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‣ Estruturas celulares, transição celular/dendritica e estruturas dendriticas na solidificação unidirecional transitoria; Cellular structures, cellular/dendritic transition and dendritic structures during transient unidirectional solidification

Daniel Monteiro Rosa
Fonte: Biblioteca Digital da Unicamp Publicador: Biblioteca Digital da Unicamp
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 31/05/2007 Português
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As morfologias das estruturas de solidificação, caracterizadas principalmente por arranjos celulares e dendríticos, e suas grandezas representadas por espaçamentos celulares e dendríticos primários, secundários e terciários, controlam os perfis de segregação e a formação de segundas fases dentro das regiões intercelulares ou interdendríticas, que determinam as propriedades finais das estruturas fundidas. O presente trabalho pretende contribuir para o entendimento do desenvolvimento microestrutural de ligas binárias através da análise de dois sistemas binários que possuem elevada importância para a indústria na fabricação de peças fundidas automotivas e grades de baterias: Al-Si e Pb-Sb, respectivamente. Os experimentos realizados utilizaram dois diferentes dispositivos em que o calor é extraído somente pelo sistema de resfriamento a água, localizado no fundo (solidificação ascendente) e no topo (solidificação descendente) da lingoteira. As variáveis térmicas de solidificação foram determinadas pela leitura de temperaturas a partir de termopares posicionados dentro da lingoteira em diferentes posições em relação à superfície refrigerada. Estas variáveis térmicas foram confrontadas com as previsões teóricas de um modelo numérico de solidificação. Os aspectos macroestruturais e microestruturais foram caracterizados ao longo dos lingotes através de microscopia óptica. Para as ligas Al-Si foi realizada uma análise complementar do efeito da convecção térmica e constitucional nos espaçamentos dendríticos terciários na solidificação unidirecional transitória descendente. Ligas hipoeutéticas Pb-Sb foram utilizadas para analisar as influências das variáveis térmicas de solidificação e da concentração de soluto nas estruturas celulares...

‣ Peyer’s patch organogenesis is intact yet formation of B lymphocyte follicles is defective in peripheral lymphoid organs of mice deficient for tumor necrosis factor and its 55-kDa receptor

Pasparakis, Manolis; Alexopoulou, Lena; Grell, Matthias; Pfizenmaier, Klaus; Bluethmann, Horst; Kollias, George
Fonte: The National Academy of Sciences of the USA Publicador: The National Academy of Sciences of the USA
Tipo: Artigo de Revista Científica
Publicado em 10/06/1997 Português
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Targeted inactivation of genes in the tumor necrosis factor (TNF)/lymphotoxin (LT) ligand and receptor system has recently revealed essential roles for these molecules in lymphoid tissue development and organization. Lymphotoxin-αβ (LTαβ)/lymphotoxin-β receptor (LTβ-R) signaling is critical for the organogenesis of lymph nodes and Peyer’s patches and for the structural compartmentalization of the splenic white pulp into distinct B and T cell areas and marginal zones. Moreover, an essential role has been demonstrated for TNF/p55 tumor necrosis factor receptor (p55TNF-R) signaling in the formation of splenic B lymphocyte follicles, follicular dendritic cell networks, and germinal centers. In contrast to a previously described essential role for the p55TNF-R in Peyer’s patch organogenesis, we show in this report that Peyer’s patches are present in both TNF and p55TNF-R knockout mice, demonstrating that these molecules are not essential for the organogenesis of this lymphoid organ. Furthermore, we show that in the absence of TNF/p55TNF-R signaling, lymphocytes segregate normally into T and B cell areas and a normal content and localization of dendritic cells is observed in both lymph nodes and Peyer’s patches. However, although B cells are found to home normally within Peyer’s patches and in the outer cortex area of lymph nodes...

