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- ItemToll-Like Receptor 2 Release by Macrophages: An Anti-inflammatory Program Induced by Glucocorticoids and Lipopolysaccharide(Lausanne : Frontiers Media, 2019) Hoppstädter, Jessica; Dembek, Anna; Linnenberger, Rebecca; Dahlem, Charlotte; Barghash, Ahmad; Fecher-Trost, Claudia; Fuhrmann, Gregor; Koch, Marcus; Kraegeloh, Annette; Huwer, Hanno; Kiemer, Alexandra K.Glucocorticoids (GCs) are widely prescribed therapeutics for the treatment of inflammatory diseases, and endogenous GCs play a key role in immune regulation. Toll-like receptors (TLRs) enable innate immune cells, such as macrophages, to recognize a wide variety of microbial ligands, thereby promoting inflammation. The interaction of GCs with macrophages in the immunosuppressive resolution phase upon prolonged TLR activation is widely unknown. Treatment of human alveolar macrophages (AMs) with the synthetic GC dexamethasone (Dex) did not alter the expression of TLRs -1, -4, and -6. In contrast, TLR2 was upregulated in a GC receptor-dependent manner, as shown by Western blot and qPCR. Furthermore, long-term lipopolysaccharide (LPS) exposure mimicking immunosuppression in the resolution phase of inflammation synergistically increased Dex-mediated TLR2 upregulation. Analyses of publicly available datasets suggested that TLR2 is induced during the resolution phase of inflammatory diseases, i.e., under conditions associated with high endogenous GC production. TLR2 induction did not enhance TLR2 signaling, as indicated by reduced cytokine production after treatment with TLR2 ligands in Dex- and/or LPS-primed AMs. Thus, we hypothesized that the upregulated membrane-bound TLR2 might serve as a precursor for soluble TLR2 (sTLR2), known to antagonize TLR2-dependent cell actions. Supernatants of LPS/Dex-primed macrophages contained sTLR2, as demonstrated by Western blot analysis. Activation of metalloproteinases resulted in enhanced sTLR2 shedding. Additionally, we detected full-length TLR2 and assumed that this might be due to the production of TLR2-containing extracellular vesicles (EVs). EVs from macrophage supernatants were isolated by sequential centrifugation. Both untreated and LPS/Dex-treated cells produced vesicles of various sizes and shapes, as shown by cryo-transmission electron microscopy. These vesicles were identified as the source of full-length TLR2 in macrophage supernatants by Western blot and mass spectrometry. Flow cytometric analysis indicated that TLR2-containing EVs were able to bind the TLR2 ligand Pam3CSK4. In addition, the presence of EVs reduced inflammatory responses in Pam3CSK4-treated endothelial cells and HEK Dual reporter cells, demonstrating that TLR2-EVs can act as decoy receptors. In summary, our data show that sTLR2 and full-length TLR2 are released by macrophages under anti-inflammatory conditions, which may contribute to GC-induced immunosuppression.
- ItemReducing conditions favor magnetosome production in magnetospirillum magneticum AMB-1(Lausanne : Frontiers Media, 2019) Olszewska-Widdrat, Agata; Schiro, Gabriele; Reichel, Victoria E.; Faivre, DamienMagnetotactic bacteria (MTB) are a heterogeneous group of Gram-negative prokaryotes, which all produce special magnetic organelles called magnetosomes. The magnetosome consists of a magnetic nanoparticle, either magnetite (Fe3O4) or greigite (Fe3S4), embedded in a membrane, which renders the systems colloidaly stable, a desirable property for biotechnological applications. Although these bacteria are able to regulate the formation of magnetosomes through a biologically-controlled mechanism, the environment in general and the physico-chemical conditions surrounding the cells in particular also influence biomineralization. This work thus aims at understanding how such external conditions, in particular the extracellular oxidation reduction potential, influence magnetite formation in the strain Magnetospirillum magneticum AMB-1. Controlled cultivation of the microorganisms was performed at different redox potential in a bioreactor and the formation of magnetosomes was assessed by microscopic and spectroscopic techniques. Our results show that the formation of magnetosomes is inhibited at the highest potential tested (0 mV), whereas biomineralization is facilitated under reduced conditions (-500 mV). This result improves the understanding of the biomineralization process in MTB and provides useful information in sight of a large scale production of magnetosomes for different applications. © 2019 Olszewska-Widdrat, Schiro, Reichel and Faivre.
