acid gene 8, a protein that is important for initiation of meiosis in mammals and birds. This study was aimed at identifying the active control area of chicken STRA8 gene core promoter, to screen optimum inducers of the STRA8 gene, thus to enhance the differentiation of embryonic stem cells (ESCs) into spermatogonial stem cells. Fragments of chicken STRA8 gene promoter were cloned into fluorescent reporter plasmids and transfected into DF-1 cells. Then Dual-Luciferase® Reporter Assay System was used to identify the activity of the STRA8 gene under different inducers. Our studies showed that the promoter fragment −1055 bp to +54 bp of Suqin chicken Stra8 revealed the strongest activity. The dual-luciferase® reporter showed that Tamibarotene (Am80) and TrichostatinA (TSA) could significantly enhance STRA8 transcription. The in vitro inductive culture of chicken ESCs demonstrated that spermatogonial stem cells (SSC)-like cells appeared and Integrinβ1 protein was expressed on day 10, indicating that Am80 and TSA can promote ESCs differentiation into SSCs via regulation of Stra8. PMID:26606052

[Experimental interaction of halophilic prokaryotes and opportunistic bacteria in brine].

PubMed

Selivanova, E A; Nemtseva, N V

2013-01-01

Study the effect of extremely halophilic archaea and moderately halophilic bacteria on preservation of opportunistic bacteria in brine. 17 strains of moderately halophilic bacteria and 2 strains of extremely halophilic archaea were isolated from continental hypersaline lake Razval of Sol-Iletsk area of Orenburg Region. Identification of pure cultures of prokaryotes was carried out taking into account their phenotype properties and based on determination of 16S RNA gene sequence. The effect of halophilic prokaryote on elimination of Escherichia coli from brine was evaluated during co-cultivation. Antagonistic activity of cell extracts of the studied microorganisms was evaluated by photometric method. A more prolonged preservation of an E. coli strain in brine in the presence of live cells of extremely halophilic archaea Halorubrum tebenquichense and moderately halophilic bacteria Marinococcus halophilus was established. Extracts of cells of extremely halophilic archaea and moderately halophilic bacteria on the contrary displayed antagonistic activity. The protective effect of live cells of halophilic prokaryotes and antagonistic activity of their cell extracts change the period of conservation of opportunistic bacteria in brine that regulates inter-microbial interactions and changes the period of self-purification that reflects the sanitary condition of a hypersaline water body.

Reprogramming T-cells for adoptive immunotherapy of ovarian cancer.

PubMed

Genta, Sofia; Ghisoni, Eleonora; Giannone, Gaia; Mittica, Gloria; Valabrega, Giorgio

2018-04-01

Epithelial ovarian cancer (EOC) is the most common cause of death among gynecological malignancies. Despite surgical and pharmacological efforts to improve patients' outcome, persistent and recurrent EOC remains an un-eradicable disease. Chimeric associated antigens (CAR) T cells are T lymphocytes expressing an engineered T cell receptor that activate the immune response after an MHC unrestricted recognition of specific antigens, including tumor associated antigens (TAAs). CART cells have been shown to be effective in the treatment of hematologic tumors even if frequently associated with potentially severe toxicity and high production costs. Areas covered: In this review, we will focus on preclinical and clinical studies evaluating CART activity in EOC in order to identify possible difficulties and advantages of their use in this particular setting. Expert Opinion: The pattern of diffusion within the peritoneal cavity, the tumor microenvironment and the high rate of TAAs make EOC a particularly interesting model for CART cells use. Data from preclinical studies indicate a potential activity of CARTs in EOC, but robust clinical data are still awaited. Further studies are needed to determine the best methods of administration and the most effective CAR type to treat EOC patients.

Intracarotid injection of fluorescence activated cell-sorted CD49d-positive neural stem cells improves targeted cell delivery and behavior after stroke in a mouse stroke model.

