FOXO1 represses PPARα-Mediated induction of FGF21 gene expression

Fibroblast growth factor 21 (FGF21) has emerged as a metabolic regulator that exerts potent anti-diabetic and lipid-lowering effects in animal models of obesity and type 2 diabetes, showing a protective role in fatty liver disease and hepatocellular carcinoma progression. Hepatic expression of FGF21 is regulated by PPARa and is induced by fasting. Ablation of FoxO1 in liver has been shown to increase FGF21 expression in hyperglycemia. To better understand the role of FOXO1 in the regulation of FGF21 expression we have modified HepG2 human hepatoma cells to overexpress FoxO1 and PPARa. Here we show that FoxO1 represses PPARa-mediated FGF21 induction, and that the repression acts on the FGF21 gene promoter without affecting other PPARa target genes. Additionally, we demonstrate that FoxO1 physically interacts with PPARa and that FoxO1/3/4 depletion in skeletal muscle contributes to increased Fgf21 tissue levels. Taken together, these data indicate that FOXO1 is a PPARa-interacting protein that antagonizes PPARa activity on the FGF21 promoter. Because other PPARa target genes remained unaffected, these results suggest a highly specific mechanism implicated in FGF21 regulation. We conclude that FGF21 can be specifically modulated by FOXO1 in a PPARa-dependent manner. (c) 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).info:eu-repo/semantics/publishedVersio

Satellites to Seafloor: Toward Fully Autonomous Ocean Sampling

Future ocean observing systems will rely heavily on autonomous vehicles to achieve the persistent and heterogeneous measurements needed to understand the ocean’s impact on the climate system. The day-to-day maintenance of these arrays will become increasingly challenging if significant human resources, such as manual piloting, are required. For this reason, techniques need to be developed that permit autonomous determination of sampling directives based on science goals and responses to in situ, remote-sensing, and model-derived information. Techniques that can accommodate large arrays of assets and permit sustained observations of rapidly evolving ocean properties are especially needed for capturing interactions between physical circulation and biogeochemical cycling. Here we document the first field program of the Satellites to Seafloor project, designed to enable a closed loop of numerical model prediction, vehicle path-planning, in situ path implementation, data collection, and data assimilation for future model predictions. We present results from the first of two field programs carried out in Monterey Bay, California, over a period of three months in 2016. While relatively modest in scope, this approach provides a step toward an observing array that makes use of multiple information streams to update and improve sampling strategies without human intervention

Satellites to seafloor : toward fully autonomous ocean sampling

Author Posting. © The Oceanography Society, 2017. This article is posted here by permission of The Oceanography Society for personal use, not for redistribution. The definitive version was published in Oceanography 30, no. 2 (2017): 160–168, doi:10.5670/oceanog.2017.238.Future ocean observing systems will rely heavily on autonomous vehicles to achieve the persistent and heterogeneous measurements needed to understand the ocean’s impact on the climate system. The day-to-day maintenance of these arrays will become increasingly challenging if significant human resources, such as manual piloting, are required. For this reason, techniques need to be developed that permit autonomous determination of sampling directives based on science goals and responses to in situ, remote-sensing, and model-derived information. Techniques that can accommodate large arrays of assets and permit sustained observations of rapidly evolving ocean properties are especially needed for capturing interactions between physical circulation and biogeochemical cycling. Here we document the first field program of the Satellites to Seafloor project, designed to enable a closed loop of numerical model prediction, vehicle path-planning, in situ path implementation, data collection, and data assimilation for future model predictions. We present results from the first of two field programs carried out in Monterey Bay, California, over a period of three months in 2016. While relatively modest in scope, this approach provides a step toward an observing array that makes use of multiple information streams to update and improve sampling strategies without human intervention.This work is funded by the Keck Institute for Space Studies (generously supported by the W.M. Keck Foundation) through the project “Science-driven Autonomous and Heterogeneous Robotic Networks: A Vision for Future Ocean Observation

Flaring Behavior of the Quasar 3C~454.3 across the Electromagnetic Spectrum

We analyze the behavior of the parsec-scale jet of the quasar 3C~454.3 during pronounced flaring activity in 2005-2008. Three major disturbances propagated down the jet along different trajectories with Lorentz factors $\Gamma>$10. The disturbances show a clear connection with millimeter-wave outbursts, in 2005 May/June, 2007 July, and 2007 December. High-amplitude optical events in the $R$-band light curve precede peaks of the millimeter-wave outbursts by 15-50 days. Each optical outburst is accompanied by an increase in X-ray activity. We associate the optical outbursts with propagation of the superluminal knots and derive the location of sites of energy dissipation in the form of radiation. The most prominent and long-lasting of these, in 2005 May, occurred closer to the black hole, while the outbursts with a shorter duration in 2005 Autumn and in 2007 might be connected with the passage of a disturbance through the millimeter-wave core of the jet. The optical outbursts, which coincide with the passage of superluminal radio knots through the core, are accompanied by systematic rotation of the position angle of optical linear polarization. Such rotation appears to be a common feature during the early stages of flares in blazars. We find correlations between optical variations and those at X-ray and $\gamma$-ray energies. We conclude that the emergence of a superluminal knot from the core yields a series of optical and high-energy outbursts, and that the mm-wave core lies at the end of the jet's acceleration and collimation zone.Comment: 57 pages, 23 figures, 8 tables (submitted to ApJ

