Disease Burden of Mild Asthma: Findings from a Cross-Sectional Real-World Survey

<p><strong>Article full text</strong></p> <p><br> The full text of this article can be found <a href="https://link.springer.com/article/10.1007/s12325-017-0520-0"><b>here</b>.</a><br> <br> <strong>Provide enhanced digital features for this article</strong><br> If you are an author of this publication and would like to provide additional enhanced digital features for your article then please contact <u>[email protected]</u>.<br> <br> The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.<br> <br> Other enhanced features include, but are not limited to:<br> • Slide decks<br> • Videos and animations<br> • Audio abstracts<br> • Audio slides<u></u></p

Characterizing Binding of Small Molecules. II. Evaluating the Potency of Small Molecules to Combat Resistance Based on Docking Structures

Drug resistance severely erodes the efficacy of therapeutic treatments for many diseases. Assessing the potency of a drug lead to combat resistance is no doubt critical for designing new drugs or new therapeutic combinations. Virtual screening is often the first step in drug discovery and a challenging problem is to accurately predict the resistant profile of an inhibitor based on the docking structures. Using a well studied system HIV-1 protease, we have illustrated the success of a computational method called MIEC-SVM on tackling this problem. We computed molecular interaction energy components (MIECs) between the ligand and the protease residues to characterize the docking poses, which were input to support vector machine (SVM) to distinguish resistant from nonresistant mutants. More importantly, the method is able to predict resistant profiles for new drugs based on the docking structures as indicated by its satisfactory performance in leave-one-drug-out and leave-drug/mutants-out tests. Therefore, the MIEC-SVM method can also facilitate designing effective therapeutic combinations by combining drugs with complementary resistant profiles

The E409V mutation affects the self-association of OsDRP1E.

<p><b>(A)</b> Yeast two-hybrid assays using the <i>HIS3</i> reporter to detect the self-interaction of OsDRP1E. Yeast cells transformed with bait and prey constructs as indicated were sequentially diluted 10-fold and plated on synthetic dextrose (SD) medium without Trp, Leu and His amino acids (SD-LTH) and with 0 mM or 40 mM 3-amino-1,2,4,-triazole (3AT), respectively. Yeast cells that either grew in the presence of 40 mM 3AT or were stained blue by X-gal indicate an interaction. <b>(B)</b> Immunoblot detection of GFP-tagged OsDRP1E and E409V expressed in <i>N</i>. <i>benthamiana</i> using Blue Native-PAGE (upper panel) and SDS-PAGE (bottom panel). Blue Native-PAGE followed by immunoblot analysis was used to detect the oligomerization of OsDRP1E-GFP and E409V-GFP. SDS-PAGE followed by immunoblot analysis was used to detect the expression levels of OsDRP1E-GFP and E409V-GFP.</p

The Rice Dynamin-Related Protein OsDRP1E Negatively Regulates Programmed Cell Death by Controlling the Release of Cytochrome <i>c</i> from Mitochondria

<div><p>Programmed cell death (PCD) mediated by mitochondrial processes has emerged as an important mechanism for plant development and responses to abiotic and biotic stresses. However, the role of translocation of cytochrome <i>c</i> from the mitochondria to the cytosol during PCD remains unclear. Here, we demonstrate that the rice dynamin-related protein 1E (OsDRP1E) negatively regulates PCD by controlling mitochondrial structure and cytochrome <i>c</i> release. We used a map-based cloning strategy to isolate <i>OsDRP1E</i> from the lesion mimic mutant <i>dj-lm</i> and confirmed that the E409V mutation in OsDRP1E causes spontaneous cell death in rice. Pathogen inoculation showed that <i>dj-lm</i> significantly enhances resistance to fungal and bacterial pathogens. Functional analysis of the E409V mutation showed that the mutant protein impairs OsDRP1E self-association and formation of a higher-order complex; this in turn reduces the GTPase activity of OsDRP1E. Furthermore, confocal microscopy showed that the E409V mutation impairs localization of OsDRP1E to the mitochondria. The E409V mutation significantly affects the morphogenesis of cristae in mitochondria and causes the abnormal release of cytochrome <i>c</i> from mitochondria into cytoplasm. Taken together, our results demonstrate that the mitochondria-localized protein OsDRP1E functions as a negative regulator of cytochrome <i>c</i> release and PCD in plants.</p></div

Phenotypic characterization of the <i>dj-lm</i> mutant.

<p><b>(A)</b> Representative leaves of Dongjin (DJ) and <i>dj-lm</i> plants. <b>(B)</b> Trypan blue staining of DJ and <i>dj-lm</i> leaves. <b>(C)</b> Diamiobenzidine (DAB) staining of DJ and <i>dj-lm</i> leaves. <b>(D)</b> DJ and <i>dj-lm</i> plants grown in the field. <b>(E)</b> Disease phenotypes of DJ and <i>dj-lm</i> after inoculation with <i>M</i>. <i>oryzae</i> isolate RO1-1. Similar results were obtained from three independent experiments. Bar = 1 cm. <b>(F)</b> Lesion length of DJ and <i>dj-lm</i> after inoculation with RO1-1. Values are means ± standard errors of 10 replications. Significance was determined at ***P<0.0001 with a Student’s <i>t</i>-test. <b>(G)</b> Relative fungal biomass of DJ and <i>dj-lm</i> after inoculation with <i>M</i>. <i>oryzae</i>. Values are means ± standard errors of 10 replications. Significance was determined at *P<0.05 with a Student’s <i>t</i>-test. <b>(H)</b> Disease phenotypes of DJ and <i>dj-lm</i> after inoculation with <i>Xoo</i> strain PXO-99. Similar results were obtained from three independent experiments. Bar = 1 cm. <b>(I)</b> Lesion length of DJ and <i>dj-lm</i> after inoculation with PXO99. Values are means ± standard errors of 10 replications. Significance was determined at ***P<0.0001 with a Student’s <i>t</i>-test.</p

ROS generation and defense-related gene expression in the <i>dj-lm</i> mutant.

