Zeitschriftenartikel: „Intracellular signals“

1

Imboden, J. B., und G. A. Koretsky. „Intracellular Signalling: Switching off signals“. Current Biology 5, Nr. 7 (Juli 1995): 727–29. http://dx.doi.org/10.1016/s0960-9822(95)00145-x.

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2

Kalaidzidis, Yannis, Hernán Morales-Navarrete, Inna Kalaidzidis und Marino Zerial. „Intracellular Background Estimation for Quantitative Fluorescence Microscopy“. Proceedings 33, Nr. 1 (06.12.2019): 22. http://dx.doi.org/10.3390/proceedings2019033022.

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Fluorescently targeted proteins are widely used for studies of intracellular organelles dynamic. Peripheral proteins are transiently associated with organelles and a significant fraction of them are located at the cytosol. Image analysis of peripheral proteins poses a problem on properly discriminating membrane-associated signal from the cytosolic one. In most cases, signals from organelles are compact in comparison with diffuse signal from cytosol. Commonly used methods for background estimation depend on the assumption that background and foreground signals are separable by spatial frequency filters. However, large non-stained organelles (e.g., nuclei) result in abrupt changes in the cytosol intensity and lead to errors in the background estimation. Such mistakes result in artifacts in the reconstructed foreground signal. We developed a new algorithm that estimates background intensity in fluorescence microscopy images and does not produce artifacts on the borders of nuclei.

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3

IKATAYAMA, Yoshiki. „Polymer Drugs Responding to Intracellular Signals“. Kobunshi 55, Nr. 5 (2006): 326–29. http://dx.doi.org/10.1295/kobunshi.55.326.

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4

Song, Jianxun, Fengyang Tylan Lei, Xiaofang Xiong und Rizwanul Haque. „Intracellular Signals of T Cell Costimulation“. Cellular & Molecular Immunology 5, Nr. 4 (August 2008): 239–47. http://dx.doi.org/10.1038/cmi.2008.30.

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5

Cao, Y., A. T. Pearman, G. A. Zimmerman, T. M. McIntyre und S. M. Prescott. „Intracellular unesterified arachidonic acid signals apoptosis“. Proceedings of the National Academy of Sciences 97, Nr. 21 (26.09.2000): 11280–85. http://dx.doi.org/10.1073/pnas.200367597.

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6

Konieczny, Vera, Michael V. Keebler und Colin W. Taylor. „Spatial organization of intracellular Ca2+ signals“. Seminars in Cell & Developmental Biology 23, Nr. 2 (April 2012): 172–80. http://dx.doi.org/10.1016/j.semcdb.2011.09.006.

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7

Rüdiger, Sten. „Stochastic models of intracellular calcium signals“. Physics Reports 534, Nr. 2 (Januar 2014): 39–87. http://dx.doi.org/10.1016/j.physrep.2013.09.002.

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8

Seuwen, Klaus, und Jaques Pouysségur. „Intracellular signals in the mitogenic response“. Fresenius' Zeitschrift für analytische Chemie 330, Nr. 4-5 (Januar 1988): 308–9. http://dx.doi.org/10.1007/bf00469223.

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9

Ramseyer, Lorenz T. H., Janet Barker-Harrel, David J. Smith, Kari A. McBride, Robert N. Jarman und Robert H. Broyles. „Intracellular signals for developmental hemoglobin switching“. Developmental Biology 133, Nr. 1 (Mai 1989): 262–71. http://dx.doi.org/10.1016/0012-1606(89)90317-5.

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10

Gruol, D. L., J. G. Netzeband und K. L. Parsons. „Ca2+ signaling pathways linked to glutamate receptor activation in the somatic and dendritic regions of cultured cerebellar purkinje neurons“. Journal of Neurophysiology 76, Nr. 5 (01.11.1996): 3325–40. http://dx.doi.org/10.1152/jn.1996.76.5.3325.

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1. Ca2+ signaling elicited by ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate (iGluR) and metabotropic (mGluR) glutamate receptor agonists was studied in the somatic and dendritic regions of cultured cerebellar Purkinje neurons using microscopic video imaging and the Ca2+ sensitive dye fura-2. 2. iGluR and mGluR agonists and K+ depolarization applied by brief micropressure pulses evoked Ca2+ signals in both the somatic and dendritic regions of all Purkinje neurons studied. The Ca2+ signals were generated simultaneously in both cellular regions. The Ca+ signals to these stimulants were similar in general form, consisting of an initial peak and slow recovery phase, but differed in details of amplitude, time course, and complexity. 3. Removal of extracellular Ca2+ abolished the Ca2+ signal to the iGluR agonist AMPA, indicating that Ca2+ influx was essential to the generation of Ca2+ signals by iGluR agonists. The Ca2+ channel blocker lanthanum almost completely eliminated the Ca2+ signals to AMPA, indicating that Ca2+ influx through voltage-sensitive Ca2+ channels was the main pathway for Ca2+ influx. Omega-agatoxin IVA, a P-type Ca2+ channel blocker, significantly reduced the Ca2+ signals to AMPA suggesting that Ca2+ influx was predominately through P-type Ca2+ channels. 4. Pharmacological manipulation of intracellular Ca2+ stores significantly reduced the Ca2+ signals to AMPA, indicating that release of Ca2+ from intracellular Ca2+ stores also plays a prominent role in the generation of the Ca2+ signals to iGluR agonists. These manipulations included blocking Ca2+ release from intracellular stores with dantrolene, an antagonist at the ryanodine receptor that controls Ca2+ release from one pool of intracellular Ca2+ stores, and depletion of intracellular Ca2+ stores with caffeine or ryanodine. 5. Ca2+ influx through voltage-sensitive Ca2+ channels did not appear to be involved in the Ca2+ signals to mGluR activation, because neither lanthanum nor omega-agatoxin IVA altered Ca2+ signals to mGluR agonists. Manipulation of intracellular stores with Ca(2+)-ATPase inhibitors and dantrolene significantly reduced the Ca2+ signal to mGluR agonists, indicating that Ca2+ signals were derived from both the inositol trisphosphate (IP3) and the ryanodine receptor-controlled intracellular Ca2+ stores. 6. Ca2+ signals to the iGluR agonist AMPA correlated temporally with the prolonged, multiphasic membrane responses elicited by similar agonist application in parallel electrophysiological studies. Pharmacological manipulation of Ca2+ influx and release of Ca2+ from intracellular stores significantly influenced components of the membrane response to AMPA, indicating a potential modulator or mediator role for Ca2+ in the membrane response to iGluR activation.