- ItemEditorial: New insights and updates on the molecular epidemiology and antimicrobial resistance of MRSA in humans in the whole-genome sequencing era(Lausanne : Frontiers Media, 2019) Coleman, David C.; Shore, Anna C.; Goering, Richard V.; Monecke, Stefan[No abstract available]
- ItemCoupling between leg muscle activation and EEG during normal walking, intentional stops, and freezing of gait in Parkinson's disease(Lausanne : Frontiers Media, 2019) Günther, Moritz; Bartsch, Ronny P.; Miron-Shahar, Yael; Hassin-Baer, Sharon; Inzelberg, Rivka; Kurths, Jürgen; Plotnik, Meir; Kantelhardt, Jan W.In this paper, we apply novel techniques for characterizing leg muscle activation patterns via electromyograms (EMGs) and for relating them to changes in electroencephalogram (EEG) activity during gait experiments. Specifically, we investigate changes of leg-muscle EMG amplitudes and EMG frequencies during walking, intentional stops, and unintended freezing-of-gait (FOG) episodes. FOG is a frequent paroxysmal gait disturbance occurring in many patients suffering from Parkinson's disease (PD). We find that EMG amplitudes and frequencies do not change significantly during FOG episodes with respect to walking, while drastic changes occur during intentional stops. Phase synchronization between EMG signals is most pronounced during walking in controls and reduced in PD patients. By analyzing cross-correlations between changes in EMG patterns and brain-wave amplitudes (from EEGs), we find an increase in EEG-EMG coupling at the beginning of stop and FOG episodes. Our results may help to better understand the enigmatic pathophysiology of FOG, to differentiate between FOG events and other gait disturbances, and ultimately to improve diagnostic procedures for patients suffering from PD. Copyright © 2019 Günther, Bartsch, Miron-Shahar, Hassin-Baer, Inzelberg, Kurths, Plotnik and Kantelhardt.
- ItemShared MRSA Strains among Nepalese Rhesus macaques (Macaca mulatta), their Environment and Hospitalized Patients(Lausanne : Frontiers Media, 2019) Roberts, Marilyn C.; Joshi, Prabhu Raj; Monecke, Stefan; Ehricht, Ralf; Müller, Elke; Gawlik, Darius; Paudel, Saroj; Acharya, Mahesh; Bhattarai, Sankalpa; Pokharel, Sujana; Tuladhar, Reshma; Chalise, Mukesh K.; Kyes, Randall C.This study looked at 227 saliva samples from Rhesus macaques (Macaca mulatta) and 218 samples from the surrounding environments. From these samples, MRSA isolates were collected from Rhesus saliva samples (n = 13) and environmental samples (n = 19) near temple areas in Kathmandu, Nepal. For comparison, selected MRSA isolates (n = 5) were obtained from patients with wound infections from a Kathmandu hospital. All isolates were characterized using Abbott StaphyType® DNA microarrays. Eighteen isolates (62%) from monkeys (n = 4; 31%) and environmental samples (n = 14; 74%), were CC22-MRSA-IV. Most (n = 16) of them carried both, the PVL locus and toxic shock toxin gene (tst1), an unusual combination which is the same as in previously characterized strain from Nepalese macaques and pigs. The five human isolates also belonged to that strain type. Eight monkey MRSA isolates were CC361-MRSA-IV. One MRSA from a monkey and one from an environmental sample, were CC88-MRSA-V. Other environmental MRSA included one each, CC121-MRSA-VT, and CC772 -MRSA-V. Two were CC779-MRSA-VT, potentially a novel clone. All MRSA carried the blaZ gene. The aacA–aphD, dfrA, and erm (C) genes were very common in isolates from all sources. One macaque MRSA carried the resistance genes aphA3 and sat, neither previously identified in primate MRSA isolates. This current study suggests