Mechanisms of Perivascular Adipose Tissue Dysfunction in Obesity

Most blood vessels are surrounded by adipose tissue. Similarly to the adventitia, perivascular adipose tissue (PVAT) was considered only as a passive structural support for the vasculature, and it was routinely removed for isolated blood vessel studies. In 1991, Soltis and Cassis demonstrated for the first time that PVAT reduced contractions to noradrenaline in rat aorta. Since then, an important number of adipocyte-derived factors with physiological and pathophysiological paracrine vasoactive effects have been identified. PVAT undergoes structural and functional changes in obesity. During early diet-induced obesity, an adaptative overproduction of vasodilator factors occurs in PVAT, probably aimed at protecting vascular function. However, in established obesity, PVAT loses its anticontractile properties by an increase of contractile, oxidative, and inflammatory factors, leading to endothelial dysfunction and vascular disease. The aim of this review is to focus on PVAT dysfunction mechanisms in obesity

Anticontractile Effect of Perivascular Adipose Tissue and Leptin are Reduced in Hypertension

Leptin causes vasodilatation both by endothelium-dependent and -independent mechanisms. Leptin is synthesized by perivascular adipose tissue (PVAT). The hypothesis of this study is that a decrease of leptin production in PVAT of spontaneously hypertensive rats (SHR) might contribute to a diminished paracrine anticontractile effect of the hormone. We have determined in aorta from Wistar-Kyoto (WKY) and SHR (i) leptin mRNA and protein levels in PVAT, (ii) the effect of leptin and PVAT on contractile responses, and (iii) leptin-induced relaxation and nitric oxide (NO) production. Leptin mRNA and protein expression were significantly lower in PVAT from SHR. Concentration-response curves to angiotensin II were significantly blunted in presence of PVAT as well as by exogenous leptin (10−9 M) only in WKY. This anticontractile effect was endothelium-dependent. Vasodilatation induced by leptin was smaller in SHR than in WKY, and was also endothelium-dependent. Moreover, release of endothelial NO in response to acute leptin was higher in WKY compared to SHR, but completely abolished in the absence of endothelium. In conclusion, the reduced anticontractile effect of PVAT in SHR might be attributed to a reduced PVAT-derived leptin and to an abrogated effect of leptin on endothelial NO release probably due to an impaired activation of endothelial NO synthase

Look-alike humans identified by facial recognition algorithms show genetic similarities

The human face is one of the most visible features of our unique identity as individuals. Interestingly, monozygotic twins share almost identical facial traits and the same DNA sequence but could exhibit differences in other biometrical parameters. The expansion of the world wide web and the possibility to exchange pictures of humans across the planet has increased the number of people identified online as virtual twins or doubles that are not family related. Herein, we have characterized in detail a set of “look-alike” humans, defined by facial recognition algorithms, for their multiomics landscape. We report that these individuals share similar genotypes and differ in their DNA methylation and microbiome landscape. These results not only provide insights about the genetics that determine our face but also might have implications for the establishment of other human anthropometric properties and even personality characteristics.This work was funded by the governments of Catalonia (2017SGR1080) and Spain (RTI2018-094049-B-I00, SAF2014-55000, and TIN2017-90124-P) and the Cellex Foundation

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

The unprecedented 2017-2018 stratospheric smoke event : Decay phase and aerosol properties observed with the EARLINET

