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Pion–kaon femtoscopy and the lifetime of the hadronic phase in Pb−Pb collisions at √sNN = 2.76 TeV
(2020)
In this paper, the first femtoscopic analysis of pion-kaon correlations at the LHC is reported. The analysis was performed on the Pb-Pb collision data at sNN−−−√ = 2.76 TeV recorded with the ALICE detector. The non-identical particle correlations probe the spatio-temporal separation between sources of different particle species as well as the average source size of the emitting system. The sizes of the pion and kaon sources increase with centrality, and pions are emitted closer to the centre of the system and/or later than kaons. This is naturally expected in a system with strong radial flow and is qualitatively reproduced by hydrodynamic models. ALICE data on pion-kaon emission asymmetry are consistent with (3+1)-dimensional viscous hydrodynamics coupled to a statistical hadronization model, resonance propagation, and decay code THERMINATOR 2 calculation, with an additional time delay between 1 and 2 fm/c for kaons. The delay can be interpreted as evidence for a significant hadronic rescattering phase in heavy-ion collisions at the LHC.
The inclusive production of the J/ψ and ψ(2S) charmonium states is studied as a function of centrality in p-Pb collisions at a centre-of-mass energy per nucleon pair sNN−−−√=8.16 TeV at the LHC. The measurement is performed in the dimuon decay channel with the ALICE apparatus in the centre-of-mass rapidity intervals −4.46<ycms<−2.96 (Pb-going direction) and 2.03<ycms<3.53 (p-going direction), down to zero transverse momentum (pT). The J/ψ and ψ(2S) production cross sections are evaluated as a function of the collision centrality, estimated through the energy deposited in the zero degree calorimeter located in the Pb-going direction. The pT-differential J/ψ production cross section is measured at backward and forward rapidity for several centrality classes, together with the corresponding average ⟨pT⟩ and ⟨p2T⟩ values. The nuclear effects affecting the production of both charmonium states are studied using the nuclear modification factor. In the p-going direction, a suppression of the production of both charmonium states is observed, which seems to increase from peripheral to central collisions. In the Pb-going direction, however, the centrality dependence is different for the two states: the nuclear modification factor of the J/ψ increases from below unity in peripheral collisions to above unity in central collisions, while for the ψ(2S) it stays below or consistent with unity for all centralities with no significant centrality dependence. The results are compared with measurements in p-Pb collisions at sNN−−−√=5.02 TeV and no significant dependence on the energy of the collision is observed. Finally, the results are compared with theoretical models implementing various nuclear matter effects.
Rationale: RBPs (RNA binding proteins) play critical roles in the cell by regulating mRNA transport, splicing, editing, and stability. The RBP SRSF3 (serine/arginine-rich splicing factor 3) is essential for blastocyst formation and for proper liver development and function. However, its role in the heart has not been explored.
Objective:To investigate the role of SRSF3 in cardiac function.
Methods and Results: Cardiac SRSF3 expression was high at mid gestation and decreased during late embryonic development. Mice lacking SRSF3 in the embryonic heart showed impaired cardiomyocyte proliferation and died in utero. In the adult heart, SRSF3 expression was reduced after myocardial infarction, suggesting a possible role in cardiac homeostasis. To determine the role of this RBP in the adult heart, we used an inducible, cardiomyocyte-specific SRSF3 knockout mouse model. After SRSF3 depletion in cardiomyocytes, mice developed severe systolic dysfunction that resulted in death within 8 days. RNA-Seq analysis revealed downregulation of mRNAs encoding sarcomeric and calcium handling proteins. Cardiomyocyte-specific SRSF3 knockout mice also showed evidence of alternative splicing of mTOR (mammalian target of rapamycin) mRNA, generating a shorter protein isoform lacking catalytic activity. This was associated with decreased phosphorylation of 4E-BP1 (eIF4E-binding protein 1), a protein that binds to eIF4E (eukaryotic translation initiation factor 4E) and prevents mRNA decapping. Consequently, we found increased decapping of mRNAs encoding proteins involved in cardiac contraction. Decapping was partially reversed by mTOR activation.
