WorldWideScience

Sample records for cop9 limits dendritic

  1. COP9 limits dendritic branching via Cullin3-dependent degradation of the actin-crosslinking BTB-domain protein Kelch.

    Directory of Open Access Journals (Sweden)

    Inna Djagaeva

    Full Text Available Components of the COP9 signalosome (CSN, a key member of the conserved 26S proteasome degradation pathway, have been detected to be altered in patients of several debilitating syndromes. These findings suggest that CSN acts in neural circuits, but the exact function of CSN in brain remains unidentified. Previously, using Drosophila peripheral nervous system (PNS as a model system, we determined that CSN is a critical regulator of dendritic morphogenesis. We found that defects in CSN led to the strikingly contrast phenotype of either reducing or stimulating dendritic branching. In particular, we have reported that CSN stimulates dendritic branching via Cullin1-mediated proteolysis. Here we describe that CSN inhibits dendritic arborization in PNS neurons acting via control of Cullin3 function: loss of Cullin3 causes excessive dendritic branching. We also identified a downstream target for Cullin3-dependent degradation in neurons--the actin-crosslinking BTB-domain protein Kelch. Inappropriate accumulation of Kelch, either due to the impaired Cullin3-dependent turnover, or ectopic expression of Kelch, leads to uncontrolled dendritic branching. These findings indicate that the CSN pathway modulates neuronal network in a multilayer manner, providing the foundation for new insight into the CSN role in human mental retardation disorders and neurodegenerative disease.

  2. COP9 signalosome function in the DDR.

    Science.gov (United States)

    Hannss, Ronny; Dubiel, Wolfgang

    2011-09-16

    The COP9 signalosome (CSN) is a platform for protein communication in eukaryotic cells. It has an intrinsic metalloprotease that removes the ubiquitin (Ub)-like protein Nedd8 from cullins. CSN-mediated deneddylation regulates culling-RING Ub ligases (CRLs) and controls ubiquitination of proteins involved in DNA damage response (DDR). CSN forms complexes with CRLs containing cullin 4 (CRL4s) which act on chromatin playing crucial roles in DNA repair, checkpoint control and chromatin remodeling. Furthermore, via associated kinases the CSN controls the stability of DDR effectors such as p53 and p27 and thereby the DDR outcome. DDR is a protection against cancer and deregulation of CSN function causes cancer making it an attractive pharmacological target. Here we review current knowledge on CSN function in DDR.

  3. COP9 signalosome: a provider of DNA building blocks

    DEFF Research Database (Denmark)

    Nielsen, Olaf

    2003-01-01

    In fission yeast, the COP9 signalosome is required to activate ribonucleotide reductase for DNA synthesis. This is mediated via the ubiquitin ligase Pcu4, activation of which leads to degradation of the scaffold protein Spd1, which anchors the small ribonucleotide reductase subunit in the nucleus...

  4. COP9 signalosome: a provider of DNA building blocks

    DEFF Research Database (Denmark)

    Nielsen, Olaf

    2003-01-01

    In fission yeast, the COP9 signalosome is required to activate ribonucleotide reductase for DNA synthesis. This is mediated via the ubiquitin ligase Pcu4, activation of which leads to degradation of the scaffold protein Spd1, which anchors the small ribonucleotide reductase subunit in the nucleus...

  5. COP9 signalosome components play a role in the mating pheromone response of S. cerevisiae

    OpenAIRE

    Maytal-Kivity, Vered; Piran, Ron; Pick, Elah; Hofmann, Kay; Glickman, Michael H.

    2003-01-01

    A family of genetically and structurally homologous complexes, the proteasome lid, Cop9 signalosome (CSN) and eukaryotic translation initiation factor 3, mediate different regulatory pathways. The CSN functions in numerous eukaryotes as a regulator of development and signaling, yet until now no evidence for a complex has been found in Saccharomyces cerevisiae. We identified a group of proteins, including a homolog of Csn5/Jab1 and four uncharacterized PCI components, that interact in a manner...

  6. Regulation of Cop9 signalosome activity by the EF-hand Ca2+-binding protein tescalcin.

    Science.gov (United States)

    Levay, Konstantin; Slepak, Vladlen Z

    2014-06-01

    The Ca(2+)-binding protein tescalcin is known to be involved in hematopoietic cell differentiation; however, this mechanism is poorly understood. Here, we identify CSN4 (subunit 4 of the COP9 signalosome) as a novel binding partner of tescalcin. The COP9 signalosome (CSN) is a multiprotein complex that is essential for development in all eukaryotes. This interaction is selective, Ca(2+)-dependent and involves the PCI domain of CSN4 subunit. We then investigated tescalcin and CSN activity in human erythroleukemia HEL and promyelocytic leukemia K562 cells and find that phorbol 12-myristate 13-acetate (PMA)-induced differentiation, resulting in the upregulation of tescalcin, coincides with reduced deneddylation of cullin-1 (Cul1) and stabilization of p27(Kip1) - molecular events that are associated with CSN activity. The knockdown of tescalcin led to an increase in Cul1 deneddylation, expression of F-box protein Skp2 and the transcription factor c-Jun, whereas the levels of cell cycle regulators p27(Kip1) and p53 decreased. These effects are consistent with the hypothesis that tescalcin might play a role as a negative regulator of CSN activity towards Cul1 in the process of induced cell differentiation.

  7. COP9 signalosome subunit 6 binds and inhibits avian leukosis virus integrase.

    Science.gov (United States)

    Wang, Zhanxin; Xu, Aotian; Hou, Xinhui; Chen, Fuyong; Cao, Weisheng; Yu, Jieshi; Liao, Ming; Tang, Jun

    2014-10-24

    The retroviral integrase plays an essential role in the integration of reverse-transcribed retroviral cDNA into the host cell genome, and serves as an important target for anti-viral therapeutics. In this study, we identified the COP9 signalosome subunit 6 (CSN6) as a novel avian leukosis virus (ALV) integrase binding protein. Co-immunoprecipitation and GST pull-down assays showed that CSN6 bound to ALV integrase likely through direct interaction of CSN6 to the catalytic core of the integrase. We further demonstrated CSN6 inhibited integrase activity in vitro; knockdown of CSN6 in DF-1 promoted ALV production. These results indicated that CSN6 may be a negative regulator of ALV replication by binding to and inhibiting integrase. Our findings provided the insight into the integrase-based host defense system and may have implications in the development of integrase-based anti-viral strategies.

  8. The COP9 signalosome interacts with SCF UFO and participates in Arabidopsis flower development.

    Science.gov (United States)

    Wang, Xiping; Feng, Suhua; Nakayama, Naomi; Crosby, W L; Irish, Vivian; Deng, Xing Wang; Wei, Ning

    2003-05-01

    The COP9 signalosome (CSN) is involved in multiple developmental processes. It interacts with SCF ubiquitin ligases and deconjugates Nedd8/Rub1 from cullins (deneddylation). CSN is highly expressed in Arabidopsis floral tissues. To investigate the role of CSN in flower development, we examined the expression pattern of CSN in developing flowers. We report here that two csn1 partially deficient Arabidopsis strains exhibit aberrant development of floral organs, decline of APETALA3 (AP3) expression, and low fertility in addition to defects in shoot and inflorescence meristems. We show that UNUSUAL FLORAL ORGANS (UFO) forms a SCF(UFO) complex, which is associated with CSN in vivo. Genetic interaction analysis indicates that CSN is necessary for the gain-of-function activity of the F-box protein UFO in AP3 activation and in floral organ transformation. Compared with the previously reported csn5 antisense and csn1 null mutants, partial deficiency of CSN1 causes a reduction in the level of CUL1 in the mutant flowers without an obvious defect in CUL1 deneddylation. We conclude that CSN is an essential regulator of Arabidopsis flower development and suggest that CSN regulates Arabidopsis flower development in part by modulating SCF(UFO)-mediated AP3 activation.

  9. Neurospora COP9 signalosome integrity plays major roles for hyphal growth, conidial development, and circadian function.

    Directory of Open Access Journals (Sweden)

    Zhipeng Zhou

    Full Text Available The COP9 signalosome (CSN is a highly conserved multifunctional complex that has two major biochemical roles: cleaving NEDD8 from cullin proteins and maintaining the stability of CRL components. We used mutation analysis to confirm that the JAMM domain of the CSN-5 subunit is responsible for NEDD8 cleavage from cullin proteins in Neurospora crassa. Point mutations of key residues in the metal-binding motif (EX(nHXHX(10D of the CSN-5 JAMM domain disrupted CSN deneddylation activity without interfering with assembly of the CSN complex or interactions between CSN and cullin proteins. Surprisingly, CSN-5 with a mutated JAMM domain partially rescued the phenotypic defects observed in a csn-5 mutant. We found that, even without its deneddylation activity, the CSN can partially maintain the stability of the SCF(FWD-1 complex and partially restore the degradation of the circadian clock protein FREQUENCY (FRQ in vivo. Furthermore, we showed that CSN containing mutant CSN-5 efficiently prevents degradation of the substrate receptors of CRLs. Finally, we found that deletion of the CAND1 ortholog in N. crassa had little effect on the conidiation circadian rhythm. Our results suggest that CSN integrity plays major roles in hyphal growth, conidial development, and circadian function in N. crassa.

  10. Structural and biochemical characterization of the Cop9 signalosome CSN5/CSN6 heterodimer.

    Directory of Open Access Journals (Sweden)

    Melissa Birol

    Full Text Available The Cop9 signalosome complex (CSN regulates the functional cycle of the major E3 ubiquitin ligase family, the cullin RING E3 ubiquitin ligases (CRLs. Activated CRLs are covalently modified by the ubiquitin-like protein Nedd8 (neural precursor cell expressed developmentally down-regulated protein 8. CSN serves an essential role in myriad cellular processes by reversing this modification through the isopeptidase activity of its CSN5 subunit. CSN5 alone is inactive due to an auto-inhibited conformation of its catalytic domain. Here we report the molecular basis of CSN5 catalytic domain activation and unravel a molecular hierarchy in CSN deneddylation activity. The association of CSN5 and CSN6 MPN (for Mpr1/Pad1 N-terminal domains activates its isopeptidase activity. The CSN5/CSN6 module, however, is inefficient in CRL deneddylation, indicating a requirement of further elements in this reaction such as other CSN subunits. A hybrid molecular model of CSN5/CSN6 provides a structural framework to explain these functional observations. Docking this model into a published CSN electron density map and using distance constraints obtained from cross-linking coupled to mass-spectrometry, we find that the C-termini of the CSN subunits could form a helical bundle in the centre of the structure. They likely play a key scaffolding role in the spatial organization of CSN and precise positioning of the dimeric MPN catalytic core.

  11. The COP9 SIGNALOSOME Is Required for Postembryonic Meristem Maintenance in Arabidopsis thaliana.

    Science.gov (United States)

    Franciosini, Anna; Moubayidin, Laila; Du, Kaiqi; Matari, Nahill H; Boccaccini, Alessandra; Butera, Simone; Vittorioso, Paola; Sabatini, Sabrina; Jenik, Pablo D; Costantino, Paolo; Serino, Giovanna

    2015-11-02

    Cullin-RING E3 ligases (CRLs) regulate different aspects of plant development and are activated by modification of their cullin subunit with the ubiquitin-like protein NEDD8 (NEural precursor cell expressed Developmentally Down-regulated 8) (neddylation) and deactivated by NEDD8 removal (deneddylation). The constitutively photomorphogenic9 (COP9) signalosome (CSN) acts as a molecular switch of CRLs activity by reverting their neddylation status, but its contribution to embryonic and early seedling development remains poorly characterized. Here, we analyzed the phenotypic defects of csn mutants and monitored the cullin deneddylation/neddylation ratio during embryonic and early seedling development. We show that while csn mutants can complete embryogenesis (albeit at a slower pace than wild-type) and are able to germinate (albeit at a reduced rate), they progressively lose meristem activity upon germination until they become unable to sustain growth. We also show that the majority of cullin proteins are progressively neddylated during the late stages of seed maturation and become deneddylated upon seed germination. This developmentally regulated shift in the cullin neddylation status is absent in csn mutants. We conclude that the CSN and its cullin deneddylation activity are required to sustain postembryonic meristem function in Arabidopsis. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

  12. COP9-Signalosome deneddylase activity is enhanced by simultaneous neddylation: insights into the regulation of an enzymatic protein complex.

    Science.gov (United States)

    Bornstein, Gil; Grossman, Chagai

    2015-01-01

    Cullin-RING ubiquitin ligases (CRLs) are regulated by neddylation, which is a post translation modification of the Cullin family proteins. Neddylation of Cul1 activates the ligase through some means of biochemical mechanisms. The rate of neddylation and its extent are regulated by 2 opposing enzymatic processes: neddylation by an enzymatic cascade, and deneddylation by COP9-Signalosome (CSN) complex protein. The mechanism by which COP9-Signalosome catalytic activity is regulated is not well understood. We set an in vitro neddylation and deneddylation reaction using as a source for specific COP9/Signalosome deneddylase activity either Hela cells extract or purified Signalosome. Neddylation reaction of either endogenic Cul1 from Hela cells extract or recombinant Cul1 was catalyzed by recombinant neddylation enzymes. Deneddylation rate was tested either simultaneous to neddylation or after termination of neddylation by using an ATP depleting reaction or by directly inhibiting the neddylation activation enzyme named APP-BP1/UBA3 by its specific inhibitor MLN-4924. We demonstrated that neddylation and deneddylation are catalytically engaged and that inhibition of Cul1 neddylation significantly causes a decline in the rate of COP9-Signalosome deneddylase activity. Since neddylation is an ATP consuming reaction we managed to isolate the 2 opposing processes which surprisingly caused a decline in COP9 activity. Using MLN-4924 we demonstrated that direct inhibition of neddylation negatively influences the rate of deneddylation. The hypothesis that phosphorylation controls deneddylation was ruled out by the fact that no change in the rate of deneddylation was exemplified while converting the use of ATP with AMP-PNP. We demonstrated that deneddylation of Cul1 is positively regulated through direct simultaneous neddylation and is not dependent upon autophosphorylation. Defining the mechanism that regulates neddylation and deneddylation of Cullin proteins is important due to

  13. Control of multicellular development by the physically interacting deneddylases DEN1/DenA and COP9 signalosome.

    Directory of Open Access Journals (Sweden)

    Martin Christmann

    Full Text Available Deneddylases remove the ubiquitin-like protein Nedd8 from modified proteins. An increased deneddylase activity has been associated with various human cancers. In contrast, we show here that a mutant strain of the model fungus Aspergillus nidulans deficient in two deneddylases is viable but can only grow as a filament and is highly impaired for multicellular development. The DEN1/DenA and the COP9 signalosome (CSN deneddylases physically interact in A. nidulans as well as in human cells, and CSN targets DEN1/DenA for protein degradation. Fungal development responds to light and requires both deneddylases for an appropriate light reaction. In contrast to CSN, which is necessary for sexual development, DEN1/DenA is required for asexual development. The CSN-DEN1/DenA interaction that affects DEN1/DenA protein levels presumably balances cellular deneddylase activity. A deneddylase disequilibrium impairs multicellular development and suggests that control of deneddylase activity is important for multicellular development.

  14. Inositol hexakisphosphate (IP6) generated by IP5K mediates cullin-COP9 signalosome interactions and CRL function.

    Science.gov (United States)

    Scherer, Paul C; Ding, Yan; Liu, Zhiqing; Xu, Jing; Mao, Haibin; Barrow, James C; Wei, Ning; Zheng, Ning; Snyder, Solomon H; Rao, Feng

    2016-03-29

    The family of cullin-RING E3 Ligases (CRLs) and the constitutive photomorphogenesis 9 (COP9) signalosome (CSN) form dynamic complexes that mediate ubiquitylation of 20% of the proteome, yet regulation of their assembly/disassembly remains poorly understood. Inositol polyphosphates are highly conserved signaling molecules implicated in diverse cellular processes. We now report that inositol hexakisphosphate (IP6) is a major physiologic determinant of the CRL-CSN interface, which includes a hitherto unidentified electrostatic interaction between the N-terminal acidic tail of CSN subunit 2 (CSN2) and a conserved basic canyon on cullins. IP6, with an EC50 of 20 nM, acts as an intermolecular "glue," increasing cullin-CSN2 binding affinity by 30-fold, thereby promoting assembly of the inactive CRL-CSN complexes. The IP6 synthase, Ins(1,3,4,5,6)P5 2-kinase (IPPK/IP5K) binds to cullins. Depleting IP5K increases the percentage of neddylated, active Cul1 and Cul4A, and decreases levels of the Cul1/4A substrates p27 and p21. Besides dysregulating CRL-mediated cell proliferation and UV-induced apoptosis, IP5K depletion potentiates by 28-fold the cytotoxic effect of the neddylation inhibitor MLN4924. Thus, IP5K and IP6 are evolutionarily conserved components of the CRL-CSN system and are potential targets for cancer therapy in conjunction with MLN4924.

  15. Current limit diagrams for dendrite formation in solid-state electrolytes for Li-ion batteries

    Science.gov (United States)

    Raj, R.; Wolfenstine, J.

    2017-03-01

    We build upon the concept that nucleation of lithium dendrites at the lithium anode-solid state electrolyte interface is instigated by the higher resistance of grain boundaries that raises the local electro-chemical potential of lithium, near the lithium-electrode. This excess electro-chemo-mechanical potential, however, is reduced by the mechanical back stress generated when the dendrite is formed within the electrolyte. These parameters are coalesced into an analytical model that prescribes a specific criterion for dendrite formation. The results are presented in the form of current limit diagrams that show the "safe" and "fail" regimes for battery function. A higher conductivity of the electrolyte can reduce dendrite formation.

  16. Over-limiting Current and Control of Dendritic Growth by Surface Conduction in Nanopores

    CERN Document Server

    Han, Ji-Hyung; Bai, Peng; Bazant, Martin Z

    2014-01-01

    Understanding over-limiting current (faster than diffusion) is a long-standing challenge in electrochemistry with applications in desalination and energy storage. Known mechanisms involve either chemical or hydrodynamic instabilities in unconfined electrolytes. Here, it is shown that over-limiting current can be sustained by surface conduction in nano pores, without any such instabilities, and used to control dendritic growth during electrodeposition. Copper electrode posits are grown in anodized aluminum oxide membranes with polyelectrolyte coatings to modify the surface charge. At low currents, uniform electroplating occurs, unaffected by surface modification due to thin electric double layers, but the morphology changes dramatically above the limiting current. With negative surface charge, growth is enhanced along the nanopore surfaces, forming surface dendrites and nanotubes behind a deionization shock. With positive surface charge, dendrites avoid the surfaces and are either guided along the nanopore cen...

  17. Prediction of a common structural scaffold for proteasome lid, COP9-signalosome and eIF3 complexes

    Directory of Open Access Journals (Sweden)

    Hofmann Kay

    2005-03-01

    Full Text Available Abstract Background The 'lid' subcomplex of the 26S proteasome and the COP9 signalosome (CSN complex share a common architecture consisting of six subunits harbouring a so-called PCI domain (proteasome, CSN, eIF3 at their C-terminus, plus two subunits containing MPN domains (Mpr1/Pad1 N-terminal. The translation initiation complex eIF3 also contains PCI- and MPN-domain proteins, but seems to deviate from the 6+2 stoichiometry. Initially, the PCI domain was defined as the region of detectable sequence similarity between the components mentioned above. Results During an exhaustive bioinformatical analysis of proteasome components, we detected multiple instances of tetratrico-peptide repeats (TPR in the N-terminal region of most PCI proteins, suggesting that their homology is not restricted to the PCI domain. We also detected a previously unrecognized PCI domain in the eIF3 component eIF3k, a protein whose 3D-structure has been determined recently. By using profile-guided alignment techniques, we show that the structural elements found in eIF3k are most likely conserved in all PCI proteins, resulting in a structural model for the canonical PCI domain. Conclusion Our model predicts that the homology domain PCI is not a true domain in the structural sense but rather consists of two subdomains: a C-terminal 'winged helix' domain with a key role in PCI:PCI interaction, preceded by a helical repeat region. The TPR-like repeats detected in the N-terminal region of PCI proteins most likely form an uninterrupted extension of the repeats found within the PCI domain boundaries. This model allows an interpretation of several puzzling experimental results.

  18. CIF-1, a Shared Subunit of the COP9/Signalosome and Eukaryotic Initiation Factor 3 Complexes, Regulates MEL-26 Levels in the Caenorhabditis elegans Embryo▿

    Science.gov (United States)

    Luke-Glaser, Sarah; Roy, Marcia; Larsen, Brett; Le Bihan, Thierry; Metalnikov, Pavel; Tyers, Mike; Peter, Matthias; Pintard, Lionel

    2007-01-01

    The COP9/signalosome (CSN) is an evolutionarily conserved macromolecular complex that regulates the cullin-RING ligase (CRL) class of E3 ubiquitin ligases, primarily by removing the ubiquitin-like protein Nedd8 from the cullin subunit. In the Caenorhabditis elegans embryo, the CSN controls the degradation of the microtubule-severing protein MEI-1 through CUL-3 deneddylation. However, the molecular mechanisms of CSN function and its subunit composition remain to be elucidated. Here, using a proteomic approach, we have characterized the CSN and CUL-3 complexes from C. elegans embryos. We show that the CSN physically interacts with the CUL-3-based CRL and regulates its activity by counteracting the autocatalytic instability of the substrate-specific adaptor MEL-26. Importantly, we identified the uncharacterized protein K08F11.3/CIF-1 (for CSN-eukaryotic initiation factor 3 [eIF3]) as a stoichiometric and functionally important subunit of the CSN complex. CIF-1 appears to be the only ortholog of Csn7 encoded by the C. elegans genome, but it also exhibits extensive sequence similarity to eIF3m family members, which are required for the initiation of protein translation. Indeed, CIF-1 binds eIF-3.F and inactivation of cif-1 impairs translation in vivo. Taken together, our results indicate that CIF-1 is a shared subunit of the CSN and eIF3 complexes and may therefore link protein translation and degradation. PMID:17403899

  19. CIF-1, a shared subunit of the COP9/signalosome and eukaryotic initiation factor 3 complexes, regulates MEL-26 levels in the Caenorhabditis elegans embryo.

    Science.gov (United States)

    Luke-Glaser, Sarah; Roy, Marcia; Larsen, Brett; Le Bihan, Thierry; Metalnikov, Pavel; Tyers, Mike; Peter, Matthias; Pintard, Lionel

    2007-06-01

    The COP9/signalosome (CSN) is an evolutionarily conserved macromolecular complex that regulates the cullin-RING ligase (CRL) class of E3 ubiquitin ligases, primarily by removing the ubiquitin-like protein Nedd8 from the cullin subunit. In the Caenorhabditis elegans embryo, the CSN controls the degradation of the microtubule-severing protein MEI-1 through CUL-3 deneddylation. However, the molecular mechanisms of CSN function and its subunit composition remain to be elucidated. Here, using a proteomic approach, we have characterized the CSN and CUL-3 complexes from C. elegans embryos. We show that the CSN physically interacts with the CUL-3-based CRL and regulates its activity by counteracting the autocatalytic instability of the substrate-specific adaptor MEL-26. Importantly, we identified the uncharacterized protein K08F11.3/CIF-1 (for CSN-eukaryotic initiation factor 3 [eIF3]) as a stoichiometric and functionally important subunit of the CSN complex. CIF-1 appears to be the only ortholog of Csn7 encoded by the C. elegans genome, but it also exhibits extensive sequence similarity to eIF3m family members, which are required for the initiation of protein translation. Indeed, CIF-1 binds eIF-3.F and inactivation of cif-1 impairs translation in vivo. Taken together, our results indicate that CIF-1 is a shared subunit of the CSN and eIF3 complexes and may therefore link protein translation and degradation.

  20. Functional limitations of plasmacytoid dendritic cells limit type I interferon, T cell responses and virus control in early life.

    Directory of Open Access Journals (Sweden)

    Elodie Belnoue

    Full Text Available Infant mortality from viral infection remains a major global health concern: viruses causing acute infections in immunologically mature hosts often follow a more severe course in early life, with prolonged or persistent viral replication. Similarly, the WE strain of lymphocytic choriomeningitis virus (LCMV-WE causes acute self-limiting infection in adult mice but follows a protracted course in infant animals, in which LCMV-specific CD8⁺ T cells fail to expand and control infection. By disrupting type I IFNs signaling in adult mice or providing IFN-α supplementation to infant mice, we show here that the impaired early life T cell responses and viral control result from limited early type I IFN responses. We postulated that plasmacytoid dendritic cells (pDC, which have been identified as one major source of immediate-early IFN-I, may not exert adult-like function in vivo in the early life microenvironment. We tested this hypothesis by studying pDC functions in vivo during LCMV infection and identified a coordinated downregulation of infant pDC maturation, activation and function: despite an adult-like in vitro activation capacity of infant pDCs, the expression of the E2-2 pDC master regulator (and of critical downstream antiviral genes such as MyD88, TLR7/TLR9, NF-κB, IRF7 and IRF8 is downregulated in vivo at baseline and during LCMV infection. A similar pattern was observed in response to ssRNA polyU, a model ligand of the TLR7 viral sensor. This suggests that the limited T cell-mediated defense against early life viral infections is largely attributable to / regulated by infant pDC responses and provides incentives for novel strategies to supplement or stimulate immediate-early IFN-α responses.

  1. The eta7/csn3-3 auxin response mutant of Arabidopsis defines a novel function for the CSN3 subunit of the COP9 signalosome.

    Directory of Open Access Journals (Sweden)

    He Huang

    Full Text Available The COP9 signalosome (CSN is an eight subunit protein complex conserved in all higher eukaryotes. In Arabidopsis thaliana, the CSN regulates auxin response by removing the ubiquitin-like protein NEDD8/RUB1 from the CUL1 subunit of the SCF(TIR1/AFB ubiquitin-ligase (deneddylation. Previously described null mutations in any CSN subunit result in the pleiotropic cop/det/fus phenotype and cause seedling lethality, hampering the study of CSN functions in plant development. In a genetic screen to identify enhancers of the auxin response defects conferred by the tir1-1 mutation, we identified a viable csn mutant of subunit 3 (CSN3, designated eta7/csn3-3. In addition to enhancing tir1-1 mutant phenotypes, the csn3-3 mutation alone confers several phenotypes indicative of impaired auxin signaling including auxin resistant root growth and diminished auxin responsive gene expression. Unexpectedly however, csn3-3 plants are not defective in either the CSN-mediated deneddylation of CUL1 or in SCF(TIR1-mediated degradation of Aux/IAA proteins. These findings suggest that csn3-3 is an atypical csn mutant that defines a novel CSN or CSN3-specific function. Consistent with this possibility, we observe dramatic differences in double mutant interactions between csn3-3 and other auxin signaling mutants compared to another weak csn mutant, csn1-10. Lastly, unlike other csn mutants, assembly of the CSN holocomplex is unaffected in csn3-3 plants. However, we detected a small CSN3-containing protein complex that is altered in csn3-3 plants. We hypothesize that in addition to its role in the CSN as a cullin deneddylase, CSN3 functions in a distinct protein complex that is required for proper auxin signaling.

  2. Electron microscopy and in vitro deneddylation reveal similar architectures and biochemistry of isolated human and Flag-mouse COP9 signalosome complexes

    Energy Technology Data Exchange (ETDEWEB)

    Rockel, Beate [Department of Molecular Structural Biology, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried (Germany); Schmaler, Tilo; Huang, Xiaohua [Division of Molecular Biology, Department of General, Visceral, Vascular and Thoracic Surgery, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin (Germany); Dubiel, Wolfgang, E-mail: Wolfgang.dubiel@charite.de [Division of Molecular Biology, Department of General, Visceral, Vascular and Thoracic Surgery, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin (Germany)

    2014-07-25

    Highlights: • Deneddylation rates of human erythrocyte and mouse fibroblast CSN are very similar. • 3D models of native human and mouse CSN reveal common architectures. • The cryo-structure of native mammalian CSN shows a horseshoe subunit arrangement. - Abstract: The COP9 signalosome (CSN) is a regulator of the ubiquitin (Ub) proteasome system (UPS). In the UPS, proteins are Ub-labeled for degradation by Ub ligases conferring substrate specificity. The CSN controls a large family of Ub ligases called cullin-RING ligases (CRLs), which ubiquitinate cell cycle regulators, transcription factors and DNA damage response proteins. The CSN possesses structural similarities with the 26S proteasome Lid complex and the translation initiation complex 3 (eIF3) indicating similar ancestry and function. Initial structures were obtained 14 years ago by 2D electron microscopy (EM). Recently, first 3D molecular models of the CSN were created on the basis of negative-stain EM and single-particle analysis, mostly with recombinant complexes. Here, we compare deneddylating activity and structural features of CSN complexes purified in an elaborate procedure from human erythrocytes and efficiently pulled down from mouse Flag-CSN2 B8 fibroblasts. In an in vitro deneddylation assay both the human and the mouse CSN complexes deneddylated Nedd8-Cul1 with comparable rates. 3D structural models of the erythrocyte CSN as well as of the mouse Flag-CSN were generated by negative stain EM and by cryo-EM. Both complexes show a central U-shaped segment from which several arms emanate. This structure, called the horseshoe, is formed by the PCI domain subunits. CSN5 and CSN6 point away from the horseshoe. Compared to 3D models of negatively stained CSN complexes, densities assigned to CSN2 and CSN4 are better defined in the cryo-map. Because biochemical and structural results obtained with CSN complexes isolated from human erythrocytes and purified by Flag-CSN pulldown from mouse B8 fibroblasts

  3. Plasticity of Cu nanoparticles: Dislocation-dendrite-induced strain hardening and a limit for displacive plasticity

    Directory of Open Access Journals (Sweden)

    Antti Tolvanen

    2013-03-01

    Full Text Available The plastic behaviour of individual Cu crystallites under nanoextrusion is studied by molecular dynamics simulations. Single-crystal Cu fcc nanoparticles are embedded in a spherical force field mimicking the effect of a contracting carbon shell, inducing pressure on the system in the range of gigapascals. The material is extruded from a hole of 1.1–1.6 nm radius under athermal conditions. Simultaneous nucleation of partial dislocations at the extrusion orifice leads to the formation of dislocation dendrites in the particle causing strain hardening and high flow stress of the material. As the extrusion orifice radius is reduced below 1.3 Å we observe a transition from displacive plasticity to solid-state amorphisation.

  4. IRAK-M expression limits dendritic cell activation and proinflammatory cytokine production in response to Helicobacter pylori.

    Directory of Open Access Journals (Sweden)

    Jessica Shiu

    Full Text Available Helicobacter pylori (H. pylori infects the gastric mucosa and persists for the life of the host. Bacterial persistence may be due to the induction of regulatory T cells (Tregs whichmay have protective effects against other diseases such as asthma. It has been shown that H. pylori modulates the T cell response through dendritic cell reprogramming but the molecular pathways involved are relatively unknown. The goal of this study was to identify critical elements of dendritic cell (DC activation and evaluate potential influence on immune activation. Microarray analysis was used to demonstrate limited gene expression changes in H. pylori stimulated bone marrow derived DCs (BMDCs compared to the BMDCs stimulated with E. coli. IRAK-M, a negative regulator of TLR signaling, was upregulated and we selectedit for investigation of its role in modulating the DC and T cell responses. IRAK-M(-/- and wild type BMDC were compared for their response to H. pylori. Cells lacking IRAK-M produced significantly greater amounts of proinflammatory MIP-2 and reduced amounts of immunomodulatory IL-10 than wild type BMDC. IRAK-M(-/- cells also demonstrated increased MHC II expression upon activation. However, IRAK-M(-/- BMDCs were comparable to wild type BMDCs in inducing T-helper 17 (TH17 and Treg responses as demonstrated in vitro using BMDC CD4+ T cells co-culture assays,and in vivo though the adoptive transfer of CD4(+ FoxP3-GFP T cells into H. pylori infected IRAK-M(-/- mice. These results suggest that H. pylori infection leads to the upregulation of anti-inflammatory molecules like IRAK-M and that IRAK-M has a direct impact on innate functions in DCs such as cytokine and costimulation molecule upregulation but may not affect T cell skewing.

  5. Distinct evolution of TLR-mediated dendritic cell cytokine secretion in patients with limited and diffuse cutaneous systemic sclerosis.

    NARCIS (Netherlands)

    Bon, L. van; Popa, C.; Huibens, R.J.F.; Vonk, M.C.; York, M.; Simms, R.; Hesselstrand, R.; Wuttge, D.M.; Lafyatis, R.; Radstake, T.R.D.J.

    2010-01-01

    BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease and accumulating evidence suggests a role for Toll-like receptor (TLR)-mediated activation of dendritic cells (DCs). OBJECTIVE: To map TLR-mediated cytokine responses of DCs from patients with SSc. METHODS: 45 patients with SSc were inclu

  6. Dendritic Cell

    OpenAIRE

    Sevda Söker

    2005-01-01

    Dendritic cells, a member of family of antigen presenting cells, are most effective cells in the primary immune response. Dendritic cells originated from dendron, in mean of tree in the Greek, because of their long and elaborate cytoplasmic branching processes. Dendritic cells constitute approximately 0.1 to 1 percent of the blood’s mononuclear cell. Dendritic cells are widely distributed, and specialized for antigen capture and T cell stimulation. In this article, structures and functions of...

  7. Caspase-8 acts as a molecular rheostat to limit RIPK1- and MyD88-mediated dendritic cell activation.

    Science.gov (United States)

    Cuda, Carla M; Misharin, Alexander V; Gierut, Angelica K; Saber, Rana; Haines, G Kenneth; Hutcheson, Jack; Hedrick, Stephen M; Mohan, Chandra; Budinger, G Scott; Stehlik, Christian; Perlman, Harris

    2014-06-15

    Caspase-8, an executioner enzyme in the death receptor pathway, was shown to initiate apoptosis and suppress necroptosis. In this study, we identify a novel, cell death-independent role for caspase-8 in dendritic cells (DCs): DC-specific expression of caspase-8 prevents the onset of systemic autoimmunity. Failure to express caspase-8 has no effect on the lifespan of DCs but instead leads to an enhanced intrinsic activation and, subsequently, more mature and autoreactive lymphocytes. Uncontrolled TLR activation in a RIPK1-dependent manner is responsible for the enhanced functionality of caspase-8-deficient DCs, because deletion of the TLR-signaling mediator, MyD88, ameliorates systemic autoimmunity induced by caspase-8 deficiency. Taken together, these data demonstrate that caspase-8 functions in a cell type-specific manner and acts uniquely in DCs to maintain tolerance.

  8. A reduced population of CD103(+)CD11b(+) dendritic cells has a limited impact on oral Salmonella infection.

    Science.gov (United States)

    Fernández-Santoscoy, María; Wenzel, Ulf Alexander; Persson, Emma; Yrlid, Ulf; Agace, William; Wick, Mary Jo

    2016-08-01

    CD103(+)CD11b(+) dendritic cells (DC) are the major migratory DC subset in the small intestine lamina propria (siLP) and their survival is dependent on the transcription factor interferon regulatory factor 4 (IRF4). Mice with a DC-specific deletion of irf4 (CD11c-cre.Irf4 mice) have reduced mucosal CD103(+)CD11b(+) DC and altered T cell differentiation to protein antigen. The influence of CD103(+)CD11b(+) DC on oral infection with the gastrointestinal pathogen Salmonella, however, is poorly understood and is investigated here. We show that, despite being infected with Salmonella, CD11c-cre.Irf4 mice (called Cre(+) mice) conserve the reduction in CD103(+)CD11b(+) DC observed in naive Cre(+) mice, particularly in the mesenteric lymph nodes (MLN) but also in the siLP at day 3 post infection. Moreover, Salmonella-infected Cre(+) mice have a similar bacterial burden in intestinal tissues (siLP, MLN and Peyer's patches) as well as the spleen compared to infected Cre(-) controls. The T cell compartment, including the frequency of IFN-γ and IL-17-producing T cells, is not altered in intestinal tissues of Salmonella-infected Cre(+) mice relative to infected Cre(-) controls. In addition, no difference between infected Cre(+) and Cre(-) mice was observed in either the concentration of IL-6 or IL-17 in whole tissue lysates of siLP, MLN or Peyer's patches or in the serum concentration of Salmonella-specific IgG and IgM. Overall the data suggest that the reduction of CD103(+)CD11b(+) DC in Cre(+) mice has little if any impact on Salmonella burden in infected tissues or eliciting effector functions important in host survival at later stages of the infection.

  9. [Inflammatory dendritic cells].

    Science.gov (United States)

    Segura, Elodie; Amigorena, Sebastian

    2014-01-01

    Dendritic cells are a rare and heterogeneous population of professional antigen-presenting cells. Several murine dendritic cell subpopulations have been identified that differ in their phenotype and functional properties. In the steady state, committed dendritic cell precursors differentiate into lymphoid organ-resident dendritic cells and migratory tissue dendritic cells. During inflammation appears an additional dendritic cell subpopulation that has been termed « inflammatory dendritic cells ». Inflammatory dendritic cells differentiate in situ from monocytes recruited to the site of inflammation. Here, we discuss how mouse inflammatory dendritic cells differ from macrophages and from other dendritic cell populations. Finally, we review recent work on human inflammatory dendritic cells.

  10. Limiter

    Science.gov (United States)

    Cohen, S.A.; Hosea, J.C.; Timberlake, J.R.

    1984-10-19

    A limiter with a specially contoured front face is provided. The front face of the limiter (the plasma-side face) is flat with a central indentation. In addition, the limiter shape is cylindrically symmetric so that the limiter can be rotated for greater heat distribution. This limiter shape accommodates the various power scrape-off distances lambda p, which depend on the parallel velocity, V/sub parallel/, of the impacting particles.

  11. Isothermal Dendritic Growth Experiment - PVA Dendrites

    Science.gov (United States)

    1997-01-01

    The Isothermal Dendritic Growth Experiment (IDGE), flown on three Space Shuttle missions, is yielding new insights into virtually all industrially relevant metal and alloy forming operations. IDGE used transparent organic liquids that form dendrites (treelike structures) similar to those inside metal alloys. Comparing Earth-based and space-based dendrite growth velocity, tip size and shape provides a better understanding of the fundamentals of dentritic growth, including gravity's effects. Shalowgraphic images of pivalic acid (PVA) dendrites forming from the melt show the subtle but distinct effects of gravity-driven heat convection on dentritic growth. In orbit, the dendrite grows as its latent heat is liberated by heat conduction. This yields a blunt dendrite tip. On Earth, heat is carried away by both conduction and gravity-driven convection. This yields a sharper dendrite tip. In addition, under terrestrial conditions, the sidebranches growing in the direction of gravity are augmented as gravity helps carry heat out of the way of the growing sidebranches as opposed to microgravity conditions where no augmentation takes place. IDGE was developed by Rensselaer Polytechnic Institute and NASA/Glenn Research Center. Advanced follow-on experiments are being developed for flight on the International Space Station. Photo Credit: NASA/Glenn Research Center

  12. Cationic liposomes promote antigen cross-presentation in dendritic cells by alkalizing the lysosomal pH and limiting the degradation of antigens

    Science.gov (United States)

    Gao, Jie; Ochyl, Lukasz J; Yang, Ellen; Moon, James J

    2017-01-01

    Cationic liposomes (CLs) have been widely examined as vaccine delivery nanoparticles since they can form complexes with biomacromolecules, promote delivery of antigens and adjuvant molecules to antigen-presenting cells (APCs), and mediate cellular uptake of vaccine components. CLs are also known to trigger antigen cross-presentation – the process by which APCs internalize extracellular protein antigens, degrade them into minimal CD8+ T-cell epitopes, and present them in the context of major histocompatibility complex-I (MHC-I). However, the precise mechanisms behind CL-mediated induction of cross-presentation and cross-priming of CD8+ T-cells remain to be elucidated. In this study, we have developed two distinct CL systems and examined their impact on the lysosomal pH in dendritic cells (DCs), antigen degradation, and presentation of peptide:MHC-I complexes to antigen-specific CD8+ T-cells. To achieve this, we have used 3β-[N-(N′,N′-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) as the prototypical components of CLs with tertiary amine groups and compared the effect of CLs and anionic liposomes on lysosomal pH, antigen degradation, and cross-presentation by DCs. Our results showed that CLs, but not anionic liposomes, elevated the lysosomal pH in DCs and reduced antigen degradation, thereby promoting cross-presentation and cross-priming of CD8+ T-cell responses. These studies shed new light on CL-mediated cross-presentation and suggest that intracellular fate of vaccine components and subsequent immunological responses can be controlled by rational design of nanomaterials. PMID:28243087

  13. Cationic liposomes promote antigen cross-presentation in dendritic cells by alkalizing the lysosomal pH and limiting the degradation of antigens.

    Science.gov (United States)

    Gao, Jie; Ochyl, Lukasz J; Yang, Ellen; Moon, James J

    2017-01-01

    Cationic liposomes (CLs) have been widely examined as vaccine delivery nanoparticles since they can form complexes with biomacromolecules, promote delivery of antigens and adjuvant molecules to antigen-presenting cells (APCs), and mediate cellular uptake of vaccine components. CLs are also known to trigger antigen cross-presentation - the process by which APCs internalize extracellular protein antigens, degrade them into minimal CD8(+) T-cell epitopes, and present them in the context of major histocompatibility complex-I (MHC-I). However, the precise mechanisms behind CL-mediated induction of cross-presentation and cross-priming of CD8(+) T-cells remain to be elucidated. In this study, we have developed two distinct CL systems and examined their impact on the lysosomal pH in dendritic cells (DCs), antigen degradation, and presentation of peptide:MHC-I complexes to antigen-specific CD8(+) T-cells. To achieve this, we have used 3β-[N-(N',N'-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) as the prototypical components of CLs with tertiary amine groups and compared the effect of CLs and anionic liposomes on lysosomal pH, antigen degradation, and cross-presentation by DCs. Our results showed that CLs, but not anionic liposomes, elevated the lysosomal pH in DCs and reduced antigen degradation, thereby promoting cross-presentation and cross-priming of CD8(+) T-cell responses. These studies shed new light on CL-mediated cross-presentation and suggest that intracellular fate of vaccine components and subsequent immunological responses can be controlled by rational design of nanomaterials.

  14. Free dendritic growth

    Science.gov (United States)

    Glicksman, M. E.

    1984-01-01

    Free dendritic growth refers to the unconstrained development of crystals within a supercooled melt, which is the classical 'dendrite problem'. Great strides have been taken in recent years in both the theoretical understanding of dendritic growth and its experimental status. The development of this field will be sketched, showing that transport theory and interfacial thermodynamics (capillarity theory) were sufficient ingredients to develop a truly predictive model of dendrite formation. The convenient, but incorrect, notion of 'maximum velocity' was used for many years to estimate the behavior of dendritic transformations until supplanted by modern dynamic stability theory. The proper combinations of transport theory and morphological stability seem to able to predict the salient aspects of dendritic growth, especially in the neighborhood of the tip. The overall development of cast microstructures, such as equiaxed zone formation, rapidly solidified microstructures, etc., also seems to contain additional non-deterministic features which lie outside the current theories discussed here.

  15. Dendritic polyurea polymers.

    Science.gov (United States)

    Tuerp, David; Bruchmann, Bernd

    2015-01-01

    Dendritic polymers, subsuming dendrimers as well as hyperbranched or highly branched polymers are well established in the field of polymer chemistry. This review article focuses on urea based dendritic polymers and summarizes their synthetic routes through both isocyanate and isocyanate-free processes. Furthermore, this article highlights applications where dendritic polyureas show their specific chemical and physical potential. For these purposes scientific publications as well as patent literature are investigated to generate a comprehensive overview on this topic.

  16. Numerical Modeling of Dendrite Growth in Al Alloys

    Institute of Scientific and Technical Information of China (English)

    许庆彦; 柳百成

    2004-01-01

    Dendritic grains are the most often observed microstructure in metals and alloys. In the past decade, more and more attention has been paid to the modeling and simulation of dendritic microstructures. This paper describes a modified diffusion-limited aggregation model to simulate the complex shape of the dendrite grains during metal solidification. The fractal model was used to simulate equiaxed dendrite growth. The fractal dimensions of simulated Al alloy structures range from 1.63-1.88 which compares well with the experimentally-measured fractal dimension of 1.85; therefore, the model accurately predicts not only the dendritic structure morphology, but also the fractal dimension of the dendrite structure formed during solidification.

  17. CTAB-Influenced Electrochemical Dissolution of Silver Dendrites.

    Science.gov (United States)

    O'Regan, Colm; Zhu, Xi; Zhong, Jun; Anand, Utkarsh; Lu, Jingyu; Su, Haibin; Mirsaidov, Utkur

    2016-04-19

    Dendrite formation on the electrodes of a rechargeable battery during the charge-discharge cycle limits its capacity and application due to short-circuits and potential ignition. However, understanding of the underlying dendrite growth and dissolution mechanisms is limited. Here, the electrochemical growth and dissolution of silver dendrites on platinum electrodes immersed in an aqueous silver nitrate (AgNO3) electrolyte solution was investigated using in situ liquid-cell transmission electron microscopy (TEM). The dissolution of Ag dendrites in an AgNO3 solution with added cetyltrimethylammonium bromide (CTAB) surfactant was compared to the dissolution of Ag dendrites in a pure aqueous AgNO3 solution. Significantly, when CTAB was added, dendrite dissolution proceeded in a step-by-step manner, resulting in nanoparticle formation and transient microgrowth stages due to Ostwald ripening. This resulted in complete dissolution of dendrites and "cleaning" of the cell of any silver metal. This is critical for practical battery applications because "dead" lithium is known to cause short circuits and high-discharge rates. In contrast to this, in a pure aqueous AgNO3 solution, without surfactant, dendrites dissolved incompletely back into solution, leaving behind minute traces of disconnected silver particles. Finally, a mechanism for the CTAB-influenced dissolution of silver dendrites was proposed based on electrical field dependent binding energy of CTA(+) to silver.

  18. Optimization principles of dendritic structure

    Directory of Open Access Journals (Sweden)

    Borst Alexander

    2007-06-01

    Full Text Available Abstract Background Dendrites are the most conspicuous feature of neurons. However, the principles determining their structure are poorly understood. By employing cable theory and, for the first time, graph theory, we describe dendritic anatomy solely on the basis of optimizing synaptic efficacy with minimal resources. Results We show that dendritic branching topology can be well described by minimizing the path length from the neuron's dendritic root to each of its synaptic inputs while constraining the total length of wiring. Tapering of diameter toward the dendrite tip – a feature of many neurons – optimizes charge transfer from all dendritic synapses to the dendritic root while housekeeping the amount of dendrite volume. As an example, we show how dendrites of fly neurons can be closely reconstructed based on these two principles alone.

  19. RAB-10 Regulates Dendritic Branching by Balancing Dendritic Transport.

    Directory of Open Access Journals (Sweden)

    Caitlin A Taylor

    2015-12-01

    Full Text Available The construction of a large dendritic arbor requires robust growth and the precise delivery of membrane and protein cargoes to specific subcellular regions of the developing dendrite. How the microtubule-based vesicular trafficking and sorting systems are regulated to distribute these dendritic development factors throughout the dendrite is not well understood. Here we identify the small GTPase RAB-10 and the exocyst complex as critical regulators of dendrite morphogenesis and patterning in the C. elegans sensory neuron PVD. In rab-10 mutants, PVD dendritic branches are reduced in the posterior region of the cell but are excessive in the distal anterior region of the cell. We also demonstrate that the dendritic branch distribution within PVD depends on the balance between the molecular motors kinesin-1/UNC-116 and dynein, and we propose that RAB-10 regulates dendrite morphology by balancing the activity of these motors to appropriately distribute branching factors, including the transmembrane receptor DMA-1.

  20. Active properties of neuronal dendrites.

    Science.gov (United States)

    Johnston, D; Magee, J C; Colbert, C M; Cristie, B R

    1996-01-01

    Dendrites of neurons in the central nervous system are the principal sites for excitatory synaptic input. Although little is known about their function, two disparate perspectives have arisen to describe the activity patterns inherent to these diverse tree-like structures. Dendrites are thus considered either passive or active in their role in integrating synaptic inputs. This review follows the history of dendritic research from before the turn of the century to the present, with a primary focus on the hippocampus. A number of recent techniques, including high-speed fluorescence imaging and dendritic patch clamping, have provided new information and perspectives about the active properties of dendrites. The results support previous notions about the dendritic propagation of action potentials and also indicate which types of voltage-gated sodium and calcium channels are expressed and functionally active in dendrites. Possible roles for the active properties of dendrites in synaptic plasticity and integration are also discussed.

  1. Dendritic gold nanowire growth observed in liquid with transmission electron microscopy.

    Science.gov (United States)

    Kraus, Tobias; de Jonge, Niels

    2013-07-02

    The growth of nanoscale gold dendrites was studied in situ in a thin liquid film with transmission electron microscopy (TEM) using a liquid cell with silicon nitride (SiN) windows. Gold nanoparticle seeds were covered by a thin liquid layer containing precursor solution. Dendrite nucleation was induced by the electron beam leading to an initial burst of growth. The growth then settled at tip velocities between 0.1 and 2.0 nm/s for different dendrites. Tip velocities fluctuated as different dendrite geometries grew from the tips. Those dendrites showing granularities in their structure experienced the largest growth speed. Comparison of the observed velocities with diffusion-limited growth rates suggests that dendrite growth in thin films at this scale is limited by diffusion. The described method may find application in research on the mechanisms behind dendrite growth and also to study other types of anisotropic growth of nanomaterials driven by crystal and twin geometries.

  2. Isothermal Dendritic Growth Experiment Video

    Science.gov (United States)

    1997-01-01

    This video, captured during the Isothermal Dendritic Growth Experiment (IDGE) flown on STS-87 as a part of the fourth United States Microgravity payload, shows the growth of a dendrite, and the surface solidification that occurred on the front and back windows of the growth chamber. Dendrites are tiny, tree like structures that form as metals solidify.

  3. Transport Processes in Dendritic Crystallization

    Science.gov (United States)

    Glicksman, M. E.

    1984-01-01

    Free dentritic growth refers to the unconstrained development of crystals within a supercooled melt, which is the classical dendrite problem. The development of theoretical understanding of dendritic growth and its experimental status is sketched showing that transport theory and interfacial thermodynamics (capillarity theory) are insufficient ingredients to develop a truly predictive model of dendrite formation. The convenient, but incorrect, notion of maximum velocity was used for many years to estimate the behavior of dendritic transformations until supplanted by modern dynamic stability theory. The proper combinations of transport theory and morphological stability seem to be able to predict the salient aspects of dendritic growth, especially in the neighborhood of the tip.

  4. Modification of dendritic development.

    Science.gov (United States)

    Feria-Velasco, Alfredo; del Angel, Alma Rosa; Gonzalez-Burgos, Ignacio

    2002-01-01

    Since 1890 Ramón y Cajal strongly defended the theory that dendrites and their processes and spines had a function of not just nutrient transport to the cell body, but they had an important conductive role in neural impulse transmission. He extensively discussed and supported this theory in the Volume 1 of his extraordinary book Textura del Sistema Nervioso del Hombre y de los Vertebrados. Also, Don Santiago significantly contributed to a detailed description of the various neural components of the hippocampus and cerebral cortex during development. Extensive investigation has been done in the last Century related to the functional role of these complex brain regions, and their association with learning, memory and some limbic functions. Likewise, the organization and expression of neuropsychological qualities such as memory, exploratory behavior and spatial orientation, among others, depend on the integrity and adequate functional activity of the cerebral cortex and hippocampus. It is known that brain serotonin synthesis and release depend directly and proportionally on the availability of its precursor, tryptophan (TRY). By using a chronic TRY restriction model in rats, we studied their place learning ability in correlation with the dendritic spine density of pyramidal neurons in field CA1 of the hippocampus during postnatal development. We have also reported alterations in the maturation pattern of the ability for spontaneous alternation and task performance evaluating short-term memory, as well as adverse effects on the density of dendritic spines of hippocampal CA1 field pyramidal neurons and on the dendritic arborization and the number of dendritic spines of pyramidal neurons from the third layer of the prefrontal cortex using the same model of TRY restriction. The findings obtained in these studies employing a modified Golgi method, can be interpreted as a trans-synaptic plastic response due to understimulation of serotoninergic receptors located in the

  5. Intratumoral Dendritic Cells and Chemoradiation for the Treatment of Murine Squamous Cell Carcinoma

    OpenAIRE

    Moyer, Jeffrey S.; Li, Ji; Wei, Shuang; Teitz-Tennenbaum, Seagal; Chang, Alfred E

    2008-01-01

    Dendritic cells are potent antigen presenting cells that have been shown to have significant antitumor effects in vitro and in vivo. However, the therapeutic efficacy of dendritic cells as an immunotherapeutic treatment has been limited by both immunologic tolerance and active immunosuppression in the tumor microenvironment. To address this problem, we examined the ability of concurrent systemic chemotherapy and local, fractionated radiation to augment intratumoral dendritic cell injections i...

  6. Phase field modeling of dendrite growth

    Institute of Scientific and Technical Information of China (English)

    Yutuo ZHANG; Chengzhi WANG; Dianzhong LI; Yiyi LI

    2009-01-01

    Single dendrite and multi-dendrite growth for A1-2 mol pct Si alloy during isothermal solidification are simulated by phase field method. In the case of single equiaxed dendrite growth, the secondary and the necking phenomenon can be observed. For multi-dendrite growth, there exists the competitive growth among the dendrites dur-ing solidification. As solidification proceeds, growing and coarsening of the primary arms occurs, together with the branching and coarsening of the secondary arms.When the diffusion fields of dendrite tips come into contact with those of the branches growing from the neighboring dendrites, the dendrites stop growing and being to ripen and thicken.

  7. Investigating the Effects of Anisotropic Mass Transport on Dendrite Growth in High Energy Density Lithium Batteries

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Jinwang; Tartakovsky, Alexandre M.; Ferris, Kim F.; Ryan, Emily M.

    2016-01-01

    Dendrite formation on the electrode surface of high energy density lithium (Li) batteries causes safety problems and limits their applications. Suppressing dendrite growth could significantly improve Li battery performance. Dendrite growth and morphology is a function of the mixing in the electrolyte near the anode interface. Most research into dendrites in batteries focuses on dendrite formation in isotropic electrolytes (i.e., electrolytes with isotropic diffusion coefficient). In this work, an anisotropic diffusion reaction model is developed to study the anisotropic mixing effect on dendrite growth in Li batteries. The model uses a Lagrangian particle-based method to model dendrite growth in an anisotropic electrolyte solution. The model is verified by comparing the numerical simulation results with analytical solutions, and its accuracy is shown to be better than previous particle-based anisotropic diffusion models. Several parametric studies of dendrite growth in an anisotropic electrolyte are performed and the results demonstrate the effects of anisotropic transport on dendrite growth and morphology, and show the possible advantages of anisotropic electrolytes for dendrite suppression.

  8. Democracy-Independence Trade-Off in Oscillating Dendrites and Its Implications for Grid Cells

    Science.gov (United States)

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

    2010-01-01

    Summary 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. PMID:20471355

  9. Dendrite Injury Triggers DLK-Independent Regeneration

    Directory of Open Access Journals (Sweden)

    Michelle C. Stone

    2014-01-01

    Full Text Available Axon injury triggers regeneration through activation of a conserved kinase cascade, which includes the dual leucine zipper kinase (DLK. Although dendrites are damaged during stroke, traumatic brain injury, and seizure, it is not known whether mature neurons monitor dendrite injury and initiate regeneration. We probed the response to dendrite damage using model Drosophila neurons. Two larval neuron types regrew dendrites in distinct ways after all dendrites were removed. Dendrite regeneration was also triggered by injury in adults. Next, we tested whether dendrite injury was initiated with the same machinery as axon injury. Surprisingly, DLK, JNK, and fos were dispensable for dendrite regeneration. Moreover, this MAP kinase pathway was not activated by injury to dendrites. Thus, neurons respond to dendrite damage and initiate regeneration without using the conserved DLK cascade that triggers axon regeneration.

  10. The phospholipid-binding protein SESTD1 negatively regulates dendritic spine density by interfering with Rac1-Trio8 signaling pathway

    OpenAIRE

    Cheng-Che Lee; Chiung-Chun Huang; Kuei-Sen Hsu

    2015-01-01

    Dendritic spines are actin-rich protrusions from neuronal dendrites that harbor the majority of excitatory synapses. The balance of spine formation and retraction may influence dendritic integrity. While knowledge of the molecular mechanisms that promote dendritic spine formation has accumulated, little is known about the factors that limit spine formation. Here, we show that SESTD1, a phospholipid-binding protein containing a lipid-binding SEC14-like domain and two spectrin-repeat cytoskelet...

  11. Optimal Current Transfer in Dendrites

    Science.gov (United States)

    Bird, Alex D.

    2016-01-01

    Integration of synaptic currents across an extensive dendritic tree is a prerequisite for computation in the brain. Dendritic tapering away from the soma has been suggested to both equalise contributions from synapses at different locations and maximise the current transfer to the soma. To find out how this is achieved precisely, an analytical solution for the current transfer in dendrites with arbitrary taper is required. We derive here an asymptotic approximation that accurately matches results from numerical simulations. From this we then determine the diameter profile that maximises the current transfer to the soma. We find a simple quadratic form that matches diameters obtained experimentally, indicating a fundamental architectural principle of the brain that links dendritic diameters to signal transmission. PMID:27145441

  12. Electrical advantages of dendritic spines.

    Directory of Open Access Journals (Sweden)

    Allan T Gulledge

    Full Text Available Many neurons receive excitatory glutamatergic input almost exclusively onto dendritic spines. In the absence of spines, the amplitudes and kinetics of excitatory postsynaptic potentials (EPSPs at the site of synaptic input are highly variable and depend on dendritic location. We hypothesized that dendritic spines standardize the local geometry at the site of synaptic input, thereby reducing location-dependent variability of local EPSP properties. We tested this hypothesis using computational models of simplified and morphologically realistic spiny neurons that allow direct comparison of EPSPs generated on spine heads with EPSPs generated on dendritic shafts at the same dendritic locations. In all morphologies tested, spines greatly reduced location-dependent variability of local EPSP amplitude and kinetics, while having minimal impact on EPSPs measured at the soma. Spine-dependent standardization of local EPSP properties persisted across a range of physiologically relevant spine neck resistances, and in models with variable neck resistances. By reducing the variability of local EPSPs, spines standardized synaptic activation of NMDA receptors and voltage-gated calcium channels. Furthermore, spines enhanced activation of NMDA receptors and facilitated the generation of NMDA spikes and axonal action potentials in response to synaptic input. Finally, we show that dynamic regulation of spine neck geometry can preserve local EPSP properties following plasticity-driven changes in synaptic strength, but is inefficient in modifying the amplitude of EPSPs in other cellular compartments. These observations suggest that one function of dendritic spines is to standardize local EPSP properties throughout the dendritic tree, thereby allowing neurons to use similar voltage-sensitive postsynaptic mechanisms at all dendritic locations.

  13. The Isothermal Dendritic Growth Experiment

    Science.gov (United States)

    Glicksman, M. E.; Koss, M. B.; Malarik, D. C.

    1998-01-01

    The growth of dendrites is one of the commonly observed forms of solidification encountered when metals and alloys freeze under low thermal gradients, as occurs in most casting and welding processes. In engineering alloys, the details of the dendritic morphology directly relates to important material responses and properties. Of more generic interest, dendritic growth is also an archetypical problem in morphogenesis, where a complex pattern evolves from simple starting conditions. Thus, the physical understanding and mathematical description of how dendritic patterns emerge during the growth process are of interest to both scientists and engineers. The Isothermal Dendritic Growth Experiment (IDGE) is a basic science experiment designed to measure, for a fundamental test of theory, the kinetics and morphology of dendritic growth without complications induced by gravity-driven convection. The IDGE, a collaboration between Rensselaer Polytechnic Institute, in Troy NY, and NASA's Lewis Research Center (LeRC) was developed over a ten year period from a ground-based research program into a space flight experiment. Important to the success of this flight experiment was provision of in situ near-real-time teleoperations during the spaceflight experiment.

  14. Convective heat transfer during dendritic growth

    Science.gov (United States)

    Glicksman, M. E.; Huang, S. C.

    1979-01-01

    Axial growth rate measurements were carried out at 17 levels of supercooling between 0.043 C and 2 C, a temperature range in which convection, instead of diffusion, becomes the controlling mechanism of heat transfer in the dentritic growth process. The growth velocity, normalized to that expected for pure diffusive heat transfer, displays a dependence on orientation. The ratio of the observed growth velocity to that for convection-free growth and the coefficients of supercooling are formulated. The dependence of normalized growth rate in supercooling is described for downward growing dendrites. These experimental correlations can be justified theoretically only to a limited extent.

  15. Coding and decoding with dendrites.

    Science.gov (United States)

    Papoutsi, Athanasia; Kastellakis, George; Psarrou, Maria; Anastasakis, Stelios; Poirazi, Panayiota

    2014-02-01

    Since the discovery of complex, voltage dependent mechanisms in the dendrites of multiple neuron types, great effort has been devoted in search of a direct link between dendritic properties and specific neuronal functions. Over the last few years, new experimental techniques have allowed the visualization and probing of dendritic anatomy, plasticity and integrative schemes with unprecedented detail. This vast amount of information has caused a paradigm shift in the study of memory, one of the most important pursuits in Neuroscience, and calls for the development of novel theories and models that will unify the available data according to some basic principles. Traditional models of memory considered neural cells as the fundamental processing units in the brain. Recent studies however are proposing new theories in which memory is not only formed by modifying the synaptic connections between neurons, but also by modifications of intrinsic and anatomical dendritic properties as well as fine tuning of the wiring diagram. In this review paper we present previous studies along with recent findings from our group that support a key role of dendrites in information processing, including the encoding and decoding of new memories, both at the single cell and the network level. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Dendritic Cells—Ontogeny—

    Directory of Open Access Journals (Sweden)

    Satoshi Takeuchi

    2007-01-01

    Full Text Available Dendritic cells (DC play key rolls in various aspects of immunity. The functions of DC depend on the subsets as well as their location or activation status. Understanding developmental lineages, precursors and inducing factors for various DC subsets would help their clinical application, but despite extensive efforts, the precise ontogeny of various DC, remain unclear and complex. Because of their many functional similarities to macrophages, DC were originally thought to be of myeloid-lineage, an idea supported by many in vitro studies where monocytes or GM-CSF (a key myeloid growth factor has been extensively used for generating DC. However, there has been considerable evidence which suggests the existence of lymphoid-lineage DC. After the confusion of myeloid-/lymphoid-DC concept regarding DC surface markers, we have now reached a consensus that each DC subset can differentiate through both myeloid- and lymphoid-lineages. The identification of committed populations (such as common myeloid- and lymphoid progenitors as precursors for every DC subsets and findings from various knockout (KO mice that have selected lymphoid- or myeloid-lineage deficiency appear to indicate flexibility of DC development rather than their lineage restriction. Why is DC development so flexible unlike other hematopoitic cells? It might be because there is developmental redundancy to maintain such important populations in any occasions, or such developmental flexibility would be advantageous for DC to be able to differentiate from any “available” precursors in situ irrespective of their lineages. This review will cover ontogeny of conventional (CD8+/- DC DC, plasmacytoid DC and skin Langerhans cells, and recently-identified many Pre-DC (immediate DC precursor populations, in addition to monocytes and plasmacytoid DC, will also be discussed.