PubMed

Guzman, Raphael; De Los Angeles, Alejandro; Cheshier, Samuel; Choi, Raymond; Hoang, Stanley; Liauw, Jason; Schaar, Bruce; Steinberg, Gary

2008-04-01

Intravascular delivery of neural stem cells (NSCs) after stroke has been limited by the low efficiency of transendothelial migration. Vascular cell adhesion molecule-1 is an endothelial adhesion molecule known to be upregulated early after stroke and is responsible for the firm adhesion of inflammatory cells expressing the surface integrin, CD49d. We hypothesize that enriching for NSCs that express CD49d and injecting them into the carotid artery would improve targeted cell delivery to the injured brain. Mouse NSCs were analyzed for the expression of CD49d by fluorescence activated cell sorting. A CD49d-enriched (CD49d(+)) (>95%) and -depleted (CD49d(-); <5%) NSC population was obtained by cell sorting. C57/Bl6 mice underwent left-sided hypoxia-ischemia surgery and were assigned to receive 3 x 10(5) CD49d(+), CD49d(-) NSCs, or vehicle injection into the left common carotid artery 48 hours after stroke. Behavioral recovery was measured using a rotarod for 2 weeks after cell injection. Fluorescence activated cell sorting analysis revealed 25% CD49d(+) NSCs. In a static adhesion assay, NSCs adhered to vascular cell adhesion molecule-1 in a dose-dependent manner. Significantly more NSCs were found in the cortex, the hippocampus, and the subventricular zone in the ischemic hemisphere in animals receiving CD49d(+) NSCs as compared with CD49d(-) NSCs (P<0.05). Animals treated with CD49d(+) cells showed a significantly better behavioral recovery as compared with CD49d(-) and vehicle-treated animals. We show that enrichment of NSCs by fluorescence activated cell sorting for the surface integrin, CD49d, and intracarotid delivery promotes cell homing to the area of stroke in mice and improves behavioral recovery.

CD24 can be used to isolate Lgr5+ putative colonic epithelial stem cells in mice

PubMed Central

King, Jeffrey B.; von Furstenberg, Richard J.; Smith, Brian J.; McNaughton, Kirk K.; Galanko, Joseph A.

2012-01-01

A growing body of evidence has implicated CD24, a cell-surface protein, as a marker of colorectal cancer stem cells and target for antitumor therapy, although its presence in normal colonic epithelium has not been fully characterized. Previously, our group showed that CD24-based cell sorting can be used to isolate a fraction of murine small intestinal epithelial cells enriched in actively cycling stem cells. Similarly, we hypothesized that CD24-based isolation of colonic epithelial cells would generate a fraction enriched in actively cycling colonic epithelial stem cells (CESCs). Immunohistochemistry performed on mouse colonic tissue showed CD24 expression in the bottom half of proximal colon crypts and the crypt base in the distal colon. This pattern of distribution was similar to enhanced green fluorescent protein (EGFP) expression in Lgr5-EGFP mice. Areas expressing CD24 contained actively proliferating cells as determined by ethynyl deoxyuridine (EdU) incorporation, with a distinct difference between the proximal colon, where EdU-labeled cells were most frequent in the midcrypt, and the distal colon, where they were primarily at the crypt base. Flow cytometric analyses of single epithelial cells, identified by epithelial cell adhesion molecule (EpCAM) positivity, from mouse colon revealed an actively cycling CD24+ fraction that contained the majority of Lgr5-EGFP+ putative CESCs. Transcript analysis by quantitative RT-PCR confirmed enrichment of active CESC markers [leucine-rich-repeat-containing G protein-coupled receptor 5 (Lgr5), ephrin type B receptor 2 (EphB2), and CD166] in the CD24+EpCAM+ fraction but also showed enrichment of quiescent CESC markers [leucine-rich repeats and immunoglobin domains (Lrig), doublecortin and calmodulin kinase-like 1 (DCAMKL-1), and murine telomerase reverse transcriptase (mTert)]. We conclude that CD24-based sorting in wild-type mice isolates a colonic epithelial fraction highly enriched in actively cycling and quiescent putative CESCs. Furthermore, the presence of CD24 expression in normal colonic epithelium may have important implications for the use of anti-CD24-based colorectal cancer therapies. PMID:22723265

Ionospheric acoustic and gravity waves associated with midlatitude thunderstorms

DOE PAGES

Lay, Erin H.; Shao, Xuan -Min; Kendrick, Alexander K.; ...

