Androgen receptor gene polymorphism influence fat accumulation: a longitudinal study from adolescence to adult age.

To determine the influence of androgen receptor CAG and GGN repeat polymorphisms on fat mass and maximal fat oxidation (MFO), CAG and GGN repeat lengths were measured in 128 young boys, from which longitudinal data were obtained in 45 of them [mean?±?SD: 12.8?±?3.6 years old at recruitment, and 27.0?±?4.8 years old at adult age]. Subjects were grouped as CAG short (CAGS ) if harboring repeat lengths ?21, the rest as CAG long (CAGL ); and GGN short (GGNS ) if GGN repeat lengths ?23, or long if >?23 (GGNL ). CAGS and GGNS were associated with lower adiposity than CAGL or GGNL (P?<?0.05). There was an association between the logarithm of CAG repeats polymorphism and the changes of body mass (r?=?0.34, P?=?0.03). At adult age, CAGS men showed lower accumulation of total body and trunk fat mass, and lower resting metabolic rate (RMR) and MFO per kg of total lean mass compared with CAGL (P?<?0.05). GGNS men also showed lower percentage of body fat (P?<?0.05). In summary, androgen receptor CAG and GGN repeat polymorphisms are associated with RMR, MFO, fat mass, and its regional distribution in healthy male adolescents, influencing fat accumulation from adolescence to adult age

BRAF activation by metabolic stress promotes glycolysis sensitizing NRASQ61-mutated melanomas to targeted therapy

NRAS-mutated melanoma lacks a specific line of treatment. Metabolic reprogramming is considered a novel target to control cancer; however, NRAS-oncogene contribution to this cancer hallmark is mostly unknown. Here, we show that NRAS(Q61)-mutated melanomas specific metabolic settings mediate cell sensitivity to sorafenib upon metabolic stress. Mechanistically, these cells are dependent on glucose metabolism, in which glucose deprivation promotes a switch from CRAF to BRAF signaling. This scenario contributes to cell survival and sustains glucose metabolism through BRAF-mediated phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-2/3 (PFKFB2/PFKFB3). In turn, this favors the allosteric activation of phosphofructokinase-1 (PFK1), generating a feedback loop that couples glycolytic flux and the RAS signaling pathway. An in vivo treatment of NRAS(Q61) mutant melanomas, including patient-derived xenografts, with 2-deoxy-D-glucose (2-DG) and sorafenib effectively inhibits tumor growth. Thus, we provide evidence for NRAS-oncogene contributions to metabolic rewiring and a proof-of-principle for the treatment of NRAS(Q61)-mutated melanoma combining metabolic stress (glycolysis inhibitors) and previously approved drugs, such as sorafenib. Targeted therapeutic options for NRAS-mutant melanoma are limited. Here, the authors show that under metabolic stress NRAS-mutant melanoma cells activate a BRAF-dependent glycolysis pathway for survival, leading to improve efficacy of sorafenib when combined with glycolysis inhibitors

Implementation and first results of the KM3NeT real-time core-collapse supernova neutrino search

The KM3NeT research infrastructure is unconstruction in the Mediterranean Sea. KM3NeT will study atmospheric and astrophysical neutrinos with two multi-purpose neutrino detectors, ARCA and ORCA, primarily aimed at GeV–PeV neutrinos. Thanks to the multi-photomultiplier tube design of the digital optical modules, KM3NeT is capable of detecting the neutrino burst from a Galactic or near-Galactic core-collapse supernova. This potential is already exploitable with the first detection units deployed in the sea. This paper describes the real-time implementation of the supernova neutrino search, operating on the two KM3NeT detectors since the first months of 2019. A quasi-online astronomy analysis is introduced to study the time profile of the detected neutrinos for especially significant events. The mechanism of generation and distribution of alerts, as well as the integration into the SNEWS and SNEWS 2.0 global alert systems, are described. The approach for the follow-up of external alerts with a search for a neutrino excess in the archival data is defined. Finally, an overview of the current detector capabilities and a report after the first two years of operation are given.Acknowledgements The authors acknowledge the financial support of the funding agencies: Agence Nationale de la Recherche (contract ANR-15-CE31-0020), Centre National de la Recherche Scientifique (CNRS), Commission Européenne (FEDER fund and Marie Curie Program), Institut Universitaire de France (IUF), LabEx UnivEarthS (ANR-10-LABX-0023 and ANR-18-IDEX-0001), Paris Île-de-France Region, France; Shota Rustaveli National Science Foundation of Georgia (SRNSFG, FR-18-1268), Georgia; Deutsche Forschungsgemeinschaft (DFG), Germany; The General Secretariat of Research and Technology (GSRT), Greece; Istituto Nazionale di Fisica Nucleare (INFN), Ministero dell’Università e della Ricerca (MIUR), PRIN 2017 program (Grant NAT-NET 2017W4HA7S) Italy; Ministry of Higher Education Scientific Research and Professional Training, ICTP through Grant AF-13, Morocco; Nederlandse organisatie voor Wetenschappelijk Onderzoek (NWO), the Netherlands; The National Science Centre, Poland (2015/18/E/ST2/00758); National Authority for Scientific Research (ANCS), Romania; Ministerio de Ciencia, Innovación, Investigación y Universidades (MCIU): Programa Estatal de Generación de Conocimiento (refs. PGC2018-096663-B-C41, -A-C42, -B-C43, -B-C44) (MCIU/FEDER), Generalitat Valenciana: Prometeo (PROMETEO/2020/019), Grisolía (ref. GRISOLIA/2018/119) and GenT (refs. CIDEGENT/2018/034, /2019/043, /2020/049) programs, Junta de Andalucía (ref. A-FQM-053-UGR18), La Caixa Foundation (ref. LCF/BQ/IN17/11620019), EU: MSC program (ref. 101025085), Spain