  17. A multifunctional core-shell nanoparticle for dendritic cell-based cancer immunotherapy

    Science.gov (United States)

    Cho, Nam-Hyuk; Cheong, Taek-Chin; Min, Ji Hyun; Wu, Jun Hua; Lee, Sang Jin; Kim, Daehong; Yang, Jae-Seong; Kim, Sanguk; Kim, Young Keun; Seong, Seung-Yong

    2011-10-01

    Dendritic cell-based cancer immunotherapy requires tumour antigens to be delivered efficiently into dendritic cells and their migration to be monitored in vivo. Nanoparticles have been explored as carriers for antigen delivery, but applications have been limited by the toxicity of the solvents used to make nanoparticles, and by the need to use transfection agents to deliver nanoparticles into cells. Here we show that an iron oxide-zinc oxide core-shell nanoparticle can deliver carcinoembryonic antigen into dendritic cells while simultaneously acting as an imaging agent. The nanoparticle-antigen complex is efficiently taken up by dendritic cells within one hour and can be detected in vitro by confocal microscopy and in vivo by magnetic resonance imaging. Mice immunized with dendritic cells containing the nanoparticle-antigen complex showed enhanced tumour antigen specific T-cell responses, delayed tumour growth and better survival than controls.

  18. The Deterministic Dendritic Cell Algorithm

    CERN Document Server

    Greensmith, Julie

    2010-01-01

    The Dendritic Cell Algorithm is an immune-inspired algorithm orig- inally based on the function of natural dendritic cells. The original instantiation of the algorithm is a highly stochastic algorithm. While the performance of the algorithm is good when applied to large real-time datasets, it is difficult to anal- yse due to the number of random-based elements. In this paper a deterministic version of the algorithm is proposed, implemented and tested using a port scan dataset to provide a controllable system. This version consists of a controllable amount of parameters, which are experimented with in this paper. In addition the effects are examined of the use of time windows and variation on the number of cells, both which are shown to influence the algorithm. Finally a novel metric for the assessment of the algorithms output is introduced and proves to be a more sensitive metric than the metric used with the original Dendritic Cell Algorithm.

  19. SK2 channel modulation contributes to compartment-specific dendritic plasticity in cerebellar Purkinje cells.

    Science.gov (United States)

    Ohtsuki, Gen; Piochon, Claire; Adelman, John P; Hansel, Christian

    2012-07-12

    Small-conductance Ca(2+)-activated K(+) channels (SK channels) modulate excitability and curtail excitatory postsynaptic potentials (EPSPs) in neuronal dendrites. Here, we demonstrate long-lasting plasticity of intrinsic excitability (IE) in dendrites that results from changes in the gain of this regulatory mechanism. Using dendritic patch-clamp recordings from rat cerebellar Purkinje cells, we find that somatic depolarization or parallel fiber (PF) burst stimulation induce long-term amplification of synaptic responses to climbing fiber (CF) or PF stimulation and enhance the amplitude of passively propagated sodium spikes. Dendritic plasticity is mimicked and occluded by the SK channel blocker apamin and is absent in Purkinje cells from SK2 null mice. Triple-patch recordings from two dendritic sites and the soma and confocal calcium imaging studies show that local stimulation limits dendritic plasticity to the activated compartment of the dendrite. This plasticity mechanism allows Purkinje cells to adjust the SK2-mediated control of dendritic excitability in an activity-dependent manner.

  20. Dendritic Properties Control Energy Efficiency of Action Potentials in Cortical Pyramidal Cells

    Directory of Open Access Journals (Sweden)

    Guosheng Yi

    2017-09-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  3. N-methyl-D-aspartate receptor blockade inhibits estrogenic support of dendritic growth in a sexually dimorphic rat spinal nucleus.

    Science.gov (United States)

    Hebbeler, Sara Louise; Verhovshek, Tom; Sengelaub, Dale Robert

    2002-09-16

    The lumbar spinal cord of rats contains the sexually dimorphic, steroid-sensitive spinal nucleus of the bulbocavernosus (SNB). Dendritic development of SNB motoneurons requires the action of both androgens and estrogens. Estrogenic effects are limited to the initial growth of SNB dendrites through 4 weeks of age. During this postnatal period, dendritic growth in other spinal motoneurons is regulated by N-methyl-D-aspartate (NMDA) receptor activation. In this study, we tested whether NMDA receptor activation was involved in SNB dendritic growth and whether the estrogenic support of SNB dendritic growth was dependent on the activation of NMDA receptors. Motoneuron morphology was assessed in normal males, intact males treated daily with the NMDA receptor antagonist MK-801, castrated males treated with estradiol benzoate (EB), and castrated males treated with both EB and MK-801. SNB motoneurons were retrogradely labeled with cholera toxin-horseradish peroxidase at 4 weeks of age (when dendritic length is normally maximal) and reconstructed in three dimensions. Somal area and dendritic length of SNB motoneurons in MK-801-treated, intact males were below those of normal males. Dendritic growth was partially supported in EB-treated castrates, but this growth was blocked by MK-801 treatment. These results suggest that, as in other motoneurons, dendritic development in the SNB involves NMDA receptors and, furthermore, that the estrogen-sensitive component of SNB dendritic development requires their activation. Copyright 2002 Wiley-Liss, Inc.

  4. Dendritic cells star in Vancouver

    OpenAIRE

    Klechevsky, Eynav; Kato, Hiroki; Sponaas, Anne-Marit

    2005-01-01

    The fast-moving field of dendritic cell (DC) biology is hard to keep pace with. Here we report on advances from the recent Keystone Symposium, “Dendritic Cells at the Center of Innate and Adaptive Immunity,” organized in Vancouver, BC on Feb. 1–7, 2005 by Anne O'Garra, Jacques Banchereau, and Alan Sher. New insights into the molecular mechanisms of DC function and their influence on immune regulation, their role in infectious and autoimmune disease, and new clinical applications are highlight...

  5. Rat bone marrow-derived dendritic cells generated with GM-CSF/IL-4 or FLT3L exhibit distinct phenotypical and functional characteristics.

    Science.gov (United States)

    N'diaye, Marie; Warnecke, Andreas; Flytzani, Sevasti; Abdelmagid, Nada; Ruhrmann, Sabrina; Olsson, Tomas; Jagodic, Maja; Harris, Robert A; Guerreiro-Cacais, Andre Ortlieb

    2016-03-01

    Dendritic cells are professional APCs that play a central role in the initiation of immune responses. The limited ex vivo availability of dendritic cells inspires the widespread use of bone marrow-derived dendritic cells as an alternative in research. However, the functional characteristics of bone marrow-derived dendritic cells are incompletely understood. Therefore, we compared functional and phenotypic characteristics of rat bone marrow-derived dendritic cells generated with GM-CSF/IL-4 or FLT3 ligand bone marrow-derived dendritic cells. A comparison of surface markers revealed that FLT3 ligand-bone marrow-derived dendritic cells expressed signal regulatory protein α, CD103, and CD4 and baseline levels of MHC class II, CD40, and CD86, which were highly up-regulated upon stimulation. Conversely, GM-CSF/IL-4-bone marrow-derived dendritic cells constitutively expressed signal regulatory protein α, CD11c, and CD11b but only mildly up-regulated MHC class II, CD40, or CD86 following stimulation. Expression of dendritic cell-associated core transcripts was restricted to FLT3 ligand-bone marrow-derived dendritic cells . GM-CSF/IL-4-bone marrow-derived dendritic cells were superior at phagocytosis but were outperformed by FLT3 ligand-bone marrow-derived dendritic cells at antigen presentation and T cell stimulation in vitro. Stimulated GM-CSF/IL-4-bone marrow-derived dendritic cells secreted more TNF, CCL5, CCL20, and NO, whereas FLT3 ligand-bone marrow-derived dendritic cells secreted more IL-6 and IL-12. Finally, whereas GM-CSF/IL-4-bone marrow-derived dendritic cell culture supernatants added to resting T cell cultures promoted forkhead box p3(+) regulatory T cell populations, FLT3 ligand-bone marrow-derived dendritic cell culture supernatants drove Th17 differentiation. We conclude that rat GM-CSF/IL-4-bone marrow-derived dendritic cells and FLT3 ligand-bone marrow-derived dendritic cells are functionally distinct. Our data support the current rationale that FLT3

  6. Dendritic growth model of multilevel marketing

    Science.gov (United States)

    Pang, James Christopher S.; Monterola, Christopher P.

    2017-02-01

    Biologically inspired dendritic network growth is utilized to model the evolving connections of a multilevel marketing (MLM) enterprise. Starting from agents at random spatial locations, a network is formed by minimizing a distance cost function controlled by a parameter, termed the balancing factor bf, that weighs the wiring and the path length costs of connection. The paradigm is compared to an actual MLM membership data and is shown to be successful in statistically capturing the membership distribution, better than the previously reported agent based preferential attachment or analytic branching process models. Moreover, it recovers the known empirical statistics of previously studied MLM, specifically: (i) a membership distribution characterized by the existence of peak levels indicating limited growth, and (ii) an income distribution obeying the 80 - 20 Pareto principle. Extensive types of income distributions from uniform to Pareto to a "winner-take-all" kind are also modeled by varying bf. Finally, the robustness of our dendritic growth paradigm to random agent removals is explored and its implications to MLM income distributions are discussed.

  7. Bone marrow-derived dendritic cells.

    Science.gov (United States)

    Roney, Kelly

    2013-01-01

    While much is understood about dendritic cells and their role in the immune system, the study of these cells is critical to gain a more complete understanding of their function. Dendritic cell isolation from mouse body tissues can be difficult and the number of cells isolated small. This protocol describes the growth of large number of dendritic cells from the culture of mouse bone marrow cells. The dendritic cells grown in culture facilitate experiments that may require large number of dendritic cells without great expense or use of large number of mice.

  8. Evaluating Primary Dendrite Trunk Diameters in Directionally Solidified Al-Si Alloys

    Science.gov (United States)

    Grugel, R. N.; Tewari, S. N.; Poirier, D. R.

    2014-01-01

    The primary dendrite trunk diameters of Al-Si alloys that were directionally solidified over a range of processing conditions have been measured. These data are analyzed with a model based primarily on an assessment of secondary dendrite arm dissolution in the mushy zone. Good fit with the experimental data is seen and it is suggested that the primary dendrite trunk diameter is a useful metric that correlates well with the actual solidification processing parameters. These results are placed in context with the limited results from the aluminium - 7 wt. % silicon samples directionally solidified aboard the International Space Station as part of the MICAST project.

  9. Evidence that dendritic mitochondria negatively regulate dendritic branching in pyramidal neurons in the neocortex.

    Science.gov (United States)

    Kimura, Toshiya; Murakami, Fujio

    2014-05-14

    The precise branching patterns of dendritic arbors have a profound impact on information processing in individual neurons and the brain. These patterns are established by positive and negative regulation of the dendritic branching. Although the mechanisms for positive regulation have been extensively investigated, little is known about those for negative regulation. Here, we present evidence that mitochondria located in developing dendrites are involved in the negative regulation of dendritic branching. We visualized mitochondria in pyramidal neurons of the mouse neocortex during dendritic morphogenesis using in utero electroporation of a mitochondria-targeted fluorescent construct. We altered the mitochondrial distribution in vivo by overexpressing Mfn1, a mitochondrial shaping protein, or the Miro-binding domain of TRAK2 (TRAK2-MBD), a truncated form of a motor-adaptor protein. We found that dendritic mitochondria were preferentially targeted to the proximal portion of dendrites only during dendritic morphogenesis. Overexpression of Mfn1 or TRAK2-MBD depleted mitochondria from the dendrites, an effect that was accompanied by increased branching of the proximal portion of the dendrites. This dendritic abnormality cannot be accounted for by changes in the distribution of membrane trafficking organelles since the overexpression of Mfn1 did not alter the distributions of the endoplasmic reticulum, Golgi, or endosomes. Additionally, neither did these constructs impair neuronal viability or mitochondrial function. Therefore, our results suggest that dendritic mitochondria play a critical role in the establishment of the precise branching pattern of dendritic arbors by negatively affecting dendritic branching.

  10. History-dependent Selection of Primary Dendritic Spacing in Directionally Solidified Alloy

    Institute of Scientific and Technical Information of China (English)

    Linlin WANG; Xin LIN; Guolu DING; Lilin WANG; Weidong HUANG

    2007-01-01

    Directional solidification experiments were carried out for succinonitrile-1.0 wt pct acetone alloy with the orientation of dendritic arrays being not parallel to the direction of the temperature gradient. Experimental results show that there exists an allowable range of primary dendritic spacing under a given growth condition.The average primary spacing depends not only on the current growth conditions but also on the way by which the conditions were achieved. The upper limit of the allowable range becomes smaller in comparison with that with direction of dendrite arrays parallel to the direction of the temperature gradient, which means that the history-dependence of dendritic growth is weaker under this condition. The lower limit obtained is compared with a self-consistent model, which shows a good agreement with experimental results.

  11. Dendritic Spines in Depression: What We Learned from Animal Models

    Directory of Open Access Journals (Sweden)

    Hui Qiao

    2016-01-01

    Full Text Available Depression, a severe psychiatric disorder, has been studied for decades, but the underlying mechanisms still remain largely unknown. Depression is closely associated with alterations in dendritic spine morphology and spine density. Therefore, understanding dendritic spines is vital for uncovering the mechanisms underlying depression. Several chronic stress models, including chronic restraint stress (CRS, chronic unpredictable mild stress (CUMS, and chronic social defeat stress (CSDS, have been used to recapitulate depression-like behaviors in rodents and study the underlying mechanisms. In comparison with CRS, CUMS overcomes the stress habituation and has been widely used to model depression-like behaviors. CSDS is one of the most frequently used models for depression, but it is limited to the study of male mice. Generally, chronic stress causes dendritic atrophy and spine loss in the neurons of the hippocampus and prefrontal cortex. Meanwhile, neurons of the amygdala and nucleus accumbens exhibit an increase in spine density. These alterations induced by chronic stress are often accompanied by depression-like behaviors. However, the underlying mechanisms are poorly understood. This review summarizes our current understanding of the chronic stress-induced remodeling of dendritic spines in the hippocampus, prefrontal cortex, orbitofrontal cortex, amygdala, and nucleus accumbens and also discusses the putative underlying mechanisms.

  12. Phase field modeling of dendritic coarsening during isothermal

    Directory of Open Access Journals (Sweden)

    Zhang Yutuo

    2011-08-01

    Full Text Available Dendritic coarsening in Al-2mol%Si alloy during isothermal solidification at 880K was investigated by phase field modeling. Three coarsening mechanisms operate in the alloy: (a melting of small dendrite arms; (b coalescence of dendrites near the tips leading to the entrapment of liquid droplets; (c smoothing of dendrites. Dendrite melting is found to be dominant in the stage of dendritic growth, whereas coalescence of dendrites and smoothing of dendrites are dominant during isothermal holding. The simulated results provide a better understanding of dendrite coarsening during isothermal solidification.

  13. Dendrite architecture organized by transcriptional control of the F-actin nucleator Spire.

    Science.gov (United States)

    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.

  14. Dendritic cells and contact dermatitis.

    Science.gov (United States)

    Sasaki, Yoshinori; Aiba, Setsuya

    2007-10-01

    Contact dermatitis is a biological response to simple chemicals in the skin. Although it is well known that allergic contact dermatitis is mediated by the immune system, it is still uncertain whether it is a kind of protective response or it is simply an unnecessary response. We have demonstrated the following: (1) haptens activate Langerhans cells in the initiation phase of murine allergic contact dermatitis in vivo, (2) haptens activate human monocyte-derived dendritic cells in vitro, (3) the activation of dendritic cells by haptens is primarily mediated by the activation of p38 mitogen-activated protein kinase (MAPK), and (4) the activation of p38 MAPK is mediated by stimulation related to an imbalance of intracellular redox. Based on these observations, we will discuss the biological significance of contact dermatitis. In addition, we will review some up-to-date findings on Langerhans cell biology.

  15. Lipid dynamics at dendritic spines.

    Science.gov (United States)

    Dotti, Carlos Gerardo; Esteban, Jose Antonio; Ledesma, María Dolores

    2014-01-01

    Dynamic changes in the structure and composition of the membrane protrusions forming dendritic spines underlie memory and learning processes. In recent years a great effort has been made to characterize in detail the protein machinery that controls spine plasticity. However, we know much less about the involvement of lipids, despite being major membrane components and structure determinants. Moreover, protein complexes that regulate spine plasticity depend on specific interactions with membrane lipids for proper function and accurate intracellular signaling. In this review we gather information available on the lipid composition at dendritic spine membranes and on its dynamics. We pay particular attention to the influence that spine lipid dynamism has on glutamate receptors, which are key regulators of synaptic plasticity.

  16. Microtubules in Dendritic Spine Development

    OpenAIRE

    2008-01-01

    It is generally believed that only the actin cytoskeleton resides in dendritic spines and controls spine morphology and plasticity. Here we report that microtubules (MTs) are present in spines and that shRNA knockdown of the MT-plus end binding protein EB3 significantly reduces spine formation. Furthermore, stabilization and inhibition of MTs by low doses of taxol and nocodazole enhance and impair spine formation elicited by BDNF, respectively. Therefore, MTs play an important role in the con...

  17. Melanoma immunotherapy: dendritic cell vaccines

    OpenAIRE

    Lozada-Requena, Ivan; Laboratorios de Inmunología #108, Laboratorio de investigación y Desarrollo, Facultad de Ciencieas y Filosofía, Universidad Cayetano Heredia. Lima, Perú Empresa de Investigación y Desarrollo en Cáncer (EMINDES) SAC. Lima, Perú.; Núñez, César; Empresa de Investigación y Desarrollo en Cáncer (EMINDES) SAC. Lima, Perú.; Aguilar, José Luis; Laboratorios de Inmunología #108, Laboratorio de investigación y Desarrollo, Facultad de Ciencieas y Filosofía, Universidad Cayetano Heredia. Lima, Perú.

    2015-01-01

    This is a narrative review that shows accessible information to the scientific community about melanoma and immunotherapy.Dendritic cells have the ability to participate in innate and adaptive immunity, but are not unfamiliar to the immune evasion oftumors. Knowing the biology and role has led to generate in vitro several prospects of autologous cell vaccines against diversetypes of cancer in humans and animal models. However, given the low efficiency they have shown, we must implementstrateg...

  18. Development of Dendritic Cell System

    Institute of Scientific and Technical Information of China (English)

    LiWu; AleksandarDakic

    2004-01-01

    The dendritic cell system contains conventional dendritic cells (DCs) and plasmacytoid pre-dendritic cells (pDCs). Both DCs and pDCs are bone marrow derived calls. Although the common functions of DCs are antigen-processing and T-lymphocyte activation, they differ in surface markers, migratory patterns, and cytokine output. These differences can determine the fate of the T cells they activate. Several subsets of mature DCs have been described in both mouse and human and the developmental processes of these specialized DC subsets have been studied extensively. The original concept that all DCs were of myeloid origin was questioned by several recent studies, which demonstrated that in addition to the DCs derived from myeloid precursors, some DCs could also be efficiently generated from lymphoid-restricted precursors. Moreover, it has been shown recently that both conventional DCs and pDCs can be generated by the Fit3 expressing hemopoietic progenitors regardless of their myeloid- or lymphoid-origin. These findings suggest an early developmental flexibility of precursors for DCs and pDCs. This review summarizes some recent observations on the development of DC system in both human and mouse. Cellular & Molecular Immunology. 2004;1(2):112-118.

  19. Development of Dendritic Cell System

    Institute of Scientific and Technical Information of China (English)

    Li Wu; Aleksandar Dakic

    2004-01-01

    The dendritic cell system contains conventional dendritic cells (DCs) and plasmacytoid pre-dendritic cells (pDCs). Both DCs and pDCs are bone marrow derived cells. Although the common functions of DCs are antigen-processing and T-lymphocyte activation, they differ in surface markers, migratory patterns, and cytokine output. These differences can determine the fate of the T cells they activate. Several subsets of mature DCs have been described in both mouse and human and the developmental processes of these specialized DC subsets have been studied extensively. The original concept that all DCs were of myeloid origin was questioned by several recent studies, which demonstrated that in addition to the DCs derived from myeloid precursors,some DCs could also be efficiently generated from lymphoid-restricted precursors. Moreover, it has been shown recently that both conventional DCs and pDCs can be generated by the Flt3 expressing hemopoietic progenitors regardless of their myeloid- or lymphoid-origin. These findings suggest an early developmental flexibility of precursors for DCs and pDCs. This review summarizes some recent observations on the development of DC system in both human and mouse.

  20. Dendritic cells and immuno-modulation in autoimmune arthritis

    OpenAIRE

    Spiering, R.

    2013-01-01

    The immune system consists of a broad array of immune cells to protect the body against invasive pathogenic microorganisms. Immune responses should however, be tightly controlled to ensure tolerance to the body’s own cells and proteins in order to limit damage to the host own cells and tissue. Autoimmune diseases can arise when the balance between pathogen-driven immunity (inflammatory immune response) and tolerance (regulatory immune response) to self products is dysregulated. Dendritic cell...

  1. Dendritic web silicon for solar cell application

    Science.gov (United States)

    Seidensticker, R. G.

    1977-01-01

    The dendritic web process for growing long thin ribbon crystals of silicon and other semiconductors is described. Growth is initiated from a thin wirelike dendrite seed which is brought into contact with the melt surface. Initially, the seed grows laterally to form a button at the melt surface; when the seed is withdrawn, needlelike dendrites propagate from each end of the button into the melt, and the web portion of the crystal is formed by the solidification of the liquid film supported by the button and the bounding dendrites. Apparatus used for dendritic web growth, material characteristics, and the two distinctly different mechanisms involved in the growth of a single crystal are examined. The performance of solar cells fabricated from dendritic web material is indistinguishable from the performance of cells fabricated from Czochralski grown material.

  2. Active dendrites enhance neuronal dynamic range.

    Directory of Open Access Journals (Sweden)

    Leonardo L Gollo

    2009-06-01

    Full Text Available Since the first experimental evidences of active conductances in dendrites, most neurons have been shown to exhibit dendritic excitability through the expression of a variety of voltage-gated ion channels. However, despite experimental and theoretical efforts undertaken in the past decades, the role of this excitability for some kind of dendritic computation has remained elusive. Here we show that, owing to very general properties of excitable media, the average output of a model of an active dendritic tree is a highly non-linear function of its afferent rate, attaining extremely large dynamic ranges (above 50 dB. Moreover, the model yields double-sigmoid response functions as experimentally observed in retinal ganglion cells. We claim that enhancement of dynamic range is the primary functional role of active dendritic conductances. We predict that neurons with larger dendritic trees should have larger dynamic range and that blocking of active conductances should lead to a decrease in dynamic range.

  3. Transcranial magnetic stimulation (TMS) inhibits cortical dendrites.

    Science.gov (United States)

    Murphy, Sean C; Palmer, Lucy M; Nyffeler, Thomas; Müri, René M; Larkum, Matthew E

    2016-03-18

    One of the leading approaches to non-invasively treat a variety of brain disorders is transcranial magnetic stimulation (TMS). However, despite its clinical prevalence, very little is known about the action of TMS at the cellular level let alone what effect it might have at the subcellular level (e.g. dendrites). Here, we examine the effect of single-pulse TMS on dendritic activity in layer 5 pyramidal neurons of the somatosensory cortex using an optical fiber imaging approach. We find that TMS causes GABAB-mediated inhibition of sensory-evoked dendritic Ca(2+) activity. We conclude that TMS directly activates fibers within the upper cortical layers that leads to the activation of dendrite-targeting inhibitory neurons which in turn suppress dendritic Ca(2+) activity. This result implies a specificity of TMS at the dendritic level that could in principle be exploited for investigating these structures non-invasively.

  4. Imaging dendritic spines of rat primary hippocampal neurons using structured illumination microscopy.

    Science.gov (United States)

    Schouten, Marijn; De Luca, Giulia M R; Alatriste González, Diana K; de Jong, Babette E; Timmermans, Wendy; Xiong, Hui; Krugers, Harm; Manders, Erik M M; Fitzsimons, Carlos P

    2014-05-04

    Dendritic spines are protrusions emerging from the dendrite of a neuron and represent the primary postsynaptic targets of excitatory inputs in the brain. Technological advances have identified these structures as key elements in neuron connectivity and synaptic plasticity. The quantitative analysis of spine morphology using light microscopy remains an essential problem due to technical limitations associated with light's intrinsic refraction limit. Dendritic spines can be readily identified by confocal laser-scanning fluorescence microscopy. However, measuring subtle changes in the shape and size of spines is difficult because spine dimensions other than length are usually smaller than conventional optical resolution fixed by light microscopy's theoretical resolution limit of 200 nm. Several recently developed super resolution techniques have been used to image cellular structures smaller than the 200 nm, including dendritic spines. These techniques are based on classical far-field operations and therefore allow the use of existing sample preparation methods and to image beyond the surface of a specimen. Described here is a working protocol to apply super resolution structured illumination microscopy (SIM) to the imaging of dendritic spines in primary hippocampal neuron cultures. Possible applications of SIM overlap with those of confocal microscopy. However, the two techniques present different applicability. SIM offers higher effective lateral resolution, while confocal microscopy, due to the usage of a physical pinhole, achieves resolution improvement at the expense of removal of out of focus light. In this protocol, primary neurons are cultured on glass coverslips using a standard protocol, transfected with DNA plasmids encoding fluorescent proteins and imaged using SIM. The whole protocol described herein takes approximately 2 weeks, because dendritic spines are imaged after 16-17 days in vitro, when dendritic development is optimal. After completion of the

  5. Dendritic Cells, New Tools for Vaccination

    Science.gov (United States)

    2003-01-01

    Review Dendritic cells , new tools for vaccination Jesus Colino, Clifford M. Snapper * Department of Pathology, Uniformed Services University of the...2003 Éditions scientifiques et médicales Elsevier SAS. All rights reserved. Keywords: Vaccines; Immunotherapy; Dendritic cells 1. Introduction During...DATE 2003 2. REPORT TYPE 3. DATES COVERED 00-00-2003 to 00-00-2003 4. TITLE AND SUBTITLE Dendritic cells , new tools for vaccination 5a

  6. Low Power Dendritic Computation for Wordspotting

    Directory of Open Access Journals (Sweden)

    Stephen Nease

    2013-05-01

    Full Text Available In this paper, we demonstrate how a network of dendrites can be used to build the state decoding block of a wordspotter similar to a Hidden Markov Model (HMM classifier structure. We present simulation and experimental data for a single line dendrite and also experimental results for a dendrite-based classifier structure. This work builds on previously demonstrated building blocks of a neural network: the channel, synapses and dendrites using CMOS circuits. These structures can be used for speech and pattern recognition. The computational efficiency of such a system is >10 MMACs/μW as compared to Digital Systems which perform 10 MMACs/mW.

  7. Neoplasms derived from plasmacytoid dendritic cells.

    Science.gov (United States)

    Facchetti, Fabio; Cigognetti, Marta; Fisogni, Simona; Rossi, Giuseppe; Lonardi, Silvia; Vermi, William

    2016-02-01

    Plasmacytoid dendritic cell neoplasms manifest in two clinically and pathologically distinct forms. The first variant is represented by nodular aggregates of clonally expanded plasmacytoid dendritic cells found in lymph nodes, skin, and bone marrow ('Mature plasmacytoid dendritic cells proliferation associated with myeloid neoplasms'). This entity is rare, although likely underestimated in incidence, and affects predominantly males. Almost invariably, it is associated with a myeloid neoplasm such as chronic myelomonocytic leukemia or other myeloid proliferations with monocytic differentiation. The concurrent myeloid neoplasm dominates the clinical pictures and guides treatment. The prognosis is usually dismal, but reflects the evolution of the associated myeloid leukemia rather than progressive expansion of plasmacytoid dendritic cells. A second form of plasmacytoid dendritic cells tumor has been recently reported and described as 'blastic plasmacytoid dendritic cell neoplasm'. In this tumor, which is characterized by a distinctive cutaneous and bone marrow tropism, proliferating cells derive from immediate CD4(+)CD56(+) precursors of plasmacytoid dendritic cells. The diagnosis of this form can be easily accomplished by immunohistochemistry, using a panel of plasmacytoid dendritic cells markers. The clinical course of blastic plasmacytoid dendritic cell neoplasm is characterized by a rapid progression to systemic disease via hematogenous dissemination. The genomic landscape of this entity is currently under intense investigation. Recurrent somatic mutations have been uncovered in different genes, a finding that may open important perspectives for precision medicine also for this rare, but highly aggressive leukemia.

  8. Interactions between airway epithelial cells and dendritic cells during viral infections using an in vitro co-culture model

    Science.gov (United States)

    Rationale: Historically, single cell culture models have been limited in pathological and physiological relevance. A co-culture model of dendritic cells (DCs) and differentiated human airway epithelial cells was developed to examine potential interactions between these two cell t...

  9. Preparation of dendritic bismuth film electrodes and their application for detection of trace Pb (II) and Cd (II)

    Institute of Scientific and Technical Information of China (English)

    Huizhu Zhou; Huanhuan Hou; Lei Dai; Yuehua Li; Jing Zhu; Ling Wang

    2016-01-01

    In this paper, dendritic Bi film electrodes with porous structure had successfully been prepared on glassy carbon electrode using a constant current electrolysis method based on hydrogen bubble dynamic templates. The elec-trode prepared using a large applied current density showed an increased internal electroactive area and a signif-icantly improved electrochemical performance. The analytical utility of the prepared dendritic Bi film electrodes for the determination of Pb (II) and Cd (II) in the range of 5–50μg·L−1 were presented in combination with square wave stripping voltammetry in model solution. Compared with non-porous Bi film electrode, the dendrit-ic Bi film electrode exhibited higher sensitivity and lower detection limit. The prepared Bi film electrode with dendritic structure was also successfully applied to real water sample analysis.

  10. Dendrite Suppression by Shock Electrodeposition in Charged Porous Media

    Science.gov (United States)

    Han, Ji-Hyung; Wang, Miao; Bai, Peng; Brushett, Fikile R.; Bazant, Martin Z.

    2016-06-01

    It is shown that surface conduction can stabilize electrodeposition in random, charged porous media at high rates, above the diffusion-limited current. After linear sweep voltammetry and impedance spectroscopy, copper electrodeposits are visualized by scanning electron microscopy and energy dispersive spectroscopy in two different porous separators (cellulose nitrate, polyethylene), whose surfaces are modified by layer-by-layer deposition of positive or negative charged polyelectrolytes. Above the limiting current, surface conduction inhibits growth in the positive separators and produces irregular dendrites, while it enhances growth and suppresses dendrites behind a deionization shock in the negative separators, also leading to improved cycle life. The discovery of stable uniform growth in the random media differs from the non-uniform growth observed in parallel nanopores and cannot be explained by classic quasi-steady “leaky membrane” models, which always predict instability and dendritic growth. Instead, the experimental results suggest that transient electro-diffusion in random porous media imparts the stability of a deionization shock to the growing metal interface behind it. Shock electrodeposition could be exploited to enhance the cycle life and recharging rate of metal batteries or to accelerate the fabrication of metal matrix composite coatings.

  11. In vivo dendrite regeneration after injury is different from dendrite development

    Science.gov (United States)

    Li, Tun; Jan, Lily Yeh; Jan, Yuh Nung

    2016-01-01

    Neurons receive information along dendrites and send signals along axons to synaptic contacts. The factors that control axon regeneration have been examined in many systems, but dendrite regeneration has been largely unexplored. Here we report that, in intact Drosophila larvae, a discrete injury that removes all dendrites induces robust dendritic growth that recreates many features of uninjured dendrites, including the number of dendrite branches that regenerate and responsiveness to sensory stimuli. However, the growth and patterning of injury-induced dendrites is significantly different from uninjured dendrites. We found that regenerated arbors cover much less territory than uninjured neurons, fail to avoid crossing over other branches from the same neuron, respond less strongly to mechanical stimuli, and are pruned precociously. Finally, silencing the electrical activity of the neurons specifically blocks injury-induced, but not developmental, dendrite growth. By elucidating the essential features of dendrites grown in response to acute injury, our work builds a framework for exploring dendrite regeneration in physiological and pathological conditions. PMID:27542831

  12. Recrystallization phenomena of solution grown paraffin dendrites

    NARCIS (Netherlands)

    Hollander, F.F.A.; Stasse, O.; Suchtelen, van J.; Enckevort, van W.J.P.

    2001-01-01

    Paraffin crystals were grown from decane solutions using a micro-Bridgman set up for in-situ observation of the morphology at the growth front. It is shown that for large imposed velocities, dendrites are obtained. After dendritic growth, aging or recrystallization processes set in rather quickly, c

  13. A Case of Plasmacytoid Dendritic Cell Leukemia

    Directory of Open Access Journals (Sweden)

    Köpeczi Judit Beáta

    2013-04-01

    Full Text Available Introduction: Plasmacytoid dendritic cell leukemia is a rare subtype of acute leukemia, which has recently been established as a distinct pathologic entity that typically follows a highly aggressive clinical course in adults. The aim of this report is to present a case of plasmacytoid dendritic cell leukemia due to its rarity and difficulty to recognize and diagnose it.

  14. Early events in axon/dendrite polarization.

    Science.gov (United States)

    Cheng, Pei-lin; Poo, Mu-ming

    2012-01-01

    Differentiation of axons and dendrites is a critical step in neuronal development. Here we review the evidence that axon/dendrite formation during neuronal polarization depends on the intrinsic cytoplasmic asymmetry inherited by the postmitotic neuron, the exposure of the neuron to extracellular chemical factors, and the action of anisotropic mechanical forces imposed by the environment. To better delineate the functions of early signals among a myriad of cellular components that were shown to influence axon/dendrite formation, we discuss their functions by distinguishing their roles as determinants, mediators, or modulators and consider selective degradation of these components as a potential mechanism for axon/dendrite polarization. Finally, we examine whether these early events of axon/dendrite formation involve local autocatalytic activation and long-range inhibition, as postulated by Alan Turing for the morphogenesis of patterned biological structure.

  15. Numerical simulation of facet dendrite growth

    Institute of Scientific and Technical Information of China (English)

    CHEN Zhi; CHEN Chang-le; HAO Li-mei

    2008-01-01

    Numerical simulation based on phase field method was performed to describe the solidification of silicon. The effect of anisotropy, undercooling and coupling parameter on dendrite growth shape was investigated. It is indicated that the entire facet dendrite shapes are obtained by using regularized phase field model. Steady state tip velocity of dendrite drives to a fixed value when γ≤0.13. With further increasing the anisotropy value, steady state tip velocity decreases and the size is smaller. With the increase in the undercooling and coupling parameter, crystal grows from facet to facet dendrite. In addition, with increasing coupling parameter, the facet part of facet dendrite decreases gradually, which is in good agreement with Wulff theory.

  16. Comparative morphology of dendritic arbors in populations of Purkinje cells in mouse sulcus and apex.

    Science.gov (United States)

    Nedelescu, Hermina; Abdelhack, Mohamed

    2013-01-01

    Foliation divides the mammalian cerebellum into structurally distinct subdivisions, including the concave sulcus and the convex apex. Purkinje cell (PC) dendritic morphology varies between subdivisions and changes significantly ontogenetically. Since dendritic morphology both enables and limits sensory-motor circuit function, it is important to understand how neuronal architectures differ between brain regions. This study employed quantitative confocal microcopy to reconstruct dendritic arbors of cerebellar PCs expressing green fluorescent protein and compared arbor morphology between PCs of sulcus and apex in young and old mice. Arbors were digitized from high z-resolution (0.25 µm) image stacks using an adaptation of Neurolucida's (MBF Bioscience) continuous contour tracing tool, designed for drawing neuronal somata. Reconstructed morphologies reveal that dendritic arbors of sulcus and apex exhibit profound differences. In sulcus, 72% of the young PC population possesses two primary dendrites, whereas in apex, only 28% do. Spatial constraints in the young sulcus cause significantly more dendritic arbor overlap than in young apex, a distinction that disappears in adulthood. However, adult sulcus PC arbors develop a greater number of branch crossings. These results suggest developmental neuronal plasticity that enables cerebellar PCs to attain correct functional adult architecture under different spatial constraints.

  17. Web-dendritic ribbon growth. Annual report, October 1, 1975--September 31, 1976

    Energy Technology Data Exchange (ETDEWEB)

    Hilborn, Jr., R. B.; Faust, Jr., J. W.

    1976-10-01

    The web furnace has been set up, calibrated, and made operational for pulling dendritic-web samples. Considerable work has been completed in the investigation of the effect of changes in the furnace thermal geometry, as accomplished by variations in the number, size, shape, and location of thermal shields, on the growth of dendritic-web. Numerous growth runs were made to grow primitive dendrites for use as the dendritic seed crystals for the web growth. Some preliminary investigations were conducted to try and determine the optimum twin spacing in the dendritic seed crystal for web growth. Models were developed and computer programs applied to ascertain the thermal geometries present in the susceptor, crucible melt, meniscus, and web. A major result of this analysis has been the prediction of an upper limit on the pull rate of approximately 4 cms. per minute with the thermal geometry presented in our furnace. The facilities for obtaining characterization data were set-up and made operational. Data on twin spacings and number of twin planes in the dendritic seed crystals and resulting web samples was obtained. Resistivity and majority charge carrier type determinations were made on a few select web samples. All samples to date have been high resistivity, undoped, p-type. (WDM)

  18. The maintenance of genetic variation due to asymmetric gene flow in dendritic metapopulations.

    Science.gov (United States)

    Morrissey, Michael B; de Kerckhove, Derrick T

    2009-12-01

    Dendritic landscapes can have ecological properties that differ importantly from simpler spatial arrangements of habitats. Most dendritic landscapes are structured by elevation, and therefore, migration is likely to be directionally biased. While the population-genetic consequences of both dendritic landscape arrangements and asymmetric migration have begun to be studied, these processes have not been considered together. Simple conceptual models predict that if migration into branch (headwater) populations is limited, such populations can act as reservoirs for potentially unique alleles. As a consequence of the fact that dendritic landscapes have, by definition, more branches than internal habitat patches, this process may lead to the maintenance of higher overall genetic diversities in metapopulations inhabiting dendritic networks where migration is directionally biased. Here we begin to address the generality of these simple predictions using genetic models and a review of empirical literature. We show, for a range of demographic parameters, that dendritic systems with asymmetric migration can maintain levels of genetic variation that are very different, sometimes very elevated, compared with more classical models of geographical population structure. Furthermore, predicted patterns of genetic variation within metapopulations--that is, stepwise increases in genetic diversity at nodes--do occur in some empirical data.

  19. Preferential control of basal dendritic protrusions by EphB2.

    Directory of Open Access Journals (Sweden)

    Matthew S Kayser

    Full Text Available The flow of information between neurons in many neural circuits is controlled by a highly specialized site of cell-cell contact known as a synapse. A number of molecules have been identified that are involved in central nervous system synapse development, but knowledge is limited regarding whether these cues direct organization of specific synapse types or on particular regions of individual neurons. Glutamate is the primary excitatory neurotransmitter in the brain, and the majority of glutamatergic synapses occur on mushroom-shaped protrusions called dendritic spines. Changes in the morphology of these structures are associated with long-lasting modulation of synaptic strength thought to underlie learning and memory, and can be abnormal in neuropsychiatric disease. Here, we use rat cortical slice cultures to examine how a previously-described synaptogenic molecule, the EphB2 receptor tyrosine kinase, regulates dendritic protrusion morphology in specific regions of the dendritic arbor in cortical pyramidal neurons. We find that alterations in EphB2 signaling can bidirectionally control protrusion length, and knockdown of EphB2 expression levels reduces the number of dendritic spines and filopodia. Expression of wild-type or dominant negative EphB2 reveals that EphB2 preferentially regulates dendritic protrusion structure in basal dendrites. Our findings suggest that EphB2 may act to specify synapse formation in a particular subcellular region of cortical pyramidal neurons.

  20. REMOD: a computational tool for remodeling neuronal dendrites

    Directory of Open Access Journals (Sweden)

    Panagiotis Bozelos

    2014-05-01

    Full Text Available In recent years, several modeling studies have indicated that dendritic morphology is a key determinant of how individual neurons acquire a unique signal processing profile. The highly branched dendritic structure that originates from the cell body, explores the surrounding 3D space in a fractal-like manner, until it reaches a certain amount of complexity. Its shape undergoes significant alterations not only in various neuropathological conditions, but in physiological, too. Yet, despite the profound effect that these alterations can have on neuronal function, the causal relationship between structure and function remains largely elusive. The lack of a systematic approach for remodeling neuronal cells and their dendritic trees is a key limitation that contributes to this problem. In this context, we developed a computational tool that allows the remodeling of any type of neurons, given a set of exemplar morphologies. The tool is written in Python and provides a simple GUI that guides the user through various options to manipulate selected neuronal morphologies. It provides the ability to load one or more morphology files (.swc or .hoc and choose specific dendrites to operate one of the following actions: shrink, remove, extend or branch (as shown in Figure 1. The user retains complete control over the extent of each alteration and if a chosen action is not possible due to pre-existing structural constraints, appropriate warnings are produced. Importantly, the tool can also be used to extract morphology statistics for one or multiple morphologies, including features such as the total dendritic length, path length to the root, branch order, diameter tapering, etc. Finally, an experimental utility enables the user to remodel entire dendritic trees based on preloaded statistics from a database of cell-type specific neuronal morphologies. To our knowledge, this is the first tool that allows (a the remodeling of existing –as opposed to the de novo

  1. Dendritic potassium channels in hippocampal pyramidal neurons.

    Science.gov (United States)

    Johnston, D; Hoffman, D A; Magee, J C; Poolos, N P; Watanabe, S; Colbert, C M; Migliore, M

    2000-05-15

    Potassium channels located in the dendrites of hippocampal CA1 pyramidal neurons control the shape and amplitude of back-propagating action potentials, the amplitude of excitatory postsynaptic potentials and dendritic excitability. Non-uniform gradients in the distribution of potassium channels in the dendrites make the dendritic electrical properties markedly different from those found in the soma. For example, the influence of a fast, calcium-dependent potassium current on action potential repolarization is progressively reduced in the first 150 micrometer of the apical dendrites, so that action potentials recorded farther than 200 micrometer from the soma have no fast after-hyperpolarization and are wider than those in the soma. The peak amplitude of back-propagating action potentials is also progressively reduced in the dendrites because of the increasing density of a transient potassium channel with distance from the soma. The activation of this channel can be reduced by the activity of a number of protein kinases as well as by prior depolarization. The depolarization from excitatory postsynaptic potentials (EPSPs) can inactivate these A-type K+ channels and thus lead to an increase in the amplitude of dendritic action potentials, provided the EPSP and the action potentials occur within the appropriate time window. This time window could be in the order of 15 ms and may play a role in long-term potentiation induced by pairing EPSPs and back-propagating action potentials.

  2. Containerless Undercooled Melts: Ordering, Nucleation, and Dendrite Growth

    Science.gov (United States)

    Herlach, Dieter M.; Binder, Sven; Galenko, Peter; Gegner, Jan; Holland-Moritz, Dirk; Klein, Stefan; Kolbe, Matthias; Volkmann, Thomas

    2015-11-01

    Electromagnetic and electrostatic levitation are applied to containerless undercool and solidify metallic melts. A large undercooling range becomes accessible with the extra benefit that the freely suspended drop is accessible directly for in situ observation. The short-range order in undercooled melts is investigated by combining levitation with elastic neutron scattering and X-ray scattering using synchrotron radiation. Muon Spin Rotation ( µSR) experiments show magnetic ordering in deeply undercooled Co80Pd20 alloys. The onset of magnetic ordering stimulates nucleation. Results on nucleation undercooling of zirconium are presented showing the limit of maximum undercoolability set by the onset of homogeneous nucleation. Metastable phase diagrams are determined by applying energy-dispersive X-ray diffraction of Ni-V alloys with varying concentration. Nucleation is followed by crystal growth. Rapid dendrite growth velocity is measured on levitation-processed samples as a function of undercooling ∆ T by using high-speed video camera technique. Solute trapping in dilute solid solutions and disorder trapping in intermetallic compounds are experimentally verified. Measurements of glass-forming Cu-Zr alloy show a maximum in the V(∆ T) relation that is indicative for diffusion-controlled growth. The influence of convection on dendrite growth of Al50Ni50 is shown by comparative measurements of dendrite growth velocity on Earth and in reduced gravity. Eventually, faceting of a rough interface by convection is presented as observed on Ni2B alloys.

  3. Non-linear dendrites can tune neurons

    Directory of Open Access Journals (Sweden)

    Romain Daniel Cazé

    2014-03-01

    Full Text Available A signature of visual, auditory, and motor cortices is the presence of neurons tuned to distinct features of the environment. While neuronal tuning can be observed in most brain areas, its origin remains enigmatic, and new calcium imaging data complicate this problem. Dendritic calcium signals, in a L2/3 neuron from the mouse visual cortex, display a wide range of tunings that could be different from the neuronal tuning (Jia et al 2010. To elucidate this observation we use multi-compartmental models of increasing complexity, from a binary to a realistic biophysical model of L2/3 neuron. These models possess non-linear dendritic subunits inside which the result of multiple excitatory inputs is smaller than their arithmetic sum. While dendritic non-linear subunits are ad-hoc in the binary model, non-linearities in the realistic model come from the passive saturation of synaptic currents. Because of these non-linearities our neuron models are scatter sensitive: the somatic membrane voltage is higher when presynaptic inputs target different dendrites than when they target a single dendrite. This spatial bias in synaptic integration is, in our models, the origin of neuronal tuning. Indeed, assemblies of presynaptic inputs encode the stimulus property through an increase in correlation or activity, and only the assembly that encodes the preferred stimulus targets different dendrites. Assemblies coding for the non-preferred stimuli target single dendrites, explaining the wide range of observed tunings and the possible difference between dendritic and somatic tuning. We thus propose, in accordance with the latest experimental observations, that non-linear integration in dendrites can generate neuronal tuning independently of the coding regime.

  4. Dendritic tellurides acting as antioxidants

    Institute of Scientific and Technical Information of China (English)

    XU Huaping; WANG Yapei; WANG Zhiqiang; LIU Junqiu; Mario Smet; Wim Dehaen

    2006-01-01

    We have described the synthesis of a series of poly(aryl ether) dendrimers with telluride in the core and oligo(ethylene oxide) chains at the periphery which act as glutathione peroxidase (GPx) mimics. These series of compounds were well characterized by 1H-NMR, 13C-NMR and ESI-MS. Using different ROOH (H2O2, cumene hydroperoxide) for testing the antioxidizing properties of these compounds, we have found that from generation 0 to 2, the activity of the dendritic GPx mimics first decreased and then increased. This can be explained on the basis of a greater steric hindrance, going from generation 0 to 1, and stronger binding interactions going from generation 1 to 2. In other words, there exists a balance between binding interactions and steric hindrance that may optimize the GPx activity.

  5. Fate mapping of dendritic cells

    Directory of Open Access Journals (Sweden)

    Barbara Ursula Schraml

    2015-05-01

    Full Text Available Dendritic cells (DCs are a heterogeneous group of mononuclear phagocytes with versatile roles in immunity. They are classified predominantly based on phenotypic and functional properties, namely their stellate morphology, expression of the integrin CD11c and major histocompatibility class II molecules, as well as their superior capacity to migrate to secondary lymphoid organs and stimulate naïve T cells. However, these attributes are not exclusive to DCs and often change within inflammatory or infectious environments. This led to debates over cell identification and questioned even the mere existence of DCs as distinct leukocyte lineage. Here, we review experimental approaches taken to fate map DCs and discuss how these have shaped our understanding of DC ontogeny and lineage affiliation. Considering the ontogenetic properties of DCs will help to overcome the inherent shortcomings of purely phenotypic- and function-based approaches to cell definition and will yield a more robust way of DC classification.

  6. Dendritic Cells for Anomaly Detection

    CERN Document Server

    Greensmith, Julie; Aickelin, Uwe

    2010-01-01

    Artificial immune systems, more specifically the negative selection algorithm, have previously been applied to intrusion detection. The aim of this research is to develop an intrusion detection system based on a novel concept in immunology, the Danger Theory. Dendritic Cells (DCs) are antigen presenting cells and key to the activation of the human signals from the host tissue and correlate these signals with proteins know as antigens. In algorithmic terms, individual DCs perform multi-sensor data fusion based on time-windows. The whole population of DCs asynchronously correlates the fused signals with a secondary data stream. The behaviour of human DCs is abstracted to form the DC Algorithm (DCA), which is implemented using an immune inspired framework, libtissue. This system is used to detect context switching for a basic machine learning dataset and to detect outgoing portscans in real-time. Experimental results show a significant difference between an outgoing portscan and normal traffic.

  7. Deciphering dendritic cell heterogenity in immunity

    Directory of Open Access Journals (Sweden)

    Michaël eChopin

    2012-02-01

    Full Text Available Dendritic cells (DCs are specialized antigen presenting cells that are exquisitely adapted to sense pathogens and induce the development of adaptive immune responses. They form a complex network of phenotypically and functionally distinct subsets. Within this network, individual DC subsets display highly specific roles in local immunosurveillance, migration and antigen presentation. This division of labor amongst DCs offers great potential to tune the immune response by harnessing subset-specific attributes of DCs in the clinical setting. Until recently, our understanding of DC subsets has been limited and paralleled by poor clinical translation and efficacy. We have now begun to unravel how different DC subsets develop within a complex multilayered system. These finding open up exciting possibilities for targeted manipulation of DC subsets. Furthermore, ground-breaking developments overcoming a major translational obstacle – identification of similar DC populations in mouse and man – now set the stage for significant advances in the field. Here we explore the determinants that underpin cellular and transcriptional heterogeneity within the DC network, how these influence DC distribution and localization at steady-state, and the capacity of DCs to present antigens via direct or cross-presentation during pathogen infection.

  8. Transcriptional regulation of dendritic cell diversity.

    Science.gov (United States)

    Chopin, Michaël; Allan, Rhys S; Belz, Gabrielle T

    2012-01-01

    Dendritic cells (DCs) are specialized antigen presenting cells that are exquisitely adapted to sense pathogens and induce the development of adaptive immune responses. They form a complex network of phenotypically and functionally distinct subsets. Within this network, individual DC subsets display highly specific roles in local immunosurveillance, migration, and antigen presentation. This division of labor amongst DCs offers great potential to tune the immune response by harnessing subset-specific attributes of DCs in the clinical setting. Until recently, our understanding of DC subsets has been limited and paralleled by poor clinical translation and efficacy. We have now begun to unravel how different DC subsets develop within a complex multilayered system. These findings open up exciting possibilities for targeted manipulation of DC subsets. Furthermore, ground-breaking developments overcoming a major translational obstacle - identification of similar DC populations in mouse and man - now sets the stage for significant advances in the field. Here we explore the determinants that underpin cellular and transcriptional heterogeneity within the DC network, how these influence DC distribution and localization at steady-state, and the capacity of DCs to present antigens via direct or cross-presentation during pathogen infection.

  9. Epigenetic regulation of axon and dendrite growth

    Directory of Open Access Journals (Sweden)

    Ephraim F Trakhtenberg

    2012-03-01

    Full Text Available Neuroregenerative therapies for central nervous system (CNS injury, neurodegenerative disease, or stroke require axons of damaged neurons to grow and reinnervate their targets. However, mature mammalian CNS neurons do not regenerate their axons, limiting recovery in these diseases (Yiu and He, 2006. CNS’ regenerative failure may be attributable to the development of an inhibitory CNS environment by glial-associated inhibitory molecules (Yiu and He, 2006, and by various cell-autonomous factors (Sun and He, 2010. Intrinsic axon growth ability also declines developmentally (Li et al., 1995; Goldberg et al., 2002; Bouslama-Oueghlani et al., 2003; Blackmore and Letourneau, 2006 and is dependent on transcription (Moore et al., 2009. Although neurons’ intrinsic capacity for axon growth may depend in part on the panoply of expressed transcription factors (Moore and Goldberg, 2011, epigenetic factors such as the accessibility of DNA and organization of chromatin are required for downstream genes to be transcribed. Thus a potential approach to overcoming regenerative failure focuses on the epigenetic mechanisms regulating regenerative gene expression in the CNS. Here we review molecular mechanisms regulating the epigenetic state of DNA through chromatin modifications, their implications for regulating axon and dendrite growth, and important new directions for this field of study.

  10. Dendritic Cells in the Cancer Microenvironment

    Directory of Open Access Journals (Sweden)

    Yang Ma, Galina V. Shurin, Zhu Peiyuan, Michael R. Shurin

    2013-01-01

    Full Text Available The complexity of the tumor immunoenvironment is underscored by the emergence and discovery of different subsets of immune effectors and regulatory cells. Tumor-induced polarization of immune cell differentiation and function makes this unique environment even more intricate and variable. Dendritic cells (DCs represent a special group of cells that display different phenotype and activity at the tumor site and exhibit differential pro-tumorigenic and anti-tumorigenic functions. DCs play a key role in inducing and maintaining the antitumor immunity, but in the tumor environment their antigen-presenting function may be lost or inefficient. DCs might be also polarized into immunosuppressive/tolerogenic regulatory DCs, which limit activity of effector T cells and support tumor growth and progression. Although various factors and signaling pathways have been described to be responsible for abnormal functioning of DCs in cancer, there are still no feasible therapeutic modalities available for preventing or reversing DC malfunction in tumor-bearing hosts. Thus, better understanding of DC immunobiology in cancer is pivotal for designing novel or improved therapeutic approaches that will allow proper functioning of DCs in patients with cancer.

  11. Dendritic cells are stressed out in tumor.

    Science.gov (United States)

    Maj, Tomasz; Zou, Weiping

    2015-09-01

    A recently paper published in Cell reports that dendritic cells (DCs) are dysfunctional in the tumor environment. Tumor impairs DC function through induction of endoplasmic reticulum stress response and subsequent disruption of lipid metabolic homeostasis.

  12. Dendritic ion channelopathy in acquired epilepsy

    Science.gov (United States)

    Poolos, Nicholas P.; Johnston, Daniel

    2012-01-01

    Summary Ion channel dysfunction or “channelopathy” is a proven cause of epilepsy in the relatively uncommon genetic epilepsies with Mendelian inheritance. But numerous examples of acquired channelopathy in experimental animal models of epilepsy following brain injury have also been demonstrated. Our understanding of channelopathy has grown due to advances in electrophysiology techniques that have allowed the study of ion channels in the dendrites of pyramidal neurons in cortex and hippocampus. The apical dendrites of pyramidal neurons comprise the vast majority of neuronal surface membrane area, and thus the majority of the neuronal ion channel population. Investigation of dendritic ion channels has demonstrated remarkable plasticity in ion channel localization and biophysical properties in epilepsy, many of which produce hyperexcitability and may contribute to the development and maintenance of the epileptic state. Here we review recent advances in dendritic physiology and cell biology, and their relevance to epilepsy. PMID:23216577

  13. Dendritic ion channelopathy in acquired epilepsy.

    Science.gov (United States)

    Poolos, Nicholas P; Johnston, Daniel

    2012-12-01

    Ion channel dysfunction or "channelopathy" is a proven cause of epilepsy in the relatively uncommon genetic epilepsies with Mendelian inheritance. But numerous examples of acquired channelopathy in experimental animal models of epilepsy following brain injury have also been demonstrated. Our understanding of channelopathy has grown due to advances in electrophysiology techniques that have allowed the study of ion channels in the dendrites of pyramidal neurons in cortex and hippocampus. The apical dendrites of pyramidal neurons comprise the vast majority of neuronal surface membrane area, and thus the majority of the neuronal ion channel population. Investigation of dendritic ion channels has demonstrated remarkable plasticity in ion channel localization and biophysical properties in epilepsy, many of which produce hyperexcitability and may contribute to the development and maintenance of the epileptic state. Herein we review recent advances in dendritic physiology and cell biology, and their relevance to epilepsy. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

  14. Artificial Dendritic Cells: Multi-faceted Perspectives

    CERN Document Server

    Greensmith, Julie

    2009-01-01

    Dendritic cells are the crime scene investigators of the human immune system. Their function is to correlate potentially anomalous invading entities with observed damage to the body. The detection of such invaders by dendritic cells results in the activation of the adaptive immune system, eventually leading to the removal of the invader from the host body. This mechanism has provided inspiration for the development of a novel bio-inspired algorithm, the Dendritic Cell Algorithm. This algorithm processes information at multiple levels of resolution, resulting in the creation of information granules of variable structure. In this chapter we examine the multi-faceted nature of immunology and how research in this field has shaped the function of the resulting Dendritic Cell Algorithm. A brief overview of the algorithm is given in combination with the details of the processes used for its development. The chapter is concluded with a discussion of the parallels between our understanding of the human immune system a...

  15. “Dermal dendritic cells” comprise two distinct populations: CD1+ dendritic cells and CD209+ macrophages

    OpenAIRE

    Ochoa,Maria Teresa; Loncaric, Anya; Krutzik, Stephan R.; Becker, Todd C.; Modlin, Robert L.

    2008-01-01

    A key cell type of the resident skin immune system is the dendritic cell, which in normal skin is located in two distinct microanatomical compartments: Langerhans cells (LC) mainly in the epidermis and dermal dendritic cells (DDC) in the dermis. Here, the lineage of dermal dendritic cells was investigated using monoclonal antibodies and immunohistology. We provide evidence that “dermal dendritic cells” comprise at least two major phenotypic populations of dendritic appearing cells: immature D...

  16. Phenotypic and functional heterogeneity of macrophages and dendritic cell subsets in the healthy and atherosclerosis-prone aorta.

    Directory of Open Access Journals (Sweden)

    Elena V Galkina

    2012-03-01

    Full Text Available Atherosclerosis continues to be the leading cause of cardiovascular disease. Development of atherosclerosis depends on chronic inflammation in the aorta and multiple immune cells are involved in this process. Importantly, resident macrophages and dendritic cells are present within the healthy aorta, but the functions of these cells remain poorly characterized. Local inflammation within the aortic wall promotes the recruitment of monocytes and dendritic cell precursors to the aorta and micro-environmental factors direct the differentiation of these emigrated cells into multiple subsets of macrophages and dendritic cells. Recent data suggest that several populations of macrophages and dendritic cells can co-exist within the aorta. Although the functions of M1, M2, Mox and M4 macrophages are well characterized in vitro, there is a limited set of data on the role of these populations in atherogenesis in vivo. Recent studies on the origin and the potential role of aortic dendritic cells provide novel insights into the biology of aortic dendritic cell subsets and prospective mechanisms of the immune response in atherosclerosis. This review integrates the results of experiments analyzing heterogeneity of dendritic cells and macrophage subsets in healthy and diseased vessels and briefly discusses the known and potential functions of these cells in atherogenesis.

  17. Phosphorylation of CRMP2 by Cdk5 Regulates Dendritic Spine Development of Cortical Neuron in the Mouse Hippocampus

    Directory of Open Access Journals (Sweden)

    Xiaohua Jin

    2016-01-01

    Full Text Available Proper density and morphology of dendritic spines are important for higher brain functions such as learning and memory. However, our knowledge about molecular mechanisms that regulate the development and maintenance of dendritic spines is limited. We recently reported that cyclin-dependent kinase 5 (Cdk5 is required for the development and maintenance of dendritic spines of cortical neurons in the mouse brain. Previous in vitro studies have suggested the involvement of Cdk5 substrates in the formation of dendritic spines; however, their role in spine development has not been tested in vivo. Here, we demonstrate that Cdk5 phosphorylates collapsin response mediator protein 2 (CRMP2 in the dendritic spines of cultured hippocampal neurons and in vivo in the mouse brain. When we eliminated CRMP2 phosphorylation in CRMP2KI/KI mice, the densities of dendritic spines significantly decreased in hippocampal CA1 pyramidal neurons in the mouse brain. These results indicate that phosphorylation of CRMP2 by Cdk5 is important for dendritic spine development in cortical neurons in the mouse hippocampus.

  18. Downregulation of transient K+ channels in dendrites of hippocampal CA1 pyramidal neurons by activation of PKA and PKC.

    Science.gov (United States)

    Hoffman, D A; Johnston, D

    1998-05-15

    We have reported recently a high density of transient A-type K+ channels located in the distal dendrites of CA1 hippocampal pyramidal neurons and shown that these channels shape EPSPs, limit the back-propagation of action potentials, and prevent dendritic action potential initiation (). Because of the importance of these channels in dendritic signal propagation, their modulation by protein kinases would be of significant interest. We investigated the effects of activators of cAMP-dependent protein kinase (PKA) and the Ca2+-dependent phospholipid-sensitive protein kinase (PKC) on K+ channels in cell-attached patches from the distal dendrites of hippocampal CA1 pyramidal neurons. Inclusion of the membrane-permeant PKA activators 8-bromo-cAMP (8-br-cAMP) or forskolin in the dendritic patch pipette resulted in a depolarizing shift in the activation curve for the transient channels of approximately 15 mV. Activation of PKC by either of two phorbol esters also resulted in a 15 mV depolarizing shift of the activation curve. Neither PKA nor PKC activation affected the sustained or slowly inactivating component of the total outward current. This downregulation of transient K+ channels in the distal dendrites may be responsible for some of the frequently reported increases in cell excitability found after PKA and PKC activation. In support of this hypothesis, we found that activation of either PKA or PKC significantly increased the amplitude of back-propagating action potentials in distal dendrites.