2015-07-30

Acoustic waves with periods of 2 - 4 minutes and gravity waves with periods of 6 - 16 minutes have been detected at ionospheric heights (250-350 km) using GPS Total Electron Content (TEC) measurements. The area disturbed by these waves and the wave amplitudes have been associated with underlying thunderstorm activity. A statistical study comparing NEXRAD radar thunderstorm measurements with ionospheric acoustic and gravity waves in the mid-latitude U.S. Great Plains region was performed for the time period of May - July 2005. An increase of ionospheric acoustic wave disturbed area and amplitude is primarily associated with large thunderstorms (mesoscalemore » convective systems). Ionospheric gravity wave disturbed area and amplitude scale with thunderstorm activity, with even small storms (i.e. individual storm cells) producing an increase of gravity waves.« less

Development of high capacity, high rate lithium ion batteries utilizing metal fiber conductive additives

NASA Astrophysics Data System (ADS)

Ahn, Soonho; Kim, Youngduk; Kim, Kyung Joon; Kim, Tae Hyung; Lee, Hyungkeun; Kim, Myung H.

As lithium ion cells dominate the battery market, the performance improvement is an utmost concern among developers and researchers. Conductive additives are routinely employed to enhance electrode conductivity and capacity. Carbon particulates—graphite or carbon black powders—are conventional and popular choices as conductive fillers. However, percolation requirements of particles demand significant volumetric content of impalpable, and thereby high area conductive fillers. As might be expected, the electrode active surface area escalates unnecessarily, resulting in overall increase in reaction with electrolytes and organic solvents. The increased reactions usually manifest as an irreversible loss of anode capacity, gradual oxidation and consumption of electrolyte on the cathode—which causes capacity decline during cycling—and an increased threat to battery safety by gas evolution and exothermic solvent oxidation. In this work we have utilized high aspect ratio, flexible, micronic metal fibers as low active area and high conductivity additives. The metal fibers appear well dispersed within the electrode and to satisfy percolation requirements very efficiently at very low volumetric content compared to conventional carbon-based conductive additives. Results from 18650-type cells indicate significant enhancements in electrode capacity and high rate capability while the irreversible capacity loss is negligible.

Comparison of Mast Cells Count in Odontogenic Cysts Using Histochemical Staining

PubMed Central

Rajabi-Moghaddam, Mahdieh; Abbaszadeh-Bidokhty, Hamid; Bijani, Ali

2015-01-01

Background & Objectives: Odontogenic cysts are among the most frequent destructive lesions of jaws which their pathogenesis and growth mechanism are not cleared. With respect to different roles of mast cells, they may play a role in the pathogenesis and growth of odontogenic cysts. The aim of present study was to evaluate mast cells in the most common odontogenic cyst. Methods: Thirty paraffin-embedded tissue blocks including 10 radicular cysts, 10 dentigerous cysts and 10 odontogenic keratocysts were used and 5 micron sections stained with toluidine blue and observed by light microscope under ×400 magnification to evaluate mast cells within these cysts. For each case, 5 high-power field areas, selected from hot-spot areas, were considered and each area divided into 3 zones: intra-epithelial zone, sub-epithelial zone and deep zone. Results: Most of the studied cyst showed presence of mast cells. There was not any significant difference in mast cell count between studied cysts ( P -values > 0.05).With respect to intra-epithelial, sub-epithelial and deep zones, there was not any significant difference between three studied cysts. There was not any significant difference between sub-epithelial zone and deep zone within each of these cysts. There was only significant difference between intra-epithelial zone and sub-epithelial zone within dentigerous cysts and odontogenic keratocysts ( P -value < 0.05). Conclusions: Prevalence of mast cells in fibrous wall of odontogenic cysts suggests their activity in these cysts. Mast cells may not be directly involved in the pathogenesis of odontogenic keratocysts. PMID:26351470

