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  • 1
    Publication Date: 2013-02-05
    Description: Cancer control by adaptive immunity involves a number of defined death and clearance mechanisms. However, efficient inhibition of exponential cancer growth by T cells and interferon-gamma (IFN-gamma) requires additional undefined mechanisms that arrest cancer cell proliferation. Here we show that the combined action of the T-helper-1-cell cytokines IFN-gamma and tumour necrosis factor (TNF) directly induces permanent growth arrest in cancers. To safely separate senescence induced by tumour immunity from oncogene-induced senescence, we used a mouse model in which the Simian virus 40 large T antigen (Tag) expressed under the control of the rat insulin promoter creates tumours by attenuating p53- and Rb-mediated cell cycle control. When combined, IFN-gamma and TNF drive Tag-expressing cancers into senescence by inducing permanent growth arrest in G1/G0, activation of p16INK4a (also known as CDKN2A), and downstream Rb hypophosphorylation at serine 795. This cytokine-induced senescence strictly requires STAT1 and TNFR1 (also known as TNFRSF1A) signalling in addition to p16INK4a. In vivo, Tag-specific T-helper 1 cells permanently arrest Tag-expressing cancers by inducing IFN-gamma- and TNFR1-dependent senescence. Conversely, Tnfr1(-/-)Tag-expressing cancers resist cytokine-induced senescence and grow aggressively, even in TNFR1-expressing hosts. Finally, as IFN-gamma and TNF induce senescence in numerous murine and human cancers, this may be a general mechanism for arresting cancer progression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Braumuller, Heidi -- Wieder, Thomas -- Brenner, Ellen -- Assmann, Sonja -- Hahn, Matthias -- Alkhaled, Mohammed -- Schilbach, Karin -- Essmann, Frank -- Kneilling, Manfred -- Griessinger, Christoph -- Ranta, Felicia -- Ullrich, Susanne -- Mocikat, Ralph -- Braungart, Kilian -- Mehra, Tarun -- Fehrenbacher, Birgit -- Berdel, Julia -- Niessner, Heike -- Meier, Friedegund -- van den Broek, Maries -- Haring, Hans-Ulrich -- Handgretinger, Rupert -- Quintanilla-Martinez, Leticia -- Fend, Falko -- Pesic, Marina -- Bauer, Jurgen -- Zender, Lars -- Schaller, Martin -- Schulze-Osthoff, Klaus -- Rocken, Martin -- England -- Nature. 2013 Feb 21;494(7437):361-5. doi: 10.1038/nature11824. Epub 2013 Feb 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Dermatology, Eberhard Karls University, Liebermeister Strasse 25, 72076 Tubingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23376950" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Polyomavirus Transforming/genetics/metabolism ; Cell Aging/*immunology ; Cell Cycle ; Cell Proliferation ; Cyclin-Dependent Kinase Inhibitor p16/deficiency/genetics/metabolism ; Cytokines/*immunology ; Disease Models, Animal ; Disease Progression ; Female ; Humans ; Interferon-gamma/immunology ; Male ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Mice, Transgenic ; Neoplasms/*immunology/*pathology ; Oncogenes/genetics ; Phosphoserine/metabolism ; Receptors, Tumor Necrosis Factor, Type I/metabolism ; Retinoblastoma Protein/chemistry/metabolism ; STAT1 Transcription Factor/metabolism ; Th1 Cells/*immunology ; Time Factors ; Tumor Cells, Cultured ; Tumor Necrosis Factor-alpha/immunology ; Tumor Suppressor Protein p53/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Electronic Resource
    Electronic Resource
    s.l. ; Stafa-Zurich, Switzerland
    Key engineering materials Vol. 132-136 (Apr. 1997), p. 1002-1005 
    ISSN: 1013-9826
    Source: Scientific.Net: Materials Science & Technology / Trans Tech Publications Archiv 1984-2008
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    s.l. ; Stafa-Zurich, Switzerland
    Materials science forum Vol. 239-241 (Nov. 1996), p. 349-352 
    ISSN: 1662-9752
    Source: Scientific.Net: Materials Science & Technology / Trans Tech Publications Archiv 1984-2008
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 84 (1998), S. 4537-4542 
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: It was previously shown that RbBr doped with Ga+ is an efficient x-ray storage phosphor with a figure of merit comparable to that of the commercially used BaFBr:Eu2+. The paramagnetic hole centers generated upon x-irradiation involved in the storage and read-out process were investigated by measuring the magnetic circular dichroism of the optical absorption (MCDA), the MCDA-detected electron paramagnetic resonance (MCDA-EPR) and the photostimulated luminescence (PSL). Two different Ga2+ hole centers with a hyperfine interaction with 69Ga of 69A=8.2 GHz and 69A=6.0 GHz, respectively, were found. No superhyperfine interaction was resolved. Therefore, the structural difference between the two Ga2+ centers could not be established from EPR. The PSL effect is correlated only to one of the two Ga2+ centers, namely that with A=8.2 GHz. The generation mechanism of the two hole centers is investigated. It is proposed that the PSL-active Ga2+ center is an isolated Ga2+ on a Rb+ site, whereas the other center is a Ga2+-cation vacancy complex. © 1998 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Cell and Developmental Biology 9 (1993), S. 345-375 