‣ Sorting and directed transport of membrane proteins during development of hippocampal neurons in culture

Silverman, M. A.; Kaech, S.; Jareb, M.; Burack, M. A.; Vogt, L.; Sonderegger, P.; Banker, G.
Fonte: The National Academy of Sciences Publicador: The National Academy of Sciences
Tipo: Artigo de Revista Científica
Publicado em 19/06/2001 Português
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Hippocampal neurons in culture develop morphological polarity in a sequential pattern; axons form before dendrites. Molecular differences, particularly those of membrane proteins, underlie the functional polarity of these domains, yet little is known about the temporal relationship between membrane protein polarization and morphological polarization. We took advantage of viral expression systems to determine when during development the polarization of membrane proteins arises. All markers were unpolarized in neurons before axonogenesis. In neurons with a morphologically distinguishable axon, even on the first day in culture, both axonal and dendritic proteins were polarized. The degree of polarization at these early stages was somewhat less than in mature cells and varied from cell to cell. The cellular mechanism responsible for the polarization of the dendritic marker protein transferrin receptor (TfR) in mature cells centers on directed transport to the dendritic domain. To examine the relationship between cell surface polarization and transport, we assessed the selectivity of transport by live cell imaging. TfR-green fluorescent protein-containing vesicles were already preferentially transported into dendrites at 2 days, the earliest time point we could measure. The selectivity of transport also varied somewhat among cells...

‣ Co-option of endocytic functions of cellular caveolae by pathogens

Shin, J-S; Abraham, S N
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /01/2001 Português
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It is increasingly becoming clear that various immune cells are infected by the very pathogens that they are supposed to attack. Although many mechanisms for microbial entry exist, it appears that a common route of entry shared by certain bacteria, viruses and parasites involves cellular lipid-rich microdomains sometimes called caveolae. These cellular entities, which are characterized by their preferential accumulation of glycosylphosphatidylinositol (GPI)-anchored molecules, cholesterol and various glycolipids, and a distinct protein (caveolin), are present in many effector cells of the immune system including neutrophils, macrophages, mast cells and dendritic cells. These structures have an innate capacity to endocytoze various ligands and traffic them to different intracellular sites and sometimes, back to the extracellular cell surface. Because caveolae do not typically fuse with lysosomes, the ligands borne by caveolar vesicles are essentially intact, which is in marked contrast to ligands endocytozed via the classical endosome–lysosome pathway. A number of microbes or their exotoxins co-opt the unique features of caveolae to enter and traffic, without any apparent loss of viability and function, to different sites within immune and other host cells. In spite of their wide disparity in size and other structural attributes...

‣ Simulation and Prediction of the Adaptive Immune Response to Influenza A Virus Infection▿

Lee, Ha Youn; Topham, David J.; Park, Sung Yong; Hollenbaugh, Joseph; Treanor, John; Mosmann, Tim R.; Jin, Xia; Ward, Brian M.; Miao, Hongyu; Holden-Wiltse, Jeanne; Perelson, Alan S.; Zand, Martin; Wu, Hulin
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
Português
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The cellular immune response to primary influenza virus infection is complex, involving multiple cell types and anatomical compartments, and is difficult to measure directly. Here we develop a two-compartment model that quantifies the interplay between viral replication and adaptive immunity. The fidelity of the model is demonstrated by accurately confirming the role of CD4 help for antibody persistence and the consequences of immune depletion experiments. The model predicts that drugs to limit viral infection and/or production must be administered within 2 days of infection, with a benefit of combination therapy when administered early, and cytotoxic CD8 T cells in the lung are as effective for viral clearance as neutralizing antibodies when present at the time of challenge. The model can be used to investigate explicit biological scenarios and generate experimentally testable hypotheses. For example, when the adaptive response depends on cellular immune cell priming, regulation of antigen presentation has greater influence on the kinetics of viral clearance than the efficiency of virus neutralization or cellular cytotoxicity. These findings suggest that the modulation of antigen presentation or the number of lung resident cytotoxic cells and the combination drug intervention are strategies to combat highly virulent influenza viruses. We further compared alternative model structures...

