Inter-individual Variability for High Fat Diet Consumption in Inbred C57BL/6 Mice

Since inbred C57BL/6 mice are known to show inter-individual phenotypic variability for some traits, we tested the hypothesis that inbred C57BL/6 mice display a different tendency to consume a high fat (HF) diet. For this purpose, we used a compilation of HF intake data from an experimental protocol in which satiated mice were exposed to a HF pellet every morning for 2-h over 4 consecutive days. We found that mice displayed a large degree of variability in HF intake. Since day 1 HF intake significantly correlated with HF intake in successive days, we applied a hierarchical clustering algorithm on HF intake measurements in days 2, 3, and 4 in order to classify mice into “low” or “high” HF intake groups. “Low” HF intake group showed a day 1 HF intake similar to that seen in mice exposed to regular chow, while “high” HF intake group showed a higher day 1 HF intake as compared to “low” HF intake group. Both groups of mice increased HF consumption over the successive days, but “high” HF intake group always displayed a higher HF consumption than the “low” HF intake group. As compared to “low” HF intake group, “high” HF intake group showed a higher number of dopamine neurons positive for c-Fos in the VTA after the last event of HF intake. Thus, inbred C57BL/6 mice show inter-individual variability for HF intake and such feature may be linked to a different response to the rewarding properties of the HF diet

LALINET: The First Latin American–Born Regional Atmospheric Observational Network

Sustained and coordinated efforts of lidar teams in Latin America at the beginning of the 21st century have built LALINET (Latin American Lidar NETwork), the only observational network in Latin America created by the agreement and commitment of Latin American scientists. They worked with limited funding but an abundance of enthusiasm and commitment toward their joint goal. Before LALINET, there were a few pioneering lidar stations operating in Latin America, described briefly here. Bi-annual Latin American Lidar Workshops, held from 2001 to the present, supported both the development of the regional lidar community and LALINET. At those meetings, lidar researchers from Latin America meet to conduct regular scientific and technical exchanges among themselves and with experts from the rest of the world. Regional and international scientific cooperation has played an important role for the development of both the individual teams and the network. The current LALINET status and activities are described, emphasizing the processes of standardization of the measurements, methodologies, calibration protocols, and retrieval algorithms. Failures and successes achieved in the buildup of LALINET are presented. In addition, the first LALINET joint measurement campaign and a set of aerosol extinction profile measurements obtained from the aerosol plume produced by the Calbuco volcano eruption on April 22, 2015, are described and discussed.Fil: Antuña Marrero, Juan Carlos. Centro Meteorológico de Camagüey; CubaFil: Landulfo, Eduardo. Instituto de Pesquisas Energéticas e Nucleares; BrasilFil: Estevan, René. Centro Meteorológico de Camagüey; CubaFil: Barja, Boris. Centro Meteorológico de Camagüey; Cuba. Universidade de Sao Paulo; BrasilFil: Robock, Alan. State University of New Jersey; Estados UnidosFil: Wolfram, Elian Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Científicas y Técnicas para la Defensa. Centro de Investigación en Láseres y Aplicaciones; ArgentinaFil: Ristori, Pablo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Científicas y Técnicas para la Defensa. Centro de Investigación en Láseres y Aplicaciones; ArgentinaFil: Clemesha, Barclay. Upper Atmosphere Research Group; BrasilFil: Zaratti, Francesco. Universidad Mayor de San Andrés; BoliviaFil: Forno, Ricardo. Universidad Mayor de San Andrés; BoliviaFil: Armandillo, Errico. ESTEC; Países BajosFil: Bastidas, Álvaro E.. Universidad Nacional de Colombia. Sede Medellin; ColombiaFil: de Frutos Baraja, Ángel Máximo. Universidad de Valladolid; EspañaFil: Whiteman, David N.. National Aeronautics and Space Administration; Estados UnidosFil: Quel, Eduardo Jaime. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Científicas y Técnicas para la Defensa. Centro de Investigación en Láseres y Aplicaciones; ArgentinaFil: Barbosa, Henrique M. J.. Universidade de Sao Paulo; BrasilFil: Lopes, Fabio. Comissao Nacional de Energia Nuclear. Centro de Lasers e Aplicacoes. Instituto de Pesquisas Energeticas e Nucleares.; BrasilFil: Montilla-Rosero, Elena. Universidad de Concepción; Chile. Universidad Escuela de Administración, Finanzas e Instituto Tecnológico; ColombiaFil: Guerrero Rascado, Juan L.. Comissao Nacional de Energia Nuclear. Centro de Lasers e Aplicacoes. Instituto de Pesquisas Energeticas e Nucleares.; Brasil. Universidad de Granada; Españ