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Christian, J. L. „Argosomes: Intracellular Transport Vehicles for Intercellular Signals?“ Science Signaling 2002, Nr. 124 (19.03.2002): pe13. http://dx.doi.org/10.1126/stke.2002.124.pe13.

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12

Neer, Eva J. „Intracellular signalling: Turning down G-protein signals“. Current Biology 7, Nr. 1 (Januar 1997): R31—R33. http://dx.doi.org/10.1016/s0960-9822(06)00014-5.

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13

Kashina, Anna, und Vladimir Rodionov. „Intracellular organelle transport: few motors, many signals“. Trends in Cell Biology 15, Nr. 8 (August 2005): 396–98. http://dx.doi.org/10.1016/j.tcb.2005.06.002.

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14

Starkova, N. N., E. P. Koroleva und T. V. Rotanova. „Intracellular proteolysis: Signals of selective protein degradation“. Russian Journal of Bioorganic Chemistry 26, Nr. 2 (Februar 2000): 71–84. http://dx.doi.org/10.1007/bf02759152.

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15

Vasquez, Nicki J., Lawrence P. Kane und Stephen M. Hedrick. „Intracellular signals that mediate thymic negative selection“. Immunity 1, Nr. 1 (April 1994): 45–56. http://dx.doi.org/10.1016/1074-7613(94)90008-6.

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16

Kozlov, Evgeny, Elena Martynova, Vladimir Popenko, Coby Schal und Dmitry Mukha. „Intracellular Localization of Blattella germanica Densovirus (BgDV1) Capsid Proteins“. Viruses 10, Nr. 7 (14.07.2018): 370. http://dx.doi.org/10.3390/v10070370.

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Densovirus genome replication and capsid assembly take place in the nucleus of the infected cells. However, the mechanisms underlying such processes as the delivery of virus proteins to the nucleus and the export of progeny virus from the nucleus remain elusive. It is evident that nuclear transport signals should be involved in these processes. We performed an in silico search for the putative nuclear localization signal (NLS) and nuclear export signal (NES) motifs in the capsid proteins of the Blattella germanica Densovirus 1 (BgDV1) densovirus. A high probability NLS motif was found in the common C-terminal of capsid proteins together with a NES motif in the unique N-terminal of VP2. We also performed a global search for the nuclear traffic signals in the densoviruses belonging to five Densovirinae genera, which revealed high diversity in the patterns of NLSs and NESs. Using a heterologous system, the HeLa mammalian cell line expressing GFP-fused BgDV1 capsid proteins, we demonstrated that both signals are functionally active. We suggest that the NLS shared by all three BgDV1 capsid proteins drives the trafficking of the newly-synthesized proteins into the nucleus, while the NES may play a role in the export of the newly-assembled BgDV1 particles into the cytoplasm through nuclear pore complexes.

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Wong, K., S. Karunanithi und H. L. Atwood. „Quantal Unit Populations at the DrosophilaLarval Neuromuscular Junction“. Journal of Neurophysiology 82, Nr. 3 (01.09.1999): 1497–511. http://dx.doi.org/10.1152/jn.1999.82.3.1497.

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Focal extracellular recording at visualized boutons of the Drosophila larval neuromuscular junction was used to determine frequency and time course of the spontaneously occurring quantal events. When simultaneous intracellular recordings from the innervated muscle cell were made, more than one class of quantal event occurred at some of the individual boutons. “True” signals (arising at the bouton within the focal macropatch electrode) were often contaminated by additional signals generated outside the lumen of the focal electrode. Inclusion of these contaminating signals gave spuriously low values for relative amplitude, and spuriously high values for spontaneous quantal emission, for the synapses within the focal electrode. The contaminating signals, which appeared to be conducted along the subsynaptic reticulum surrounding the nerve terminals, generally were characterized by relatively small extracellular signals associated with normal intracellular events in the muscle fiber. From plots of simultaneous extracellular and intracellular recordings, the individual data points were classified according to the angles they subtended with the x axis (extracellular signal axis). Statistical procedures were developed to separate the true signals and contaminants with a high level of confidence. Populations of quantal events were found to be well described by Gaussian mixtures of two or three components, one of which could be characterized as the true signal population. Separation of signals from contaminants provides a basis for improving the estimates of quantal size and spontaneous frequency for the synapses sampled by the focal extracellular electrode.