    ISSN: 0743-4634
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Plant, cell & environment 22 (1999), S. 0 
    ISSN: 1365-3040
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: Numerous studies conducted on both whole plants and isolated epidermes have documented stomatal sensitivity to CO2. In general, CO2 concentrations below ambient stimulate stomatal opening, or an inhibition of stomatal closure, while CO2 concentrations above ambient have the opposite effect. The rise in atmospheric CO2 concentrations which has occurred since the industrial revolution, and which is predicted to continue, will therefore alter rates of transpirational water loss and CO2 uptake in terrestrial plants. An understanding of the cellular basis for guard cell CO2 sensing could allow us to better predict, and perhaps ultimately to manipulate, such vegetation responses to climate change. However, the mechanisms by which guard cells sense and respond to the CO2 signal remain unknown. It has been hypothesized that cytosolic pH and malate levels, cytosolic Ca2+ levels, chloroplastic zeaxanthin levels, or plasma-membrane anion channel regulation by apoplastic malate are involved in guard cell perception and response to CO2. In this review, these hypotheses are discussed, and the evidence for guard cell acclimation to prevailing CO2 concentrations is also considered.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Plant, cell & environment 13 (1990), S. 0 
    ISSN: 1365-3040
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: Abstract. The effect of atmospheric humidity on the kinetics of stomatal responses was quantified in gas exchange experiments using sugarcane (Saccharum spp. hybrid) and soybean (Glycine max). Pulses of blue light were used to elicit pulses of stomatal conductance that were mediated by the specific blue light response of guard cells. Kinetic parameters of the conductance response were more closely related to leaf-air vapour pressure difference (VPD) than to relative humidity or transpiration. Increasing VPD significantly accelerated stomatal opening in both sugarcane and soybean, despite an approximately five-fold faster response in sugarcane. In contrast, the kinetics of stomatal recovery (closure) following the pulse were similar in the two species. Acceleration of opening by high VPD was observed even under conditions where soybean exhibited a feedforward response of decreasing transpiration (E) with increasing evaporative demand (VPD). This result suggests that epidermal, rather than bulk leaf, water status mediates the VPD effect on stomatal kinetics. The data are consistent with the hypothesis that increased cpidermal water loss at high VPD decreases the backpressure exerted by neighbouring cells on guard cells. allowing more rapid stomatal opening per unit of guard cell metabolic response to blue light.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Plant, cell & environment 14 (1991), S. 0 
    ISSN: 1365-3040
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: Abstract. An Ohm's law analogy is frequently employed to calculate parameters of leaf gas exchange. For example, resistance to water vapour loss is calculated as the quotient of vapour pressure difference (VPD) and vapour loss by transpiration. In the present research, this electrical analogy was extended. Steady-state transpiration as a function of VPD, assayed in leaflets of Vicia faba using gas exchange techniques, was compared with steady-state K+ current magnitude as a function of voltage in isolated guard cell protoplasts of Vicia faba, assayed using the patch clamping technique in the whole cell configuration. An electrophysiological model originally developed to explain the kinetics of current changes following step changes in voltage across a cell membrane was used to fit the kinetics of transpiration changes following step changes in VPD applied to leaflets of Vicia faba. Following step increases in VPD, transpiration exhibited an initial increase, reflecting the increased driving force for water loss and, for large step increases in VPD, a transient decrease in stomatal resistance. Transpiration subsequently declined, reflecting stomatal closure. By analogy to electrophysiological responses, it is hypothesized that the humidity parameter that is sensed by guard cells is VPD. Two models based on epidermal water relations were also applied to transpiration kinetics. In the first model, the transient increase in transpiration following a step increase in VPD was attributed partially to an increase in the Physical driving force (VPD) and partially to a transient decrease in stomatal resistance resulting from reduced epidermal backpressure. In the second model, the transient decrease in stomatal resistance was attributed to a direct response of the guard cells to VPD. Both models based on water relations gave good fits of the data, emphasizing the need for further study regarding the metabolic nature of the guard cell response to humidity.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Plant, cell & environment 14 (1991), S. 0 