Nanoelectronics-biology frontier: From nanoscopic probes for action potential recording in live cells to three-dimensional cyborg tissues.

PubMed

Duan, Xiaojie; Fu, Tian-Ming; Liu, Jia; Lieber, Charles M

2013-08-01

Semiconductor nanowires configured as the active channels of field-effect transistors (FETs) have been used as detectors for high-resolution electrical recording from single live cells, cell networks, tissues and organs. Extracellular measurements with substrate supported silicon nanowire (SiNW) FETs, which have projected active areas orders of magnitude smaller than conventional microfabricated multielectrode arrays (MEAs) and planar FETs, recorded action potential and field potential signals with high signal-to-noise ratio and temporal resolution from cultured neurons, cultured cardiomyocytes, acute brain slices and whole animal hearts. Measurements made with modulation-doped nanoscale active channel SiNW FETs demonstrate that signals recorded from cardiomyocytes are highly localized and have improved time resolution compared to larger planar detectors. In addition, several novel three-dimensional (3D) transistor probes, which were realized using advanced nanowire synthesis methods, have been implemented for intracellular recording. These novel probes include (i) flexible 3D kinked nanowire FETs, (ii) branched intracellular nanotube SiNW FETs, and (iii) active silicon nanotube FETs. Following phospholipid modification of the probes to mimic the cell membrane, the kinked nanowire, branched intracellular nanotube and active silicon nanotube FET probes recorded full-amplitude intracellular action potentials from spontaneously firing cardiomyocytes. Moreover, these probes demonstrated the capability of reversible, stable, and long-term intracellular recording, thus indicating the minimal invasiveness of the new nanoscale structures and suggesting biomimetic internalization via the phospholipid modification. Simultaneous, multi-site intracellular recording from both single cells and cell networks were also readily achieved by interfacing independently addressable nanoprobe devices with cells. Finally, electronic and biological systems have been seamlessly merged in 3D for the first time using macroporous nanoelectronic scaffolds that are analogous to synthetic tissue scaffold and the extracellular matrix in tissue. Free-standing 3D nanoelectronic scaffolds were cultured with neurons, cardiomyocytes and smooth muscle cells to yield electronically-innervated synthetic or 'cyborg' tissues. Measurements demonstrate that innervated tissues exhibit similar cell viability as with conventional tissue scaffolds, and importantly, demonstrate that the real-time response to drugs and pH changes can be mapped in 3D through the tissues. These results open up a new field of research, wherein nanoelectronics are merged with biological systems in 3D thereby providing broad opportunities, ranging from a nanoelectronic/tissue platform for real-time pharmacological screening in 3D to implantable 'cyborg' tissues enabling closed-loop monitoring and treatment of diseases. Furthermore, the capability of high density scale-up of the above extra- and intracellular nanoscopic probes for action potential recording provide important tools for large-scale high spatio-temporal resolution electrical neural activity mapping in both 2D and 3D, which promises to have a profound impact on many research areas, including the mapping of activity within the brain.

Nanoelectronics-biology frontier: From nanoscopic probes for action potential recording in live cells to three-dimensional cyborg tissues

PubMed Central

Duan, Xiaojie; Fu, Tian-Ming; Liu, Jia; Lieber, Charles M.

