沿岸海洋景観のGISデータベースの構築

<p>Superimposition of the top poses of LASSBio-448 obtained by docking with PDE4A and PDE4C (light purple surface, PDE4A) (A), PDE4B and PDE4D (gold surface, PDE4D) (B). Hydrogen atoms have been omitted for clarity.</p

Genesis concept of sulfonamides (5 and 6a-k) designed as PDE4 inhibitors.

<p>Genesis concept of sulfonamides (5 and 6a-k) designed as PDE4 inhibitors.</p

PDE4 Inhibition of rolipram and sulfonamides 5 and 6a-k.

<p>PDE4 Inhibition of rolipram and sulfonamides 5 and 6a-k.</p

Examples of PDE4 inhibitors of first and second generations.

<p>Examples of PDE4 inhibitors of first and second generations.</p

Effect of rolipram and LASSBio-448 on ovalbumin (OVA)-induced infiltration of eosinophils in the lung tissue from A/J mice.

<p>Animals were sensitized on days 0 and 7 and then challenged with OVA (25 μg/mouse) or saline on days 14, 21, 28 and 35. Animals were treated with rolipram (10 mg/Kg, oral) or LASSBio-448 (100 mg/Kg, oral) on days 26 and 22, 1 h before OVA challenge, and analyses performed 24 h after the last challenge. Values represent mean ± SEM from at least 7 animals. + P<0.05 as compared to saline-challenged group; *<i>P</i><0.05 as compared to OVA-challenged group.</p

Eukaryotic linear motifs of several Mps1 plant orthologs.

<p>Color codes: LIG_APCC_Dbox_1 (light green); Cyclin recognition site LIG_CYCLIN_1 (cyan); MAD2 binding motif LIG_MAD2 (orange); MAPK docking motif LIG_MAPK_1 (blue), NES Nuclear Export Signal TRG_NES_CRM1_1 (red), NLS classical Nuclear Localization Signals (green). AtMps1 (<i>A. thaliana</i>; 28416703); PtMps1 (<i>P. trichocarpa</i>; 224063138); RcMps1 (<i>R. communis</i>; 255545510); OsMps1 (<i>O. sativa</i> Indica Group; 125545426); SbMps1 (<i>S. bicolor</i>; 242038411).</p

Effect of rolipram and LASSBio-448 on ovalbumin (OVA)-induced changes in lungs from A/J mice.

<p>Airway responsiveness was measured by changes in airway resistance (A) and elastance (B) induced by increasing concentrations of methacholine, 24 h after the last ovalbumin or saline challenge. Animals were sensitized on days 0 and 7 and then challenged with OVA (25 μg/mouse) or saline on days 14, 21, 28 and 35. Animals were treated with rolipram (10 mg/Kg, oral) or LASSBio-448 (100 mg/Kg, oral) on days 26 and 22, 1 h before OVA challenge, and analyses performed 24 h after the last challenge. Values represent mean ± SEM from at least 7 animals. + <i>P</i><0.05 as compared to saline-challenged group; *<i>P</i><0.05 as compared to OVA-challenged group.</p

Structural and Functional Characterization of the Protein Kinase Mps1 in <em>Arabidopsis thaliana</em>

<div><p>In eukaryotes, protein kinases catalyze the transfer of a gamma-phosphate from ATP (or GTP) to specific amino acids in protein targets. In plants, protein kinases have been shown to participate in signaling cascades driving responses to environmental stimuli and developmental processes. Plant meristems are undifferentiated tissues that provide the major source of cells that will form organs throughout development. However, non-dividing specialized cells can also dedifferentiate and re-initiate cell division if exposed to appropriate conditions. Mps1 (<b>M</b>ono<b>p</b>olar <b>s</b>pindle) is a dual-specificity protein kinase that plays a critical role in monitoring the accuracy of chromosome segregation in the mitotic checkpoint mechanism. Although Mps1 functions have been clearly demonstrated in animals and fungi, its role in plants is so far unclear. Here, using structural and biochemical analyses here we show that Mps1 has highly similar homologs in many plant genomes across distinct lineages (e.g. AtMps1 in <em>Arabidopsis thaliana</em>). Several structural features (i.e. catalytic site, DFG motif and threonine triad) are clearly conserved in plant Mps1 kinases. Structural and sequence analysis also suggest that AtMps1 interact with other cell cycle proteins, such as Mad2 and MAPK1. By using a very specific Mps1 inhibitor (SP600125) we show that compromised AtMps1 activity hampers the development of <em>A. thaliana</em> seedlings in a dose-dependent manner, especially in secondary roots. Moreover, concomitant administration of the auxin IAA neutralizes the AtMps1 inhibition phenotype, allowing secondary root development. These observations let us to hypothesize that AtMps1 might be a downstream regulator of IAA signaling in the formation of secondary roots. Our results indicate that Mps1 might be a universal component of the Spindle Assembly Checkpoint machinery across very distant lineages of eukaryotes.</p> </div

Synthesis sulfonamide derivatives.

<p>Reagents and conditions: a) 1) H₂SO₄ /Ac₂O /AcOEt, 0°C, 2 h; 2) AcOK / EtOH, 25°C, 30 min, 93%. b) SOCl₂, DMF, 75°C, 4 h, 92%. c) CH₂Cl₂, Et₃N, 2-(3,4-dimethoxyphenyl)ethanamine (<b>6a</b>) or 2-phenylethanamine (5), 25°C, 2–2.5 h, 70%-81% respectively. d) K₂CO₃, acetone, RX (X = I, Br), (<b>6b-6e, 6g-6i</b> and <b>6k</b>), 40°C, 1.5 h, 34–96%. e) CH₂Cl₂, Et₃N, 2-(3,4-dimethoxyphenyl)ethanamine (<b>6f, 6j</b>) 25°C, 2–2.5 h, 53%-83% respectively.</p

Comparative ADME properties of rolipram (1) and LASSBio-448 predicted <i>in silico</i> using the Program ACD/Percepta 14.0.

<p>Comparative ADME properties of rolipram (1) and LASSBio-448 predicted <i>in silico</i> using the Program ACD/Percepta 14.0.</p