that humans could be a potential source of the MRSA in the macaques/environment and transmission may be linked to humans feeding the primates and/or living in close proximity to each other.This study looked at 227 saliva samples from Rhesus macaques (Macaca mulatta) and 218 samples from the surrounding environments. From these samples, MRSA isolates were collected from Rhesus saliva samples (n = 13) and environmental samples (n = 19) near temple areas in Kathmandu, Nepal. For comparison, selected MRSA isolates (n = 5) were obtained from patients with wound infections from a Kathmandu hospital. All isolates were characterized using Abbott StaphyType® DNA microarrays. Eighteen isolates (62%) from monkeys (n = 4; 31%) and environmental samples (n = 14; 74%), were CC22-MRSA-IV. Most (n = 16) of them carried both, the PVL locus and toxic shock toxin gene (tst1), an unusual combination which is the same as in previously characterized strain from Nepalese macaques and pigs. The five human isolates also belonged to that strain type. Eight monkey MRSA isolates were CC361-MRSA-IV. One MRSA from a monkey and one from an environmental sample, were CC88-MRSA-V. Other environmental MRSA included one each, CC121-MRSA-VT, and CC772 -MRSA-V. Two were CC779-MRSA-VT, potentially a novel clone. All MRSA carried the blaZ gene. The aacA–aphD, dfrA, and erm (C) genes were very common in isolates from all sources. One macaque MRSA carried the resistance genes aphA3 and sat, neither previously identified in primate MRSA isolates. This current study suggests that humans could be a potential source of the MRSA in the macaques/environment and transmission may be linked to humans feeding the primates and/or living in close proximity to each other.
- ItemPolyethylene glycol-modified poly(styrene-co-ethylene/butylene-co-styrene)/carbon nanotubes composite for humidity sensing(Lausanne : Frontiers Media, 2019) Mičušík, Matej; Chatzimanolis, Christos; Tabačiarová, Jana; Kollár, Jozef; Kyritsis, Apostolos; Pissis, Polycarpos; Pionteck, Jürgen; Vegso, Karol; Siffalovic, Peter; Majkova, Eva; Omastová, MáriaPolymeric composites of the linear triblock copolymer poly(styrene-co-ethylene/butylene-co-styrene) grafted with maleic anhydride units (SEBS-MA) or MA modified by hydrophilic polyethylene glycol (PEG) and containing various amounts of multiwall carbon nanotubes (MWCNTs) as conducting filler—were prepared by solvent casting. The MWCNT surface was modified by a non-covalent approach with a pyrene-based surfactant to achieve a homogeneous dispersion of the conducting filler within the polymeric matrix. The dispersion of the unmodified and surfactant-modified MWCNTs within the elastomeric SEBS-MA and SEBS-MA-PEG matrices was characterized by studying the morphology by TEM and SAXS. Dynamical mechanical analysis was used to evaluate the interaction between the MWCNTs and copolymer matrix. The electrical conductivity of the prepared composites was measured by dielectric relaxation spectroscopy, and the percolation threshold was calculated. The prepared elastomeric composites were characterized and studied as humidity sensor. Our results demonstrated that at MWCNTs concentration slightly above the percolation threshold could result in large signal changes. In our system, good results were obtained for MWCNT loading of 2 wt% and an ~0.1 mm thin composite film. The thickness of the tested elastomeric composites and the source current appear to be very important factors that influence the sensing performance. © 2019 Mičušík, Chatzimanolis, Tabačiarová, Kollár, Kyritsis, Pissis, Pionteck, Vegso, Siffalovic, Majkova and Omastová.