2013-01-01

Summary Semiconductor nanowires configured as the active channels of field-effect transistors (FETs) have been used as detectors for high-resolution electrical recording from single live cells, cell networks, tissues and organs. Extracellular measurements with substrate supported silicon nanowire (SiNW) FETs, which have projected active areas orders of magnitude smaller than conventional microfabricated multielectrode arrays (MEAs) and planar FETs, recorded action potential and field potential signals with high signal-to-noise ratio and temporal resolution from cultured neurons, cultured cardiomyocytes, acute brain slices and whole animal hearts. Measurements made with modulation-doped nanoscale active channel SiNW FETs demonstrate that signals recorded from cardiomyocytes are highly localized and have improved time resolution compared to larger planar detectors. In addition, several novel three-dimensional (3D) transistor probes, which were realized using advanced nanowire synthesis methods, have been implemented for intracellular recording. These novel probes include (i) flexible 3D kinked nanowire FETs, (ii) branched intracellular nanotube SiNW FETs, and (iii) active silicon nanotube FETs. Following phospholipid modification of the probes to mimic the cell membrane, the kinked nanowire, branched intracellular nanotube and active silicon nanotube FET probes recorded full-amplitude intracellular action potentials from spontaneously firing cardiomyocytes. Moreover, these probes demonstrated the capability of reversible, stable, and long-term intracellular recording, thus indicating the minimal invasiveness of the new nanoscale structures and suggesting biomimetic internalization via the phospholipid modification. Simultaneous, multi-site intracellular recording from both single cells and cell networks were also readily achieved by interfacing independently addressable nanoprobe devices with cells. Finally, electronic and biological systems have been seamlessly merged in 3D for the first time using macroporous nanoelectronic scaffolds that are analogous to synthetic tissue scaffold and the extracellular matrix in tissue. Free-standing 3D nanoelectronic scaffolds were cultured with neurons, cardiomyocytes and smooth muscle cells to yield electronically-innervated synthetic or ‘cyborg’ tissues. Measurements demonstrate that innervated tissues exhibit similar cell viability as with conventional tissue scaffolds, and importantly, demonstrate that the real-time response to drugs and pH changes can be mapped in 3D through the tissues. These results open up a new field of research, wherein nanoelectronics are merged with biological systems in 3D thereby providing broad opportunities, ranging from a nanoelectronic/tissue platform for real-time pharmacological screening in 3D to implantable ‘cyborg’ tissues enabling closed-loop monitoring and treatment of diseases. Furthermore, the capability of high density scale-up of the above extra- and intracellular nanoscopic probes for action potential recording provide important tools for large-scale high spatio-temporal resolution electrical neural activity mapping in both 2D and 3D, which promises to have a profound impact on many research areas, including the mapping of activity within the brain. PMID:24073014

Activating Endogenous Neural Precursor Cells Using Metformin Leads to Neural Repair and Functional Recovery in a Model of Childhood Brain Injury.

PubMed

Dadwal, Parvati; Mahmud, Neemat; Sinai, Laleh; Azimi, Ashkan; Fatt, Michael; Wondisford, Fredric E; Miller, Freda D; Morshead, Cindi M

2015-08-11

The development of cell replacement strategies to repair the injured brain has gained considerable attention, with a particular interest in mobilizing endogenous neural stem and progenitor cells (known as neural precursor cells [NPCs]) to promote brain repair. Recent work demonstrated metformin, a drug used to manage type II diabetes, promotes neurogenesis. We sought to determine its role in neural repair following brain injury. We find that metformin administration activates endogenous NPCs, expanding the size of the NPC pool and promoting NPC migration and differentiation in the injured neonatal brain in a hypoxia-ischemia (H/I) injury model. Importantly, metformin treatment following H/I restores sensory-motor function. Lineage tracking reveals that metformin treatment following H/I causes an increase in the absolute number of subependyma-derived NPCs relative to untreated H/I controls in areas associated with sensory-motor function. Hence, activation of endogenous NPCs is a promising target for therapeutic intervention in childhood brain injury models. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Protein kinase inhibitors against malignant lymphoma

