class iv dendrite: Topics by Science.gov

Sample records for class iv dendrite

Simulation of dendritic growth reveals necessary and sufficient parameters to describe the shapes of dendritic trees

NASA Astrophysics Data System (ADS)

Trottier, Olivier; Ganguly, Sujoy; Bowne-Anderson, Hugo; Liang, Xin; Howard, Jonathon

For the last 120 years, the development of neuronal shapes has been of great interest to the scientific community. Over the last 30 years, significant work has been done on the molecular processes responsible for dendritic development. In our ongoing research, we use the class IV sensory neurons of the Drosophila melanogaster larva as a model system to understand the growth of dendritic arbors. Our main goal is to elucidate the mechanisms that the neuron uses to determine the shape of its dendritic tree. We have observed the development of the class IV neuron's dendritic tree in the larval stage and have concluded that morphogenesis is defined by 3 distinct processes: 1) branch growth, 2) branching and 3) branch retraction. As the first step towards understanding dendritic growth, we have implemented these three processes in a computational model. Our simulations are able to reproduce the branch length distribution, number of branches and fractal dimension of the class IV neurons for a small range of parameters.
Mathematical Relationships between Neuron Morphology and Neurite Growth Dynamics in Drosophila melanogaster Larva Class IV Sensory Neurons

NASA Astrophysics Data System (ADS)

Ganguly, Sujoy; Liang, Xin; Grace, Michael; Lee, Daniel; Howard, Jonathon

The morphology of neurons is diverse and reflects the diversity of neuronal functions, yet the principles that govern neuronal morphogenesis are unclear. In an effort to better understand neuronal morphogenesis we will be focusing on the development of the dendrites of class IV sensory neuron in Drosophila melanogaster. In particular we attempt to determine how the the total length, and the number of branches of dendrites are mathematically related to the dynamics of neurite growth and branching. By imaging class IV neurons during early embryogenesis we are able to measure the change in neurite length l (t) as a function of time v (t) = dl / dt . We found that the distribution of v (t) is well characterized by a hyperbolic secant distribution, and that the addition of new branches per unit time is well described by a Poisson process. Combining these measurements with the assumption that branching occurs with equal probability anywhere along the dendrite we were able to construct a mathematical model that provides reasonable agreement with the observed number of branches, and total length of the dendrites of the class IV sensory neuron.
Nutrient-dependent increased dendritic arborization of somatosensory neurons.

PubMed

Watanabe, Kaori; Furumizo, Yuki; Usui, Tadao; Hattori, Yukako; Uemura, Tadashi

2017-01-01

Suboptimal nutrition imposes developmental constraints on infant animals, which marshal adaptive responses to eventually become mature adults. Such responses are mounted at multiple levels from systemic to cellular. At the cellular level, the underlying mechanisms of cell proliferation control have been intensively studied. However, less is known about how growth of postmitotic and morphologically complex cells, such as neurons, is controlled by nutritional status. We address this question using Class I and Class IV dendritic arborization neurons in Drosophila larvae. Class IV neurons have been shown to sense nociceptive thermal, mechanical and light stimuli, whereas Class I neurons are proprioceptors. We reared larvae on diets with different protein and carbohydrate content throughout larval stages and examined how morphologies of Class I or Class IV neurons were affected. Dendritic arbors of Class IV neurons became more complex when larvae were reared on a low-yeast diet, which contains lower amounts of amino acids and other ingredients, compared to a high-yeast diet. In contrast, such low-yeast-dependent hyperarborization was not seen in Class I neurons. The physiological and metabolic implications of the hyperarborization phenotype are discussed in relation to a recent hypothesis that Class IV neurons sense protein-deficient stress and to our characterization of how the dietary yeast contents impacted larval metabolism. © 2016 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.
Dynein-Dependent Transport of nanos RNA in Drosophila Sensory Neurons Requires Rumpelstiltskin and the Germ Plasm Organizer Oskar

PubMed Central

Xu, Xin; Brechbiel, Jillian L.

2013-01-01

Intracellular mRNA localization is a conserved mechanism for spatially regulating protein production in polarized cells, such as neurons. The mRNA encoding the translational repressor Nanos (Nos) forms ribonucleoprotein (RNP) particles that are dendritically localized in Drosophila larval class IV dendritic arborization (da) neurons. In nos mutants, class IV da neurons exhibit reduced dendritic branching complexity, which is rescued by transgenic expression of wild-type nos mRNA but not by a localization-compromised nos derivative. While localization is essential for nos function in dendrite morphogenesis, the mechanism underlying the transport of nos RNP particles was unknown. We investigated the mechanism of dendritic nos mRNA localization by analyzing requirements for nos RNP particle motility in class IV da neuron dendrites through live imaging of fluorescently labeled nos mRNA. We show that dynein motor machinery components mediate transport of nos mRNA in proximal dendrites. Two factors, the RNA-binding protein Rumpelstiltskin and the germ plasm protein Oskar, which are required for diffusion/entrapment-mediated localization of nos during oogenesis, also function in da neurons for formation and transport of nos RNP particles. Additionally, we show that nos regulates neuronal function, most likely independent of its dendritic localization and function in morphogenesis. Our results reveal adaptability of localization factors for regulation of a target transcript in different cellular contexts. PMID:24027279
Dynein-dependent transport of nanos RNA in Drosophila sensory neurons requires Rumpelstiltskin and the germ plasm organizer Oskar.

PubMed

Xu, Xin; Brechbiel, Jillian L; Gavis, Elizabeth R

2013-09-11

Intracellular mRNA localization is a conserved mechanism for spatially regulating protein production in polarized cells, such as neurons. The mRNA encoding the translational repressor Nanos (Nos) forms ribonucleoprotein (RNP) particles that are dendritically localized in Drosophila larval class IV dendritic arborization (da) neurons. In nos mutants, class IV da neurons exhibit reduced dendritic branching complexity, which is rescued by transgenic expression of wild-type nos mRNA but not by a localization-compromised nos derivative. While localization is essential for nos function in dendrite morphogenesis, the mechanism underlying the transport of nos RNP particles was unknown. We investigated the mechanism of dendritic nos mRNA localization by analyzing requirements for nos RNP particle motility in class IV da neuron dendrites through live imaging of fluorescently labeled nos mRNA. We show that dynein motor machinery components mediate transport of nos mRNA in proximal dendrites. Two factors, the RNA-binding protein Rumpelstiltskin and the germ plasm protein Oskar, which are required for diffusion/entrapment-mediated localization of nos during oogenesis, also function in da neurons for formation and transport of nos RNP particles. Additionally, we show that nos regulates neuronal function, most likely independent of its dendritic localization and function in morphogenesis. Our results reveal adaptability of localization factors for regulation of a target transcript in different cellular contexts.
Nanos-mediated repression of hid protects larval sensory neurons after a global switch in sensitivity to apoptotic signals

PubMed Central

Bhogal, Balpreet; Plaza-Jennings, Amara

2016-01-01

Dendritic arbor morphology is a key determinant of neuronal function. Once established, dendrite branching patterns must be maintained as the animal develops to ensure receptive field coverage. The translational repressors Nanos (Nos) and Pumilio (Pum) are required to maintain dendrite growth and branching of Drosophila larval class IV dendritic arborization (da) neurons, but their specific regulatory role remains unknown. We show that Nos-Pum-mediated repression of the pro-apoptotic gene head involution defective (hid) is required to maintain a balance of dendritic growth and retraction in class IV da neurons and that upregulation of hid results in decreased branching because of an increase in caspase activity. The temporal requirement for nos correlates with an ecdysone-triggered switch in sensitivity to apoptotic stimuli that occurs during the mid-L3 transition. We find that hid is required during pupariation for caspase-dependent pruning of class IV da neurons and that Nos and Pum delay pruning. Together, these results suggest that Nos and Pum provide a crucial neuroprotective regulatory layer to ensure that neurons behave appropriately in response to developmental cues. PMID:27256879
Nanos-mediated repression of hid protects larval sensory neurons after a global switch in sensitivity to apoptotic signals.

PubMed

Bhogal, Balpreet; Plaza-Jennings, Amara; Gavis, Elizabeth R

2016-06-15

Dendritic arbor morphology is a key determinant of neuronal function. Once established, dendrite branching patterns must be maintained as the animal develops to ensure receptive field coverage. The translational repressors Nanos (Nos) and Pumilio (Pum) are required to maintain dendrite growth and branching of Drosophila larval class IV dendritic arborization (da) neurons, but their specific regulatory role remains unknown. We show that Nos-Pum-mediated repression of the pro-apoptotic gene head involution defective (hid) is required to maintain a balance of dendritic growth and retraction in class IV da neurons and that upregulation of hid results in decreased branching because of an increase in caspase activity. The temporal requirement for nos correlates with an ecdysone-triggered switch in sensitivity to apoptotic stimuli that occurs during the mid-L3 transition. We find that hid is required during pupariation for caspase-dependent pruning of class IV da neurons and that Nos and Pum delay pruning. Together, these results suggest that Nos and Pum provide a crucial neuroprotective regulatory layer to ensure that neurons behave appropriately in response to developmental cues. © 2016. Published by The Company of Biologists Ltd.
Turtle Functions Downstream of Cut in Differentially Regulating Class Specific Dendrite Morphogenesis in Drosophila

PubMed Central

Sulkowski, Mikolaj J.; Iyer, Srividya Chandramouli; Kurosawa, Mathieu S.; Iyer, Eswar Prasad R.; Cox, Daniel N.

2011-01-01

Background Dendritic morphology largely determines patterns of synaptic connectivity and electrochemical properties of a neuron. Neurons display a myriad diversity of dendritic geometries which serve as a basis for functional classification. Several types of molecules have recently been identified which regulate dendrite morphology by acting at the levels of transcriptional regulation, direct interactions with the cytoskeleton and organelles, and cell surface interactions. Although there has been substantial progress in understanding the molecular mechanisms of dendrite morphogenesis, the specification of class-specific dendritic arbors remains largely unexplained. Furthermore, the presence of numerous regulators suggests that they must work in concert. However, presently, few genetic pathways regulating dendrite development have been defined. Methodology/Principal Findings The Drosophila gene turtle belongs to an evolutionarily conserved class of immunoglobulin superfamily members found in the nervous systems of diverse organisms. We demonstrate that Turtle is differentially expressed in Drosophila da neurons. Moreover, MARCM analyses reveal Turtle acts cell autonomously to exert class specific effects on dendritic growth and/or branching in da neuron subclasses. Using transgenic overexpression of different Turtle isoforms, we find context-dependent, isoform-specific effects on mediating dendritic branching in class II, III and IV da neurons. Finally, we demonstrate via chromatin immunoprecipitation, qPCR, and immunohistochemistry analyses that Turtle expression is positively regulated by the Cut homeodomain transcription factor and via genetic interaction studies that Turtle is downstream effector of Cut-mediated regulation of da neuron dendrite morphology. Conclusions/Significance Our findings reveal that Turtle proteins differentially regulate the acquisition of class-specific dendrite morphologies. In addition, we have established a transcriptional regulatory interaction between Cut and Turtle, representing a novel pathway for mediating class specific dendrite development. PMID:21811639
Dendrite architecture organized by transcriptional control of the F-actin nucleator Spire.

PubMed

Ferreira, Tiago; Ou, Yimiao; Li, Sally; Giniger, Edward; van Meyel, Donald J

2014-02-01

The architectures of dendritic trees are crucial for the wiring and function of neuronal circuits because they determine coverage of receptive territories, as well as the nature and strength of sensory or synaptic inputs. Here, we describe a cell-intrinsic pathway sculpting dendritic arborization (da) neurons in Drosophila that requires Longitudinals Lacking (Lola), a BTB/POZ transcription factor, and its control of the F-actin cytoskeleton through Spire (Spir), an actin nucleation protein. Loss of Lola from da neurons reduced the overall length of dendritic arbors, increased the expression of Spir, and produced inappropriate F-actin-rich dendrites at positions too near the cell soma. Selective removal of Lola from only class IV da neurons decreased the evasive responses of larvae to nociception. The increased Spir expression contributed to the abnormal F-actin-rich dendrites and the decreased nocifensive responses because both were suppressed by reduced dose of Spir. Thus, an important role of Lola is to limit expression of Spir to appropriate levels within da neurons. We found Spir to be expressed in dendritic arbors and to be important for their development. Removal of Spir from class IV da neurons reduced F-actin levels and total branch number, shifted the position of greatest branch density away from the cell soma, and compromised nocifensive behavior. We conclude that the Lola-Spir pathway is crucial for the spatial arrangement of branches within dendritic trees and for neural circuit function because it provides balanced control of the F-actin cytoskeleton.
Morphological analysis of Drosophila larval peripheral sensory neuron dendrites and axons using genetic mosaics.

PubMed

Karim, M Rezaul; Moore, Adrian W

2011-11-07

Nervous system development requires the correct specification of neuron position and identity, followed by accurate neuron class-specific dendritic development and axonal wiring. Recently the dendritic arborization (DA) sensory neurons of the Drosophila larval peripheral nervous system (PNS) have become powerful genetic models in which to elucidate both general and class-specific mechanisms of neuron differentiation. There are four main DA neuron classes (I-IV)(1). They are named in order of increasing dendrite arbor complexity, and have class-specific differences in the genetic control of their differentiation(2-10). The DA sensory system is a practical model to investigate the molecular mechanisms behind the control of dendritic morphology(11-13) because: 1) it can take advantage of the powerful genetic tools available in the fruit fly, 2) the DA neuron dendrite arbor spreads out in only 2 dimensions beneath an optically clear larval cuticle making it easy to visualize with high resolution in vivo, 3) the class-specific diversity in dendritic morphology facilitates a comparative analysis to find key elements controlling the formation of simple vs. highly branched dendritic trees, and 4) dendritic arbor stereotypical shapes of different DA neurons facilitate morphometric statistical analyses. DA neuron activity modifies the output of a larval locomotion central pattern generator(14-16). The different DA neuron classes have distinct sensory modalities, and their activation elicits different behavioral responses(14,16-20). Furthermore different classes send axonal projections stereotypically into the Drosophila larval central nervous system in the ventral nerve cord (VNC)(21). These projections terminate with topographic representations of both DA neuron sensory modality and the position in the body wall of the dendritic field(7,22,23). Hence examination of DA axonal projections can be used to elucidate mechanisms underlying topographic mapping(7,22,23), as well as the wiring of a simple circuit modulating larval locomotion(14-17). We present here a practical guide to generate and analyze genetic mosaics(24) marking DA neurons via MARCM (Mosaic Analysis with a Repressible Cell Marker)(1,10,25) and Flp-out(22,26,27) techniques (summarized in Fig. 1).
Dendrite regeneration of adult Drosophila sensory neurons diminishes with aging and is inhibited by epidermal-derived matrix metalloproteinase 2.

PubMed

DeVault, Laura; Li, Tun; Izabel, Sarah; Thompson-Peer, Katherine L; Jan, Lily Yeh; Jan, Yuh Nung

2018-03-01

Dendrites possess distinct structural and functional properties that enable neurons to receive information from the environment as well as other neurons. Despite their key role in neuronal function, current understanding of the ability of neurons to regenerate dendrites is lacking. This study characterizes the structural and functional capacity for dendrite regeneration in vivo in adult animals and examines the effect of neuronal maturation on dendrite regeneration. We focused on the class IV dendritic arborization (c4da) neuron of the Drosophila sensory system, which has a dendritic arbor that undergoes dramatic remodeling during the first 3 d of adult life and then maintains a relatively stable morphology thereafter. Using a laser severing paradigm, we monitored regeneration after acute and spatially restricted injury. We found that the capacity for regeneration was present in adult neurons but diminished as the animal aged. Regenerated dendrites recovered receptive function. Furthermore, we found that the regenerated dendrites show preferential alignment with the extracellular matrix (ECM). Finally, inhibition of ECM degradation by inhibition of matrix metalloproteinase 2 (Mmp2) to preserve the extracellular environment characteristics of young adults led to increased dendrite regeneration. These results demonstrate that dendrites retain regenerative potential throughout adulthood and that regenerative capacity decreases with aging. © 2018 DeVault et al.; Published by Cold Spring Harbor Laboratory Press.
Extensive Use of RNA-Binding Proteins in Drosophila Sensory Neuron Dendrite Morphogenesis

PubMed Central

Olesnicky, Eugenia C.; Killian, Darrell J.; Garcia, Evelyn; Morton, Mary C.; Rathjen, Alan R.; Sola, Ismail E.; Gavis, Elizabeth R.

2013-01-01

The large number of RNA-binding proteins and translation factors encoded in the Drosophila and other metazoan genomes predicts widespread use of post-transcriptional regulation in cellular and developmental processes. Previous studies identified roles for several RNA-binding proteins in dendrite branching morphogenesis of Drosophila larval sensory neurons. To determine the larger contribution of post-transcriptional gene regulation to neuronal morphogenesis, we conducted an RNA interference screen to identify additional Drosophila proteins annotated as either RNA-binding proteins or translation factors that function in producing the complex dendritic trees of larval class IV dendritic arborization neurons. We identified 88 genes encoding such proteins whose knockdown resulted in aberrant dendritic morphology, including alterations in dendritic branch number, branch length, field size, and patterning of the dendritic tree. In particular, splicing and translation initiation factors were associated with distinct and characteristic phenotypes, suggesting that different morphogenetic events are best controlled at specific steps in post-transcriptional messenger RNA metabolism. Many of the factors identified in the screen have been implicated in controlling the subcellular distributions and translation of maternal messenger RNAs; thus, common post-transcriptional regulatory strategies may be used in neurogenesis and in the generation of asymmetry in the female germline and embryo. PMID:24347626
Morphology and kainate-receptor immunoreactivity of identified neurons within the entorhinal cortex projecting to superior temporal sulcus in the cynomolgus monkey

NASA Technical Reports Server (NTRS)

Good, P. F.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

1995-01-01

Projections of the entorhinal cortex to the hippocampus are well known from the classical studies of Cajal (Ramon y Cajal, 1904) and Lorente de No (1933). Projections from the entorhinal cortex to neocortical areas are less well understood. Such connectivity is likely to underlie the consolidation of long-term declarative memory in neocortical sites. In the present study, a projection arising in layer V of the entorhinal cortex and terminating in a polymodal association area of the superior temporal gyrus has been identified with the use of retrograde tracing. The dendritic arbors of neurons giving rise to this projection were further investigated by cell filling and confocal microscopy with computer reconstruction. This analysis demonstrated that the dendritic arbor of identified projection neurons was largely confined to layer V, with the exception of a solitary, simple apical dendrite occasionally ascending to superficial laminae but often confined to the lamina dissecans (layer IV). Finally, immunoreactivity for glutamate-receptor subunit proteins GluR 5/6/7 of the dendritic arbor of identified entorhinal projection neurons was examined. The solitary apical dendrite of identified entorhinal projection neurons was prominently immunolabeled for GluR 5/6/7, as was the dendritic arbor of basilar dendrites of these neurons. The restriction of the large bulk of the dendritic arbor of identified entorhinal projection neurons to layer V implies that these neurons are likely to be heavily influenced by hippocampal output arriving in the deep layers of the entorhinal cortex. Immunoreactivity for GluR 5/6/7 throughout the dendritic arbor of such neurons indicates that this class of glutamate receptor is in a position to play a prominent role in mediating excitatory neurotransmission within hippocampal-entorhinal circuits.
The Impact of Development and Sensory Deprivation on Dendritic Protrusions in the Mouse Barrel Cortex

PubMed Central

Chen, Chia-Chien; Bajnath, Adesh; Brumberg, Joshua C.

2015-01-01

Dendritic protrusions (spines and filopodia) are structural indicators of synapses that have been linked to neuronal learning and memory through their morphological alterations induced by development and experienced-dependent activities. Although previous studies have demonstrated that depriving sensory experience leads to structural changes in neocortical organization, the more subtle effects on dendritic protrusions remain unclear, mostly due to focus on only one specific cell type and/or age of manipulation. Here, we show that sensory deprivation induced by whisker trimming influences the dendritic protrusions of basilar dendrites located in thalamocortical recipient lamina (IV and VI) of the mouse barrel cortex in a layer-specific manner. Following 1 month of whisker trimming after birth, the density of dendritic protrusions increased in layer IV, but decreased in layer VI. Whisker regrowth for 1 month returned protrusion densities to comparable level of age-matched controls in layer VI, but not in layer IV. In adults, chronic sensory deprivation led to an increase in protrusion densities in layer IV, but not in layer VI. In addition, chronic pharmacological blockade of N-methyl-d-aspartate receptors (NMDARs) increased protrusion density in both layers IV and VI, which returned to the control level after 1 month of drug withdrawal. Our data reveal that different cortical layers respond to chronic sensory deprivation in different ways, with more pronounced effects during developmental critical periods than adulthood. We also show that chronically blocking NMDARs activity during developmental critical period also influences the protrusion density and morphology in the cerebral cortex. PMID:24408954
[Quantitative analysis of the structure of neuronal dendritic spines in the striatum using the Leitz-ASM system].

PubMed

Leontovich, T A; Zvegintseva, E G

1985-10-01

Two principal classes of striatum long axonal neurons (sparsely ramified reticular cells and densely ramified dendritic cells) were analyzed quantitatively in four animal species: hedgehog, rabbit, dog and monkey. The cross section area, total dendritic length and the area of dendritic field were measured using "LEITZ-ASM" system. Classes of neurons studied were significantly different in dogs and monkeys, while no differences were noted between hedgehog and rabbit. Reticular neurons of different species varied much more than dendritic ones. Quantitative analysis has revealed the progressive increase in the complexity of dendritic tree in mammals from rabbit to monkey.
The effect of axial ligands on the quantum yield of singlet oxygen of new silicon phthalocyanine

NASA Astrophysics Data System (ADS)

Lv, Huafei; Zhang, Xuemei; Yu, Xinxin; Pan, Sujuan; Xie, Shusen; Yang, Hongqin; Peng, Yiru

2016-10-01

The singlet oxygen (1O2) production abilitity is an important factor to assess their potential as effective of photosensitizers. In this paper, the 1O2 production rate, production rate constant and quantum yield of silicon(IV) phthalocyanine axially bearing 1-3 generation dendritic substituents were evaluated by a high performance liquid chromatographic method. The results show that the 1O2 production rate and production rate constant of these compounds increase gradually with dendritic generations increase. And the 1O2 quantum yield of silicon(IV) phthalocyanine with first generation dendritic ligand was the highest. This may be due to the isolation effect of the dendritic ligands on the phthalocyanine core. The parameters of the observed 1O2 production properties will provide valuable data for these dendrimer phthalocyanines as promising photosensitizer in PDT application.
Comprehensive Morpho-Electrotonic Analysis Shows 2 Distinct Classes of L2 and L3 Pyramidal Neurons in Human Temporal Cortex

PubMed Central

Deitcher, Yair; Eyal, Guy; Kanari, Lida; Verhoog, Matthijs B; Atenekeng Kahou, Guy Antoine; Mansvelder, Huibert D; de Kock, Christiaan P J; Segev, Idan

2017-01-01

Abstract There have been few quantitative characterizations of the morphological, biophysical, and cable properties of neurons in the human neocortex. We employed feature-based statistical methods on a rare data set of 60 3D reconstructed pyramidal neurons from L2 and L3 in the human temporal cortex (HL2/L3 PCs) removed after brain surgery. Of these cells, 25 neurons were also characterized physiologically. Thirty-two morphological features were analyzed (e.g., dendritic surface area, 36 333 ± 18 157 μm2; number of basal trees, 5.55 ± 1.47; dendritic diameter, 0.76 ± 0.28 μm). Eighteen features showed a significant gradual increase with depth from the pia (e.g., dendritic length and soma radius). The other features showed weak or no correlation with depth (e.g., dendritic diameter). The basal dendritic terminals in HL2/L3 PCs are particularly elongated, enabling multiple nonlinear processing units in these dendrites. Unlike the morphological features, the active biophysical features (e.g., spike shapes and rates) and passive/cable features (e.g., somatic input resistance, 47.68 ± 15.26 MΩ, membrane time constant, 12.03 ± 1.79 ms, average dendritic cable length, 0.99 ± 0.24) were depth-independent. A novel descriptor for apical dendritic topology yielded 2 distinct classes, termed hereby as “slim-tufted” and “profuse-tufted” HL2/L3 PCs; the latter class tends to fire at higher rates. Thus, our morpho-electrotonic analysis shows 2 distinct classes of HL2/L3 PCs. PMID:28968789
The neuronal structure of paramamillary nuclei in Bison bonasus: Nissl and Golgi pictures.

PubMed

Robak, A; Szteyn, S; Równiak, M

1998-01-01

The studies were carried out on the hypothalamus of bison bonasus aged 2 and 3 months. Sections were made by means of Bagiński's technique and Nissl and Klüver-Barrera methods. Four types of neurons were distinguished in the paramamillary nuclei: nucleus supramamillaris (Sm) and nucleus tuberomammillaris pars posterior (Tmp). Type I, small and medium-size, triangular or fusiform cells, which have 2-3 slender, poorly ramified dendrites; typical leptodendritic neurons. Type II, medium size neurons with quadrangular or spindle-shaped perikaryons. Most of them have 3-4 thick dendritic trunks with ramifying relatively long dendrites. These cells show stalked-appearance and possess different appendages sparsely distributed. Type III is similar to type II, but is made of medium-size to large multipolar cells having quadrangular, triangular or fusiform perikaryons and relatively short dendrites. Type IV, small and medium-size, globular cells with 2 or 3 dendritic trunks, which dichotomously subdivide into quaternary dendrites. In all types of neurons, axons emerge from the perikaryon or initial portion of a dendritic trunk. Type I was found in both studied nuclei. Types II and III constitute mainly the nucleus tuberomamillaris pars posterior. Type IV preponderate in the nucleus supramamillaris. The characteristic feature of Tmp cells, in Nissl picture was irregular contour of their somas and clumps of rough Nisls granules, which appear to lie outside the perikaryons. In Sm there were also lightly stained small rounded cells having both small amount of the cytoplasm and tigroid matter.
Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor

PubMed Central

1992-01-01

Antigen-presenting, major histocompatibility complex (MHC) class II- rich dendritic cells are known to arise from bone marrow. However, marrow lacks mature dendritic cells, and substantial numbers of proliferating less-mature cells have yet to be identified. The methodology for inducing dendritic cell growth that was recently described for mouse blood now has been modified to MHC class II- negative precursors in marrow. A key step is to remove the majority of nonadherent, newly formed granulocytes by gentle washes during the first 2-4 d of culture. This leaves behind proliferating clusters that are loosely attached to a more firmly adherent "stroma." At days 4-6 the clusters can be dislodged, isolated by 1-g sedimentation, and upon reculture, large numbers of dendritic cells are released. The latter are readily identified on the basis of their distinct cell shape, ultrastructure, and repertoire of antigens, as detected with a panel of monoclonal antibodies. The dendritic cells express high levels of MHC class II products and act as powerful accessory cells for initiating the mixed leukocyte reaction. Neither the clusters nor mature dendritic cells are generated if macrophage colony-stimulating factor rather than granulocyte/macrophage colony-stimulating factor (GM-CSF) is applied. Therefore, GM-CSF generates all three lineages of myeloid cells (granulocytes, macrophages, and dendritic cells). Since > 5 x 10(6) dendritic cells develop in 1 wk from precursors within the large hind limb bones of a single animal, marrow progenitors can act as a major source of dendritic cells. This feature should prove useful for future molecular and clinical studies of this otherwise trace cell type. PMID:1460426
Models and simulation of 3D neuronal dendritic trees using Bayesian networks.

PubMed

López-Cruz, Pedro L; Bielza, Concha; Larrañaga, Pedro; Benavides-Piccione, Ruth; DeFelipe, Javier

2011-12-01

Neuron morphology is crucial for neuronal connectivity and brain information processing. Computational models are important tools for studying dendritic morphology and its role in brain function. We applied a class of probabilistic graphical models called Bayesian networks to generate virtual dendrites from layer III pyramidal neurons from three different regions of the neocortex of the mouse. A set of 41 morphological variables were measured from the 3D reconstructions of real dendrites and their probability distributions used in a machine learning algorithm to induce the model from the data. A simulation algorithm is also proposed to obtain new dendrites by sampling values from Bayesian networks. The main advantage of this approach is that it takes into account and automatically locates the relationships between variables in the data instead of using predefined dependencies. Therefore, the methodology can be applied to any neuronal class while at the same time exploiting class-specific properties. Also, a Bayesian network was defined for each part of the dendrite, allowing the relationships to change in the different sections and to model heterogeneous developmental factors or spatial influences. Several univariate statistical tests and a novel multivariate test based on Kullback-Leibler divergence estimation confirmed that virtual dendrites were similar to real ones. The analyses of the models showed relationships that conform to current neuroanatomical knowledge and support model correctness. At the same time, studying the relationships in the models can help to identify new interactions between variables related to dendritic morphology.

"Subpial Fan Cell" - A Class of Calretinin Neuron in Layer 1 of Adult Monkey Prefrontal Cortex.

PubMed

Gabbott, Paul L A

2016-01-01

Layer 1 of the cortex contains populations of neurochemically distinct neurons and afferent fibers which markedly affect neural activity in the apical dendritic tufts of pyramidal cells. Understanding the causal mechanisms requires knowledge of the cellular architecture and synaptic organization of layer 1. This study has identified eight morphological classes of calretinin immunopositive (CRet+) neurons (including Cajal-Retzius cells) in layer 1 of the prefrontal cortex (PFC) in adult monkey (Macaca fasicularis), with a distinct class - termed "subpial fan (SPF) cell" - described in detail. SPF cells were rare horizontal unipolar CRet+ cells located directly beneath the pia with a single thick primary dendrite that branched into a characteristic fan-like dendritic tree tangential to the pial surface. Dendrites had spines, filamentous processes and thorny branchlets. SPF cells lay millimeters apart with intralaminar axons that ramified widely in upper layer 1. Such cells were GABA immunonegative (-) and occurred in areas beyond PFC. Interspersed amidst SPF cells displaying normal structural integrity were degenerating CRet+ neurons (including SPF cells) and clumps of lipofuscin-rich cellular debris. The number of degenerating SPF cells increased during adulthood. Ultrastructural analyses indicated SPF cell somata received asymmetric (A - presumed excitatory) and symmetric (S - presumed inhibitory) synaptic contacts. Proximal dendritic shafts received mainly S-type and distal shafts mostly A-type input. All dendritic thorns and most dendritic spines received both synapse types. The tangential areal density of SPF cell axonal varicosities varied radially from parent somata - with dense clusters in more distal zones. All boutons formed A-type contacts with CRet- structures. The main post-synaptic targets were dendritic shafts (67%; mostly spine-bearing) and dendritic spines (24%). SPF-SPF cell innervation was not observed. Morphometry of SPF cells indicated a unique class of CRet+/GABA- neuron in adult monkey PFC - possibly a subtype of persisting Cajal-Retzius cell. The distribution and connectivity of SPF cells suggest they act as integrative hubs in upper layer 1 during postnatal maturation. The main synaptic output of SPF cells likely provides a transminicolumnar excitatory influence across swathes of apical dendritic tufts - thus affecting information processing in discrete patches of layer 1 in adult monkey PFC.
Morphology, classification, and distribution of the projection neurons in the dorsal lateral geniculate nucleus of the rat.

PubMed

Ling, Changying; Hendrickson, Michael L; Kalil, Ronald E

2012-01-01

The morphology of confirmed projection neurons in the dorsal lateral geniculate nucleus (dLGN) of the rat was examined by filling these cells retrogradely with biotinylated dextran amine (BDA) injected into the visual cortex. BDA-labeled projection neurons varied widely in the shape and size of their cell somas, with mean cross-sectional areas ranging from 60-340 µm(2). Labeled projection neurons supported 7-55 dendrites that spanned up to 300 µm in length and formed dendritic arbors with cross-sectional areas of up to 7.0 × 10(4) µm(2). Primary dendrites emerged from cell somas in three broad patterns. In some dLGN projection neurons, primary dendrites arise from the cell soma at two poles spaced approximately 180° apart. In other projection neurons, dendrites emerge principally from one side of the cell soma, while in a third group of projection neurons primary dendrites emerge from the entire perimeter of the cell soma. Based on these three distinct patterns in the distribution of primary dendrites from cell somas, we have grouped dLGN projection neurons into three classes: bipolar cells, basket cells and radial cells, respectively. The appendages seen on dendrites also can be grouped into three classes according to differences in their structure. Short "tufted" appendages arise mainly from the distal branches of dendrites; "spine-like" appendages, fine stalks with ovoid heads, typically are seen along the middle segments of dendrites; and "grape-like" appendages, short stalks that terminate in a cluster of ovoid bulbs, appear most often along the proximal segments of secondary dendrites of neurons with medium or large cell somas. While morphologically diverse dLGN projection neurons are intermingled uniformly throughout the nucleus, the caudal pole of the dLGN contains more small projection neurons of all classes than the rostral pole.
Contribution of sublinear and supralinear dendritic integration to neuronal computations

PubMed Central

Tran-Van-Minh, Alexandra; Cazé, Romain D.; Abrahamsson, Therése; Cathala, Laurence; Gutkin, Boris S.; DiGregorio, David A.

2015-01-01

Nonlinear dendritic integration is thought to increase the computational ability of neurons. Most studies focus on how supralinear summation of excitatory synaptic responses arising from clustered inputs within single dendrites result in the enhancement of neuronal firing, enabling simple computations such as feature detection. Recent reports have shown that sublinear summation is also a prominent dendritic operation, extending the range of subthreshold input-output (sI/O) transformations conferred by dendrites. Like supralinear operations, sublinear dendritic operations also increase the repertoire of neuronal computations, but feature extraction requires different synaptic connectivity strategies for each of these operations. In this article we will review the experimental and theoretical findings describing the biophysical determinants of the three primary classes of dendritic operations: linear, sublinear, and supralinear. We then review a Boolean algebra-based analysis of simplified neuron models, which provides insight into how dendritic operations influence neuronal computations. We highlight how neuronal computations are critically dependent on the interplay of dendritic properties (morphology and voltage-gated channel expression), spiking threshold and distribution of synaptic inputs carrying particular sensory features. Finally, we describe how global (scattered) and local (clustered) integration strategies permit the implementation of similar classes of computations, one example being the object feature binding problem. PMID:25852470
Feline atopic dermatitis. A model for Langerhans cell participation in disease pathogenesis.

PubMed

Roosje, P J; Whitaker-Menezes, D; Goldschmidt, M H; Moore, P F; Willemse, T; Murphy, G F

1997-10-01

Atopic dermatitis is a disorder characterized by cutaneous exanthemata as a consequence of exaggerated eczematous reactions to topical and systemic allergens. Langerhans cells, expressing CD1a and HLA-DR, and dermal dendritic cells, expressing HLA-DR, are known to be potent antigen-presenting cells and are thought to play an important role in the pathogenesis of atopic dermatitis. The immunophenotype of lesional skin in atopic dermatitis in humans involves increased numbers of CD1a+/MHC class II+ dendritic cells in addition to activated T cells, mast cells, and macrophages. To establish feline skin as a model for the study of human atopic dermatitis, and to elucidate the role of dendritic cells in feline atopic dermatitis, we investigated the presence of CD1a+ cells and MHC class II+ cells in the epidermis and dermis of lesional feline skin and in skin of healthy control animals. Immunohistochemistry revealed that MHC class II+ epidermal dendritic cells were CD1a+ in normal feline skin and significantly increased numbers of CD1a+ cells and MHC class II+ cells were present in the epidermis and dermis of lesional skin. These data provide the first correlative documentation of CD1a expression by feline dendritic cells containing Birbeck granules, and indicate the utility of feline skin in the study of human cutaneous atopy.
“Subpial Fan Cell” — A Class of Calretinin Neuron in Layer 1 of Adult Monkey Prefrontal Cortex

PubMed Central

Gabbott, Paul L. A.

2016-01-01

Layer 1 of the cortex contains populations of neurochemically distinct neurons and afferent fibers which markedly affect neural activity in the apical dendritic tufts of pyramidal cells. Understanding the causal mechanisms requires knowledge of the cellular architecture and synaptic organization of layer 1. This study has identified eight morphological classes of calretinin immunopositive (CRet+) neurons (including Cajal-Retzius cells) in layer 1 of the prefrontal cortex (PFC) in adult monkey (Macaca fasicularis), with a distinct class — termed “subpial fan (SPF) cell” — described in detail. SPF cells were rare horizontal unipolar CRet+ cells located directly beneath the pia with a single thick primary dendrite that branched into a characteristic fan-like dendritic tree tangential to the pial surface. Dendrites had spines, filamentous processes and thorny branchlets. SPF cells lay millimeters apart with intralaminar axons that ramified widely in upper layer 1. Such cells were GABA immunonegative (-) and occurred in areas beyond PFC. Interspersed amidst SPF cells displaying normal structural integrity were degenerating CRet+ neurons (including SPF cells) and clumps of lipofuscin-rich cellular debris. The number of degenerating SPF cells increased during adulthood. Ultrastructural analyses indicated SPF cell somata received asymmetric (A — presumed excitatory) and symmetric (S — presumed inhibitory) synaptic contacts. Proximal dendritic shafts received mainly S-type and distal shafts mostly A-type input. All dendritic thorns and most dendritic spines received both synapse types. The tangential areal density of SPF cell axonal varicosities varied radially from parent somata — with dense clusters in more distal zones. All boutons formed A-type contacts with CRet- structures. The main post-synaptic targets were dendritic shafts (67%; mostly spine-bearing) and dendritic spines (24%). SPF-SPF cell innervation was not observed. Morphometry of SPF cells indicated a unique class of CRet+/GABA- neuron in adult monkey PFC — possibly a subtype of persisting Cajal-Retzius cell. The distribution and connectivity of SPF cells suggest they act as integrative hubs in upper layer 1 during postnatal maturation. The main synaptic output of SPF cells likely provides a transminicolumnar excitatory influence across swathes of apical dendritic tufts — thus affecting information processing in discrete patches of layer 1 in adult monkey PFC. PMID:27147978
Separate transcriptionally regulated pathways specify distinct classes of sister dendrites in a nociceptive neuron.

PubMed

O'Brien, Barbara M J; Palumbos, Sierra D; Novakovic, Michaela; Shang, Xueying; Sundararajan, Lakshmi; Miller, David M

2017-12-15

The dendritic processes of nociceptive neurons transduce external signals into neurochemical cues that alert the organism to potentially damaging stimuli. The receptive field for each sensory neuron is defined by its dendritic arbor, but the mechanisms that shape dendritic architecture are incompletely understood. Using the model nociceptor, the PVD neuron in C. elegans, we determined that two types of PVD lateral branches project along the dorsal/ventral axis to generate the PVD dendritic arbor: (1) Pioneer dendrites that adhere to the epidermis, and (2) Commissural dendrites that fasciculate with circumferential motor neuron processes. Previous reports have shown that the LIM homeodomain transcription factor MEC-3 is required for all higher order PVD branching and that one of its targets, the claudin-like membrane protein HPO-30, preferentially promotes outgrowth of pioneer branches. Here, we show that another MEC-3 target, the conserved TFIIA-like zinc finger transcription factor EGL-46, adopts the alternative role of specifying commissural dendrites. The known EGL-46 binding partner, the TEAD transcription factor EGL-44, is also required for PVD commissural branch outgrowth. Double mutants of hpo-30 and egl-44 show strong enhancement of the lateral branching defect with decreased numbers of both pioneer and commissural dendrites. Thus, HPO-30/Claudin and EGL-46/EGL-44 function downstream of MEC-3 and in parallel acting pathways to direct outgrowth of two distinct classes of PVD dendritic branches. Copyright © 2017 Elsevier Inc. All rights reserved.
Morphological characterization of rat entorhinal neurons in vivo: soma-dendritic structure and axonal domains.

PubMed

Lingenhöhl, K; Finch, D M

1991-01-01

We used in vivo intracellular labeling with horseradish peroxidase in order to study the soma-dendritic morphology and axonal projections of rat entorhinal neurons. The cells responded to hippocampal stimulation with inhibitory postsynaptic potentials, and thus likely received direct or indirect hippocampal input. All cells (n = 24) showed extensive dendritic domains that extended in some cases for more than 1 mm. The dendrites of layer II neurons were largely restricted to layers I and II or layers I-III, while the dendrites of deeper cells could extend through all cortical layers. Computed 3D rotations showed that the basilar dendrites of deep pyramids extended roughly parallel to the cortical layering, and that they were mostly confined to the layer containing the soma and layers immediately adjacent. Total dendritic lengths averaged 9.8 mm +/- 3.8 (SD), and ranged from 5 mm to more than 18 mm. Axonal processes could be visualized in 21 cells. Most of these showed axonal branching within the entorhinal cortex, sometimes extensive. Efferent axonal domains were reconstructed in detail in 3 layer II stellate cells. All 3 projected axons across the subicular complex to the dentate gyrus. One of these cells showed an extensive net-like axonal domain that also projected to several other structures, including the hippocampus proper, subicular complex, and the amygdalo-piriform transition area. The axons of layer III and IV cells projected to the angular bundle, where they continued in a rostral direction. In contrast to the layer II, III and IV cells, no efferent axonal branches leaving the entorhinal cortex could be visualized in 5 layer V neurons. The data indicate that entorhinal neurons can integrate input from a considerable volume of entorhinal cortex by virtue of their extensive dendritic domains, and provide a further basis for specifying the layers in which cells receive synaptic input. The extensive axonal branching pattern seen in most of the cells would support divergent propagation of their activity.
Direct antigen presentation and gap junction mediated cross-presentation during apoptosis.

PubMed

Pang, Baoxu; Neijssen, Joost; Qiao, Xiaohang; Janssen, Lennert; Janssen, Hans; Lippuner, Christoph; Neefjes, Jacques

2009-07-15

MHC class I molecules present peptides from endogenous proteins. Ags can also be presented when derived from extracellular sources in the form of apoptotic bodies. Cross-presentation of such Ags by dendritic cells is required for proper CTL responses. The fate of Ags in cells initiated for apoptosis is unclear as is the mechanism of apoptosis-derived Ag transfer into dendritic cells. Here we show that novel Ags can be generated by caspases and be presented by MHC class I molecules of apoptotic cells. Since gap junctions function until apoptotic cells remodel to form apoptotic bodies, transfer and cross-presentation of apoptotic peptides by neighboring and dendritic cells occurs. We thus define a novel phase in classical Ag presentation and cross-presentation by MHC class I molecules: presentation of Ags created by caspase activities in cells in apoptosis.
Drosophila Nociceptors Mediate Larval Aversion to Dry Surface Environments Utilizing Both the Painless TRP Channel and the DEG/ENaC Subunit, PPK1

PubMed Central

Johnson, Wayne A.; Carder, Justin W.

2012-01-01

A subset of sensory neurons embedded within the Drosophila larval body wall have been characterized as high-threshold polymodal nociceptors capable of responding to noxious heat and noxious mechanical stimulation. They are also sensitized by UV-induced tissue damage leading to both thermal hyperalgesia and allodynia very similar to that observed in vertebrate nociceptors. We show that the class IV multiple-dendritic(mdIV) nociceptors are also required for a normal larval aversion to locomotion on to a dry surface environment. Drosophila melanogaster larvae are acutely susceptible to desiccation displaying a strong aversion to locomotion on dry surfaces severely limiting the distance of movement away from a moist food source. Transgenic inactivation of mdIV nociceptor neurons resulted in larvae moving inappropriately into regions of low humidity at the top of the vial reflected as an increased overall pupation height and larval desiccation. This larval lethal desiccation phenotype was not observed in wild-type controls and was completely suppressed by growth in conditions of high humidity. Transgenic hyperactivation of mdIV nociceptors caused a reciprocal hypersensitivity to dry surfaces resulting in drastically decreased pupation height but did not induce the writhing nocifensive response previously associated with mdIV nociceptor activation by noxious heat or harsh mechanical stimuli. Larvae carrying mutations in either the Drosophila TRP channel, Painless, or the degenerin/epithelial sodium channel subunit Pickpocket1(PPK1), both expressed in mdIV nociceptors, showed the same inappropriate increased pupation height and lethal desiccation observed with mdIV nociceptor inactivation. Larval aversion to dry surfaces appears to utilize the same or overlapping sensory transduction pathways activated by noxious heat and harsh mechanical stimulation but with strikingly different sensitivities and disparate physiological responses. PMID:22403719
WASp-dependent actin cytoskeleton stability at the dendritic cell immunological synapse is required for extensive, functional T cell contacts.

PubMed

Malinova, Dessislava; Fritzsche, Marco; Nowosad, Carla R; Armer, Hannah; Munro, Peter M G; Blundell, Michael P; Charras, Guillaume; Tolar, Pavel; Bouma, Gerben; Thrasher, Adrian J

2016-05-01

The immunological synapse is a highly structured and molecularly dynamic interface between communicating immune cells. Although the immunological synapse promotes T cell activation by dendritic cells, the specific organization of the immunological synapse on the dendritic cell side in response to T cell engagement is largely unknown. In this study, confocal and electron microscopy techniques were used to investigate the role of dendritic cell actin regulation in immunological synapse formation, stabilization, and function. In the dendritic cell-restricted absence of the Wiskott-Aldrich syndrome protein, an important regulator of the actin cytoskeleton in hematopoietic cells, the immunological synapse contact with T cells occupied a significantly reduced surface area. At a molecular level, the actin network localized to the immunological synapse exhibited reduced stability, in particular, of the actin-related protein-2/3-dependent, short-filament network. This was associated with decreased polarization of dendritic cell-associated ICAM-1 and MHC class II, which was partially dependent on Wiskott-Aldrich syndrome protein phosphorylation. With the use of supported planar lipid bilayers incorporating anti-ICAM-1 and anti-MHC class II antibodies, the dendritic cell actin cytoskeleton organized into recognizable synaptic structures but interestingly, formed Wiskott-Aldrich syndrome protein-dependent podosomes within this area. These findings demonstrate that intrinsic dendritic cell cytoskeletal remodeling is a key regulatory component of normal immunological synapse formation, likely through consolidation of adhesive interaction and modulation of immunological synapse stability. © The Author(s).
Histone Deacetylase Rpd3 Regulates Olfactory Projection Neuron Dendrite Targeting via the Transcription Factor Prospero

PubMed Central

Tea, Joy S.; Chihara, Takahiro; Luo, Liqun

2010-01-01

Compared to the mechanisms of axon guidance, relatively little is known about the transcriptional control of dendrite guidance. The Drosophila olfactory system with its stereotyped organization provides an excellent model to study the transcriptional control of dendrite wiring specificity. Each projection neuron (PN) targets its dendrites to a specific glomerulus in the antennal lobe and its axon stereotypically to higher brain centers. Using a forward genetic screen, we identified a mutation in Rpd3 that disrupts PN targeting specificity. Rpd3 encodes a class I histone deacetylase (HDAC) homologous to mammalian HDAC1 and HDAC2. Rpd3−/− PN dendrites that normally target to a dorsolateral glomerulus mistarget to medial glomeruli in the antennal lobe, and axons exhibit a severe overbranching phenotype. These phenotypes can be rescued by postmitotic expression of Rpd3 but not HDAC3, the only other class I HDAC in Drosophila. Furthermore, disruption of the atypical homeodomain transcription factor Prospero (Pros) yields similar phenotypes, which can be rescued by Pros expression in postmitotic neurons. Strikingly, overexpression of Pros can suppress Rpd3−/− phenotypes. Our study suggests a specific function for the general chromatin remodeling factor Rpd3 in regulating dendrite targeting in neurons, largely through the postmitotic action of the Pros transcription factor. PMID:20660276
Classic cadherin expressions balance postnatal neuronal positioning and dendrite dynamics to elaborate the specific cytoarchitecture of the mouse cortical area.

PubMed

Egusa, Saki F; Inoue, Yukiko U; Asami, Junko; Terakawa, Youhei W; Hoshino, Mikio; Inoue, Takayoshi

2016-04-01

A unique feature of the mammalian cerebral cortex is in its tangential parcellation via anatomical and functional differences. However, the cellular and/or molecular machinery involved in cortical arealization remain largely unknown. Here we map expression profiles of classic cadherins in the postnatal mouse barrel field of the primary somatosensory area (S1BF) and generate a novel bacterial artificial chromosome transgenic (BAC-Tg) mouse line selectively illuminating nuclei of cadherin-6 (Cdh6)-expressing layer IV barrel neurons to confirm that tangential cellular assemblage of S1BF is established by postnatal day 5 (P5). When we electroporate the cadherins expressed in both barrel neurons and thalamo-cortical axon (TCA) terminals limited to the postnatal layer IV neurons, S1BF cytoarchitecture is disorganized with excess elongation of dendrites at P7. Upon delivery of dominant negative molecules for all classic cadherins, tangential cellular positioning and biased dendritic arborization of barrel neurons are significantly altered. These results underscore the value of classic cadherin-mediated sorting among neuronal cell bodies, dendrites and TCA terminals in postnatally elaborating the S1BF-specific tangential cytoarchitecture. Additionally, how the "protocortex" machinery affects classic cadherin expression profiles in the process of cortical arealization is examined and discussed. Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
The expression and function of cathepsin E in dendritic cells.

PubMed

Chain, Benjamin M; Free, Paul; Medd, Patrick; Swetman, Claire; Tabor, Alethea B; Terrazzini, Nadia

2005-02-15

Cathepsin E is an aspartic proteinase that has been implicated in Ag processing within the class II MHC pathway. In this study, we document the presence of cathepsin E message and protein in human myeloid dendritic cells, the preeminent APCs of the immune system. Cathepsin E is found in a perinuclear compartment, which is likely to form part of the endoplasmic reticulum, and also a peripheral compartment just beneath the cell membrane, with a similar distribution to that of Texas Red-dextran within 2 min of endocytosis. To investigate the function of cathepsin E in processing, a new soluble targeted inhibitor was synthesized by linking the microbial aspartic proteinase inhibitor pepstatin to mannosylated BSA via a cleavable disulfide linker. This inhibitor was shown to block cathepsin D/E activity in cell-free assays and within dendritic cells. The inhibitor blocked the ability of dendritic cells from wild-type as well as cathepsin D-deficient mice to present intact OVA, but not an OVA-derived peptide, to cognate T cells. The data therefore support the hypothesis that cathepsin E has an important nonredundant role in the class II MHC Ag processing pathway within dendritic cells.
Treatment with chemotherapy and dendritic cells pulsed with multiple Wilms' tumor 1 (WT1)-specific MHC class I/II-restricted epitopes for pancreatic cancer.

PubMed

Koido, Shigeo; Homma, Sadamu; Okamoto, Masato; Takakura, Kazuki; Mori, Masako; Yoshizaki, Shinji; Tsukinaga, Shintaro; Odahara, Shunichi; Koyama, Seita; Imazu, Hiroo; Uchiyama, Kan; Kajihara, Mikio; Arakawa, Hiroshi; Misawa, Takeyuki; Toyama, Yoichi; Yanagisawa, Satoru; Ikegami, Masahiro; Kan, Shin; Hayashi, Kazumi; Komita, Hideo; Kamata, Yuko; Ito, Masaki; Ishidao, Takefumi; Yusa, Sei-Ichi; Shimodaira, Shigetaka; Gong, Jianlin; Sugiyama, Haruo; Ohkusa, Toshifumi; Tajiri, Hisao

2014-08-15

We performed a phase I trial to investigate the safety, clinical responses, and Wilms' tumor 1 (WT1)-specific immune responses following treatment with dendritic cells (DC) pulsed with a mixture of three types of WT1 peptides, including both MHC class I and II-restricted epitopes, in combination with chemotherapy. Ten stage IV patients with pancreatic ductal adenocarcinoma (PDA) and 1 patient with intrahepatic cholangiocarcinoma (ICC) who were HLA-positive for A*02:01, A*02:06, A*24:02, DRB1*04:05, DRB1*08:03, DRB1*15:01, DRB1*15:02, DPB1*05:01, or DPB1*09:01 were enrolled. The patients received one course of gemcitabine followed by biweekly intradermal vaccinations with mature DCs pulsed with MHC class I (DC/WT1-I; 2 PDA and 1 ICC), II (DC/WT1-II; 1 PDA), or I/II-restricted WT1 peptides (DC/WT1-I/II; 7 PDA), and gemcitabine. The combination therapy was well tolerated. WT1-specific IFNγ-producing CD4(+) T cells were significantly increased following treatment with DC/WT1-I/II. WT1 peptide-specific delayed-type hypersensitivity (DTH) was detected in 4 of the 7 patients with PDA vaccinated with DC/WT1-I/II and in 0 of the 3 patients with PDA vaccinated with DC/WT1-I or DC/WT1-II. The WT1-specific DTH-positive patients showed significantly improved overall survival (OS) and progression-free survival (PFS) compared with the negative control patients. In particular, all 3 patients with PDA with strong DTH reactions had a median OS of 717 days. The activation of WT1-specific immune responses by DC/WT1-I/II combined with chemotherapy may be associated with disease stability in advanced pancreatic cancer. ©2014 American Association for Cancer Research.
Alterations of epidermal proliferation and cytokeratin expression in skin biopsies from heavy draught horses with chronic pastern dermatitis.

PubMed

Geburek, Florian; Ohnesorge, Bernhard; Deegen, Eckehard; Doeleke, Renate; Hewicker-Trautwein, Marion

2005-12-01

We report the historical, clinical and histopathological characteristics of skin lesions in biopsies from 37 heavy draught horses with chronic pastern dermatitis. The skin lesions were divided into four macroscopic groups: scaling (group I, n=5), hyperkeratotic and hyperplastic plaque-like lesions (group II, n=14), nodular skin masses (group III, n=16) and verrucous skin lesions (group IV, n=2). The principal histological findings were hyperkeratosis and epidermal hyperplasia. There was a gradual increase in epidermal hyperplasia from groups I to IV, suggesting that the lesions represent different stages of disease. In all cases, there was perivascular dermatitis dominated by T lymphocytes with an increase in MHC class II-positive dendritic-like cells. Immunohistochemical labelling for cytokeratins CK5/6(4), CK10 and CK14 indicated a change in their expression pattern. This correlated with the degree of epidermal hyperplasia, indicating abnormal differentiation of keratinocytes. There was a statistically significant correlation between the severity of skin lesions and several other factors including increasing age, increasing cannon circumference, prominence of anatomical structures such as fetlock tufts of hairs, ergots and chestnuts, and bulges in the fetlock region.
A new computational approach to simulate pattern formation in Paenibacillus dendritiformis bacterial colonies

NASA Astrophysics Data System (ADS)

Tucker, Laura Jane

Under the harsh conditions of limited nutrient and hard growth surface, Paenibacillus dendritiformis in agar plates form two classes of patterns (morphotypes). The first class, called the dendritic morphotype, has radially directed branches. The second class, called the chiral morphotype, exhibits uniform handedness. The dendritic morphotype has been modeled successfully using a continuum model on a regular lattice; however, a suitable computational approach was not known to solve a continuum chiral model. This work details a new computational approach to solving the chiral continuum model of pattern formation in P. dendritiformis. The approach utilizes a random computational lattice and new methods for calculating certain derivative terms found in the model.
Electrolyte-free Amperometric Immunosensor using a Dendritic Nanotip.

PubMed

Kim, Jong-Hoon; Hiraiwa, Morgan; Lee, Hyun-Boo; Lee, Kyong-Hoon; Cangelosi, Gerard A; Chung, Jae-Hyun

2013-01-01

Electric detection using a nanocomponent may lead to platforms for rapid and simple biosensing. Sensors composed of nanotips or nanodots have been described for highly sensitive amperometry enabled by confined geometry. However, both fabrication and use of nanostructured sensors remain challenging. This paper describes a dendritic nanotip used as an amperometric biosensor for highly sensitive detection of target bacteria. A dendritic nanotip is structured by Si nanowires coated with single-walled carbon nanotubes (SWCNTs) for generation of a high electric field. For reliable measurement using the dendritic structure, Si nanowires were uniformly fabricated by ultraviolet (UV) lithography and etching. The dendritic structure effectively increased the electric current density near the terminal end of the nanotip according to numerical computation. The electrical characteristics of a dendritic nanotip with additional protein layers was studied by cyclic voltammetry and I-V measurement in deionized (DI) water. When the target bacteria dielectrophoretically captured onto a nanotip were bound with fluorescence antibodies, the electric current through DI water decreased. Measurement results were consistent with fluorescence- and electron microscopy. The sensitivity of the amperometry was 10 cfu/sample volume (10 3 cfu/mL), which was equivalent to the more laborious fluorescence measurement method. The simple configuration of a dendritic nanotip can potentially offer an electrolyte-free detection platform for sensitive and rapid biosensors.
A population of large neurons in laminae III and IV of the rat spinal cord that have long dorsal dendrites and lack the neurokinin 1 receptor

PubMed Central

Polgár, Erika; Thomson, Suzanne; Maxwell, David J; Al-Khater, Khulood; Todd, Andrew J

2007-01-01

The dorsal horn of the rat spinal cord contains a population of large neurons with cell bodies in laminae III or IV, that express the neurokinin 1 receptor (NK1r) and have long dorsal dendrites that branch extensively within the superficial laminae. In this study, we have identified a separate population of neurons that have similar dendritic morphology, but lack the NK1r. These cells also differ from the NK1r-expressing neurons in that they have significantly fewer contacts from substance P-containing axons and are not retrogradely labelled following injection of tracer into the caudal ventrolateral medulla. We also provide evidence that these cells do not belong to the postsynaptic dorsal column pathway or the spinothalamic tract. It is therefore likely that these cells do not have supraspinal projections. They may provide a route through which information transmitted by C fibres that lack neuropeptides is conveyed to deeper laminae. The present findings demonstrate the need for caution when attempting to classify neurons solely on the basis of somatodendritic morphology. PMID:17880393
Democracy-independence trade-off in oscillating dendrites and its implications for grid cells.

PubMed

Remme, Michiel W H; Lengyel, Máté; Gutkin, Boris S

2010-05-13

Dendritic democracy and independence have been characterized for near-instantaneous processing of synaptic inputs. However, a wide class of neuronal computations requires input integration on long timescales. As a paradigmatic example, entorhinal grid fields have been thought to be generated by the democratic summation of independent dendritic oscillations performing direction-selective path integration. We analyzed how multiple dendritic oscillators embedded in the same neuron integrate inputs separately and determine somatic membrane voltage jointly. We found that the interaction of dendritic oscillations leads to phase locking, which sets an upper limit on the timescale for independent input integration. Factors that increase this timescale also decrease the influence that the dendritic oscillations exert on somatic voltage. In entorhinal stellate cells, interdendritic coupling dominates and causes these cells to act as single oscillators. Our results suggest a fundamental trade-off between local and global processing in dendritic trees integrating ongoing signals. Copyright 2010 Elsevier Inc. All rights reserved.
40 CFR 144.23 - Class IV wells.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 23 2011-07-01 2011-07-01 false Class IV wells. 144.23 Section 144.23... INJECTION CONTROL PROGRAM Authorization of Underground Injection by Rule § 144.23 Class IV wells. (a) Injection into existing Class IV wells is authorized for up to six months after approval or promulgation of...

40 CFR 144.23 - Class IV wells.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 24 2012-07-01 2012-07-01 false Class IV wells. 144.23 Section 144.23... INJECTION CONTROL PROGRAM Authorization of Underground Injection by Rule § 144.23 Class IV wells. (a) Injection into existing Class IV wells is authorized for up to six months after approval or promulgation of...
40 CFR 144.23 - Class IV wells.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Class IV wells. 144.23 Section 144.23... INJECTION CONTROL PROGRAM Authorization of Underground Injection by Rule § 144.23 Class IV wells. (a) Injection into existing Class IV wells is authorized for up to six months after approval or promulgation of...
Spinal cord neuron classes in embryos of the smooth newt Triturus vulgaris: a horseradish peroxidase and immunocytochemical study.

PubMed

Harper, C E; Roberts, A

1993-04-29

Spinal cord neurons were investigated in embryos of Triturus vulgaris, the smooth newt, just prior to hatching. These embryos can swim if freed from their egg membranes. Horseradish peroxidase (HRP) labelling, together with GABA and glycine immunocytochemistry (ICC), revealed nine distinct anatomical classes of neuron. 1. Ventrolateral motoneurons with mainly dorsal dendrites, sometimes a descending central axon and peripheral axon innervating the trunk muscles. 2. Dorsal primary sensory Rohon-Beard neurons innervating skin and with dorsal ascending and descending axons in spinal cord. 3. Commissural interneurons with mid-cord unipolar soma, glycine-like immunoreactivity, dendrites on initial segment of ventral axon which crosses cord to ascend or branch. 4. Dorsolateral commissural interneurons with multipolar soma in dorsolateral position with dorsal dendrites and ventral axon which crosses and ascends or branches. 5. Giant dorsolateral commissural interneurons with large dorsolateral somata widely spaced (130-250 microns spacing) with process projecting dorsally to other side, dorsolateral dendrites and ventral axon which crosses to ascend and branch. 6. Dorsolateral ascending interneurons in dorsolateral position with multipolar soma and ascending axon on same side. 7. Ascending interneurons with unipolar soma, GABA-like immunoreactivity and ascending axon on same side. 8. Descending interneurons with bi- or multi-polar soma, extensive dorsal and ventral dendrites, and descending axon on same side. They may also have ascending axons. 9. Kolmer-Agduhr cerebrospinal fluid contacting neurons with cilia and microvilli in lateral corners of neural canal. GABA-like immunoreactivity, no dendrites and ascending axon. Eight of the nine cells classes were found to bear a marked resemblance to neurons previously described in zebrafish and Xenopus embryos in terms of their anatomy, distribution and immunoreactivity to GABA and glycine. Homologies and possible functions are discussed. Giant dorsolateral commissural neurons, were not found in Xenopus or teleosts but were present in Ambystoma mexicanum and Neoceratodus. The regular, possibly segmental longitudinal distribution pattern of these cells within the cord is unusual among amphibian spinal neurons.
Double-bromo and extraterminal (BET) domain proteins regulate dendrite morphology and mechanosensory function

PubMed Central

Bagley, Joshua A.; Yan, Zhiqiang; Zhang, Wei; Wildonger, Jill

2014-01-01

A complex array of genetic factors regulates neuronal dendrite morphology. Epigenetic regulation of gene expression represents a plausible mechanism to control pathways responsible for specific dendritic arbor shapes. By studying the Drosophila dendritic arborization (da) neurons, we discovered a role of the double-bromodomain and extraterminal (BET) family proteins in regulating dendrite arbor complexity. A loss-of-function mutation in the single Drosophila BET protein encoded by female sterile 1 homeotic [fs(1)h] causes loss of fine, terminal dendritic branches. Moreover, fs(1)h is necessary for the induction of branching caused by a previously identified transcription factor, Cut (Ct), which regulates subtype-specific dendrite morphology. Finally, disrupting fs(1)h function impairs the mechanosensory response of class III da sensory neurons without compromising the expression of the ion channel NompC, which mediates the mechanosensitive response. Thus, our results identify a novel role for BET family proteins in regulating dendrite morphology and a possible separation of developmental pathways specifying neural cell morphology and ion channel expression. Since the BET proteins are known to bind acetylated histone tails, these results also suggest a role of epigenetic histone modifications and the “histone code,” in regulating dendrite morphology. PMID:25184680
Two-Photon Na+ Imaging Reports Somatically Evoked Action Potentials in Rat Olfactory Bulb Mitral and Granule Cell Neurites.

PubMed

Ona-Jodar, Tiffany; Gerkau, Niklas J; Sara Aghvami, S; Rose, Christine R; Egger, Veronica

2017-01-01

Dendrodendritic synaptic interactions are a hallmark of neuronal processing in the vertebrate olfactory bulb. Many classes of olfactory bulb neurons including the principal mitral cells (MCs) and the axonless granule cells (GCs) dispose of highly efficient propagation of action potentials (AP) within their dendrites, from where they can release transmitter onto each other. So far, backpropagation in GC dendrites has been investigated indirectly via Ca 2+ imaging. Here, we used two-photon Na + imaging to directly report opening of voltage-gated sodium channels due to AP propagation in both cell types. To this end, neurons in acute slices from juvenile rat bulbs were filled with 1 mM SBFI via whole-cell patch-clamp. Calibration of SBFI signals revealed that a change in fluorescence Δ F / F by 10% corresponded to a Δ[Na + ] i of ∼22 mM. We then imaged proximal axon segments of MCs during somatically evoked APs (sAP). While single sAPs were detectable in ∼50% of axons, trains of 20 sAPs at 50 Hz always resulted in substantial Δ F / F of ∼15% (∼33 mM Δ[Na + ] i ). Δ F / F was significantly larger for 80 Hz vs. 50 Hz trains, and decayed with half-durations τ 1/2 ∼0.6 s for both frequencies. In MC lateral dendrites, AP trains yielded small Δ F / F of ∼3% (∼7 mM Δ[Na + ] i ). In GC apical dendrites and adjacent spines, single sAPs were not detectable. Trains resulted in an average dendritic Δ F / F of 7% (16 mM Δ[Na + ] i ) with τ 1/2 ∼1 s, similar for 50 and 80 Hz. Na + transients were indistinguishable between large GC spines and their adjacent dendrites. Cell-wise analysis revealed two classes of GCs with the first showing a decrease in Δ F / F along the dendrite with distance from the soma and the second an increase. These classes clustered with morphological parameters. Simulations of Δ[Na + ] i replicated these behaviors via negative and positive gradients in Na + current density, assuming faithful AP backpropagation. Such specializations of dendritic excitability might confer specific temporal processing capabilities to bulbar principal cell-GC subnetworks. In conclusion, we show that Na + imaging provides a valuable tool for characterizing AP invasion of MC axons and GC dendrites and spines.
Two-Photon Na+ Imaging Reports Somatically Evoked Action Potentials in Rat Olfactory Bulb Mitral and Granule Cell Neurites

PubMed Central

Ona-Jodar, Tiffany; Gerkau, Niklas J.; Sara Aghvami, S.; Rose, Christine R.; Egger, Veronica

2017-01-01

Dendrodendritic synaptic interactions are a hallmark of neuronal processing in the vertebrate olfactory bulb. Many classes of olfactory bulb neurons including the principal mitral cells (MCs) and the axonless granule cells (GCs) dispose of highly efficient propagation of action potentials (AP) within their dendrites, from where they can release transmitter onto each other. So far, backpropagation in GC dendrites has been investigated indirectly via Ca2+ imaging. Here, we used two-photon Na+ imaging to directly report opening of voltage-gated sodium channels due to AP propagation in both cell types. To this end, neurons in acute slices from juvenile rat bulbs were filled with 1 mM SBFI via whole-cell patch-clamp. Calibration of SBFI signals revealed that a change in fluorescence ΔF/F by 10% corresponded to a Δ[Na+]i of ∼22 mM. We then imaged proximal axon segments of MCs during somatically evoked APs (sAP). While single sAPs were detectable in ∼50% of axons, trains of 20 sAPs at 50 Hz always resulted in substantial ΔF/F of ∼15% (∼33 mM Δ[Na+]i). ΔF/F was significantly larger for 80 Hz vs. 50 Hz trains, and decayed with half-durations τ1/2 ∼0.6 s for both frequencies. In MC lateral dendrites, AP trains yielded small ΔF/F of ∼3% (∼7 mM Δ[Na+]i). In GC apical dendrites and adjacent spines, single sAPs were not detectable. Trains resulted in an average dendritic ΔF/F of 7% (16 mM Δ[Na+]i) with τ1/2 ∼1 s, similar for 50 and 80 Hz. Na+ transients were indistinguishable between large GC spines and their adjacent dendrites. Cell-wise analysis revealed two classes of GCs with the first showing a decrease in ΔF/F along the dendrite with distance from the soma and the second an increase. These classes clustered with morphological parameters. Simulations of Δ[Na+]i replicated these behaviors via negative and positive gradients in Na+ current density, assuming faithful AP backpropagation. Such specializations of dendritic excitability might confer specific temporal processing capabilities to bulbar principal cell-GC subnetworks. In conclusion, we show that Na+ imaging provides a valuable tool for characterizing AP invasion of MC axons and GC dendrites and spines. PMID:28293175
The Trophic Life Cycle Stage of the Opportunistic Fungal Pathogen Pneumocystis murina Hinders the Ability of Dendritic Cells To Stimulate CD4+ T Cell Responses

PubMed Central

Evans, Heather M.; Simpson, Andrew; Shen, Shu; Stromberg, Arnold J.; Pickett, Carol L.

2017-01-01

ABSTRACT The life cycle of the opportunistic fungal pathogen Pneumocystis murina consists of a trophic stage and an ascus-like cystic stage. Infection with the cyst stage induces proinflammatory immune responses, while trophic forms suppress the cytokine response to multiple pathogen-associated molecular patterns (PAMPs), including β-glucan. A targeted gene expression assay was used to evaluate the dendritic cell response following stimulation with trophic forms alone, with a normal mixture of trophic forms and cysts, or with β-glucan. We demonstrate that stimulation with trophic forms downregulated the expression of multiple genes normally associated with the response to infection, including genes encoding transcription factors. Trophic forms also suppressed the expression of genes related to antigen processing and presentation, including the gene encoding the major histocompatibility complex (MHC) class II transactivator, CIITA. Stimulation of dendritic cells with trophic forms, but not a mixture of trophic forms and cysts, reduced the expression of MHC class II and the costimulatory molecule CD40 on the surface of the cells. These defects in the expression of MHC class II and costimulatory molecules corresponded with a reduced capacity for trophic form-loaded dendritic cells to stimulate CD4+ T cell proliferation and polarization. These data are consistent with the delayed innate and adaptive responses previously observed in immunocompetent mice inoculated with trophic forms compared to responses in mice inoculated with a mixture of trophic forms and cysts. We propose that trophic forms broadly inhibit the ability of dendritic cells to fulfill their role as antigen-presenting cells. PMID:28694293
Human cytomegalovirus alters localization of MHC class II and dendrite morphology in mature Langerhans cells.

PubMed

Lee, Andrew W; Hertel, Laura; Louie, Ryan K; Burster, Timo; Lacaille, Vashti; Pashine, Achal; Abate, Davide A; Mocarski, Edward S; Mellins, Elizabeth D

2006-09-15

Hemopoietic stem cell-derived mature Langerhans-type dendritic cells (LC) are susceptible to productive infection by human CMV (HCMV). To investigate the impact of infection on this cell type, we examined HLA-DR biosynthesis and trafficking in mature LC cultures exposed to HCMV. We found decreased surface HLA-DR levels in viral Ag-positive as well as in Ag-negative mature LC. Inhibition of HLA-DR was independent of expression of unique short US2-US11 region gene products by HCMV. Indeed, exposure to UV-inactivated virus, but not to conditioned medium from infected cells, was sufficient to reduce HLA-DR on mature LC, implicating particle binding/penetration in this effect. Reduced surface levels reflected an altered distribution of HLA-DR because total cellular HLA-DR was not diminished. Accumulation of HLA-DR was not explained by altered cathepsin S activity. Mature, peptide-loaded HLA-DR molecules were retained within cells, as assessed by the proportion of SDS-stable HLA-DR dimers. A block in egress was implicated, as endocytosis of surface HLA-DR was not increased. Immunofluorescence microscopy corroborated the intracellular retention of HLA-DR and revealed markedly fewer HLA-DR-positive dendritic projections in infected mature LC. Unexpectedly, light microscopic analyses showed a dramatic loss of the dendrites themselves and immunofluorescence revealed that cytoskeletal elements crucial for the formation and maintenance of dendrites are disrupted in viral Ag-positive cells. Consistent with these dendrite effects, HCMV-infected mature LC exhibit markedly reduced chemotaxis in response to lymphoid chemokines. Thus, HCMV impedes MHC class II molecule trafficking, dendritic projections, and migration of mature LC. These changes likely contribute to the reduced activation of CD4+ T cells by HCMV-infected mature LC.
Dendritic release of neurotransmitters

PubMed Central

Ludwig, Mike; Apps, David; Menzies, John; Patel, Jyoti C.; Rice, Margaret E.

2017-01-01

Release of neuroactive substances by exocytosis from dendrites is surprisingly widespread and is not confined to a particular class of transmitters: it occurs in multiple brain regions, and includes a range of neuropeptides, classical neurotransmitters and signaling molecules such as nitric oxide, carbon monoxide, ATP and arachidonic acid. This review is focused on hypothalamic neuroendocrine cells that release vasopressin and oxytocin and midbrain neurons that release dopamine. For these two model systems, the stimuli, mechanisms and physiological functions of dendritic release have been explored in greater detail than is yet available for other neurons and neuroactive substances. PMID:28135005
FoxO regulates microtubule dynamics and polarity to promote dendrite branching in Drosophila sensory neurons

PubMed Central

Sears, James C.; Broihier, Heather T.

2016-01-01

The size and shape of dendrite arbors are defining features of neurons and critical determinants of neuronal function. The molecular mechanisms establishing arborization patterns during development are not well understood, though properly regulated microtubule (MT) dynamics and polarity are essential. We previously found that FoxO regulates axonal MTs, raising the question of whether it also regulates dendritic MTs and morphology. Here we demonstrate that FoxO promotes dendrite branching in all classes of Drosophila dendritic arborization (da) neurons. FoxO is required both for initiating growth of new branches and for maintaining existing branches. To elucidate FoxO function, we characterized MT organization in both foxO null and overexpressing neurons. We find that FoxO directs MT organization and dynamics in dendrites. Moreover, it is both necessary and sufficient for anterograde MT polymerization, which is known to promote dendrite branching. Lastly, FoxO promotes proper larval nociception, indicating a functional consequence of impaired da neuron morphology in foxO mutants. Together, our results indicate that FoxO regulates dendrite structure and function and suggest that FoxO-mediated pathways control MT dynamics and polarity. PMID:27546375
Structure–property study of cross-linked hydrocarbon/poly(ethylene oxide) electrolytes with superior conductivity and dendrite resistance† †Electronic supplementary information (ESI) available: Synthetic procedures, characterization data, electrochemical impedance spectra and additional SEM images. See DOI: 10.1039/c6sc01813k Click here for additional data file.

PubMed Central

Zheng, Qi; Ma, Lin; Khurana, Rachna

2016-01-01

Lithium dendrite growth is a fundamental problem that precludes the practical use of lithium metal batteries. Solid polymer electrolytes (SPEs) have been widely studied to resist the growth of lithium dendrites but the underlying mechanisms are still unclear. Most SPEs sacrifice high ionic conductivities for increased dendrite suppression performance by using components with high mechanical stiffness. We report a class of cross-linked hydrocarbon/poly(ethylene oxide) SPEs with both high ionic conductivities (approaching 1 × 10–3 S cm–1 at 25 °C) and superior dendrite suppression characteristics. A systematic structure–property study shows that the crystallinity of the hydrocarbon backbones plays a key role in regulating size and morphology of lithium dendrites, as well as the ability to suppress their growth. PMID:28451125
Dacarbazine (DTIC) versus vaccination with autologous peptide-pulsed dendritic cells (DC) in first-line treatment of patients with metastatic melanoma: a randomized phase III trial of the DC study group of the DeCOG.

PubMed

Schadendorf, D; Ugurel, S; Schuler-Thurner, B; Nestle, F O; Enk, A; Bröcker, E-B; Grabbe, S; Rittgen, W; Edler, L; Sucker, A; Zimpfer-Rechner, C; Berger, T; Kamarashev, J; Burg, G; Jonuleit, H; Tüttenberg, A; Becker, J C; Keikavoussi, P; Kämpgen, E; Schuler, G

2006-04-01

This randomized phase III trial was designed to demonstrate the superiority of autologous peptide-loaded dendritic cell (DC) vaccination over standard dacarbazine (DTIC) chemotherapy in stage IV melanoma patients. DTIC 850 mg/m2 intravenously was applied in 4-week intervals. DC vaccines loaded with MHC class I and II-restricted peptides were applied subcutaneously at 2-week intervals for the first five vaccinations and every 4 weeks thereafter. The primary study end point was objective response (OR); secondary end points were toxicity, overall (OS) and progression-free survival (PFS). At the time of the first interim analysis 55 patients had been enrolled into the DTIC and 53 into the DC-arm (ITT). OR was low (DTIC: 5.5%, DC: 3.8%), but not significantly different in the two arms. The Data Safety & Monitoring Board recommended closure of the study. Unscheduled subset analyses revealed that patients with normal serum LDH and/or stage M1a/b survived longer in both arms than those with elevated serum LDH and/or stage M1c. Only in the DC-arm did those patients with (i) an initial unimpaired general health status (Karnofsky = 100) or (ii) an HLA-A2+/HLA-B44- haplotype survive significantly longer than patients with a Karnofsky index <100 (P = 0.007 versus P = 0.057 in the DTIC-arm) or other HLA haplotypes (P = 0.04 versus P = 0.57 in DTIC-treated patients). DC vaccination could not be demonstrated to be more effective than DTIC chemotherapy in stage IV melanoma patients. The observed association of overall performance status and HLA haplotype with overall survival for patients treated by DC vaccination should be tested in future trials employing DC vaccines.
Dendritic Core-Multishell Nanocarriers in Murine Models of Healthy and Atopic Skin

NASA Astrophysics Data System (ADS)

Radbruch, Moritz; Pischon, Hannah; Ostrowski, Anja; Volz, Pierre; Brodwolf, Robert; Neumann, Falko; Unbehauen, Michael; Kleuser, Burkhard; Haag, Rainer; Ma, Nan; Alexiev, Ulrike; Mundhenk, Lars; Gruber, Achim D.

2017-01-01

Dendritic hPG-amid-C18-mPEG core-multishell nanocarriers (CMS) represent a novel class of unimolecular micelles that hold great potential as drug transporters, e.g., to facilitate topical therapy in skin diseases. Atopic dermatitis is among the most common inflammatory skin disorders with complex barrier alterations which may affect the efficacy of topical treatment.
Double-bromo and extraterminal (BET) domain proteins regulate dendrite morphology and mechanosensory function.

PubMed

Bagley, Joshua A; Yan, Zhiqiang; Zhang, Wei; Wildonger, Jill; Jan, Lily Yeh; Jan, Yuh Nung

2014-09-01

A complex array of genetic factors regulates neuronal dendrite morphology. Epigenetic regulation of gene expression represents a plausible mechanism to control pathways responsible for specific dendritic arbor shapes. By studying the Drosophila dendritic arborization (da) neurons, we discovered a role of the double-bromodomain and extraterminal (BET) family proteins in regulating dendrite arbor complexity. A loss-of-function mutation in the single Drosophila BET protein encoded by female sterile 1 homeotic [fs(1)h] causes loss of fine, terminal dendritic branches. Moreover, fs(1)h is necessary for the induction of branching caused by a previously identified transcription factor, Cut (Ct), which regulates subtype-specific dendrite morphology. Finally, disrupting fs(1)h function impairs the mechanosensory response of class III da sensory neurons without compromising the expression of the ion channel NompC, which mediates the mechanosensitive response. Thus, our results identify a novel role for BET family proteins in regulating dendrite morphology and a possible separation of developmental pathways specifying neural cell morphology and ion channel expression. Since the BET proteins are known to bind acetylated histone tails, these results also suggest a role of epigenetic histone modifications and the "histone code," in regulating dendrite morphology. © 2014 Bagley et al.; Published by Cold Spring Harbor Laboratory Press.
Neurons of human nucleus accumbens.