  19. Free energy and dendritic self-organisation

    Directory of Open Access Journals (Sweden)

    Stefan J Kiebel

    2011-10-01

    Full Text Available In this paper, we pursue recent observations that, through selective dendritic filtering, single neurons respond to specific sequences of presynaptic inputs. We try to provide a principled and mechanistic account of this selectivity by applying the free energy principle to a dendrite that is immersed in its neuropil or environment. We assume that neurons self-organize to minimise a free energy bound on the self-information or surprise of presynaptic inputs that are sampled. We model this as a selective pruning of dendritic spines that are expressed on a dendritic branch. This pruning occurs when the optimized postsynaptic gain falls below a threshold. Crucially, postsynaptic gain is itself optimized with respect to free energy. Pruning suppresses free energy as the dendrite selects presynaptic signals that conform to its expectations, specified by a generative model implicit in its intracellular kinetics. Not only does this provide a principled account of how neurons organize and selectively sample the myriad of potential presynaptic inputs they are exposed to, but it also connects the optimization of elemental neuronal (dendritic processing to generic (surprise or evidence-based schemes in statistics and machine learning, such as Bayesian model selection and automatic relevance determination.

  20. Synaptic Control of Secretory Trafficking in Dendrites

    Directory of Open Access Journals (Sweden)

    Cyril Hanus

    2014-06-01

    Full Text Available Localized signaling in neuronal dendrites requires tight spatial control of membrane composition. Upon initial synthesis, nascent secretory cargo in dendrites exits the endoplasmic reticulum (ER from local zones of ER complexity that are spatially coupled to post-ER compartments. Although newly synthesized membrane proteins can be processed locally, the mechanisms that control the spatial range of secretory cargo transport in dendritic segments are unknown. Here, we monitored the dynamics of nascent membrane proteins in dendritic post-ER compartments under regimes of low or increased neuronal activity. In response to activity blockade, post-ER carriers are highly mobile and are transported over long distances. Conversely, increasing synaptic activity dramatically restricts the spatial scale of post-ER trafficking along dendrites. This activity-induced confinement of secretory cargo requires site-specific phosphorylation of the kinesin motor KIF17 by Ca2+/calmodulin-dependent protein kinases (CaMK. Thus, the length scales of early secretory trafficking in dendrites are tuned by activity-dependent regulation of microtubule-dependent transport.

  1. Basal Dendritic Morphology of Cortical Pyramidal Neurons in Williams Syndrome: Prefrontal Cortex and Beyond

    Directory of Open Access Journals (Sweden)

    Branka Hrvoj-Mihic

    2017-08-01

    Full Text Available Williams syndrome (WS is a unique neurodevelopmental disorder with a specific behavioral and cognitive profile, which includes hyperaffiliative behavior, poor social judgment, and lack of social inhibition. Here we examined the morphology of basal dendrites on pyramidal neurons in the cortex of two rare adult subjects with WS. Specifically, we examined two areas in the prefrontal cortex (PFC—the frontal pole (Brodmann area 10 and the orbitofrontal cortex (Brodmann area 11—and three areas in the motor, sensory, and visual cortex (BA 4, BA 3-1-2, BA 18. The findings suggest that the morphology of basal dendrites on the pyramidal neurons is altered in the cortex of WS, with differences that were layer-specific, more prominent in PFC areas, and displayed an overall pattern of dendritic organization that differentiates WS from other disorders. In particular, and unlike what was expected based on typically developing brains, basal dendrites in the two PFC areas did not display longer and more branched dendrites compared to motor, sensory and visual areas. Moreover, dendritic branching, dendritic length, and the number of dendritic spines differed little within PFC and between the central executive region (BA 10 and BA 11 that is part of the orbitofrontal region involved into emotional processing. In contrast, the relationship between the degree of neuronal branching in supra- versus infra-granular layers was spared in WS. Although this study utilized tissue held in formalin for a prolonged period of time and the number of neurons available for analysis was limited, our findings indicate that WS cortex, similar to that in other neurodevelopmental disorders such as Down syndrome, Rett syndrome, Fragile X, and idiopathic autism, has altered morphology of basal dendrites on pyramidal neurons, which appears more prominent in selected areas of the PFC. Results were examined from developmental perspectives and discussed in the context of other

  2. Basal Dendritic Morphology of Cortical Pyramidal Neurons in Williams Syndrome: Prefrontal Cortex and Beyond.

    Science.gov (United States)

    Hrvoj-Mihic, Branka; Hanson, Kari L; Lew, Caroline H; Stefanacci, Lisa; Jacobs, Bob; Bellugi, Ursula; Semendeferi, Katerina

    2017-01-01

    Williams syndrome (WS) is a unique neurodevelopmental disorder with a specific behavioral and cognitive profile, which includes hyperaffiliative behavior, poor social judgment, and lack of social inhibition. Here we examined the morphology of basal dendrites on pyramidal neurons in the cortex of two rare adult subjects with WS. Specifically, we examined two areas in the prefrontal cortex (PFC)-the frontal pole (Brodmann area 10) and the orbitofrontal cortex (Brodmann area 11)-and three areas in the motor, sensory, and visual cortex (BA 4, BA 3-1-2, BA 18). The findings suggest that the morphology of basal dendrites on the pyramidal neurons is altered in the cortex of WS, with differences that were layer-specific, more prominent in PFC areas, and displayed an overall pattern of dendritic organization that differentiates WS from other disorders. In particular, and unlike what was expected based on typically developing brains, basal dendrites in the two PFC areas did not display longer and more branched dendrites compared to motor, sensory and visual areas. Moreover, dendritic branching, dendritic length, and the number of dendritic spines differed little within PFC and between the central executive region (BA 10) and BA 11 that is part of the orbitofrontal region involved into emotional processing. In contrast, the relationship between the degree of neuronal branching in supra- versus infra-granular layers was spared in WS. Although this study utilized tissue held in formalin for a prolonged period of time and the number of neurons available for analysis was limited, our findings indicate that WS cortex, similar to that in other neurodevelopmental disorders such as Down syndrome, Rett syndrome, Fragile X, and idiopathic autism, has altered morphology of basal dendrites on pyramidal neurons, which appears more prominent in selected areas of the PFC. Results were examined from developmental perspectives and discussed in the context of other neurodevelopmental disorders

  3. Velocity selection in the symmetric model of dendritic crystal growth

    Science.gov (United States)

    Barbieri, Angelo; Hong, Daniel C.; Langer, J. S.

    1987-01-01

    An analytic solution of the problem of velocity selection in a fully nonlocal model of dendritic crystal growth is presented. The analysis uses a WKB technique to derive and evaluate a solvability condition for the existence of steady-state needle-like solidification fronts in the limit of small under-cooling Delta. For the two-dimensional symmetric model with a capillary anisotropy of strength alpha, it is found that the velocity is proportional to (Delta to the 4th) times (alpha exp 7/4). The application of the method in three dimensions is also described.

  4. In Situ Observation of Cell-to-Dendrite Transition

    Institute of Scientific and Technical Information of China (English)

    PAN Xiu-Hong; HONG Yong; JIN Wei-Qing

    2005-01-01

    @@ The cell-to-dendrite transition of succinonitrile melt suspended on a loop-shaped Pt heater is observed in real time by a differential interference microscope coupled with Schlieren technique. The transition is divided into two parts: a dendrite coalition process and a subsequent dendrite elimination process. Firstly the dendrites from the same cell are united into a single dendrite. Secondly the competitive growth of dendrites from different cells leads to the elimination of dendrites. The two processes can be understood when involving crystallographic orientation. In addition, the tip velocity and primary spacing of a cell/dendrite are also measured. It turns out that the primary spacing has a significant jump, whereas the growth velocity has no abrupt change during the cell-to-dendrite transition.

  5. Dendritic cells in melanoma - immunohistochemical study and research trends.

    Science.gov (United States)

    Nedelcu, Roxana Ioana; Ion, Daniela Adriana; Holeab, Cosmin Adrian; Cioplea, Mirela Daniela; Brînzea, Alice; Zurac, Sabina Andrada

    2015-01-01

    Cutaneous dendritic cells play multiple physiological roles and are involved in various pathophysiological processes. Research studies of dendritic cells abound in the medical literature. Nevertheless, the role of dendritic cells in melanoma regression phenomenon is not completely understood. We conducted a scientometric analysis in order to highlight the current state on research regarding dendritic cells and melanoma. We also performed an immunohistochemical study, using specific markers for dendritic cells (CD1a, langerin). We evaluated the frequency and distribution of dendritic cells in areas of tumor regression compared to the areas of inflammatory infiltrate of melanoma without regression. The immunohistochemical study we performed revealed that dendritic cells are more frequent in the regressed areas, comparing with non-regressed ones. In regressed areas, dendritic cells have a predominant nodular pattern (19 cases), followed by diffuse isolate pattern (eight cases) and mixed pattern (diffuse and nodular) (three cases). In melanoma without regression, most cases presented a diffuse pattern (27 cases) of dendritic cells distribution. In conclusion, our immunohistochemical study stressed differences between frequency and distribution of dendritic cells located in the melanoma with regression and melanoma without regression. These data suggest that dendritic cells are involved in the regression phenomenon. Following the literature analysis we obtained, we observed that dendritic cells profile in melanoma with regression was poorly studied. Insights into antitumor immune response and dendritic cells may be essential for the understanding of the potential prognostic role of dendritic cells in melanoma and for the development of new promising therapeutic strategies for melanoma.

  6. Architecture of apical dendrites in the murine neocortex: dual apical dendritic systems.

    Science.gov (United States)

    Escobar, M I; Pimienta, H; Caviness, V S; Jacobson, M; Crandall, J E; Kosik, K S

    1986-04-01

    A monoclonal antibody (5F9) against microtubule-associated protein 2 is a selective and sensitive marker for neocortical dendrites in the mouse. The marker stains all dendrites. It affords a particularly comprehensive picture of the patterns of arrangements of apical dendrites which are most intensely stained with this antibody. Dual systems of apical dendrites arise from the polymorphic neurons of layer VI, on the one hand, and the pyramidal neurons of layers II-V, on the other. Terminal arborization of the former is concentrated principally at the interface of layers V and IV, while that of the latter is in the molecular layer. Apical dendrites of both systems are grouped into fascicles. In supragranular layers and in upper layer VI-lower layer V, where apical dendrites are most abundant, the fascicles coalesce into septa. These generate a honeycomb-like pattern, subdividing these cortical levels into columnar spaces of approximately 20-40 micron diameter. At the level of layer IV, where the number of apical dendrites is greatly reduced, the fascicles are isolated bundles. These bundles have the form of circular, elliptical or rectangular columns in the primary somatosensory, temporal and frontal regions, respectively. Those in the barrel field are preferentially concentrated in the sides of barrels and the interbarrel septa. The configurations of the dendritic fascicles, particularly the midcortical bundles, may conform to the spatial configuration of investing axons of interneurons.

  7. Metastatic melanoma patients treated with dendritic cell vaccination, Interleukin-2 and metronomic cyclophosphamide

    DEFF Research Database (Denmark)

    Ellebaek, Eva; Engell-Noerregaard, Lotte; Iversen, Trine Zeeberg

    2012-01-01

    Dendritic cells (DC) are the most potent antigen presenting cells and have proven effective in stimulation of specific immune responses in vivo. Competing immune inhibition could limit the clinical efficacy of DC vaccination. In this phase II trial, metronomic Cyclophosphamide and a Cox-2 inhibit...

  8. Targeting vaccines to dendritic cells.

    Science.gov (United States)

    Foged, Camilla; Sundblad, Anne; Hovgaard, Lars

    2002-03-01

    Dendritic cells (DC) are specialized antigen presenting cells (APC) with a remarkable ability to take up antigens and stimulate major histocompatibility complex (MHC)-restricted specific immune responses. Recent discoveries have shown that their role in initiating primary immune responses seems to be far superior to that of B-cells and macrophages. DC are localized at strategic places in the body at sites used by pathogens to enter the organism, and are thereby in an optimal position to capture antigens. In general, vaccination strategies try to mimic the invasiveness of the pathogens. DC are considered to play a central role for the provocation of primary immune responses by vaccination. A rational way of improving the potency and safety of new and already existing vaccines could therefore be to direct vaccines specifically to DC. There is a need for developing multifunctional vaccine drug delivery systems (DDS) with adjuvant effect that target DC directly and induce optimal immune responses. This paper will review the current knowledge of DC physiology as well as the progress in the field of novel vaccination strategies that directly or indirectly aim at targeting DC.

  9. Heterogeneous nucleation and dendritic growth within undercooled liquid niobium under electrostatic levitation condition

    Science.gov (United States)

    Yang, S. J.; Hu, L.; Wang, L.; Wei, B.

    2017-09-01

    The physical mechanisms of crystal nucleation and dendritic growth within undercooled niobium were systematically studied by electrostatic levitation and molecular dynamics methods. The maximum undercooling was achieved as 454 K (0.16Tm), while the hypercooling limit was determined as 706 K (0.26Tm). The undercooling probability displayed Poisson distribution and indicated the occurrence of heterogeneous nucleation. The calculated critical nucleus size reduced rapidly with undercooling and the solid-liquid interface energy was deduced to be 0.367 J m-2. In addition, the dendritic growth velocity of pure niobium exhibited a power relation versus undercooling, and reached 41 m s-1 at the maximum undercooling.

  10. Up-regulation of HP1γ expression during neuronal maturation promotes axonal and dendritic development in mouse embryonic neocortex.

    Science.gov (United States)

    Oshiro, Hiroaki; Hirabayashi, Yusuke; Furuta, Yasuhide; Okabe, Shigeo; Gotoh, Yukiko

    2015-02-01

    Immature neurons undergo morphological and physiological changes including axonal and dendritic development to establish neuronal networks. As the transcriptional status changes at a large number of genes during neuronal maturation, global changes in chromatin modifiers may take place in this process. We now show that the amount of heterochromatin protein 1γ (HP1γ) increases during neuronal maturation in the mouse neocortex. Knockdown of HP1γ suppressed axonal and dendritic development in mouse embryonic neocortical neurons in culture, and either knockdown or knockout of HP1γ impaired the projection of callosal axons of superficial layer neurons to the contralateral hemisphere in the developing neocortex. Conversely, forced expression of HP1γ facilitated axonal and dendritic development, suggesting that the increase of HP1γ is a rate limiting step in neuronal maturation. These results together show an important role for HP1γ in promoting axonal and dendritic development in maturing neurons.

  11. Theoretical - Experimental Analysis of Cellular and Primary Dendritic Spacings during Unidirectional Solidification of Sn-Pb Alloys

    Directory of Open Access Journals (Sweden)

    Otávio F.L. da Rocha

    2002-09-01

    Full Text Available Structural parameters as grain size, dendritic and cellular spacings, segregated products, porosity and other phases are strongly influenced by the thermal behavior of the metal/mold system during solidification, imposing a close correlation between this and the resulting microstructure. Several unidirectional solidification studies with the objective of characterizing cellular and dendritic spacings have been developed in large scale involving solidification in steady-state heat flow. The main objective of this work is to determine the thermal solidification parameters during the cellular/dendritic transition as well as to compare theoretical models that predict cellular and primary dendritic spacings with experimental results for solidification situations in unsteady-state heat flow. Experiments were carried out in a water cooled unidirectional solidification apparatus and dilute alloys of the Sn-Pb system were used (Sn 1.5wt%Pb, Sn 2.5wt%Pb and Sn 5wt%Pb. The upper limit of the Hunt-Lu cellular growth model closely matched the experimental spacings. The lower limit calculated with the Hunt-Lu dendritic model best generated the experimental results. The cellular/dendritic transition was observed to occur for the Sn 2.5wt%Pb alloy over a range of analytical cooling rates from 0.28 K/s to 1.8 K/s.

  12. In-situ study of the dendritic growth in lithium/polymer electrolyte-salt/lithium cells; Etude in-situ de la croissance dendritique dans des cellules lithium/POE-sel/lithium

    Energy Technology Data Exchange (ETDEWEB)

    Brissot, C.; Rosso, M.; Chazalviel, J.N. [Ecole Polytechnique, 91 - Palaiseau (France); Baudry, P.; Lascaud, S. [Electricite de France, 77 - Moret sur Loing (France). Direction des Etudes et Recherches

    1996-12-31

    The in-situ observation of dendritic growth in lithium/polymer electrolyte-LiTFSI/lithium battery cells shows that dendrites grow up with about the same rate as anion migration. Memory effects have been evidenced in cycling experiments and limit the dendrites length. An overall movement of the electrolyte due to variations of electrolyte concentration in the vicinity of the electrodes has been observed too. (J.S.) 13 refs.

  13. In-situ Dendrite/Metallic Glass Matrix Composites: A Review

    Institute of Scientific and Technical Information of China (English)

    Junwei Qiao

    2013-01-01

    The advanced fabrication of in-situ dendrite/metallic glass matrix (MGM) composites is reviewed.Herein,the semisolid processing and Bridgman solidification are two methods,which can make the dendrites homogeneously dispersed within the metallic glass matrix.Upon quasi-static compressive loading at room temperature,almost all the in-situ composites exhibit improved plasticity,due to the effective block to the fast propagation of shear bands.Upon quasi-static tensile loading at room temperature,although the composites possess tensile ductility,the inhomogeneous deformation and associated softening dominates.High volume-fractioned dendrites and network structures make in-situ composites distinguishingly plastic upon dynamic compression.In-situ composite exhibits high tensile strength and softening (necking) in the supercooled liquid region,since the presence of high volume-fractioned dendrites lowers the rheology of the viscous glass matrix at high temperatures.At cryogenic temperatures,a distinguishingly-increased maximum strength is available; however,a ductile-to-brittle transition seems to be present by lowering the temperature.Besides,improved tension-tension fatigue limit of 473 MPa and four-point-bending fatigue limit of 567 MPa are gained for Zr58.5Ti14.3Nb5.2Cu6.1Ni4.9Be11.o MGM composites.High volume-fraction dendrites within the glass matrix induce increased effectiveness on the blunting and propagating resistance of the fatigue-crack tip.The fracture toughness of in-situ composites is comparable to those of the toughest steels and crystalline Ti alloys.During steady-state crack-growth,the confinement of damage by in-situ dendrites results in enhancement of the toughness.

  14. Nerve Conduction Through Dendrites via Proton Hopping.

    Science.gov (United States)

    Kier, Lemont B

    2017-01-01

    In our previous studies of nerve conduction conducted by proton hopping, we have considered the axon, soma, synapse and the nodes of Ranvier. The role of proton hopping described the passage of information through each of these units of a typical nerve system. The synapse projects information from the axon to the dendrite and their associated spines. We have invoked the passage of protons via a hopping mechanism to illustrate the continuum of the impulse through the system, via the soma following the dendrites. This is proposed to be a continuum invoked by the proton hopping method. With the proposal of the activity through the dendrites, via proton hopping, a complete model of the nerve function is invoked. At each step to the way, a water pathway is present and is invoked in the proposed model as the carrier of the message via proton hopping. The importance of the dendrites is evident by the presence of a vast number of spines, each possessing the possibility to carry unique messages through the nervous system. With this model of the role of dendrites, functioning with the presence of proton hopping, a complete model of the nerve system is presented. The validity of this model will be available for further studies and models to assess it's validity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Estimating intracellular Ca2+ concentrations and buffering in a dendritic inhibitory hippocampal interneuron.

    Science.gov (United States)

    Liao, C W; Lien, C C

    2009-12-29

    Calcium is known to regulate several phenomena like neuronal excitability and plasticity. Interestingly, the spatiotemporal profile of dendritic calcium depends on several processes, specific to each neuronal type. In this study, we investigated Ca(2+) buffering and action potential (AP)-evoked Ca(2+) signaling in the dendrites of anatomically identified oriens lacunosum-moleculare (O-LM) cells, a major type of dendrite-targeting interneurons in the hippocampal CA1 region, using a combination of whole-cell patch-clamp recording and fast Ca(2+) imaging in acute rat brain slices. Cells were loaded with fluorescent Ca(2+) indicators fura-2 or Oregon Green BAPTA-1 (OGB-1) via patch-clamping electrode, and the effect of fura-2 on AP-evoked dendritic Ca(2+) transients was determined by ratiometric Ca(2+) imaging. To estimate intracellular Ca(2+) concentrations ([Ca(2+)](i)) and endogenous Ca(2+)-binding ratio (kappa(s)) in the proximal dendrite, fluorescence signals were converted into [Ca(2+)](i) using the ratioing method and were analyzed on the basis of the "single compartment model." Resting [Ca(2+)](i) was 22+/-5 nM and the build-up of [Ca(2+)](i) during a single AP was up to 656+/-226 nM. Analysis of Ca(2+) transients revealed that O-LM cells have a relatively low endogenous Ca(2+)-binding ratio (kappa(s)): the kappa(s) was 20+/-8 estimated during fura-2 loading and 27 estimated under steady-state fura-2 concentrations, respectively. To further examine the spatial profile of dendritic Ca(2+) transients, we measured somatic AP-evoked Ca(2+) transients beyond proximal dendrites using OGB-1. Dendritic Ca(2+) transients evoked by single APs or AP trains are not limited to regions close to the soma. The amplitude and decay of [Ca(2+)](i) associated with backpropagating APs are relatively independent of the distance from the soma. In sum, O-LM cells exhibit low endogenous Ca(2+)-binding ratios and relatively distance-independent Ca(2+) dynamics in the dendrites. These

  16. Detecting Danger: The Dendritic Cell Algorithm

    CERN Document Server

    Greensmith, Julie; Cayzer, Steve

    2010-01-01

    The Dendritic Cell Algorithm (DCA) is inspired by the function of the dendritic cells of the human immune system. In nature, dendritic cells are the intrusion detection agents of the human body, policing the tissue and organs for potential invaders in the form of pathogens. In this research, and abstract model of DC behaviour is developed and subsequently used to form an algorithm, the DCA. The abstraction process was facilitated through close collaboration with laboratory- based immunologists, who performed bespoke experiments, the results of which are used as an integral part of this algorithm. The DCA is a population based algorithm, with each agent in the system represented as an 'artificial DC'. Each DC has the ability to combine multiple data streams and can add context to data suspected as anomalous. In this chapter the abstraction process and details of the resultant algorithm are given. The algorithm is applied to numerous intrusion detection problems in computer security including the detection of p...

  17. Single dendrite-targeting interneurons generate branch-specific inhibition.

    Directory of Open Access Journals (Sweden)

    Caleb eStokes

    2014-11-01

    Full Text Available Microcircuits composed of dendrite-targeting inhibitory interneurons and pyramidal cells are fundamental elements of cortical networks, however, the impact of individual interneurons on pyramidal dendrites is unclear. Here, we combine paired recordings and calcium imaging to determine the spatial domain over which single dendrite-targeting interneurons influence pyramidal cells in olfactory cortex. We show that a major action of individual interneurons is to inhibit dendrites in a branch-specific fashion.

  18. Semiautomated analysis of dendrite morphology in cell culture.

    Science.gov (United States)

    Sweet, Eric S; Langhammer, Chris L; Kutzing, Melinda K; Firestein, Bonnie L

    2013-01-01

    Quantifying dendrite morphology is a method for determining the effect of biochemical pathways and extracellular agents on neuronal development and differentiation. Quantification can be performed using Sholl analysis, dendrite counting, and length quantification. These procedures can be performed on dendrite-forming cell lines or primary neurons grown in culture. In this protocol, we describe the use of a set of computer programs to assist in quantifying many aspects of dendrite morphology, including changes in total and localized arbor complexity.

  19. Role of active dendritic conductances in subthreshold input integration

    OpenAIRE

    Rinzel John; Remme Michiel

    2010-01-01

    Dendrites of many types of neurons contain voltage-dependent conductances that are active at subthreshold membrane potentials. To understand the computations neurons perform it is key to understand the role of active dendrites in the subthreshold processing of synaptic inputs. We examine systematically how active dendritic conductances affect the time course of postsynaptic potentials propagating along dendrites, and how they affect the interaction between such signals. Voltage-dependent curr...

  20. Infection of Dendritic Cells by the Maedi-Visna Lentivirus

    OpenAIRE

    Ryan, Susanna; Tiley, Laurence; McConnell, Ian; Blacklaws, Barbara

    2000-01-01

    The early stages of lentivirus infection of dendritic cells have been studied in an in vivo model. Maedi-visna virus (MVV) is a natural pathogen of sheep with a tropism for macrophages, but the infection of dendritic cells has not been proven, largely because of the difficulties of definitively distinguishing the two cell types. Afferent lymphatic dendritic cells from sheep have been phenotypically characterized and separated from macrophages. Dendritic cells purified from experimentally infe...

  1. Actin remodeling and polymerization forces control dendritic spine morphology

    OpenAIRE

    2015-01-01

    Dendritic spines are small membranous structures that protrude from the neuronal dendrite. Each spine contains a synaptic contact site that may connect its parent dendrite to the axons of neighboring neurons. Dendritic spines are markedly distinct in shape and size, and certain types of stimulation prompt spines to evolve, in fairly predictable fashion, from thin nascent morphologies to the mushroom-like shapes associated with mature spines. This striking progression is coincident with the (r...

  2. Dendritic Cells Stimulated by Cationic Liposomes.

    Science.gov (United States)

    Vitor, Micaela Tamara; Bergami-Santos, Patrícia Cruz; Cruz, Karen Steponavicius Piedade; Pinho, Mariana Pereira; Barbuto, José Alexandre Marzagão; De La Torre, Lucimara Gaziola

    2016-01-01

    Immunotherapy of cancer aims to harness the immune system to detect and destroy cancer cells. To induce an immune response against cancer, activated dendritic cells (DCs) must present tumor antigens to T lymphocytes of patients. However, cancer patients' DCs are frequently defective, therefore, they are prone to induce rather tolerance than immune responses. In this context, loading tumor antigens into DCs and, at the same time, activating these cells, is a tempting goal within the field. Thus, we investigated the effects of cationic liposomes on the DCs differentiation/maturation, evaluating their surface phenotype and ability to stimulate T lymphocytes proliferation in vitro. The cationic liposomes composed by egg phosphatidylcholine, 1,2-dioleoyl-3-trimethylammonium propane and 1,2-dioleoylphosphatidylethanolamine (50/25/25% molar) were prepared by the thin film method followed by extrusion (65 nm, polydispersity of 0.13) and by the dehydration-rehydration method (95% of the population 107 nm, polydispersity of 0.52). The phenotypic analysis of dendritic cells and the analysis of T lymphocyte proliferation were performed by flow cytometry and showed that both cationic liposomes were incorporated and activated dendritic cells. Extruded liposomes were better incorporated and induced higher CD86 expression for dendritic cells than dehydrated-rehydrated vesicles. Furthermore, dendritic cells which internalized extruded liposomes also provided stronger T lymphocyte stimulation. Thus, cationic liposomes with a smaller size and polydispersity seem to be better incorporated by dendritic cells. Hence, these cationic liposomes could be used as a potential tool in further cancer immunotherapy strategies and contribute to new strategies in immunotherapy.

  3. Sequence learning in differentially activated dendrites

    DEFF Research Database (Denmark)

    Nielsen, Bjørn Gilbert

    2003-01-01

    . It is proposed that the neural machinery required in such a learning/retrieval mechanism could involve the NMDA receptor, in conjunction with the ability of dendrites to maintain differentially activated regions. In particular, it is suggested that such a parcellation of the dendrite allows the neuron...... to participate in multiple sequences, which can be learned without suffering from the 'wash-out' of synaptic efficacy associated with superimposition of training patterns. This is a biologically plausible solution to the stability-plasticity dilemma of learning in neural networks....

  4. Seaweed to dendrite transition in directional solidification.

    Science.gov (United States)

    Provatas, Nikolas; Wang, Quanyong; Haataja, Mikko; Grant, Martin

    2003-10-10

    We simulate directional solidification using a phase-field model solved with adaptive mesh refinement. For small surface tension anisotropy directed at 45 degrees relative to the pulling direction we observe a crossover from a seaweed to a dendritic morphology as the thermal gradient is lowered, consistent with recent experimental findings. We show that the morphology of crystal structures can be unambiguously characterized through the local interface velocity distribution. We derive semiempirically an estimate for the crossover from seaweed to dendrite as a function of thermal gradient and pulling speed.

  5. Dendritic Cells Endocytose Bacillus Anthracis Spores: Implications for Anthrax Pathogenesis

    Science.gov (United States)

    2007-11-02

    Dendritic Cells Endocytose Bacillus anthracis Spores: Implications for Anthrax Pathogenesis1 Katherine C. Brittingham,* Gordon Ruthel,* Rekha G...germination and dissemination of spores. Found in high frequency throughout the respiratory track, dendritic cells (DCs) routinely take up foreign...COVERED - 4. TITLE AND SUBTITLE Dendritic cells endocytose Bacillus anthracis spores: implications for anthrax pathogenesis, The Journal of

  6. IT-24DEVELOPMENT OF A NOVEL AUTOLOGOUS DENDRITIC CELL / ALLOGENEIC GLIOBLASTOMA LYSATE VACCINE PROTOCOL

    OpenAIRE

    Parney, Ian; Peterson, Timothy; Gustafson, Michael; Dietz, Allan

    2014-01-01

    BACKGROUND: Dendritic cell (DC) vaccines for glioblastoma (GBM) are promising but significant conceptual shortcomings may have limited their clinical efficacy. First, most trials have not employed optimal DC culture techniques resulting in large numbers of immature (immunosuppressive) DC's. Second, most have used autologous tumor lysate. While highly personalized, this limits vaccine availability and precludes antigen-specific response testing. Finally, GBM-mediated immunosuppression has been...

  7. Interactions with Astroglia Influence the Shape of the Developing Dendritic Arbor and Restrict Dendrite Growth Independent of Promoting Synaptic Contacts

    Science.gov (United States)

    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

  8. Active dendrites support efficient initiation of dendritic spikes in hippocampal CA3 pyramidal neurons

    OpenAIRE

    Kim, Sooyun; Guzman, Segundo J.; Hu, Hua; Jonas, Peter

    2012-01-01

    CA3 pyramidal neurons are important for memory formation and pattern completion in the hippocampal network. It is generally thought that proximal synapses from the mossy fibers activate these neurons most efficiently, whereas distal inputs from the perforant path have a weaker modulatory influence. We used confocally targeted patch-clamp recording from dendrites and axons to map the activation of rat CA3 pyramidal neurons at the subcellular level. Our results reveal two distinct dendritic dom...

  9. Ebola virus infection induces irregular dendritic cell gene expression.

    Science.gov (United States)

    Melanson, Vanessa R; Kalina, Warren V; Williams, Priscilla

    2015-02-01

    Filoviruses subvert the human immune system in part by infecting and replicating in dendritic cells (DCs). Using gene arrays, a phenotypic profile of filovirus infection in human monocyte-derived DCs was assessed. Monocytes from human donors were cultured in GM-CSF and IL-4 and were infected with Ebola virus Kikwit variant for up to 48 h. Extracted DC RNA was analyzed on SuperArray's Dendritic and Antigen Presenting Cell Oligo GEArray and compared to uninfected controls. Infected DCs exhibited increased expression of cytokine, chemokine, antiviral, and anti-apoptotic genes not seen in uninfected controls. Significant increases of intracellular antiviral and MHC I and II genes were also noted in EBOV-infected DCs. However, infected DCs failed to show any significant difference in co-stimulatory T-cell gene expression from uninfected DCs. Moreover, several chemokine genes were activated, but there was sparse expression of chemokine receptors that enabled activated DCs to home to lymph nodes. Overall, statistically significant expression of several intracellular antiviral genes was noted, which may limit viral load but fails to stop replication. EBOV gene expression profiling is of vital importance in understanding pathogenesis and devising novel therapeutic treatments such as small-molecule inhibitors.

  10. Numerical Simulations of Equiaxed Dendrite Growth Using Phase Field Method

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Phase field method offers the prospect of being able to perform realistic numerical experiments on dendrite growthin a metallic system. In this paper, the equiaxed dendrite evolution during the solidification of a pure material wasnumerically simulated using the phase field model. The equiaxed dendrite growth in a two-dimensional square domainof undercooled melt (nickel) with four-fold anisotropy was simulated. The phase field model equations was solvedusing the explicit finite difference method on a uniform mesh. The formation of various equiaxed dendrite patternswas shown by a series of simulations, and the effect of anisotropy on equiaxed dendrite morphology was investigated.

  11. The role of dendritic cells in cancer

    DEFF Research Database (Denmark)

    Hansen, Morten; Andersen, Mads Hald

    2017-01-01

    Though present in low numbers, dendritic cells (DCs) are recognized as major players in the control of cancer by adaptive immunity. The roles of cytotoxic CD8+ T-cells and Th1 helper CD4+ T-cells are well-documented in murine models of cancer and associated with a profound prognostic impact when...... treatment regimens against cancer....

  12. Characterization of chicken dendritic cell markers

    Science.gov (United States)

    Animal and Natural Resources Institute, ARS-USDA, Beltsville, MD, USA. New mouse monoclonal antibodies which detect CD80 and CD83 were developed to characterize chicken dendritic cells (DCs). The characteristics of these molecules have been studied in human, swine, ovine, feline, and canine but not ...

  13. ISOLATION OF CHICKEN FOLLICULAR DENDRITIC CELLS

    Science.gov (United States)

    The aim of the present study was to isolate chicken follicular dendritic cells (FDC). A combination of methods involving panning, iodixanol density gradient centrifugation, and magnetic cell separation technology made it possible to obtain functional FDC from the cecal tonsils from chickens, which h...

  14. Dendritic cells in peripheral tolerance and immunity

    DEFF Research Database (Denmark)

    Gad, Monika; Claesson, Mogens Helweg; Pedersen, Anders Elm

    2003-01-01

    Dendritic cells capable of influencing immunity exist as functionally distinct subsets, T cell-tolerizing and T cell-immunizing subsets. The present paper reviews how these subsets of DCs develop, differentiate and function in vivo and in vitro at the cellular and molecular level. In particular...

  15. Dendritic mitochondria reach stable positions during circuit development.

    Science.gov (United States)

    Faits, Michelle C; Zhang, Chunmeng; Soto, Florentina; Kerschensteiner, Daniel

    2016-01-07

    Mitochondria move throughout neuronal dendrites and localize to sites of energy demand. The prevailing view of dendritic mitochondria as highly motile organelles whose distribution is continually adjusted by neuronal activity via Ca(2+)-dependent arrests is based on observations in cultured neurons exposed to artificial stimuli. Here, we analyze the movements of mitochondria in ganglion cell dendrites in the intact retina. We find that whereas during development 30% of mitochondria are motile at any time, as dendrites mature, mitochondria all but stop moving and localize stably to synapses and branch points. Neither spontaneous nor sensory-evoked activity and Ca(2+) transients alter motility of dendritic mitochondria; and pathological hyperactivity in a mouse model of retinal degeneration elevates rather than reduces motility. Thus, our findings indicate that dendritic mitochondria reach stable positions during a critical developmental period of high motility, and challenge current views about the role of activity in regulating mitochondrial transport in dendrites.

  16. Inositol hexakisphosphate (IP6) generated by IP5K mediates cullin-COP9 signalosome interactions and CRL function

    National Research Council Canada - National Science Library

    Paul C. Scherer; Yan Ding; Zhiqing Liu; Jing Xu; Haibin Mao; James C. Barrow; Ning Wei; Ning Zheng; Solomon H. Snyder; Feng Rao

    2016-01-01

    .... We now report that inositol hexakisphosphate (IP6) is a major physiologic determinant of the CRL-CSN interface, which includes a hitherto unidentified electrostatic interaction between the N-terminal acidic tail of CSN subunit 2 (CSN2...

  17. Differentiation of apical and basal dendrites in pyramidal cells and granule cells in dissociated hippocampal cultures.

    Science.gov (United States)

    Wu, You Kure; Fujishima, Kazuto; Kengaku, Mineko

    2015-01-01

    Hippocampal pyramidal cells and dentate granule cells develop morphologically distinct dendritic arbors, yet also share some common features. Both cell types form a long apical dendrite which extends from the apex of the cell soma, while short basal dendrites are developed only in pyramidal cells. Using quantitative morphometric analyses of mouse hippocampal cultures, we evaluated the differences in dendritic arborization patterns between pyramidal and granule cells. Furthermore, we observed and described the final apical dendrite determination during dendritic polarization by time-lapse imaging. Pyramidal and granule cells in culture exhibited similar dendritic patterns with a single principal dendrite and several minor dendrites so that the cell types were not readily distinguished by appearance. While basal dendrites in granule cells are normally degraded by adulthood in vivo, cultured granule cells retained their minor dendrites. Asymmetric growth of a single principal dendrite harboring the Golgi was observed in both cell types soon after the onset of dendritic growth. Time-lapse imaging revealed that up until the second week in culture, final principal dendrite designation was not stabilized, but was frequently replaced by other minor dendrites. Before dendritic polarity was stabilized, the Golgi moved dynamically within the soma and was repeatedly repositioned at newly emerging principal dendrites. Our results suggest that polarized growth of the apical dendrite is regulated by cell intrinsic programs, while regression of basal dendrites requires cue(s) from the extracellular environment in the dentate gyrus. The apical dendrite designation is determined from among multiple growing dendrites of young developing neurons.

  18. Asymmetry in signal propagation between the soma and dendrites plays a key role in determining dendritic excitability in motoneurons.

    Science.gov (United States)

    Kim, Hojeong; Jones, Kelvin E; Heckman, C J

    2014-01-01

    It is widely recognized that propagation of electrophysiological signals between the soma and dendrites of neurons differs depending on direction, i.e. it is asymmetric. How this asymmetry influences the activation of voltage-gated dendritic channels, and consequent neuronal behavior, remains unclear. Based on the analysis of asymmetry in several types of motoneurons, we extended our previous methodology for reducing a fully reconstructed motoneuron model to a two-compartment representation that preserved asymmetric signal propagation. The reduced models accurately replicated the dendritic excitability and the dynamics of the anatomical model involving a persistent inward current (PIC) dispersed over the dendrites. The relationship between asymmetric signal propagation and dendritic excitability was investigated using the reduced models while varying the asymmetry in signal propagation between the soma and the dendrite with PIC density constant. We found that increases in signal attenuation from soma to dendrites increased the activation threshold of a PIC (hypo-excitability), whereas increases in signal attenuation from dendrites to soma decreased the activation threshold of a PIC (hyper-excitability). These effects were so strong that reversing the asymmetry in the soma-to-dendrite vs. dendrite-to-soma attenuation, reversed the correlation between PIC threshold and distance of this current source from the soma. We propose the tight relation of the asymmetric signal propagation to the input resistance in the dendrites as a mechanism underlying the influence of the asymmetric signal propagation on the dendritic excitability. All these results emphasize the importance of maintaining the physiological asymmetry in dendritic signaling not only for normal function of the cells but also for biophysically realistic simulations of dendritic excitability.

  19. Stochastic ion channel gating in dendritic neurons: morphology dependence and probabilistic synaptic activation of dendritic spikes.

    Directory of Open Access Journals (Sweden)

    Robert C Cannon

    Full Text Available Neuronal activity is mediated through changes in the probability of stochastic transitions between open and closed states of ion channels. While differences in morphology define neuronal cell types and may underlie neurological disorders, very little is known about influences of stochastic ion channel gating in neurons with complex morphology. We introduce and validate new computational tools that enable efficient generation and simulation of models containing stochastic ion channels distributed across dendritic and axonal membranes. Comparison of five morphologically distinct neuronal cell types reveals that when all simulated neurons contain identical densities of stochastic ion channels, the amplitude of stochastic membrane potential fluctuations differs between cell types and depends on sub-cellular location. For typical neurons, the amplitude of membrane potential fluctuations depends on channel kinetics as well as open probability. Using a detailed model of a hippocampal CA1 pyramidal neuron, we show that when intrinsic ion channels gate stochastically, the probability of initiation of dendritic or somatic spikes by dendritic synaptic input varies continuously between zero and one, whereas when ion channels gate deterministically, the probability is either zero or one. At physiological firing rates, stochastic gating of dendritic ion channels almost completely accounts for probabilistic somatic and dendritic spikes generated by the fully stochastic model. These results suggest that the consequences of stochastic ion channel gating differ globally between neuronal cell-types and locally between neuronal compartments. Whereas dendritic neurons are often assumed to behave deterministically, our simulations suggest that a direct consequence of stochastic gating of intrinsic ion channels is that spike output may instead be a probabilistic function of patterns of synaptic input to dendrites.

  20. REMOD: A Tool for Analyzing and Remodeling the Dendritic Architecture of Neural Cells.

    Science.gov (United States)

    Bozelos, Panagiotis; Stefanou, Stefanos S; Bouloukakis, Georgios; Melachrinos, Constantinos; Poirazi, Panayiota

    2015-01-01

    Dendritic morphology is a key determinant of how individual neurons acquire a unique signal processing profile. The highly branched dendritic structure that originates from the cell body, explores the surrounding 3D space in a fractal-like manner, until it reaches a certain amount of complexity. Its shape undergoes significant alterations under various physiological or neuropathological conditions. Yet, despite the profound effect that these alterations can have on neuronal function, the causal relationship between the two remains largely elusive. The lack of a systematic approach for remodeling neural cells and their dendritic trees is a key limitation that contributes to this problem. Such causal relationships can be inferred via the use of large-scale neuronal models whereby the anatomical plasticity of neurons is accounted for, in order to enhance their biological relevance and hence their predictive performance. To facilitate this effort, we developed a computational tool named REMOD that allows the structural remodeling of any type of virtual neuron. REMOD is written in Python and can be accessed through a dedicated web interface that guides the user through various options to manipulate selected neuronal morphologies. REMOD can also be used to extract meaningful morphology statistics for one or multiple reconstructions, including features such as sholl analysis, total dendritic length and area, path length to the soma, centrifugal branch order, diameter tapering and more. As such, the tool can be used both for the analysis and/or the remodeling of neuronal morphologies of any type.

  1. Dendritic Ni(Cu)-polypyrrole hybrid films for a pseudo-capacitor

    Science.gov (United States)

    Choi, Bit Na; Chun, Woo Won; Qian, Aniu; Lee, So Jeong; Chung, Chan-Hwa

    2015-11-01

    Dendritic Ni(Cu)-polypyrrole hybrid films are fabricated for a pseudo-capacitor in a unique morphology using two simple methods: electro-deposition and electrochemical de-alloying. Three-dimensional structures of porous dendrites are prepared by electro-deposition within the hydrogen evolution reaction (HER) at a high cathodic potential; the high-surface-area structure provides sufficient redox reactions between the electrodes and the electrolyte. The dependence of the active-layer thickness on the super-capacitor performance is also investigated, and the 60 μm-thick Ni(Cu)PPy hybrid electrode presents the highest performance of 659.52 F g-1 at the scan rate of 5 mV s-1. In the thicker layers, the specific capacitance became smaller due to the diffusion limitation of the ions in an electrolyte. The polypyrrole-hybridization on the porous dendritic Ni(Cu) electrode provides superior specific capacitance and excellent cycling stability due to the improvement in electric conductivity by the addition of conducting polypyrrole in the matrices of the dendritic nano-porous Ni(Cu) layer and the synergistic effect of composite materials.

  2. REMOD: a tool for analyzing and remodeling the dendritic architecture of neural cells

    Directory of Open Access Journals (Sweden)

    Panagiotis eBozelos

    2016-01-01

    Full Text Available Dendritic morphology is a key determinant of how individual neurons acquire a unique signal processing profile. The highly branched dendritic structure that originates from the cell body, explores the surrounding 3D space in a fractal-like manner, until it reaches a certain amount of complexity. Its shape undergoes significant alterations under various physiological or neuropathological conditions. Yet, despite the profound effect that these alterations can have on neuronal function, the causal relationship between the two remains largely elusive. The lack of a systematic approach for remodeling neural cells and their dendritic trees is a key limitation that contributes to this problem. Such causal relationships can be inferred via the use of large-scale neuronal models whereby the anatomical plasticity of neurons is accounted for, in order to enhance their biological relevance and hence their predictive performance. To facilitate this effort, we developed a computational tool named REMOD that allows the structural remodeling of any type of virtual neuron. REMOD is written in Python and can be accessed through a dedicated web interface that guides the user through various options to manipulate selected neuronal morphologies. REMOD can also be used to extract meaningful morphology statistics for one or multiple reconstructions, including features such as sholl analysis, total dendritic length and area, path length to the soma, centrifugal branch order, diameter tapering and more. As such, the tool can be used both for the analysis and/or the remodeling of neuronal morphologies of any type.

  3. Improvement of human dendritic cell culture for immunotoxicological investigations.

    Science.gov (United States)

    Hymery, N; Sibiril, Y; Parent-Massin, D

    2006-07-01

    A toxic injury such as a decrease in the number of immature dendritic cells caused by a cytotoxic effect or a disturbance in their maturation process can be responsible for immunodepression. There is a need to improve in vitro assays on human dendritic cells used to detect and evaluate adverse effects of xenobiotics. Two aspects were explored in this work: cytotoxic effects of xenobiotics on immature dendritic cells, and the interference of xenobiotics with dendritic cell maturation. Dendritic cells of two different origins were tested. Dendritic cells obtained either from umbilical cord blood CD34(+) cells or, for the first time, from umbilical cord blood monocytes. The cytotoxicity assay on immature dendritic cells has been improved. For the study of the potential adverse effects of xenobiotics on the maturation process of dendritic cells, several parameters were selected such as expression of markers (CD86, CD83, HLA-DR), secretion of interleukins 10 and 12, and proliferation of autologous lymphocytes. The relevance and the efficiency of the protocol applied were tested using two mycotoxins, T-2 toxin and deoxynivalence, DON, which are known to be immunosuppressive, and one phycotoxin, domoic acid, which is known not to have any immunotoxic effect. Assays using umbilical cord monocyte dendritic cell cultures with the protocol defined in this work, which involves a cytotoxicity study followed by evaluation of several markers of adverse effects on the dendritic cell maturation process, revealed their usefulness for investigating xenobiotic immunotoxicity toward immune primary reactions.

  4. Remodeling of monoplanar Purkinje cell dendrites during cerebellar circuit formation.

    Directory of Open Access Journals (Sweden)

    Megumi Kaneko

    Full Text Available Dendrite arborization patterns are critical determinants of neuronal connectivity and integration. Planar and highly branched dendrites of the cerebellar Purkinje cell receive specific topographical projections from two major afferent pathways; a single climbing fiber axon from the inferior olive that extend along Purkinje dendrites, and parallel fiber axons of granule cells that contact vertically to the plane of dendrites. It has been believed that murine Purkinje cell dendrites extend in a single parasagittal plane in the molecular layer after the cell polarity is determined during the early postnatal development. By three-dimensional confocal analysis of growing Purkinje cells, we observed that mouse Purkinje cells underwent dynamic dendritic remodeling during circuit maturation in the third postnatal week. After dendrites were polarized and flattened in the early second postnatal week, dendritic arbors gradually expanded in multiple sagittal planes in the molecular layer by intensive growth and branching by the third postnatal week. Dendrites then became confined to a single plane in the fourth postnatal week. Multiplanar Purkinje cells in the third week were often associated by ectopic climbing fibers innervating nearby Purkinje cells in distinct sagittal planes. The mature monoplanar arborization was disrupted in mutant mice with abnormal Purkinje cell connectivity and motor discoordination. The dendrite remodeling was also impaired by pharmacological disruption of normal afferent activity during the second or third postnatal week. Our results suggest that the monoplanar arborization of Purkinje cells is coupled with functional development of the cerebellar circuitry.

  5. Dendritic cell maturation and cross-presentation: timing matters!

    Science.gov (United States)

    Alloatti, Andrés; Kotsias, Fiorella; Magalhaes, Joao Gamelas; Amigorena, Sebastian

    2016-07-01

    As a population, dendritic cells (DCs) appear to be the best cross-presenters of internalized antigens on major histocompatibility complex class I molecules in the mouse. To do this, DCs have developed a number of unique and dedicated means to control their endocytic and phagocytic pathways: among them, the capacity to limit acidification of their phagosomes, to prevent proteolytic degradation, to delay fusion of phagosomes to lysosomes, to recruit ER proteins to phagosomes, and to export phagocytosed antigens to the cytosol. The regulation of phagocytic functions, and thereby of antigen processing and presentation by innate signaling, represents a critical level of integration of adaptive and innate immune responses. Understanding how innate signals control antigen cross-presentation is critical to define effective vaccination strategies for CD8(+) T-cell responses.

  6. Sleeping dendrites: fiber-optic measurements of dendritic calcium activity in freely moving and sleeping animals

    Directory of Open Access Journals (Sweden)

    Julie Seibt

    2014-03-01

    Full Text Available Dendrites are the post-synaptic sites of most excitatory and inhibitory synapses in the brain, making them the main location of cortical information processing and synaptic plasticity. Although current hypotheses suggest a central role for sleep in proper cognitive function and brain plasticity, virtually nothing is known about changes in dendritic activity across the sleep-wake cycle and how waking experience modifies this activity. To start addressing these questions, we developed a method that allows long-term recordings of EEGs/EMG combined with in vivo cortical calcium (Ca2+ activity in freely moving and sleeping rats. We measured Ca2+ activity from populations of dendrites of layer (L 5 pyramidal neurons (n = 13 rats that we compared with Ca2+ activity from populations of neurons in L2/3 (n = 11 rats. L5 and L2/3 neurons were labelled using bolus injection of OGB1-AM or GCaMP6 (1. Ca2+ signals were detected using a fiber-optic system (cannula diameter = 400µm, transmitting the changes in fluorescence to a photodiode. Ca2+ fluctuations could then be correlated with ongoing changes in brain oscillatory activity during 5 major brain states: active wake [AW], quiet wake [QW], NREM, REM and NREM-REM transition (or intermediate state, [IS]. Our Ca2+ recordings show large transients in L5 dendrites and L2/3 neurons that oscillate predominantly at frequencies In summary, we show that this technique is successful in monitoring fluctuations in ongoing dendritic Ca2+ activity during natural brain states and allows, in principle, to combine behavioral measurement with imaging from various brain regions (e.g. deep structures in freely behaving animals. Using this method, we show that Ca2+ transients from populations of L2/3 neurons and L5 dendrites are deferentially regulated across the sleep/wake cycle, with dendritic activity being the highest during the IS sleep. Our correlation analysis suggests that specific sleep EEG activity during NREM and IS

  7. Generation, description and storage of dendritic morphology data.

    Science.gov (United States)

    Ascoli, G A; Krichmar, J L; Nasuto, S J; Senft, S L

    2001-08-29

    from an experimental database and generate virtual neurons whose anatomy is statistically indistinguishable from that of their real counterparts, a great deal of data compression and amplification can be achieved. Data compression results from the quantitative and complete description of thousands of neurons with a handful of statistical distributions of parameters. Data amplification is possible because, from a set of experimental neurons, many more virtual analogues can be generated. This approach could allow one, in principle, to create and store a neuroanatomical database containing data for an entire human brain in a personal computer. We are using two programs, L-NEURON and ARBORVITAE, to investigate systematically the potential of several different algorithms for the generation of virtual neurons. Using these programs, we have generated anatomically plausible virtual neurons for several morphological classes, including guinea pig cerebellar Purkinje cells and cat spinal cord motor neurons. These virtual neurons are stored in an online electronic archive of dendritic morphology. This process highlights the potential and the limitations of the 'computational neuroanatomy' strategy for neuroscience databases.

  8. Macrophages, Dendritic Cells, and Regression of Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Jonathan E. Feig

    2012-07-01

    Full Text Available Atherosclerosis is the number one cause of death in the Western world. It results from the interaction between modified lipoproteins and monocyte-derived cells such as macrophages, dendritic cells, T cells, and other cellular elements of the arterial wall. This inflammatory process can ultimately lead to the development of complex lesions, or plaques, that protrude into the arterial lumen. Ultimately, plaque rupture and thrombosis can occur leading to the clinical complications of myocardial infarction or stroke. Although each of the cell types plays roles in the pathogenesis of atherosclerosis, in this review, the focus will be primarily on the monocyte derived cells- macrophages and dendritic cells. The roles of these cell types in atherogenesis will be highlighted. Finally, the mechanisms of atherosclerosis regression as it relates to these cells will be discussed.

  9. Dendritic nanocomposite for delivery of antibacterial agent

    Institute of Scientific and Technical Information of China (English)

    Pureti Madhu Kumar; PSrinivasa Babu; Shaik Rasheed; Ramadoss Karthikeyan

    2013-01-01

    Objective: To develop and explore the use of PEGylated poly (propylene imine) dendritic architecture for the delivery of an anti bacterial bioactive, Trimethoprim. Methods: For this study, PEGylated poly(propylene imine) dendritic architecture was synthesized and loaded with Trimethoprim and targeted to the resistant producing strains of both gram positive and gram negative. The antibacterial activity was carried out by agar well-diffusion method to compare zone of inhibition with standard drug and plain PPI dendrimer. Results: The study showed that the Trimethoprim loaded dendrimer has significant antibacterial activity than the plain PPI dendrimer, but standard drug was not shown zone of inhibition upon both microorganisms butKlebsiella pneumoniae (K. pneumoniae) the pure drug showed activity. Conclusions: In this study antibacterial activity of synthesized system is also relatively safer and holds potential to deliver any other antibacterial agent to the resistant producing strains.

  10. Sensitivity of Dendritic Cells to Microenvironment Signals

    Science.gov (United States)

    Motta, Juliana Maria; Rumjanek, Vivian Mary

    2016-01-01

    Dendritic cells are antigen-presenting cells capable of either activating the immune response or inducing and maintaining immune tolerance. They do this by integrating stimuli from the environment and changing their functional status as a result of plasticity. The modifications suffered by these cells have consequences in the way the organism may respond. In the present work two opposing situations known to affect dendritic cells are analyzed: tumor growth, leading to a microenvironment that favors the induction of a tolerogenic profile, and organ transplantation, which leads to a proinflammatory profile. Lessons learned from these situations may help to understand the mechanisms of modulation resulting not only from the above circumstances, but also from other pathologies. PMID:27088097

  11. Sensitivity of Dendritic Cells to Microenvironment Signals

    Directory of Open Access Journals (Sweden)

    Juliana Maria Motta

    2016-01-01

    Full Text Available Dendritic cells are antigen-presenting cells capable of either activating the immune response or inducing and maintaining immune tolerance. They do this by integrating stimuli from the environment and changing their functional status as a result of plasticity. The modifications suffered by these cells have consequences in the way the organism may respond. In the present work two opposing situations known to affect dendritic cells are analyzed: tumor growth, leading to a microenvironment that favors the induction of a tolerogenic profile, and organ transplantation, which leads to a proinflammatory profile. Lessons learned from these situations may help to understand the mechanisms of modulation resulting not only from the above circumstances, but also from other pathologies.

  12. Dendritic Cells for SYN Scan Detection

    CERN Document Server

    Greensmith, Julie

    2010-01-01

    Artificial immune systems have previously been applied to the problem of intrusion detection. The aim of this research is to develop an intrusion detection system based on the function of Dendritic Cells (DCs). DCs are antigen presenting cells and key to activation of the human immune system, behaviour which has been abstracted to form the Dendritic Cell Algorithm (DCA). In algorithmic terms, individual DCs perform multi-sensor data fusion, asynchronously correlating the the fused data signals with a secondary data stream. Aggregate output of a population of cells, is analysed and forms the basis of an anomaly detection system. In this paper the DCA is applied to the detection of outgoing port scans using TCP SYN packets. Results show that detection can be achieved with the DCA, yet some false positives can be encountered when simultaneously scanning and using other network services. Suggestions are made for using adaptive signals to alleviate this uncovered problem.

  13. Divergent Effects of Dendritic Cells on Pancreatitis

    Science.gov (United States)

    2015-09-01

    cells, Gr1+ inflammatory monocytes and neutrophils, or TNF production were induced to develop chronic pancreatitis in the context of DC overexpansion...Z. Yao, W. Cao, and Y.J. Liu. 2005. TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand. J. Exp...Public reporting burden for this collection of information is estimated to average 1 hour per response , including the time for reviewing instructions

  14. Signaling in dendritic spines and spine microdomains

    OpenAIRE

    2012-01-01

    The specialized morphology of dendritic spines creates an isolated compartment that allows for localized biochemical signaling. Recent studies have revealed complexity in the function of the spine head as a signaling domain and indicate that (1) the spine is functionally subdivided into multiple independent microdomains and (2) not all biochemical signals are equally compartmentalized within the spine. Here we review these findings as well as the developments in fluorescence microscopy that a...

  15. Dendrite fragmentation by catastrophic elastic remelting

    OpenAIRE

    Ananiev, S.; Nikrityuk, P.; Eckert, K.

    2008-01-01

    The paper proposes a new fragmentation mechanism of dendrite arms. The theoretical basis of this mechanism is a shift in the thermodynamical equilibrium at the solid-liquid interface due to the presence of elastic energy. This effect is modelled by the generalized Gibbs-Thomson condition [1], where each term is calculated analytically using a simple Bernoulli-Euler beam model. The resulting nonlinear system of ordinary differential equations is integrated in time using a fully implicit scheme...

  16. Role of Dendritic Cells in Immune Dysfunction

    Science.gov (United States)

    Savary, Cherylyn A.

    1997-01-01

    Specific aims include: (1) Application of the bioreactor to enhance cytokine-regulated proliferation and maturation of dendritic cells (DC); (2) Based on clues from spaceflight: compare the frequency and function of DC in normal donors and immunocompromised cancer patients; and (3) Initiate studies on the efficiency of cytokine therapy and DC-assisted immunotherapy (using bioreactor-expanded DC) in animal models of experimental fungal infections.

  17. Novel murine dendritic cell lines: a powerful auxiliary tool for dendritic cell research

    Directory of Open Access Journals (Sweden)

    Silvia A Fuertes Marraco

    2012-11-01

    Full Text Available Research in vitro facilitates discovery, screening and pilot experiments, often preceding research in vivo. Several technical difficulties render Dendritic Cell (DC research particularly challenging, including the low frequency of DC in vivo, thorough isolation requirements, and the vulnerability of DC ex vivo. Critically, there is not as yet a widely accepted human or murine DC line and in vitro systems of DC research are limited. In this study, we report the generation of new murine DC lines, named MutuDC, originating from cultures of splenic CD8α conventional DC (cDC tumors. By direct comparison to normal WT splenic cDC subsets, we describe the phenotypic and functional features of the MutuDC lines and show that they have retained all the major features of their natural counterpart in vivo, the splenic CD8α cDC. These features include expression of surface markers Clec9A, DEC205, and CD24, positive response to TLR3 and TLR9 but not TLR7 stimuli, secretion of cytokines and chemokines upon activation, as well as cross-presentation capacity. In addition to the close resemblance to normal splenic CD8α cDC, a major advantage is the ease of derivation and maintenance of the MutuDC lines, using standard culture medium and conditions, importantly without adding supplementary growth factors or maturation-inducing stimuli to the medium. Furthermore, genetically modified MutuDC lines have been successfully obtained either by lentiviral transduction or by culture of DC tumors originating from genetically modified mice.In view of the current lack of stable and functional DC lines, these novel murine DC lines have the potential to serve as an important auxiliary tool for DC research.

  18. The Isothermal Dendritic Growth Experiment Archive

    Science.gov (United States)

    Koss, Matthew

    2009-03-01

    The growth of dendrites is governed by the interplay between two simple and familiar processes---the irreversible diffusion of energy, and the reversible work done in the formation of new surface area. To advance our understanding of these processes, NASA sponsored a project that flew on the Space Shuttle Columbia is 1994, 1996, and 1997 to record and analyze benchmark data in an apparent-microgravity ``laboratory.'' In this laboratory, energy transfer by gravity driven convection was essentially eliminated and one could test independently, for the first time, both components of dendritic growth theory. The analysis of this data shows that although the diffusion of energy can be properly accounted for, the results from interfacial physics appear to be in disagreement and alternate models should receive increased attention. Unfortunately, currently and for the foreseeable future, there is no access or financial support to develop and conduct additional experiments of this type. However, the benchmark data of 35mm photonegatives, video, and all supporting instrument data are now available at the IDGE Archive at the College of the Holy Cross. This data may still have considerable relevance to researchers working specifically with dendritic growth, and more generally those working in the synthesis, growth & processing of materials, multiscale computational modeling, pattern formation, and systems far from equilibrium.

  19. Plasmacytoid dendritic cell role in cutaneous malignancies.

    Science.gov (United States)

    Saadeh, Dana; Kurban, Mazen; Abbas, Ossama

    2016-07-01

    Plasmacytoid dendritic cells (pDCs) correspond to a specialized dendritic cell population that exhibit plasma cell morphology, express CD4, CD123, HLA-DR, blood-derived dendritic cell antigen-2 (BDCA-2), and Toll-like receptor (TLR)7 and TLR9 within endosomal compartments. Through their production of type I interferons (IFNs) and other pro-inflammatory cytokines, pDCs provide anti-viral resistance and link the innate and adaptive immunity by controlling the function of myeloid DCs, lymphocytes, and natural killer (NK) cells. While lacking from normal skin, pDCs are usually recruited to the skin in several cutaneous pathologies where they appear to be involved in the pathogenesis of several infectious, inflammatory/autoimmune, and neoplastic entities. Among the latter group, pDCs have the potential to induce anti-tumour immunity; however, the complex interaction of pDCs with tumor cells and their micro-environment appears to contribute to immunologic tolerance. In this review, we aim at highlighting the role played by pDCs in cutaneous malignancies with special emphasis on the underlying mechanisms.