- ItemSocial innovation in community energy in Europe: A review of the evidence(Lausanne : Frontiers Media, 2019) Hewitt, Richard J.; Bradley, Nicholas; Compagnucci, Andrea Baggio; Barlagne, Carla; Ceglarz, Andrzej; Cremades, Roger; McKeen, Margaret; Otto, Ilona M.; Slee, BillCitizen-driven Renewable Energy (RE) projects of various kinds, known collectively as community energy (CE), have an important part to play in the worldwide transition to cleaner energy systems. On the basis of evidence from 8 European countries, we investigate CE, over approximately the last 50 years (c.1970-2018), through the lens of Social Innovation (SI). We carry out a detailed review of literature around the social dimension of renewable energy; we collect, describe and map CE initiatives from Belgium, France, Germany, Italy, Poland, Spain, Sweden, and the UK; and we unpack the SI concept into 4 operational criteria which we suggest are essential to recognizing SI in CE. These are: (1) Crises and opportunities; (2) the agency of civil society; (3) reconfiguration of social practices, institutions and networks; (4) new ways of working. We identify three main phases of SI in CE. The environmental movements of the 1960s and the "oil shocks" of the 1970s provided the catalyst for a series of innovative societal responses around energy and self-sufficiency. A second wave of SI relates to the mainstreaming of RE and associated government support mechanisms. In this phase, with some important exceptions, successful CE initiatives were mainly confined to those countries where they were already embedded as innovators in the previous phase. The third phase of CE innovation relates to the societal response to the Great Recession that began in 2008 and lasted most of the subsequent decade. CE initiatives formed around this time were also strongly focused around democratization of energy and citizen empowerment in the context of rising energy prices, a weak economy, and a production and supply system dominated by excessively powerful multinational energy firms. CE initiatives today are more diverse than at any time previously, and are likely to continue to act as incubators for pioneering initiatives addressing virtually all aspects of energy. However, large multinational energy firms remain the dominant vehicle for delivery of the energy transition, and the apparent excitement in European policy circles for "community energy" does not extend to democratization of energy or genuine empowerment of citizens. © 2019 Hewitt, Bradley, Baggio Compagnucci, Barlagne, Ceglarz, Cremades, McKeen, Otto and Slee.
- ItemA Rigorous Statistical Assessment of Recent Trends in Intensity of Heavy Precipitation Over Germany(Lausanne : Frontiers Media, 2019) Passow, Christian; Donner, Reik V.Comprehensive and robust statistical estimates of trends during heavy precipitation events are essential in understanding the impact of past and future climate changes in the hydrological cycle. However, methods commonly used in extreme value statistics (EVS) are often unable to detect significant trends, because of their methodologically motivated reduction of the sample size and strong assumptions regarding the underlying distribution. Here, we propose linear quantile regression (QR) as a complementary and robust alternative to estimating trends in heavy precipitation events. QR does not require any assumptions on the underlying distribution and is also able to estimate trends for the full span of the distribution without any reduction of the available data. As an example, we study here a very dense and homogenized data set of daily precipitation amounts over Germany for the period between 1951 and 2006 to compare the results of QR and the so-called block maxima approach, a classical method in EVS. Both methods indicate an overall increase in the intensity of heavy precipitation events. The strongest trends can be found in regions with an elevation of about 500 m above sea level. In turn, larger spatial clusters of moderate or even decreasing trends can only be found in Northeastern Germany. In conclusion, both methods show comparable results. QR, however, allows for a more flexible and comprehensive study of precipitation events. © Copyright © 2019 Passow and Donner.