<p><b>(A)</b> ROS bursts of DJ and <i>dj-lm</i> after chitin treatment. Values are means ± standard errors of three biological replications. Similar results were obtained from three independent experiments. <b>(B)</b> ROS bursts of DJ and <i>dj-lm</i> after flg22 treatment. Values are means ± standard errors of three biological replications. Similar results were obtained from three independent experiments. <b>(C)</b> Transcript levels of cell death-related and PR genes in DJ and <i>dj-lm</i> plants. Values are means and standard errors of three biological replications. White and gray bars represent the transcript levels of the genes tested in DJ and <i>dj-lm</i>, respectively. Significance was determined at ***P<0.0001 with a Student’s <i>t</i>-test.</p

Subcellular localization of OsDRP1E-GFP and E409V-GFP <i>in planta</i>.

<p>(A) Confocal images of OsDRP1E-GFP and E409V-GFP transiently expressed in rice protoplasts. MitoTracker was used as the mitochondrial marker. Bar = 10 μm. (B) Confocal images of OsDRP1E-GFP and E409V-GFP transiently expressed in <i>N</i>. <i>benthamiana</i>. Ds-RED-tagged COX4 was used as the mitochondrial marker. Bar = 10 μm.</p

Carbon-Encapsulated F‑Doped Li₄Ti₅O₁₂ as a High Rate Anode Material for Li⁺ Batteries

TiO₂ nanoparticles aggregated into a regular ball-in-ball morphology were synthesized by hydrothermal processing and converted to carbon-encapsulated F-doped Li₄Ti₅O₁₂ (LTO) composites (C-FLTO) by solid state lithiation at high temperatures. Through the careful control of the amount of carbon precursor (d(+)-glucose monohydrate) used in the process, LTO encapsulated with a continuous layer of nanoscale carbon was formed. The carbon encapsulation served a dual function: preserving the ball-in-ball morphology during the transformation from TiO₂ to LTO and decreasing the external electron transport resistance. The fluoride doping of LTO not only increased the electron conductivity of LTO through trivalent titanium (Ti³⁺) generation, but also increased the robustness of the structure to repeated lithiation and delithiation. The best-performing composite, C-FLTO-2, therefore delivered a very satisfying performance for a LTO anode: a high charge capacity of ∼158 mA h g^–1 at the 1 C rate with negligible capacity fading for 200 cycles and an extremely high rate performance up to 140 C

Immunoblot detection of cytochrome <i>c</i> in cytosol and mitochondria from DJ and <i>dj-lm</i> plants.

<p>HSP90 and VDAC1 served as the loading control for cytosolic and mitochondrial protein, respectively. Y: Young leaves from four-week-old plants. O: Old leaves from eight-week-old plants. Numbers below the band in first panel represent the relative cytochrome <i>c</i> levels in cytosol and mitochondria as compared to HSP90 and VDAC1, respectively, using the Image J software.</p

Map-based cloning of <i>OsDRP1E</i>.

<p><b>(A)</b> Fine physical map of the <i>dj-lm</i> candidate locus. The two thick black bars represent PAC clones AP006162 and AP006450. Words above and below the bars indicate SSR markers, InDel markers and the physical distance between the two markers, respectively. The numbers below the maps represent the number of recombination events. (<b>B)</b> Predicted ORFs in the <i>dj-lm</i> mutant. The thick black bars represent PAC clone AP006450. Arrows indicate the order and orientation of 16 ORFs within the PAC clone AP006450. ORFs in gray are retrotransposon genes. (<b>C)</b> Gene structure of <i>OsDRP1E</i>. The schematic map shows the coding region (black boxes), the 5’ and 3’ untranslated regions (white boxes) and the intron region (lines). Arrow indicates the mutated nucleotide. <b>(D)</b> OsDRP1E protein structure. The three boxes indicate the domains of OsDRP1E. The numbers below the box indicate the size of the protein. Arrow represents the mutated amino acid residue. GED: Dynamin GTPase effector domain. (<b>E)</b> Genetic complementation of <i>OsDRP1E</i>. Left panel: Leaves from transgenic lines (1300 (EV)-1/2) transformed with the pCAMBIA1300 empty vector and their sequencing chromatograms at the <i>OsDRP1E</i> locus. Right panel: Leaves from complemented lines (1300-<i>OsDRP1E-</i>2/7) transformed with the pCAMBIA1300-<i>OsDPR1E</i> construct and their sequencing chromatograms at the <i>OsDRP1E</i> locus. </p