827 research outputs found
The Inorganic Side of NGF: Copper(II) And Zinc(II) Affect the NGF Mimicking Signalling of the N-Terminus Peptides Encompassing the Recognition Domain of TrkA Receptor
The nerve growth factor (NGF) N-terminus peptide, NGF(1-14), and its acetylated form, Ac-NGF(1-14), were investigated to scrutinise the ability of this neurotrophin domain to mimic the whole protein.
Theoretical calculations demonstrated that non-covalent forces assist the molecular recognition of TrkA receptor for both peptides. Combined parallel tempering/docking simulations discriminated the effect of the N-terminal acetylation on the recognition of NGF(1-14) towards the domain 5 of TrkA (TrkA-D5). Experimental findings demonstrated that both NGF(1-14) and Ac-NGF(1-14) activate TrkA signaling pathways essential for neuronal survival. The NGF-induced TrkA internalization was slightly inhibited in the presence of Cu2+ and Zn2+ ions, whereas the metal ions elicited the NGF(1-14)-induced internalization of TrkA and no significant differences were found in the weak Ac-NGF(1-14)-induced receptor internalization. The crucial role of the metals was confirmed by experiments with the metal-chelator bathocuproine disulfonic acid, which discriminated different levels of inhibitory effects in the signalling cascade, due to different metal affinity of NGF, the free amino and the acetylated peptides.
The NGF signaling cascade, activated by NGF (1â14) and Ac-NGF(1-14), induced CREB phosphorylation, but the copper addition further stimulated the Akt, ERK and CREB phosphorylation only for NGF and NGF(1-14). A dynamic and quick influx of both peptides into PC12 cells was tracked by live cell imaging with confocal microscopy. A significant role of copper ions was found in the modulation of peptide sub-cellular localization, especially at the nuclear level. Furthermore, a strong copper ionophoric ability of NGF(1-14) was measured. The Ac-NGF(1-14) peptide, which binds copper ions with a lower stability constant than NGF(1-14), exhibited a lower nuclear localization with respect to the total cellular uptake. These findings were correlated to the metal-induced increase of CREB and BDNF expression upon NGF(1-14) stimulation.
In summary, we here validate NGF(1-14) and Ac-NGF(1-14) as first examples of monomer and linear peptides able to activate the NGF-TrkA signaling cascade. Metal ions modulate the activity of both NGF protein and the NGF-mimicking peptides. Such findings demonstrate that NGF(1-14) sequence can reproduce the signal transduction of whole protein, therefore represent a very promising drug candidate for further preclinical studies
REUNICE Research with and for society
This paper presents a new European project namely REUNICE which focuses on research with and for society. Specifically, REUNICE aims to promote cooperation between universities and other sectors in order to enhance the quality and competitiveness of the research activities and innovation. In order to attain this objective, the project focuses on four main topics, in particular open science, diversity, ties with industry, and sustainable science. Specifically, in this paper, we present the European university action plan in each topic and how external stakeholders can collaborate with the consortium in this project
Coordination environment of Cu(II) ions bound to N-terminal peptide fragments of angiogenin protein
Angiogenin (Ang) is a potent angiogenic factor, strongly overexpressed in patients affected by different types of cancers. The specific Ang cellular receptors have not been identified, but it is known that Angâactin interaction induces changes both in the cell cytoskeleton and in the extracellular matrix. Most in vitro studies use the recombinant form (r-Ang) instead of the form that is normally present in vivo (âwild-typeâ, wt-Ang). The first residue of r-Ang is a methionine, with a free amino group, whereas wt-Ang has a glutamic acid, whose amino group spontaneously cyclizes in the pyro-glutamate form. The Ang biological activity is influenced by copper ions. To elucidate the role of such a free amino group on the proteinâcopper binding, we scrutinized the copper(II) complexes with the peptide fragments Ang(1â17) and AcAng(1â17), which encompass the sequence 1â17 of angiogenin (QDNSRYTHFLTQHYDAK-NH2), with free amino and acetylated N-terminus, respectively. Potentiometric, ultraviolet-visible (UV-vis), nuclear magnetic resonance (NMR) and circular dichroism (CD) studies demonstrate that the two peptides show a different metal coordination environment. Confocal microscopy imaging of neuroblastoma cells with the actin staining supports the spectroscopic results, with the finding of different responses in the cytoskeleton organization upon the interaction, in the presence or not of copper ions, with the free amino and the acetylated N-terminus peptides