‣ Modulation of ubiquitin dynamics and suppression of DALIS formation by the Legionella pneumophila Dot/Icm system

Ivanov, Stanimir S.; Roy, Craig R.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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Legionella pneumophila is an intracellular pathogen that uses effector proteins translocated by the Dot/Icm type IV secretion system to modulate host cellular processes. Here we investigate the dynamics of subcellular structures containing ubiquitin during L. pneumophila infection of phagocytic host cells. The Dot/Icm system mediated the formation of K48 and K63 poly-ubiquitin conjugates to proteins associated with L. pneumophila-containing vacuoles in macrophages and dendritic cells, suggesting that regulatory events and degradative events involving ubiquitin are regulated by bacterial effectors during infection. Stimulation of TLR2 on the surface of macrophages and dendritic cells by L. pneumophila-derived molecules resulted in the production of ubiquitin-rich dendritic cell aggresome-like structures (DALIS). Cells infected by L. pneumophila with a functional Dot/Icm system, however, failed to produce DALIS. Suppression of DALIS formation did not affect the accumulation of ubiquitinated proteins on vacuoles containing L. pneumophila. Examining other species of Legionella revealed that L. jordanis was unable to suppress DALIS formation after creating a ubiquitin-decorated vacuole. Thus, the L. pneumophila Dot/Icm system has the ability to modulate host processes to promote K48 and K63 ubiquitin conjugates on proteins at the vacuole membrane...

‣ Dendritic vulnerability in neurodegenerative disease: insights from analyses of cortical pyramidal neurons in transgenic mouse models

Luebke, Jennifer I.; Weaver, Christina M.; Rocher, Anne B.; Rodriguez, Alfredo; Crimins, Johanna L.; Dickstein, Dara L.; Wearne, Susan L.; Hof, Patrick R.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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In neurodegenerative disorders, such as Alzheimer’s disease, neuronal dendrites and dendritic spines undergo significant pathological changes. Because of the determinant role of these highly dynamic structures in signaling by individual neurons and ultimately in the functionality of neuronal networks that mediate cognitive functions, a detailed understanding of these changes is of paramount importance. Mutant murine models, such as the Tg2576 APP mutant mouse and the rTg4510 tau mutant mouse have been developed to provide insight into pathogenesis involving the abnormal production and aggregation of amyloid and tau proteins, because of the key role that these proteins play in neurodegenerative disease. This review showcases the multidimensional approach taken by our collaborative group to increase understanding of pathological mechanisms in neurodegenerative disease using these mouse models. This approach includes analyses of empirical 3D morphological and electrophysiological data acquired from frontal cortical pyramidal neurons using confocal laser scanning microscopy and whole-cell patch-clamp recording techniques, combined with computational modeling methodologies. These collaborative studies are designed to shed insight on the repercussions of dystrophic changes in neocortical neurons...

‣ How HIV-1 Takes Advantage of the Cytoskeleton during Replication and Cell-to-Cell Transmission

Lehmann, Martin; Nikolic, Damjan S.; Piguet, Vincent
Fonte: Molecular Diversity Preservation International (MDPI) Publicador: Molecular Diversity Preservation International (MDPI)
Tipo: Artigo de Revista Científica
Publicado em 15/09/2011 Português
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Human immunodeficiency virus 1 (HIV-1) infects T cells, macrophages and dendritic cells and can manipulate their cytoskeleton structures at multiple steps during its replication cycle. Based on pharmacological and genetic targeting of cytoskeleton modulators, new imaging approaches and primary cell culture models, important roles for actin and microtubules during entry and cell-to-cell transfer have been established. Virological synapses and actin-containing membrane extensions can mediate HIV-1 transfer from dendritic cells or macrophage cells to T cells and between T cells. We will review the role of the cytoskeleton in HIV-1 entry, cellular trafficking and cell-to-cell transfer between primary cells.

‣ Rhythmic dendritic Ca2+ oscillations in thalamocortical neurons during slow non-REM sleep-related activity in vitro