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Griffin, Stephen, Dean Clarke, Christopher McCormick, David Rowlands und Mark Harris. „Signal Peptide Cleavage and Internal Targeting Signals Direct the Hepatitis C Virus p7 Protein to Distinct Intracellular Membranes“. Journal of Virology 79, Nr. 24 (15.12.2005): 15525–36. http://dx.doi.org/10.1128/jvi.79.24.15525-15536.2005.

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ABSTRACT The hepatitis C virus (HCV) p7 protein forms an amantadine-sensitive ion channel required for viral replication in chimpanzees, though its precise role in the life cycle of HCV is unknown. In an attempt to gain some insights into p7 function, we examined the intracellular localization of p7 using epitope tags and an anti-p7 peptide antibody, antibody 1055. Immunofluorescence labeling of p7 at its C terminus revealed an endoplasmic reticulum (ER) localization independent of the presence of its signal peptide, whereas labeling the N terminus gave a mitochondrial-type distribution in brightly labeled cells. Both of these patterns could be visualized within individual cells, suggestive of separate pools of p7 where the N and C termini differed in accessibility to antibody. These patterns were disrupted by preventing signal peptide cleavage. Subcellular fractionation revealed that p7 was enriched in a heavy membrane fraction associated with mitochondria as well as normal ER-derived microsomes. The complex regulation of the intracellular distribution of p7 suggests that p7 plays multiple roles in the HCV life cycle either intracellularly or as a virion component.

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Wu, Cuichen Sam, Lu Peng, Mingxu You, Da Han, Tao Chen, Kathryn R. Williams, Chaoyong James Yang und Weihong Tan. „Engineering Molecular Beacons for Intracellular Imaging“. International Journal of Molecular Imaging 2012 (06.11.2012): 1–10. http://dx.doi.org/10.1155/2012/501579.

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Molecular beacons (MBs) represent a class of nucleic acid probes with unique DNA hairpin structures that specifically target complementary DNA or RNA. The inherent “OFF” to “ON” signal transduction mechanism of MBs makes them promising molecular probes for real-time imaging of DNA/RNA in living cells. However, conventional MBs have been challenged with such issues as false-positive signals and poor biostability in complex cellular matrices. This paper describes the novel engineering steps used to improve the fluorescence signal and reduce to background fluorescence, as well as the incorporation of unnatural nucleotide bases to increase the resistance of MBs to nuclease degradation for application in such fields as chemical analysis, biotechnology, and clinical medicine. The applications of these de novo MBs for single-cell imaging will be also discussed.

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Sanchez, J. A., und J. Vergara. „Modulation of Ca2+ transients by photorelease of caged nucleotides in frog skeletal muscle fibers“. American Journal of Physiology-Cell Physiology 266, Nr. 5 (01.05.1994): C1291—C1300. http://dx.doi.org/10.1152/ajpcell.1994.266.5.c1291.

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Action potentials and intracellular Ca2+ transients were monitored in current-clamped segments of frog skeletal muscle fibers using the triple vaseline-gap technique. Calcium signals were measured with the fluorescent indicator rhod 2. Action potentials produced a transient increase in intracellular Ca2+ that was estimated, by deconvolution of the fluorescence signals, to range between 3 and 12 microM. The comparative effects of flash photolysis of caged adenosine 3',5'-cyclic monophosphate (cAMP) and caged ATP on action potentials and Ca signals in muscle were investigated. The photorelease of both nucleotides produced a reduction in the amplitude of the afterpotential that follows the spike. Photorelease of cAMP and ATP prolonged the rate of decay of the Ca signals. No changes in either the rate of rise or in the latent period between stimulation and onset of the Ca signal were observed. Release of cAMP reduced the amplitude of Ca signals, whereas release of ATP had the opposite effect. Our results show that cAMP and ATP, released above their endogenous levels, modulate intracellular Ca2+ release. The cAMP modulation is more significant and may be of physiological importance.

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Tran, Tuan-Khanh, Napapon Sailasuta, Ulrike Kreutzer, Ralph Hurd, Youngran Chung, Paul Mole, Shinya Kuno und Thomas Jue. „Comparative analysis of NMR and NIRS measurements of intracellular P O 2 in human skeletal muscle“. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 276, Nr. 6 (01.06.1999): R1682—R1690. http://dx.doi.org/10.1152/ajpregu.1999.276.6.r1682.

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1H NMR has detected both the deoxygenated proximal histidyl NδH signals of myoglobin (deoxyMb) and deoxygenated Hb (deoxyHb) from human gastrocnemius muscle. Exercising the muscle or pressure cuffing the leg to reduce blood flow elicits the appearance of the deoxyMb signal, which increases in intensity as cellular[Formula: see text] decreases. The deoxyMb signal is detected with a 45-s time resolution and reaches a steady-state level within 5 min of pressure cuffing. Its desaturation kinetics match those observed in the near-infrared spectroscopy (NIRS) experiments, implying that the NIRS signals are actually monitoring Mb desaturation. That interpretation is consistent with the signal intensity and desaturation of the deoxyHb proximal histidyl NδH signal from the β-subunit at 73 parts per million. The experimental results establish the feasibility and methodology to observe the deoxyMb and Hb signals in skeletal muscle, help clarify the origin of the NIRS signal, and set a stage for continuing study of O2regulation in skeletal muscle.

