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41.
Marina Azevêdo Souza Susana Johann Luciana Alves Rodrigues dos Santos Lima Fernanda Fraga Campos Isolda Castro Mendes Heloisa Beraldo Elaine Maria de Souza-Fagundes Patrícia Silva Cisalpino Carlos Augusto Rosa Tania Maria de Almeida Alves Nívea Pereira de Sá Carlos Leomar Zani 《Memórias do Instituto Oswaldo Cruz》2013,108(3):342-351
Lapachol was chemically modified to obtain its thiosemicarbazone and semicarbazone derivatives. These compounds were tested for antimicrobial activity against several bacteria and fungi by the broth microdilution method. The thiosemicarbazone and semicarbazone derivatives of lapachol exhibited antimicrobial activity against the bacteria Enterococcus faecalis and Staphylococcus aureus with minimal inhibitory concentrations (MICs) of 0.05 and 0.10 µmol/mL, respectively. The thiosemicarbazone and semicarbazone derivatives were also active against the pathogenic yeast Cryptococcus gattii (MICs of 0.10 and 0.20 µmol/mL, respectively). In addition, the lapachol thiosemicarbazone derivative was active against 11 clinical isolates of Paracoccidioides brasiliensis, with MICs ranging from 0.01-0.10 µmol/mL. The lapachol-derived thiosemicarbazone was not cytotoxic to normal cells at the concentrations that were active against fungi and bacteria. We synthesised, for the first time, thiosemicarbazone and semicarbazone derivatives of lapachol. The MICs for the lapachol-derived thiosemicarbazone against S. aureus, E. faecalis, C. gattii and several isolates of P. brasiliensis indicated that this compound has the potential to be developed into novel drugs to treat infections caused these microbes. 相似文献
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Johann B?hm Frédéric Chevessier André?Maues De?Paula Catherine Koch Shahram Attarian Claire Feger Daniel Hanta? Pascal Laforêt Karima Ghorab Jean-Michel Vallat Michel Fardeau Dominique Figarella-Branger Jean Pouget Norma?B. Romero Marc Koch Claudine Ebel Nicolas Levy Martin Krahn Bruno Eymard Marc Bartoli Jocelyn Laporte 《American journal of human genetics》2013,92(2):271-278
Tubular aggregates are regular arrays of membrane tubules accumulating in muscle with age. They are found as secondary features in several muscle disorders, including alcohol- and drug-induced myopathies, exercise-induced cramps, and inherited myasthenia, but also exist as a pure genetic form characterized by slowly progressive muscle weakness. We identified dominant STIM1 mutations as a genetic cause of tubular-aggregate myopathy (TAM). Stromal interaction molecule 1 (STIM1) is the main Ca2+ sensor in the endoplasmic reticulum, and all mutations were found in the highly conserved intraluminal Ca2+-binding EF hands. Ca2+ stores are refilled through a process called store-operated Ca2+ entry (SOCE). Upon Ca2+-store depletion, wild-type STIM1 oligomerizes and thereby triggers extracellular Ca2+ entry. In contrast, the missense mutations found in our four TAM-affected families induced constitutive STIM1 clustering, indicating that Ca2+ sensing was impaired. By monitoring the calcium response of TAM myoblasts to SOCE, we found a significantly higher basal Ca2+ level in TAM cells and a dysregulation of intracellular Ca2+ homeostasis. Because recessive STIM1 loss-of-function mutations were associated with immunodeficiency, we conclude that the tissue-specific impact of STIM1 loss or constitutive activation is different and that a tight regulation of STIM1-dependent SOCE is fundamental for normal skeletal-muscle structure and function. 相似文献
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A population of multipotent stem cells capable of differentiating into neurons and glia has been isolated from adult intestine in humans and rodents. While these cells may provide a pool of stem cells for neurogenesis in the enteric nervous system (ENS), such a function has been difficult to demonstrate in vivo. An extensive study by Joseph et al. involving 108 rats and 51 mice submitted to various insults demonstrated neuronal uptake of thymidine analog BrdU in only 1 rat. Here we introduce a novel approach to study neurogenesis in the ENS using an ex vivo organotypic tissue culturing system. Culturing longitudinal muscle and myenteric plexus tissue, we show that the enteric nervous system has tremendous replicative capacity with the majority of neural crest cells demonstrating EdU uptake by 48 hours. EdU+ cells express both neuronal and glial markers. Proliferation appears dependent on the PTEN/PI3K/Akt pathway with decreased PTEN mRNA expression and increased PTEN phosphorylation (inactivation) corresponding to increased Akt activity and proliferation. Inhibition of PTEN with bpV(phen) augments proliferation while , a PI3K inhibitor, blocks it. These data suggest that the ENS is capable of neurogenesis in a PTEN dependent manner. LY294002相似文献
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Barbara Messner Johann Kern Dominik Wiedemann Stefan Schwaiger Adrian Türkcan Christian Ploner Alexander Trockenbacher Klaus Aumayr Nikolaos Bonaros Günther Laufer Hermann Stuppner Gerold Untergasser David Bernhard 《PloS one》2013,8(3)
Background
Insufficient angiogenesis and arteriogenesis in cardiac tissue after myocardial infarction (MI) is a significant factor hampering the functional recovery of the heart. To overcome this problem we screened for compounds capable of stimulating angiogenesis, and herein investigate the most active molecule, 5-Methoxyleoligin (5ML), in detail.Methods and Results
5ML potently stimulated endothelial tube formation, angiogenic sprouting, and angiogenesis in a chicken chorioallantoic membrane assay. Further, microarray- and knock down- based analyses revealed that 5ML induces angiogenesis by upregulation of CYP26B1. In an in vivo rat MI model 5ML potently increased the number of arterioles in the peri-infarction and infarction area, reduced myocardial muscle loss, and led to a significant increase in LV function (plus 21% 28 days after MI).Conclusion
The present study shows that 5ML induces CYP26B1-dependent angiogenesis in vitro, and arteriogenesis in vivo. Whether or not CYP26B1 is relevant for in vivo arteriogenesis is not clear at the moment. Importantly, 5ML-induced arteriogenesis in vivo makes the compound even more interesting for a post MI therapy. 5ML may constitute the first low molecular weight compound leading to an improvement of myocardial function after MI. 相似文献47.
