Experimentelle Kaninchensyphilis und das Reticuloendothelialsystem

Bei experimenteller Kaninchensyphilis fuhrte der Verfasser seine Versuche aus, berucksichtigt auf die klinischen Befunde und die Wassermannsche Reaktion des mit Sp. pallida geimpften Kaninchens bei der Splenektomie, bei der Blockierung des Reticuloendothelialsystemes und bei der Einspritzung des Milzextractes. Die Resultate sind die folgenden: 1. Nachdem Spirochaeta pallida dem Kaninchen in den Hoden geimpft wurde, wurde die Blockierung mit Tusche ausgefuhrt. Im Verlaufe der Infektion zeigten sich lokale Befunde und Wassermannsche Reaktion die in jeder Hinsicht denen der Kontrollen glichen. 2. Beim Kaninchen, welches gleichzeizig entmilzt und mit Sp. pallida geimpft wurde, trat der Lokalaffekt etwas fruhzeizig auf und die Wassermannsche Reaktion war kurzdauernd positiv. 3. Falls die Impfung nach der Entmilzung ausgefuhrt war, stimmten die Resultate fast mit den obigen ein. 4. Wenn die Versuchstiere erst geimpft und dann entmilzt wurden, so wurde eine bemerkenswerte oedematose Anschwellung des Hodensacks und ein Kurzdauernder positive Ausfall der Wa. R. beobachtet. 5. Wenn die Entmilzung, Impfung und Blockierung gleichzeizig ausgefuhrt wurden, so zeigten sich die lokalen sowie metastatischen Befunde bei Versuchstieren wie ohne Entmilzung, doch war die positive Phase der Wa. R. bedeutend verkurzt und dabei ihre Grad niederwertig. 6. Erst geimpft und dann mit Milzextract wiederhohlt gespritzt, so verliefen die lokalen sowie metastatischen Befunde leichter und die Wa. R. brach fruhzeizig positiv aus und dauerte langer. (Autoreferat.

VfoldCPX Server: Predicting RNA-RNA Complex Structure and Stability

<div><p>RNA-RNA interactions are essential for genomic RNA dimerization, mRNA splicing, and many RNA-related gene expression and regulation processes. The prediction of the structure and folding stability of RNA-RNA complexes is a problem of significant biological importance and receives substantial interest in the biological community. The VfoldCPX server provides a new web interface to predict the two-dimensional (2D) structures of RNA-RNA complexes from the nucleotide sequences. The VfoldCPX server has several novel advantages including the ability to treat RNAs with tertiary contacts (crossing base pairs) such as loop-loop kissing interactions and the use of physical loop entropy parameters. Based on a partition function-based algorithm, the server enables prediction for structure with and without tertiary contacts. Furthermore, the server outputs a set of energetically stable structures, ranked by their stabilities. The results allow users to gain extensive physical insights into RNA-RNA interactions and their roles in RNA function. The web server is freely accessible at “<a href="http://rna.physics.missouri.edu/vfoldCPX" target="_blank">http://rna.physics.missouri.edu/vfoldCPX</a>”.</p></div

Hierarchical Assembly of RNA Three-Dimensional Structures Based on Loop Templates

The current RNA structure prediction methods cannot keep up the pace of the rapidly increasing number of sequences and the emerging new functions of RNAs. Template-based RNA three-dimensional structure prediction methods are restricted by the limited number of known RNA structures, and traditional motif-based search for the templates does not always lead to successful results. Here we report a new template search and assembly algorithm, the hierarchical loop template-assembly method (VfoldLA). The method searches for templates for single strand loop/junctions instead of the whole motifs, which often renders no available templates, or short fragments (several nucleotides), which requires a long computational time to assemble and refine. The VfoldLA method has the advantage of accounting for local and nonlocal interloop interactions. Benchmark tests indicate that this new method can provide low-resolution predictions for RNA conformations at different levels of structural complexities. Furthermore, the VfoldLA-predicted conformations may also serve as reliable putative models for further structure prediction and refinements. VfoldLA is accessible at http://rna.physics.missouri.edu/vfoldLA

A snapshot of the output of the VfoldCPX server. Based on the total length of the input effective one-RNA system, the server provides up to three sets of predicted structures, corresponding to the three structural ensembles shown in Fig 2(B).