  20. Probing synaptic function in dendrites with calcium imaging.

    Science.gov (United States)

    Siegel, Friederike; Lohmann, Christian

    2013-04-01

    Calcium imaging has become a widely used technique to probe neuronal activity on the cellular and subcellular levels. In contrast to standard electrophysiological methods, calcium imaging resolves sub- and suprathreshold activation patterns in structures as small as fine dendritic branches and spines. This review highlights recent findings gained on the subcellular level using calcium imaging, with special emphasis on synaptic transmission and plasticity in individual spines. Since imaging allows monitoring activity across populations of synapses, it has recently been adopted to investigate how dendrites integrate information from many synapses. Future experiments, ideally carried out in vivo, will reveal how the dendritic tree integrates and computes afferent signals. For example, it is now possible to directly test the concept that dendritic inputs are clustered and that single dendrites or dendritic stretches act as independent computational units.

  1. Inducible expression of endomorphins in murine dendritic cells.

    Science.gov (United States)

    Yang, Xiaohuai; Xia, Hui; Chen, Yong; Liu, Xiaofen; Zhou, Cheng; Gao, Qin; Li, Zhenghong

    2012-12-15

    Bone marrow precursor cells were extracted from C57BL/6J mice aged 7-8 weeks, and dendritic cells were purified using anti-CD11c (a specific marker for dendritic cells) antibody-coated magnetic beads. Immunofluorescence staining revealed that the expression levels of endomorphin-1 and endomorphin-2 were upregulated in dendritic cells activated by lipopolysaccharide. An enzyme immunoassay showed that lipopolysaccharide and other Toll-like receptor ligands promoted the secretion of endomorphin-1 and endomorphin-2 from activated dendritic cells. [(3)H]-thymidine incorporation demonstrated that endomorphin-1 and endomorphin-2 both inhibited the proliferation of T lymphocyte induced by activated dendritic cells. Furthermore, this immunosuppressive effect was blocked by CTOP, a specific antagonist of µ-opioid receptors. Our experimental findings indicate that activated dendritic cells can induce the expression and secretion of endomorphins, and that endomorphins suppress T lymphocyte proliferation through activation of µ-opioid receptors.

  2. Dendritic spine actin dynamics in neuronal maturation and synaptic plasticity.

    Science.gov (United States)

    Hlushchenko, Iryna; Koskinen, Mikko; Hotulainen, Pirta

    2016-09-01

    The majority of the postsynaptic terminals of excitatory synapses in the central nervous system exist on small bulbous structures on dendrites known as dendritic spines. The actin cytoskeleton is a structural element underlying the proper development and morphology of dendritic spines. Synaptic activity patterns rapidly change actin dynamics, leading to morphological changes in dendritic spines. In this mini-review, we will discuss recent findings on neuronal maturation and synaptic plasticity-induced changes in the dendritic spine actin cytoskeleton. We propose that actin dynamics in dendritic spines decrease through actin filament crosslinking during neuronal maturation. In long-term potentiation, we evaluate the model of fast breakdown of actin filaments through severing and rebuilding through polymerization and later stabilization through crosslinking. We will discuss the role of Ca(2+) in long-term depression, and suggest that actin filaments are dissolved through actin filament severing. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. Inducible expression of endomorphins in murine dendritic cells

    Institute of Scientific and Technical Information of China (English)

    Xiaohuai Yang; Hui Xia; Yong Chen; Xiaofen Liu; Cheng Zhou; Qin Gao; Zhenghong Li

    2012-01-01

    Bone marrow precursor cells were extracted from C57BL/6J mice aged 7–8 weeks, and dendritic cells were purified using anti-CD11c (a specific marker for dendritic cells) antibody-coated magnetic beads. Immunofluorescence staining revealed that the expression levels of endomorphin-1 and endomorphin-2 were upregulated in dendritic cells activated by lipopolysaccharide. An enzyme immunoassay showed that lipopolysaccharide and other Toll-like receptor ligands promoted the secretion of endomorphin-1 and endomorphin-2 from activated dendritic cells. [3H]-thymidine incorporation demonstrated that endomorphin-1 and endomorphin-2 both inhibited the proliferation of T lymphocyte induced by activated dendritic cells. Furthermore, this immunosuppressive effect was blocked by CTOP, a specific antagonist of μ-opioid receptors. Our experimental findings indicate that activated dendritic cells can induce the expression and secretion of endomorphins, and that endomorphins suppress T lymphocyte proliferation through activation of μ-opioid receptors.

  4. Dendritic spine detection using curvilinear structure detector and LDA classifier.

    Science.gov (United States)

    Zhang, Yong; Zhou, Xiaobo; Witt, Rochelle M; Sabatini, Bernardo L; Adjeroh, Donald; Wong, Stephen T C

    2007-06-01

    Dendritic spines are small, bulbous cellular compartments that carry synapses. Biologists have been studying the biochemical pathways by examining the morphological and statistical changes of the dendritic spines at the intracellular level. In this paper a novel approach is presented for automated detection of dendritic spines in neuron images. The dendritic spines are recognized as small objects of variable shape attached or detached to multiple dendritic backbones in the 2D projection of the image stack along the optical direction. We extend the curvilinear structure detector to extract the boundaries as well as the centerlines for the dendritic backbones and spines. We further build a classifier using Linear Discriminate Analysis (LDA) to classify the attached spines into valid and invalid types to improve the accuracy of the spine detection. We evaluate the proposed approach by comparing with the manual results in terms of backbone length, spine number, spine length, and spine density.

  5. Commonly used prophylactic vaccines as an alternative for synthetically produced TLR ligands to mature monocyte-derived dendritic cells.

    NARCIS (Netherlands)

    Schreibelt, G.; Benitez-Ribas, D.; Schuurhuis, D.; Lambeck, A.J.A.; Hout-Kuijer, M.A. van; Schaft, N.; Punt, C.J.A.; Figdor, C.G.; Adema, G.J.; Vries, I.J.M. de

    2010-01-01

    Currently dendritic cell (DC)-based vaccines are explored in clinical trials, predominantly in cancer patients. Murine studies showed that only maturation with Toll-like receptor (TLR) ligands generates mature DCs that produce interleukin-12 and promote optimal T-cell help. Unfortunately, the limite

  6. Inducible expression of endomorphins in murine dendritic cells★

    OpenAIRE

    Yang, Xiaohuai; Xia, Hui; Chen, Yong; Liu, Xiaofen; Zhou, Cheng; Gao, Qin; Li, Zhenghong

    2012-01-01

    Bone marrow precursor cells were extracted from C57BL/6J mice aged 7–8 weeks, and dendritic cells were purified using anti-CD11c (a specific marker for dendritic cells) antibody-coated magnetic beads. Immunofluorescence staining revealed that the expression levels of endomorphin-1 and endomorphin-2 were upregulated in dendritic cells activated by lipopolysaccharide. An enzyme immunoassay showed that lipopolysaccharide and other Toll-like receptor ligands promoted the secretion of endomorphin-...

  7. Assessment of scaling factor in modified dendrite growth model

    Institute of Scientific and Technical Information of China (English)

    张瑞丰; 沈宁福; 曹文博

    2002-01-01

    A model for dendrite growth during rapid solidification was established on the basis of BCT model and marginal stability criterion through modified Peclet numbers. Taking into account the interaction of diffusion fields, including solute diffusion field and thermal diffusion field around the dendrite tip, the model obtain a satisfactory results to predict the dendrite velocity and the tip radius, which agrees well with the experimental data from references in Cu-Ni alloy.

  8. In vitro effects of trichothecenes on human dendritic cells.

    Science.gov (United States)

    Hymery, N; Sibiril, Y; Parent-Massin, D

    2006-09-01

    The aim of this work was to study the in vitro effects of trichothecenes on human dendritic cells. Trichothecenes are mycotoxins produced by fungi such as Fusarium, Myrothecium, and Stachybotrys. Two aspects have been explored in this work: the cytotoxicity of trichothecenes on immature dendritic cells to determine IC 50 (inhibition concentration), and the effects of trichothecenes on dendritic cell maturation process. Two mycotoxins (T-2 and DON) known to be immunotoxic have been tested on a model of monocyte-derived dendritic cells culture. Cytotoxic effects of T-2 toxin and DON on immature dendritic cells showed that DON is less potent than T-2 toxin. The exposure to trichothecenes during dendritic cell maturation upon addition of LPS or TNF-alpha markedly inhibited the up-regulation of maturation markers such as CD-86, HLA-DR and CCR7. Features of LPS or TNF-alpha -mediated maturation of dendritic cells, such as IL-10 and IL-12 secretions and endocytosis, were also impaired in response to trichothecenes treatment. These results suggest trichothecenes have adverse effects on dendritic cells and dendritic cell maturation process.

  9. Mapping homeostatic synaptic plasticity using cable properties of dendrites.

    Science.gov (United States)

    Queenan, B N; Lee, K J; Tan, H; Huganir, R L; Vicini, S; Pak, D T S

    2016-02-19

    When chronically silenced, cortical and hippocampal neurons homeostatically upregulate excitatory synaptic function. However, the subcellular position of such changes on the dendritic tree is not clear. We exploited the cable-filtering properties of dendrites to derive a parameter, the dendritic filtering index (DFI), to map the spatial distribution of synaptic currents. Our analysis indicates that young rat cortical neurons globally scale AMPA receptor-mediated currents, while mature hippocampal neurons do not, revealing distinct homeostatic strategies between brain regions and developmental stages. The DFI presents a useful tool for mapping the dendritic origin of synaptic currents and the location of synaptic plasticity changes.

  10. Dendritic planarity of Purkinje cells is independent of Reelin signaling.

    Science.gov (United States)

    Kim, Jinkyung; Park, Tae-Ju; Kwon, Namseop; Lee, Dongmyeong; Kim, Seunghwan; Kohmura, Yoshiki; Ishikawa, Tetsuya; Kim, Kyong-Tai; Curran, Tom; Je, Jung Ho

    2015-07-01

    The dendritic planarity of Purkinje cells is critical for cerebellar circuit formation. In the absence of Crk and CrkL, the Reelin pathway does not function resulting in partial Purkinje cell migration and defective dendritogenesis. However, the relationships among Purkinje cell migration, dendritic development and Reelin signaling have not been clearly delineated. Here, we use synchrotron X-ray microscopy to obtain 3-D images of Golgi-stained Purkinje cell dendrites. Purkinje cells that failed to migrate completely exhibited conical dendrites with abnormal 3-D arborization and reduced dendritic complexity. Furthermore, their spines were fewer in number with a distorted morphology. In contrast, Purkinje cells that migrated successfully displayed planar dendritic and spine morphologies similar to normal cells, despite reduced dendritic complexity. These results indicate that, during cerebellar formation, Purkinje cells migrate into an environment that supports development of dendritic planarity and spine formation. While Reelin signaling is important for the migration process, it does not make a direct major contribution to dendrite formation.

  11. Semi-solid Forming of a Damper Housing with Dendritic and Non-dendritic Al-Si-Mg Alloy

    Institute of Scientific and Technical Information of China (English)

    ChenCM; YangCC; ChaoCG

    2001-01-01

    A motorcycle component of damper housing was made by semi-solid forming process. This was used to investigate the effect of microstructures of feedstock on the formability of semisolid process. The soundness and microstructures of casting parts made by dendritic and non-dendritic feedstock were investigated. Separating of liquid phase was found in the casting produced by dendritic feedstock, which might result in defects of porosity, while uniform microstructures were found in the casting produced by no...

  12. Ternary eutectic dendrites: Pattern formation and scaling properties

    Energy Technology Data Exchange (ETDEWEB)

    Rátkai, László; Szállás, Attila; Pusztai, Tamás [Institute for Solid State Physics and Optics, Wigner Research Centre for Physics, P.O. Box 49, H-1525 Budapest (Hungary); Mohri, Tetsuo [Center for Computational Materials Science, Institute for Materials Research, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577 (Japan); Gránásy, László, E-mail: granasy.laszlo@wigner.mta.hu [Institute for Solid State Physics and Optics, Wigner Research Centre for Physics, P.O. Box 49, H-1525 Budapest (Hungary); Brunel University, Uxbridge, Middlesex UB8 3PH (United Kingdom)

    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 dendritesdendrites 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 the 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.

  13. Crosstalk between dendritic cell subsets and implications for dendritic cell-based anticancer immunotherapy

    NARCIS (Netherlands)

    Bakdash, G.; Schreurs, I.; Schreibelt, G.; Tel, J.

    2014-01-01

    Dendritic cells (DCs) are a family of professional antigen-presenting cells that have an indispensable role in the initiation of innate and adaptive immune responses against pathogens and tumor cells. The DC family is very heterogeneous. Two main types of naturally occurring DCs circulate in periphe

  14. Impact of Dendritic Size and Dendritic Topology on Burst Firing in Pyramidal Cells

    NARCIS (Netherlands)

    van Elburg, Ronald A. J.; van Ooyen, Arjen

    2010-01-01

    Neurons display a wide range of intrinsic firing patterns. A particularly relevant pattern for neuronal signaling and synaptic plasticity is burst firing, the generation of clusters of action potentials with short interspike intervals. Besides ion-channel composition, dendritic morphology appears to

  15. CTLA-4 blockade during dendritic cell based booster vaccination influences dendritic cell survival and CTL expansion

    DEFF Research Database (Denmark)

    Pedersen, Anders E; Ronchese, Franca

    2007-01-01

    Dendritic cells (DCs) are potent antigen-presenting cells and critical for the priming of CD8+ T cells. Therefore the use of these cells as adjuvant cells has been tested in a large number of experimental and clinical vaccination studies, in particular cancer vaccine studies. A number of protocols...

  16. Fine structure of synapses on dendritic spines

    Directory of Open Access Journals (Sweden)

    Michael eFrotscher

    2014-09-01

    Full Text Available Camillo Golgi’s Reazione Nera led to the discovery of dendritic spines, small appendages originating from dendritic shafts. With the advent of electron microscopy (EM they were identified as sites of synaptic contact. Later it was found that changes in synaptic strength were associated with changes in the shape of dendritic spines. While live-cell imaging was advantageous in monitoring the time course of such changes in spine structure, EM is still the best method for the simultaneous visualization of all cellular components, including actual synaptic contacts, at high resolution. Immunogold labeling for EM reveals the precise localization of molecules in relation to synaptic structures. Previous EM studies of spines and synapses were performed in tissue subjected to aldehyde fixation and dehydration in ethanol, which is associated with protein denaturation and tissue shrinkage. It has remained an issue to what extent fine structural details are preserved when subjecting the tissue to these procedures. In the present review, we report recent studies on the fine structure of spines and synapses using high-pressure freezing (HPF, which avoids protein denaturation by aldehydes and results in an excellent preservation of ultrastructural detail. In these studies, HPF was used to monitor subtle fine-structural changes in spine shape associated with chemically induced long-term potentiation (cLTP at identified hippocampal mossy fiber synapses. Changes in spine shape result from reorganization of the actin cytoskeleton. We report that cLTP was associated with decreased immunogold labeling for phosphorylated cofilin (p-cofilin, an actin-depolymerizing protein. Phosphorylation of cofilin renders it unable to depolymerize F-actin, which stabilizes the actin cytoskeleton. Decreased levels of p-cofilin, in turn, suggest increased actin turnover, possibly underlying the changes in spine shape associated with cLTP. The findings reviewed here establish HPF as

  17. Dendrite Spacing Selection during Directional Solidification of Pivalic Acid-Ethanol System

    Institute of Scientific and Technical Information of China (English)

    Myung-Jin Suk; Young-Min Park; Youn-Che Kim

    2008-01-01

    Unidirectional solidification of pivalic acid (PVA)-ethanol (Eth) mixture was performed to examine whether an allowable range of primary dendrite spacing definitely exists at a given growth velocity and how the range is history-dependent. PVA-0.59 wt pct Eth was unidirectionally solidified in the range of growth velocity 0.5-64 μm/s at the temperature gradient of 2.3 K/mm. Sequential change in growth velocity was imposed to determine the upper and lower limits for the allowable range of stable spacing. An allowable range of the steady state primary spacing was observed at a given growth velocity, and the extent of the range seems to be dependent on the degree to which step-increase or step-decrease in growth velocity is accomplished. As the degree of sequential change in growth velocity increases, the history-dependence of the selection for the primary dendrite spacing tends to disappear.

  18. Dendritic Cells as Danger-Recognizing Biosensors

    Directory of Open Access Journals (Sweden)

    Seokmann Hong

    2009-08-01

    Full Text Available Dendritic cells (DCs are antigen presenting cells that are characterized by a potent capacity to initiate immune responses. DCs comprise several subsets with distinct phenotypes. After sensing any danger(s to the host via their innate immune receptors such as Toll-like receptors, DCs become mature and subsequently present antigens to CD4+ T cells. Since DCs possess the intrinsic capacity to polarize CD4+ helper cells, it is critical to understand the immunological roles of DCs for clinical applications. Here, we review the different DC subsets, their danger-sensing receptors and immunological functions. Furthermore, the cytokine reporter mouse model for studying DC activation is introduced.

  19. Viruses, dendritic cells and the lung

    Directory of Open Access Journals (Sweden)

    Graham Barney S

    2001-06-01

    Full Text Available Abstract The interaction between viruses and dendritic cells (DCs is varied and complex. DCs are key elements in the development of a host response to pathogens such as viruses, but viruses have developed survival tactics to either evade or diminish the immune system that functions to kill and eliminate these micro-organisms. In the present review we summarize current concepts regarding the function of DCs in the immune system, our understanding of how viruses alter DC function to attenuate both the virus-specific and global immune response, and how we may be able to exploit DC function to prevent or treat viral infections.

  20. Convective heat transfer during dendritic solidification

    Science.gov (United States)

    Glicksman, M. E.; Huang, S. C.

    1978-01-01

    Experiments on succinonitrile are described in which the dependence of dendritic growth velocity is studied as a function of orientation with respect to gravity. Growth rate measurements were carried out at a relatively small supercooling, requiring high specimen purity as well as extreme thermal stability and precision temperature measurement. The normalized growth velocity showed a dependence on orientation described by the ratio of observed growth velocity to that expected for convection-free growth being equal to 3.52 times the n-th power of Cos half the orientation angle, where n lies between 0.5 and 0.75.

  1. Metamaterial absorber with random dendritic cells

    Science.gov (United States)

    Zhu, Weiren; Zhao, Xiaopeng

    2010-05-01

    The metamaterial absorber composed of random dendritic cells has been investigated at microwave frequencies. It is found that the absorptivities come to be weaker and the resonant frequency get red shift as the disordered states increasing, however, the random metamaterial absorber still presents high absorptivity more than 95%. The disordered structures can help understanding of the metamaterial absorber and may be employed for practical design of infrared metamaterial absorber, which may play important roles in collection of radiative heat energy and directional transfer enhancement.

  2. Dopaminergic regulation of dendritic calcium: fast multisite calcium imaging.

    Science.gov (United States)

    Zhou, Wen-Liang; Oikonomou, Katerina D; Short, Shaina M; Antic, Srdjan D

    2013-01-01

    Optimal dopamine tone is required for the normal cortical function; however it is still unclear how cortical-dopamine-release affects information processing in individual cortical neurons. Thousands of glutamatergic inputs impinge onto elaborate dendritic trees of neocortical pyramidal neurons. In the process of ensuing synaptic integration (information processing), a variety of calcium transients are generated in remote dendritic compartments. In order to understand the cellular mechanisms of dopaminergic modulation it is important to know whether and how dopaminergic signals affect dendritic calcium transients. In this chapter, we describe a relatively inexpensive method for monitoring dendritic calcium fluctuations at multiple loci across the pyramidal dendritic tree, at the same moment of time (simultaneously). The experiments have been designed to measure the amplitude, time course and spatial extent of action potential-associated dendritic calcium transients before and after application of dopaminergic drugs. In the examples provided here the dendritic calcium transients were evoked by triggering the somatic action potentials (backpropagation-evoked), and puffs of exogenous dopamine were applied locally onto selected dendritic branches.

  3. Contribution of sublinear and supralinear dendritic integration to neuronal computations.

    Science.gov (United States)

    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.

  4. Human plasmacytoid dendritic cells: from molecules to intercellular communication network

    NARCIS (Netherlands)

    Mathan, T.S.M.; Figdor, C.G.; Buschow, S.I.

    2013-01-01

    Plasmacytoid dendritic cells (pDCs) are a specific subset of naturally occurring dendritic cells, that secrete large amounts of Type I interferon and play an important role in the immune response against viral infection. Several studies have highlighted that they are also effective antigen presentin

  5. Cold-induced exodus of postsynaptic proteins from dendritic spines.

    Science.gov (United States)

    Cheng, Hui-Hsuan; Huang, Zu-Han; Lin, Wei-Hsiang; Chow, Wei-Yuan; Chang, Yen-Chung

    2009-02-01

    Dendritic spines are small protrusions on neuronal dendrites and the major target of the excitatory inputs in mammalian brains. Cultured neurons and brain slices are important tools in studying the biochemical and cellular properties of dendritic spines. During the processes of immunocytochemical studies of neurons and the preparation of brain slices, neurons were often kept at temperatures lower than 37 degrees C for varied lengths of time. This study sought to investigate whether and how cold treatment would affect the protein composition of dendritic spines. The results indicated that upon cold treatment four postsynaptic proteins, namely, alpha,beta-tubulins, calcium, calmodulin-dependent protein kinase IIalpha, and cytoplasmic dynein heavy chain and microtubule-associated protein 2, but not PSD-95 or AMPA receptors, exited from the majority of dendritic spines of cultured rat hippocampal neurons in a Gd(3+)-sensitive manner. The cold-induced exit of tubulins from dendritic spines was further found to be an energy-dependent process involving the activation of Gd(3+)-sensitive calcium channels and ryanodine receptors. The results thus indicate that changes in temperature, calcium concentration, and energy supply of the medium surrounding neurons would affect the protein composition of the dendritic spines and conceivably the protein composition of the subcellular organizations, such as the postsynaptic density, in the cytoplasm of dendritic spines.

  6. Barriers in the brain : resolving dendritic spine morphology and compartmentalization

    NARCIS (Netherlands)

    Adrian, Max; Kusters, Remy; Wierenga, Corette J; Storm, Cornelis; Hoogenraad, Casper C; Kapitein, Lukas C

    2014-01-01

    Dendritic spines are micron-sized protrusions that harbor the majority of excitatory synapses in the central nervous system. The head of the spine is connected to the dendritic shaft by a 50-400 nm thin membrane tube, called the spine neck, which has been hypothesized to confine biochemical and elec

  7. Contribution of sublinear and supralinear dendritic integration to neuronal computations

    Directory of Open Access Journals (Sweden)

    Alexandra eTran-Van-Minh

    2015-03-01

    Full Text Available 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 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.

  8. Channelopathies and dendritic dysfunction in fragile X syndrome.

    Science.gov (United States)

    Brager, Darrin H; Johnston, Daniel

    2014-04-01

    Dendritic spine abnormalities and the metabotropic glutamate receptor theory put the focus squarely on synapses and protein synthesis as the cellular locus of fragile X syndrome. Synapses however, are only partly responsible for information processing in neuronal networks. Neurotransmitter triggered excitatory postsynaptic potentials (EPSPs) are shaped and integrated by dendritic voltage-gated ion channels. These EPSPs, and in some cases the resultant dendritic spikes, are further modified by dendritic voltage-gated ion channels as they propagate to the soma. If the resultant somatic depolarization is large enough, action potential(s) will be triggered and propagate both orthodromically down the axon, where it may trigger neurotransmitter release, and antidromically back into the dendritic tree, where it can activate and modify dendritic voltage-gated and receptor activated ion channels. Several channelopathies, both soma-dendritic (L-type calcium channels, Slack potassium channels, h-channels, A-type potassium channels) and axo-somatic (BK channels and delayed rectifier potassium channels) were identified in the fmr1-/y mouse model of fragile X syndrome. Pathological function of these channels will strongly influence the excitability of individual neurons as well as overall network function. In this chapter we discuss the role of voltage-gated ion channels in neuronal processing and describe how identified channelopathies in models of fragile X syndrome may play a role in dendritic pathophysiology. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Modeling of dendritic growth in the presence of convection

    Institute of Scientific and Technical Information of China (English)

    ZHU; Mingfang; DAI; Ting; LEE; Sungyoon; HONG; Chunpyo

    2005-01-01

    A two-dimensional coupling modified cellular automaton (MCA)-transport model has been employed to investigate the asymmetrical dendritic growth behavior in a flowing melt. In the present model, the cellular automaton method for crystal growth is incorporated with a transport model, for numerical calculating of the fluid flow and mass transport by both convection and diffusion. The MCA takes into account the effects of the thermal, the constitutional and the curvature undercoolings on dendritic growth. It also considers the preferred growth orientation of crystal and solute redistribution during solidification. In the transport model, the SIMPLE scheme and a fully implicit finite volume method are employed to solve the governing equations of momentum and species transfers. The present model was applied to simulating the evolution of a single dendrite and multi-dendrites of an Al-3mass%Cu alloy in a forced flow. The simulated results show that dendritic growth morphology is strongly influenced by melt convection.

  10. Immune Monitoring Using mRNA-Transfected Dendritic Cells

    DEFF Research Database (Denmark)

    Borch, Troels Holz; Svane, Inge Marie; Met, Özcan

    2016-01-01

    Dendritic cells are known to be the most potent antigen presenting cell in the immune system and are used as cellular adjuvants in therapeutic anticancer vaccines using various tumor-associated antigens or their derivatives. One way of loading antigen into the dendritic cells is by m......RNA electroporation, ensuring presentation of antigen through major histocompatibility complex I and potentially activating T cells, enabling them to kill the tumor cells. Despite extensive research in the field, only one dendritic cell-based vaccine has been approved. There is therefore a great need to elucidate...... and understand the immunological impact of dendritic cell vaccination in order to improve clinical benefit. In this chapter, we describe a method for performing immune monitoring using peripheral blood mononuclear cells and autologous dendritic cells transfected with tumor-associated antigen-encoding mRNA....

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

    Directory of Open Access Journals (Sweden)

    Shira eRosenzweig

    2011-03-01

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

  12. Dendritic cells modified by vitamin D

    DEFF Research Database (Denmark)

    Pedersen, Ayako Wakatsuki; Claesson, Mogens Helweg; Zocca, Mai-Britt

    2011-01-01

    Dendritic cells (DCs), the most potent antigen-presenting cells of the immune system, express nuclear receptors for 1,25-dihydroxyvitamin D(3) (VD3) and they are one of its main targets. In the presence of VD3, DCs differentiate into a phenotype that resembles semimature DCs, with reduced T cell ...... and the optimal frequency, dose, and route of DC administration to achieve therapeutic effects in humans, adoptive VD3-DC transfer represents one of the most promising approaches to future treatment of autoimmune diseases.......Dendritic cells (DCs), the most potent antigen-presenting cells of the immune system, express nuclear receptors for 1,25-dihydroxyvitamin D(3) (VD3) and they are one of its main targets. In the presence of VD3, DCs differentiate into a phenotype that resembles semimature DCs, with reduced T cell...... costimulatory molecules and hampered IL-12 production. These VD3-modulated DCs induce T cell tolerance in vitro using multiple mechanisms such as rendering T cells anergic, dampening of Th1 responses, and recruiting and differentiating regulatory T cells. Due to their ability to specifically target pathological...

  13. Dendritic Cells in vivo and in vitro

    Institute of Scientific and Technical Information of China (English)

    Hui Wan; Marcel Dupasquier

    2005-01-01

    Dendritic cells (DC) are crucial cells of the immune system, and bridged the essential connection between innate and adaptive immunity. They reside in the periphery as sentinels where they take up antigens. Upon activation,they migrate to lymphoid organs and present there the processed antigens to T cells, thereby activating them and eliciting a potent immune response. Dendritic cells are bone marrow-derived cells, still big controversies exist about their in vivo development. In vitro, DC can be generated from multiple precursor cells, among them lymphoid and myeloid committed progenitors. Although it remains unknown how DC are generated in vivo,studying the functions of in vitro generated DC results in fundamental knowledge of the DC biology with promising applications for future medicine. Therefore, in this review, we present current protocols for the generation of DC from precursors in vitro. We will do this for the mouse system, where most research occurs and for the human system, where research concentrates on implementing DC biology in disease treatments.

  14. Dendritic Cells in vivo and in vitro

    Institute of Scientific and Technical Information of China (English)

    HuiWan; MarcelDupasquier

    2005-01-01

    Dendritic cells (DC) are crucial cells of the immune system, and bridged the essential connection between innate and adaptive immunity. They reside in the periphery as sentinels where they take up antigens. Upon activation, they migrate to lymphoid organs and present there the processed antigens to T cells, thereby activating them and eliciting a potent immune response. Dendritic cells are bone marrow-derived cells, still big controversies exist about their in vivo development. In vitro, DC can be generated from multiple precursor cells, among them lymphoid and myeloid committed progenitors. Although it remains unknown how DC are generated in vivo, studying the functions of in vitro generated DC results in fundamental knowledge of the DC biology with promising applications for future medicine. Therefore, in this review, we present current protocols for the generation of DC from precursors in vitro. We will do this for the mouse system, where most research occurs and for the human system, where research concentrates on implementing DC biology in disease treatments. Cellular & Molecular Immunology. 2005;2(1):28-35.

  15. The effects of early-life seizures on hippocampal dendrite development and later-life learning and memory.

    Science.gov (United States)

    Casanova, J R; Nishimura, Masataka; Swann, John W

    2014-04-01

    Severe childhood epilepsy is commonly associated with intellectual developmental disabilities. The reasons for these cognitive deficits are likely multifactorial and will vary between epilepsy syndromes and even among children with the same syndrome. However, one factor these children have in common is the recurring seizures they experience - sometimes on a daily basis. Supporting the idea that the seizures themselves can contribute to intellectual disabilities are laboratory results demonstrating spatial learning and memory deficits in normal mice and rats that have experienced recurrent seizures in infancy. Studies reviewed here have shown that seizures in vivo and electrographic seizure activity in vitro both suppress the growth of hippocampal pyramidal cell dendrites. A simplification of dendritic arborization and a resulting decrease in the number and/or properties of the excitatory synapses on them could help explain the observed cognitive disabilities. There are a wide variety of candidate mechanisms that could be involved in seizure-induced growth suppression. The challenge is designing experiments that will help focus research on a limited number of potential molecular events. Thus far, results suggest that growth suppression is NMDA receptor-dependent and associated with a decrease in activation of the transcription factor CREB. The latter result is intriguing since CREB is known to play an important role in dendrite growth. Seizure-induced dendrite growth suppression may not occur as a single process in which pyramidal cells dendrites simply stop growing or grow slower compared to normal neurons. Instead, recent results suggest that after only a few hours of synchronized epileptiform activity in vitro dendrites appear to partially retract. This acute response is also NMDA receptor dependent and appears to be mediated by the Ca(+2)/calmodulin-dependent phosphatase, calcineurin. An understanding of the staging of seizure-induced growth suppression and the

  16. Loss of Dendritic Complexity Precedes Neurodegeneration in a Mouse Model with Disrupted Mitochondrial Distribution in Mature Dendrites

    Directory of Open Access Journals (Sweden)

    Guillermo López-Doménech

    2016-10-01

    Full Text Available Correct mitochondrial distribution is critical for satisfying local energy demands and calcium buffering requirements and supporting key cellular processes. The mitochondrially targeted proteins Miro1 and Miro2 are important components of the mitochondrial transport machinery, but their specific roles in neuronal development, maintenance, and survival remain poorly understood. Using mouse knockout strategies, we demonstrate that Miro1, as opposed to Miro2, is the primary regulator of mitochondrial transport in both axons and dendrites. Miro1 deletion leads to depletion of mitochondria from distal dendrites but not axons, accompanied by a marked reduction in dendritic complexity. Disrupting postnatal mitochondrial distribution in vivo by deleting Miro1 in mature neurons causes a progressive loss of distal dendrites and compromises neuronal survival. Thus, the local availability of mitochondrial mass is critical for generating and sustaining dendritic arbors, and disruption of mitochondrial distribution in mature neurons is associated with neurodegeneration.

  17. Differential gating of dendritic spikes by compartmentalized inhibition

    Directory of Open Access Journals (Sweden)

    Katharina Anna Wilmes

    2014-03-01

    Full Text Available Different types of local inhibitory interneurons innervate different dendritic sites of pyramidal neurons in cortex and hippocampus (Klausberger 2009. What could be the functional role of compartmentalized inhibition? Pyramidal cell dendrites support different forms of active signal propagation, which are important not only for dendritic and neuronal signal processing (Smith et al. 2013, but also for synaptic plasticity. While back-propagating action potentials signal post-synaptic activity to synapses in apical oblique and basal dendrites (Markram et al. 1997, Cho et al. 2006, calcium spikes cause plasticity of distal apical tuft synapses (Golding et al. 2002. Suspiciously, the associated regions of the dendrite are targeted by different interneuron populations. Parvalbumin-positive interneurons typically target the proximal dendritic and somatic parts of the neuron, while somatostatin-positive interneurons target the apical dendrite. The matching compartmentalization in terms of dendritic spikes and inhibitory control suggests that inhibition could differentially regulate different dendritic spikes and thereby introduce a compartment-specific modulation of synaptic plasticity. We evaluate this hypothesis in a biophysical multi-compartment model of a pyramidal neuron, receiving shunting inhibition at different locations on the dendrite. The model shows that, first, inhibition can gate dendritic spikes in an all-or-none manner. Second, spatially selective inhibition can individually suppress back-propagating action potentials and calcium spikes, thereby allowing a compartment-specific switch for synaptic plasticity. In our model, proximal inhibition on the apical dendrite eliminated both the back-propagating action potential and the calcium spike, thus influencing plasticity in the whole apical dendrite. Distal apical inhibition could selectively affect calcium spikes and thus distal plasticity, without suppressing back­propagation of action

  18. Differentiation of apical and basal dendrites in pyramidal cells and granule cells in dissociated hippocampal cultures.

    Directory of Open Access Journals (Sweden)

    You Kure Wu

    Full Text Available Hippocampal pyramidal cells and dentate granule cells develop morphologically distinct dendritic arbors, yet also share some common features. Both cell types form a long apical dendrite which extends from the apex of the cell soma, while short basal dendrites are developed only in pyramidal cells. Using quantitative morphometric analyses of mouse hippocampal cultures, we evaluated the differences in dendritic arborization patterns between pyramidal and granule cells. Furthermore, we observed and described the final apical dendrite determination during dendritic polarization by time-lapse imaging. Pyramidal and granule cells in culture exhibited similar dendritic patterns with a single principal dendrite and several minor dendrites so that the cell types were not readily distinguished by appearance. While basal dendrites in granule cells are normally degraded by adulthood in vivo, cultured granule cells retained their minor dendrites. Asymmetric growth of a single principal dendrite harboring the Golgi was observed in both cell types soon after the onset of dendritic growth. Time-lapse imaging revealed that up until the second week in culture, final principal dendrite designation was not stabilized, but was frequently replaced by other minor dendrites. Before dendritic polarity was stabilized, the Golgi moved dynamically within the soma and was repeatedly repositioned at newly emerging principal dendrites. Our results suggest that polarized growth of the apical dendrite is regulated by cell intrinsic programs, while regression of basal dendrites requires cue(s from the extracellular environment in the dentate gyrus. The apical dendrite designation is determined from among multiple growing dendrites of young developing neurons.

  19. Linking Memories across Time via Neuronal and Dendritic Overlaps in Model Neurons with Active Dendrites

    Directory of Open Access Journals (Sweden)

    George Kastellakis

    2016-11-01

    Full Text Available Memories are believed to be stored in distributed neuronal assemblies through activity-induced changes in synaptic and intrinsic properties. However, the specific mechanisms by which different memories become associated or linked remain a mystery. Here, we develop a simplified, biophysically inspired network model that incorporates multiple plasticity processes and explains linking of information at three different levels: (1 learning of a single associative memory, (2 rescuing of a weak memory when paired with a strong one, and (3 linking of multiple memories across time. By dissecting synaptic from intrinsic plasticity and neuron-wide from dendritically restricted protein capture, the model reveals a simple, unifying principle: linked memories share synaptic clusters within the dendrites of overlapping populations of neurons. The model generates numerous experimentally testable predictions regarding the cellular and sub-cellular properties of memory engrams as well as their spatiotemporal interactions.

  20. Statistical Physics of Neural Systems with Nonadditive Dendritic Coupling

    Directory of Open Access Journals (Sweden)

    David Breuer

    2014-03-01

    Full Text Available How neurons process their inputs crucially determines the dynamics of biological and artificial neural networks. In such neural and neural-like systems, synaptic input is typically considered to be merely transmitted linearly or sublinearly by the dendritic compartments. Yet, single-neuron experiments report pronounced supralinear dendritic summation of sufficiently synchronous and spatially close-by inputs. Here, we provide a statistical physics approach to study the impact of such nonadditive dendritic processing on single-neuron responses and the performance of associative-memory tasks in artificial neural networks. First, we compute the effect of random input to a neuron incorporating nonlinear dendrites. This approach is independent of the details of the neuronal dynamics. Second, we use those results to study the impact of dendritic nonlinearities on the network dynamics in a paradigmatic model for associative memory, both numerically and analytically. We find that dendritic nonlinearities maintain network convergence and increase the robustness of memory performance against noise. Interestingly, an intermediate number of dendritic branches is optimal for memory functionality.

  1. Control of dendritic morphogenesis by Trio in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Madhuri Shivalkar

    Full Text Available Abl tyrosine kinase and its effectors among the Rho family of GTPases each act to control dendritic morphogenesis in Drosophila. It has not been established, however, which of the many GTPase regulators in the cell link these signaling molecules in the dendrite. In axons, the bifunctional guanine exchange factor, Trio, is an essential link between the Abl tyrosine kinase signaling pathway and Rho GTPases, particularly Rac, allowing these systems to act coordinately to control actin organization. In dendritic morphogenesis, however, Abl and Rac have contrary rather than reinforcing effects, raising the question of whether Trio is involved, and if so, whether it acts through Rac, Rho or both. We now find that Trio is expressed in sensory neurons of the Drosophila embryo and regulates their dendritic arborization. trio mutants display a reduction in dendritic branching and increase in average branch length, whereas over-expression of trio has the opposite effect. We further show that it is the Rac GEF domain of Trio, and not its Rho GEF domain that is primarily responsible for the dendritic function of Trio. Thus, Trio shapes the complexity of dendritic arbors and does so in a way that mimics the effects of its target, Rac.

  2. Dendritic growth in the presence of convection. Ph.D. Thesis

    Science.gov (United States)

    Beaghton, Pantelis John

    1988-01-01

    The motion of the freezing front between a dendritic crystal and a supercooled liquid is studied using an interface evolution equation derived from a boundary integral transformation of the transient convective-diffusion equation. A new steady-state theory is introduced that incorporates the effects of convection in dendritic growth. It is shown that in the absence of capillary effects the shape of the crystal-melt interface is a paraboloid of revolution, similar to that found in situations where diffusion is the sole heat transfer mechanism. A relation between the supercooling, the product of the tip velocity and tip radius, and the strength of the flow is derived which reduces to the well-known Ivantsov theory in the absence of convection. A non-linear interface-tracking algorithm is developed and used to study the temporal and spatial evolution of the dendritic interface. The important role of capillarity and convection on the interface dynamics is established and the response of the interface to finite amplitude disturbances is examined for the first time. Tip splitting is identified as the dominant destabilization mechanism in the limit of zero surface tension. Finite surface tension leads to interface stabilization, irrespective of the magnitude and structure of the external perturbations. Finally, convection significantly decreases the magnitude of the freezing velocity.

  3. Iron acquisition by Mycobacterium tuberculosis residing within myeloid dendritic cells.

    Science.gov (United States)

    Olakanmi, Oyebode; Kesavalu, Banurekha; Abdalla, Maher Y; Britigan, Bradley E

    2013-12-01

    The pathophysiology of Mycobacterium tuberculosis (M.tb) infection is linked to the ability of the organism to grow within macrophages. Lung myeloid dendritic cells are a newly recognized reservoir of M.tb during infection. Iron (Fe) acquisition is critical for M.tb growth. In vivo, extracellular Fe is chelated to transferrin (TF) and lactoferrin (LF). We previously reported that M.tb replicating in human monocyte-dervied macrophages (MDM) can acquire Fe bound to TF, LF, and citrate, as well as from the MDM cytoplasm. Access of M.tb to Fe may influence its growth in macrophages and dendritic cells. In the present work we confirmed the ability of different strains of M.tb to grow in human myeloid dendritic cells in vitro. Fe acquired by M.tb replicating within dendritic cells from externally added Fe chelates varied with the Fe chelate present in the external media: Fe-citrate > Fe-LF > Fe-TF. Fe acquisition rates from each chelate did not vary over 7 days. M.tb within dendritic cells also acquired Fe from the dendritic cell cytoplasm, with the efficiency of Fe acquisition greater from cytoplasmic Fe sources, regardless of the initial Fe chelate from which that cytoplasmic Fe was derived. Growth and Fe acquisition results with human MDM were similar to those with dendritic cells. M.tb grow and replicate within myeloid dendritic cells in vitro. Fe metabolism of M.tb growing in either MDM or dendritic cells in vitro is influenced by the nature of Fe available and the organism appears to preferentially access cytoplasmic rather than extracellular Fe sources. Whether these in vitro data extend to in vivo conditions should be examined in future studies.

  4. Effects of Reducing Suppressors of Cytokine Signaling-3 (SOCS3 Expression on Dendritic Outgrowth and Demyelination after Spinal Cord Injury.

    Directory of Open Access Journals (Sweden)

    Keun Woo Park

    Full Text Available Suppressors of cytokine signaling-3 (SOCS3 is associated with limitations of nerve growth capacity after injury to the central nervous system. Although genetic manipulations of SOCS3 can enhance axonal regeneration after optic injury, the role of SOCS3 in dendritic outgrowth after spinal cord injury (SCI is still unclear. The present study investigated the endogenous expression of SOCS3 and its role in regulating neurite outgrowth in vitro. Interleukin-6 (IL-6 induces SOCS3 expression at the mRNA and protein levels in neuroscreen-1 (NS-1 cells. In parallel to SOCS3 expression, IL-6 induced tyrosine phosphorylation of signal transducer and activator of transcription 3 (STAT3 in NS-1 cells. Lentiviral delivery of short hairpin RNA (shSOCS3 (Lenti-shSOCS3 to decrease SOCS3 expression into NS-1 cells enhanced IL-6-induced tyrosine phosphorylation of STAT3 (P-STAT3 Tyr705 and promoted neurite outgrowth. In addition, we determined if reduction of SOCS3 expression by microinjection of Lenti-shSOCS3 into spinal cord enhances dendrite outgrowth in spinal cord neurons after SCI. Knocking down of SOCS3 in spinal cord neurons with Lenti-shSOCS3 increased complete SCI-induced P-STAT3 Tyr705. Immunohistochemical analysis showed that complete SCI induced a significant reduction of microtubule association protein 2-positive (MAP-2+ dendrites in the gray and white matter at 1 and 4 weeks after injury. The SCI-induced reduction of MAP-2+ dendrites was inhibited by infection with Lenti-shSOCS3 in areas both rostral and caudal to the lesion at 1 and 4 weeks after complete SCI. Furthermore, shSOCS3 treatment enhanced up-regulation of growth associated protein-43 (GAP-43 expression, which co-localized with MAP-2+ dendrites in white matter and with MAP-2+ cell bodies in gray matter, indicating Lenti-shSOCS3 may induce dendritic regeneration after SCI. Moreover, we demonstrated that Lenti-shSOCS3 decreased SCI-induced demyelination in white matter of spinal cord both

  5. Follicular Dendritic Cell Sarcoma of the Abdomen: the Imaging Findings

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Tae Wook; Lee, Soon Jin; Song, Hye Jong [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2010-04-15

    Follicular dendritic cell sarcoma is a rare neoplasm that originates from follicular dendritic cells in lymphoid follicles. This disease usually involves the lymph nodes, and especially the head and neck area. Rarely, extranodal sites may be affected, including tonsil, the oral cavity, liver, spleen and the gastrointestinal tract. We report here on the imaging findings of follicular dendritic cell sarcoma of the abdomen that involved the retroperitoneal lymph nodes and colon. It shows as a well-defined, enhancing homogenous mass with internal necrosis and regional lymphadenopathy.

  6. NUMERICAL SIMULATION OF CELLULAR/DENDRITIC PRIMARY SPACING

    Institute of Scientific and Technical Information of China (English)

    W.Q.Zhang; L.Xiao

    2004-01-01

    A numerical model has been established to calculate the primary spacing of cellular or dendritic structure with fluid flow considered. The computing results show that the primary spacing depends on the growing velocity, the temperature gradient on the interface and fluid flow. There is a critical growing velocity for the cell-dendrite transition, which has a relationship with the temperature gradient: Rcr=(3-4)×10-9GT. Fluid flow leads to an increase of the primary spacing for dendritic growth but a decrease for cellular growth,resulting in an instability on the interface.

  7. Phase field simulation of dendrite growth under convection

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The phase-field model coupled with a flow field was used to simulate the solidification of pure materials by the finite difference method.The effects of initial crystal radius,the space step and the interface thickness on the dendrite growth were studied.Results indicate that the grain grows into an equiaxial dendrite during free flow and into a typical branched structure under forced flow.The radius of an initial crystal can affect the growth of side-branches but not the stability of the dendrite s tip whe...

  8. Information Fusion for Anomaly Detection with the Dendritic Cell Algorithm

    CERN Document Server

    Greensmith, Julie; Tedesco, Gianni

    2010-01-01

    Dendritic cells are antigen presenting cells that provide a vital link between the innate and adaptive immune system, providing the initial detection of pathogenic invaders. Research into this family of cells has revealed that they perform information fusion which directs immune responses. We have derived a Dendritic Cell Algorithm based on the functionality of these cells, by modelling the biological signals and differentiation pathways to build a control mechanism for an artificial immune system. We present algorithmic details in addition to experimental results, when the algorithm was applied to anomaly detection for the detection of port scans. The results show the Dendritic Cell Algorithm is sucessful at detecting port scans.

  9. Learning rules and persistence of dendritic spines.

    Science.gov (United States)

    Kasai, Haruo; Hayama, Tatsuya; Ishikawa, Motoko; Watanabe, Satoshi; Yagishita, Sho; Noguchi, Jun

    2010-07-01

    Structural plasticity of dendritic spines underlies learning, memory and cognition in the cerebral cortex. We here summarize fifteen rules of spine structural plasticity, or 'spine learning rules.' Together, they suggest how the spontaneous generation, selection and strengthening (SGSS) of spines represents the physical basis for learning and memory. This SGSS mechanism is consistent with Hebb's learning rule but suggests new relations between synaptic plasticity and memory. We describe the cellular and molecular bases of the spine learning rules, such as the persistence of spine structures and the fundamental role of actin, which polymerizes to form a 'memory gel' required for the selection and strengthening of spine synapses. We also discuss the possible link between transcriptional and translational regulation of structural plasticity. The SGSS mechanism and spine learning rules elucidate the integral nature of synaptic plasticity in neuronal network operations within the actual brain tissue.

  10. Harnessing dendritic cells in inflammatory skin diseases.

    Science.gov (United States)

    Chu, Chung-Ching; Di Meglio, Paola; Nestle, Frank O

    2011-02-01

    The skin immune system harbors a complex network of dendritic cells (DCs). Recent studies highlight a diverse functional specialization of skin DC subsets. In addition to generating cellular and humoral immunity against pathogens, skin DCs are involved in tolerogenic mechanisms to ensure the maintenance of immune homeostasis, as well as in pathogenesis of chronic inflammation in the skin when excessive immune responses are initiated and unrestrained. Harnessing DCs by directly targeting DC-derived molecules or selectively modulate DC subsets is a convincing strategy to tackle inflammatory skin diseases. In this review we discuss recent advances underlining the functional specialization of skin DCs and discuss the potential implication for future DC-based therapeutic strategies.

  11. Harnessing Dendritic Cells for Tumor Antigen Presentation

    Energy Technology Data Exchange (ETDEWEB)

    Nierkens, Stefan [Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Geert Grooteplein 28, Nijmegen 6525 GA (Netherlands); Janssen, Edith M., E-mail: edith.janssen@cchmc.org [Division of Molecular Immunology, Cincinnati Children' s Hospital Research Foundation, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229 (United States)

    2011-04-26

    Dendritic cells (DC) are professional antigen presenting cells that are crucial for the induction of anti-tumor T cell responses. As a consequence, research has focused on the harnessing of DCs for therapeutic interventions. Although current strategies employing ex vivo-generated and tumor-antigen loaded DCs have been proven feasible, there are still many obstacles to overcome in order to improve clinical trial successes and offset the cost and complexity of customized cell therapy. This review focuses on one of these obstacles and a pivotal step for the priming of tumor-specific CD8{sup +} and CD4{sup +} T cells; the in vitro loading of DCs with tumor antigens.

  12. Modulation of tolerogenic dendritic cells and autoimmunity.

    Science.gov (United States)

    Kim, Sun Jung; Diamond, Betty

    2015-05-01

    A key function of dendritic cells (DCs) is to induce either immune tolerance or immune activation. Many new DC subsets are being recognized, and it is now clear that each DC subset has a specialized function. For example, different DC subsets may express different cell surface molecules and respond differently to activation by secretion of a unique cytokine profile. Apart from intrinsic differences among DC subsets, various immune modulators in the microenvironment may influence DC function; inappropriate DC function is closely related to the development of immune disorders. The most exciting recent advance in DC biology is appreciation of human DC subsets. In this review, we discuss functionally different mouse and human DC subsets both in lymphoid organs and non-lymphoid organs, the molecules that regulate DC function, and the emerging understanding of the contribution of DCs to autoimmune diseases.

  13. Unsteady growth of ammonium chloride dendrites

    Science.gov (United States)

    Martyushev, L. M.; Terentiev, P. S.; Soboleva, A. S.

    2016-02-01

    Growth of ammonium chloride dendrites from aqueous solution is experimentally investigated. The growth rate υ and the radius ρ of curvature of branches are measured as a function of the relative supersaturation Δ for steady and unsteady growth conditions. It is shown that the experimental results are quantitatively described by the dependences ρ=a/Δ+b, υ=cΔ2, where the factors for primary branches are a=(1.3±0.2)·10-7 m, b=(2.5±0.4)·10-7 m, and c=(2.2±0.3)·10-4 m/s. The factor c is found to be approximately 7 times smaller for the side branches than that for the primary branches.

  14. Role of Dendritic Cells in Immune Dysfunction

    Science.gov (United States)

    Savary, Cherylyn A.

    1998-01-01

    The specific aims of the project were: (1) Application of the NASA bioreactor to enhance cytokine-regulated proliferation and maturation of dendritic cells (DC). (2) Compare the frequency and function of DC in normal donors and immunocompromised cancer patients. (3) Analyze the effectiveness of cytokine therapy and DC-assisted immunotherapy (using bioreactor-expanded DC) in a murine model of experimental fungal disease. Our investigations have provided new insight into DC immunobiology and have led to the development of methodology to evaluate DC in blood of normal donors and patients. Information gained from these studies has broadened our understanding of possible mechanisms involved in the immune dysfunction of space travelers and earth-bound cancer patients, and could contribute to the design of novel therapies to restore/preserve immunity in these individuals. Several new avenues of investigation were also revealed. The results of studies completed during Round 2 are summarized.

  15. Dendritic Kv3.3 potassium channels in cerebellar purkinje cells regulate generation and spatial dynamics of dendritic Ca2+ spikes.

    Science.gov (United States)

    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.

  16. Differential Gene Expression in Thrombomodulin (TM; CD141)+ and TM− Dendritic Cell Subsets

    OpenAIRE

    Masaaki Toda; Zhifei Shao; Yamaguchi, Ken D.; Takehiro Takagi; Corina N D'Alessandro-Gabazza; Osamu Taguchi; Hugh Salamon; Leung, Lawrence L. K.; Gabazza, Esteban C.; John Morser

    2013-01-01

    Previously we have shown in a mouse model of bronchial asthma that thrombomodulin can convert immunogenic conventional dendritic cells into tolerogenic dendritic cells while inducing its own expression on their cell surface. Thrombomodulin(+) dendritic cells are tolerogenic while thrombomodulin(-) dendritic cells are pro-inflammatory and immunogenic. Here we hypothesized that thrombomodulin treatment of dendritic cells would modulate inflammatory gene expression. Murine bone marrow-derived de...

  17. Dendritic cells a double-edge sword in autoimmune responses

    Directory of Open Access Journals (Sweden)

    Giada eAmodio

    2012-08-01

    Full Text Available Dendritic cells (DC are antigen-presenting cells that play a pivotal role in regulating innate and adaptive immune responses. In autoimmunity, DC act as a double-edged sword since on one hand they initiate adaptive self-reactive responses and on the other they play a pivotal role in promoting and maintaining tolerance. Thus, DC are the most important cells in either triggering self-specific responses or in negatively regulating auto-reactive responses. DC in the steady state or specialized subsets of DC, named tolerogenic DC, are involved in the latter function. Clinical and experimental evidence indicate that prolonged presentation of self-antigens by DC is crucial for the development of destructive autoimmune diseases, and defects in tolerogenic DC functions contribute to eradication of self-tolerance. In recent years, DC have emerged as therapeutic targets for limiting their immunogenicity against self-antigens, while tolerogenic DC have been conceived as therapeutic tools to restore tolerance. The purpose of this review is to give a general overview of the current knowledge on the pathogenic role of DC in patients affected by autoimmune diseases. In addition, the protective role of tolerogenic DC will be addressed. The currently applied strategies to block immune activation or to exploit the tolerogenic potential of DC will be discussed.

  18. A new mechanism for dendritic pattern formation in dense systems

    Science.gov (United States)

    Oikawa, Noriko; Kurita, Rei

    2016-06-01

    Patterns are often formed when particles cluster: Since patterns reflect the connectivity of different types of material, the emergence of patterns affects the physical and chemical properties of systems and shares a close relationship to their macroscopic functions. A radial dendritic pattern (RDP) is observed in many systems such as snow crystals, polymer crystals and biological systems. Although most of these systems are considered as dense particle suspensions, the mechanism of RDP formation in dense particle systems is not yet understood. It should be noted that the diffusion limited aggregation model is not applicable to RDP formation in dense systems, but in dilute particle systems. Here, we propose a simple model that exhibits RDP formation in a dense particle system. The model potential for the inter-particle interaction is composed of two parts, a repulsive and an attractive force. The repulsive force is applied to all the particles all the time and the attractive force is exerted only among particles inside a circular domain, which expands at a certain speed as a wave front propagating from a preselected centre. It is found that an RDP is formed if the velocity of the wave front that triggers the attractive interaction is of the same order of magnitude as the time scale defined by the aggregation speed.

  19. Unique proteomic signatures distinguish macrophages and dendritic cells.

    Directory of Open Access Journals (Sweden)

    Lev Becker

    Full Text Available Monocytes differentiate into heterogeneous populations of tissue macrophages and dendritic cells (DCs that regulate inflammation and immunity. Identifying specific populations of myeloid cells in vivo is problematic, however, because only a limited number of proteins have been used to assign cellular phenotype. Using mass spectrometry and bone marrow-derived cells, we provided a global view of the proteomes of M-CSF-derived macrophages, classically and alternatively activated macrophages, and GM-CSF-derived DCs. Remarkably, the expression levels of half the plasma membrane proteins differed significantly in the various populations of cells derived in vitro. Moreover, the membrane proteomes of macrophages and DCs were more distinct than those of classically and alternatively activated macrophages. Hierarchical cluster and dual statistical analyses demonstrated that each cell type exhibited a robust proteomic signature that was unique. To interrogate the phenotype of myeloid cells in vivo, we subjected elicited peritoneal macrophages harvested from wild-type and GM-CSF-deficient mice to mass spectrometric and functional analysis. Unexpectedly, we found that peritoneal macrophages exhibited many features of the DCs generated in vitro. These findings demonstrate that global analysis of the membrane proteome can help define immune cell phenotypes in vivo.

  20. Chronic Ethanol During Adolescence Impacts Corticolimbic Dendritic Spines and Behavior.

    Science.gov (United States)

    Jury, Nicholas J; Pollack, Gabrielle A; Ward, Meredith J; Bezek, Jessica L; Ng, Alexandra J; Pinard, Courtney R; Bergstrom, Hadley C; Holmes, Andrew

    2017-07-01

    Risk for alcohol use disorders (AUDs) in adulthood is linked to alcohol drinking during adolescence, but understanding of the neural and behavioral consequences of alcohol exposure during adolescence remains incomplete. Here, we examined the neurobehavioral impact of adolescent chronic intermittent EtOH (CIE) vapor exposure in mice. C57BL/6J-background Thy1-EGFP mice were CIE-exposed during adolescence or adulthood and examined, as adults, for alterations in the density and morphology of dendritic spines in infralimbic (IL) cortex, prelimbic (PL) cortex, and basolateral amygdala (BLA). In parallel, adolescent- and adult-exposed C57BL/6J mice were tested as adults for 2-bottle EtOH drinking, sensitivity to EtOH intoxication (loss of righting reflex [LORR]), blood EtOH clearance, and measures of operant responding for food reward. CIE during adolescence decreased IL neuronal spine density and increased the head width of relatively wide-head IL and BLA spines, whereas CIE decreased head width of relatively narrow-head BLA spines. Adolescents had higher EtOH consumption prior to CIE than adults, while CIE during adulthood, but not adolescence, increased EtOH consumption relative to pre-CIE baseline. CIE produced a tolerance-like decrease in LORR sensitivity to EtOH challenge, irrespective of the age at which mice received CIE exposure. Mice exposed to CIE during adolescence, but not adulthood, required more sessions than AIR controls to reliably respond for food reward on a fixed-ratio (FR) 1, but not subsequent FR3, reinforcement schedule. On a progressive ratio reinforcement schedule, break point responding was higher in the adolescent- than the adult-exposed mice, regardless of CIE. Finally, footshock punishment markedly suppressed responding for reward in all groups. Exposure to CIE during adolescence altered dendritic spine density and morphology in IL and BLA neurons, in parallel with a limited set of behavioral alterations. Together, these data add to growing

  1. Cyclin-Dependent Kinase 5 Regulates Dendritic Spine Formation and Maintenance of Cortical Neuron in the Mouse Brain.

    Science.gov (United States)

    Mita, Naoki; He, Xiaojuan; Sasamoto, Kodai; Mishiba, Tomohide; Ohshima, Toshio

    2016-03-01

    Cyclin-dependent kinase 5 (Cdk5) activity is dependent on its association with 1 of 2 neuron-specific activators, p35 or p39. Cdk5 and its activators play an important role in brain development as well as higher functions like synaptic plasticity, learning, and memory. Reduction in p35 was reported in postmortem schizophrenia brain, in which reduced dendritic spine density was observed. Previous in vitro experiments have shown that Cdk5 is involved in dendritic spine formation, although in vivo evidence is limited. We examined dendritic spine formation in inducible-p35 conditional knockout (p35 cKO); p39 KO mice. When we deleted the p35 gene either during early postnatal days or at adult stage, we observed reduced spine densities of layer V neurons in the cerebral cortex and CA1 pyramidal neurons in the hippocampus. We further generated CA1-specific p35 conditional knockout (CA1-p35 cKO) mice and also CA1-p35 cKO; p39 KO mice in which have specific deletion of p35 in the CA1 region of hippocampus. We found a greater reduction in spine densities in CA1 pyramidal neurons in CA1-p35 cKO; p39 KO mice than in CA1-p35 cKO mice. These results indicate that dendritic spine formation and neuronal maintenance are dependent on Cdk5 activity.

  2. A dry method to synthesize dendritic Ag2Se nanostructures utilizing CdSe quantum dots and Ag thin films

    Science.gov (United States)

    Hu, Lian; Zhang, Bingpo; Xu, Tianning; Li, Ruifeng; Wu, Huizhen

    2015-01-01

    Dendritic Ag2Se nanostructures are synthesized in a dry environment by UV irradiating the hybrids composed of CdSe quantum dots (QDs) and silver (Ag). UV irradiation on CdSe QDs induces a photooxidation effect on the QD surface and leads to the formation of SeO2 components. Then SeO2 reacts with the Ag atoms in either Ag film or QD layer to produce the Ag2Se. The growth mechanism of Ag2Se dendrites on solid Ag films is explored and explained by a diffusion limited aggregation model in which the QD layer provides enough freedom for Ag2Se motion. Since the oxidation of the CdSe QDs is the critical step for the Ag2Se dendrites formation this dry chemical interaction between QDs and Ag film can be applied in the study of the QD surface chemical properties. With this dry synthesis method, the Ag2Se dendrites can also be facilely formed at the designed area on Ag substrates.

  3. CD163 positive subsets of blood dendritic cells

    DEFF Research Database (Denmark)

    Maniecki, Maciej Bogdan; Møller, Holger Jon; Moestrup, Søren Kragh

    2006-01-01

    CD163 and CD91 are scavenging receptors with highly increased expression during the differentiation of monocytes into the anti-inflammatory macrophage phenotype. In addition, CD91 is expressed in monocyte-derived dendritic cells (MoDCs), where the receptor is suggested to be important for interna......CD163 and CD91 are scavenging receptors with highly increased expression during the differentiation of monocytes into the anti-inflammatory macrophage phenotype. In addition, CD91 is expressed in monocyte-derived dendritic cells (MoDCs), where the receptor is suggested to be important...... for internalization of CD91-targeted antigens to be presented on the dendritic cell surface for T-cell stimulation. Despite their overlap in functionality, the expression of CD91 and CD163 has never been compared and the expression of CD163 in the monocyte-dendritic cell lineage is not yet characterized. CD163...

  4. Actin Remodeling and Polymerization Forces Control Dendritic Spine Morphology

    CERN Document Server

    Miermans, Karsten; Storm, Cornelis; Hoogenraad, Casper

    2015-01-01

    Dendritic spines are small membranous structures that protrude from the neuronal dendrite. Each spine contains a synaptic contact site that may connect its parent dendrite to the axons of neighboring neurons. Dendritic spines are markedly distinct in shape and size, and certain types of stimulation prompt spines to evolve, in fairly predictable fashion, from thin nascent morphologies to the mushroom-like shapes associated with mature spines. This striking progression is coincident with the (re)configuration of the neuronal network during early development, learning and memory formation, and has been conjectured to be part of the machinery that encodes these processes at the scale of individual neuronal connections. It is well established that the structural plasticity of spines is strongly dependent upon the actin cytoskeleton inside the spine. A general framework that details the precise role of actin in directing the transitions between the various spine shapes is lacking. We address this issue, and present...