© Author(s) 2019. This open access work is distributed under the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/).Six months of stratospheric aerosol observations with the European Aerosol Research Lidar Network (EARLINET) from August 2017 to January 2018 are presented. The decay phase of an unprecedented, record-breaking stratospheric perturbation caused by wildfire smoke is reported and discussed in terms of geometrical, optical, and microphysical aerosol properties. Enormous amounts of smoke were injected into the upper troposphere and lower stratosphere over fire areas in western Canada on 12 August 2017 during strong thunderstorm-pyrocumulonimbus activity. The stratospheric fire plumes spread over the entire Northern Hemisphere in the following weeks and months. Twenty-eight European lidar stations from northern Norway to southern Portugal and the eastern Mediterranean monitored the strong stratospheric perturbation on a continental scale. The main smoke layer (over central, western, southern, and eastern Europe) was found at heights between 15 and 20 km since September 2017 (about 2 weeks after entering the stratosphere). Thin layers of smoke were detected at heights of up to 22-23 km. The stratospheric aerosol optical thickness at 532 nm decreased from values > 0.25 on 21-23 August 2017 to 0.005-0.03 until 5-10 September and was mainly 0.003-0.004 from October to December 2017 and thus was still significantly above the stratospheric background (0.001-0.002). Stratospheric particle extinction coefficients (532 nm) were as high as 50-200 Mm-1 until the beginning of September and on the order of 1 Mm-1 (0.5- 5 Mm-1) from October 2017 until the end of January 2018. The corresponding layer mean particle mass concentration was on the order of 0.05-0.5 μg m-3 over these months. Soot particles (light-absorbing carbonaceous particles) are efficient ice-nucleating particles (INPs) at upper tropospheric (cirrus) temperatures and available to influence cirrus formation when entering the tropopause from above. We estimated INP concentrations of 50-500 L-1 until the first days in September and afterwards 5-50 L-1 until the end of the year 2017 in the lower stratosphere for typical cirrus formation temperatures of -55 ?C and an ice supersaturation level of 1.15. The measured profiles of the particle linear depolarization ratio indicated a predominance of nonspherical smoke particles. The 532 nm depolarization ratio decreased slowly with time in the main smoke layer from values of 0.15-0.25 (August-September) to values of 0.05-0.10 (October-November) and < 0.05 (December-January). The decrease of the depolarization ratio is consistent with aging of the smoke particles, growing of a coating around the solid black carbon core (aggregates), and thus change of the shape towards a spherical form. We found ascending aerosol layer features over the most southern European stations, especially over the eastern Mediterranean at 32-35? N, that ascended from heights of about 18-19 to 22-23 km from the beginning of October to the beginning of December 2017 (about 2 km per month). We discuss several transport and lifting mechanisms that may have had an impact on the found aerosol layering structures.Peer reviewe

The unprecedented 2017–2018 stratospheric smoke event: decay phase and aerosol properties observed with the EARLINET

Six months of stratospheric aerosol observations with the European Aerosol Research Lidar Network (EARLINET) from August 2017 to January 2018 are presented. The decay phase of an unprecedented, record-breaking stratospheric perturbation caused by wildfire smoke is reported and discussed in terms of geometrical, optical, and microphysical aerosol properties. Enormous amounts of smoke were injected into the upper troposphere and lower stratosphere over fire areas in western Canada on 12 August 2017 during strong thunderstorm–pyrocumulonimbus activity. The stratospheric fire plumes spread over the entire Northern Hemisphere in the following weeks and months. Twenty-eight European lidar stations from northern Norway to southern Portugal and the eastern Mediterranean monitored the strong stratospheric perturbation on a continental scale. The main smoke layer (over central, western, southern, and eastern Europe) was found at heights between 15 and 20 km since September 2017 (about 2 weeks after entering the stratosphere). Thin layers of smoke were detected at heights of up to 22–23 km. The stratospheric aerosol optical thickness at 532 nm decreased from values > 0.25 on 21–23 August 2017 to 0.005–0.03 until 5–10 September and was mainly 0.003–0.004 from October to December 2017 and thus was still significantly above the stratospheric background (0.001–0.002). Stratospheric particle extinction coefficients (532 nm) were as high as 50–200 Mm−1 until the beginning of September and on the order of 1 Mm−1 (0.5–5 Mm−1) from October 2017 until the end of January 2018. The corresponding layer mean particle mass concentration was on the order of 0.05–0.5 µg m−3 over these months. Soot particles (light-absorbing carbonaceous particles) are efficient ice-nucleating particles (INPs) at upper tropospheric (cirrus) temperatures and available to influence cirrus formation when entering the tropopause from above. We estimated INP concentrations of 50–500 L−1 until the first days in September and afterwards 5–50 L−1 until the end of the year 2017 in the lower stratosphere for typical cirrus formation temperatures of −55 ∘C and an ice supersaturation level of 1.15. The measured profiles of the particle linear depolarization ratio indicated a predominance of nonspherical smoke particles. The 532 nm depolarization ratio decreased slowly with time in the main smoke layer from values of 0.15–0.25 (August–September) to values of 0.05–0.10 (October–November) and < 0.05 (December–January). The decrease of the depolarization ratio is consistent with aging of the smoke particles, growing of a coating around the solid black carbon core (aggregates), and thus change of the shape towards a spherical form. We found ascending aerosol layer features over the most southern European stations, especially over the eastern Mediterranean at 32–35∘ N, that ascended from heights of about 18–19 to 22–23 km from the beginning of October to the beginning of December 2017 (about 2 km per month). We discuss several transport and lifting mechanisms that may have had an impact on the found aerosol layering structures

