Estimate of the theoretical uncertainty of the cross sections for nucleon knockout in neutral-current neutrino-oxygen interactions

Free nucleons propagating in water are known to produce gamma rays, which form a background to the searches for diffuse supernova neutrinos and sterile neutrinos carried out with Cherenkov detectors. As a consequence, the process of nucleon knockout induced by neutral-current quasielastic interactions of atmospheric (anti)neutrinos with oxygen needs to be under control at the quantitative level in the background simulations of the ongoing and future experiments. In this paper, we provide a quantitative assessment of the uncertainty associated with the theoretical description of the nuclear cross sections, estimating it from the discrepancies between the predictions of different models.Comment: 7 pages, 2 figure

Role of bulge epidermal stem cells and TSLP signaling in psoriasis

Psoriasis is a common inflammatory skin disease involving a cross-talk between epidermal and immune cells. The role of specific epidermal stem cell populations, including hair follicle stem cells (HF-SCs) in psoriasis is not well defined. Here, we show reduced expression of c-JUN and JUNB in bulge HF-SCs in patients with scalp psoriasis. Using lineage tracing in mouse models of skin inflammation with inducible deletion of c-Jun and JunB, we found that mutant bulge HF-SCs initiate epidermal hyperplasia and skin inflammation. Mechanistically, thymic stromal lymphopoietin (TSLP) was identified in mutant cells as a paracrine factor stimulating proliferation of neighboring non-mutant epidermal cells, while mutant inter-follicular epidermal (IFE) cells are lost over time. Blocking TSLP in psoriasis-like mice reduced skin inflammation and decreased epidermal proliferation, VEGFα expression, and STAT5 activation. These findings unravel distinct roles of HF-SCs and IFE cells in inflammatory skin disease and provide novel mechanistic insights into epidermal cell interactions in inflammation.We thank Drs. M. Serrano and M. Perez-Moreno for the Gt(ROSA)26Sortrn4(ACTB-tdTomato,-EGFP)Luo/J and K15-Cre-PGR mouse lines. We are very grateful to Drs. M. Perez-Moreno, F. Real, O. Uluckan, L. Bakiri and the laboratory members of the Sibilia and Wagner groups for critical reading of the manuscript and valuable suggestions. We thank V. Bermeo, G. Medrano, S. Leceta, O. Grana, and M. Perez for their technical help and IT support. We acknowledge R. Paus laboratory members for the shipment of hair follicle samples. N.G.L. received funding from the People programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no 608765. A.I is funded by the Institute of Health Carlos III (PI16/01430). The Wagner laboratory was funded by a grant from the Spanish Ministry of Economy and competitiveness (SAF2015-70857RE, cofounded by the European Regional Development Fund) and is supported by the ERC (ERC-AdG 2016 CSI-Fun).S

Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics): Preface

Peer Reviewe

Inelastic neutrino-nucleus scattering in the superscaling model

International audienceCharged-current inclusive neutrino cross sections on $^{12}$C and ^{40}Ar target are analyzed using the susperscaling model SuSAv2, for the first time extended to the full inelastic region. The model contains two new ingredients: the first is a scaling function used to describe the $\Delta$ resonance region, built after subtracting from ($e,e'$) experimental cross sections the quasielastic, two-particle two-hole, higher resonances and deep inelastic scattering (DIS) contributions arising from the SuSAv2-MEC model; the second is the description of the resonance and DIS regimes through the extension to the neutrino sector of the SuSAv2-inelastic model already available for ($e,e'$) reactions, which combines phenomenological structure functions with a nuclear scaling function. Two different options for the description of the $\Delta$ region are presented and discussed.The results of the model are tested against ($e,e'$) data and inclusive neutrino cross-section measurements from the T2K and ArgoNEUT experiments, thus covering several kinematical regions

Neutrino-nucleus scattering in the SuSA model

The super-scaling approach (SuSA) model, based on the analogies between electron and neutrino interactions with nuclei, is reviewed and its application to the description of neutrino-nucleus scattering is presented. The contribution of both one- and two-body relativistic currents is considered. The model is validated with the (e, e′) data, including also inelastic contributions for the inclusive reaction. A discussion of semi-inclusive reactions and their implications for charge-changing reactions of neutrinos is also presented. A selection of results for the inclusive neutrino reactions with change of charge is presented where theoretical predictions are compared with cross-section measurements from the main ongoing neutrino oscillation experiments.FQM-225FIS2017-85053-C2-1-

AMPK and PFKFB3 mediate glycolysis and survival in response to mitophagy during mitotic arrest