  5. Dendritic Cells, Viruses, and the Development of Atopic Disease

    Directory of Open Access Journals (Sweden)

    Jonathan S. Tam

    2012-01-01

    Full Text Available Dendritic cells are important residents of the lung environment. They have been associated with asthma and other inflammatory diseases of the airways. In addition to their antigen-presenting functions, dendritic cells have the ability to modulate the lung environment to promote atopic disease. While it has long been known that respiratory viral infections associate with the development and exacerbation of atopic diseases, the exact mechanisms have been unclear. Recent studies have begun to show the critical importance of the dendritic cell in this process. This paper focuses on these data demonstrating how different populations of dendritic cells are capable of bridging the adaptive and innate immune systems, ultimately leading to the translation of viral illness into atopic disease.

  6. Observation of dendritic growth under the influence of forced convection

    Science.gov (United States)

    Roshchupkina, O.; Shevchenko, N.; Eckert, S.

    2015-06-01

    The directional solidification of Ga-25wt%In alloys within a Hele-Shaw cell was visualized by X-ray radioscopy. The investigations are focused on the impact of melt convection on the dendritic growth. Natural convection occurs during a bottom up solidification because lighter solute is rejected during crystallization. Forced convection was produced by a specific electromagnetic pump. The direction of forced melt flow is almost horizontal at the solidification front. Melt flow induces various effects on grain morphology primarily caused by convective transport of solute, such as a facilitation of the growth of primary trunks or lateral branches, dendrite remelting, fragmentation or freckle formation depending on the dendrite orientation, the flow direction and intensity. Forced flow eliminates solutal plumes and damps local fluctuations of solute. A preferential growth of the secondary arms occurs at the upstream side of the dendrites, whereas high solute concentration at the downstream side inhibits the formation of secondary branches.

  7. Derivation and Utilization of Functional CD8(+) Dendritic Cell Lines.

    Science.gov (United States)

    Pigni, Matteo; Ashok, Devika; Acha-Orbea, Hans

    2016-01-01

    It is notoriously difficult to obtain large quantities of non-activated dendritic cells ex vivo. For this reason, we produced and characterized a mouse model expressing the large T oncogene under the CD11c promoter (Mushi mice), in which CD8α(+) dendritic cells transform after 4 months. We derived a variety of stable cell lines from these primary lines. These cell lines reproducibly share with freshly isolated dendritic cells most surface markers, mRNA and protein expression, and all tested biological functions. Cell lines can be derived from various strains and knockout mice and can be easily transduced with lentiviruses. In this article, we describe the derivation, culture, and lentiviral transduction of these dendritic cell lines.

  8. Transcriptional profiling of dendritic cells matured in different osmolarities

    Directory of Open Access Journals (Sweden)

    Federica Chessa

    2016-03-01

    Full Text Available Tissue-specific microenvironments shape the fate of mononuclear phagocytes [1–3]. Interstitial osmolarity is a tissue biophysical parameter which considerably modulates the phenotype and function of dendritic cells [4]. In the present report we provide a detailed description of our experimental workflow and bioinformatic analysis applied to our gene expression dataset (GSE72174, aiming to investigate the influence of different osmolarity conditions on the gene expression signature of bone marrow-derived dendritic cells. We established a cell culture system involving murine bone marrow cells, cultured under different NaCl-induced osmolarity conditions in the presence of the dendritic cell growth factor GM-CSF. Gene expression analysis was applied to mature dendritic cells (day 7 developed in different osmolarities, with and without prior stimulation with the TLR2/4 ligand LPS.

  9. CD56 marks human dendritic cell subsets with cytotoxic potential

    NARCIS (Netherlands)

    Roothans, D.; Smits, E.; Lion, E.; Tel, J.; Anguille, S.

    2013-01-01

    Human plasmacytoid and myeloid dendritic cells (DCs), when appropriately stimulated, can express the archetypal natural killer (NK)-cell surface marker CD56. In addition to classical DC functions, CD56+ DCs are endowed with an unconventional cytotoxic capacity.

  10. Metabolism Is Central to Tolerogenic Dendritic Cell Function

    Directory of Open Access Journals (Sweden)

    Wen Jing Sim

    2016-01-01

    Full Text Available Immunological tolerance is a fundamental tenant of immune homeostasis and overall health. Self-tolerance is a critical component of the immune system that allows for the recognition of self, resulting in hyporeactivity instead of immunogenicity. Dendritic cells are central to the establishment of dominant immune tolerance through the secretion of immunosuppressive cytokines and regulatory polarization of T cells. Cellular metabolism holds the key to determining DC immunogenic or tolerogenic cell fate. Recent studies have demonstrated that dendritic cell maturation leads to a shift toward a glycolytic metabolic state and preferred use of glucose as a carbon source. In contrast, tolerogenic dendritic cells favor oxidative phosphorylation and fatty acid oxidation. This dichotomous metabolic reprogramming of dendritic cells drives differential cellular function and plays a role in pathologies, such as autoimmune disease. Pharmacological alterations in metabolism have promising therapeutic potential.

  11. A Convenient Synthetic Method of Metal Dendritic Porphyrins

    Institute of Scientific and Technical Information of China (English)

    Wen Bin CUI; Jie ZHOU; Lei CHEN; Xiao Bin DENG; Chun GUO

    2006-01-01

    A convenient synthetic method of metal dendritic porphyrins through the convergent synthetic strategy is described. The porphyrin core were linked with the synthetic fragments by forming ether or ester bonds to give five target compounds were prepared.

  12. NUMERICAL SIMULATION OF SUCCINONITRITE DENDRITIC GROWTH IN A FORCED FLOW

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Numerical simulation based on phase field method is performed to describe solidifica-tion process of pure material in a free or forced flow. The evolution of the interface is showed, and the effects of mesh grid and flow velocity on succinonitrite shape are studied. These results indicate that crystal grows into an equiaxial dendrite in a free flow and into an asymmetrical dendritic in a forced flow. With increasing flow velo-city, the upstream dendritic arm tip grows faster and the downstream arm grows slower. However, the evolution of the perpendicular tip has no significant change. In addition, mesh grid has no influence on dendritic growth shape when mesh grid is above 300×300.

  13. 3D Modeling and Simulation of Dendritic Growth during Solidification

    Institute of Scientific and Technical Information of China (English)

    Zuojian LIANG; Qingyan XU; Baicheng LIU

    2003-01-01

    A mathematical model for the three-dimensional simulation of free dendritic growth and microstructure evolutionwas developed based on the growth mechanism of crystal grains and basic transfer equations such as heat, massand momentum transfer equations. Ma

  14. A Simple Transfer Function for Nonlinear Dendritic Integration

    Directory of Open Access Journals (Sweden)

    Matt eSingh

    2015-08-01

    Full Text Available Relatively recent advances in patch clamp recordings and iontophoresis have enabled unprecedented study of neuronal post-synaptic integration (dendritic integration. Findings support a separate layer of integration in the dendritic branches before potentials reach the cell’s soma. While integration between branches obeys previous linear assumptions, proximal inputs within a branch produce threshold nonlinearity, which some authors have likened to the sigmoid function. Here we show the implausibility of a sigmoidal relation and present a more realistic transfer function in both an elegant artificial form and a biophysically derived form that further considers input locations along the dendritic arbor. As the distance between input locations determines their ability to produce nonlinear interactions, models incorporating dendritic topology are essential to understanding the computational power afforded by these early stages of integration. We use the biophysical transfer function to emulate empirical data using biophysical parameters and describe the conditions under which the artificial and biophysically derived forms are equivalent.

  15. Barriers in the brain: resolving dendritic spine morphology and compartmentalization

    OpenAIRE

    2014-01-01

    Dendritic spines are micron-sized protrusions that harbor the majority of excitatory synapses in the central nervous system. The head of the spine is connected to the dendritic shaft by a 50–400 nm thin membrane tube, called the spine neck, which has been hypothesized to confine biochemical and electric signals within the spine compartment. Such compartmentalization could minimize interspinal crosstalk and thereby support spine-specific synapse plasticity. However, to what extent compartmenta...

  16. Dendritic biomimicry: microenvironmental hydrogen-bonding effects on tryptophan fluorescence.

    Science.gov (United States)

    Koenig, S; Müller, L; Smith, D K

    2001-03-02

    Two series of dendritically modified tryptophan derivatives have been synthesised and their emission spectra measured in a range of different solvents. This paper presents the syntheses of these novel dendritic structures and discusses their emission spectra in terms of both solvent and dendritic effects. In the first series of dendrimers, the NH group of the indole ring is available for hydrogen bonding, whilst in the second series, the indole NH group has been converted to NMe. Direct comparison of the emission wavelengths of analogous NH and NMe derivatives indicates the importance of the Kamlet-Taft solvent beta3 parameter, which reflects the ability of the solvent to accept a hydrogen bond from the NH group, an effect not possible for the NMe series of dendrimers. For the NH dendrimers, the attachment of a dendritic shell to the tryptophan subunit leads to a red shift in emission wavelength. This dendritic effect only operates in non-hydrogen-bonding solvents. For the NMe dendrimers, however, the attachment of a dendritic shell has no effect on the emission spectra of the indole ring. This proves the importance of hydrogen bonding between the branched shell and the indole NH group in causing the dendritic effect. This is the first time a dendritic effect has been unambiguously assigned to individual hydrogen-bonding interactions and indicates that such intramolecular interactions are important in dendrimers, just as they are in proteins. Furthermore, this paper sheds light on the use of tryptophan residues as a probe of the microenvironment within proteins--in particular, it stresses the importance of hydrogen bonds formed by the indole NH group.

  17. Voltage-sensitive dye recording from axons, dendrites and dendritic spines of individual neurons in brain slices.

    Science.gov (United States)

    Popovic, Marko; Gao, Xin; Zecevic, Dejan

    2012-11-29

    Understanding the biophysical properties and functional organization of single neurons and how they process information is fundamental for understanding how the brain works. The primary function of any nerve cell is to process electrical signals, usually from multiple sources. Electrical properties of neuronal processes are extraordinarily complex, dynamic, and, in the general case, impossible to predict in the absence of detailed measurements. To obtain such a measurement one would, ideally, like to be able to monitor, at multiple sites, subthreshold events as they travel from the sites of origin on neuronal processes and summate at particular locations to influence action potential initiation. This goal has not been achieved in any neuron due to technical limitations of measurements that employ electrodes. To overcome this drawback, it is highly desirable to complement the patch-electrode approach with imaging techniques that permit extensive parallel recordings from all parts of a neuron. Here, we describe such a technique - optical recording of membrane potential transients with organic voltage-sensitive dyes (V(m)-imaging) - characterized by sub-millisecond and sub-micrometer resolution. Our method is based on pioneering work on voltage-sensitive molecular probes (2). Many aspects of the initial technology have been continuously improved over several decades (3, 5, 11). Additionally, previous work documented two essential characteristics of V(m)-imaging. Firstly, fluorescence signals are linearly proportional to membrane potential over the entire physiological range (-100 mV to +100 mV; (10, 14, 16)). Secondly, loading neurons with the voltage-sensitive dye used here (JPW 3028) does not have detectable pharmacological effects. The recorded broadening of the spike during dye loading is completely reversible (4, 7). Additionally, experimental evidence shows that it is possible to obtain a significant number (up to hundreds) of recordings prior to any detectable

  18. Dendritic bundles, minicolumns, columns, and cortical output units

    Directory of Open Access Journals (Sweden)

    Giorgio Innocenti

    2010-03-01

    Full Text Available The search for the fundamental building block of the cerebral cortex has highlighted three structures, perpendicular to the cortical surface: i columns of neurons with radially invariant response properties, e.g., receptive field position, sensory modality, stimulus orientation or direction, frequency tuning etc. ii minicolumns of radially aligned cell bodies and iii bundles, constituted by the apical dendrites of pyramidal neurons with cell bodies in different layers. The latter were described in detail, and sometimes quantitatively, in several species and areas. It was recently suggested that the dendritic bundles consist of apical dendrites belonging to neurons projecting their axons to specific targets. We review the concept above and suggest that another structural and computational unit of cerebral cortex is the cortical output unit (COU, i.e. an assembly of bundles of apical dendrites and their parent cell bodies including each of the outputs to distant cortical or subcortical structures, of a given cortical locus (area or part of an area. This somato-dendritic assembly receives inputs some of which are common to the whole assembly and determine its radially invariant response properties, others are specific to one or more dendritic bundles, and determine the specific response signature of neurons in the different cortical layers and projecting to different targets.

  19. An extracellular adhesion molecule complex patterns dendritic branching and morphogenesis.

    Science.gov (United States)

    Dong, Xintong; Liu, Oliver W; Howell, Audrey S; Shen, Kang

    2013-10-10

    Robust dendrite morphogenesis is a critical step in the development of reproducible neural circuits. However, little is known about the extracellular cues that pattern complex dendrite morphologies. In the model nematode Caenorhabditis elegans, the sensory neuron PVD establishes stereotypical, highly branched dendrite morphology. Here, we report the identification of a tripartite ligand-receptor complex of membrane adhesion molecules that is both necessary and sufficient to instruct spatially restricted growth and branching of PVD dendrites. The ligand complex SAX-7/L1CAM and MNR-1 function at defined locations in the surrounding hypodermal tissue, whereas DMA-1 acts as the cognate receptor on PVD. Mutations in this complex lead to dramatic defects in the formation, stabilization, and organization of the dendritic arbor. Ectopic expression of SAX-7 and MNR-1 generates a predictable, unnaturally patterned dendritic tree in a DMA-1-dependent manner. Both in vivo and in vitro experiments indicate that all three molecules are needed for interaction.

  20. Dendritic position is a major determinant of presynaptic strength.

    Science.gov (United States)

    de Jong, Arthur P H; Schmitz, Sabine K; Toonen, Ruud F G; Verhage, Matthijs

    2012-04-16

    Different regulatory principles influence synaptic coupling between neurons, including positional principles. In dendrites of pyramidal neurons, postsynaptic sensitivity depends on synapse location, with distal synapses having the highest gain. In this paper, we investigate whether similar rules exist for presynaptic terminals in mixed networks of pyramidal and dentate gyrus (DG) neurons. Unexpectedly, distal synapses had the lowest staining intensities for vesicular proteins vGlut, vGAT, Synaptotagmin, and VAMP and for many nonvesicular proteins, including Bassoon, Munc18, and Syntaxin. Concomitantly, distal synapses displayed less vesicle release upon stimulation. This dependence of presynaptic strength on dendritic position persisted after chronically blocking action potential firing and postsynaptic receptors but was markedly reduced on DG dendrites compared with pyramidal dendrites. These data reveal a novel rule, independent of neuronal activity, which regulates presynaptic strength according to dendritic position, with the strongest terminals closest to the soma. This gradient is opposite to postsynaptic gradients observed in pyramidal dendrites, and different cell types apply this rule to a different extent.

  1. SIRT1 regulates dendritic development in hippocampal neurons.

    Directory of Open Access Journals (Sweden)

    Juan F Codocedo

    Full Text Available Dendritic arborization is required for proper neuronal connectivity. SIRT1, a NAD+ dependent histone deacetylase, has been associated to ageing and longevity, which in neurons is linked to neuronal differentiation and neuroprotection. In the present study, the role of SIRT1 in dendritic development was evaluated in cultured hippocampal neurons which were transfected at 3 days in vitro with a construct coding for SIRT1 or for the dominant negative SIRT1H363Y, which lacks the catalytic activity. Neurons overexpressing SIRT1 showed an increased dendritic arborization, while neurons overexpressing SIRT1H363Y showed a reduction in dendritic arbor complexity. The effect of SIRT1 was mimicked by treatment with resveratrol, a well known activator of SIRT1, which has no effect in neurons overexpressing SIRT1H363Y indicating that the effect of resveratrol was specifically mediated by SIRT1. Moreover, hippocampal neurons overexpressing SIRT1 were resistant to dendritic dystrophy induced by Aβ aggregates, an effect that was dependent on the deacetylase activity of SIRT1. Our findings indicate that SIRT1 plays a role in the development and maintenance of dendritic branching in hippocampal neurons, and suggest that these effects are mediated by the ROCK signaling pathway.

  2. SIRT1 Regulates Dendritic Development in Hippocampal Neurons

    Science.gov (United States)

    Godoy, Juan A.; Varela-Nallar, Lorena; Inestrosa, Nibaldo C.

    2012-01-01

    Dendritic arborization is required for proper neuronal connectivity. SIRT1, a NAD+ dependent histone deacetylase, has been associated to ageing and longevity, which in neurons is linked to neuronal differentiation and neuroprotection. In the present study, the role of SIRT1 in dendritic development was evaluated in cultured hippocampal neurons which were transfected at 3 days in vitro with a construct coding for SIRT1 or for the dominant negative SIRT1H363Y, which lacks the catalytic activity. Neurons overexpressing SIRT1 showed an increased dendritic arborization, while neurons overexpressing SIRT1H363Y showed a reduction in dendritic arbor complexity. The effect of SIRT1 was mimicked by treatment with resveratrol, a well known activator of SIRT1, which has no effect in neurons overexpressing SIRT1H363Y indicating that the effect of resveratrol was specifically mediated by SIRT1. Moreover, hippocampal neurons overexpressing SIRT1 were resistant to dendritic dystrophy induced by Aβ aggregates, an effect that was dependent on the deacetylase activity of SIRT1. Our findings indicate that SIRT1 plays a role in the development and maintenance of dendritic branching in hippocampal neurons, and suggest that these effects are mediated by the ROCK signaling pathway. PMID:23056585

  3. Dendritic cells and their role in periodontal disease.

    Science.gov (United States)

    Wilensky, A; Segev, H; Mizraji, G; Shaul, Y; Capucha, T; Shacham, M; Hovav, A-H

    2014-03-01

    T cells, particularly CD4+ T cells, play a central role in both progression and control of periodontal disease, whereas the contribution of the various CD4+ T helper subsets to periodontal destruction remains controversial, the activation, and regulation of these cells is orchestrated by dendritic cells. As sentinels of the oral mucosa, dendritic cells encounter and capture oral microbes, then migrate to the lymph node where they regulate the differentiation of CD4+ T cells. It is thus clear that dendritic cells are of major importance in the course of periodontitis, as they hold the immunological cues delivered by the pathogen and the surrounding environment, allowing them to induce destructive immunity. In recent years, advanced immunological techniques and new mouse models have facilitated in vivo studies that have provided new insights into the developmental and functional aspects of dendritic cells. This progress has also benefited the characterization of oral dendritic cells, as well as to their function in periodontitis. Here, we provide an overview of the various gingival dendritic cell subsets and their distribution, while focusing on their role in periodontal bone loss.

  4. Ovariectomy attenuates dendritic growth in hormone-sensitive spinal motoneurons.

    Science.gov (United States)

    Hebbeler, S L; Verhovshek, T; Sengelaub, D R

    2001-09-15

    The lumbar spinal cord of rats contains the sexually dimorphic, steroid-sensitive spinal nucleus of the bulbocavernosus (SNB). Dendritic development of SNB motoneurons in male rats is biphasic, initially showing exuberant growth through 4 weeks of age followed by a retraction to mature lengths by 7 weeks of age. The initial growth is steroid dependent, attenuated by castration or aromatase inhibition, and supported by hormone replacement. Dendritic retraction is also steroid sensitive and can be prevented by testosterone treatment, but is unaffected by aromatase inhibition. Together, these results suggest a role for estrogens during the initial growth phase of SNB development. In this study, we tested whether ovarian hormones could support SNB somal and dendritic development. Motoneuron morphology was assessed in normal males and in females perinatally masculinized with dihydrotestosterone and then either ovariectomized or left intact. SNB motoneurons were retrogradely labeled with cholera toxin-HRP at 4 or 7 weeks of age and reconstructed in three dimensions. Initial growth of SNB dendrites was reduced after ovariectomy in masculinized females. However, no differences in dendritic length were seen at 7 weeks of age between intact and ovariectomized masculinized females, and lengths in both groups were significantly lower than those of normal males. Together with previous findings, these results suggest that estrogens are involved in the early growth of SNB dendrites, but not in their subsequent retraction.

  5. Equine dendritic cells generated with horse serum have enhanced functionality in comparison to dendritic cells generated with fetal bovine serum

    OpenAIRE

    Ziegler, A; Everett, H.; Hamza, E; Garbani, M; Gerber, V.; Marti, E; Steinbach, F

    2016-01-01

    Background: Dendritic cells are professional antigen-presenting cells that play an essential role in the initiation and modulation of T cell responses. They have been studied widely for their potential clinical applications, but for clinical use to be successful, alternatives to xenogeneic substances like fetal bovine serum (FBS) in cell culture need to be found. Protocols for the generation of dendritic cells ex vivo from monocytes are well established for several species, including horses. ...

  6. Direction selectivity is computed by active dendritic integration in retinal ganglion cells.

    Science.gov (United States)

    Sivyer, Benjamin; Williams, Stephen R

    2013-12-01

    Active dendritic integration is thought to enrich the computational power of central neurons. However, a direct role of active dendritic processing in the execution of defined neuronal computations in intact neural networks has not been established. Here we used multi-site electrophysiological recording techniques to demonstrate that active dendritic integration underlies the computation of direction selectivity in rabbit retinal ganglion cells. Direction-selective retinal ganglion cells fire action potentials in response to visual image movement in a preferred direction. Dendritic recordings revealed that preferred-direction moving-light stimuli led to dendritic spike generation in terminal dendrites, which were further integrated and amplified as they spread through the dendritic arbor to the axon to drive action potential output. In contrast, when light bars moved in a null direction, synaptic inhibition vetoed neuronal output by directly inhibiting terminal dendritic spike initiation. Active dendritic integration therefore underlies a physiologically engaged circuit-based computation in the retina.

  7. Dendritic cell-based immunotherapy for myeloid leukemias.

    Science.gov (United States)

    Schürch, Christian M; Riether, Carsten; Ochsenbein, Adrian F

    2013-12-31

    Acute and chronic myeloid leukemia (AML, CML) are hematologic malignancies arising from oncogene-transformed hematopoietic stem/progenitor cells known as leukemia stem cells (LSCs). LSCs are selectively resistant to various forms of therapy including irradiation or cytotoxic drugs. The introduction of tyrosine kinase inhibitors has dramatically improved disease outcome in patients with CML. For AML, however, prognosis is still quite dismal. Standard treatments have been established more than 20 years ago with only limited advances ever since. Durable remission is achieved in less than 30% of patients. Minimal residual disease (MRD), reflected by the persistence of LSCs below the detection limit by conventional methods, causes a high rate of disease relapses. Therefore, the ultimate goal in the treatment of myeloid leukemia must be the eradication of LSCs. Active immunotherapy, aiming at the generation of leukemia-specific cytotoxic T cells (CTLs), may represent a powerful approach to target LSCs in the MRD situation. To fully activate CTLs, leukemia antigens have to be successfully captured, processed, and presented by mature dendritic cells (DCs). Myeloid progenitors are a prominent source of DCs under homeostatic conditions, and it is now well established that LSCs and leukemic blasts can give rise to "malignant" DCs. These leukemia-derived DCs can express leukemia antigens and may either induce anti-leukemic T cell responses or favor tolerance to the leukemia, depending on co-stimulatory or -inhibitory molecules and cytokines. This review will concentrate on the role of DCs in myeloid leukemia immunotherapy with a special focus on their generation, application, and function and how they could be improved in order to generate highly effective and specific anti-leukemic CTL responses. In addition, we discuss how DC-based immunotherapy may be successfully integrated into current treatment strategies to promote remission and potentially cure myeloid leukemias.

  8. Dendritic cell-based immunotherapy for myeloid leukemias

    Directory of Open Access Journals (Sweden)

    Christian Martijn Schürch

    2013-12-01

    Full Text Available Acute and chronic myeloid leukemia (AML, CML are hematologic malignancies arising from oncogene-transformed hematopoietic stem/progenitor cells known as leukemia stem cells (LSCs. LSCs are selectively resistant to various forms of therapy including irradiation or cytotoxic drugs. The introduction of tyrosine kinase inhibitors has dramatically improved disease outcome in patients with CML. For AML, however, prognosis is still quite dismal. Standard treatments have been established more than 20 years ago with only limited advances ever since. Durable remission is achieved in less than 30% of patients. Minimal residual disease (MRD, reflected by the persistence of LSCs below the detection limit by conventional methods, causes a high rate of disease relapses. Therefore, the ultimate goal in the treatment of myeloid leukemia must be the eradication of LSCs. Active immunotherapy, aiming at the generation of leukemia-specific cytotoxic T cells (CTLs, may represent a powerful approach to target LSCs in the MRD situation. To fully activate CTLs, leukemia antigens have to be successfully captured, processed and presented by mature dendritic cells (DCs. Myeloid progenitors are a prominent source of DCs under homeostatic conditions, and it is now well established that LSCs and leukemic blasts can give rise to malignant DCs. These leukemia-derived DCs can express leukemia antigens and may either induce anti-leukemic T cell responses or favor tolerance to the leukemia, depending on co-stimulatory or -inhibitory molecules and cytokines. This review will concentrate on the role of DCs in myeloid leukemia immunotherapy with a special focus on their generation, application and function and how they could be improved in order to generate highly effective and specific anti-leukemic CTL responses. In addition, we discuss how DC-based immunotherapy may be successfully integrated into current treatment strategies to promote remission and potentially cure myeloid

  9. Current limiters

    Energy Technology Data Exchange (ETDEWEB)

    Loescher, D.H. [Sandia National Labs., Albuquerque, NM (United States). Systems Surety Assessment Dept.; Noren, K. [Univ. of Idaho, Moscow, ID (United States). Dept. of Electrical Engineering

    1996-09-01

    The current that flows between the electrical test equipment and the nuclear explosive must be limited to safe levels during electrical tests conducted on nuclear explosives at the DOE Pantex facility. The safest way to limit the current is to use batteries that can provide only acceptably low current into a short circuit; unfortunately this is not always possible. When it is not possible, current limiters, along with other design features, are used to limit the current. Three types of current limiters, the fuse blower, the resistor limiter, and the MOSFET-pass-transistor limiters, are used extensively in Pantex test equipment. Detailed failure mode and effects analyses were conducted on these limiters. Two other types of limiters were also analyzed. It was found that there is no best type of limiter that should be used in all applications. The fuse blower has advantages when many circuits must be monitored, a low insertion voltage drop is important, and size and weight must be kept low. However, this limiter has many failure modes that can lead to the loss of over current protection. The resistor limiter is simple and inexpensive, but is normally usable only on circuits for which the nominal current is less than a few tens of milliamperes. The MOSFET limiter can be used on high current circuits, but it has a number of single point failure modes that can lead to a loss of protective action. Because bad component placement or poor wire routing can defeat any limiter, placement and routing must be designed carefully and documented thoroughly.

  10. Activated protein C modulates the proinflammatory activity of dendritic cells

    Directory of Open Access Journals (Sweden)

    Matsumoto T

    2015-05-01

    Full Text Available Takahiro Matsumoto,1,2* Yuki Matsushima,1* Masaaki Toda,1 Ziaurahman Roeen,1 Corina N D'Alessandro-Gabazza,1,5 Josephine A Hinneh,1 Etsuko Harada,1,3 Taro Yasuma,4 Yutaka Yano,4 Masahito Urawa,1,5 Tetsu Kobayashi,5 Osamu Taguchi,5 Esteban C Gabazza1 1Department of Immunology, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, 2BONAC Corporation, BIO Factory 4F, Fukuoka, 3Iwade Research Institute of Mycology, 4Department of Endocrinology, Diabetes and Metabolism, 5Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Tsu, Mie Prefecture, Japan *These authors contributed equally to this work Background: Previous studies have demonstrated the beneficial activity of activated protein C in allergic diseases including bronchial asthma and rhinitis. However, the exact mechanism of action of activated protein C in allergies is unclear. In this study, we hypothesized that pharmacological doses of activated protein C can modulate allergic inflammation by inhibiting dendritic cells. Materials and methods: Dendritic cells were prepared using murine bone marrow progenitor cells and human peripheral monocytes. Bronchial asthma was induced in mice that received intratracheal instillation of ovalbumin-pulsed dendritic cells. Results: Activated protein C significantly increased the differentiation of tolerogenic plasmacytoid dendritic cells and the secretion of type I interferons, but it significantly reduced lipopolysaccharide-mediated maturation and the secretion of inflammatory cytokines in myeloid dendritic cells. Activated protein C also inhibited maturation and the secretion of inflammatory cytokines in monocyte-derived dendritic cells. Activated protein C-treated dendritic cells were less effective when differentiating naïve CD4 T-cells from Th1 or Th2 cells, and the cellular effect of activated protein C was mediated by its receptors. Mice that received adoptive transfer of activated protein C

  11. Mycobacterium avium subspecies impair dendritic cell maturation.

    Science.gov (United States)

    Basler, Tina; Brumshagen, Christina; Beineke, Andreas; Goethe, Ralph; Bäumer, Wolfgang

    2013-10-01

    Mycobacterium avium ssp. paratuberculosis (MAP) causes Johne's disease, a chronic, granulomatous enteritis of ruminants. Dendritic cells (DC) of the gut are ideally placed to combat invading mycobacteria; however, little is known about their interaction with MAP. Here, we investigated the interaction of MAP and the closely related M. avium ssp. avium (MAA) with murine DC and the effect of infected macrophages on DC maturation. The infection of DC with MAP or MAA induced DC maturation, which differed to that of LPS as maturation was accompanied by higher production of IL-10 and lower production of IL-12. Treatment of maturing DC with supernatants from mycobacteria-infected macrophages resulted in impaired DC maturation, leading to a semi-mature, tolerogenic DC phenotype expressing low levels of MHCII, CD86 and TNF-α after LPS stimulation. Though the cells were not completely differentiated they responded with an increased IL-10 and a decreased IL-12 production. Using recombinant cytokines we provide evidence that the semi-mature DC phenotype results from a combination of secreted cytokines and released antigenic mycobacterial components of the infected macrophage. Our results indicate that MAP and MAA are able to subvert DC function directly by infecting and indirectly via the milieu created by infected macrophages.

  12. Triggering of dendritic cell apoptosis by xanthohumol.

    Science.gov (United States)

    Xuan, Nguyen Thi; Shumilina, Ekaterina; Gulbins, Erich; Gu, Shuchen; Götz, Friedrich; Lang, Florian

    2010-07-01

    Xanthohumol, a flavonoid from beer with anticancer activity is known to trigger apoptosis in a variety of tumor cells. Xanthohumol further has anti-inflammatory activity. However, little is known about the effect of xanthohumol on survival and function of immune cells. The present study thus addressed the effect of xanthohumol on dendritic cells (DCs), key players in the regulation of innate and adaptive immunity. To this end, mouse bone marrow-derived DCs were treated with xanthohumol with subsequent assessment of enzymatic activity of acid sphingomyelinase (Asm), ceramide formation determined with anti-ceramide antibodies in FACS and immunohistochemical analysis, caspase activity utilizing FITC conjugated anti-active caspase 8 or caspase 3 antibodies in FACS and by Western blotting, DNA fragmentation by determining the percentage of cells in the sub-G1 phase and cell membrane scrambling by annexin V binding in FACS analysis. As a result, xanthohumol stimulated Asm, enhanced ceramide formation, activated caspases 8 and 3, triggered DNA fragmentation and led to cell membrane scrambling, all effects virtually absent in DCs from gene targeted mice lacking functional Asm or in wild-type cells treated with sphingomyelinase inhibitor amitriptyline. In conclusion, xanthohumol stimulated Asm leading to caspase activation and apoptosis of bone marrow-derived DCs.

  13. Tumor's other immune targets: dendritic cells.

    Science.gov (United States)

    Esche, C; Lokshin, A; Shurin, G V; Gastman, B R; Rabinowich, H; Watkins, S C; Lotze, M T; Shurin, M R

    1999-08-01

    The induction of apoptosis in T cells is one of several mechanisms by which tumors escape immune recognition. We have investigated whether tumors induce apoptosis in dendritic cells (DC) by co-culture of murine or human DC with different tumor cell lines for 4-48 h. Analysis of DC morphological features, JAM assay, TUNEL, caspase-3-like and transglutaminase activity, Annexin V binding, and DNA fragmentation assays revealed a time- and dose-dependent induction of apoptosis in DC by tumor-derived factors. This finding is both effector and target specific. The mechanism of tumor-induced DC apoptosis involved regulation of Bcl-2 and Bax expression. Double staining of both murine and human tumor tissues confirmed that tumor-associated DC undergo apoptotic death in vivo. DC isolated from tumor tissue showed significantly higher levels of apoptosis as determined by TUNEL assay when compared with DC isolated from spleen. These findings demonstrate that tumors induce apoptosis in DC and suggest a new mechanism of tumor escape from immune recognition. DC protection from apoptosis will lead to improvement of DC-based immunotherapies for cancer and other immune diseases.

  14. Dendritic spine changes associated with normal aging.

    Science.gov (United States)

    Dickstein, D L; Weaver, C M; Luebke, J I; Hof, P R

    2013-10-22

    Given the rapid rate of population aging and the increased incidence of cognitive decline and neurodegenerative diseases with advanced age, it is important to ascertain the determinants that result in cognitive impairment. It is also important to note that much of the aged population exhibit 'successful' cognitive aging, in which cognitive impairment is minimal. One main goal of normal aging studies is to distinguish the neural changes that occur in unsuccessful (functionally impaired) subjects from those of successful (functionally unimpaired) subjects. In this review, we present some of the structural adaptations that neurons and spines undergo throughout normal aging and discuss their likely contributions to electrophysiological properties and cognition. Structural changes of neurons and dendritic spines during aging, and the functional consequences of such changes, remain poorly understood. Elucidating the structural and functional synaptic age-related changes that lead to cognitive impairment may lead to the development of drug treatments that can restore or protect neural circuits and mediate cognition and successful aging.

  15. Giant dendritic carbonaceous particles in Soweto aerosols

    Energy Technology Data Exchange (ETDEWEB)

    Wentzel, M.; Annegarn, H.J.; Helas, G.; Weinbruch, S.; Balogh, A.G.; Sithole, J.S. [Max Planck Institute of Chemistry, Mainz (Germany). Biogeochemistry Dept.

    1999-03-01

    Gravimetric analyses of aerosol filter samples from Soweto, southwest of Johannesburg, have revealed an anomalous mass-size distribution. Instead of the coal fire generated aerosol forming sub-micron aerosols as expected, most of the mass of the winter smoke is in particles greater than 3{mu}m aerodynamic diameter. A high-resolution scanning electron microscope was used to examine coarse and fine-mode aerosol fractions from two contrasting sites in the conurbation. Unanticipated giant carbonaceous conglomerates (10-100 {mu}m diameter), which comprise the bulk of the aerosol mass on the filters examined, were found. The outer shape of the conglomerates tends towards spherical, rather than the branched, chain-like structures of high-temperature soot. Internal structure varies from highly dendritic with 20-nm-wide branches, through a coarser sponge-like structure to an almost solid `melted toffee` irregular surface. Possible modes of formation of these conglomerates are discussed in terms of condensation aerosols conglomeration, and subsequent partial melting or solvent condensation. The occurrence of the giant carbonaceous conglomerates as a general feature of the Soweto winter atmosphere explains the anomalous size-mass distribution results from bulk filter analyses.

  16. Macrophages and Dendritic Cells: Partners in Atherogenesis.

    Science.gov (United States)

    Cybulsky, Myron I; Cheong, Cheolho; Robbins, Clinton S

    2016-02-19

    Atherosclerosis is a complex chronic disease. The accumulation of myeloid cells in the arterial intima, including macrophages and dendritic cells (DCs), is a feature of early stages of disease. For decades, it has been known that monocyte recruitment to the intima contributes to the burden of lesion macrophages. Yet, this paradigm may require reevaluation in light of recent advances in understanding of tissue macrophage ontogeny, their capacity for self-renewal, as well as observations that macrophages proliferate throughout atherogenesis and that self-renewal is critical for maintenance of macrophages in advanced lesions. The rate of atherosclerotic lesion formation is profoundly influenced by innate and adaptive immunity, which can be regulated locally within atherosclerotic lesions, as well as in secondary lymphoid organs, the bone marrow and the blood. DCs are important modulators of immunity. Advances in the past decade have cemented our understanding of DC subsets, functions, hematopoietic origin, gene expression patterns, transcription factors critical for differentiation, and provided new tools for study of DC biology. The functions of macrophages and DCs overlap to some extent, thus it is important to reassess the contributions of each of these myeloid cells taking into account strict criteria of cell identification, ontogeny, and determine whether their key roles are within atherosclerotic lesions or secondary lymphoid organs. This review will highlight key aspect of macrophage and DC biology, summarize how these cells participate in different stages of atherogenesis and comment on complexities, controversies, and gaps in knowledge in the field.

  17. Review of clinical studies on dendritic cell-based vaccination of patients with malignant melanoma: assessment of correlation between clinical response and vaccine parameters

    DEFF Research Database (Denmark)

    Engell-Noerregaard, Lotte; Hansen, Troels Holz; Andersen, Mads Hald

    2009-01-01

    During the past years numerous clinical trials have been carried out to assess the ability of dendritic cell (DC) based immunotherapy to induce clinically relevant immune responses in patients with malignant diseases. A broad range of cancer types have been targeted including malignant melanoma...... which in the disseminated stage have a very poor prognosis and only limited treatment options with moderate effectiveness. Herein we describe the results of a focused search of recently published clinical studies on dendritic cell vaccination in melanoma and review different vaccine parameters which...

  18. Modeling the dendritic evolution and micro-segregation of cast alloy with cellular automaton

    Institute of Scientific and Technical Information of China (English)

    Qiang Li; Dianzhong Li; Bainian Qian

    2004-01-01

    In order to precisely describe the dendritic morphology and micro-segregation during solidification process, a novel continuous model concerning the different physical properties in the solid phase, liquid phase and interface is developed. Coupling the heat and solute diffusion with the transition rules, the dendrite evolution is simulated by cellular automaton method. Then, the solidification microstructure evolution of a small ingot is simulated by using this method. The simulated results indicate that this model can simulate the dendrite growth, show the second dendrite arm and tertiary dendrite arm, and reveal the micro-segregation in the inter-dendritic zones. Furthermore, the columnar-to-equiaxed transition (CET) is predicted.

  19. Regeneration of Drosophila sensory neuron axons and dendrites is regulated by the Akt pathway involving Pten and microRNA bantam

    Science.gov (United States)

    Song, Yuanquan; Ori-McKenney, Kassandra M.; Zheng, Yi; Han, Chun; Jan, Lily Yeh; Jan, Yuh Nung

    2012-01-01

    Both cell-intrinsic and extrinsic pathways govern axon regeneration, but only a limited number of factors have been identified and it is not clear to what extent axon regeneration is evolutionarily conserved. Whether dendrites also regenerate is unknown. Here we report that, like the axons of mammalian sensory neurons, the axons of certain Drosophila dendritic arborization (da) neurons are capable of substantial regeneration in the periphery but not in the CNS, and activating the Akt pathway enhances axon regeneration in the CNS. Moreover, those da neurons capable of axon regeneration also display dendrite regeneration, which is cell type-specific, developmentally regulated, and associated with microtubule polarity reversal. Dendrite regeneration is restrained via inhibition of the Akt pathway in da neurons by the epithelial cell-derived microRNA bantam but is facilitated by cell-autonomous activation of the Akt pathway. Our study begins to reveal mechanisms for dendrite regeneration, which depends on both extrinsic and intrinsic factors, including the PTEN–Akt pathway that is also important for axon regeneration. We thus established an important new model system—the fly da neuron regeneration model that resembles the mammalian injury model—with which to study and gain novel insights into the regeneration machinery. PMID:22759636

  20. Limited Neutrality

    DEFF Research Database (Denmark)

    Nielsen, Morten Ebbe Juul

    2006-01-01

    Article Concerning the prospect of a kind of limited neutrality in place of the standard liberal egalitarian "neutrality of justification."......Article Concerning the prospect of a kind of limited neutrality in place of the standard liberal egalitarian "neutrality of justification."...

  1. Limiting Skepticism

    DEFF Research Database (Denmark)

    Hendricks, Vincent Fella; Symons, John

    2011-01-01

    Skeptics argue that the acquisition of knowledge is impossible given the standing possibility of error. We present the limiting convergence strategy for responding to skepticism and discuss the relationship between conceivable error and an agent’s knowledge in the limit. We argue that the skeptic...

  2. Limited Neutrality

    DEFF Research Database (Denmark)

    Nielsen, Morten Ebbe Juul

    2006-01-01

    Article Concerning the prospect of a kind of limited neutrality in place of the standard liberal egalitarian "neutrality of justification."......Article Concerning the prospect of a kind of limited neutrality in place of the standard liberal egalitarian "neutrality of justification."...

  3. Simultaneous patch-clamping and calcium imaging in developing dendrites.

    Science.gov (United States)

    Kleindienst, Thomas; Lohmann, Christian

    2014-03-01

    Calcium imaging has been used extensively to explore the role of action potential (AP) firing in the development of neuronal structure and synaptic function because increases in intracellular calcium ([Ca(2+)]i) reliably and, within a certain range, linearly reflect neuronal spiking activity. Patterns of APs in individual cells can be deduced from calcium recordings, which have typically been performed at the level of cell bodies. However, neurons are particularly susceptible to phototoxicity when they are illuminated at the soma. Furthermore, for some imaging experiments (e.g., those that address the interactions between dendrites and axons during synapse formation), the cell body of a given neuron may simply not be in the field of view. In these situations, it would be helpful to determine the spiking patterns of a neuron from the calcium activity in its subcellular compartments such as stretches of dendrites or axons. Here, we describe an approach for determining the relationship between AP firing and dendritic calcium transients by simultaneously imaging calcium transients in small dendritic stretches of hippocampal pyramidal neurons in slice cultures from neonatal rats and recording spiking activity with whole-cell patch-clamp recordings in these neurons. These experiments allow us to correlate the electrophysiological spiking pattern with the accompanying changes in the calcium concentration in individual dendritic segments.

  4. Location-dependent excitatory synaptic interactions in pyramidal neuron dendrites.

    Directory of Open Access Journals (Sweden)

    Bardia F Behabadi

    Full Text Available Neocortical pyramidal neurons (PNs receive thousands of excitatory synaptic contacts on their basal dendrites. Some act as classical driver inputs while others are thought to modulate PN responses based on sensory or behavioral context, but the biophysical mechanisms that mediate classical-contextual interactions in these dendrites remain poorly understood. We hypothesized that if two excitatory pathways bias their synaptic projections towards proximal vs. distal ends of the basal branches, the very different local spike thresholds and attenuation factors for inputs near and far from the soma might provide the basis for a classical-contextual functional asymmetry. Supporting this possibility, we found both in compartmental models and electrophysiological recordings in brain slices that the responses of basal dendrites to spatially separated inputs are indeed strongly asymmetric. Distal excitation lowers the local spike threshold for more proximal inputs, while having little effect on peak responses at the soma. In contrast, proximal excitation lowers the threshold, but also substantially increases the gain of distally-driven responses. Our findings support the view that PN basal dendrites possess significant analog computing capabilities, and suggest that the diverse forms of nonlinear response modulation seen in the neocortex, including uni-modal, cross-modal, and attentional effects, could depend in part on pathway-specific biases in the spatial distribution of excitatory synaptic contacts onto PN basal dendritic arbors.

  5. Human intestinal dendritic cells as controllers of mucosal immunity

    Directory of Open Access Journals (Sweden)

    David Bernardo

    2013-06-01

    Full Text Available Dendritic cells are the most potent, professional antigen-presenting cells in the body; following antigen presentation they control the type (proinflammatory/regulatory of immune response that will take place, as well as its location. Given their high plasticity and maturation ability in response to local danger signals derived from innate immunity, dendritic cells are key actors in the connection between innate immunity and adaptive immunity responses. In the gut dendritic cells control immune tolerance mechanisms against food and/or commensal flora antigens, and are also capable of initiating an active immune response in the presence of invading pathogens. Dendritic cells are thus highly efficient in controlling the delicate balance between tolerance and immunity in an environment so rich in antigens as the gut, and any factor involving these cells may impact their function, ultimately leading to the development of bowel conditions such as celiac disease or inflammatory bowel disease. In this review we shall summarize our understanding of human intestinal dendritic cells, their ability to express and induce migration markers, the various environmental factors modulating their properties, their subsets in the gut, and the problems entailed by their study, including identification strategies, differences between humans and murine models, and phenotypical variations along the gastrointestinal tract.

  6. Dendrite growth characteristics within liquid Fe-Sb alloy

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Bulk samples and small droplets of liquid Fe-10%Sb alloys are undercooled up to 429 K (0.24TL) and 568 K (0.32TL), respectively, with glass fluxing and free fall techniques. The high undercooling does not change the phase constitution, and only the αFe solid solution is found in the rapidly solidified alloy. The experimental results show that when the undercooling is below 296 K, the growth velocity of αFe dendrite rises exponentially with the increase of undercooling and reaches a maximum value 1.38 m/s. Subsequently, the growth velocity begins to decrease if undercooling further increases. The αFe phase grows into coarse dendrites under small undercooling conditions, whereas it becomes vermicular dendrites in highly undercooled melts. The solute trapping is closely related to the dendrite growth velocity and cooling rate rather than undercooling. Although the solute trapping can be remarkably suppressed by the rapid dendrite growth, the segregationless solidification is not observed in the present experiments due to the large solidification temperature range.

  7. Dendrite growth characteristics within liquid Fe-Sb alloy

    Institute of Scientific and Technical Information of China (English)

    WANG WeiLi; Lü YongJun; QIN HaiYan; WEI BingBo

    2009-01-01

    Bulk samples and small droplets of liquid Fe-10%Sb alloys are undercooled up to 429 K (0.24TL) and 568 K (0.32 TL), respectively, with glass fluxing and free fall techniques. The high undercooling does not change the phase constitution, and only the αFe solid solution is found in the rapidly solidified alloy.The experimental results show that when the undercooling is below 296 K, the growth velocity of αFe dendrite rises exponentially with the increase of undercooling and reaches a maximum value 1.38 m/s.Subsequently, the growth velocity begins to decrease if undercooling further increases. The αFe phase grows into coarse dendrites under small undercooling conditions, whereas it becomes vermicular dendrites in highly undercooled melts. The solute trapping is closely related to the dendrite growth velocity and cooling rate rather than undercooling. Although the solute trapping can be remarkably suppressed by the rapid dendrite growth, the segregationless solidification is not observed in the present experiments due to the large solidification temperature range.

  8. Homophilic Protocadherin Cell-Cell Interactions Promote Dendrite Complexity

    Directory of Open Access Journals (Sweden)

    Michael J. Molumby

    2016-05-01

    Full Text Available Growth of a properly complex dendrite arbor is a key step in neuronal differentiation and a prerequisite for neural circuit formation. Diverse cell surface molecules, such as the clustered protocadherins (Pcdhs, have long been proposed to regulate circuit formation through specific cell-cell interactions. Here, using transgenic and conditional knockout mice to manipulate γ-Pcdh repertoire in the cerebral cortex, we show that the complexity of a neuron’s dendritic arbor is determined by homophilic interactions with other cells. Neurons expressing only one of the 22 γ-Pcdhs can exhibit either exuberant or minimal dendrite complexity, depending only on whether surrounding cells express the same isoform. Furthermore, loss of astrocytic γ-Pcdhs, or disruption of astrocyte-neuron homophilic matching, reduces dendrite complexity cell non-autonomously. Our data indicate that γ-Pcdhs act locally to promote dendrite arborization via homophilic matching, and they confirm that connectivity in vivo depends on molecular interactions between neurons and between neurons and astrocytes.

  9. Slowing down light using a dendritic cell cluster metasurface waveguide

    Science.gov (United States)

    Fang, Z. H.; Chen, H.; Yang, F. S.; Luo, C. R.; Zhao, X. P.

    2016-11-01

    Slowing down or even stopping light is the first task to realising optical information transmission and storage. Theoretical studies have revealed that metamaterials can slow down or even stop light; however, the difficulty of preparing metamaterials that operate in visible light hinders progress in the research of slowing or stopping light. Metasurfaces provide a new opportunity to make progress in such research. In this paper, we propose a dendritic cell cluster metasurface consisting of dendritic structures. The simulation results show that dendritic structure can realise abnormal reflection and refraction effects. Single- and double-layer dendritic metasurfaces that respond in visible light were prepared by electrochemical deposition. Abnormal Goos-Hänchen (GH) shifts were experimentally obtained. The rainbow trapping effect was observed in a waveguide constructed using the dendritic metasurface sample. The incident white light was separated into seven colours ranging from blue to red light. The measured transmission energy in the waveguide showed that the energy escaping from the waveguide was zero at the resonant frequency of the sample under a certain amount of incident light. The proposed metasurface has a simple preparation process, functions in visible light, and can be readily extended to the infrared band and communication wavelengths.

  10. Study of the twinned dendrite tip shape II: Experimental assessment

    Energy Technology Data Exchange (ETDEWEB)

    Salgado-Ordorica, M.A., E-mail: mario.salgado@novelis.com [Laboratoire de Simulation des Materiaux LSMX, Ecole Polytechnique Federale de Lausanne, Station 12, 1015 Lausanne (Switzerland); Burdet, P.; Cantoni, M. [Centre Interdisciplinaire de Microscopie Electronique CIME, Ecole Polytechnique Federale de Lausanne, Station 12, 1015 Lausanne (Switzerland); Rappaz, M. [Laboratoire de Simulation des Materiaux LSMX, Ecole Polytechnique Federale de Lausanne, Station 12, 1015 Lausanne (Switzerland)

    2011-08-15

    The favorable growth kinetics of twinned dendrites can be explained by their complex morphology, multiple side branching mechanisms, growth undercooling and tip morphology. Three models were proposed for the twinned dendrite tip shape: (i) a grooved tip satisfying the Smith condition at the triple line; (ii) a doublon , i.e. a double-tip dendrite that grows with a narrow and deep liquid channel in its center; and (iii) a pointed (or edgy) tip, with consideration of the solid-liquid interfacial energy anisotropy. In the first part of this work, phase field simulations of half a twinned dendrite with an appropriate boundary condition to reproduce the Smith condition supported the doublon conjecture, with a narrow liquid channel ending its solidification with the formation of small liquid droplets. In this part, experimental observations of twinned dendrite tips reveal the presence of a small, but well-defined, groove, thus definitely eliminating the edged tip hypothesis. Focused ion beam nanotomography and energy-dispersive spectroscopy chemical analysis in a transmission electron microscope reveal the existence of a positive solute gradient in a region localized within 2 {mu}m around the twin plane. In Al-Zn specimens, small particles aligned within the twin plane further support the doublon conjecture and the predicted formation of small liquid droplets below the doublon root.

  11. Noise tolerant dendritic lattice associative memories

    Science.gov (United States)

    Ritter, Gerhard X.; Schmalz, Mark S.; Hayden, Eric; Tucker, Marc

    2011-09-01

    Linear classifiers based on computation over the real numbers R (e.g., with operations of addition and multiplication) denoted by (R, +, x), have been represented extensively in the literature of pattern recognition. However, a different approach to pattern classification involves the use of addition, maximum, and minimum operations over the reals in the algebra (R, +, maximum, minimum) These pattern classifiers, based on lattice algebra, have been shown to exhibit superior information storage capacity, fast training and short convergence times, high pattern classification accuracy, and low computational cost. Such attributes are not always found, for example, in classical neural nets based on the linear inner product. In a special type of lattice associative memory (LAM), called a dendritic LAM or DLAM, it is possible to achieve noise-tolerant pattern classification by varying the design of noise or error acceptance bounds. This paper presents theory and algorithmic approaches for the computation of noise-tolerant lattice associative memories (LAMs) under a variety of input constraints. Of particular interest are the classification of nonergodic data in noise regimes with time-varying statistics. DLAMs, which are a specialization of LAMs derived from concepts of biological neural networks, have successfully been applied to pattern classification from hyperspectral remote sensing data, as well as spatial object recognition from digital imagery. The authors' recent research in the development of DLAMs is overviewed, with experimental results that show utility for a wide variety of pattern classification applications. Performance results are presented in terms of measured computational cost, noise tolerance, classification accuracy, and throughput for a variety of input data and noise levels.

  12. Inverse Limits

    CERN Document Server

    Ingram, WT

    2012-01-01

    Inverse limits provide a powerful tool for constructing complicated spaces from simple ones. They also turn the study of a dynamical system consisting of a space and a self-map into a study of a (likely more complicated) space and a self-homeomorphism. In four chapters along with an appendix containing background material the authors develop the theory of inverse limits. The book begins with an introduction through inverse limits on [0,1] before moving to a general treatment of the subject. Special topics in continuum theory complete the book. Although it is not a book on dynamics, the influen

  13. Epidermal cells are the primary phagocytes in the fragmentation and clearance of degenerating dendrites in Drosophila.

    Science.gov (United States)

    Han, Chun; Song, Yuanquan; Xiao, Hui; Wang, Denan; Franc, Nathalie C; Jan, Lily Yeh; Jan, Yuh-Nung

    2014-02-05

    During developmental remodeling, neurites destined for pruning often degenerate on-site. Physical injury also induces degeneration of neurites distal to the injury site. Prompt clearance of degenerating neurites is important for maintaining tissue homeostasis and preventing inflammatory responses. Here we show that in both dendrite pruning and dendrite injury of Drosophila sensory neurons, epidermal cells rather than hemocytes are the primary phagocytes in clearing degenerating dendrites. Epidermal cells act via Draper-mediated recognition to facilitate dendrite degeneration and to engulf and degrade degenerating dendrites. Using multiple dendritic membrane markers to trace phagocytosis, we show that two members of the CD36 family, croquemort (crq) and debris buster (dsb), act at distinct stages of phagosome maturation for dendrite clearance. Our finding reveals the physiological importance of coordination between neurons and their surrounding epidermis, for both dendrite fragmentation and clearance.

  14. Dendritic network models: Improving isoscapes and quantifying influence of landscape and in-stream processes on strontium isotopes in rivers

    Science.gov (United States)

    Brennan, Sean R.; Torgersen, Christian E.; Hollenbeck, Jeff P.; Fernandez, Diego P.; Jensen, Carrie K.; Schindler, Daniel E.

    2016-05-01

    A critical challenge for the Earth sciences is to trace the transport and flux of matter within and among aquatic, terrestrial, and atmospheric systems. Robust descriptions of isotopic patterns across space and time, called "isoscapes," form the basis of a rapidly growing and wide-ranging body of research aimed at quantifying connectivity within and among Earth's systems. However, isoscapes of rivers have been limited by conventional Euclidean approaches in geostatistics and the lack of a quantitative framework to apportion the influence of processes driven by landscape features versus in-stream phenomena. Here we demonstrate how dendritic network models substantially improve the accuracy of isoscapes of strontium isotopes and partition the influence of hydrologic transport versus local geologic features on strontium isotope ratios in a large Alaska river. This work illustrates the analytical power of dendritic network models for the field of isotope biogeochemistry, particularly for provenance studies of modern and ancient animals.

  15. Dendritic network models: Improving isoscapes and quantifying influence of landscape and in-stream processes on strontium isotopes in rivers

    Science.gov (United States)

    Brennan, Sean R.; Torgersen, Christian; Hollenbeck, Jeff P.; Fernandez, Diego P.; Jensen, Carrie K; Schindler, Daniel E.

    2016-01-01

    A critical challenge for the Earth sciences is to trace the transport and flux of matter within and among aquatic, terrestrial, and atmospheric systems. Robust descriptions of isotopic patterns across space and time, called “isoscapes,” form the basis of a rapidly growing and wide-ranging body of research aimed at quantifying connectivity within and among Earth's systems. However, isoscapes of rivers have been limited by conventional Euclidean approaches in geostatistics and the lack of a quantitative framework to apportion the influence of processes driven by landscape features versus in-stream phenomena. Here we demonstrate how dendritic network models substantially improve the accuracy of isoscapes of strontium isotopes and partition the influence of hydrologic transport versus local geologic features on strontium isotope ratios in a large Alaska river. This work illustrates the analytical power of dendritic network models for the field of isotope biogeochemistry, particularly for provenance studies of modern and ancient animals.

  16. [State of the art about new therapeutic vaccines in prostate cancer: dendritic cells, engineered tumor cells and recombinant virus].

    Science.gov (United States)

    Eymard, Jean-Christophe; Gervais, Alban; Jarcau, Rosana; Bernard, Jacky

    2007-07-01

    Therapeutic vaccines for prostate cancer were initially reported as limited with low immunological responses and uncertain clinical benefit. Recently, new methods become available, such preparations of well-characterized autologous dendritic cells, and use of gene therapy tools to increase whole-tumor cells or host tissue immunogenicity. These are able to enhance and diversify therapeutic options. Indeed, several vaccinal approaches are being investigated, including optimized mature dendritic cells, allogeneic genetically modified tumor cells, or viral vectors. Due to the description of immunological and clinical responses, large phase III randomized trials are now conducted. After summarizing the mechanistic basis for these approaches, this review describes the experience with the most recent and promising clinical studies and introduces short-term perspectives that could lead to improvement in healthcare offer for prostate cancer patients.

  17. Effects of temperature boundary conditions on equiaxed dendritic growth in phase-field simulations of binary alloy

    Institute of Scientific and Technical Information of China (English)

    于艳梅; 杨根仓; 赵达文; 吕衣礼

    2002-01-01

    By the phase-field approach, the dendritic growth in binary alloy melt was simulated respectively using two types of temperature boundary conditions, i.e., the constant temperature boundary by which the boundary temperature was fixed at the initial temperature, and Zero-Neumann temperature boundary. The influences of the temperature boundary conditions on numerical results are investigated. How to choose appropriate temperature boundary conditions is proposed. The results show that: 1) when the computation region is limited to a changeless size, the Zero-Neumann and constant temperature boundary conditions lead to the different dendritic growth behaviors, and the Zero-Neumann condition is preferable to the constant temperature condition; 2) when the computation region is enlarged continually with the computational time according to the increasing thermal diffusion scale, the two types of temperature boundary conditions achieve the consistent tip velocities and tip radii, and they both are appropriate choices.

  18. MicroRNA-9 controls dendritic development by targeting REST

    Science.gov (United States)

    Giusti, Sebastian A; Vogl, Annette M; Brockmann, Marisa M; Vercelli, Claudia A; Rein, Martin L; Trümbach, Dietrich; Wurst, Wolfgang; Cazalla, Demian; Stein, Valentin; Deussing, Jan M; Refojo, Damian

    2014-01-01

    MicroRNAs (miRNAs) are conserved noncoding RNAs that function as posttranscriptional regulators of gene expression. miR-9 is one of the most abundant miRNAs in the brain. Although the function of miR-9 has been well characterized in neural progenitors, its role in dendritic and synaptic development remains largely unknown. In order to target miR-9 in vivo, we developed a transgenic miRNA sponge mouse line allowing conditional inactivation of the miR-9 family in a spatio-temporal-controlled manner. Using this novel approach, we found that miR-9 controls dendritic growth and synaptic transmission in vivo. Furthermore, we demonstrate that miR-9-mediated downregulation of the transcriptional repressor REST is essential for proper dendritic growth. DOI: http://dx.doi.org/10.7554/eLife.02755.001 PMID:25406064

  19. A Model of Dendritic Cell Therapy for Melanoma

    Directory of Open Access Journals (Sweden)

    Ami eRadunskaya

    2013-03-01

    Full Text Available Dendritic cells are a promising immunotherapy tool for boosting an individual's antigen specific immune response to cancer. We develop a mathematical model using differential and delay-differential equations to describe the interactions between dendritic cells, effector-immune cells and tumor cells. We account for the trafficking of immune cells between lymph, blood, and tumor compartments. Our model reflects experimental results both for dendritic-cell trafficking and for immune suppression of tumor growth in mice. In addition, in silico experiments suggest more effective immunotherapy treatment protocols can be achieved by modifying dose location and schedule. A sensitivity analysis of the model reveals which patient-specific parameters have the greatest impact on treatment efficacy.

  20. Involvement of dendritic cells in autoimmune diseases in children

    Directory of Open Access Journals (Sweden)

    Reed Ann M

    2007-07-01

    Full Text Available Abstract Dendritic cells (DCs are professional antigen-presenting cells that are specialized in the uptake of antigens and their transport from peripheral tissues to the lymphoid organs. Over the last decades, the properties of DCs have been intensely studied and much knowledge has been gained about the role of DCs in various diseases and health conditions where the immune system is involved, particularly in cancer and autoimmune disorders. Emerging clues in autoimmune diseases, suggest that dendritic cell dysregulation might be involved in the development of various autoimmune disorders in both adults and children. However, studies investigating a possible contribution of DCs in autoimmune diseases in the pediatric population alone are scanty. The purpose of this review is to give a general overview of the current literature on the relevance of dendritic cells in the most common autoimmune conditions of childhood.

  1. Growth and microstructure of AlN whiskers and dendrites

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    AlN whiskers or dendrites were synthesized with a sublimation-recrystallization method by using Al, AlN powders and some additives as raw materials. Whiskers with different sizes that featured high purity and good crystallinity were obtained by controlling temperature and gas supersaturation in the reaction container. The whiskers were described as long and straight single crystals of approximately 1-30 (m in diameter by the centimeter range in length. However, AlN dendrites were about 1 mm in diameter by 0.5 cm in length, and showed an obviously preferential growth orientation, i.e., perpendicular to and planes. It is concluded that the whiskers or dendrites grow via the vapor-solid mechanism.

  2. Facile fabrication of dendritic silver structures and their surface enhanced Raman spectroscopic properties

    Indian Academy of Sciences (India)

    Jisheng Yang; Zhengdong Jiang

    2015-01-01

    A simple and efficient approach was developed to fabricate silver dendrites by Cu reducing Ag+ in AgNO3 solution. The growth speed, morphologies and structures of the silver dendrites strongly depend on AgNO3 concentration and reaction time. The silver dendrites were formed from nanosheets and the crystal structure is face-centered cubic. Rhodamine 6G was used as probe molecule to show that the silver dendrites have high sensitivity to surface enhanced Raman spectroscopy response.