PubMed Central

D’Cruz, Osmond J; Uckun, Fatih M

2013-01-01

Introduction Tyrosine kinases (TKs) are intimately involved in multiple signal transduction pathways regulating survival, activation, proliferation and differentiation of lymphoid cells. Deregulation or overexpression of specific oncogenic TKs is implicated in maintaining the malignant phenotype in B-lineage lymphoid malignancies. Several novel targeted TK inhibitors (TKIs) have recently emerged as active in the treatment of relapsed or refractory B-cell lymphomas that inhibit critical signaling pathways, promote apoptotic mechanisms or modulate the tumor microenvironment. Areas covered In this review, the authors summarize the clinical outcomes of newer TKIs in various B-cell lymphomas from published and ongoing clinical studies and abstracts from major cancer and hematology conferences. Expert opinion Multiple clinical trials have demonstrated that robust antitumor activity can be obtained with TKIs directed toward specific oncogenic TKs that are genetically deregulated in various subtypes of B-cell lymphomas. Clinical success of targeting TKIs is dependent upon on identifying reliable molecular and clinical markers associated with select cohorts of patients. Further understanding of the signaling pathways should stimulate the identification of novel molecular targets and expand the development of new therapeutic options and individualized therapies. PMID:23496343

Carbachol induces burst firing of dopamine cells in the ventral tegmental area by promoting calcium entry through L-type channels in the rat

PubMed Central

Zhang, Lei; Liu, Yudan; Chen, Xihua

2005-01-01

Enhanced activity of the central dopamine system has been implicated in many psychiatric disorders including schizophrenia and addiction. Besides terminal mechanisms that boost dopamine levels at the synapse, the cell body of dopamine cells enhances terminal dopamine concentration through encoding action potentials in bursts. This paper presents evidence that burst firing of dopamine cells in the ventral tegmental area was under cholinergic control using nystatin-perforated patch clamp recording from slice preparations. The non-selective cholinergic agonist carbachol excited the majority of recorded neurones, an action that was not affected by blocking glutamate and GABA ionotropic receptors. Twenty per cent of dopamine cells responded to carbachol with robust bursting, an effect mediated by both muscarinic and nicotinic cholinoceptors postsynaptically. Burst firing induced as such was completely dependent on calcium entry as it could be blocked by cadmium and more specifically the L-type blocker nifedipine. In the presence of the sodium channel blocker tetrodotoxin, carbachol induced membrane potential oscillation that had similar kinetics and frequency as burst firing cycles and could also be blocked by cadmium and nifedipine. Direct activation of the L-type channel with Bay K8644 induced strong bursting which could be blocked by nifedipine but not by depleting internal calcium stores. These results indicate that carbachol increases calcium entry into the postsynaptic cell through L-type channels to generate calcium-dependent membrane potential oscillation and burst firing. This could establish the L-type channel as a target for modulating the function of the central dopamine system in disease conditions. PMID:16081481

Influence of anode thickness on the power output of solid oxide fuel cells with (La,Sr)(Co,Fe)-type cathode

NASA Astrophysics Data System (ADS)

Menzler, Norbert H.; Haanappel, Vincent A. C.

The influence of the thickness of the anode (functional layer) on the power output of anode-supported solid oxide fuel cells with a lanthanum-strontium-cobalt-ferrite cathode was investigated. The anode was applied by vacuum slip casting and the thickness varied between 1 and 22 μm. All other material and microstructural parameters were kept constant. Single cells with dimensions of 50 mm × 50 mm and with an active cathode area of 40 mm × 40 mm were manufactured and tested in an alumina housing with air as oxidant and hydrogen with 3% water vapour as the fuel gas. Results have shown that SOFCs with anodes between 1 and 13 μm have slightly better performance than those with thicker anodes (∼1.7 A cm -2 versus 1.5 A cm -2 at 800 °C and 0.7 V). The current densities were discussed with respect to cell area specific resistance, helium leak rate of the half-cell, and microstructure.