Tropospheric and stratospheric smoke over Europe as observed within EARLINET/ACTRIS in summer 2017

For several weeks in summer 2017, strong smoke layers were observed over Europe at numerous EARLINET stations. EARLINET is the European research lidar network and part of ACTRIS and comprises more than 30 ground-based lidars. The smoke layers were observed in the troposphere as well as in the stratosphere up to 25 km from Northern Scandinavia over whole western and central Europe to the Mediterranean regions. Backward trajectory analysis among other tools revealed that these smoke layers originated from strong wild fires in western Canada in combination with pyrocumulus convection. An extraordinary fire event in the mid of August caused intense smoke layers that were observed across Europe for several weeks starting on 18 August 2017. Maximum aerosol optical depths up to 1.0 at 532 nm were observed at Leipzig, Germany, on 22 August 2017 during the peak of this event. The stratospheric smoke layers reached extinction coefficient values of more than 600 Mm−1 at 532 nm, a factor of 10 higher than observed for volcanic ash after the Pinatubo eruption in the 1990s. First analyses of the intensive optical properties revealed low particle depolarization values at 532 nm for the tropospheric smoke (spherical particles) and rather high values (up to 20%) in the stratosphere. However, a strong wavelength dependence of the depolarization ratio was measured for the stratospheric smoke. This indicates irregularly shaped stratospheric smoke particles in the size range of the accumulation mode. This unique depolarization feature makes it possible to distinguish clearly smoke aerosol from cirrus clouds or other aerosol types by polarization lidar measurements. Particle extinction-to-backscatter ratios were rather low in the order of 40 to 50 sr at 355 nm, while values between 70-90 sr were measured at higher wavelengths. In the western and central Mediterranean, stratospheric smoke layers were most prominent in the end of August at heights between 16 and 20 km. In contrast, stratospheric smoke started to occur in the eastern Mediterranean (Cyprus and Israel) in the beginning of September between 18 and 23 km. Stratospheric smoke was still visible in the beginning of October at certain locations (e.g. Evora, Portugal), while tropospheric smoke was mainly observed until the end of August within Europe. An overview of the smoke layers measured at several EARLINET sites will be given. The temporal development of these layers as well as their geometrical and optical properties will be presented

Overview of recent TJ-II stellarator results

The main results obtained in the TJ-II stellarator in the last two years are reported. The most important topics investigated have been modelling and validation of impurity transport, validation of gyrokinetic simulations, turbulence characterisation, effect of magnetic configuration on transport, fuelling with pellet injection, fast particles and liquid metal plasma facing components. As regards impurity transport research, a number of working lines exploring several recently discovered effects have been developed: the effect of tangential drifts on stellarator neoclassical transport, the impurity flux driven by electric fields tangent to magnetic surfaces and attempts of experimental validation with Doppler reflectometry of the variation of the radial electric field on the flux surface. Concerning gyrokinetic simulations, two validation activities have been performed, the comparison with measurements of zonal flow relaxation in pellet-induced fast transients and the comparison with experimental poloidal variation of fluctuations amplitude. The impact of radial electric fields on turbulence spreading in the edge and scrape-off layer has been also experimentally characterized using a 2D Langmuir probe array. Another remarkable piece of work has been the investigation of the radial propagation of small temperature perturbations using transfer entropy. Research on the physics and modelling of plasma core fuelling with pellet and tracer-encapsulated solid-pellet injection has produced also relevant results. Neutral beam injection driven Alfvénic activity and its possible control by electron cyclotron current drive has been examined as well in TJ-II. Finally, recent results on alternative plasma facing components based on liquid metals are also presentedThis work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014–2018 under Grant Agreement No. 633053. It has been partially funded by the Ministerio de Ciencia, Inovación y Universidades of Spain under projects ENE2013-48109-P, ENE2015-70142-P and FIS2017-88892-P. It has also received funds from the Spanish Government via mobility grant PRX17/00425. The authors thankfully acknowledge the computer resources at MareNostrum and the technical support provided by the Barcelona S.C. It has been supported as well by The Science and Technology Center in Ukraine (STCU), Project P-507F

Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9-RAGE-NF-κB-JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary melanoma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity.info:eu-repo/semantics/publishedVersio