<p>In this example, the predicted most probable 2D structure (plotted using VARNA [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163454#pone.0163454.ref035" target="_blank">35</a>]) has the free energy of -50.24 kcal/mol. The predicted base pairing distributions shown by the density plot and the alternative stable structures provide important information about the structures and stabilities.</p

Schematic diagrams to show the recursive partition function calculation (in black) and the backtracking procedure (in red), for the total (A) and type <i>LR</i> (B) partition functions, respectively.

<p>For a given segment [a, b], we classify six types of conformations (<i>t</i> = <i>coil</i>, <i>C</i>, <i>L</i>, <i>R</i>, <i>LR</i>, <i>M</i>). The total partition function . The backtracking begins with and proceeds differently for each type of conformational ensemble. As an example of the total conformational ensemble: the backtracking proceeds through . Here, <i>N</i> is the RNA length and . The recursive relationship of other type of partition functions is shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163454#pone.0163454.s001" target="_blank">S1 Data</a></p

RNA-RNA complex system and three structural ensembles.

<p>(A) The input of two RNA sequences are linked by a three-nucleotide phantom linker to transform the original two-RNA system into an effective one-RNA system. (B) Three different structural types: (B-1) secondary, (B-2) H-type pseudoknotted, and (B-3) hairpin-hairpin kissed structures. The curved links in the diagrams denote base pairs (helix stems).</p

Kinetic Mechanism of Conformational Switch between Bistable RNA Hairpins

Transitions between the different conformational states play a critical role in many RNA catalytic and regulatory functions. In this study, we use the Kinetic Monte Carlo method to investigate the kinetic mechanism for the conformational switches between bistable RNA hairpins. We find three types of conformational switch pathways for RNA hairpins: refolding after complete unfolding, folding through basepair-exchange pathways and through pseudoknot-assisted pathways, respectively. The result of the competition between the three types of pathways depends mainly on the location of the rate-limiting base stacks (such as the GC base stacks) in the structures. Depending on the structural relationships between the two bistable hairpins, the conformational switch can follow single or multiple dominant pathways. The predicted folding pathways are supported by the activation energy results derived from the Arrhenius plot as well as the NMR spectroscopy data

Osthole induces cell cycle arrest in gastric cancer cells.

<p>HGC-27 (A) and SGC-7901 (B) cells were treated with or without osthole for 48 h and the cell cycle proportions were determined by PI staining and flow cytometry. Quantitative data indicate cell cycle distribution of osthole-treated HGC-27 (C) and SGC-7901 (D) cells. HGC-27 cells were treated with or without osthole for 48 h and the cell apoptosis were assessed by Annexin V-PI staining (E). Quantitative data indicates cell apoptosis of osthole-treated HGC-27 cells (F). **P<0.01 vs. control.</p

Osthole suppresses the expression of cyclinB1 and cdc2 proteins in gastric cancer cells.

<p>HGC-27 (A) and SGC-7901 (B) cells were treated with or without osthole for 48 h and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and analyzed by western blot assay. The expression of cyclinB1 and cdc2 was measured by western blot assay. Densitometric analyses of cyclinB1 and cdc2 proteins were expressed as the mean ± SD from three independent experiments (C: HGC-27, D: SGC-7901). *P<0.05, **P<0.01 vs. control.</p

Osthole represses PI3K-AKT signaling in gastric cancer cells.

<p>HGC-27 cells were treated with or without osthole for 48 h and the cell lysates were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and analyzed by western blot assay (A). The expression of PI3K, pAKT and AKT proteins was determined by western blot assay. Densitometric analyses of PI3K, pAKT and AKT proteins were expressed as the mean ± SD from three independent experiments (B). HGC-27 cells were pretreated with PI3K specific inhibitor LY294002 for 2 h and followed by the indicated concentration of osthole, the cell lysates were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and analyzed by western blot assay. The expression of pAKT, AKT, cyclin B1, and cdc2 proteins was determined by western blot assay (C). Densitometric analyses of these proteins were expressed as the mean ± SD from three independent experiments (D: pAKT, AKT; E: cyclin B1; F: cdc2). **P<0.01 vs. control; ## P<0.01 vs osthole group.</p