Osteogenic differentiation of human dental papilla mesenchymal cells

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

Ikeda, Etsuko; Hirose, Motohiro; Kotobuki, Noriko

We isolated dental papilla from impacted human molar and proliferated adherent fibroblastic cells after collagenase treatment of the papilla. The cells were negative for hematopoietic markers but positive for CD29, CD44, CD90, CD105, and CD166. When the cells were further cultured in the presence of {beta}-glycerophosphate, ascorbic acid, and dexamethasone for 14 days, mineralized areas together with osteogenic differentiation evidenced by high alkaline phosphatase activity and osteocalcin contents were observed. The differentiation was confirmed at both protein and gene expression levels. The cells can also be cryopreserved and, after thawing, could show in vivo bone-forming capability. These results indicate thatmore » mesenchymal type cells localize in dental papilla and that the cells can be culture expanded/utilized for bone tissue engineering.« less

Cell Signaling Pathways that Regulate Ag Presentation

PubMed Central

Brutkiewicz, Randy R.

2016-01-01

Cell signaling pathways regulate much in the life of a cell: from shuttling cargo through intracellular compartments and onto the cell surface, how it should respond to stress, protecting itself from harm (environmental insults or infections), to ultimately, death by apoptosis. These signaling pathways are important for various aspects of the immune response as well. However, not much is known in terms of the participation of cell signaling pathways in Ag presentation--a necessary first step in the activation of innate and adaptive T cells. In this brief review, I will discuss the known signaling molecules (and pathways) that regulate how Ags are presented to T cells and the mechanism(s) if identified. Studies in this area have important implications in vaccine development and new treatment paradigms against infectious diseases, autoimmunity and cancer. PMID:27824592

Initial analysis of peripheral lymphocytic extracellular signal related kinase activation in autism.

PubMed

Erickson, Craig A; Ray, Balmiki; Wink, Logan K; Bayon, Baindu L; Pedapati, Ernest V; Shaffer, Rebecca; Schaefer, Tori L; Lahiri, Debomoy K

2017-01-01

Dysregulation of extracellular signal-related kinase (ERK) activity has been potentially implicated in the pathophysiology of autistic disorder (autism). ERK is part of a central intracellular signaling cascade responsible for a myriad of cellular functions. ERK is expressed in peripheral blood lymphocytes, and measurement of activated (phosphorylated) lymphocytic ERK is commonly executed in many areas of medicine. We sought to conduct the first study of ERK activation in humans with autism by utilizing a lymphocytic ERK activation assay. We hypothesized that ERK activation would be enhanced in peripheral blood lymphocytes from persons with autism compared to those of neurotypical control subjects. We conducted an initial study of peripheral lymphocyte ERK activation in 45 subjects with autism and 26 age- and gender-matched control subjects (total n = 71). ERK activation was measured using a lymphocyte counting method (primary outcome expressed as lymphocytes staining positive for cytosolic phosphorylated ERK divided by total cells counted) and additional Western blot analysis of whole cell phosphorylated ERK adjusted for total ERK present in the lymphocyte lysate sample. Cytosolic/nuclear localization of pERK activated cells were increased by almost two-fold in the autism subject group compared to matched neurotypical control subjects (cell count ratio of 0.064 ± 0.044 versus 0.034 ± 0.031; p = 0.002). Elevated phosphorylated ERK levels in whole cell lysates also showed increased activated ERK in the autism group compared to controls (n = 54 total) in Western blot analysis. The results of this first in human ERK activation study are consistent with enhanced peripheral lymphocytic ERK activation in autism, as well as suggesting that cellular compartmentalization of activated ERK may be altered in this disorder. Future work will be required to explore the impact of concomitant medication use and other subject characteristics such as level of cognitive functioning on ERK activation. Not applicable. Copyright © 2016 Elsevier Ltd. All rights reserved.