E.D., C.M. and M.S.-R. were supported by the Spanish Fondo de Investigaciones Sanitarias (Madrid), MINECO (Juan de la Cierva programme) and Asociación Española contra el Cáncer (AECC), respectively. L.E.-M. is a recipient of a JAE predoctoral fellowship from the CSIC. A.K.S. was supported by USPHS grants RO1DK19514, RO1DK67509. G.V. was supported by grants from the Spanish Ministry of Economy and Competitiveness (MINECO) and Fondo Europeo de Desarrollo Regional (FEDER) (PI12/02248), Fundació La Marató de TV3 (m12 20134031), and Fundación Mutua Madrileña (AP101042012). M.L. was supported by the European Community’s Seventh Framework Programme under grant agreement no. 281854—the ObERStress (European Research Council project). E.R. was financially supported by a MINECO grant (SAF 2010-20256). Work in the R.M. laboratory was supported by the Fundación Botín, Banco Santander and MINECO (BFU2011-30121, BFU2014-52125-REDT and Consolider RNAREG CSD2009-00080). Work in the P.B. laboratory is supported by a grant from the Spanish Ministry for Economy and Competitiveness (MINECO; SAF2012-36079). Work in the M.M. laboratory was supported by grants from the MINECO (SAF2012-38215), Consolider-Ingenio 2010 Programme (SAF2014-57791-REDC), Excellence Network CellSYS (BFU2014-52125-REDT), the OncoCycle Programme (S2010/BMD-2470) from the Comunidad de Madrid, Worldwide Cancer Research (WCR no. 15-0278), and the European Union Seventh Framework Programme (MitoSys project; HEALTH-F5-2010-241548).Blocking mitotic progression has been proposed as an attractive therapeutic strategy to impair proliferation of tumour cells. However, how cells survive during prolonged mitotic arrest is not well understood. We show here that survival during mitotic arrest is affected by the special energetic requirements of mitotic cells. Prolonged mitotic arrest results in mitophagy-dependent loss of mitochondria, accompanied by reduced ATP levels and the activation of AMPK. Oxidative respiration is replaced by glycolysis owing to AMPK-dependent phosphorylation of PFKFB3 and increased production of this protein as a consequence of mitotic-specific translational activation of its mRNA. Induction of autophagy or inhibition of AMPK or PFKFB3 results in enhanced cell death in mitosis and improves the anti-tumoral efficiency of microtubule poisons in breast cancer cells. Thus, survival of mitotic-arrested cells is limited by their metabolic requirements, a feature with potential implications in cancer therapies aimed to impair mitosis or metabolism in tumour cells.Depto. de Bioquímica y Biología MolecularFac. de Ciencias BiológicasTRUEpu

AMPK and PFKFB3 mediate glycolysis and survival in response to mitophagy during mitotic arrest

E.D., C.M. and M.S.-R. were supported by the Spanish Fondo de Investigaciones Sanitarias (Madrid), MINECO (Juan de la Cierva programme) and Asociación Española contra el Cáncer (AECC), respectively. L.E.-M. is a recipient of a JAE predoctoral fellowship from the CSIC. A.K.S. was supported by USPHS grants RO1DK19514, RO1DK67509. G.V. was supported by grants from the Spanish Ministry of Economy and Competitiveness (MINECO) and Fondo Europeo de Desarrollo Regional (FEDER) (PI12/02248), Fundació La Marató de TV3 (m12 20134031), and Fundación Mutua Madrileña (AP101042012). M.L. was supported by the European Community’s Seventh Framework Programme under grant agreement no. 281854—the ObERStress (European Research Council project). E.R. was financially supported by a MINECO grant (SAF 2010-20256). Work in the R.M. laboratory was supported by the Fundación Botín, Banco Santander and MINECO (BFU2011-30121, BFU2014-52125-REDT and Consolider RNAREG CSD2009-00080). Work in the P.B. laboratory is supported by a grant from the Spanish Ministry for Economy and Competitiveness (MINECO; SAF2012-36079). Work in the M.M. laboratory was supported by grants from the MINECO (SAF2012-38215), Consolider-Ingenio 2010 Programme (SAF2014-57791-REDC), Excellence Network CellSYS (BFU2014-52125-REDT), the OncoCycle Programme (S2010/BMD-2470) from the Comunidad de Madrid, Worldwide Cancer Research (WCR no. 15-0278), and the European Union Seventh Framework Programme (MitoSys project; HEALTH-F5-2010-241548).Blocking mitotic progression has been proposed as an attractive therapeutic strategy to impair proliferation of tumour cells. However, how cells survive during prolonged mitotic arrest is not well understood. We show here that survival during mitotic arrest is affected by the special energetic requirements of mitotic cells. Prolonged mitotic arrest results in mitophagy-dependent loss of mitochondria, accompanied by reduced ATP levels and the activation of AMPK. Oxidative respiration is replaced by glycolysis owing to AMPK-dependent phosphorylation of PFKFB3 and increased production of this protein as a consequence of mitotic-specific translational activation of its mRNA. Induction of autophagy or inhibition of AMPK or PFKFB3 results in enhanced cell death in mitosis and improves the anti-tumoral efficiency of microtubule poisons in breast cancer cells. Thus, survival of mitotic-arrested cells is limited by their metabolic requirements, a feature with potential implications in cancer therapies aimed to impair mitosis or metabolism in tumour cells.Asociación Española contra el CáncerFundació La Marató de TV3Fundación Mutua MadrileñaComunidad de MadridMinisterio de Economía y Competitividad (España)European CommissionDepto. de Bioquímica y Biología MolecularFac. de Ciencias BiológicasTRUEpu