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22

Ruskoaho, H., M. Toth, D. Ganten, T. Unger und R. E. Lang. „Intracellular Signals Regulating Atrial Natriuretic Peptide (ANP) Secretion“. Journal of Cardiovascular Pharmacology 8, Nr. 6 (November 1986): 1305. http://dx.doi.org/10.1097/00005344-198611000-00105.

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23

Moenke, Gregor, Martin Falcke und Keven Thurley. „Hierarchic Stochastic Modelling Applied to Intracellular Ca2+ Signals“. PLoS ONE 7, Nr. 12 (27.12.2012): e51178. http://dx.doi.org/10.1371/journal.pone.0051178.

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24

Arimura, Nariko, und Kozo Kaibuchi. „Neuronal polarity: from extracellular signals to intracellular mechanisms“. Nature Reviews Neuroscience 8, Nr. 3 (März 2007): 194–205. http://dx.doi.org/10.1038/nrn2056.

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25

Cabrita, Inês, Roberta Benedetto, Ana Fonseca, Podchanart Wanitchakool, Lalida Sirianant, Boris V. Skryabin, Laura K. Schenk, Hermann Pavenstädt, Rainer Schreiber und Karl Kunzelmann. „Differential effects of anoctamins on intracellular calcium signals“. FASEB Journal 31, Nr. 5 (09.02.2017): 2123–34. http://dx.doi.org/10.1096/fj.201600797rr.

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26

Tsien, R. Y., A. Minta, M. Poenie, J. P. Y. Kao und A. Harootunian. „Fluorescence ratio imaging of dynamic intracellular ionic signals“. Proceedings, annual meeting, Electron Microscopy Society of America 46 (1988): 42–43. http://dx.doi.org/10.1017/s0424820100102298.

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Recent technical advances now enable the continuous imaging of important ionic signals inside individual living cells with micron spatial resolution and subsecond time resolution. This methodology relies on the molecular engineering of indicator dyes whose fluorescence is strong and highly sensitive to ions such as Ca2+, H+, or Na+, or Mg2+. The Ca2+ indicators, exemplified by fura-2 and indo-1, derive their high affinity (Kd near 200 nM) and selectivity for Ca2+ to a versatile tetracarboxylate binding site3 modeled on and isosteric with the well known chelator EGTA. The most commonly used pH indicators are fluorescein dyes (such as BCECF) modified to adjust their pKa's and improve their retention inside cells. Na+ indicators are crown ethers with cavity sizes chosen to select Na+ over K+: Mg2+ indicators use tricarboxylate binding sites truncated from those of the Ca2+ chelators, resulting in a more compact arrangement of carboxylates to suit the smaller ion.

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Kaibuchi, Kozo. „Neuronal polarity: From extracellular signals to intracellular mechanisms“. Neuroscience Research 65 (Januar 2009): S2. http://dx.doi.org/10.1016/j.neures.2009.09.013.

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Sheng, Rong, Sten Rüdiger und Jianwei Shuai. „Coherent calcium puff signals driven by intracellular noises“. Physica A: Statistical Mechanics and its Applications 390, Nr. 6 (März 2011): 1117–23. http://dx.doi.org/10.1016/j.physa.2010.11.036.

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CHUANG1, Lea-yea, und Jinn-Yuh GUH2. „Extracellular signals and intracellular pathways in diabetic nephropathy“. Nephrology 6, Nr. 4 (August 2001): 165–72. http://dx.doi.org/10.1046/j.1440-1797.2001.00043.x.

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Hackenthal, Eberhard, und Roland Taugner. „Hormonal signals and intracellular messengers for renin secretion“. Molecular and Cellular Endocrinology 47, Nr. 1-2 (September 1986): 1–12. http://dx.doi.org/10.1016/0303-7207(86)90010-9.

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31

Stennicke, Henning R., und Guy S. Salvesen. „Caspases – controlling intracellular signals by protease zymogen activation“. Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology 1477, Nr. 1-2 (März 2000): 299–306. http://dx.doi.org/10.1016/s0167-4838(99)00281-2.

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32

Imboden, John B. „The regulation of intracellular signals during lymphocyte activation“. Immunology Today 9, Nr. 1 (Januar 1988): 17–18. http://dx.doi.org/10.1016/0167-5699(88)91350-3.

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González-Pleiter, M., F. Leganés und F. Fernández-Piñas. „Intracellular free Ca2+signals antibiotic exposure in cyanobacteria“. RSC Advances 7, Nr. 56 (2017): 35385–93. http://dx.doi.org/10.1039/c7ra03001k.

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Hallett, Maurice B. „Localisation of Intracellular Signals and Responses during Phagocytosis“. International Journal of Molecular Sciences 24, Nr. 3 (01.02.2023): 2825. http://dx.doi.org/10.3390/ijms24032825.