PubMed

Sazdanović, Maja; Sazdanović, Predrag; Zivanović-Macuzić, Ivana; Jakovljević, Vladimir; Jeremić, Dejan; Peljto, Amir; Tosevski, Jovo

2011-08-01

Nucleus accumbens is a part of the ventral striatum also known as a drug active brain region, especially related with drug addiction. The aim of the study was to investigate the Golgi morphology of the nucleus accumbens neurons. The study was performed on the frontal and sagittal sections of 15 human brains by the Golgi Kopsch method. We classified neurons in the human nucleus accumbens according to their morphology and size into four types: type I--fusiform neurons; type II--fusiform neurons with lateral dendrite, arising from a part of the cell body; type III--pyramidal-like neuron; type IV--multipolar neuron. The medium spiny neurons, which are mostly noted regarding to the drug addictive conditions of the brain, correspond to the type IV--multipolar neurons. Two regions of human nucleus accumbens could be clearly recognized on Nissl and Golgi preparations each containing different predominant neuronal types. Central part of nucleus accumbens, core region, has a low density of impregnated neurons with predominant type III, pyramidal-like neurons, with spines on secondary branches and rare type IV, multipolar neurons. Contrary to the core, peripheral region, shell of nucleus, has a high density of impregnated neurons predominantly contained of type I and type IV--multipolar neurons, which all are rich in spines on secondary and tertiary dendritic branches. Our results indicate great morphological variability of human nucleus accumbens neurons. This requires further investigations and clarifying clinical significance of this important brain region.
Long-Peptide Cross-Presentation by Human Dendritic Cells Occurs in Vacuoles by Peptide Exchange on Nascent MHC Class I Molecules.

PubMed

Ma, Wenbin; Zhang, Yi; Vigneron, Nathalie; Stroobant, Vincent; Thielemans, Kris; van der Bruggen, Pierre; Van den Eynde, Benoît J

2016-02-15

Cross-presentation enables dendritic cells to present on their MHC class I molecules antigenic peptides derived from exogenous material, through a mechanism that remains partly unclear. It is particularly efficient with long peptides, which are used in cancer vaccines. We studied the mechanism of long-peptide cross-presentation using human dendritic cells and specific CTL clones against melanoma Ags gp100 and Melan-A/MART1. We found that cross-presentation of those long peptides does not depend on the proteasome or the transporter associated with Ag processing, and therefore follows a vacuolar pathway. We also observed that it makes use of newly synthesized MHC class I molecules, through peptide exchange in vesicles distinct from the endoplasmic reticulum and classical secretory pathway, in an SEC22b- and CD74-independent manner. Our results indicate a nonclassical secretion pathway followed by nascent HLA-I molecules that are used for cross-presentation of those long melanoma peptides in the vacuolar pathway. Our results may have implications for the development of vaccines based on long peptides. Copyright © 2016 by The American Association of Immunologists, Inc.
[Role of Langerhans cells in the physiopathology of atopic dermatitis].

PubMed

Bieber, T

1995-12-01

The demonstration of IgE receptors on the surface of epidermal dendritic cells and on other antigen presenting cells is a crucial element in the understanding of the pathophysiological role of these cells in the genesis of atopic disease, and especially the atopic dermatitis (AD). The sensibilisation phase to an aeroallergen at the level of nasal or bronchial mucosa and even at the skin may be mediated by dendritic cells expressing Fc epsilon RI. Distinct forms of AD may then represent the equivalent of the ellicitation phase of the classical allergic contact dermatitis. Fc epsilon RI would lead, via specific IgE, to an efficient antigen capture, to the activation of the dendritic cells and finally to an antigen presentation. Thus, AD may represent the paradigma of an IgE-mediated type IV reaction.
Treatment burden in patients with at least one class IV or V CFTR mutation.

PubMed

Dewulf, Jonas; Vermeulen, François; Wanyama, Simeon; Thomas, Muriel; Proesmans, Marijke; Dupont, Lieven; De Boeck, Kris

2015-12-01

CFTR mutations are grouped according to disease-causing mechanism. Several studies demonstrated that patients having at least one mutation of class IV/V, present with a milder phenotype, but little is known about their relative treatment burden. We compared treatment burden between patients with two class I, II, or III mutations and patients with at least one mutation of class IV/V in the 2010 database of the Belgian CF Registry. We calculated a "Treatment Burden Index" (TBI) by assigning long term therapies to categories low, medium and high intensity, for differential weighing in the total score. There were 779 patients with two known class I/II/III mutations and 94 patients with at least one class IV/V mutation. Compared to class I/II/III, class IV/V patients had a lower median number of clinic visits (4 vs. 5; P < 0.001), a lower risk of hospitalization (24.7% vs. 50.8%; P < 0.001) and intravenous antibiotic treatment (23.5% vs. 46.0%; P < 0.001) and a lower median TBI (6 vs. 9; P < 0.001). These differences remained significant when only class IV/V patients with pancreatic insufficiency (n = 31) were considered. This study clearly demonstrates the significantly lower treatment burden in patients with CF and at least one class IV/V mutation compared to patients with two class I/II/III mutations and contributes to providing better individual counseling at time of diagnosis. © 2015 Wiley Periodicals, Inc.
Control of axonal sprouting and dendrite branching by the Nrg-Ank complex at the neuron-glia interface.

PubMed

Yamamoto, Misato; Ueda, Ryu; Takahashi, Kuniaki; Saigo, Kaoru; Uemura, Tadashi

2006-08-22

Neurons are highly polarized cells with distinct subcellular compartments, including dendritic arbors and an axon. The proper function of the nervous system relies not only on correct targeting of axons, but also on development of neuronal-class-specific geometry of dendritic arbors [1-4]. To study the intercellular control of the shaping of dendritic trees in vivo, we searched for cell-surface proteins expressed by Drosophila dendritic arborization (da) neurons [5-7]. One of them was Neuroglian (Nrg), a member of the Ig superfamily ; Nrg and vertebrate L1-family molecules have been implicated in various aspects of neuronal wiring, such as axon guidance, axonal myelination, and synapse formation [9-12]. A subset of the da neurons in nrg mutant embryos exhibited deformed dendritic arbors and abnormal axonal sprouting. Our functional analysis in a cell-type-selective manner strongly suggested that those da neurons employed Nrg to interact with the peripheral glia for suppressing axonal sprouting and for forming second-order dendritic branches. At least for the former role, Nrg functioned in concert with the intracellular adaptor protein Ankyrin (Ank) [13]. Thus, the neuron-glia interaction that is mediated by Nrg, together with Ank under some situations, contributes to axonal and dendritic morphogenesis.
Phase I dendritic cell p53 peptide vaccine for head and neck cancer.

PubMed

Schuler, Patrick J; Harasymczuk, Malgorzata; Visus, Carmen; Deleo, Albert; Trivedi, Sumita; Lei, Yu; Argiris, Athanassios; Gooding, William; Butterfield, Lisa H; Whiteside, Theresa L; Ferris, Robert L

2014-05-01

p53 accumulation in head and neck squamous cell carcinoma (HNSCC) cells creates a targetable tumor antigen. Adjuvant dendritic cell (DC)-based vaccination against p53 was tested in a phase I clinical trial. Monocyte-derived DC from 16 patients were loaded with two modified HLA-class I p53 peptides (Arm 1), additional Th tetanus toxoid peptide (Arm 2), or additional Th wild-type (wt) p53-specific peptide (Arm 3). Vaccine DCs (vDC) were delivered to inguinal lymph nodes at three time points. vDC phenotype, circulating p53-specific T cells, and regulatory T cells (Treg) were serially monitored by flow cytometry and cytokine production by Luminex. vDC properties were compared with those of DC1 generated with an alternative maturation regimen. No grade II-IV adverse events were observed. Two-year disease-free survival of 88% was favorable. p53-specific T-cell frequencies were increased postvaccination in 11 of 16 patients (69%), with IFN-γ secretion detected in four of 16 patients. Treg frequencies were consistently decreased (P = 0.006) relative to prevaccination values. The phenotype and function of DC1 were improved relative to vDC. Adjuvant p53-specific vaccination of patients with HNSCC was safe and associated with promising clinical outcome, decreased Treg levels, and modest vaccine-specific immunity. HNSCC patients' DC required stronger maturation stimuli to reverse immune suppression and improve vaccine efficacy. ©2014 AACR.

Crystal growth and fluid mechanics problems in directional solidification

NASA Technical Reports Server (NTRS)

Tanveer, Saleh; Baker, Gregory R.; Foster, Michael R.

1994-01-01

Broadly speaking, our efforts have been concentrated in two aspects of directional solidification: (A) a more complete theoretical understanding of convection effects in a Bridgman apparatus; and (B) a clear understanding of scalings of various features of dendritic crystal growth in the sensitive limit of small capillary effects. For studies that fall within class A, the principal objectives are as follows: (A1) Derive analytical formulas for segregation, interfacial shape and fluid velocities in mathematically amenable asymptotic limits. (A2) Numerically verify and extend asymptotic results to other ranges of parameter space with a view to a broader physical understanding of the general trends. With respect to studies that fall within class B, the principal objectives include answering the following questions about dendritic crystal growth: (B1) Are there unsteady dendrite solutions in 2-D to the completely nonlinear time evolving equations in the small surface tension limit with only a locally steady tip region with well defined tip radius and velocity? Is anisotropy in surface tension necessary for the existence of such solutions as it is for a true steady state needle crystal? How does the size of such a local region depend on capillary effects, anisotropy and undercooling? (B2) How do the different control parameters affect the nonlinear amplification of tip noise and dendritic side branch coarsening?
Dendritic mechanisms underlying the coupling of the dendritic with the axonal action potential initiation zone of adult rat layer 5 pyramidal neurons

PubMed Central

Larkum, M E; Zhu, J J; Sakmann, B

2001-01-01

Double, triple and quadruple whole-cell voltage recordings were made simultaneously from different parts of the apical dendritic arbor and the soma of adult layer 5 (L5) pyramidal neurons. We investigated the membrane mechanisms that support the conduction of dendritic action potentials (APs) between the dendritic and axonal AP initiation zones and their influence on the subsequent AP pattern. The duration of the current injection to the distal dendritic initiation zone controlled the degree of coupling with the axonal initiation zone and the AP pattern. Two components of the distally evoked regenerative potential were pharmacologically distinguished: a rapidly rising peak potential that was TTX sensitive and a slowly rising plateau-like potential that was Cd2+ and Ni2+ sensitive and present only with longer-duration current injection. The amplitude of the faster forward-propagating Na+-dependent component and the amplitude of the back-propagating AP fell into two classes (more distinctly in the forward-propagating case). Current injection into the dendrite altered propagation in both directions. Somatic current injections that elicited single Na+ APs evoked bursts of Na+ APs when current was injected simultaneously into the proximal apical dendrite. The mechanism did not depend on dendritic Na+–Ca2+ APs. A three-compartment model of a L5 pyramidal neuron is proposed. It comprises the distal dendritic and axonal AP initiation zones and the proximal apical dendrite. Each compartment contributes to the initiation and to the pattern of AP discharge in a distinct manner. Input to the three main dendritic arbors (tuft dendrites, apical oblique dendrites and basal dendrites) has a dominant influence on only one of these compartments. Thus, the AP pattern of L5 pyramids reflects the laminar distribution of synaptic activity in a cortical column. PMID:11389204
Passive dendrites enable single neurons to compute linearly non-separable functions.

PubMed

Cazé, Romain Daniel; Humphries, Mark; Gutkin, Boris

2013-01-01

Local supra-linear summation of excitatory inputs occurring in pyramidal cell dendrites, the so-called dendritic spikes, results in independent spiking dendritic sub-units, which turn pyramidal neurons into two-layer neural networks capable of computing linearly non-separable functions, such as the exclusive OR. Other neuron classes, such as interneurons, may possess only a few independent dendritic sub-units, or only passive dendrites where input summation is purely sub-linear, and where dendritic sub-units are only saturating. To determine if such neurons can also compute linearly non-separable functions, we enumerate, for a given parameter range, the Boolean functions implementable by a binary neuron model with a linear sub-unit and either a single spiking or a saturating dendritic sub-unit. We then analytically generalize these numerical results to an arbitrary number of non-linear sub-units. First, we show that a single non-linear dendritic sub-unit, in addition to the somatic non-linearity, is sufficient to compute linearly non-separable functions. Second, we analytically prove that, with a sufficient number of saturating dendritic sub-units, a neuron can compute all functions computable with purely excitatory inputs. Third, we show that these linearly non-separable functions can be implemented with at least two strategies: one where a dendritic sub-unit is sufficient to trigger a somatic spike; another where somatic spiking requires the cooperation of multiple dendritic sub-units. We formally prove that implementing the latter architecture is possible with both types of dendritic sub-units whereas the former is only possible with spiking dendrites. Finally, we show how linearly non-separable functions can be computed by a generic two-compartment biophysical model and a realistic neuron model of the cerebellar stellate cell interneuron. Taken together our results demonstrate that passive dendrites are sufficient to enable neurons to compute linearly non-separable functions.
Passive Dendrites Enable Single Neurons to Compute Linearly Non-separable Functions

PubMed Central

Cazé, Romain Daniel; Humphries, Mark; Gutkin, Boris

2013-01-01

Local supra-linear summation of excitatory inputs occurring in pyramidal cell dendrites, the so-called dendritic spikes, results in independent spiking dendritic sub-units, which turn pyramidal neurons into two-layer neural networks capable of computing linearly non-separable functions, such as the exclusive OR. Other neuron classes, such as interneurons, may possess only a few independent dendritic sub-units, or only passive dendrites where input summation is purely sub-linear, and where dendritic sub-units are only saturating. To determine if such neurons can also compute linearly non-separable functions, we enumerate, for a given parameter range, the Boolean functions implementable by a binary neuron model with a linear sub-unit and either a single spiking or a saturating dendritic sub-unit. We then analytically generalize these numerical results to an arbitrary number of non-linear sub-units. First, we show that a single non-linear dendritic sub-unit, in addition to the somatic non-linearity, is sufficient to compute linearly non-separable functions. Second, we analytically prove that, with a sufficient number of saturating dendritic sub-units, a neuron can compute all functions computable with purely excitatory inputs. Third, we show that these linearly non-separable functions can be implemented with at least two strategies: one where a dendritic sub-unit is sufficient to trigger a somatic spike; another where somatic spiking requires the cooperation of multiple dendritic sub-units. We formally prove that implementing the latter architecture is possible with both types of dendritic sub-units whereas the former is only possible with spiking dendrites. Finally, we show how linearly non-separable functions can be computed by a generic two-compartment biophysical model and a realistic neuron model of the cerebellar stellate cell interneuron. Taken together our results demonstrate that passive dendrites are sufficient to enable neurons to compute linearly non-separable functions. PMID:23468600
Differential interactions of virulent and non-virulent H. parasuis strains with naïve or swine influenza virus pre-infected dendritic cells.

PubMed

Mussá, Tufária; Rodríguez-Cariño, Carolina; Sánchez-Chardi, Alejandro; Baratelli, Massimiliano; Costa-Hurtado, Mar; Fraile, Lorenzo; Domínguez, Javier; Aragon, Virginia; Montoya, María

2012-11-16

Pigs possess a microbiota in the upper respiratory tract that includes Haemophilus parasuis. Pigs are also considered the reservoir of influenza viruses and infection with this virus commonly results in increased impact of bacterial infections, including those by H. parasuis. However, the mechanisms involved in host innate responses towards H. parasuis and their implications in a co-infection with influenza virus are unknown. Therefore, the ability of a non-virulent H. parasuis serovar 3 (SW114) and a virulent serovar 5 (Nagasaki) strains to interact with porcine bone marrow dendritic cells (poBMDC) and their modulation in a co-infection with swine influenza virus (SwIV) H3N2 was examined. At 1 hour post infection (hpi), SW114 interaction with poBMDC was higher than that of Nagasaki, while at 8 hpi both strains showed similar levels of interaction. The co-infection with H3N2 SwIV and either SW114 or Nagasaki induced higher levels of IL-1β, TNF-α, IL-6, IL-12 and IL-10 compared to mock or H3N2 SwIV infection alone. Moreover, IL-12 and IFN-α secretion differentially increased in cells co-infected with H3N2 SwIV and Nagasaki. These results pave the way for understanding the differences in the interaction of non-virulent and virulent strains of H. parasuis with the swine immune system and their modulation in a viral co-infection.
Morphology and current-voltage characteristics of nanostructured pentacene thin films probed by atomic force microscopy.

PubMed

Zorba, S; Le, Q T; Watkins, N J; Yan, L; Gao, Y

2001-09-01

Atomic force microscopy was used to study the growth modes (on SiO2, MoS2, and Au substrates) and the current-voltage (I-V) characteristics of organic semiconductor pentacene. Pentacene films grow on SiO2 substrate in a layer-by-layer manner with full coverage at an average thickness of 20 A and have the highest degree of molecular ordering with large dendritic grains among the pentacene films deposited on the three different substrates. Films grown on MoS2 substrate reveal two different growth modes, snowflake-like growth and granular growth, both of which seem to compete with each other. On the other hand, films deposited on Au substrate show granular structure for thinner coverages (no crystal structure) and dendritic growth for higher coverages (crystal structure). I-V measurements were performed with a platinum tip on a pentacene film deposited on a Au substrate. The I-V curves on pentacene film reveal symmetric tunneling type character. The field dependence of the current indicates that the main transport mechanism at high field intensities is hopping (Poole-Frenkel effect). From these measurements, we have estimated a field lowering coefficient of 9.77 x 10(-6) V-1/2 m1/2 and an ideality factor of 18 for pentacene.
Interlaminar differences in the pyramidal cell phenotype in parietal cortex of an Indian bat, cynopterus sphinx.

PubMed

Srivastava, U C; Pathak, S V

2010-10-30

To study interlaminar phenotypic variations in the pyramidal neurons of parietal isocortex in bat (Cynopterus sphinx), Golgi and Nissl methods have been employed. The parietal isocortex is relatively thin in the bat as compared to prototheria with layer III, V and VI accounting for more than two—thirds of total cortical thickness. Thick cell free layer I and thinnest accentuated layer II are quite in connotation with other chiropterids. Poor demarcation of layer III/IV in the present study is also in connotation with primitive eutherian mammal (i.e. prototherian) and other chiropterids. Most of the pyramidal cells in the different layers of the parietal isocortex are of typical type as seen in other eutherians but differ significantly in terms of soma shape and size, extent of dendritic arbor, diameter of dendrites and spine density. Percentage of pyramidal neurons, diameter of apical dendrite and spine density on apical dendrite appear to follow an increasing trend from primitive to advanced mammals; but extent of dendrites are probably governed by the specific life patterns of these mammals. It is thus concluded that 'typical' pyramidal neurons in parietal isocortex are similar in therians but different from those in prototherians. It is possible that these cells might have arisen among early eutherians after divergence from prototherian stock.
Prolonged survival of dendritic cell-vaccinated melanoma patients correlates with tumor-specific delayed type IV hypersensitivity response and reduction of tumor growth factor beta-expressing T cells.

PubMed

López, Mercedes N; Pereda, Cristian; Segal, Gabriela; Muñoz, Leonel; Aguilera, Raquel; González, Fermín E; Escobar, Alejandro; Ginesta, Alexandra; Reyes, Diego; González, Rodrigo; Mendoza-Naranjo, Ariadna; Larrondo, Milton; Compán, Alvaro; Ferrada, Carlos; Salazar-Onfray, Flavio

2009-02-20

The aim of this work was to assess immunologic response, disease progression, and post-treatment survival of melanoma patients vaccinated with autologous dendritic cells (DCs) pulsed with a novel allogeneic cell lysate (TRIMEL) derived from three melanoma cell lines. Forty-three stage IV and seven stage III patients were vaccinated four times with TRIMEL/DC vaccine. Specific delayed type IV hypersensitivity (DTH) reaction, ex vivo cytokine production, and regulatory T-cell populations were determined. Overall survival and disease progression rates were analyzed using Kaplan-Meier curves and compared with historical records. The overall survival for stage IV patients was 15 months. More than 60% of patients showed DTH-positive reaction against the TRIMEL. Stage IV/DTH-positive patients displayed a median survival of 33 months compared with 11 months observed for DTH-negative patients (P = .0014). All stage III treated patients were DTH positive and remained alive and tumor free for a median follow-up period of 48 months (range, 33 to 64 months). DTH-positive patients showed a marked reduction in the proportion of CD4+ transforming growth factor (TGF) beta+ regulatory T cells compared to DTH-negative patients (1.54% v 5.78%; P < .0001). Our findings strongly suggest that TRIMEL-pulsed DCs provide a standardized and widely applicable source of melanoma antigens, very effective in evoking antimelanoma immune response. To our knowledge, this is the first report describing a correlation between vaccine-induced reduction of CD4+TGFbeta+ regulatory T cells and in vivo antimelanoma immune response associated to improved patient survival and disease stability.
Immunological Characterization of Whole Tumour Lysate-Loaded Dendritic Cells for Cancer Immunotherapy

PubMed Central

Ottobrini, Luisa; Biasin, Mara; Borelli, Manuela; Lucignani, Giovanni; Trabattoni, Daria; Clerici, Mario

2016-01-01

Introduction Dendritic cells play a key role as initiators of T-cell responses, and even if tumour antigen-loaded dendritic cells can induce anti-tumour responses, their efficacy has been questioned, suggesting a need to enhance immunization strategies. Matherials & Methods We focused on the characterization of bone marrow-derived dendritic cells pulsed with whole tumour lysate (TAA-DC), as a source of known and unknown antigens, in a mouse model of breast cancer (MMTV-Ras). Dendritic cells were evaluated for antigen uptake and for the expression of MHC class I/II and costimulatory molecules and markers associated with maturation. Results Results showed that antigen-loaded dendritic cells are characterized by a phenotypically semi-mature/mature profile and by the upregulation of genes involved in antigen presentation and T-cell priming. Activated dendritic cells stimulated T-cell proliferation and induced the production of high concentrations of IL-12p70 and IFN-γ but only low levels of IL-10, indicating their ability to elicit a TH1-immune response. Furthermore, administration of Antigen loaded-Dendritic Cells in MMTV-Ras mice evoked a strong anti-tumour response in vivo as demonstrated by a general activation of immunocompetent cells and the release of TH1 cytokines. Conclusion Data herein could be useful in the design of antitumoral DC-based therapies, showing a specific activation of immune system against breast cancer. PMID:26795765
Spiking Neural Classifier with Lumped Dendritic Nonlinearity and Binary Synapses: A Current Mode VLSI Implementation and Analysis.

PubMed

Bhaduri, Aritra; Banerjee, Amitava; Roy, Subhrajit; Kar, Sougata; Basu, Arindam

2018-03-01

We present a neuromorphic current mode implementation of a spiking neural classifier with lumped square law dendritic nonlinearity. It has been shown previously in software simulations that such a system with binary synapses can be trained with structural plasticity algorithms to achieve comparable classification accuracy with fewer synaptic resources than conventional algorithms. We show that even in real analog systems with manufacturing imperfections (CV of 23.5% and 14.4% for dendritic branch gains and leaks respectively), this network is able to produce comparable results with fewer synaptic resources. The chip fabricated in [Formula: see text]m complementary metal oxide semiconductor has eight dendrites per cell and uses two opposing cells per class to cancel common-mode inputs. The chip can operate down to a [Formula: see text] V and dissipates 19 nW of static power per neuronal cell and [Formula: see text] 125 pJ/spike. For two-class classification problems of high-dimensional rate encoded binary patterns, the hardware achieves comparable performance as software implementation of the same with only about a 0.5% reduction in accuracy. On two UCI data sets, the IC integrated circuit has classification accuracy comparable to standard machine learners like support vector machines and extreme learning machines while using two to five times binary synapses. We also show that the system can operate on mean rate encoded spike patterns, as well as short bursts of spikes. To the best of our knowledge, this is the first attempt in hardware to perform classification exploiting dendritic properties and binary synapses.
CDK-5 regulates the polarized trafficking of neuropeptide-containing dense-core vesicles in C. elegans motor neurons

PubMed Central

Goodwin, Patricia R.; Sasaki, Jennifer M.; Juo, Peter

2012-01-01

The polarized trafficking of axonal and dendritic proteins is essential for the structure and function of neurons. Cyclin-dependent kinase-5 (CDK-5) and its activator CDKA-1/p35 regulate diverse aspects of nervous system development and function. Here, we show that CDK-5 and CDKA-1/p35 are required for the polarized distribution of neuropeptide-containing dense-core vesicles (DCVs) in C. elegans cholinergic motor neurons. In cdk-5 or cdka-1/p35 mutants, the predominantly axonal localization of DCVs containing INS-22 neuropeptides was disrupted and DCVs accumulated in dendrites. Time-lapse microscopy in DB class motor neurons revealed decreased trafficking of DCVs in axons and increased trafficking and accumulation of DCVs in cdk-5 mutant dendrites. The polarized distribution of several axonal and dendritic markers, including synaptic vesicles, was unaltered in cdk-5 mutant DB neurons. We found that microtubule polarity is plus-end out in axons and predominantly minus-end out in dendrites of DB neurons. Surprisingly, cdk-5 mutants had increased amounts of plus-end-out microtubules in dendrites, suggesting that CDK-5 regulates microtubule orientation. However, these changes in microtubule polarity are not responsible for the increased trafficking of DCVs into dendrites. Genetic analysis of cdk-5 and the plus-end-directed axonal DCV motor unc-104/KIF1A suggest that increased trafficking of UNC-104 into dendrites cannot explain the dendritic DCV accumulation. Instead, we found that mutations in the minus-end-directed motor cytoplasmic dynein, completely block the increased DCVs observed in cdk-5 mutant dendrites without affecting microtubule polarity. We propose a model where CDK-5 regulates DCV polarity by both promoting DCV trafficking in axons and preventing dynein-dependent DCV trafficking into dendrites. PMID:22699897
Bushy sphere dendrites with husk-shaped branches axially spreading out from the core for photo-catalytic oxidation/remediation of toxins.

PubMed

Shenashen, Mohamed A; Kawada, Satoshi; Selim, Mahmoud M; Morsy, Wafaa M; Yamaguchi, Hitoshi; Alhamid, Abdulaziz A; Ohashi, Naoki; Ichinose, Izumi; El-Safty, Sherif A

2017-06-14

This work describes densely interlinked bushy "tree-like chains" characterized by neatly branched sphere dendrites (bushy sphere dendrites, BSD) with long fan-like, husk-shaped branching paths that extend longitudinally from the core axis of the {110}-exposed plane. We confirmed that the hierarchical dendrite surfaces created bowls of swirled caves along the tree-tube in the mat-like branches. These surfaces had high-index catalytic site facets associated with the formation of ridges/defects on the dominant {110}-top-cover surface. These swirled caves along the branches were completely filled with 50-100 nm poly-CN nano-sphere-fossils with orb-like appearance. Such structural features are key issues of the inherent surface reactivity of a powerful catalyst/trapper, enabling photocatalytic oxidation and trapping of extremely toxic arsenite (AsO 3 3- ) species and photo-induced recovery of arsenate (AsO 4 3- ) products from catalyst surfaces. The light-induced release of produced AsO 4 3- from BSD indicates (i) highly controlled waste collection/management (i.e., recovery), (ii) low cost and ecofriendly photo-adsorbent, (iii) selective trapping of real sample water to produce water-free arsenite species; (iv) multiple reuse cycles of catalysts (i.e., reduced waste volume). Matrixed dendrites, covered with 3D microscopic sphere cores that capture solar-light, trap toxins, and are triggered by light, were designed. These dendrites can withstand indoor and outdoor recovery of toxins from water sources.
Th-1 polarization is regulated by dendritic-cell comparison of MHC class I and class II antigens

PubMed Central

Xing, Dongxia; Li, Sufang; Robinson, Simon N.; Yang, Hong; Steiner, David; Komanduri, Krishna V.; Shpall, Elizabeth J.

2009-01-01

In the control of T-helper type I (Th-1) polarization, dendritic cells (DCs) must interpret a complex array of stimuli, many of which are poorly understood. Here we demonstrate that Th-1 polarization is heavily influenced by DC-autonomous phenomena triggered by the loading of DCs with antigenically matched major histocompatibility complex (MHC) class I and class II determinants, that is, class I and II peptide epitopes exhibiting significant amino acid sequence overlap (such as would be physiologically present during infectious processes requiring Th-1 immunity for clearance). Data were derived from 13 independent antigenic models including whole-cell systems, single-protein systems, and 3 different pairs of overlapping class I and II binding epitopes. Once loaded with matched class I and II antigens, these “Th-1 DCs” exhibited differential cytokine secretion and surface marker expression, a distinct transcriptional signature, and acquired the ability to enhance generation of CD8+ T lymphocytes. Mechanistically, tRNA-synthetases were implicated as components of a putative sensor complex involved in the comparison of class I and II epitopes. These data provide rigorous conceptual explanations for the process of Th-1 polarization and the antigenic specificity of cognate T-cell help, enhance the understanding of Th-1 responses, and should contribute to the formulation of more effective vaccination strategies. PMID:19171878
Dendritic growth shapes in kinetic Monte Carlo models

NASA Astrophysics Data System (ADS)

Krumwiede, Tim R.; Schulze, Tim P.

2017-02-01

For the most part, the study of dendritic crystal growth has focused on continuum models featuring surface energies that yield six pointed dendrites. In such models, the growth shape is a function of the surface energy anisotropy, and recent work has shown that considering a broader class of anisotropies yields a correspondingly richer set of growth morphologies. Motivated by this work, we generalize nanoscale models of dendritic growth based on kinetic Monte Carlo simulation. In particular, we examine the effects of extending the truncation radius for atomic interactions in a bond-counting model. This is done by calculating the model’s corresponding surface energy and equilibrium shape, as well as by running KMC simulations to obtain nanodendritic growth shapes. Additionally, we compare the effects of extending the interaction radius in bond-counting models to that of extending the number of terms retained in the cubic harmonic expansion of surface energy anisotropy in the context of continuum models.
Non-equivalent antigen presenting capabilities of dendritic cells and macrophages in generating brain-infiltrating CD8 + T cell responses.

PubMed

Malo, Courtney S; Huggins, Matthew A; Goddery, Emma N; Tolcher, Heather M A; Renner, Danielle N; Jin, Fang; Hansen, Michael J; Pease, Larry R; Pavelko, Kevin D; Johnson, Aaron J

2018-02-12

The contribution of antigen-presenting cell (APC) types in generating CD8 + T cell responses in the central nervous system (CNS) is not fully defined, limiting the development of vaccines and understanding of immune-mediated neuropathology. Here, we generate a transgenic mouse that enables cell-specific deletion of the H-2Kb MHC class I molecule. By deleting H-2K b on dendritic cells and macrophages, we compare the effect of each APC in three distinct models of neuroinflammation: picornavirus infection, experimental cerebral malaria, and a syngeneic glioma. Dendritic cells and macrophages both activate CD8 + T cell responses in response to these CNS immunological challenges. However, the extent to which each of these APCs contributes to CD8 + T cell priming varies. These findings reveal distinct functions for dendritic cells and macrophages in generating CD8 + T cell responses to neurological disease.
40 CFR 147.650 - State-administrative program-Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2010 CFR

2010-07-01

... CONTROL PROGRAMS Idaho § 147.650 State-administrative program—Class I, II, III, IV, and V wells. The UIC program for Class I, II, III, IV, and V wells in the State of Idaho, other than those on Indian lands, is the program administered by the Idaho Department of Water Resources, approved by EPA pursuant to...
Differential interactions of virulent and non-virulent H. parasuis strains with naïve or swine influenza virus pre-infected dendritic cells

PubMed Central

2012-01-01

Pigs possess a microbiota in the upper respiratory tract that includes Haemophilus parasuis. Pigs are also considered the reservoir of influenza viruses and infection with this virus commonly results in increased impact of bacterial infections, including those by H. parasuis. However, the mechanisms involved in host innate responses towards H. parasuis and their implications in a co-infection with influenza virus are unknown. Therefore, the ability of a non-virulent H. parasuis serovar 3 (SW114) and a virulent serovar 5 (Nagasaki) strains to interact with porcine bone marrow dendritic cells (poBMDC) and their modulation in a co-infection with swine influenza virus (SwIV) H3N2 was examined. At 1 hour post infection (hpi), SW114 interaction with poBMDC was higher than that of Nagasaki, while at 8 hpi both strains showed similar levels of interaction. The co-infection with H3N2 SwIV and either SW114 or Nagasaki induced higher levels of IL-1β, TNF-α, IL-6, IL-12 and IL-10 compared to mock or H3N2 SwIV infection alone. Moreover, IL-12 and IFN-α secretion differentially increased in cells co-infected with H3N2 SwIV and Nagasaki. These results pave the way for understanding the differences in the interaction of non-virulent and virulent strains of H. parasuis with the swine immune system and their modulation in a viral co-infection. PMID:23157617
Laminar Differences in Dendritic Structure of Pyramidal Neurons in the Juvenile Rat Somatosensory Cortex.

PubMed

Rojo, Concepción; Leguey, Ignacio; Kastanauskaite, Asta; Bielza, Concha; Larrañaga, Pedro; DeFelipe, Javier; Benavides-Piccione, Ruth

2016-06-01

Pyramidal cell structure varies between different cortical areas and species, indicating that the cortical circuits that these cells participate in are likely to be characterized by different functional capabilities. Structural differences between cortical layers have been traditionally reported using either the Golgi method or intracellular labeling, but the structure of pyramidal cells has not previously been systematically analyzed across all cortical layers at a particular age. In the present study, we investigated the dendritic architecture of complete basal arbors of pyramidal neurons in layers II, III, IV, Va, Vb, and VI of the hindlimb somatosensory cortical region of postnatal day 14 rats. We found that the characteristics of basal dendritic morphologies are statistically different in each cortical layer. The variations in size and branching pattern that exist between pyramidal cells of different cortical layers probably reflect the particular functional properties that are characteristic of the cortical circuit in which they participate. This new set of complete basal dendritic arbors of 3D-reconstructed pyramidal cell morphologies across each cortical layer will provide new insights into interlaminar information processing in the cerebral cortex. © The Author 2016. Published by Oxford University Press.
Dendritic cell immunization route determines CD8+ T cell trafficking to inflamed skin: role for tissue microenvironment and dendritic cells in establishment of T cell-homing subsets.

PubMed

Dudda, Jan C; Simon, Jan C; Martin, Stefan

2004-01-15

The effector/memory T cell pool branches in homing subsets selectively trafficking to organs such as gut or skin. Little is known about the critical factors in the generation of skin-homing CD8+ T cells, although they are crucial effectors in skin-restricted immune responses such as contact hypersensitivity and melanoma defense. In this study, we show that intracutaneous, but not i.v. injection of bone marrow-derived dendritic cells induced skin-homing CD8+ T cells with up-regulated E-selectin ligand expression and effector function in contact hypersensitivity. The skin-homing potential and E-selectin ligand expression remained stable in memory phase without further Ag contact. In contrast, i.p. injection induced T cells expressing the gut-homing integrin alpha(4)beta(7). Although differential expression of these adhesion molecules was strictly associated with the immunization route, the postulated skin-homing marker CCR4 was transiently up-regulated in all conditions. Interestingly, dendritic cells from different tissues effectively induced the corresponding homing markers on T cells in vitro. Our results suggest a crucial role for the tissue microenvironment and dendritic cells in the instruction of T cells for tissue-selective homing and demonstrate that Langerhans cells are specialized to target T cells to inflamed skin.
Investigation into the Emerging Role of the Basic Amino Acid L-Lysine in Enhancing Solubility and Permeability of BCS Class II and BCS Class IV Drugs.

PubMed

Abdelkader, Hamdy; Fathalla, Zeinab

2018-06-18

The search for a simple and scalable approach that can improve the two key biopharmaceutical processes (solubility and permeability) for BCS Class II and BCS Class IV has still been unmet need. In this study, L-lysine was investigated as a potential excipient to tackle problems with solubility and permeability. Bendazac (Class II); quercetin and rutin (Class IV) were employed. Drugs-lysine complexes in 1:1 M ratios were prepared by co-precipitation and co-grinding; characterized for solubility, partition coefficient, DSC, FTIR, SEM, dissolution rate and permeability. Chemical stability of quercetin-lysine and rutin-lysine was studied by assessing antioxidant capacity using Trolox and CUPRAC assays. Drugs-lysine salt/complexes were confirmed. Solubility enhancement factors ranged from 68- to 433-fold increases and dissolution rates were also significantly enhanced by up to 6-times, compared with drugs alone. With the exception of rutin-lysine, P app for bendazac-lysine and quercetin-lysine enhanced by 2.3- to 4-fold. P app for quercetin (Class IV) benefited more than bendazac (Class II) when complexed with lysine. This study warrants the use of L-lysine as a promising excipient for enhanced solubility and permeability of Class II and Class IV, providing that the solubility of the drug is ensured at 'the door step' of absorption sites.

40 CFR 147.2200 - State-administered program-Class I, III, IV, and V wells.

Code of Federal Regulations, 2010 CFR

2010-07-01

... the in situ combustion of coal are regulated by the Rail Road Commission of Texas under a separate UIC... program for Class I, III, IV, and V wells in the State of Texas, except for those wells on Indian lands... (SDWA). Notice of the original approval for Class I, III, IV, and V wells was published in the Federal...
40 CFR 147.2200 - State-administered program-Class I, III, IV, and V wells.

Code of Federal Regulations, 2012 CFR

2012-07-01

... the in situ combustion of coal are regulated by the Rail Road Commission of Texas under a separate UIC... program for Class I, III, IV, and V wells in the State of Texas, except for those wells on Indian lands... (SDWA). Notice of the original approval for Class I, III, IV, and V wells was published in the Federal...
Class IV polyhydroxyalkanoate (PHA) synthases and PHA-producing Bacillus.

PubMed

Tsuge, Takeharu; Hyakutake, Manami; Mizuno, Kouhei

2015-08-01

This review highlights the recent investigations of class IV polyhydroxyalkanoate (PHA) synthases, the newest classification of PHA synthases. Class IV synthases are prevalent in organisms of the Bacillus genus and are composed of a catalytic subunit PhaC (approximately 40 kDa), which has a PhaC box sequence ([GS]-X-C-X-[GA]-G) at the active site, and a second subunit PhaR (approximately 20 kDa). The representative PHA-producing Bacillus strains are Bacillus megaterium and Bacillus cereus; the nucleotide sequence of phaC and the genetic organization of the PHA biosynthesis gene locus are somewhat different between these two strains. It is generally considered that class IV synthases favor short-chain-length monomers such as 3-hydroxybutyrate (C4) and 3-hydroxyvalerate (C5) for polymerization, but can polymerize some unusual monomers as minor components. In Escherichia coli expressing PhaRC from B. cereus YB-4, the biosynthesized PHA undergoes synthase-catalyzed alcoholytic cleavage using endogenous and exogenous alcohols. This alcoholysis is thought to be shared among class IV synthases, and this reaction is useful not only for the regulation of PHA molecular weight but also for the modification of the PHA carboxy terminus. The novel properties of class IV synthases will open up the possibility for the design of new PHA materials.
Multiclass Classification by Adaptive Network of Dendritic Neurons with Binary Synapses Using Structural Plasticity

PubMed Central

Hussain, Shaista; Basu, Arindam

2016-01-01

The development of power-efficient neuromorphic devices presents the challenge of designing spike pattern classification algorithms which can be implemented on low-precision hardware and can also achieve state-of-the-art performance. In our pursuit of meeting this challenge, we present a pattern classification model which uses a sparse connection matrix and exploits the mechanism of nonlinear dendritic processing to achieve high classification accuracy. A rate-based structural learning rule for multiclass classification is proposed which modifies a connectivity matrix of binary synaptic connections by choosing the best “k” out of “d” inputs to make connections on every dendritic branch (k < < d). Because learning only modifies connectivity, the model is well suited for implementation in neuromorphic systems using address-event representation (AER). We develop an ensemble method which combines several dendritic classifiers to achieve enhanced generalization over individual classifiers. We have two major findings: (1) Our results demonstrate that an ensemble created with classifiers comprising moderate number of dendrites performs better than both ensembles of perceptrons and of complex dendritic trees. (2) In order to determine the moderate number of dendrites required for a specific classification problem, a two-step solution is proposed. First, an adaptive approach is proposed which scales the relative size of the dendritic trees of neurons for each class. It works by progressively adding dendrites with fixed number of synapses to the network, thereby allocating synaptic resources as per the complexity of the given problem. As a second step, theoretical capacity calculations are used to convert each neuronal dendritic tree to its optimal topology where dendrites of each class are assigned different number of synapses. The performance of the model is evaluated on classification of handwritten digits from the benchmark MNIST dataset and compared with other spike classifiers. We show that our system can achieve classification accuracy within 1 − 2% of other reported spike-based classifiers while using much less synaptic resources (only 7%) compared to that used by other methods. Further, an ensemble classifier created with adaptively learned sizes can attain accuracy of 96.4% which is at par with the best reported performance of spike-based classifiers. Moreover, the proposed method achieves this by using about 20% of the synapses used by other spike algorithms. We also present results of applying our algorithm to classify the MNIST-DVS dataset collected from a real spike-based image sensor and show results comparable to the best reported ones (88.1% accuracy). For VLSI implementations, we show that the reduced synaptic memory can save upto 4X area compared to conventional crossbar topologies. Finally, we also present a biologically realistic spike-based version for calculating the correlations required by the structural learning rule and demonstrate the correspondence between the rate-based and spike-based methods of learning. PMID:27065782
Proteomic Analyses of the Effects of Drugs of Abuse on Monocyte-Derived Mature Dendritic Cells

PubMed Central

Reynolds, Jessica L.; Mahajan, Supriya D.; Aalinkeel, Ravikunar; Nair, B.; Sykes, Donald E.; Schwartz, Stanley A.

2010-01-01

Drug abuse has become a global health concern. Understanding how drug abuse modulates the immune system and how the immune system responds to pathogens associated with drug abuse, such hepatitis C virus (HCV) and human immunodeficiency virus (HIV-1), can be assessed by an integrated approach comparing proteomic analyses and quantitation of gene expression. Two-dimensional (2D) difference gel electrophoresis was used to determine the molecular mechanisms underlying the proteomic changes that alter normal biological processes when monocyte-derived mature dendritic cells were treated with cocaine or methamphetamine. Both drugs differentially regulated the expression of several functional classes of proteins including those that modulate apoptosis, protein folding, protein kinase activity, and metabolism and proteins that function as intracellular signal transduction molecules. Proteomic data were validated using a combination of quantitative, real-time PCR and Western blot analyses. These studies will help to identify the molecular mechanisms, including the expression of several functionally important classes of proteins that have emerged as potential mediators of pathogenesis. These proteins may predispose immunocompetent cells, including dendritic cells, to infection with viruses such as HCV and HIV-1, which are associated with drug abuse. PMID:19811410
Deciphering the role of CA1 inhibitory circuits in sharp wave-ripple complexes.

PubMed

Cutsuridis, Vassilis; Taxidis, Jiannis

2013-01-01

Sharp wave-ripples (SWRs) are population oscillatory patterns in hippocampal LFPs during deep sleep and immobility, involved in the replay of memories acquired during wakefulness. SWRs have been extensively studied, but their exact generation mechanism is still unknown. A computational model has suggested that fast perisomatic inhibition may generate the high frequency ripples (~200 Hz). Another model showed how replay of memories can be controlled by various classes of inhibitory interneurons targeting specific parts of pyramidal cells (PC) and firing at particular SWR phases. Optogenetic studies revealed new roles for interneuronal classes and rich dynamic interplays between them, shedding new light in their potential role in SWRs. Here, we integrate these findings in a conceptual model of how dendritic and somatic inhibition may collectively contribute to the SWR generation. We suggest that sharp wave excitation and basket cell (BC) recurrent inhibition synchronises BC spiking in ripple frequencies. This rhythm is imposed on bistratified cells which prevent pyramidal bursting. Axo-axonic and stratum lacunosum/moleculare interneurons are silenced by inhibitory inputs originating in the medial septum. PCs receiving rippling inhibition in both dendritic and perisomatic areas and excitation in their apical dendrites, exhibit sparse ripple phase-locked spiking.
Dendritic Cell Immune Responses in HIV-1 Controllers.

PubMed

Martin-Gayo, Enrique; Yu, Xu G

2017-02-01

Robust HIV-1-specific CD8 T cell responses are currently regarded as the main correlate of immune defense in rare individuals who achieve natural, drug-free control of HIV-1; however, the mechanisms that support evolution of such powerful immune responses are not well understood. Dendritic cells (DCs) are specialized innate immune cells critical for immune recognition, immune regulation, and immune induction, but their possible contribution to HIV-1 immune defense in controllers remains ill-defined. Recent studies suggest that myeloid DCs from controllers have improved abilities to recognize HIV-1 through cytoplasmic immune sensors, resulting in more potent, cell-intrinsic type I interferon secretion in response to viral infection. This innate immune response may facilitate DC-mediated induction of highly potent antiviral HIV-1-specific T cells. Moreover, protective HLA class I isotypes restricting HIV-1-specific CD8 T cells may influence DC function through specific interactions with innate myelomonocytic MHC class I receptors from the leukocyte immunoglobulin-like receptor family. Bi-directional interactions between dendritic cells and HIV-1-specific T cells may contribute to natural HIV-1 immune control, highlighting the importance of a fine-tuned interplay between innate and adaptive immune activities for effective antiviral immune defense.
Wiring Economy of Pyramidal Cells in the Juvenile Rat Somatosensory Cortex

PubMed Central

Bielza, Concha; Larrañaga, Pedro; DeFelipe, Javier

2016-01-01

Ever since Cajal hypothesized that the structure of neurons is designed in such a way as to save space, time and matter, numerous researchers have analyzed wiring properties at different scales of brain organization. Here we test the hypothesis that individual pyramidal cells, the most abundant type of neuron in the cerebral cortex, optimize brain connectivity in terms of wiring length. In this study, we analyze the neuronal wiring of complete basal arborizations of pyramidal neurons in layer II, III, IV, Va, Vb and VI of the hindlimb somatosensory cortical region of postnatal day 14 rats. For each cell, we search for the optimal basal arborization and compare its length with the length of the real dendritic structure. Here the optimal arborization is defined as the arborization that has the shortest total wiring length provided that all neuron bifurcations are respected and the extent of the dendritic arborizations remain unchanged. We use graph theory and evolutionary computation techniques to search for the minimal wiring arborizations. Despite morphological differences between pyramidal neurons located in different cortical layers, we found that the neuronal wiring is near-optimal in all cases (the biggest difference between the shortest synthetic wiring found for a dendritic arborization and the length of its real wiring was less than 5%). We found, however, that the real neuronal wiring was significantly closer to the best solution found in layers II, III and IV. Our studies show that the wiring economy of cortical neurons is related not to the type of neurons or their morphological complexities but to general wiring economy principles. PMID:27832100
Wiring Economy of Pyramidal Cells in the Juvenile Rat Somatosensory Cortex.

PubMed

Anton-Sanchez, Laura; Bielza, Concha; Larrañaga, Pedro; DeFelipe, Javier

2016-01-01

Ever since Cajal hypothesized that the structure of neurons is designed in such a way as to save space, time and matter, numerous researchers have analyzed wiring properties at different scales of brain organization. Here we test the hypothesis that individual pyramidal cells, the most abundant type of neuron in the cerebral cortex, optimize brain connectivity in terms of wiring length. In this study, we analyze the neuronal wiring of complete basal arborizations of pyramidal neurons in layer II, III, IV, Va, Vb and VI of the hindlimb somatosensory cortical region of postnatal day 14 rats. For each cell, we search for the optimal basal arborization and compare its length with the length of the real dendritic structure. Here the optimal arborization is defined as the arborization that has the shortest total wiring length provided that all neuron bifurcations are respected and the extent of the dendritic arborizations remain unchanged. We use graph theory and evolutionary computation techniques to search for the minimal wiring arborizations. Despite morphological differences between pyramidal neurons located in different cortical layers, we found that the neuronal wiring is near-optimal in all cases (the biggest difference between the shortest synthetic wiring found for a dendritic arborization and the length of its real wiring was less than 5%). We found, however, that the real neuronal wiring was significantly closer to the best solution found in layers II, III and IV. Our studies show that the wiring economy of cortical neurons is related not to the type of neurons or their morphological complexities but to general wiring economy principles.
2003-2013, a valuable study: Autologous tumor lysate-pulsed dendritic cell immunotherapy with cytokine-induced killer cells improves survival in stage IV breast cancer.

PubMed

Lin, Mao; Liang, Shuzhen; Jiang, Feng; Xu, Jiongyuan; Zhu, Weibing; Qian, Wei; Hu, Yong; Zhou, Zhanchun; Chen, Jibing; Niu, Lizhi; Xu, Kecheng; Lv, Youyong

2017-03-01

Dendritic cells (DCs) and cytokine-induced killer (CIK) cells have both shown activity as immunotherapy in some malignancies. Our aim was to prospective assess the effect of this immunotherapy in patients with stage IV breast cancer. Between Aug 2003 and Dec 2013, we collected 368 patients who met inclusion criteria and divided into immunotherapy group (treatment group: 188 patients) and chemotherapy group (control group: 180 patients). DCs were prepared from the mononuclear cells isolated from patients in the treatment group using IL-2/GM-CSF and were loaded with tumour antigens; CIK cells were prepared by incubating peripheral blood lymphocytes with IL-2, IFN-γ, and CD3 antibodies. After the patients had received low-dose chemotherapy, those in the treatment group also received the DC-CIK therapy, which was repeated four times in a fortnight to form one cycle. At least three cycles of DC-CIK therapy were given. Immune function was measured in treatment group patients' sera. Disease-free survival (DFS) and Overall survival (OS) after the diagnosis of stage IV breast cancer was assessed after a 10-year follow-up. The result demonstrated that immune function is obviously enhanced after DC-CIK therapy. By Cox regression analysis, DC-CIK therapy reduced the risk of disease progression (p<0.01) with an increased OS (p<0.01). After low-dose chemotherapy, active immunization with DC-CIK immunotherapy is a potentially effective approach for the control of tumour growth in stage IV breast cancer patients. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.
Esterified dendritic TAM radicals with very high stability and enhanced oxygen sensitivity.

PubMed

Song, Yuguang; Liu, Yangping; Hemann, Craig; Villamena, Frederick A; Zweier, Jay L

2013-02-15

In this work, we have developed a new class of dendritic TAM radicals (TG, TdG, and dTdG) through a convergent method based on the TAM core CT-03 or its deuterated analogue dCT-03 and trifurcated Newkome-type monomer. Among these radicals, dTdG exhibits the best EPR properties with sharpest EPR singlet and highest O(2) sensitivity due to deuteration of both the ester linker groups and the TAM core CT-03. Like the previous dendritic TAM radicals, these new compounds also show extremely high stability toward various reactive species owing to the dendritic encapsulation. The highly charged nature of these molecules resulting from nine carboxylate groups prevents concentration-dependent EPR line broadening at physiological pH. Furthermore, we demonstrate that these TAM radicals can be easily derivatized (e.g., PEGylation) at the nine carboxylate groups and the resulting PEGylated analogue dTdG-PEG completely inhibits the albumin binding, thereby enhancing suitability for in vivo applications. These new dendritic TAM radicals show great potential for in vivo EPR oximetric applications and provide insights on approaches to develop improved and targeted EPR oximetric probes for biomedical applications.
Chloride Cotransporters as a Molecular Mechanism underlying Spreading Depolarization-Induced Dendritic Beading.

PubMed

Steffensen, Annette B; Sword, Jeremy; Croom, Deborah; Kirov, Sergei A; MacAulay, Nanna

2015-09-02

Spreading depolarizations (SDs) are waves of sustained neuronal and glial depolarization that propagate massive disruptions of ion gradients through the brain. SD is associated with migraine aura and recently recognized as a novel mechanism of injury in stroke and brain trauma patients. SD leads to neuronal swelling as assessed in real time with two-photon laser scanning microscopy (2PLSM). Pyramidal neurons do not express aquaporins and thus display low inherent water permeability, yet SD rapidly induces focal swelling (beading) along the dendritic shaft by unidentified molecular mechanisms. To address this issue, we induced SD in murine hippocampal slices by focal KCl microinjection and visualized the ensuing beading of dendrites expressing EGFP by 2PLSM. We confirmed that dendritic beading failed to arise during large (100 mOsm) hyposmotic challenges, underscoring that neuronal swelling does not occur as a simple osmotic event. SD-induced dendritic beading was not prevented by pharmacological interference with the cytoskeleton, supporting the notion that dendritic beading may result entirely from excessive water influx. Dendritic beading was strictly dependent on the presence of Cl(-), and, accordingly, combined blockade of Cl(-)-coupled transporters led to a significant reduction in dendritic beading without interfering with SD. Furthermore, our in vivo data showed a strong inhibition of dendritic beading during pharmacological blockage of these cotransporters. We propose that SD-induced dendritic beading takes place as a consequence of the altered driving forces and thus activity for these cotransporters, which by transport of water during their translocation mechanism may generate dendritic beading independently of osmotic forces. Spreading depolarization occurs during pathological conditions such as stroke, brain injury, and migraine and is characterized as a wave of massive ion translocation between intracellular and extracellular space in association with recurrent transient focal swelling (beading) of dendrites. Numerous ion channels have been demonstrated to be involved in generation and propagation of spreading depolarization, but the molecular machinery responsible for the dendritic beading has remained elusive. Using real-time in vitro and in vivo two-photon laser scanning microscopy, we have identified the transport mechanisms involved in the detrimental focal swelling of dendrites. These findings have clear clinical significance because they may point to a new class of pharmacological targets for prevention of neuronal swelling that consequently will serve as neuroprotective agents. Copyright © 2015 the authors 0270-6474/15/3512172-16$15.00/0.
[Preoperative risk assessment with the ASA classification. A prospective study of morbidity and mortality in various ASA classes in 2,937 patients in general surgery].

PubMed

Menke, H; John, K D; Klein, A; Lorenz, W; Junginger, T

1992-12-01

The value of ASA classification in assessment of perioperative risk, i.e. especially postoperative morbidity, was analyzed prospectively using the data of 2937 patients. The analysis took into account the criteria validity, reliability, and sensitivity. The incidence of post-operative morbidity after elective surgery rose from 3.9% in ASA class I to 36% in ASA class IV. Mortality was 0.6% in ASA class II, whereas 9.3% died in ASA class IV. Morbidity, mortality respectively, after emergency surgery was 10.2% in ASA class II compared to 69% in class IV, mortality 1.4% compared to 21.5%. Differences between the ASA classes were confirmed (p-value < 0.05) considering separate kinds of complications and different periods. Furthermore, ASA classification was a valuable reference to length of stay and severity of necessary therapy at the ICU.
Pemetrexed plus dendritic cells as second-line treatment for patients with stage IIIB/IV non-small cell lung cancer who had treatment with TKI.

PubMed

Hu, Rong-Hang; Shi, Sheng-Bin; Qi, Jie-Lin; Tian, Jing; Tang, Xiao-Yong; Liu, Guo-Fang; Chang, Chun-Xiao

2014-08-01

The aim of this study was to determine the efficacy and toxicity of pemetrexed plus dendritic cells (DCs) in patients suffering from stage IIIB or IV lung adenocarcinoma, who had undergone maintenance treatment with gefitinib or erlotinib. Patients who had failed gefitinib or erlotinib maintenance treatment had ECOG performance statuses ranging from 0 to 2.27 patients received pemetrexed plus DCs as second-line treatment. Dosage: 500 mg/m(2) pemetrexed was administered on day 1 of a 21-day cycle. DCs were given for one cycle of 21 days. Three patients (11.1 %) experienced a partial response and 14 patients (51.9 %) showed stable disease. Ten patients (37.0 %) had progressive disease. The median time to progression-free survival (PFS) was 4.8 months [95 % confidence interval (CI) 4.4-5.2], and the median overall survival was 10.7 months (95 % CI 10.3-11.2). In the subgroup analysis, PFS had a significant difference between the low ratio of CD4/CD8 and normal ratio of CD4/CD8, with 4.5 months (95 % CI 4.2-4.9) and 5.0 months (95 % CI 4.5-5.7), (Log Rank = 0.039), respectively. No one patient experienced grade 4 toxicity. A regimen of pemetrexed combined with DCs is marginally effective and well tolerated in patients with stage IIIB or IV lung adenocarcinoma who had received gefitinib or erlotinib first-line treatment.
40 CFR 147.251 - EPA-administered program-Class I, III, IV and V wells and Indian lands.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., IV and V wells and Indian lands. 147.251 Section 147.251 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS California § 147.251 EPA-administered program—Class I, III, IV and V wells and...
40 CFR 147.301 - EPA-administered program-Class I, III, IV, V wells and Indian lands.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., IV, V wells and Indian lands. 147.301 Section 147.301 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Colorado § 147.301 EPA-administered program—Class I, III, IV, V wells and Indian...
40 CFR 147.251 - EPA-administered program-Class I, III, IV and V wells and Indian lands.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., IV and V wells and Indian lands. 147.251 Section 147.251 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS California § 147.251 EPA-administered program—Class I, III, IV and V wells and...
40 CFR 147.301 - EPA-administered program-Class I, III, IV, V wells and Indian lands.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., IV, V wells and Indian lands. 147.301 Section 147.301 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Colorado § 147.301 EPA-administered program—Class I, III, IV, V wells and Indian...
Effects of antidepressant drugs on synaptic protein levels and dendritic outgrowth in hippocampal neuronal cultures.

PubMed

Seo, Mi Kyoung; Lee, Chan Hong; Cho, Hye Yeon; Lee, Jung Goo; Lee, Bong Ju; Kim, Ji Eun; Seol, Wongi; Kim, Young Hoon; Park, Sung Woo

2014-04-01

The alteration of hippocampal plasticity has been proposed to play a critical role in both the pathophysiology and treatment of depression. In this study, the ability of different classes of antidepressant drugs (escitalopram, fluoxetine, paroxetine, sertraline, imipramine, tranylcypromine, and tianeptine) to mediate the expression of synaptic proteins and dendritic outgrowth in rat hippocampal neurons was investigated under toxic conditions induced by B27 deprivation, which causes hippocampal cell death. Postsynaptic density protein-95 (PSD-95), brain-derived neurotrophic factor (BDNF), and synaptophysin (SYP) levels were evaluated using Western blot analyses. Additionally, dendritic outgrowth was examined to determine whether antidepressant drugs affect the dendritic morphology of hippocampal neurons in B27-deprived cultures. Escitalopram, fluoxetine, paroxetine, sertraline, imipramine, tranylcypromine, and tianeptine significantly prevented B27 deprivation-induced decreases in levels of PSD-95, BDNF, and SYP. Moreover, the independent application of fluoxetine, paroxetine, and sertraline significantly increased levels of BDNF under normal conditions. All antidepressant drugs significantly increased the total outgrowth of hippocampal dendrites under B27 deprivation. Specific inhibitors of calcium/calmodulin kinase II (CaMKII), KN-93, protein kinase A (PKA), H-89, or phosphatidylinositol 3-kinase (PI3K), LY294002, significantly decreased the effects of antidepressant drugs on dendritic outgrowth, whereas this effect was observed only with tianeptine for the PI3K inhibitor. Taken together, these results suggest that certain antidepressant drugs can enhance synaptic protein levels and encourage dendritic outgrowth in hippocampal neurons. Furthermore, effects on dendritic outgrowth likely require CaMKII, PKA, or PI3K signaling pathways. The observed effects may be may be due to chronic treatment with antidepressant drugs. Copyright © 2013 Elsevier Ltd. All rights reserved.
40 CFR 146.10 - Plugging and abandoning Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) The plugging and abandonment plan required in 40 CFR 144.51(o) and 144.52(a)(6) shall, in the case of... deems it necessary and feasible to insure adequate protection of USDWs. (b) Requirements for Class IV... with 40 CFR 144.23(b). (c) Requirements for Class V wells. (1) Prior to abandoning a Class V well, the...

40 CFR 146.10 - Plugging and abandoning Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) The plugging and abandonment plan required in 40 CFR 144.51(o) and 144.52(a)(6) shall, in the case of... deems it necessary and feasible to insure adequate protection of USDWs. (b) Requirements for Class IV... with 40 CFR 144.23(b). (c) Requirements for Class V wells. (1) Prior to abandoning a Class V well, the...
40 CFR 146.10 - Plugging and abandoning Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) The plugging and abandonment plan required in 40 CFR 144.51(o) and 144.52(a)(6) shall, in the case of... deems it necessary and feasible to insure adequate protection of USDWs. (b) Requirements for Class IV... with 40 CFR 144.23(b). (c) Requirements for Class V wells. (1) Prior to abandoning a Class V well, the...
Tubulation of class II MHC compartments is microtubule dependent and involves multiple endolysosomal membrane proteins in primary dendritic cells.

PubMed

Vyas, Jatin M; Kim, You-Me; Artavanis-Tsakonas, Katerina; Love, J Christopher; Van der Veen, Annemarthe G; Ploegh, Hidde L

2007-06-01

Immature dendritic cells (DCs) capture exogenous Ags in the periphery for eventual processing in endolysosomes. Upon maturation by TLR agonists, DCs deliver peptide-loaded class II MHC molecules from these compartments to the cell surface via long tubular structures (endolysosomal tubules). The nature and rules that govern the movement of these DC compartments are unknown. In this study, we demonstrate that the tubules contain multiple proteins including the class II MHC molecules and LAMP1, a lysosomal resident protein, as well as CD63 and CD82, members of the tetraspanin family. Endolysosomal tubules can be stained with acidotropic dyes, indicating that they are extensions of lysosomes. However, the proper trafficking of class II MHC molecules themselves is not necessary for endolysosomal tubule formation. DCs lacking MyD88 can also form endolysosomal tubules, demonstrating that MyD88-dependent TLR activation is not necessary for the formation of this compartment. Endolysosomal tubules in DCs exhibit dynamic and saltatory movement, including bidirectional travel. Measured velocities are consistent with motor-based movement along microtubules. Indeed, nocodazole causes the collapse of endolysosomal tubules. In addition to its association with microtubules, endolysosomal tubules follow the plus ends of microtubules as visualized in primary DCs expressing end binding protein 1 (EB1)-enhanced GFP.
40 CFR 147.2650 - State-administered program-Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2010 CFR

2010-07-01

... CONTROL PROGRAMS Puerto Rico § 147.2650 State-administered program—Class I, II, III, IV, and V wells. The Underground Injection Control Program for all classes of wells in the Commonwealth of Puerto Rico, other than those on Indian lands, is the program administered by Puerto Rico's Environmental Quality Board (EQB...
40 CFR 147.2650 - State-administered program-Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2011 CFR

2011-07-01

... CONTROL PROGRAMS Puerto Rico § 147.2650 State-administered program—Class I, II, III, IV, and V wells. The Underground Injection Control Program for all classes of wells in the Commonwealth of Puerto Rico, other than those on Indian lands, is the program administered by Puerto Rico's Environmental Quality Board (EQB...
40 CFR 147.2650 - State-administered program-Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2013 CFR

2013-07-01

... CONTROL PROGRAMS Puerto Rico § 147.2650 State-administered program—Class I, II, III, IV, and V wells. The Underground Injection Control Program for all classes of wells in the Commonwealth of Puerto Rico, other than those on Indian lands, is the program administered by Puerto Rico's Environmental Quality Board (EQB...
The first crystal structures of a family 19 class IV chitinase: the enzyme from Norway spruce.

PubMed

Ubhayasekera, Wimal; Rawat, Reetika; Ho, Sharon Wing Tak; Wiweger, Malgorzata; Von Arnold, Sara; Chye, Mee-Len; Mowbray, Sherry L

2009-10-01

Chitinases help plants defend themselves against fungal attack, and play roles in other processes, including development. The catalytic modules of most plant chitinases belong to glycoside hydrolase family 19. We report here x-ray structures of such a module from a Norway spruce enzyme, the first for any family 19 class IV chitinase. The bi-lobed structure has a wide cleft lined by conserved residues; the most interesting for catalysis are Glu113, the proton donor, and Glu122, believed to be a general base that activate a catalytic water molecule. Comparisons to class I and II enzymes show that loop deletions in the class IV proteins make the catalytic cleft shorter and wider; from modeling studies, it is predicted that only three N-acetylglucosamine-binding subsites exist in class IV. Further, the structural comparisons suggest that the family 19 enzymes become more closed on substrate binding. Attempts to solve the structure of the complete protein including the associated chitin-binding module failed, however, modeling studies based on close relatives indicate that the binding module recognizes at most three N-acetylglucosamine units. The combined results suggest that the class IV enzymes are optimized for shorter substrates than the class I and II enzymes, or alternatively, that they are better suited for action on substrates where only small regions of chitin chain are accessible. Intact spruce chitinase is shown to possess antifungal activity, which requires the binding module; removing this module had no effect on measured chitinase activity.
Computer modeling of dendritic web growth processes and characterization of the material

NASA Technical Reports Server (NTRS)

Seidensticker, R. G.; Kothmann, R. E.; Mchugh, J. P.; Duncan, C. S.; Hopkins, R. H.; Blais, P. D.; Davis, J. R.; Rohatgi, A.

1978-01-01

High area throughput rate will be required for the economical production of silicon dendritic web for solar cells. Web width depends largely on the temperature distribution on the melt surface while growth speed is controlled by the dissipation of the latent heat of fusion. Thermal models were developed to investigate each of these aspects, and were used to engineer the design of laboratory equipment capable of producing crystals over 4 cm wide; growth speeds up to 10 cm/min were achieved. The web crystals were characterized by resistivity, lifetime and etch pit density data as well as by detailed solar cell I-V data. Solar cells ranged in efficiency from about 10 to 14.5% (AM-1) depending on growth conditions. Cells with lower efficiency displayed lowered bulk lifetime believed to be due to surface contamination.
Influenza A Virus Infection of Human Primary Dendritic Cells Impairs Their Ability to Cross-Present Antigen to CD8 T Cells

PubMed Central

Smed-Sörensen, Anna; Chalouni, Cécile; Chatterjee, Bithi; Cohn, Lillian; Blattmann, Peter; Nakamura, Norihiro; Delamarre, Lélia; Mellman, Ira

2012-01-01

Influenza A virus (IAV) infection is normally controlled by adaptive immune responses initiated by dendritic cells (DCs). We investigated the consequences of IAV infection of human primary DCs on their ability to function as antigen-presenting cells. IAV was internalized by both myeloid DCs (mDCs) and plasmacytoid DCs but only mDCs supported viral replication. Although infected mDCs efficiently presented endogenous IAV antigens on MHC class II, this was not the case for presentation on MHC class I. Indeed, cross-presentation by uninfected cells of minute amounts of endocytosed, exogenous IAV was ∼300-fold more efficient than presentation of IAV antigens synthesized by infected cells and resulted in a statistically significant increase in expansion of IAV-specific CD8 T cells. Furthermore, IAV infection also impaired cross-presentation of other exogenous antigens, indicating that IAV infection broadly attenuates presentation on MHC class I molecules. Our results suggest that cross-presentation by uninfected mDCs is a preferred mechanism of antigen-presentation for the activation and expansion of CD8 T cells during IAV infection. PMID:22412374
Corruption of dendritic cell antigen presentation during acute GVHD leads to regulatory T-cell failure and chronic GVHD

PubMed Central

Leveque-El mouttie, Lucie; Koyama, Motoko; Le Texier, Laetitia; Markey, Kate A.; Cheong, Melody; Kuns, Rachel D.; Lineburg, Katie E.; Teal, Bianca E.; Alexander, Kylie A.; Clouston, Andrew D.; Blazar, Bruce R.; Hill, Geoffrey R.

2016-01-01

Chronic graft-versus-host disease (cGVHD) is a major cause of late mortality following allogeneic bone marrow transplantation (BMT) and is characterized by tissue fibrosis manifesting as scleroderma and bronchiolitis obliterans. The development of acute GVHD (aGVHD) is a powerful clinical predictor of subsequent cGVHD, suggesting that aGVHD may invoke the immunologic pathways responsible for cGVHD. In preclinical models in which sclerodermatous cGVHD develops after a preceding period of mild aGVHD, we show that antigen presentation within major histocompatibility complex (MHC) class II of donor dendritic cells (DCs) is markedly impaired early after BMT. This is associated with a failure of regulatory T-cell (Treg) homeostasis and cGVHD. Donor DC-restricted deletion of MHC class II phenocopied this Treg deficiency and cGVHD. Moreover, specific depletion of donor Tregs after BMT also induced cGVHD, whereas adoptive transfer of Tregs ameliorated it. These data demonstrate that the defect in Treg homeostasis seen in cGVHD is a causative lesion and is downstream of defective antigen presentation within MHC class II that is induced by aGVHD. PMID:27338097
Corruption of dendritic cell antigen presentation during acute GVHD leads to regulatory T-cell failure and chronic GVHD.

PubMed

Leveque-El Mouttie, Lucie; Koyama, Motoko; Le Texier, Laetitia; Markey, Kate A; Cheong, Melody; Kuns, Rachel D; Lineburg, Katie E; Teal, Bianca E; Alexander, Kylie A; Clouston, Andrew D; Blazar, Bruce R; Hill, Geoffrey R; MacDonald, Kelli P A

2016-08-11

Chronic graft-versus-host disease (cGVHD) is a major cause of late mortality following allogeneic bone marrow transplantation (BMT) and is characterized by tissue fibrosis manifesting as scleroderma and bronchiolitis obliterans. The development of acute GVHD (aGVHD) is a powerful clinical predictor of subsequent cGVHD, suggesting that aGVHD may invoke the immunologic pathways responsible for cGVHD. In preclinical models in which sclerodermatous cGVHD develops after a preceding period of mild aGVHD, we show that antigen presentation within major histocompatibility complex (MHC) class II of donor dendritic cells (DCs) is markedly impaired early after BMT. This is associated with a failure of regulatory T-cell (Treg) homeostasis and cGVHD. Donor DC-restricted deletion of MHC class II phenocopied this Treg deficiency and cGVHD. Moreover, specific depletion of donor Tregs after BMT also induced cGVHD, whereas adoptive transfer of Tregs ameliorated it. These data demonstrate that the defect in Treg homeostasis seen in cGVHD is a causative lesion and is downstream of defective antigen presentation within MHC class II that is induced by aGVHD. © 2016 by The American Society of Hematology.
Thermal noise due to surface-charge effects within the Debye layer of endogenous structures in dendrites.

PubMed

Poznanski, Roman R

2010-02-01

An assumption commonly used in cable theory is revised by taking into account electrical amplification due to intracellular capacitive effects in passive dendritic cables. A generalized cable equation for a cylindrical volume representation of a dendritic segment is derived from Maxwell's equations under assumptions: (i) the electric-field polarization is restricted longitudinally along the cable length; (ii) extracellular isopotentiality; (iii) quasielectrostatic conditions; and (iv) homogeneous medium with constant conductivity and permittivity. The generalized cable equation is identical to Barenblatt's equation arising in the theory of infiltration in fissured strata with a known analytical solution expressed in terms of a definite integral involving a modified Bessel function and the solution to a linear one-dimensional classical cable equation. Its solution is used to determine the impact of thermal noise on voltage attenuation with distance at any particular time. A regular perturbation expansion for the membrane potential about the linear one-dimensional classical cable equation solution is derived in terms of a Green's function in order to describe the dynamics of free charge within the Debye layer of endogenous structures in passive dendritic cables. The asymptotic value of the first perturbative term is explicitly evaluated for small values of time to predict how the slowly fluctuating (in submillisecond range) electric field attributed to intracellular capacitive effects alters the amplitude of the membrane potential. It was found that capacitive effects are almost negligible for cables with electrotonic lengths L>0.5 , contributes up to 10% of the signal for cables with electrotonic lengths in the range between 0.25
Finite element analysis of maxillary bone stress caused by Aramany Class IV obturator prostheses.

PubMed

Miyashita, Elcio Ricardo; Mattos, Beatriz Silva Câmara; Noritomi, Pedro Yoshito; Navarro, Hamilton

2012-05-01

The retention of an Aramany Class IV removable partial dental prosthesis can be compromised by a lack of support. The biomechanics of this obturator prosthesis result in an unusual stress distribution on the residual maxillary bone. This study evaluated the biomechanics of an Aramany Class IV obturator prosthesis with finite element analysis and a digital 3-dimensional (3-D) model developed from a computed tomography scan; bone stress was evaluated according to the load placed on the prosthesis. A 3-D model of an Aramany Class IV maxillary resection and prosthesis was constructed. This model was used to develop a finite element mesh. A 120 N load was applied to the occlusal and incisal platforms corresponding to the prosthetic teeth. Qualitative analysis was based on the scale of maximum principal stress; values obtained through quantitative analysis were expressed in MPa. Under posterior load, tensile and compressive stresses were observed; the tensile stress was greater than the compressive stress, regardless of the bone region, and the greatest compressive stress was observed on the anterior palate near the midline. Under an anterior load, tensile stress was observed in all of the evaluated bone regions; the tensile stress was greater than the compressive stress, regardless of the bone region. The Aramany Class IV obturator prosthesis tended to rotate toward the surgical resection when subjected to posterior or anterior loads. The amount of tensile and compressive stress caused by the Aramany Class IV obturator prosthesis did not exceed the physiological limits of the maxillary bone tissue. (J Prosthet Dent 2012;107:336-342). Copyright © 2012 The Editorial Council of the Journal of Prosthetic Dentistry. Published by Mosby, Inc. All rights reserved.
Understanding MHC Class I Presentation of Viral Antigens by Human Dendritic Cells as a Basis for Rational Design of Therapeutic Vaccines

PubMed Central

van Montfoort, Nadine; van der Aa, Evelyn; Woltman, Andrea M.

2014-01-01

Effective viral clearance requires the induction of virus-specific CD8+ cytotoxic T lymphocytes (CTL). Since dendritic cells (DC) have a central role in initiating and shaping virus-specific CTL responses, it is important to understand how DC initiate virus-specific CTL responses. Some viruses can directly infect DC, which theoretically allow direct presentation of viral antigens to CTL, but many viruses target other cells than DC and thus the host depends on the cross-presentation of viral antigens by DC to activate virus-specific CTL. Research in mouse models has highly enhanced our understanding of the mechanisms underlying cross-presentation and the dendritic cells (DC) subsets involved, however, these results cannot be readily translated toward the role of human DC in MHC class I-antigen presentation of human viruses. Here, we summarize the insights gained in the past 20 years on MHC class I presentation of viral antigen by human DC and add to the current debate on the capacities of different human DC subsets herein. Furthermore, possible sources of viral antigens and essential DC characteristics for effective induction of virus-specific CTL are evaluated. We conclude that cross-presentation is not only an efficient mechanism exploited by DC to initiate immunity to viruses that do not infect DC but also to viruses that do infect DC, because cross-presentation has many conceptual advantages and bypasses direct immune modulatory effects of the virus on its infected target cells. Since knowledge on the mechanism of viral antigen presentation and the preferred DC subsets is crucial for rational vaccine design, the obtained insights are very instrumental for the development of effective anti-viral immunotherapy. PMID:24795724
49 CFR 572.127 - Test conditions and instrumentation.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Forces—Class 1000; (ii) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation—Class 60 (if used). (3) Thorax: (i) Rib acceleration—Class 1000; (ii) Spine and pendulum accelerations—Class...
49 CFR 572.127 - Test conditions and instrumentation.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) Forces—Class 1000; (ii) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation—Class 60 (if used). (3) Thorax: (i) Rib acceleration—Class 1000; (ii) Spine and pendulum accelerations—Class...
49 CFR 572.127 - Test conditions and instrumentation.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) Forces—Class 1000; (ii) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation—Class 60 (if used). (3) Thorax: (i) Rib acceleration—Class 1000; (ii) Spine and pendulum accelerations—Class...
49 CFR 572.127 - Test conditions and instrumentation.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) Forces—Class 1000; (ii) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation—Class 60 (if used). (3) Thorax: (i) Rib acceleration—Class 1000; (ii) Spine and pendulum accelerations—Class...
49 CFR 572.127 - Test conditions and instrumentation.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) Forces—Class 1000; (ii) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation—Class 60 (if used). (3) Thorax: (i) Rib acceleration—Class 1000; (ii) Spine and pendulum accelerations—Class...
49 CFR 572.146 - Test conditions and instrumentation.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) Head acceleration—Class 1000 (2) Neck (i) Force—Class 1000 (ii) Moments—Class 600 (iii) Pendulum... acceleration—Class 1000 (ii) Spine and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv...

49 CFR 572.146 - Test conditions and instrumentation.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) Head acceleration—Class 1000 (2) Neck (i) Force—Class 1000 (ii) Moments—Class 600 (iii) Pendulum... acceleration—Class 1000 (ii) Spine and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv...
49 CFR 572.146 - Test conditions and instrumentation.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) Head acceleration—Class 1000 (2) Neck (i) Force—Class 1000 (ii) Moments—Class 600 (iii) Pendulum... acceleration—Class 1000 (ii) Spine and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv...
49 CFR 572.146 - Test conditions and instrumentation.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Head acceleration—Class 1000 (2) Neck (i) Force—Class 1000 (ii) Moments—Class 600 (iii) Pendulum... acceleration—Class 1000 (ii) Spine and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv...
49 CFR 572.146 - Test conditions and instrumentation.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) Head acceleration—Class 1000 (2) Neck (i) Force—Class 1000 (ii) Moments—Class 600 (iii) Pendulum... acceleration—Class 1000 (ii) Spine and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv...
Equivalence between a generalized dendritic network and a set of one-dimensional networks as a ground of linear dynamics.

PubMed

Koda, Shin-ichi

2015-05-28

It has been shown by some existing studies that some linear dynamical systems defined on a dendritic network are equivalent to those defined on a set of one-dimensional networks in special cases and this transformation to the simple picture, which we call linear chain (LC) decomposition, has a significant advantage in understanding properties of dendrimers. In this paper, we expand the class of LC decomposable system with some generalizations. In addition, we propose two general sufficient conditions for LC decomposability with a procedure to systematically realize the LC decomposition. Some examples of LC decomposable linear dynamical systems are also presented with their graphs. The generalization of the LC decomposition is implemented in the following three aspects: (i) the type of linear operators; (ii) the shape of dendritic networks on which linear operators are defined; and (iii) the type of symmetry operations representing the symmetry of the systems. In the generalization (iii), symmetry groups that represent the symmetry of dendritic systems are defined. The LC decomposition is realized by changing the basis of a linear operator defined on a dendritic network into bases of irreducible representations of the symmetry group. The achievement of this paper makes it easier to utilize the LC decomposition in various cases. This may lead to a further understanding of the relation between structure and functions of dendrimers in future studies.
High-throughput identification and dendritic cell-based functional validation of MHC class I-restricted Mycobacterium tuberculosis epitopes

PubMed Central

Nair, Smita K.; Tomaras, Georgia D.; Sales, Ana Paula; Boczkowski, David; Chan, Cliburn; Plonk, Kelly; Cai, Yongting; Dannull, Jens; Kepler, Thomas B.; Pruitt, Scott K.; Weinhold, Kent J.

2014-01-01

Emergence of drug-resistant strains of the pathogen Mycobacterium tuberculosis (Mtb) and the ineffectiveness of BCG in curtailing Mtb infection makes vaccine development for tuberculosis an important objective. Identifying immunogenic CD8+ T cell peptide epitopes is necessary for peptide-based vaccine strategies. We present a three-tiered strategy for identifying and validating immunogenic peptides: first, identify peptides that form stable complexes with class I MHC molecules; second, determine whether cytotoxic T lymphocytes (CTLs) raised against the whole protein antigen recognize and lyse target cells pulsed with peptides that passed step 1; third, determine whether peptides that passed step 2, when administered in vivo as a vaccine in HLA-A2 transgenic mice, elicit CTLs that lyse target cells expressing the whole protein antigen. Our innovative approach uses dendritic cells transfected with Mtb antigen-encoding mRNA to drive antigen expression. Using this strategy, we have identified five novel peptide epitopes from the Mtb proteins Apa, Mtb8.4 and Mtb19. PMID:24755960
Immunolocalization of vesicular glutamate transporters 1 and 2 in the rat inferior colliculus.

