Tcf7l2 plays pleiotropic roles in the control of glucose homeostasis, pancreas morphology, vascularization and regeneration

Type 2 diabetes (T2D) is a disease characterized by impaired insulin secretion. The Wnt signaling transcription factor Tcf7l2 is to date the T2D-associated gene with the largest effect on disease susceptibility. However, the mechanisms by which TCF7L2 variants affect insulin release from β-cells are not yet fully understood. By taking advantage of a tcf7l2 zebrafish mutant line, we first show that these animals are characterized by hyperglycemia and impaired islet development. Moreover, we demonstrate that the zebrafish tcf7l2 gene is highly expressed in the exocrine pancreas, suggesting potential bystander effects on β-cell growth, differentiation and regeneration. Finally, we describe a peculiar vascular phenotype in tcf7l2 mutant larvae, characterized by significant reduction in the average number and diameter of pancreatic islet capillaries. Overall, the zebrafish Tcf7l2 mutant, characterized by hyperglycemia, pancreatic and vascular defects, and reduced regeneration proves to be a suitable model to study the mechanism of action and the pleiotropic effects of Tcf7l2, the most relevant T2D GWAS hit in human populations. © 2017 The Author(s)

Dual-initiation promoters with intertwined canonical and TCT/TOP transcription start sites diversify transcript processing

Variations in transcription start site (TSS) selection reflect diversity of preinitiation complexes and can impact on post-transcriptional RNA fates. Most metazoan polymerase II-transcribed genes carry canonical initiation with pyrimidine/purine (YR) dinucleotide, while translation machinery-associated genes carry polypyrimidine initiator (5'-TOP or TCT). By addressing the developmental regulation of TSS selection in zebrafish we uncovered a class of dual-initiation promoters in thousands of genes, including snoRNA host genes. 5'-TOP/TCT initiation is intertwined with canonical initiation and used divergently in hundreds of dual-initiation promoters during maternal to zygotic transition. Dual-initiation in snoRNA host genes selectively generates host and snoRNA with often different spatio-temporal expression. Dual-initiation promoters are pervasive in human and fruit fly, reflecting evolutionary conservation. We propose that dual-initiation on shared promoters represents a composite promoter architecture, which can function both coordinately and divergently to diversify RNAs

Measurement of the neutron flux at the Canfranc Underground Laboratory with HENSA

We have performed a long-term measurement of the neutron flux with the High Efficiency Neutron Spectrometry Array HENSA in the Hall A of the Canfranc Underground Laboratory. The Hall A measurement campaign lasted from October 2019 to March 2021, demonstrating an excellent stability of the HENSA setup. Preliminary results on the neutron flux from this campaign are presented for the first time. In Phase 1 (113 live days) a total neutron flux of 1.66(2) $\times$10$^{-5}$ cm$^{-2}$ s$^{-1}$ is obtained. Our results are in good agreement with those from our previous shorter measurement where a reduced experimental setup was employed.Comment: Proceedings of the 17th International Conference on Topics in Astroparticle and Underground Physics (TAUP 2021

Long-term evolution of the neutron rate at the Canfranc Underground Laboratory

We report results on the long-term variation of the neutron counting rate at the Canfranc Underground Laboratory, of importance for several low-background experiments installed there, including rare-event searches. The measurement campaign was performed employing the High Efficiency Neutron Spectrometry Array (HENSA) mounted in Hall A and lasted 412 live days. The present study is the first long-term measurement of the neutron rate with sensitivity over a wide range of neutron energies (from thermal up to 0.1 GeV and beyond) performed in any underground laboratory so far. Data on the environmental variables inside the experimental hall (radon concentration, air temperature, air pressure and humidity) were also acquired during all the measurement campaign. We have investigated for the first time the evolution of the neutron rate for different energies of the neutrons and its correlation with the ambient variables.Comment: 12 pages, 5 figures, 2 table

Measurement of the neutron-induced fission cross section of Th 230 at the CERN n_TOF facility