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Phagocytosis is one of the most polarised of all cellular activities. Both the stimulus (the target for phagocytosis) and the response (its internalisation) are focussed at just one part of the cell. At the locus, and this locus alone, pseudopodia form a phagocytic cup around the particle, the cytoskeleton is rearranged, the plasma membrane is reorganised, and a new internal organelle, the phagosome, is formed. The effect of signals from the stimulus must, thus, both be complex and yet be restricted in space and time to enable an effective focussed response. While many aspects of phagocytosis are being uncovered, the mechanism for the restriction of signalling or the effects of signalling remains obscure. In this review, the details of the problem of restricting chemical intracellular signalling are presented, with a focus on diffusion into the cytosol and of signalling lipids along the plasma membrane. The possible ways in which simple diffusion is overcome so that the restriction of signalling and effective phagocytosis can be achieved are discussed in the light of recent advances in imaging, biophysics, and cell biochemistry which together are providing new insights into this area.

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Scott, John D., und Tony Pawson. „Cell Signaling in Space and Time: Where Proteins Come Together and When They’re Apart“. Science 326, Nr. 5957 (26.11.2009): 1220–24. http://dx.doi.org/10.1126/science.1175668.

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Signal transduction can be defined as the coordinated relay of messages derived from extracellular cues to intracellular effectors. More simply put, information received on the cell surface is processed across the plasma membrane and transmitted to intracellular targets. This requires that the activators, effectors, enzymes, and substrates that respond to cellular signals come together when they need to.

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Suzuka, Hisaaki, Atsushi Mimura, Yoshimi Inaoka und Kenya Murase. „Magnetic Nanoparticles in Macrophages and Cancer Cells Exhibit Different Signal Behavior on Magnetic Particle Imaging“. Journal of Nanoscience and Nanotechnology 19, Nr. 11 (01.11.2019): 6857–65. http://dx.doi.org/10.1166/jnn.2019.16619.

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Cell labeling with magnetic nanoparticles (MNPs) is a promising method of cell tracking. In particular, a novel quantitative tomography method called magnetic particle imaging (MPI) has the potential to estimate the number of successfully transplanted MNP-labeled cells, thereby helping predict clinical outcomes. However, the biological factors that shape the MPI signals of MNPs during cell labeling are not well understood. To better understand these factors, the MPI signals of MNPs in various extracellular and intracellular conditions were assessed. Firstly, carboxydextran-coated MNPs (Resovist®) in the presence or absence of the transfection agents heparin and/or protamine were subjected to dynamic light scattering analysis and magnetic particle spectroscopy. Secondly, RAW264 macrophages and Colon26 carcinoma cells were labeled with Resovist® by using their intrinsic phagocytic activity or with the assistance of the transfection agents, respectively, after which the cells were visualized by our MPI scanner and transmission electron microscopy, and their absolute amounts of intracellular iron were measured by thiocyanate colorimetry. The MPI pixel values were normalized to intracellular iron concentrations. Finally, the effect of cell lysis on the MPI signal was assessed with magnetic particle spectroscopy. The presence of protamine, but not heparin, increased the hydrodynamic diameter of the MNPs and inhibited their MPI signals. Cell uptake drastically decreased the normalized MPI pixel values. This was particularly marked in the colon cancer cells. The transfection agents did not further alter the MPI signal of the MNP-labeled colon cancer cells. Transmission electron microscopy showed that there was much more MNP aggregation in colon cancer cells than in macrophages. After the MNP-labeled cells were lysed, the MPI signal recovered partially. In conclusion, MPI pixel values can be influenced by the cell-labeling process and cellular uptake. The MPI signals from intracellular magnetic nanoparticles may also differ depending on the cell type.

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Delgado, Pilar, und Balbino Alarcón. „An orderly inactivation of intracellular retention signals controls surface expression of the T cell antigen receptor“. Journal of Experimental Medicine 201, Nr. 4 (21.02.2005): 555–66. http://dx.doi.org/10.1084/jem.20041133.

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Exit from the endoplasmic reticulum (ER) is an important checkpoint for proper assembly of multimeric plasma membrane receptors. The six subunits of the T cell receptor (TCR; TCRα, TCRβ, CD3γ, CD3δ, CD3ε, and CD3ζ) are each endowed with ER retention/retrieval signals, and regulation of its targeting to the plasma membrane is therefore especially intriguing. We have studied the importance of the distinct ER retention signals at different stages of TCR intracellular assembly. To this end, we have characterized first the presence of ER retention signals in CD3γ. Despite the presence of multiple ER retention signals in CD3γ, εγ dimers reach the cell surface when the single CD3ε ER retention signal is deleted. Furthermore, inclusion of this CD3ε mutant promoted plasma membrane expression of incomplete αβγε and αβδε complexes without CD3ζ. It therefore appears that the CD3ε ER retention signal is dominant and that it is only overridden upon the incorporation of CD3ζ. We propose that the stepwise assembly of the TCR complex guarantees that all assembly intermediates have at least one functional ER retention signal and that only a full signaling-competent TCR complex is expressed on the cell surface.

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Michie, Alison M., und Juan Carlos Zúñiga-Pflücker. „InVivoDetection of Intracellular Signaling Pathways in Developing Thymocytes“. Developmental Immunology 8, Nr. 1 (2000): 31–45. http://dx.doi.org/10.1155/2000/97820.