Errington, Adam C; Hughes, Stuart W; Crunelli, Vincenzo
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Português
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The distribution of T-type Ca2+ channels along the entire somatodendritic axis of sensory thalamocortical (TC) neurons permits regenerative propagation of low threshold spikes (LTS) accompanied by global dendritic Ca2+ influx. Furthermore, T-type Ca2+ channels play an integral role in low frequency oscillatory activity (<1–4 Hz) that is a defining feature of TC neurons. Nonetheless, the dynamics of T-type Ca2+ channel-dependent dendritic Ca2+ signalling during slow sleep-associated oscillations remains unknown. Here we demonstrate using patch clamp recording and two-photon Ca2+ imaging of dendrites from cat TC neurons undergoing spontaneous slow oscillatory activity that somatically recorded δ (1–4 Hz) and slow (<1 Hz) oscillations are associated with rhythmic and sustained global oscillations in dendritic Ca2+. In addition, our data reveal the presence of LTS-dependent Ca2+ transients (Δ[Ca2+]) in dendritic spine-like structures on proximal TC neuron dendrites during slow (<1 Hz) oscillations whose amplitudes are similar to those observed in the dendritic shaft. We find that the amplitude of oscillation associated Δ[Ca2+] do not vary significantly with distance from the soma whereas the decay time constant (τdecay) of Δ[Ca2+] decreases significantly in more distal dendrites. Furthermore...

‣ Synovial biology and T cells in rheumatoid arthritis

Tran, Chinh N.; Lundy, Steven K.; Fox, David A.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/2005 Português
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Events that occur in rheumatoid arthritis synovial tissues are responsible for the signs and symptoms of joint inflammation and for the eventual destruction of articular and periarticular structures that lead to joint dysfunction and disability. The three most abundant cell populations in RA synovium are synovial macrophages (type A synoviocytes), synovial fibroblasts (type B synoviocytes) and infiltrating T lymphocytes. Other important cell populations include B lymphocytes, dendritic cells, plasma cells, mast cells and osteoclasts. Our current understanding of rheumatoid arthritis is moving beyond previous concepts that view this disease as the consequence of a specific and focused humoral or cellular autoimmune response to a single autoantigen. Rather, a new view of rheumatoid arthritis is emerging, which seeks to understand this disease as the product of pathologic cell–cell interactions occurring within a unique and defined environment, the synovium. T lymphocytes in rheumatoid arthritis synovium interact closely with dendritic cells, the most potent antigen-presenting cell population in the immune system. T cells also interact with monocytes and macrophages and cytokine-activated T cells may be, especially, suited to trigger production of the important cytokine TNFα by synovial macrophages. Recent evidence also suggests a potent bidirectional interaction between synovial T cells and synovial fibroblasts...

‣ Primary Cilia and Dendritic Spines: Different but Similar Signaling Compartments

Nechipurenko, Inna V.; Doroquez, David B.; Sengupta, Piali
Fonte: Korea Society for Molecular and Cellular Biology Publicador: Korea Society for Molecular and Cellular Biology
Tipo: Artigo de Revista Científica
Português
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Primary non-motile cilia and dendritic spines are cellular compartments that are specialized to sense and transduce environmental cues and presynaptic signals, respectively. Despite their unique cellular roles, both compartments exhibit remarkable parallels in the general principles, as well as molecular mechanisms, by which their protein composition, membrane domain architecture, cellular interactions, and structural and functional plasticity are regulated. We compare and contrast the pathways required for the generation and function of cilia and dendritic spines, and suggest that insights from the study of one may inform investigations into the other of these critically important signaling structures.

‣ Cellular and subcellular localization of PKMζ

Hernández, A. Iván; Oxberry, William C.; Crary, John F.; Mirra, Suzanne S.; Sacktor, Todd Charlton
Fonte: The Royal Society Publicador: The Royal Society
Tipo: Artigo de Revista Científica
Publicado em 05/01/2014 Português
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In contrast to protein kinases that participate in long-term potentiation (LTP) induction and memory consolidation, the autonomously active atypical protein kinase C isoform, protein kinase Mzeta (PKMζ), functions in the core molecular mechanism of LTP maintenance and long-term memory storage. Here, using multiple complementary techniques for light and electron microscopic immunolocalization, we present the first detailed characterization of the cellular and subcellular distribution of PKMζ in rat hippocampus and neocortex. We find that PKMζ is widely expressed in forebrain with prominent immunostaining in hippocampal and neocortical grey matter, and weak label in white matter. In hippocampal and cortical pyramidal cells, PKMζ expression is predominantly somatodendritic, and electron microscopy highlights the kinase at postsynaptic densities and in clusters within spines. In addition, nuclear label and striking punctate immunopositive structures in a paranuclear and dendritic distribution are seen by confocal microscopy, occasionally at dendritic bifurcations. PKMζ immunoreactive granules are observed by electron microscopy in cell bodies and dendrites, including endoplasmic reticulum. The widespread distribution of PKMζ in nuclei...