Report of the Scientific Council Meeting 01 -15 June 2017

Council met at the Sobey Building, Saint Mary’s University, Halifax, NS, Canada, during 01 – 15 June 2017, to consider the various matters in its Agenda. Representatives attended from Canada, Denmark (in respect of Faroe Islands and Greenland), the European Union (France, Germany (via WebEx), Portugal, Spain, the United Kingdom and the European Commission), Japan, the Russian Federation and the United States of America. Observers from the Ecology Action Centre and Dalhousie University were also present. The Executive Secretary, Scientific Council Coordinator and other members of the Secretariat were in attendance. The Executive Committee met prior to the opening session of the Council to discuss the provisional agenda and plan of work. The Council was called to order at 1000 hours on 01 June 2017. The provisional agenda was adopted with modification. The Scientific Council Coordinator was appointed the rapporteur. The Council was informed that the meeting was quorate and authorization had been received by the Executive Secretary for proxy votes from the European Union, Denmark (in respect of Faroe Islands and Greenland), Iceland, Japan, Republic of Korea, and Norway. The opening session was adjourned at 1200 hours on 01 June 2017. Several sessions were held throughout the course of the meeting to deal with specific items on the agenda. The Council considered adopted the STACFEN report on 8 June 2017, and the STACPUB, STACFIS and STACREC reports on 15 June 2017. The concluding session was called to order at 0830 hours on 15 June 2017. The Council considered and adopted the report the Scientific Council Report of this meeting of 01 -15 June 2017. The Chair received approval to leave the report in draft form for about two weeks to allow for minor editing and proof-reading on the usual strict understanding there would be no substantive changes. The meeting was adjourned at 1430 hours on 15 June 2017. The Reports of the Standing Committees as adopted by the Council are appended as follows: Appendix I - Report of the Standing Committee on Fisheries Environment (STACFEN), Appendix II - Report of Standing Committee on Publications (STACPUB), Appendix III - Report of Standing Committee on Research Coordination (STACREC), and Appendix IV - Report of Standing Committee on Fisheries Science (STACFIS). The Agenda, List of Research (SCR) and Summary (SCS) Documents, and List of Representatives, Advisers and Experts, are given in Appendix V-VII. The Council’s considerations on the Standing Committee Reports, and other matters addressed by the Council follow in Sections II-XV

Probing the Inner Jet of the Quasar PKS 1510-089 with Multi-waveband Monitoring during Strong Gamma-ray Activity

We present results from monitoring the multi-waveband flux, linear polarization, and parsec-scale structure of the quasar PKS 1510-089, concentrating on eight major gamma-ray flares that occurred during the interval 2009.0-2009.5. The gamma-ray peaks were essentially simultaneous with maxima at optical wavelengths, although the flux ratio of the two wavebands varied by an order of magnitude. The optical polarization vector rotated by 720 degrees during a 5-day period encompassing six of these flares. This culminated in a very bright, roughly 1 day, optical and gamma-ray flare as a bright knot of emission passed through the highest-intensity, stationary feature (the "core") seen in 43 GHz Very Long Baseline Array images. The knot continued to propagate down the jet at an apparent speed of 22c and emit strongly at gamma-ray energies as a months-long X-ray/radio outburst intensified. We interpret these events as the result of the knot following a spiral path through a mainly toroidal magnetic field pattern in the acceleration and collimation zone of the jet, after which it passes through a standing shock in the 43 GHz core and then continues downstream. In this picture, the rapid gamma-ray flares result from scattering of infrared seed photons from a relatively slow sheath of the jet as well as from optical synchrotron radiation in the faster spine. The 2006-2009.7 radio and X-ray flux variations are correlated at very high significance; we conclude that the X-rays are mainly from inverse Compton scattering of infrared seed photons by 20-40 MeV electrons.Comment: 10 pages of text + 5 figures, to be published in Astrophysical Journal Letters in 201

On the Location of the Gamma-ray Emission in the 2008 Outburst in the BL Lacertae Object AO 0235+164 through Observations across the Electromagnetic Spectrum

We present observations of a major outburst at centimeter, millimeter, optical, X-ray, and gamma-ray wavelengths of the BL Lacertae object AO 0235+164. We analyze the timing of multi-waveband variations in the flux and linear polarization, as well as changes in Very Long Baseline Array (VLBA) images at 7mm with 0.15 milliarcsecond resolution. The association of the events at different wavebands is confirmed at high statistical significance by probability arguments and Monte-Carlo simulations. A series of sharp peaks in optical linear polarization, as well as a pronounced maximum in the 7 mm polarization of a superluminal jet knot, indicate rapid fluctuations in the degree of ordering of the magnetic field. These results lead us to conclude that the outburst occurred in the jet both in the quasi-stationary "core" and in the superluminal knot, both parsecs downstream of the supermassive black hole. We interpret the outburst as a consequence of the propagation of a disturbance, elongated along the line of sight by light-travel time delays, that passes through a standing recollimation shock in the core and propagates down the jet to create the superluminal knot. The multi-wavelength light curves vary together on long time-scales (months/years), but the correspondence is poorer on shorter time-scales. This, as well as the variability of the polarization and the dual location of the outburst, agrees with the expectations of a multi-zone emission model in which turbulence plays a major role in modulating the synchrotron and inverse Compton fluxes.Comment: Accepted for Publication in the Astrophysical Journal Letters. 7 pages (including 5 figures). Minor corrections with regard to previous version, as proposed by the refere