A population of gamma-ray emitting globular clusters seen with the Fermi Large Area Telescope

Globular clusters with their large populations of millisecond pulsars (MSPs) are believed to be potential emitters of high-energy gamma-ray emission. Our goal is to constrain the millisecond pulsar populations in globular clusters from analysis of gamma-ray observations. We use 546 days of continuous sky-survey observations obtained with the Large Area Telescope aboard the Fermi Gamma-ray Space Telescope to study the gamma-ray emission towards 13 globular clusters. Steady point-like high-energy gamma-ray emission has been significantly detected towards 8 globular clusters. Five of them (47 Tucanae, Omega Cen, NGC 6388, Terzan 5, and M 28) show hard spectral power indices $(0.7 < \Gamma <1.4)$ and clear evidence for an exponential cut-off in the range 1.0-2.6 GeV, which is the characteristic signature of magnetospheric emission from MSPs. Three of them (M 62, NGC 6440 and NGC 6652) also show hard spectral indices $(1.0 < \Gamma < 1.7)$, however the presence of an exponential cut-off can not be unambiguously established. Three of them (Omega Cen, NGC 6388, NGC 6652) have no known radio or X-ray MSPs yet still exhibit MSP spectral properties. From the observed gamma-ray luminosities, we estimate the total number of MSPs that is expected to be present in these globular clusters. We show that our estimates of the MSP population correlate with the stellar encounter rate and we estimate 2600-4700 MSPs in Galactic globular clusters, commensurate with previous estimates. The observation of high-energy gamma-ray emission from a globular cluster thus provides a reliable independent method to assess their millisecond pulsar populations that can be used to make constraints on the original neutron star X-ray binary population, essential for understanding the importance of binary systems in slowing the inevitable core collapse of globular clusters.Comment: Accepted for publication in A&A. Corresponding authors: J. Kn\"odlseder, N. Webb, B. Pancraz

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Safety and efficacy of atezolizumab in patients with autoimmune disease: subgroup analysis of the SAUL study in locally advanced/metastatic urinary tract carcinoma

Aim Patients with pre-existing autoimmune disease (AID) are typically excluded from clinical trials of immune checkpoint inhibitors, and there are limited data on outcomes in this population. The single-arm international SAUL study of atezolizumab enrolled a broader ‘real-world’ patient population. We present outcomes in patients with a history of AID. Methods Patients with locally advanced/metastatic urinary tract carcinoma received atezolizumab 1200 mg every 3 weeks until loss of clinical benefit or unacceptable toxicity. The primary end-point was safety. Overall survival (OS) was a secondary end-point. Subgroup analyses of AID patients were prespecified. Results Thirty-five of 997 treated patients had AID at baseline, most commonly psoriasis ( n = 15). Compared with non-AID patients, AID patients experienced numerically more adverse events (AEs) of special interest (46% versus 30%; grade ≥3 14% versus 6%) and treatment-related grade 3/4 AEs (26% versus 12%), but without relevant increases in treatment-related deaths (0% versus 1%) or AEs necessitating treatment discontinuation (9% versus 6%). Pre-existing AID worsened in four patients (11%; two flares in two patients); three of the six flares resolved, one was resolving, and two were unresolved. Efficacy was similar in AID and non-AID patients (median OS, 8.2 versus 8.8 months, respectively; median progression-free survival, 4.4 versus 2.2 months; disease control rate, 51% versus 39%). Conclusions In 35 atezolizumab-treated patients with pre-existing AID, incidences of special- interest and treatment-related AEs appeared acceptable. AEs were manageable, rarely requiring atezolizumab discontinuation. Treating these patients requires caution, but pre-existing AID does not preclude atezolizumab therapy