PubMed

Altschuler, R A; Tong, L; Holt, A G; Oliver, D L

2008-06-12

The inferior colliculus is a major relay nucleus in the ascending auditory pathways that receives multiple glutamatergic inputs. Vesicular glutamate transporters 1 and 2 (VGLUT1, VGLUT2) most often have complementary non-overlapping distributions and can be used to differentiate glutamatergic inputs. The present study therefore examined co-immunolabeling of VGLUT1 and VGLUT2 in three divisions of the rat inferior colliculus. Additional co-immunolabeling of microtubule-associated protein 2 and neuronal class III beta-tubulin provided visualization of neuronal soma and processes and allowed identification of axo-somatic versus axo-dendritic contacts. Results showed numerous VGLUT1 and 2 immunolabeled terminals in the central nucleus, lateral cortex and dorsal cortex. In all three divisions there was little to no co-containment of the two vesicular glutamate transporters indicating a complementary distribution. VGLUT1 made predominantly axo-dendritic connections in the neuropil, while VGLUT2 had many axo-somatic contacts in addition to axo-dendritic contacts. VGLUT2 immunolabeled terminals were numerous on the soma and proximal dendrites of many medium-to-large and large neurons in the central nucleus and medium to large neurons in the dorsal cortex. There were more VGLUT2 terminals than VGLUT1 in all divisions and more VGLUT2 terminals in dorsal and lateral cortices than in the central nucleus. This study shows that VGLUT1 and VGLUT2 differentiate complementary patterns of glutamatergic inputs into the central nucleus, lateral and dorsal cortex of the inferior colliculus with VGLUT1 endings predominantly on the dendrites and VGLUT2 on both dendrites and somas.
Tubulation of Class II MHC Compartments Is Microtubule Dependent and Involves Multiple Endolysosomal Membrane Proteins in Primary Dendritic Cells1

PubMed Central

Vyas, Jatin M.; Kim, You-Me; Artavanis-Tsakonas, Katerina; Love, J. Christopher; Van der Veen, Annemarthe G.; Ploegh, Hidde L.

2009-01-01

Immature dendritic cells (DCs) capture exogenous Ags in the periphery for eventual processing in endolysosomes. Upon maturation by TLR agonists, DCs deliver peptide-loaded class II MHC molecules from these compartments to the cell surface via long tubular structures (endolysosomal tubules). The nature and rules that govern the movement of these DC compartments are unknown. In this study, we demonstrate that the tubules contain multiple proteins including the class II MHC molecules and LAMP1, a lysosomal resident protein, as well as CD63 and CD82, members of the tetraspanin family. Endolysosomal tubules can be stained with acidotropic dyes, indicating that they are extensions of lysosomes. However, the proper trafficking of class II MHC molecules themselves is not necessary for endolysosomal tubule formation. DCs lacking MyD88 can also form endolysosomal tubules, demonstrating that MyD88-dependent TLR activation is not necessary for the formation of this compartment. Endolysosomal tubules in DCs exhibit dynamic and saltatory movement, including bidirectional travel. Measured velocities are consistent with motor-based movement along microtubules. Indeed, nocodazole causes the collapse of endolysosomal tubules. In addition to its association with microtubules, endolysosomal tubules follow the plus ends of microtubules as visualized in primary DCs expressing end binding protein 1 (EB1)-enhanced GFP. PMID:17513769
Lupus nephritis in Lebanon.

PubMed

Uthman, I W; Muffarij, A A; Mudawar, W A; Nasr, F W; Masri, A F

2001-01-01

This is a retrospective study of the clinicopathological characteristics of 50 systemic lupus erythematosus patients with nephritis who underwent a kidney biopsy and were admitted to the American University of Beirut Medical Center, in Lebanon, between 1979 and 1999. There were 43 females and seven males, with a median age of 24 y. Renal histology slides from these patients were assessed according to the World Health Organization classification, and were distributed as follows: class I (n = 3, 6%); class II (n = 14, 28%); class III (n = 11, 22%); class IV (n = 19, 38%); class V (n = 1, 2%); class VI (n = 2, 4%). All the patients received oral prednisone, in addition the following treatments were used: pulse intravenous (i.v.) cyclophosphamide (n = 23, 46%); azathioprine (n = 22, 44%); pulse i.v. steroids (n = 19, 38%); chloroquine sulfate (n = 17, 34%); methotrexate (n = 5, 10%); and plasmapheresis (n = 2, 4%). The median duration of follow-up was 5 y (range 1-33 y). On their last evaluation, out of 37 patients who were followed, 20 patients (54%) had controlled disease, eight patients (22%) were still on active medical treatment, four patients (11%) were on chronic hemodialysis, and five patients (13%) had died. Unlike three other Arab populations studies from Kuwait, United Arab Emirates and Saudi Arabia, where the most frequent histopathologic abnormality was class III, diffuse proliferative LN (class IV) was the most common type of lupus nephritis in Lebanon, similarly to reports from USA, France, Netherlands, South Africa, Thailand and Taiwan.
[Phase II clinical trial of autologous dendritic cell vaccine with immunologic adjuvant in cutaneous melanoma patients].

PubMed

Baldueva, I A; Novik, A V; Moiseenko, V M; Nekhaeva, T L; Danilova, A B; Danilov, A O; Protsenko, S A; Petrova, T Iu; Uleĭskaia, G I; Shchekina, L A; Semenova, A I; Mikhaĭlichenko, T D; Teletaeva, G M; Zhabina, A S; Volkov, N V; Komarov, Iu I

2012-01-01

This paper describes the clinical results and immunologic changes in cutaneous melanoma patients receiving active specific immunotherapy with autologous dendritic cell vaccine (DCV) in combination with cyclophosphamide used as immunologic adjuvant. Twenty eight patients with morphologically verified stage III-IV cutaneous melanoma receiving therapy in N. N. Petrov Research Institute of Oncology between 2008 and 2011 were included in the study. All patients signed an informed consent form. Nineteen patients (67,9%) received DCV in therapeutic setting, 9 (32,1%) received it in adjuvant setting. DCV therapy was well tolerated. No serious adverse events were registered. Frequent adverse events included Grade 1-2 unspecific symptoms (fever, fatigue, flu-like symptoms) observed in 22% patients after 3,5% of vaccinations. In therapeutic settings the use DCV lead to clinical effect (PR+SD) in 36,6% of patients. PR was observed in 5% of (95% CI 0-15%) patients, SD in 31,6% (95% CI 13-56%). Duration of the objective responses was 168-965+days. Addition of immunologic adjuvant (cyclophosphamide 300 mg/m2 IV 2 hours) 3 days before vaccination increased its efficacy. In this patients group (n=12) the therapy lead to clinical benefit in 42% (95% CI 17-69%) of cases, median time to progression was 91 (95% CI 55-126) days. This regimen was selected for adjuvant therapy. In the adjuvant therapy group (n=9) the median time to progression was 112 (95% CI 58-166) days. Immunologic monitoring showed correlation ofT- and B-cell immune response with DCV clinical efficacy (p<0,05), no correlation with delayed hypersensivity reaction was observed (p>0,1). DCV is well tolerated and shows immunological and clinical response in stage III-IV skin melanoma patients.
49 CFR 572.137 - Test conditions and instrumentation.

Code of Federal Regulations, 2011 CFR

2011-10-01

...—Class 1000 (2) Neck: (i) Forces—Class 1000 (ii) Moments—Class 600 (iii) Pendulum acceleration—Class 180... and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv) Forces—Class 1000 (v...—Class 180 (6) Femur forces and knee pendulum—Class 600 (n) Coordinate signs for instrumentation polarity...
49 CFR 572.137 - Test conditions and instrumentation.

Code of Federal Regulations, 2010 CFR

2010-10-01

...—Class 1000 (2) Neck: (i) Forces—Class 1000 (ii) Moments—Class 600 (iii) Pendulum acceleration—Class 180... and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv) Forces—Class 1000 (v...—Class 180 (6) Femur forces and knee pendulum—Class 600 (n) Coordinate signs for instrumentation polarity...
49 CFR 572.137 - Test conditions and instrumentation.

Code of Federal Regulations, 2013 CFR

2013-10-01

...—Class 1000 (2) Neck: (i) Forces—Class 1000 (ii) Moments—Class 600 (iii) Pendulum acceleration—Class 180... and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv) Forces—Class 1000 (v...—Class 180 (6) Femur forces and knee pendulum—Class 600 (n) Coordinate signs for instrumentation polarity...
49 CFR 572.137 - Test conditions and instrumentation.

Code of Federal Regulations, 2014 CFR

2014-10-01

...—Class 1000 (2) Neck: (i) Forces—Class 1000 (ii) Moments—Class 600 (iii) Pendulum acceleration—Class 180... and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv) Forces—Class 1000 (v...—Class 180 (6) Femur forces and knee pendulum—Class 600 (n) Coordinate signs for instrumentation polarity...
49 CFR 572.137 - Test conditions and instrumentation.

Code of Federal Regulations, 2012 CFR

2012-10-01

...—Class 1000 (2) Neck: (i) Forces—Class 1000 (ii) Moments—Class 600 (iii) Pendulum acceleration—Class 180... and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv) Forces—Class 1000 (v...—Class 180 (6) Femur forces and knee pendulum—Class 600 (n) Coordinate signs for instrumentation polarity...
Biochemistry of plant class IV chitinases and fungal chitinase-modifying proteins

USDA-ARS?s Scientific Manuscript database

Plant class IV chitinases have 2 domains, a small (3 kDa) amino-terminal domain with homology to carbohydrate binding peptides, and a larger (25 kDa) catalytic domain. The biological function of these chitinases is not known. But it is known that some pathogenic fungi secrete chitinase modifying pro...
Polyglycine hydrolases secreted by Pleosporineae fungi that target the linker region of plant class IV chitinases*

USDA-ARS?s Scientific Manuscript database

Chitinase modifying proteins (cmps) are fungal proteases that truncate plant class IV chitinases by cleaving near their amino termini. We previously described Fv-cmp, a fungalysin protease that cleaves a conserved glycine-cysteine bond within the hevein domain. Here we describe a new type of cmp—pol...
Alcoholytic Cleavage of Polyhydroxyalkanoate Chains by Class IV Synthases Induced by Endogenous and Exogenous Ethanol

PubMed Central

Hyakutake, Manami; Tomizawa, Satoshi; Mizuno, Kouhei; Abe, Hideki

2014-01-01

Polyhydroxyalkanoate (PHA)-producing Bacillus strains express class IV PHA synthase, which is composed of the subunits PhaR and PhaC. Recombinant Escherichia coli expressing PHA synthase from Bacillus cereus strain YB-4 (PhaRCYB-4) showed an unusual reduction of the molecular weight of PHA produced during the stationary phase of growth. Nuclear magnetic resonance analysis of the low-molecular-weight PHA revealed that its carboxy end structure was capped by ethanol, suggesting that the molecular weight reduction was the result of alcoholytic cleavage of PHA chains by PhaRCYB-4 induced by endogenous ethanol. This scission reaction was also induced by exogenous ethanol in both in vivo and in vitro assays. In addition, PhaRCYB-4 was observed to have alcoholysis activity for PHA chains synthesized by other synthases. The PHA synthase from Bacillus megaterium (PhaRCBm) from another subgroup of class IV synthases was also assayed and was shown to have weak alcoholysis activity for PHA chains. These results suggest that class IV synthases may commonly share alcoholysis activity as an inherent feature. PMID:24334666
Cell migration and antigen capture are antagonistic processes coupled by myosin II in dendritic cells

PubMed Central

Chabaud, Mélanie; Heuzé, Mélina L.; Bretou, Marine; Vargas, Pablo; Maiuri, Paolo; Solanes, Paola; Maurin, Mathieu; Terriac, Emmanuel; Le Berre, Maël; Lankar, Danielle; Piolot, Tristan; Adelstein, Robert S.; Zhang, Yingfan; Sixt, Michael; Jacobelli, Jordan; Bénichou, Olivier; Voituriez, Raphaël; Piel, Matthieu; Lennon-Duménil, Ana-Maria

2015-01-01

The immune response relies on the migration of leukocytes and on their ability to stop in precise anatomical locations to fulfil their task. How leukocyte migration and function are coordinated is unknown. Here we show that in immature dendritic cells, which patrol their environment by engulfing extracellular material, cell migration and antigen capture are antagonistic. This antagonism results from transient enrichment of myosin IIA at the cell front, which disrupts the back-to-front gradient of the motor protein, slowing down locomotion but promoting antigen capture. We further highlight that myosin IIA enrichment at the cell front requires the MHC class II-associated invariant chain (Ii). Thus, by controlling myosin IIA localization, Ii imposes on dendritic cells an intermittent antigen capture behaviour that might facilitate environment patrolling. We propose that the requirement for myosin II in both cell migration and specific cell functions may provide a general mechanism for their coordination in time and space. PMID:26109323
Sensory Neuron Fates Are Distinguished by a Transcriptional Switch that Regulates Dendrite Branch Stabilization

PubMed Central

Smith, Cody J.; O’Brien, Timothy; Chatzigeorgiou, Marios; Spencer, W. Clay; Feingold-Link, Elana; Husson, Steven J.; Hori, Sayaka; Mitani, Shohei; Gottschalk, Alexander; Schafer, William R.; Miller, David M.

2013-01-01

SUMMARY Sensory neurons adopt distinct morphologies and functional modalities to mediate responses to specific stimuli. Transcription factors and their downstream effectors orchestrate this outcome but are incompletely defined. Here, we show that different classes of mechanosensory neurons in C. elegans are distinguished by the combined action of the transcription factors MEC-3, AHR-1, and ZAG-1. Low levels of MEC-3 specify the elaborate branching pattern of PVD nociceptors, whereas high MEC-3 is correlated with the simple morphology of AVM and PVM touch neurons. AHR-1 specifies AVM touch neuron fate by elevating MEC-3 while simultaneously blocking expression of nociceptive genes such as the MEC-3 target, the claudin-like membrane protein HPO-30, that promotes the complex dendritic branching pattern of PVD. ZAG-1 exercises a parallel role to prevent PVM from adopting the PVD fate. The conserved dendritic branching function of the Drosophila AHR-1 homolog, Spineless, argues for similar pathways in mammals. PMID:23889932

Home inotropic therapy in advanced heart failure: cost analysis and clinical outcomes.

PubMed

Harjai, K J; Mehra, M R; Ventura, H O; Lapeyre, Y M; Murgo, J P; Stapleton, D D; Smart, F W

1997-11-05

This study was conducted to assess cost savings and clinical outcomes associated with the use of home i.v. inotropic therapy in patients with advanced (New York Heart Association [NYHA] class IV) heart failure. Retrospective analysis. Tertiary care referral center. Twenty-four patients (13 men, 11 women; age, 61+/-12 years) with left ventricular ejection fraction <30% and heart failure refractory to oral agents required home i.v. inotropic therapy for at least 4 consecutive weeks between May 1994 and April 1996. Inotropic agents used included dobutamine (n=20; dose, 5.0+/-2.2 microg/kg/min) or milrinone (n=7; dose, 0.53+/-0.05 microg/kg/min). Cost of care and clinical outcomes (hospital admissions, length of hospital stay, NYHA functional class) were compared during the period of inotropic therapy (study period) and the immediate preceding period of equal duration (control period). In comparison to the control period, the study period (3.9+/-2.7 months) was associated with a 16% reduction in cost, amounting to a calculated savings of $5,700 per patient or $1,465 per patient per month. Concomitantly, a decrease in the number of hospital admissions from 2.7+/-2.6 to 1.3+/-1.3 (p=0.056) and length of hospital stay from 20.9+/-12.7 to 5.5+/-5.4 days (p=0.0004) was observed with improvement in NYHA functional class from 4.0+/-0.0 to 2.7+/-0.9 (p<0.0001). Eight patients (38%) died after 2.8+/-1.7 months of home i.v. inotropic therapy. Home i.v. inotropic therapy reduces hospital admissions, length of stay, and cost of care and improves functional class in patients with advanced (NYHA class IV) heart failure.
Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of thefirst phase I clinical trial

PubMed Central

Escudier, Bernard; Dorval, Thierry; Chaput, Nathalie; André, Fabrice; Caby, Marie-Pierre; Novault, Sophie; Flament, Caroline; Leboulaire, Christophe; Borg, Christophe; Amigorena, Sebastian; Boccaccio, Catherine; Bonnerot, Christian; Dhellin, Olivier; Movassagh, Mojgan; Piperno, Sophie; Robert, Caroline; Serra, Vincent; Valente, Nancy; Le Pecq, Jean-Bernard; Spatz, Alain; Lantz, Olivier; Tursz, Thomas; Angevin, Eric; Zitvogel, Laurence

2005-01-01

Background DC derived-exosomes are nanomeric vesicles harboring functional MHC/peptide complexes capable of promoting T cell immune responses and tumor rejection. Here we report the feasability and safety of the first Phase I clinical trial using autologous exosomes pulsed with MAGE 3 peptides for the immunization of stage III/IV melanoma patients. Secondary endpoints were the monitoring of T cell responses and the clinical outcome. Patients and methods Exosomes were purified from day 7 autologous monocyte derived-DC cultures. Fifteen patients fullfilling the inclusion criteria (stage IIIB and IV, HLA-A1+, or -B35+ and HLA-DPO4+ leukocyte phenotype, tumor expressing MAGE3 antigen) were enrolled from 2000 to 2002 and received four exosome vaccinations. Two dose levels of either MHC class II molecules (0.13 versus 0.40 × 1014 molecules) or peptides (10 versus 100 μg/ml) were tested. Evaluations were performed before and 2 weeks after immunization. A continuation treatment was performed in 4 cases of non progression. Results The GMP process allowed to harvest about 5 × 1014 exosomal MHC class II molecules allowing inclusion of all 15 patients. There was no grade II toxicity and the maximal tolerated dose was not achieved. One patient exhibited a partial response according to the RECIST criteria. This HLA-B35+/A2+ patient vaccinated with A1/B35 defined CTL epitopes developed halo of depigmentation around naevi, a MART1-specific HLA-A2 restricted T cell response in the tumor bed associated with progressive loss of HLA-A2 and HLA-BC molecules on tumor cells during therapy with exosomes. In addition, one minor, two stable and one mixed responses were observed in skin and lymph node sites. MAGE3 specific CD4+ and CD8+ T cell responses could not be detected in peripheral blood. Conclusion The first exosome Phase I trial highlighted the feasibility of large scale exosome production and the safety of exosome administration. PMID:15740633
Drosophila Nociceptive Sensitization Requires BMP Signaling via the Canonical SMAD Pathway.

PubMed

Follansbee, Taylor L; Gjelsvik, Kayla J; Brann, Courtney L; McParland, Aidan L; Longhurst, Colin A; Galko, Michael J; Ganter, Geoffrey K

2017-08-30

Nociceptive sensitization is a common feature in chronic pain, but its basic cellular mechanisms are only partially understood. The present study used the Drosophila melanogaster model system and a candidate gene approach to identify novel components required for modulation of an injury-induced nociceptive sensitization pathway presumably downstream of Hedgehog. This study demonstrates that RNAi silencing of a member of the Bone Morphogenetic Protein (BMP) signaling pathway, Decapentaplegic (Dpp), specifically in the Class IV multidendritic nociceptive neuron, significantly attenuated ultraviolet injury-induced sensitization. Furthermore, overexpression of Dpp in Class IV neurons was sufficient to induce thermal hypersensitivity in the absence of injury. The requirement of various BMP receptors and members of the SMAD signal transduction pathway in nociceptive sensitization was also demonstrated. The effects of BMP signaling were shown to be largely specific to the sensitization pathway and not associated with changes in nociception in the absence of injury or with changes in dendritic morphology. Thus, the results demonstrate that Dpp and its pathway play a crucial and novel role in nociceptive sensitization. Because the BMP family is so strongly conserved between vertebrates and invertebrates, it seems likely that the components analyzed in this study represent potential therapeutic targets for the treatment of chronic pain in humans. SIGNIFICANCE STATEMENT This report provides a genetic analysis of primary nociceptive neuron mechanisms that promote sensitization in response to injury. Drosophila melanogaster larvae whose primary nociceptive neurons were reduced in levels of specific components of the BMP signaling pathway, were injured and then tested for nocifensive responses to a normally subnoxious stimulus. Results suggest that nociceptive neurons use the BMP2/4 ligand, along with identified receptors and intracellular transducers to transition to a sensitized state. These findings are consistent with the observation that BMP receptor hyperactivation correlates with bone abnormalities and pain sensitization in fibrodysplasia ossificans progressiva (Kitterman et al., 2012). Because nociceptive sensitization is associated with chronic pain, these findings indicate that human BMP pathway components may represent targets for novel pain-relieving drugs. Copyright © 2017 the authors 0270-6474/17/378524-10$15.00/0.
Drosophila Nociceptive Sensitization Requires BMP Signaling via the Canonical SMAD Pathway

PubMed Central

Follansbee, Taylor L.; Gjelsvik, Kayla J.; Brann, Courtney L.; McParland, Aidan L.

2017-01-01

Nociceptive sensitization is a common feature in chronic pain, but its basic cellular mechanisms are only partially understood. The present study used the Drosophila melanogaster model system and a candidate gene approach to identify novel components required for modulation of an injury-induced nociceptive sensitization pathway presumably downstream of Hedgehog. This study demonstrates that RNAi silencing of a member of the Bone Morphogenetic Protein (BMP) signaling pathway, Decapentaplegic (Dpp), specifically in the Class IV multidendritic nociceptive neuron, significantly attenuated ultraviolet injury-induced sensitization. Furthermore, overexpression of Dpp in Class IV neurons was sufficient to induce thermal hypersensitivity in the absence of injury. The requirement of various BMP receptors and members of the SMAD signal transduction pathway in nociceptive sensitization was also demonstrated. The effects of BMP signaling were shown to be largely specific to the sensitization pathway and not associated with changes in nociception in the absence of injury or with changes in dendritic morphology. Thus, the results demonstrate that Dpp and its pathway play a crucial and novel role in nociceptive sensitization. Because the BMP family is so strongly conserved between vertebrates and invertebrates, it seems likely that the components analyzed in this study represent potential therapeutic targets for the treatment of chronic pain in humans. SIGNIFICANCE STATEMENT This report provides a genetic analysis of primary nociceptive neuron mechanisms that promote sensitization in response to injury. Drosophila melanogaster larvae whose primary nociceptive neurons were reduced in levels of specific components of the BMP signaling pathway, were injured and then tested for nocifensive responses to a normally subnoxious stimulus. Results suggest that nociceptive neurons use the BMP2/4 ligand, along with identified receptors and intracellular transducers to transition to a sensitized state. These findings are consistent with the observation that BMP receptor hyperactivation correlates with bone abnormalities and pain sensitization in fibrodysplasia ossificans progressiva (Kitterman et al., 2012). Because nociceptive sensitization is associated with chronic pain, these findings indicate that human BMP pathway components may represent targets for novel pain-relieving drugs. PMID:28855331
Microbiota regulate the ability of lung dendritic cells to induce IgA class-switch recombination and generate protective gastrointestinal immune responses

PubMed Central

Ruane, Darren; Chorny, Alejo; Lee, Haekyung; Faith, Jeremiah; Pandey, Gaurav; Shan, Meimei; Simchoni, Noa; Rahman, Adeeb; Garg, Aakash; Weinstein, Erica G.; Oropallo, Michael; Gaylord, Michelle; Ungaro, Ryan; Cunningham-Rundles, Charlotte; Alexandropoulos, Konstantina; Mucida, Daniel; Merad, Miriam; Cerutti, Andrea

2016-01-01

Protective immunoglobulin A (IgA) responses to oral antigens are usually orchestrated by gut dendritic cells (DCs). Here, we show that lung CD103+ and CD24+CD11b+ DCs induced IgA class-switch recombination (CSR) by activating B cells through T cell–dependent or –independent pathways. Compared with lung DCs (LDC), lung CD64+ macrophages had decreased expression of B cell activation genes and induced significantly less IgA production. Microbial stimuli, acting through Toll-like receptors, induced transforming growth factor-β (TGF-β) production by LDCs and exerted a profound influence on LDC-mediated IgA CSR. After intranasal immunization with inactive cholera toxin (CT), LDCs stimulated retinoic acid–dependent up-regulation of α4β7 and CCR9 gut-homing receptors on local IgA-expressing B cells. Migration of these B cells to the gut resulted in IgA-mediated protection against an oral challenge with active CT. However, in germ-free mice, the levels of LDC-induced, CT–specific IgA in the gut are significantly reduced. Herein, we demonstrate an unexpected role of the microbiota in modulating the protective efficacy of intranasal vaccination through their effect on the IgA class-switching function of LDCs. PMID:26712806
On the classification of normally distributed neurons: an application to human dentate nucleus.

PubMed

Ristanović, Dušan; Milošević, Nebojša T; Marić, Dušica L

2011-03-01

One of the major goals in cellular neurobiology is the meaningful cell classification. However, in cell classification there are many unresolved issues that need to be addressed. Neuronal classification usually starts with grouping cells into classes according to their main morphological features. If one tries to test quantitatively such a qualitative classification, a considerable overlap in cell types often appears. There is little published information on it. In order to remove the above-mentioned shortcoming, we undertook the present study with the aim to offer a novel method for solving the class overlapping problem. To illustrate our method, we analyzed a sample of 124 neurons from adult human dentate nucleus. Among them we qualitatively selected 55 neurons with small dendritic fields (the small neurons), and 69 asymmetrical neurons with large dendritic fields (the large neurons). We showed that these two samples are normally and independently distributed. By measuring the neuronal soma areas of both samples, we observed that the corresponding normal curves cut each other. We proved that the abscissa of the point of intersection of the curves could represent the boundary between the two adjacent overlapping neuronal classes, since the error done by such division is minimal. Statistical evaluation of the division was also performed.
Positive regulation of plasmacytoid dendritic cell function via Ly49Q recognition of class I MHC

PubMed Central

Tai, Lee-Hwa; Goulet, Marie-Line; Belanger, Simon; Toyama-Sorimachi, Noriko; Fodil-Cornu, Nassima; Vidal, Silvia M.; Troke, Angela D.; McVicar, Daniel W.; Makrigiannis, Andrew P.

2008-01-01

Plasmacytoid dendritic cells (pDCs) are an important source of type I interferon (IFN) during initial immune responses to viral infections. In mice, pDCs are uniquely characterized by high-level expression of Ly49Q, a C-type lectin-like receptor specific for class I major histocompatibility complex (MHC) molecules. Despite having a cytoplasmic immunoreceptor tyrosine-based inhibitory motif, Ly49Q was found to enhance pDC function in vitro, as pDC cytokine production in response to the Toll-like receptor (TLR) 9 agonist CpG-oligonucleotide (ODN) could be blocked using soluble monoclonal antibody (mAb) to Ly49Q or H-2Kb. Conversely, CpG-ODN–dependent IFN-α production by pDCs was greatly augmented upon receptor cross-linking using immobilized anti-Ly49Q mAb or recombinant H-2Kb ligand. Accordingly, Ly49Q-deficient pDCs displayed a severely reduced capacity to produce cytokines in response to TLR7 and TLR9 stimulation both in vitro and in vivo. Finally, TLR9-dependent antiviral responses were compromised in Ly49Q-null mice infected with mouse cytomegalovirus. Thus, class I MHC recognition by Ly49Q on pDCs is necessary for optimal activation of innate immune responses in vivo. PMID:19075287
49 CFR 572.155 - Test conditions and instrumentation.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation potentiometer response (if used)—CFC 60. (3) Thorax: (i) Spine and pendulum accelerations—Class 180; (ii) Shoulder forces—Class 600; (4...
49 CFR 572.155 - Test conditions and instrumentation.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation potentiometer response (if used)—CFC 60. (3) Thorax: (i) Spine and pendulum accelerations—Class 180; (ii) Shoulder forces—Class 600; (4...
49 CFR 572.155 - Test conditions and instrumentation.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation potentiometer response (if used)—CFC 60. (3) Thorax: (i) Spine and pendulum accelerations—Class 180; (ii) Shoulder forces—Class 600; (4...
49 CFR 572.155 - Test conditions and instrumentation.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation potentiometer response (if used)—CFC 60. (3) Thorax: (i) Spine and pendulum accelerations—Class 180; (ii) Shoulder forces—Class 600; (4...
49 CFR 572.155 - Test conditions and instrumentation.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation potentiometer response (if used)—CFC 60. (3) Thorax: (i) Spine and pendulum accelerations—Class 180; (ii) Shoulder forces—Class 600; (4...
Classification and Short-Term Course of DSM-IV Cannabis, Hallucinogen, Cocaine, and Opioid Disorders in Treated Adolescents

ERIC Educational Resources Information Center

Chung, Tammy; Martin, Christoper S.

2005-01-01

This study examined the latent class structure of Diagnostic and Statistical Manual of Mental Disorders (text rev.; DSM-IV; American Psychiatric Association, 2000) symptoms used to diagnose cannabis, hallucinogen, cocaine, and opiate disorders among 501 adolescents recruited from addictions treatment. Latent class results were compared with the…
40 CFR 147.2800 - State-administered program-Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 23 2011-07-01 2011-07-01 false State-administered program-Class I, II, III, IV, and V wells. 147.2800 Section 147.2800 Protection of Environment ENVIRONMENTAL PROTECTION... Federal Register effective July 31, 1985. (1) CNMI Environmental Protection Act, 2 CMC sections 3101, et...
40 CFR 147.2800 - State-administered program-Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 23 2014-07-01 2014-07-01 false State-administered program-Class I, II, III, IV, and V wells. 147.2800 Section 147.2800 Protection of Environment ENVIRONMENTAL PROTECTION... Federal Register effective July 31, 1985. (1) CNMI Environmental Protection Act, 2 CMC sections 3101, et...
40 CFR 147.2800 - State-administered program-Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 22 2010-07-01 2010-07-01 false State-administered program-Class I, II, III, IV, and V wells. 147.2800 Section 147.2800 Protection of Environment ENVIRONMENTAL PROTECTION... Federal Register effective July 31, 1985. (1) CNMI Environmental Protection Act, 2 CMC sections 3101, et...
40 CFR 147.2800 - State-administered program-Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 24 2012-07-01 2012-07-01 false State-administered program-Class I, II, III, IV, and V wells. 147.2800 Section 147.2800 Protection of Environment ENVIRONMENTAL PROTECTION... Federal Register effective July 31, 1985. (1) CNMI Environmental Protection Act, 2 CMC sections 3101, et...
40 CFR 147.2800 - State-administered program-Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 24 2013-07-01 2013-07-01 false State-administered program-Class I, II, III, IV, and V wells. 147.2800 Section 147.2800 Protection of Environment ENVIRONMENTAL PROTECTION... Federal Register effective July 31, 1985. (1) CNMI Environmental Protection Act, 2 CMC sections 3101, et...
Abundance of truncated and full-length ChitA and ChitB chitinases in healthy and diseased maize tissues

USDA-ARS?s Scientific Manuscript database

Chitinase modifying proteins, cmps, are secreted fungal proteases that combat plant defenses by truncating plant class IV chitinases. We initially discovered that ChitA and ChitB, two plant class IV chitinases that are abundant in developing and mature kernels of corn, are truncated by cmps during e...
Cloning and identification of Fv-cmp, a protease from Fusarium verticillioides that truncates Zea mays and Arabidopsis thaliana class IV chitinases

USDA-ARS?s Scientific Manuscript database

Chitinase modifying proteins (cmps) are proteases, secreted by fungal pathogens, that were originally identified as proteins that truncate class IV chitinases of maize during ear rot. Cmps from Bipolaris zeicola and Stenocarpella maydis have been characterized, but the identities of the proteases h...

40 CFR 147.2550 - State-administered program-Class I, III, IV and V wells.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Rules and Regulations, Wyoming Department of Environmental Quality, Chapter XXI: In Situ Mining... program for Class I, III, IV and V wells in the State of Wyoming, except those on Indian lands is the... section 1422 of the SDWA. Notice of this approval was published in the Federal Register on July 15, 1983...
40 CFR 147.2550 - State-administered program-Class I, III, IV and V wells.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Rules and Regulations, Wyoming Department of Environmental Quality, Chapter XXI: In Situ Mining... program for Class I, III, IV and V wells in the State of Wyoming, except those on Indian lands is the... section 1422 of the SDWA. Notice of this approval was published in the Federal Register on July 15, 1983...
Large variability in synaptic N-methyl-D-aspartate receptor density on interneurons and a comparison with pyramidal-cell spines in the rat hippocampus.

PubMed

Nyíri, G; Stephenson, F A; Freund, T F; Somogyi, P

2003-01-01

Pyramidal cells receive input from several types of GABA-releasing interneurons and innervate them reciprocally. Glutamatergic activation of interneurons involves both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) type glutamate receptors expressed in type I synapses, mostly on their dendritic shafts. On average, the synaptic AMPA receptor content is several times higher on interneurons than in the spines of pyramidal cells. To compare the NMDA receptor content of synapses, we used a quantitative postembedding immunogold technique on serial electron microscopic sections, and analysed the synapses on interneuron dendrites and pyramidal cell spines in the CA1 area. Because all NMDA receptors contain the obligatory NR1 subunit, receptor localisation was carried out using antibodies recognising all splice variants of the NR1 subunit. Four populations of synapse were examined: i). on spines of pyramidal cells in stratum (str.) radiatum and str. oriens; ii). on parvalbumin-positive interneuronal dendritic shafts in str. radiatum; iii). on randomly found dendritic shafts in str. oriens and iv). on somatostatin-positive interneuronal dendritic shafts and somata in str. oriens. On average, the size of the synapses on spines was about half of those on interneurons. The four populations of synapse significantly differed in labelling for the NR1 subunit. The median density of NR1 subunit labelling was highest on pyramidal cell spines. It was lowest in the synapses on parvalbumin-positive dendrites in str. radiatum, where more than half of these synapses were immunonegative. In str. oriens, synapses on interneurons had a high variability of receptor content; some dendrites were similar to those in str. radiatum, including the proximal synapses of somatostatin-positive cells, whereas others had immunoreactivity for the NR1 subunit similar to or higher than synapses on pyramidal cell spines. These results show that synaptic NMDA receptor density differs between pyramidal cells and interneurons. Some interneurons may have a high NMDA receptor content, whereas others, like some parvalbumin-expressing cells, a particularly low synaptic NMDA receptor content. Consequently, fast glutamatergic activation of interneurons is expected to show cell type-specific time course and state-dependent dynamics.
Outer membrane protein a of Salmonella enterica serovar Typhimurium activates dendritic cells and enhances Th1 polarization

PubMed Central

2010-01-01

Background Typhoid, which is caused by Salmonella enterica serovar Typhimurium, remains a major health concern worldwide. Multidrug-resistant strains of Salmonella have emerged which exhibit increased survivability and virulence, thus leading to increased morbidity. However, little is known about the protective immune response against this microorganism. The outer membrane protein (Omp)A of bacteria plays an important role in pathogenesis. Results We purified OmpA from S. enterica serovar Typhimurium (OmpA-sal) and characterized the role of OmpA-sal in promoting adaptive and innate immune responses. OmpA-sal functionally activated bone marrow-derived dendritic cells by augmenting expression of CD80, CD86, and major histocompatibility complex classes I and II. Interestingly, OmpA-sal induced production of interferon-γ from T cells in mixed lymphocyte reactions, thus indicating Th1-polarizing capacity. The expression of surface markers and cytokine production in dendritic cells was mediated by the TLR4 signaling pathway in a TLR4 Knock-out system. Conclusions Our findings suggest that OmpA-sal modulates the adaptive immune responses to S. enterica serovar Typhimurium by activating dendritic cells and driving Th1 polarization, which are important properties to consider in the development of effective S. enterica serovar Typhimurium vaccines and immunotherapy adjuvant. PMID:20950448
Matching and selection of a specific subjective experience: conjugate matching and experience.

PubMed

Vimal, Ram Lakhan Pandey

2010-06-01

We incorporate the dual-mode concept in our dual-aspect PE-SE (proto-experience-subjective experience) framework. The two modes are: (1) the non-tilde mode that is the physical (material) and mental aspect of cognition (memory and attention) related feedback signals in a neural-network, which refers to the cognitive nearest past approaching towards present; and (2) the tilde mode that is the material and mental aspect of the feed-forward signals due to external environmental input and internal endogenous input, which pertains to the nearest future approaching towards present and is a entropy-reversed representation of non-tilde mode. Furthermore, one could argue that there are at least five sub-pathways in the stimulus-dependent feed-forward pathway and cognitive feedback pathway for information transfer in the brain dynamics: (i) classical axonal-dendritic neural sub-pathway including electromagnetic information field sub-pathway; (ii) quantum dendritic-dendritic microtubule (MT) (dendritic webs) sub-pathway; (iii) Ca(++)-related astroglial-neural sub-pathway; (iv) (a) the sub-pathway related to extrasynaptic signal transmission between fine distal dendrites of cortical neurons for the local subtle modulation due to voltages created by intradendritic dual-aspect charged surface effects within the Debye layer around endogenous structures such as microtubules (MT) and endoplasmic reticulum (ER) in dendrites, and (b) the sub-pathway related to extracellular volume transmission as fields of neural activity for the global modulation in axonal-dendritic neural sub-pathway; and (v) the sub-pathway related to information transmission via soliton propagation. We propose that: (i) the quantum conjugate matching between experiences in the mental aspect of the tilde mode and that of the non-tilde mode is related more to the mental aspect of the quantum microtubule-dendritic-web and less to that of the non-quantum sub-pathways; and (ii) the classical matching between experiences in the mental aspect of the tilde mode and that of the non-tilde mode is related to the mental aspect of the non-quantum sub-pathways (such as classical axonal-dendritic neural sub-pathway). In both cases, a specific SE is selected when the tilde mode interacts with the non-tilde mode to match for a specific SE, and when the necessary ingredients of SEs (such as the formation of neural networks, wakefulness, re-entry, attention, working memory, and so on) are satisfied. When the conjugate match is made between the two modes, the world-presence (Now) is disclosed. The material aspects in the tilde mode and that in the non-tilde mode are matched to link structure with function, whereas the mental aspects in the tilde mode and that in the non-tilde mode are matched to link experience with structure and function.
Visual deprivation alters dendritic bundle architecture in layer 4 of rat visual cortex.

PubMed

Gabbott, P L; Stewart, M G

2012-04-05

The effect of visual deprivation followed by light exposure on the tangential organisation of dendritic bundles passing through layer 4 of the rat visual cortex was studied quantitatively in the light microscope. Four groups of animals were investigated: (I) rats reared in an environment illuminated normally--group 52 dL; (II) rats reared in the dark until 21 days postnatum (DPN) and subsequently light exposed for 31 days-group 21/31; (III) rats dark reared until 52 DPN and then subsequently light exposed for 3 days--group 3 dL; and (IV) rats totally dark reared until 52 DPN--group 52 DPN. Each group contained five animals. Semithin 0.5-1-μm thick resin-embedded sections were collected from tangential sampling levels through the middle of layer 4 in area 17 and stained with Toluidine Blue. These sections were used to quantitatively analyse the composition and distribution of dendritic clusters in the tangential plane. The key result of this study indicates a significant reduction in the mean number of medium- and small-sized dendritic profiles (diameter less than 2 μm) contributing to clusters in layer 4 of groups 3 dL and 52 dD compared with group 21/31. No differences were detected in the mean number of large-sized dendritic profiles composing a bundle in these experimental groups. Moreover, the mean number of clusters and their tangential distribution in layer 4 did not vary significantly between all four groups. Finally, the clustering parameters were not significantly different between groups 21/31 and the normally reared group 52 dL. This study demonstrates, for the first time, that extended periods of dark rearing followed by light exposure can alter the morphological composition of dendritic bundles in thalamorecipient layer 4 of rat visual cortex. Because these changes occur in the primary region of thalamocortical input, they may underlie specific alterations in the processing of visual information both cortically and subcortically during periods of dark rearing and light exposure. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
The Effect of Solar Irradiated Vibrio cholerae on the Secretion of Pro-Inflammatory Cytokines and Chemokines by the JAWS II Dendritic Cell Line In Vitro

PubMed Central

Ssemakalu, Cornelius Cano; Ubomba-Jaswa, Eunice; Motaung, Keolebogile Shirley; Pillay, Michael

2015-01-01

The use of solar irradiation to sterilize water prior to its consumption has resulted in the reduction of water related illnesses in waterborne disease endemic communities worldwide. Currently, research on solar water disinfection (SODIS) has been directed towards understanding the underlying mechanisms through which solar irradiation inactivates the culturability of microorganisms in water, enhancement of the disinfection process, and the health impact of SODIS water consumption. However, the immunological consequences of SODIS water consumption have not been explored. In this study, we investigated the effect that solar irradiated V. cholerae may have had on the secretion of cytokines and chemokines by the JAWS II dendritic cell line in vitro. The JAWS II dendritic cell line was stimulated with the different strains of V. cholerae that had been: (i) prepared in PBS, (ii) inactivated through a combination of heat and chemical, (iii) solar irradiated, and (iv) non-solar irradiated, in bottled water. As controls, LPS (1 μg/ml) and CTB (1 μg/ml) were used as stimulants. After 48 hours of stimulation the tissue culture media from each treatment was qualitatively and quantitatively analysed for the presence of IL-1α, IL-1β, IL-6, IL-7, IL-10, IL-12p40, IL-12p70, IL-15, MIP-1α, MIP-1β, MIP-2, RANTES, TNF-α, IL-23 and IL-27. Results showed that solar irradiated cultures of V. cholerae induced dendritic cells to secrete significant (p<0.05) levels of pro-inflammatory cytokines in comparison to the unstimulated dendritic cells. Furthermore, the amount of pro-inflammatory cytokines secreted by the dendritic cells in response to solar irradiated cultures of V. cholerae was not as high as observed in treatments involving non-solar irradiated cultures of V. cholerae or LPS. Our results suggest that solar irradiated microorganisms are capable of inducing the secretion of pro-inflammatory cytokines and chemokines. This novel finding is key towards understanding the possible immunological consequences of consuming SODIS treated water. PMID:26066787
[Microinvasive dental treatment in pre-school children].

PubMed

Korolenkova, M V

The aim of the study was to assess the efficiency of atraumatic restorative treatment (ART) with cavity preparation by means of dental endo motor. ART method was applied in 94 children (50 females and 44 males, 301 teeth treated) aged 21-96 months. Wireless dental endo motor (Endo Mate TC2, NSK, Japan) was used for cavity preparation. The cavities (102 (33.9%) class I, 156 (51.8%) class V, 20 (6.6%) class II, 18 (6%) class III and 5 (1.7%) class IV) were then filled with glass-ionomer cement (Fuji IX, GC, Japan). Success rate was assessed 3, 6, 12 and 18 months after treatment. Overall ART procedure success rate (good marginal fit, no occlusal wearing or restoration fractures) at 18-month follow up was 88.7% (267 fillings out of 301) with the highest survival in class I (96.1%) and class V (96.2%) restoration and poorest in class II (50%), class III (44.4%) and class IV (20%) restorations. Cavity preparation with wireless dental endo motor was well tolerated even by infants (12 children were younger than 24 months), as it is noiseless and significantly faster than conventional manual preparation. ART method with the use of dental endo motor showed good success rate and proved to be highly efficient in small and apprehensive children. The method, however, should be avoided in class III and IV cavities as the success rate is poor mostly because of restoration fractures.
How Y-Family DNA polymerase IV is more accurate than Dpo4 at dCTP insertion opposite an N2-dG adduct of benzo[a]pyrene.

PubMed

Sholder, Gabriel; Creech, Amanda; Loechler, Edward L

2015-11-01

To bypass DNA damage, cells have Y-Family DNA polymerases (DNAPs). One Y-Family-class includes DNAP κ and DNAP IV, which accurately insert dCTP opposite N(2)-dG adducts, including from the carcinogen benzo[a]pyrene (BP). Another class includes DNAP η and DNAP V, which insert accurately opposite UV-damage, but inaccurately opposite BP-N(2)-dG. To investigate structural differences between Y-Family-classes, regions are swapped between DNAP IV (a κ/IV-class-member) and Dpo4 (a η/V-class-member); the kinetic consequences are evaluated via primer-extension studies with a BP-N(2)-dG-containing template. Four key structural elements are revealed. (1) Y-Family DNAPs have discreet non-covalent contacts between their little finger-domain (LF-Domain) and their catalytic core-domain (CC-Domain), which we call "non-covalent bridges" (NCBs). Arg37 and Arg38 in DNAP IV's CC-Domain near the active site form a non-covalent bridge (AS-NCB) by interacting with Glu251 and Asp252, respectively, in DNAP IV's LF-Domain. Without these interactions dATP/dGTP/dTTP misinsertions increase. DNAP IV's AS-NCB suppresses misinsertions better than Dpo4's equivalent AS-NCB. (2) DNAP IV also suppresses dATP/dGTP/dTTP misinsertions via a second non-covalent bridge, which is ∼8Å from the active site (Distal-NCB). Dpo4 has no Distal-NCB, rendering it inferior at dATP/dGTP/dTTP suppression. (3) dCTP insertion is facilitated by the larger minor groove opening near the active site in DNAP IV versus Dpo4, which is sensible given that Watson/Crick-like [dCTP:BP-N(2)-dG] pairing requires the BP-moiety to be in the minor groove. (4) Compared to Dpo4, DNAP IV has a smaller major groove opening, which suppresses dGTP misinsertion, implying BP-N(2)-dG bulk in the major groove during Hoogsteen syn-adduct-dG:dGTP pairing. In summary, DNAP IV has a large minor groove opening to enhance dCTP insertion, a plugged major groove opening to suppress dGTP misinsertion, and two non-covalent bridges (near and distal to the active site) to suppress dATP/dGTP/dTTP misinsertions; collectively these four structural features enhance DNAP IV's dNTP insertion fidelity opposite a BP-N(2)-dG adduct compared to Dpo4. Copyright © 2015 Elsevier B.V. All rights reserved.
Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices.

PubMed

Bajema, Ingeborg M; Wilhelmus, Suzanne; Alpers, Charles E; Bruijn, Jan A; Colvin, Robert B; Cook, H Terence; D'Agati, Vivette D; Ferrario, Franco; Haas, Mark; Jennette, J Charles; Joh, Kensuke; Nast, Cynthia C; Noël, Laure-Hélène; Rijnink, Emilie C; Roberts, Ian S D; Seshan, Surya V; Sethi, Sanjeev; Fogo, Agnes B

2018-04-01

We present a consensus report pertaining to the improved clarity of definitions and classification of glomerular lesions in lupus nephritis that derived from a meeting of 18 members of an international nephropathology working group in Leiden, Netherlands, in 2016. Here we report detailed recommendations on issues for which we can propose adjustments based on existing evidence and current consensus opinion (phase 1). New definitions are provided for mesangial hypercellularity and for cellular, fibrocellular, and fibrous crescents. The term "endocapillary proliferation" is eliminated and the definition of endocapillary hypercellularity considered in some detail. We also eliminate the class IV-S and IV-G subdivisions of class IV lupus nephritis. The active and chronic designations for class III/IV lesions are replaced by a proposal for activity and chronicity indices that should be applied to all classes. In the activity index, we include fibrinoid necrosis as a specific descriptor. We also make recommendations on issues for which there are limited data at present and that can best be addressed in future studies (phase 2). We propose to proceed to these investigations, with clinicopathologic studies and tests of interobserver reproducibility to evaluate the applications of the proposed definitions and to classify lupus nephritis lesions. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
Examining the Stability of "DSM-IV" and Empirically Derived Eating Disorder Classification: Implications for "DSM-5"

ERIC Educational Resources Information Center

Peterson, Carol B.; Crow, Scott J.; Swanson, Sonja A.; Crosby, Ross D.; Wonderlich, Stephen A.; Mitchell, James E.; Agras, W. Stewart; Halmi, Katherine A.

2011-01-01

Objective: The purpose of this investigation was to derive an empirical classification of eating disorder symptoms in a heterogeneous eating disorder sample using latent class analysis (LCA) and to examine the longitudinal stability of these latent classes (LCs) and the stability of DSM-IV eating disorder (ED) diagnoses. Method: A total of 429…
The role of single immediate loading implant in long Class IV Kennedy mandibular partial denture.

PubMed

Mohamed, Gehan F; El Sawy, Amal A

2012-10-01

The treatment of long-span Kennedy class IV considers a prosthodontic challenge. This study evaluated the integrity of principle abutments in long Kennedy class IV clinically and radiographically, when rehabilitated with conventional metallic partial denture as a control group and mandibular partial overdentures supported with single immediately loaded implant in symphyseal as a study group. Twelve male patients were divided randomly allotted into two equal groups. First group patients received removable metallic partial denture, whereas in the second group, patients received partial overdentures supported with single immediately loaded implant in symphyseal region. The partial dentures design in both groups was the same. Long-cone paralleling technique and transmission densitometer were used at the time of denture insertion, 3, 6, and 12 months. Gingival index, bone loss, and optical density were measured for principle abutments during the follow-up. A significant reduction in bone loss and density were detected in group II comparing with group I. Gingival index had no significant change (p-value < 0.05). A single symphyseal implant in long span class IV Kennedy can play a pivotal role to improve the integrity of the principle abutments and alveolar bone support. © 2010 Wiley Periodicals, Inc.
Antitumour activity mediated by CD4+ cytotoxic T lymphocytes against MHC class II-negative mouse hepatocellular carcinoma induced by dendritic cell vaccine and interleukin-12.

PubMed

Homma, Sadamu; Komita, Hideo; Sagawa, Yukiko; Ohno, Tsuneya; Toda, Gotaro

2005-08-01

When BALA/c mice with BNL hepatocellular carcinoma (HCC) were treated with dendritic cells fused with BNL cells (DC/BNL) and recombinant murine interleukin (IL)-12, tumour development was significantly suppressed, whereas treatment with either DC/BNL or IL-12 alone did not show a tumour-suppressive effect. Antitumour activity induced by DC/BNL + IL-12 was abrogated by depletion of CD4+ T cells, but not by depletion of CD8+ T cells or natural killer cells. Splenic CD4+ T cells and CD8+ T cells from DC/BNL-treated mice showed cytotoxic activity against BNL cells after 3 days of incubation with DC/BNL, although BNL cells do not express major histocompatibility complex (MHC) class II molecules even after treatment with interferon (INF)-gamma. Furthermore, CD4+ T cells killed syngeneic-irrelevant CT26 cells and even allogeneic Hepa1-6 cells. This cytotoxicity was blocked by concanamycin A, but not by an anti-Fas ligand (FasL) monoclonal antibody, indicating that cytotoxic activity was mediated by perforin. Immunofluorescence microscopy demonstrated that abundant CD4+ T cells and MHC class II-positive macrophages, but not CD8(+) T cells, had infiltrated tumour tissue in mice treated with DC/BNL + IL-12. Flow cytometric analysis of tumour-infiltrating cells in mice treated with DC/BNL + IL-12 showed increases in CD4+ T cells and MHC class II+ CD11b+ cells but not in CD8+ T cells or MHC class I+ CD11b+ cells. Our results suggest that, in BNL-bearing mice treated with DC/BNL + IL-12, tumour macrophages activated by INF-gamma produced by IL-12-stimulated T cells might present BNL tumour antigens and activate DC/BNL-primed CD4+ cytotoxic T lymphocytes (CTLs) in a MHC class II-dependent manner, leading to perforin-mediated bystander killing of neighbouring MHC class II-negative tumour cells.
Antitumour activity mediated by CD4+ cytotoxic T lymphocytes against MHC class II-negative mouse hepatocellular carcinoma induced by dendritic cell vaccine and interleukin-12

PubMed Central

Homma, Sadamu; Komita, Hideo; Sagawa, Yukiko; Ohno, Tsuneya; Toda, Gotaro

2005-01-01

When BALA/c mice with BNL hepatocellular carcinoma (HCC) were treated with dendritic cells fused with BNL cells (DC/BNL) and recombinant murine interleukin (IL)-12, tumour development was significantly suppressed, whereas treatment with either DC/BNL or IL-12 alone did not show a tumour-suppressive effect. Antitumour activity induced by DC/BNL + IL-12 was abrogated by depletion of CD4+ T cells, but not by depletion of CD8+ T cells or natural killer cells. Splenic CD4+ T cells and CD8+ T cells from DC/BNL-treated mice showed cytotoxic activity against BNL cells after 3 days of incubation with DC/BNL, although BNL cells do not express major histocompatibility complex (MHC) class II molecules even after treatment with interferon (INF)-γ. Furthermore, CD4+ T cells killed syngeneic-irrelevant CT26 cells and even allogeneic Hepa1-6 cells. This cytotoxicity was blocked by concanamycin A, but not by an anti-Fas ligand (FasL) monoclonal antibody, indicating that cytotoxic activity was mediated by perforin. Immunofluorescence microscopy demonstrated that abundant CD4+ T cells and MHC class II-positive macrophages, but not CD8+ T cells, had infiltrated tumour tissue in mice treated with DC/BNL + IL-12. Flow cytometric analysis of tumour-infiltrating cells in mice treated with DC/BNL + IL-12 showed increases in CD4+ T cells and MHC class II+ CD11b+ cells but not in CD8+ T cells or MHC class I+ CD11b+ cells. Our results suggest that, in BNL-bearing mice treated with DC/BNL + IL-12, tumour macrophages activated by INF-γ produced by IL-12-stimulated T cells might present BNL tumour antigens and activate DC/BNL-primed CD4+ cytotoxic T lymphocytes (CTLs) in a MHC class II-dependent manner, leading to perforin-mediated bystander killing of neighbouring MHC class II-negative tumour cells. PMID:16011514
Latent class instrumental variables: A clinical and biostatistical perspective

PubMed Central

Baker, Stuart G.; Kramer, Barnett S.; Lindeman, Karen S.

2015-01-01

In some two-arm randomized trials, some participants receive the treatment assigned to the other arm as a result of technical problems, refusal of a treatment invitation, or a choice of treatment in an encouragement design. In some before-and-after studies, the availability of a new treatment changes from one time period to this next. Under assumptions that are often reasonable, the latent class instrumental variable (IV) method estimates the effect of treatment received in the aforementioned scenarios involving all-or-none compliance and all-or-none availability. Key aspects are four initial latent classes (sometimes called principal strata) based on treatment received if in each randomization group or time period, the exclusion restriction assumption (in which randomization group or time period is an instrumental variable), the monotonicity assumption (which drops an implausible latent class from the analysis), and the estimated effect of receiving treatment in one latent class (sometimes called efficacy, the local average treatment effect, or the complier average causal effect). Since its independent formulations in the biostatistics and econometrics literatures, the latent class IV method (which has no well-established name) has gained increasing popularity. We review the latent class IV method from a clinical and biostatistical perspective, focusing on underlying assumptions, methodological extensions, and applications in our fields of obstetrics and cancer research. PMID:26239275
Autophagy-related protein Vps34 controls the homeostasis and function of antigen cross-presenting CD8α+ dendritic cells.

PubMed

Parekh, Vrajesh V; Pabbisetty, Sudheer K; Wu, Lan; Sebzda, Eric; Martinez, Jennifer; Zhang, Jianhua; Van Kaer, Luc

2017-08-01

The class III PI3K Vacuolar protein sorting 34 (Vps34) plays a role in both canonical and noncanonical autophagy, key processes that control the presentation of antigens by dendritic cells (DCs) to naive T lymphocytes. We generated DC-specific Vps34 -deficient mice to assess the contribution of Vps34 to DC functions. We found that DCs from these animals have a partially activated phenotype, spontaneously produce cytokines, and exhibit enhanced activity of the classic MHC class I and class II antigen-presentation pathways. Surprisingly, these animals displayed a defect in the homeostatic maintenance of splenic CD8α + DCs and in the capacity of these cells to cross-present cell corpse-associated antigens to MHC class I-restricted T cells, a property that was associated with defective expression of the T-cell Ig mucin (TIM)-4 receptor. Importantly, mice deficient in the Vps34-associated protein Rubicon, which is critical for a noncanonical form of autophagy called "Light-chain 3 (LC3)-associated phagocytosis" (LAP), lacked such defects. Finally, consistent with their defect in the cross-presentation of apoptotic cells, DC-specific Vps34 -deficient animals developed increased metastases in response to challenge with B16 melanoma cells. Collectively, our studies have revealed a critical role of Vps34 in the regulation of CD8α + DC homeostasis and in the capacity of these cells to process and present antigens associated with apoptotic cells to MHC class I-restricted T cells. Our findings also have important implications for the development of small-molecule inhibitors of Vps34 for therapeutic purposes.
Intravenous Vancomycin Associated With the Development of Nephrotoxicity in Patients With Class III Obesity.

PubMed

Choi, Yookyung Christy; Saw, Stephen; Soliman, Daniel; Bingham, Angela L; Pontiggia, Laura; Hunter, Krystal; Chuang, Linda; Siemianowski, Laura A; Ereshefsky, Benjamin; Hollands, James M

2017-11-01

A consensus statement recommends initial intravenous (IV) vancomycin dosing of 15-20 mg/kg every 8- 24 hours, with an optional 25- to 30-mg/kg loading dose. Although some studies have shown an association between weight and the development of vancomycin-associated nephrotoxicity, results have been inconsistent. To evaluate the correlation between incidence of nephrotoxicity associated with weight-based IV vancomycin dosing strategies in nonobese and obese patients. This retrospective cohort study evaluated hospitalized adult patients admitted who received IV vancomycin. Patients were stratified into nonobese (body mass index [BMI] <25 kg/m 2 ), obesity class I and II (BMI 30-39.9kg/m 2 ), and obesity class III (BMI≥40 kg/m 2 ) groups; patients who were overweight but not obese were excluded. Incidence of nephrotoxicity and serum vancomycin trough concentrations were evaluated. Of a total of 62 documented cases of nephrotoxicity (15.1%), 13 (8.7%), 23 (14.3%), and 26 (26.3%) cases were observed in nonobese, obesity class I and II, and obesity class III groups, respectively ( P=0.002). Longer durations of therapy ( P<0.0001), higher initial maintenance doses in both total milligrams/day ( P=0.0137) and milligrams/kilogram ( P=0.0307), and any trough level >20 mg/L ( P<0.0001) were identified as predictors of development of nephrotoxicity. Concomitant administration of piperacillin/tazobactam, diuretics, and IV contrast were associated with development of nephrotoxicity ( P<0.005, all). Patients with class III obesity were 3-times as likely to develop nephrotoxicity when compared with nonobese patients (odds ratio [OR]=2.99; CI=1.12-7.94) and obesity class I and II patients (OR=3.14; CI=1.27-7.75). Obesity and other factors are associated with a higher risk of vancomycin-associated nephrotoxicity.
Mice completely lacking immunoproteasomes display major alterations in antigen presentation

PubMed Central

Kincaid, Eleanor Z; Che, Jenny W; York, Ian; Escobar, Hernando; Reyes-Vargas, Eduardo; Delgado, Julio C.; Welsh, Raymond M; Karow, Margaret L.; Murphy, Andrew J.; Valenzuela, David M.; Yancopoulos, George D.; Rock, Kenneth L

2011-01-01

The importance of immunoproteasomes to antigen presentation has been unclear because animals totally lacking immunoproteasomes have not been previously developed. Here we show that dendritic cells from mice lacking the three immunoproteasome catalytic subunits display defects in presenting multiple major histocompatability (MHC) class I epitopes. During viral infection in vivo, the presentation of a majority of MHC class I epitopes is markedly reduced in immunoproteasome-deficient animals, while presentation of MHC class II peptides is unaffected. By mass spectrometry the repertoire of MHC class I-presented peptides is ~50% different and these differences are sufficient to stimulate robust transplant rejection of wild type cells in mutant mice. These results indicate that immunoproteasomes play a much more important role in antigen presentation than previously thought. PMID:22197977
Brucella β 1,2 Cyclic Glucan Is an Activator of Human and Mouse Dendritic Cells

PubMed Central

Martirosyan, Anna; Pérez-Gutierrez, Camino; Banchereau, Romain; Dutartre, Hélène; Lecine, Patrick; Dullaers, Melissa; Mello, Marielle; Pinto Salcedo, Suzana; Muller, Alexandre; Leserman, Lee; Levy, Yves; Zurawski, Gerard; Zurawski, Sandy; Moreno, Edgardo; Moriyón, Ignacio; Klechevsky, Eynav; Banchereau, Jacques; Oh, SangKon; Gorvel, Jean-Pierre

2012-01-01

Bacterial cyclic glucans are glucose polymers that concentrate within the periplasm of alpha-proteobacteria. These molecules are necessary to maintain the homeostasis of the cell envelope by contributing to the osmolarity of Gram negative bacteria. Here, we demonstrate that Brucella β 1,2 cyclic glucans are potent activators of human and mouse dendritic cells. Dendritic cells activation by Brucella β 1,2 cyclic glucans requires TLR4, MyD88 and TRIF, but not CD14. The Brucella cyclic glucans showed neither toxicity nor immunogenicity compared to LPS and triggered antigen-specific CD8+ T cell responses in vivo. These cyclic glucans also enhanced antigen-specific CD4+ and CD8+ T cell responses including cross-presentation by different human DC subsets. Brucella β 1,2 cyclic glucans increased the memory CD4+ T cell responses of blood mononuclear cells exposed to recombinant fusion proteins composed of anti-CD40 antibody and antigens from both hepatitis C virus and Mycobacterium tuberculosis. Thus cyclic glucans represent a new class of adjuvants, which might contribute to the development of effective antimicrobial therapies. PMID:23166489
Prominent role for plasmacytoid dendritic cells in mucosal T cell-independent IgA induction.

PubMed

Tezuka, Hiroyuki; Abe, Yukiko; Asano, Jumpei; Sato, Taku; Liu, Jiajia; Iwata, Makoto; Ohteki, Toshiaki

2011-02-25

Although both conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs) are present in the gut-associated lymphoid tissues (GALT), the roles of pDCs in the gut remain largely unknown. Here we show a critical role for pDCs in T cell-independent (TI) IgA production by B cells in the GALT. When pDCs of the mesenteric lymph nodes (MLNs) and Peyer's patches (PPs) (which are representative GALT) were cultured with naive B cells to induce TI IgA class switch recombination (CSR), IgA production was substantially higher than in cocultures of these cells with cDCs. IgA production was dependent on APRIL and BAFF production by pDCs. Importantly, pDC expression of APRIL and BAFF was dependent on stromal cell-derived type I IFN signaling under steady-state conditions. Our findings provide insight into the molecular basis of pDC conditioning to induce mucosal TI IgA production, which may lead to improvements in vaccination strategies and treatment for mucosal-related disorders. Copyright © 2011 Elsevier Inc. All rights reserved.

Digitized Speech Characteristics in Patients with Maxillectomy Defects.

PubMed

Elbashti, Mahmoud E; Sumita, Yuka I; Hattori, Mariko; Aswehlee, Amel M; Taniguchi, Hisashi

2017-12-06

Accurate evaluation of speech characteristics through formant frequency measurement is important for proper speech rehabilitation in patients after maxillectomy. This study aimed to evaluate the utility of digital acoustic analysis and vowel pentagon space for the prediction of speech ability after maxillectomy, by comparing the acoustic characteristics of vowel articulation in three classes of maxillectomy defects. Aramany's classifications I, II, and IV were used to group 27 male patients after maxillectomy. Digital acoustic analysis of five Japanese vowels-/a/, /e/, /i/, /o/, and /u/-was performed using a speech analysis system. First formant (F1) and second formant (F2) frequencies were calculated using an autocorrelation method. Data were plotted on an F1-F2 plane for each patient, and the F1 and F2 ranges were calculated. The vowel pentagon spaces were also determined. One-way ANOVA was applied to compare all results between the three groups. Class II maxillectomy patients had a significantly higher F2 range than did Class I and Class IV patients (p = 0.002). In contrast, there was no significant difference in the F1 range between the three classes. The vowel pentagon spaces were significantly larger in class II maxillectomy patients than in Class I and Class IV patients (p = 0.014). The results of this study indicate that the acoustic characteristics of maxillectomy patients are affected by the defect area. This finding may provide information for obturator design based on vowel articulation and defect class. © 2017 by the American College of Prosthodontists.
Drug formulations intended for the global market should be tested for stability under tropical climatic conditions.

PubMed

Risha, P G; Vervaet, C; Vergote, G; Bortel, L Van; Remon, J P

2003-06-01

The quality of drugs imported into developing countries having a tropical climate may be adversely affected if their formulations have not been optimized for stability under these conditions. The present study investigated the influence of tropical climate conditions (class IV: 40 degrees C, 75% relative humidity) on the drug content, in vitro dissolution and oral bioavailability of different formulations of two essential drugs marketed in Tanzania: diclofenac sodium and ciprofloxacin tablets. Before and after 3 and 6 months storage under class IV conditions the drug content and in vitro dissolution were evaluated using United States Pharmacopoeia (USP) 24 methods. Following a randomized four-period cross-over study, the pharmacokinetic parameters of drug formulations stored for 3 months under class IV conditions were compared with those stored at ambient conditions. Drug content and drug release from all tested ciprofloxacin formulations were within USP-24 requirements and remained stable during storage at simulated tropical conditions. Oral bioavailability was also not influenced by tropical conditions. The dissolution rate of two diclofenac formulations (Diclo 50 manufactured by Camden and Dicloflame 50 manufactured by Intas) reduced significantly during storage under class IV conditions. After oral administration Camden tablets stored for 3 months under class IV conditions showed a reduction in C(max) (90% CI of C(max) ratio: 0.59 - 0.76). This reduction was smaller than expected based on the in vitro tests. Some drug formulations imported into Tanzania are not optimized for stability in a tropical climate. Manufacturers and regulatory authorities should pay more attention to the WHO recommendations for testing the stability of drugs under tropical climate conditions. Efforts should be made to improve the in vitro tests to better predict the bioavailability.
Interobserver agreement on histopathological lesions in class III or IV lupus nephritis.

PubMed

Wilhelmus, Suzanne; Cook, H Terence; Noël, Laure-Hélène; Ferrario, Franco; Wolterbeek, Ron; Bruijn, Jan A; Bajema, Ingeborg M

2015-01-07

To treat lupus nephritis effectively, proper identification of the histologic class is essential. Although the classification system for lupus nephritis is nearly 40 years old, remarkably few studies have investigated interobserver agreement. Interobserver agreement among nephropathologists was studied, particularly with respect to the recognition of class III/IV lupus nephritis lesions, and possible causes of disagreement were determined. A link to a survey containing pictures of 30 glomeruli was provided to all 360 members of the Renal Pathology Society; 34 responses were received from 12 countries (a response rate of 9.4%). The nephropathologist was asked whether glomerular lesions were present that would categorize the biopsy as class III/IV. If so, additional parameters were scored. To determine the interobserver agreement among the participants, κ or intraclass correlation values were calculated. The intraclass correlation or κ-value was also calculated for two separate levels of experience (specifically, nephropathologists who were new to the field or moderately experienced [less experienced] and nephropathologists who were highly experienced). Intraclass correlation for the presence of a class III/IV lesion was 0.39 (poor). The κ/intraclass correlation values for the additional parameters were as follows: active, chronic, or both: 0.36; segmental versus global: 0.39; endocapillary proliferation: 0.46; influx of inflammatory cells: 0.32; swelling of endothelial cells: 0.46; extracapillary proliferation: 0.57; type of crescent: 0.46; and wire loops: 0.35. The highly experienced nephropathologists had significantly less interobserver variability compared with the less experienced nephropathologists (P=0.004). There is generally poor agreement in terms of recognizing class III/IV lesions. Because experience clearly increases interobserver agreement, this agreement may be improved by training nephropathologists. These results also underscore the importance of a central review by experienced nephropathologists in clinical trials. Copyright © 2015 by the American Society of Nephrology.
A 3-tier classification of cerebral arteriovenous malformations. Clinical article.

PubMed

Spetzler, Robert F; Ponce, Francisco A

2011-03-01

The authors propose a 3-tier classification for cerebral arteriovenous malformations (AVMs). The classification is based on the original 5-tier Spetzler-Martin grading system, and reflects the treatment paradigm for these lesions. The implications of this modification in the literature are explored. Class A combines Grades I and II AVMs, Class B are Grade III AVMs, and Class C combines Grades IV and V AVMs. Recommended management is surgery for Class A AVMs, multimodality treatment for Class B, and observation for Class C, with exceptions to the latter including recurrent hemorrhages and progressive neurological deficits. To evaluate whether combining grades is warranted from the perspective of surgical outcomes, the 3-tier system was applied to 1476 patients from 7 surgical series in which results were stratified according to Spetzler-Martin grades. Pairwise comparisons of individual Spetzler-Martin grades in the series analyzed showed the fewest significant differences (p < 0.05) in outcomes between Grades I and II AVMs and between Grades IV and V AVMs. In the pooled data analysis, significant differences in outcomes were found between all grades except IV and V (p = 0.38), and the lowest relative risks were found between Grades I and II (1.066) and between Grades IV and V (1.095). Using the pooled data, the predictive accuracies for surgical outcomes of the 5-tier and 3-tier systems were equivalent (receiver operating characteristic curve area 0.711 and 0.713, respectively). Combining Grades I and II AVMs and combining Grades IV and V AVMs is justified in part because the differences in surgical results between these respective pairs are small. The proposed 3-tier classification of AVMs offers simplification of the Spetzler-Martin system, provides a guide to treatment, and is predictive of outcome. The revised classification not only simplifies treatment recommendations; by placing patients into 3 as opposed to 5 groups, statistical power is markedly increased for series comparisons.
Information processing in dendrites I. Input pattern generalisation.

PubMed

Gurney, K N

2001-10-01

In this paper and its companion, we address the question as to whether there are any general principles underlying information processing in the dendritic trees of biological neurons. In order to address this question, we make two assumptions. First, the key architectural feature of dendrites responsible for many of their information processing abilities is the existence of independent sub-units performing local non-linear processing. Second, any general functional principles operate at a level of abstraction in which neurons are modelled by Boolean functions. To accommodate these assumptions, we therefore define a Boolean model neuron-the multi-cube unit (MCU)-which instantiates the notion of the discrete functional sub-unit. We then use this model unit to explore two aspects of neural functionality: generalisation (in this paper) and processing complexity (in its companion). Generalisation is dealt with from a geometric viewpoint and is quantified using a new metric-the set of order parameters. These parameters are computed for threshold logic units (TLUs), a class of random Boolean functions, and MCUs. Our interpretation of the order parameters is consistent with our knowledge of generalisation in TLUs and with the lack of generalisation in randomly chosen functions. Crucially, the order parameters for MCUs imply that these functions possess a range of generalisation behaviour. We argue that this supports the general thesis that dendrites facilitate input pattern generalisation despite any local non-linear processing within functionally isolated sub-units.
37 CFR 2.6 - Trademark fees.

Code of Federal Regulations, 2010 CFR

2010-07-01

... filing an application on paper, per class $375.00 (ii) For filing an application through TEAS, per class $325.00 (iii) For filing a TEAS Plus application under § 2.22, per class $275.00 (iv) Additional...
Cloning and heterologous expression of a novel subgroup of class IV polyhydroxyalkanoate synthase genes from the genus Bacillus.

PubMed

Mizuno, Kouhei; Kihara, Takahiro; Tsuge, Takeharu; Lundgren, Benjamin R; Sarwar, Zaara; Pinto, Atahualpa; Nomura, Christopher T

2017-01-01

Many microorganisms harbor genes necessary to synthesize biodegradable plastics known as polyhydroxyalkanoates (PHAs). We surveyed a genomic database and discovered a new cluster of class IV PHA synthase genes (phaRC). These genes are different in sequence and operon structure from any previously reported PHA synthase. The newly discovered PhaRC synthase was demonstrated to produce PHAs in recombinant Escherichia coli.
Incipient class II mixed valency in a plutonium solid-state compound

NASA Astrophysics Data System (ADS)

Cary, Samantha K.; Galley, Shane S.; Marsh, Matthew L.; Hobart, David L.; Baumbach, Ryan E.; Cross, Justin N.; Stritzinger, Jared T.; Polinski, Matthew J.; Maron, Laurent; Albrecht-Schmitt, Thomas E.

2017-09-01

Electron transfer in mixed-valent transition-metal complexes, clusters and materials is ubiquitous in both natural and synthetic systems. The degree to which intervalence charge transfer (IVCT) occurs, dependent on the degree of delocalization, places these within class II or III of the Robin-Day system. In contrast to the d-block, compounds of f-block elements typically exhibit class I behaviour (no IVCT) because of localization of the valence electrons and poor spatial overlap between metal and ligand orbitals. Here, we report experimental and computational evidence for delocalization of 5f electrons in the mixed-valent PuIII/PuIV solid-state compound, Pu3(DPA)5(H2O)2 (DPA = 2,6-pyridinedicarboxylate). The properties of this compound are benchmarked by the pure PuIII and PuIV dipicolinate complexes, [PuIII(DPA)(H2O)4]Br and PuIV(DPA)2(H2O)3·3H2O, as well as by a second mixed-valent compound, PuIII[PuIV(DPA)3H0.5]2, that falls into class I instead. Metal-to-ligand charge transfer is involved in both the formation of Pu3(DPA)5(H2O)2 and in the IVCT.
Optical radiation hazards of laser welding processes. Part II: CO2 laser.

PubMed

Rockwell, R J; Moss, C E

1989-08-01

There has been an extensive growth within the last five years in the use of high-powered lasers in various metalworking processes. The two types of lasers used most frequently for laser welding/cutting processes are the Neodymium-yttrium-aluminum-garnet (Nd:YAG) and the carbon dioxide (CO2) systems. When such lasers are operated in an open beam configuration, they are designated as a Class IV laser system. Class IV lasers are high-powered lasers that may present an eye and skin hazard under most common exposure conditions, either directly or when the beam has been diffusely scattered. Significant control measures are required for unenclosed (open beam), Class IV laser systems since workers may be exposed to scattered or reflected beams during the operation, maintenance, and service of these lasers. In addition to ocular and/or skin exposure hazards, such lasers also may present a multitude of nonlaser beam occupational concerns. Radiant energy measurements are reported for both the scattered laser radiation and the plasma-related plume radiations released during typical high-powered CO2 laser-target interactions. In addition, the application of the nominal hazard zone (NHZ) and other control measures also are discussed with special emphasis on Class IV industrial CO2 laser systems.
Organization and variation analysis of 5S rDNA in different ploidy-level hybrids of red crucian carp × topmouth culter.

PubMed

He, Weiguo; Qin, Qinbo; Liu, Shaojun; Li, Tangluo; Wang, Jing; Xiao, Jun; Xie, Lihua; Zhang, Chun; Liu, Yun

2012-01-01

Through distant crossing, diploid, triploid and tetraploid hybrids of red crucian carp (Carassius auratus red var., RCC♀, Cyprininae, 2n = 100) × topmouth culter (Erythroculter ilishaeformis Bleeker, TC♂, Cultrinae, 2n = 48) were successfully produced. Diploid hybrids possessed 74 chromosomes with one set from RCC and one set from TC; triploid hybrids harbored 124 chromosomes with two sets from RCC and one set from TC; tetraploid hybrids had 148 chromosomes with two sets from RCC and two sets from TC. The 5S rDNA of the three different ploidy-level hybrids and their parents were sequenced and analyzed. There were three monomeric 5S rDNA classes (designated class I: 203 bp; class II: 340 bp; and class III: 477 bp) in RCC and two monomeric 5S rDNA classes (designated class IV: 188 bp, and class V: 286 bp) in TC. In the hybrid offspring, diploid hybrids inherited three 5S rDNA classes from their female parent (RCC) and only class IV from their male parent (TC). Triploid hybrids inherited class II and class III from their female parent (RCC) and class IV from their male parent (TC). Tetraploid hybrids gained class II and class III from their female parent (RCC), and generated a new 5S rDNA sequence (designated class I-N). The specific paternal 5S rDNA sequence of class V was not found in the hybrid offspring. Sequence analysis of 5S rDNA revealed the influence of hybridization and polyploidization on the organization and variation of 5S rDNA in fish. This is the first report on the coexistence in vertebrates of viable diploid, triploid and tetraploid hybrids produced by crossing parents with different chromosome numbers, and these new hybrids are novel specimens for studying the genomic variation in the first generation of interspecific hybrids, which has significance for evolution and fish genetics.
Rotavirus Activates Lymphocytes from Non-Obese Diabetic Mice by Triggering Toll-Like Receptor 7 Signaling and Interferon Production in Plasmacytoid Dendritic Cells

PubMed Central

Pane, Jessica A.; Webster, Nicole L.; Coulson, Barbara S.

2014-01-01

It has been proposed that rotavirus infection promotes the progression of genetically-predisposed children to type 1 diabetes, a chronic autoimmune disease marked by infiltration of activated lymphocytes into pancreatic islets. Non-obese diabetic (NOD) mice provide a model for the human disease. Infection of adult NOD mice with rhesus monkey rotavirus (RRV) accelerates diabetes onset, without evidence of pancreatic infection. Rather, RRV spreads to the pancreatic and mesenteric lymph nodes where its association with antigen-presenting cells, including dendritic cells, induces cellular maturation. RRV infection increases levels of the class I major histocompatibility complex on B cells and proinflammatory cytokine expression by T cells at these sites. In autoimmunity-resistant mice and human mononuclear cells from blood, rotavirus-exposed plasmacytoid dendritic cells contribute to bystander polyclonal B cell activation through type I interferon expression. Here we tested the hypothesis that rotavirus induces bystander activation of lymphocytes from NOD mice by provoking dendritic cell activation and proinflammatory cytokine secretion. NOD mouse splenocytes were stimulated with rotavirus and assessed for activation by flow cytometry. This stimulation activated antigen-presenting cells and B cells independently of virus strain and replicative ability. Instead, activation depended on virus dose and was prevented by blockade of virus decapsidation, inhibition of endosomal acidification and interference with signaling through Toll-like receptor 7 and the type I interferon receptor. Plasmacytoid dendritic cells were more efficiently activated than conventional dendritic cells by RRV, and contributed to the activation of B and T cells, including islet-autoreactive CD8+ T cells. Thus, a double-stranded RNA virus can induce Toll-like receptor 7 signaling, resulting in lymphocyte activation. Our findings suggest that bystander activation mediated by type I interferon contributes to the lymphocyte activation observed following RRV infection of NOD mice, and may play a role in diabetes acceleration by rotavirus. PMID:24676425
Calcium Dynamics in Basal Dendrites of Layer 5A and 5B Pyramidal Neurons Is Tuned to the Cell-Type Specific Physiological Action Potential Discharge

PubMed Central

Krieger, Patrik; de Kock, Christiaan P. J.; Frick, Andreas

2017-01-01

Layer 5 (L5) is a major neocortical output layer containing L5A slender-tufted (L5A-st) and L5B thick-tufted (L5B-tt) pyramidal neurons. These neuron types differ in their in vivo firing patterns, connectivity and dendritic morphology amongst other features, reflecting their specific functional role within the neocortical circuits. Here, we asked whether the active properties of the basal dendrites that receive the great majority of synaptic inputs within L5 differ between these two pyramidal neuron classes. To quantify their active properties, we measured the efficacy with which action potential (AP) firing patterns backpropagate along the basal dendrites by measuring the accompanying calcium transients using two-photon laser scanning microscopy in rat somatosensory cortex slices. For these measurements we used both “artificial” three-AP patterns and more complex physiological AP patterns that were previously recorded in anesthetized rats in L5A-st and L5B-tt neurons in response to whisker stimulation. We show that AP patterns with relatively few APs (3APs) evoke a calcium response in L5B-tt, but not L5A-st, that is dependent on the temporal pattern of the three APs. With more complex in vivo recorded AP patterns, the average calcium response was similar in the proximal dendrites but with a decay along dendrites (measured up to 100 μm) of L5B-tt but not L5A-st neurons. Interestingly however, the whisker evoked AP patterns—although very different for the two cell types—evoke similar calcium responses. In conclusion, although the effectiveness with which different AP patterns evoke calcium transients vary between L5A-st and L5B-tt cell, the calcium influx appears to be tuned such that whisker-evoked calcium transients are within the same dynamic range for both cell types. PMID:28744201
Latent class instrumental variables: a clinical and biostatistical perspective.