Conclusions: We show that cardiomyocyte-specific loss of SRSF3 expression results in decapping of critical mRNAs involved in cardiac contraction. The molecular mechanism underlying this effect likely involves the generation of a short mTOR isoform by alternative splicing, resulting in reduced 4E-BP1 phosphorylation. The identification of mRNA decapping as a mechanism of systolic heart failure may open the way to the development of urgently needed therapeutic tools.
Kant, Piaget et Unityp
(1988)
Le livre de H. Seiler, "Apprehension. Language, Object and Order", présente un grand intérêt même pour und épistémologue ne disposant pas d'une formation de linguíste. A cela il y a au moins deux raísons: en premier lieu "Apprehension. Language, Object and Order" étudie la notion d'objet introduisant la DIMENSION de l'APPREHENSION et, en deuxième lieu, à travers l'étude des langues elle vise une universalité fonctionelle de l'activité cognitive. La notion d'objet est traditionellement importante pour toute recherche épistémologique et ces dernières années elle a été définitivement liée aux recherches sémantiques (Tugendhat 1976: 48). "Apprehension. Language, Object, and order" englobe cet aspect; en effet, le terme de APPREHENSION indique l'activité de saisie notionelle de l'objet telle qu'elle apparaît dans les langues. La structure des langues, mise en évidence dans cette DIMENSION de l'APPREHENSION, est considerée comme la manifestation (REPRAESENTATIO) d'un concept, le REPRAESENTANDUM. Dans notre cas, il s'agit du concept d'objet, dont la richesse esst détectable par la complexité de la REPRAESENTATIO línguistique, qui en met en évidence la nature fonctionelle. Mais sa nature polymorphe, apparaissant dans les TECHNIQUES de la DIMENSION, fait que la saisie due réel mise en oeuvre par ce concept ne pourra pas se reduire à une simple perception de l'objet. En developpant les recherches de "Apprehension. Language, Object and Order", on purra dépasser non seulement les conceptions de la sémantique fondées sur la notion d'adéquation (ou de satisfaction), mais aussi celle qui se réclament d'un 'jeu de vérification' (Tugendhat 1976: 265). Ces conceptions, loin de se vider de leur sens, seront intégrées dans un cadre plus général. En effet, la nature même de l'objet dépend, dans sa définition et dans sa saisie, de cette activité. Le dépassement de la notion d'adéquation amène à une reformulation de l'ontologie, que l'ensemble de "Apprehension. Language, Object and Order" suggère. Il faudra introduire, à mon avis, une conception constructiviste.
RATIONALE: RBPs (RNA-binding proteins) play critical roles in human biology and disease. Aberrant RBP expression affects various steps in RNA processing, altering the function of the target RNAs. The RBP SRSF4 (serine/arginine-rich splicing factor 4) has been linked to neuropathies and cancer. However, its role in the heart is completely unknown. OBJECTIVE: To investigate the role of SRSF4 in the heart. METHODS AND RESULTS: Echocardiography of mice specifically lacking SRSF4 in the heart (SRSF4 KO) revealed left ventricular hypertrophy and increased cardiomyocyte area, which led to progressive diastolic dysfunction with age. SRSF4 KO mice showed altered electrophysiological activity under isoproterenol-induced cardiac stress, with a post-QRS depression and a longer QT interval, indicating an elevated risk of sudden cardiac death. RNA-Seq analysis revealed expression changes in several long noncoding RNAs, including GAS5 (growth arrest-specific 5), which we identified as a direct SRSF4 target in cardiomyocytes by individual-nucleotide- resolution cross-linking and immuno-precipitation. GAS5 is a repressor of the GR (glucocorticoid receptor) and was downregulated in SRSF4 KO hearts. This corresponded with elevated GR transcriptional activity in cardiomyocytes, leading to increases in hypertrophy markers and cell size. Furthermore, hypertrophy in SRSF4 KO cardiomyocytes was reduced by overexpressing GAS5. CONCLUSIONS: Loss of SRSF4 expression results in cardiac hypertrophy, diastolic dysfunction, and abnormal repolarization. The molecular mechanism underlying this effect involves GAS5 downregulation and consequent elevation of GR transcriptional activity. Our findings may help to develop new therapeutic tools for the treatment of cardiac hypertrophy and myocardial pathology in patients with Cushing syndrome.