‣ Morphology, Distribution and Phenotype of Polycystin Kidney Disease 2-like 1-Positive Cerebrospinal Fluid Contacting Neurons in The Brainstem of Adult Mice

Orts-Del’Immagine, Adeline; Kastner, Anne; Tillement, Vanessa; Tardivel, Catherine; Trouslard, Jérôme; Wanaverbecq, Nicolas
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 04/02/2014 Português
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The mammalian spinal cord and medulla oblongata harbor unique neurons that remain in contact with the cerebrospinal fluid (CSF-cNs). These neurons were shown recently to express a polycystin member of the TRP channels family (PKD2L1) that potentially acts as a chemo- or mechanoreceptor. Recent studies carried out in young rodents indicate that spinal CSF-cNs express immature neuronal markers that appear to persist even in adult cells. Nevertheless, little is known about the phenotype and morphological properties of medullar CSF-cNs. Using immunohistochemistry and confocal microscopy techniques on tissues obtained from three-month old PKD2L1:EGFP transgenic mice, we analyzed the morphology, distribution, localization and phenotype of PKD2L1+ CSF-cNs around the brainstem and cervical spinal cord central canal. We show that PKD2L1+ CSF-cNs are GABAergic neurons with a subependymal localization, projecting a dendrite towards the central canal and an axon-like process running through the parenchyma. These neurons display a primary cilium on the soma and the dendritic process appears to bear ciliary-like structures in contact with the CSF. PKD2L1+ CSF-cNs present a conserved morphology along the length of the medullospinal central canal with a change in their density...

‣ Adolescent cocaine exposure simplifies orbitofrontal cortical dendritic arbors

DePoy, Lauren M.; Perszyk, Riley E.; Zimmermann, Kelsey S.; Koleske, Anthony J.; Gourley, Shannon L.
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Publicado em 27/10/2014 Português
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Cocaine and amphetamine remodel dendritic spines within discrete cortico-limbic brain structures including the orbitofrontal cortex (oPFC). Whether dendrite structure is similarly affected, and whether pre-existing cellular characteristics influence behavioral vulnerabilities to drugs of abuse, remain unclear. Animal models provide an ideal venue to address these issues because neurobehavioral phenotypes can be defined both before, and following, drug exposure. We exposed mice to cocaine from postnatal days 31–35, corresponding to early adolescence, using a dosing protocol that causes impairments in an instrumental reversal task in adulthood. We then imaged and reconstructed excitatory neurons in deep-layer oPFC. Prior cocaine exposure shortened and simplified arbors, particularly in the basal region. Next, we imaged and reconstructed orbital neurons in a developmental-genetic model of cocaine vulnerability—the p190rhogap+/– mouse. p190RhoGAP is an actin cytoskeleton regulatory protein that stabilizes dendrites and dendritic spines, and p190rhogap+/– mice develop rapid and robust locomotor activation in response to cocaine. Despite this, oPFC dendritic arbors were intact in drug-naïve p190rhogap+/– mice. Together, these findings provide evidence that adolescent cocaine exposure has long-term effects on dendrite structure in the oPFC...

‣ Highly differentiated cellular and circuit properties of infralimbic pyramidal neurons projecting to the periaqueductal gray and amygdala

Ferreira, Ashley N.; Yousuf, Hanna; Dalton, Sarah; Sheets, Patrick L.
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Publicado em 28/04/2015 Português
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The infralimbic (IL) cortex is a key node in an inter-connected network involved in fear and emotion processing. The cellular and circuit-level mechanisms whereby IL neurons receive, filter, and modulate incoming signals they project onward to diverse downstream nodes in this complex network remain poorly understood. Using the mouse as our model, we applied anatomical labeling strategies, brain slice electrophysiology, and focal activation of caged glutamate via laser scanning photostimulation (glu-LSPS) for quantitative neurophysiological analysis of projectionally defined neurons in IL. Injection of retrograde tracers into the periaqueductal gray (PAG) and basolateral amygdala (BLA) was used to identify cortico-PAG (CP) and cortico-BLA (CA) neurons in IL. CP neurons were found exclusively in layer 5 (L5) of IL whereas CA neurons were detected throughout layer 2, 3, and 5 of IL. We also identified a small percentage of IL neurons that project to both the PAG and the BLA. We found that L5 CP neurons have a more extensive dendritic structure compared to L5 CA neurons. Neurophysiological recordings performed on retrogradely labeled neurons in acute brain slice showed that CP and CA neurons in IL could be broadly classified in two groups: neuronal resonators and non-resonators. Layer 2 CA neurons were the only class that was exclusively non-resonating. CP...