The neutron-induced fission cross section of 230 Th has been measured at the neutron time-of-flight facility n_TOF located at CERN. The experiment was performed at the experimental area EAR-1 with a neutron flight path of 185 m, using Micromegas detectors for the detection of the fission fragments. The 230 Th(n, f ) cross section was determined relative to the 235 U(n, f ) one, covering the energy range from the fission threshold up to 400 MeV. The results from the present work are compared with existing cross-section datasets and the observed discrepancies are discussed and analyzed. Finally, using the code EMPIRE 3.2.3 a theoretical study, based on the statistical model, was performed leading to a satisfactory reproduction of the experimental results with the proper tuning of the respective parameters, while for incident neutron energy beyond 200 MeV the fission of 230 Th was described by Monte Carlo simulations.This project received funding from the Euratom “Support safe operation of nuclear systems” program 2014–2018 under Grant Agreement No. 847552 (SANDA) and by the funding agencies of the participating institutes. This research is imple- mented through the IKY scholarships program and cofinanced by the European Union (European Social Fund ’ESF) and Greek national funds through the action entitled “Reinforce- ment of Postdoctoral Researchers - 2nd call (MIS 5033021)”, in the framework of the Operational Programme “Human Resources Development Program, Education and Lifelong Learning” of the National Strategic Reference Framework.Article signat per 137 autors/es: V. Michalopoulou, A. Stamatopoulos, M. Diakaki, A. Tsinganis, R. Vlastou, M. Kokkoris, N. Patronis, Z. Eleme, D. Macina, L. Tassan-Got, N. Colonna, E. Chiaveri, A. Ventura, P. Schillebeeckx, J. Heyse, G. Sibbens, G. Alaerts, A. Borella, A. Moens, D. Vanleeuw, O. Aberle, V. Alcayne, S. Amaducci, J. Andrzejewski, L. Audouin, V. Babiano-Suarez, M. Bacak, M. Barbagallo, S. Bennett, E. Berthoumieux, J. Billowes, D. Bosnar, A. Brown, M. Busso, M. Caamaño, L. Caballero, F. Calviño, M. Calviani, D. Cano-Ott, A. Casanovas, F. Cerutti, G. Cortés, M. A. Cortés-Giraldo, L. Cosentino, S. Cristallo, L. A. Damone, P. J. Davies, M. Dietz, C. Domingo-Pardo, R. Dressler, Q. Ducasse, E. Dupont, I. Durán, B. Fernández-Domínguez, A. Ferrari, P. Finocchiaro, V. Furman, K. Göbel, R. Garg, A. Gawlik-Ramiega, S. Gilardoni, I. F. Gonçalves, E. González-Romero, C. Guerrero, F. Gunsing, H. Harada, S. Heinitz, D. G. Jenkins, A. Junghans, F. Käppeler, Y. Kadi, A. Kimura, I. Knapová, Y. Kopatch, M. Krticka, D. Kurtulgil, I. Ladarescu, C. Lederer-Woods, H. Leeb, J. Lerendegui-Marco, S. J. Lonsdale, A. Manna, T. Martínez, A. Masi, C. Massimi, P. Mastinu, M. Mastromarco, E. A. Maugeri, A. Mazzone, E. Mendoza, A. Mengoni, P. M. Milazzo, F. Mingrone, J. Moreno-Soto, A. Musumarra, A. Negret, R. Nolte, F. Ogállar, A. Oprea, A. Pavlik, J. Perkowski, C. Petrone, L. Piersanti, E. Pirovano, I. Porras, J. Praena, J. M. Quesada, D. Ramos-Doval, T. Rauscher, R. Reifarth, D. Rochman, Y. Romanets, C. Rubbia, M. Sabaté-Gilarte, A. Saxena, D. Schumann, A. Sekhar, A. G. Smith, N. V. Sosnin, P. Sprung, G. Tagliente, J. L. Tain, A. Tarifeño-Saldivia, Th. Thomas, P. Torres-Sánchez, J. Ulrich, S. Urlass, S. Valenta, G. Vannini, V. Variale, P. Vaz, D. Vescovi, V. Vlachoudis, A. Wallner, P. J. Woods, T. Wright, and P. Žugec.Postprint (published version

Recent highlights and prospects on (n,γ\gamma) measurements at the CERN n_TOF facility

Neutron capture cross-section measurements are fundamental in the study of the slow neutron capture (s-) process of nucleosynthesis and for the development of innovative nuclear technologies. One of the best suited methods to measure radiative neutron capture (n,$\gamma$) cross sections over the full stellar range of interest for all the applications is the time-of-flight (TOF) technique. Overcoming the current experimental limitations for TOF measurements, in particular on low mass unstable samples, requires the combination of facilities with high instantaneous flux, such as the CERN n_TOF facility, with detection systems with an enhanced detection sensitivity and high counting rate capabilities. This contribution presents a summary about the recent highlights in the field of (n,$\gamma$) measurements at n_TOF. The recent upgrades in the facility and in new detector concepts for (n,\g) measurements are described. Last, an overview is given on the existing limitations and prospects for TOF measurements involving unstable targets and the outlook for activation measurements at the brand new high-flux n_TOF-NEAR station.Comment: 7 pages, 5 figures (8 panels). Proceedings of the CGS-17 conference. To be published in EPJ Web of Conference