PubMed

Baker, Stuart G; Kramer, Barnett S; Lindeman, Karen S

2016-01-15

In some two-arm randomized trials, some participants receive the treatment assigned to the other arm as a result of technical problems, refusal of a treatment invitation, or a choice of treatment in an encouragement design. In some before-and-after studies, the availability of a new treatment changes from one time period to this next. Under assumptions that are often reasonable, the latent class instrumental variable (IV) method estimates the effect of treatment received in the aforementioned scenarios involving all-or-none compliance and all-or-none availability. Key aspects are four initial latent classes (sometimes called principal strata) based on treatment received if in each randomization group or time period, the exclusion restriction assumption (in which randomization group or time period is an instrumental variable), the monotonicity assumption (which drops an implausible latent class from the analysis), and the estimated effect of receiving treatment in one latent class (sometimes called efficacy, the local average treatment effect, or the complier average causal effect). Since its independent formulations in the biostatistics and econometrics literatures, the latent class IV method (which has no well-established name) has gained increasing popularity. We review the latent class IV method from a clinical and biostatistical perspective, focusing on underlying assumptions, methodological extensions, and applications in our fields of obstetrics and cancer research. Copyright © 2015 John Wiley & Sons, Ltd.
Induction of dendritic spines by β2-containing nicotinic receptors.

PubMed

Lozada, Adrian F; Wang, Xulong; Gounko, Natalia V; Massey, Kerri A; Duan, Jingjing; Liu, Zhaoping; Berg, Darwin K

2012-06-13

Glutamatergic synapses are located mostly on dendritic spines in the adult nervous system. The spines serve as postsynaptic compartments, containing components that mediate and control the synaptic signal. Early in development, when glutamatergic synapses are initially forming, waves of excitatory activity pass through many parts of the nervous system and are driven in part by a class of heteropentameric β2-containing nicotinic acetylcholine receptors (β2*-nAChRs). These β2*-nAChRs are widely distributed and, when activated, can depolarize the membrane and elevate intracellular calcium levels in neurons. We show here that β2*-nAChRs are essential for acquisition of normal numbers of dendritic spines during development. Mice constitutively lacking the β2-nAChR gene have fewer dendritic spines than do age-matched wild-type mice at all times examined. Activation of β2*-nAChRs by nicotine either in vivo or in organotypic slice culture quickly elevates the number of spines. RNA interference studies both in vivo and in organotypic culture demonstrate that the β2*-nAChRs act in a cell-autonomous manner to increase the number of spines. The increase depends on intracellular calcium and activation of calcium, calmodulin-dependent protein kinase II. Absence of β2*-nAChRs in vivo causes a disproportionate number of glutamatergic synapses to be localized on dendritic shafts, rather than on spines as occurs in wild type. This shift in synapse location is found both in the hippocampus and cortex, indicating the breadth of the effect. Because spine synapses differ from shaft synapses in their signaling capabilities, the shift observed is likely to have significant consequences for network function.
Three-dimensional synaptic analyses of mitral cell and external tufted cell dendrites in rat olfactory bulb glomeruli.

PubMed

Bourne, Jennifer N; Schoppa, Nathan E

2017-02-15

Recent studies have suggested that the two excitatory cell classes of the mammalian olfactory bulb, the mitral cells (MCs) and tufted cells (TCs), differ markedly in physiological responses. For example, TCs are more sensitive and broadly tuned to odors than MCs and also are much more sensitive to stimulation of olfactory sensory neurons (OSNs) in bulb slices. To examine the morphological bases for these differences, we performed quantitative ultrastructural analyses of glomeruli in rat olfactory bulb under conditions in which specific cells were labeled with biocytin and 3,3'-diaminobenzidine. Comparisons were made between MCs and external TCs (eTCs), which are a TC subtype in the glomerular layer with large, direct OSN signals and capable of mediating feedforward excitation of MCs. Three-dimensional analysis of labeled apical dendrites under an electron microscope revealed that MCs and eTCs in fact have similar densities of several chemical synapse types, including OSN inputs. OSN synapses also were distributed similarly, favoring a distal localization on both cells. Analysis of unlabeled putative MC dendrites further revealed gap junctions distributed uniformly along the apical dendrite and, on average, proximally with respect to OSN synapses. Our results suggest that the greater sensitivity of eTCs vs. MCs is due not to OSN synapse number or absolute location but rather to a conductance in the MC dendrite that is well positioned to attenuate excitatory signals passing to the cell soma. Functionally, such a mechanism could allow rapid and dynamic control of OSN-driven action potential firing in MCs through changes in gap junction properties. J. Comp. Neurol. 525:592-609, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
40 CFR Appendix I to Part 1054 - Summary of Previous Emission Standards

Code of Federal Regulations, 2014 CFR

2014-07-01

... Engines (g/kW-hr) a Engine displacement class HC NOX CO Class III 295 5.36 805 Class IV 241 5.36 805 Class...—Phase 2 Emission Standards for Handheld Engines (g/kW-hr) a Engine displacement class HC+NOX CO Class...-hr) a Engine displacement class HC+NOX CO Class I 16.1 519 Class II 13.4 519 a Phase 1 standards are...
40 CFR Appendix I to Part 1054 - Summary of Previous Emission Standards

Code of Federal Regulations, 2012 CFR

2012-07-01

... Engines (g/kW-hr) a Engine displacement class HC NOX CO Class III 295 5.36 805 Class IV 241 5.36 805 Class...—Phase 2 Emission Standards for Handheld Engines (g/kW-hr) a Engine displacement class HC+NOX CO Class...-hr) a Engine displacement class HC+NOX CO Class I 16.1 519 Class II 13.4 519 a Phase 1 standards are...
40 CFR Appendix I to Part 1054 - Summary of Previous Emission Standards

Code of Federal Regulations, 2013 CFR

2013-07-01

... Engines (g/kW-hr) a Engine displacement class HC NOX CO Class III 295 5.36 805 Class IV 241 5.36 805 Class...—Phase 2 Emission Standards for Handheld Engines (g/kW-hr) a Engine displacement class HC+NOX CO Class...-hr) a Engine displacement class HC+NOX CO Class I 16.1 519 Class II 13.4 519 a Phase 1 standards are...
40 CFR Appendix I to Part 1054 - Summary of Previous Emission Standards

Code of Federal Regulations, 2010 CFR

2010-07-01

... Engines (g/kW-hr) a Engine displacement class HC NOX CO Class III 295 5.36 805 Class IV 241 5.36 805 Class...—Phase 2 Emission Standards for Handheld Engines (g/kW-hr) a Engine displacement class HC+NOX CO Class...-hr) a Engine displacement class HC+NOX CO Class I 16.1 519 Class II 13.4 519 a Phase 1 standards are...
40 CFR Appendix I to Part 1054 - Summary of Previous Emission Standards

Code of Federal Regulations, 2011 CFR

2011-07-01

... Engines (g/kW-hr) a Engine displacement class HC NOX CO Class III 295 5.36 805 Class IV 241 5.36 805 Class...—Phase 2 Emission Standards for Handheld Engines (g/kW-hr) a Engine displacement class HC+NOX CO Class...-hr) a Engine displacement class HC+NOX CO Class I 16.1 519 Class II 13.4 519 a Phase 1 standards are...

14 CFR 61.5 - Certificates and ratings issued under this part.

Code of Federal Regulations, 2013 CFR

2013-01-01

...-control aircraft. (2) Airplane class ratings— (i) Single-engine land. (ii) Multiengine land. (iii) Single-engine sea. (iv) Multiengine sea. (3) Rotorcraft class ratings— (i) Helicopter. (ii) Gyroplane. (4) Lighter-than-air class ratings— (i) Airship. (ii) Balloon. (5) Weight-shift-control aircraft class ratings...
14 CFR 61.5 - Certificates and ratings issued under this part.

Code of Federal Regulations, 2014 CFR

2014-01-01

...-control aircraft. (2) Airplane class ratings— (i) Single-engine land. (ii) Multiengine land. (iii) Single-engine sea. (iv) Multiengine sea. (3) Rotorcraft class ratings— (i) Helicopter. (ii) Gyroplane. (4) Lighter-than-air class ratings— (i) Airship. (ii) Balloon. (5) Weight-shift-control aircraft class ratings...
14 CFR 61.5 - Certificates and ratings issued under this part.

Code of Federal Regulations, 2012 CFR

2012-01-01

...-control aircraft. (2) Airplane class ratings— (i) Single-engine land. (ii) Multiengine land. (iii) Single-engine sea. (iv) Multiengine sea. (3) Rotorcraft class ratings— (i) Helicopter. (ii) Gyroplane. (4) Lighter-than-air class ratings— (i) Airship. (ii) Balloon. (5) Weight-shift-control aircraft class ratings...
Characterizing the Spatial Density Functions of Neural Arbors

NASA Astrophysics Data System (ADS)

Teeter, Corinne Michelle

Recently, it has been proposed that a universal function describes the way in which all arbors (axons and dendrites) spread their branches over space. Data from fish retinal ganglion cells as well as cortical and hippocampal arbors from mouse, rat, cat, monkey and human provide evidence that all arbor density functions (adf) can be described by a Gaussian function truncated at approximately two standard deviations. A Gaussian density function implies that there is a minimal set of parameters needed to describe an adf: two or three standard deviations (depending on the dimensionality of the arbor) and an amplitude. However, the parameters needed to completely describe an adf could be further constrained by a scaling law found between the product of the standard deviations and the amplitude of the function. In the following document, I examine the scaling law relationship in order to determine the minimal set of parameters needed to describe an adf. First, I find that the at, two-dimensional arbors of fish retinal ganglion cells require only two out of the three fundamental parameters to completely describe their density functions. Second, the three-dimensional, volume filling, cortical arbors require four fundamental parameters: three standard deviations and the total length of an arbor (which corresponds to the amplitude of the function). Next, I characterize the shape of arbors in the context of the fundamental parameters. I show that the parameter distributions of the fish retinal ganglion cells are largely homogenous. In general, axons are bigger and less dense than dendrites; however, they are similarly shaped. The parameter distributions of these two arbor types overlap and, therefore, can only be differentiated from one another probabilistically based on their adfs. Despite artifacts in the cortical arbor data, different types of arbors (apical dendrites, non-apical dendrites, and axons) can generally be differentiated based on their adfs. In addition, within arbor type, there is evidence of different neuron classes (such as interneurons and pyramidal cells). How well different types and classes of arbors can be differentiated is quantified using the Random ForestTM supervised learning algorithm.
Charge transport in highly efficient iridium cored electrophosphorescent dendrimers

NASA Astrophysics Data System (ADS)

Markham, Jonathan P. J.; Samuel, Ifor D. W.; Lo, Shih-Chun; Burn, Paul L.; Weiter, Martin; Bässler, Heinz

2004-01-01

Electrophosphorescent dendrimers are promising materials for highly efficient light-emitting diodes. They consist of a phosphorescent core onto which dendritic groups are attached. Here, we present an investigation into the optical and electronic properties of highly efficient phosphorescent dendrimers. The effect of dendrimer structure on charge transport and optical properties is studied using temperature-dependent charge-generation-layer time-of-flight measurements and current voltage (I-V) analysis. A model is used to explain trends seen in the I-V characteristics. We demonstrate that fine tuning the mobility by chemical structure is possible in these dendrimers and show that this can lead to highly efficient bilayer dendrimer light-emitting diodes with neat emissive layers. Power efficiencies of 20 lm/W were measured for devices containing a second-generation (G2) Ir(ppy)3 dendrimer with a 1,3,5-tris(2-N-phenylbenzimidazolyl)benzene electron transport layer.
Hemodynamic-GUIDEd Management of Heart Failure

ClinicalTrials.gov

2018-03-29

Heart Failure; Heart Failure, Systolic; Heart Failure, Diastolic; Heart Failure NYHA Class II; Heart Failure NYHA Class III; Heart Failure NYHA Class IV; Heart Failure，Congestive; Heart Failure With Reduced Ejection Fraction; Heart Failure With Normal Ejection Fraction; Heart Failure; With Decompensation
The Activity of Class I-IV Alcohol Dehydrogenase Isoenzymes and Aldehyde Dehydrogenase in Bladder Cancer Cells.

PubMed

Orywal, Karolina; Jelski, Wojciech; Werel, Tadeusz; Szmitkowski, Maciej

2018-01-02

The aim of this study was to determine the differences in the activity of Alcohol Dehydrogenase (ADH) isoenzymes and Aldehyde Dehydrogenase (ALDH) in normal and cancerous bladder cells. Class III, IV of ADH and total ADH activity were measured by the photometric method and class I, II ADH and ALDH activity by the fluorometric method. Significantly higher total activity of ADH was found in both, low-grade and high-grade bladder cancer, in comparison to healthy tissues. The increased activity of total ADH in bladder cancer cells may be the cause of metabolic disorders in cancer cells, which may intensify carcinogenesis.
New laser protective eyewear

NASA Astrophysics Data System (ADS)

McLear, Mark

1996-04-01

Laser technology has significantly impacted our everyday life. Lasers are now used to correct your vision, clear your arteries, and are used in the manufacturing of such diverse products as automobiles, cigarettes, and computers. Lasers are no longer a research tool looking for an application. They are now an integral part of manufacturing. In the case of Class IV lasers, this explosion in laser applications has exposed thousands of individuals to potential safety hazards including eye damage. Specific protective eyewear designed to attenuate the energy of the laser beam below the maximum permissible exposure is required for Class 3B and Class IV lasers according to laser safety standards.
EF24 suppresses maturation and inflammatory response in dendritic cells.

PubMed

Vilekar, Prachi; Awasthi, Shanjana; Natarajan, Aravindan; Anant, Shrikant; Awasthi, Vibhudutta

2012-07-01

Synthetic curcuminoid EF24 was studied for its effect on the maturation and inflammatory response in murine bone marrow derived immortalized JAWS II dendritic cells (DCs). EF24 reduced the expression of LPS-induced MHC class II, CD80 and CD86 molecules. It also abrogated the appearance of dendrites, a typical characteristic of mature DCs. These effects were accompanied by the inhibition of LPS-induced activation of transcription factor nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB). Simultaneous reduction of pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, IL-6] both at the mRNA and secreted levels was also observed. To investigate the dependency of LPS effects on MyD88 adaptor protein, we transfected JAWS II DCs with dominant negative MyD88 plasmid construct (MyD88-DN). EF24 reduced NF-κB activity and TNF-α secretion in a MyD88-dependent manner. These results suggest that EF24 modulates DCs by suppressing their maturation and reducing the secretion of inflammatory cytokines. Further, it appears that EF24 acts at or upstream of MyD88 in the LPS-TLR4/MyD88/NF-κB pathway.
EF24 suppresses maturation and inflammatory response in dendritic cells

PubMed Central

Vilekar, Prachi; Natarajan, Aravindan; Anant, Shrikant

2012-01-01

Synthetic curcuminoid EF24 was studied for its effect on the maturation and inflammatory response in murine bone marrow derived immortalized JAWS II dendritic cells (DCs). EF24 reduced the expression of LPS-induced MHC class II, CD80 and CD86 molecules. It also abrogated the appearance of dendrites, a typical characteristic of mature DCs. These effects were accompanied by the inhibition of LPS-induced activation of transcription factor nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB). Simultaneous reduction of pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, IL-6] both at the mRNA and secreted levels was also observed. To investigate the dependency of LPS effects on MyD88 adaptor protein, we transfected JAWS II DCs with dominant negative MyD88 plasmid construct (MyD88-DN). EF24 reduced NF-κB activity and TNF-α secretion in a MyD88-dependent manner. These results suggest that EF24 modulates DCs by suppressing their maturation and reducing the secretion of inflammatory cytokines. Further, it appears that EF24 acts at or upstream of MyD88 in the LPS-TLR4/MyD88/NF-κB pathway. PMID:22378503
Independent Review of the Defense Logistics Agencys Roles and Missions

DTIC Science & Technology

2014-12-01

remaining wholesale consumables missions of tires, packaged petroleum, oils , and lubricants, and gases and cylinders were transferred from the...housekeeping supplies and equipment. Class III: Petroleum, oils , and lubricants. Class IV: Construction materials. Class V: Ammunition. Class VI...own appropriated funds that are deposited 9 The Construction and Equipment program within DLA Troop Support provides some Class VII non- weapons
Generation of dendrite fragments and their transport from within the mushy zone

NASA Astrophysics Data System (ADS)

Liu, Shan

Five steps have been identified for the grain structure evolution of a casting by an intrinsic mechanism: (i) fragmentation of dendrites in the mushy region; (ii) transport of these dendrite fragments from within this region; (iii) their survival in the bulk liquid; (iv) growth of the survivors; and (v) blockage of the columnar crystal growth front and formation of the equiaxed grains in a casting. Of these, the first two steps remain unclear and are explored in this study. It is found that deceleration of the growth interface leads to fragmentation of side arms from primary stems. This process can be characterized by the Fragmentation Percentage which is related to the magnitude and range of the deceleration, time, and the alloy composition. With decelerations, though temperature gradient at the interface does not change, the dendrite array exhibits important microstructural variations: the dendrite, tip restabilizes rather rapidly (<10 min) and correlates well with the instantaneous tip velocity; and the primary arm spacing restabilization takes ˜5 times longer than the tip readjustment. The difference between the rates of restabilization of the tip radius and primary arm spacing causes slight solute enrichment in the interdendritic region, resulting in side arm detachment. Through a comparative study with the steady state growth process, the magnitude of this solute enrichment is estimated. Further analysis for the dissolution kinetics shows that the excessive solute can only cause a partial dissolution at the neck of a side arm, but this is sufficient to upset the curvature balance between the different sections of a dendritic structure and the continual dissolution at the neck is subsequently driven by the curvature difference until a side arm is detached from the primary stalk. The solidification interface of most castings generally proceeds in a decelerated manner; therefore dendrite fragments already exist in the mushy region. These dendrite fragments can become the nuclei for the central equiaxed zone of a casting or ingot if they are transported out of the mushy zone and into the bulk liquid. The transport may be carried out by natural convection, with channel/plume flow as the most effective carrier; plume velocity and channel diameter are critical for the escape of the dendrite fragments. The selection criteria for them are investigated herein. A new experimental technique of constrained plume promotion has been devised to study the fluid flow behavior. With the simultaneous measurements of the interface advancing velocities, plume flow velocity, composition and temperature of both the plume and the bulk liquid (therefore the buoyancy), the overall flow behavior is quantified and the permeability of the dendrite mushy region is obtained. A model is established to describe natural plume flow and determine the factors for channel size/plume velocity selection. With the results of the constrained case, it is found that the size of a channel is determined by the ratio of the pressure effecting the entrainment in the mush and the pressure necessary for the vertical plume flow, while the absolute value of the pressure controls the plume velocity. Estimates agree well with previous experimental observations. With the number of fragments generated by deceleration and that transported by the entrainment flow, an estimate is made of how many fragments are convected out from the mushy region; this agrees with experimental observations reasonably well.
Usefulness of the brain natriuretic peptide to atrial natriuretic peptide ratio in determining the severity of mitral regurgitation.

PubMed

Shimamoto, Ken; Kusumoto, Miyako; Sakai, Rieko; Watanabe, Hirota; Ihara, Syunichi; Koike, Natsuka; Kawana, Masatoshi

2007-03-15

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels were characterized in subjects with mitral regurgitation (MR). Sixty-two cases of moderate or severe chronic MR were studied. The blood levels of neurohormonal factors were stratified by the known MR prognostic factors of New York Heart Association (NYHA) functional class, left ventricular end-diastolic diameters, left ventricular end-systolic diameter (LVDs), ejection fraction (EF), left atrial diameter and presence of atrial fibrillation (AF). ANP levels were higher in NYHA class II and lower in classes I and III/IV (P=0.0206). BNP levels were higher in NYHA class II than class I (P=0.0355). The BNP/ANP ratio was significantly higher in NYHA classes II and III/IV than in class I (P=0.0007). To differentiate between NYHA classes I/II and III/IV, a cut-off BNP/ANP ratio of 2.97 produced a sensitivity of 78% and specificity of 87%. Compared with subjects in sinus rhythm, patients with AF had an enlarged left atrium and lower ANP levels. The BNP/ANP ratio correlated significantly with left atrial diameter, LVDs and EF (r=0.429, P=0.0017; r=0.351, P=0.0117; and r=-0.349, P=0.0122; respectively), and was significantly higher among all the known operative indications for MR tested (LVDs 45 mm or more, EF 60% or less, NYHA class II or greater and AF; P=0.0073, P=0.003, P=0.0102 and P=0.0149, respectively). In chronic MR, levels of ANP and BNP, and the BNP/ANP ratio are potential indicators of disease severity.
Redo surgery risk in patients with cardiac prosthetic valve dysfunction

PubMed Central

Maciejewski, Marek; Piestrzeniewicz, Katarzyna; Bielecka-Dąbrowa, Agata; Piechowiak, Monika; Jaszewski, Ryszard

2011-01-01

Introduction The aim of the study was to analyse the risk factors of early and late mortality in patients undergoing the first reoperation for prosthetic valve dysfunction. Material and methods A retrospective observational study was performed in 194 consecutive patients (M = 75, F = 119; mean age 53.2 ±11 years) with a mechanical prosthetic valve (n = 103 cases; 53%) or bioprosthesis (91; 47%). Univariate and multivariate Cox statistical analysis was performed to determine risk factors of early and late mortality. Results The overall early mortality was 18.6%: 31.4% in patients with symptoms of NYHA functional class III-IV and 3.4% in pts in NYHA class I-II. Multivariate analysis identified symptoms of NYHA class III-IV and endocarditis as independent predictors of early mortality. The overall late mortality (> 30 days) was 8.2% (0.62% year/patient). Multivariate analysis identified age at the time of reoperation as a strong independent predictor of late mortality. Conclusions Reoperation in patients with prosthetic valves, performed urgently, especially in patients with symptoms of NYHA class III-IV or in the case of endocarditis, bears a high mortality rate. Risk of planned reoperation, mostly in patients with symptoms of NYHA class I-II, does not differ from the risk of the first operation. PMID:22291767
The Capsicum annuum class IV chitinase ChitIV interacts with receptor-like cytoplasmic protein kinase PIK1 to accelerate PIK1-triggered cell death and defence responses

PubMed Central

Kim, Dae Sung; Kim, Nak Hyun; Hwang, Byung Kook

2015-01-01

The pepper receptor-like cytoplasmic protein kinase, CaPIK1, which mediates signalling of plant cell death and defence responses was previously identified. Here, the identification of a class IV chitinase, CaChitIV, from pepper plants (Capsicum annuum), which interacts with CaPIK1 and promotes CaPIK1-triggered cell death and defence responses, is reported. CaChitIV contains a signal peptide, chitin-binding domain, and glycol hydrolase domain. CaChitIV expression was up-regulated by Xanthomonas campestris pv. vesicatoria (Xcv) infection. Notably, avirulent Xcv infection rapidly induced CaChitIV expression in pepper leaves. Bimolecular fluorescence complementation and co-immunoprecipitation revealed that CaPIK1 interacts with CaChitIV in planta, and that the CaPIK1–CaChitIV complex is localized mainly in the cytoplasm and plasma membrane. CaChitIV is also localized in the endoplasmic reticulum. Transient co-expression of CaChitIV with CaPIK1 enhanced CaPIK1-triggered cell death response and reactive oxygen species (ROS) and nitric oxide (NO) bursts. Co-silencing of both CaChitIV and CaPIK1 in pepper plants conferred enhanced susceptibility to Xcv infection, which was accompanied by a reduced induction of cell death response, ROS and NO bursts, and defence response genes. Ectopic expression of CaPIK1 in Arabidopsis enhanced basal resistance to Hyaloperonospora arabidopsidis infection. Together, the results suggest that CaChitIV positively regulates CaPIK1-triggered cell death and defence responses through its interaction with CaPIK1. PMID:25694549
The Capsicum annuum class IV chitinase ChitIV interacts with receptor-like cytoplasmic protein kinase PIK1 to accelerate PIK1-triggered cell death and defence responses.

PubMed

Kim, Dae Sung; Kim, Nak Hyun; Hwang, Byung Kook

2015-04-01

The pepper receptor-like cytoplasmic protein kinase, CaPIK1, which mediates signalling of plant cell death and defence responses was previously identified. Here, the identification of a class IV chitinase, CaChitIV, from pepper plants (Capsicum annuum), which interacts with CaPIK1 and promotes CaPIK1-triggered cell death and defence responses, is reported. CaChitIV contains a signal peptide, chitin-binding domain, and glycol hydrolase domain. CaChitIV expression was up-regulated by Xanthomonas campestris pv. vesicatoria (Xcv) infection. Notably, avirulent Xcv infection rapidly induced CaChitIV expression in pepper leaves. Bimolecular fluorescence complementation and co-immunoprecipitation revealed that CaPIK1 interacts with CaChitIV in planta, and that the CaPIK1-CaChitIV complex is localized mainly in the cytoplasm and plasma membrane. CaChitIV is also localized in the endoplasmic reticulum. Transient co-expression of CaChitIV with CaPIK1 enhanced CaPIK1-triggered cell death response and reactive oxygen species (ROS) and nitric oxide (NO) bursts. Co-silencing of both CaChitIV and CaPIK1 in pepper plants conferred enhanced susceptibility to Xcv infection, which was accompanied by a reduced induction of cell death response, ROS and NO bursts, and defence response genes. Ectopic expression of CaPIK1 in Arabidopsis enhanced basal resistance to Hyaloperonospora arabidopsidis infection. Together, the results suggest that CaChitIV positively regulates CaPIK1-triggered cell death and defence responses through its interaction with CaPIK1. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.
Cancer Immunotherapy Utilized Bubble Liposomes and Ultrasound as Antigen Delivery System

NASA Astrophysics Data System (ADS)

Oda, Yusuke; Otake, Shota; Suzuki, Ryo; Otake, Shota; Nishiie, Norihito; Hirata, Keiichi; Taira, Yuichiro; Utoguchi, Naoki; Maruyama, Kazuo

2010-03-01

In dendritic cells (DCs)-based cancer immunotherapy, it is important to present the epitope peptide derived from tumor associated antigens (TAAs) on MHC class I in order to induce tumor specific cytotoxic T lymphocytes (CTLs). However, MHC class I molecules generally present the epitope peptides derived from endogenous antigens for DCs but not exogenous ones such as TAAs. Recently, we developed the novel liposomal bubbles (Bubble liposomes) encapsulating perfluoropropane nanobubbles. In this study, we attempted to establish the novel antigen delivery system to induce MHC class I presentation using the combination of ultrasound and Bubble liposomes. Using ovalbumin (OVA) as model antigen, the combination of Bubble liposomes and ultrasound exposure for the DC could induce MHC class I presentation. In addition, the viability of DCs was more than 80%. These results suggest that Bubble liposomes might be a novel ultrasound enhanced antigen delivery tool in DC-based cancer immunotherapy.
Evidence That the [beta] Subunit of Chlamydia trachomatis Ribonucleotide Reductase Is Active with the Manganese Ion of Its Manganese(IV)/Iron(III) Cofactor in Site 1

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

Dassama, Laura M.K.; Boal, Amie K.; Krebs, Carsten

2014-10-02

The reaction of a class I ribonucleotide reductase (RNR) begins when a cofactor in the {beta} subunit oxidizes a cysteine residue {approx}35 {angstrom} away in the {alpha} subunit, generating a thiyl radical. In the class Ic enzyme from Chlamydia trachomatis (Ct), the cysteine oxidant is the Mn{sup IV} ion of a Mn{sup IV}/Fe{sup III} cluster, which assembles in a reaction between O{sub 2} and the Mn{sup II}/Fe{sup II} complex of {beta}. The heterodinuclear nature of the cofactor raises the question of which site, 1 or 2, contains the Mn{sup IV} ion. Because site 1 is closer to the conserved locationmore » of the cysteine-oxidizing tyrosyl radical of class Ia and Ib RNRs, we suggested that the Mn{sup IV} ion most likely resides in this site (i.e., {sup 1}Mn{sup IV}/{sup 2}Fe{sup III}), but a subsequent computational study favored its occupation of site 2 ({sup 1}Fe{sup III}/{sup 2}Mn{sup IV}). In this work, we have sought to resolve the location of the Mn{sup IV} ion in Ct RNR-{beta} by correlating X-ray crystallographic anomalous scattering intensities with catalytic activity for samples of the protein reconstituted in vitro by two different procedures. In samples containing primarily Mn{sup IV}/Fe{sup III} clusters, Mn preferentially occupies site 1, but some anomalous scattering from site 2 is observed, implying that both {sup 1}Mn{sup II}/{sup 2}Fe{sup II} and {sup 1}Fe{sup II}/{sup 2}Mn{sup II} complexes are competent to react with O{sub 2} to produce the corresponding oxidized states. However, with diminished Mn{sup II} loading in the reconstitution, there is no evidence for Mn occupancy of site 2, and the greater activity of these 'low-Mn' samples on a per-Mn basis implies that the {sup 1}Mn{sup IV}/{sup 2}Fe{sup III}-{beta} is at least the more active of the two oxidized forms and may be the only active form.« less
[High Pressure Gas Tanks

NASA Technical Reports Server (NTRS)

Quintana, Rolando

2002-01-01

Four high-pressure gas tanks, the basis of this study, were especially made by a private contractor and tested before being delivered to NASA Kennedy Space Center. In order to insure 100% reliability of each individual tank the staff at KSC decided to again submit the four tanks under more rigorous tests. These tests were conducted during a period from April 10 through May 8 at KSC. This application further validates the predictive safety model for accident prevention and system failure in the testing of four high-pressure gas tanks at Kennedy Space Center, called Continuous Hazard Tracking and Failure Prediction Methodology (CHTFPM). It is apparent from the variety of barriers available for a hazard control that some barriers will be more successful than others in providing protection. In order to complete the Barrier Analysis of the system, a Task Analysis and a Biomechanical Study were performed to establish the relationship between the degree of biomechanical non-conformities and the anomalies found within the system on particular joints of the body. This relationship was possible to obtain by conducting a Regression Analysis to the previously generated data. From the information derived the body segment with the lowest percentage of non-conformities was the neck flexion with 46.7%. Intense analysis of the system was conducted including Preliminary Hazard Analysis (PHA), Failure Mode and Effect Analysis (FMEA), and Barrier Analysis. These analyses resulted in the identification of occurrences of conditions, which may be becoming hazardous in the given system. These conditions, known as dendritics, may become hazards and could result in an accident, system malfunction, or unacceptable risk conditions. A total of 56 possible dendritics were identified. Work sampling was performed to observe the occurrence each dendritic. The out of control points generated from a Weighted c control chart along with a Pareto analysis indicate that the dendritics "Personnel not Wearing Proper Protective and Hose/tubing located in high-traffic area" which account for 59.18% of total dendritic frequency need to be addressed to reduce the chance of a hazard from occurring. However, the occurrences of some dendritics are more important than others. As a result immediate, from a Weighted c perspective, corrective action should be taken to ameliorate the cause of the Class A dendritic "Personnel located under suspended or moving loads" rather than just the most commonly occurring dendritics. In any case the vast majority of data obtained indicates that testing operations possess a relatively high degree of safety.
Leptin deficiency impairs maturation of dendritic cells and enhances induction of regulatory T and Th17 cells

PubMed Central

Moraes-Vieira, Pedro M.M.; Larocca, Rafael A.; Bassi, Enio J.; Peron, Jean Pierre S.; Andrade-Oliveira, Vinícius; Wasinski, Frederick; Araujo, Ronaldo; Thornley, Thomas; Quintana, Francisco J.; Basso, Alexandre S.; Strom, Terry B.; Câmara, Niels O.S.

2016-01-01

Leptin is an adipose-secreted hormone that plays an important role in both metabolism and immunity. Leptin has been shown to induce Th1-cell polarization and inhibit Th2-cell responses. Additionally, leptin induces Th17-cell responses, inhibits regulatory T (Treg) cells and modulates autoimmune diseases. Here, we investigated whether leptin mediates its activity on T cells by influencing dendritic cells (DCs) to promote Th17 and Treg-cell immune responses in mice. We observed that leptin deficiency (i) reduced the expression of DC maturation markers, (ii) decreased DC production of IL-12, TNF-α, and IL-6, (iii) increased DC production of TGF-β, and (iv) limited the capacity of DCs to induce syngeneic CD4+ T-cell proliferation. As a consequence of this unique phenotype, DCs generated under leptin-free conditions induced Treg or TH17 cells more efficiently than DCs generated in the presence of leptin. These data indicate important roles for leptin in DC homeostasis and the initiation and maintenance of inflammatory and regulatory immune responses by DCs. PMID:24271843

Clinical profile of patients with biopsy proven lupus nephritis at a tertiary care hospital from Northern Pakistan, 1995 to 2012.

PubMed

Ali, Akhtar; Mehmood, Anjum; Ali, Muhammad Usman

2017-01-01

TTo highlight the clinical spectrum of biopsy-proven lupus nephritis by analysing any variations in its histological subtypes across gender, varying age groups, serum creatinine levels and anti-double stranded deoxyribonucleic acid levels. This retrospective, observational study was conducted at the Lady Reading Hospital in collaboration with the Fauji Foundation Hospital, Peshawar, Pakistan, and comprised patient records of biopsy-proven lupus nephritis from 1995 to 2012. The cases were analysed according to clinical presentations and histological pattern of systemic lupus erythematosus nephritis. EpiData 3.1 and SPSS 17 were used for data analyses. Of the 2,000 renal biopsies performed, lupus nephritis was found in 74(3.7%) cases. Of them, 63(85.1%) were females and 11(14.9%) males. The mean age of the cases was 23.88±9.73 years (range: 10-55 years). Class IV lupus nephritis was seen in 38(51.4%) patients, followed by Class II in 15(20.3%), Class III in 10(13.5%), Class V and VI in 4(5.4%) each and Class I in 3(4.1%). Out of the combined Class III and IV cases, 25(52.08%) had serum creatinine levels of >1.2 mg/dL, whereas positive anti-double stranded deoxyribonucleic acid titers up to 50 IU/L were seen in all of the 48(100%) such patients. Overall, microscopic haematuria was found in 52(70.3%) cases, followed by arthralgia in 40(54.1%). Moreover, 32(50.8%) females and 6(54.5%) males had Type IV nephritis. Class VI lupus nephritis, in particular, were significantly more prominent in 31-40 years of age group when compared to other histological subtypes and age groups (p=0.0096, odds ratio: 23.25, 95% confidence interval: 2.15-251.21). Female predominance was observed in all histological sub-types of lupus nephritis. Class IV lupus was the most common histological pattern. Microscopic haematuria was the most common clinical presentation.
A new class of relativistic stellar models

NASA Astrophysics Data System (ADS)

Haggag, Salah

1995-03-01

Einstein field equations for a static and spherically symmetric perfect fluid are considered. A formulation given by Patino and Rago is used to obtain a class of nine solutions, two of them are Tolman solutions I, IV and the remaining seven are new. The solutions are the correct ones corresponding to expressions derived by Patino and Rago which have been shown by Knutsen to be incorrect. Similar to Tolan solution IV each of the new solutions satisfies energy conditions inside a sphere in some range of two independent parameters. Besides, each solution could be matched to the exterior Schwarzschild solution at a boundary where the pressure vanishes and thus the solutions constitute a class of new physically reasonable stellar models.
The effect of a class IV hurricane on emergency department operations.

PubMed

Sheppa, C M; Stevens, J; Philbrick, J T; Canada, M

1993-09-01

The objective of this study was to determine the impact on emergency department (ED) operations of Hurricane Hugo, a class IV hurricane that struck Charleston, South Carolina, on September 21, 1989. The study design was a retrospective record-based descriptive study and mail survey of the ED of a 300-bed regional medical center directly in the path of the storm. During the 3 weeks after the storm, ED patient volume increased 19% over that of the 3 weeks before the storm. Increased visit volumes were evident for at least 3 months. Compared with a similar period of the previous year, there was an increase in the proportion of patients seen for lacerations of all types, puncture wounds, stings, and falls. Sixty-two percent of physician offices were still closed 7 days after the storm. The direct effects of a class IV hurricane on ED operations included major alterations in the volume and types of patient visits. Because of the evacuation of approximately 40% of the coastal population and storm damage hindering travel, the increase in visit volume was less in magnitude but of longer duration has been reported in class III hurricanes.
Predictors of Operative Mortality for Coronary Bypass Grafting in Patients with Ischemic Heart Disease

PubMed Central

Langou, Rene A.; Wiles, John C.; Peduzzi, Peter N.; Hammond, Graeme; Cohen, Lawrence S.

1978-01-01

Predictors for operative mortality (OM) were studied in 172 consecutive patients (pts) undergoing coronary artery grafts (CAG) for angina pectoris. Seventy eight pts had Class IV angina; of the 147 patients given propranolol, 41 were gradually withdrawn from propranolol and finally discontinued 24 hours before surgery, and 106 were abruptly withdrawn from propranolol 24 hours before CAG; 20 pts had left main coronary disease; 156 pts had cardiopulmonary bypass (CPB) time shorter than 20 minutes, and 16 pts had a CPB longer than 120 minutes. The operative mortality was 5.2% (9/172) for the entire group. Class IV angina (OM 7%), abrupt propranolol withdrawal (OM 6.6%), left main coronary artery disease (OM 25%), and CPB longer than 120 minutes (OM 50%), all significantly increased OM. These variables were interdependent, however, as many pts belonged to several predictor categories, combinations of predictors were examined, in order to more accurately predict the risk of individual pts. The combination of left main coronary artery disease and CPB longer than 120 minutes; and Class IV angina and CPB longer than 120 minutes were significantly associated with higher operative mortality. We conclude that Class IV angina, abrupt propranolol withdrawal, left main coronary artery disease and prolonged CPB are potent, interdependent predictors of OM in pts undergoing CAG. Consideration of these predictors, alone and in combination, allows effective prediction of OM for CAG in patients with stable angina pectoris. PMID:307873
Biomechanical 3-Dimensional Finite Element Analysis of Obturator Protheses Retained with Zygomatic and Dental Implants in Maxillary Defects

PubMed Central

Akay, Canan; Yaluğ, Suat

2015-01-01

Background The objective of this study was to investigate the stress distribution in the bone around zygomatic and dental implants for 3 different implant-retained obturator prostheses designs in a Aramany class IV maxillary defect using 3-dimensional finite element analysis (FEA). Material\\Methods A 3-dimensional finite element model of an Aramany class IV defect was created. Three different implant-retained obturator prostheses were modeled: model 1 with 1 zygomatic implant and 1 dental implant, model 2 with 1 zygomatic implant and 2 dental implants, and model 3 with 2 zygomatic implants. Locator attachments were used as a superstructure. A 150-N load was applied 3 different ways. Qualitative analysis was based on the scale of maximum principal stress; values obtained through quantitative analysis are expressed in MPa. Results In all loading conditions, model 3 (when compared models 1 and 2) showed the lowest maximum principal stress value. Model 3 is the most appropirate reconstruction in Aramany class IV maxillary defects. Two zygomatic implants can reduce the stresses in model 3. The distribution of stresses on prostheses were more rational with the help of zygoma implants, which can distribute the stresses on each part of the maxilla. Conclusions Aramany class IV obturator prosthesis placement of 2 zygomatic implants in each side of the maxilla is more advantageous than placement of dental implants. In the non-defective side, increasing the number of dental implants is not as suitable as zygomatic implants. PMID:25714086
Early postnatal development of vasoactive intestinal polypeptide- and peptide histidine isoleucine-immunoreactive structures in the cat visual cortex.

PubMed

Wahle, P; Meyer, G

1989-04-08

The early postnatal development of neurons containing vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI) has been analyzed in visual areas 17 and 18 of cats aged from postnatal day (P) 0 to adulthood. Neuronal types are established mainly by axonal criteria. Both peptides occur in the same neuronal types and display the same postnatal chronology of appearance. Several cell types are transient, which means that they are present in the cortex only for a limited period of development. According to their chronology of appearance the VIP/PHI-immunoreactive (ir) cell types are grouped into three neuronal populations. The first population comprises six cell types which appear early in postnatal life. The pseudohorsetail cells of layer I possess a vertically descending axon which initially gives rise to recurrent collaterals, then forms a bundle passing layers III to V, and finally, horizontal terminal fibers in layer VI. The neurons differentiate at P 4 and disappear by degeneration around P 30. The neurons with columnar dendritic fields of layers IV/V are characterized by a vertical arrangement of long dendrites ascending or descending parallel to each other, thus forming an up to 600 microns long dendritic column. Their axons always descend and terminate in broad fields in layer VI. The neurons appear at P 7 and are present until P 20. The multipolar neurons of layer VI occur in isolated positions and have broad axonal territories. The neurons differentiate at P 7 and persist into adulthood. Bitufted to multipolar neurons of layers II/III have axons descending as a single fiber to layer VI, where they terminate. The neurons appear at P 12 and persist into adulthood. The four cell types described above issue a vertically oriented fiber architecture in layers II-V and a horizontal terminal plexus in layer VI which is dense during the second, third and fourth week. Concurrent with the disappearance of the two transient types the number of descending axonal bundles and the density of the layer VI plexus is reduced, but the latter is maintained during adulthood by the two persisting cell types. Two further cell types belong to the first population: The transient bipolar cells of layers IV, V, and VI have long dendrites which extend through the entire cortical width. Their axons always descend, leave the gray matter, and apparently terminate in the upper white matter. The neurons differentiate concurrently with the pseudohorsetail cells at P 4, are very frequent during the following weeks, and eventually disappear at P 30.(ABSTRACT TRUNCATED AT 400 WORDS)
Tetherin/BST-2 promotes dendritic cell activation and function during acute retrovirus infection.

PubMed

Li, Sam X; Barrett, Bradley S; Guo, Kejun; Kassiotis, George; Hasenkrug, Kim J; Dittmer, Ulf; Gibbert, Kathrin; Santiago, Mario L

2016-02-05

Tetherin/BST-2 is a host restriction factor that inhibits retrovirus release from infected cells in vitro by tethering nascent virions to the plasma membrane. However, contradictory data exists on whether Tetherin inhibits acute retrovirus infection in vivo. Previously, we reported that Tetherin-mediated inhibition of Friend retrovirus (FV) replication at 2 weeks post-infection correlated with stronger natural killer, CD4+ T and CD8+ T cell responses. Here, we further investigated the role of Tetherin in counteracting retrovirus replication in vivo. FV infection levels were similar between wild-type (WT) and Tetherin KO mice at 3 to 7 days post-infection despite removal of a potent restriction factor, Apobec3/Rfv3. However, during this phase of acute infection, Tetherin enhanced myeloid dendritic cell (DC) function. DCs from infected, but not uninfected, WT mice expressed significantly higher MHC class II and the co-stimulatory molecule CD80 compared to Tetherin KO DCs. Tetherin-associated DC activation during acute FV infection correlated with stronger NK cell responses. Furthermore, Tetherin+ DCs from FV-infected mice more strongly stimulated FV-specific CD4+ T cells ex vivo compared to Tetherin KO DCs. The results link the antiretroviral and immunomodulatory activity of Tetherin in vivo to improved DC activation and MHC class II antigen presentation.
Tetherin/BST-2 promotes dendritic cell activation and function during acute retrovirus infection

PubMed Central

Li, Sam X.; Barrett, Bradley S.; Guo, Kejun; Kassiotis, George; Hasenkrug, Kim J.; Dittmer, Ulf; Gibbert, Kathrin; Santiago, Mario L.

2016-01-01

Tetherin/BST-2 is a host restriction factor that inhibits retrovirus release from infected cells in vitro by tethering nascent virions to the plasma membrane. However, contradictory data exists on whether Tetherin inhibits acute retrovirus infection in vivo. Previously, we reported that Tetherin-mediated inhibition of Friend retrovirus (FV) replication at 2 weeks post-infection correlated with stronger natural killer, CD4+ T and CD8+ T cell responses. Here, we further investigated the role of Tetherin in counteracting retrovirus replication in vivo. FV infection levels were similar between wild-type (WT) and Tetherin KO mice at 3 to 7 days post-infection despite removal of a potent restriction factor, Apobec3/Rfv3. However, during this phase of acute infection, Tetherin enhanced myeloid dendritic cell (DC) function. DCs from infected, but not uninfected, WT mice expressed significantly higher MHC class II and the co-stimulatory molecule CD80 compared to Tetherin KO DCs. Tetherin-associated DC activation during acute FV infection correlated with stronger NK cell responses. Furthermore, Tetherin+ DCs from FV-infected mice more strongly stimulated FV-specific CD4+ T cells ex vivo compared to Tetherin KO DCs. The results link the antiretroviral and immunomodulatory activity of Tetherin in vivo to improved DC activation and MHC class II antigen presentation. PMID:26846717
Seasonal fluctuation in the neuronal classes of parahippocampal area of P. krameri (Scopoli, 1769) and E. scolopaceus (Linnaeus, 1758).

PubMed

Srivastava, U C; Singh, S; Singh, D

2012-10-08

Hippocampus in birds is a relatively narrow, curved strip of tissue that lies on the dorsomedial surface of telencephalon. It is widest dorsally at the junction with parahippocampal area, and it tapers with septum. Parahippocampal area (APH), the most prominent field of hippocampus is a long structure that lies at the most rostral level and continues upto caudal extent. It has been indicated by behavioral studies that hippocampus in birds plays an important role in process of learning, memory formation, food storage and spatial navigation. The present study enlightens some interesting fluctuations occurring in the neuronal classes of parahippocampal area of two seasonally breeding birds viz. P. krameri and E. scolopaceus in terms of dendritic thickness, spine density and spine morphology during breeding and non-breeding time period of birds. The Golgi-impregnated sections were used to study these fluctuations and it was noticed that there was a significant increase in dendritic thickness, spine density, spine length and spine head diameter during breeding as compared to non-breeding period. The results obtained were comparable in two different seasonally breeding birds, supporting the view that avian parahippocampal area shows neuroanatomical plasticity associated with breeding and non-breeding period because of variations in endocrinology.
Framing of Transitional Pedagogic Practices in the Sciences: Enabling Access

ERIC Educational Resources Information Center

Ellery, Karen

2017-01-01

Educational literature shows that students from working-class backgrounds are significantly less likely to persist to completion in higher education than middle-class students. This paper draws theoretically and analytically on Bernstein's ([1990. "Class, Codes and Control, Volume IV: The Structuring of Pedagogic Discourse." London:…
Analysis of class II (hydrolytic) and class I (beta-lyase) apurinic/apyrimidinic endonucleases with a synthetic DNA substrate.

PubMed Central

Levin, J D; Demple, B

1990-01-01

We have developed simple and sensitive assays that distinguish the main classes of apurinic/apyrimidinic (AP) endonucleases: Class I enzymes that cleave on the 3' side of AP sites by beta-elimination, and Class II enzymes that cleave by hydrolysis on the 5' side. The distinction of the two types depends on the use of a synthetic DNA polymer that contains AP sites with 5'-[32P]phosphate residues. Using this approach, we now show directly that Escherichia coli endonuclease IV and human AP endonuclease are Class II enzymes, as inferred previously on the basis of indirect assays. The assay method does not exhibit significant interference by nonspecific nucleases or primary amines, which allows the ready determination of different AP endonuclease activities in crude cell extracts. In this way, we show that virtually all of the Class II AP endonuclease activity in E. coli can be accounted for by two enzymes: exonuclease III and endonuclease IV. In the yeast Saccharomyces cerevisiae, the Class II AP endonuclease activity is totally dependent on a single enzyme, the Apn1 protein, but there are probably multiple Class I enzymes. The versatility and ease of our approach should be useful for characterizing this important class of DNA repair enzymes in diverse systems. PMID:1698278
How the Change in IBS Criteria From Rome III to Rome IV Impacts on Clinical Characteristics and Key Pathophysiological Factors.

PubMed

Aziz, Imran; Törnblom, Hans; Palsson, Olafur S; Whitehead, William E; Simrén, Magnus

2018-06-08

The diagnostic criteria for irritable bowel syndrome (IBS) have recently been updated from Rome III to Rome IV. Whereas in Rome III a diagnosis of IBS entailed chronic abdominal pain or discomfort at least 3 days per month, in Rome IV the term discomfort has been removed and the frequency of abdominal pain increased to at least 1 day per week. We examined how this change in IBS criteria impacts on clinical characteristics and pathophysiological factors. A total of 542 Swedish subjects with Rome III IBS completed a baseline questionnaire enquiring for the number of abdominal pain days in the last 10 days; this was subsequently used as a surrogate marker to identify Rome IV IBS, in that (a) those with 0 or 1 day of pain were classed as Rome IV-negative, and (b) those with ≥2 days of pain were classed as Rome IV-positive. Comparisons were made between Rome IV-positive and -negative IBS groups for demographics, IBS subtype, gastrointestinal and psychological symptoms, somatisation, fatigue, disease-specific quality of life, rectal sensitivity, and oro-anal transit time. Overall, 85% of Rome III IBS patients fulfilled the Rome IV criteria for IBS, but 15% did not. Rome IV-positive subjects were significantly more likely to be female, have poorer quality of life, greater pain severity, bloating, somatisation, fatigue, and rectal sensitivity than Rome IV-negative subjects. There were no differences in severity of anxiety or depression, IBS subtypes, bowel habit dissatisfaction, or oro-anal transit time. Finally, increasing number of pain days correlated positively with symptoms and visceral hypersensitivity. Most Rome III-positive IBS patients seeking healthcare fulfil the Rome IV IBS criteria. They constitute a more severe group than those who lose their IBS diagnosis.
Regulatory T cell effects in antitumor laser immunotherapy: a mathematical model and analysis

NASA Astrophysics Data System (ADS)

Dawkins, Bryan A.; Laverty, Sean M.

2016-03-01

Regulatory T cells (Tregs) have tremendous influence on treatment outcomes in patients receiving immunotherapy for cancerous tumors. We present a mathematical model incorporating the primary cellular and molecular components of antitumor laser immunotherapy. We explicitly model developmental classes of dendritic cells (DCs), cytotoxic T cells (CTLs), primary and metastatic tumor cells, and tumor antigen. Regulatory T cells have been shown to kill antigen presenting cells, to influence dendritic cell maturation and migration, to kill activated killer CTLs in the tumor microenvironment, and to influence CTL proliferation. Since Tregs affect explicitly modeled cells, but we do not explicitly model dynamics of Treg themselves, we use model parameters to analyze effects of Treg immunosuppressive activity. We will outline a systematic method for assigning clinical outcomes to model simulations and use this condition to associate simulated patient treatment outcome with Treg activity.
Running exercise enhances motor functional recovery with inhibition of dendritic regression in the motor cortex after collagenase-induced intracerebral hemorrhage in rats.

PubMed

Takamatsu, Yasuyuki; Tamakoshi, Keigo; Waseda, Yuya; Ishida, Kazuto

2016-03-01

Rehabilitative approaches benefit motor functional recovery after stroke and relate to neuronal plasticity. We investigated the effects of a treadmill running exercise on the motor functional recovery and neuronal plasticity after collagenase-induced striatal intracerebral hemorrhage (ICH) in rats. Male Wistar rats were injected with type IV collagenase into the left striatum to induce ICH. Sham-operated animals were injected with saline instead of collagenase. The animals were randomly assigned to the sham control (SC), the sham exercise (SE), the ICH control (IC), or the ICH exercise (IE) group. The exercise groups were forced to run on a treadmill at a speed of 9 m/min for 30 min/day between days 4 and 14 after surgery. Behavioral tests were performed using a motor deficit score, a beam-walking test and a cylinder test. At fifteen days after surgery, the animals were sacrificed, and their brains were removed. The motor function of the IE group significantly improved compared with the motor function of the IC group. No significant differences in cortical thickness were found between the groups. The IC group had fewer branches and shorter dendrite lengths compared with the sham groups. However, dendritic branches and lengths were not significantly different between the IE and the other groups. Tropomyosin-related kinase B (TrkB) expression levels increased in the IE compared with IC group, but no significant differences in other protein (brain-derived neurotrophic factor, BDNF; Nogo-A; Rho-A/Rho-associated protein kinase 2, ROCK2) expression levels were found between the groups. These results suggest that improved motor function after a treadmill running exercise after ICH may be related to the prevention of dendritic regression due to TrkB upregulation. Copyright © 2015. Published by Elsevier B.V.
Prolonged deficits in parvalbumin neuron stimulation-evoked network activity despite recovery of dendritic structure and excitability in the somatosensory cortex following global ischemia in mice.

PubMed

Xie, Yicheng; Chen, Shangbin; Wu, Yujin; Murphy, Timothy H

2014-11-05

Relatively few studies have examined plasticity of inhibitory neuronal networks following stroke in vivo, primarily due to the inability to selectively monitor inhibition. We assessed the structure of parvalbumin (PV) interneurons during a 5 min period of global ischemia and reperfusion in mice, which mimicked cerebral ischemia during cardiac arrest or forms of transient ischemic attack. The dendritic structure of PV-neurons in cortical superficial layers was rapidly swollen and beaded during global ischemia, but recovered within 5-10 min following reperfusion. Using optogenetics and a multichannel optrode, we investigated the function of PV-neurons in mouse forelimb somatosensory cortex. We demonstrated pharmacologically that PV-channelrhodopsin-2 (ChR2) stimulation evoked activation in layer IV/V, which resulted in rapid current sinks mediated by photocurrent and action potentials (a measure of PV-neuron excitability), which was then followed by current sources mediated by network GABAergic synaptic activity. During ischemic depolarization, the PV-ChR2-evoked current sinks (excitability) were suppressed, but recovered rapidly following reperfusion concurrent with repolarization of the DC-EEG. In contrast, the current sources reflecting GABAergic synaptic network activity recovered slowly and incompletely, and was coincident with the partial recovery of the forepaw stimulation-evoked current sinks in layer IV/V 30 min post reperfusion. Our in vivo data suggest that the excitability of PV inhibitory neurons was suppressed during global ischemia and rapidly recovered during reperfusion. In contrast, PV-ChR2 stimulation-evoked GABAergic synaptic network activity exhibited a prolonged suppression even ∼1 h after reperfusion, which could contribute to the dysfunction of sensation and cognition following transient global ischemia. Copyright © 2014 the authors 0270-6474/14/3414890-12$15.00/0.
Psychosocial stressors and the prognosis of major depression: a test of Axis IV

PubMed Central

Gilman, Stephen E.; Trinh, Nhi-Ha; Smoller, Jordan W.; Fava, Maurizio; Murphy, Jane M.; Breslau, Joshua

2013-01-01

Background Axis IV is for reporting “psychosocial and environmental problems that may affect the diagnosis, treatment, and prognosis of mental disorders.” No studies have examined the prognostic value of Axis IV in DSM-IV. Method We analyzed data from 2,497 participants in the National Epidemiologic Survey on Alcohol and Related Conditions with major depressive episode (MDE). We hypothesized that psychosocial stressors predict a poor prognosis of MDE. Secondarily, we hypothesized that psychosocial stressors predict a poor prognosis of anxiety and substance use disorders. Stressors were defined according to DSM-IV’s taxonomy, and empirically using latent class analysis. Results Primary support group problems, occupational problems, and childhood adversity increased the risks of depressive episodes and suicidal ideation by 20–30%. Associations of the empirically derived classes of stressors with depression were larger in magnitude. Economic stressors conferred a 1.5-fold increase in risk for a depressive episode (CI=1.2–1.9); financial and interpersonal instability conferred a 1.3-fold increased risk of recurrent depression (CI=1.1–1.6). These two classes of stressors also predicted the recurrence of anxiety and substance use disorders. Stressors were not related to suicidal ideation independent from depression severity. Conclusions Psychosocial and environmental problems are associated with the prognosis of MDE and other Axis I disorders. Though DSM-IV’s taxonomy of stressors stands to be improved, these results provide empirical support for the prognostic value of Axis IV. Future work is needed to determine the reliability of Axis IV assessments in clinical practice, and the usefulness of this information to improving the clinical course of mental disorders. PMID:22640506
Mechanisms and consequences of action potential burst firing in rat neocortical pyramidal neurons

PubMed Central

Williams, Stephen R; Stuart, Greg J

1999-01-01

Electrophysiological recordings and pharmacological manipulations were used to investigate the mechanisms underlying the generation of action potential burst firing and its postsynaptic consequences in visually identified rat layer 5 pyramidal neurons in vitro.Based upon repetitive firing properties and subthreshold membrane characteristics, layer 5 pyramidal neurons were separated into three classes: regular firing and weak and strong intrinsically burst firing.High frequency (330 ± 10 Hz) action potential burst firing was abolished or greatly weakened by the removal of Ca2+ (n = 5) from, or by the addition of the Ca2+ channel antagonist Ni2+ (250–500 μm; n = 8) to, the perfusion medium.The blockade of apical dendritic sodium channels by the local dendritic application of TTX (100 nm; n = 5) abolished or greatly weakened action potential burst firing, as did the local apical dendritic application of Ni2+ (1 mm; n = 5).Apical dendritic depolarisation resulted in low frequency (157 ± 26 Hz; n = 6) action potential burst firing in regular firing neurons, as classified by somatic current injection. The intensity of action potential burst discharges in intrinsically burst firing neurons was facilitated by dendritic depolarisation (n = 11).Action potential amplitude decreased throughout a burst when recorded somatically, suggesting that later action potentials may fail to propagate axonally. Axonal recordings demonstrated that each action potential in a burst is axonally initiated and that no decrement in action potential amplitude is apparent in the axon > 30 μm from the soma.Paired recordings (n = 16) from synaptically coupled neurons indicated that each action potential in a burst could cause transmitter release. EPSPs or EPSCs evoked by a presynaptic burst of action potentials showed use-dependent synaptic depression.A postsynaptic, TTX-sensitive voltage-dependent amplification process ensured that later EPSPs in a burst were amplified when generated from membrane potentials positive to -60 mV, providing a postsynaptic mechanism that counteracts use-dependent depression at synapses between layer 5 pyramidal neurons. PMID:10581316
Changes in the social class gradient of cirrhosis mortality in England and Wales across the 20th century.

PubMed

Crombie, Iain K; Precious, Elaine

2011-01-01

To explore the nature of the social class gradient of cirrhosis mortality in England and Wales across the 20th century. Data on male cirrhosis mortality by social class were obtained from the Registrar General's Decennial Supplements for the years 1921-1991. Data for 1941 were not collected because of the second World War. In 1921, cirrhosis mortality was substantially higher among the professional and managerial classes (I and II) than among the other social classes (III-V). This marked social class difference persisted until 1961 when the differences between the social classes were inconsistent. By 1991, the gradient had reversed and the lower social classes (IV and V) had the higher mortality. The excess mortality was greatest for social class V. The change in the mortality gradient is stark: in 1921social classes I and II had a cirrhosis mortality at least twice that of social classes IV and V, but by 1991 this ratio had reversed. The reversal in the social class gradient of cirrhosis mortality indicates a major change in risk factor distribution across social classes. Differential changes in alcohol consumption are a possible explanation for this change, although the 1991 social class gradient in cirrhosis is inconsistent with alcohol consumption data from national surveys. Further research is required to clarify the explanation for the observed gradient, so that appropriate preventive measures can be put into place.
40 CFR 144.26 - Inventory requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... “Inventory of Injection Wells,” OMB No. 158-R0170. (b) Additional contents. For EPA administered programs...) Class II enhanced recovery wells; (ii) Class IV wells; (iii) The following Class V wells: (A) Sand or... (40 CFR 146.5 (e)(11)) (C) Geothermal energy recovery wells [§ 146.5(e)(12)]; (D) Brine return flow...
Dexamethasone Suppresses Oxysterol-Induced Differentiation of Monocytic Cells

PubMed Central

Son, Yonghae; Kim, Bo-Young; Eo, Seong-Kug; Park, Young Chul; Kim, Koanhoi

2016-01-01

Oxysterol like 27-hydroxycholesterol (27OHChol) has been reported to induce differentiation of monocytic cells into a mature dendritic cell phenotype. We examined whether dexamethasone (Dx) affects 27OHChol-induced differentiation using THP-1 cells. Treatment of monocytic cells with Dx resulted in almost complete inhibition of transcription and surface expression of CD80, CD83, and CD88 induced by 27OHChol. Elevated surface levels of MHC class I and II molecules induced by 27OHChol were reduced to basal levels by treatment with Dx. A decreased endocytosis ability caused by 27OHChol was recovered by Dx. We also examined effects of Dx on expression of CD molecules involved in atherosclerosis. Increased levels of surface protein and transcription of CD105, CD137, and CD166 by treatment with 27OHChol were significantly inhibited by cotreatment with Dx. These results indicate that Dx inhibits 27OHChol-induced differentiation of monocytic cells into a mature dendritic cell phenotype and expression of CD molecules whose levels are associated with atherosclerosis. In addition, we examined phosphorylation of AKT induced by 27OHChol and effect of Dx, where cotreatment with Dx inhibited the phosphorylation of AKT. The current study reports that Dx regulates oxysterol-mediated dendritic cell differentiation of monocytic cells. PMID:27340507

Dexamethasone Suppresses Oxysterol-Induced Differentiation of Monocytic Cells.

PubMed

Son, Yonghae; Kim, Bo-Young; Eo, Seong-Kug; Park, Young Chul; Kim, Koanhoi

2016-01-01

Oxysterol like 27-hydroxycholesterol (27OHChol) has been reported to induce differentiation of monocytic cells into a mature dendritic cell phenotype. We examined whether dexamethasone (Dx) affects 27OHChol-induced differentiation using THP-1 cells. Treatment of monocytic cells with Dx resulted in almost complete inhibition of transcription and surface expression of CD80, CD83, and CD88 induced by 27OHChol. Elevated surface levels of MHC class I and II molecules induced by 27OHChol were reduced to basal levels by treatment with Dx. A decreased endocytosis ability caused by 27OHChol was recovered by Dx. We also examined effects of Dx on expression of CD molecules involved in atherosclerosis. Increased levels of surface protein and transcription of CD105, CD137, and CD166 by treatment with 27OHChol were significantly inhibited by cotreatment with Dx. These results indicate that Dx inhibits 27OHChol-induced differentiation of monocytic cells into a mature dendritic cell phenotype and expression of CD molecules whose levels are associated with atherosclerosis. In addition, we examined phosphorylation of AKT induced by 27OHChol and effect of Dx, where cotreatment with Dx inhibited the phosphorylation of AKT. The current study reports that Dx regulates oxysterol-mediated dendritic cell differentiation of monocytic cells.
Regulation of GM-CSF-induced dendritic cell development by TGF-beta1 and co-developing macrophages.

PubMed

Yamaguchi, Y

1998-01-01

Using a culture system of bone marrow progenitor cells with GM-CSF and TGF-beta1, a study was performed to analyze the effect of TGF-beta1 on the development of dendritic cells (DC) and to elucidate the regulatory role of macrophages co-developing with dendritic cells. The results demonstrate that DC generated in the presence of TGF-beta1 were immature with respect to the expression of CD86, nonspecific esterase activity and cell shape. Such inhibitory effects of TGF-beta1 were dependent on FcR+ macrophages, which were depleted by panning. TGF-beta1 did not appear to inhibit the commitment of progenitor cells to the DC lineage. In addition, TGF-beta1 also acted directly on the intermediate stage of DC to prevent their over-maturation, which results in a preferential decrease in MHC class II, but not in CD86, in the presence of TNF-alpha. FcR+ suppressive macrophages were also shown to facilitate DC maturation when stimulated via FcR-mediated signals even in the presence of TGF-beta1. These results indicate that TGF-beta1 indirectly and directly regulate the development of DC and that co-developing macrophages have a regulatory role in DC maturation.
Superior Conductive Solid-like Electrolytes: Nanoconfining Liquids within the Hollow Structures

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

Zhang, Jinshui; Bai, Ying; Sun, Xiao-Guang

2015-01-01

The growth and proliferation of lithium (Li) dendrites during cell recharge is unavoidable, which seriously hinders the development and application of rechargeable Li metal batteries. Solid electrolytes with robust mechanical modulus are regarded as a promising approach to overcome the dendrite problems. However, their room-temperature ionic conductivities are usually too low to reach the level required for normal battery operation. Here, a class of novel solid electrolytes with liquid-like room-temperature ionic conductivities (> 1 mS cm-1) has been successfully synthesized by taking advantage of the unique nanoarchitectures of hollow silica (HS) spheres to confine liquid electrolytes in hollow space tomore » afford high conductivities. In a symmetric lithium/lithium cell, such kind of solid-like electrolytes demonstrates a robust performance against Li dendrite problems, well stabilizing the cell system from short circuiting in a long-time operation at current densities ranging from 0.16 to 0.32 mA cm-2. Moreover, the high flexibility and compatibility of HS nanoarchitectures, in principle, enables broad tunability to choose desired liquids for the fabrication of other kinds of solid-like electrolytes, such as those containing Na+, Mg2+ or Al3+ as conductive media, providing a useful alternative strategy for the development of next generation rechargeable batteries.« less
Statistical analysis and data mining of digital reconstructions of dendritic morphologies.

PubMed

Polavaram, Sridevi; Gillette, Todd A; Parekh, Ruchi; Ascoli, Giorgio A

2014-01-01

Neuronal morphology is diverse among animal species, developmental stages, brain regions, and cell types. The geometry of individual neurons also varies substantially even within the same cell class. Moreover, specific histological, imaging, and reconstruction methodologies can differentially affect morphometric measures. The quantitative characterization of neuronal arbors is necessary for in-depth understanding of the structure-function relationship in nervous systems. The large collection of community-contributed digitally reconstructed neurons available at NeuroMorpho.Org constitutes a "big data" research opportunity for neuroscience discovery beyond the approaches typically pursued in single laboratories. To illustrate these potential and related challenges, we present a database-wide statistical analysis of dendritic arbors enabling the quantification of major morphological similarities and differences across broadly adopted metadata categories. Furthermore, we adopt a complementary unsupervised approach based on clustering and dimensionality reduction to identify the main morphological parameters leading to the most statistically informative structural classification. We find that specific combinations of measures related to branching density, overall size, tortuosity, bifurcation angles, arbor flatness, and topological asymmetry can capture anatomically and functionally relevant features of dendritic trees. The reported results only represent a small fraction of the relationships available for data exploration and hypothesis testing enabled by sharing of digital morphological reconstructions.
Ovarian phagocyte subsets and their distinct tissue distribution patterns.

PubMed

Carlock, Colin; Wu, Jean; Zhou, Cindy; Ross, April; Adams, Henry; Lou, Yahuan

2013-01-01

Ovarian macrophages, which play critical roles in various ovarian events, are probably derived from multiple lineages. Thus, a systemic classification of their subsets is a necessary first step for determination of their functions. Utilizing antibodies to five phagocyte markers, i.e. IA/IE (major histocompatibility complex class II), F4/80, CD11b (Mac-1), CD11c, and CD68, this study investigated subsets of ovarian phagocytes in mice. Three-color immunofluorescence and flow cytometry, together with morphological observation on isolated ovarian cells, demonstrated complicated phenotypes of ovarian phagocytes. Four macrophage and one dendritic cell subset, in addition to many minor phagocyte subsets, were identified. A dendritic cell-like population with a unique phenotype of CD11c(high)IA/IE⁻F4/80⁻ was also frequently observed. A preliminary age-dependent study showed dramatic increases in IA/IE⁺ macrophages and IA/IE⁺ dendritic cells after puberty. Furthermore, immunofluorescences on ovarian sections showed that each subset displayed a distinct tissue distribution pattern. The pattern for each subset may hint to their role in an ovarian function. In addition, partial isolation of ovarian macrophage subset using CD11b antibodies was attempted. Establishment of this isolation method may have provided us a tool for more precise investigation of each subset's functions at the cellular and molecular levels.
Intravenous Solutions for Exploration Missions

NASA Technical Reports Server (NTRS)

Miller, Fletcher J.; Niederhaus, Charles; Barlow, Karen; Griffin, DeVon

2007-01-01

This paper describes the intravenous (IV) fluids requirements being developed for medical care during NASA s future exploration class missions. Previous research on IV solution generation and mixing in space is summarized. The current exploration baseline mission profiles are introduced, potential medical conditions described and evaluated for fluidic needs, and operational issues assessed. We briefly introduce potential methods for generating IV fluids in microgravity. Conclusions on the recommended fluid volume requirements are presented.
ADHD latent class clusters: DSM-IV subtypes and comorbidity

PubMed Central

Elia, Josephine; Arcos-Burgos, Mauricio; Bolton, Kelly L.; Ambrosini, Paul J.; Berrettini, Wade; Muenke, Maximilian

2014-01-01

ADHD (Attention Deficit Hyperactivity Disorder) has a complex, heterogeneous phenotype only partially captured by Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. In this report, latent class analyses (LCA) are used to identify ADHD phenotypes using K-SADS-IVR (Schedule for Affective Disorders & Schizophrenia for School Age Children-IV-Revised) symptoms and symptom severity data from a clinical sample of 500 ADHD subjects, ages 6–18, participating in an ADHD genetic study. Results show that LCA identified six separate ADHD clusters, some corresponding to specific DSM-IV subtypes while others included several subtypes. DSM-IV comorbid anxiety and mood disorders were generally similar across all clusters, and subjects without comorbidity did not aggregate within any one cluster. Age and gender composition also varied. These results support findings from population-based LCA studies. The six clusters provide additional homogenous groups that can be used to define ADHD phenotypes in genetic association studies. The limited age ranges aggregating in the different clusters may prove to be a particular advantage in genetic studies where candidate gene expression may vary during developmental phases. DSM-IV comorbid mood and anxiety disorders also do not appear to increase cluster heterogeneity; however, longitudinal studies that cover period of risk are needed to support this finding. PMID:19900717
Information and Biological Revolutions: Global Governance Challenges Summary of a Study Group

DTIC Science & Technology

2000-01-01

instruction and organize the classes. This change will come about slowly and then only if it proves to increase learning in the classroom. See Thomas K...dendrites and to form synaptic connections, then help to maintain and regulate synaptic activity responsible for learning and cognitive functions...testosterone may foster violent behavior is by the promotion of positive illusions about competitive ability . 77 Thus, an evolutionary history of raiding
Co-ordination of incoming and outgoing traffic in antigen-presenting cells by pattern recognition receptors and T cells.

PubMed

Nair, Priyanka; Amsen, Derk; Blander, J Magarian

2011-12-01

Dendritic cells are innate sentinels of the immune system and potent activators of naÏve T cells. Mechanisms must exist to enable these cells to achieve maximal activation of T cells specific for microbial antigens, while avoiding activation of T cells specific for self-antigens. Here we discuss how a combination of signals from pattern recognition receptors and T cells co-ordinates subcellular trafficking of antigen with both major histocompatibility complex class I and class II molecules and T-cell costimulatory molecules, resulting in the preferential presentation of microbial peptides within a stimulatory context. © 2011 John Wiley & Sons A/S.
The "index cutback technique": a three-dimensional guided layering approach in direct class IV composite restorations.

PubMed

Ammannato, Riccardo; Ferraris, Federico; Allegri, Mario

One of the main difficulties encountered with conventional class IV direct composite restorations is the layering management in terms of three-dimensionality and shape control. The major concern is the predictability of the esthetic outcome, which is closely linked to the clinician's skills. This article presents a predictable approach to treat class IV direct composite restorations. The technique allows for the shape and thickness of different composite layers to be guided through transparent indexes that have been carried out previously on a planned wax-up. The final goal is to achieve a good esthetic outcome in an easy and fast way through a copy-and-paste approach. The "index cutback technique" is a complementary variant of the "index technique" for class IV direct restorations. After the casts have been generated, the technician creates a full wax-up of the tooth to be restored. A transparent silicone key of the full wax-up provides the full enamel index that is then cut with a blade along the incisal edge to achieve two enamel indexes, one palatal and one buccal. Then, the required amount of wax is removed from the full wax-up through a cutback step. The aim of this step is to remove a suitable amount of wax to leave a predetermined space for the composite enamel layers, both on the palatal and buccal surfaces. A second transparent silicone key is built on the cutback wax-up to achieve the cutback dentin index, which is then used to press the composite dentin onto the prepared tooth.
Protective role of curcumin against sulfite-induced structural changes in rats' medial prefrontal cortex.

PubMed

Noorafshan, Ali; Asadi-Golshan, Reza; Abdollahifar, Mohammad-Amin; Karbalay-Doust, Saied

2015-08-01

Sodium metabisulfite as a food preservative can affect the central nervous system. Curcumin, the main ingredient of turmeric has neuroprotective activity. This study was designed to evaluate the effects of sulfite and curcumin on the medial prefrontal cortex (mPFC) using stereological methods. Thirty rats were randomly divided into five groups. The rats in groups I-V received distilled water, olive oil, curcumin (100 mg/kg/day), sodium metabisulfite (25 mg/kg/day), and sulfite + curcumin, respectively, for 8 weeks. The brains were subjected to the stereological methods. Cavalieri and optical disector techniques were used to estimate the total volume of mPFC and the number of neurons and glial cells. Intersections counting were applied on the thick vertical uniform random sections to estimate the dendrites length, and classify the spines. Non-parametric tests were used to analyze the data. The mean mPFC volume, neurons number, glia number, dendritic length, and total spines per neuron were 3.7 mm(3), 365,000, 180,000, 1820 µm, and 1700 in distilled water group, respectively. A reduction was observed in the volume of mPFC (∼8%), number of neurons (∼15%), and number of glia (∼14%) in mPFC of the sulfite group compared to the control groups (P < 0.005). Beside, dendritic length per neuron (∼10%) and the total spines per neuron (mainly mushroom spines) (∼25%) were reduced in the sulfite group (P < 0.005). The sulfite-induced structural changes in mPFC and curcumin had a protective role against the changes in the rats.
2D and 3D T2-weighted MR sequences for the assessment of neurovascular bundle changes after nerve-sparing radical retropubic prostatectomy with erectile function correlation.

PubMed

Panebianco, Valeria; Sciarra, Alessandro; Osimani, Marcello; Lisi, Danilo; Ciccariello, Mauro; Salciccia, Stefano; Gentile, Vincenzo; Di Silverio, Franco; Passariello, Roberto

2009-01-01

The aim of this study was to assess the capability of a 3D isotropic MRI T2-weighted sequence (3D T2 ISO) in the depiction of changes of neurovascular bundles (NVBs) after bilateral nerve-sparing radical retropubic prostatectomy (RRP). Furthermore, our aim was also to introduce a new MRI classification score of the NVB alteration patterns using the International Index Erectile Function Five-Item (IIEF-5) score as standard of reference. Fifty-three consecutive patients were postoperatively submitted to two MR examinations, including both 2D TSE T2-weighted (2D T2) and 3D T2 ISO sequences. Image findings were scored using a relative five-point classification and correlated with the postoperative IIEF-5 score. Radiologists attributed 13.2% of patients to class 0, 11.3% to class I, 34% to class II, 24.5% to class III, and 16.9% to class IV. With 3D T2 ISO images, the same radiologists determined 43.3% class 0, 32% class I, 11.4% class II, 7.5% class III, and 5.7% class IV. In all cases, the correlation and regression analysis between the 3D T2 ISO and IIEF-5 score resulted in higher coefficients values. The 3D sequence correlated most closely with patients' grading of erectile function.
40 CFR 90.104 - Compliance with emission standards.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Volume Engine Families Engine class Two-stroke engines 1 HC+NOX CO Four-stroke engines HC+NOX CO Engines...). Class IV 1.1 1.1 1.5 1.1 Class V 1.1 1.1 1.5 1.1 1 Two-stroke technologies to which these assigned deterioration factors apply include conventional two-strokes, compression wave designs, and stratified...
40 CFR 90.104 - Compliance with emission standards.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Volume Engine Families Engine class Two-stroke engines 1 HC+NOX CO Four-stroke engines HC+NOX CO Engines...). Class IV 1.1 1.1 1.5 1.1 Class V 1.1 1.1 1.5 1.1 1 Two-stroke technologies to which these assigned deterioration factors apply include conventional two-strokes, compression wave designs, and stratified...
40 CFR 90.104 - Compliance with emission standards.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Volume Engine Families Engine class Two-stroke engines 1 HC+NOX CO Four-stroke engines HC+NOX CO Engines...). Class IV 1.1 1.1 1.5 1.1 Class V 1.1 1.1 1.5 1.1 1 Two-stroke technologies to which these assigned deterioration factors apply include conventional two-strokes, compression wave designs, and stratified...
40 CFR 90.104 - Compliance with emission standards.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Volume Engine Families Engine class Two-stroke engines 1 HC+NOX CO Four-stroke engines HC+NOX CO Engines...). Class IV 1.1 1.1 1.5 1.1 Class V 1.1 1.1 1.5 1.1 1 Two-stroke technologies to which these assigned deterioration factors apply include conventional two-strokes, compression wave designs, and stratified...
40 CFR 90.104 - Compliance with emission standards.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Volume Engine Families Engine class Two-stroke engines 1 HC+NOX CO Four-stroke engines HC+NOX CO Engines...). Class IV 1.1 1.1 1.5 1.1 Class V 1.1 1.1 1.5 1.1 1 Two-stroke technologies to which these assigned deterioration factors apply include conventional two-strokes, compression wave designs, and stratified...
76 FR 56833 - Self-Regulatory Organizations; BATS Y-Exchange, Inc.; Notice of Filing of Proposed Rule Change To...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-14

... respective voting rights and of Class A and Class B common stock, (iv) setting forth certain limitations on... Incorporation, shares of Non-Voting Common Stock possess the same rights, preferences, powers, privileges... B Common Stock. Except for voting rights and certain conversion features, as described below, Class...
76 FR 56840 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing of Proposed Rule Change To...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-14

... respective voting rights and of Class A and Class B common stock, (iv) setting forth certain limitations on... Incorporation, shares of Non-Voting Common Stock possess the same rights, preferences, powers, privileges...-Voting Class B Common Stock. Except for voting rights and certain conversion features, as described below...
77 FR 24978 - Notice of Proposed Class II Reinstatement of Terminated Oil and Gas Leases, Utah.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-26

... Proposed Class II Reinstatement of Terminated Oil and Gas Leases, Utah. AGENCY: Bureau of Land Management, Interior. ACTION: Notice of Proposed Class II Reinstatement of Terminated Oil and Gas Leases, Utah. SUMMARY: In accordance with Title IV of the Federal Oil and Gas Royalty Management Act (Pub. L. 97-451...