‣ Slit2N/Robo1 Inhibit HIV-gp120-Induced Migration and Podosome Formation in Immature Dendritic Cells by Sequestering LSP1 and WASp

Prasad, Anil; Kuzontkoski, Paula Marie; Shrivastava, Ashutosh; Zhu, Weiquan; Li, Dean Y.; Groopman, Jerome Elliot
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Português
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Cell-mediated transmission and dissemination of sexually-acquired human immunodeficiency virus 1 (HIV-1) in the host involves the migration of immature dendritic cells (iDCs). iDCs migrate in response to the HIV-1 envelope protein, gp120, and inhibiting such migration may limit the mucosal transmission of HIV-1. In this study, we elucidated the mechanism of HIV-1-gp120-induced transendothelial migration of iDCs. We found that gp120 enhanced the binding of Wiskott-Aldrich Syndrome protein (WASp) and the Actin-Related Protein 2/3 (Arp2/3) complex with β-actin, an interaction essential for the proper formation of podosomes, specialized adhesion structures required for the migration of iDCs through different tissues. We further identified Leukocyte-Specific Protein 1 (LSP1) as a novel component of the WASp-Arp2/3-β-actin complex. Pretreating iDCs with an active fragment of the secretory glycoprotein Slit2 (Slit2N) inhibited HIV-1-gp120-mediated migration and podosome formation, by inducing the cognate receptor Roundabout 1 (Robo1) to bind to and sequester WASp and LSP1 from β-actin. Slit2N treatment also inhibited Src signaling and the activation of several downstream molecules, including Rac1, Pyk2, paxillin, and CDC42, a major regulator of podosome formation. Taken together...

‣ Early Murine T-lymphocyte Activation Is Accompanied by a Switch from N-Glycolyl- to N-Acetyl-neuraminic Acid and Generation of Ligands for Siglec-E*

Redelinghuys, Pierre; Antonopoulos, Aristotelis; Liu, Yan; Campanero-Rhodes, Maria A.; McKenzie, Emma; Haslam, Stuart M.; Dell, Anne; Feizi, Ten; Crocker, Paul R.
Fonte: American Society for Biochemistry and Molecular Biology Publicador: American Society for Biochemistry and Molecular Biology
Tipo: Artigo de Revista Científica
Português
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It is well established that murine T-lymphocyte activation is accompanied by major changes in cell-surface sialylation, potentially influencing interactions with sialic acid-binding immunoglobulin-like lectins (siglecs). In the present study, we analyzed early activation of murine CD4+ and CD8+ T-lymphocytes at 24 h. We observed a striking and selective up-regulation in the binding of a recombinant soluble form of siglec-E, an inhibitory siglec, which is expressed on several myeloid cell types including antigen-presenting dendritic cells. In contrast, much lower levels of T cell binding were observed with other siglecs, including sialoadhesin, CD22, and siglec-F and the plant lectins Maackia amurensis leukoagglutinin and Sambucus nigra agglutinin. By mass spectrometry, the sialic acid content of 24-h-activated CD4+ and CD8+ T-lymphocytes exhibited an increased proportion of N-acetyl-neuraminic acid (NeuAc) to N-glycolyl-neuraminic acid (NeuGc) in N-glycans. Reduced levels of NeuGc on the surface of activated T cells were demonstrated using an antibody specific for NeuGc and the expression levels of the gene encoding NeuAc- to NeuGc-converting enzyme, CMP-NeuAc hydroxylase, were also reduced. Siglec-E bound a wide range of sialylated structures in glycan arrays...