First results from the HENSA/ANAIS collaboration at the Canfranc Underground Laboratory

The HENSA/ANAIS collaboration aims for the precise determination of the neutron flux that could affect ANAIS-112, an experiment looking for the dark matter annual modulation using NaI(Tl) scintillators. In this work, the first measurements of the neutron flux and Monte Carlo simulations of the neutron spectrum are reported

Constraints on the dipole photon strength for the odd uranium isotopes

Nuclear level densities (NLDs) and photon strength functions (PSFs), also called ¿ -ray or radiation strength functions, represent average properties of the nucleus in the regime of excitation where individual levels and transition probabilities by ¿ decay are not readily accessible by experimental or theoretical means. They are key ingredients for statistical calculations of the reaction cross sections involving ¿ rays via the Hauser-Feshbach approach [1], like inelastic scattering or neutron capture reactions.Peer ReviewedAquest article té 124 autors/autores J. Moreno-Soto, S. Valenta, E. Berthoumieux, A. Chebboubi, M. Diakaki, W. Dridi, E. Dupont, F. Gunsing, M. Krticka, O. Litaize, O. Serot, O. Aberle, V. Alcayne, S. Amaducci, J. Andrzejewski, L. Audouin, V. Bécares, V. Babiano-Suarez, M. Bacak, M. Barbagallo, Th. Benedikt, S. Bennett, J. Billowes, D. Bosnar, A. Brown, M. Busso, M. Caamaño, L. Caballero-Ontanaya, F. Calviño, M. Calviani, D. Cano-Ott, A. Casanovas, F. Cerutti, E. Chiaveri, N. Colonna, G. Cortés, M. A. Cortés-Giraldo, L. Cosentino, Cristallo, L. A. Damone, P. J. Davies, M. Dietz, C. Domingo-Pardo, R. Dressler, Q. Ducasse, I. Durán, Z. Eleme, B. Fernández-Domínguez, A. Ferrari, P. Finocchiaro, V. Furman, K. Göbel, A. Gawlik-Rami, S. Gilardoni, I. F. Gonçalves, E. González-RomeroC. Guerrero, S. Heinitz, J. Heyse, D. G. Jenkins, A. Junghans, F. Käppeler, Y. Kadi, A. Kimura, I. Knapová, M. Kokkoris, Y. Kopatch, D. Kurtulgil, I. Ladarescu, C. Lampoudis, C. Lederer-Woods, S. J. Lonsdale, D. Macina, A. Manna, T. Martínez, A. Masi, C. Massimi, P. Mastinu, M. Mastromarco, E. A. Maugeri, A. Mazzone, E. Mendoza, A. Mengoni, V. Michalopoulou, P. M. Milazzo, F. MingroneA. Musumarra, A. Negret, R. Nolte, F. Ogállar, A. Oprea, N. Patronis, A. Pavlik, J. Perkowski, L. Piersanti, C. Petrone, E. Pirovano, I. Porras, J. Praena, J. M. Quesada, D. Ramos-Doval, T. Rauscher, R. Reifarth, D. Rochman, M. Sabaté-Gilarte, A. Saxena, P. Schillebeeckx, D. Schumann, A. Sekhar, A. G. Smith, N. V. Sosnin, P. Sprung, A. Stamatopoulos, G. Tagliente, J. L. Tain, A. Tarifeño-Saldivia, L. Tassan-Got, P. Torres-Sánchez, A. Tsinganis, J. Ulrich, S. Urlass, G. Vannini, V. Variale, P. Vaz, A. Ventura, D. Vescovi, V. Vlachoudis, R. Vlastou, A. Wallner, P. J. Woods, T. Wright, P. ŽugecPostprint (published version

The 33S(n,α)30Si cross section measurement at n-TOF-EAR2 (CERN) : From 0.01 eV to the resonance region

The 33S(n,α)30Si cross section measurement, using 10B(n,α) as reference, at the n-TOF Experimental Area 2 (EAR2) facility at CERN is presented. Data from 0.01 eV to 100 keV are provided and, for the first time, the cross section is measured in the range from 0.01 eV to 10 keV. These data may be used for a future evaluation of the cross section because present evaluations exhibit large discrepancies. The 33S(n,α)30Si reaction is of interest in medical physics because of its possible use as a cooperative target to boron in Neutron Capture Therapy (NCT)