41 research outputs found

    Development of NASH in Obese Mice is Confounded by Adipose Tissue Increase in Inflammatory NOV and Oxidative Stress

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    Aim. Nonalcoholic steatohepatitis (NASH) is the consequence of insulin resistance, fatty acid accumulation, oxidative stress, and lipotoxicity.We hypothesize that an increase in the inflammatory adipokine NOV decreases antioxidant Heme Oxygenase 1 (HO- 1) levels in adipose and hepatic tissue, resulting in the development of NASH in obese mice. Methods. Mice were fed a high fat diet (HFD) and obese animals were administered an HO-1 inducer with or without an inhibitor of HO activity to examine levels of adipose-derived NOV and possible links between increased synthesis of inflammatory adipokines and hepatic pathology. Results. NASH mice displayed decreased HO-1 levels and HO activity, increased levels of hepatic heme, NOV, MMP2, hepcidin, and increased NAS scores and hepatic fibrosis. IncreasedHO-1 levels are associated with a decrease in NOV, improved hepatic NAS score, ameliorated fibrosis, and increases in mitochondrial integrity and insulin receptor phosphorylation. Adipose tissue function is disrupted in obesity as evidenced by an increase in proinflammatory molecules such as NOV and a decrease in adiponectin. Importantly, increased HO-1 levels are associated with a decrease of NOV, increased adiponectin levels, and increased levels of thermogenic and mitochondrial signaling associated genes in adipose tissue. Conclusions.These results suggest that the metabolic abnormalities in NASH are driven by decreased levels of hepatic HO-1 that is associated with an increase in the adipose-derived proinflammatory adipokine NOV in our obese mouse model of NASH. Concurrently, induction of HO-1 provides protection against insulin resistance as seen by increased insulin receptor phosphorylation. Pharmacological increases in HO-1 associated with decreases in NOV may offer a potential therapeutic approach in preventing fibrosis, mitochondrial dysfunction, and the development of NASH

    The Control of Zoonotic Soil-Transmitted Helminthoses Using Saprophytic Fungi

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    Soil-transmitted helminths (STHs) are parasites transmitted through contact with soil contaminated with their infective eggs/larvae. People are infected by exposure to human-specific species or animal species (zoonotic agents). Fecal samples containing eggs of Ascaris suum or Lemurostrongylus sp. were sprayed with spores of the soil saprophytic filamentous fungi Clonostachys rosea (CR) and Trichoderma atrobrunneum (TA). The antagonistic effect was assessed by estimating the viability of eggs and their developmental rate. Compared to the controls (unexposed to fungi), the viability of the eggs of A. suum was halved in CR and decreased by two thirds in TA, while the viability of the eggs of Lemurostrongylus sp. was reduced by one quarter and one third in CR and TA treatments, respectively. The Soil Contamination Index (SCI), defined as the viable eggs that attained the infective stage, reached the highest percentages for A. suum in the controls after four weeks (66%), with 21% in CL and 11% in TA. For Lemurostrongylus sp., the values were 80%, 49%, and 41% for control, CR and TA treatments, respectively. We concluded that spreading spores of C. rosea or T. atrobrunneum directly onto the feces of animal species represents a sustainable approach under a One Health context to potentially reduce the risk of zoonotic STHs in humansThis research was funded by the Research Projects CTM2015-65954-R and RYC-2016-21407 (Ministerio de Economía y Competitividad, Spain; FEDER), and ED431F 2018/03 (Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia, Spain). María Sol Arias Vázquez is recipient of a Ramón y Cajal (Ministerio de Economía y Competitividad, Spain) contractS