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Information regarding the intracellular signaling processes that occur during the development of T cells has largely been obtained with the use of transgenic mouse models, which although providing invaluable information are time consuming and costly. To this end, we have developed a novel system that facilitates theInVivoanalysis of signal transduction pathways during T-lymphocyte development. This approach uses reporter-plasmids for the detection of intracellular signals mediated by the mitogen-activated protein kinase or cyclic AMP-dependent protein kinase. Reporter-plasmids are transfected into thymocytes in fetal thymic organ culture by accelerated DNA/particle bombardment (gene gun), and the activation of a signaling pathway is determined in the form of a standard luciferase assay. Importantly, this powerful technique preserves the structural integrity of the thymus, and will provide an invaluable tool to study how thymocytes respond to normal environmental stimuli encountered during differentiation within the thymic milieu. Thus, this method allows for the monitoring of signals that occur in a biological time frame, such as during differentiation, and within the natural environment of differentiating cells.

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Bretschneider, Till, Hans G. Othmer und Cornelis J. Weijer. „Progress and perspectives in signal transduction, actin dynamics, and movement at the cell and tissue level: lessons from Dictyostelium“. Interface Focus 6, Nr. 5 (06.10.2016): 20160047. http://dx.doi.org/10.1098/rsfs.2016.0047.

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Movement of cells and tissues is a basic biological process that is used in development, wound repair, the immune response to bacterial invasion, tumour formation and metastasis, and the search for food and mates. While some cell movement is random, directed movement stimulated by extracellular signals is our focus here. This involves a sequence of steps in which cells first detect extracellular chemical and/or mechanical signals via membrane receptors that activate signal transduction cascades and produce intracellular signals. These intracellular signals control the motile machinery of the cell and thereby determine the spatial localization of the sites of force generation needed to produce directed motion. Understanding how force generation within cells and mechanical interactions with their surroundings, including other cells, are controlled in space and time to produce cell-level movement is a major challenge, and involves many issues that are amenable to mathematical modelling.

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Leong, D. A. „A complex mechanism of facilitation in pituitary ACTH cells: recent single-cell studies“. Journal of Experimental Biology 139, Nr. 1 (01.09.1988): 151–68. http://dx.doi.org/10.1242/jeb.139.1.151.

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The transfer of information by chemical signals during complex biological processes can, with increasing frequency, be described in terms of interacting signal pairs. External signalling is rarely monolithic; rather, signal pairs are utilized in processes such as hormone secretion, neurotransmission, cell growth and differentiation. The dualism of external signalling often results in the occurrence of synergy. One signal appears to turn the cell on or off, and its synergistic partner increases cell responsiveness, providing gain control of the cellular response. ACTH release provoked by certain stressors arises from a synergistic interaction between two hypothalamic hormones: corticotropin releasing hormone (CRH) and a modulator such as vasopressin (AVP). The pituitary ACTH cell has been used to unravel the intracellular messenger equivalents of an external signal interaction that generates synergy. Research emphasizes the single cell approach. Direct measurements of intracellular free Ca2+ were performed using the Ca2+-sensitive fluorescent probe fura-2/AM and instrumentation for digital image processing. A reverse haemolytic plaque assay was used to measure cumulative ACTH release from single pituitary cells in culture. What is the physiological role of intracellular Ca2+ as a messenger? What are the feedforward and feedback relationships between major second messengers [cyclic AMP, diacylglycerol (DAG), inositol 1,4,5-trisphosphate (Ins(1,4,5)P3)] and intracellular Ca2+? That is, how are individual messenger circuits “wired' within ACTH cells. Intracellular Ca2+ may act as a common signal into which interacting second messenger signals [cyclic AMP, Ins(1,4,5)P3, DAG] are transduced and integrated to govern ACTH release. A novel circuit of messenger pathways linked by Ca2+ is proposed as the intracellular basis for the synergistic interaction of CRH- and AVP-regulated ACTH release.

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Shivnan, E., und D. R. Alexander. „Protein kinase C activation inhibits TCR-mediated calcium influx but not inositol trisphosphate production in HPB-ALL T cells.“ Journal of Immunology 154, Nr. 3 (01.02.1995): 1146–56. http://dx.doi.org/10.4049/jimmunol.154.3.1146.

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Abstract The regulation by protein kinase C (PKC) of TCR-mediated changes in phosphoinositide metabolism and intracellular calcium ([Ca2+]i) was investigated in HPB-ALL T cells. Low concentrations (< 1 microgram/ml) of the anti-CD3 OKT3 mAb triggered large calcium signals but not detectable increase in D-myo-inositol 1,4,5-trisophate (IP3) production. CD3-CD4 coligation amplified the calcium signal twofold, compared with CD3 cross-linking alone, but this protocol also did not stimulate IP3 production. At higher OKT3 concentrations (> 2.5 micrograms/ml), IP3 production was detected but was not inhibited by activating PKC with phorbol ester. In contrast, PKC activation caused a marked inhibition (53 to 64%) of the CD3- or CD3-CD4-triggered calcium signals, but had only a small inhibitory effect (20 to 30%) on the release of intracellular Ca2+. PKC activation also inhibited by 47% calcium signals triggered by thapsigargin, an inhibition that was completely reversed by addition of the specific PKC inhibitor RO 31-8220 (1 microM). Addition of 1 microM RO 31-8220 caused a twofold stimulation of CD3-induced calcium signals. This effect was not mediated at the level of Ca2+ influx, because RO 31-8220 did not significantly increase thapsigargin-triggered calcium signals. However, RO 31-8220 did slightly increase the CD3-induced release of intracellular Ca2+, suggesting that amplification of Ca2+ influx may be secondary to increased release of Ca2+ from intracellular stores. Our results indicate that PKC regulates TCR-mediated changes in [Ca2+]i in HPB-ALL T cells by two distinct mechanisms. First, PKC activation causes a marked inhibition of Ca2+ influx by a mechanism independent of changes in IP3 production, possibly involving inhibition of ion channels. Second, PKC activity causes a small inhibition of intracellular Ca2+ release, most likely by promoting Ca2+ sequestration.