  3. Adipose Tissue Dendritic Cells Are Independent Contributors to Obesity-Induced Inflammation and Insulin Resistance.

    Science.gov (United States)

    Cho, Kae Won; Zamarron, Brian F; Muir, Lindsey A; Singer, Kanakadurga; Porsche, Cara E; DelProposto, Jennifer B; Geletka, Lynn; Meyer, Kevin A; O'Rourke, Robert W; Lumeng, Carey N

    2016-11-01

    Dynamic changes of adipose tissue leukocytes, including adipose tissue macrophage (ATM) and adipose tissue dendritic cells (ATDCs), contribute to obesity-induced inflammation and metabolic disease. However, clear discrimination between ATDC and ATM in adipose tissue has limited progress in the field of immunometabolism. In this study, we use CD64 to distinguish ATM and ATDC, and investigated the temporal and functional changes in these myeloid populations during obesity. Flow cytometry and immunostaining demonstrated that the definition of ATM as F4/80(+)CD11b(+) cells overlaps with other leukocytes and that CD45(+)CD64(+) is specific for ATM. The expression of core dendritic cell genes was enriched in CD11c(+)CD64(-) cells (ATDC), whereas core macrophage genes were enriched in CD45(+)CD64(+) cells (ATM). CD11c(+)CD64(-) ATDCs expressed MHC class II and costimulatory receptors, and had similar capacity to stimulate CD4(+) T cell proliferation as ATMs. ATDCs were predominantly CD11b(+) conventional dendritic cells and made up the bulk of CD11c(+) cells in adipose tissue with moderate high-fat diet exposure. Mixed chimeric experiments with Ccr2(-/-) mice demonstrated that high-fat diet-induced ATM accumulation from monocytes was dependent on CCR2, whereas ATDC accumulation was less CCR2 dependent. ATDC accumulation during obesity was attenuated in Ccr7(-/-) mice and was associated with decreased adipose tissue inflammation and insulin resistance. CD45(+)CD64(+) ATM and CD45(+)CD64(-)CD11c(+) ATDCs were identified in human obese adipose tissue and ATDCs were increased in s.c. adipose tissue compared with omental adipose tissue. These results support a revised strategy for unambiguous delineation of ATM and ATDC, and suggest that ATDCs are independent contributors to adipose tissue inflammation during obesity. Copyright © 2016 by The American Association of Immunologists, Inc.

  4. Downregulation of the Syk Signaling Pathway in Intestinal Dendritic Cells Is Sufficient To Induce Dendritic Cells That Inhibit Colitis.

    Science.gov (United States)

    Hang, Long; Blum, Arthur M; Kumar, Sangeeta; Urban, Joseph F; Mitreva, Makedonka; Geary, Timothy G; Jardim, Armando; Stevenson, Mary M; Lowell, Clifford A; Weinstock, Joel V

    2016-10-01

    Helminthic infections modulate host immunity and may protect people in less-developed countries from developing immunological diseases. In a murine colitis model, the helminth Heligmosomoides polygyrus bakeri prevents colitis via induction of regulatory dendritic cells (DCs). The mechanism driving the development of these regulatory DCs is unexplored. There is decreased expression of the intracellular signaling pathway spleen tyrosine kinase (Syk) in intestinal DCs from H. polygyrus bakeri-infected mice. To explore the importance of this observation, it was shown that intestinal DCs from DC-specific Syk(-/-) mice were powerful inhibitors of murine colitis, suggesting that loss of Syk was sufficient to convert these cells into their regulatory phenotype. DCs sense gut flora and damaged epithelium via expression of C-type lectin receptors, many of which signal through the Syk signaling pathway. It was observed that gut DCs express mRNA encoding for C-type lectin (CLEC) 7A, CLEC9A, CLEC12A, and CLEC4N. H. polygyrus bakeri infection downmodulated CLEC mRNA expression in these cells. Focusing on CLEC7A, which encodes for the dectin-1 receptor, flow analysis showed that H. polygyrus bakeri decreases dectin-1 expression on the intestinal DC subsets that drive Th1/Th17 development. DCs become unresponsive to the dectin-1 agonist curdlan and fail to phosphorylate Syk after agonist stimulation. Soluble worm products can block CLEC7A and Syk mRNA expression in gut DCs from uninfected mice after a brief in vitro exposure. Thus, downmodulation of Syk expression and phosphorylation in intestinal DCs could be important mechanisms through which helminths induce regulatory DCs that limit colitis.

  5. Cryptococcus gattii is killed by dendritic cells, but evades adaptive immunity by failing to induce dendritic cell maturation.

    Science.gov (United States)

    Huston, Shaunna M; Li, Shu Shun; Stack, Danuta; Timm-McCann, Martina; Jones, Gareth J; Islam, Anowara; Berenger, Byron M; Xiang, Richard F; Colarusso, Pina; Mody, Christopher H

    2013-07-01

    During adaptive immunity to pathogens, dendritic cells (DCs) capture, kill, process, and present microbial Ags to T cells. Ag presentation is accompanied by DC maturation driven by appropriate costimulatory signals. However, current understanding of the intricate regulation of these processes remains limited. Cryptococcus gattii, an emerging fungal pathogen in the Pacific Northwest of Canada and the United States, fails to stimulate an effective immune response in otherwise healthy hosts leading to morbidity or death. Because immunity to fungal pathogens requires intact cell-mediated immunity initiated by DCs, we asked whether C. gattii causes dysregulation of DC functions. C. gattii was efficiently bound and internalized by human monocyte-derived DCs, trafficked to late phagolysosomes, and killed. Yet, even with this degree of DC activation, the organism evaded pathways leading to DC maturation. Despite the ability to recognize and kill C. gattii, immature DCs failed to mature; there was no increased expression of MHC class II, CD86, CD83, CD80, and CCR7, or decrease of CD11c and CD32, which resulted in suboptimal T cell responses. Remarkably, no increase in TNF-α was observed in the presence of C. gattii. However, addition of recombinant TNF-α or stimulation that led to TNF-α production restored DC maturation and restored T cell responses. Thus, despite early killing, C. gattii evades DC maturation, providing a potential explanation for its ability to infect immunocompetent individuals. We have also established that DCs retain the ability to recognize and kill C. gattii without triggering TNF-α, suggesting independent or divergent activation pathways among essential DC functions.

  6. Blastic plasmacytoid dendritic cell neoplasm with absolute monocytosis at presentation

    Directory of Open Access Journals (Sweden)

    Jaworski JM

    2015-02-01

    Full Text Available Joseph M Jaworski,1,2 Vanlila K Swami,1 Rebecca C Heintzelman,1 Carrie A Cusack,3 Christina L Chung,3 Jeremy Peck,3 Matthew Fanelli,3 Micheal Styler,4 Sanaa Rizk,4 J Steve Hou1 1Department of Pathology and Laboratory Medicine, Hahnemann University Hospital/Drexel University College of Medicine, Philadelphia, PA, USA; 2Department of Pathology, Mercy Fitzgerald Hospital, Darby, PA, USA; 3Department of Dermatology, Hahnemann University Hospital/Drexel University College of Medicine, Philadelphia, PA, USA; 4Department of Hematology/Oncology, Hahnemann University Hospital/Drexel University College of Medicine, Philadelphia, PA, USA Abstract: Blastic plasmacytoid dendritic cell neoplasm is an uncommon malignancy derived from precursors of plasmacytoid dendritic cells. Nearly all patients present initially with cutaneous manifestations, with many having extracutaneous disease additionally. While response to chemotherapy initially is effective, relapse occurs in most, with a leukemic phase ultimately developing. The prognosis is dismal. While most of the clinical and pathologic features are well described, the association and possible prognostic significance between peripheral blood absolute monocytosis (>1.0 K/µL and blastic plasmacytoid dendritic cell neoplasm have not been reported. We report a case of a 68-year-old man who presented with a rash for 4–5 months. On physical examination, there were multiple, dull-pink, indurated plaques on the trunk and extremities. Complete blood count revealed thrombocytopenia, absolute monocytosis of 1.7 K/µL, and a negative flow cytometry study. Biopsy of an abdominal lesion revealed typical features of blastic plasmacytoid dendritic cell neoplasm. Patients having both hematologic and nonhematologic malignancies have an increased incidence of absolute monocytosis. Recent studies examining Hodgkin and non-Hodgkin lymphoma patients have suggested that this is a negative prognostic factor. The association between

  7. Macrophages as APC and the dendritic cell myth.

    Science.gov (United States)

    Hume, David A

    2008-11-01

    Dendritic cells have been considered an immune cell type that is specialized for the presentation of Ag to naive T cells. Considerable effort has been applied to separate their lineage, pathways of differentiation, and effectiveness in Ag presentation from those of macrophages. This review summarizes evidence that dendritic cells are a part of the mononuclear phagocyte system and are derived from a common precursor, responsive to the same growth factors (including CSF-1), express the same surface markers (including CD11c), and have no unique adaptation for Ag presentation that is not shared by other macrophages.

  8. File list: ALL.Bld.50.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.50.AllAg.Dendritic_Cells hg19 All antigens Blood Dendritic Cells SRX818200,...96,SRX818181 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Bld.50.AllAg.Dendritic_Cells.bed ...

  9. File list: Oth.Bld.20.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.20.AllAg.Dendritic_Cells mm9 TFs and others Blood Dendritic Cells SRX122407...RX122577,SRX122506,SRX122505 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.20.AllAg.Dendritic_Cells.bed ...

  10. File list: InP.Bld.20.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.20.AllAg.Dendritic_Cells mm9 Input control Blood Dendritic Cells SRX122480,...83,SRX667878,SRX667880,SRX667876,SRX667874 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.20.AllAg.Dendritic_Cells.bed ...

  11. Dendritic cell maturation results in pronounced changes in glycan expression affecting recognition by siglecs and galectins

    NARCIS (Netherlands)

    Bax, Marieke; Garcia-Vallejo, Juan J.; Jang-Lee, Jihye; North, Simon J.; Gilmartin, Tim J.; Hernandez, Gilberto; Crocker, Paul R.; Leffler, Hakon; Head, Steven R.; Haslam, Stuart M.; Dell, Anne; van Kooyk, Yvette

    2007-01-01

    Dendritic cells (DC) are the most potent APC in the organism. Immature dendritic cells (iDC) reside in the tissue where they capture pathogens whereas mature dendritic cells (mDC) are able to activate T cells in the lymph node. This dramatic functional change is mediated by an important genetic repr

  12. File list: His.Bld.05.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.05.AllAg.Dendritic_Cells mm9 Histone Blood Dendritic Cells SRX835924,SRX835...2835,SRX742821,SRX742837 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.05.AllAg.Dendritic_Cells.bed ...

  13. File list: ALL.Bld.05.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.05.AllAg.Dendritic_Cells hg19 All antigens Blood Dendritic Cells SRX818200,...95,SRX818194 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Bld.05.AllAg.Dendritic_Cells.bed ...

  14. File list: His.Bld.10.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.10.AllAg.Dendritic_Cells mm9 Histone Blood Dendritic Cells SRX835924,SRX835...2836,SRX742837,SRX742834 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.10.AllAg.Dendritic_Cells.bed ...

  15. File list: Unc.Bld.05.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.05.AllAg.Dendritic_Cells mm9 Unclassified Blood Dendritic Cells SRX185717,S...RX122424,SRX122426,SRX122422,SRX122425,SRX122427,SRX122423 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Bld.05.AllAg.Dendritic_Cells.bed ...

  16. File list: Pol.Bld.10.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.10.AllAg.Dendritic_Cells mm9 RNA polymerase Blood Dendritic Cells SRX330713...88,SRX891789 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Bld.10.AllAg.Dendritic_Cells.bed ...

  17. File list: Unc.Bld.20.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.20.AllAg.Dendritic_Cells mm9 Unclassified Blood Dendritic Cells SRX185717,S...RX122427,SRX122425,SRX122423,SRX122424,SRX122422,SRX122426 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Bld.20.AllAg.Dendritic_Cells.bed ...

  18. File list: ALL.Bld.20.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.20.AllAg.Dendritic_Cells mm9 All antigens Blood Dendritic Cells SRX122407,S...424,SRX122422,SRX122426 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.20.AllAg.Dendritic_Cells.bed ...

  19. File list: ALL.Bld.05.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.05.AllAg.Dendritic_Cells mm9 All antigens Blood Dendritic Cells SRX835924,S...575,SRX122519,SRX122577 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.05.AllAg.Dendritic_Cells.bed ...

  20. File list: His.Bld.20.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.20.AllAg.Dendritic_Cells mm9 Histone Blood Dendritic Cells SRX835924,SRX835...2820,SRX742836,SRX742834 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.20.AllAg.Dendritic_Cells.bed ...

  1. File list: Unc.Bld.10.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.10.AllAg.Dendritic_Cells hg19 Unclassified Blood Dendritic Cells SRX818200,...195,SRX818202,SRX818181,SRX818188,SRX818194,SRX818182 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Bld.10.AllAg.Dendritic_Cells.bed ...

  2. File list: InP.Bld.50.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.50.AllAg.Dendritic_Cells hg19 Input control Blood Dendritic Cells SRX627427...,SRX627429 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Bld.50.AllAg.Dendritic_Cells.bed ...

  3. File list: Oth.Bld.05.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.05.AllAg.Dendritic_Cells hg19 TFs and others Blood Dendritic Cells SRX62742...8,SRX627430 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Bld.05.AllAg.Dendritic_Cells.bed ...

  4. File list: InP.Bld.10.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.10.AllAg.Dendritic_Cells hg19 Input control Blood Dendritic Cells SRX627429...,SRX627427 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Bld.10.AllAg.Dendritic_Cells.bed ...

  5. File list: Unc.Bld.05.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.05.AllAg.Dendritic_Cells hg19 Unclassified Blood Dendritic Cells SRX818200,...181,SRX818182,SRX818188,SRX818202,SRX818195,SRX818194 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Bld.05.AllAg.Dendritic_Cells.bed ...

  6. File list: ALL.Bld.10.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.10.AllAg.Dendritic_Cells hg19 All antigens Blood Dendritic Cells SRX818200,...94,SRX818182 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Bld.10.AllAg.Dendritic_Cells.bed ...

  7. File list: Unc.Bld.20.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.20.AllAg.Dendritic_Cells hg19 Unclassified Blood Dendritic Cells SRX818200,...189,SRX818202,SRX818182,SRX818195,SRX818196,SRX818181 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Bld.20.AllAg.Dendritic_Cells.bed ...

  8. File list: Oth.Bld.05.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.05.AllAg.Dendritic_Cells mm9 TFs and others Blood Dendritic Cells SRX390504...RX122575,SRX122519,SRX122577 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.05.AllAg.Dendritic_Cells.bed ...

  9. File list: InP.Bld.05.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.05.AllAg.Dendritic_Cells mm9 Input control Blood Dendritic Cells SRX885956,...76,SRX122481,SRX667880,SRX667874,SRX667878 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.05.AllAg.Dendritic_Cells.bed ...

  10. File list: Oth.Bld.50.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.50.AllAg.Dendritic_Cells mm9 TFs and others Blood Dendritic Cells SRX122407...RX708765,SRX041328,SRX041331 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.50.AllAg.Dendritic_Cells.bed ...

  11. File list: Unc.Bld.50.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.50.AllAg.Dendritic_Cells hg19 Unclassified Blood Dendritic Cells SRX818200,...203,SRX818202,SRX818182,SRX818195,SRX818196,SRX818181 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Bld.50.AllAg.Dendritic_Cells.bed ...

  12. File list: ALL.Bld.20.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.20.AllAg.Dendritic_Cells hg19 All antigens Blood Dendritic Cells SRX818200,...96,SRX818181 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Bld.20.AllAg.Dendritic_Cells.bed ...

  13. File list: Pol.Bld.50.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.50.AllAg.Dendritic_Cells mm9 RNA polymerase Blood Dendritic Cells SRX330713...88,SRX122458 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Bld.50.AllAg.Dendritic_Cells.bed ...

  14. File list: Pol.Bld.20.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.20.AllAg.Dendritic_Cells mm9 RNA polymerase Blood Dendritic Cells SRX330713...90,SRX891788 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Bld.20.AllAg.Dendritic_Cells.bed ...

  15. File list: Pol.Bld.05.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.05.AllAg.Dendritic_Cells mm9 RNA polymerase Blood Dendritic Cells SRX330713...59,SRX891788 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Bld.05.AllAg.Dendritic_Cells.bed ...

  16. File list: InP.Bld.20.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.20.AllAg.Dendritic_Cells hg19 Input control Blood Dendritic Cells SRX627429...,SRX627427 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Bld.20.AllAg.Dendritic_Cells.bed ...

  17. File list: ALL.Bld.50.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.50.AllAg.Dendritic_Cells mm9 All antigens Blood Dendritic Cells SRX122407,S...765,SRX041328,SRX041331 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.50.AllAg.Dendritic_Cells.bed ...

  18. File list: ALL.Bld.10.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.10.AllAg.Dendritic_Cells mm9 All antigens Blood Dendritic Cells SRX835924,S...427,SRX122423,SRX122425 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.10.AllAg.Dendritic_Cells.bed ...

  19. File list: Oth.Bld.50.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.50.AllAg.Dendritic_Cells hg19 TFs and others Blood Dendritic Cells SRX62742...8,SRX627430 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Bld.50.AllAg.Dendritic_Cells.bed ...

  20. File list: His.Bld.50.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.50.AllAg.Dendritic_Cells mm9 Histone Blood Dendritic Cells SRX835922,SRX835...2837,SRX742836,SRX742834 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.50.AllAg.Dendritic_Cells.bed ...

  1. File list: InP.Bld.05.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.05.AllAg.Dendritic_Cells hg19 Input control Blood Dendritic Cells SRX627429...,SRX627427 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Bld.05.AllAg.Dendritic_Cells.bed ...

  2. File list: Oth.Bld.10.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.10.AllAg.Dendritic_Cells mm9 TFs and others Blood Dendritic Cells SRX122407...RX122520,SRX122522,SRX122577 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.10.AllAg.Dendritic_Cells.bed ...

  3. File list: Unc.Bld.50.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.50.AllAg.Dendritic_Cells mm9 Unclassified Blood Dendritic Cells SRX185717,S...RX122427,SRX122425,SRX122423,SRX122424,SRX122422,SRX122426 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Bld.50.AllAg.Dendritic_Cells.bed ...

  4. File list: Oth.Bld.10.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.10.AllAg.Dendritic_Cells hg19 TFs and others Blood Dendritic Cells SRX62742...8,SRX627430 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Bld.10.AllAg.Dendritic_Cells.bed ...

  5. File list: InP.Bld.50.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.50.AllAg.Dendritic_Cells mm9 Input control Blood Dendritic Cells SRX122480,...82,SRX667878,SRX667880,SRX667876,SRX667874 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.50.AllAg.Dendritic_Cells.bed ...

  6. File list: Unc.Bld.10.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.10.AllAg.Dendritic_Cells mm9 Unclassified Blood Dendritic Cells SRX122426,S...RX185717,SRX122424,SRX122422,SRX122427,SRX122423,SRX122425 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Bld.10.AllAg.Dendritic_Cells.bed ...

  7. A general principle governs vision-dependent dendritic patterning of retinal ganglion cells.

    Science.gov (United States)

    Xu, Hong-Ping; Sun, Jin Hao; Tian, Ning

    2014-10-15

    Dendritic arbors of retinal ganglion cells (RGCs) collect information over a certain area of the visual scene. The coverage territory and the arbor density of dendrites determine what fraction of the visual field is sampled by a single cell and at what resolution. However, it is not clear whether visual stimulation is required for the establishment of branching patterns of RGCs, and whether a general principle directs the dendritic patterning of diverse RGCs. By analyzing the geometric structures of RGC dendrites, we found that dendritic arbors of RGCs underwent a substantial spatial rearrangement after eye-opening. Light deprivation blocked both the dendritic growth and the branch patterning, suggesting that visual stimulation is required for the acquisition of specific branching patterns of RGCs. We further showed that vision-dependent dendritic growth and arbor refinement occurred mainly in the middle portion of the dendritic tree. This nonproportional growth and selective refinement suggest that the late-stage dendritic development of RGCs is not a passive stretching with the growth of eyes, but rather an active process of selective growth/elimination of dendritic arbors of RGCs driven by visual activity. Finally, our data showed that there was a power law relationship between the coverage territory and dendritic arbor density of RGCs on a cell-by-cell basis. RGCs were systematically less dense when they cover larger territories regardless of their cell type, retinal location, or developmental stage. These results suggest that a general structural design principle directs the vision-dependent patterning of RGC dendrites.

  8. Cellular source-specific effects of apolipoprotein (apo) E4 on dendrite arborization and dendritic spine development.

    Science.gov (United States)

    Jain, Sachi; Yoon, Seo Yeon; Leung, Laura; Knoferle, Johanna; Huang, Yadong

    2013-01-01

    Apolipoprotein (apo) E4 is the leading genetic risk factor for Alzheimer's disease (AD), and it has a gene dose-dependent effect on the risk and age of onset of AD. Although apoE4 is primarily produced by astrocytes in the brain, neurons can also produce apoE4 under stress conditions. ApoE4 is known to inhibit neurite outgrowth and spine development in vitro and in vivo, but the potential influence of apoE4's cellular source on dendritic arborization and spine development has not yet been investigated. In this study, we report impairments in dendritic arborization and a loss of spines, especially thin (learning) and mushroom (memory) spines, in the hippocampus and entorhinal cortex of 19-21-month-old female neuron-specific-enolase (NSE)-apoE4 and apoE4-knockin (KI) mice compared to their respective apoE3-expressing counterparts. In general, NSE-apoE4 mice had more severe and widespread deficits in dendritic arborization as well as spine density and morphology than apoE4-KI mice. The loss of dendritic spines, especially mushroom spines, occurred in NSE-apoE4 mice as early as 7-8 months of age. In contrast, glial fibrillary acidic protein (GFAP)-apoE4 mice, which express apoE4 solely in astrocytes, did not have impairments in their dendrite arborization or spine density and morphology compared to GFAP-apoE3 mice at both ages. These results indicate that the effects of apoE4 on dendrite arborization, spine density, and spine morphology depend critically on its cellular source, with neuronal apoE4 having more detrimental effects than astrocytic apoE4.

  9. Cellular source-specific effects of apolipoprotein (apo E4 on dendrite arborization and dendritic spine development.

    Directory of Open Access Journals (Sweden)

    Sachi Jain

    Full Text Available Apolipoprotein (apo E4 is the leading genetic risk factor for Alzheimer's disease (AD, and it has a gene dose-dependent effect on the risk and age of onset of AD. Although apoE4 is primarily produced by astrocytes in the brain, neurons can also produce apoE4 under stress conditions. ApoE4 is known to inhibit neurite outgrowth and spine development in vitro and in vivo, but the potential influence of apoE4's cellular source on dendritic arborization and spine development has not yet been investigated. In this study, we report impairments in dendritic arborization and a loss of spines, especially thin (learning and mushroom (memory spines, in the hippocampus and entorhinal cortex of 19-21-month-old female neuron-specific-enolase (NSE-apoE4 and apoE4-knockin (KI mice compared to their respective apoE3-expressing counterparts. In general, NSE-apoE4 mice had more severe and widespread deficits in dendritic arborization as well as spine density and morphology than apoE4-KI mice. The loss of dendritic spines, especially mushroom spines, occurred in NSE-apoE4 mice as early as 7-8 months of age. In contrast, glial fibrillary acidic protein (GFAP-apoE4 mice, which express apoE4 solely in astrocytes, did not have impairments in their dendrite arborization or spine density and morphology compared to GFAP-apoE3 mice at both ages. These results indicate that the effects of apoE4 on dendrite arborization, spine density, and spine morphology depend critically on its cellular source, with neuronal apoE4 having more detrimental effects than astrocytic apoE4.

  10. Dendritic orientation and branching distinguish a class of multifunctional turtle spinal interneurons.

    Science.gov (United States)

    Holmes, Jonathan R; Berkowitz, Ari

    2014-01-01

    Spinal interneurons can integrate diverse propriospinal and supraspinal inputs that trigger or modulate locomotion and other limb movements. These synaptic inputs can occur on distal dendrites and yet must remain effective at the soma. Active dendritic conductances may amplify distal dendritic inputs, but appear to play a minimal role during scratching, at least. Another possibility is that spinal interneurons that integrate inputs on distal dendrites have unusually simple dendritic trees that effectively funnel current to the soma. We previously described a class of spinal interneurons, called transverse interneurons (or T neurons), in adult turtles. T neurons were defined as having dendrites that extend further in the transverse plane than rostrocaudally and a soma that extends further mediolaterally than rostrocaudally. T neurons are multifunctional, as they were activated during both swimming and scratching motor patterns. T neurons had higher peak firing rates and larger membrane potential oscillations during scratching than scratch-activated interneurons with different dendritic morphologies ("non-T" neurons). These characteristics make T neurons good candidates to play an important role in integrating diverse inputs and generating or relaying rhythmic motor patterns. Here, we quantitatively investigated additional dendritic morphological characteristics of T neurons as compared to non-T neurons. We found that T neurons have less total dendritic length, a greater proportion of dendritic length in primary dendrites, and dendrites that are oriented more mediolaterally. Thus, T neuron dendritic trees extend far mediolaterally, yet are unusually simple, which may help channel synaptic current from distal dendrites in the lateral and ventral funiculi to the soma. In combination with T neuron physiological properties, these dendritic properties may help integrate supraspinal and propriospinal inputs and generate and/or modulate rhythmic limb movements.

  11. Immune therapy including dendritic cell based therapy in chronic hepatitis B virus infection

    Institute of Scientific and Technical Information of China (English)

    Sk Md Fazle Akbar; Norio Horiike; Morikazu Onji

    2006-01-01

    Hepatitis B virus (HBV) infection is a global public health problem. Of the approximately 2 billion people who have been infected worldwide, more than 400 million are chronic carriers of HBV. Considerable numbers of chronic HBV carriers suffer from progressive liver diseases. In addition, all HBV carriers are permanent source of this virus. There is no curative therapy for chronic HBV carriers. Antiviral drugs are recommended for about 10% patients, however, these drugs are costly, have limited efficacy, and possess considerable side effects.Recent studies have shown that immune responses of the host to the HBV are critically involved at every stage of chronic HBV infection: (1) These influence acquisition of chronic HBV carrier state, (2) They are important in the context of liver damages, (3) Recovery from chronic HBV-related liver diseases is dependent on nature and extent of HBV-specific immune responses.However, induction of adequate levels of HBV-specific immune responses in chronic HBV carriers is difficult.During the last one decade, hepatitis B vaccine has been administered to chronic HBV carriers as a therapeutic approach (vaccine therapy). The present regimen of vaccine therapy is safe and cheap, but not so effective.A dendritic cell-based therapeutic vaccine has recently been developed for treating chronic HBV infection. In this review, we will discuss about the concept, scientific logics, strategies and techniques of development of HBV-specific immune therapies including vaccine therapy and dendritic cell-based vaccine therapy for treating chronic HBV infection.

  12. Antigen Gene Transfer to Human Plasmacytoid Dendritic Cells Using Recombinant Adenovirus and Vaccinia Virus Vectors

    Directory of Open Access Journals (Sweden)

    Hetty J. Bontkes

    2005-01-01

    Full Text Available Recombinant adenoviruses (RAd and recombinant vaccinia viruses (RVV expressing tumour-associated antigens (TAA are used as anti-tumour vaccines. It is important that these vaccines deliver the TAA to dendritic cells (DC for the induction of a strong immune response. Infection of myeloid DC (MDC with RAd alone is relatively inefficient but CD40 retargeting significantly increases transduction efficiency and DC maturation. Infection with RVV is efficient without DC maturation. Plasmacytoid dendritic cells (PDC play a role in the innate immune response to viral infections through the secretion of IFNα but may also play a role in specific T-cell induction. The aim of our study was to investigate whether PDC are better targets for RAd and RVV based vaccines. RAd alone hardly infected PDC (2% while CD40 retargeting did not improve transduction efficiency, but it did increase PDC maturation (25% CD83 positive cells. Accordingly, specific CTL activation by RAd infected PDC was limited (the number of IFNγ producing CTL was reduced by 75% compared to stimulation with peptide loaded PDC. RVV infected PDC specifically stimulated CTL but PDC were not activated. These Results indicate that PDC are not ideal targets for RAd and RVV based vaccines. However, PDC induced specific CTL activation after pulsing with recombinant protein, indicating that PDC can also cross-present antigens released from surrounding infected cells.

  13. Automated three-dimensional detection and shape classification of dendritic spines from fluorescence microscopy images.

    Directory of Open Access Journals (Sweden)

    Alfredo Rodriguez

    Full Text Available A fundamental challenge in understanding how dendritic spine morphology controls learning and memory has been quantifying three-dimensional (3D spine shapes with sufficient precision to distinguish morphologic types, and sufficient throughput for robust statistical analysis. The necessity to analyze large volumetric data sets accurately, efficiently, and in true 3D has been a major bottleneck in deriving reliable relationships between altered neuronal function and changes in spine morphology. We introduce a novel system for automated detection, shape analysis and classification of dendritic spines from laser scanning microscopy (LSM images that directly addresses these limitations. The system is more accurate, and at least an order of magnitude faster, than existing technologies. By operating fully in 3D the algorithm resolves spines that are undetectable with standard two-dimensional (2D tools. Adaptive local thresholding, voxel clustering and Rayburst Sampling generate a profile of diameter estimates used to classify spines into morphologic types, while minimizing optical smear and quantization artifacts. The technique opens new horizons on the objective evaluation of spine changes with synaptic plasticity, normal development and aging, and with neurodegenerative disorders that impair cognitive function.

  14. Thermal diffusion dominated dendritic growth — an analysis of the wall proximity effect

    Science.gov (United States)

    Pines, Vladimir; Chait, Arnon; Zlatkowski, Marianne

    1996-09-01

    It is demonstrated that using a simple correction to the original Ivantsov solution to account for wall proximity effects is sufficient to describe the Peclet number microgravity data of Glicksman et al. [M.E. Glicksman, M.B. Koss and E.A. Winsa, Phys. Rev. Lett. 73 (1994) 573; M.E. Glicksman, M.B. Koss, L.T. Bushnell, J.C. LaCombe and E.A. Winsa, ISLJ International 35 (1995) 1216; MRS Fall Meeting, Symp. P, Boston MA, 1995, in press] at low supercooling. The analytical correction provides for the enhanced diffusive heat transfer when the thermal diffusion length becomes comparable to the physical chamber dimension. The wall proximity effect is also responsible for the existence of a lower supercooling limit below which the dendrite cannot grow in a steady-state manner. It is concluded that Glicksman's USMP-2 microgravity data is thermal diffusion dominated and thus entirely appropriate for comparison with dendritic growth theories.

  15. Phase-field simulation of dendritic solidification using a full threaded tree with adaptive meshing

    Institute of Scientific and Technical Information of China (English)

    Yin Yajun; Zhou Jianxin; Liao Dunming; Pang Shengyong; Shen Xu

    2014-01-01

    Simulation of the microstructure evolution during solidification is greatly beneficial to the control of solidification microstructures. A phase-field method based on the ful threaded tree (FTT) for the simulation of casting solidification microstructure was proposed in this paper, and the structure of the ful threaded tree and the mesh refinement method was discussed. During dendritic growth in solidification, the mesh for simulation is adaptively refined at the liquid-solid interface, and coarsened in other areas. The numerical results of a three-dimension dendrite growth indicate that the phase-field method based on FTT is suitable for microstructure simulation. Most importantly, the FTT method can increase the spatial and temporal resolutions beyond the limits imposed by the available hardware compared with the conventional uniform mesh. At the simulation time of 0.03 s in this study, the computer memory used for computation is no more than 10 MB with the FTT method, while it is about 50 MB with the uniform mesh method. In addition, the proposed FTT method is more efficient in computation time when compared with the uniform mesh method. It would take about 20 h for the uniform mesh method, while only 2 h for the FTT method for computation when the solidification time is 0.17 s in this study.

  16. Thymic anlage is colonized by progenitors restricted to T, NK, and dendritic cell lineages.

    Science.gov (United States)

    Masuda, Kyoko; Itoi, Manami; Amagai, Takashi; Minato, Nagahiro; Katsura, Yoshimoto; Kawamoto, Hiroshi

    2005-03-01

    It remains controversial whether the thymus-colonizing progenitors are committed to the T cell lineage. A major problem that has impeded the characterization of thymic immigrants has been that the earliest intrathymic progenitors thus far identified do not necessarily represent the genuine thymic immigrants, because their developmental potential should have been influenced by contact with the thymic microenvironment. In the present study, we examined the developmental potential of the ontogenically earliest thymic progenitors of day 11 murine fetus. These cells reside in the surrounding mesenchymal region and have not encountered thymic epithelial components. Flow cytometric and immunohistochemical analyses demonstrated that these cells are exclusively Lin(-)c-kit(+)IL-7R(+). Limiting dilution analyses disclosed that the progenitors with T cell potential were abundant, while those with B cell potential were virtually absent in the region of day 11 thymic anlage. Clonal analyses reveled that they are restricted to T, NK, and dendritic cell lineages. Each progenitor was capable of forming a large number of precursors that may clonally accommodate highly diverse TCRbeta chains. These results provide direct evidence that the progenitors restricted to the T/NK/dendritic cell lineage selectively immigrate into the thymus.

  17. Amphiphilic dendritic peptides: Synthesis and behavior as an organogelator and liquid crystal

    Directory of Open Access Journals (Sweden)

    Xinwu Ba

    2011-02-01

    Full Text Available New amphiphilic dendritic peptides on dendritic polyaspartic acid were designed and synthesized. The organogel and liquid crystal properties of these amphiphilic dendritic peptides were fully studied by field-emission SEM, temperature dependent FT-IR, differential scanning calorimetry, polarization optical microscopy and X-ray diffraction experiments. Amphiphilic dendritic peptides G3 show good organogel properties with a minimum gelation concentration as low as 1 wt %. Furthermore, amphiphilic dendritic peptides G3 can form a hexagonal columnar liquid crystal assembly over a wide temperature range.

  18. Dendritic SNAREs add a new twist to the old neuron theory

    Science.gov (United States)

    Ovsepian, Saak V.; Dolly, J. Oliver

    2011-01-01

    Dendritic exocytosis underpins a broad range of integrative and homeostatic synaptic functions. Emerging data highlight the essential role of SNAREs in trafficking and fusion of secretory organelles with release of peptides and neurotransmitters from dendrites. This Perspective analyzes recent evidence inferring axo-dendritic polarization of vesicular release machinery and pinpoints progress made with existing challenges in this rapidly progressing field of dendritic research. Interpreting the relation of new molecular data to physiological results on secretion from dendrites would greatly advance our understanding of this facet of neuronal mechanisms. PMID:22080607

  19. Characteristics of the Dendrite Growth in the Electrochemical Alane Production Process

    Directory of Open Access Journals (Sweden)

    Park Hyun-Kyu

    2016-01-01

    Full Text Available The electrochemical alane production process was proposed for a feasible production of alane. The operation of process was difficult because of short circuit by a dendrite growth in the reactor. Therefore, characteristics of the dendrite growth in the process were investigated. We conducted the electrochemical alane production process using Teflon block for inhibition of the dendrite growth. The obtained dendrite was characterized by XRD, SEM and ICP-AES. It was concluded that the dendrite growth was attributed to a melting and agglomeration of Al fine particles existed in the solution.

  20. Acute myeloid dendritic cell leukaemia with specific cutaneous involvement: a diagnostic challenge.

    Science.gov (United States)

    Ferran, M; Gallardo, F; Ferrer, A M; Salar, A; Pérez-Vila, E; Juanpere, N; Salgado, R; Espinet, B; Orfao, A; Florensa, L; Pujol, R M

    2008-05-01

    Myeloid or type 1 dendritic cell leukaemia is an exceedingly rare haematopoietic neoplasm characterized by a specific immunophenotypic profile close to plasmacytoid dendritic cell and acute myelogenous leukaemia. A 77-year-old man presenting specific cutaneous infiltration by myeloid dendritic cell leukaemia is reported. The clinical features as well as the cutaneous histopathological and immunohistochemical features led to the initial diagnosis of CD4+/CD56+ haematodermic neoplasm. However, extensive immunophenotypic studies performed from peripheral blood blasts disclosed that leukaemic cells expressed myeloid dendritic cell markers, confirming the diagnosis. The diagnostic difficulties of specific cutaneous involvement by myeloid dendritic cell leukaemia on the basis of routine histopathological and immunohistochemical features are highlighted.

  1. Semaphorin 7A Promotes Chemokine-Driven Dendritic Cell Migration

    NARCIS (Netherlands)

    van Rijn, Anoek; Paulis, Leonie; te Riet, Joost; Vasaturo, Angela; Reinieren-Beeren, Inge; van der Schaaf, Alie; Kuipers, Arthur J.; Schulte, Luuk P.; Jongbloets, Bart C.; Pasterkamp, R. Jeroen; Figdor, Carl G.; van Spriel, Annemiek B.; Buschow, Sonja I.

    2016-01-01

    Dendritic cell (DC) migration is essential for efficient host defense against pathogens and cancer, as well as for the efficacy of DC-based immunotherapies. However, the molecules that induce the migratory phenotype of DCs are poorly defined. Based on a largescale proteome analysis of maturing DCs,

  2. In vivo evidence for dendritic cell lysis by NK cells

    OpenAIRE

    Ferlazzo, Guido

    2012-01-01

    By using an experimental model of anticancer vaccination, we have recently lent support to the assumption, so far only sustained by in vitro data, that natural killer cells can restrain less immunogenic, allegedly tolerogenic, dendritic cells (DCs). This in vivo selection of immunogenic DCs appears to depend on perforin and to be associated with a more protective tumor-specific T lymphocyte response.

  3. Lung Dendritic cells: Targets for therapy in allergic disease

    NARCIS (Netherlands)

    B.N.M. Lambrecht (Bart)

    2008-01-01

    textabstractDendritic cells are crucial in determining the functional outcome of allergen encounter in the lung. Antigen presentation by myeloid DCs leads to Th2 sensitization typical of allergic disease, whereas antigen presentation by plasmacytoid DCs serves to dampen inflammation. It is increasin

  4. Dendritic cell-tumor cell hybrids and immunotherapy

    DEFF Research Database (Denmark)

    Cathelin, Dominique; Nicolas, Alexandra; Bouchot, André

    2011-01-01

    Dendritic cells (DC) are professional antigen-presenting cells currently being used as a cellular adjuvant in cancer immunotherapy strategies. Unfortunately, DC-based vaccines have not demonstrated spectacular clinical results. DC loading with tumor antigens and DC differentiation and activation...

  5. Harnessing human plasmacytoid dendritic cells as professional APCs

    NARCIS (Netherlands)

    Tel, J.; Leun, A.M. van der; Figdor, C.G.; Torensma, R.; Vries, I.J.M. de

    2012-01-01

    The plasmacytoid dendritic cell (pDC) constitutes a unique DC subset that links the innate and adaptive arm of the immune system. Whereas the unique capability of pDCs to produce large amounts of type I IFNs in response to pathogen recognition is generally accepted,their antigen-presenting function

  6. Migration of dendritic cell based cancer vaccines: in vivo veritas?

    NARCIS (Netherlands)

    Adema, G.J.; Vries, I.J.M. de; Punt, C.J.A.; Figdor, C.G.

    2005-01-01

    Ex vivo generated cancer vaccines based on dendritic cells (DCs) are currently applied in the clinic. The migration of DCs from the tissues to the lymph nodes is tightly controlled and involves many different mediators and their receptors. A recent study demonstrated that the rate of migration of

  7. Dynamic microtubules regulate dendritic spine morphology and synaptic plasticity

    NARCIS (Netherlands)

    Jaworski, J.; Kapitein, L.C.; Montenegro Gouveia, S.; Dortland, B.R.; Wulf, P.S.; Grigoriev, I.; Camera, P.; Spangler, S.A.; Di Stefano, P.; Demmers, J.; Krugers, H.; Defilippi, P.; Akhmanova, A.; Hoogenraad, C.C.

    2009-01-01

    Dendritic spines are the major sites of excitatory synaptic input, and their morphological changes have been linked to learning and memory processes. Here, we report that growing microtubule plus ends decorated by the microtubule tip-tracking protein EB3 enter spines and can modulate spine morpholog

  8. Phenotypical and functional characterization of clinical-grade dendritic cells.

    NARCIS (Netherlands)

    Vries, I.J.M. de; Adema, G.J.; Punt, C.J.A.; Figdor, C.G.

    2005-01-01

    Dendritic cells (DC) are the most potent antigen-presenting cells and form a promising new treatment modality. Fully activated DC loaded with antigen are very useful in stimulating immune responses, in particular those to combat cancer. Immature DC can either cause immunological tolerance or induce

  9. Avian dendritic cells: Phenotype and ontogeny in lymphoid organs.

    Science.gov (United States)

    Nagy, Nándor; Bódi, Ildikó; Oláh, Imre

    2016-05-01

    Dendritic cells (DC) are critically important accessory cells in the innate and adaptive immune systems. Avian DCs were originally identified in primary and secondary lymphoid organs by their typical morphology, displaying long cell processes with cytoplasmic granules. Several subtypes are known. Bursal secretory dendritic cells (BSDC) are elongated cells which express vimentin intermediate filaments, MHC II molecules, macrophage colony-stimulating factor 1 receptor (CSF1R), and produce 74.3+ secretory granules. Avian follicular dendritic cells (FDC) highly resemble BSDC, express the CD83, 74.3 and CSF1R molecules, and present antigen in germinal centers. Thymic dendritic cells (TDC), which express 74.3 and CD83, are concentrated in thymic medulla while interdigitating DC are found in T cell-rich areas of secondary lymphoid organs. Avian Langerhans cells are a specialized 74.3-/MHC II+ cell population found in stratified squamous epithelium and are capable of differentiating into 74.3+ migratory DCs. During organogenesis hematopoietic precursors of DC colonize the developing lymphoid organ primordia prior to immigration of lymphoid precursor cells. This review summarizes our current understanding of the ontogeny, cytoarchitecture, and immunophenotype of avian DC, and offers an antibody panel for the in vitro and in vivo identification of these heterogeneous cell types.

  10. Multimodal imaging of nanovaccine carriers targeted to human dendritic cells

    NARCIS (Netherlands)

    Cruz, L.J.; Tacken, P.J.; Bonetto, F.J.; Buschow, S.I.; Croes, H.J.E.; Wijers-Rouw, M.J.P.; Vries, I.J.M. de; Figdor, C.G.

    2011-01-01

    Dendritic cells (DCs) are key players in the initiation of adaptive immune responses and are currently exploited in immunotherapy against cancer and infectious diseases. The targeted delivery of nanovaccine particles (NPs) to DCs in vivo is a promising strategy to enhance immune responses. Here, tar

  11. Kicking off adaptive immunity: the discovery of dendritic cells

    OpenAIRE

    Katsnelson, Alla

    2006-01-01

    In 1973, Ralph Steinman and Zanvil Cohn discovered an unusual looking population of cells with an unprecedented ability to activate naive T cells. Dubbed “dendritic cells,” these cells are now known as the primary instigators of adaptive immunity.

  12. MIM-Induced Membrane Bending Promotes Dendritic Spine Initiation.

    Science.gov (United States)

    Saarikangas, Juha; Kourdougli, Nazim; Senju, Yosuke; Chazal, Genevieve; Segerstråle, Mikael; Minkeviciene, Rimante; Kuurne, Jaakko; Mattila, Pieta K; Garrett, Lillian; Hölter, Sabine M; Becker, Lore; Racz, Ildikó; Hans, Wolfgang; Klopstock, Thomas; Wurst, Wolfgang; Zimmer, Andreas; Fuchs, Helmut; Gailus-Durner, Valérie; Hrabě de Angelis, Martin; von Ossowski, Lotta; Taira, Tomi; Lappalainen, Pekka; Rivera, Claudio; Hotulainen, Pirta

    2015-06-22

    Proper morphogenesis of neuronal dendritic spines is essential for the formation of functional synaptic networks. However, it is not known how spines are initiated. Here, we identify the inverse-BAR (I-BAR) protein MIM/MTSS1 as a nucleator of dendritic spines. MIM accumulated to future spine initiation sites in a PIP2-dependent manner and deformed the plasma membrane outward into a proto-protrusion via its I-BAR domain. Unexpectedly, the initial protrusion formation did not involve actin polymerization. However, PIP2-dependent activation of Arp2/3-mediated actin assembly was required for protrusion elongation. Overexpression of MIM increased the density of dendritic protrusions and suppressed spine maturation. In contrast, MIM deficiency led to decreased density of dendritic protrusions and larger spine heads. Moreover, MIM-deficient mice displayed altered glutamatergic synaptic transmission and compatible behavioral defects. Collectively, our data identify an important morphogenetic pathway, which initiates spine protrusions by coupling phosphoinositide signaling, direct membrane bending, and actin assembly to ensure proper synaptogenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Dendritic Immunotherapy Improvement for an Optimal Control Murine Model

    Directory of Open Access Journals (Sweden)

    J. C. Rangel-Reyes

    2017-01-01

    Full Text Available Therapeutic protocols in immunotherapy are usually proposed following the intuition and experience of the therapist. In order to deduce such protocols mathematical modeling, optimal control and simulations are used instead of the therapist’s experience. Clinical efficacy of dendritic cell (DC vaccines to cancer treatment is still unclear, since dendritic cells face several obstacles in the host environment, such as immunosuppression and poor transference to the lymph nodes reducing the vaccine effect. In view of that, we have created a mathematical murine model to measure the effects of dendritic cell injections admitting such obstacles. In addition, the model considers a therapy given by bolus injections of small duration as opposed to a continual dose. Doses timing defines the therapeutic protocols, which in turn are improved to minimize the tumor mass by an optimal control algorithm. We intend to supplement therapist’s experience and intuition in the protocol’s implementation. Experimental results made on mice infected with melanoma with and without therapy agree with the model. It is shown that the dendritic cells’ percentage that manages to reach the lymph nodes has a crucial impact on the therapy outcome. This suggests that efforts in finding better methods to deliver DC vaccines should be pursued.

  14. Computational modeling of memory allocation in neuronal and dendritic populations

    Directory of Open Access Journals (Sweden)

    George I Kastellakis

    2014-03-01

    Full Text Available Recent studies using molecular and cellular approaches have established that memory is supported by distributed and sparse populations of neurons. The allocation of neurons and synapses to store a long term memory engram is not random, but depends on properties such as neuronal excitability and CREB activation. The consolidation of synaptic plasticity, which is believed to serve long-term memory storage, is dependent on protein availability, and shaped by the mechanism of synaptic tagging and capture. In addition, dendritic protein synthesis allows for compartmentalized plasticity and synapse clustering. The implications of the rules governing long-term memory allocation in neurons and their dendrites are not yet known. To this aim, we present a model that incorporates multiple plasticity-related mechanisms which are known to be active during memory allocation and consolidation. Using this model, we show that memory allocation in neurons and their dendrites is affected by dendritic protein synthesis, and that the late-LTP associativity mechanisms allow related memories to be stored in overlapping populations of neurons.

  15. Computational implications of cooperative plasticity induction at nearby dendritic sites.

    Science.gov (United States)

    Morita, Kenji

    2009-01-06

    Recent studies have revealed that plasticity is not regulated independently at individual synapses but rather that there is cooperativity or associativity between nearby synapses in the dendritic tree of individual cortical pyramidal cells. Here, I summarize experimental results regarding such cooperative plasticity and its underlying mechanisms and consider their computational implications.

  16. Dendritic cells and their role in tumor immunosurveillance

    NARCIS (Netherlands)

    Strioga, M.M.; Schijns, V.E.J.C.; Powell, D.J.; Pasukoniene, V.; Dobrovolskiene, N.T.; Michalek, J.

    2013-01-01

    Dendritic cells (DCs) comprise a heterogeneous population of cells that play a key role in initiating, directing and regulating adaptive immune responses, including those critically involved in tumor immunosurveillance. As a riposte to the central role of DCs in the generation of antitumor immune re

  17. Molecular Mechanisms Regulating Human Dendritic Cell Development, Survival and Function

    NARCIS (Netherlands)

    L. van de Laar (Lianne)

    2011-01-01

    textabstractDendritic cells (DC) are professional antigen presenting cells (APC) with a dual function in the immune system. On the one hand, these specialized leukocytes are equipped to alert the immune system to invading pathogens or other danger signals. On the other, DC can promote tolerogenic re

  18. Monocyte-derived dendritic cells in bipolar disorder

    NARCIS (Netherlands)

    Knijff, EM; Ruwhof, C; de Wit, HJ; Kupka, RW; Vonk, R; Akkerhuis, GW; Nolen, WA; Drexhage, HA

    2006-01-01

    Background: Dendritic cells (DC) are key regulators of the immune system, which is compromised in patients with bipolar disorder. We sought to study monocyte-derived DC in bipolar disorder. Methods: Monocytes purified from blood collected from DSM-IV bipolar disorder outpatients (n = 53, 12 without

  19. Nomenclature of monocytes and dendritic cells in blood

    NARCIS (Netherlands)

    L. Ziegler-Heitbrock (Loems); P. Ancuta (Petronela); S. Crowe (Suzanne); M. Dalod (Marc); V. Grau (Veronika); D.N. Hart (Derek); P.J. Leenen (Pieter); Y.J. Liu; G. MacPherson (Gordon); G.J. Randolph (Gwendalyn); J. Scherberich (Juergen); J. Schmitz (Juergen); K. Shortman (Ken); S. Sozzani (Silvano); H. Strobl (Herbert); M. Zembala (Marek); J.M. Austyn (Jonathan); M.B. Lutz (Manfred)

    2010-01-01

    textabstractMonocytes and cells of the dendritic cell lineage circulate in blood and eventually migrate into tissue where they further mature and serve various functions, most notably in immune defense. Over recent years these cells have been characterized in detail with the use of cell surface mark

  20. Synthesis, magnetic and microwave electromagnetic properties of dendritic iron

    Science.gov (United States)

    Yan, Gongqin; He, Fei; Zhao, Guanlin; Wei, Pengwan; Jiang, Anbang

    2015-09-01

    Iron dendritic micropines are synthesized by a hydrogen reduction, where the hematite dendritic micropines prepared by a hydrothermal method are used as starting materials. The as-obtained dendritic iron exhibits enhanced coercivity and remanent magnetization at room temperature and high complex permittivity at 2-18 GHz due to the peculiar shape anisotropy and good crystallinity. The negative imaginary permeability is observed at 14.5-18.0 GHz, suggesting it has a potential as a left-handed material. The paraffin-based composites containing 30 wt% dendritic irons show large permittivity resulting from the charge polarization and the conductivity and have a minimal reflection loss (RL) of -37.4 dB at 7.4 GHz when the thickness ( d) is 2.0 mm. The RL values less than -20 dB are obtained in the frequency range of 5.5-12.9 GHz when d increases from 0.9 to 3.0 mm.

  1. Interaction of classical swine fever virus with dendritic cells

    NARCIS (Netherlands)

    Carrasco, C.P.; Rigden, R.C.; Vincent, I.E.; Balmelli, C.; Ceppi, M.; Bauhofer, O.; Tache, V.; Hjertner, B.; McNeilly, F.; Gennip, van H.G.P.; McCullough, K.C.; Summerfield, A.

    2004-01-01

    Functional disruption of dendritic cells (DCs) is an important strategy for viral pathogens to evade host defences. Monocytotropic viruses such as classical swine fever virus (CSFV) could employ such a mechanism, since the virus can suppress immune responses and induce apoptosis without infecting ly

  2. IL-10 control of dendritic cells in the skin

    NARCIS (Netherlands)

    B.E. Clausen (Bjorn); M.J.H. Girard-Madoux (Mathilde)

    2013-01-01

    textabstractInterleukin-10 (IL-10) is a potent immunomodulatory cytokine, whose cellular targets have not yet been precisely identified. Mice bearing a dendritic cell (DC)-specific defect in the IL-10 receptor mice exhibit exaggerated T-cell reactivation in the skin, highlighting a key function of D

  3. Multiple modes of action potential initiation and propagation in mitral cell primary dendrite

    DEFF Research Database (Denmark)

    Chen, Wei R; Shen, Gongyu Y; Shepherd, Gordon M

    2002-01-01

    The mitral cell primary dendrite plays an important role in transmitting distal olfactory nerve input from olfactory glomerulus to the soma-axon initial segment. To understand how dendritic active properties are involved in this transmission, we have combined dual soma and dendritic patch...... recordings with computational modeling to analyze action-potential initiation and propagation in the primary dendrite. In response to depolarizing current injection or distal olfactory nerve input, fast Na(+) action potentials were recorded along the entire length of the primary dendritic trunk. With weak......-initiation site reflected an independent thresholding mechanism in the distal dendrite. When strong olfactory nerve excitation was paired with strong inhibition to the mitral cell basal secondary dendrites, a small fast prepotential was recorded at the soma, which indicated that an action potential was initiated...

  4. The "conscious pilot"-dendritic synchrony moves through the brain to mediate consciousness.

    Science.gov (United States)

    Hameroff, Stuart

    2010-01-01

    Cognitive brain functions including sensory processing and control of behavior are understood as "neurocomputation" in axonal-dendritic synaptic networks of "integrate-and-fire" neurons. Cognitive neurocomputation with consciousness is accompanied by 30- to 90-Hz gamma synchrony electroencephalography (EEG), and non-conscious neurocomputation is not. Gamma synchrony EEG derives largely from neuronal groups linked by dendritic-dendritic gap junctions, forming transient syncytia ("dendritic webs") in input/integration layers oriented sideways to axonal-dendritic neurocomputational flow. As gap junctions open and close, a gamma-synchronized dendritic web can rapidly change topology and move through the brain as a spatiotemporal envelope performing collective integration and volitional choices correlating with consciousness. The "conscious pilot" is a metaphorical description for a mobile gamma-synchronized dendritic web as vehicle for a conscious agent/pilot which experiences and assumes control of otherwise non-conscious auto-pilot neurocomputation.

  5. Study of protein and RNA in dendritic spines using multi-isotope imaging mass spectrometry (MIMS).

    Science.gov (United States)

    Brismar, H; Aperia, A; Westin, L; Moy, J; Wang, M; Guillermier, C; Poczatek, C; Lechene, C

    2014-11-01

    The classical view of neuronal protein synthesis is that proteins are made in the cell body and then transported to their functional sites in the dendrites and the dendritic spines. Indirect evidence, however, suggests that protein synthesis can directly occur in the distal dendrites, far from the cell body. We are developing protocols for dual labeling of RNA and proteins using (15)N-uridine and (18)O- or (13)C-leucine pulse chase in cultured neurons to identify and localize both protein synthesis and fate of newly synthesized proteins. Pilot experiments show discrete localization of both RNA and newly synthesized proteins in dendrites, close to dendritic spines. We have for the first time directly imaged and measured the production of proteins at the subcellular level in the neuronal dendrites, close to the functional sites, the dendritic spines. This will open a powerful way to study neural growth and synapse plasticity in health and disease.

  6. Self-organizing mechanism for development of space-filling neuronal dendrites.

    Directory of Open Access Journals (Sweden)

    Kaoru Sugimura

    2007-11-01

    Full Text Available Neurons develop distinctive dendritic morphologies to receive and process information. Previous experiments showed that competitive dendro-dendritic interactions play critical roles in shaping dendrites of the space-filling type, which uniformly cover their receptive field. We incorporated this finding in constructing a new mathematical model, in which reaction dynamics of two chemicals (activator and suppressor are coupled to neuronal dendrite growth. Our numerical analysis determined the conditions for dendritic branching and suggested that the self-organizing property of the proposed system can underlie dendritogenesis. Furthermore, we found a clear correlation between dendrite shape and the distribution of the activator, thus providing a morphological criterion to predict the in vivo distribution of the hypothetical molecular complexes responsible for dendrite elongation and branching.

  7. Differential Dendritic Integration of Synaptic Potentials and Calcium in Cerebellar Interneurons.

    Science.gov (United States)

    Tran-Van-Minh, Alexandra; Abrahamsson, Therése; Cathala, Laurence; DiGregorio, David A

    2016-08-17

    Dendritic voltage integration determines the transformation of synaptic inputs into output firing, while synaptic calcium integration drives plasticity mechanisms thought to underlie memory storage. Dendritic calcium integration has been shown to follow the same synaptic input-output relationship as dendritic voltage, but whether similar operations apply to neurons exhibiting sublinear voltage integration is unknown. We examined the properties and cellular mechanisms of these dendritic operations in cerebellar molecular layer interneurons using dendritic voltage and calcium imaging, in combination with synaptic stimulation or glutamate uncaging. We show that, while synaptic potentials summate sublinearly, concomitant dendritic calcium signals summate either linearly or supralinearly depending on the number of synapses activated. The supralinear dendritic calcium triggers a branch-specific, short-term suppression of neurotransmitter release that alters the pattern of synaptic activation. Thus, differential voltage and calcium integration permits dynamic regulation of neuronal input-output transformations without altering intrinsic nonlinear integration mechanisms.

  8. Structure simulation in unidirectionally solidified turbine blade by dendrite envelope tracking model(Ⅰ): numerical modeling

    Institute of Scientific and Technical Information of China (English)

    WANG Tong-min; I. Ohnaka; H.Yasuda; SU Yan-qing; GUO Jing-jie

    2006-01-01

    A 3D dendrite envelope tracking model was developed for estimating the solidification structure of unidirectionally solidified turbine blade. The normal vector of dendrite envelope was estimated by the gradient of dendrite volume fraction, and growth velocity of the dendrite envelope (dendrite tips) was calculated with considering the anisotropy of grain growth. The solute redistribution at dendrite envelope was calculated by introducing an effective solute partition coefficient(ke). Simulation results show that the solute-build-up due to the rejection at envelope affects grain competition and consequently the solidification structure. The lower value of ke leads to more waved dendrite growth front and higher solute rejection. The model was applied to predict the structure of turbine-blade-shape samples showing good ability to reproduce the columnar and single grain structures.

  9. A Rayleigh number based dendrite fragmentation criterion for detachment of solid crystals during solidification

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Arvind; Dutta, Pradip [Department of Mechanical Engineering, Indian Institute of Science, Bangalore 560012 (India)], E-mail: pradip@mecheng.iisc.ernet.in

    2008-08-07

    Movement of solid crystals in the form of dendrite fragments causes severe macro-segregation in solidified products. Dendrite fragmentation in the developing mushy zone occurs as a result of remelting (causing dissolution) and subsequent breakage of dendritic side arms from the dendritic stalks. An understanding of the mechanisms of dendrite fragmentation is essential for predicting the transport of fragmented solid crystals for possible control of macro-segregation. In this work, a Rayleigh number based fragmentation criterion is developed for detachment of dendrites from the developing mushy zone, which determines the conditions favourable for fragmentation of dendrites. The Rayleigh number, defined in this paper, measures the ratio of the driving buoyancy force for the flow in the mushy zone to the retarding frictional force associated with the permeability of the mush. The criterion developed is a function of the concentration difference, liquid fraction, permeability, growth rate of mushy layer and thermophysical properties of the material.

  10. Signal transfer in passive dendrites with nonuniform membrane conductance.

    Science.gov (United States)

    London, M; Meunier, C; Segev, I

    1999-10-01

    In recent years it became clear that dendrites possess a host of ion channels that may be distributed nonuniformly over their membrane surface. In cortical pyramids, for example, it was demonstrated that the resting membrane conductance G(m)(x) is higher (the membrane is "leakier") at distal dendritic regions than at more proximal sites. How does this spatial nonuniformity in G(m)(x) affect the input-output function of the neuron? The present study aims at providing basic insights into this question. To this end, we have analytically studied the fundamental effects of membrane non-uniformity in passive cable structures. Keeping the total membrane conductance over a given modeled structure fixed (i.e., a constant number of passive ion channels), the classical case of cables with uniform membrane conductance is contrasted with various nonuniform cases with the following general conclusions. (1) For cylindrical cables with "sealed ends," monotonic increase in G(m)(x) improves voltage transfer from the input location to the soma. The steeper the G(m)(x), the larger the improvement. (2) This effect is further enhanced when the stimulation is distal and consists of a synaptic input rather than a current source. (3) Any nonuniformity in G(m)(x) decreases the electrotonic length, L, of the cylinder. (4) The system time constant tau(0) is larger in the nonuniform case than in the corresponding uniform case. (5) When voltage transients relax with tau(0), the dendritic tree is not isopotential in the nonuniform case, at variance with the uniform case. The effect of membrane nonuniformity on signal transfer in reconstructed dendritic trees and on the I/f relation of the neuron is also considered, and experimental methods for assessing membrane nonuniformity in dendrites are discussed.

  11. Characterization of small, mononuclear blood cells from salmon having high phagocytic capacity and ability to differentiate into dendritic like cells.

    Directory of Open Access Journals (Sweden)

    Gyri T Haugland

    Full Text Available Phagocytes are the principal component of the innate immune system, playing a key role in the clearance of foreign particles that include potential pathogens. In vertebrates, both neutrophils and mononuclear cells like monocytes, macrophages and dendritic cells are all professional phagocytes. In teleosts, B-lymphocytes also have potent phagocytic ability. We have isolated a population of small (<5 µm, mononuclear blood cells from Atlantic salmon (Salmo salar L. not previously characterized. In order to identify them, we have performed morphological, gene expression, flow cytometry, cytochemical, ultrastructural and functional analyses. Interestingly, they highly express the gene encoding CD83, the most characteristic cell surface marker for dendritic cells in mammals, and MHC class II limited to professional antigen presenting cells. They did not express genes nor did they have cell markers for B-cells, T-cells, monocytes/macrophages or neutrophils as shown by qRT-PCR, flow cytometry and immunoblotting. A remarkable feature of these cells is their potent phagocytic capacity. Their oxygen-independent killing mechanism, as shown by intense acid phosphatase staining, is supported by lack of respiratory burst and myeloperoxidase activity and the acid phosphatase's sensitivity to tartrate. They show a high level of morphological plasticity, as, upon stimulation with mitogens, they change morphology and obtain branching protrusions similarly to dendritic cells. We suggest, based on our findings, that the small, round cells described here are progenitor cells with potential to differentiate into dendritic like cells, although we can not exclude the possibility that they represent a novel cell type.