    ISSN: 1365-3040
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: Abstract. The significance of blue light-stimulated stomatal conductance for carbon assimilation (A), stomatal conductance (g), intercellular CO2 (Ci), stomatal limitation of A (L), transpiration (E) and water use efficiency (W = A/E), was determined in a C4 and a C3 species. W and L were evaluated for steady-state gas exchange with constant, saturating red light (As, gs, Es), and for the integrated gas exchange above the steady state baseline induced by a single, brief pulse of blue light (Ap, gp, Ep). Sugarcane (Saccharum spp. hybrid), a C4 grass, and soybean (Glycine max) a C3 dicot, were compared. Sugarcane exhibited typical C4 behaviour, with A saturing at Ci of ca. 200 μmol mol−1, compared to 〉500 μmol mol−1 in soybean. Steady-state W was also considerably higher in sugarcane. The extent of stomatal opening in response to a blue light pulse, from baseline (gs) to the maximum value of conductance during the opening response (gm), was similar in the two species. More rapid opening and closing of stomata in sugarcane resulted in a smaller integrated magnitude of the conductance response (gp) than in soybean. At the peak of the blue light response, both species exhibited similar levels of L. During the response to the pulse of blue light, A and Ci increased and L decreased to a greater extent in sugarcane than in soybean. As a result, the gas exchange attributed to the stomatal response to blue light exhibited a higher ratio of Ap to Ep (Wp) in sugarcane than in soybean. This Wp was lower in both species than was the Ws associated with the steady state gas exchange. The two species did not differ in the rate of induction of photosynthetic utilization of elevated Ci. The greater stimulation of A in sugarcane was attributed to its C4 attributes of greater carboxylation efficiency (slope of the A versus Ci relationship), lower gs and prevailing Ci,s, and greater Ls under steady-state red illumination. Despite saturation of A at low levels of Ci in C4 species, the gas exchange attributed to the stomatal response to blue light decreased L and contributed considerably to carbon acquisition, while maintaining the high level of W associated with C4 metabolism.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Plant, cell & environment 11 (1988), S. 0 
    ISSN: 1365-3040
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: Abstract Environmental stresses can decrease photosynthesis by a direct effect on photosynthetic capacity of the mesophyll or by a CO2 limitation resulting from stomatal closure. In the present study, a ‘path-dependent method’ (Jones, 1985) for the partitioning of a stress-related decline in assimilation rate between non-stomatal and stomatal factors was evaluated, using light quality as a ‘stress’. Kinetic data on assimilation rate and conductance of Phragmipedium longifolium following a change in light quality from 95 μmol m−2s−1 white light to 95 μmol m−2s−1 red light failed to generate a smooth response curve for conductance. Partitioning of limitations on assimilation by a path-dependent method that utilizes the actual trajectories of conductance and assimilation was therefore not feasible. A simplified path-dependent method (Jones, 1985) which assumes that either mesophyll cells or guard cells respond first to a stress was applied to steady-state measurements of assimilation and conductance under red and white illumination. Either 5% or 23% of the observed reduction in assimilation rate under white light was attributable to stomatal factors, depending on whether the ‘stomatal first’ or the ‘mesophyll first’ path was assumed. In the absence of additional information indicating the appropriate choice of path, arbitrary choice may therefore lead to widely divergent estimates, and potentially erroneous conclusions. An alternative approach to the evaluation of the importance to carbon assimilation of stomatal and non-stomatal factors is suggested.
    Type of Medium: Electronic Resource
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