Initial analysis of peripheral lymphocytic extracellular signal related kinase activation in autism

PubMed Central

Erickson, Craig A.; Ray, Balmiki; Wink, Logan K.; Bayon, Baindu L.; Pedapati, Ernest V.; Shaffer, Rebecca; Schaefer, Tori L.; Lahiri, Debomoy K.

2018-01-01

Background Dysregulation of extracellular signal-related kinase (ERK) activity has been potentially implicated in the pathophysiology of autistic disorder (autism). ERK is part of a central intracellular signaling cascade responsible for a myriad of cellular functions. ERK is expressed in peripheral blood lymphocytes, and measurement of activated (phosphorylated) lymphocytic ERK is commonly executed in many areas of medicine. We sought to conduct the first study of ERK activation in humans with autism by utilizing a lymphocytic ERK activation assay. We hypothesized that ERK activation would be enhanced in peripheral blood lymphocytes from persons with autism compared to those of neurotypical control subjects. Method We conducted an initial study of peripheral lymphocyte ERK activation in 45 subjects with autism and 26 age- and gender-matched control subjects (total n = 71). ERK activation was measured using a lymphocyte counting method (primary outcome expressed as lymphocytes staining positive for cytosolic phosphorylated ERK divided by total cells counted) and additional Western blot analysis of whole cell phosphorylated ERK adjusted for total ERK present in the lymphocyte lysate sample. Results Cytosolic/nuclear localization of pERK activated cells were increased by almost two-fold in the autism subject group compared to matched neurotypical control subjects (cell count ratio of 0.064 ± 0.044 versus 0.034 ± 0.031; p = 0.002). Elevated phosphorylated ERK levels in whole cell lysates also showed increased activated ERK in the autism group compared to controls (n = 54 total) in Western blot analysis. Conclusions The results of this first in human ERK activation study are consistent with enhanced peripheral lymphocytic ERK activation in autism, as well as suggesting that cellular compartmentalization of activated ERK may be altered in this disorder. Future work will be required to explore the impact of concomitant medication use and other subject characteristics such as level of cognitive functioning on ERK activation. Trial Registration Not applicable. PMID:27743527

Thyroid hormone affects secretory activity and uncoupling protein-3 expression in rat harderian gland.

PubMed

Chieffi Baccari, Gabriella; Monteforte, Rossella; de Lange, Pieter; Raucci, Franca; Farina, Paola; Lanni, Antonia

2004-07-01

The effects of T(3) administration on the rat Harderian gland were examined at morphological, biochemical, and molecular levels. T(3) induced hypertrophy of the two cell types (A and B) present in the glandular epithelium. In type A cells, the hypertrophy was mainly due to an increase in the size of the lipid compartment. The acinar lumina were filled with lipoproteic substances, and the cells often showed an olocrine secretory pattern. In type B cells, the hypertrophy largely consisted of a marked proliferation of mitochondria endowed with tightly packed cristae, the mitochondrial number being nearly doubled (from 62 to 101/100 microm(2)). Although the average area of individual mitochondria decreased by about 50%, the total area of the mitochondrial compartment increased by about 80% (from 11 to 19/100 microm(2)). This could be ascribed to T(3)-induced mitochondrial proliferation. The morphological and morphometric data correlated well with our biochemical results, which indicated that mitochondrial respiratory activity is increased in hyperthyroid rats. T(3), by influencing the metabolic function of the mitochondrial compartment, induces lipogenesis and the release of secretory product by type A cells. Mitochondrial uncoupling proteins 2 and 3 were expressed at both mRNA and protein levels in the euthyroid rat Harderian gland. T(3) treatment increased the mRNA levels of both uncoupling protein 2 (UCP2) and UCP3, but the protein level only of UCP3. A possible role for these proteins in the Harderian gland is discussed.