  12. Platinum nanoparticles decorated dendrite-like gold nanostructure on glassy carbon electrodes for enhancing electrocatalysis performance to glucose oxidation

    Science.gov (United States)

    Jia, Hongmei; Chang, Gang; Lei, Ming; He, Hanping; Liu, Xiong; Shu, Honghui; Xia, Tiantian; Su, Jie; He, Yunbin

    2016-10-01

    Platinum nanoparticles decorated dendrite-like gold nanostructure, bimetal composite materials on glassy carbon electrode (Pt/DGNs/GC) for enhancing electrocatalysis to glucose oxidation was designed and successfully fabricated by a facile two-step deposition method without any templates, surfactants, or stabilizers. Dendrite-like gold nanostructure was firstly deposited on the GC electrode via the potentiostatic method, and then platinum nanoparticles were decorated on the surface of gold substrate through chemical reduction deposition. X-ray diffraction (XRD), field-emission scanning electron microscope (FE-SEM), energy-dispersive X-ray spectroscopy (EDS) were applied to characterize the evolution of morphology and structure of the as-prepared Pt/DGNs/GC. Based on electrochemical measurements such as cyclic voltammetry, linear voltammetry and chronoamperometry, Pt/DGNs/GC exhibited significantly enhanced electrocatalytic performance to glucose oxidation compared those of pure dendrite-like Au nanoparticles in our previous report. Controlling chemical reduction deposition time, the amount of platinum nanoparticles on Au surface could be regulated, which further tuned electrocatalytic properties toward glucose oxidation. The dendrite-like gold surface partially covered by platinum nanoparticles dramatically enhanced the electrocatalytic performance for the oxidation of glucose because of excellent synergetic effects between gold and platinum species and the increased electrochemical active area from Pt nanoparticles loading. The non-enzymatic glucose biosensor based on Pt/DGNs/GC showed a rapid respond time (within 2 s), wide linear range (from 0.1 mM to 14 mM), low detection limit (0.01 mM), supernal sensitivity (275.44 μA cm-2 mM-1, R = 0.993), satisfactory reproducibility and good stability for glucose sensing. It was demonstrated that Pt/DGNs/GC could work as promising candidate for factual non-enzymatic glucose detection.

  13. Serum inducible kinase is a positive regulator of cortical dendrite development and is required for BDNF-promoted dendritic arborization

    Institute of Scientific and Technical Information of China (English)

    Shun-Ling Guo; Guo-He Tan; Shuai Li; Xue-Wen Cheng; Ya Zhou; Yun-Fang Jia; Hui Xiong; Jiong Tao; Zhi-Qi Xiong

    2012-01-01

    Serum inducible kinase (SNK),also known as (p)olo-(l)ike (k)inase 2 (PLK2),is a known regulator of mitosis,synaptogenesis and synaptic homeostasis.However,its role in early cortical development is unknown.Herein,we show that snk is expressed in the cortical plate from embryonic day 14,but not in the ventricular/subventricular zones (VZ/SVZ),and SNK protein localizes to the soma and dendrites of cultured immature cortical neurons.Loss of SNK impaired dendritic but not axonal arborization in a dose-dependent manner and overexpression had opposite effects,both in vitro and in vivo.Overexpression of SNK also caused abnormal branching of the leading process of migrating cortical neurons in electroporated cortices.The kinase activity was necessary for these effects.Extracellular signalregulated kinase (ERK) pathway activity downstream of brain-derived neurotrophic factor (BDNF) stimulation led to increases in SNK protein expression via transcriptional regulation,and this upregulation was necessary for the growth-promoting effect of BDNF on dendritic arborization.Taken together,our results indicate that SNK is essential for dendrite morphogenesis in cortical neurons.

  14. Conditional self-discrimination enhances dendritic spine number and dendritic length at prefrontal cortex and hippocampal neurons of rats.

    Science.gov (United States)

    Penagos-Corzo, Julio C; Bonilla, Andrea; Rodríguez-Moreno, Antonio; Flores, Gonzalo; Negrete-Díaz, José V

    2015-11-01

    We studied conditional self-discrimination (CSD) in rats and compared the neuronal cytoarchitecture of untrained animals and rats that were trained in self-discrimination. For this purpose, we used thirty 10-week-old male rats were randomized into three groups: one control group and two conditioning groups: a comparison group (associative learning) and an experimental group (self-discrimination). At the end of the conditioning process, the experimental group managed to discriminate their own state of thirst. After the conditioning process, dendritic morphological changes in the pyramidal neurons of the prefrontal cortex and CA1 region of the dorsal hippocampus were evaluated using Golgi-Cox stain method and then analyzed by the Sholl method. Differences were found in total dendritic length and spine density. Animals trained in self-discrimination showed an increase in the dendritic length and the number of dendritic spines of neurons of the prefrontal cortex and CA1 region of the dorsal hippocampus. Our data suggest that conditional self-discrimination improves the connectivity of the prefrontal cortex and dorsal CA1, which has implications for memory and learning processes.

  15. The analysis of purkinje cell dendritic morphology in organotypic slice cultures.

    Science.gov (United States)

    Kapfhammer, Josef P; Gugger, Olivia S

    2012-03-21

    Purkinje cells are an attractive model system for studying dendritic development, because they have an impressive dendritic tree which is strictly oriented in the sagittal plane and develops mostly in the postnatal period in small rodents (3). Furthermore, several antibodies are available which selectively and intensively label Purkinje cells including all processes, with anti-Calbindin D28K being the most widely used. For viewing of dendrites in living cells, mice expressing EGFP selectively in Purkinje cells (11) are available through Jackson labs. Organotypic cerebellar slice cultures cells allow easy experimental manipulation of Purkinje cell dendritic development because most of the dendritic expansion of the Purkinje cell dendritic tree is actually taking place during the culture period (4). We present here a short, reliable and easy protocol for viewing and analyzing the dendritic morphology of Purkinje cells grown in organotypic cerebellar slice cultures. For many purposes, a quantitative evaluation of the Purkinje cell dendritic tree is desirable. We focus here on two parameters, dendritic tree size and branch point numbers, which can be rapidly and easily determined from anti-calbindin stained cerebellar slice cultures. These two parameters yield a reliable and sensitive measure of changes of the Purkinje cell dendritic tree. Using the example of treatments with the protein kinase C (PKC) activator PMA and the metabotropic glutamate receptor 1 (mGluR1) we demonstrate how differences in the dendritic development are visualized and quantitatively assessed. The combination of the presence of an extensive dendritic tree, selective and intense immunostaining methods, organotypic slice cultures which cover the period of dendritic growth and a mouse model with Purkinje cell specific EGFP expression make Purkinje cells a powerful model system for revealing the mechanisms of dendritic development.

  16. Dynamics of intrinsic dendritic calcium signaling during tonic firing of thalamic reticular neurons.

    Directory of Open Access Journals (Sweden)

    Patrick Chausson

    Full Text Available The GABAergic neurons of the nucleus reticularis thalami that control the communication between thalamus and cortex are interconnected not only through axo-dendritic synapses but also through gap junctions and dendro-dendritic synapses. It is still unknown whether these dendritic communication processes may be triggered both by the tonic and the T-type Ca(2+ channel-dependent high frequency burst firing of action potentials displayed by nucleus reticularis neurons during wakefulness and sleep, respectively. Indeed, while it is known that activation of T-type Ca(2+ channels actively propagates throughout the dendritic tree, it is still unclear whether tonic action potential firing can also invade the dendritic arborization. Here, using two-photon microscopy, we demonstrated that dendritic Ca(2+ responses following somatically evoked action potentials that mimic wake-related tonic firing are detected throughout the dendritic arborization. Calcium influx temporally summates to produce dendritic Ca(2+ accumulations that are linearly related to the duration of the action potential trains. Increasing the firing frequency facilitates Ca(2+ influx in the proximal but not in the distal dendritic compartments suggesting that the dendritic arborization acts as a low-pass filter in respect to the back-propagating action potentials. In the more distal compartment of the dendritic tree, T-type Ca(2+ channels play a crucial role in the action potential triggered Ca(2+ influx suggesting that this Ca(2+ influx may be controlled by slight changes in the local dendritic membrane potential that determine the T-type channels' availability. We conclude that by mediating Ca(2+ dynamic in the whole dendritic arborization, both tonic and burst firing of the nucleus reticularis thalami neurons might control their dendro-dendritic and electrical communications.

  17. Passive Dendrites Enable Single Neurons to Compute Linearly Non-separable Functions

    Science.gov (United States)

    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

  18. Limits on $\

    CERN Document Server

    Perego, D L

    2002-01-01

    A limit on the tau neutrino mass is obtained using all the $Z^{0} \\to \\tau^{+} \\tau^{-}$ data collected at LEP by the DELPHI detector between 1992 and 1995. In this analysis events in which one of the taus decays into one charged particle, while the second $\\tau$ decays into f{}ive charged pions (1-5 topology) have been used. The neutrino mass is determined from a bidimensional \\fit ~on the invariant mass $m^{*}_{5 \\pi}$ and on the energy $E_{5 \\pi}$ of the f{}ive $\\pi^{\\pm}$ system. The result found is $m_{\

  19. Environmental alkylphenols modulate cytokine expression in plasmacytoid dendritic cells.

    Directory of Open Access Journals (Sweden)

    Chih-Hsing Hung

    Full Text Available BACKGROUND: Alkylphenols, such as nonylphenol (NP and 4-octylphenol (4-OP, have the potential to disturb immune system due to their weak estrogen-like activity, an effect with potential serious public health impact due to the worldwide distribution of these substances. Plasmacytoid dendritic cells (PDCs can secrete large amounts of type I IFNs and are critical in immune regulation. However, there has been limited study about the influence of alkylphenols on the function of pDCs. OBJECTIVE: The aim of this study was to examine the effect of alkylphenols on pDC functions in vitro and in vivo and then further explored the involved signaling pathways and epigenetic changes. METHODS: Circulating pDCs from human peripheral blood mononuclear cells were treated with alkylphenols with or without CpG stimulation. Alkylphenol-associated cytokine responses, signaling events, histone modifications and viral activity were further examined. In NP-exposed mice, the effect of NP on splenic pDC function and allergic lung inflammation were also assessed. RESULTS: The results showed that NP increased the expression of TNF-α, but suppressed IL-10 production in the range of physiological doses, concomitant with activation of the MKK3/6-p38 signaling pathway and enhanced levels of acetylated histone 3 as well as histone 4 at the TNFA gene locus. Further, in CpG-stimulated pDCs, NP suppressed type I IFNs production, associated with down-regulation of IRF-7 and MKK1/2-ERK-Elk-1 pathways and led to the impaired anti-enterovirus 71 activity in vitro. Additionally, splenic pDCs from NP-exposed mice showed similar cytokine changes upon CpG stimulation under conditions relevant to route and level of exposure in humans. NP treatment also enhanced allergic lung inflammation in vivo. CONCLUSION: Alkylphenols may influence pDCs' functions via their abilities to induce expression of a pro-inflammatory cytokine, TNF-α, and to suppress regulatory cytokines, including IL-10, IFN

  20. Recognition of enteroinvasive Escherichia coli and Shigella flexneri by dendritic cells: distinct dendritic cell activation states

    Directory of Open Access Journals (Sweden)

    Ana Carolina Ramos Moreno

    2012-02-01

    Full Text Available The innate and adaptive immune responses of dendritic cells (DCs to enteroinvasive Escherichia coli (EIEC infection were compared with DC responses to Shigella flexneri infection. EIEC triggered DCs to produce interleukin (IL-10, IL-12 and tumour necrosis factor (TNF-α, whereas S. flexneri induced only the production of TNF-α. Unlike S. flexneri, EIEC strongly increased the expression of toll like receptor (TLR-4 and TLR-5 in DCs and diminished the expression of co-stimulatory molecules that may cooperate to inhibit CD4+ T-lymphocyte proliferation. The inflammation elicited by EIEC seems to be related to innate immunity both because of the aforementioned results and because only EIEC were able to stimulate DC transmigration across polarised Caco-2 cell monolayers, a mechanism likely to be associated with the secretion of CC chemokine ligands (CCL20 and TNF-α. Understanding intestinal DC biology is critical to unravelling the infection strategies of EIEC and may aid in the design of treatments for infectious diseases.

  1. Dendritic cell SIRPα regulates homeostasis of dendritic cells in lymphoid organs.

    Science.gov (United States)

    Washio, Ken; Kotani, Takenori; Saito, Yasuyuki; Respatika, Datu; Murata, Yoji; Kaneko, Yoriaki; Okazawa, Hideki; Ohnishi, Hiroshi; Fukunaga, Atsushi; Nishigori, Chikako; Matozaki, Takashi

    2015-06-01

    Signal regulatory protein α (SIRPα), an immunoglobulin superfamily protein that is expressed predominantly in myeloid lineage cells such as dendritic cells (DCs) or macrophages, mediates cell-cell signaling. In the immune system, SIRPα is thought to be important for homeostasis of DCs, but it remains unclear whether SIRPα intrinsic to DCs is indeed indispensable for such functional role. Thus, we here generated the mice, in which SIRPα was specifically ablated in CD11c(+) DCs (Sirpa(Δ) (DC) ). Sirpa(Δ) (DC) mice manifested a marked reduction of CD4(+) CD8α(-) conventional DCs (cDCs) in the secondary lymphoid organs, as well as of Langerhans cells in the epidermis. Such reduction of cDCs in Sirpa(Δ) (DC) mice was comparable to that apparent with the mice, in which SIRPα was systemically ablated. Expression of SIRPα in DCs was well correlated with that of either endothelial cell-selective adhesion molecule (ESAM) or Epstein-Barr virus-induced molecule 2 (EBI2), both of which were also implicated in the regulation of DC homeostasis. Indeed, ESAM(+) or EBI2(+) cDCs were markedly reduced in the spleen of Sirpa(Δ) (DC) mice. Thus, our results suggest that SIRPα intrinsic to CD11c(+) DCs is essential for homeostasis of cDCs in the secondary lymphoid organs and skin.

  2. Cigarette smoke promotes dendritic cell accumulation in COPD; a Lung Tissue Research Consortium study

    Directory of Open Access Journals (Sweden)

    Yi Eunhee S

    2010-04-01

    Full Text Available Abstract Background Abnormal immune responses are believed to be highly relevant in the pathogenesis of chronic obstructive pulmonary disease (COPD. Dendritic cells provide a critical checkpoint for immunity by their capacity to both induce and suppress immunity. Although evident that cigarette smoke, the primary cause of COPD, significantly influences dendritic cell functions, little is known about the roles of dendritic cells in the pathogenesis of COPD. Methods The extent of dendritic cell infiltration in COPD tissue specimens was determined using immunohistochemical localization of CD83+ cells (marker of matured myeloid dendritic cells, and CD1a+ cells (Langerhans cells. The extent of tissue infiltration with Langerhans cells was also determined by the relative expression of the CD207 gene in COPD versus control tissues. To determine mechanisms by which dendritic cells accumulate in COPD, complimentary studies were conducted using monocyte-derived human dendritic cells exposed to cigarette smoke extract (CSE, and dendritic cells extracted from mice chronically exposed to cigarette smoke. Results In human COPD lung tissue, we detected a significant increase in the total number of CD83+ cells, and significantly higher amounts of CD207 mRNA when compared with control tissue. Human monocyte-derived dendritic cells exposed to CSE (0.1-2% exhibited enhanced survival in vitro when compared with control dendritic cells. Murine dendritic cells extracted from mice exposed to cigarette smoke for 4 weeks, also demonstrated enhanced survival compared to dendritic cells extracted from control mice. Acute exposure of human dendritic cells to CSE induced the cellular pro-survival proteins heme-oxygenase-1 (HO-1, and B cell lymphoma leukemia-x(L (Bcl-xL, predominantly through oxidative stress. Although activated human dendritic cells conditioned with CSE expressed diminished migratory CCR7 expression, their migration towards the CCR7 ligand CCL21 was not

  3. Fast and Selective Preconcentration of Europium from Wastewater and Coal Soil by Graphene Oxide/Silane@Fe3O4 Dendritic Nanostructure.

    Science.gov (United States)

    Patra, Santanu; Roy, Ekta; Madhuri, Rashmi; Sharma, Prashant K

    2015-05-19

    In this study, nanocomposite of graphene oxide and silane modified magnetic nanoparticles (silane@Fe3O4) were synthesized in a form of dendritic structure. For this, silane@Fe3O4 nanoparticle gets sandwiched between two layers of graphene oxide by chemical synthesis route. The synthesized dendritic structure was used as a monomer for synthesis of europium ion imprinted polymer. The synthesis of imprinted polymer was contemplated onto the surface of the vinyl group modified silica fiber by activated generated free radical atom-transfer radical polymerization, that is, AGET-ATRP technique. The synthesized dendritic monomer was characterized by XRD, FT-IR, VSM, FE-SEM, and TEM analyses. The imprinted polymer modified silica fiber was first validated in the aqueous and blood samples for successful extraction and detection of europium ion with limit of detection = 0.050 pg mL(-1) (signal/noise = 3). The imprinted polymer modified silica fiber was also used for preconcentration and separation of europium metal ion from various soil samples of coal mine areas. However, the same silica fiber was also used for wastewater treatment and shows 100% performance for europium removal. The findings herein suggested that dendritic nanocomposite could be potentially used as a highly effective material for the enrichment and preconcentration of europium or other trivalent lanthanides/actinides in nuclear waste management.

  4. Graphene Paper Decorated with a 2D Array of Dendritic Platinum Nanoparticles for Ultrasensitive Electrochemical Detection of Dopamine Secreted by Live Cells.

    Science.gov (United States)

    Zan, Xiaoli; Bai, Hongwei; Wang, Chenxu; Zhao, Faqiong; Duan, Hongwei

    2016-04-01

    To circumvent the bottlenecks of non-flexibility, low sensitivity, and narrow workable detection range of conventional biosensors for biological molecule detection (e.g., dopamine (DA) secreted by living cells), a new hybrid flexible electrochemical biosensor has been created by decorating closely packed dendritic Pt nanoparticles (NPs) on freestanding graphene paper. This innovative structural integration of ultrathin graphene paper and uniform 2D arrays of dendritic NPs by tailored wet chemical synthesis has been achieved by a modular strategy through a facile and delicately controlled oil-water interfacial assembly method, whereby the uniform distribution of catalytic dendritic NPs on the graphene paper is maximized. In this way, the performance is improved by several orders of magnitude. The developed hybrid electrode shows a high sensitivity of 2 μA cm(-2) μM(-1), up to about 33 times higher than those of conventional sensors, a low detection limit of 5 nM, and a wide linear range of 87 nM to 100 μM. These combined features enable the ultrasensitive detection of DA released from pheochromocytoma (PC 12) cells. The unique features of this flexible sensor can be attributed to the well-tailored uniform 2D array of dendritic Pt NPs and the modular electrode assembly at the oil-water interface. Its excellent performance holds much promise for the future development of optimized flexible electrochemical sensors for a diverse range of electroactive molecules to better serve society.

  5. Graphene Paper Decorated with a 2D Array of Dendritic Platinum Nanoparticles for Ultrasensitive Electrochemical Detection of Dopamine Secreted by Live Cells

    Science.gov (United States)

    Zan, Xiaoli; Wang, Chenxu

    2016-01-01

    Abstract To circumvent the bottlenecks of non‐flexibility, low sensitivity, and narrow workable detection range of conventional biosensors for biological molecule detection (e.g., dopamine (DA) secreted by living cells), a new hybrid flexible electrochemical biosensor has been created by decorating closely packed dendritic Pt nanoparticles (NPs) on freestanding graphene paper. This innovative structural integration of ultrathin graphene paper and uniform 2D arrays of dendritic NPs by tailored wet chemical synthesis has been achieved by a modular strategy through a facile and delicately controlled oil–water interfacial assembly method, whereby the uniform distribution of catalytic dendritic NPs on the graphene paper is maximized. In this way, the performance is improved by several orders of magnitude. The developed hybrid electrode shows a high sensitivity of 2 μA cm−2 μm −1, up to about 33 times higher than those of conventional sensors, a low detection limit of 5 nm, and a wide linear range of 87 nm to 100 μm. These combined features enable the ultrasensitive detection of DA released from pheochromocytoma (PC 12) cells. The unique features of this flexible sensor can be attributed to the well‐tailored uniform 2D array of dendritic Pt NPs and the modular electrode assembly at the oil–water interface. Its excellent performance holds much promise for the future development of optimized flexible electrochemical sensors for a diverse range of electroactive molecules to better serve society. PMID:26918612

  6. Noncrystallographic calcite dendrites from hot-spring deposits at Lake Bogoria, Kenya

    Energy Technology Data Exchange (ETDEWEB)

    Jones, B. [Univ. of Alberta, Edmonton, Alberta (Canada). Dept. of Geology; Renaut, R.W. [Univ. of Saskatchewan, Saskatoon (Canada). Dept. of Geological Sciences

    1995-01-02

    Complex calcite crystals are an integral component of precipitates that form around the orifices of the Loburu and Mawe Moto hot springs on the shores of Lake bogoria, Kenya. Two types of large (up to 4 cm long) noncrystallographic dendrites are important components of these deposits. Feather dendrites are characterized by multiple levels of branching with individual branches developed through crystal splitting and spherulitic growth. Scandulitic (from Latin meaning shingle) dendrites are formed of stacked calcite crystals and are generally more compact than feather dendrites. These developed through the incremental stacking of rectangular-shaped calcite crystals that initially grew as skeletal crystals. Feather and scandulitic dendrites precipitated from the same waters in the same springs. The difference in morphology is therefore related to microenvironments in which they grew. Feather dendrites grew in any direction in pools of free-standing water provided that they were in constant contact with the solute. Conversely, scandulitic dendrites grew on rims of dams where water flowed over the surface in concert with the pulses of spring water. Thus, each calcite crystal in these dendrites represents one episode of crystal growth. The orientation of the component crystals in scandulitic dendrites is controlled by the topography of the dam or surface, not crystallographic criteria. The noncrystallographic dendrites formed from spring waters with initial temperatures of 90--99 C. Surficial water cooling, loss of CO{sub 2}, and presence of other elements that can interfere with crystal growth contributed to the formation of these unusual crystals.

  7. Molecular programming of steady-state dendritic cells: impact on autoimmunity and tumor immune surveillance.

    Science.gov (United States)

    Johnson, Dylan J; Ohashi, Pamela S

    2013-05-01

    Dendritic cells are master regulators of immunity. Immature dendritic cells are essential for maintaining self-tolerance, while mature dendritic cells initiate a variety of specialized immune responses. Dendritic cell quiescence is often viewed as a default state that requires exogenous stimuli to induce maturation. However, recent studies have identified dendritic cell quiescence factors that actively program dendritic cells to an immature state. In the absence of these factors, dendritic cells spontaneously become immunogenic and can induce autoimmune responses. Herein we discuss two such factors, NF-κB1 and A20, that preserve dendritic cell immaturity through their regulation of NF-κB signaling. Loss of either of these factors increases dendritic cell immunogenicity, suggesting that they may be important targets for enhancing dendritic cell-based cancer immunotherapies. Alternatively, defects in molecules critical for maintaining steady-state DCs may provide novel biomarkers that identify patients who have enhanced natural antitumor immunity or that correlate with better responses to various immunotherapies.

  8. Murine and Human Model Systems for the Study of Dendritic Cell Immunobiology.

    Science.gov (United States)

    Hargadon, Kristian M

    2016-01-01

    Dendritic cells are a population of innate immune cells that possess their own effector functions as well as numerous regulatory properties that shape the activity of other innate and adaptive cells of the immune system. Following their development from either lymphoid or myeloid progenitors, the function of dendritic cells is tightly linked to their maturation and activation status. Differentiation into specialized subsets of dendritic cells also contributes to the diverse immunologic functions of these cells. Because of the key role played by dendritic cells in the regulation of both immune tolerance and activation, significant efforts have been focused on understanding dendritic cell biology. This review highlights the model systems currently available to study dendritic cell immunobiology and emphasizes the advantages and disadvantages to each system in both murine and human settings. In particular, in vitro cell culture systems involving immortalized dendritic cell lines, ex vivo systems for differentiating and expanding dendritic cells from their precursor populations, and systems for expanding, ablating, and manipulating dendritic cells in vivo are discussed. Emphasis is placed on the contribution of these systems to our current understanding of the development, function, and immunotherapeutic applications of dendritic cells, and insights into how these models might be extended in the future to answer remaining questions in the field are discussed.

  9. A novel approach for three dimensional dendrite spine segmentation and classification

    Science.gov (United States)

    He, Tiancheng; Xue, Zhong; Wong, Stephen T. C.

    2012-02-01

    Dendritic spines are small, bulbous cellular compartments that carry synapses. Biologists have been studying the biochemical and genetic pathways by examining the morphological changes of the dendritic spines at the intracellular level. Automatic dendritic spine detection from high resolution microscopic images is an important step for such morphological studies. In this paper, a novel approach to automated dendritic spine detection is proposed based on a nonlinear degeneration model. Dendritic spines are recognized as small objects with variable shapes attached to dendritic backbones. We explore the problem of dendritic spine detection from a different angle, i.e., the nonlinear degeneration equation (NDE) is utilized to enhance the morphological differences between the dendrite and spines. Using NDE, we simulated degeneration for dendritic spine detection. Based on the morphological features, the shrinking rate on dendrite pixels is different from that on spines, so that spines can be detected and segmented after degeneration simulation. Then, to separate spines into different types, Gaussian curvatures were employed, and the biomimetic pattern recognition theory was applied for spine classification. In the experiments, we compared quantitatively the spine detection accuracy with previous methods, and the results showed the accuracy and superiority of our methods.

  10. Atypical protein kinase C regulates primary dendrite specification of cerebellar Purkinje cells by localizing Golgi apparatus.

    Science.gov (United States)

    Tanabe, Koji; Kani, Shuichi; Shimizu, Takashi; Bae, Young-Ki; Abe, Takaya; Hibi, Masahiko

    2010-12-15

    Neurons have highly polarized structures that determine what parts of the soma elaborate the axon and dendrites. However, little is known about the mechanisms that establish neuronal polarity in vivo. Cerebellar Purkinje cells extend a single primary dendrite from the soma that ramifies into a highly branched dendritic arbor. We used the zebrafish cerebellum to investigate the mechanisms by which Purkinje cells acquire these characteristics. To examine dendritic morphogenesis in individual Purkinje cells, we marked the cell membrane using a Purkinje cell-specific promoter to drive membrane-targeted fluorescent proteins. We found that zebrafish Purkinje cells initially extend multiple neurites from the soma and subsequently retract all but one, which becomes the primary dendrite. In addition, the Golgi apparatus specifically locates to the root of the primary dendrite, and its localization is already established in immature Purkinje cells that have multiple neurites. Inhibiting secretory trafficking through the Golgi apparatus reduces dendritic growth, suggesting that the Golgi apparatus is involved in the dendritic morphogenesis. We also demonstrated that in a mutant of an atypical protein kinase C (aPKC), Prkci, Purkinje cells retain multiple primary dendrites and show disrupted localization of the Golgi apparatus. Furthermore, a mosaic inhibition of Prkci in Purkinje cells recapitulates the aPKC mutant phenotype. These results suggest that the aPKC cell autonomously controls the Golgi localization and thereby regulates the specification of the primary dendrite of Purkinje cells.

  11. Bimodal control of dendritic and axonal growth by the dual leucine zipper kinase pathway.

    Directory of Open Access Journals (Sweden)

    Xin Wang

    Full Text Available Knowledge of the molecular and genetic mechanisms underlying the separation of dendritic and axonal compartments is not only crucial for understanding the assembly of neural circuits, but also for developing strategies to correct defective dendrites or axons in diseases with subcellular precision. Previous studies have uncovered regulators dedicated to either dendritic or axonal growth. Here we investigate a novel regulatory mechanism that differentially directs dendritic and axonal growth within the same neuron in vivo. We find that the dual leucine zipper kinase (DLK signaling pathway in Drosophila, which consists of Highwire and Wallenda and controls axonal growth, regeneration, and degeneration, is also involved in dendritic growth in vivo. Highwire, an evolutionarily conserved E3 ubiquitin ligase, restrains axonal growth but acts as a positive regulator for dendritic growth in class IV dendritic arborization neurons in the larva. While both the axonal and dendritic functions of highwire require the DLK kinase Wallenda, these two functions diverge through two downstream transcription factors, Fos and Knot, which mediate the axonal and dendritic regulation, respectively. This study not only reveals a previously unknown function of the conserved DLK pathway in controlling dendrite development, but also provides a novel paradigm for understanding how neuronal compartmentalization and the diversity of neuronal morphology are achieved.

  12. Interaction of dendritic cells with antigen-containing liposomes: effect of bilayer composition

    DEFF Research Database (Denmark)

    Foged, Camilla; Arigita, Carmen; Sundblad, Anne

    2004-01-01

    Vaccine efficacy might be improved by exploiting the potent antigen presenting properties of dendrite cells (DCs), since their ability to stimulate specific major histocompatibility complex-restricted immune responses has been well documented during the recent years. In that light, we investigated...... how the interaction of antigen-containing liposomes with DCs was affected by the bilayer composition. Monocyte-derived human DCs and murine bone marrow-derived DCs were analysed and compared upon in vitro incubation with liposomes by flow cytometry and confocal microscopy. Anionic liposomes...... with a bilayer composition of phosphatidylcholine, cholesterol and phosphatidylglycerol or phosphatidylserine interacted with a limited fraction of the total DC population in case of both DC types. Inclusion of mannosylated phosphatidylethanolamine (Man-PE) for targeting to the mannose receptor (MR) increased...

  13. Regulation of protein synthesis and autophagy in activated dendritic cells: implications for antigen processing and presentation.

    Science.gov (United States)

    Argüello, Rafael J; Reverendo, Marisa; Gatti, Evelina; Pierre, Philippe

    2016-07-01

    Antigenic peptides presented in the context of major histocompatibility complex (MHC) molecules originate from the degradation of both self and non-self proteins. T cells can therefore recognize at the surface of surveyed cells, the self-peptidome produced by the cell itself (mostly inducing tolerance) or immunogenic peptides derived from exogenous origins. The initiation of adaptive immune responses by dendritic cells (DCs), through the antigenic priming of naïve T cells, is associated to microbial pattern recognition receptors engagement. Activation of DCs by microbial product or inflammatory cytokines initiates multiple processes that maximize DC capacity to present exogenous antigens and stimulate T cells by affecting major metabolic and membrane traffic pathways. These include the modulation of protein synthesis, the regulation of MHC and co-stimulatory molecules transport, as well as the regulation of autophagy, that, all together promote exogenous antigen presentation while limiting the display of self-antigens by MHC molecules.

  14. Immunologic Monitoring of Cellular Responses by Dendritic/Tumor Cell Fusion Vaccines

    Directory of Open Access Journals (Sweden)

    Shigeo Koido

    2011-01-01

    Full Text Available Although dendritic cell (DC- based cancer vaccines induce effective antitumor activities in murine models, only limited therapeutic results have been obtained in clinical trials. As cancer vaccines induce antitumor activities by eliciting or modifying immune responses in patients with cancer, the Response Evaluation Criteria in Solid Tumors (RECIST and WHO criteria, designed to detect early effects of cytotoxic chemotherapy in solid tumors, may not provide a complete assessment of cancer vaccines. The problem may, in part, be resolved by carrying out immunologic cellular monitoring, which is one prerequisite for rational development of cancer vaccines. In this review, we will discuss immunologic monitoring of cellular responses for the evaluation of cancer vaccines including fusions of DC and whole tumor cell.

  15. Vortioxetine promotes early changes in dendritic morphology compared to fluoxetine in rat hippocampus.

    Science.gov (United States)

    Chen, Fenghua; du Jardin, Kristian Gaarn; Waller, Jessica A; Sanchez, Connie; Nyengaard, Jens R; Wegener, Gregers

    2016-02-01

    Preclinical studies reveal that the multimodal antidepressant vortioxetine enhances long-term potentiation and dendritic branching compared to a selective serotonin reuptake inhibitor (SSRI). In the present study, we investigated vortioxetine׳s effects on spines and dendritic morphology in rat hippocampus at two time points compared to the SSRI, fluoxetine. Rats were dosed for 1 and 4 weeks with vortioxetine and fluoxetine at doses relevant for antidepressant activity. Dendritic morphology of pyramidal neurons (i.e., dendritic length, dendritic branch, spine number and density, and Sholl analysis) was examined in Golgi-stained sections from hippocampal CA1. After 1 week of treatment, vortioxetine significantly increased spine number (apical and basal dendrites), spine density (only basal), dendritic length (only apical), and dendritic branch number (apical and basal), whereas fluoxetine had no effect. After 4 weeks of treatment, vortioxetine significantly increased all measures of dendritic spine morphology as did fluoxetine except for spine density of basal dendrites. The number of intersections in the apical and basal dendrites was also significantly increased for both treatments after 4 weeks compared to control. In addition, 4 weeks of vortioxetine treatment, but not fluoxetine, promoted a decrease in spine neck length. In conclusion, 1-week vortioxetine treatment induced changes in spine number and density and dendritic morphology, whereas an equivalent dose of fluoxetine had no effects. Decreased spine neck length following 4-week vortioxetine treatment suggests a transition to mature spine morphology. This implies that vortioxetine׳s effects on spine and dendritic morphology are mediated by mechanisms that go beyond serotonin reuptake inhibition.

  16. Dendritic thickness: a morphometric parameter to classify mouse retinal ganglion cells

    Directory of Open Access Journals (Sweden)

    L.D. Loopuijt

    2007-10-01

    Full Text Available To study the dendritic morphology of retinal ganglion cells in wild-type mice we intracellularly injected these cells with Lucifer yellow in an in vitro preparation of the retina. Subsequently, quantified values of dendritic thickness, number of branching points and level of stratification of 73 Lucifer yellow-filled ganglion cells were analyzed by statistical methods, resulting in a classification into 9 groups. The variables dendritic thickness, number of branching points per cell and level of stratification were independent of each other. Number of branching points and level of stratification were independent of eccentricity, whereas dendritic thickness was positively dependent (r = 0.37 on it. The frequency distribution of dendritic thickness tended to be multimodal, indicating the presence of at least two cell populations composed of neurons with dendritic diameters either smaller or larger than 1.8 µm ("thin" or "thick" dendrites, respectively. Three cells (4.5% were bistratified, having thick dendrites, and the others (95.5% were monostratified. Using k-means cluster analysis, monostratified cells with either thin or thick dendrites were further subdivided according to level of stratification and number of branching points: cells with thin dendrites were divided into 2 groups with outer stratification (0-40% and 2 groups with inner (50-100% stratification, whereas cells with thick dendrites were divided into one group with outer and 3 groups with inner stratification. We postulate, that one group of cells with thin dendrites resembles cat ß-cells, whereas one group of cells with thick dendrites includes cells that resemble cat a-cells.

  17. Dynamic Range of Vertebrate Retina Ganglion Cells: Importance of Active Dendrites and Coupling by Electrical Synapses

    Science.gov (United States)

    Publio, Rodrigo; Ceballos, Cesar Celis; Roque, Antonio C.

    2012-01-01

    The vertebrate retina has a very high dynamic range. This is due to the concerted action of its diverse cell types. Ganglion cells, which are the output cells of the retina, have to preserve this high dynamic range to convey it to higher brain areas. Experimental evidence shows that the firing response of ganglion cells is strongly correlated with their total dendritic area and only weakly correlated with their dendritic branching complexity. On the other hand, theoretical studies with simple neuron models claim that active and large dendritic trees enhance the dynamic range of single neurons. Theoretical models also claim that electrical coupling between ganglion cells via gap junctions enhances their collective dynamic range. In this work we use morphologically reconstructed multi-compartmental ganglion cell models to perform two studies. In the first study we investigate the relationship between single ganglion cell dynamic range and number of dendritic branches/total dendritic area for both active and passive dendrites. Our results support the claim that large and active dendrites enhance the dynamic range of a single ganglion cell and show that total dendritic area has stronger correlation with dynamic range than with number of dendritic branches. In the second study we investigate the dynamic range of a square array of ganglion cells with passive or active dendritic trees coupled with each other via dendrodendritic gap junctions. Our results suggest that electrical coupling between active dendritic trees enhances the dynamic range of the ganglion cell array in comparison with both the uncoupled case and the coupled case with cells with passive dendrites. The results from our detailed computational modeling studies suggest that the key properties of the ganglion cells that endow them with a large dynamic range are large and active dendritic trees and electrical coupling via gap junctions. PMID:23144767

  18. Spiny Neurons of Amygdala, Striatum and Cortex Use Dendritic Plateau Potentials to Detect Network UP States

    Directory of Open Access Journals (Sweden)

    Katerina D Oikonomou

    2014-09-01

    Full Text Available Spiny neurons of amygdala, striatum, and cerebral cortex share four interesting features: [1] they are the most abundant cell type within their respective brain area, [2] covered by thousands of thorny protrusions (dendritic spines, [3] possess high levels of dendritic NMDA conductances, and [4] experience sustained somatic depolarizations in vivo and in vitro (UP states. In all spiny neurons of the forebrain, adequate glutamatergic inputs generate dendritic plateau potentials (dendritic UP states characterized by (i fast rise, (ii plateau phase lasting several hundred milliseconds and (iii abrupt decline at the end of the plateau phase. The dendritic plateau potential propagates towards the cell body decrementally to induce a long-lasting (longer than 100 ms, most often 200 – 800 ms steady depolarization (~20 mV amplitude, which resembles a neuronal UP state. Based on voltage-sensitive dye imaging, the plateau depolarization in the soma is precisely time-locked to the regenerative plateau potential taking place in the dendrite. The somatic plateau rises after the onset of the dendritic voltage transient and collapses with the breakdown of the dendritic plateau depolarization. We hypothesize that neuronal UP states in vivo reflect the occurrence of dendritic plateau potentials (dendritic UP states. We propose that the somatic voltage waveform during a neuronal UP state is determined by dendritic plateau potentials. A mammalian spiny neuron uses dendritic plateau potentials to detect and transform coherent network activity into a ubiquitous neuronal UP state. The biophysical properties of dendritic plateau potentials allow neurons to quickly attune to the ongoing network activity, as well as secure the stable amplitudes of successive UP states.

  19. Dynamic range of vertebrate retina ganglion cells: importance of active dendrites and coupling by electrical synapses.

    Science.gov (United States)

    Publio, Rodrigo; Ceballos, Cesar Celis; Roque, Antonio C

    2012-01-01

    The vertebrate retina has a very high dynamic range. This is due to the concerted action of its diverse cell types. Ganglion cells, which are the output cells of the retina, have to preserve this high dynamic range to convey it to higher brain areas. Experimental evidence shows that the firing response of ganglion cells is strongly correlated with their total dendritic area and only weakly correlated with their dendritic branching complexity. On the other hand, theoretical studies with simple neuron models claim that active and large dendritic trees enhance the dynamic range of single neurons. Theoretical models also claim that electrical coupling between ganglion cells via gap junctions enhances their collective dynamic range. In this work we use morphologically reconstructed multi-compartmental ganglion cell models to perform two studies. In the first study we investigate the relationship between single ganglion cell dynamic range and number of dendritic branches/total dendritic area for both active and passive dendrites. Our results support the claim that large and active dendrites enhance the dynamic range of a single ganglion cell and show that total dendritic area has stronger correlation with dynamic range than with number of dendritic branches. In the second study we investigate the dynamic range of a square array of ganglion cells with passive or active dendritic trees coupled with each other via dendrodendritic gap junctions. Our results suggest that electrical coupling between active dendritic trees enhances the dynamic range of the ganglion cell array in comparison with both the uncoupled case and the coupled case with cells with passive dendrites. The results from our detailed computational modeling studies suggest that the key properties of the ganglion cells that endow them with a large dynamic range are large and active dendritic trees and electrical coupling via gap junctions.

  20. Age Limits.

    Science.gov (United States)

    Antfolk, Jan

    2017-03-01

    Whereas women of all ages prefer slightly older sexual partners, men-regardless of their age-have a preference for women in their 20s. Earlier research has suggested that this difference between the sexes' age preferences is resolved according to women's preferences. This research has not, however, sufficiently considered that the age range of considered partners might change over the life span. Here we investigated the age limits (youngest and oldest) of considered and actual sex partners in a population-based sample of 2,655 adults (aged 18-50 years). Over the investigated age span, women reported a narrower age range than men and women tended to prefer slightly older men. We also show that men's age range widens as they get older: While they continue to consider sex with young women, men also consider sex with women their own age or older. Contrary to earlier suggestions, men's sexual activity thus reflects also their own age range, although their potential interest in younger women is not likely converted into sexual activity. Compared to homosexual men, bisexual and heterosexual men were more unlikely to convert young preferences into actual behavior, supporting female-choice theory.

  1. Efficient large volume electroporation of dendritic cells through micrometer scale manipulation of flow in a disposable polymer chip

    DEFF Research Database (Denmark)

    Selmeczi, Dávid; Hansen, Thomas Steen; Met, Özcan

    2011-01-01

    of the micrometer sized holes in the meshes compared to the main channel enforces an almost homogeneous flow velocity between the meshes. Thereby, very uniform electroporation of the cells can be accomplished. Successful electroporation of 20 million human dendritic cells with mRNA is demonstrated. The performance...... of the chip is similar to that of the traditional electroporation cuvette, but without an upper limit on the number of cells to be electroporated. The device is constructed with two female Luer parts and can easily be integrated with other microfluidic components. Furthermore it is fabricated from injection...

  2. Dengue virus-infected human dendritic cells reveal hierarchies of naturally expressed novel NS3 CD8 T cell epitopes.

    Science.gov (United States)

    Piazza, P; Campbell, D; Marques, E; Hildebrand, W H; Buchli, R; Mailliard, R; Rinaldo, C R

    2014-09-01

    Detailed knowledge of dengue virus (DENV) cell-mediated immunity is limited. In this study we characterize CD8(+) T lymphocytes recognizing three novel and two known non-structural protein 3 peptide epitopes in DENV-infected dendritic cells. Three epitopes displayed high conservation (75-100%), compared to the others (0-50%). A hierarchy ranking based on magnitude and polyfunctionality of the antigen-specific response showed that dominant epitopes were both highly conserved and cross-reactive against multiple DENV serotypes. These results are relevant to DENV pathogenesis and vaccine design.

  3. Elongation factor-2 phosphorylation in dendrites and the regulation of dendritic mRNA translation in neurons

    Directory of Open Access Journals (Sweden)

    Christopher eHeise

    2014-02-01

    Full Text Available Neuronal activity results in long lasting changes in synaptic structure and function by regulating mRNA translation in dendrites. These activity dependent events yield the synthesis of proteins known to be important for synaptic modifications and diverse forms of synaptic plasticity. Worthy of note, there is accumulating evidence that the eukaryotic Elongation Factor 2 Kinase (eEF2K/eukaryotic Elongation Factor 2 (eEF2 pathway may be strongly involved in this process. Upon activation, eEF2K phosphorylates and thereby inhibits eEF2, resulting in a dramatic reduction of mRNA translation. eEF2K is activated by elevated levels of calcium and binding of Calmodulin (CaM, hence its alternative name calcium/CaM-dependent protein kinase III (CaMKIII. In dendrites, this process depends on glutamate signaling and N-methyl-D-aspartate receptor (NMDAR activation. Interestingly, it has been shown that eEF2K can be activated in dendrites by the metabotropic glutamate receptor (mGluR 1/5 signaling, as well. Therefore, neuronal activity can induce local proteomic changes at the postsynapse by altering eEF2K activity. Well-established targets of eEF2K in dendrites include Brain-derived neurotrophic factor (BDNF, activity-regulated cytoskeletal-associated protein (Arc, the alpha subunit of calcium/CaM-dependent protein kinase II (αCaMKII, and Microtubule-associated protein 1B (MAP1B, all of which have well-known functions in different forms of synaptic plasticity.In this review we will give an overview of the involvement of the eEF2K/eEF2 pathway at dendrites in regulating the translation of dendritic mRNA in the context of altered NMDAR- and neuronal activity, and diverse forms of synaptic plasticity, such as metabotropic glutamate receptor-dependent-long-term depression (mGluR-LTD. For this, we draw on studies carried out both in vitro and in vivo.

  4. Dendritic Cells and HIV-1 Trans-Infection

    Directory of Open Access Journals (Sweden)

    David McDonald

    2010-08-01

    Full Text Available Dendritic cells initiate and sustain immune responses by migrating to sites of pathogenic insult, transporting antigens to lymphoid tissues and signaling immune specific activation of T cells through the formation of the immunological synapse. Dendritic cells can also transfer intact, infectious HIV-1 to CD4 T cells through an analogous structure, the infectious synapse. This replication independent mode of HIV-1 transmission, known as trans-infection, greatly increases T cell infection in vitro and is thought to contribute to viral dissemination in vivo. This review outlines the recent data defining the mechanisms of trans-infection and provides a context for the potential contribution of trans-infection in HIV-1 disease.

  5. Human plasmacytoid dendritic cells: from molecules to intercellular communication network

    Directory of Open Access Journals (Sweden)

    Till Sebastian Manuel Mathan

    2013-11-01

    Full Text Available Plasmacytoid Dendritic Cells (pDCs are a specific subset of naturally occurring dendritic cells, that secrete large amounts of Type I interferon and play an important role in the immune response against viral infection. Several studies have highlighted that they are also effective antigen presenting cells (APCs, making them an interesting target for immunotherapy against cancer. However, the modes of action of pDCs are not restricted to antigen presentation and IFN secretion alone. In this review we will highlight a selection of cell surface proteins expressed by human pDCs that may facilitate communication with other immune cells, and we will discuss the implications of these molecules for pDC-driven immune responses.

  6. Dendritic Cell Apoptosis and the Pathogenesis of Dengue

    Directory of Open Access Journals (Sweden)

    Lysangela R. Alves

    2012-11-01

    Full Text Available Dengue viruses and other members of the Flaviviridae family are emerging human pathogens. Dengue is transmitted to humans by Aedes aegypti female mosquitoes. Following infection through the bite, cells of the hematopoietic lineage, like dendritic cells, are the first targets of dengue virus infection. Dendritic cells (DCs are key antigen presenting cells, sensing pathogens, processing and presenting the antigens to T lymphocytes, and triggering an adaptive immune response. Infection of DCs by dengue virus may induce apoptosis, impairing their ability to present antigens to T cells, and thereby contributing to dengue pathogenesis. This review focuses on general mechanisms by which dengue virus triggers apoptosis, and possible influence of DC-apoptosis on dengue disease severity.

  7. Therapeutic dendritic-cell vaccine for simian AIDS

    Institute of Scientific and Technical Information of China (English)

    Lu,W; Wu,XX; Lu,YZ; Guo,WZ; Andrieu,JM

    2005-01-01

    An effective immune response against human immunodeficiency virus or simian immunodeficiency virus (SIV) is critical in achieving control of viral replication. Here, we show in SIV-infected rhesus monkeys that an effective and durable SIV-specific cellular and humoral immunity is elicited by a vaccination with chemically inactivated SIV-pulsed dendritic cells. After three immunizations made at two-week intervals, the animals exhibited a 50-fold decrease of SIV DNA and a 1,000-fold decrease of SIV RNA in peripheral blood. Such reduced viral load levels were maintained over the remaining 34 weeks of the study. Molecular and cellular analyses of axillary and inguinal node lymphocytes of vaccinated monkeys revealed a correlation between decreased SIV DNA and RNA levels and increased SIV-specific T-cell responses. Neutralizing antibody responses were augmented and remained elevated. Inactivated whole virus-pulsed dendritic cell vaccines are promising means to control diseases caused by immunodeficiency viruses.

  8. Rapid dendrite growth in quaternary Ni-based alloys

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The high undercooling and rapid solidification of Ni-10%Cu-10%Fe-10%Co quaternary alloy were achieved by electromagnetic levitation and glass fluxing techniques. The maximum undercooling of 276 K (0.16TL) was obtained in the experiments. All the solidified samples are determined to be α-Ni single-phase solid solutions by DSC thermal analysis and X-ray diffraction analysis. The microstructure of the α-Ni solid solution phase transfers from dendrite to equiaxed grain with an increase in undercooling, accompanied by the grain refinement effect. When the undercooling is very large, the solute trapping effect becomes quite significant and the microsegregation is suppressed. The experimental measurement of α-Ni dendrite growth velocity indicates that it increases with undercooling according to the relation, V=8×10-2×△T1.2.

  9. Colored visible light metamaterials based on random dendritic cells

    CERN Document Server

    Song, K; Liu, B Q; Zhao, X P

    2011-01-01

    Optical metamaterials(OMs) at visible wavelengths have been extensively developed. OMs reported presently are all composed of periodic structure, and fabricated by top-down approaches. Here, the colored visible light frequencies metamaterials composed of double layer array disordered and geometrical variational dendritic cells are demonstrated, fabricating by a novel bottom-up approach. The experiment demonstrated that the OMs composed of random silver dendritic cells caused the appearance of multiple transmission passbands at red and yellow light frequencies. The slab focusing experiment reveals a clear point image in the range of half-wavelength with an intensity of 5% higher than that of the light source. Proposed colored OMs will open a new way to prepare the cloak and the perfect lens suitable for optical frequency.

  10. Improved automatic centerline tracing for dendritic and axonal structures.

    Science.gov (United States)

    Jiménez, David; Labate, Demetrio; Kakadiaris, Ioannis A; Papadakis, Manos

    2015-04-01

    Centerline tracing in dendritic structures acquired from confocal images of neurons is an essential tool for the construction of geometrical representations of a neuronal network from its coarse scale up to its fine scale structures. In this paper, we propose an algorithm for centerline extraction that is both highly accurate and computationally efficient. The main novelties of the proposed method are (1) the use of a small set of Multiscale Isotropic Laplacian filters, acting as self-steerable filters, for a quick and efficient binary segmentation of dendritic arbors and axons; (2) an automated centerline seed points detection method based on the application of a simple 3D finite-length filter. The performance of this algorithm, which is validated on data from the DIADEM set appears to be very competitive when compared with other state-of-the-art algorithms.

  11. Two cases of extranodal follicular dendritic cell sarcoma

    Institute of Scientific and Technical Information of China (English)

    王坚; 孔蕴仪; 陆洪芬; 许越香

    2003-01-01

    @@ Follicular dendritic cell (FDC) is an essential component of the nonlymphoid, nonphagocytic immunoaccessory reticulum cells of the peripheral lymphoid tissue.1 Follicular dendritic cell sarcoma (FDCs) are confined largely to the primary and secondary B-cell follicles, where they form a tight interlacing meshwork. They play a role in the capture and presentation of antigens, generation and regulation of immune complexes. FDCs can be recognized morphologically by their indistinct cellular borders, pale eosinophilic cytoplasm, round-to-ovoid nuclei with delicate nuclear membranes and clear-to-vesicular chromatin with inconspicuous or small nucleoli. FDCs are best identified through immunostaining using CD21, CD35, R4/23, KiM4, KiM4p and Ki-FDC1p.

  12. Dendritic Morphology Simulation Using the Phase Field Method

    Institute of Scientific and Technical Information of China (English)

    张光跃; 荆涛; 柳百成

    2003-01-01

    Dendritic morphology was simulated using a macro- and micro-coupled method. Since the microstructure of a whole casting cannot be easily analyzed, a scheme was developed to calculate the temperature of the whole casting with the microstructure analyzed by selecting one cell in the central region of the casting. The heterogeneous nucleation was described using a Gaussian distribution with the dendritic growth controlled by the solution of the phase field equation. The initial temperature distribution in the microdomain was obtained by interpolating the cell temperatures near the selected cell with the interface undercooling assumed to be the sum of thermal, solute, and curvature effects. The solute distribution was calculated from the mixed solute conservation equation with noise introduced to produce the side branches. The simulation results agree well with experimental results.

  13. Human XCR1+ Dendritic Cells Derived In Vitro from CD34+ Progenitors Closely Resemble Blood Dendritic Cells, Including Their Adjuvant Responsiveness, Contrary to Monocyte-Derived Dendritic Cells

    OpenAIRE

    S. Balan; Ollion, V.; Colletti, N.; Chelbi, R.; Montanana-Sanchis, F.; LIU, H.; Vu Manh, T.-P.; Sanchez, C.; Savoret, J.; Perrot, I.; Doffin, A.-C.; Fossum, E.; Bechlian, D.; Chabannon, C.; Bogen, B

    2014-01-01

    Human monocyte-derived dendritic cell (MoDC) have been used in the clinic with moderately encouraging results. Mouse XCR1+ DC excel at cross-presentation, can be targeted in vivo to induce protective immunity, and share characteristics with XCR1+ human DC. Assessment of the immunoactivation potential of XCR1+ human DC is hindered by their paucity in vivo and by their lack of a well-defined in vitro counterpart. We report in this study a protocol generating both XCR1+ and XCR1− human DC in CD3...

  14. Supporting the model of ductile iron dendritic solidification

    Energy Technology Data Exchange (ETDEWEB)

    Santos, H.M.C.M. [Porto Univ. (Portugal). Metall. and Mater. Dept.; Pinto, A.M.P. [Minho Univ. (Portugal). Mechanical Engineering Dept.; Jacinto, M.C.P.L. [Porto Polytechnic Inst. and INEGI, Porto (Portugal). Mechanical Engineering Dept.; Sa, C.P.M. [Porto Univ. (Portugal). Materials Center

    2000-08-01

    Microsegregation in ductile iron is generally accepted as modelled by a regular pattern: the graphite promoter elements are assumed to concentrate in the neighborhood of the graphite nodules and the carbide forming elements in the eutectic cell boundaries. The authors have conducted several microanalyses in several ductile irons and concluded that the microsegregation pattern does not agree with this model but supports the mechanism of dendritic ductile iron solidification. (orig.)

  15. Molecular Characterization of Dendritic Cell-Derived Exosomes

    OpenAIRE

    Théry, Clotilde; Regnault, Armelle; Garin, Jérôme; Wolfers, Joseph; Zitvogel, Laurence; Ricciardi-Castagnoli, Paola; Raposo, Graça; Amigorena, Sebastian

    1999-01-01

    Exosomes are membrane vesicles secreted by hematopoietic cells upon fusion of late multivesicular endosomes with the plasma membrane. Dendritic cell (DC)-derived exosomes induce potent antitumor immune responses in mice, resulting in the regression of established tumors (Zitvogel, L., A. Regnault, A. Lozier, J. Wolfers, C. Flament, D. Tenza, P. Ricciardi-Castagnoli, G. Raposo, and S. Amigorena. 1998. Nat. Med. 4:594–600). To unravel the molecular basis of exosome-induced immune stimulation, w...

  16. Modulation of respiratory dendritic cells during Klebsiella pneumonia infection

    OpenAIRE

    Hackstein, Holger; Kranz, Sabine; Lippitsch, Anne; Wachtendorf, Andreas; Kershaw, Olivia; Achim D Gruber; Michel, Gabriela; Lohmeyer, Jürgen; Bein, Gregor; Baal, Nelli; Herold, Susanne

    2013-01-01

    Background: Klebsiella pneumoniae is a leading cause of severe hospital-acquired respiratory tract infections and death but little is known regarding the modulation of respiratory dendritic cell (DC) subsets. Plasmacytoid DC (pDC) are specialized type 1 interferon producing cells and considered to be classical mediators of antiviral immunity. Method: By using multiparameter flow cytometry analysis we have analysed the modulation of respiratory DC subsets after intratracheal Klebsi...

  17. Paradoxical signaling regulates structural plasticity in dendritic spines

    OpenAIRE

    2016-01-01

    Transient spine enlargement (3- to 5-min timescale) is an important event associated with the structural plasticity of dendritic spines. Many of the molecular mechanisms associated with transient spine enlargement have been identified experimentally. Here, we use a systems biology approach to construct a mathematical model of biochemical signaling and actin-mediated transient spine expansion in response to calcium influx caused by NMDA receptor activation. We have identified that a key featur...

  18. The role of the vascular dendritic cell network in atherosclerosis

    OpenAIRE

    Alberts-Grill, Noah; Denning, Timothy L.; Rezvan, Amir; Jo, Hanjoong

    2013-01-01

    A complex role has been described for dendritic cells (DCs) in the potentiation and control of vascular inflammation and atherosclerosis. Resident vascular DCs are found in the intima of atherosclerosis-prone vascular regions exposed to disturbed blood flow patterns. Several phenotypically and functionally distinct vascular DC subsets have been described. The functional heterogeneity of these cells and their contributions to vascular homeostasis, inflammation, and atherosclerosis are only rec...

  19. Cancer Vaccine by Fusions of Dendritic and Cancer Cells

    OpenAIRE

    Shigeo Koido; Eiichi Hara; Sadamu Homma; Yoshihisa Namiki; Toshifumi Ohkusa; Jianlin Gong; Hisao Tajiri

    2010-01-01

    Dendritic cells (DCs) are potent antigen-presenting cells and play a central role in the initiation and regulation of primary immune responses. Therefore, their use for the active immunotherapy against cancers has been studied with considerable interest. The fusion of DCs with whole tumor cells represents in many ways an ideal approach to deliver, process, and subsequently present a broad array of tumor-associated antigens, including those yet to be unidentified, in the context of DCs-derived...

  20. Estimating neuronal connectivity from axonal and dendritic density fields

    Science.gov (United States)

    van Pelt, Jaap; van Ooyen, Arjen

    2013-01-01

    Neurons innervate space by extending axonal and dendritic arborizations. When axons and dendrites come in close proximity of each other, synapses between neurons can be formed. Neurons vary greatly in their morphologies and synaptic connections with other neurons. The size and shape of the arborizations determine the way neurons innervate space. A neuron may therefore be characterized by the spatial distribution of its axonal and dendritic “mass.” A population mean “mass” density field of a particular neuron type can be obtained by averaging over the individual variations in neuron geometries. Connectivity in terms of candidate synaptic contacts between neurons can be determined directly on the basis of their arborizations but also indirectly on the basis of their density fields. To decide when a candidate synapse can be formed, we previously developed a criterion defining that axonal and dendritic line pieces should cross in 3D and have an orthogonal distance less than a threshold value. In this paper, we developed new methodology for applying this criterion to density fields. We show that estimates of the number of contacts between neuron pairs calculated from their density fields are fully consistent with the number of contacts calculated from the actual arborizations. However, the estimation of the connection probability and the expected number of contacts per connection cannot be calculated directly from density fields, because density fields do not carry anymore the correlative structure in the spatial distribution of synaptic contacts. Alternatively, these two connectivity measures can be estimated from the expected number of contacts by using empirical mapping functions. The neurons used for the validation studies were generated by our neuron simulator NETMORPH. An example is given of the estimation of average connectivity and Euclidean pre- and postsynaptic distance distributions in a network of neurons represented by their population mean density

  1. Functionalized Carbosilane Dendritic Species as Soluble Support in Organic Synthesis

    NARCIS (Netherlands)

    Koten, G. van; Hovestad, N.J.; Ford, A.; Jastrzebski, J.T.B.H.

    2000-01-01

    A new methodology, which is compatible with the use of reactive organometallic reagents, has been developed for the use of carbosilane dendrimers as soluble supports in organic synthesis. Hydroxy-functionalized dendritic carbosilanes Si[CH2CH2CH2SiMe2(C6H4CH(R)OH)]4 (G0-OH, R = H or (S)-Me) and Si[C

  2. Receptor-Dependent Coronavirus Infection of Dendritic Cells

    Science.gov (United States)

    Turner, Brian C.; Hemmila, Erin M.; Beauchemin, Nicole; Holmes, Kathryn V.

    2004-01-01

    In several mammalian species, including humans, coronavirus infection can modulate the host immune response. We show a potential role of dendritic cells (DC) in murine coronavirus-induced immune modulation and pathogenesis by demonstrating that the JAW SII DC line and primary DC from BALB/c mice and p/p mice with reduced expression of the murine coronavirus receptor, murine CEACAM1a, are susceptible to murine coronavirus infection by a receptor-dependent pathway. PMID:15113927

  3. Immunity and Tolerance Induced by Intestinal Mucosal Dendritic Cells

    OpenAIRE

    Julio Aliberti

    2016-01-01

    Dendritic cells present in the digestive tract are constantly exposed to environmental antigens, commensal flora, and invading pathogens. Under steady-state conditions, these cells have high tolerogenic potential, triggering differentiation of regulatory T cells to protect the host from unwanted proinflammatory immune responses to innocuous antigens or commensals. On the other hand, these cells must discriminate between commensal flora and invading pathogens and mount powerful immune response...

  4. Immunohistochemical analysis of small plaque parapsoriasis: involvement of dendritic cells.

    Science.gov (United States)

    Zeybek, N Dilara; Asan, Esin; Erbil, A Hakan; Dagdeviren, Attila

    2008-01-01

    Small plaque parapsoriasis (SPP) is one of the cutaneous T-cell lymphoproliferative disorders. The aim of the present study was to show the antigenic profile of a subset of dendritic cells and lymphocytes in SPP in comparison with normal cells to provide data on the role of these two cell types in the pathogenesis of SPP. Skin biopsy specimens of lesions were obtained from 8 patients with SPP. Biopsies of the healthy skin from 9 control individuals were also analyzed. Immunohistochemistry was performed on the frozen tissue sections to reveal binding of anti-HLA Class II, anti-CD1a, anti-CD4, anti-CD8, anti-CD44, anti-CD45, and anti-CD68 monoclonal antibodies. There was a statistically significant increase in the number of CD1a(+), Langerhans cells (LCs), HLA-DR-immunoreactive and, CD1a-positive dermal dendritic cells and CD68(+) macrophages in the SPP group (p=0.008, 0.008, 0.002 and <0.0009, respectively). The number of lymphocytes positive for CD4, CD8 and CD45 was significantly higher than normal in the SPP group (p=0.015, <0.0009 and <0.0009, respectively). Our study demonstrates that both peptide- and lipid-based antigens are involved in the persistent antigenic exposure in SPP. Dendritic cells play a pivotal role in SPP by presenting antigens by both LC and dermal dendritic cells via MHC Class II and CD1a molecules. The CD68(+) macrophages are thought to be involved in the immune response in this pathology as an antigen-presenting cell.

  5. Articulation and Clarification of the Dendritic Cell Algorithm

    CERN Document Server

    Greensmith, Julie; Twycross, Jamie

    2009-01-01

    The Dendritic Cell algorithm (DCA) is inspired by recent work in innate immunity. In this paper a formal description of the DCA is given. The DCA is described in detail, and its use as an anomaly detector is illustrated within the context of computer security. A port scan detection task is performed to substantiate the influence of signal selection on the behaviour of the algorithm. Experimental results provide a comparison of differing input signal mappings.