76 FR 14686 - Notice of Proposed Class II Reinstatement of Terminated Oil and Gas Lease, Utah

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-17

... Proposed Class II Reinstatement of Terminated Oil and Gas Lease, Utah AGENCY: Bureau of Land Management, Interior. ACTION: Notice of Proposed Class II Reinstatement of Terminated Oil and Gas Lease, Utah. SUMMARY: In accordance with Title IV of the Federal Oil and Gas Royalty Management Act (Pub. L. 97-451...
Multidisciplinary and multisetting team management programme in heart failure patients affects hospitalisation and costing.

PubMed

Piepoli, M F; Villani, G Q; Aschieri, D; Bennati, S; Groppi, F; Pisati, M S; Rosi, A; Capucci, A

2006-08-28

We evaluated whether multidisciplinary disease management programme developed with collaboration of physicians and nurses inside and outside general district hospital settings can affect clinical outcomes in heart failure population over a 12-month period. 571 patients hospitalised with CHF were referred to our unit and 509 patients agreed to participation. The intervention team included physicians and nurses from Internal Medicine and Cardiac Dept., and the patient's general practitioners. Contacts were on a pre-specified schedule, included a computerised programme of hospital visits and phone calls; in case of NYHA functional class III and IV patients, home visits were also planned. The median age of patients was 77.7+/-9 years (43.3% women). At baseline the percentage of patients with NYHA class III and IV was 56.0% vs. 26.0% after 12 months (P<0.05). Programme enrolment reduced total hospital admissions (82 vs. 190, -56%, P<0.05), number of patients hospitalised (62 vs. 146, 57%, P<0.05). All NYHA functional class benefited (class I=75%, class IV=67%), with reduction in the costing (-48%, P<0.05). Improvement in symptoms (-9.0+/-3.2) and signs (-5.2+/-3.1) scores was measured (P<0.01). Therapy optimisation was obtained by 20.5% increase in patients taking betablockade and 21.0% increase in those on anti-aldosterone drugs. Multidisciplinary approach to CHF management can improve clinical management, reducing hospitalisation rate and costing.
Repellent and Anti-quorum Sensing Activity of Six Aromatic Plants Occurring in Colombia.

PubMed

Cervantes-Ceballos, Leonor; Caballero-Gallardo, Karina; Olivero-Verbel, Jesus

2015-10-01

Essential oils (EOs) are widely used as biopesticides and to control bacterial infections. This study describes the ability of six EOs isolated from plants cultivated in Colombia to perform as repellents against Ulomoides dermestoides and as quorum sensing (QS) inhibitors. EOs from Aloysia triphylla, Cymbopogon nardus, Lippia origanoides, Hyptis suaveolens, Swinglea glutinosa and Eucalyptus globulus were repellents classified as Class IV, IV, IV, III, II, and II, respectively, whereas the commercial repellent IR3535 only reached Class II after 2 h exposure. All EOs presented small, but significant inhibitory properties against the QS system in Escherichia coli (pJBA132) at 25 μg/mL after 4 h exposure. These data suggest evaluated EOs from Colombia are sustainable, promising new sources of natural repellents and could be important as anti-quorum sensing molecules.
14 CFR 61.5 - Certificates and ratings issued under this part.

Code of Federal Regulations, 2010 CFR

2010-01-01

.... (iii) Glider. (iv) Lighter-than-air. (v) Powered-lift. (vi) Powered parachute. (vii) Weight-shift...—Airplane. (ii) Instrument—Helicopter. (iii) Instrument—Powered-lift. (c) The following ratings are placed.... (iii) Glider. (iv) Powered-lift. (2) Airplane class ratings— (i) Single-engine. (ii) Multiengine. (3...
14 CFR 61.5 - Certificates and ratings issued under this part.

Code of Federal Regulations, 2011 CFR

2011-01-01

.... (iii) Glider. (iv) Lighter-than-air. (v) Powered-lift. (vi) Powered parachute. (vii) Weight-shift...—Airplane. (ii) Instrument—Helicopter. (iii) Instrument—Powered-lift. (c) The following ratings are placed.... (iii) Glider. (iv) Powered-lift. (2) Airplane class ratings— (i) Single-engine. (ii) Multiengine. (3...
Biodistribution, cellular localization, and in vivo tolerability of 35S-labeled antiinflammatory dendritic polyglycerol sulfate amine

NASA Astrophysics Data System (ADS)

Holzhausen, Cornelia; Gröger, Dominic; Mundhenk, Lars; Donat, Cornelius K.; Schnorr, Jörg; Haag, Rainer; Gruber, Achim D.

2015-03-01

Antiinflammatory dendritic polyglycerol sulfate (dPGS) holds great potential in the treatment and imaging of inflammatory processes. Here, we studied its biokinetic behavior, biodistribution, target cells, and in vivo toxicology. Following intravenous or subcutaneous application of 35sulfur-labeled dPGS amine with a molecular weight of 10.05 kDa and a hydrodynamic diameter of 5.7 ± 1.5 nm to mice, tissues were collected at specific time points (2, 15 min; 1, 24 h; 5, 21 days) and analyzed by liquid scintillation counting, autoradiography, radioluminography, and light microscopic autoradiography. The blood half-life of dPGS amine was 12 days. The major route of elimination was via the bile and feces. Elimination via the kidney and urine was only initially observed after i.v., but not after s.c. injection. Regardless of the administration mode, liver and spleen were late target organs where dPGS amine accumulated in phagocytic cells. Despite bioaccumulation, toxicological histopathology failed to identify any adverse effects at any time and in any tissues examined suggesting a high in vivo biocompatibility and encouraging future investigation for biomedical applications.
Plasmacytoid dendritic cells play a major role in apoptotic leukocyte-induced immune modulation.

PubMed

Bonnefoy, Francis; Perruche, Sylvain; Couturier, Mélanie; Sedrati, Abdeslem; Sun, Yunwei; Tiberghien, Pierre; Gaugler, Béatrice; Saas, Philippe

2011-05-15

Several APCs participate in apoptotic cell-induced immune modulation. Whether plasmacytoid dendritic cells (PDCs) are involved in this process has not yet been characterized. Using a mouse model of allogeneic bone marrow engraftment, we demonstrated that donor bone marrow PDCs are required for both donor apoptotic cell-induced engraftment and regulatory T cell (Treg) increase. We confirmed in naive mice receiving i.v. syngeneic apoptotic cell infusion that PDCs from the spleen induce ex vivo Treg commitment. We showed that PDCs did not interact directly with apoptotic cells. In contrast, in vivo macrophage depletion experiments using clodronate-loaded liposome infusion and coculture experiments with supernatant from macrophages incubated with apoptotic cells showed that PDCs required macrophage-derived soluble factors--including TGF-β--to exert their immunomodulatory functions. Overall, PDCs may be considered as the major APC involved in Treg stimulation/generation in the setting of an immunosuppressive environment obtained by apoptotic cell infusion. These findings show that like other APCs, PDC functions are influenced, at least indirectly, by exposure to blood-borne apoptotic cells. This might correspond with an additional mechanism preventing unwanted immune responses against self-antigens clustered at the cell surface of apoptotic cells occurring during normal cell turnover.
A novel dendritic cell-based immunization approach for the induction of durable Th1-polarized anti-HER-2/neu responses in women with early breast cancer

PubMed Central

Koski, Gary K.; Koldovsky, Ursula; Xu, Shuwen; Mick, Rosemarie; Sharma, Anupama; Fitzpatrick, Elizabeth; Weinstein, Susan; Nisenbaum, Harvey; Levine, Bruce L; Fox, Kevin; Zhang, Paul; Czerniecki, Brian J

2011-01-01

Twenty-seven subjects with HER-2/neu over-expressing ductal carcinoma in situ of the breast were enrolled in a neoadjuvant immunization trial for safety and immunogenicity of DC1-polarized dendritic cells (DC1) pulsed with six HER-2/neu promiscuous MHC class II-binding peptides, plus two additional HLA-A2.1 class I-binding peptides. DC1 were generated with IFN-γ plus a special clinical-grade bacterial endotoxin (LPS) and administered directly into groin lymph nodes four times at weekly intervals prior to scheduled surgical resection of DCIS. Subjects were monitored for the induction of new or enhanced anti-peptide reactivity by IFN-γ ELIspot and ELISA assays performed on Th cells obtained from peripheral blood or excised sentinel lymph nodes. Responses by CTL against HLA-A2.1-binding peptides were measured using peptide-pulsed T2 target cells or HER-2/neu-expressing or non-expressing tumor cell lines. DC1 showed surface phenotype indistinct from “gold standard” inflammatory cocktail-activated DC, but displayed a number of distinguishing functional characteristics including the secretion of soluble factors and enhanced “killer DC” capacity against tumor cells in vitro. Post-immunization, we observed sensitization of Th cells to at least 1 class II peptide in 22 of 25 (88%, 95% exact CI 68.8 – 97.5%) evaluable subjects, while eleven of 13 (84.6%, 95% exact CI 64 – 99.8%) HLA-A2.1 subjects were successfully sensitized to class I peptides. Perhaps most importantly, anti-HER-2/neu peptide responses were observed up to 52 months post-immunization. These data show even in the presence of early breast cancer such DC1 are potent inducers of durable type I-polarized immunity, suggesting potential clinical value for development of cancer immunotherapy. PMID:22130160
Exploring new classification criteria for the earliest type stars: the 3400 Aregion

NASA Astrophysics Data System (ADS)

Morrell, Nidia I.; Walborn, Nolan R.; Arias, Julia I.

2002-02-01

We propose spectroscopic observations of a sample of standard O2-O4 stars in the wavelength region containing the N IV 3479-83-85 Aand O IV 3381-85-3412 Alines, in order to analyze the behavior of these spectral features as a function of the spectral type. We aim to define new classification criteria for the hottest stars, evaluating these N IV and O IV lines near 3400 Aas possible temperature and luminosity discriminators. The former spectral class O3 has just been split into three different classes: O2, O3 and O3.5 (Walborn et al. 2001). The paucity of classification criteria at these types in the traditional wavelength domain (4000 - 4700 Å), makes clear the need to explore other spectral ranges in order to define additional constraints on the determination of spectral types and luminosity classes. The wavelength range around 3400 Ahas been observed in many faint, crowded early O-type stars by HST/FOS, the corresponding data being available from the HST archive. This enhances our interest in observing this spectral range in the classification standards for the early O-type stars in order to make these existing HST observations even more useful, allowing the determination of accurate spectral types for unknown objects from them, once the behavior of the new criteria in the standards has been charted.
Drosophila Insulin receptor regulates the persistence of injury-induced nociceptive sensitization

PubMed Central

Patel, Atit A.

2018-01-01

ABSTRACT Diabetes-associated nociceptive hypersensitivity affects diabetic patients with hard-to-treat chronic pain. Because multiple tissues are affected by systemic alterations in insulin signaling, the functional locus of insulin signaling in diabetes-associated hypersensitivity remains obscure. Here, we used Drosophila nociception/nociceptive sensitization assays to investigate the role of Insulin receptor (Insulin-like receptor, InR) in nociceptive hypersensitivity. InR mutant larvae exhibited mostly normal baseline thermal nociception (absence of injury) and normal acute thermal hypersensitivity following UV-induced injury. However, their acute thermal hypersensitivity persists and fails to return to baseline, unlike in controls. Remarkably, injury-induced persistent hypersensitivity is also observed in larvae that exhibit either type 1 or type 2 diabetes. Cell type-specific genetic analysis indicates that InR function is required in multidendritic sensory neurons including nociceptive class IV neurons. In these same nociceptive sensory neurons, only modest changes in dendritic morphology were observed in the InRRNAi-expressing and diabetic larvae. At the cellular level, InR-deficient nociceptive sensory neurons show elevated calcium responses after injury. Sensory neuron-specific expression of InR rescues the persistent thermal hypersensitivity of InR mutants and constitutive activation of InR in sensory neurons ameliorates the hypersensitivity observed with a type 2-like diabetic state. Our results suggest that a sensory neuron-specific function of InR regulates the persistence of injury-associated hypersensitivity. It is likely that this new system will be an informative genetically tractable model of diabetes-associated hypersensitivity. PMID:29752280
Peripheral dendritic cells are essential for both the innate and adaptive antiviral immune responses in the central nervous system

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

Steel, Christina D.; Hahto, Suzanne M.; Ciavarra, Richard P., E-mail: ciavarrp@evms.ed

2009-04-25

Intranasal application of vesicular stomatitis virus (VSV) causes acute infection of the central nervous system (CNS). However, VSV encephalitis is not invariably fatal, suggesting that the CNS may contain a professional antigen-presenting cell (APC) capable of inducing or propagating a protective antiviral immune response. To examine this possibility, we first characterized the cellular elements that infiltrate the brain as well as the activation status of resident microglia in the brains of normal and transgenic mice acutely ablated of peripheral dendritic cells (DCs) in vivo. VSV encephalitis was characterized by a pronounced infiltrate of myeloid cells (CD45{sup high}CD11b{sup +}) and CD8{supmore » +} T cells containing a subset that was specific for the immunodominant VSV nuclear protein epitope. This T cell response correlated temporally with a rapid and sustained upregulation of MHC class I expression on microglia, whereas class II expression was markedly delayed. Ablation of peripheral DCs profoundly inhibited the inflammatory response as well as infiltration of virus-specific CD8{sup +} T cells. Unexpectedly, the VSV-induced interferon-gamma (IFN-gamma) response in the CNS remained intact in DC-deficient mice. Thus, both the inflammatory and certain components of the adaptive primary antiviral immune response in the CNS are dependent on peripheral DCs in vivo.« less
Critical role of the tumor suppressor tuberous sclerosis complex 1 in dendritic cell activation of CD4 T cells by promoting MHC class II expression via IRF4 and CIITA.

PubMed

Pan, Hongjie; O'Brien, Thomas F; Wright, Gabriela; Yang, Jialong; Shin, Jinwook; Wright, Kenneth L; Zhong, Xiao-Ping

2013-07-15

Dendritic cell (DC) maturation is characterized by upregulation of cell-surface MHC class II (MHC-II) and costimulatory molecules, and production of a variety of cytokines that can shape both innate and adaptive immunity. Paradoxically, transcription of the MHC-II genes, as well as its activator, CIITA, is rapidly silenced during DC maturation. The mechanisms that control CIITA/MHC-II expression and silencing have not been fully understood. We report in this article that the tumor suppressor tuberous sclerosis complex 1 (TSC1) is a critical regulator of DC function for both innate and adaptive immunity. Its deficiency in DCs results in increased mammalian target of rapamycin (mTOR) complex 1 but decreased mTORC2 signaling, altered cytokine production, impaired CIITA/MHC-II expression, and defective Ag presentation to CD4 T cells after TLR4 stimulation. We demonstrate further that IFN regulatory factor 4 can directly bind to CIITA promoters, and decreased IFN regulatory factor 4 expression is partially responsible for decreased CIITA/MHC-II expression in TSC1-deficient DCs. Moreover, we identify that CIITA/MHC-II silencing during DC maturation requires mTOR complex 1 activity. Together, our data reveal unexpected roles of TSC1/mTOR that control multifaceted functions of DCs.
Dendritic cells and follicular dendritic cells express a novel ligand for CD38 which influences their maturation and antibody responses

PubMed Central

Wykes, Michelle N; Beattie, Lynette; MacPherson, Gordon G; Hart, Derek N

2004-01-01

CD38 is a cell surface molecule with ADP-ribosyl cyclase activity, which is predominantly expressed on lymphoid and myeloid cells. CD38 has a significant role in B-cell function as some anti-CD38 antibodies can deliver potent growth and differentiation signals, but the ligand that delivers this signal in mice is unknown. We used a chimeric protein of mouse CD38 and human immunogobulin G (IgG) (CD38-Ig) to identify a novel ligand for murine CD38 (CD38L) on networks of follicular dendritic cells (FDCs) as well as dendritic cells (DCs) in the spleen. Flow-cytometry found that all DC subsets expressed cytoplasmic CD38L but only fresh ex vivo CD11c+ CD11b− DCs had cell surface CD38L. Anti-CD38 antibody blocked the binding of CD38-Ig to CD38L, confirming the specificity of detection. CD38-Ig immuno-precipitated ligands of 66 and 130 kDa. Functional studies found that CD38-Ig along with anti-CD40 and anti-major histocompatibility complex (MHC) class II antibody provided maturation signals to DCs in vitro. When CD38-Ig was administered in vivo with antigen, IgG2a responses were significantly reduced, suggesting that B and T cells expressing CD38 may modulate the isotype of antibodies produced through interaction with CD38L on DCs. CD38-Ig also expanded FDC networks when administered in vivo. In conclusion, this study has identified a novel ligand for CD38 which has a role in functional interactions between lymphocytes and DCs or FDCs. PMID:15500618
Dendritic cells and follicular dendritic cells express a novel ligand for CD38 which influences their maturation and antibody responses.

PubMed

Wykes, Michelle N; Beattie, Lynette; Macpherson, Gordon G; Hart, Derek N

2004-11-01

CD38 is a cell surface molecule with ADP-ribosyl cyclase activity, which is predominantly expressed on lymphoid and myeloid cells. CD38 has a significant role in B-cell function as some anti-CD38 antibodies can deliver potent growth and differentiation signals, but the ligand that delivers this signal in mice is unknown. We used a chimeric protein of mouse CD38 and human immunogobulin G (IgG) (CD38-Ig) to identify a novel ligand for murine CD38 (CD38L) on networks of follicular dendritic cells (FDCs) as well as dendritic cells (DCs) in the spleen. Flow-cytometry found that all DC subsets expressed cytoplasmic CD38L but only fresh ex vivo CD11c+ CD11b- DCs had cell surface CD38L. Anti-CD38 antibody blocked the binding of CD38-Ig to CD38L, confirming the specificity of detection. CD38-Ig immuno-precipitated ligands of 66 and 130 kDa. Functional studies found that CD38-Ig along with anti-CD40 and anti-major histocompatibility complex (MHC) class II antibody provided maturation signals to DCs in vitro. When CD38-Ig was administered in vivo with antigen, IgG2a responses were significantly reduced, suggesting that B and T cells expressing CD38 may modulate the isotype of antibodies produced through interaction with CD38L on DCs. CD38-Ig also expanded FDC networks when administered in vivo. In conclusion, this study has identified a novel ligand for CD38 which has a role in functional interactions between lymphocytes and DCs or FDCs.
Assessment: transcranial Doppler ultrasonography: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

PubMed

Sloan, M A; Alexandrov, A V; Tegeler, C H; Spencer, M P; Caplan, L R; Feldmann, E; Wechsler, L R; Newell, D W; Gomez, C R; Babikian, V L; Lefkowitz, D; Goldman, R S; Armon, C; Hsu, C Y; Goodin, D S

2004-05-11

To review the use of transcranial Doppler ultrasonography (TCD) and transcranial color-coded sonography (TCCS) for diagnosis. The authors searched the literature for evidence of 1) if TCD provides useful information in specific clinical settings; 2) if using this information improves clinical decision making, as reflected by improved patient outcomes; and 3) if TCD is preferable to other diagnostic tests in these clinical situations. TCD is of established value in the screening of children aged 2 to 16 years with sickle cell disease for stroke risk (Type A, Class I) and the detection and monitoring of angiographic vasospasm after spontaneous subarachnoid hemorrhage (Type A, Class I to II). TCD and TCCS provide important information and may have value for detection of intracranial steno-occlusive disease (Type B, Class II to III), vasomotor reactivity testing (Type B, Class II to III), detection of cerebral circulatory arrest/brain death (Type A, Class II), monitoring carotid endarterectomy (Type B, Class II to III), monitoring cerebral thrombolysis (Type B, Class II to III), and monitoring coronary artery bypass graft operations (Type B to C, Class II to III). Contrast-enhanced TCD/TCCS can also provide useful information in right-to-left cardiac/extracardiac shunts (Type A, Class II), intracranial occlusive disease (Type B, Class II to IV), and hemorrhagic cerebrovascular disease (Type B, Class II to IV), although other techniques may be preferable in these settings.
Risk prediction with procalcitonin and clinical rules in community-acquired pneumonia

PubMed Central

Huang, David T.; Weissfeld, Lisa A.; Kellum, John A.; Yealy, Donald M.; Kong, Lan; Martino, Michael; Angus, Derek C.

2009-01-01

Objective The Pneumonia Severity Index (PSI) and CURB-65 predict outcomes in community acquired pneumonia (CAP), but have limitations. Procalcitonin, a biomarker of bacterial infection, may provide prognostic information in CAP. Our objective was to describe the pattern of procalcitonin in CAP, and determine if procalcitonin provides prognostic information beyond PSI and CURB-65. Methods We conducted a multi-center prospective cohort study in 28 community and teaching emergency departments. Patients presenting with a clinical and radiographic diagnosis of CAP were enrolled. We stratified procalcitonin levels a priori into four tiers – I: < 0.1; II: ≥ 0.1 to <0.25; III: ≥ 0.25 to < 0.5; and IV: ≥ 0.5 ng/ml. Primary outcome was 30d mortality. Results 1651 patients formed the study cohort. Procalcitonin levels were broadly spread across tiers: 32.8% (I), 21.6% (II), 10.2% (III), 35.4% (IV). Used alone, procalcitonin had modest test characteristics: specificity (35%), sensitivity (92%), positive likelihood ratio (LR) (1.41), and negative LR (0.22). Adding procalcitonin to PSI in all subjects minimally improved performance. Adding procalcitonin to low risk PSI subjects (Class I–III) provided no additional information. However, subjects in procalcitonin tier I had low 30d mortality regardless of clinical risk, including those in higher risk classes (1.5% vs. 1.6% for those in PSI Class I–III vs. Class IV/V). Among high risk PSI subjects (Class IV/V), one quarter (126/546) were in procalcitonin tier I, and the negative LR of procalcitonin tier I was 0.09. Procalcitonin tier I was also associated with lower burden of other adverse outcomes. Similar results were seen with CURB-65 stratification. Conclusions Selective use of procalcitonin as an adjunct to existing rules may offer additional prognostic information in high risk patients. PMID:18342993
Long-term benefit of early pre-reperfusion metoprolol administration in patients with acute myocardial infarction: results from the METOCARD-CNIC trial (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction).

PubMed

Pizarro, Gonzalo; Fernández-Friera, Leticia; Fuster, Valentin; Fernández-Jiménez, Rodrigo; García-Ruiz, José M; García-Álvarez, Ana; Mateos, Alonso; Barreiro, María V; Escalera, Noemí; Rodriguez, Maite D; de Miguel, Antonio; García-Lunar, Inés; Parra-Fuertes, Juan J; Sánchez-González, Javier; Pardillos, Luis; Nieto, Beatriz; Jiménez, Adriana; Abejón, Raquel; Bastante, Teresa; Martínez de Vega, Vicente; Cabrera, José A; López-Melgar, Beatriz; Guzman, Gabriela; García-Prieto, Jaime; Mirelis, Jesús G; Zamorano, José Luis; Albarrán, Agustín; Goicolea, Javier; Escaned, Javier; Pocock, Stuart; Iñiguez, Andrés; Fernández-Ortiz, Antonio; Sánchez-Brunete, Vicente; Macaya, Carlos; Ibanez, Borja

2014-06-10

The goal of this trial was to study the long-term effects of intravenous (IV) metoprolol administration before reperfusion on left ventricular (LV) function and clinical events. Early IV metoprolol during ST-segment elevation myocardial infarction (STEMI) has been shown to reduce infarct size when used in conjunction with primary percutaneous coronary intervention (pPCI). The METOCARD-CNIC (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction) trial recruited 270 patients with Killip class ≤II anterior STEMI presenting early after symptom onset (<6 h) and randomized them to pre-reperfusion IV metoprolol or control group. Long-term magnetic resonance imaging (MRI) was performed on 202 patients (101 per group) 6 months after STEMI. Patients had a minimal 12-month clinical follow-up. Left ventricular ejection fraction (LVEF) at the 6 months MRI was higher after IV metoprolol (48.7 ± 9.9% vs. 45.0 ± 11.7% in control subjects; adjusted treatment effect 3.49%; 95% confidence interval [CI]: 0.44% to 6.55%; p = 0.025). The occurrence of severely depressed LVEF (≤35%) at 6 months was significantly lower in patients treated with IV metoprolol (11% vs. 27%, p = 0.006). The proportion of patients fulfilling Class I indications for an implantable cardioverter-defibrillator (ICD) was significantly lower in the IV metoprolol group (7% vs. 20%, p = 0.012). At a median follow-up of 2 years, occurrence of the pre-specified composite of death, heart failure admission, reinfarction, and malignant arrhythmias was 10.8% in the IV metoprolol group versus 18.3% in the control group, adjusted hazard ratio (HR): 0.55; 95% CI: 0.26 to 1.04; p = 0.065. Heart failure admission was significantly lower in the IV metoprolol group (HR: 0.32; 95% CI: 0.015 to 0.95; p = 0.046). In patients with anterior Killip class ≤II STEMI undergoing pPCI, early IV metoprolol before reperfusion resulted in higher long-term LVEF, reduced incidence of severe LV systolic dysfunction and ICD indications, and fewer heart failure admissions. (Effect of METOprolol in CARDioproteCtioN During an Acute Myocardial InfarCtion. The METOCARD-CNIC Trial; NCT01311700). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
BONE MARROW–DERIVED DENDRITIC CELL PROGENITORS (NLDC 145+, MHC CLASS II+, B7–1dim, B7–2−) INDUCE ALLOANTIGEN-SPECIFIC HYPORESPONSIVENESS IN MURINE T LYMPHOCYTES12

PubMed Central

Lu, Lina; McCaslin, Delbert; Starzl, Thomas E.; Thomson, Angus W.

2010-01-01

The functional maturation of dendritic cells (DC) and other antigen-presenting cells is believed to reflect the upregulation of cell surface major histocompatibility complex (MHC) class II and other T cell co-stimulatory molecules, especially the CD28 ligands B7–1 (CD80) and B7–2 (CD86). In this study, we propagated cells exhibiting characteristics of DC precursors from the bone marrow (BM) of BIO mice (H-2b; I-A1) in response to granulocyte-macrophage colony stimulating factor (GM-CSF). The methods used were similar to those employed previously to propagate DC progenitors from normal mouse liver. Cells expressing DC lineage markers (NLDC 145+, 33D1+ N418+) harvested from 8–10-day GM-CSF stimulated BM cell cultures were CD45+, heat-stable antigen+, CD54+, CD44+, MHC class II+, B7–1dim but B7–2− (costimulatory molecule-deficient). Supplementation of cultures with interleukin-4 (IL-4) in addition to GM-CSF however, resulted in marked upregulation of MHC class II and B7–2 expression. These latter cells exhibited potent allostimulatory activity in primary mixed leukocyte cultures. In contrast, the cells stimulated with GM-CSF alone were relatively weak stimulators and induced alloantigen-specific hyporesponsiveness in allogeneic T cells (C3H; H-2k; I-E+) detected upon re-stimulation in secondary MLR. This was associated with blockade of IL-2 production. Reactivity to third-party stimulators was intact. The hyporesponsiveness induced by the GM-CSF stimulated, costimulatory molecule-deficient cells was prevented by incorporation of anti-CD28 monoclonal antibody in the primary MLR and was reversed by addition of IL-2 to restimulated T cells. The findings show that MHC class II+ B7–2− cells with a DC precursor phenotype can induce alloantigen-specific hyporesponsiveness in vitro. Under the appropriate conditions, such costimulatory molecule-deficient cells could contribute to the induction of donor-specific unresponsiveness in vivo. PMID:8545887
Investigating the Capability of IRS-P6-LISS IV Satellite Image for Pistachio Forests Density Mapping (case Study: Northeast of Iran)

NASA Astrophysics Data System (ADS)

Hoseini, F.; Darvishsefat, A. A.; Zargham, N.

2012-07-01

In order to investigate the capability of satellite images for Pistachio forests density mapping, IRS-P6-LISS IV data were analyzed in an area of 500 ha in Iran. After geometric correction, suitable training areas were determined based on fieldwork. Suitable spectral transformations like NDVI, PVI and PCA were performed. A ground truth map included of 34 plots (each plot 1 ha) were prepared. Hard and soft supervised classifications were performed with 5 density classes (0-5%, 5-10%, 10-15%, 15-20% and > 20%). Because of low separability of classes, some classes were merged and classifications were repeated with 3 classes. Finally, the highest overall accuracy and kappa coefficient of 70% and 0.44, respectively, were obtained with three classes (0-5%, 5-20%, and > 20%) by fuzzy classifier. Considering the low kappa value obtained, it could be concluded that the result of the classification was not desirable. Therefore, this approach is not appropriate for operational mapping of these valuable Pistachio forests.
State laser regulations: Arizona's approach and experience

NASA Astrophysics Data System (ADS)

Barat, Kenneth L.

1992-06-01

Approximately a dozen states have regulatory or statutory authority in the area of nonionizing radiation. With only half that number having established laser regulations. Examples are Texas, Florida, Arizona, Mass. many more are considering establishing such rules, such as N.J., Il., Neb. On the federal level, the Food and Drug Administration has been the most active entity. OSHA has just recently established laser safety guidelines for its inspection staff. In March of 1990 the State of Arizona enacted rules for the control of Nonionizing radiation. This fell under Article 14 of Tittle 12 of the Arizona Administrative Code, which is under the authority of the Arizona Radiation Regulatory Agency. The rules cover a wide range of nonionizing sources, but the major emphasis is in the area of laser devices. While all class lasers fall under Article 14, only Class IIIb and Class IV laser use facilities are required to be registered and inspected by the agency. The rules apply to all Class IIIb and Class IV laser users, meaning medical, industrial, entertainment, and also research facilities.

75 FR 27785 - Final Effect of Designation of a Class of Employees for Addition to the Special Exposure Cohort

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-18

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Final Effect of Designation of a Class of Employees for Addition to the Special Exposure Cohort AGENCY: National Institute for Occupational Safety and Health... concerning the final effect of the decision to designate a class of employees from Area IV of the Santa...
[Evaluation of a chronic fatigue in patients with moderate-to-severe chronic heart failure].

PubMed

Jasiukeviciene, Lina; Vasiliauskas, Donatas; Kavoliūniene, Ausra; Marcinkeviciene, Jolanta; Grybauskiene, Regina; Grizas, Vytautas; Tumyniene, Vida

2008-01-01

To evaluate the chronic fatigue and its relation to the function of hypothalamus-pituitary-adrenal axis in patients with New York Heart Association (NYHA) functional class III-IV chronic heart failure. A total of 170 patients with NYHA functional class III-IV chronic heart failure completed MFI-20L, DUFS, and DEFS questionnaires assessing chronic fatigue and underwent echocardiography. Blood cortisol concentration was assessed at 8:00 am and 3:00 pm, and plasma N-terminal brain natriuretic pro-peptide (NT-proBNP) concentration was measured at 8:00 am. Neurohumoral investigations were repeated before cardiopulmonary exercise test and after it. The results of all questionnaires showed that 100% of patients with NYHA functional class III-IV heart failure complained of chronic fatigue. The level of overall fatigue was 54.5+/-31.5 points; physical fatigue - 56.8+/-24.6 points. Blood cortisol concentration at 8:00 am was normal (410.1+/-175.1 mmol/L) in majority of patients. Decreased concentration was only in four patients (122.4+/-15.5 mmol/L); one of these patients underwent heart transplantation. In the afternoon, blood cortisol concentration was insufficiently decreased (355.6+/-160.3 mmol/L); reaction to a physical stress was attenuated (Delta 92.9 mmol/L). Plasma NT-proBNP concentration was 2188.9+/-1852.2 pg/L; reaction to a physical stress was diminished (Delta 490.3 pg/L). All patients with NYHA class III-IV heart failure complained of daily chronic fatigue. Insufficiently decreased blood cortisol concentration in the afternoon showed that in the presence of chronic fatigue in long-term cardiovascular organic disease, disorder of a hypothalamus-pituitary-adrenal axis is involved.
Antimicrobial peptide inhibition of fungalysin proteases that target plant type 19 Family IV defense chitinases

USDA-ARS?s Scientific Manuscript database

Cereal crops and other plants produce secreted seed chitinases that reduce pathogenic infection, most likely by targeting the fungal chitinous cell wall. We have shown that corn (Zea mays) produces three GH family 19, plant class IV chitinases, that help in protecting the plant against Fusarium and ...
chs-4, a class IV chitin synthase gene from Neurospora crassa.

PubMed

Din, A B; Specht, C A; Robbins, P W; Yarden, O

1996-02-05

In Saccharomyces cerevisiae, most of the cellular chitin is produced by chitin synthase III, which requires the product encoded by the CSD2/CAL1/DIT101/KT12 gene. We have identified, isolated and structurally characterized as CSD2/CAL1/DIT101/KT12 homologue in the filamentous ascomycete Neurospora crassa and have used a "reverse genetics" approach to determine its role in vivo. The yeast gene was used as a heterologous probe for the isolation of a N. crassa gene(designated chs-4) encoding a polypeptide belonging to a class of chitin synthases which we have designated class IV. The predicted polypeptide encoded by this gene is highly similar to those of S. cerevisiae and Candida albicans. N. crassa strains in which chs-4 had been inactivated by the Repeat-Induced point mutation (RIP) process grew and developed in a normal manner under standard growth conditions. However, when grown in the presence of sorbose (a carbon source which induces morphological changes accompanied by elevated chitin content), chitin levels in the chs-4RIP strain were significantly lower than those observed in the wild type. We suggest that CHS4 may serve as an auxiliary enzyme in N. crassa and that, in contrast to yeasts, it is possible that filamentous fungi may have more than one class IV chitin synthase.
Identification of branched-chain amino acid aminotransferases active towards (R)-(+)-1-phenylethylamine among PLP fold type IV transaminases.

PubMed

Bezsudnova, Ekaterina Yu; Dibrova, Daria V; Nikolaeva, Alena Yu; Rakitina, Tatiana V; Popov, Vladimir O

2018-04-10

New class IV transaminases with activity towards L-Leu, which is typical of branched-chain amino acid aminotransferases (BCAT), and with activity towards (R)-(+)-1-phenylethylamine ((R)-PEA), which is typical of (R)-selective (R)-amine:pyruvate transaminases, were identified by bioinformatics analysis, obtained in recombinant form, and analyzed. The values of catalytic activities in the reaction with L-Leu and (R)-PEA are comparable to those measured for characteristic transaminases with the corresponding specificity. Earlier, (R)-selective class IV transaminases were found to be active, apart from (R)-PEA, only with some other (R)-primary amines and D-amino acids. Sequences encoding new transaminases with mixed type of activity were found by searching for changes in the conserved motifs of sequences of BCAT by different bioinformatics tools. Copyright © 2018 Elsevier B.V. All rights reserved.
Generation of CTL responses against pancreatic cancer in vitro using dendritic cells co-transfected with MUC4 and survivin RNA.

PubMed

Chen, Jiang; Guo, Xiao-Zhong; Li, Hong-Yu; Liu, Xu; Ren, Li-Nan; Wang, Di; Zhao, Jia-Jun

2013-09-23

Pancreatic cancer (PC) is one of the most devastating human malignancies without effective therapies. Tumor vaccine based on RNA-transfected dendritic cells (DCs) has emerged as an alternative therapeutic approach for a variety of human cancers including advanced PC. In the present study we compared the cytotoxic T lymphocyte (CTL) responses against PC cells in vitro, which were induced by DCs co-transfected with two mRNAs of tumor associated-antigens (TAA) MUC4 and survivin, versus DCs transfected with a single mRNA encoding either MUC4 or survivin. DCs co-transfected with two TAA mRNAs were found to induce stronger CTL responses against PC target cells in vitro, compared with the DCs transfected with a single mRNA. Moreover, the antigen-specific CTL responses were MHC class I-restricted. These results provide an experimental foundation for further clinical investigations of DC vaccines encoding multiple TAA epitopes for metastatic PC. Copyright © 2013 Elsevier Ltd. All rights reserved.
The active translation of MHCII mRNA during dendritic cells maturation supplies new molecules to the cell surface pool.

PubMed

Malanga, Donatella; Barba, Pasquale; Harris, Paul E; Maffei, Antonella; Del Pozzo, Giovanna

2007-04-01

The transition of human dendritic cells (DCs) from the immature to the mature phenotype is characterized by an increased density of MHC class II (MHCII) molecules on the plasma membrane, a key requirement of their competence as professional antigen presenting cells (APCs). MHCII molecules on the cell surface derive from newly synthesized as well as from preexisting proteins. So far, all the studies done on DCs during maturation, to establish the relative contribution of newly synthesized MHCII molecules to the cell surface pool did not produced a clear, unified scenario. We report that, in human DCs stimulated ex vivo with LPS, the changes in the RNA accumulation specific for at least two MHCII genes (HLA-DRA and HLA-DQA1) due to transcriptional upregulation, is associated with the active translation at high rate of these transcripts. Our finding reveals that, across the 24h of the maturation process in human DCs, newly synthesized MHCII proteins are supplied to the APCs cell surface pool.
Outcome of bipolar electrocoagulation with lesionectomy in the treatment of epilepsy involving eloquent areas.

PubMed

Zhai, Feng; Zhou, Jian; Li, Tianfu; Cui, Zhiqiang; Luan, Guoming

2015-01-01

We have demonstrated previously that bipolar electrocoagulation on functional cortex (BCFC) is a safe and effective approach for epilepsy involving eloquent areas. Here, we report the results of BCFC with lesionectomy for patients with epileptogenic foci partially overlapping eloquent areas. Forty patients who had been treated with lesionectomy with BCFC were retrospectively reviewed with regard to seizure outcome and neurological deficits. Ten similar patients who had received lesionectomy with multiple subpial transections (MST) were examined as a control group. In the lesionectomy group with BCFC, Engel class I was achieved in 18 (45%) patients, class II in 8 (20%) patients, class III in 8 (20%) patients and class IV in 6 (15%) patients. Five (12.5%) patients developed mild hemiparesis and 1 (2.5%) patient mild sensory dysphasia. In the lesionectomy group with MST, Engel class I was achieved in 3 (30%) patients, class II in 2 (20%) patients, class III in 3 (30%) patients and class IV in 2 (20%) patients. Two (20%) patients developed mild hemiparesis and 1 (10%) patient moderate hemiparesis. All these complications recovered within 1-12 months. Compared with MST, the outcome of BCFC with lesionectomy is similar. But since MST leads to mechanical injury, while BCFC causes thermal injury, the complications of BCFC seem less severe. © 2014 S. Karger AG, Basel.
Heterogonous expression and characterization of a plant class IV chitinase from the pitcher of the carnivorous plant Nepenthes alata.

PubMed

Ishisaki, Kana; Honda, Yuji; Taniguchi, Hajime; Hatano, Naoya; Hamada, Tatsuro

2012-03-01

A class IV chitinase belonging to the glycoside hydrolase 19 family from Nepenthes alata (NaCHIT1) was expressed in Escherichia coli. The enzyme exhibited weak activity toward polymeric substrates and significant activity toward (GlcNAc)(n) [β-1,4-linked oligosaccharide of GlcNAc with a polymerization degree of n (n = 4-6)]. The enzyme hydrolyzed the third and fourth glycosidic linkages from the non-reducing end of (GlcNAc)(6). The pH optimum of the enzymatic reaction was 5.5 at 37°C. The optimal temperature for activity was 60°C in 50 mM sodium acetate buffer (pH 5.5). The anomeric form of the products indicated that it was an inverting enzyme. The k(cat)/K(m) of the (GlcNAc)(n) hydrolysis increased with an increase in the degree of polymerization. Amino acid sequence alignment analysis between NaCHIT1 and a class IV chitinase from a Picea abies (Norway spruce) suggested that the deletion of four loops likely led the enzyme to optimize the (GlcNAc)(n) hydrolytic reaction rather than the hydrolysis of polymeric substrates.
In vitro characterization of the antibacterial spectrum of novel bacterial type II topoisomerase inhibitors of the aminobenzimidazole class.

PubMed

Mani, Nagraj; Gross, Christian H; Parsons, Jonathan D; Hanzelka, Brian; Müh, Ute; Mullin, Steve; Liao, Yusheng; Grillot, Anne-Laure; Stamos, Dean; Charifson, Paul S; Grossman, Trudy H

2006-04-01

Antibiotics with novel mechanisms of action are becoming increasingly important in the battle against bacterial resistance to all currently used classes of antibiotics. Bacterial DNA gyrase and topoisomerase IV (topoIV) are the familiar targets of fluoroquinolone and coumarin antibiotics. Here we present the characterization of two members of a new class of synthetic bacterial topoII ATPase inhibitors: VRT-125853 and VRT-752586. These aminobenzimidazole compounds were potent inhibitors of both DNA gyrase and topoIV and had excellent antibacterial activities against a wide spectrum of problematic pathogens responsible for both nosocomial and community-acquired infections, including staphylococci, streptococci, enterococci, and mycobacteria. Consistent with the novelty of their structures and mechanisms of action, antibacterial potency was unaffected by commonly encountered resistance phenotypes, including fluoroquinolone resistance. In time-kill assays, VRT-125853 and VRT-752586 were bactericidal against Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis, and Haemophilus influenzae, causing 3-log reductions in viable cells within 24 h. Finally, similar to the fluoroquinolones, relatively low frequencies of spontaneous resistance to VRT-125853 and VRT-752586 were found, a property consistent with their in vitro dual-targeting activities.
In Vitro Characterization of the Antibacterial Spectrum of Novel Bacterial Type II Topoisomerase Inhibitors of the Aminobenzimidazole Class

PubMed Central

Mani, Nagraj; Gross, Christian H.; Parsons, Jonathan D.; Hanzelka, Brian; Müh, Ute; Mullin, Steve; Liao, Yusheng; Grillot, Anne-Laure; Stamos, Dean; Charifson, Paul S.; Grossman, Trudy H.

2006-01-01

Antibiotics with novel mechanisms of action are becoming increasingly important in the battle against bacterial resistance to all currently used classes of antibiotics. Bacterial DNA gyrase and topoisomerase IV (topoIV) are the familiar targets of fluoroquinolone and coumarin antibiotics. Here we present the characterization of two members of a new class of synthetic bacterial topoII ATPase inhibitors: VRT-125853 and VRT-752586. These aminobenzimidazole compounds were potent inhibitors of both DNA gyrase and topoIV and had excellent antibacterial activities against a wide spectrum of problematic pathogens responsible for both nosocomial and community-acquired infections, including staphylococci, streptococci, enterococci, and mycobacteria. Consistent with the novelty of their structures and mechanisms of action, antibacterial potency was unaffected by commonly encountered resistance phenotypes, including fluoroquinolone resistance. In time-kill assays, VRT-125853 and VRT-752586 were bactericidal against Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis, and Haemophilus influenzae, causing 3-log reductions in viable cells within 24 h. Finally, similar to the fluoroquinolones, relatively low frequencies of spontaneous resistance to VRT-125853 and VRT-752586 were found, a property consistent with their in vitro dual-targeting activities. PMID:16569833
TAPCells, the Chilean dendritic cell vaccine against melanoma and prostate cancer.

PubMed

Salazar-Onfray, Flavio; Pereda, Cristián; Reyes, Diego; López, Mercedes N

2013-01-01

Here we summarize 10 years of effort in the development of a biomedical innovation with global projections. This innovation consists of a novel method for the production of therapeutic dendritic-like cells called Tumor Antigen Presenting Cells (TAPCells®). TAPCells-based immunotherapy was tested in more than 120 stage III and IV melanoma patients and 20 castration-resistant prostate cancer patients in a series of phase I and I/II clinical trials. TAPCells vaccines induced T cell-mediated memory immune responses that correlated with increased survival in melanoma patients and prolonged prostate-specific antigen doubling time in prostate cancer patients. Importantly, more than 60% of tested patients showed a Delayed Type Hypersensitivity (DTH) reaction against the lysates, indicating the development of anti-tumor immunological memory that correlates with clinical benefits. The in vitro analysis of the lysate mix showed that it contains damage-associated molecular patterns such as HMBG-1 protein which are capable to improve, through Toll-like receptor-4, maturation and antigen cross-presentation of the dendritic cells (DC). In fact, a Toll-like receptor-4 polymorphism correlates with patient clinical outcomes. Moreover, Concholepas concholepas hemocyanin (CCH) used as adjuvant proved to be safe and capable of enhancing the immunological response. Furthermore, we observed that DC vaccination resulted in a three-fold increase of T helper-1 lymphocytes releasing IFN-γ and a two-fold increase of T helper-17 lymphocytes capable of producing IL-17 in DTH+ with respect to DTH- patients. Important steps have been accomplished for TAPCells technology transfer, including patenting, packaging and technology assessment. Altogether, our results indicate that TAPCells vaccines constitute an exceptional Chilean national innovation of international value.
Advanced Oxidation Protein Products-Modified Albumin Induces Differentiation of RAW264.7 Macrophages into Dendritic-Like Cells Which Is Modulated by Cell Surface Thiols.

PubMed

Garibaldi, Silvano; Barisione, Chiara; Marengo, Barbara; Ameri, Pietro; Brunelli, Claudio; Balbi, Manrico; Ghigliotti, Giorgio

2017-01-10

Local accumulation of Advanced Oxidation Protein Products (AOPP) induces pro-inflammatory and pro-fibrotic processes in kidneys and is an independent predictor of renal fibrosis and of rapid decline of eGFR in patients with chronic kidney disease (CKD). In addition to kidney damage, circulating AOPP may be regarded as mediators of systemic oxidative stress and, in this capacity, they might play a role in the progression of atherosclerotic damage of arterial walls. Atherosclerosis is a chronic inflammatory disease that involves activation of innate and adaptive immunity. Dendritic cells (DCs) are key cells in this process, due to their role in antigen presentation, inflammation resolution and T cell activation. AOPP consist in oxidative modifications of proteins (such as albumin and fibrinogen) that mainly occur through myeloperoxidase (MPO)-derived hypochlorite (HOCl). HOCl modified proteins have been found in atherosclerotic lesions. The oxidizing environment and the shifts in cellular redox equilibrium trigger inflammation, activate immune cells and induce immune responses. Thus, surface thiol groups contribute to the regulation of immune functions. The aims of this work are: (1) to evaluate whether AOPP-proteins induce activation and differentiation of mature macrophages into dendritic cells in vitro; and (2) to define the role of cell surface thiol groups and of free radicals in this process. AOPP-proteins were prepared by in vitro incubation of human serum albumin (HSA) with HOCl. Mouse macrophage-like RAW264.7 were treated with various concentrations of AOPP-HSA with or without the antioxidant N -acetyl cysteine (NAC). Following 48 h of HSA-AOPP treatment, RAW264.7 morphological changes were evaluated by microscopic observation, while markers of dendritic lineage and activation (CD40, CD86, and MHC class II) and allogeneic T cell proliferation were evaluated by flow cytometry. Cell surface thiols were measured by AlexaFluor-maleimide binding, and ROS production was assessed as DCF fluorescence by flow cytometry. HSA-AOPP induced the differentiation of RAW264.7 cells into a dendritic-like phenotype, as shown by morphological changes, by increased CD40, CD86 and MHC class II surface expression and by induction of T cell proliferation. The cell surface thiols dose dependently decreased following HSA-AOPP treatment, while ROS production increased. NAC pre-treatment enhanced the amount of cell surface thiols and prevented their reduction due to treatment with AOPP. Both ROS production and RAW264.7 differentiation into DC-like cells induced by HSA-AOPP were reduced by NAC. Our results highlight that oxidized plasma proteins modulate specific immune responses of macrophages through a process involving changes in the thiol redox equilibrium. We suggest that this mechanism may play a role in determining the rapid progression of the atherosclerotic process observed in CKD patients.
Printed-Circuit-Board Soldering Training for Group IV Personnel.

ERIC Educational Resources Information Center

Hooprich, E. A.; Matlock, E. W.

As part of a larger program to determine which Navy skills can be learned by lower aptitude personnel, and which methods and techniques would be most effective, an experimental course in printed circuit board soldering was given to 186 Group IV students in 13 classes. Two different training approaches--one stressing instructor guidance and the…
Regulation of dendrite growth and maintenance by exocytosis

PubMed Central

Peng, Yun; Lee, Jiae; Rowland, Kimberly; Wen, Yuhui; Hua, Hope; Carlson, Nicole; Lavania, Shweta; Parrish, Jay Z.; Kim, Michael D.

2015-01-01

ABSTRACT Dendrites lengthen by several orders of magnitude during neuronal development, but how membrane is allocated in dendrites to facilitate this growth remains unclear. Here, we report that Ras opposite (Rop), the Drosophila ortholog of the key exocytosis regulator Munc18-1 (also known as STXBP1), is an essential factor mediating dendrite growth. Neurons with depleted Rop function exhibit reduced terminal dendrite outgrowth followed by primary dendrite degeneration, suggestive of differential requirements for exocytosis in the growth and maintenance of different dendritic compartments. Rop promotes dendrite growth together with the exocyst, an octameric protein complex involved in tethering vesicles to the plasma membrane, with Rop–exocyst complexes and exocytosis predominating in primary dendrites over terminal dendrites. By contrast, membrane-associated proteins readily diffuse from primary dendrites into terminals, but not in the reverse direction, suggesting that diffusion, rather than targeted exocytosis, supplies membranous material for terminal dendritic growth, revealing key differences in the distribution of materials to these expanding dendritic compartments. PMID:26483382
19 CFR Appendix to Part 146 - Guidelines for Determining Producibility and Relative Values for Oil Refinery Zones

Code of Federal Regulations, 2012 CFR

2012-04-01

... × .20). Likewise, the class IV crude oil could produce aviation gasoline in an amount up to 8,500 pounds... Class III PF Crude 35,000 24,500 31,850 14,000 31,150 10,150 Class III D Crude 20,000 14,000 18,200 8,000 17,800 5,800 Class III NPF Crude 20,000 14,000 18,200 8,000 17,800 5,800 Feedstock factors are...
19 CFR Appendix to Part 146 - Guidelines for Determining Producibility and Relative Values for Oil Refinery Zones

Code of Federal Regulations, 2014 CFR

2014-04-01

... × .20). Likewise, the class IV crude oil could produce aviation gasoline in an amount up to 8,500 pounds... Class III PF Crude 35,000 24,500 31,850 14,000 31,150 10,150 Class III D Crude 20,000 14,000 18,200 8,000 17,800 5,800 Class III NPF Crude 20,000 14,000 18,200 8,000 17,800 5,800 Feedstock factors are...
Three-Dimensional Dendrite Growth Within the Shrouds of Single Crystal Blades of a Nickel-Based Superalloy

NASA Astrophysics Data System (ADS)

Wang, Fu; Wu, Zining; Huang, Can; Ma, Dexin; Jakumeit, Jürgen; Bührig-Polaczek, Andreas

2017-12-01

The effect of withdrawal rates on the three-dimensional dendrite growth within the shrouds of single crystal blades during directional solidification was studied by both experiments and numerical simulations. The results showed that at given withdrawal rates, the dendrite pattern within the shrouds comprised three zones: primary dendrite zone, secondary dendrite spread zone, and a higher-order dendrite branched zone. With increasing withdrawal rate, the average primary dendrite arm spacing in the primary dendrite zone and the average secondary dendrite arm spacings in both the secondary dendrite spread zone and the higher-order dendrite branched zone were reduced. Independent of the variation in withdrawal rate, two analogous dendrite growth routes were observed within the shrouds of the employed blade geometry. These routes originated from the primary dendrites in the primary dendrite zone and filled in the shrouds by directly spreading secondary or successively branching higher-order dendrites. Except for a withdrawal rate of 6 mm min-1, these dendrites impinged at the shroud's highest extremity and could be explained by the simulated moving isotherms. As the withdrawal rate was increased to 2.5 mm min-1, undercooling and contraction stress-related equiaxed grains were observed in the interdendritic region at the lowest shroud extremity. With increasing withdrawal rate, the amount of the defects was increased. Since the defects destroy the integrity of single crystal blades, the solidification condition within the shroud should be controlled to avoid their occurrence. Along the dendrite growth route, an accumulated misorientation of the dendrites was observed. At the same positions, this accumulation increased with increasing withdrawal rate.
Classes and continua of hippocampal CA1 inhibitory neurons revealed by single-cell transcriptomics.

PubMed

Harris, Kenneth D; Hochgerner, Hannah; Skene, Nathan G; Magno, Lorenza; Katona, Linda; Bengtsson Gonzales, Carolina; Somogyi, Peter; Kessaris, Nicoletta; Linnarsson, Sten; Hjerling-Leffler, Jens

2018-06-18

Understanding any brain circuit will require a categorization of its constituent neurons. In hippocampal area CA1, at least 23 classes of GABAergic neuron have been proposed to date. However, this list may be incomplete; additionally, it is unclear whether discrete classes are sufficient to describe the diversity of cortical inhibitory neurons or whether continuous modes of variability are also required. We studied the transcriptomes of 3,663 CA1 inhibitory cells, revealing 10 major GABAergic groups that divided into 49 fine-scale clusters. All previously described and several novel cell classes were identified, with three previously described classes unexpectedly found to be identical. A division into discrete classes, however, was not sufficient to describe the diversity of these cells, as continuous variation also occurred between and within classes. Latent factor analysis revealed that a single continuous variable could predict the expression levels of several genes, which correlated similarly with it across multiple cell types. Analysis of the genes correlating with this variable suggested it reflects a range from metabolically highly active faster-spiking cells that proximally target pyramidal cells to slower-spiking cells targeting distal dendrites or interneurons. These results elucidate the complexity of inhibitory neurons in one of the simplest cortical structures and show that characterizing these cells requires continuous modes of variation as well as discrete cell classes.
BCI Competition IV – Data Set I: Learning Discriminative Patterns for Self-Paced EEG-Based Motor Imagery Detection

PubMed Central

Zhang, Haihong; Guan, Cuntai; Ang, Kai Keng; Wang, Chuanchu

2012-01-01

Detecting motor imagery activities versus non-control in brain signals is the basis of self-paced brain-computer interfaces (BCIs), but also poses a considerable challenge to signal processing due to the complex and non-stationary characteristics of motor imagery as well as non-control. This paper presents a self-paced BCI based on a robust learning mechanism that extracts and selects spatio-spectral features for differentiating multiple EEG classes. It also employs a non-linear regression and post-processing technique for predicting the time-series of class labels from the spatio-spectral features. The method was validated in the BCI Competition IV on Dataset I where it produced the lowest prediction error of class labels continuously. This report also presents and discusses analysis of the method using the competition data set. PMID:22347153

Self-organized perturbations enhance class IV behavior and 1/f power spectrum in elementary cellular automata.

PubMed

Nakajima, Kohei; Haruna, Taichi

2011-09-01

In this paper, we propose a new class of cellular automata based on the modification of its state space. It is introduced to model a computation which is exposed to an environment. We formalized the computation as extension and projection processes of its state space and resulting misidentifications of the state. This is motivated to embed the role of an environment into the system itself, which naturally induces self-organized internal perturbations rather than the usual external perturbations. Implementing this structure into the elementary cellular automata, we characterized its effect by means of input entropy and power spectral analysis. As a result, the cellular automata with this structure showed robust class IV behavior and a 1/f power spectrum in a wide range of rule space comparative to the notion of the edge of chaos. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Provision of Atraumatic Restorative Treatment (ART) restorations to Chinese pre-school children--a 30-month evaluation.

PubMed

Lo, E C; Holmgren, C J

2001-01-01

The objectives of this study were: to provide restorations using the ART approach to pre-school children in Southern China in a kindergarten environment, using a high-strength glass-ionomer restorative material; to assess the acceptability of this approach and to evaluate on a longitudinal basis the restorations placed. A total of 170 ART restorations were placed in 95 children, aged 5.1 +/- 0.7 years, by seven final-year dental students using standard ART procedures and hand instruments. The restorations were evaluated every six months thereafter by two calibrated independent examiners using explorers and mouth-mirrors. 93% of the children reported that they did not feel pain during treatment and 86% were willing to receive ART restorations again. The cumulative 12- and 30-month survival rates of Class I restorations were 91% and 79%, respectively. The corresponding figures for Class V restorations were 79% and 70%, while those for Class II restorations were 75% and 51%. The failure rates of Class III and IV restorations were high with more than half of them scored as missing within the first year. The ART approach was shown to be acceptable to Chinese pre-school children for providing restorative dental care outside the traditional clinical setting. The success rates were high for Class I and V restorations in primary teeth, modest for Class II, and low for Class III and IV restorations.
Tau-Dependent Kv4.2 Depletion and Dendritic Hyperexcitability in a Mouse Model of Alzheimer's Disease

PubMed Central

Hall, Alicia M.; Throesch, Benjamin T.; Buckingham, Susan C.; Markwardt, Sean J.; Peng, Yin; Wang, Qin

2015-01-01

Neuronal hyperexcitability occurs early in the pathogenesis of Alzheimer's disease (AD) and contributes to network dysfunction in AD patients. In other disorders with neuronal hyperexcitability, dysfunction in the dendrites often contributes, but dendritic excitability has not been directly examined in AD models. We used dendritic patch-clamp recordings to measure dendritic excitability in the CA1 region of the hippocampus. We found that dendrites, more so than somata, of hippocampal neurons were hyperexcitable in mice overexpressing Aβ. This dendritic hyperexcitability was associated with depletion of Kv4.2, a dendritic potassium channel important for regulating dendritic excitability and synaptic plasticity. The antiepileptic drug, levetiracetam, blocked Kv4.2 depletion. Tau was required, as crossing with tau knock-out mice also prevented both Kv4.2 depletion and dendritic hyperexcitability. Dendritic hyperexcitability induced by Kv4.2 deficiency exacerbated behavioral deficits and increased epileptiform activity in hAPP mice. We conclude that increased dendritic excitability, associated with changes in dendritic ion channels including Kv4.2, may contribute to neuronal dysfunction in early stages AD. PMID:25878292
A new protocol for the propagation of dendritic cells from rat bone marrow using recombinant GM-CSF, and their quantification using the mAb OX-62

PubMed Central

Chen-Woan, M.; Delaney, C.P.; Fournier, V.; Wakizaka, Y.; Murase, N.; Fung, J.; Starzl, T.E.; Demetris, A.J.

2010-01-01

Bone marrow (BM)-derived dendritic cells (DC) are the most potent known antigen (Ag) presenting cell in vivo and in vitro. Detailed analysis of their properties and mechanisms of action requires an ability to produce large numbers of DC. Although DC have been isolated from several rat tissues, including BM, the yield is uniformly low. We describe a simple method for the propagation of large numbers of DC from rat BM and document cell yield with the rat DC marker, OX-62. After depletion of plastic-adherent and Fc+ cells by panning on dishes coated with normal serum, residual BM cells were cultured in gelatin coated flasks using murine rGM-CSF supplemented medium. Prior to analysis, non-adherent cells were re-depleted of contaminating Fc+ cells. Propagation of DC was monitored by double staining for FACS analysis (major histocompatibility complex (MHC) class II+/OX-62+, OX-19−). Functional assay, morphological analysis and evaluation of homing patterns of cultured cells revealed typical DC characteristics. MHC class II and OX-62 antigen expression increased with time in culture and correlated with allostimulatory ability. DC yield increased until day 7, when 3.3 × 106 DC were obtained from an initial 3 × 108 unfractionated BM cells. Significant numbers of DC can be generated from rat BM using these simple methods. This should permit analysis and manipulation of rat DC functions in vivo and in vitro. PMID:7836778
Epstein-Barr Virus Promotes Interferon-α Production by Plasmacytoid Dendritic Cells

PubMed Central

Quan, Timothy E.; Roman, Robert M.; Rudenga, Benjamin J.; Holers, V. Michael; Craft, Joe

2010-01-01

Objective Epstein-Barr virus (EBV) infection has been linked to systemic lupus erythematosus (SLE) as demonstrated by the presence of increased seroprevalence and elevated viral loads, but the mechanism of this linkage has not been elucidated. Increased IFN-α levels and signatures, associated with innate immune responses, have been found in patients with SLE. Plasmacytoid dendritic cells (pDC) are innate immune cells that mediate viral immunity by producing large quantities of interferon alpha (IFN-α), but the role they play during infection with EBV remains unclear. To address this issue, we investigated the ability of EBV to promote IFN-α production by pDC in healthy subjects. Methods Human pDC were sorted and cultured in the presence of EBV, EBV small RNA (EBER), and EBV double-stranded DNA (dsDNA). IFN-α production by pDC was measured by enzyme-linked immunosorbent assay (ELISA), with activation of these cells measured by flow cytometry. Results We demonstrate that EBV DNA and RNA promote IFN-α production by human pDC through engagement of Toll-like receptor (TLR) 9 and TLR7, respectively, with initial viral recognition by pDC mediated by binding to major histocompatibility (MHC) class II molecules. Conclusion These data demonstrate that MHC class II-specific engagement by virus and subsequent viral nucleic acid recognition mediates IFN-α production by pDC. Our results suggest that elevated levels of IFN-α found in lupus patients may be a result of aberrantly controlled chronic viral infection. PMID:20178121
Ly49 Receptors: Innate and Adaptive Immune Paradigms

PubMed Central

Rahim, Mir Munir A.; Tu, Megan M.; Mahmoud, Ahmad Bakur; Wight, Andrew; Abou-Samra, Elias; Lima, Patricia D. A.; Makrigiannis, Andrew P.

2014-01-01

The Ly49 receptors are type II C-type lectin-like membrane glycoproteins encoded by a family of highly polymorphic and polygenic genes within the mouse natural killer (NK) gene complex. This gene family is designated Klra, and includes genes that encode both inhibitory and activating Ly49 receptors in mice. Ly49 receptors recognize class I major histocompatibility complex-I (MHC-I) and MHC-I-like proteins on normal as well as altered cells. Their functional homologs in humans are the killer cell immunoglobulin-like receptors, which recognize HLA class I molecules as ligands. Classically, Ly49 receptors are described as being expressed on both the developing and mature NK cells. The inhibitory Ly49 receptors are involved in NK cell education, a process in which NK cells acquire function and tolerance toward cells that express “self-MHC-I.” On the other hand, the activating Ly49 receptors recognize altered cells expressing activating ligands. New evidence shows a broader Ly49 expression pattern on both innate and adaptive immune cells. Ly49 receptors have been described on multiple NK cell subsets, such as uterine NK and memory NK cells, as well as NKT cells, dendritic cells, plasmacytoid dendritic cells, macrophages, neutrophils, and cells of the adaptive immune system, such as activated T cells and regulatory CD8+ T cells. In this review, we discuss the expression pattern and proposed functions of Ly49 receptors on various immune cells and their contribution to immunity. PMID:24765094
Effect of Foot-and-Mouth Disease Virus Infection on the Frequency, Phenotype and Function of Circulating Dendritic Cells in Cattle

PubMed Central

Sei, Janet J.; Waters, Ryan A.; Kenney, Mary; Barlow, John W.; Golde, William T.

2016-01-01

Foot-and-mouth disease virus (FMDV) is a highly contagious virus that causes one of the most devastating diseases in cloven-hoofed animals. Disease symptoms develop within 2 to 3 days of exposure and include fever and vesicular lesions on the tongue and hooves. Dendritic cells (DC) play an essential role in protective immune responses against pathogens. Therefore, investigating their role during FMDV infection would lead to a better understanding of host-pathogen interactions. In this study, following infection of cattle with FMDV, we investigated the frequency and function of conventional (cDC) and plasmacytoid DC (pDC) in blood by using multi-color flow cytometry. We show that the frequency of cDC and pDC increased following FMDV infection and peaked 3 to 4 days post-infection. During peak viremia, the cattle became lymphopenic, the expression of MHC class II molecules on cDC and pDC was dramatically down-regulated, the processing of exogenous antigen by cDC and pDC was impaired, and there was an increase in IL-10 production by DC and monocytes. Notably, after clearance of FMDV from the blood, MHC class II expression returned to pre-infection levels. Altogether, our study demonstrates that in cattle, FMDV inhibits the function of DC, thereby retarding the initiation of adaptive immune responses, potentially enhancing virus shedding during the acute phase of infection. PMID:27008425
Characterization of inflammatory cell infiltration in feline allergic skin disease.

PubMed

Taglinger, K; Day, M J; Foster, A P

2007-11-01

Sixteen cats with allergic dermatitis and six control cats with no skin disease were examined. Lymphoid and histiocytic cells in skin sections were examined immunohistochemically and mast cells were identified by toluidine blue staining. The 16 allergic cats showed one or more of several features (alopecia, eosinophilic plaques or granulomas, papulocrusting lesions), and histopathological findings were diverse. In control cats there were no cells that expressed IgM or MAC387, a few that were immunolabelled for IgG, IgA or CD3, and moderate numbers of mast cells. In allergic cats, positively labelled inflammatory cells were generally more numerous in lesional than in non-lesional skin sections, and were particularly associated with the superficial dermis and perifollicular areas. There were low numbers of plasma cells expressing cytoplasmic immunoglobulin; moderate numbers of MHC II-, MAC387- and CD3-positive cells; and moderate to numerous mast cells. MHC class II expression was associated with inflammatory cells morphologically consistent with dermal dendritic cells and macrophages, and epidermal Langerhans cells. Dendritic cells expressing MHC class II were usually associated with an infiltrate of CD3 lymphocytes, suggesting that these cells participate in maintenance of the local immune response by presenting antigen to T lymphocytes. These findings confirm that feline allergic skin disease is characterized by infiltration of activated antigen-presenting cells and T lymphocytes in addition to increased numbers of dermal mast cells. This pattern mimics the dermal inflammation that occurs in the chronic phase of both canine and human atopic dermatitis.
Stress-Induced Neurogenic Inflammation in Murine Skin Skews Dendritic Cells Towards Maturation and Migration

PubMed Central

Joachim, Ricarda Alcira; Handjiski, Bori; Blois, Sandra Maria; Hagen, Evelin; Paus, Ralf; Arck, Petra Clara

2008-01-01

The skin continuously serves as a biosensor of multiple exogenous stressors and integrates the resulting responses with an individual’s central and peripheral endogenous response systems to perceived stress; it also acts to protect against external challenges such as wounding and infection. We have previously shown in mice that stress induces nerve growth factor- and substance P-dependent neurogenic inflammation, which includes the prominent clustering of MHC class II+ cells. Because the contribution of dendritic cells (DCs) in response to stress is not well understood, we examined the role of DCs in neurogenic inflammation in murine skin using a well-established murine stress model. We show that sound stress increases the number of intradermal langerin+ and CD11c+ DCs and induces DC maturation, as indicated by the up-regulated expression of CD11c, MHC class II, and intercellular adhesion molecule-1 (ICAM-1). Blocking of ICAM-1/leukocyte function-associated antigen-1 interactions significantly abrogated the stress-induced numeric increase, maturation, and migration of dermal DCs in vivo and also reduced stress-induced keratinocyte apoptosis and endothelial cell expression of ICAM-1. In conclusion, stress exposure causes a state of immune alertness in the skin. Such adaptation processes may ensure protection from possible infections on wounding by stressors, such as attack by predators. However, present-day stressors have changed and such adaptations appear redundant and may overrun skin homeostasis by inducing immune dermatoses. PMID:18832583
Ascophyllan Purified from Ascophyllum nodosum Induces Th1 and Tc1 Immune Responses by Promoting Dendritic Cell Maturation

PubMed Central

Zhang, Wei; Du, Jiang-Yuan; Jiang, Zedong; Okimura, Takasi; Oda, Tatsuya; Yu, Qing; Jin, Jun-O

2014-01-01

Marine-derived sulfated polysaccharides have been shown to possess certain anti-virus, anti-tumor, anti-inflammatory and anti-coagulant activities. However, the in vivo immunomodulatory effects of marine-derived pure compounds have been less well characterized. In this study, we investigated the effect of ascophyllan, a sulfated polysaccharide purified from Ascophyllum nodosum, on the maturation of mouse dendritic cells (DCs) in vitro and in vivo. Ascophyllan induced up-regulation of co-stimulatory molecules and production of pro-inflammatory cytokines in bone marrow-derived DCs (BMDCs). Moreover, in vivo administration of ascophyllan promotes up-regulation of CD40, CD80, CD86, MHC class I and MHC class II and production of IL-6, IL-12 and TNF-α in spleen cDCs. Interestingly, ascophyllan induced a higher degree of co-stimulatory molecule up-regulation and pro-inflammatory cytokine production than fucoidan, a marine-derived polysaccharide with well-defined effect for promoting DC maturation. Ascophyllan also promoted the generation of IFN-γ-producing Th1 and Tc1 cells in the presence of DCs in an IL-12-dependent manner. Finally, myeloid differentiation primary response 88 (MyD88) signaling pathway was essential for DC maturation induced by ascophyllan. Taken together, these results demonstrate that ascophyllan induces DC maturation, and consequently enhances Th1 and Tc1 responses in vivo. This knowledge could facilitate the development of novel therapeutic strategies to combat infectious diseases and cancer. PMID:25026264
Primary biliary cirrhosis degree assessment by acoustic radiation force impulse imaging and hepatic fibrosis indicators.

PubMed

Zhang, Hai-Chun; Hu, Rong-Fei; Zhu, Ting; Tong, Ling; Zhang, Qiu-Qin

2016-06-14

To evaluate the assessment of primary biliary cirrhosis degree by acoustic radiation force impulse imaging (ARFI) and hepatic fibrosis indicators. One hundred and twenty patients who developed liver cirrhosis secondary to primary biliary cirrhosis were selected as the observation group, with the degree of patient liver cirrhosis graded by Child-Pugh (CP) score. Sixty healthy individuals were selected as the control group. The four indicators of hepatic fibrosis were detected in all research objects, including hyaluronic acid (HA), laminin (LN), type III collagen (PC III), and type IV collagen (IV-C). The liver parenchyma hardness value (LS) was then measured by ARFI technique. LS and the four indicators of liver fibrosis (HA, LN, PC III, and IV-C) were observed in different grade CP scores. The diagnostic value of LS and the four indicators of liver fibrosis in determining liver cirrhosis degree with PBC, whether used alone or in combination, were analyzed by receiver operating characteristic (ROC) curve. LS and the four indicators of liver fibrosis within the three classes (A, B, and C) of CP scores in the observation group were higher than in the control group, with C class > B class > A class; the differences were statistically significant (P < 0.01). Although AUC values of LS within the three classes of CP scores were higher than in the four indicators of liver fibrosis, sensitivity and specificity were unstable. The ROC curves of LS combined with the four indicators of liver fibrosis revealed that: AUC and sensitivity in all indicators combined in the A class of CP score were higher than in LS alone, albeit with slightly decreased specificity; AUC and specificity in all indicators combined in the B class of CP score were higher than in LS alone, with unchanged sensitivity; AUC values (0.967), sensitivity (97.4%), and specificity (90%) of all indicators combined in the C class of CP score were higher than in LS alone (0.936, 92.1%, 83.3%). The diagnostic value of PBC cirrhosis degree in liver cirrhosis degree assessment by ARFI combined with the four indicators of serum liver fibrosis is of satisfactory effectiveness and has important clinical application value.
Joint Tactical Information Distribution System (JTIDS). Class 3 Terminal Conceptual Study. Volume 4. Appendix A. Mission Profile Detail. Appendix B. Moments of the Decision Variable for preamble Detection

DTIC Science & Technology

1978-07-07

i on CM . ’ oil ■ «) rH H O W CO rH 0) H H <: o I »d • •o H i ! • M CO X -H | i iQ M 4> m u...referred to Electronic Systems Division, Hanscom AFB, MA. Document partially illegible. AFGL ltr 15 May 1981 A I ’ ESD-ra-7B-l6l, Vol. IV V,^^7 -J...BEPORE COMPLETING FORM ESD-TR-78-161, Vol. IV 2 COVT ACCESSION NO I RCCIFICNT’S CATALOG NUMBCn 4. TITLE (mid Submit) JTIDS Class
Relationship between renal pathology and the size of circulating immune complexes in patients with systemic lupus erythematosus

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

Wener, M.H.; Mannik, M.; Schwartz, M.M.

1987-03-01

Sera from 35 patients with biopsy-proven diffuse proliferative (WHO class IV) or membranous (WHO class V) lupus nephritis were analyzed for the presence and size of circulating immune complexes. Elevations of the C1q solid-phase assay (C1qSP) for immune complexes were found in sera from all patients with diffuse proliferative nephritis, with a mean +/- 1 SEM of 166.8 +/- 42.0 micrograms/AHG-equivalents/ml serum, and in 71.4% of the patients with membranous nephritis (83.1 +/- 26.7, p = 0.06). Using the WHO criteria for subclasses of membranous lupus nephritis, we also designated renal biopsies as nonproliferative (WHO classes Va and Vb) ormore » proliferative (WHO classes IV and Vc). Employing the latter groupings, we observed significant differences between C1qSP results of patients with nonproliferative (30.3 +/- 8.8) and proliferative (172.8 +/- 36.8, p less than 0.001) lupus nephritis. These data suggest that the presence of C1q-binding material in serum is pathophysiologically related to proliferative glomerular lesions, and that levels of C1qSP binding reflect renal lesions in SLE patients. Sucrose density gradient ultracentrifugation was performed on each serum, and gradient fractions analyzed for C1qSP-binding and total IgG, using techniques to minimize losses of immune complexes. The predominant peak of C1qSP activity sedimented with the 6.6S monomeric IgG. The 6.6S C1q-binding IgG was increased only in 1 of 10 patients with membranous lupus nephritis without proliferative changes, and was elevated in 16 of 25 patients with proliferative lesions (WHO classes IV and Vc).« less
Inflammatory mediators in chronic heart failure in North India.

PubMed

Fedacko, Jan; Singh, Ram B; Gupta, Aditya; Hristova, Krasimira; Toda, Eri; Kumar, Adarsh; Saxena, Manoj; Baby, Anjum; Singh, Ranjana; Toru, Takahashi; Wilson, Douglas W

2014-08-01

Recent evidence shows that pro-inflammatory cytokines may be important in the assessment of severity and prognosis in congestive heart failure (CHF). In the present study, we examine the association of cytokines with causes, grade and prognosis of CHF patients. Of 127 patients with CHF, 11 were excluded and the remaining 116 patients with different aetiologies of CHF, and 250 age- and sex-matched control subjects, were evaluated in this case study. Severity of disease based on the New York Heart Association (NYHA) standards, fell within functional classes II to IV. The diagnosis of HF was based on clinical manifestations as well as on echocardiographic heart enlargement. Cytokines were measured by chemiluminescence. Causes of death were assessed based on death certificates. Multivariate logistic regression analysis was used to determine the risk factors of heart failure. Echocardiographic ejection fraction was 39.1 +/- 8.2% (mean +/- SD) in the study group indicating class II-IV heart failure. Laboratory data showed increase in biomarkers of oxidative stress, among HF patients compared to healthy subjects. Pro-inflammatory cytokines; IL-6 and TNF-alpha were significantly higher among HF patients compared to healthy subjects. TNF-alpha and IL-6, showed significant increase among patients with CHF due to ischaemic heart disease and cardiomyopathy compared to levels among CHF patients with valvular heart disease and hypertensive heart diseases. The levels of the cytokines were significantly higher among patients with class III and IV heart failure and those who died, compared to patients with class II heart failure. Multivariate logistic regression analysis revealed that CAD, cardiomyopathy, and IL-6 were strongly associated--and low ejection fraction and TNF-alpha--weakly associated with HF. Of 116 patients, 20 (17.2%) died during a follow-up of two years, and the deaths were mainly among NYHA class III and IV patients in whom the cause of CHF was CAD (10.9%) and cardiomyopathy (6.9%) which had greater levels of cytokines. The findings indicated that pro-inflammatory cytokines may be important indicators of causes, severity of CHF and prognosis among these patients.
Interactions with Astroglia Influence the Shape of the Developing Dendritic Arbor and Restrict Dendrite Growth Independent of Promoting Synaptic Contacts

PubMed Central

Farley, Jennifer R.; Sterritt, Jeffrey R.; Crane, Andrés B.; Wallace, Christopher S.

2017-01-01

Astroglia play key roles in the development of neurons, ranging from regulating neuron survival to promoting synapse formation, yet basic questions remain about whether astrocytes might be involved in forming the dendritic arbor. Here, we used cultured hippocampal neurons as a simple in vitro model that allowed dendritic growth and geometry to be analyzed quantitatively under conditions where the extent of interactions between neurons and astrocytes varied. When astroglia were proximal to neurons, dendrites and dendritic filopodia oriented toward them, but the general presence of astroglia significantly reduced overall dendrite growth. Further, dendritic arbors in partial physical contact with astroglia developed a pronounced pattern of asymmetrical growth, because the dendrites in direct contact were significantly smaller than the portion of the arbor not in contact. Notably, thrombospondin, the astroglial factor shown previously to promote synapse formation, did not inhibit dendritic growth. Thus, while astroglia promoted the formation of presynaptic contacts onto dendrites, dendritic growth was constrained locally within a developing arbor at sites where dendrites contacted astroglia. Taken together, these observations reveal influences on spatial orientation of growth as well as influences on morphogenesis of the dendritic arbor that have not been previously identified. PMID:28081563
Study of Default Options in Advance Directives

ClinicalTrials.gov

2015-06-29

COPD; Severe or Very Severe Airflow Obstruction and/or Receiving or Eligible to Receive Long-term Oxygen Therapy; Idiopathic Pulmonary Fibrosis; Other Interstitial Lung Disease Without Curative Therapy; Congestive Heart Failure; NYHA Class IV or NYHA Class III Plus 1 Hospitalization in the Past Year; Malignancy; Any Stage 3B or 4 Solid Tumor
78 FR 56732 - Submission of Information Collection Extensions Under the Paperwork Reduction Act

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-13

... Control Number 3141-0006; and (iv) issuance to tribes of certificates of self- regulation for Class II... the Commission for a certificate of self-regulation for its Class II gaming operation(s). The... to issue the certificate of self- regulation. Once a certificate of self-regulation has been issued...
78 FR 40766 - Renewals of Information Collections Under the Paperwork Reduction Act

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-08

... Control Number 3141-0006; and (iv) issuance to tribes of certificates of self-regulation for Class II.... Estimated Total Non-hour Cost Burden: $14,846,686. Title: Issuance of Certificates of Self-Regulation to... Commission for a certificate of self-regulation for its Class II gaming operation(s). The Commission will...
40 CFR 146.10 - Plugging and abandoning Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (CONTINUED) WATER PROGRAMS (CONTINUED) UNDERGROUND INJECTION CONTROL PROGRAM: CRITERIA AND STANDARDS General... of drinking water. The Director may allow Class III wells to use other plugging materials if the... sources of drinking water. (2) Placement of the cement plugs shall be accomplished by one of the following...
40 CFR 147.751 - EPA-administered program.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Indiana § 147.751 EPA-administered program. (a) Contents. The UIC program for all classes of wells on Indian lands, and for Class I, III, IV, and V wells on non-Indian lands in the State of Indiana is administered by the EPA. The...

40 CFR 147.751 - EPA-administered program.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Indiana § 147.751 EPA-administered program. (a) Contents. The UIC program for all classes of wells on Indian lands, and for Class I, III, IV, and V wells on non-Indian lands in the State of Indiana is administered by the EPA. The...
40 CFR 147.101 - EPA-administered program.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Alaska § 147.101 EPA-administered program. (a) Contents. The UIC program in the State of Alaska for Class I, III, IV, and V wells, and for all classes of wells on Indian lands, is administered by EPA. This program consists of the UIC...
Working Smarter, Not Harder (Part IV).

ERIC Educational Resources Information Center

LaBelle, Sandy

2003-01-01

Discusses ways of improving student attitudes and motivation, such as changing the focus of tests, making students responsible for their work, using a grid to show test results, instituting in-class breaks, using a personal grade book, discussing with students the effects of sleep deprivation, and using separate folders for papers of each class.…
The social class gradient in health in Spain and the health status of the Spanish Roma.