    Raster zur Evaluation von Software f√ľr das Sprachenlernen

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    Die informelle Arbeitsgruppe "Medial gest√ľtztes, selbstorganisiertes Lernen" im Bereich Fremdsprachenunterricht trifft sich seit rund drei Jahren regelm√§ssig (unter dem Namen "Nachtclub") und besch√§ftigt sich mit medial unterst√ľtztem Sprachenlernen. Die Arbeitsgruppe ist breit zusammengesetzt: l√§nder√ľbergreifend (Deutschland, √Ėsterreich, Schweiz), zielgruppen√ľbergreifend (Erwachsenenbildung und Universit√§t) und sprachen√ľbergreifend (Software f√ľr Deutsch, Englisch, Franz√∂sisch usw.). Das gemeinsame Ziel des "Nachtclub" ist es, Kriterien f√ľr die Beurteilung von mediengest√ľtzten Angeboten (Lernsoftware, Webseiten) f√ľr das Lernen von Fremdsprachen zu entwickeln und auf dieser Grundlage unabh√§ngige Rezensionen zu erstellen. Die Beurteilungen werden in der Form einer Online-Datenbank der √Ėffentlichkeit zug√§nglich gemacht und sollen als Nachschlagewerk und Entscheidungshilfe f√ľr Lehrpersonen, LernberaterInnen, MediathekarInnen usw. dienen. Vorgesehen ist die Publikation der Rezensionen unter der Internetadresse www.nachtclub.org. Dort findet man auch das leere Raster in elektronischer Form auf Deutsch, Franz√∂sisch und Englisch (Winword-Datei / PDF-Datei) sowie Beispiele von Rezensionen, die mit dem Raster erstellt worden sind. (Diese Dateien sind auch von hier abzurufen

    ACS Nano

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    open access articleUnderstanding the effect of variability in the interaction of individual cells with nanoparticles on the overall response of the cell population to a nanoagent is a fundamental challenge in bionanotechnology. Here, we show that the technique of time-resolved, high-throughput microscopy can be used in this endeavor. Mass measurement with single-cell resolution provides statistically robust assessments of cell heterogeneity, while the addition of a temporal element allows assessment of separate processes leading to deconvolution of the effects of particle supply and biological response. We provide a specific demonstration of the approach, in vitro, through time-resolved measurement of fibroblast cell (HFF-1) death caused by exposure to cationic nanoparticles. The results show that heterogeneity in cell area is the major source of variability with area-dependent nanoparticle capture rates determining the time of cell death and hence the form of the exposure‚Äďresponse characteristic. Moreover, due to the particulate nature of the nanoparticle suspension, there is a reduction in the particle concentration over the course of the experiment, eventually causing saturation in the level of measured biological outcome. A generalized mathematical description of the system is proposed, based on a simple model of particle depletion from a finite supply reservoir. This captures the essential aspects of the nanoparticle‚Äďcell interaction dynamics and accurately predicts the population exposure‚Äďresponse curves from individual cell heterogeneity distributions

    Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

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    The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

    Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

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    We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file

    Measurement of the cosmic ray spectrum above 4√ó10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

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    A measurement of the cosmic-ray spectrum for energies exceeding 4√ó10184{\times}10^{18} eV is presented, which is based on the analysis of showers with zenith angles greater than 60‚ąė60^{\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√ó10185.3{\times}10^{18} eV, the "ankle", the flux can be described by a power law E‚ąíő≥E^{-\gamma} with index ő≥=2.70¬Ī0.02‚ÄČ(stat)¬Ī0.1‚ÄČ(sys)\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)} followed by a smooth suppression region. For the energy (EsE_\text{s}) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find Es=(5.12¬Ī0.25‚ÄČ(stat)‚ąí1.2+1.0‚ÄČ(sys))√ó1019E_\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

    TET1 is a tumor suppressor of hematopoietic malignancy

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    The methylcytosine dioxygenase TET1 (‚Äėten-eleven translocation 1‚Äô) is an important regulator of 5-hydroxymethylcytosine (5hmC) in embryonic stem cells. The diminished expression of TET proteins and loss of 5hmC in many tumors suggests a critical role for the maintenance of this epigenetic modification. Here we found that deletion of Tet1 promoted the development of B cell lymphoma in mice. TET1 was required for maintenance of the normal abundance and distribution of 5hmC, which prevented hypermethylation of DNA, and for regulation of the B cell lineage and of genes encoding molecules involved in chromosome maintenance and DNA repair. Whole-exome sequencing of TET1-deficient tumors revealed mutations frequently found in non-Hodgkin B cell lymphoma (B-NHL), in which TET1 was hypermethylated and transcriptionally silenced. Our findings provide in vivo evidence of a function for TET1 as a tumor suppressor of hematopoietic malignancy.National Institutes of Health (U.S.) (5RO1HD045022)National Institutes of Health (U.S.) (5R37CA084198
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