PARP-14 Promotes Survival of Mammalian α but Not ÎČ Pancreatic Cells Following Cytokine Treatment
PARP-14 (poly-ADP Ribose Polymerase-14), a member of the PARP family, belongs to the group of Bal proteins (B Aggressive Lymphoma). PARP-14 has recently appeared to be involved in the transduction pathway mediated by JNKs (c Jun N terminal Kinases), among which JNK2 promotes cancer cell survival. Several pharmacological PARP inhibitors are currently used as antitumor agents, even though they have also proved to be effective in many inflammatory diseases. Cytokine release from immune system cells characterizes many autoimmune inflammatory disorders, including type I diabetes, in which the inflammatory state causes ÎČ cell loss. Nevertheless, growing evidence supports a concomitant implication of glucagon secreting α cells in type I diabetes progression. Here, we provide evidence on the activation of a survival pathway, mediated by PARP-14, in pancreatic α cells, following treatment of αTC1.6 glucagonoma and ÎČTC1 insulinoma cell lines with a cytokine cocktail: interleukin 1 beta (IL-1ÎČ), interferon gamma (IFN-Îł) and tumor necrosis factor alpha (TNF-α). Through qPCR, western blot and confocal analysis, we demonstrated higher expression levels of PARP-14 in αTC1.6 cells with respect to ÎČTC1 cells under inflammatory stimuli. By cytofluorimetric and caspase-3 assays, we showed the higher resistance of α cells compared to ÎČ cells to apoptosis induced by cytokines. Furthermore, the ability of PJ-34 to modulate the expression of the proteins involved in the survival pathway suggests a protective role of PARP-14. These data shed light on a poorly characterized function of PARP-14 in αTC1.6 cells in inflammatory contexts, widening the potential pharmacological applications of PARP inhibitors
Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires
The production of tt⟠, W+bb⟠and W+cc⟠is studied in the forward region of protonâproton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fbâ1 . The W bosons are reconstructed in the decays WââÎœ , where â denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of , and is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 0.02 \mbox{fb}^{-1}. The bosons are reconstructed in the decays , where denotes muon or electron, while the and quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions
Multidifferential study of identified charged hadron distributions in -tagged jets in proton-proton collisions at 13 TeV
Jet fragmentation functions are measured for the first time in proton-proton
collisions for charged pions, kaons, and protons within jets recoiling against
a boson. The charged-hadron distributions are studied longitudinally and
transversely to the jet direction for jets with transverse momentum 20 GeV and in the pseudorapidity range . The
data sample was collected with the LHCb experiment at a center-of-mass energy
of 13 TeV, corresponding to an integrated luminosity of 1.64 fb. Triple
differential distributions as a function of the hadron longitudinal momentum
fraction, hadron transverse momentum, and jet transverse momentum are also
measured for the first time. This helps constrain transverse-momentum-dependent
fragmentation functions. Differences in the shapes and magnitudes of the
measured distributions for the different hadron species provide insights into
the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any
supplementary material and additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb
public pages
Study of the decay
The decay is studied
in proton-proton collisions at a center-of-mass energy of TeV
using data corresponding to an integrated luminosity of 5
collected by the LHCb experiment. In the system, the
state observed at the BaBar and Belle experiments is
resolved into two narrower states, and ,
whose masses and widths are measured to be where the first uncertainties are statistical and the second
systematic. The results are consistent with a previous LHCb measurement using a
prompt sample. Evidence of a new
state is found with a local significance of , whose mass and width
are measured to be and , respectively. In addition, evidence of a new decay mode
is found with a significance of
. The relative branching fraction of with respect to the
decay is measured to be , where the first