‣ Dendritic Spines and Development: Towards a Unifying Model of Spinogenesis—A Present Day Review of Cajal's Histological Slides and Drawings

García-López, Pablo; García-Marín, Virginia; Freire, Miguel
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
Português
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Dendritic spines receive the majority of excitatory connections in the central nervous system, and, thus, they are key structures in the regulation of neural activity. Hence, the cellular and molecular mechanisms underlying their generation and plasticity, both during development and in adulthood, are a matter of fundamental and practical interest. Indeed, a better understanding of these mechanisms should provide clues to the development of novel clinical therapies. Here, we present original results obtained from high-quality images of Cajal's histological preparations, stored at the Cajal Museum (Instituto Cajal, CSIC), obtained using extended focus imaging, three-dimensional reconstruction, and rendering. Based on the data available in the literature regarding the formation of dendritic spines during development and our results, we propose a unifying model for dendritic spine development.

‣ NOD2 Stimulation by Staphylococcus aureus-Derived Peptidoglycan Is Boosted by Toll-Like Receptor 2 Costimulation with Lipoproteins in Dendritic Cells

Schäffler, Holger; Demircioglu, Dogan Doruk; Kühner, Daniel; Menz, Sarah; Bender, Annika; Autenrieth, Ingo B.; Bodammer, Peggy; Lamprecht, Georg; Götz, Friedrich; Frick, Julia-Stefanie
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /11/2014 Português
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Mutations in the nucleotide-binding oligomerization domain-containing protein 2 (NOD2) play an important role in the pathogenesis of Crohn's disease. NOD2 is an intracellular pattern recognition receptor (PRR) that senses bacterial peptidoglycan (PGN) structures, e.g., muramyl dipeptide (MDP). Here we focused on the effect of more-cross-linked, polymeric PGN fragments (PGNpol) in the activation of the innate immune system. In this study, the effect of combined NOD2 and Toll-like receptor 2 (TLR2) stimulation was examined compared to single stimulation of the NOD2 receptor alone. PGNpol species derived from a lipoprotein-containing Staphylococcus aureus strain (SA113) and a lipoprotein-deficient strain (SA113 Δlgt) were isolated. While PGNpol constitutes a combined NOD2 and TLR2 ligand, lipoprotein-deficient PGNpolΔlgt leads to activation of the immune system only via the NOD2 receptor. Murine bone marrow-derived dendritic cells (BMDCs), J774 cells, and Mono Mac 6 (MM6) cells were stimulated with these ligands. Cytokines (interleukin-6 [IL-6], IL-12p40, and tumor necrosis factor alpha [TNF-α]) as well as DC activation and maturation parameters were measured. Stimulation with PGNpolΔlgt did not lead to enhanced cytokine secretion or DC activation and maturation. However...

‣ The function of dendritic spines: devices subserving biochemical rather than electrical compartmentalization

Koch, Christof; Zador, Anthony
Fonte: Society for Neuroscience Publicador: Society for Neuroscience
Tipo: Article; PeerReviewed Formato: application/pdf
Publicado em 01/02/1993 Português
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Dendritic spines are tiny, specialized protoplasmic protuberances that cover the surface of many neurons. First described by Ramon y Cajal ( 1991) in light microscopic studies of Golgistained tissue, they are among the most striking subcellular features of many neurons. Spines serve as the major target for excitatory synaptic input onto principal neurons in the hippocampus, the neocortex, and other brain regions. Their intimate association with synaptic traffic suggests some critical role in synaptic transmission and plasticity. We here review experimental data and theoretical models with respect to the putative role of dendritic spines in the induction and retention of synaptic plasticity. The ubiquity of spines demands explanation, yet their small size- near the limit of resolution of light microscopy- impedes an experimental frontal assault. Until recently, most theoretical studies focused on the role of the spine neck geometry in regulating the amplitude of the EPSP received at the soma. However, recent experimental evidence suggests that the spine shape may not be able to modulate the "synaptic weight" effectively. Consequently, both theoretical models and calcium-imaging experiments are now focusing on the role of spines in amplifying and isolating calcium signals...