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Senseman, David M. „Correspondence between visually evoked voltage-sensitive dye signals and synaptic activity recorded in cortical pyramidal cells with intracellular microelectrodes“. Visual Neuroscience 13, Nr. 5 (September 1996): 963–77. http://dx.doi.org/10.1017/s0952523800009196.

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AbstractFast, multiple-site optical recording of voltage-sensitive dye (VSD) signals and intracellular microelectrode recordings were combined to characterize visually evoked neuronal responses in the visual cortex of the pond turtle, Pseudemys scripta. By using an in vitro, eye-brain preparation stained with the merocyanine oxazolone voltage-sensitive dye, NK-2495 or a close analog, NK-2761, large VSD signals relatively free of vibrational noise could be recorded in single trials following a stroboscopic light flash to the contralateral eye. VSD signals recorded from the same cortical location in repeated trials exhibited considerable variability in the onset, duration, and amplitude of secondary depolarizations. Because of this variability, secondary depolarizations were largely absent in signal-averaged responses. Superposition of VSD signals with intracellular recordings obtained from cortical pyramidal cells revealed a close correspondence between their signal waveforms. The two signals were virtually identical in their onset, initial rate of rise, and time-to-peak. At later periods (>500 ms), the correspondence was less close, especially for large cortical depolarizations. Some of this disparity could be attributed to contamination of the VSD signal by a large intrinsic optical response. A second contribution was a failure of the VSD signal to register asynchronous regenerative effects occurring in single pyramidal cells. It is suggested that the close correspondence between the microelectrode and optical recordings in the early phase of the response may reflect the organization of pyramidal cells into clusters that receive virtually identical synaptic inputs.

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Odorizzi, C. G., I. S. Trowbridge, L. Xue, C. R. Hopkins, C. D. Davis und J. F. Collawn. „Sorting signals in the MHC class II invariant chain cytoplasmic tail and transmembrane region determine trafficking to an endocytic processing compartment.“ Journal of Cell Biology 126, Nr. 2 (15.07.1994): 317–30. http://dx.doi.org/10.1083/jcb.126.2.317.

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Targeting of MHC class II molecules to the endocytic compartment where they encounter processed antigen is determined by the invariant chain (Ii). By analysis of Ii-transferrin receptor (TR) chimera trafficking, we have identified sorting signals in the Ii cytoplasmic tail and transmembrane region that mediate this process. Two non-tyrosine-based sorting signals in the Ii cytoplasmic tail were identified that mediate localization to plasma membrane clathrin-coated pits and promote rapid endocytosis. Leu7 and Ile8 were required for the activity of the signal most distal to the cell membrane whereas Pro15 Met16 Leu17 were important for the membrane-proximal signal. The same or overlapping non-tyrosine-based sorting signals are essential for delivery of Ii-TR chimeras, either by an intracellular route or via the plasma membrane, to an endocytic compartment where they are rapidly degraded. The Ii transmembrane region is also required for efficient delivery to this endocytic processing compartment and contains a signal distinct from the Ii cytoplasmic tail. More than 80% of the Ii-TR chimera containing the Ii cytoplasmic tail and transmembrane region is delivered directly to the endocytic pathway by an intracellular route, implying that the Ii sorting signals are efficiently recognized by sorting machinery located in the trans-Golgi.

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Ziskind-Conhaim, Lea, und Stephen Redman. „Spatiotemporal Patterns of Dorsal Root–Evoked Network Activity in the Neonatal Rat Spinal Cord: Optical and Intracellular Recordings“. Journal of Neurophysiology 94, Nr. 3 (September 2005): 1952–61. http://dx.doi.org/10.1152/jn.00209.2005.

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Spatiotemporal patterns of dorsal root–evoked potentials were studied in transverse slices of the rat spinal cord by monitoring optical signals from a voltage-sensitive dye with multiple-photodiode optic camera. Typically, dorsal root stimulation generated two basic waveforms of voltage images: dual-component images consisting of fast, spike-like signal followed by a slow signal in the dorsal horn, and small, slow signals in the ventral horn. To qualitatively relate the optical signals to membrane potentials, whole cell recordings were combined with measurements of light absorption in the area around the soma. The slow optical signals correlated closely with subthreshold postsynaptic potentials in all regions of the cord. The spike-like component was not associated with postsynaptic action potentials, suggesting that the fast signal was generated by presynaptic action potentials. Firing in a single neuron could not be detected optically, implying that local voltage images originated from synchronously activated neuronal ensembles. Blocking glutamatergic synaptic transmission inhibited excitatory postsynaptic potentials (EPSPs) and significantly reduced the slow optical signals, indicating that they were mediated by glutamatergic synapses. Suppressing glycine-mediated inhibition increased the amplitude of both optical signals and EPSPs, while blocking GABAA receptor–mediated synapses, increased the amplitude and time course of EPSPs and prolonged the duration of voltage images in larger areas of the slice. The close correlation between evoked EPSPs and their respective local voltage images shows the advantage of the high temporal resolution optical system in measuring both the spatiotemporal dynamics of segmental network excitation and integrated potentials of neuronal ensembles at identified sites.