All-sky Search for High-Energy Neutrinos from Gravitational Wave Event GW170104 with the ANTARES Neutrino Telescope

Advanced LIGO detected a significant gravitational wave signal (GW170104) originating from the coalescence of two black holes during the second observation run on January 4$^{\textrm{th}}$, 2017. An all-sky high-energy neutrino follow-up search has been made using data from the ANTARES neutrino telescope, including both upgoing and downgoing events in two separate analyses. No neutrino candidates were found within $\pm500$ s around the GW event time nor any time clustering of events over an extended time window of $\pm3$ months. The non-detection is used to constrain isotropic-equivalent high-energy neutrino emission from GW170104 to less than $\sim4\times 10^{54}$ erg for a $E^{-2}$ spectrum

The ANTARES Collaboration: Contributions to ICRC 2017 Part I: Neutrino astronomy (diffuse fluxes and point sources)

Papers on neutrino astronomy (diffuse fluxes and point sources, prepared for the 35th International Cosmic Ray Conference (ICRC 2017, Busan, South Korea) by the ANTARES Collaboratio

The ANTARES Collaboration: Contributions to ICRC 2017 Part III: Searches for dark matter and exotics, neutrino oscillations and detector calibration

Papers on the searches for dark matter and exotics, neutrino oscillations and detector calibration, prepared for the 35th International Cosmic Ray Conference (ICRC 2017, Busan, South Korea) by the ANTARES Collaboratio

The ANTARES Collaboration: Contributions to ICRC 2017 Part II: The multi-messenger program

Papers on the ANTARES multi-messenger program, prepared for the 35th International Cosmic Ray Conference (ICRC 2017, Busan, South Korea) by the ANTARES Collaboratio

Status and Recent Results of the Acoustic Neutrino Detection Test System AMADEUS

The AMADEUS system is an integral part of the ANTARES neutrino telescope in the Mediterranean Sea. The project aims at the investigation of techniques for acoustic neutrino detection in the deep sea. Installed at a depth of more than 2000m, the acoustic sensors of AMADEUS are based on piezo-ceramics elements for the broad-band recording of signals with frequencies ranging up to 125kHz. AMADEUS was completed in May 2008 and comprises six "acoustic clusters", each one holding six acoustic sensors that are arranged at distances of roughly 1m from each other. The clusters are installed with inter-spacings ranging from 15m to 340m. Acoustic data are continuously acquired and processed at a computer cluster where online filter algorithms are applied to select a high-purity sample of neutrino-like signals. 1.6 TB of data were recorded in 2008 and 3.2 TB in 2009. In order to assess the background of neutrino-like signals in the deep sea, the characteristics of ambient noise and transient signals have been investigated. In this article, the AMADEUS system will be described and recent results will be presented.Comment: 7 pages, 8 figures. Proceedings of ARENA 2010, the 4th International Workshop on Acoustic and Radio EeV Neutrino Detection Activitie

Measurement of Atmospheric Neutrino Oscillations with the ANTARES Neutrino Telescope

The data taken with the ANTARES neutrino telescope from 2007 to 2010, a total live time of 863 days, are used to measure the oscillation parameters of atmospheric neutrinos. Muon tracks are reconstructed with energies as low as 20 GeV. Neutrino oscillations will cause a suppression of vertical upgoing muon neutrinos of such energies crossing the Earth. The parameters determining the oscillation of atmospheric neutrinos are extracted by fitting the event rate as a function of the ratio of the estimated neutrino energy and reconstructed flight path through the Earth. Measurement contours of the oscillation parameters in a two-flavour approximation are derived. Assuming maximum mixing, a mass difference of $\Delta m_{32}^2=(3.1\pm 0.9)\cdot 10^{-3}$ eV$^2$ is obtained, in good agreement with the world average value.Comment: 9 pages, 5 figure