  6. Dendritic web - A viable material for silicon solar cells

    Science.gov (United States)

    Seidensticker, R. G.; Scudder, L.; Brandhorst, H. W., Jr.

    1975-01-01

    The dendritic web process is a technique for growing thin silicon ribbon from liquid silicon. The material is suitable for solar cell fabrication and, in fact, cells fabricated on web material are equivalent in performance to cells fabricated on Czochralski-grown material. A recently concluded study has delineated the thermal requirements for silicon web crucibles, and a detailed conceptual design has been developed for a laboratory growth apparatus.

  7. Dendritic Cells for Real-Time Anomaly Detection

    CERN Document Server

    Greensmith, Julie

    2010-01-01

    Dendritic Cells (DCs) are innate immune system cells which have the power to activate or suppress the immune system. The behaviour of human of human DCs is abstracted to form an algorithm suitable for anomaly detection. We test this algorithm on the real-time problem of port scan detection. Our results show a significant difference in artificial DC behaviour for an outgoing portscan when compared to behaviour for normal processes.

  8. Loss of CD103~+ intestinal dendritic cells during colonic inflammation

    Institute of Scientific and Technical Information of China (English)

    Ulrike; G; Strauch; Nicole; Grunwald; Florian; Obermeier; Sonja; Gürster; Heiko; C; Rath

    2010-01-01

    AIM:To investigate possible differences in dendritic cells(DC)within intestinal tissue of mice before and after induction of colitis. METHODS:Mucosal DC derived from intestinal tissue,as well as from mesenteric lymph nodes and spleen,were analyzed by fluorescence activated cell sorting(FACS) analysis.Supernatants of these cells were analyzed for secretion of different pro-and anti-inflammatory cytokines. Immunohistochemistry and immunofluorescence were performed on cryosections of mucosal tissue derived fro...

  9. Dextromethorphan Inhibits Activations and Functions in Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Der-Yuan Chen

    2013-01-01

    Full Text Available Dendritic cells (DCs play an important role in connecting innate and adaptive immunity. Thus, DCs have been regarded as a major target for the development of immunomodulators. In this study, we examined the effect of dextromethorphan (DXM, a common cough suppressant with a high safety profile, on the activation and function of DCs. In the presence of DXM, the LPS-induced expression of the costimulatory molecules in murine bone marrow-derived dendritic cells (BMDCs was significantly suppressed. In addition, DXM treatment reduced the production of reactive oxygen species (ROS, proinflammatory cytokines, and chemokines in maturing BMDCs that were activated by LPS. Therefore, DXM abrogated the ability of LPS-stimulated DCs to induce Ag-specific T-cell activation, as determined by their decreased proliferation and IFN-γ secretion in mixed leukocyte cultures. Moreover, the inhibition of LPS-induced MAPK activation and NF-κB translocation may contribute to the suppressive effect of DXM on BMDCs. Remarkably, DXM decreased the LPS-induced surface expression of CD80, CD83, and HLA-DR and the secretion of IL-6 and IL-12 in human monocyte-derived dendritic cells (MDDCs. These findings provide a new insight into the impact of DXM treatment on DCs and suggest that DXM has the potential to be used in treating DC-related acute and chronic diseases.

  10. Dextromethorphan Inhibits Activations and Functions in Dendritic Cells

    Science.gov (United States)

    Chen, Der-Yuan; Song, Pei-Shan; Hong, Jau-Shyong; Chu, Ching-Liang; Pan, I-Horng; Chen, Yi-Ming; Lin, Ching-Hsiung; Lin, Sheng-Hao; Lin, Chi-Chen

    2013-01-01

    Dendritic cells (DCs) play an important role in connecting innate and adaptive immunity. Thus, DCs have been regarded as a major target for the development of immunomodulators. In this study, we examined the effect of dextromethorphan (DXM), a common cough suppressant with a high safety profile, on the activation and function of DCs. In the presence of DXM, the LPS-induced expression of the costimulatory molecules in murine bone marrow-derived dendritic cells (BMDCs) was significantly suppressed. In addition, DXM treatment reduced the production of reactive oxygen species (ROS), proinflammatory cytokines, and chemokines in maturing BMDCs that were activated by LPS. Therefore, DXM abrogated the ability of LPS-stimulated DCs to induce Ag-specific T-cell activation, as determined by their decreased proliferation and IFN-γ secretion in mixed leukocyte cultures. Moreover, the inhibition of LPS-induced MAPK activation and NF-κB translocation may contribute to the suppressive effect of DXM on BMDCs. Remarkably, DXM decreased the LPS-induced surface expression of CD80, CD83, and HLA-DR and the secretion of IL-6 and IL-12 in human monocyte-derived dendritic cells (MDDCs). These findings provide a new insight into the impact of DXM treatment on DCs and suggest that DXM has the potential to be used in treating DC-related acute and chronic diseases. PMID:23781253

  11. A dendritic disinhibitory circuit mechanism for pathway-specific gating

    Science.gov (United States)

    Yang, Guangyu Robert; Murray, John D.; Wang, Xiao-Jing

    2016-01-01

    While reading a book in a noisy café, how does your brain ‘gate in' visual information while filtering out auditory stimuli? Here we propose a mechanism for such flexible routing of information flow in a complex brain network (pathway-specific gating), tested using a network model of pyramidal neurons and three classes of interneurons with connection probabilities constrained by data. We find that if inputs from different pathways cluster on a pyramidal neuron dendrite, a pathway can be gated-on by a disinhibitory circuit motif. The branch-specific disinhibition can be achieved despite dense interneuronal connectivity, even with random connections. Moreover, clustering of input pathways on dendrites can naturally emerge through synaptic plasticity regulated by dendritic inhibition. This gating mechanism in a neural circuit is further demonstrated by performing a context-dependent decision-making task. The model suggests that cognitive flexibility engages top-down signalling of behavioural rule or context that targets specific classes of inhibitory neurons. PMID:27649374

  12. Dendritic Heterojunction Nanowire Arrays for High-Performance Supercapacitors

    Science.gov (United States)

    Zou, Rujia; Zhang, Zhenyu; Yuen, Muk Fung; Hu, Junqing; Lee, Chun-Sing; Zhang, Wenjun

    2015-01-01

    Herein, we designed and synthesized for the first time a series of 3D dendritic heterojunction arrays on Ni foam substrates, with NiCo2S4 nanowires as cores and NiCo2O4, NiO, Co3O4, and MnO2 nanowires as branches, and studied systematically their electrochemical performance in comparison with their counterparts in core/shell structure. Attributed to the following reasons: (1) both core and branch are pseudocapacitively active materials, (2) the special dendritic structure with considerable inter-nanowire space enables easy access of electrolyte to the core and branch surfaces, and (3) the highly conductive NiCo2S4 nanowire cores provide ``superhighways'' for charge transition, NiCo2S4-cored dendritic heterojunction electrodes synergistically lead to ultrahigh specific capacitance, good rate capability, and excellent cycling life. These results of core/branch dentritic heterojunction arrays is universially superior to their core/shell conterparts, thus this is a significant improvement of overall electrochemical performance.

  13. Barriers in the brain: resolving dendritic spine morphology and compartmentalization.

    Science.gov (United States)

    Adrian, Max; Kusters, Remy; Wierenga, Corette J; Storm, Cornelis; Hoogenraad, Casper C; Kapitein, Lukas C

    2014-01-01

    Dendritic spines are micron-sized protrusions that harbor the majority of excitatory synapses in the central nervous system. The head of the spine is connected to the dendritic shaft by a 50-400 nm thin membrane tube, called the spine neck, which has been hypothesized to confine biochemical and electric signals within the spine compartment. Such compartmentalization could minimize interspinal crosstalk and thereby support spine-specific synapse plasticity. However, to what extent compartmentalization is governed by spine morphology, and in particular the diameter of the spine neck, has remained unresolved. Here, we review recent advances in tool development - both experimental and theoretical - that facilitate studying the role of the spine neck in compartmentalization. Special emphasis is given to recent advances in microscopy methods and quantitative modeling applications as we discuss compartmentalization of biochemical signals, membrane receptors and electrical signals in spines. Multidisciplinary approaches should help to answer how dendritic spine architecture affects the cellular and molecular processes required for synapse maintenance and modulation.

  14. The Current Immune Function of Hepatic Dendritic Cells

    Institute of Scientific and Technical Information of China (English)

    Willy Hsu; Shang-An Shu; Eric Gershwin; Zhe-Xiong Lian

    2007-01-01

    While only a small percentage of the liver as dendritic cells, they play a major role in the regulation of liver immunity. Four major types of dendritic cell subsets include myeloid CD8α-B220-, lymphoid CD8α+B220-,plasmacytoid CD8α-B220+, and natural killer dendritic cell with CD8α-B220-NK1.1+ phenotype. Although these subsets have slightly different characteristics, they are all poor na(i)ve T cell stimulators. In exchange for their reduced capacity for allostimulation, hepatic DCs are equipped with an enhanced ability to secrete cytokines in response to TLR stimulation. In addition, they have increased level of phagocytosis. Both of these traits suggest hepatic DC as part of the innate immune system. With such a high rate of exposure to the dietary and commensal antigens, it is important for the hepatic DCs to have an enhanced innate response while maintaining a tolerogenic state to avoid chronic inflammation. Only upon secondary infectivity does the hepatic DC activate memory T cells for rapid eradication of recurring pathogen. On the other hand, overly tolerogenic characteristics of hepatic DC may be responsible for the increase prevalence of autoimmunity or liver malignancies.

  15. Evaluation of two different dendritic cell preparations with BCG reactivity

    Directory of Open Access Journals (Sweden)

    Fol Marek

    2016-01-01

    Full Text Available Dendritic cells (DCs play a key-role in the immune response against intracellular bacterial pathogens, including mycobacteria. Monocyte-derived dendritic cells (MoDCs are considered to behave as inflammatory cell populations. Different immunomagnetic methods (positive and negative can be used to purify monocytes before their in vitro differentiation and their culture behavior can be expected to be different. In this study we evaluated the reactivity of two dendritic cell populations towards the Bacillus Calmette-Guérin (BCG antigen. Monocytes were obtained from the blood of healthy donors, using positive and negative immunomagnetic separation methods. The expression of DC-SIGN, CD86, CD80, HLA-DR and CD40 on MoDCs was estimated by flow cytometry. The level of IL-12p70, IL-10 and TNF-α was measured by ELISA. Neither of the tested methods affected the surface marker expression of DCs. No significant alteration in immunological response, measured by cytokine production, was noted either. After BCG stimulation, the absence of IL-12, but the IL-23 production was observed in both cell preparations. Positive and negative magnetic separation methods are effective techniques to optimize the preparation of monocytes as the source of MoDCs for potential clinical application.

  16. Overview of the Tusas Code for Simulation of Dendritic Solidification

    Energy Technology Data Exchange (ETDEWEB)

    Trainer, Amelia J. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Newman, Christopher Kyle [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Francois, Marianne M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-01-07

    The aim of this project is to conduct a parametric investigation into the modeling of two dimensional dendrite solidification, using the phase field model. Specifically, we use the Tusas code, which is for coupled heat and phase-field simulation of dendritic solidification. Dendritic solidification, which may occur in the presence of an unstable solidification interface, results in treelike microstructures that often grow perpendicular to the rest of the growth front. The interface may become unstable if the enthalpy of the solid material is less than that of the liquid material, or if the solute is less soluble in solid than it is in liquid, potentially causing a partition [1]. A key motivation behind this research is that a broadened understanding of phase-field formulation and microstructural developments can be utilized for macroscopic simulations of phase change. This may be directly implemented as a part of the Telluride project at Los Alamos National Laboratory (LANL), through which a computational additive manufacturing simulation tool is being developed, ultimately to become part of the Advanced Simulation and Computing Program within the U.S. Department of Energy [2].

  17. Selection Theory of Dendritic Growth with Anisotropic Diffusion

    Directory of Open Access Journals (Sweden)

    Martin von Kurnatowski

    2015-01-01

    Full Text Available Dendritic patterns frequently arise when a crystal grows into its own undercooled melt. Latent heat released at the two-phase boundary is removed by some transport mechanism, and often the problem can be described by a simple diffusion model. Its analytic solution is based on a perturbation expansion about the case without capillary effects. The length scale of the pattern is determined by anisotropic surface tension, which provides the mechanism for stabilizing the dendrite. In the case of liquid crystals, diffusion can be anisotropic too. Growth is faster in the direction of less efficient heat transport (inverted growth. Any physical solution should include this feature. A simple spatial rescaling is used to reduce the bulk equation in 2D to the case of isotropic diffusion. Subsequently, an eigenvalue problem for the growth mode results from the interface conditions. The eigenvalue is calculated numerically and the selection problem of dendritic growth with anisotropic diffusion is solved. The length scale is predicted and a quantitative description of the inverted growth phenomenon is given. It is found that anisotropic diffusion cannot take the stabilizing role of anisotropic surface tension.

  18. Barriers in the Brain: Resolving Dendritic Spine Morphology and Compartmentalization

    Directory of Open Access Journals (Sweden)

    Max eAdrian

    2014-12-01

    Full Text Available Dendritic spines are micron-sized protrusions that harbor the majority of excitatory synapses in the central nervous system. The head of the spine is connected to the dendritic shaft by a 50-400 nm thin membrane tube, called the spine neck, which has been hypothesized to confine biochemical and electric signals within the spine compartment. Such compartmentalization could minimize interspinal crosstalk and thereby support spine-specific synapse plasticity. However, to what extent compartmentalization is governed by spine morphology, and in particular the diameter of the spine neck, has remained unresolved. Here, we review recent advances in tool development - both experimental and theoretical - that facilitate studying the role of the spine neck in compartmentalization. Special emphasis is given to recent advances in microscopy methods and quantitative modeling applications as we discuss compartmentalization of biochemical signals, membrane receptors and electrical signals in spines. Multidisciplinary approaches should help to answer how dendritic spine architecture affects the cellular and molecular processes required for synapse maintenance and modulation.

  19. Automated 4D analysis of dendritic spine morphology: applications to stimulus-induced spine remodeling and pharmacological rescue in a disease model

    Directory of Open Access Journals (Sweden)

    Swanger Sharon A

    2011-10-01

    Full Text Available Abstract Uncovering the mechanisms that regulate dendritic spine morphology has been limited, in part, by the lack of efficient and unbiased methods for analyzing spines. Here, we describe an automated 3D spine morphometry method and its application to spine remodeling in live neurons and spine abnormalities in a disease model. We anticipate that this approach will advance studies of synapse structure and function in brain development, plasticity, and disease.

  20. Automated 4D analysis of dendritic spine morphology: applications to stimulus-induced spine remodeling and pharmacological rescue in a disease model

    OpenAIRE

    2011-01-01

    Abstract Uncovering the mechanisms that regulate dendritic spine morphology has been limited, in part, by the lack of efficient and unbiased methods for analyzing spines. Here, we describe an automated 3D spine morphometry method and its application to spine remodeling in live neurons and spine abnormalities in a disease model. We anticipate that this approach will advance studies of synapse structure and function in brain development, plasticity, and disease.

  1. Effect of cooling rates on dendrite spacings of directionally solidified DZ125 alloy under high thermal gradient

    Institute of Scientific and Technical Information of China (English)

    ZHANG Weiguo; LIU Lin; ZHAO Xinbao; HUANG Taiwen; YU Zhuhuan; QU Min; FU Hengzhi

    2009-01-01

    The dendrite morphologies and spacings of directionally solidified DZ125 superalloy were investigated under high thermal gradient about 500 K/cm. The results reveal that, with increasing cooling rate, both the spacings of primary and secondary dendrite arms decrease, and the dendrite morphologies transit from coarse to superfine dendrite. The secondary dendrite arms trend to be refined and be well developed, and the tertiary dendrite will occur. The predictions of the Kurz/Fisher model and the Hunt/Lu model accord basically with the experimental data for primary dendrite arm spacing. The regression equation of the primary dendrite arm spacings λ_1 and the cooling rate V_c is λ_1=0.013V_c~(-0.32). The regression equation of the secondary dendrite arm spacing λ_2 and the cooling rate V_c is λ_2=0.00258V_c~(-0.31), which gives good agreement with the Feurer/Wunderlin model.

  2. Dendritic Cells in Kidney Transplant Biopsy Samples Are Associated with T Cell Infiltration and Poor Allograft Survival.

    Science.gov (United States)

    Batal, Ibrahim; 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

    2015-12-01

    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.

  3. Dendritic DNA-porphyrin as mimetic enzyme for amplified fluorescent detection of DNA.

    Science.gov (United States)

    Xu, Nan; Lei, Jianping; Wang, Quanbo; Yang, Qianhui; Ju, Huangxian

    2016-04-01

    In this work, a novel dendritic DNA-porphyrin superstructure was designed as mimetic enzyme for the amplified fluorescent detection of DNA. The dendritic DNA superstructure was in situ assembled with three auxiliary DNAs via hybridization chain reaction. With groove interaction between iron porphyrin (FeTMPyP) and double-stranded DNA, the dendritic DNA superstructure is capable to gather abundant FeTMPyP molecules to form dendritic DNA-FeTMPyP mimetic enzyme. Using tyramine as a substrate, the dendritic DNA-FeTMPyP demonstrated excellent peroxidase-like catalytic oxidation of tyramine into fluorescent dityramine in the presence of H2O2. Based on an amplified fluorescence signal, a signal on strategy is proposed for DNA detection with high sensitivity, good specificity and practicability. The assembly of porphyrin with dendritic DNA not only provided the new avenue to construct mimetic enzyme but also established label-free sensing platform for a wide range of analytes.

  4. Statistical physics of neural systems with non-additive dendritic coupling

    CERN Document Server

    Breuer, David; Memmesheimer, Raoul-Martin

    2015-01-01

    How neurons process their inputs crucially determines the dynamics of biological and artificial neural networks. In such neural and neural-like systems, synaptic input is typically considered to be merely transmitted linearly or sublinearly by the dendritic compartments. Yet, single-neuron experiments report pronounced supralinear dendritic summation of sufficiently synchronous and spatially close-by inputs. Here, we provide a statistical physics approach to study the impact of such non-additive dendritic processing on single neuron responses and the performance of associative memory tasks in artificial neural networks. First, we compute the effect of random input to a neuron incorporating nonlinear dendrites. This approach is independent of the details of the neuronal dynamics. Second, we use those results to study the impact of dendritic nonlinearities on the network dynamics in a paradigmatic model for associative memory, both numerically and analytically. We find that dendritic nonlinearities maintain net...

  5. Dendritic cell podosome dynamics does not depend on the F-actin regulator SWAP-70.

    Directory of Open Access Journals (Sweden)

    Anne Götz

    Full Text Available In addition to classical adhesion structures like filopodia or focal adhesions, dendritic cells similar to macrophages and osteoclasts assemble highly dynamic F-actin structures called podosomes. They are involved in cellular processes such as extracellular matrix degradation, bone resorption by osteoclasts, and trans-cellular diapedesis of lymphocytes. Besides adhesion and migration, podosomes enable dendritic cells to degrade connective tissue by matrix metalloproteinases. SWAP-70 interacts with RhoGTPases and F-actin and regulates migration of dendritic cells. SWAP-70 deficient osteoclasts are impaired in F-actin-ring formation and bone resorption. In the present study, we demonstrate that SWAP-70 is not required for podosome formation and F-actin turnover in dendritic cells. Furthermore, we found that toll-like receptor 4 ligand induced podosome disassembly and podosome-mediated matrix degradation is not affected by SWAP-70 in dendritic cells. Thus, podosome formation and function in dendritic cells is independent of SWAP-70.

  6. Properties of mouse retinal ganglion cell dendritic growth during postnatal development

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The property of dendritic growth dynamics during development is a subject of intense interest.Here,we investigated the dendritic motility of retinal ganglion cells (RGCs) during different developmental stages,using ex vivo mouse retina explant culture,Semliki Forest Virus transfection and time-lapse observations.The results illustrated that during development,the dendritic motility underwent a change from rapid growth to a relatively stable state,i.e.,at P0 (day of birth),RGC dendrites were in a highly active state,whereas at postnatal 13 (P13) they were more stable,and at P3 and P8,the RGCs were in an intermediate state.At any given developmental stage,RGCs of different types displayed the same dendritic growth rate and extent.Since the mouse is the most popular mammalian model for genetic manipulation,this study provided a methodological foundation for further exploring the regulatory mechanisms of dendritic development.

  7. Phase-field-lattice Boltzmann studies for dendritic growth with natural convection

    Science.gov (United States)

    Takaki, Tomohiro; Rojas, Roberto; Sakane, Shinji; Ohno, Munekazu; Shibuta, Yasushi; Shimokawabe, Takashi; Aoki, Takayuki

    2017-09-01

    Simulating dendritic growth with natural convection is challenging because of the size of the computational domain required when compared to the dendrite scale. In this study, a phase-field-lattice Boltzmann model was used to simulate dendritic growth in the presence of natural convection due to a difference in solute concentration. To facilitate and accelerate the large-scale simulation, a parallel computing code with multiple graphics processing units was developed. The effects of the computational domain size as well as those of gravity on the dendritic morphologies were examined by performing two-dimensional free dendritic growth simulations with natural convection. The effects of the gravity direction on the dendrite spacing and morphology were also investigated by simulating unidirectional solidification from multiple seeds.

  8. Changes in dendritic architecture: Not your "usual suspect" in control of the onset of puberty.

    Directory of Open Access Journals (Sweden)

    Peter eHemond

    2013-06-01

    Full Text Available Until the recent past, the search for the underlying drive for the pubertal increase in gonadotropin-releasing hormone (GnRH hormone from the GnRH-containing neurons in the hypothalamus was largely focused on extrinsic factors. The most recent evidence however indicates changes in the structure of GnRH neurons themselves may contribute to this fundamental event in development. Based on our studies in males, dendritic architecture is not static from birth until adulthood. Instead, dendrites undergo a dramatic remodeling during the postnatal period which is independent of testosterone and occurs before the pubertal increase in GnRH release. First, the number of dendrites emanating from somata is reduced between infancy and adulthood. Moreover, a dendrite of adult GnRH neurons invariability arises at angle of 180° from the axon as opposed to the extraordinary variability in location during infancy. In fact, in some neurons from infants, no dendrite even resides in the adult location. Thus, there is a spatially selective remodeling of primary dendrites. Secondly, dendrites of GnRH neurons from infants were highly branched prior to assuming the compact morphology of adults. Finally, other morphological aspects of GnRH neurons such as total dendritic length, the numbers of dendrite branches and the lengths of higher order branches were significantly greater in infants than adults, indicating a consolidation of dendritic arbors. Activity in multi-compartment models of GnRH neurons, suggest the impact of structure on neuronal activity is exerted with both active and passive dendrites. Thus, passive properties make a defining contribution to function. Accordingly, changes in morphology alone are likely to have functional consequences for the pattern of activity in GnRH neurons. Our findings suggest structural remodeling of dendrites during the postnatal period likely facilitates repetitive action potentials and thus, GnRH release at the time of puberty.

  9. SUBTYPE CHARACTERICS OF DENDRITIC CELLS FROM PERIPHERAL BLOOD OF PATIENTS WITH RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    S. A. Falaleeva

    2013-01-01

    Full Text Available Abstract. Characteristics of myeloid and plasmacytoid dendritic cells from peripheral blood were studied in healthy donors and patients with rheumatoid arthritis (RA. We evaluated relative amounts of dendritic cell by their subtypes, degree of their maturity, and ability to respond to the maturation factors (toll-like receptor 4, 7 and 8 agonists. The results of in vitro experiments have shown that the patients with rheumatoid arthritis exhibited a significant reduction in numbers of plasmacytoid dendritic cells from peripheral blood. A sufficient decrease in CD83, CD80 expression on dendritic cell subtypes in RA patients was significantly less, than in healthy donors. In patients with RA, a significant increase in the number of CCR7-expressing plasmacytoid dendritic cells was shown in peripheral blood. In stimulated cultures, maturation of dendritic cells expressing maturation markers (CD83, CD80, CCR7 proved to be increased up to normal values. It should be noted that the counts of plasmacytoid dendritic cells in peripheral blood of RA patients expressing CCR7 was significantly higher than among healthy donors. Meanwhile, expression of CD83 and CD80 increased tovalues of healthy donors.Hence, we have found a significant reduction in relative counts of blood-derived myeloid and plasmacytoid dendritic cells expressing markers of mature dendritic cells (CD83, CD80 in patients with rheumatoid arthritis. Upon stimulated in vitro maturation, the counts of myeloid and plasmacytoid dendritic cells expressing CD83 and CD80 increased to the values corresponding to those of control group. RA patients showed significantly higher numbers of plasmacytoid dendritic cells expressing CCR7. This could indicate some changes in functional activity of dendritic cells in peripheral blood of patients with RA.

  10. The Analysis of Purkinje Cell Dendritic Morphology in Organotypic Slice Cultures

    OpenAIRE

    Kapfhammer, Josef P.; Gugger, Olivia S.

    2012-01-01

    Purkinje cells are an attractive model system for studying dendritic development, because they have an impressive dendritic tree which is strictly oriented in the sagittal plane and develops mostly in the postnatal period in small rodents 3. Furthermore, several antibodies are available which selectively and intensively label Purkinje cells including all processes, with anti-Calbindin D28K being the most widely used. For viewing of dendrites in living cells, mice expressing EGFP selectively i...

  11. Organ-derived dendritic cells have differential effects on alloreactive T cells

    OpenAIRE

    Kim, Theo D.; Terwey, Theis H.; Zakrzewski, Johannes L; Suh, David; Kochman, Adam A.; Chen, Megan E.; King, Chris G.; Borsotti, Chiara; Grubin, Jeremy; Smith, Odette M.; Heller, Glenn; Liu, Chen; Murphy, George F.; Alpdogan, Onder; Marcel R. M. van den Brink

    2008-01-01

    Dendritic cells (DCs) are considered critical for the induction of graft-versus-host disease (GVHD) after bone marrow transplantation (BMT). In addition to their priming function, dendritic cells have been shown to induce organ-tropism through induction of specific homing molecules on T cells. Using adoptive transfer of CFSE-labeled cells, we first demonstrated that alloreactive T cells differentially up-regulate specific homing molecules in vivo. Host-type dendritic cells from the GVHD targe...

  12. The role of dendritic non-linearities in single neuron computation

    Directory of Open Access Journals (Sweden)

    Boris Gutkin

    2014-05-01

    Full Text Available Experiment has demonstrated that summation of excitatory post-synaptic protientials (EPSPs in dendrites is non-linear. The sum of multiple EPSPs can be larger than their arithmetic sum, a superlinear summation due to the opening of voltage-gated channels and similar to somatic spiking. The so-called dendritic spike. The sum of multiple of EPSPs can also be smaller than their arithmetic sum, because the synaptic current necessarily saturates at some point. While these observations are well-explained by biophysical models the impact of dendritic spikes on computation remains a matter of debate. One reason is that dendritic spikes may fail to make the neuron spike; similarly, dendritic saturations are sometime presented as a glitch which should be corrected by dendritic spikes. We will provide solid arguments against this claim and show that dendritic saturations as well as dendritic spikes enhance single neuron computation, even when they cannot directly make the neuron fire. To explore the computational impact of dendritic spikes and saturations, we are using a binary neuron model in conjunction with Boolean algebra. We demonstrate using these tools that a single dendritic non-linearity, either spiking or saturating, combined with somatic non-linearity, enables a neuron to compute linearly non-separable Boolean functions (lnBfs. These functions are impossible to compute when summation is linear and the exclusive OR is a famous example of lnBfs. Importantly, the implementation of these functions does not require the dendritic non-linearity to make the neuron spike. Next, We show that reduced and realistic biophysical models of the neuron are capable of computing lnBfs. Within these models and contrary to the binary model, the dendritic and somatic non-linearity are tightly coupled. Yet we show that these neuron models are capable of linearly non-separable computations.

  13. Dendritic branch intersections are structurally regulated targets for efficient axonal wiring and synaptic clustering.

    Directory of Open Access Journals (Sweden)

    Monika Pinchas

    Full Text Available Synaptic clustering on dendritic branches enhances plasticity, input integration and neuronal firing. However, the mechanisms guiding axons to cluster synapses at appropriate sites along dendritic branches are poorly understood. We searched for such a mechanism by investigating the structural overlap between dendritic branches and axons in a simplified model of neuronal networks--the hippocampal cell culture. Using newly developed software, we converted images of meshes of overlapping axonal and dendrites into topological maps of intersections, enabling quantitative study of overlapping neuritic geometry at the resolution of single dendritic branch-to-branch and axon-to-branch crossings. Among dendro-dendritic crossing configurations, it was revealed that the orientations through which dendritic branches cross is a regulated attribute. While crossing angle distribution among branches thinner than 1 µm appeared to be random, dendritic branches 1 µm or wider showed a preference for crossing each other at angle ranges of either 50°-70° or 80°-90°. It was then found that the dendro-dendritic crossings themselves, as well as their selective angles, both affected the path of axonal growth. Axons displayed 4 fold stronger tendency to traverse within 2 µm of dendro-dendritic intersections than at farther distances, probably to minimize wiring length. Moreover, almost 70% of the 50°-70° dendro-denritic crossings were traversed by axons from the obtuse angle's zone, whereas only 15% traversed through the acute angle's zone. By contrast, axons showed no orientation restriction when traversing 80°-90° crossings. When such traverse behavior was repeated by many axons, they converged in the vicinity of dendro-dendritic intersections, thereby clustering their synaptic connections. Thus, the vicinity of dendritic branch-to-branch crossings appears to be a regulated structure used by axons as a target for efficient wiring and as a preferred site for

  14. Decreased dendritic spine density and abnormal spine morphology in Fyn knockout mice

    OpenAIRE

    2011-01-01

    Fyn is a Src-family tyrosine kinase that affects long term potentiation (LTP), synapse formation, and learning and memory. Fyn is also implicated in dendritic spine formation both in vitro and in vivo. However, whether Fyn’s regulation of dendritic spine formation is brain-region specific and age-dependent is unknown. In the present study, we systematically examined whether Fyn altered dendritic spine density and morphology in the cortex and hippocampus and if these effects were age-dependent...

  15. Preparing Methods and Its Influencing Factors about Nanoparticles Based on Dendritic Polymer

    Directory of Open Access Journals (Sweden)

    Zhang Jianwei

    2017-01-01

    Full Text Available Based on the properties, structure and application of dendritic polymer, this paper analysed the methods of the preparation of nanoparticles using dendritic polymer, detailed preparation process, technical parameters and application effect about a single metal nanoparticles, bimetallic nanoparticles, sulfide and halide nanoparticles. The influencing factors of the preparation about nanoparticles were discussed, including the molecular algebra, the molar ratio of the metal ions to the dendritic polymer, and so on.

  16. Contextual Learning Induces Dendritic Spine Clustering in Retrosplenial Cortex

    Directory of Open Access Journals (Sweden)

    Adam C Frank

    2014-03-01

    Full Text Available Molecular and electrophysiological studies find convergent evidence suggesting that plasticity within a dendritic tree is not randomly dispersed, but rather clustered into functional groups. Further, results from in silico neuronal modeling show that clustered plasticity is able to increase storage capacity 45 times compared to dispersed plasticity. Recent in vivo work utilizing chronic 2-photon microscopy tested the clustering hypothesis and showed that repetitive motor learning is able to induce clustered addition of new dendritic spines on apical dendrites of L5 neurons in primary motor cortex; moreover, clustered spines were found to be more stable than non-clustered spines, suggesting a physiological role for spine clustering. To further test this hypothesis we used in vivo 2-photon imaging in Thy1-YFP-H mice to chronically examine dendritic spine dynamics in retrosplenial cortex (RSC during spatial learning. RSC is a key component of an extended spatial learning and memory circuit that includes hippocampus and entorhinal cortex. Importantly, RSC is known from both lesion and immediate early gene studies to be critically involved in spatial learning and more specifically in contextual fear conditioning. We utilized a modified contextual fear conditioning protocol wherein animals received a mild foot shock each day for five days; this protocol induces gradual increases in context freezing over several days before the animals reach a behavioral plateau. We coupled behavioral training with four separate in vivo imaging sessions, two before training begins, one early in training, and a final session after training is complete. This allowed us to image spine dynamics before training as well as early in learning and after animals had reached behavioral asymptote. We find that this contextual learning protocol induces a statistically significant increase in the formation of clusters of new dendritic spines in trained animals when compared to home

  17. EBSD Characterization of Dendrites in Synthetic and Natural Rocks

    Science.gov (United States)

    Hammer, J. E.; Tiley, J.; Shiveley, A.; Knox, S.; Viswanathan, G.

    2011-12-01

    Arborescent crystals in igneous rocks are associated with extreme crystallization environments: the protoplanary disk (chondrules), Earth's ultramafic Archean mantle (komatiite), and terrestrial submarine-erupted lavas (pillow basalts), although the role of morphological instabilities in more mundane settings such as magma reservoirs of modern oceanic islands is increasingly appreciated (see Welsch et al., V16). Fundamentals of dendrite formation are presumably well understood: branching morphologies belie crystal growth conditions in which the driving force for solidification produces a kinetic roughening transition, transforming an atomically smooth crystal-liquid interface into a rough, adhesive interface capable of extremely rapid advancement. However, not since photomicrograhic advances made possible close observations of snow crystals (Nakaya 1936), has there been a more promising set of analytical tools to characterize dendrites in natural and synthetic materials in pursuit of new insights. We are investigating clinopyroxene (cpx) in the quenched top of Fe-rich tholeiitic lava (Munro Township, Northeast Ontario; Fig. 1) and a synthetic basalt of similar character (Hammer 2006) with electron backscatter diffraction (EBSD), 3D reconstruction of optical serial sections, and TEM. Here we report intriguing phenomena observed with EBSD common to both samples. Severe thinning of dendrite trunks and repeated tip splitting destroys the self-similarity associated with classical dendrites and instead presages 'seaweed' morphology. Split tips manifest incremental trajectory deflections, producing gently arched trunks (Fig. 1A) as well as tightly curved (r, producing distinctive misorientation maps and pole figures (Fig. 1C). Parallel branches exhibit similar rotational trajectories, carving parallel arcs in the pole figure. The high incidence of side branching and tip splitting is consistent with very rapid growth velocity, associated with extremely high kinetic

  18. A THREE-DIMENSIONAL CELLULAR AUTOMATON SIMULATION FOR DENDRITIC GROWTH%枝晶生长的三维元胞自动机模拟

    Institute of Scientific and Technical Information of China (English)

    江鸿翔; 赵九洲

    2011-01-01

    Perhaps dendrite is the most observed solidification microstructure of many metallic materials. The dendritic morphologies show a dominating effect on the performance of casting products. A lot of work has been carried out to investigate the formation mechanism of dendritic microstructure. It is found that the development of dendritic microstructures is a complicated process controlled by the interplay of many factors such as thermal and solute transfer, capillary etc. Cellular automaton (CA) can simulate the solidification process with a high computational efficiency, thus, attracts great attentions. In recent years, progress has been made on the two dimensional CA models for the solidification microstructure formation. But up to date researches on three dimensional CA model are very limited. A combined cellular automaton-finite difference (CA-FD) model for the three dimensional simulation of dendritic growth was developed in this paper. Simulations were performed to investigate the dendritic growth in an undercooled Al-Cu alloy as well as in a directionally solidified Al-Cu alloy. The numerical results showed clearly the development of the free dendrite in the under-cooled melt and the microstructure evolution in the directionally solidified alloy and agreed well with the theoretical predictions and the experimental results.%通过将元胞自动机和有限差分方法相耦合,建立了立方体系金属和合金枝晶生长的三维模型.应用该模型,模拟了Al-Cu合金过冷熔体中自由枝晶的生长和定向凝固条件下Al-Cu合金凝固组织演变过程.模拟结果清楚展现了过冷熔体中自由枝晶的生长过程和定向凝固过程中枝晶的形成与淹没,与理论预测和实验结果相吻合,表明所发展的模型能够较准确地描述立方体系金属和合金的凝固组织演变过程.

  19. Electroless Growth of Aluminum Dendrites in NaCl-AlCl3 Melts

    DEFF Research Database (Denmark)

    Li, Qingfeng; Hjuler, H.A.; Berg, Rolf W.

    1989-01-01

    The spontaneous growth of aluminum dendrites after deposition was observed and examined in sodium chloride-aluminumchloride melts. The concentration gradient of AlCl3 in the vicinity of the cathode surface resulting from electrolysisconstitutes a type of concentration cell with aluminum dendrites...... as electrodes. The short-circuit discharge of thecell is found to be the driving force for the growth of aluminum dendrites. Such a concentration gradient is proposed to beone of the causes for dendrite formation in the case of metal deposition....

  20. Effect of strontium on primary dendrite and eutectic temperature of A357 aluminum alloy

    Directory of Open Access Journals (Sweden)

    Chen Zhongwei

    2010-05-01

    Full Text Available Solidification process of A357 alloy with Sr addition was investigated in this paper. In particular, the effects of strontium and cooling rate on α-Al dendrite and Al-Si eutectic characteristic temperature were characterized by differential thermal analysis (DTA. Sr addition not only modifies the Al-Si eutectic, but also affects the morphology and structure of primary α-Al dendrite. Sr decreases the growth temperature of α-Al dendrite and Al-Si eutectic, and it also affects the dendrite growth mechanism. It has been found that such effect becomes more significant with higher cooling rate.

  1. State-dependent firing determines intrinsic dendritic Ca2+ signaling in thalamocortical neurons.

    Science.gov (United States)

    Errington, Adam C; Renger, John J; Uebele, Victor N; Crunelli, Vincenzo

    2010-11-01

    Activity-dependent dendritic Ca(2+) signals play a critical role in multiple forms of nonlinear cellular output and plasticity. In thalamocortical neurons, despite the well established spatial separation of sensory and cortical inputs onto proximal and distal dendrites, respectively, little is known about the spatiotemporal dynamics of intrinsic dendritic Ca(2+) signaling during the different state-dependent firing patterns that are characteristic of these neurons. Here we demonstrate that T-type Ca(2+) channels are expressed throughout the entire dendritic tree of rat thalamocortical neurons and that they mediate regenerative propagation of low threshold spikes, typical of, but not exclusive to, sleep states, resulting in global dendritic Ca(2+) influx. In contrast, actively backpropagating action potentials, typical of wakefulness, result in smaller Ca(2+) influxes that can temporally summate to produce dendritic Ca(2+) accumulations that are linearly related to firing frequency but spatially confined to proximal dendritic regions. Furthermore, dendritic Ca(2+) transients evoked by both action potentials and low-threshold spikes are shaped by Ca(2+) uptake by sarcoplasmic/endoplasmic reticulum Ca(2+) ATPases but do not rely on Ca(2+)-induced Ca(2+) release. Our data demonstrate that thalamocortical neurons are endowed with intrinsic dendritic Ca(2+) signaling properties that are spatially and temporally modified in a behavioral state-dependent manner and suggest that backpropagating action potentials faithfully inform proximal sensory but not distal corticothalamic synapses of neuronal output, whereas corticothalamic synapses only "detect" Ca(2+) signals associated with low-threshold spikes.

  2. Molecular architecture of synaptic actin cytoskeleton in hippocampal neurons reveals a mechanism of dendritic spine morphogenesis.

    Science.gov (United States)

    Korobova, Farida; Svitkina, Tatyana

    2010-01-01

    Excitatory synapses in the brain play key roles in learning and memory. The formation and functions of postsynaptic mushroom-shaped structures, dendritic spines, and possibly of presynaptic terminals, rely on actin cytoskeleton remodeling. However, the cytoskeletal architecture of synapses remains unknown hindering the understanding of synapse morphogenesis. Using platinum replica electron microscopy, we characterized the cytoskeletal organization and molecular composition of dendritic spines, their precursors, dendritic filopodia, and presynaptic boutons. A branched actin filament network containing Arp2/3 complex and capping protein was a dominant feature of spine heads and presynaptic boutons. Surprisingly, the spine necks and bases, as well as dendritic filopodia, also contained a network, rather than a bundle, of branched and linear actin filaments that was immunopositive for Arp2/3 complex, capping protein, and myosin II, but not fascin. Thus, a tight actin filament bundle is not necessary for structural support of elongated filopodia-like protrusions. Dynamically, dendritic filopodia emerged from densities in the dendritic shaft, which by electron microscopy contained branched actin network associated with dendritic microtubules. We propose that dendritic spine morphogenesis begins from an actin patch elongating into a dendritic filopodium, which tip subsequently expands via Arp2/3 complex-dependent nucleation and which length is modulated by myosin II-dependent contractility.

  3. hamlet, a binary genetic switch between single- and multiple- dendrite neuron morphology.

    Science.gov (United States)

    Moore, Adrian W; Jan, Lily Yeh; Jan, Yuh Nung

    2002-08-23

    The dendritic morphology of neurons determines the number and type of inputs they receive. In the Drosophila peripheral nervous system (PNS), the external sensory (ES) neurons have a single nonbranched dendrite, whereas the lineally related multidendritic (MD) neurons have extensively branched dendritic arbors. We report that hamlet is a binary genetic switch between these contrasting morphological types. In hamlet mutants, ES neurons are converted to an MD fate, whereas ectopic hamlet expression in MD precursors results in transformation of MD neurons into ES neurons. Moreover, hamlet expression induced in MD neurons undergoing dendrite outgrowth drastically reduces arbor branching.

  4. Control of dendrite growth by a magnetic field during directional solidification

    Science.gov (United States)

    Dai, Yanchao; Du, Dafan; Hou, Long; Gagnoud, Annie; Ren, Zhongming; Fautrelle, Yves; Moreau, Rene; Li, Xi

    2016-04-01

    In this work, the alignment behavior of three kinds of dendrites (Al3Ni, α-Al and Al2Cu dendrites) with a remarkable crystalline anisotropy during directional solidification under an axial magnetic field is studied by the EBSD technology. Experimental results reveal that the magnetic field is capable of tailoring the dendrite alignment during directional solidification. Further, based on the crystalline anisotropy, a method to control the dendrite alignment by adjusting the angle between the magnetic field and the solidification direction is proposed.

  5. Large-Scale mRNA Transfection of Dendritic Cells by Electroporation in Continuous Flow Systems

    DEFF Research Database (Denmark)

    Selmeczi, Dávid; Hansen, Thomas Steen; Met, Özcan

    2016-01-01

    Electroporation is well established for transient mRNA transfection of many mammalian cells, including immune cells such as dendritic cells used in cancer immunotherapy. Therapeutic application requires methods to efficiently electroporate and transfect millions of immune cells in a fast process...... the instrumentation and methods needed for the efficient transfection by electroporation of millions of dendritic cells in one continuous flow process....... with high cell survival. Continuous flow of suspended dendritic cells through a channel incorporating spatially separated microporous meshes with a synchronized electrical pulsing sequence can yield dendritic cell transfection rates of >75 % with survival rates of >90 %. This chapter describes...

  6. Dendritic cell-nerve clusters are sites of T cell proliferation in allergic airway inflammation.

    Science.gov (United States)

    Veres, Tibor Z; Shevchenko, Marina; Krasteva, Gabriela; Spies, Emma; Prenzler, Frauke; Rochlitzer, Sabine; Tschernig, Thomas; Krug, Norbert; Kummer, Wolfgang; Braun, Armin

    2009-03-01

    Interactions between T cells and dendritic cells in the airway mucosa precede secondary immune responses to inhaled antigen. The purpose of this study was to identify the anatomical locations where dendritic cell-T cell interactions occur, resulting in T cells activation by dendritic cells. In a mouse model of allergic airway inflammation, we applied whole-mount immunohistology and confocal microscopy to visualize dendritic cells and T cells together with nerves, epithelium, and smooth muscle in three dimensions. Proliferating T cells were identified by the detection of the incorporation of the nucleotide analogue 5-ethynyl-2'-deoxyuridine into the DNA. We developed a novel quantification method that enabled the accurate determination of cell-cell contacts in a semi-automated fashion. Dendritic cell-T cell interactions occurred beneath the smooth muscle layer, but not in the epithelium. Approximately 10% of the dendritic cells were contacted by nerves, and up to 4% of T cells formed clusters with these dendritic cells. T cells that were clustered with nerve-contacting dendritic cells proliferated only in the airways of mice with allergic inflammation but not in the airways of negative controls. Taken together, these results suggest that during the secondary immune response, sensory nerves influence dendritic cell-driven T cell activation in the airway mucosa.

  7. The serotonin receptor 5-HT₇R regulates the morphology and migratory properties of dendritic cells.

    Science.gov (United States)

    Holst, Katrin; Guseva, Daria; Schindler, Susann; Sixt, Michael; Braun, Armin; Chopra, Himpriya; Pabst, Oliver; Ponimaskin, Evgeni

    2015-08-01

    Dendritic cells are potent antigen-presenting cells endowed with the unique ability to initiate adaptive immune responses upon inflammation. Inflammatory processes are often associated with an increased production of serotonin, which operates by activating specific receptors. However, the functional role of serotonin receptors in regulation of dendritic cell functions is poorly understood. Here, we demonstrate that expression of serotonin receptor 5-HT7 (5-HT7R) as well as its downstream effector Cdc42 is upregulated in dendritic cells upon maturation. Although dendritic cell maturation was independent of 5-HT7R, receptor stimulation affected dendritic cell morphology through Cdc42-mediated signaling. In addition, basal activity of 5-HT7R was required for the proper expression of the chemokine receptor CCR7, which is a key factor that controls dendritic cell migration. Consistent with this, we observed that 5-HT7R enhances chemotactic motility of dendritic cells in vitro by modulating their directionality and migration velocity. Accordingly, migration of dendritic cells in murine colon explants was abolished after pharmacological receptor inhibition. Our results indicate that there is a crucial role for 5-HT7R-Cdc42-mediated signaling in the regulation of dendritic cell morphology and motility, suggesting that 5-HT7R could be a new target for treatment of a variety of inflammatory and immune disorders.

  8. Dendritic grain growth simulation in weld pool of nickel base alloy

    Institute of Scientific and Technical Information of China (English)

    Zhan Xiaohong; Wei Yanhong; Ma Rui; Dong Zhibo

    2008-01-01

    Dendritic grain growth at the edge of the weld pool is simulated using a stochastic numerical model of cellular automaton algorithm. The grain growth model is established based upon the balance of solute in the solid/liquid interface of the dendrite tip. Considering the complicated nucleation condition and competitive growth, the dendrite morphologies of different nucleation condition are simulated. The simulated results reproduced the dendrite grain evolution process at the edge of the weld pool. It is indicated that the nucleation condition is an important factor influencing the grain morphologies especially the morphologies of secondary and tertiary arms.

  9. Phase field modeling of multiple dendrite growth of AI-Si binary alloy under isothermal solidification

    Institute of Scientific and Technical Information of China (English)

    Sun Qiang; Zhang Yutuo; Cui Haixia; Wang Chengzhi

    2008-01-01

    Phase field method offers the prospect of being able to perform realistic numerical experiments on dendrite growth in metallic systems. In this study, the growth process of multiple dendrites in Ai-2-mole-%-Si binary alloy under isothermal solidification was simulated using phase field model. The simulation results showed the impingement of arbitrarily oriented crystals and the competitive growth among the grains during solidification. With the increase of growing time, the grains begin to coalesce and impinge the adjacent grains. When the dendrites start to impinge, the dendrite growth is obviously inhibited.

  10. Rapid dendritic growth of Al-Ge hypoeutectic alloy in a drop tube

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Dendritic growth in Al-45% Ge hypoeutectic alloy has been investigated during free fall in a 3 m drop tube. Calculations indicate that the undercooling obtained for the falling Al-45% Ge droplets ranges from 13 K to 201 K. The maximum undercooling attains 0.27TL. With the increase of undercooling, the primary (Al) phase undergoes a "columnar dendrite to equiaxed dendrite" structural transition. According to the current rapid dendritic growth theory, the growth of primary (Al) phase is always controlled by solute diffusion.

  11. GPU phase-field lattice Boltzmann simulations of growth and motion of a binary alloy dendrite

    Science.gov (United States)

    Takaki, T.; Rojas, R.; Ohno, M.; Shimokawabe, T.; Aoki, T.

    2015-06-01

    A GPU code has been developed for a phase-field lattice Boltzmann (PFLB) method, which can simulate the dendritic growth with motion of solids in a dilute binary alloy melt. The GPU accelerated PFLB method has been implemented using CUDA C. The equiaxed dendritic growth in a shear flow and settling condition have been simulated by the developed GPU code. It has been confirmed that the PFLB simulations were efficiently accelerated by introducing the GPU computation. The characteristic dendrite morphologies which depend on the melt flow and the motion of the dendrite could also be confirmed by the simulations.

  12. GABAergic interneurons targeting dendrites of pyramidal cells in the CA1 area of the hippocampus.

    Science.gov (United States)

    Klausberger, Thomas

    2009-09-01

    The dendrites of pyramidal cells are active compartments capable of independent computations, input/output transformation and synaptic plasticity. Pyramidal cells in the CA1 area of the hippocampus receive 92% of their GABAergic input onto dendrites. How does this GABAergic input participate in dendritic computations of pyramidal cells? One key to understanding their contribution to dendritic computation lies in the timing of GABAergic input in relation to excitatory transmission, back-propagating action potentials, Ca(2+) spikes and subthreshold membrane dynamics. The issue is further complicated by the fact that dendritic GABAergic inputs originate from numerous distinct sources operating with different molecular machineries and innervating different subcellular domains of pyramidal cell dendrites. The GABAergic input from distinct sources is likely to contribute differentially to dendritic computations. In this review, I describe four groups of GABAergic interneuron according to their expression of parvalbumin, cholecystokinin, axonal arborization density and long-range projections. These four interneuron groups contain at least 12 distinct cell types, which innervate mainly or exclusively the dendrites of CA1 pyramidal cells. Furthermore, I summarize the different spike timing of distinct interneuron types during gamma, theta and ripple oscillations in vivo, and I discuss some of the open questions on how GABAergic input modulates dendritic operations in CA1 pyramidal cells.

  13. Molecular signatures of maturing dendritic cells: implications for testing the quality of dendritic cell therapies

    Directory of Open Access Journals (Sweden)

    Wang Ena

    2010-01-01

    Full Text Available Abstract Background Dendritic cells (DCs are often produced by granulocyte-macrophage colony-stimulating factor (GM-CSF and interleukin-4 (IL-4 stimulation of monocytes. To improve the effectiveness of DC adoptive immune cancer therapy, many different agents have been used to mature DCs. We analyzed the kinetics of DC maturation by lipopolysaccharide (LPS and interferon-γ (IFN-γ induction in order to characterize the usefulness of mature DCs (mDCs for immune therapy and to identify biomarkers for assessing the quality of mDCs. Methods Peripheral blood mononuclear cells were collected from 6 healthy subjects by apheresis, monocytes were isolated by elutriation, and immature DCs (iDCs were produced by 3 days of culture with GM-CSF and IL-4. The iDCs were sampled after 4, 8 and 24 hours in culture with LPS and IFN-γ and were then assessed by flow cytometry, ELISA, and global gene and microRNA (miRNA expression analysis. Results After 24 hours of LPS and IFN-γ stimulation, DC surface expression of CD80, CD83, CD86, and HLA Class II antigens were up-regulated. Th1 attractant genes such as CXCL9, CXCL10, CXCL11 and CCL5 were up-regulated during maturation but not Treg attractants such as CCL22 and CXCL12. The expression of classical mDC biomarker genes CD83, CCR7, CCL5, CCL8, SOD2, MT2A, OASL, GBP1 and HES4 were up-regulated throughout maturation while MTIB, MTIE, MTIG, MTIH, GADD45A and LAMP3 were only up-regulated late in maturation. The expression of miR-155 was up-regulated 8-fold in mDCs. Conclusion DCs, matured with LPS and IFN-γ, were characterized by increased levels of Th1 attractants as opposed to Treg attractants and may be particularly effective for adoptive immune cancer therapy.

  14. Phase-field simulation of micropores constrained by the dendritic network during solidification

    Energy Technology Data Exchange (ETDEWEB)

    Meidani, H., E-mail: hossein.meidani@epfl.ch [Computational Materials Laboratory, Institute of Materials, Ecole Polytechnique Federale de Lausanne, 1015 Lausanne (Switzerland); Jacot, A. [Computational Materials Laboratory, Institute of Materials, Ecole Polytechnique Federale de Lausanne, 1015 Lausanne (Switzerland); Calcom ESI SA, Parc Scientifique, PSE-A, 1015 Lausanne (Switzerland)

    2011-05-15

    Highlights: > Direct description of the complex morphology of micropores in using phase-field. > Presence of solid substantially influences the pressure and volume of the pores. > Hydrogen content is an influencing factor that was not considered previously. > Pore curvature depends on the statistical distribution of liquid channel widths. - Abstract: A phase-field model has been developed to describe the morphology of pores constrained by a dendritic solid network, and are forced to adopt complex non-spherical shapes. The distribution of the solid, liquid and gas phases was calculated with a multiphase-field approach which accounts for the pressure difference between the liquid and the gas. The model considers the partitioning of the dissolved gas at interfaces, gas diffusion and capillary forces at the solid/liquid, liquid/gas and gas/solid interfaces. The model was used to study the influence of the dendrite arm spacing (DAS) and the solid fraction on the state of a pore. The calculations show that a pore constrained to grow in a narrow liquid channel exhibits a substantially higher mean curvature, a larger pressure and a smaller volume than an unconstrained pore. Comparisons with simple geometrical models indicate that analytical approaches show a good trend but tend to underestimate the pore curvature, in particular at high solid fractions, where pores have to penetrate the thin liquid channels. For pores spanning over distances larger than the average DAS, the simulations showed that the radius of curvature can vary between two limits, which are given by the size of the narrowest section that the pore needs to pass in order to expand and by the largest sphere that can be fitted in the interdendritic liquid. The pore curvature is therefore a complex non-monotonic function of the DAS, the solid fraction, the hydrogen content and statistical variations of the liquid channel width.

  15. Acetyl-L-carnitine improves behavior and dendritic morphology in a mouse model of Rett syndrome.

    Directory of Open Access Journals (Sweden)

    Laura R Schaevitz

    Full Text Available Rett syndrome (RTT is a devastating neurodevelopmental disorder affecting 1 in 10,000 girls. Approximately 90% of cases are caused by spontaneous mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2. Girls with RTT suffer from severe motor, respiratory, cognitive and social abnormalities attributed to early deficits in synaptic connectivity which manifest in the adult as a myriad of physiological and anatomical abnormalities including, but not limited to, dimished dendritic complexity. Supplementation with acetyl-L-carnitine (ALC, an acetyl group donor, ameliorates motor and cognitive deficits in other disease models through a variety of mechanisms including altering patterns of histone acetylation resulting in changes in gene expression, and stimulating biosynthetic pathways such as acetylcholine. We hypothesized ALC treatment during critical periods in cortical development would promote normal synaptic maturation, and continuing treatment would improve behavioral deficits in the Mecp2(1lox mouse model of RTT. In this study, wildtype and Mecp2(1lox mutant mice received daily injections of ALC from birth until death (postnatal day 47. General health, motor, respiratory, and cognitive functions were assessed at several time points during symptom progression. ALC improved weight gain, grip strength, activity levels, prevented metabolic abnormalities and modestly improved cognitive function in Mecp2 null mice early in the course of treatment, but did not significantly improve motor or cognitive functions assessed later in life. ALC treatment from birth was associated with an almost complete rescue of hippocampal dendritic morphology abnormalities with no discernable side effects in the mutant mice. Therefore, ALC appears to be a promising therapeutic approach to treating early RTT symptoms and may be useful in combination with other therapies.

  16. Effect of strontium on columnar growth of dendritic α phase in near-eutectic Al-11.6%Si alloys

    Institute of Scientific and Technical Information of China (English)

    廖恒成; 丁毅; 孙国雄

    2004-01-01

    For Al-11.6 % Si alloy, the influence of the addition of Sr on the morphology of the dendrite α phase was investigated, and the characteristic parameters of the dendrite α phase, the primary dendrite spacing and the secondary dendrite arm spacing, were also measured. The addition of strontium promotes the columnar dendrite growth and leads to a decrease of both the primary dendrite spacing and secondary dendrite arm spacing with the increase of the content of strontium in the modified near-eutectic Al-Si alloys. It is thought that the addition of Sr leads to a reduction of the solid-liquid interfacial energy of the dendrite α phase, consequently resulting in a decrease of the growth undercooling of dendrite tips. And hence, the nucleation of the equiaxed grains in the liquid in front of the columnar dendrite tips is restrained, thus the addition of strontium in Al-Si alloys promotes the growth of the columnar dendrites. The reduction of the solid-liquid interfacial energy also leads to the decreases in the primary dendrite spacing and the secondary dendrite arm spacing.

  17. Identification of genes influencing dendrite morphogenesis in developing peripheral sensory and central motor neurons

    Directory of Open Access Journals (Sweden)

    Chwalla Barbara

    2008-07-01

    Full Text Available Abstract Background Developing neurons form dendritic trees with cell type-specific patterns of growth, branching and targeting. Dendrites of Drosophila peripheral sensory neurons have emerged as a premier genetic model, though the molecular mechanisms that underlie and regulate their morphogenesis remain incompletely understood. Still less is known about this process in central neurons and the extent to which central and peripheral dendrites share common organisational principles and molecular features. To address these issues, we have carried out two comparable gain-of-function screens for genes that influence dendrite morphologies in peripheral dendritic arborisation (da neurons and central RP2 motor neurons. Results We found 35 unique loci that influenced da neuron dendrites, including five previously shown as required for da dendrite patterning. Several phenotypes were class-specific and many resembled those of known mutants, suggesting that genes identified in this study may converge with and extend known molecular pathways for dendrite development in da neurons. The second screen used a novel technique for cell-autonomous gene misexpression in RP2 motor neurons. We found 51 unique loci affecting RP2 dendrite morphology, 84% expressed in the central nervous system. The phenotypic classes from both screens demonstrate that gene misexpression can affect specific aspects of dendritic development, such as growth, branching and targeting. We demonstrate that these processes are genetically separable. Targeting phenotypes were specific to the RP2 screen, and we propose that dendrites in the central nervous system are targeted to territories defined by Cartesian co-ordinates along the antero-posterior and the medio-lateral axes of the central neuropile. Comparisons between the screens suggest that the dendrites of peripheral da and central RP2 neurons are shaped by regulatory programs that only partially overlap. We focused on one common

  18. Turtle functions downstream of Cut in differentially regulating class specific dendrite morphogenesis in Drosophila.

    Directory of Open Access Journals (Sweden)

    Mikolaj J Sulkowski

    Full Text Available 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

  19. Reactive oxygen species are involved in BMP-induced dendritic growth in cultured rat sympathetic neurons.

    Science.gov (United States)

    Chandrasekaran, Vidya; Lea, Charlotte; Sosa, Jose Carlo; Higgins, Dennis; Lein, Pamela J

    2015-07-01

    Previous studies have shown that bone morphogenetic proteins (BMPs) promote dendritic growth in sympathetic neurons; however, the downstream signaling molecules that mediate the dendrite promoting activity of BMPs are not well characterized. Here we test the hypothesis that reactive oxygen species (ROS)-mediated signaling links BMP receptor activation to dendritic growth. In cultured rat sympathetic neurons, exposure to any of the three mechanistically distinct antioxidants, diphenylene iodinium (DPI), nordihydroguaiaretic acid (NGA) or desferroxamine (DFO), blocked de novo BMP-induced dendritic growth. Addition of DPI to cultures previously induced with BMP to extend dendrites caused dendritic retraction while DFO and NGA prevented further growth of dendrites. The inhibition of the dendrite promoting activity of BMPs by antioxidants was concentration-dependent and occurred without altering axonal growth or neuronal cell survival. Antioxidant treatment did not block BMP activation of SMAD 1,5 as determined by nuclear localization of these SMADs. While BMP treatment did not cause a detectable increase in intracellular ROS in cultured sympathetic neurons as assessed using fluorescent indicator dyes, BMP treatment increased the oxygen consumption rate in cultured sympathetic neurons as determined using the Seahorse XF24 Analyzer, suggesting increased mitochondrial activity. In addition, BMPs upregulated expression of NADPH oxidase 2 (NOX2) and either pharmacological inhibition or siRNA knockdown of NOX2 significantly decreased BMP-7 induced dendritic growth. Collectively, these data support the hypothesis that ROS are involved in the downstream signaling events that mediate BMP7-induced dendritic growth in sympathetic neurons, and suggest that ROS-mediated signaling positively modulates dendritic complexity in peripheral neurons.

  20. Autologous tumor lysate-pulsed dendritic cell immunotherapy for pediatric patients with newly diagnosed or recurrent high-grade gliomas.

    Science.gov (United States)

    Lasky, Joseph L; Panosyan, Eduard H; Plant, Ashley; Davidson, Tom; Yong, William H; Prins, Robert M; Liau, Linda M; Moore, Theodore B

    2013-05-01

    Immunotherapy has the potential to improve clinical outcomes with little toxicity for pediatric patients with brain tumors. We conducted a pilot feasibility study of tumor lysate-pulsed dendritic cell (DC) vaccination in pediatric patients (1 to 18 years old) with newly diagnosed or recurrent high-grade glioma (HGG). A total of nine DC vaccine doses, each containing 1 × 10(6) cells per dose were administered to three out of the seven originally enrolled patients. Toxicities were limited to mild side-effects, except in one case of elevated alkaline phosphatase, which resolved without clinical consequences. Two patients with primary lesions amongst the three vaccinated were alive at the time of writing, both without evidence of disease. Pre- and post-vaccination tumor samples from a patient with an anaplastic oligoastrocytoma that recurred failed to demonstrate immune cell infiltration by immunohistochemistry. Peripheral cytokine levels were evaluated in one patient following DC vaccination and demonstrated some changes in relation to vaccination. DC vaccine is tolerable and feasible with some limitations for pediatric patients with HGG. Dendritic cell based immunotherapy may provide some clinical benefit in pediatric patients with glioma, especially for patients with minimal residual disease, but further investigation of this modality is required.