PubMed

La Parra Casado, Daniel; Gil González, Diana; de la Torre Esteve, María

2016-10-01

To determine the social class gradient in health in general Spain population and the health status of the Spanish Roma. The National Health Survey of Spanish Roma 2006 (sample size = 993 people; average age: 33.6 years; 53.1% women) and the National Health Surveys for Spain 2003 (sample size: 21,650 people; average age: 45.5 years; 51.2% women) and 2006 (sample size: 29,478 people; average age: 46 years; 50.7% women) are compared. Several indicators were chosen: self-perceived health, activity limitation, chronic diseases, hearing and sight problems, caries, and obesity. Analysis was based on age-standardised rates and logistic regression models. According to most indicators, Roma's health is worse than that of social class IV-V (manual workers). Some indicators show a remarkable difference between Roma and social class IV-V: experiencing three or more health problems, sight problems, and caries, in both sexes, and hearing problems and obesity, in women. Roma people are placed on an extreme position on the social gradient in health, a situation of extreme health inequality.
Pea Chaperones under Centrifugation

NASA Astrophysics Data System (ADS)

Talalaiev, Oleksandr

2008-06-01

Etiolated Pisum sativum seedlings were subjected to altered g-forces by centrifugation (3-14g). By using semiquantitative RT-PCR, we studied transcripts of pea genes coding for chaperones that are representatives of small heat shock proteins (sHsps) family. Four members from the different classes of sHsps: cytosolic Hsp17.7 and Hsp18.1 (class I and class II accordingly), chloroplast Hsp21 (class III) and endoplasmic reticulum Hsp22.7 (class IV) were investigated. We conclude that exposure to 3, 7, 10 and 14g for 1h did not affect the level of sHsp transcripts.
Inkjet Printing of Drug-Loaded Mesoporous Silica Nanoparticles-A Platform for Drug Development.

PubMed

Wickström, Henrika; Hilgert, Ellen; Nyman, Johan O; Desai, Diti; Şen Karaman, Didem; de Beer, Thomas; Sandler, Niklas; Rosenholm, Jessica M

2017-11-21

Mesoporous silica nanoparticles (MSNs) have shown great potential in improving drug delivery of poorly water soluble (BCS class II, IV) and poorly permeable (BCS class III, IV) drugs, as well as facilitating successful delivery of unstable compounds. The nanoparticle technology would allow improved treatment by reducing adverse reactions of currently approved drugs and possibly reintroducing previously discarded compounds from the drug development pipeline. This study aims to highlight important aspects in mesoporous silica nanoparticle (MSN) ink formulation development for digital inkjet printing technology and to advice on choosing a method (2D/3D) for nanoparticle print deposit characterization. The results show that both unfunctionalized and polyethyeleneimine (PEI) surface functionalized MSNs, as well as drug-free and drug-loaded MSN-PEI suspensions, can be successfully inkjet-printed. Furthermore, the model BCS class IV drug remained incorporated in the MSNs and the suspension remained physically stable during the processing time and steps. This proof-of-concept study suggests that inkjet printing technology would be a flexible deposition method of pharmaceutical MSN suspensions to generate patterns according to predefined designs. The concept could be utilized as a versatile drug screening platform in the future due to the possibility of accurately depositing controlled volumes of MSN suspensions on various materials.
2005 NDIA Combat Vehicles Conference. Volume 2- Thursday Presentations and Videos

DTIC Science & Technology

2005-09-22

Mounted Combat System MULE: (Countermine) MULE: (Transport) Class II Class III Class IV Armed Robotic Vehicle ARV RSTA ARV Assault FCS Recovery and...Vehicles – Infantry Carrier Vehicle (ICV) – Armed Robotic Vehicle - Assault (ARV (A)) – Recon & Surveillance Vehicle (RSV)  Training Ammo for AP & AB...Holtz and Mr. Dick Williams, Boeing Mr. Dean Vanderstelt, General Dynamics Land Systems ( GDLS ) Mr. Mike Zoltoski, TARDEC Mr. Peter DeMasi, Program
Clinical features and histological patterns of lupus nephritis in a single center of South India.

PubMed

Devadass, Clement Wilfred; Mysorekar, Vijaya Viswanath; Eshwarappa, Mahesh; Mekala, Lakshminarayanan; Siddaiah, M Gireesh; Channabasappa, K Gurudev

2016-01-01

Renal involvement occurs in up to 60% of patients with systemic lupus erythematosus (SLE) and signifies a poor prognosis. The class of lupus nephritis (LN), determined on renal biopsy evaluation, guides the therapeutic management and has prognostic connotations. Our aim is to determine the clinicolaboratory features and histopathological patterns of LN at presentation in our local (South Indian) population. The study was conducted in a tertiary care hospital in South India between 2009 and 2014 on SLE patients with clinical evidence of LN. The renal biopsies were examined by light and immunofluorescence microscopy and were classified according to the International Society of Nephrology/Renal Pathology Society Classification of LN. A total of 46 patients were included, with age range of 12-60 years and a female to male ratio of 8.2:1. Arthritis, dermatological manifestations, and fever occurred, respectively, in 43.5%, 39.1%, and 30.4% of the cases. Class IV LN was present in 17 (37.1%), Class III LN in ten (21.7%), Class II LN in nine (19.5%), Class V LN in eight (17.4%), Class I LN in one (2.2%), and Class VI LN in one (2.2%) patients. Antinuclear antibody (ANA) and dsDNA positivity were present, respectively, in 82.6% and 65.2% of the patients. The most common pattern of LN was Class IV LN followed by Class III LN. Relatively higher proportions of ANA and anti-dsDNA positivity were present in proliferative LN, and there was a high frequency of arthritis at presentation in our LN patients.
Latent classes of emotional and behavioural problems in epidemiological and referred samples and their relations to DSM-IV diagnoses.

PubMed

Bianchi, Valentina; Brambilla, Paolo; Garzitto, Marco; Colombo, Paola; Fornasari, Livia; Bellina, Monica; Bonivento, Carolina; Tesei, Alessandra; Piccin, Sara; Conte, Stefania; Perna, Giampaolo; Frigerio, Alessandra; Castiglioni, Isabella; Fabbro, Franco; Molteni, Massimo; Nobile, Maria

2017-05-01

Researchers' interest have recently moved toward the identification of recurrent psychopathological profiles characterized by concurrent elevations on different behavioural and emotional traits. This new strategy turned to be useful in terms of diagnosis and outcome prediction. We used a person-centred statistical approach to examine whether different groups could be identified in a referred sample and in a general-population sample of children and adolescents, and we investigated their relation to DSM-IV diagnoses. A latent class analysis (LCA) was performed on the Child Behaviour Checklist (CBCL) syndrome scales of the referred sample (N = 1225), of the general-population sample (N = 3418), and of the total sample. Models estimating 1-class through 5-class solutions were compared and agreement in the classification of subjects was evaluated. Chi square analyses, a logistic regression, and a multinomial logistic regression analysis were used to investigate the relations between classes and diagnoses. In the two samples and in the total sample, the best-fitting models were 4-class solutions. The identified classes were Internalizing Problems (15.68%), Severe Dysregulated (7.82%), Attention/Hyperactivity (10.19%), and Low Problems (66.32%). Subsequent analyses indicated a significant relationship between diagnoses and classes as well as a main association between the severe dysregulated class and comorbidity. Our data suggested the presence of four different psychopathological profiles related to different outcomes in terms of psychopathological diagnoses. In particular, our results underline the presence of a profile characterized by severe emotional and behavioural dysregulation that is mostly associated with the presence of multiple diagnosis.
Microleakage in conservative cavities varying the preparation method and surface treatment

PubMed Central

ATOUI, Juliana Abdallah; CHINELATTI, Michelle Alexandra; PALMA-DIBB, Regina Guenka; CORONA, Silmara Aparecida Milori

2010-01-01

Objective To assess microleakage in conservative class V cavities prepared with aluminum-oxide air abrasion or turbine and restored with self-etching or etch-and-rinse adhesive systems. Material and Methods Forty premolars were randomly assigned to 4 groups (I and II: air abrasion; III and IV: turbine) and class V cavities were prepared on the buccal surfaces. Conditioning approaches were: groups I/III - 37% phosphoric acid; groups II/IV -self-priming etchant (Tyrian-SPe). Cavities were restored with One Step Plus/Filtek Z250. After finishing, specimens were thermocycled, immersed in 50% silver nitrate, and serially sectioned. Microleakage at the occlusal and cervical interfaces was measured in mm and calculated by a software. Data were subjected to ANOVA and Tukey’s test (α=0.05). Results Forty premolars were randomly assigned to 4 groups (I and II: air abrasion; III and IV: turbine) and class V cavities were prepared on the buccal surfaces. Conditioning approaches were: groups I/III - 37% phosphoric acid; groups II/IV -self-priming etchant (Tyrian-SPe). Cavities were restored with One Step Plus/Filtek Z250. After finishing, specimens were thermocycled, immersed in 50% silver nitrate, and serially sectioned. Microleakage at the occlusal and cervical interfaces was measured in mm and calculated by a software. Data were subjected to ANOVA and Tukey’s test (α=0.05). Conclusion Marginal seal of cavities prepared with aluminum-oxide air abrasion was different from that of conventionally prepared cavities, and the etch-and-rinse system promoted higher marginal seal at both enamel and dentin margins. PMID:20835580
A new, empirically established hypochondriasis diagnosis.

PubMed

Fink, Per; Ørnbøl, Eva; Toft, Tomas; Sparle, Kaj Christensen; Frostholm, Lisbeth; Olesen, Frede

2004-09-01

The narrow ICD-10 and DSM-IV definition of hypochondriasis makes it rarely used yet does not prevent extensive diagnosis overlap. This study identified a distinct hypochondriasis symptom cluster and defined diagnostic criteria. Consecutive patients (N=1,785) consulting primary care physicians for new illness were screened for somatization, anxiety, depression, and alcohol abuse. A stratified subgroup of 701 patients were interviewed with the Schedules for Clinical Assessment in Neuropsychiatry and questions addressing common hypochondriasis symptoms. Symptom patterns were analyzed by latent class analysis. Patients fell into three classes based on six symptoms: preoccupation with the idea of harboring an illness or with bodily function, rumination about illness, suggestibility, unrealistic fear of infection, fascination with medical information, and fear of prescribed medication. All symptoms, particularly rumination, were frequent in one of the classes. Classification allowed definition of new diagnostic criteria for hypochondriasis and division of the cases into "mild" and "severe." The weighted prevalence of severe cases was 9.5% versus 5.8% for DSM-IV hypochondriasis. Compared with DSM-IV hypochondriasis, this approach produced less overlap with other somatoform disorders, similar overlap with nonsomatoform psychiatric disorders, and similar assessments by primary care physicians. Severe cases of the new hypochondriasis lasted 2 or more years in 54.3% of the subjects and 1 month or less in 27.2%. These results suggest that rumination about illness plus at least one of five other symptoms form a distinct diagnostic entity performing better than the current DSM-IV hypochondriasis diagnosis. However, these criteria are preliminary, awaiting cross-validation in other subject groups.
Algorithms for Hyperspectral Endmember Extraction and Signature Classification with Morphological Dendritic Networks

NASA Astrophysics Data System (ADS)

Schmalz, M.; Ritter, G.

Accurate multispectral or hyperspectral signature classification is key to the nonimaging detection and recognition of space objects. Additionally, signature classification accuracy depends on accurate spectral endmember determination [1]. Previous approaches to endmember computation and signature classification were based on linear operators or neural networks (NNs) expressed in terms of the algebra (R, +, x) [1,2]. Unfortunately, class separation in these methods tends to be suboptimal, and the number of signatures that can be accurately classified often depends linearly on the number of NN inputs. This can lead to poor endmember distinction, as well as potentially significant classification errors in the presence of noise or densely interleaved signatures. In contrast to traditional CNNs, autoassociative morphological memories (AMM) are a construct similar to Hopfield autoassociatived memories defined on the (R, +, ?,?) lattice algebra [3]. Unlimited storage and perfect recall of noiseless real valued patterns has been proven for AMMs [4]. However, AMMs suffer from sensitivity to specific noise models, that can be characterized as erosive and dilative noise. On the other hand, the prior definition of a set of endmembers corresponds to material spectra lying on vertices of the minimum convex region covering the image data. These vertices can be characterized as morphologically independent patterns. It has further been shown that AMMs can be based on dendritic computation [3,6]. These techniques yield improved accuracy and class segmentation/separation ability in the presence of highly interleaved signature data. In this paper, we present a procedure for endmember determination based on AMM noise sensitivity, which employs morphological dendritic computation. We show that detected endmembers can be exploited by AMM based classification techniques, to achieve accurate signature classification in the presence of noise, closely spaced or interleaved signatures, and simulated camera optical distortions. In particular, we examine two critical cases: (1) classification of multiple closely spaced signatures that are difficult to separate using distance measures, and (2) classification of materials in simulated hyperspectral images of spaceborne satellites. In each case, test data are derived from a NASA database of space material signatures. Additional analysis pertains to computational complexity and noise sensitivity, which are superior to classical NN based techniques.
Surface LAMP-2 Is an Endocytic Receptor That Diverts Antigen Internalized by Human Dendritic Cells into Highly Immunogenic Exosomes.

PubMed

Leone, Dario Armando; Peschel, Andrea; Brown, Markus; Schachner, Helga; Ball, Miriam J; Gyuraszova, Marianna; Salzer-Muhar, Ulrike; Fukuda, Minoru; Vizzardelli, Caterina; Bohle, Barbara; Rees, Andrew J; Kain, Renate

2017-07-15

The lysosome-associated membrane protein (LAMP) family includes the dendritic cell endocytic receptors DC-LAMP and CD68, as well as LAMP-1 and LAMP-2. In this study we identify LAMP-1 (CD107a) and LAMP-2 (CD107b) on the surface of human monocyte-derived dendritic cells (MoDC) and show only LAMP-2 is internalized after ligation by specific Abs, including H4B4, and traffics rapidly but transiently to the MHC class II loading compartment, as does Ag conjugated to H4B4. However, pulsing MoDC with conjugates of primary (keyhole limpet hemocyanin; KLH) and recall (Bet v 1) Ags (H4B4*KLH and H4B4*Bet v 1) induced significantly less CD4 cell proliferation than pulsing with native Ag or Ag conjugated to control mAb (ISO*KLH and ISO*Bet v 1). In H4B4*KLH-pulsed MoDC, the duration of KLH residence in MHC class II loading compartments was significantly reduced, as were surface HLA-DR and DR-bound KLH-derived peptides. Paradoxically, MoDC pulsed with H4B4*KLH, but not the other KLH preparations, induced robust proliferation of CD4 cells separated from them by a transwell membrane, indicating factors in the supernatant were responsible. Furthermore, extracellular vesicles from supernatants of H4B4*KLH-pulsed MoDC contained significantly more HLA-DR and KLH than those purified from control MoDC, and KLH was concentrated specifically in exosomes that were a uniquely effective source of Ag in standard T cell proliferation assays. In summary, we identify LAMP-2 as an endocytic receptor on human MoDC that routes cargo into unusual Ag processing pathways, which reduces surface expression of Ag-derived peptides while selectively enriching Ag within immunogenic exosomes. This novel pathway has implications for the initiation of immune responses both locally and at distant sites. Copyright © 2017 by The American Association of Immunologists, Inc.
Effect of Solute Diffusion on Dendrite Growth in the Molten Pool of Al-Cu Alloy

NASA Astrophysics Data System (ADS)

Zhan, Xiaohong; Gu, Cheng; Liu, Yun; Wei, Yanhong

2017-10-01

A cellular automaton (CA)-finite difference model is developed to simulate dendrite growth and solute diffusion during solidification process in the molten pool of Al-Cu alloy. In order to explain the interaction between the dendritic growth and solute distribution, a series of CA simulations with different solute diffusion velocity coefficients are carried out. It is concluded that the solute concentration increases with dendrite growing and solute accumulation in the dendrite tip. Converged value of the dendrite tip growth velocity is about 480 μm/s if the mesh size is refined to 2 μm or less. Growth of the primary dendrite and the secondary dendrite is mainly influenced by solute diffusion at the dendrite tips. And growth of secondary and tertiary dendrites is mainly influenced by solute diffusion at interdendrite.
Dendritic Kv3.3 potassium channels in cerebellar purkinje cells regulate generation and spatial dynamics of dendritic Ca2+ spikes.

PubMed

Zagha, Edward; Manita, Satoshi; Ross, William N; Rudy, Bernardo

2010-06-01

Purkinje cell dendrites are excitable structures with intrinsic and synaptic conductances contributing to the generation and propagation of electrical activity. Voltage-gated potassium channel subunit Kv3.3 is expressed in the distal dendrites of Purkinje cells. However, the functional relevance of this dendritic distribution is not understood. Moreover, mutations in Kv3.3 cause movement disorders in mice and cerebellar atrophy and ataxia in humans, emphasizing the importance of understanding the role of these channels. In this study, we explore functional implications of this dendritic channel expression and compare Purkinje cell dendritic excitability in wild-type and Kv3.3 knockout mice. We demonstrate enhanced excitability of Purkinje cell dendrites in Kv3.3 knockout mice, despite normal resting membrane properties. Combined data from local application pharmacology, voltage clamp analysis of ionic currents, and assessment of dendritic Ca(2+) spike threshold in Purkinje cells suggest a role for Kv3.3 channels in opposing Ca(2+) spike initiation. To study the physiological relevance of altered dendritic excitability, we measured [Ca(2+)](i) changes throughout the dendritic tree in response to climbing fiber activation. Ca(2+) signals were specifically enhanced in distal dendrites of Kv3.3 knockout Purkinje cells, suggesting a role for dendritic Kv3.3 channels in regulating propagation of electrical activity and Ca(2+) influx in distal dendrites. These findings characterize unique roles of Kv3.3 channels in dendrites, with implications for synaptic integration, plasticity, and human disease.
Inhibition of Progenitor Dendritic Cell Maturation by Plasma from Patients with Peripartum Cardiomyopathy: Role in Pregnancy-associated Heart Disease

PubMed Central

Ellis, Jane E.; Ansari, Aftab A.; Fett, James D.; Carraway, Robert D.; Randall, Hugh W.; Mosunjac, Mario I.; Sundstrom, J. Bruce

2005-01-01

Dendritic cells (DCs) play dual roles in innate and adaptive immunity based on their functional maturity, and both innate and adaptive immune responses have been implicated in myocardial tissue remodeling associated with cardiomyopathies. Peripartum cardiomyopathy (PPCM) is a rare disorder which affects women within one month antepartum to five months postpartum. A high occurrence of PPCM in central Haiti (1 in 300 live births) provided the unique opportunity to study the relationship of immune activation and DC maturation to the etiology of this disorder. Plasma samples from two groups (n = 12) of age- and parity-matched Haitian women with or without evidence of PPCM were tested for levels of biomarkers of cardiac tissue remodeling and immune activation. Significantly elevated levels of GM-CSF, endothelin-1, proBNP and CRP and decreased levels of TGF- were measured in PPCM subjects relative to controls. Yet despite these findings, in vitro maturation of normal human cord blood derived progenitor dendritic cells (CBDCs) was significantly reduced (p < 0.001) in the presence of plasma from PPCM patients relative to plasma from post-partum control subjects as determined by expression of CD80, CD86, CD83, CCR7, MHC class II and the ability of these matured CBDCs to induce allo-responses in PBMCs. These results represent the first findings linking inhibition of DC maturation to the dysregulation of normal physiologic cardiac tissue remodeling during pregnancy and the pathogenesis of PPCM. PMID:16584112
Functional somato-dendritic α7-containing nicotinic acetylcholine receptors in the rat basolateral amygdala complex

PubMed Central

Klein, Rebecca C; Yakel, Jerrel L

2006-01-01

Multiple subtypes of nicotinic acetylcholine receptors (nAChRs) are expressed in the CNS. The amygdala complex, the limbic structure important for emotional memory formation, receives cholinergic innervation from the basal forebrain. Although cholinergic drugs have been shown to regulate passive avoidance performance via the amygdala, the neuronal subtypes and circuits involved in this regulation are unknown. In the present study, whole-cell patch-clamp electrophysiological techniques were used to identify and characterize the presence of functional somato-dendritic nAChRs within the basolateral complex of the amygdala. Pressure-application of acetylcholine (ACh; 2 mm) evoked inward current responses in a subset of neurons from both the lateral (49%) and basolateral nuclei (72%). All responses displayed rapid activation kinetics, and were blocked by the α7-selective antagonist methyllycaconitine. In addition, the α7-selective agonist choline induced inward current responses that were similar to ACh-evoked responses. Spiking patterns were consistent with pyramidal class I neurons (the major neuronal type in the basolateral complex); however, there was no correlation between firing frequency and the response to ACh. The local photolysis of caged carbachol demonstrated that the functional expression of nAChRs is located both on the soma and dendrites. This is the first report demonstrating the presence of functional nAChR-mediated current responses from rat amygdala slices, where they may be playing a significant role in fear and aversively motivated memory. PMID:16931547
Podocytes Are Nonhematopoietic Professional Antigen-Presenting Cells

PubMed Central

Burkard, Miriam; Ölke, Martha; Daniel, Christoph; Amann, Kerstin; Hugo, Christian; Kurts, Christian; Steinkasserer, Alexander; Gessner, André

2013-01-01

Podocytes are essential to the structure and function of the glomerular filtration barrier; however, they also exhibit increased expression of MHC class II molecules under inflammatory conditions, and they remove Ig and immune complexes from the glomerular basement membrane (GBM). This finding suggests that podocytes may act as antigen-presenting cells, taking up and processing antigens to initiate specific T cell responses, similar to professional hematopoietic cells such as dendritic cells or macrophages. Here, MHC–antigen complexes expressed exclusively on podocytes of transgenic mice were sufficient to activate CD8+ T cells in vivo. In addition, deleting MHC class II exclusively on podocytes prevented the induction of experimental anti-GBM nephritis. Podocytes ingested soluble and particulate antigens, activated CD4+ T cells, and crosspresented exogenous antigen on MHC class I molecules to CD8+ T cells. In conclusion, podocytes participate in the antigen-specific activation of adaptive immune responses, providing a potential target for immunotherapies of inflammatory kidney diseases and transplant rejection. PMID:23539760
Levofloxacin 750-mg for 5 days for the treatment of hospitalized Fine Risk Class III/IV community-acquired pneumonia patients.

PubMed

Shorr, Andrew F; Khashab, Mohammed M; Xiang, Jim X; Tennenberg, Alan M; Kahn, James B

2006-12-01

The efficacy and safety of 750-mg, 5-day levofloxacin was recently shown to be comparable to 500-mg, 10-day levofloxacin in a randomized, double-blind, multicentre clinical trial for mild-to-severe community-acquired pneumonia (CAP). This subgroup analysis attempted to compare the safety and efficacy of a short-course levofloxacin regimen with traditional levofloxacin dosing for PSI Class III/IV patients. This retrospective, subgroup analysis focused on Pneumonia Severity Index Class III and IV patients enrolled in the study. Measurements included clinical and microbiological success rates, adverse events, and symptom resolution by day 3 of therapy. Of the 528 patients in the ITT population, 219 (41.5%) were categorized as PSI Class III/IV and included in this analysis. Among the clinically evaluable patients, 90.8% (69/76) of patients treated with the 750-mg regimen achieved clinical success, compared with 85.5% (71/83) treated with 500-mg levofloxacin (95% CI,-15.9 to 5.4). Eradication rates in the microbiologically evaluable population were comparable for the 750- and 500-mg regimens (88.9% vs 87.5%, respectively; 95% CI,-18.3 to 15.6). Both regimens were well tolerated and had comparable safety profiles. A greater proportion of patients in the 750-mg treatment group experienced resolution of fever (48.4% vs 34.0%; P=.046) and purulent sputum (48.4% vs 27.5%; P=.007) by day 3 of therapy. The 750-mg, 5-day levofloxacin course achieved comparable clinical and microbiologic efficacy to the 500-mg, 10-day regimen. By day 3 of therapy, a greater proportion of patients in the 750-mg group had objective and subjective resolution of fever. Further research is needed to determine the economic significance of short-course levofloxacin therapy.
Evaluation of a technique for color correction in restoring anterior teeth.

PubMed

Rauber, Gabrielle Branco; Bernardon, Jussara Karina; Vieira, Luiz Clovis Cardoso; Baratieri, Luiz Narciso

2017-09-01

This study aimed to evaluate the ability of the proposed technique in producing restorations that exhibit mimesis with tooth structure and to define a restorative clinical protocol. For this study a typodont was used. The right upper central incisor with Class IV lesion was restored with the layering technique (reference tooth, RT). For the left upper central incisor with Class IV lesion, six teeth were restored monochromatically (test teeth, TT), using DA3.5 (n = 3) and DA4 (n = 3) composite resins-resulting in six unsatisfactory color restorations. TT were divided into six groups depending on the color of unsatisfactory restoration and preparation depth. First, a preparation was realized on the labial surface with 0.5 mm, 0.7 mm or 1.0 mm of depth. A second preparation was then performed to reproduce the dentinal mamelons. Next, adhesive procedures were performed and the teeth restored. Opaque halo, opalescent halo and vestibular enamel were then reproduced by the addition of different composite resins. The RT and TT were photographed side by side in typodont to obtain six photographic prints. The photographs of the groups were subjected to visual evaluation by 120 volunteers via a questionnaire. Data were analyzed by the prevalence of answers, and Chi-square test was used to investigate the association between variables at .05 significance. Furthermore, ΔE of groups was evaluated in comparison RT. The results demonstrated that the moderate intensity restorations (DA3.5) with depths of 0.5 mm and 0.7 mm had the highest prevalence of acceptance. For severe intensity restorations (DA4), the preparation depth of 1.0 mm obtained better acceptance. The technique was able to modify the final color of Class IV restorations, producing satisfactory color restorations. This technique can be used for color correction in cases of Class IV restorations, in situations where there is no time for immediate layered restoration, and as a restorative technique. © 2017 Wiley Periodicals, Inc.

Equatorial Ligand Perturbations Influence the Reactivity of Manganese(IV)-Oxo Complexes.

PubMed

Massie, Allyssa A; Denler, Melissa C; Cardoso, Luísa Thiara; Walker, Ashlie N; Hossain, M Kamal; Day, Victor W; Nordlander, Ebbe; Jackson, Timothy A

2017-04-03

Manganese(IV)-oxo complexes are often invoked as intermediates in Mn-catalyzed C-H bond activation reactions. While many synthetic Mn IV -oxo species are mild oxidants, other members of this class can attack strong C-H bonds. The basis for these reactivity differences is not well understood. Here we describe a series of Mn IV -oxo complexes with N5 pentadentate ligands that modulate the equatorial ligand field of the Mn IV center, as assessed by electronic absorption, electron paramagnetic resonance, and Mn K-edge X-ray absorption methods. Kinetic experiments show dramatic rate variations in hydrogen-atom and oxygen-atom transfer reactions, with faster rates corresponding to weaker equatorial ligand fields. For these Mn IV -oxo complexes, the rate enhancements are correlated with both 1) the energy of a low-lying 4 E excited state, which has been postulated to be involved in a two-state reactivity model, and 2) the Mn III/IV reduction potentials. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Relationship of serum uric acid and Killip class on mortality after acute ST-segment elevation myocardial infarction and primary percutaneous coronary intervention.

PubMed

Liu, Cheng-Wei; Liao, Pen-Chih; Chen, Kuo-Chin; Chiu, Yu-Wei; Liu, Yuan-Hung; Ke, Shin-Rong; Wu, Yen-Wen

2017-01-01

There is conflicting information regarding the association between hyperuricemia and survival in STEMI patients. Our study examined the interaction between hyperuricemia and Killip class on mortality of STEMI patients. We analyzed 951 consecutive STEMI patients between February 2006 and September 2012. Hyperuricemia was defined as SUA of at least 7mg/dL in males and 6mg/dL in females. Killip class I patients were divided into hyperuricemia and normouricemia groups. The Killip class I hyperuricemia and normouricemia groups had similar baseline and procedural characteristics, but the hyperuricemia group had significantly greater BMI, serum creatinine, and SUA, and a lower TIMI risk score (2, IQR: 1-4 vs. 3, IQR: 2-4, p=0.019). The hyperuricemia group also had greater 30-day and 1-year mortality rates (2.9% vs. 0.3%, p=0.022; 6.5% vs. 1.1%, p=0.002, respectively). However, hyperuricemia was not associated with mortality of patients in Killip classes II-IV or in the overall study population. Hyperuricemia was associated with increased mortality in subgroups of patients who were at least 65years-old, male, had BMI of 25kg/m 2 or less, were in Killip class I, without diabetes, and who did not receive intra-aortic balloon pump support. Hyperuricemia interacted with Killip class I in increasing the risk for 1-year mortality (p for interaction=0.038). Hyperuricemia increased the 1-year mortality of STEMI patients in Killip class I, but not of patients in Killip classes II-IV. An interaction of hyperuricemia and Killip class significantly affects the mortality of STEMI patients. Copyright Â© 2016 Elsevier Ireland Ltd. All rights reserved.
Maintenance of dendritic spine morphology by partitioning-defective 1b through regulation of microtubule growth.

PubMed

Hayashi, Kenji; Suzuki, Atsushi; Hirai, Syu-ichi; Kurihara, Yasuyuki; Hoogenraad, Casper C; Ohno, Shigeo

2011-08-24

Dendritic spines are postsynaptic structures that receive excitatory synaptic input from presynaptic terminals. Actin and its regulatory proteins play a central role in morphogenesis of dendritic spines. In addition, recent studies have revealed that microtubules are indispensable for the maintenance of mature dendritic spine morphology by stochastically invading dendritic spines and regulating dendritic localization of p140Cap, which is required for actin reorganization. However, the regulatory mechanisms of microtubule dynamics remain poorly understood. Partitioning-defective 1b (PAR1b), a cell polarity-regulating serine/threonine protein kinase, is thought to regulate microtubule dynamics by inhibiting microtubule binding of microtubule-associated proteins. Results from the present study demonstrated that PAR1b participates in the maintenance of mature dendritic spine morphology in mouse hippocampal neurons. Immunofluorescent analysis revealed PAR1b localization in the dendrites, which was concentrated in dendritic spines of mature neurons. PAR1b knock-down cells exhibited decreased mushroom-like dendritic spines, as well as increased filopodia-like dendritic protrusions, with no effect on the number of protrusions. Live imaging of microtubule plus-end tracking proteins directly revealed decreases in distance and duration of microtubule growth following PAR1b knockdown in a neuroblastoma cell line and in dendrites of hippocampal neurons. In addition, reduced accumulation of GFP-p140Cap in dendritic protrusions was confirmed in PAR1b knock-down neurons. In conclusion, the present results suggested a novel function for PAR1b in the maintenance of mature dendritic spine morphology by regulating microtubule growth and the accumulation of p140Cap in dendritic spines.
Effect of the environment on the dendritic morphology of the rat auditory cortex

PubMed Central

Bose, Mitali; Muñoz-Llancao, Pablo; Roychowdhury, Swagata; Nichols, Justin A.; Jakkamsetti, Vikram; Porter, Benjamin; Byrapureddy, Rajasekhar; Salgado, Humberto; Kilgard, Michael P.; Aboitiz, Francisco; Dagnino-Subiabre, Alexies; Atzori, Marco

2010-01-01

The present study aimed to identify morphological correlates of environment-induced changes at excitatory synapses of the primary auditory cortex (A1). We used the Golgi-Cox stain technique to compare pyramidal cells dendritic properties of Sprague-Dawley rats exposed to different environmental manipulations. Sholl analysis, dendritic length measures, and spine density counts were used to monitor the effects of sensory deafness and an auditory version of environmental enrichment (EE). We found that deafness decreased apical dendritic length leaving basal dendritic length unchanged, whereas EE selectively increased basal dendritic length without changing apical dendritic length. On the contrary, deafness decreased while EE increased spine density in both basal and apical dendrites of A1 layer 2/3 (LII/III) neurons. To determine whether stress contributed to the observed morphological changes in A1, we studied neural morphology in a restraint-induced model that lacked behaviorally relevant acoustic cues. We found that stress selectively decreased apical dendritic length in the auditory but not in the visual primary cortex. Similar to the acoustic manipulation, stress-induced changes in dendritic length possessed a layer specific pattern displaying LII/III neurons from stressed animals with normal apical dendrites but shorter basal dendrites, while infragranular neurons (layers V and VI) displayed shorter apical dendrites but normal basal dendrites. The same treatment did not induce similar changes in the visual cortex, demonstrating that the auditory cortex is an exquisitely sensitive target of neocortical plasticity, and that prolonged exposure to different acoustic as well as emotional environmental manipulation may produce specific changes in dendritic shape and spine density. PMID:19771593
Dendritic Cells in Kidney Transplant Biopsy Samples Are Associated with T Cell Infiltration and Poor Allograft Survival

PubMed Central

De Serres, Sacha A.; Safa, Kassem; Bijol, Vanesa; Ueno, Takuya; Onozato, Maristela L.; Iafrate, A. John; Herter, Jan M.; Lichtman, Andrew H.; Mayadas, Tanya N.; Guleria, Indira; Rennke, Helmut G.; Najafian, Nader; Chandraker, Anil

2015-01-01

Progress in long-term renal allograft survival continues to lag behind the progress in short-term transplant outcomes. Dendritic cells are the most efficient antigen-presenting cells, but surprisingly little attention has been paid to their presence in transplanted kidneys. We used dendritic cell–specific intercellular adhesion molecule-3–grabbing nonintegrin as a marker of dendritic cells in 105 allograft biopsy samples from 105 kidney transplant recipients. High dendritic cell density was associated with poor allograft survival independent of clinical variables. Moreover, high dendritic cell density correlated with greater T cell proliferation and poor outcomes in patients with high total inflammation scores, including inflammation in areas of tubular atrophy. We then explored the association between dendritic cells and histologic variables associated with poor prognosis. Multivariate analysis revealed an independent association between the densities of dendritic cells and T cells. In biopsy samples with high dendritic cell density, electron microscopy showed direct physical contact between infiltrating lymphocytes and cells that have the ultrastructural morphologic characteristics of dendritic cells. The origin of graft dendritic cells was sought in nine sex-mismatched recipients using XY fluorescence in situ hybridization. Whereas donor dendritic cells predominated initially, the majority of dendritic cells in late allograft biopsy samples were of recipient origin. Our data highlight the prognostic value of dendritic cell density in allograft biopsy samples, suggest a new role for these cells in shaping graft inflammation, and provide a rationale for targeting dendritic cell recruitment to promote long-term allograft survival. PMID:25855773
Mathematical foundations of the dendritic growth models.

PubMed

Villacorta, José A; Castro, Jorge; Negredo, Pilar; Avendaño, Carlos

2007-11-01

At present two growth models describe successfully the distribution of size and topological complexity in populations of dendritic trees with considerable accuracy and simplicity, the BE model (Van Pelt et al. in J. Comp. Neurol. 387:325-340, 1997) and the S model (Van Pelt and Verwer in Bull. Math. Biol. 48:197-211, 1986). This paper discusses the mathematical basis of these models and analyzes quantitatively the relationship between the BE model and the S model assumed in the literature by developing a new explicit equation describing the BES model (a dendritic growth model integrating the features of both preceding models; Van Pelt et al. in J. Comp. Neurol. 387:325-340, 1997). In numerous studies it is implicitly presupposed that the S model is conditionally linked to the BE model (Granato and Van Pelt in Brain Res. Dev. Brain Res. 142:223-227, 2003; Uylings and Van Pelt in Network 13:397-414, 2002; Van Pelt, Dityatev and Uylings in J. Comp. Neurol. 387:325-340, 1997; Van Pelt and Schierwagen in Math. Biosci. 188:147-155, 2004; Van Pelt and Uylings in Network. 13:261-281, 2002; Van Pelt, Van Ooyen and Uylings in Modeling Dendritic Geometry and the Development of Nerve Connections, pp 179, 2000). In this paper we prove the non-exactness of this assumption, quantify involved errors and determine the conditions under which the BE and S models can be separately used instead of the BES model, which is more exact but considerably more difficult to apply. This study leads to a novel expression describing the BE model in an analytical closed form, much more efficient than the traditional iterative equation (Van Pelt et al. in J. Comp. Neurol. 387:325-340, 1997) in many neuronal classes. Finally we propose a new algorithm in order to obtain the values of the parameters of the BE model when this growth model is matched to experimental data, and discuss its advantages and improvements over the more commonly used procedures.
Method of inhibiting dislocation generation in silicon dendritic webs

DOEpatents

Spitznagel, John A.; Seidensticker, Raymond G.; McHugh, James P.

1990-11-20

A method of tailoring the heat balance of the outer edge of the dendrites adjacent the meniscus to produce thinner, smoother dendrites, which have substantially less dislocation sources contiguous with the dendrites, by changing the view factor to reduce radiation cooling or by irradiating the dendrites with light from a quartz lamp or a laser to raise the temperature of the dendrites.
Amplitude Normalization of Dendritic EPSPs at the Soma of Binaural Coincidence Detector Neurons of the Medial Superior Olive

PubMed Central

Winters, Bradley D.; Jin, Shan-Xue; Ledford, Kenneth R.

2017-01-01

The principal neurons of the medial superior olive (MSO) encode cues for horizontal sound localization through comparisons of the relative timing of EPSPs. To understand how the timing and amplitude of EPSPs are maintained during propagation in the dendrites, we made dendritic and somatic whole-cell recordings from MSO principal neurons in brain slices from Mongolian gerbils. In somatic recordings, EPSP amplitudes were largely uniform following minimal stimulation of excitatory synapses at visualized locations along the dendrites. Similar results were obtained when excitatory synaptic transmission was eliminated in a low calcium solution and then restored at specific dendritic sites by pairing input stimulation and focal application of a higher calcium solution. We performed dual dendritic and somatic whole-cell recordings to measure spontaneous EPSPs using a dual-channel template-matching algorithm to separate out those events initiated at or distal to the dendritic recording location. Local dendritic spontaneous EPSP amplitudes increased sharply in the dendrite with distance from the soma (length constant, 53.6 μm), but their attenuation during propagation resulted in a uniform amplitude of ∼0.2 mV at the soma. The amplitude gradient of dendritic EPSPs was also apparent in responses to injections of identical simulated excitatory synaptic currents in the dendrites. Compartmental models support the view that these results extensively reflect the influence of dendritic cable properties. With relatively few excitatory axons innervating MSO neurons, the normalization of dendritic EPSPs at the soma would increase the importance of input timing versus location during the processing of interaural time difference cues in vivo. SIGNIFICANCE STATEMENT The neurons of the medial superior olive analyze cues for sound localization by detecting the coincidence of binaural excitatory synaptic inputs distributed along the dendrites. Previous studies have shown that dendritic voltages undergo severe attenuation as they propagate to the soma, potentially reducing the influence of distal inputs. However, using dendritic and somatic patch recordings, we found that dendritic EPSP amplitude increased with distance from the soma, compensating for dendritic attenuation and normalizing EPSP amplitude at the soma. Much of this normalization reflected the influence of dendritic morphology. As different combinations of presynaptic axons may be active during consecutive cycles of sound stimuli, somatic EPSP normalization renders spike initiation more sensitive to synapse timing than dendritic location. PMID:28213442
Structural Basis for Assembly of the MnIV/FeIII Cofactor in the Class Ic Ribonucleotide Reductase from Chlamydia trachomatis‡

PubMed Central

Dassama, Laura M.K.; Krebs, Carsten; Bollinger, J. Martin; Rosenzweig, Amy C.; Boal, Amie K.

2013-01-01

The class Ic ribonucleotide reductase (RNR) from Chlamydia trachomatis (Ct) employs a MnIV/FeIII cofactor in each monomer of its β2 subunit to initiate nucleotide reduction. The cofactor forms by reaction of MnII/FeII-β2 with O2. Previously, in vitro cofactor assembly from apo β2 and divalent metal ions produced a mixture of two forms, with Mn in site 1 (MnIV/FeIII) or site 2 (FeIII/MnIV), of which the more active MnIV/FeIII product predominates. Here we have addressed the basis for metal site-selectivity by solving X-ray crystal structures of apo, MnII, and MnII/FeII complexes of Ct β2. A structure obtained anaerobically with equimolar MnII, FeII, and apo protein reveals exclusive incorporation of MnII in site 1 and FeII in site 2, in contrast to the more modest site-selectivity achieved previously. Site-specificity is controlled thermodynamically by the apo protein structure, as only minor adjustments of ligands occur upon metal binding. Additional structures imply that, by itself, MnII binds in either site. Together the structures are consistent with a model for in vitro cofactor assembly in which FeII specificity for site 2 drives assembly of the appropriately configured heterobimetallic center, provided that FeII is substoichiometric. This model suggests that use of an MnIV/FeIII cofactor in vivo could be an adaptation to FeII limitation. A 1.8 Å resolution model of the MnII/FeII-β2 complex reveals additional structural determinants for activation of the cofactor, including a proposed site for side-on (η2) addition of O2 to FeII and a short (3.2 Å) MnII-FeII interionic distance, promoting formation of the MnIV/FeIV activation intermediate. PMID:23924396
25 CFR 547.12 - What are the minimum technical standards for downloading on a Class II gaming system?

Code of Federal Regulations, 2013 CFR

2013-04-01

... limited to software, files, data, and prize schedules. (2) Downloads must use secure methodologies that... date of the completion of the download; (iii) The Class II gaming system components to which software was downloaded; (iv) The version(s) of download package and any software downloaded. Logging of the...
25 CFR 547.12 - What are the minimum technical standards for downloading on a Class II gaming system?

Code of Federal Regulations, 2014 CFR

2014-04-01

... limited to software, files, data, and prize schedules. (2) Downloads must use secure methodologies that... date of the completion of the download; (iii) The Class II gaming system components to which software was downloaded; (iv) The version(s) of download package and any software downloaded. Logging of the...
Wisconsin Technical College System Board Equity Staff Development Workshops and Services--Phase IV. Final Report.

ERIC Educational Resources Information Center

Baldus, Lorayne

A staff development program on gender equity was conducted for personnel in Wisconsin's technical colleges using the train-the-trainer method. The training took two approaches: a class for college personnel and career challenge training for project directors of single parent and displaced homemaker grants. The inservice class resulted in increased…
76 FR 46838 - Notice of Proposed Class II Reinstatement of Terminated Oil and Gas Leases, Utah

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-03

... Proposed Class II Reinstatement of Terminated Oil and Gas Leases, Utah AGENCY: Bureau of Land Management, Interior. ACTION: Notice. SUMMARY: In accordance with Title IV of the Federal Oil and Gas Royalty... petition for reinstatement of oil and gas leases UTU-85226 and UTU-85230 lands in Uintah County, Utah, and...
77 FR 76069 - Notice of Proposed Class II Reinstatement of Terminated Oil and Gas Lease, Utah

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-26

... Proposed Class II Reinstatement of Terminated Oil and Gas Lease, Utah AGENCY: Bureau of Land Management, Interior. ACTION: Notice. SUMMARY: In accordance with Title IV of the Federal Oil and Gas Royalty Management Act, Quinex Energy Corporation timely filed a petition for reinstatement of oil and gas lease...
76 FR 66080 - Notice of Proposed Class II Reinstatement of Terminated Oil and Gas Lease, Utah

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-25

... Proposed Class II Reinstatement of Terminated Oil and Gas Lease, Utah AGENCY: Bureau of Land Management, Interior. ACTION: Notice. SUMMARY: In accordance with Title IV of the Federal Oil and Gas Royalty Management Act, Bro Energy LLC timely filed a petition for reinstatement of oil and gas lease UTU85562 lands...
The nociception genes painless and Piezo are required for the cellular immune response of Drosophila larvae to wasp parasitization.

PubMed

Tokusumi, Yumiko; Tokusumi, Tsuyoshi; Schulz, Robert A

2017-05-13

In vertebrates, interaction between the nervous system and immune system is important to protect a challenged host from stress inputs from external sources. In this study, we demonstrate that sensory neurons are involved in the cellular immune response elicited by wasp infestation of Drosophila larvae. Multidendritic class IV neurons sense contacts from external stimuli and induce avoidance behaviors for host defense. Our findings show that inactivation of these sensory neurons impairs the cellular response against wasp parasitization. We also demonstrate that the nociception genes encoding the mechanosensory receptors Painless and Piezo, both expressed in class IV neurons, are essential for the normal cellular immune response to parasite challenge. Copyright © 2017. Published by Elsevier Inc.
[Evaluation of view points in forest park based on landscape sensitivity].

PubMed

Zhou, Rui; Li, Yue-hui; Hu, Yuan-man; Liu, Miao

2008-11-01

Based on topographical characteristics, five factors including comparative slope, comparative distance, mutual visibility, vision probability, and striking degree were chosen to assess the landscape sensitivity of major view points in Houshi National Forest Park. Spatial analysis in GIS was used for exploring the theory and method of landscape sensitivity of view points. The results showed that in the Park, there were totally 23 view points, but none of them reached up to class I. Among the 23 points, 10 were of class II , accounting for 43.5% of the total, 8 were of class III, accounting for 34.8%, and 5 were of classes IV and V, accounting for 21.7%. Around the view points of class II, the landscape should be strictly protected to maintain their natural feature; around the view points of class III, human-made landscape points should be developed according to the natural landscape feature, and wide tourism roads and small-size buildings could be constructed but the style of the buildings should be harmonious with surrounding nature landscape; while around the view points of classes IV and V, large-size multifunctional items and roads could be built to perfect the natural landscape. Through the multi-perspective and quantitative evaluation of landscape sensitivity, this study enriched the theory of landscape visual assessment and landscape apperception, and provided scientific base and direction for the planning and management of forest parks and other tourism areas.
Modern freshwater microbialite analogues for ancient dendritic reef structures

NASA Technical Reports Server (NTRS)

Laval, B.; Cady, S. L.; Pollack, J. C.; McKay, C. P.; Bird, J. S.; Grotzinger, J. P.; Ford, D. C.; Bohm, H. R.

2000-01-01

Microbialites are organosedimentary structures that can be constructed by a variety of metabolically distinct taxa. Consequently, microbialite structures abound in the fossil record, although the exact nature of the biogeochemical processes that produced them is often unknown. One such class of ancient calcareous structures, Epiphyton and Girvanella, appear in great abundance during the Early Cambrian. Together with Archeocyathids, stromatolites and thrombolites, they formed major Cambrian reef belts. To a large extent, Middle to Late Cambrian reefs are similar to Precambrian reefs, with the exception that the latter, including terminal Proterozoic reefs, do not contain Epiphyton or Girvanella. Here we report the discovery in Pavilion Lake, British Columbia, Canada, of a distinctive assemblage of freshwater calcite microbialites, some of which display microstructures similar to the fabrics displayed by Epiphyton and Girvanella. The morphologies of the modern microbialites vary with depth, and dendritic microstructures of the deep water (> 30 m) mounds indicate that they may be modern analogues for the ancient calcareous structures. These microbialites thus provide an opportunity to study the biogeochemical interactions that produce fabrics similar to those of some enigmatic Early Cambrian reef structures.
Polymer therapeutics: concepts and applications.

PubMed

Haag, Rainer; Kratz, Felix

2006-02-13

Polymer therapeutics encompass polymer-protein conjugates, drug-polymer conjugates, and supramolecular drug-delivery systems. Numerous polymer-protein conjugates with improved stability and pharmacokinetic properties have been developed, for example, by anchoring enzymes or biologically relevant proteins to polyethylene glycol components (PEGylation). Several polymer-protein conjugates have received market approval, for example the PEGylated form of adenosine deaminase. Coupling low-molecular-weight anticancer drugs to high-molecular-weight polymers through a cleavable linker is an effective method for improving the therapeutic index of clinically established agents, and the first candidates have been evaluated in clinical trials, including, N-(2-hydroxypropyl)methacrylamide conjugates of doxorubicin, camptothecin, paclitaxel, and platinum(II) complexes. Another class of polymer therapeutics are drug-delivery systems based on well-defined multivalent and dendritic polymers. These include polyanionic polymers for the inhibition of virus attachment, polycationic complexes with DNA or RNA (polyplexes), and dendritic core-shell architectures for the encapsulation of drugs. In this Review an overview of polymer therapeutics is presented with a focus on concepts and examples that characterize the salient features of the drug-delivery systems.
The melanocortin receptor agonist NDP-MSH impairs the allostimulatory function of dendritic cells.

PubMed

Rennalls, La'Verne P; Seidl, Thomas; Larkin, James M G; Wellbrock, Claudia; Gore, Martin E; Eisen, Tim; Bruno, Ludovica

2010-04-01

As alpha-melanocyte-stimulating hormone (alpha-MSH) is released by immunocompetent cells and has potent immunosuppressive properties, it was determined whether human dendritic cells (DCs) express the receptor for this hormone. Reverse transcription-polymerase chain reaction detected messenger RNA specific for all of the known melanocortin receptors in DCs. Mixed lymphocyte reactions also revealed that treatment with [Nle(4), DPhe(7)]-alpha-MSH (NDP-MSH), a potent alpha-MSH analogue, significantly reduced the ability of DCs to stimulate allogeneic T cells. The expression of various cell surface adhesion, maturation and costimulatory molecules on DCs was also investigated. Although treatment with NDP-MSH did not alter the expression of CD83 and major histocompatibility complex class I and II, the surface expression of CD86 (B7.2), intercellular adhesion molecule (ICAM-1/CD54) and CD1a was reduced. In summary, our data indicate that NDP-MSH inhibits the functional activity of DCs, possibly by down-regulating antigen-presenting and adhesion molecules and that these events may be mediated via the extracellular signal-regulated kinase 1 and 2 pathway.

Zoledronic acid modulates maturation of human monocyte-derived dendritic cells.

PubMed

Orsini, Giulia; Failli, Alessandra; Legitimo, Annalisa; Adinolfi, Barbara; Romanini, Antonella; Consolini, Rita

2011-12-01

Zoledronic acid (ZA) is a drug of the bisphosphonate class, which is widely used for the treatment of both osteoporosis and skeletal metastasis. Besides its main bone antiresorptive activity, ZA displays antitumor properties, by triggering the expansion and activation of γδ T-cells, which exert an antitumor effect through dendritic cells (DCs). Several studies have reported the interaction between ZA and γδ T-cells, but the potential immunoregulatory activity of this drug on DCs has scarcely been investigated. Therefore, in this paper, we evaluated the effects of a therapeutic dose of ZA on the in vitro generation and maturation of DCs derived from peripheral blood monocytes of healthy adult donors. We demonstrate that ZA treatment did not affect DC differentiation, but inhibited DC maturation on lipopolysaccharide activation, as shown by the impaired expression of maturation surface markers and reduced ability to induce allogeneic T-cell proliferation. Interestingly, IL-10 secretion by mature DCs was significantly lower in ZA-treated cells than in controls. We conclude that ZA exerts its immunological in vitro activity also by modulating the maturation of DCs.
Avian influenza A virus PB2 promotes interferon type I inducing properties of a swine strain in porcine dendritic cells

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

Ocana-Macchi, Manuela; Ricklin, Meret E.; Python, Sylvie

2012-05-25

The 2009 influenza A virus (IAV) pandemic resulted from reassortment of avian, human and swine strains probably in pigs. To elucidate the role of viral genes in host adaptation regarding innate immune responses, we focussed on the effect of genes from an avian H5N1 and a porcine H1N1 IAV on infectivity and activation of porcine GM-CSF-induced dendritic cells (DC). The highest interferon type I responses were achieved by the porcine virus reassortant containing the avian polymerase gene PB2. This finding was not due to differential tropism since all viruses infected DC equally. All viruses equally induced MHC class II, butmore » porcine H1N1 expressing the avian viral PB2 induced more prominent nuclear NF-{kappa}B translocation compared to its parent IAV. The enhanced activation of DC may be detrimental or beneficial. An over-stimulation of innate responses could result in either pronounced tissue damage or increased resistance against IAV reassortants carrying avian PB2.« less
Cytoskeletal stabilization of inhibitory interactions in immunologic synapses of mature human dendritic cells with natural killer cells

PubMed Central

Barreira da Silva, Rosa; Graf, Claudine

2011-01-01

Human mature dendritic cells (DCs) can efficiently stimulate natural killer (NK)–cell responses without being targeted by their cytotoxicity. To understand this important regulatory crosstalk, we characterized the development of the immunologic synapse between mature DCs and resting NK cells. Conjugates between these 2 innate leukocyte populations formed rapidly, persisted for prolonged time periods and matured with DC-derived f-actin polymerization at the synapse. Polarization of IL-12 and IL-12R to the synapse coincided with f-actin polymerization, while other activating and inhibitory molecules were enriched at the interface between DCs and NK cells earlier. Functional assays revealed that inhibition of f-actin polymerization in mature synapses led to an increase of IFN-γ secretion and cytotoxicity by NK cells. This elevated NK-cell reactivity resulted from decreased inhibitory signaling in the absence of MHC class I polarization at the interface, which was observed on inhibition of f-actin polymerization in DCs. Thus, inhibitory signaling is stabilized by f-actin at the synapse between mature DCs and resting NK cells. PMID:21917751
Minocycline promotes the generation of dendritic cells with regulatory properties.

PubMed

Kim, Narae; Park, Chan-Su; Im, Sun-A; Kim, Ji-Wan; Lee, Jae-Hee; Park, Young-Jun; Song, Sukgil; Lee, Chong-Kil

2016-08-16

Minocycline, which has long been used as a broad-spectrum antibiotic, also exhibits non-antibiotic properties such as inhibition of inflammation and angiogenesis. In this study, we show that minocycline significantly enhances the generation of dendritic cells (DCs) from mouse bone marrow (BM) cells when used together with GM-CSF and IL-4. DCs generated from BM cells in the presence of minocycline (Mino-DCs) demonstrate the characteristics of regulatory DCs. Compared with control DCs, Mino-DCs are resistant to subsequent maturation stimuli, impaired in MHC class II-restricted exogenous Ag presentation, and show decreased cytokine secretion. Mino-DCs also show decreased ability to prime allogeneic-specific T cells, while increasing the expansion of CD4+CD25+Foxp3+ T regulatory cells both in vitro and in vivo. In addition, pretreatment with MOG35-55 peptide-pulsed Mino-DCs ameliorates clinical signs of experimental autoimmune encephalitis induced by MOG peptide injection. Our study identifies minocycline as a new pharmacological agent that could be potentially used to increase the production of regulatory DCs for cell therapy to treat autoimmune disorders, allergy, and transplant rejection.
T regulatory cells and dendritic cells protect against transfusion-related acute lung injury via IL-10

PubMed Central

Kapur, Rick; Kim, Michael; Aslam, Rukhsana; McVey, Mark J.; Tabuchi, Arata; Luo, Alice; Liu, Jonathan; Li, Yuan; Shanmugabhavananthan, Shanjeevan; Speck, Edwin R.; Zufferey, Anne; Yousef, George; Zhang, Haibo; Rondina, Matthew T.; Weyrich, Andrew S.; Porcelijn, Leendert; Kuebler, Wolfgang M.; Slutsky, Arthur S.

2017-01-01

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related fatalities and is characterized by acute respiratory distress following blood transfusion. Donor antibodies are frequently involved; however, the pathogenesis and protective mechanisms in the recipient are poorly understood, and specific therapies are lacking. Using newly developed murine TRALI models based on injection of anti–major histocompatibility complex class I antibodies, we found CD4+CD25+FoxP3+ T regulatory cells (Tregs) and CD11c+ dendritic cells (DCs) to be critical effectors that protect against TRALI. Treg or DC depletion in vivo resulted in aggravated antibody-mediated acute lung injury within 90 minutes with 60% mortality upon DC depletion. In addition, resistance to antibody-mediated TRALI was associated with increased interleukin-10 (IL-10) levels, and IL-10 levels were found to be decreased in mice suffering from TRALI. Importantly, IL-10 injection completely prevented and rescued the development of TRALI in mice and may prove to be a promising new therapeutic approach for alleviating lung injury in this serious complication of transfusion. PMID:28202460
Endocytic pathways downregulate the L1-type cell adhesion molecule neuroglian to promote dendrite pruning in Drosophila.

PubMed

Zhang, Heng; Wang, Yan; Wong, Jack Jing Lin; Lim, Kah-Leong; Liou, Yih-Cherng; Wang, Hongyan; Yu, Fengwei

2014-08-25

Pruning of unnecessary axons and/or dendrites is crucial for maturation of the nervous system. However, little is known about cell adhesion molecules (CAMs) that control neuronal pruning. In Drosophila, dendritic arborization neurons, ddaCs, selectively prune their larval dendrites. Here, we report that Rab5/ESCRT-mediated endocytic pathways are critical for dendrite pruning. Loss of Rab5 or ESCRT function leads to robust accumulation of the L1-type CAM Neuroglian (Nrg) on enlarged endosomes in ddaC neurons. Nrg is localized on endosomes in wild-type ddaC neurons and downregulated prior to dendrite pruning. Overexpression of Nrg alone is sufficient to inhibit dendrite pruning, whereas removal of Nrg causes precocious dendrite pruning. Epistasis experiments indicate that Rab5 and ESCRT restrain the inhibitory role of Nrg during dendrite pruning. Thus, this study demonstrates the cell-surface molecule that controls dendrite pruning and defines an important mechanism whereby sensory neurons, via endolysosomal pathway, downregulate the cell-surface molecule to trigger dendrite pruning. Copyright © 2014 Elsevier Inc. All rights reserved.
Microtubule nucleation and organization in dendrites

PubMed Central

Delandre, Caroline; Amikura, Reiko; Moore, Adrian W.

2016-01-01

ABSTRACT Dendrite branching is an essential process for building complex nervous systems. It determines the number, distribution and integration of inputs into a neuron, and is regulated to create the diverse dendrite arbor branching patterns characteristic of different neuron types. The microtubule cytoskeleton is critical to provide structure and exert force during dendrite branching. It also supports the functional requirements of dendrites, reflected by differential microtubule architectural organization between neuron types, illustrated here for sensory neurons. Both anterograde and retrograde microtubule polymerization occur within growing dendrites, and recent studies indicate that branching is enhanced by anterograde microtubule polymerization events in nascent branches. The polarities of microtubule polymerization events are regulated by the position and orientation of microtubule nucleation events in the dendrite arbor. Golgi outposts are a primary microtubule nucleation center in dendrites and share common nucleation machinery with the centrosome. In addition, pre-existing dendrite microtubules may act as nucleation sites. We discuss how balancing the activities of distinct nucleation machineries within the growing dendrite can alter microtubule polymerization polarity and dendrite branching, and how regulating this balance can generate neuron type-specific morphologies. PMID:27097122
Disruption of HLA class II antigen presentation in Burkitt lymphoma: implication of a 47 000 MW acid labile protein in CD4+ T-cell recognition

PubMed Central

God, Jason M; Zhao, Dan; Cameron, Christine A; Amria, Shereen; Bethard, Jennifer R; Haque, Azizul

2014-01-01

While Burkitt lymphoma (BL) has a well-known defect in HLA class I-mediated antigen presentation, the exact role of BL-associated HLA class II in generating a poor CD4+ T-cell response remains unresolved. Here, we found that BL cells are deficient in their ability to optimally stimulate CD4+ T cells via the HLA class II pathway. This defect in CD4+ T-cell recognition was not associated with low levels of co-stimulatory molecules on BL cells, as addition of external co-stimulation failed to elicit CD4+ T-cell activation by BL. Further, the defect was not caused by faulty antigen/class II interaction, because antigenic peptides bound with measurable affinity to BL-associated class II molecules. Interestingly, functional class II–peptide complexes were formed at acidic pH 5·5, which restored immune recognition. Acidic buffer (pH 5·5) eluate from BL cells contained molecules that impaired class II-mediated antigen presentation and CD4+ T-cell recognition. Biochemical analysis showed that these molecules were greater than 30 000 molecular weight in size, and proteinaceous in nature. In addition, BL was found to have decreased expression of a 47 000 molecular weight enolase-like molecule that enhances class II-mediated antigen presentation in B cells, macrophages and dendritic cells, but not in BL cells. These findings demonstrate that BL likely has multiple defects in HLA class II-mediated antigen presentation and immune recognition, which may be exploited for future immunotherapies. PMID:24628049
Discovery of 2-[4-{{2-(2S,5R)-2-cyano-5-ethynyl-1-pyrrolidinyl]-2-oxoethyl]amino]- 4-methyl-1-piperidinyl]-4-pyridinecarboxylic acid (ABT-279): a very potent, selective, effective, and well-tolerated inhibitor of dipeptidyl peptidase-IV, useful for the treatment of diabetes.

PubMed

Madar, David J; Kopecka, Hana; Pireh, Daisy; Yong, Hong; Pei, Zhonghua; Li, Xiaofeng; Wiedeman, Paul E; Djuric, Stevan W; Von Geldern, Thomas W; Fickes, Michael G; Bhagavatula, Lakshmi; McDermott, Todd; Wittenberger, Steven; Richards, Steven J; Longenecker, Kenton L; Stewart, Kent D; Lubben, Thomas H; Ballaron, Stephen J; Stashko, Michael A; Long, Michelle A; Wells, Heidi; Zinker, Bradley A; Mika, Amanda K; Beno, David W A; Kempf-Grote, Anita J; Polakowski, James; Segreti, Jason; Reinhart, Glenn A; Fryer, Ryan M; Sham, Hing L; Trevillyan, James M

2006-10-19

Dipeptidyl peptidase-IV (DPP-IV) inhibitors are poised to be the next major drug class for the treatment of type 2 diabetes. Structure-activity studies of substitutions at the C5 position of the 2-cyanopyrrolidide warhead led to the discovery of potent inhibitors of DPP-IV that lack activity against DPP8 and DPP9. Further modification led to an extremely potent (Ki(DPP)(-)(IV) = 1.0 nM) and selective (Ki(DPP8) > 30 microM; Ki(DPP9) > 30 microM) clinical candidate, ABT-279, that is orally available, efficacious, and remarkably safe in preclinical safety studies.
Somatic spikes regulate dendritic signaling in small neurons in the absence of backpropagating action potentials.

PubMed

Myoga, Michael H; Beierlein, Michael; Regehr, Wade G

2009-06-17

Somatic spiking is known to regulate dendritic signaling and associative synaptic plasticity in many types of large neurons, but it is unclear whether somatic action potentials play similar roles in small neurons. Here we ask whether somatic action potentials can also influence dendritic signaling in an electrically compact neuron, the cerebellar stellate cell (SC). Experiments were conducted in rat brain slices using a combination of imaging and electrophysiology. We find that somatic action potentials elevate dendritic calcium levels in SCs. There was little attenuation of calcium signals with distance from the soma in SCs from postnatal day 17 (P17)-P19 rats, which had dendrites that averaged 60 microm in length, and in short SC dendrites from P30-P33 rats. Somatic action potentials evoke dendritic calcium increases that are not affected by blocking dendritic sodium channels. This indicates that dendritic signals in SCs do not rely on dendritic sodium channels, which differs from many types of large neurons, in which dendritic sodium channels and backpropagating action potentials allow somatic spikes to control dendritic calcium signaling. Despite the lack of active backpropagating action potentials, we find that trains of somatic action potentials elevate dendritic calcium sufficiently to release endocannabinoids and retrogradely suppress parallel fiber to SC synapses in P17-P19 rats. Prolonged SC firing at physiologically realistic frequencies produces retrograde suppression when combined with low-level group I metabotropic glutamate receptor activation. Somatic spiking also interacts with synaptic stimulation to promote associative plasticity. These findings indicate that in small neurons the passive spread of potential within dendrites can allow somatic spiking to regulate dendritic calcium signaling and synaptic plasticity.
Prediction of future uniform milk prices in Florida federal milk marketing order 6 from milk futures markets.

PubMed

De Vries, A; Feleke, S

2008-12-01

This study assessed the accuracy of 3 methods that predict the uniform milk price in Federal Milk Marketing Order 6 (Florida). Predictions were made for 1 to 12 mo into the future. Data were from January 2003 to May 2007. The CURRENT method assumed that future uniform milk prices were equal to the last announced uniform milk price. The F+BASIS and F+UTIL methods were based on the milk futures markets because the futures prices reflect the market's expectation of the class III and class IV cash prices that are announced monthly by USDA. The F+BASIS method added an exponentially weighted moving average of the difference between the class III cash price and the historical uniform milk price (also known as basis) to the class III futures price. The F+UTIL method used the class III and class IV futures prices, the most recently announced butter price, and historical utilizations to predict the skim milk prices, butterfat prices, and utilizations in all 4 classes. Predictions of future utilizations were made with a Holt-Winters smoothing method. Federal Milk Marketing Order 6 had high class I utilization (85 +/- 4.8%). Mean and standard deviation of the class III and class IV cash prices were $13.39 +/- 2.40/cwt (1 cwt = 45.36 kg) and $12.06 +/- 1.80/cwt, respectively. The actual uniform price in Tampa, Florida, was $16.62 +/- 2.16/cwt. The basis was $3.23 +/- 1.23/cwt. The F+BASIS and F+UTIL predictions were generally too low during the period considered because the class III cash prices were greater than the corresponding class III futures prices. For the 1- to 6-mo-ahead predictions, the root of the mean squared prediction errors from the F+BASIS method were $1.12, $1.20, $1.55, $1.91, $2.16, and $2.34/cwt, respectively. The root of the mean squared prediction errors ranged from $2.50 to $2.73/cwt for predictions up to 12 mo ahead. Results from the F+UTIL method were similar. The accuracies of the F+BASIS and F+UTIL methods for all 12 fore-cast horizons were not significantly different. Application of the modified Mariano-Diebold tests showed that no method included all the information contained in the other methods. In conclusion, both F+BASIS and F+UTIL methods tended to more accurately predict the future uniform milk prices than the CURRENT method, but prediction errors could be substantial even a few months into the future. The majority of the prediction error was caused by the inefficiency of the futures markets to predict the class III cash prices.
Permanent work incapacity, mortality and survival without work incapacity among occupations and social classes: a cohort study of ageing men in Geneva.

PubMed

Gubéran, E; Usel, M

1998-12-01

The objective of this retrospective cohort study was to investigate the burden of disability and death in men, from middle age to age of retirement, among occupational groups and classes in Geneva. Men were included if they resided in the Canton of Geneva, were 45 years of age in 1970-1972, and were not receiving a disability pension at the start of the follow-up. The cohort of 5137 men was followed up for 20 years and linked to national registers of disability pension allowance and of causes of death. There was a steep upward trend in incidence of permanent work incapacity with lower social class for all causes as well as for the seven causes of disability studied. Compared with professional occupations (social class I), the relative risk (RR) of permanent work incapacity was 11.4 for partly skilled and unskilled occupations (class IV+V) (95% confidence interval [CI]: 5.2-28.0). The social class gradient in mortality was in the same direction as that in work incapacity although much less steep (RR class IV+V to class I = 1.6, 95% CI : 1.1-2.2). Survival without work incapacity at the time of the 65th birthday ranged from only 57% in construction workers and labourers to 89% in science and related professionals. Unemployment in Geneva was below 1.5% during almost all the study period. Medically-ascertained permanent work incapacity and survival without work incapacity have shown considerably greater socioeconomic differentials than the mortality differentials.
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.
Prolonged expression of MHC class I - peptide expression in bone marrow derived retrovirus transfected matured dendritic cells by continuous centrifugation in the presence of IL-4.

PubMed

Hettihewa, L M

2011-11-01

Dendritic cells (DCs) are potent antigen presenting cells which proceed from immature to a mature stage during their differentiation. There are several methods of obtaining long lasting mature antigen expressing DCs and different methods show different levels of antigen expressions. We investigated bone marrow derived DCs for the degree of maturation and genetically engineered antigen presentation in the presence of interleukin-4 (IL-4) as a maturity enhancer. DCs and transfected retrovirus were cultured together in the presence of granulocyte-macrophage colony stimulating factor (GMCSF)-IL4, GMCSF +IL4, lipopolysaccharide (LPS). B 7.1, B7.2 and CD11c were measured by the degree of immune fluorescence using enhanced green fluorescent protein (EGFP) shuttled retrovirus transfected antigen. Degree of MHC class I molecule with antigen presentation of antigen was also evaluated by fluorescence activated cell sorting. The antigen presenting capacity of transfected DCs was investigated. Bone marrow DCs were generated in the presence of GMCSF and IL-4 in vitro. Dividing bone marrow cells were infected with EGFP shuttled retrovirus expressing SSP2 by prolonged centrifugation for three consecutive days from day 5, 6 and 7 and continued to culture in the presence of GMSCF and IL-4 until day 8. IL-4 as a cytokine increased the maturation of retrovirus transfected DCs by high expression of B 7-1 and B 7-2. Also, IL-4 induced DC enhanced by the prolonged centrifugation and it was shown by increased antigen presentation of these dendric cells as antigen presenting cell (APC). Cytolytic effects were significantly higher in cytotoxic T cell response (CTLs) mixed with transfected DCs than CTLs mixed with pulsed DCs. There was an enhanced antigen presentation by prolonged expression of antigen loaded MHC class I receptors in DCs in the presence of IL-4 by prolonged centrifugation.
Endothelial cell-derived microparticles induce plasmacytoid dendritic cell maturation: potential implications in inflammatory diseases.

PubMed

Angelot, Fanny; Seillès, Estelle; Biichlé, Sabeha; Berda, Yael; Gaugler, Béatrice; Plumas, Joel; Chaperot, Laurence; Dignat-George, Françoise; Tiberghien, Pierre; Saas, Philippe; Garnache-Ottou, Francine

2009-11-01

Increased circulating endothelial microparticles, resulting from vascular endothelium dysfunction, and plasmacytoid dendritic cell activation are both encountered in common inflammatory disorders. The aim of our study was to determine whether interactions between endothelial microparticles and plasmacytoid dendritic cells could contribute to such pathologies. Microparticles generated from endothelial cell lines, platelets or activated T cells were incubated with human plasmacytoid dendritic cells sorted from healthy donor blood or with monocyte-derived dendritic cells. Dendritic cell maturation was evaluated by flow cytometry, cytokine secretion as well as naive T-cell activation and polarization. Labeled microparticles were also used to study cellular interactions. Endothelial microparticles induced plasmacytoid dendritic cell maturation. In contrast, conventional dendritic cells were resistant to endothelial microparticle-induced maturation. In addition to upregulation of co-stimulatory molecules, endothelial microparticle-matured plasmacytoid dendritic cells secreted inflammatory cytokines (interleukins 6 and 8, but no interferon-alpha) and also induced allogeneic naive CD4(+) T cells to proliferate and to produce type 1 cytokines such as interferon-gamma and tumor necrosis factor-alpha. Endothelial microparticle endocytosis by plasmacytoid dendritic cells appeared to be required for plasmacytoid dendritic cell maturation. Importantly, the ability of endothelial microparticles to induce plasmacytoid dendritic cells to mature was specific as microparticles derived from activated T cells or platelets (the major source of circulating microparticules in healthy subjects) did not induce such plasmacytoid dendritic cell maturation. Our data show that endothelial microparticles specifically induce plasmacytoid dendritic cell maturation and production of inflammatory cytokines. This novel activation pathway may be implicated in various inflammatory disorders and endothelial microparticles could be an important immunmodulatory therapeutic target.
Behavioral, Neurophysiological, and Synaptic Impairment in a Transgenic Neuregulin1 (NRG1-IV) Murine Schizophrenia Model

PubMed Central

Papaleo, Francesco; Yang, Feng; Paterson, Clare; Palumbo, Sara; Carr, Gregory V.; Wang, Yanhong; Floyd, Kirsten; Huang, Wenwei; Thomas, Craig J.; Chen, Jingshan; Weinberger, Daniel R.

2016-01-01

Schizophrenia is a chronic, disabling neuropsychiatric disorder with complex genetic origins. The development of strategies for genome manipulation in rodents provides a platform for understanding the pathogenic role of genes and for testing novel therapeutic agents. Neuregulin 1 (NRG1), a critical developmental neurotrophin, is associated with schizophrenia. The NRG1 gene undergoes extensive alternative splicing and, to date, little is known about the neurobiology of a novel NRG1 isoform, NRG1-IV, which is increased in the brains of individuals with schizophrenia and associated with genetic risk variation. Here, we developed a transgenic mouse model (NRG1-IV/NSE-tTA) in which human NRG1-IV is selectively overexpressed in a neuronal specific manner. Using a combination of molecular, biochemical, electrophysiological, and behavioral analyses, we demonstrate that NRG1-IV/NSE-tTA mice exhibit abnormal behaviors relevant to schizophrenia, including impaired sensorimotor gating, discrimination memory, and social behaviors. These neurobehavioral phenotypes are accompanied by increases in cortical expression of the NRG1 receptor, ErbB4 and the downstream signaling target, PIK3-p110δ, along with disrupted dendritic development, synaptic pathology, and altered prefrontal cortical excitatory–inhibitory balance. Pharmacological inhibition of p110δ reversed sensorimotor gating and cognitive deficits. These data demonstrate a novel role for NRG1-IV in learning, memory, and neural circuit formation and a potential neurobiological mechanism for schizophrenia risk; show that deficits are pharmacologically reversible in adulthood; and further highlight p110δ as a target for antipsychotic drug development. SIGNIFICANCE STATEMENT Schizophrenia is a disabling psychiatric disorder with neurodevelopmental origins. Genes that increase risk for schizophrenia have been identified. Understanding how these genes affect brain development and function is necessary. This work is the first report of a newly generated humanized transgenic mouse model engineered to express human NRG1-IV, an isoform of the NRG1 (Neuregulin 1) gene that is increased in the brains of patients with schizophrenia in association with genetic risk. Using behavioral neuroscience, molecular biology, electrophysiology, and pharmacology, we identify a role for NRG1-IV in learning, memory, and cognition and determine that this relates to brain excitatory–inhibitory balance and changes in ErbB4/PI3K/AKT signaling. Moreover, the study further highlights the potential of targeting the PI3K pathway for the treatment of schizophrenia. PMID:27122041
Amplitude Normalization of Dendritic EPSPs at the Soma of Binaural Coincidence Detector Neurons of the Medial Superior Olive.

PubMed

Winters, Bradley D; Jin, Shan-Xue; Ledford, Kenneth R; Golding, Nace L

2017-03-22

The principal neurons of the medial superior olive (MSO) encode cues for horizontal sound localization through comparisons of the relative timing of EPSPs. To understand how the timing and amplitude of EPSPs are maintained during propagation in the dendrites, we made dendritic and somatic whole-cell recordings from MSO principal neurons in brain slices from Mongolian gerbils. In somatic recordings, EPSP amplitudes were largely uniform following minimal stimulation of excitatory synapses at visualized locations along the dendrites. Similar results were obtained when excitatory synaptic transmission was eliminated in a low calcium solution and then restored at specific dendritic sites by pairing input stimulation and focal application of a higher calcium solution. We performed dual dendritic and somatic whole-cell recordings to measure spontaneous EPSPs using a dual-channel template-matching algorithm to separate out those events initiated at or distal to the dendritic recording location. Local dendritic spontaneous EPSP amplitudes increased sharply in the dendrite with distance from the soma (length constant, 53.6 μm), but their attenuation during propagation resulted in a uniform amplitude of ∼0.2 mV at the soma. The amplitude gradient of dendritic EPSPs was also apparent in responses to injections of identical simulated excitatory synaptic currents in the dendrites. Compartmental models support the view that these results extensively reflect the influence of dendritic cable properties. With relatively few excitatory axons innervating MSO neurons, the normalization of dendritic EPSPs at the soma would increase the importance of input timing versus location during the processing of interaural time difference cues in vivo SIGNIFICANCE STATEMENT The neurons of the medial superior olive analyze cues for sound localization by detecting the coincidence of binaural excitatory synaptic inputs distributed along the dendrites. Previous studies have shown that dendritic voltages undergo severe attenuation as they propagate to the soma, potentially reducing the influence of distal inputs. However, using dendritic and somatic patch recordings, we found that dendritic EPSP amplitude increased with distance from the soma, compensating for dendritic attenuation and normalizing EPSP amplitude at the soma. Much of this normalization reflected the influence of dendritic morphology. As different combinations of presynaptic axons may be active during consecutive cycles of sound stimuli, somatic EPSP normalization renders spike initiation more sensitive to synapse timing than dendritic location. Copyright © 2017 the authors 0270-6474/17/373138-12$15.00/0.
Assessment of feasibility and efficacy of Class IV laser therapy for postoperative pain relief in off-pump coronary artery bypass surgery patients: A pilot study

PubMed Central

Karlekar, Anil; Bharati, Saswata; Saxena, Ravindra; Mehta, Kanchan

2015-01-01

Background: Laser therapy, for its established analgesic properties with minimal side effects, has been used for the treatment of chronic pain. However, it has not been used for the treatment of acute postoperative pain. This pilot study was designed to assess the feasibility and efficacy of Class IV laser on postoperative pain relief following off-pump coronary artery bypass graft (OPCABG) surgery, as a component of multimodal analgesia (MMA) technique. Methods: This open observational prospective study comprised of 100 adult patients (84 male, 16 female) who underwent OPCABG through sternotomy. For postoperative analgesia, they were subjected to laser therapy subjected to laser therapy in addition to the standard institutional pain management protocol comprising of IV infusion/bolus of tramadol and paracetamol and fentanyl bolus as rescue analgesic. Pain intensity was measured by Verbal Rating Scale (VRS). The laser therapy was scheduled as once a day regime for three consecutive postoperative days (PODs) starting on POD 1, 30 min following tracheal extubation. The subsequent laser applications were also scheduled at the same time of the day as on day 1 if VRS was ≥5. 10 W Class IV laser was applied over 150 cm2 sternal wound area for 150 s. VRS was used to assess pain severity and was recorded for statistical analysis using Friedman Test. Results: The mean (standard deviation [SD]) VRS of all the 100 patients just before application of the first dose of laser was 7.31 (0.94) while on MMT; the same fell to 4.0 (1.279) and 3.40 (2.697) at 1 h and 24 h respectively following first dose of laser. The change of VRS over first 24 h among all the 100 patients was statistically significant (P = 0.000). Laser was re-applied in 40 patients whose VRS was ≥5 (mean [SD] – 6.38 [0.868]) at 24th h. After receiving the 2nd dose of laser the VRS scores fell significantly (P = 0.000) and became 0 at 54th h. No patients required 3rd dose of the laser. No patient required rescue analgesic while on laser therapy. Conclusion: Class IV laser can be an effective technique for postoperative analgesia following OPCABG surgery through sternotomy when included as a component of MMA technique. PMID:26139735
Social class inequalities in the use of and access to health services in Catalonia, Spain: what is the influence of supplemental private health insurance?

PubMed

Borrell, C; Fernandez, E; Schiaffino, A; Benach, J; Rajmil, L; Villalbi, J R; Segura, A

2001-04-01

To analyse social class inequalities in the access to and utilization of health services in Catalonia (Spain), and the influence of having private health insurance supplementing the National Health System (NHS) coverage. 1994 Catalan Health Interview Survey, a cross-sectional survey conducted in 1994. Catalonia (Spain). The participants were a representative sample of people aged over 14 years from the non-institutionalized population of Catalonia (n = 12,245). Health services utilization, perceived health, having only NHS or NHS plus a private health insurance, and social class. Although one-quarter of the population of Catalonia had a supplemental private health insurance, percentages were very different according to social class, ranging from almost 50% for classes I and II to 16% for classes IV and V in both sexes. No inequalities by social class were observed for the utilization of non-preventive health care services (consultation with a health professional in the last 2 weeks and hospitalization in the last year) among persons with poor self-perceived health status, i.e. those in most need. However, social inequalities still remain in the use of health services provided only partially by the NHS, and when characteristics of last consultation are taken into account. Subjects who paid for a private service waited an average of 18.8 minutes less than those attending the NHS. Within the NHS, social classes IV and V waited longer (35.5 minutes) than social classes I and II (28.4 minutes). The NHS in Catalonia, Spain, has reduced inequalities in the use of health services. Social inequalities remain in the use of those health services provided only partially by the NHS.
Dendritic solidification. I - Analysis of current theories and models. II - A model for dendritic growth under an imposed thermal gradient

NASA Technical Reports Server (NTRS)

Laxmanan, V.

