147 research outputs found

    c-Abl phosphorylation of ΔNp63α is critical for cell viability

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    The p53 family member p63 has been shown to be critical for growth, proliferation and chemosensitivity. Here we demonstrate that the c-Abl tyrosine kinase phosphorylates the widely expressed ΔNp63α isoform and identify multiple sites by mass spectrometry in vitro and in vivo. Phopshorylation by c-Abl results in greater protein stability of both ectopically expressed and endogenous ΔNp63α. c-Abl phosphorylation of ΔNp63α induces its binding to Yes-associated protein (YAP) and silencing of YAP by siRNA reduces the c-Abl-induced increase of ΔNp63α levels. We further show that cisplatin induces c-Abl phosphorylation of ΔNp63α and its binding to YAP. Overexpression of ΔNp63α, but not the c-Abl phosphosites mutant, protects cells from cisplatin treatment. Finally, we demonstrate the rescue of p63 siRNA-mediated loss of viability with p63siRNA insensitive construct of ΔNp63α but not the phosphosites mutant. These results demonstrate that c-Abl phosphorylation of ΔNp63α regulates its protein stability, by inducing binding of YAP, and is critical for cell viability

    Choice of allocations and constructs for attributional or consequential life cycle assessment and input-output analysis

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    The divide between attributional and consequential research perspectives partly overlaps with the long-standing methodological discussions in the life cycle assessment (LCA) and input-output analysis (IO) research communities on the choice of techniques and models for dealing with situations of coproduction. The recent harmonization of LCA allocations and IO constructs revealed a more diverse set of coproduction models than had previously been understood. This increased flexibility and transparency in inventory modeling warrants a re-evaluation of the treatment of coproduction in analyses with attributional and consequential perspectives. In the present article, the main types of coproductions situations and of coproduction models are reviewed, along with key desirable characteristics of attributional and consequential studies. A concordance analysis leads to clear recommendations, which call for important refinements to current guidelines for both LCA/IO practitioners and database developers. We notably challenge the simple association between, on the one hand, attributional LCA and partition allocation, and on the one hand, consequential LCA and substitution modeling

    Study of multi-muon events produced in p\bar{p} interactions at \sqrt{s}=1.96 TeV

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    68 pages, 46 figures, 11 tables. Submitted to Phys. Rev. D. Removed typos from the authors' listWe report the results of a study of multi-muon events produced at the Fermilab Tevatron collider and acquired with the CDF II detector using a dedicated dimuon trigger. The production cross section and kinematics of events in which both muon candidates are produced inside the beam pipe of radius 1.5 cm are successfully modeled by known processes which include heavy flavor production. In contrast, we are presently unable to fully account for the number and properties of the remaining events, in which at least one muon candidate is produced outside of the beam pipe, in terms of the same understanding of the CDF II detector, trigger, and event reconstruction.Peer reviewe

    Comments and Reply on: “Study of multi-muon events produced in pˉp interactions at √s=1.96 TeV”

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    The European Physical Journal C—Particles and Fields—publishes scientific manuscripts of relevance to the scientific community following careful and strict peer reviewing and, whenever appropriate and necessary, through discussion with the authors, so as to optimise scientific content and style of presentation prior to publication. In some cases significant disagreement between authors and referees (and/or editors) of the journal cannot be resolved despite all efforts and best of intentions. While the journal—notwithstanding any appeals—retains the right to reject such manuscripts, the editors of this journal may decide, in cases deemed of exceptional interest and potential significance for the field, to accept the manuscript for publication, to amend it by “comments” of the editor(s) in charge and, if appropriate, by a “reply” of the authors of the commented manuscript. The present comment is on “Study of multi-muon events produced in ppˉp\bar{p} interactions at s=1.96\sqrt{s}=1.96 TeV” by T. Aaltonen et al. (the CDF Collaboration, Eur. Phys. J. C, 2010,Peer reviewe

    Dynamic Pricing and Learning: Historical Origins, Current Research, and New Directions

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    Search for gravitational waves associated with gamma-ray bursts detected by Fermi and Swift during the LIGO–Virgo run O3b

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    We search for gravitational-wave signals associated with gamma-ray bursts (GRBs) detected by the Fermi and Swift satellites during the second half of the third observing run of Advanced LIGO and Advanced Virgo (2019 November 1 15:00 UTC–2020 March 27 17:00 UTC). We conduct two independent searches: a generic gravitational-wave transients search to analyze 86 GRBs and an analysis to target binary mergers with at least one neutron star as short GRB progenitors for 17 events. We find no significant evidence for gravitational-wave signals associated with any of these GRBs. A weighted binomial test of the combined results finds no evidence for subthreshold gravitational-wave signals associated with this GRB ensemble either. We use several source types and signal morphologies during the searches, resulting in lower bounds on the estimated distance to each GRB. Finally, we constrain the population of low-luminosity short GRBs using results from the first to the third observing runs of Advanced LIGO and Advanced Virgo. The resulting population is in accordance with the local binary neutron star merger rate

    SIGNAL FLOWS FROM 2 PHOSPHOLIPASE-C LINKED RECEPTORS ARE INDEPENDENT IN PC12 CELLS

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    Bradykinin (BK) receptor and P-2-purinergic receptor are known to be coupled to phospholipase C (FLC) in PC12 cells. To study the interaction between these two PLC-linked receptors, the presence of both receptors on individual cells was demonstrated by sequential Ca2+ spikes caused by BK and ATP in a single fura-2-loaded cell. BK- and ATP-induced catecholamine (CA) secretions were desensitized within 5 min. However, in the sequential experiment, the BK-induced homologous desensitization of CA secretion did not block the ATP-induced secretion, and vice versa. Each agonist-induced an increase in inositol 1,4,5-trisphosphate (IP3) production and intracellular free Ca2+ concentration also led to homologous desensitization. However, there was no heterologous desensitization between the two agonists. When the cells were treated with both BK and ATP simultaneously, the amounts of CA secretion, IF, production, internal Ca2+ mobilization, and Ca2+ influx were all additive. We also found that both IP3-induced Ca2+ release from intracellular Ca2+ stores and Ca2+ influx from extracellular space were able to release [H-3]norepinephrine, and the secretion induced by both agonists was exactly additive in the absence or presence of extracellular Ca2+. The data suggest that the CA secretions caused by BK or ATP may have separate secretory pathways even though they activate identical second messenger pathways.X1137sciescopu

    Abscisic acid-induced phosphoinositide turnover in guard cell protoplasts of Vicia faba

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    Guard cell protoplasts of Vicia faba treated with 10 mu M (+)abscisic acid (ABA) in the light exhibited a 20% decrease in diameter within 1.5 h, from 24.1 to 19.6 mu m. Within 10 s of administration of ABA, a 90% increase in levels of inositol 1,4,5-trisphosphate was observed, provided that cells were treated with Li+, an inhibitor of inositol phosphatase activity, prior to incubation. Concomitantly, levels of P-32-labeled phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4-phosphate decreased 20% compared to levels in control cells; levels of label in the membrane lipids phosphatidylcholine, phosphatidylethanolamine, and phosphatidylglycerol did not change significantly in response to ABA treatment. These results show that phosphoinositide turnover is activated in response to ABA in guard cells. We conclude that phosphoinositide signaling is likely to be a step in the biochemical cascade that couples ABA to guard cell shrinking and stomatal closure.X11132sciescopu
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