uncertainty is statistical, the second systematic and the third originates from
the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb
public pages
Measurement of the ratios of branching fractions and
The ratios of branching fractions
and are measured, assuming isospin symmetry, using a
sample of proton-proton collision data corresponding to 3.0 fb of
integrated luminosity recorded by the LHCb experiment during 2011 and 2012. The
tau lepton is identified in the decay mode
. The measured values are
and
, where the first uncertainty is
statistical and the second is systematic. The correlation between these
measurements is . Results are consistent with the current average
of these quantities and are at a combined 1.9 standard deviations from the
predictions based on lepton flavor universality in the Standard Model.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-039.html (LHCb
public pages
A study of CP violation in B-+/- -> DK +/- and B-+/- -> D pi(+/-) decays with D -> (KSK +/-)-K-0 pi(-/+) final states
A first study of CP violation in the decay modes and , where labels a or meson and labels a or meson, is performed. The analysis uses the LHCb data set collected in collisions, corresponding to an integrated luminosity of 3 fb. The analysis is sensitive to the CP-violating CKM phase through seven observables: one charge asymmetry in each of the four modes and three ratios of the charge-integrated yields. The results are consistent with measurements of using other decay modes
Study of the rare B-s(0) and B-0 decays into the pi(+) pi(-) mu(+) mu(-) final state
A search for the rare decays and is performed in a data set corresponding to an integrated luminosity of 3.0 fb collected by the LHCb detector in proton-proton collisions at centre-of-mass energies of 7 and 8 TeV. Decay candidates with pion pairs that have invariant mass in the range 0.5-1.3 GeV/ and with muon pairs that do not originate from a resonance are considered. The first observation of the decay and the first evidence of the decay are obtained and the branching fractions are measured to be and , where the third uncertainty is due to the branching fraction of the decay , used as a normalisation.A search for the rare decays Bs0âÏ+ÏâÎŒ+ÎŒâ and B0âÏ+ÏâÎŒ+ÎŒâ is performed in a data set corresponding to an integrated luminosity of 3.0 fbâ1 collected by the LHCb detector in protonâproton collisions at centre-of-mass energies of 7 and 8 TeV . Decay candidates with pion pairs that have invariant mass in the range 0.5â1.3 GeV/c2 and with muon pairs that do not originate from a resonance are considered. The first observation of the decay Bs0âÏ+ÏâÎŒ+ÎŒâ and the first evidence of the decay B0âÏ+ÏâÎŒ+ÎŒâ are obtained and the branching fractions, restricted to the dipion-mass range considered, are measured to be B(Bs0âÏ+ÏâÎŒ+ÎŒâ)=(8.6±1.5 (stat)±0.7 (syst)±0.7(norm))Ă10â8 and B(B0âÏ+ÏâÎŒ+ÎŒâ)=(2.11±0.51(stat)±0.15(syst)±0.16(norm))Ă10â8 , where the third uncertainty is due to the branching fraction of the decay B0âJ/Ï(âÎŒ+ÎŒâ)Kâ(892)0(âK+Ïâ) , used as a normalisation.A search for the rare decays Bs0âÏ+ÏâÎŒ+ÎŒâ and B0âÏ+ÏâÎŒ+ÎŒâ is performed in a data set corresponding to an integrated luminosity of 3.0 fbâ1 collected by the LHCb detector in protonâproton collisions at centre-of-mass energies of 7 and 8 TeV . Decay candidates with pion pairs that have invariant mass in the range 0.5â1.3 GeV/c2 and with muon pairs that do not originate from a resonance are considered. The first observation of the decay Bs0âÏ+ÏâÎŒ+ÎŒâ and the first evidence of the decay B0âÏ+ÏâÎŒ+ÎŒâ are obtained and the branching fractions, restricted to the dipion-mass range considered, are measured to be B(Bs0âÏ+ÏâÎŒ+ÎŒâ)=(8.6±1.5 (stat)±0.7 (syst)±0.7(norm))Ă10â8 and B(B0âÏ+ÏâÎŒ+ÎŒâ)=(2.11±0.51(stat)±0.15(syst)±0.16(norm))Ă10â8 , where the third uncertainty is due to the branching fraction of the decay B0âJ/Ï(âÎŒ+ÎŒâ)Kâ(892)0(âK+Ïâ) , used as a normalisation.A search for the rare decays and is performed in a data set corresponding to an integrated luminosity of 3.0 fb collected by the LHCb detector in proton-proton collisions at centre-of-mass energies of 7 and 8 TeV. Decay candidates with pion pairs that have invariant mass in the range 0.5-1.3 GeV/ and with muon pairs that do not originate from a resonance are considered. The first observation of the decay and the first evidence of the decay are obtained and the branching fractions, restricted to the dipion-mass range considered, are measured to be and , where the third uncertainty is due to the branching fraction of the decay , used as a normalisation
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