1985-01-01

A critical review of the present dendritic growth theories and models is presented. Mathematically rigorous solutions to dendritic growth are found to rely on an ad hoc assumption that dendrites grow at the maximum possible growth rate. This hypothesis is found to be in error and is replaced by stability criteria which consider the conditions under which a dendrite tip advances in a stable fashion in a liquid. The important elements of a satisfactory model for dendritic solidification are summarized and a theoretically consistent model for dendritic growth under an imposed thermal gradient is proposed and described. The model is based on the modification of an analysis due to Burden and Hunt (1974) and predicts correctly in all respects, the transition from a dendritic to a planar interface at both very low and very large growth rates.

A role for a rat homolog of staufen in the transport of RNA to neuronal dendrites.

PubMed

Tang, S J; Meulemans, D; Vazquez, L; Colaco, N; Schuman, E

2001-11-08

RNAs are present in dendrites and may be used for local protein synthesis in response to synaptic activity. To begin to understand dendritic RNA targeting, we cloned a rat homolog of staufen, a Drosophila gene that participates in mRNA targeting during development. In hippocampal neurons, rat staufen protein displays a microtubule-dependent somatodendritic distribution pattern that overlaps with dendritic RNAs. To determine whether r-staufen is required for dendritic RNA targeting, we constructed a mutant version containing the RNA binding domains (stau-RBD) but lacking the C-terminal portion potentially involved in dendritic targeting. Stau-RBD expression was restricted to the cell bodies and proximal dendrites. Expression of stau-RBD significantly decreased, while overexpression of wild-type r-staufen increased, the amount of dendritic mRNA. Taken together, these results suggest that the rat staufen protein plays an important role in the delivery of RNA to dendrites.
Active action potential propagation but not initiation in thalamic interneuron dendrites

PubMed Central

Casale, Amanda E.; McCormick, David A.

2012-01-01

Inhibitory interneurons of the dorsal lateral geniculate nucleus of the thalamus modulate the activity of thalamocortical cells in response to excitatory input through the release of inhibitory neurotransmitter from both axons and dendrites. The exact mechanisms by which release can occur from dendrites are, however, not well understood. Recent experiments using calcium imaging have suggested that Na/K based action potentials can evoke calcium transients in dendrites via local active conductances, making the back-propagating action potential a candidate for dendritic neurotransmitter release. In this study, we employed high temporal and spatial resolution voltage-sensitive dye imaging to assess the characteristics of dendritic voltage deflections in response to Na/K action potentials in interneurons of the mouse dorsal lateral geniculate nucleus. We found that trains or single action potentials elicited by somatic current injection or local synaptic stimulation led to action potentials that rapidly and actively back-propagated throughout the entire dendritic arbor and into the fine filiform dendritic appendages known to release GABAergic vesicles. Action potentials always appeared first in the soma or proximal dendrite in response to somatic current injection or local synaptic stimulation, and the rapid back-propagation into the dendritic arbor depended upon voltage-gated sodium and TEA-sensitive potassium channels. Our results indicate that thalamic interneuron dendrites integrate synaptic inputs that initiate action potentials, most likely in the axon initial segment, that then back-propagate with high-fidelity into the dendrites, resulting in a nearly synchronous release of GABA from both axonal and dendritic compartments. PMID:22171033
The Src-like adaptor protein regulates GM-CSFR signaling and monocytic dendritic cell maturation.

PubMed

Liontos, Larissa M; Dissanayake, Dilan; Ohashi, Pamela S; Weiss, Arthur; Dragone, Leonard L; McGlade, C Jane

2011-02-15

GM-CSF is an important cytokine involved in myeloid differentiation and inflammatory processes. Signaling through the GM-CSFR also plays a critical role in the generation of monocyte-derived dendritic cells (DC). In this article, we report that the Src-like adaptor protein (SLAP) functions as a negative regulator of the GM-CSFR. In bone marrow-derived DC (BM-DC) lacking SLAP and the closely related SLAP2, downregulation of GM-CSFRβ is impaired, leading to enhanced phosphorylation of Jak2 and prolonged activation of Akt and Erk1/2 in response to GM-CSF stimulation. Compared with wild-type bone marrow, SLAP/SLAP2(-/-) bone marrow gave rise to similar numbers of CD11c(+) and CD11b(+) DC, but SLAP/SLAP2(-/-) BM-DC failed to acquire high levels of MHC class II, CD80, and CD86, indicating an impairment in maturation. Furthermore, MHC class II expression in SLAP/SLAP2(-/-) BM-DC was rescued by decreasing GM-CSF concentration, suggesting that enhanced GM-CSF signaling mediates the block in maturation. In addition, SLAP/SLAP2(-/-) BM-DC produced less IL-12 and TNF-α in response to LPS compared with controls and failed to stimulate T cells in an MLR. Ag-specific T cell activation assays showed that SLAP/SLAP2(-/-) BM-DC were less robust at inducing IFN-γ secretion by DO11.10 T cells. These results indicated that SLAP-mediated GM-CSFR regulation is important for the generation of functionally mature monocytic DC.
Antigen presentation by MART-1 adenovirus-transduced interleukin-10-polarized human monocyte-derived dendritic cells

PubMed Central

Mehrotra, Shikhar; Chhabra, Arvind; Chakraborty, Abolokita; Chattopadhyay, Subhasis; Slowik, Mark; Stevens, Robert; Zengou, Ryan; Mathias, Clinton; Butterfield, Lisa H; Dorsky, David I; Economou, James S; Mukherji, Bijay; Chakraborty, Nitya G

2004-01-01

Dendritic cells (DC) play critical roles in generating an immune response and in inducing tolerance. Diverse microenvironmental factors can ‘polarize’ DC toward an immunogenic or non-immunogenic phenotype. Among the various microenvironmental factors, interleukin-10 (IL-10) exhibits a potent immunosuppressive effect on antigen-presenting cells (APC). Here, we show that monocyte-derived DC generated in the presence of IL-10 exhibit a profound down-regulation of many genes that are associated with immune activation and show that the IL-10-grown DC are poor stimulators of CD8+ T cells in a strictly autologous and major histocompatibility complex (MHC) class I-restricted melanoma antigen recognized by T cells (MART-1) epitope presentation system. However, these IL-10-grown DC can efficiently activate the epitope-specific CD8+ T cells when they are made to present the epitope following transduction with an adenoviral vector expressing the MART-1 antigen. In addition, we show that the MART-1 protein colocalizes with the MHC class I protein, equally well, in the iDC and in the DC cultured in presence of IL-10 when both DC types are infected with the viral vector. We also show that the vector transduced DC present the MART-127–35 epitope for a sustained period compared to the peptide pulsed DC. These data suggest that although DCs generated in the presence of IL-10 tend to be non-immunogenic, they are capable of processing and presenting an antigen when the antigen is synthesized within the DC. PMID:15554925
A novel CD4-CD8alpha+CD205+CD11b- murine spleen dendritic cell line: establishment, characterization and functional analysis in a model of vaccination to toxoplasmosis.

PubMed

Ruiz, Sophie; Beauvillain, Céline; Mévélec, Marie-Noëlle; Roingeard, Philippe; Breton, Pascal; Bout, Daniel; Dimier-Poisson, Isabelle

2005-11-01

Dendritic cells (DCs) play an essential role in the induction of immune responses to pathogen infections. Native DCs are difficult to obtain in large numbers and consequently the vast majority of DCs employed in all experiments are derived from bone marrow progenitors. In an attempt to solve this problem, we have established a novel CD8alpha(+) DC line (H-2(k)) from spleen, which we have named SRDC line, and which is easy to culture in vitro. These cells display similar morphology, phenotype and activity to CD4(-)CD8alpha(+)CD205(+)CD11b(-) DCs purified ex vivo. Toxoplasma gondii antigen was shown to be taken up by these cells and to increase class I and class II major histocompatibility complex (MHC), CD40, CD80 and CD86 surface expression. We report that vaccination with T. gondii antigen-pulsed SRDCs, which synthesize large amounts of interleukin-12, induced protective immune responses against this intracellular pathogen in syngeneic CBA/J mice. This protection was associated with strong cellular and humoral immune responses at systemic and intestinal levels. Spleen and mesenteric lymph node cell proliferations were correlated with a Th1/Th2-type response and a specific SRDC homing to spleen and intestine was observed. The SRDC or CD4(-)CD8alpha(+)CD205(+)CD11b(-) DC line can be expected to be a very useful tool for immunobiology studies of DC.
Influence of benzoporphyrin-derivative monoacid ring A (BPD-MA, verteporfin) on murine dendritic cells

NASA Astrophysics Data System (ADS)

Hunt, David W. C.; King, Diane E.; Levy, Julia G.

1997-05-01

The impact of bensoporphyrin derivative monoacid ring A, and visible light was determined for mouse splenic dendritic cells (DC), potent antigen-presenting cells (APC) of the immune system. It was discovered that sub-lethal doses of BPD-MA and light significantly altered the surface receptor pattern of DC as well as diminishing the capacity of these cells to activate allogeneic T cells. Treatment of highly purified DC with BPD-MA and 690 nm wavelength light decreased DC expression of major histocompatibility (MHC) Class I and II antigens, leukocyte common antigen CD45, intercellular adhesion molecule-1 (ICAM-1, CD54), the co- stimulatory molecules CD80 and CD86, CD95 as well as integrin CD11c. In contrast, DC expression of leukocyte function-associated-1 (LFA-1, CD11a), CD11b, CD18, CD40, and the DC DEC-205 receptor increased after the treatment. Changes in receptor levels occurred rapidly. DC MHC Class I and ICAM-1 expression declined to 40 percent of control levels by 2 hours post-PDT. DC treated with BPD-MA and light were poor stimulators of allogeneic T cells in the mixed leukocyte reaction. BPD-MA, in the absence of light, had no effect on the immunostimulatory properties of these cells. The changes in DC receptor expression pattern produced by BPD-MA and light were comparable to those produced by ultraviolet B light, a treatment known to alter the immunostimulatory characteristics of DC. Photodynamic therapy with BPD-MA represents an innovative approach for the modification of immune reactivity.
Hepatic dendritic cell subsets in the mouse.

PubMed

Jomantaite, Ieva; Dikopoulos, Nektarios; Kröger, Andrea; Leithäuser, Frank; Hauser, Hansjörg; Schirmbeck, Reinhold; Reimann, Jörg

2004-02-01

The CD11c(+) cell population in the non-parenchymal cell population of the mouse liver contains dendritic cells (DC), NK cells, B cells and T cells. In the hepatic CD11c(+) DC population from immunocompetent or immunodeficient [recombinase-activating gene-1 (RAG1)(-/-)] C57BL/6 mice (rigorously depleted of T cells, B cells and NK cells), we identified a B220(+) CD11c(int) subset of 'plasmacytoid' DC, and a B220(-) CD11c(+) DC subset. The latter DC population could be subdivided into a major, immature (CD40(lo) CD80(lo) CD86(lo) MHC class II(lo)) CD11c(int) subset, and a minor, mature (CD40(hi) CD80(hi) CD86(hi) MHC class II(hi)) CD11c(hi) subset. Stimulated B220(+) but not B220(-) DC produced type I interferon. NKT cell activation in vivo increased the number of liver B220(-) DC three- to fourfold within 18 h post-injection, and up-regulated their surface expression of activation marker, while it contracted the B220(+) DC population. Early in virus infection, the hepatic B220(+) DC subset expanded, and both, the B220(+) as well as B220(-) DC populations in the liver matured. In vitro, B220(-) but not B220(+) DC primed CD4(+) or CD8(+)T cells. Expression of distinct marker profiles and functions, and distinct early reaction to activation signals hence identify two distinct B220(+) and B220(-) subsets in CD11c(+) DC populations freshly isolated from the mouse liver.
Modulation of hippocampal rhythms by subthreshold electric fields and network topology

PubMed Central

Berzhanskaya, Julia; Chernyy, Nick; Gluckman, Bruce J.; Schiff, Steven J.; Ascoli, Giorgio A.

2012-01-01

Theta (4–12 Hz) and gamma (30–80 Hz) rhythms are considered important for cortical and hippocampal function. Although several neuron types are implicated in rhythmogenesis, the exact cellular mechanisms remain unknown. Subthreshold electric fields provide a flexible, area-specific tool to modulate neural activity and directly test functional hypotheses. Here we present experimental and computational evidence of the interplay among hippocampal synaptic circuitry, neuronal morphology, external electric fields, and network activity. Electrophysiological data are used to constrain and validate an anatomically and biophysically realistic model of area CA1 containing pyramidal cells and two interneuron types: dendritic- and perisomatic-targeting. We report two lines of results: addressing the network structure capable of generating theta-modulated gamma rhythms, and demonstrating electric field effects on those rhythms. First, theta-modulated gamma rhythms require specific inhibitory connectivity. In one configuration, GABAergic axo-dendritic feedback on pyramidal cells is only effective in proximal but not distal layers. An alternative configuration requires two distinct perisomatic interneuron classes, one exclusively receiving excitatory contacts, the other additionally targeted by inhibition. These observations suggest novel roles for particular classes of oriens and basket cells. The second major finding is that subthreshold electric fields robustly alter the balance between different rhythms. Independent of network configuration, positive electric fields decrease, while negative fields increase the theta/gamma ratio. Moreover, electric fields differentially affect average theta frequency depending on specific synaptic connectivity. These results support the testable prediction that subthreshold electric fields can alter hippocampal rhythms, suggesting new approaches to explore their cognitive functions and underlying circuitry. PMID:23053863
Endothelial cell-derived microparticles induce plasmacytoid dendritic cell maturation: potential implications in inflammatory diseases

PubMed Central

Angelot, Fanny; Seillès, Estelle; Biichlé, Sabeha; Berda, Yael; Gaugler, Béatrice; Plumas, Joel; Chaperot, Laurence; Dignat-George, Françoise; Tiberghien, Pierre; Saas, Philippe; Garnache-Ottou, Francine

2009-01-01

Background Increased circulating endothelial microparticles, resulting from vascular endothelium dysfunction, and plasmacytoid dendritic cell activation are both encountered in common inflammatory disorders. The aim of our study was to determine whether interactions between endothelial microparticles and plasmacytoid dendritic cells could contribute to such pathologies. Design and Methods Microparticles generated from endothelial cell lines, platelets or activated T cells were incubated with human plasmacytoid dendritic cells sorted from healthy donor blood or with monocyte-derived dendritic cells. Dendritic cell maturation was evaluated by flow cytometry, cytokine secretion as well as naive T-cell activation and polarization. Labeled microparticles were also used to study cellular interactions. Results Endothelial microparticles induced plasmacytoid dendritic cell maturation. In contrast, conventional dendritic cells were resistant to endothelial microparticle-induced maturation. In addition to upregulation of co-stimulatory molecules, endothelial microparticle-matured plasmacytoid dendritic cells secreted inflammatory cytokines (interleukins 6 and 8, but no interferon-α) and also induced allogeneic naive CD4+ T cells to proliferate and to produce type 1 cytokines such as interferon-γ and tumor necrosis factor-α. Endothelial microparticle endocytosis by plasmacytoid dendritic cells appeared to be required for plasmacytoid dendritic cell maturation. Importantly, the ability of endothelial microparticles to induce plasmacytoid dendritic cells to mature was specific as microparticles derived from activated T cells or platelets (the major source of circulating microparticules in healthy subjects) did not induce such plasmacytoid dendritic cell maturation. Conclusions Our data show that endothelial microparticles specifically induce plasmacytoid dendritic cell maturation and production of inflammatory cytokines. This novel activation pathway may be implicated in various inflammatory disorders and endothelial microparticles could be an important immunmodulatory therapeutic target. PMID:19648164
Primary biliary cirrhosis degree assessment by acoustic radiation force impulse imaging and hepatic fibrosis indicators

PubMed Central

Zhang, Hai-Chun; Hu, Rong-Fei; Zhu, Ting; Tong, Ling; Zhang, Qiu-Qin

2016-01-01

AIM: To evaluate the assessment of primary biliary cirrhosis degree by acoustic radiation force impulse imaging (ARFI) and hepatic fibrosis indicators. METHODS: One hundred and twenty patients who developed liver cirrhosis secondary to primary biliary cirrhosis were selected as the observation group, with the degree of patient liver cirrhosis graded by Child-Pugh (CP) score. Sixty healthy individuals were selected as the control group. The four indicators of hepatic fibrosis were detected in all research objects, including hyaluronic acid (HA), laminin (LN), type III collagen (PC III), and type IV collagen (IV-C). The liver parenchyma hardness value (LS) was then measured by ARFI technique. LS and the four indicators of liver fibrosis (HA, LN, PC III, and IV-C) were observed in different grade CP scores. The diagnostic value of LS and the four indicators of liver fibrosis in determining liver cirrhosis degree with PBC, whether used alone or in combination, were analyzed by receiver operating characteristic (ROC) curve. RESULTS: LS and the four indicators of liver fibrosis within the three classes (A, B, and C) of CP scores in the observation group were higher than in the control group, with C class > B class > A class; the differences were statistically significant (P < 0.01). Although AUC values of LS within the three classes of CP scores were higher than in the four indicators of liver fibrosis, sensitivity and specificity were unstable. The ROC curves of LS combined with the four indicators of liver fibrosis revealed that: AUC and sensitivity in all indicators combined in the A class of CP score were higher than in LS alone, albeit with slightly decreased specificity; AUC and specificity in all indicators combined in the B class of CP score were higher than in LS alone, with unchanged sensitivity; AUC values (0.967), sensitivity (97.4%), and specificity (90%) of all indicators combined in the C class of CP score were higher than in LS alone (0.936, 92.1%, 83.3%). CONCLUSION: The diagnostic value of PBC cirrhosis degree in liver cirrhosis degree assessment by ARFI combined with the four indicators of serum liver fibrosis is of satisfactory effectiveness and has important clinical application value. PMID:27298571
49 CFR 232.205 - Class I brake test-initial terminal inspection.

Code of Federal Regulations, 2010 CFR

2010-10-01

... § 232.205 Class I brake test-initial terminal inspection. (a) Each train and each car in the train shall... tested solid block of cars to the train; (iii) Changing motive power; (iv) Removing or changing the... conduct a brake test pursuant to § 232.209 on those cars added to the train. (B) [Reserved] (b) Except as...
Assessment of the Treatability of Toxic Organics by Overland Flow,

DTIC Science & Technology

1983-01-01

Tab’ I . Occunrence of organic chemsicals in household products . (After Hathaway 1980.1 Product Classter of organ iCs Product Classe of organirs...volatilization. the various classes of organics and their presence in Another important property of organic chemicals household products are given in Table 1...23 iv TABLES Table Page I. Occurrence of organic chemicals in household
78 FR 24334 - Milk in the Northeast and Other Marketing Areas; Order Amending the Orders

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-25

...) allowances for cheese, butter, nonfat dry milk (NFDM) and dry whey contained in the Class III and Class IV....1715 per pound); NFDM ($0.1678 per pound); and dry whey ($0.1991 per pound). In addition, the butterfat... dry whey continues to be $0.1991 per pound (initially increased from $0.1956 per pound). Finally, the...
40 CFR 144.28 - Requirements for Class I, II, and III wells authorized by rule.

Code of Federal Regulations, 2010 CFR

2010-07-01

... proposed test or measurement to be made; (D) The amount, size, and location (by depth) of casing to be left..., internal pressure, and axial loading; (iv) Hole size; (v) Size and grade of all casing strings; and (vi... Class III wells the owner or operator shall provide to the Director a qualitative analysis and ranges in...
40 CFR 90.410 - Engine test cycle.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Engine test cycle. 90.410 Section 90... Procedures § 90.410 Engine test cycle. (a) Follow the appropriate 6-mode test cycle for Class I, I-B and II engines and 2-mode test cycle for Class I-A, III, IV, and V engines when testing spark-ignition engines...
Neurons immunoreactive for vasoactive intestinal polypeptide in the rat primary somatosensory cortex: morphology and spatial relationship to barrel-related columns.

PubMed

Bayraktar, T; Welker, E; Freund, T F; Zilles, K; Staiger, J F

2000-05-08

Vasoactive intestinal polypeptide (VIP) in neocortex affects neuronal excitability as well as cortical blood flow and metabolism. Interneurons immunoreactive for VIP (VIP-IR neurons) are characterized by their predominantly bipolar appearance and the radial orientation of their main dendrites. In order to determine whether the morphology of VIP-IR neurons is related to the functional organization of the cortex into vertical columns, we combined both immunostaining of neurons containing VIP and cytochrome oxidase histochemistry for visualizing barrels, morphological layer IV correlates of functional columns, in the primary somatosensory (barrel) cortex of rats. VIP-IR neurons were localized in supragranular (48%), granular (16%), and infragranular layers (36%) as well as in the white matter. In the granular layer, a clear trend that more neurons were located in interbarrel septa rather than in barrels could be observed, resulting in a neuronal density which was about one-third higher in the septal area. VIP-IR neurons from the different cortical layers were three-dimensionally reconstructed from serial sections by using a computer microscope system. The neurons were mostly bipolar. Striking morphological differences in both axonal and dendritic trees were found between neurons whose cell bodies were located in supragranular, granular, and the upper part of infragranular layers, and those whose cell bodies were located in the area below. The former had dendrites which often reached layer I, where they bifurcated several times, and axonal trees which were particularly oriented vertically, with a tangential extent smaller than the width of barrels. Therefore, these neurons were mostly confined to either a barrel- or septum-related column. By contrast, the dendrites of neurons of the latter group did not reach the granular layer. Furthermore, these neurons had axons with sometimes very long horizontal collaterals, which often spanned two, in one case three, barrel columns. It is proposed that the differential morphology of neurons with different locations as stated above parallels to some extent the divergence of input streaming into the corresponding layer-defined areas. As a possible consequence of this, VIP-IR neurons may be capable of adapting the excitability and metabolism of cortical compartments either in a spatially limited or more extensive way. Copyright 2000 Wiley-Liss, Inc.
The morphology and electrical geometry of rat jaw-elevator motoneurones.

PubMed Central

Moore, J A; Appenteng, K

1991-01-01

1. The aim of this work was to quantify both the morphology and electrical geometry of the dendritic trees of jaw-elevator motoneurones. To do this we have made intracellular recordings from identified motoneurones in anaesthetized rats, determined their membrane properties and then filled them with horseradish peroxidase by ionophoretic ejection. Four neurones were subsequently fully reconstructed and the lengths and diameters of all the dendritic segments measured. 2. The mean soma diameter was 25 microns and values of mean dendritic length for individual cells ranged from 514 to 773 microns. Dendrites branched on average 9.1 times to produce 10.2 end-terminations. Dendritic segments could be represented as constant diameter cylinders between branch points. Values of dendritic surface area ranged from 1.08 to 2.52 x 10(5) microns 2 and values of dendritic to total surface area from 98 to 99%. 3. At branch points the ratio of the summed diameters of the daughter dendrites to the 3/2 power against the parent dendrite to the 3/2 power was exactly 1.0. Therefore the individual branch points could be collapsed into a single cylinder. Furthermore for an individual dendrite the diameter of this cylinder remained constant with increasing electrical distance from the soma. Thus individual dendrites can be represented electrically as cylinders of constant diameter. 4. However dendrites of a given neurone terminated at different electrical distances from the soma. The equivalent-cylinder diameter of the combined dendritic tree remained constant over the proximal half and then showed a pronounced reduction over the distal half. The reduction in equivalent diameter could be ascribed to the termination of dendrites at differing electrical distances from the soma. Therefore the complete dendritic tree of these motoneurones is best represented as a cylinder over the proximal half of their electrical length but as a cone over the distal half. PMID:1804966
Dynamics of action potential backpropagation in basal dendrites of prefrontal cortical pyramidal neurons.

PubMed

Zhou, Wen-Liang; Yan, Ping; Wuskell, Joseph P; Loew, Leslie M; Antic, Srdjan D

2008-02-01

Basal dendrites of neocortical pyramidal neurons are relatively short and directly attached to the cell body. This allows electrical signals arising in basal dendrites to strongly influence the neuronal output. Likewise, somatic action potentials (APs) should readily propagate back into the basilar dendritic tree to influence synaptic plasticity. Two recent studies, however, determined that sodium APs are severely attenuated in basal dendrites of cortical pyramidal cells, so that they completely fail in distal dendritic segments. Here we used the latest improvements in the voltage-sensitive dye imaging technique (Zhou et al., 2007) to study AP backpropagation in basal dendrites of layer 5 pyramidal neurons of the rat prefrontal cortex. With a signal-to-noise ratio of > 15 and minimal temporal averaging (only four sweeps) we were able to sample AP waveforms from the very last segments of individual dendritic branches (dendritic tips). We found that in short- (< 150 microm) and medium (150-200 microm in length)-range basal dendrites APs backpropagated with modest changes in AP half-width or AP rise-time. The lack of substantial changes in AP shape and dynamics of rise is inconsistent with the AP-failure model. The lack of substantial amplitude boosting of the third AP in the high-frequency burst also suggests that in short- and medium-range basal dendrites backpropagating APs were not severely attenuated. Our results show that the AP-failure concept does not apply in all basal dendrites of the rat prefrontal cortex. The majority of synaptic contacts in the basilar dendritic tree actually received significant AP-associated electrical and calcium transients.
Golgi-type I and Golgi-type II neurons in the ventral anterior thalamic nucleus of the adult human: morphological features and quantitative analysis.

PubMed

Al-Hussain Bani Hani, Saleh M; El-Dwairi, Qasim A; Bataineh, Ziad M; Al-Haidari, Mohammad S; Al-Alami, Jamil

2008-05-01

The morphological and quantitative features of neurons in the adult human ventral anterior thalamic nucleus were studied in Golgi preparations. Two neuronal types were found and their quantitative features were studied. Golgi-type I neurons were medium to large cells with dense dendritic trees and dendritic protrusions and short hair-like appendages. They have somatic mean diameter of 30.8 microm (+/-9.4, n = 85). They have an average 100.3 dendritic branches, 48.97 dendritic branching points, and 58.85 dendritic tips. The mean diameters of their primary, secondary, and tertiary dendrites were 3.1 microm (+/-1, n = 80), 1.85 microm (+/-0.8, n = 145), and 1.5 microm (+/-0.4, n = 160), respectively. Golgi-type II neurons were small to medium cells with few sparsely branching dendrites and dendritic stalked appendages with or without terminal swellings. They have somatic mean diameters of 22.2 microm (+/-5.8, n = 120). They have an average 33.76 dendritic branches, 16.49 dendritic branching points, and 21.97 dendritic tips. The mean diameters of their primary, secondary, and tertiary dendrites were 1.6 microm (+/-0.86, n = 70), 1.15 microm (+/-0.55, n = 118), and 1 microm (+/-0.70, n = 95), respectively. These quantitative data may form the basis for further quantitative studies involving aging or some degenerative diseases that may affect cell bodies and/or dendritic trees of the Golgi-type I and/or Golgi-type II thalamic neurons.
Fine and distributed subcellular retinotopy of excitatory inputs to the dendritic tree of a collision-detecting neuron

PubMed Central

Zhu, Ying

2016-01-01

Individual neurons in several sensory systems receive synaptic inputs organized according to subcellular topographic maps, yet the fine structure of this topographic organization and its relation to dendritic morphology have not been studied in detail. Subcellular topography is expected to play a role in dendritic integration, particularly when dendrites are extended and active. The lobula giant movement detector (LGMD) neuron in the locust visual system is known to receive topographic excitatory inputs on part of its dendritic tree. The LGMD responds preferentially to objects approaching on a collision course and is thought to implement several interesting dendritic computations. To study the fine retinotopic mapping of visual inputs onto the excitatory dendrites of the LGMD, we designed a custom microscope allowing visual stimulation at the native sampling resolution of the locust compound eye while simultaneously performing two-photon calcium imaging on excitatory dendrites. We show that the LGMD receives a distributed, fine retinotopic projection from the eye facets and that adjacent facets activate overlapping portions of the same dendritic branches. We also demonstrate that adjacent retinal inputs most likely make independent synapses on the excitatory dendrites of the LGMD. Finally, we show that the fine topographic mapping can be studied using dynamic visual stimuli. Our results reveal the detailed structure of the dendritic input originating from individual facets on the eye and their relation to that of adjacent facets. The mapping of visual space onto the LGMD's dendrites is expected to have implications for dendritic computation. PMID:27009157

Wnt5 and Drl/Ryk Gradients Pattern the Drosophila Olfactory Dendritic Map

PubMed Central

Wu, Yuping; Helt, Jay-Christian; Wexler, Emily; Petrova, Iveta M.; Noordermeer, Jasprina N.; Fradkin, Lee G.

2014-01-01

During development, dendrites migrate to their correct locations in response to environmental cues. The mechanisms of dendritic guidance are poorly understood. Recent work has shown that the Drosophila olfactory map is initially formed by the spatial segregation of the projection neuron (PN) dendrites in the developing antennal lobe (AL). We report here that between 16 and 30 h after puparium formation, the PN dendrites undergo dramatic rotational reordering to achieve their final glomerular positions. During this period, a novel set of AL-extrinsic neurons express high levels of the Wnt5 protein and are tightly associated with the dorsolateral edge of the AL. Wnt5 forms a dorsolateral-high to ventromedial-low pattern in the antennal lobe neuropil. Loss of Wnt5 prevents the ventral targeting of the dendrites, whereas Wnt5 overexpression disrupts dendritic patterning. We find that Drl/Ryk, a known Wnt5 receptor, is expressed in a dorsolateral-to-ventromedial (DL > VM) gradient by the PN dendrites. Loss of Drl in the PNs results in the aberrant ventromedial targeting of the dendrites, a defect that is suppressed by reduction in Wnt5 gene dosage. Conversely, overexpression of Drl in the PNs results in the dorsolateral targeting of their dendrites, an effect that requires Drl's cytoplasmic domain. We propose that Wnt5 acts as a repulsive guidance cue for the PN dendrites, whereas Drl signaling in the dendrites inhibits Wnt5 signaling. In this way, the precise expression patterns of Wnt5 and Drl orient the PN dendrites allowing them to target their final glomerular positions. PMID:25378162
Neocortical dendritic complexity is controlled during development by NOMA-GAP-dependent inhibition of Cdc42 and activation of cofilin.

PubMed

Rosário, Marta; Schuster, Steffen; Jüttner, René; Parthasarathy, Srinivas; Tarabykin, Victor; Birchmeier, Walter

2012-08-01

Neocortical neurons have highly branched dendritic trees that are essential for their function. Indeed, defects in dendritic arborization are associated with human neurodevelopmental disorders. The molecular mechanisms regulating dendritic arbor complexity, however, are still poorly understood. Here, we uncover the molecular basis for the regulation of dendritic branching during cortical development. We show that during development, dendritic branching requires post-mitotic suppression of the RhoGTPase Cdc42. By generating genetically modified mice, we demonstrate that this is catalyzed in vivo by the novel Cdc42-GAP NOMA-GAP. Loss of NOMA-GAP leads to decreased neocortical volume, associated specifically with profound oversimplification of cortical dendritic arborization and hyperactivation of Cdc42. Remarkably, dendritic complexity and cortical thickness can be partially restored by genetic reduction of post-mitotic Cdc42 levels. Furthermore, we identify the actin regulator cofilin as a key regulator of dendritic complexity in vivo. Cofilin activation during late cortical development depends on NOMA-GAP expression and subsequent inhibition of Cdc42. Strikingly, in utero expression of active cofilin is sufficient to restore postnatal dendritic complexity in NOMA-GAP-deficient animals. Our findings define a novel cell-intrinsic mechanism to regulate dendritic branching and thus neuronal complexity in the cerebral cortex.
A Novel Class of Bis- and Tris-Chelate Diam(m)inebis(dicarboxylato)platinum(IV) Complexes as Potential Anticancer Prodrugs

PubMed Central

Varbanov, Hristo P.; Göschl, Simone; Heffeter, Petra; Theiner, Sarah; Roller, Alexander; Jensen, Frank; Jakupec, Michael A.; Berger, Walter; Galanski, Markus; Keppler, Bernhard K.

2015-01-01

A novel class of platinum(IV) complexes of the type [Pt(Am)-(R(COO)2)2], where Am is a chelating diamine or two monodentate am(m)ine ligands and R(COO)2 is a chelating dicarboxylato moiety, was synthesized. For this purpose, the reaction between the corresponding tetrahydroxidoplatinum(IV) precursors and various dicarboxylic acids, such as oxalic, malonic, 3-methylmalonic, and cyclobutanedicarboxylic acid, was utilized. All new compounds were characterized in detail, using 1D and 2D NMR techniques, ESI-MS, FTIR spectroscopy, elemental analysis, TGA, and X-ray diffraction. Their in vitro cytotoxicity was determined in a panel of human tumor cell lines (CH1, SW480 and A549) by means of the MTT colorimetric assay. Furthermore, the lipophilicity and redox properties of the novel complexes were evaluated in order to better understand their pharmacological behavior. The most promising drug candidate, 4b (Pt(DACH)(mal)2), demonstrated low in vivo toxicity but profound anticancer activity against both the L1210 leukemia and CT-26 colon carcinoma models. PMID:25032896
Targeted delivery of antigen processing inhibitors to antigen presenting cells via mannose receptors.

PubMed

Raiber, Eun-Ang; Tulone, Calogero; Zhang, Yanjing; Martinez-Pomares, Luisa; Steed, Emily; Sponaas, Anna M; Langhorne, Jean; Noursadeghi, Mahdad; Chain, Benjamin M; Tabor, Alethea B

2010-05-21

Improved chemical inhibitors are required to dissect the role of specific antigen processing enzymes and to complement genetic models. In this study we explore the in vitro and in vivo properties of a novel class of targeted inhibitor of aspartic proteinases, in which pepstatin is coupled to mannosylated albumin (MPC6), creating an inhibitor with improved solubility and the potential for selective cell tropism. Using these compounds, we have demonstrated that MPC6 is taken up via mannose receptor facilitated endocytosis, leading to a slow but continuous accumulation of inhibitor within large endocytic vesicles within dendritic cells and a parallel inhibition of intracellular aspartic proteinase activity. Inhibition of intracellular proteinase activity is associated with reduction in antigen processing activity, but this is epitope-specific, preferentially inhibiting processing of T cell epitopes buried within compact proteinase-resistant protein domains. Unexpectedly, we have also demonstrated, using quenched fluorescent substrates, that little or no cleavage of the disulfide linker takes place within dendritic cells. This does not appear to affect the activity of MPC6 as an inhibitor of cathepsins D and E in vitro and in vivo. Finally, we have shown that MPC6 selectively targets dendritic cells and macrophages in spleen in vivo. Preliminary results suggest that access to nonlymphoid tissues is very limited in the steady state but is strongly enhanced at local sites of inflammation. The strategy adopted for MPC6 synthesis may therefore represent a more general way to deliver chemical inhibitors to cells of the innate immune system, especially at sites of inflammation.
Parallel prefrontal pathways reach distinct excitatory and inhibitory systems in memory-related rhinal cortices.

PubMed

Bunce, Jamie G; Zikopoulos, Basilis; Feinberg, Marcia; Barbas, Helen

2013-12-15

To investigate how prefrontal cortices impinge on medial temporal cortices we labeled pathways from the anterior cingulate cortex (ACC) and posterior orbitofrontal cortex (pOFC) in rhesus monkeys to compare their relationship with excitatory and inhibitory systems in rhinal cortices. The ACC pathway terminated mostly in areas 28 and 35 with a high proportion of large terminals, whereas the pOFC pathway terminated mostly through small terminals in area 36 and sparsely in areas 28 and 35. Both pathways terminated in all layers. Simultaneous labeling of pathways and distinct neurochemical classes of inhibitory neurons, followed by analyses of appositions of presynaptic and postsynaptic fluorescent signal, or synapses, showed overall predominant association with spines of putative excitatory neurons, but also significant interactions with presumed inhibitory neurons labeled for calretinin, calbindin, or parvalbumin. In the upper layers of areas 28 and 35 the ACC pathway was associated with dendrites of neurons labeled with calretinin, which are thought to disinhibit neighboring excitatory neurons, suggesting facilitated hippocampal access. In contrast, in area 36 pOFC axons were associated with dendrites of calbindin neurons, which are poised to reduce noise and enhance signal. In the deep layers, both pathways innervated mostly dendrites of parvalbumin neurons, which strongly inhibit neighboring excitatory neurons, suggesting gating of hippocampal output to other cortices. These findings suggest that the ACC, associated with attention and context, and the pOFC, associated with emotional valuation, have distinct contributions to memory in rhinal cortices, in processes that are disrupted in psychiatric diseases. Copyright © 2013 Wiley Periodicals, Inc.
A comprehensive analysis of transfection-assisted delivery of iron oxide nanoparticles to dendritic cells.

PubMed

Toki, Shinji; Omary, Reed A; Wilson, Kevin; Gore, John C; Peebles, R Stokes; Pham, Wellington

2013-11-01

Polylysine (PL) has been used to facilitate dendritic cell (DC) uptake of super paramagnetic iron oxide (SPIO) nanoparticles for use in magnetic resonance imaging (MRI). In this work, we examined the effect of PL on cell toxicity and induction of cell maturation as manifested by the up-regulation of surface molecules. We found that PL became toxic to bone marrow-derived DCs (BMDCs) at the 10 μg/ml threshold. Incubation of BMDCs with 20 μg/ml of PL for 1h resulted in approximately 90% cell death. However, addition of SPIO nanoparticles rescued DCs from PL-induced death as the combination of SPIO with PL did not cause cytotoxicity until the PL concentration was 1000 μg/ml. Prolonged exposure to PL induced BMDC maturation as noted by the expression of surface molecules such as MHC class II, CD40, CCR7 and CD86. However, the combination of SPIO and PL did not induce BMDC maturation at 1h. However prolonged exposure to SPIO nanoparticles induced CD40 expression and protein expression of TNFα and KC. The data suggest that the use of PL to enhance the labeling of DCs with SPIO nanoparticles is a dedicated work. Appropriate calibration of the incubation time and concentrations of PL and SPIO nanoparticles is crucial to the development of MRI technology for noninvasive imaging of DCs in vivo. The authors of this study present detailed data on toxicity and efficiency of polylysine-facilitated uptake of USPIO-s by dendritic cells for cell-specific MR imaging. Copyright © 2013. Published by Elsevier Inc.
SNAP-25 requirement for dendritic growth of hippocampal neurons.

PubMed

Grosse, G; Grosse, J; Tapp, R; Kuchinke, J; Gorsleben, M; Fetter, I; Höhne-Zell, B; Gratzl, M; Bergmann, M

1999-06-01

Structure and dimension of the dendritic arbor are important determinants of information processing by the nerve cell, but mechanisms and molecules involved in dendritic growth are essentially unknown. We investigated early mechanisms of dendritic growth using mouse fetal hippocampal neurons in primary culture, which form processes during the first week in vitro. We detected a key component of regulated exocytosis, SNAP-25 (synaptosomal associated protein of 25 kDa), in axons and axonal terminals as well as in dendrites identified by the occurrence of the dendritic markers transferrin receptor and MAP2. Selective inactivation of SNAP-25 by botulinum neurotoxin A (BoNTA) resulted in inhibition of axonal growth and of vesicle recycling in axonal terminals. In addition, dendritic growth of hippocampal pyramidal and granule neurons was significantly inhibited by BoNTA. In contrast, cleavage of synaptobrevin by tetanus toxin had an effect on neither axonal nor dendritic growth. Our observations indicate that SNAP-25, but not synaptobrevin, is involved in constitutive axonal growth and dendrite formation by hippocampal neurons.
Nak regulates localization of clathrin sites in higher-order dendrites to promote local dendrite growth.

PubMed

Yang, Wei-Kang; Peng, Yu-Huei; Li, Hsun; Lin, Hsiu-Chen; Lin, Yu-Ching; Lai, Tzu-Ting; Suo, Hsien; Wang, Chien-Hsiang; Lin, Wei-Hsiang; Ou, Chan-Yen; Zhou, Xin; Pi, Haiwei; Chang, Henry C; Chien, Cheng-Ting

2011-10-20

During development, dendrites arborize in a field several hundred folds of their soma size, a process regulated by intrinsic transcription program and cell adhesion molecule (CAM)-mediated interaction. However, underlying cellular machineries that govern distal higher-order dendrite extension remain largely unknown. Here, we show that Nak, a clathrin adaptor-associated kinase, promotes higher-order dendrite growth through endocytosis. In nak mutants, both the number and length of higher-order dendrites are reduced, which are phenocopied by disruptions of clathrin-mediated endocytosis. Nak interacts genetically with components of the endocytic pathway, colocalizes with clathrin puncta, and is required for dendritic localization of clathrin puncta. More importantly, these Nak-containing clathrin structures preferentially localize to branching points and dendritic tips that are undergoing active growth. We present evidence that the Drosophila L1-CAM homolog Neuroglian is a relevant cargo of Nak-dependent internalization, suggesting that localized clathrin-mediated endocytosis of CAMs facilitates the extension of nearby higher-order dendrites. Copyright © 2011 Elsevier Inc. All rights reserved.
Dendritic Na+ spikes enable cortical input to drive action potential output from hippocampal CA2 pyramidal neurons

PubMed Central

Sun, Qian; Srinivas, Kalyan V; Sotayo, Alaba; Siegelbaum, Steven A

2014-01-01

Synaptic inputs from different brain areas are often targeted to distinct regions of neuronal dendritic arbors. Inputs to proximal dendrites usually produce large somatic EPSPs that efficiently trigger action potential (AP) output, whereas inputs to distal dendrites are greatly attenuated and may largely modulate AP output. In contrast to most other cortical and hippocampal neurons, hippocampal CA2 pyramidal neurons show unusually strong excitation by their distal dendritic inputs from entorhinal cortex (EC). In this study, we demonstrate that the ability of these EC inputs to drive CA2 AP output requires the firing of local dendritic Na+ spikes. Furthermore, we find that CA2 dendritic geometry contributes to the efficient coupling of dendritic Na+ spikes to AP output. These results provide a striking example of how dendritic spikes enable direct cortical inputs to overcome unfavorable distal synaptic locale to trigger axonal AP output and thereby enable efficient cortico-hippocampal information flow. DOI: http://dx.doi.org/10.7554/eLife.04551.001 PMID:25390033
Golgi-independent secretory trafficking through recycling endosomes in neuronal dendrites and spines

PubMed Central

Bowen, Aaron B; Bourke, Ashley M; Hiester, Brian G; Hanus, Cyril

2017-01-01

Neurons face the challenge of regulating the abundance, distribution and repertoire of integral membrane proteins within their immense, architecturally complex dendritic arbors. While the endoplasmic reticulum (ER) supports dendritic translation, most dendrites lack the Golgi apparatus (GA), an essential organelle for conventional secretory trafficking. Thus, whether secretory cargo is locally trafficked in dendrites through a non-canonical pathway remains a fundamental question. Here we define the dendritic trafficking itinerary for key synaptic molecules in rat cortical neurons. Following ER exit, the AMPA-type glutamate receptor GluA1 and neuroligin 1 undergo spatially restricted entry into the dendritic secretory pathway and accumulate in recycling endosomes (REs) located in dendrites and spines before reaching the plasma membrane. Surprisingly, GluA1 surface delivery occurred even when GA function was disrupted. Thus, in addition to their canonical role in protein recycling, REs also mediate forward secretory trafficking in neuronal dendrites and spines through a specialized GA-independent trafficking network. PMID:28875935
Stress-driven lithium dendrite growth mechanism and dendrite mitigation by electroplating on soft substrates

NASA Astrophysics Data System (ADS)

Wang, Xu; Zeng, Wei; Hong, Liang; Xu, Wenwen; Yang, Haokai; Wang, Fan; Duan, Huigao; Tang, Ming; Jiang, Hanqing

2018-03-01

Problems related to dendrite growth on lithium-metal anodes such as capacity loss and short circuit present major barriers to next-generation high-energy-density batteries. The development of successful lithium dendrite mitigation strategies is impeded by an incomplete understanding of the Li dendrite growth mechanisms, and in particular, Li-plating-induced internal stress in Li metal and its effect on Li growth morphology are not well addressed. Here, we reveal the enabling role of plating residual stress in dendrite formation through depositing Li on soft substrates and a stress-driven dendrite growth model. We show that dendrite growth is mitigated on such soft substrates through surface-wrinkling-induced stress relaxation in the deposited Li film. We demonstrate that this dendrite mitigation mechanism can be utilized synergistically with other existing approaches in the form of three-dimensional soft scaffolds for Li plating, which achieves higher coulombic efficiency and better capacity retention than that for conventional copper substrates.
Outcome of nonsurgical intervention in patients with perforated peptic ulcers.

PubMed

Lay, Ping-Lien; Huang, Hsin-Hung; Chang, Wei-Kuo; Hsieh, Tsai-Yuan; Huang, Tien-Yu; Lin, Hsuan-Hwai

2016-08-01

Although surgical intervention is the favorable treatment modality for perforated peptic ulcer, nonsurgical treatment is another option. The aim of this study is to analyze the results of conservative treatment for perforated peptic ulcer. Between 2003 and 2014, 403 patients were admitted to our hospital for perforated peptic ulcer, and 383 patients underwent surgery, whereas 20 were allocated to conservative treatment. The results of nonsurgical intervention in these patients were analyzed retrospectively. The overall mortality rate of conservative treatment was 40%. Eleven patients remained hospitalized less than 2 weeks; among them, patients with a high (≥IV) American Society of Anesthesiologists class at admission had higher mortality than those with a low (
[Clinical policy for management and risk stratification of community-acquired pneumonia in patients hospitalized on the basis of conventional admission criteria].

PubMed

Putinati, Stefano; Ballerin, Licia; Piattella, Marco; Ritrovato, Lucia; Zabini, Franco; Potena, Alfredo

2003-05-01

To identify discrepancies between Pneumonia Severity Index (PSI) risk class and the conventional criteria for deciding the site of care we performed a prospective observational study on 229 patients hospitalized for community-acquired pneumonia. PSI classes and corresponding mortality rates were as following: class I, 41 patients (0%); class II, 20 (0%); class III, 58 (1.7%); class IV, 86 (8.1%); class V, 24 (33.3%). Overall, 119 patients (52%) who were hospitalized according to conventional criteria were assigned to low-risk classes (I-III). Among these low risk patients, 58 (49%) had complications as respiratory failure, pleural effusion, hypotension or shock; among remaining patients, no reasons for admission were found. This latter group deserves prospective evaluation in randomized studies comparing in-hospital versus outpatient management.
Initial Interpretation and Evaluation of a Profile-Based Classification System for the Anxiety and Mood Disorders: Incremental Validity Compared to DSM-IV Categories

PubMed Central

Rosellini, Anthony J.; Brown, Timothy A.

2014-01-01

Limitations in anxiety and mood disorder diagnostic reliability and validity due to the categorical approach to classification used by the Diagnostic and Statistical Manual of Mental Disorders (DSM) have been long recognized. Although these limitations have led researchers to forward alternative classification schemes, few have been empirically evaluated. In a sample of 1,218 outpatients with anxiety and mood disorders, the present study examined the validity of Brown and Barlow's (2009) proposal to classify the anxiety and mood disorders using an integrated dimensional-categorical approach based on transdiagnostic emotional disorder vulnerabilities and phenotypes. Latent class analyses of seven transdiagnostic dimensional indicators suggested that a six-class (i.e., profile) solution provided the best model fit and was the most conceptually interpretable. Interpretation of the classes was further supported when compared with DSM-IV diagnoses (i.e., within-class prevalence of diagnoses, using diagnoses to predict class membership). In addition, hierarchical multiple regression models were used to demonstrate the incremental validity of the profiles; class probabilities consistently accounted for unique variance in anxiety and mood disorder outcomes above and beyond DSM diagnoses. These results provide support for the potential development and utility of a hybrid dimensional-categorical profile approach to anxiety and mood disorder classification. In particular, the availability of dimensional indicators and corresponding profiles may serve as a useful complement to DSM diagnoses for both researchers and clinicians. PMID:25265416
Orientations of dendritic growth during solidification

NASA Astrophysics Data System (ADS)

Lee, Dong Nyung

2017-03-01

Dendrites are crystalline forms which grow far from the limit of stability of the plane front and adopt an orientation which is as close as possible to the heat flux direction. Dendritic growth orientations for cubic metals, bct Sn, and hcp Zn, can be controlled by thermal conductivity, Young's modulus, and surface energy. The control factors have been elaborated. Since the dendrite is a single crystal, its properties such as thermal conductivity that influences the heat flux direction, the minimum Young's modulus direction that influences the strain energy minimization, and the minimum surface energy plane that influences the crystal/liquid interface energy minimization have been proved to control the dendritic growth direction. The dendritic growth directions of cubic metals are determined by the minimum Young's modulus direction and/or axis direction of symmetry of the minimum crystal surface energy plane. The dendritic growth direction of bct Sn is determined by its maximum thermal conductivity direction and the minimum surface energy plane normal direction. The primary dendritic growth direction of hcp Zn is determined by its maximum thermal conductivity direction and the minimum surface energy plane normal direction and the secondary dendrite arm direction of hcp Zn is normal to the primary dendritic growth direction.
The Evolution of Dendrite Morphology during Isothermal Coarsening

NASA Technical Reports Server (NTRS)

Alkemper, Jens; Mendoza, Roberto; Kammer, Dimitris; Voorhees, Peter W.

2003-01-01

Dendrite coarsening is a common phenomenon in casting processes. From the time dendrites are formed until the inter-dendritic liquid is completely solidified dendrites are changing shape driven by variations in interfacial curvature along the dendrite and resulting in a reduction of total interfacial area. During this process the typical length-scale of the dendrite can change by orders of magnitude and the final microstructure is in large part determined by the coarsening parameters. Dendrite coarsening is thus crucial in setting the materials parameters of ingots and of great commercial interest. This coarsening process is being studied in the Pb-Sn system with Sn-dendrites undergoing isothermal coarsening in a Pb-Sn liquid. Results are presented for samples of approximately 60% dendritic phase, which have been coarsened for different lengths of times. Presented are three-dimensional microstructures obtained by serial-sectioning and an analysis of these microstructures with regard to interface orientation and interfacial curvatures. These graphs reflect the evolution of not only the microstructure itself, but also of the underlying driving forces of the coarsening process. As a visualization of the link between the microstructure and the driving forces a three-dimensional microstructure with the interfaces colored according to the local interfacial mean curvature is shown.
Bi-stable dendrite in constant electric field: a model analysis.

PubMed

Baginskas, A; Gutman, A; Svirskis, G

1993-03-01

Some neurons possess dendritic persistent inward current, which is activated during depolarization. Dendrites can be stably depolarized, i.e. they are bi-stable if the net current is inward. A proper method to show the existence of dendritic bi-stability is putting the neuron into the electric field to induce transmembrane potential changes along the dendrites. Here we present analytical and computer simulation of the bi-stable dendrite in the d.c. field. A prominent jump to a depolarization plateau can be seen in the soma upon initial hyperpolarization of its membrane. If a considerable portion of dendrites are parallel to the field it is impossible to switch off the depolarization plateau by changing the direction and the strength of the electric field. There is nothing similar in neurons with ohmic dendrites. The results of the simulation conform to the experimental observations in turtle motoneurons [Hounsgaard J. and Kiehn O. (1993) J. Physiol., Lond. (in press)]; comparison of the theoretical and the experimental results makes semi-quantitative estimation of some electrical parameters of dendrites possible. We propose modifications of the experiment which enable one to measure dendritic length constants and other parameters of stained neurons.
A Comparison of the Effects of Intraosseous and Intravenous 5% Albumin on Infusion Time and Hemodynamic Measures in a Swine Model of Hemorrhagic Shock.

PubMed

Muir, Stacy L; Sheppard, Lance B; Maika-Wilson, Anne; Burgert, James M; Garcia-Blanco, Jose; Johnson, Arthur D; Coyner, Jennifer L

2016-08-01

Introduction Obtaining intravenous (IV) access in patients in hemorrhagic shock is often difficult and prolonged. Failed IV attempts delay life-saving treatment. Intraosseous (IO) access may often be obtained faster than IV access. Albumin (5%) is an option for prehospital volume expansion because of the absence of interference with coagulation and platelet function. Hypothesis/Problem There are limited data comparing the performance of IO and IV administered 5% albumin. The aims of this study were to compare the effects of tibial IO (TIO) and IV administration of 500 mL of 5% albumin on infusion time and hemodynamic measurements of heart rate (HR), mean arterial pressure (MAP), cardiac output (CO), and stroke volume (SV) in a swine model of hemorrhagic shock. Sixteen male swine were divided into two groups: TIO and IV. All subjects were anesthetized and a Class III hemorrhage was achieved by exsanguination of 31% of estimated blood volume (EBV) from a femoral artery catheter. Following exsanguination, 500 mL of 5% albumin was administered under pressurized infusion (300 mmHg) by the TIO or IV route and infusion time was recorded. Hemodynamic measurements of HR, MAP, CO, and SV were collected before and after exsanguination and every 20 seconds for 180 seconds during 5% albumin infusion. An independent t-test determined that IV 5% albumin infusion was significantly faster compared to IO (P=.01). Mean infusion time for TIO was seven minutes 35 seconds (SD=two minutes 44 seconds) compared to four minutes 32 seconds (SD=one minute 08 seconds) in the IV group. Multivariate Analysis of Variance was performed on hemodynamic data collected during the 5% albumin infusion. Analyses indicated there were no significant differences between the TIO and IV groups relative to MAP, CO, HR, or SV (P>.05). While significantly longer to infuse 5% albumin by the TIO route, the longer TIO infusion time may be negated as IO devices can be placed more quickly compared to repeated IV attempts. The lack of significant difference between the TIO and IV routes relative to hemodynamic measures indicate the TIO route is a viable route for the infusion of 5% albumin in a swine model of Class III hemorrhage. Muir SL , Sheppard LB , Maika-Wilson A , Burgert JM , Garcia-Blanco J , Johnson AD , Coyner JL . A comparison of the effects of intraosseous and intravenous 5% albumin on infusion time and hemodynamic measures in a swine model of hemorrhagic shock. Prehosp Disaster Med. 2016;31(4):436-442.
Antigen-B Cell Receptor Complexes Associate with Intracellular major histocompatibility complex (MHC) Class II Molecules*

PubMed Central

Barroso, Margarida; Tucker, Heidi; Drake, Lisa; Nichol, Kathleen; Drake, James R.

2015-01-01

Antigen processing and MHC class II-restricted antigen presentation by antigen-presenting cells such as dendritic cells and B cells allows the activation of naïve CD4+ T cells and cognate interactions between B cells and effector CD4+ T cells, respectively. B cells are unique among class II-restricted antigen-presenting cells in that they have a clonally restricted antigen-specific receptor, the B cell receptor (BCR), which allows the cell to recognize and respond to trace amounts of foreign antigen present in a sea of self-antigens. Moreover, engagement of peptide-class II complexes formed via BCR-mediated processing of cognate antigen has been shown to result in a unique pattern of B cell activation. Using a combined biochemical and imaging/FRET approach, we establish that internalized antigen-BCR complexes associate with intracellular class II molecules. We demonstrate that the M1-paired MHC class II conformer, shown previously to be critical for CD4 T cell activation, is incorporated selectively into these complexes and loaded selectively with peptide derived from BCR-internalized cognate antigen. These results demonstrate that, in B cells, internalized antigen-BCR complexes associate with intracellular MHC class II molecules, potentially defining a site of class II peptide acquisition, and reveal a selective role for the M1-paired class II conformer in the presentation of cognate antigen. These findings provide key insights into the molecular mechanisms used by B cells to control the source of peptides charged onto class II molecules, allowing the immune system to mount an antibody response focused on BCR-reactive cognate antigen. PMID:26400081
Distribution of Trauma Care Facilities in Oman in Relation to High-Incidence Road Traffic Injury Sites: Pilot study.

PubMed

Al-Kindi, Sara M; Naiem, Ahmed A; Taqi, Kadhim M; Al-Gheiti, Najla M; Al-Toobi, Ikhtiyar S; Al-Busaidi, Nasra Q; Al-Harthy, Ahmed Z; Taqi, Alaa M; Ba-Alawi, Sharif A; Al-Qadhi, Hani A

2017-11-01

Road traffic injuries (RTIs) are considered a major public health problem worldwide. In Oman, high numbers of RTIs and RTI-related deaths are frequently registered. This study aimed to evaluate the distribution of trauma care facilities in Oman with regards to their proximity to RTI-prevalent areas. This descriptive pilot study analysed RTI data recorded in the national Royal Oman Police registry from January to December 2014. The distribution of trauma care facilities was analysed by calculating distances between areas of peak RTI incidence and the closest trauma centre using Google Earth and Google Maps software (Google Inc., Googleplex, Mountain View, California, USA). A total of 32 trauma care facilities were identified. Four facilities (12.5%) were categorised as class V trauma centres. Of the facilities in Muscat, 42.9% were ranked as class IV or V. There were no class IV or V facilities in Musandam, Al-Wusta or Al-Buraimi. General surgery, orthopaedic surgery and neurosurgery services were available in 68.8%, 59.3% and 12.5% of the centres, respectively. Emergency services were available in 75.0% of the facilities. Intensive care units were available in 11 facilities, with four located in Muscat. The mean distance between a RTI hotspot and the nearest trauma care facility was 34.7 km; however, the mean distance to the nearest class IV or V facility was 83.3 km. The distribution and quality of trauma care facilities in Oman needs modification. It is recommended that certain centres upgrade their levels of trauma care in order to reduce RTI-associated morbidity and mortality in Oman.

Cost-Effectiveness of Sacubitril-Valsartan in Patients With Heart Failure With Reduced Ejection Fraction.

PubMed

Sandhu, Alexander T; Ollendorf, Daniel A; Chapman, Richard H; Pearson, Steven D; Heidenreich, Paul A

2016-11-15

Sacubitril-valsartan therapy reduces cardiovascular mortality compared with enalapril therapy in patients with heart failure with reduced ejection fraction. To evaluate the cost-effectiveness of sacubitril-valsartan versus angiotensin-converting enzyme inhibitor therapy in patients with chronic heart failure. Markov decision model. Clinical trials, observational analyses, reimbursement data from the Centers for Medicare & Medicaid Services, drug pricing databases, and Centers for Disease Control and Prevention life tables. Patients at an average age of 64 years, New York Heart Association (NYHA) class II to IV heart failure, and left ventricular ejection fraction of 0.40 or less. Lifetime. Societal. Treatment with sacubitril-valsartan or lisinopril. Life-years, quality-adjusted life-years (QALYs), costs, heart failure hospitalizations, and incremental cost-effectiveness ratios. The sacubitril-valsartan group experienced 0.08 fewer heart failure hospitalization, 0.69 additional life-year, 0.62 additional QALY, and $29 203 in incremental costs, equating to a cost per QALY gained of $47 053. The cost per QALY gained was $44 531 in patients with NYHA class II heart failure and $58 194 in those with class III or IV heart failure. Sacubitril-valsartan treatment was most sensitive to the duration of improved outcomes, with a cost per QALY gained of $120 623 if the duration was limited to the length of the trial (median, 27 months). No variations in other parameters caused the cost to exceed $100 000 per QALY gained. The benefit of sacubitril-valsartan is based on a single clinical trial. Treatment with sacubitril-valsartan provides reasonable value in reducing cardiovascular mortality and morbidity in patients with NYHA class II to IV heart failure. U.S. Department of Veterans Affairs and Institute for Clinical and Economic Review.
Septic shock sera containing circulating histones induce dendritic cell-regulated necrosis in fatal septic shock patients.

PubMed

Raffray, Loic; Douchet, Isabelle; Augusto, Jean-Francois; Youssef, Jihad; Contin-Bordes, Cecile; Richez, Christophe; Duffau, Pierre; Truchetet, Marie-Elise; Moreau, Jean-Francois; Cazanave, Charles; Leroux, Lionel; Mourrissoux, Gaelle; Camou, Fabrice; Clouzeau, Benjamin; Jeannin, Pascale; Delneste, Yves; Gabinski, Claude; Guisset, Olivier; Lazaro, Estibaliz; Blanco, Patrick

2015-04-01

Innate immune system alterations, including dendritic cell loss, have been reproducibly observed in patients with septic shock and correlated to adverse outcomes or nosocomial infections. The goal of this study is to better understand the mechanisms behind this observation in order to better assess septic shock pathogenesis. Prospective, controlled experimental study. Research laboratory at an academic medical center. The study enrolled 71 patients, 49 with septic shock and 22 with cardiogenic shock. Seventeen healthy controls served as reference. In vitro monocyte-derived dendritic cells were generated from healthy volunteers. Sera were assessed for their ability to promote in vitro dendritic cell death through flow cytometry detection in each group of patients. The percentage of apoptotic or necrotic dendritic cells was evaluated by annexin-V and propidium iodide staining. We observed that only patients with septic shock and not patients with pure cardiogenic shock were characterized by a rapid and profound loss of circulating dendritic cells. In vitro analysis revealed that sera from patients with septic shock induced higher dendritic cell death compared to normal sera or cardiogenic shock (p<0.005). Sera from surviving patients induced dendritic cell death through a caspase-dependent apoptotic pathway, whereas sera from nonsurviving patients induced dendritic cell-regulated necrosis. Dendritic cell necrosis was not due to necroptosis but was dependent of the presence of circulating histone. The toxicity of histones toward dendritic cell could be prevented by recombinant human activated protein C. Finally, we observed a direct correlation between the levels of circulating histones in patients and the ability of the sera to promote dendritic cell-regulated necrosis. The study demonstrates a differential mechanism of dendritic cell death in patients with septic shock that is dependent on the severity of the disease.
Three-dimensional spatial modeling of spines along dendritic networks in human cortical pyramidal neurons

PubMed Central

Larrañaga, Pedro; Benavides-Piccione, Ruth; Fernaud-Espinosa, Isabel; DeFelipe, Javier; Bielza, Concha

2017-01-01

We modeled spine distribution along the dendritic networks of pyramidal neurons in both basal and apical dendrites. To do this, we applied network spatial analysis because spines can only lie on the dendritic shaft. We expanded the existing 2D computational techniques for spatial analysis along networks to perform a 3D network spatial analysis. We analyzed five detailed reconstructions of adult human pyramidal neurons of the temporal cortex with a total of more than 32,000 spines. We confirmed that there is a spatial variation in spine density that is dependent on the distance to the cell body in all dendrites. Considering the dendritic arborizations of each pyramidal cell as a group of instances of the same observation (the neuron), we used replicated point patterns together with network spatial analysis for the first time to search for significant differences in the spine distribution of basal dendrites between different cells and between all the basal and apical dendrites. To do this, we used a recent variant of Ripley’s K function defined to work along networks. The results showed that there were no significant differences in spine distribution along basal arbors of the same neuron and along basal arbors of different pyramidal neurons. This suggests that dendritic spine distribution in basal dendritic arbors adheres to common rules. However, we did find significant differences in spine distribution along basal versus apical networks. Therefore, not only do apical and basal dendritic arborizations have distinct morphologies but they also obey different rules of spine distribution. Specifically, the results suggested that spines are more clustered along apical than in basal dendrites. Collectively, the results further highlighted that synaptic input information processing is different between these two dendritic domains. PMID:28662210
Three-dimensional spatial modeling of spines along dendritic networks in human cortical pyramidal neurons.

PubMed

Anton-Sanchez, Laura; Larrañaga, Pedro; Benavides-Piccione, Ruth; Fernaud-Espinosa, Isabel; DeFelipe, Javier; Bielza, Concha

2017-01-01

We modeled spine distribution along the dendritic networks of pyramidal neurons in both basal and apical dendrites. To do this, we applied network spatial analysis because spines can only lie on the dendritic shaft. We expanded the existing 2D computational techniques for spatial analysis along networks to perform a 3D network spatial analysis. We analyzed five detailed reconstructions of adult human pyramidal neurons of the temporal cortex with a total of more than 32,000 spines. We confirmed that there is a spatial variation in spine density that is dependent on the distance to the cell body in all dendrites. Considering the dendritic arborizations of each pyramidal cell as a group of instances of the same observation (the neuron), we used replicated point patterns together with network spatial analysis for the first time to search for significant differences in the spine distribution of basal dendrites between different cells and between all the basal and apical dendrites. To do this, we used a recent variant of Ripley's K function defined to work along networks. The results showed that there were no significant differences in spine distribution along basal arbors of the same neuron and along basal arbors of different pyramidal neurons. This suggests that dendritic spine distribution in basal dendritic arbors adheres to common rules. However, we did find significant differences in spine distribution along basal versus apical networks. Therefore, not only do apical and basal dendritic arborizations have distinct morphologies but they also obey different rules of spine distribution. Specifically, the results suggested that spines are more clustered along apical than in basal dendrites. Collectively, the results further highlighted that synaptic input information processing is different between these two dendritic domains.
Lethal graft-versus-host disease in congenital neutropenia caused by p14 deficiency after allogeneic bone marrow transplantation from an HLA-identical sibling.

PubMed

Bohn, Georg; Hardtke-Wolenski, Matthias; Zeidler, Cornelia; Maecker, Britta; Sauer, Martin; Sykora, Karl-Walter; Grigull, Lorenz; Welte, Karl; Klein, Christoph

2008-09-01

The molecular heterogeneity of severe congenital neutropenia (SCN) is increasingly recognized and may influence the risk-benefit assessment of therapeutic strategies. We report on a patient with p14 deficiency who succumbed to severe grade IV graft-versus-host disease (GvHD) after a human leukocyte antigen-identical bone marrow transplantion (BMT) from a sibling donor. Before BMT, in vitro generated p14-deficient dendritic cells showed a markedly elevated tumor necrosis factor (TNF-) alpha production upon toll-like receptor stimulation. We hypothesize that p14 deficiency predisposes to GvHD through increased TNF-alpha production. Adequate genetic testing is needed to prospectively assess potential risk factors for GvHD in defined SCN subgroups. (c) 2008 Wiley-Liss, Inc.
Investigations of the functional states of dendritic cells under different conditioned microenvironments by Fourier transformed infrared spectroscopy.

PubMed

Dong, Rong; Long, Jinhua; Xu, Xiaoli; Zhang, Chunlin; Wen, Zongyao; Li, Long; Yao, Weijuan; Zeng, Zhu

2014-01-10

Dendritic cells are potent and specialized antigen presenting cells, which play a crucial role in initiating and amplifying both the innate and adaptive immune responses. The dendritic cell-based vaccination against cancer has been clinically achieved promising successes. But there are still many challenges in its clinical application, especially for how to identify the functional states. The CD14+ monocytes were isolated from human peripheral blood after plastic adherence and purified to approximately 98% with cocktail immunomagnetic beads. The immature dendritic cells and mature dendritic cells were induced by traditional protocols. The resulting dendritic cells were cocultured with normal cells and cancer cells. The functional state of dendritic cells including immature dendritic cells (imDCs) and mature dendritic cells (mDCs) under different conditioned microenvironments were investigated by Fourier transformed infrared spectroscopy (FTIR) and molecular biological methods. The results of Fourier transformed infrared spectroscopy showed that the gene transcription activity and energy states of dendritic cells were specifically suppressed by tumor cells (P < 0.05 or 0.01). The expression levels of NF-kappa B (NF-κB) in dendritic cells were also specifically inhibited by tumor-derived factors (P < 0.05 or 0.01). Moreover, the ratios of absorption intensities of Fourier transformed infrared spectroscopy at given wave numbers were closely correlated with the expression levels of NF-κB (R2:0.69 and R2:0.81, respectively). Our results confirmed that the ratios of absorption intensities of Fourier transformed infrared spectroscopy at given wave numbers were positively correlated with the expression levels of NF-κB, suggesting that Fourier transformed infrared spectroscopy technology could be clinically applied to identify the functional states of dendritic cell when performing dendritic cell-based vaccination. It's significant for the simplification and standardization of dendritic cell-based vaccination clinical preparation protocols.
Institutional Research, Fiscal Year 1977: Report on Publicity Activities. Research Monograph IV.

ERIC Educational Resources Information Center

South Oklahoma City Junior Coll., OK.

During the first week of December, a 10% random sample of day classes and a 10% sample of night classes at South Oklahoma City Junior College were given a questionnaire dealing with the publicity activities used prior to and during the fall 1976 enrollment period. A total of 314 students responded, 179 night and 135 day students. Day students were…
Microstructural and Mechanical-Property Manipulation through Rapid Dendrite Growth and Undercooling in an Fe-based Multinary Alloy

PubMed Central

Ruan, Ying; Mohajerani, Amirhossein; Dao, Ming

2016-01-01

Rapid dendrite growth in single- or dual-phase multicomponent alloys can be manipulated to improve the mechanical properties of such metallic materials. Rapid growth of (αFe) dendrites was realized in an undercooled Fe-5Ni-5Mo-5Ge-5Co (wt.%) multinary alloy using the glass fluxing method. The relationship between rapid dendrite growth and the micro-/nano-mechanical properties of the alloy was investigated by analyzing the grain refinement and microstructural evolution resulting from the rapid dendrite growth. It was found that (αFe) dendrites grow sluggishly within a low but wide undercooling range. Once the undercooling exceeds 250 K, the dendritic growth velocity increases steeply until reaching a plateau of 31.8 ms−1. The increase in the alloy Vickers microhardness with increasing dendritic growth velocity results from the hardening effects of increased grain/phase boundaries due to the grain refinement, the more homogeneous distribution of the second phase along the boundaries, and the more uniform distribution of solutes with increased contents inside the grain, as verified also by nanohardness maps. Once the dendritic growth velocity exceeds ~8 ms−1, the rate of Vickers microhardness increase slows down significantly with a further increase in dendritic growth velocity, owing to the microstructural transition of the (αFe) phase from a trunk-dendrite to an equiaxed-grain microstructure. PMID:27539749
Numerical simulation of dendrite growth in nickel-based superalloy and validated by in-situ observation using high temperature confocal laser scanning microscopy

NASA Astrophysics Data System (ADS)

Yan, Xuewei; Xu, Qingyan; Liu, Baicheng

2017-12-01

Dendritic structures are the predominant microstructural constituents of nickel-based superalloys, an understanding of the dendrite growth is required in order to obtain the desirable microstructure and improve the performance of castings. For this reason, numerical simulation method and an in-situ observation technology by employing high temperature confocal laser scanning microscopy (HT-CLSM) were used to investigate dendrite growth during solidification process. A combined cellular automaton-finite difference (CA-FD) model allowing for the prediction of dendrite growth of binary alloys was developed. The algorithm of cells capture was modified, and a deterministic cellular automaton (DCA) model was proposed to describe neighborhood tracking. The dendrite and detail morphology, especially hundreds of dendrites distribution at a large scale and three-dimensional (3-D) polycrystalline growth, were successfully simulated based on this model. The dendritic morphologies of samples before and after HT-CLSM were both observed by optical microscope (OM) and scanning electron microscope (SEM). The experimental observations presented a reasonable agreement with the simulation results. It was also found that primary or secondary dendrite arm spacing, and segregation pattern were significantly influenced by dendrite growth. Furthermore, the directional solidification (DS) dendritic evolution behavior and detail morphology were also simulated based on the proposed model, and the simulation results also agree well with experimental results.
Tri-city study of Ecstasy use problems: a latent class analysis.

PubMed

Scheier, Lawrence M; Ben Abdallah, Arbi; Inciardi, James A; Copeland, Jan; Cottler, Linda B

2008-12-01

This study used latent class analysis to examine distinctive subtypes of Ecstasy users based on 24 abuse and dependence symptoms underlying standard DSM-IV criteria. Data came from a three site, population-based, epidemiological study to examine diagnostic nosology for Ecstasy use. Subject inclusion criteria included lifetime Ecstasy use exceeding five times and once in the past year, with participants ranging in age between 16 and 47 years of age from St. Louis, Miami, U.S. and Sydney, Australia. A satisfactory model typified four latent classes representing clearly differentiated diagnostic clusters including: (1) a group of sub-threshold users endorsing few abuse and dependence symptoms (negatives), (2) a group of 'diagnostic orphans' who had characteristic features of dependence for a select group of symptoms (mild dependent), (3) a 'transitional group' mimicking the orphans with regard to their profile of dependence also but reporting some abuse symptoms (moderate dependent), and (4) a 'severe dependent' group with a distinct profile of abuse and dependence symptoms. A multinomial logistic regression model indicated that certain latent classes showed unique associations with external non-diagnostic markers. Controlling for demographic characteristics and lifetime quantity of Ecstasy pill use, criminal behavior and motivational cues for Ecstasy use were the most efficient predictors of cluster membership. This study reinforces the heuristic utility of DSM-IV criteria applied to Ecstasy but with a different collage of symptoms that produced four distinct classes of Ecstasy users.
Quantitating protein synthesis, degradation, and endogenous antigen processing.

PubMed

Princiotta, Michael F; Finzi, Diana; Qian, Shu-Bing; Gibbs, James; Schuchmann, Sebastian; Buttgereit, Frank; Bennink, Jack R; Yewdell, Jonathan W

2003-03-01

Using L929 cells, we quantitated the macroeconomics of protein synthesis and degradation and the microeconomics of producing MHC class I associated peptides from viral translation products. To maintain a content of 2.6 x 10(9) proteins, each cell's 6 x 10(6) ribosomes produce 4 x 10(6) proteins min(-1). Each of the cell's 8 x 10(5) proteasomes degrades 2.5 substrates min(-1), creating one MHC class I-peptide complex for each 500-3000 viral translation products degraded. The efficiency of complex formation is similar in dendritic cells and macrophages, which play a critical role in activating T cells in vivo. Proteasomes create antigenic peptides at different efficiencies from two distinct substrate pools: rapidly degraded newly synthesized proteins that clearly represent defective ribosomal products (DRiPs) and a less rapidly degraded pool in which DRiPs may also predominate.
Control of adaptive immunity by the innate immune system.

PubMed

Iwasaki, Akiko; Medzhitov, Ruslan

2015-04-01

Microbial infections are recognized by the innate immune system both to elicit immediate defense and to generate long-lasting adaptive immunity. To detect and respond to vastly different groups of pathogens, the innate immune system uses several recognition systems that rely on sensing common structural and functional features associated with different classes of microorganisms. These recognition systems determine microbial location, viability, replication and pathogenicity. Detection of these features by recognition pathways of the innate immune system is translated into different classes of effector responses though specialized populations of dendritic cells. Multiple mechanisms for the induction of immune responses are variations on a common design principle wherein the cells that sense infections produce one set of cytokines to induce lymphocytes to produce another set of cytokines, which in turn activate effector responses. Here we discuss these emerging principles of innate control of adaptive immunity.
Morphological analysis of dendrites and spines by hybridization of ridge detection with twin support vector machine.

PubMed

Wang, Shuihua; Chen, Mengmeng; Li, Yang; Shao, Ying; Zhang, Yudong; Du, Sidan; Wu, Jane

2016-01-01

Dendritic spines are described as neuronal protrusions. The morphology of dendritic spines and dendrites has a strong relationship to its function, as well as playing an important role in understanding brain function. Quantitative analysis of dendrites and dendritic spines is essential to an understanding of the formation and function of the nervous system. However, highly efficient tools for the quantitative analysis of dendrites and dendritic spines are currently undeveloped. In this paper we propose a novel three-step cascaded algorithm-RTSVM- which is composed of ridge detection as the curvature structure identifier for backbone extraction, boundary location based on differences in density, the Hu moment as features and Twin Support Vector Machine (TSVM) classifiers for spine classification. Our data demonstrates that this newly developed algorithm has performed better than other available techniques used to detect accuracy and false alarm rates. This algorithm will be used effectively in neuroscience research.
40 CFR 205.155 - Motorcycle class and manufacturer abbreviation.

Code of Federal Regulations, 2014 CFR

2014-07-01

... separate combinations of the following parameters: (1) Engine type: (i) Gasoline—two stroke. (ii) Gasoline—four stroke. (iii) Gasoline—rotary. (iv) Other. (2) Engine displacement. (3) Engine configuration: (i...
40 CFR 205.155 - Motorcycle class and manufacturer abbreviation.

Code of Federal Regulations, 2012 CFR

2012-07-01

... separate combinations of the following parameters: (1) Engine type: (i) Gasoline—two stroke. (ii) Gasoline—four stroke. (iii) Gasoline—rotary. (iv) Other. (2) Engine displacement. (3) Engine configuration: (i...
40 CFR 205.155 - Motorcycle class and manufacturer abbreviation.

Code of Federal Regulations, 2013 CFR

2013-07-01

... separate combinations of the following parameters: (1) Engine type: (i) Gasoline—two stroke. (ii) Gasoline—four stroke. (iii) Gasoline—rotary. (iv) Other. (2) Engine displacement. (3) Engine configuration: (i...
40 CFR 205.155 - Motorcycle class and manufacturer abbreviation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... separate combinations of the following parameters: (1) Engine type: (i) Gasoline—two stroke. (ii) Gasoline—four stroke. (iii) Gasoline—rotary. (iv) Other. (2) Engine displacement. (3) Engine configuration: (i...
40 CFR 205.155 - Motorcycle class and manufacturer abbreviation.

Code of Federal Regulations, 2011 CFR

2011-07-01

... separate combinations of the following parameters: (1) Engine type: (i) Gasoline—two stroke. (ii) Gasoline—four stroke. (iii) Gasoline—rotary. (iv) Other. (2) Engine displacement. (3) Engine configuration: (i...
21 CFR 520.1780 - Pimobendan.

Code of Federal Regulations, 2010 CFR

2010-04-01

... severe (modified New York Heart Association Class II, III, or IV) congestive heart failure due to... heart failure as appropriate on a case-by-case basis. (3) Limitations. Federal law restricts this drug...
21 CFR 520.1780 - Pimobendan.

Code of Federal Regulations, 2012 CFR

2012-04-01

... severe (modified New York Heart Association Class II, III, or IV) congestive heart failure due to... heart failure as appropriate on a case-by-case basis. (3) Limitations. Federal law restricts this drug...

21 CFR 520.1780 - Pimobendan.

Code of Federal Regulations, 2013 CFR

2013-04-01

... severe (modified New York Heart Association Class II, III, or IV) congestive heart failure due to... heart failure as appropriate on a case-by-case basis. (3) Limitations. Federal law restricts this drug...
21 CFR 520.1780 - Pimobendan.

Code of Federal Regulations, 2011 CFR

2011-04-01

... severe (modified New York Heart Association Class II, III, or IV) congestive heart failure due to... heart failure as appropriate on a case-by-case basis. (3) Limitations. Federal law restricts this drug...
21 CFR 520.1780 - Pimobendan.