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Rahmi, Rahmi. „Molecular Review: Effects of Physical Exercise in Skeletal Muscle Glucose Uptake“. Sumatera Medical Journal 4, Nr. 1 (20.01.2021): 1–9. http://dx.doi.org/10.32734/sumej.v4i1.4785.

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Muscle contraction requires glucose as its main fuel. Glucose enters the muscle cells through diffusion facilitated by GLUT4. GLUT4 must be translocated from intracellular to the plasma membrane and T tubules during muscle contraction. This literature review will discuss how physical exercise can signal GLUT4 translocation for glucose uptake. Molecular signals induced by physical exercise are very complex and involve various molecules, one of which is AMPK and intracellular Ca concentration.

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Zhou, Feng-Quan, und William D. Snider. „Intracellular control of developmental and regenerative axon growth“. Philosophical Transactions of the Royal Society B: Biological Sciences 361, Nr. 1473 (28.07.2006): 1575–92. http://dx.doi.org/10.1098/rstb.2006.1882.

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Axon growth is a highly regulated process that requires stimulating signals from extracellular factors. The extracellular signals are then transduced to regulate coordinately gene expression and local axon assembly. Growth factors, especially neurotrophins that act via receptor tyrosine kinases, have been heavily studied as extracellular factors that stimulate axon growth. Downstream of receptor tyrosine kinases, recent studies have suggested that phosphatidylinositol-3 kinase (PI3K) regulates local assembly of axonal cytoskeleton, especially microtubules, via glycogen synthase kinase 3β (GSK-3β) and multiple microtubule binding proteins. The role of extracellular signal regulated kinase (ERK) signalling in regulation of local axon assembly is less clear, but may involve the regulation of local protein translation. Gene expression during axon growth is regulated by transcription factors, among which cyclic AMP response element binding protein and nuclear factors of activated T-cells (NFATs) are known to be required for neurotrophin (NT)-induced axon extension. In addition to growth factors, extracellular matrix molecules and neuronal activity contribute importantly to control axon growth. Increasingly, evidence suggests that these influences act to enhance growth via coordinating with growth factor signalling. Finally, evidence is emerging that developmental versus regenerative axon growth may be mediated by distinct signalling pathways, both at the level of gene transcription and at the level of local axon assembly.

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Hogan, Perry M., und Stephen R. Besch. „A Dual Wavelength Microfluorimeter for Measuring Fast Intracellular Calcium Signals“. Microscopy and Microanalysis 1, Nr. 2 (Juni 1995): 55–63. http://dx.doi.org/10.1017/s1431927695110557.

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A dual excitation microfluorimeter is described for measuring rapidly changing, intracellular calcium signals. A spinning sector wheel is used in conjunction with a beam masking device to provide rapid, efficient switching between the 2 excitation wavelengths. Exposure intervals as short as 120 μs can be achieved, yielding ratio samples at a rate of 6 kHz. Emission photons are collected using a photomultiplier tube operating in counting mode. When tested using FURA-2 as the calcium reporting dye, throughput noise in the system is demonstrated to be due to the statistical fluctuation inherent in photon counting. An example of the operation of the system, using a guinea pig cardiac myocyte, demonstrates that sufficient ratio data may be acquires to fully characterize the fastest components of the intracellular calcium signal.

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LaBonne, C., und M. Whitman. „Mesoderm induction by activin requires FGF-mediated intracellular signals“. Development 120, Nr. 2 (01.02.1994): 463–72. http://dx.doi.org/10.1242/dev.120.2.463.

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We have examined the role of FGF signaling during activin-mediated mesoderm induction in Xenopus. Using dominant inhibitory mutants of FGF signal transducers to disrupt the FGF-signaling pathway at the plasma membrane or in the cytosol prevents animal cap blastomeres from expressing several mesodermal markers in response to exogenous activin. Dominant inhibitory mutants of the FGF receptor, c-ras or c-raf inhibit the ability of activin to induce molecular markers of both dorsal and ventral mesoderm including Xbra, Mix1 and Xnot. Some transcriptional responses to activin such as goosecoid and Xwnt8 are inhibited less effectively than others, however, suggesting that there may differing requirements for an FGF signal in the responses of mesoderm-specific genes to activin induction. Despite the requirement for this signaling pathway during activin induction, downstream components of this pathway are not activated in response to activin, suggesting that activin does not signal directly through this pathway.

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Martin-Cano, Francisco E., Cristina Camello-Almaraz, Jesús González Macías, Maria J. Pozo und Pedro J. Camello. „Propagation of Intracellular Ca2+Signals in Aged Exocrine Cells“. Journals of Gerontology Series A: Biological Sciences and Medical Sciences 71, Nr. 2 (24.03.2015): 145–52. http://dx.doi.org/10.1093/gerona/glv018.

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Schramek, Herbert. „MAP Kinases: From Intracellular Signals to Physiology and Disease“. Physiology 17, Nr. 2 (April 2002): 62–67. http://dx.doi.org/10.1152/nips.01365.2001.

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Although differentiated cells will usually maintain their specialized character, conversion of cellular specificities can be observed during adaptation or reparative regeneration. In pathological conditions, such as inflammation and carcinogenesis, even highly specialized cells can alter their properties, leading to a deranged control of cell differentiation and/or proliferation. Mitogen-activated protein kinases are central regulators of these processes.

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