Storm impacts on phytoplankton community dynamics in lakes

In many regions across the globe, extreme weather events, such as storms, have increased in frequency, intensity and duration. Ecological theory predicts that such extreme events should have large impacts on ecosystem structure and function. For lake ecosystems, high winds and rainfall associated with storms are linked by short term runoff events from catchments and physical mixing of the water column. Although we have a well-developed understanding of how such wind and precipitation events alter lake physical processes, our mechanistic understanding of how these short-term disturbances 48 translate from physical forcing to changes in phytoplankton communities is poor. Here, we provide a conceptual model that identifies how key storm features (i.e., the frequency, intensity, and duration of wind and precipitation) interact with attributes of lakes and their watersheds to generate changes in a lake’s physical and chemical environment and subsequently phytoplankton community structure and dynamics. We summarize the current understanding of storm-phytoplankton dynamics, identify knowledge gaps with a systematic review of the literature, and suggest future research directions by generating testable hypotheses across a global gradient of lake types and environmental conditions.Fil: Stockwell, Jason D.. University of Vermont; Estados UnidosFil: Adrian, Rita. Leibniz Institute of Freshwater Ecology and Inland Fisheries; AlemaniaFil: Andersen, Mikkel. Dundalk Institute of Technology; IrlandaFil: Anneville, Orlane. Institut National de la Recherche Agronomique; FranciaFil: Bhattacharya, Ruchi. University of Missouri; Estados UnidosFil: Burns, Wilton G.. University of Vermont; Estados UnidosFil: Carey, Cayelan C.. Virginia Tech University; Estados UnidosFil: Carvalho, Laurence. Freshwater Restoration & Sustainability Group; Reino UnidoFil: Chang, ChunWei. National Taiwan University; República de ChinaFil: De Senerpont Domis, Lisette N.. Netherlands Institute of Ecology; Países BajosFil: Doubek, Jonathan P.. University of Vermont; Estados UnidosFil: Dur, Gaël. Shizuoka University; JapónFil: Frassl, Marieke A.. Griffith University; AustraliaFil: Gessner, Mark O.. Leibniz Institute of Freshwater Ecology and Inland Fisheries; AlemaniaFil: Hejzlar, Josef. Biology Centre of the Czech Academy of Sciences; República ChecaFil: Ibelings, Bas W.. University of Geneva; SuizaFil: Janatian, Nasim. Estonian University of Life Sciences; EstoniaFil: Kpodonu, Alfred T. N. K.. City University of New York; Estados UnidosFil: Lajeunesse, Marc J.. University of South Florida; Estados UnidosFil: Lewandowska, Aleksandra M.. Tvarminne Zoological Station; FinlandiaFil: Llames, Maria Eugenia del Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Matsuzaki, Shin-ichiro S.. National Institute for Environmental Studies; JapónFil: Nodine, Emily R.. Rollins College; Estados UnidosFil: Nõges, Peeter. Estonian University of Life Sciences; EstoniaFil: Park, Ho-Dong. Shinshu University; JapónFil: Patil, Vijay P.. US Geological Survey; Estados UnidosFil: Pomati, Francesco. Swiss Federal Institute of Water Science and Technology; SuizaFil: Rimmer, Alon. Kinneret Limnological Laboratory; IsraelFil: Rinke, Karsten. Helmholtz-Centre for Environmental Research; AlemaniaFil: Rudstam, Lars G.. Cornell University; Estados UnidosFil: Rusak, James A.. Ontario Ministry of the Environment and Climate Change; CanadáFil: Salmaso, Nico. Research and Innovation Centre - Fondazione Mach; ItaliaFil: Schmitt, François. Laboratoire d’Océanologie et de Géosciences; FranciaFil: Seltmann, Christian T.. Dundalk Institute of Technology; IrlandaFil: Souissi, Sami. Universite Lille; FranciaFil: Straile, Dietmar. University of Konstanz; AlemaniaFil: Thackeray, Stephen J.. Lancaster Environment Centre; Reino UnidoFil: Thiery, Wim. Vrije Unviversiteit Brussel; Bélgica. Institute for Atmospheric and Climate Science; SuizaFil: Urrutia Cordero, Pablo. Uppsala University; SueciaFil: Venail, Patrick. Universidad de Ginebra; SuizaFil: Verburg, Piet. 8National Institute of Water and Atmospheric Research; Nueva ZelandaFil: Williamson, Tanner J.. Miami University; Estados UnidosFil: Wilson, Harriet L.. Dundalk Institute of Technology; IrlandaFil: Zohary, Tamar. Israel Oceanographic & Limnological Research; IsraelGLEON 20: All Hands' MeetingRottnest IslandAustraliaUniversity of Western AustraliaUniversity of AdelaideGlobal Lake Ecological Observatory Networ