Code of Federal Regulations, 2014 CFR

2014-04-01

... severe (modified New York Heart Association Class II, III, or IV) congestive heart failure due to... heart failure as appropriate on a case-by-case basis. (3) Limitations. Federal law restricts this drug...
Divergent Effects of Dendritic Cells on Pancreatitis

DTIC Science & Technology

2015-09-01

role of dendritic cells in pancreatitis. Dendritic cells are professional antigen presenting cells which initiate innate and adaptive immune... Lymphoid -tissue-specific homing of bone- marrow-derived dendritic cells . Blood. 113:6638–6647. http://dx.doi .org/10.1182/blood-2009-02-204321 Dapito...Award Number: W81XWH-12-1-0313 TITLE: Divergent Effects of Dendritic Cells on Pancreatitis PRINCIPAL INVESTIGATOR: Dr. George Miller
A novel CARD containing splice-isoform of CIITA regulates nitric oxide synthesis in dendritic cells.

PubMed

Huang, Dachuan; Lim, Sylvia; Chua, Rong Yuan Ray; Shi, Hong; Ng, Mah Lee; Wong, Siew Heng

2010-03-01

MHC class II expression is controlled mainly at transcriptional level by class II transactivator (CIITA), which is a non-DNA binding coactivator and serves as a master control factor for MHC class II genes expression. Here, we describe the function of a novel splice-isoform of CIITA, DC-expressed caspase inhibitory isoform of CIITA (or DC-CASPIC), and we show that the expression of DCCASPIC in DC is upregulated upon lipopolysaccharides (LPS) induction. DC-CASPIC localizes to mitochondria, and protein-protein interaction study demonstrates that DC-CASPIC interacts with caspases and inhibits its activity in DC. Consistently, DC-CASPIC suppresses caspases-induced degradation of nitric oxide synthase-2 (NOS2) and subsequently promotes the synthesis of nitric oxide (NO). NO is an essential regulatory molecule that modulates the capability of DC in stimulating T cell proliferation/activation in vitro; hence, overexpression of DC-CASPIC in DC enhances this stimulation. Collectively, our findings reveal that DC-CASPIC is a key molecule that regulates caspases activity and NO synthesis in DC.
Exosomal cancer immunotherapy is independent of MHC molecules on exosomes.

PubMed

Hiltbrunner, Stefanie; Larssen, Pia; Eldh, Maria; Martinez-Bravo, Maria-Jose; Wagner, Arnika K; Karlsson, Mikael C I; Gabrielsson, Susanne

2016-06-21

Peptide-loaded exosomes are promising cancer treatment vehicles; however, moderate T cell responses in human clinical trials indicate a need to further understand exosome-induced immunity. We previously demonstrated that antigen-loaded exosomes carry whole protein antigens and require B cells for inducing antigen-specific T cells. Therefore, we investigated the relative importance of exosomal major histocompatibility complex (MHC) class I for the induction of antigen-specific T cell responses and tumour protection. We show that ovalbumin-loaded dendritic cell-derived exosomes from MHCI-/- mice induce antigen-specific T cells at the same magnitude as wild type exosomes. Furthermore, exosomes lacking MHC class I, as well as exosomes with both MHC class I and II mismatch, induced tumour infiltrating T cells and increased overall survival to the same extent as syngeneic exosomes in B16 melanoma. In conclusion, T cell responses are independent of exosomal MHC/peptide complexes if whole antigen is present. This establishes the prospective of using impersonalised exosomes, and will greatly increase the feasibility of designing exosome-based vaccines or therapeutic approaches in humans.
Ternary eutectic dendrites: Pattern formation and scaling properties

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

Rátkai, László; Szállás, Attila; Pusztai, Tamás

2015-04-21

Extending previous work [Pusztai et al., Phys. Rev. E 87, 032401 (2013)], we have studied the formation of eutectic dendrites in a model ternary system within the framework of the phase-field theory. We have mapped out the domain in which two-phase dendritic structures grow. With increasing pulling velocity, the following sequence of growth morphologies is observed: flat front lamellae → eutectic colonies → eutectic dendrites → dendrites with target pattern → partitionless dendrites → partitionless flat front. We confirm that the two-phase and one-phase dendrites have similar forms and display a similar scaling of the dendrite tip radius with themore » interface free energy. It is also found that the possible eutectic patterns include the target pattern, and single- and multiarm spirals, of which the thermal fluctuations choose. The most probable number of spiral arms increases with increasing tip radius and with decreasing kinetic anisotropy. Our numerical simulations confirm that in agreement with the assumptions of a recent analysis of two-phase dendrites [Akamatsu et al., Phys. Rev. Lett. 112, 105502 (2014)], the Jackson-Hunt scaling of the eutectic wavelength with pulling velocity is obeyed in the parameter domain explored, and that the natural eutectic wavelength is proportional to the tip radius of the two-phase dendrites. Finally, we find that it is very difficult/virtually impossible to form spiraling two-phase dendrites without anisotropy, an observation that seems to contradict the expectations of Akamatsu et al. Yet, it cannot be excluded that in isotropic systems, two-phase dendrites are rare events difficult to observe in simulations.« less
Synthesis of ZnTe dendrites on multi-walled carbon nanotubes/polyimide nanocomposite membrane by electrochemical atomic layer deposition and photoelectrical property research

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

Jiang, Yimin; Kou, Huanhuan; Li, Jiajia

2012-10-15

We report on the electrochemical atomic layer deposition (EC-ALD) of ZnTe dendrites on the carboxyl-functionalized multi-walled carbon nanotubes/polyimide (COOH-MWCNTs/PI) membrane. Electrochemical characteristics were studied by cyclic voltammetry (CV) and the deposition of ZnTe dendrites was completed using amperometric method (I-t). The prepared ZnTe dendrites were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The growth mechanism of ZnTe dendrites was elucidated to give a deep understanding of crystal growth. The concentration of reagents and deposition cycle had a significant effect on the morphology and structure of deposits. UV-vis transmission study indicated a direct bandmore » gap of 2.26 eV. Photoelectrical measurement confirmed the p-type conductivity of ZnTe dendrites, which indicated that the dendritic ZnTe crystals may have potential practical application in optoelectronic devices. - Graphical abstract: Representative SEM images of ZnTe dendrites. (a) Panorama of ZnTe dendrites; (b) a single dendrite. The regular branches appeared like leaves and showed a parallel arrangement layer upon layer between each other. Highlights: Black-Right-Pointing-Pointer ZnTe dendrites were successfully synthesized on CNTs/PI membrane by electrodeposition. Black-Right-Pointing-Pointer The growth mechanism of ZnTe dendritic structures was investigated in detail. Black-Right-Pointing-Pointer The concentration and deposition cycle greatly affected the morphology of ZnTe. Black-Right-Pointing-Pointer OCP and I-t studies showed that ZnTe can be beneficial to photoelectric applications.« less
Slice cultures of the imprinting-relevant forebrain area MNH of the domestic chick: quantitative characterization of neuronal morphology.

PubMed

Hofmann, H; Braun, K

1995-05-26

The persistence of morphological features of neurons in slice cultures of the imprinting-relevant forebrain area MNH (mediorostral neostriatum and hyperstriatum ventrale) of the domestic chick was analysed at 7, 14, 21 and 28 days in vitro. After having been explanted and kept in culture the neurons in vitro have larger soma areas, longer and more extensively branched dendritic trees and lower spine frequencies compared to the neurons in vivo. During the analyzed culturing period, the parameters soma area, total and mean dendritic length, number of dendrites, number of dendritic nodes per dendrite and per neuron as well as the spine densities in different dendritic segments showed no significant differences between early and late periods. Highly correlated in every age group were the total dendritic length and the number of dendritic nodes per neuron, indicating regular ramification during dendritic growth. Since these morphological parameters remain stable during the first 4 weeks in vitro, this culture system may provide a suitable model to investigate experimentally induced morphological changes.
Maximization of the connectivity repertoire as a statistical principle governing the shapes of dendritic arbors

PubMed Central

Wen, Quan; Stepanyants, Armen; Elston, Guy N.; Grosberg, Alexander Y.; Chklovskii, Dmitri B.

2009-01-01

The shapes of dendritic arbors are fascinating and important, yet the principles underlying these complex and diverse structures remain unclear. Here, we analyzed basal dendritic arbors of 2,171 pyramidal neurons sampled from mammalian brains and discovered 3 statistical properties: the dendritic arbor size scales with the total dendritic length, the spatial correlation of dendritic branches within an arbor has a universal functional form, and small parts of an arbor are self-similar. We proposed that these properties result from maximizing the repertoire of possible connectivity patterns between dendrites and surrounding axons while keeping the cost of dendrites low. We solved this optimization problem by drawing an analogy with maximization of the entropy for a given energy in statistical physics. The solution is consistent with the above observations and predicts scaling relations that can be tested experimentally. In addition, our theory explains why dendritic branches of pyramidal cells are distributed more sparsely than those of Purkinje cells. Our results represent a step toward a unifying view of the relationship between neuronal morphology and function. PMID:19622738
Selected mode of dendritic growth with n-fold symmetry in the presence of a forced flow

NASA Astrophysics Data System (ADS)

Alexandrov, D. V.; Galenko, P. K.

2017-07-01

The effect of n-fold crystal symmetry is investigated for a two-dimensional stable dendritic growth in the presence of a forced convective flow. We consider dendritic growth in a one-component undercooled liquid. The theory is developed for the parabolic solid-liquid surface of dendrite growing at arbitrary growth Péclet numbers keeping in mind small anisotropies of surface energy and growth kinetics. The selection criterion determining the stable growth velocity of the dendritic tip and its stable tip diameter is found on the basis of solvability analysis. The obtained criterion includes previously developed theories of thermally and kinetically controlled dendritic growth with convection for the case of four-fold crystal symmetry. The obtained nonlinear system of equations (representing the selection criterion and undercooling balance) for the determination of dendrite tip velocity and dendrite tip diameter is analytically solved in a parametric form. These exact solutions clearly demonstrate a transition between thermally and kinetically controlled growth regimes. In addition, we show that the dendrites with larger crystal symmetry grow faster than those with smaller symmetry.
42 CFR 416.195 - Determination of membership in new classes of new technology IOLs.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) Reduced risk of intraoperative or postoperative complication or trauma; (ii) Accelerated postoperative recovery; (iii) Reduced induced astigmatism; (iv) Improved postoperative visual acuity; (v) More stable...
42 CFR 416.195 - Determination of membership in new classes of new technology IOLs.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) Reduced risk of intraoperative or postoperative complication or trauma; (ii) Accelerated postoperative recovery; (iii) Reduced induced astigmatism; (iv) Improved postoperative visual acuity; (v) More stable...
Psychological Effects of Chemical Defense Ensemble Imposed Heat Stress on Army Aviators

DTIC Science & Technology

1982-11-01

INTRODUCTION Army aviation is currently increasing its emphasis on Chemical Defense (CD) training . In fact, Interim Change 101 (23 Dec 1981) to the...Aircrew Training Manual (TC 1-135) makes ir-flight training in full Mission Oriented Protective Posture (MOPP) IV mandatory. Training in MOPP IV will...Wing Class and had similar training and flight histories. All were acclimaite1d to the 2ocal environment, in good physical condition, and between the
Biologic Disease-modifying Antirheumatic Drug (bDMARD)-induced Neutropenia: A Registry from a Retrospective Cohort of Patients with Rheumatic Diseases Treated with 3 Classes of Intravenous bDMARD.

PubMed

Espinoza, Francisco; Le Blay, Pierre; Combe, Bernard

2017-06-01

To examine the rate, risks factors, and consequences of neutropenia induced by intravenous (IV) biologic disease-modifying antirheumatic drugs (bDMARD). We conducted a retrospective cohort study in 499 patients with rheumatic diseases treated by IV abatacept (ABA), infliximab (IFX), or tocilizumab (TCZ). Rheumatoid arthritis (RA) was the most frequent diagnosis (72%). Fifty-two patients (10.4%) experienced at least 1 episode of neutropenia. No episodes of grade 4 neutropenia were documented. TCZ was more frequently related to neutropenia than ABA or IFX (18.6% vs 3.8% and 2.8%, respectively, p < 0.001). The following factors were identified as predictors of experiencing neutropenia with IV bDMARD: history of neutropenia with methotrexate (MTX; synthetic DMARD; OR 1.56, 95% CI 1.17-7.14), concomitant treatment by MTX (OR 1.21, 95% CI 1.01-2.64), and TCZ treatment (OR 2.72, 95% CI 1.53-9.05). Patients experiencing a TCZ-induced neutropenia did not show a higher risk of severe infections; however, this group had a shorter drug survival (9 mos vs 20 mos, p < 0.02) compared with TCZ patients without neutropenia. Among 3 different classes of IV bDMARD, TCZ is associated with the higher risk of neutropenia. No increased frequency of infection episodes was documented in this group.
Minimizing shrinkage of interdental papilla height when treating multiple Miller Class III gingival recession defects.

PubMed

Mahn, Douglas H

2015-04-01

Miller Class III and IV gingival recession defects have interdental bone and soft-tissue loss that limit root coverage. Given the importance of the interdental papilla, protecting the integrity of this structure would seem prudent. Tunnel techniques have been successfully used to protect the interdental papilla. This article discusses the results of two cases in which multiple Miller Class III gingival recession defects were treated using tunnel-grafting techniques and an acellular dermal matrix. In both cases, root coverage was achieved while protecting the interdental papilla height.
Convection Effects in Three-dimensional Dendritic Growth

NASA Technical Reports Server (NTRS)

Lu, Yili; Beckermann, C.; Karma, A.

2003-01-01

A phase-field model is developed to simulate free dendritic growth coupled with fluid flow for a pure material in three dimensions. The preliminary results presented here illustrate the strong influence of convection on the three-dimensional (3D) dendrite growth morphology. The detailed knowledge of the flow and temperature fields in the melt around the dendrite from the simulations allows for a detailed understanding of the convection effects on dendritic growth.
Orientation Dependence of Columnar Dendritic Growth with Sidebranching Behaviors in Directional Solidification: Insights from Phase-Field Simulations

NASA Astrophysics Data System (ADS)

Xing, Hui; Dong, Xianglei; Wang, Jianyuan; Jin, Kexin

2018-04-01

In this study, a thin-interface phase-field model was employed to study the orientation dependence of the columnar dendritic growth with sidebranching behaviors in directional solidification. It was found that the dimensionless tip undercooling increases with the increase of misorientation angle for three pulling velocities. The primary spacing is found to be a function of misorientation angle, and the dimensionless primary spacing with respect to the misorientation angle follows the orientation correction given by Gandin and Rappaz (Acta. Metall. 42:2233-2246, 1994). For the analysis of the dendritic tip, the two-dimensional (2-D) form of the nonaxisymmetric needle crystal was used to determine the radius of the tilted columnar dendrite. Based on the definitions of open side and constrained side of the dendrite, the analysis of the width active sidebranches and the dendritic area in 2-D with respect to the distance from the dendritic tip was carried out to investigate the asymmetrical dendrite envelop and sidebranching behaviors on the two sides in directional solidification. The obtained prefactor and exponent with respect to misorientation angle are discussed, showing that the sidebranching behaviors of a tilted columnar dendritic array obey a similar power-law relationship with that of a free dendritic growth.
Color-color diagrams in near infrared: (J-H)/(H-K). I

NASA Astrophysics Data System (ADS)

Gyulbudaghian, Armen L.; Baloian, N.; Sanchez, I. A.

2017-12-01

In the paper are presented the color-color diagrams (J-H)/(H-K) for all stars with visible values B<11, for which in the known catalogs the values of J, H, K, and also spectral classes and luminosity classes of these stars are given. The diagrams are constructed for luminosity classes Ia, Ib, II, III, IV, V. The similarity of diagrams for classes Ia and Ib (super giants) and II (giants), is obvious from these diagrams. The diagrams obtained by us can be used for discovering of new young stars and also for determining of color excesses of investigating stars. Maximal amounts of stars are registered in the classes V and III. There is a tendency of increasing of J-H and H-K along the sequence of spectral classes O - M, which is correct for all luminosity classes.
Dauer-specific dendrite arborization in C. elegans is regulated by KPC-1/Furin.

PubMed

Schroeder, Nathan E; Androwski, Rebecca J; Rashid, Alina; Lee, Harksun; Lee, Junho; Barr, Maureen M

2013-08-19

Dendrites often display remarkably complex and diverse morphologies that are influenced by developmental and environmental cues. Neuroplasticity in response to adverse environmental conditions entails both hypertrophy and resorption of dendrites. How dendrites rapidly alter morphology in response to unfavorable environmental conditions is unclear. The nematode Caenorhabditis elegans enters into a stress-resistant dauer larval stage in response to an adverse environment. Here we show that the IL2 bipolar sensory neurons undergo dendrite arborization and axon remodeling during dauer development. When dauer larvae are returned to favorable environmental conditions, animals resume reproductive development and IL2 dendritic branches retract, leaving behind remnant branches in postdauer L4 and adult animals. The C. elegans furin homolog KPC-1 is required for dauer IL2 dendritic arborization and dauer-specific nictation behavior. KPC-1 is also necessary for dendritic arborization of PVD and FLP sensory neurons. In mammals, furin is essential, ubiquitously expressed, and associated with numerous pathologies, including neurodegenerative diseases. While broadly expressed in C. elegans neurons and epithelia, KPC-1 acts cell autonomously in IL2 neurons to regulate dauer-specific dendritic arborization and nictation. Neuroplasticity of the C. elegans IL2 sensory neurons provides a paradigm to study stress-induced and reversible dendritic branching, and the role of environmental and developmental cues in this process. The newly discovered role of KPC-1 in dendrite morphogenesis provides insight into the function of proprotein convertases in nervous system development. Copyright © 2013 Elsevier Ltd. All rights reserved.

Phase-field-crystal investigation of the morphology of a steady-state dendrite tip on the atomic scale

NASA Astrophysics Data System (ADS)

Tang, Sai; Wang, Jincheng; Li, Junjie; Wang, Zhijun; Guo, Yaolin; Guo, Can; Zhou, Yaohe

2017-06-01

Through phase-field-crystal (PFC) simulations, we investigated, on the atomic scale, the crucial role played by interface energy anisotropy and growth driving force during the morphological evolution of a dendrite tip at low growth driving force. In the layer-by-layer growth manner, the interface energy anisotropy drives the forefront of the dendrite tip to evolve to be highly similar to the corner of the corresponding equilibrium crystal from the aspects of atom configuration and morphology, and thus affects greatly the formation and growth of a steady-state dendrite tip. Meanwhile, the driving force substantially influences the part behind the forefront of the dendrite tip, rather than the forefront itself. However, as the driving force increases enough to change the layer-by-layer growth to the multilayer growth, the morphology of the dendrite tip's forefront is completely altered. Parabolic fitting of the dendrite tip reveals that an increase in the influence of interface energy anisotropy makes dendrite tips deviate increasingly from a parabolic shape. By quantifying the deviations under various interface energy anisotropies and growth driving forces, it is suggested that a perfect parabola is an asymptotic limit for the shape of the dendrite tips. Furthermore, the atomic scale description of the dendrite tip obtained in the PFC simulation is compatible with the mesoscopic results obtained in the phase-field simulation in terms of the dendrite tip's morphology and the stability criterion constant.
Immunosuppressant effect of IDS 30, a stinging nettle leaf extract, on myeloid dendritic cells in vitro.

PubMed

Broer, Johanna; Behnke, Bert

2002-04-01

Dendritic cells are important antigen presenting cells that play a role in the initiation of rheumatoid arthritis (RA). The stinging nettle leaf extract IDS 30 (Hox alpha) has been recommended for adjuvant therapy of rheumatic diseases. We investigated the immunomodulating effect of IDS 30 extract on the maturation of hematopoietic dendritic cells. Human dendritic cells were generated from peripheral blood mononuclear cells cultured in granulocyte macrophage-colony stimulating factor and interleukin 4 (IL-4). Dendritic cell maturation was induced by keyhole limped hemocyanin (KLH). Dendritic cell phenotype was characterized by flow cytometric analysis; dendritic cell cytokine production was measured by ELISA. The ability of dendritic cells to activate naive autologous T cells was evaluated by mixed leukocyte reaction. IDS 30 prevented the maturation of dendritic cells, but did not affect their viability. IDS 30 reduced the expression of CD83 and CD86. It increased the expression of chemokine receptor 5 and CD36 in a dose dependent manner. The secretion of tumor necrosis factor-alpha was reduced. Application of IDS 30 to dendritic cells in culture caused a high endocytosis of dextran and a low capacity to stimulate T cell proliferation. Our in vitro results showed the suppressive effect of IDS 30 on the maturation of human myeloid dendritic cells, leading to reduced induction of primary T cell responses. This may contribute to the therapeutic effect of IDS 30 on T cell mediated inflammatory diseases like RA.
Mapping of dendritic lesions in patients with herpes simplex keratitis using in vivo confocal microscopy

PubMed Central

Yokogawa, Hideaki; Kobayashi, Akira; Mori, Natsuko; Sugiyama, Kazuhisa

2015-01-01

Purpose To produce a two-dimensional reconstruction map of dendritic lesions in patients with herpes simplex keratitis (HSK) using in vivo confocal microscopy. Methods Four eyes of four patients (mean 65.8 years) with HSK presenting with a dendritic lesion were enrolled. Slit-lamp biomicroscopy and in vivo laser confocal microscopy were performed. Acquired confocal images at the level of the epithelium were arranged and mapped into subconfluent montages. Changes in the shape and degree of light reflection of abnormal cells and deposits around dendritic lesions as well as other corneal layers were qualitatively evaluated. Results Mapping of dendritic lesion was successful in all cases, and the subconfluent montages clearly showed the larger image of dendritic lesion. In all cases, the dendritic lesion consisted of hyperreflective irregular epithelial cells, and was surrounded by distorted and elongated epithelial cells. In three cases, hyperreflective deposits were noted at the midline of the lesion. The corneal stroma showed a hyperreflective honeycomb pattern. In two cases, inflammatory cells were observed at the level of endothelial cell layer. Conclusion Mapping of dendritic lesions in patients with HSK was successful in all patients using in vivo confocal microscopy. Cellular level observation of dendritic lesion at a relatively larger magnification may help understand the in vivo morphological change of HSK. Further study in more patients with HSK and nonherpetic dendritic lesion is needed to utilize confocal microscopy images in differential diagnosis and follow-up of the epithelial lesions with dendrite. PMID:26445524
Mapping of dendritic lesions in patients with herpes simplex keratitis using in vivo confocal microscopy.

PubMed

Yokogawa, Hideaki; Kobayashi, Akira; Mori, Natsuko; Sugiyama, Kazuhisa

2015-01-01

To produce a two-dimensional reconstruction map of dendritic lesions in patients with herpes simplex keratitis (HSK) using in vivo confocal microscopy. Four eyes of four patients (mean 65.8 years) with HSK presenting with a dendritic lesion were enrolled. Slit-lamp biomicroscopy and in vivo laser confocal microscopy were performed. Acquired confocal images at the level of the epithelium were arranged and mapped into subconfluent montages. Changes in the shape and degree of light reflection of abnormal cells and deposits around dendritic lesions as well as other corneal layers were qualitatively evaluated. Mapping of dendritic lesion was successful in all cases, and the subconfluent montages clearly showed the larger image of dendritic lesion. In all cases, the dendritic lesion consisted of hyperreflective irregular epithelial cells, and was surrounded by distorted and elongated epithelial cells. In three cases, hyperreflective deposits were noted at the midline of the lesion. The corneal stroma showed a hyperreflective honeycomb pattern. In two cases, inflammatory cells were observed at the level of endothelial cell layer. Mapping of dendritic lesions in patients with HSK was successful in all patients using in vivo confocal microscopy. Cellular level observation of dendritic lesion at a relatively larger magnification may help understand the in vivo morphological change of HSK. Further study in more patients with HSK and nonherpetic dendritic lesion is needed to utilize confocal microscopy images in differential diagnosis and follow-up of the epithelial lesions with dendrite.
Perceived psychological pressure at work, social class, and risk of stroke: a 30-year follow-up in Copenhagen male study.

PubMed

Suadicani, Poul; Andersen, Lars L; Holtermann, Andreas; Mortensen, Ole S; Gyntelberg, Finn

2011-12-01

Investigate if the association between perceived psychological work pressure and risk of stroke is modified by socioeconomic status. Thirty-year follow-up of 4943 middle-aged men without cardiovascular disease. In the higher social classes (I, II, and III), perceived regular exposure to psychological work pressure was common and a significant predictor of stroke; almost 10% of the stroke events could be attributed to this exposure in the higher social classes; among lower social classes (IV and V), perceived psychological pressure was no predictor at all. Regular psychological work pressure is a highly prevalent and independent risk factor for stroke among men in higher social classes. In contrast, no association to stroke risk was found among low social class men.
Onset of Curved Dendrite Growth in an Al-Cu Welding Pool: A Phase Field Study

NASA Astrophysics Data System (ADS)

Wang, Lei; Wei, Yanhong

2018-02-01

A phase field model is developed to predict curved dendrite growth in the gas tungsten arc (GTA) welding pool of an Al-Cu alloy. The equations of temperature gradient, pulling velocity and dendrite growth orientation are proposed to consider the transient solidification process during welding. Solidification microstructures and solute diffusion along the fusion boundary in the welding pool are predicted by using the phase field model coupled with transient solidification conditions. Predicted primary dendrites are curved and point toward the welding direction. Welding experiments are carried out to observe solidification microstructures of the weld. Comparisons of simulation results with experimental measurements are conducted. Predicted dendritic morphology, dendrite growth orientation, primary dendrite arm spacing and initial cell spacing give a good agreement with experimental measurements.
A stable Fe{sup III}-Fe{sup IV} replacement of tyrosyl radical in a class I ribonucleotide reductase

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

Voevodskaya, N.; Lendzian, F.; Graeslund, A.

2005-05-20

Ribonucleotide reductase (RNR) of Chlamydia trachomatis is a class I RNR enzyme composed of two homodimeric components, proteins R1 and R2. In class I RNR, R1 has the substrate binding site, whereas R2 has a diferric site and normally in its active form a stable tyrosyl free radical. C. trachomatis RNR is unusual, because its R2 component has a phenylalanine in the place of the radical carrier tyrosine. Replacing the tyrosyl radical, a paramagnetic Fe{sup III}-Fe{sup IV} species (species X, normally a transient intermediate in the process leading to radical formation) may provide the oxidation equivalent needed to start themore » catalytic process via long range electron transfer from the active site in R1. Here EPR spectroscopy shows that in C. trachomatis RNR, species X can become essentially stable when formed in a complete RNR (R1/R2/substrate) complex, adding further weight to the possible role of this species X in the catalytic reaction.« less
Equiaxed and columnar dendrite growth simulation in Al-7Si- Mg ternary alloys using cellular automaton method

NASA Astrophysics Data System (ADS)

Chen, Rui; Xu, Qingyan; Liu, Baicheng

2015-06-01

In this paper, a modified cellular automaton (MCA) model allowing for the prediction of dendrite growth of Al-Si-Mg ternary alloys in two and three dimensions is presented. The growth kinetic of S/L interface is calculated based on the solute equilibrium approach. In order to describe the dendrite growth with arbitrarily crystallographic orientations, this model introduces a modified decentered octahedron algorithm for neighborhood tracking to eliminate the effect of mesh dependency on dendrite growth. The thermody namic and kinetic data needed for dendrite growth is obtained through coupling with Pandat software package in combination with thermodynamic/kinetic/equilibrium phase diagram calculation databases. The effect of interactions between various alloying elements on solute diffusion coefficient is considered in the model. This model has first been used to simulate Al-7Si (weight percent) binary dendrite growth followed by a validation using theoretical predictions. For ternary alloy, Al-7Si-0.5Mg dendrite simulation has been carried out and the effects of solute interactions on diffusion matrix as well as the differences of Si and Mg in solute distribution have been analyzed. For actual application, this model has been applied to simulate the equiaxed dendrite growth with various crystallographic orientations of Al-7Si-0.36Mg ternary alloy, and the predicted secondary dendrite arm spacing (SDAS) shows a reasonable agreement with the experimental ones. Furthermore, the columnar dendrite growth in directional solidification has also been simulated and the predicted primary dendrite arm spacing (PDAS) is in good agreement with experiments. The simulated results effectively demonstrate the abilities of the model in prediction of dendritic microstructure of Al-Si-Mg ternary alloy.
Effect of Temperature and Fluid Flow on Dendrite Growth During Solidification of Al-3 Wt Pct Cu Alloy by the Two-Dimensional Cellular Automaton Method

NASA Astrophysics Data System (ADS)

Gu, Cheng; Wei, Yanhong; Liu, Renpei; Yu, Fengyi

2017-12-01

A two-dimensional cellular automaton-finite volume model was developed to simulate dendrite growth of Al-3 wt pct Cu alloy during solidification to investigate the effect of temperature and fluid flow on dendrite morphology, solute concentration distribution, and dendrite growth velocity. Different calculation conditions that may influence the results of the simulation, including temperature and flow, were considered. The model was also employed to study the effect of different undercoolings, applied temperature fields, and forced flow velocities on solute segregation and dendrite growth. The initial temperature and fluid flow have a significant impact on the dendrite morphologies and solute profiles during solidification. The release of energy is operated with solidification and results in the increase of temperature. A larger undercooling leads to larger solute concentration near the solid/liquid interface and solute concentration gradient at the same time-step. Solute concentration in the solid region tends to increase with the increase of undercooling. Four vortexes appear under the condition when natural flow exists: the two on the right of the dendrite rotate clockwise, and those on the left of the dendrite rotate counterclockwise. With the increase of forced flow velocity, the rejected solute in the upstream region becomes easier to be washed away and enriched in the downstream region, resulting in acceleration of the growth of the dendrite in the upstream and inhibiting the downstream dendrite growth. The dendrite perpendicular to fluid flow shows a coarser morphology in the upstream region than that of the downstream. Almost no secondary dendrite appears during the calculation process.
Dendritic Alloy Solidification Experiment (DASE)

NASA Technical Reports Server (NTRS)

Beckermann, C.; Karma, A.; Steinbach, I.; deGroh, H. C., III

2001-01-01

A space experiment, and supporting ground-based research, is proposed to study the microstructural evolution in free dendritic growth from a supercooled melt of the transparent model alloy succinonitrile-acetone (SCN-ACE). The research is relevant to equiaxed solidification of metal alloy castings. The microgravity experiment will establish a benchmark for testing of equiaxed dendritic growth theories, scaling laws, and models in the presence of purely diffusive, coupled heat and solute transport, without the complicating influences of melt convection. The specific objectives are to: determine the selection of the dendrite tip operating state, i.e. the growth velocity and tip radius, for free dendritic growth of succinonitrile-acetone alloys; determine the growth morphology and sidebranching behavior for freely grown alloy dendrites; determine the effects of the thermal/solutal interactions in the growth of an assemblage of equiaxed alloy crystals; determine the effects of melt convection on the free growth of alloy dendrites; measure the surface tension anisotropy strength of succinon itrile -acetone alloys establish a theoretical and modeling framework for the experiments. Microgravity experiments on equiaxed dendritic growth of alloy dendrites have not been performed in the past. The proposed experiment builds on the Isothermal Dendritic Growth Experiment (IDGE) of Glicksman and coworkers, which focused on the steady growth of a single crystal from pure supercooled melts (succinonitrile and pivalic acid). It also extends the Equiaxed Dendritic Solidification Experiment (EDSE) of the present investigators, which is concerned with the interactions and transients arising in the growth of an assemblage of equiaxed crystals (succinonitrile). However, these experiments with pure substances are not able to address the issues related to coupled heat and solute transport in growth of alloy dendrites.
Temporal, Diagnostic, and Tissue-Specific Regulation of NRG3 Isoform Expression in Human Brain Development and Affective Disorders.

PubMed

Paterson, Clare; Wang, Yanhong; Hyde, Thomas M; Weinberger, Daniel R; Kleinman, Joel E; Law, Amanda J

2017-03-01

Genes implicated in schizophrenia are enriched in networks differentially regulated during human CNS development. Neuregulin 3 (NRG3), a brain-enriched neurotrophin, undergoes alternative splicing and is implicated in several neurological disorders with developmental origins. Isoform-specific increases in NRG3 are observed in schizophrenia and associated with rs10748842, a NRG3 risk polymorphism, suggesting NRG3 transcriptional dysregulation as a molecular mechanism of risk. The authors quantitatively mapped the temporal trajectories of NRG3 isoforms (classes I-IV) in the neocortex throughout the human lifespan, examined whether tissue-specific regulation of NRG3 occurs in humans, and determined if abnormalities in NRG3 transcriptomics occur in mood disorders and are genetically determined. NRG3 isoform classes I-IV were quantified using quantitative real-time polymerase chain reaction in human postmortem dorsolateral prefrontal cortex from 286 nonpsychiatric control individuals, from gestational week 14 to 85 years old, and individuals diagnosed with either bipolar disorder (N=34) or major depressive disorder (N=69). Tissue-specific mapping was investigated in several human tissues. rs10748842 was genotyped in individuals with mood disorders, and association with NRG3 isoform expression examined. NRG3 classes displayed individually specific expression trajectories across human neocortical development and aging; classes I, II, and IV were significantly associated with developmental stage. NRG3 class I was increased in bipolar and major depressive disorder, consistent with observations in schizophrenia. NRG3 class II was increased in bipolar disorder, and class III was increased in major depression. The rs10748842 risk genotype predicted elevated class II and III expression, consistent with previous reports in the brain, with tissue-specific analyses suggesting that classes II and III are brain-specific isoforms of NRG3. Mapping the temporal expression of genes during human brain development provides vital insight into gene function and identifies critical sensitive periods whereby genetic factors may influence risk for psychiatric disease. Here the authors provide comprehensive insight into the transcriptional landscape of the psychiatric risk gene, NRG3, in human neocortical development and expand on previous findings in schizophrenia to identify increased expression of developmentally and genetically regulated isoforms in the brain of patients with mood disorders. Principally, the finding that NRG3 classes II and III are brain-specific isoforms predicted by rs10748842 risk genotype and are increased in mood disorders further implicates a molecular mechanism of psychiatric risk at the NRG3 locus and identifies a potential developmental role for NRG3 in bipolar disorder and major depression. These observations encourage investigation of the neurobiology of NRG3 isoforms and highlight inhibition of NRG3 signaling as a potential target for psychiatric treatment development.
Temporal, Diagnostic, and Tissue-Specific Regulation of NRG3 Isoform Expression in Human Brain Development and Affective Disorders

PubMed Central

Paterson, Clare; Wang, Yanhong; Hyde, Thomas M.; Weinberger, Daniel R.; Kleinman, Joel E.; Law, Amanda J.

2018-01-01

Objective Genes implicated in schizophrenia are enriched in networks differentially regulated during human CNS development. Neuregulin 3 (NRG3), a brain-enriched neurotrophin, undergoes alternative splicing and is implicated in several neurological disorders with developmental origins. Isoform-specific increases in NRG3 are observed in schizophrenia and associated with rs10748842, a NRG3 risk polymorphism, suggesting NRG3 transcriptional dysregulation as a molecular mechanism of risk. The authors quantitatively mapped the temporal trajectories of NRG3 isoforms (classes I–IV) in the neocortex throughout the human lifespan, examined whether tissue-specific regulation of NRG3 occurs in humans, and determined if abnormalities in NRG3 transcriptomics occur in mood disorders and are genetically determined. Method NRG3 isoform classes I–IV were quantified using quantitative real-time polymerase chain reaction in human postmortem dorsolateral prefrontal cortex from 286 nonpsychiatric control individuals, from gestational week 14 to 85 years old, and individuals diagnosed with either bipolar disorder (N=34) or major depressive disorder (N=69). Tissue-specific mapping was investigated in several human tissues. rs10748842 was genotyped in individuals with mood disorders, and association with NRG3 isoform expression examined. Results NRG3 classes displayed individually specific expression trajectories across human neocortical development and aging; classes I, II, and IV were significantly associated with developmental stage. NRG3 class I was increased in bipolar and major depressive disorder, consistent with observations in schizophrenia. NRG3 class II was increased in bipolar disorder, and class III was increased in major depression. The rs10748842 risk genotype predicted elevated class II and III expression, consistent with previous reports in the brain, with tissue-specific analyses suggesting that classes II and III are brain-specific isoforms of NRG3. Conclusions Mapping the temporal expression of genes during human brain development provides vital insight into gene function and identifies critical sensitive periods whereby genetic factors may influence risk for psychiatric disease. Here the authors provide comprehensive insight into the transcriptional landscape of the psychiatric risk gene, NRG3, in human neocortical development and expand on previous findings in schizophrenia to identify increased expression of developmentally and genetically regulated isoforms in the brain of patients with mood disorders. Principally, the finding that NRG3 classes II and III are brain-specific isoforms predicted by rs10748842 risk genotype and are increased in mood disorders further implicates a molecular mechanism of psychiatric risk at the NRG3 locus and identifies a potential developmental role for NRG3 in bipolar disorder and major depression. These observations encourage investigation of the neurobiology of NRG3 isoforms and highlight inhibition of NRG3 signaling as a potential target for psychiatric treatment development. PMID:27771971
Toxoplasma gondii Antigen-Pulsed-Dendritic Cell-Derived Exosomes Induce a Protective Immune Response against T. gondii Infection

PubMed Central

Aline, Fleur; Bout, Daniel; Amigorena, Sébastian; Roingeard, Philippe; Dimier-Poisson, Isabelle

2004-01-01

It was previously demonstrated that immunizing mice with spleen dendritic cells (DCs) that had been pulsed ex vivo with Toxoplasma gondii antigens triggers a systemic Th1-biased specific immune response and induces protection against infection. T. gondii can cause severe sequelae in the fetuses of mothers who acquire the infection during pregnancy, as well as life-threatening neuropathy in immunocompromised patients, in particular those with AIDS. Here, we investigate the efficacy of a novel cell-free vaccine composed of DC exosomes, which are secreted antigen-presenting vesicles that express functional major histocompatibility complex class I and II and T-cell-costimulatory molecules. They have already been shown to induce potent antitumor immune responses. We investigated the potential of DC2.4 cell line-derived exosomes to induce protective immunity against toxoplasmosis. Our data show that most adoptively transferred T. gondii-pulsed DC-derived exosomes were transferred to the spleen, elicited a strong systemic Th1-modulated Toxoplasma-specific immune response in vivo, and conferred good protection against infection. These findings support the possibility that DC-derived exosomes can be used for T. gondii immunoprophylaxis and for immunoprophylaxis against many other pathogens. PMID:15213158
Trichothecenes NIV and DON modulate the maturation of murine dendritic cells.

PubMed

Luongo, D; Severino, L; Bergamo, P; D'Arienzo, R; Rossi, M

2010-01-01

Nivalenol (NIV) and Deoxynivalenol (DON), mycotoxins of the trichothecene family are considered very common food contaminants. In this work, we investigated whether the immunotoxic effects ascribed to these trichothecenes may be mediated by perturbations in the activity of dendritic cells (DCs). Murine bone marrow-derived DCs were used to evaluate the effects of NIV and DON on the LPS-induced maturation process. We found that the expression of the class II MHC and of the accessory CD11c molecules, but not of the costimulatory CD86 marker, was down-regulated by NIV and DON exposure in LPS-treated DCs, as well as nitric oxide (NO) production. Interestingly, NIV, but not DON, induced DC necrosis. Moreover, the analysis of the cytokine pattern showed that IL-12 and IL-10 expressions induced by LPS exposure were suppressed by both trichothecenes in a dose-dependent fashion. On the other hand, the secretion of the proinflammatory cytokine TNF-alpha was increased as a direct consequence of DON and NIV exposure. Taken together, our data indicated that the immunotoxicity of NIV and DON was related to the capacity of both trichothecenes to interfere with phenotypic and functional features of maturing DCs.
Examination of Multiphase (Zr,Ti)(V,Cr,Mn,Ni)2 Ni-MH Electrode Alloys: Part I. Dendritic Solidification Structure

NASA Astrophysics Data System (ADS)

Boettinger, W. J.; Newbury, D. E.; Wang, K.; Bendersky, L. A.; Chiu, C.; Kattner, U. R.; Young, K.; Chao, B.

2010-08-01

The solidification microstructures of three nine-element Zr-Ni-based AB2 type C14/C15 Laves hydrogen storage alloys are determined. The selected compositions represent a class of alloys being examined for usage as an MH electrode in nickel metal-hydride batteries that often have their best properties in the cast state. Solidification is accomplished by dendritic growth of hexagonal C14 Laves phase, peritectic solidification of cubic C15 Laves phase, and formation of cubic B2 phase in the interdendritic regions. The B2 phase decomposes in the solid state into a complex multivariate platelike structure containing Zr-Ni-rich intermetallics. The observed sequence C14/C15 upon solidification agrees with predictions using effective compositions and thermodynamic assessments of the ternary systems, Ni-Cr-Zr and Cr-Ti-Zr. Experimentally, the closeness of the compositions of the C14 and C15 phases required the use of compositional mapping with an energy dispersive detector capable of processing a very high X-ray flux to locate regions in the microstructure for quantitative composition measurement and transmission electron microscope examination.
Progress of dendritic cell-based cancer vaccines for patients with hematological malignancies.

PubMed

Ni, Ming; Hoffmann, Jean-Marc; Schmitt, Michael; Schmitt, Anita

2016-09-01

Dendritic cells (DCs) are the most professional antigen-presenting cells eliciting cellular and humoral immune responses against cancer cells by expressing these antigens on MHC class I/II complexes to T cells. Therefore, they have been employed in many clinical trials as cancer vaccines for patients with cancer. This review focuses on the use of DCs in leukemia patients expressing leukemia-associated antigens (LAAs). The contribution of both stimulating vs. tolerogenic DCs as well as of other factors to the milieu of anti-leukemia immune responses are discussed. Several DC vaccination strategies like leukemia lysate, proteins and peptides have been developed. Next generation DC vaccines comprise transduction of DCs with retroviral vectors encoding for LAAs, cytokines and costimulatory molecules as well as transfection of DCs with naked RNA encoding for LAAs. Published as well as ongoing clinical trials are reported and critically reviewed. Future results will demonstrate whether next-generation DCs are really superior to conventional pulsing with peptide, protein or tumor lysate. However, currently available methods based on nucleic acid transfection/transduction are tempting in terms of material production costs and time for clinical application according to good manufacturing practice (GMP).
Dendritic cells produce eicosanoids, which modulate generation and functions of antigen-presenting cells.

PubMed

Harizi, H; Gualde, N

2002-01-01

Eicosanoids have been shown to be potent immunoregulatory arachidonic acid (AA) metabolites. AA is the precursor of prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)) which are able to modulate both inflammation and the immune response. Dendritic cells process and present antigens to T lymphocytes. They are highly specialized antigen-presenting cells (APC) and usually considered as 'professional APC'. In the present paper, we report some data on the biosynthetic capacity of murine APC from the bone marrow (BM-DCs) to produce AA metabolites. Using an ELISA we have observed that BM-DCs spontaneously produce both PGE(2) and LTB(4) whose production increased in response to bacterial lipopolysaccharides (LPS). In addition we found that LTB(4) production was twice as high when both COX pathways were blocked with selective COX-inhibitors. We have also investigated the effect of PGE(2) and LTB(4) on the in vitro generation of the so-called BM-DCs. Exogenous PGE(2) and LTB(4) added to bone marrow cultures inhibit and promote, respectively, BM-DC generation. PGE(2) added to the maturing BM-DCs reduces their MHC class-II expression.
Activation of antigen-specific cytotoxic T lymphocytes by beta 2-microglobulin or TAP1 gene disruption and the introduction of recipient-matched MHC class I gene in allogeneic embryonic stem cell-derived dendritic cells.

PubMed

Matsunaga, Yusuke; Fukuma, Daiki; Hirata, Shinya; Fukushima, Satoshi; Haruta, Miwa; Ikeda, Tokunori; Negishi, Izumi; Nishimura, Yasuharu; Senju, Satoru

2008-11-01

A method for the genetic modification of dendritic cells (DC) was previously established based on the in vitro differentiation of embryonic stem (ES) cells to DC (ES-DC). The unavailability of human ES cells genetically identical to the patients will be a problem in the future clinical application of this technology. This study attempted to establish a strategy to overcome this issue. The TAP1 or beta(2)-microglobulin (beta(2)m) gene was disrupted in 129 (H-2(b))-derived ES cells and then expression vectors for the H-2K(d) or beta(2)m-linked form of K(d) (beta2m-K(d)) were introduced, thus resulting in two types of genetically engineered ES-DC, TAP1(-/-)/K(d) ES-DC and beta(2)m(-/-)/beta(2)m-K(d) ES-DC. As intended, both of the transfectant ES-DC expressed K(d) but not the intrinsic H-2(b) haplotype-derived MHC class I. Beta(2)m(-/-)/beta(2)m-K(d) and TAP1(-/-)/K(d) ES-DC were not recognized by pre-activated H-2(b)-reactive CTL and did not prime H-2(b) reactive CTL in vitro or in vivo. Beta(2)m(-/-)/beta(2)m-K(d) ES-DC and TAP1(-/-)/K(d) ES-DC had a survival advantage in comparison to beta(2)m(+/-)/beta(2)m-K(d) ES-DC and TAP1(+/+)/K(d) ES-DC, when transferred into BALB/c mice. K(d)-restricted RSV-M2-derived peptide-loaded ES-DC could prime the epitope-specific CTL upon injection into the BALB/c mice, irrespective of the cell surface expression of intrinsic H-2(b) haplotype-encoded MHC class I. Beta(2)m(-/-)/beta(2)m-K(d) ES-DC were significantly more efficient in eliciting immunity against RSV M2 protein-expressing tumor cells than beta(2)m(+/-)/beta(2)m-K(d) ES-DC. The modification of the beta(2)m or TAP gene may therefore be an effective strategy to resolve the problem of HLA class I allele mismatch between human ES or induced pluripotent stem cells and the recipients to be treated.
Directing lateral growth of lithium dendrites in micro-compartmented anode arrays for safe lithium metal batteries.

PubMed

Zou, Peichao; Wang, Yang; Chiang, Sum-Wai; Wang, Xuanyu; Kang, Feiyu; Yang, Cheng

2018-01-31

Uncontrolled growth of lithium dendrites during cycling has remained a challenging issue for lithium metal batteries. Thus far, various approaches have been proposed to delay or suppress dendrite growth, yet little attention has been paid to the solutions that can make batteries keep working when lithium dendrites are already extensively present. Here we develop an industry-adoptable technology to laterally direct the growth of lithium dendrites, where all dendrites are retained inside the compartmented copper current collector in a given limited cycling capacity. This featured electrode layout renders superior cycling stability (e.g., smoothly running for over 150 cycles at 0.5 mA cm -2 ). Numerical simulations indicate that reduced dendritic stress and damage to the separator are achieved when the battery is abusively running over the ceiling capacity to generate protrusions. This study may contribute to a deeper comprehension of metal dendrites and provide a significant step towards ultimate safe batteries.
Activity-dependent trafficking of lysosomes in dendrites and dendritic spines.

PubMed

Goo, Marisa S; Sancho, Laura; Slepak, Natalia; Boassa, Daniela; Deerinck, Thomas J; Ellisman, Mark H; Bloodgood, Brenda L; Patrick, Gentry N

2017-08-07

In neurons, lysosomes, which degrade membrane and cytoplasmic components, are thought to primarily reside in somatic and axonal compartments, but there is little understanding of their distribution and function in dendrites. Here, we used conventional and two-photon imaging and electron microscopy to show that lysosomes traffic bidirectionally in dendrites and are present in dendritic spines. We find that lysosome inhibition alters their mobility and also decreases dendritic spine number. Furthermore, perturbing microtubule and actin cytoskeletal dynamics has an inverse relationship on the distribution and motility of lysosomes in dendrites. We also find trafficking of lysosomes is correlated with synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors. Strikingly, lysosomes traffic to dendritic spines in an activity-dependent manner and can be recruited to individual spines in response to local activation. These data indicate the position of lysosomes is regulated by synaptic activity and thus plays an instructive role in the turnover of synaptic membrane proteins. © 2017 Goo et al.

Activity-dependent trafficking of lysosomes in dendrites and dendritic spines

PubMed Central

Sancho, Laura; Slepak, Natalia; Boassa, Daniela; Deerinck, Thomas J.; Ellisman, Mark H.

2017-01-01

In neurons, lysosomes, which degrade membrane and cytoplasmic components, are thought to primarily reside in somatic and axonal compartments, but there is little understanding of their distribution and function in dendrites. Here, we used conventional and two-photon imaging and electron microscopy to show that lysosomes traffic bidirectionally in dendrites and are present in dendritic spines. We find that lysosome inhibition alters their mobility and also decreases dendritic spine number. Furthermore, perturbing microtubule and actin cytoskeletal dynamics has an inverse relationship on the distribution and motility of lysosomes in dendrites. We also find trafficking of lysosomes is correlated with synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid–type glutamate receptors. Strikingly, lysosomes traffic to dendritic spines in an activity-dependent manner and can be recruited to individual spines in response to local activation. These data indicate the position of lysosomes is regulated by synaptic activity and thus plays an instructive role in the turnover of synaptic membrane proteins. PMID:28630145
Nasal potential difference in cystic fibrosis considering severe CFTR mutations.

PubMed

Ng, Ronny Tah Yen; Marson, Fernando Augusto de Lima; Ribeiro, Jose Dirceu; Ribeiro, Antonio Fernando; Bertuzzo, Carmen Silvia; Ribeiro, Maria Angela Gonçalves de Oliveira; Severino, Silvana Dalge; Sakano, Eulalia

2015-01-01

The gold standard for diagnosing cystic fibrosis (CF) is a sweat chloride value above 60 mEq/L. However, this historical and important tool has limitations; other techniques should be studied, including the nasal potential difference (NPD) test. CFTR gene sequencing can identify CFTR mutations, but this method is time-consuming and too expensive to be used in all CF centers. The present study compared CF patients with two classes I-III CFTR mutations (10 patients) (G1), CF patients with classes IV-VI CFTR mutations (five patients) (G2), and 21 healthy subjects (G3). The CF patients and healthy subjects also underwent the NPD test. A statistical analysis was performed using the Mann-Whitney, Kruskal-Wallis, χ(2), and Fisher's exact tests, α = 0.05. No differences were observed between the CF patients and healthy controls for the PDMax, Δamiloride, and Δchloride + free + amiloride markers from the NPD test. For the finger value, a difference between G2 and G3 was described. The Wilschanski index values were different between G1 and G3. In conclusion, our data showed that NPD is useful for CF diagnosis when classes I-III CFTR mutations are screened. However, if classes IV-VI are considered, the NPD test showed an overlap in values with healthy subjects.
Nasal Potential Difference in Cystic Fibrosis considering Severe CFTR Mutations

PubMed Central

Ng, Ronny Tah Yen; Marson, Fernando Augusto de Lima; Ribeiro, Jose Dirceu; Ribeiro, Antonio Fernando; Bertuzzo, Carmen Silvia; Ribeiro, Maria Angela Gonçalves de Oliveira; Severino, Silvana Dalge; Sakano, Eulalia

2015-01-01

The gold standard for diagnosing cystic fibrosis (CF) is a sweat chloride value above 60 mEq/L. However, this historical and important tool has limitations; other techniques should be studied, including the nasal potential difference (NPD) test. CFTR gene sequencing can identify CFTR mutations, but this method is time-consuming and too expensive to be used in all CF centers. The present study compared CF patients with two classes I-III CFTR mutations (10 patients) (G1), CF patients with classes IV-VI CFTR mutations (five patients) (G2), and 21 healthy subjects (G3). The CF patients and healthy subjects also underwent the NPD test. A statistical analysis was performed using the Mann-Whitney, Kruskal-Wallis, χ 2, and Fisher's exact tests, α = 0.05. No differences were observed between the CF patients and healthy controls for the PDMax, Δamiloride, and Δchloride + free + amiloride markers from the NPD test. For the finger value, a difference between G2 and G3 was described. The Wilschanski index values were different between G1 and G3. In conclusion, our data showed that NPD is useful for CF diagnosis when classes I-III CFTR mutations are screened. However, if classes IV-VI are considered, the NPD test showed an overlap in values with healthy subjects. PMID:25667564
Optical radiation hazards of laser welding processes. Part 1: Neodymium-YAG laser.

PubMed

Rockwell, R J; Moss, C E

1983-08-01

High power laser devices are being used for numerous metalworking processes such as welding, cutting and heat treating. Such laser devices are totally enclosed either by the manufacturer or the end-user. When this is done, the total laser system is usually certified by the manufacturer following the federal requirements of the Code of Federal Regulations (CFR) 1040.10 and 10.40.11 as a Class I laser system. Similarly, the end-user may also reclassify an enclosed high-power laser into the Class I category following the requirements of the American National Standards Institute (ANSI) Z-136.1 (1980) standard. There are, however, numerous industrial laser applications where Class IV systems are required to be used in an unenclosed manner. In such applications, there is concern for both ocular and skin hazards caused by direct and scattered laser radiation, as well as potential hazards caused by the optical radiation created by the laser beam's interaction with the metal (i.e. the plume radiation). Radiant energy measurements are reported for both the scattered laser radiation and the resultant plume radiations which were produced during typical unenclosed Class IV Neodymium-YAG laser welding processes. Evaluation of the plume radiation was done with both radiometric and spectroradiometric measurement equipment. The data obtained were compared to applicable safety standards.
COPD predicts mortality in HF: the Norwegian Heart Failure Registry.

PubMed

De Blois, Jonathan; Simard, Serge; Atar, Dan; Agewall, Stefan

2010-03-01

Chronic obstructive pulmonary disease (COPD) and chronic heart failure (HF) are common clinical conditions that share tobacco as a risk factor. Our aim was to evaluate the prognostic impact of COPD on HF patients. The Norwegian Heart Failure Registry was used. The study included 4132 HF patients (COPD, n = 699) from 22 hospitals (mean follow-up, 13.3 months). COPD patients were older, more often smokers and diabetics, less often on beta-blockers and had a higher heart rate. They were more often in New York Heart Association (NYHA) Class III or IV (COPD, 63%; no COPD, 51%), although left ventricular ejection fraction (LVEF) distribution was similar. COPD independently predicted death (adjusted hazard ratio [HR], 1.188; 95% CI: 1.015 to 1.391; P = 0.03) along with age, creatinine, NYHA Class III/IV (HR, 1.464; 95% CI: 1.286 to 1.667) and diabetes. beta-blockers at baseline were associated with improved survival in patients with LVEF < or =40% independently of COPD. COPD is associated with a poorer survival in HF patients. COPD patients are overrated in terms of NYHA class in comparison with patients with similar LVEF. Nonetheless, NYHA class remains the strongest predictor of death in these patients. Copyright (c) 2010 Elsevier Inc. All rights reserved.
The activation threshold of CD4+ T cells is defined by TCR/peptide-MHC class II interactions in the thymic medulla.

PubMed

Stephen, Tom Li; Tikhonova, Anastasia; Riberdy, Janice M; Laufer, Terri M

2009-11-01

Immature thymocytes that are positively selected based upon their response to self-peptide-MHC complexes develop into mature T cells that are not overtly reactive to those same complexes. Developmental tuning is the active process through which TCR-associated signaling pathways of single-positive thymocytes are attenuated to respond appropriately to the peptide-MHC molecules that will be encountered in the periphery. In this study, we explore the mechanisms that regulate the tuning of CD4(+) single-positive T cells to MHC class II encountered in the thymic medulla. Experiments with murine BM chimeras demonstrate that tuning can be mediated by MHC class II expressed by either thymic medullary epithelial cells or thymic dendritic cells. Tuning does not require the engagement of CD4 by MHC class II on stromal cells. Rather, it is mediated by interactions between MHC class II and the TCR. To understand the molecular changes that distinguish immature hyperactive T cells from tuned mature CD4(+) T cells, we compared their responses to TCR stimulation. The altered response of mature CD4 single-positive thymocytes is characterized by the inhibition of ERK activation by low-affinity self-ligands and increased expression of the inhibitory tyrosine phosphatase SHP-1. Thus, persistent TCR engagement by peptide-MHC class II on thymic medullary stroma inhibits reactivity to self-Ags and prevents autoreactivity in the mature repertoire.
Spatial separation of the processing and MHC class I loading compartments for cross-presentation of the tumor-associated antigen HER2/neu by human dendritic cells

PubMed Central

Baleeiro, Renato B; Rietscher, René; Diedrich, Andrea; Czaplewska, Justyna A; Lehr, Claus-Michael; Scherließ, Regina; Hanefeld, Andrea; Gottschaldt, Michael; Walden, Peter

2015-01-01

Cross-presentation is the process by which professional antigen presenting cells (APCs) (B cells, dendritic cells (DCs) and macrophages) present endocytosed antigens (Ags) via MHC-I to CD8+ T cells. This process is crucial for induction of adaptive immune responses against tumors and infected cells. The pathways and cellular compartments involved in cross-presentation are unresolved and controversial. Among the cells with cross-presenting capacity, DCs are the most efficient, which was proposed to depend on prevention of endosomal acidification to block degradation of the epitopes. Contrary to this view, we show in this report that some cargoes induce strong endosomal acidification following uptake by human DCs, while others not. Moreover, processing of the tumor-associated antigen HER2/neu delivered in nanoparticles (NP) for cross-presentation of the epitope HER2/neu369–377 on HLA-A2 depended on endosomal acidification and cathepsin activity as well as proteasomes, and newly synthesized HLA class I. However, the HLA-A*0201/HER2/neu369–377 complexes were not found in the endoplasmic reticulum (ER) nor in endolysosomes but in hitherto not described vesicles. The data thus indicate spatial separation of antigen processing and loading of MHC-I for cross-presentation: antigen processing occurs in the uptake compartment and the cytosol whereas MHC-I loading with peptide takes place in a distinct subcellular compartment. The findings further elucidate the cellular pathways involved in the cross-presentation of a full-length, clinically relevant tumor-associated antigen by human DCs, and the impact of the vaccine formulation on antigen processing and CD8+ T cell induction. PMID:26985398
Comparison of monocyte-derived dendritic cells from colorectal cancer patients, non-small-cell-lung-cancer patients and healthy donors.

PubMed

Kvistborg, P; Bechmann, C M; Pedersen, A W; Toh, H C; Claesson, M H; Zocca, M B

2009-12-11

Dendritic cells (DCs) are bone marrow-derived professional antigen presenting cells. Due to their role as potent inducers of immune responses, these cells are widely used as adjuvant in experimental clinical settings for cancer immune therapy. We have developed a DC-based vaccine using autologous blood monocytes loaded with allogeneic tumor cell lysate rich in cancer/testis antigens. This vaccine has at present been tested for activity in three phase II clinical trials including two cohorts of patients with advanced colorectal cancer (CRC) and one cohort of patients with advanced non-small-cell-lung-cancer (NSCLC). In the present paper we retrospectively compare the maturation profile based on surface marker expression on DCs generated from the three patient cohorts and between cancer patient cohorts and a cohort of healthy donors. Vaccines were generated under cGMP conditions and phenotypic profiles of DC were analyzed by flow cytometry and the obtained data were used as a basis to set guideline values for our quality control of GMP produced DC vaccines. Each vaccine batch was analyzed for the expression of the surface maturation and differentiation molecules CD14, CD1a, CD83, CD86, MHC class II and CCR7, and the optimal expression pattern is considered as CD14(low), CD1a, CD83(high), CD86(high), MHC class II(high) and CCR7(high). In accordance with data from other studies including other types of cancer patients, especially breast cancer patients, we found that the maturation status of the DC batches depends on cancer type and correlates with clinical status of cancer patients included.
Encephalitozoon intestinalis Inhibits Dendritic Cell Differentiation through an IL-6-Dependent Mechanism

PubMed Central

Bernal, Carmen E.; Zorro, Maria M.; Sierra, Jelver; Gilchrist, Katherine; Botero, Jorge H.; Baena, Andres; Ramirez-Pineda, Jose R.

2016-01-01

Microsporidia are a group of intracellular pathogens causing self-limited and severe diseases in immunocompetent and immunocompromised individuals, respectively. A cellular type 1 adaptive response, mediated by IL-12, IFNγ, CD4+, and CD8+ T cells has been shown to be essential for host resistance, and dendritic cells (DC) play a key role at eliciting anti-microsporidial immunity. We investigated the in vitro response of DC and DC precursors/progenitors to infection with Encephalitozoon intestinalis (Ei), a common agent of human microsporidosis. Ei-exposed DC cultures up-regulated the surface expression of MHC class II and the costimulatory molecules CD86 and CD40, only when high loads of spores were used. A vigorous secretion of IL-6 but not of IL-1β or IL-12p70 was also observed in these cultures. Ei-exposed DC cultures consisted of immature infected and mature bystander DC, as assessed by MHC class II and costimulatory molecules expression, suggesting that intracellular Ei spores deliver inhibitory signals in DC. Moreover, Ei selectively inhibited the secretion of IL-12p70 in LPS-stimulated DC. Whereas Ei-exposed DC promoted allogeneic naïve T cell proliferation and IL-2 and IFNγ secretion in DC-CD4+ T cell co-cultures, separated co-cultures with bystander or infected DCs showed stimulation or inhibition of IFNγ secretion, respectively. When DC precursors/progenitors were exposed to Ei spores, a significant inhibition of DC differentiation was observed without shifting the development toward cells phenotypically or functionally compatible with myeloid-derived suppressor cells. Neutralization experiments demonstrated that this inhibitory effect is IL-6-dependent. Altogether this investigation reveals a novel potential mechanism of immune escape of microsporidian parasites through the modulation of DC differentiation and maturation. PMID:26870700
Bordetella pertussis Proteins Dominating the Major Histocompatibility Complex Class II-Presented Epitope Repertoire in Human Monocyte-Derived Dendritic Cells

PubMed Central

Stenger, Rachel M.; Meiring, Hugo D.; Kuipers, Betsy; Poelen, Martien; van Gaans-van den Brink, Jacqueline A. M.; Boog, Claire J. P.; de Jong, Ad P. J. M.

2014-01-01

Knowledge of naturally processed Bordetella pertussis-specific T cell epitopes may help to increase our understanding of the basis of cell-mediated immune mechanisms to control this reemerging pathogen. Here, we elucidate for the first time the dominant major histocompatibility complex (MHC) class II-presented B. pertussis CD4+ T cell epitopes, expressed on human monocyte-derived dendritic cells (MDDC) after the processing of whole bacterial cells by use of a platform of immunoproteomics technology. Pertussis epitopes identified in the context of HLA-DR molecules were derived from two envelope proteins, i.e., putative periplasmic protein (PPP) and putative peptidoglycan-associated lipoprotein (PAL), and from two cytosolic proteins, i.e., 10-kDa chaperonin groES protein (groES) and adenylosuccinate synthetase (ASS). No epitopes were detectable from known virulence factors. CD4+ T cell responsiveness in healthy adults against peptide pools representing epitope regions or full proteins confirmed the immunogenicity of PAL, PPP, groES, and ASS. Elevated lymphoproliferative activity to PPP, groES, and ASS in subjects within a year after the diagnosis of symptomatic pertussis suggested immunogenic exposure to these proteins during clinical infection. The PAL-, PPP-, groES-, and ASS-specific responses were associated with secretion of functional Th1 (tumor necrosis factor alpha [TNF-α] and gamma interferon [IFN-γ]) and Th2 (interleukin 5 [IL-5] and IL-13) cytokines. Relative paucity in the natural B. pertussis epitope display of MDDC, not dominated by epitopes from known protective antigens, can interfere with the effectiveness of immune recognition of B. pertussis. A more complete understanding of hallmarks in B. pertussis-specific immunity may advance the design of novel immunological assays and prevention strategies. PMID:24599530
Bordetella pertussis proteins dominating the major histocompatibility complex class II-presented epitope repertoire in human monocyte-derived dendritic cells.

PubMed

Stenger, Rachel M; Meiring, Hugo D; Kuipers, Betsy; Poelen, Martien; van Gaans-van den Brink, Jacqueline A M; Boog, Claire J P; de Jong, Ad P J M; van Els, Cécile A C M

2014-05-01

Knowledge of naturally processed Bordetella pertussis-specific T cell epitopes may help to increase our understanding of the basis of cell-mediated immune mechanisms to control this reemerging pathogen. Here, we elucidate for the first time the dominant major histocompatibility complex (MHC) class II-presented B. pertussis CD4(+) T cell epitopes, expressed on human monocyte-derived dendritic cells (MDDC) after the processing of whole bacterial cells by use of a platform of immunoproteomics technology. Pertussis epitopes identified in the context of HLA-DR molecules were derived from two envelope proteins, i.e., putative periplasmic protein (PPP) and putative peptidoglycan-associated lipoprotein (PAL), and from two cytosolic proteins, i.e., 10-kDa chaperonin groES protein (groES) and adenylosuccinate synthetase (ASS). No epitopes were detectable from known virulence factors. CD4(+) T cell responsiveness in healthy adults against peptide pools representing epitope regions or full proteins confirmed the immunogenicity of PAL, PPP, groES, and ASS. Elevated lymphoproliferative activity to PPP, groES, and ASS in subjects within a year after the diagnosis of symptomatic pertussis suggested immunogenic exposure to these proteins during clinical infection. The PAL-, PPP-, groES-, and ASS-specific responses were associated with secretion of functional Th1 (tumor necrosis factor alpha [TNF-α] and gamma interferon [IFN-γ]) and Th2 (interleukin 5 [IL-5] and IL-13) cytokines. Relative paucity in the natural B. pertussis epitope display of MDDC, not dominated by epitopes from known protective antigens, can interfere with the effectiveness of immune recognition of B. pertussis. A more complete understanding of hallmarks in B. pertussis-specific immunity may advance the design of novel immunological assays and prevention strategies.
Caveolin-mediated endocytosis of the Chlamydia M278 outer membrane peptide encapsulated in poly(lactic acid)-Poly(ethylene glycol) nanoparticles by mouse primary dendritic cells enhances specific immune effectors mediated by MHC class II and CD4+ T cells.

PubMed

Dixit, Saurabh; Sahu, Rajnish; Verma, Richa; Duncan, Skyla; Giambartolomei, Guillermo H; Singh, Shree R; Dennis, Vida A

2018-03-01

We previously developed a Chlamydia trachomatis nanovaccine (PPM) by encapsulating a chlamydial M278 peptide within poly(lactic acid)-poly(ethylene glycol) biodegradable nanoparticles that immunopotentiated Chlamydia-specific immune effector responses in mice. Herein, we investigated the mechanistic interactions of PPM with mouse bone marrow-derived dendritic cells (DCs) for its uptake, trafficking, and T cell activation. Our results reveal that PPM triggered enhanced expression of effector cytokines and chemokines, surface activation markers (Cd1d2, Fcgr1), pathogen-sensing receptors (TLR2, Nod1), co-stimulatory (CD40, CD80, CD86) and MHC class I and II molecules. Co-culturing of PPM-primed DCs with T cells from C. muridarum vaccinated mice yielded an increase in Chlamydia-specific immune effector responses including CD3 + lymphoproliferation, CD3 + CD4 + IFN-γ-secreting cells along with CD3 + CD4 + memory (CD44 high and CD62L high ) and effector (CD44 high and CD62L low ) phenotypes. Intracellular trafficking analyses revealed an intense expression and colocalization of PPM predominantly in endosomes. PPM also upregulated the transcriptional and protein expression of the endocytic mediator, caveolin-1 in DCs. More importantly, the specific inhibition of caveolin-1 led to decreased expression of PPM-induced cytokines and co-stimulatory molecules. Our investigation shows that PPM provided enhancement of uptake, probably by exploiting the caveolin-mediated endocytosis pathway, endosomal processing, and MHC II presentation to immunopotentiate Chlamydia-specific immune effector responses mediated by CD4 + T cells. Copyright © 2017 Elsevier Ltd. All rights reserved.
Ambient particulate matter activates the aryl hydrocarbon receptor in dendritic cells and enhances Th17 polarization.

PubMed

Castañeda, Alejandro R; Pinkerton, Kent E; Bein, Keith J; Magaña-Méndez, Alfonso; Yang, Houa T; Ashwood, Paul; Vogel, Christoph F A

2018-08-01

The objective of this study was to explore the role of the aryl hydrocarbon receptor (AhR) in ambient particulate matter (PM)-mediated activation of dendritic cells (DCs) and Th17-immune responses in vitro. To assess the potential role of the AhR in PM-mediated activation of DCs, co-stimulation, and cytokine expression, bone marrow (BM)-derived macrophages and DCs from C57BL/6 wildtype or AhR knockout (AhR -/- ) mice were treated with PM. Th17 differentiation was assessed via co-cultures of wildtype or AhR -/- BMDCs with autologous naive T cells. PM 2.5 significantly induced AhR DNA binding activity to dioxin responsive elements (DRE) and expression of the AhR repressor (AhRR), cytochrome P450 (CYP) 1A1, and CYP1B1, indicating activation of the AhR. In activated (OVA sensitized) BMDCs, PM 2.5 induced interleukin (IL)-1β, CD80, CD86, and MHC class II, suggesting enhanced DC activation, co-stimulation, and antigen presentation; responses that were abolished in AhR deficient DCs. DC-T cell co-cultures treated with PM and lipopolysaccharide (LPS) led to elevated IL-17A and IL-22 expression at the mRNA level, which is mediated by the AhR. PM-treated DCs were essential in endowing T cells with a Th17-phenotype, which was associated with enhanced expression of MHC class II and cyclooxygenase (COX)-2. In conclusion, PM enhances DC activation that primes naive T cell differentiation towards a Th17-like phenotype in an AhR-dependent manner. Copyright © 2018 Elsevier B.V. All rights reserved.
Murine lung eosinophil activation and chemokine production in allergic airway inflammation

PubMed Central

Rose, C Edward; Lannigan, Joanne A; Kim, Paul; Lee, James J; Fu, Shu Man; Sung, Sun-sang J

2010-01-01

Eosinophils play important roles in asthma and lung infections. Murine models are widely used for assessing the functional significance and mechanistic basis for eosinophil involvements in these diseases. However, little is known about tissue eosinophils in homeostasis. In addition, little data on eosinophil chemokine production during allergic airway inflammation are available. In this study, the properties and functions of homeostatic and activated eosinophils were compared. Eosinophils from normal tissues expressed costimulation and adhesion molecules B7-1, B7-2 and ICAM-1 for Ag presentation but little major histocompatibility complex (MHC) class II, and were found to be poor stimulators of T-cell proliferation. However, these eosinophils expressed high levels of chemokine mRNA including C10, macrophage inflammatory protein (MIP)-1α, MIP-1γ, MIP-2, eotaxin and monocyte chemoattractant protein-5 (MCP-5), and produced chemokine proteins. Eosinophil intracellular chemokines decreased rapidly with concomitant surface marker downregulation upon in vitro culturing consistent with piecemeal degranulation. Lung eosinophils from mice with induced allergic airway inflammation exhibited increased chemokines mRNA expression and chemokines protein production and upregulated MHC class II and CD11c expression. They were also found to be the predominant producers of the CCR1 ligands CCL6/C10 and CCL9/MIP-1γ in inflamed lungs. Eosinophil production of C10 and MIP-1γ correlated with the marked influx of CD11bhigh lung dendritic cells during allergic airway inflammation and the high expression of CCR1 on these dendritic cells (DCs). The study provided baseline information on tissue eosinophils, documented the upregulation of activation markers and chemokine production in activated eosinophils, and indicated that eosinophils were a key chemokine-producing cell type in allergic lung inflammation. PMID:20622891
Nanoscale stiffness of individual dendritic molecules and their aggregates

NASA Astrophysics Data System (ADS)

Tsukruk, Vladimir V.; Shulha, Hennady; Zhai, Xiaowen

2003-02-01

We demonstrate that carefully designed micromapping of the surface stiffness with nanoscale resolution could reveal quantitative data on the elastic properties of compliant, dendritic organic molecules with nanoparticulate dimensions below 3 nm. Much higher elastic modulus was observed for individual, fourth generation dendritic molecules due to their more shape persistent conformation. Large, reversible, elastic deformation is a distinct characteristic of the nanomechanical response observed for individual dendritic molecules. Such a "rubbery" response could be an indication of spatial constraints imposed on vitrification of dendritic molecules tethered to the functionalized interface. Surprisingly, an increased stiffness was also found for the third generation dendritic molecules within long aggregates.
Mechanisms underlying subunit independence in pyramidal neuron dendrites

PubMed Central

Behabadi, Bardia F.; Mel, Bartlett W.

2014-01-01

Pyramidal neuron (PN) dendrites compartmentalize voltage signals and can generate local spikes, which has led to the proposal that their dendrites act as independent computational subunits within a multilayered processing scheme. However, when a PN is strongly activated, back-propagating action potentials (bAPs) sweeping outward from the soma synchronize dendritic membrane potentials many times per second. How PN dendrites maintain the independence of their voltage-dependent computations, despite these repeated voltage resets, remains unknown. Using a detailed compartmental model of a layer 5 PN, and an improved method for quantifying subunit independence that incorporates a more accurate model of dendritic integration, we first established that the output of each dendrite can be almost perfectly predicted by the intensity and spatial configuration of its own synaptic inputs, and is nearly invariant to the rate of bAP-mediated “cross-talk” from other dendrites over a 100-fold range. Then, through an analysis of conductance, voltage, and current waveforms within the model cell, we identify three biophysical mechanisms that together help make independent dendritic computation possible in a firing neuron, suggesting that a major subtype of neocortical neuron has been optimized for layered, compartmentalized processing under in-vivo–like spiking conditions. PMID:24357611
Dendritic Properties Control Energy Efficiency of Action Potentials in Cortical Pyramidal Cells

PubMed Central

Yi, Guosheng; Wang, Jiang; Wei, Xile; Deng, Bin

2017-01-01

Neural computation is performed by transforming input signals into sequences of action potentials (APs), which is metabolically expensive and limited by the energy available to the brain. The metabolic efficiency of single AP has important consequences for the computational power of the cell, which is determined by its biophysical properties and morphologies. Here we adopt biophysically-based two-compartment models to investigate how dendrites affect energy efficiency of APs in cortical pyramidal neurons. We measure the Na+ entry during the spike and examine how it is efficiently used for generating AP depolarization. We show that increasing the proportion of dendritic area or coupling conductance between two chambers decreases Na+ entry efficiency of somatic AP. Activating inward Ca2+ current in dendrites results in dendritic spike, which increases AP efficiency. Activating Ca2+-activated outward K+ current in dendrites, however, decreases Na+ entry efficiency. We demonstrate that the active and passive dendrites take effects by altering the overlap between Na+ influx and internal current flowing from soma to dendrite. We explain a fundamental link between dendritic properties and AP efficiency, which is essential to interpret how neural computation consumes metabolic energy and how biophysics and morphologies contribute to such consumption. PMID:28919852
Dendritic Properties Control Energy Efficiency of Action Potentials in Cortical Pyramidal Cells.

PubMed

Yi, Guosheng; Wang, Jiang; Wei, Xile; Deng, Bin

2017-01-01

Neural computation is performed by transforming input signals into sequences of action potentials (APs), which is metabolically expensive and limited by the energy available to the brain. The metabolic efficiency of single AP has important consequences for the computational power of the cell, which is determined by its biophysical properties and morphologies. Here we adopt biophysically-based two-compartment models to investigate how dendrites affect energy efficiency of APs in cortical pyramidal neurons. We measure the Na + entry during the spike and examine how it is efficiently used for generating AP depolarization. We show that increasing the proportion of dendritic area or coupling conductance between two chambers decreases Na + entry efficiency of somatic AP. Activating inward Ca 2+ current in dendrites results in dendritic spike, which increases AP efficiency. Activating Ca 2+ -activated outward K + current in dendrites, however, decreases Na + entry efficiency. We demonstrate that the active and passive dendrites take effects by altering the overlap between Na + influx and internal current flowing from soma to dendrite. We explain a fundamental link between dendritic properties and AP efficiency, which is essential to interpret how neural computation consumes metabolic energy and how biophysics and morphologies contribute to such consumption.
Dendrites are dispensable for basic motoneuron function but essential for fine tuning of behavior.

PubMed

Ryglewski, Stefanie; Kadas, Dimitrios; Hutchinson, Katie; Schuetzler, Natalie; Vonhoff, Fernando; Duch, Carsten

2014-12-16

Dendrites are highly complex 3D structures that define neuronal morphology and connectivity and are the predominant sites for synaptic input. Defects in dendritic structure are highly consistent correlates of brain diseases. However, the precise consequences of dendritic structure defects for neuronal function and behavioral performance remain unknown. Here we probe dendritic function by using genetic tools to selectively abolish dendrites in identified Drosophila wing motoneurons without affecting other neuronal properties. We find that these motoneuron dendrites are unexpectedly dispensable for synaptic targeting, qualitatively normal neuronal activity patterns during behavior, and basic behavioral performance. However, significant performance deficits in sophisticated motor behaviors, such as flight altitude control and switching between discrete courtship song elements, scale with the degree of dendritic defect. To our knowledge, our observations provide the first direct evidence that complex dendrite architecture is critically required for fine-tuning and adaptability within robust, evolutionarily constrained behavioral programs that are vital for mating success and survival. We speculate that the observed scaling of performance deficits with the degree of structural defect is consistent with gradual increases in intellectual disability during continuously advancing structural deficiencies in progressive neurological disorders.
Different roles of the small GTPases Rac1, Cdc42, and RhoG in CALEB/NGC-induced dendritic tree complexity.

PubMed

Schulz, Jana; Franke, Kristin; Frick, Manfred; Schumacher, Stefan

2016-10-01

Rho GTPases play prominent roles in the regulation of cytoskeletal reorganization. Many aspects have been elaborated concerning the individual functions of Rho GTPases in distinct signaling pathways leading to cytoskeletal rearrangements. However, major questions have yet to be answered regarding the integration and the signaling hierarchy of different Rho GTPases in regulating the cytoskeleton in fundamental physiological events like neuronal process differentiation. Here, we investigate the roles of the small GTPases Rac1, Cdc42, and RhoG in defining dendritic tree complexity stimulated by the transmembrane epidermal growth factor family member CALEB/NGC. Combining gain-of-function and loss-of-function analysis in primary hippocampal neurons, we find that Rac1 is essential for CALEB/NGC-mediated dendritic branching. Cdc42 reduces the complexity of dendritic trees. Interestingly, we identify the palmitoylated isoform of Cdc42 to adversely affect dendritic outgrowth and dendritic branching, whereas the prenylated Cdc42 isoform does not. In contrast to Rac1, CALEB/NGC and Cdc42 are not directly interconnected in regulating dendritic tree complexity. Unlike Rac1, the Rac1-related GTPase RhoG reduces the complexity of dendritic trees by acting upstream of CALEB/NGC. Mechanistically, CALEB/NGC activates Rac1, and RhoG reduces the amount of CALEB/NGC that is located at the right site for Rac1 activation at the cell membrane. Thus, Rac1, Cdc42, and RhoG perform very specific and non-redundant functions at different levels of hierarchy in regulating dendritic tree complexity induced by CALEB/NGC. Rho GTPases play a prominent role in dendritic branching. CALEB/NGC is a transmembrane member of the epidermal growth factor (EGF) family that mediates dendritic branching, dependent on Rac1. CALEB/NGC stimulates Rac1 activity. RhoG inhibits CALEB/NGC-mediated dendritic branching by decreasing the amount of CALEB/NGC at the plasma membrane. Palmitoylated, but not prenylated form of the GTPase Cdc42 decreases dendritic branching. CALEB/NGC and Cdc42 are not directly interconnected in regulating dendritic branching. Thus, CALEB/NGC organizes a Rho GTPase signaling module at the plasma membrane for shaping dendritic trees. © 2016 International Society for Neurochemistry.

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