Birthe Thormann Dirk Ahrens Diego Marín Armijos Marcell K. Peters Thomas Wagner Johann W. W?gele 《PloS one》2016,11(2)
Background
Tropical mountain forests are hotspots of biodiversity hosting a huge but little known diversity of insects that is endangered by habitat destruction and climate change. Therefore, rapid assessment approaches of insect diversity are urgently needed to complement slower traditional taxonomic approaches. We empirically compare different DNA-based species delimitation approaches for a rapid biodiversity assessment of hyperdiverse leaf beetle assemblages along an elevational gradient in southern Ecuador and explore their effect on species richness estimates.Methodology/Principal Findings
Based on a COI barcode data set of 674 leaf beetle specimens (Coleoptera: Chrysomelidae) of 266 morphospecies from three sample sites in the Podocarpus National Park, we employed statistical parsimony analysis, distance-based clustering, GMYC- and PTP-modelling to delimit species-like units and compared them to morphology-based (parataxonomic) species identifications. The four different approaches for DNA-based species delimitation revealed highly similar numbers of molecular operational taxonomic units (MOTUs) (n = 284–289). Estimated total species richness was considerably higher than the sampled amount, 414 for morphospecies (Chao2) and 469–481 for the different MOTU types. Assemblages at different elevational levels (1000 vs. 2000 m) had similar species numbers but a very distinct species composition for all delimitation methods. Most species were found only at one elevation while this turnover pattern was even more pronounced for DNA-based delimitation.Conclusions/Significance
Given the high congruence of DNA-based delimitation results, probably due to the sampling structure, our study suggests that when applied to species communities on a regionally limited level with high amount of rare species (i.e. ~50% singletons), the choice of species delimitation method can be of minor relevance for assessing species numbers and turnover in tropical insect communities. Therefore, DNA-based species delimitation is confirmed as a valuable tool for evaluating biodiversity of hyperdiverse insect communities, especially when exact taxonomic identifications are missing. 相似文献48.
High‐Performance Liquid Chromatographic Resolution of Neutral and Cationic Hetero[6]Helicenes
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Geraldine M. Labrador Johann Bosson Zachary S. Breitbach Yeeun Lim Eric R. Francotte Rocchina Sabia Claudio Villani Daniel W. Armstrong Jérôme Lacour 《Chirality》2016,28(4):282-289
Cationic hetero[6]helicenes 1+ , 2+ and 3+ have been recently disclosed. Herein we report on their enantiomeric separation using high‐performance liquid chromatography. Separation of the antipodes can be achieved in preparative scale on neutral adducts with Chiralcel OD‐I or Chiralpak ID CSP. Selectivity factors of 1.90, 1.67, and 1.96 were obtained for 1-H , 2-H , and 3-H , respectively. Separation can also be performed on the carbenium ions on regular Chiralpak IA CSP using water‐containing eluents, thus allowing for enantiomeric purity determinations in aqueous environments. Resolution of neutral and cationic helicenes is also achieved on more recently developed LARIHC columns. The versatility of the cyclofructan phases allows for baseline separations for both cases and their loading capabilities are demonstrated. Finally, the configurational stability of 1+ , 2+ , and 3+ was measured. For each replacement of an oxygen atom by an amino group, the racemization barrier increases significantly (ΔG? = 29.8, 36.3 and >37 kcal mol‐1 for 1+ , 2+ , and 3+ respectively). Chirality 28:282–289, 2016. © 2016 Wiley Periodicals, Inc. 相似文献
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Quan Liu Johann Toudert Tengfei Li Mariia Kramarenko Guillermo Martínez‐Denegri Laura Ciammaruchi Xiaowei Zhan Jordi Martorell 《Liver Transplantation》2019,9(20)
In the subwavelength regime, several nanophotonic configurations have been proposed to overcome the conventional light trapping or light absorption enhancement limit in solar cells also known as the Yablonovitch limit. It has been recently suggested that establishing such limit should rely on computational inverse electromagnetic design instead of the traditional approach combining intuition and a priori known physical effect. In the present work, by applying an inverse full wave vector electromagnetic computational approach, a 1D nanostructured optical cavity with a new resonance configuration is designed that provides an ultrabroadband (≈450 nm) light absorption enhancement when applied to a 107 nm thick active layer organic solar cell based on a low‐bandgap (1.32 eV) nonfullerene acceptor. It is demonstrated computationally and experimentally that the absorption enhancement provided by such a cavity surpasses the conventional limit resulting from an ergodic optical geometry by a 7% average over a 450 nm band and by more than 20% in the NIR. In such a cavity configuration the solar cells exhibit a maximum power conversion efficiency above 14%, corresponding to the highest ever measured for devices based on the specific nonfullerene acceptor used. 相似文献