Heptaketides from an Endolichenic Fungus <i>Biatriospora</i> sp. and Their Antifungal Activity

Twelve new heptaketides, biatriosporins A–L (<b>1</b>–<b>12</b>), biatriosporin M (<b>13</b>) (a ramulosin derivative), and 19 known compounds (<b>14</b>–<b>32</b>) were isolated from the endolichenic fungus <i>Biatriospora</i> sp. (8331C). The structures of these compounds were determined by analyzing MS and NMR data. The absolute configurations of compounds <b>1</b>, <b>2</b>, <b>7</b>, and <b>9</b> were determined by single-crystal X-ray diffraction analysis, whereas compound <b>10</b> was deduced with Mosher’s method. Four of the compounds were active in an antifungal assay. The most potent compound, compound <b>4</b>, also sensitized clinically derived azole-resistant <i>Candida albicans</i> strains to fluconazole (FLC). A mechanistic investigation revealed that <b>4</b> inhibited the function of efflux pumps and reduced the transcriptional expression of the efflux-pump-related genes <i>CDR1</i> and <i>CDR2</i>

Emodin ameliorates high-glucose induced mesangial p38 over-activation and hypocontractility via activation of PPARγ

Early stage diabetic nephropathy is characterized by elevated glomerular filtration. Recent studies have identified high-glucose induced p38 MAPK (p38) over-activation in mesangial cells. Mesangial hypocontractility is the major underlying mechanism, however, no ameliorating agents are currently available. We investigated the protective effects of emodin on high-glucose induced mesangial cell hypocontractility. Mesangial cells were cultured under normal (5.6 mM) and high glucose (30 mM) conditions. Emodin was administrated at doses of 50 mg/l and 100 mg/l. Angiotension II stimulated cell surface reductions were measured to evaluate cell contractility. p38 activity was detected using Western blotting. To further explore the possible mechanism of emodin, expression of the peroxisome proliferator-activated receptor γ (PPARγ) was measured and its specific inhibitor, gw9662, was administrated. Our results showed: (1) high-glucose resulted in a 280% increase in p38 activity associated with significant impairment of mesangial contractility; (2) emodin treatment dose-dependently inhibited high-glucose induced p38 over-activation (a 40% decrease for 50 mg/l emodin and a 73% decrease for 100 mg/l emodin), and mesangial hypocontractility was ameriolated by emodin; (3) both the PPARγ mRNA and protein levels were elevated after emodin treatment; (4) inhibition of PPARγ using gw9662 effectively blocked the ameliorating effects of emodin on high-glucose induced p38 over-activation and mesangial hypocontractility. Emodin effectively ameliorated p38 over-activation and hypocontractility in high-glucose induced mesangial cells, possibly via activation of PPARγ

Additional file 2: of A practical community-based response strategy to interrupt Ebola transmission in sierra Leone, 2014–2015

Technical supplementary for practical community-based response strategy to interrupt Ebola transmission in Sierra Leone, 2014-2015. (DOC 721 kb

Additional file 1: of A practical community-based response strategy to interrupt Ebola transmission in sierra Leone, 2014–2015

Multilingual abstracts in the six official working languages of the United Nations. (PDF 299 kb

Search for gamma-ray spectral lines with the DArk Matter Particle Explorer

The DArk Matter Particle Explorer (DAMPE) is well suitable for searching for monochromatic and sharp γ-ray structures in the GeV–TeV range thanks to its unprecedented high energy resolution. In this work, we search for γ-ray line structures using five years of DAMPE data. To improve the sensitivity, we develop two types of dedicated data sets (including the BgoOnly data which is the first time to be used in the data analysis for the calorimeter-based gamma-ray observatories) and adopt the signal-to-noise ratio optimized regions of interest (ROIs) for different DM density profiles. No line signals or candidates are found between 10 and 300 GeV in the Galaxy. The constraints on the velocity-averaged cross section for χχ→γγ and the decay lifetime for χ→γν, both at 95% confidence level, have been calculated and the systematic uncertainties have been taken into account. Comparing to the previous Fermi-LAT results, though DAMPE has an acceptance smaller by a factor of ∼10, similar constraints on the DM parameters are achieved and below 100 GeV the lower limits on the decay lifetime are even stronger by a factor of a few. Our results demonstrate the potential of high-energy-resolution observations on dark matter detection

Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356

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