- ItemA nexus approach for the MENA region-from concept to knowledge to action(Lausanne : Frontiers Media, 2019) Hoff, Holger; Alrahaife, Sajed Aqel; El Hajj, Rana; Lohr, Kerstin; Mengoub, Fatima Ezzahra; Farajalla, Nadim; Fritzsche, Kerstin; Jobbins, Guy; Özerol, Gül; Schultz, Robert; Ulrich, AnneThere is wide agreement that a nexus or integrated approach to managing and governing natural resources such as land, water, and energy can improve environmental, climate, human, and political security. However, few if any countries in the MENA region have made progress in implementing such an approach. There appear to be several constraints inhibiting the development and adoption of nexus approaches. These constraints include strong sectoral silos, insufficient incentives for integrated planning and policy making at all levels, and limited vision, knowledge, and practical experience to guide successful implementation. In turn, the limited implementation and hence lack of empirical evidence of a nexus approach, which could demonstrate its benefits, does little to strengthen political will for the development of adequate incentives, structures, and procedures. Against this backdrop, this paper presents five case studies which take an integrated approach, in three MENA countries, namely Jordan, Lebanon, and Morocco. Based on an analytical framework developed here, the paper analyses and compares the success factors for nexus implementation, and also for transfer and upscaling. The analysis emphasizes the need for appropriate framework conditions, targeted investments and pioneering actors, to make integrated approaches across sectors and levels work. With the evidence presented, the paper aims to set in motion a positive or virtuous cycle of generating more nexus evidence, improved framework conditions, further nexus implementation on the ground, and from that even more nexus evidence. Finally, the paper contributes to overcoming the repeated requests for better definition and conceptualization of the nexus, which often has slowed down adoption of the concept. © 2019 Hoff, Alrahaife, El Hajj, Lohr, Mengoub, Farajalla, Fritzsche, Jobbins, özerol, Schultz and Ulrich.
- ItemFluoride-Sulfophosphate/Silica Hybrid Fiber as a Platform for Optically Active Materials(Lausanne : Frontiers Media, 2019) Wang, Wei-Chao; Yang, Xu; Wieduwilt, Torsten; Schmidt, Markus A.; Zhang, Qin-Yuan; Wondraczek, LotharPressure-assisted melt filling (PAMF) of pre-fabricated micro-capillaries has been proven an effective way of fabricating hybrid optical fiber (HOF) from unusual combinations of materials. Here, we extend the applicability of PAMF to multi-anionic fluoride-sulfophosphate (FPS) glasses. FPS glasses provide extended transmission windows and high solubility for various transition metal (TM) and rare earth (RE) ion species. Using PAMF for fabricating FPS/silica HOFs can therefore act as a platform for a broad variety of optically active fiber devices. For the present demonstration purposes, we selected Cr3+- and Mn2+-doped FPS. For both glasses, we demonstrate how the spectral characteristics of the bulk material persist also in the HOF. Using a double-core fiber structure in which waveguiding is conducted in a primary GeO2-SiO2 core, mode coupling to the secondary FPS-filled core allows one to exploit the optical activity of the doped FPS glass even when the intrinsic optical loss is high.Pressure-assisted melt filling (PAMF) of pre-fabricated micro-capillaries has been proven an effective way of fabricating hybrid optical fiber (HOF) from unusual combinations of materials. Here, we extend the applicability of PAMF to multi-anionic fluoride-sulfophosphate (FPS) glasses. FPS glasses provide extended transmission windows and high solubility for various transition metal (TM) and rare earth (RE) ion species. Using PAMF for fabricating FPS/silica HOFs can therefore act as a platform for a broad variety of optically active fiber devices. For the present demonstration purposes, we selected Cr3+- and Mn2+-doped FPS. For both glasses, we demonstrate how the spectral characteristics of the bulk material persist also in the HOF. Using a double-core fiber structure in which waveguiding is conducted in a primary GeO2-SiO2 core, mode coupling to the secondary FPS-filled core allows one to exploit the optical activity of the doped FPS glass even when the intrinsic optical loss is high.
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