Storm impacts on phytoplankton community dynamics in lakes

In many regions across the globe, extreme weather events such as storms have increased in frequency, intensity, and duration due to climate change. Ecological theory predicts that such extreme events should have large impacts on ecosystem structure and function. High winds and precipitation associated with storms can affect lakes via short-term runoff events from watersheds and physical mixing of the water column. In addition, lakes connected to rivers and streams will also experience flushing due to high flow rates. Although we have a well-developed understanding of how wind and precipitation events can alter lake physical processes and some aspects of biogeochemical cycling, our mechanistic understanding of the emergent responses of phytoplankton communities is poor. Here we provide a comprehensive synthesis that identifies how storms interact with lake and watershed attributes and their antecedent conditions to generate changes in lake physical and chemical environments. Such changes can restructure phytoplankton communities and their dynamics, as well as result in altered ecological function (e.g., carbon, nutrient and energy cycling) in the short- and long-term. We summarize the current understanding of storm-induced phytoplankton dynamics, identify knowledge gaps with a systematic review of the literature, and suggest future research directions across a gradient of lake types and environmental conditions.Peer reviewe

Genome-Wide Association Study of Multiple Sclerosis Confirms a Novel Locus at 5p13.1

Multiple Sclerosis (MS) is the most common progressive and disabling neurological condition affecting young adults in the world today. From a genetic point of view, MS is a complex disorder resulting from the combination of genetic and non-genetic factors. We aimed to identify previously unidentified loci conducting a new GWAS of Multiple Sclerosis (MS) in a sample of 296 MS cases and 801 controls from the Spanish population. Meta-analysis of our data in combination with previous GWAS was done. A total of 17 GWAS-significant SNPs, corresponding to three different loci were identified:HLA, IL2RA, and 5p13.1. All three have been previously reported as GWAS-significant. We confirmed our observation in 5p13.1 for rs9292777 using two additional independent Spanish samples to make a total of 4912 MS cases and 7498 controls (ORpooled = 0.84; 95%CI: 0.80–0.89; p = 1.36×10-9). This SNP differs from the one reported within this locus in a recent GWAS. Although it is unclear whether both signals are tapping the same genetic association, it seems clear that this locus plays an important role in the pathogenesis of MS

Gamma-ray and radio properties of six pulsars detected by the fermi large area telescope

We report the detection of pulsed γ-rays for PSRs J0631+1036, J0659+1414, J0742-2822, J1420-6048, J1509-5850, and J1718-3825 using the Large Area Telescope on board the Fermi Gamma-ray Space Telescope (formerly known as GLAST). Although these six pulsars are diverse in terms of their spin parameters, they share an important feature: their γ-ray light curves are (at least given the current count statistics) single peaked. For two pulsars, there are hints for a double-peaked structure in the light curves. The shapes of the observed light curves of this group of pulsars are discussed in the light of models for which the emission originates from high up in the magnetosphere. The observed phases of the γ-ray light curves are, in general, consistent with those predicted by high-altitude models, although we speculate that the γ-ray emission of PSR J0659+1414, possibly featuring the softest spectrum of all Fermi pulsars coupled with a very low efficiency, arises from relatively low down in the magnetosphere. High-quality radio polarization data are available showing that all but one have a high degree of linear polarization. This allows us to place some constraints on the viewing geometry and aids the comparison of the γ-ray light curves with high-energy beam models