Who is a leader? Understanding leadership from a different perspective

No description supplie

Improved Biopharmaceutical Properties of Oral Formulations of 1,2,4-Thiadiazole Derivative with Cyclodextrins: in Vitro and in Vivo Evaluation

The synthesized 1,2,4-thiadiazole derivative displaying biological activity has low aqueous solubility and dissolution rate. Novel oral formulations of thiadiazole with β- and hydroxypropyl-β-cyclodextrins were obtained by grinding and freeze-drying methods with the purpose to improve the aqueous solubility. Complex formation of 1,2,4-thiadiazole derivative with cyclodextrins was confirmed by means of solid-state ¹³C MAS CP/TOSS NMR. Solubility, dissolution rate and permeability of the solid inclusion complexes were evaluated in different biorelevant media (SGF, FaSSGF, FaSSIF) simulating the conditions in the gastrointestinal tract. It was demonstrated that the content of biorelevant media affects the properties of the inclusion complexes. In particular, solubilizing effect of cyclodextrins became less pronounced when the micelles of taurocholic acid and lecithin are formed in the dissolution media. The inclusion of thiadiazole into cyclodextrin cavity is in competition with its partitioning into the micelles and this should be taken into account when the in vivo behavior is predicted. The results of in vitro and in vivo experiments were found to be in agreement and showed the highest solubility, dissolution rate and bioavailability of the freeze-dried complexes of thiadiazole with hydroxypropyl-β-cyclodextrin. These complexes can be proposed as more effective dosage forms for oral administration

Comparison of secretomes of <i>R. irregularis</i> and other 43 fungi.

<p>Percentage of predicted proteome representing putative effectors, using stringent (lacking transmembrane domains; yellow bars) or relaxed criteria (including proteins with predicted single transmembrane domain that overlapped with the signal peptide; blue bars).</p

Characteristics of the seven genome assemblies from <i>R. irregularis</i> DAOM197198w.

<p>N50: the length for which the contigs (scaffolds) of that length or longer contains at least half of the total lengths of the contigs (scaffolds).</p

ML tree derived from the concatenation of 35 widespread, single-copy genes.

<p>The amino acid alignment was trimmed as explained in the <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004078#s3" target="_blank">Materials and methods</a> section to remove non-informative positions, resulting in 26,604 positions. The tree was estimated using the rtREV evolutionary model implemented in RAxML. Bootstrap analysis was performed based on 100 replicates, and the three nodes with support below 100 are indicated. Scale bar indicates average number of amino acid substitutions per site.</p

Genome sequence of single <i>R. irregularis</i> DAOM197198w nuclei.

<p>(<b>A</b>) Sytox Green stained spore containing numerous nuclei. (<b>B</b>) Single Sytox-stained nucleus trapped with a micropipette. (<b>C</b>) Level of homology between four individual nuclei (N6, N31, N33 and N36) and 2 mycelium DNA samples (DNA1 and DNA2). Presented are the 10 largest contigs of the reference genome (representing ∼1,278 kb). The occurrence of SNPs (marked in blue) and INDELs (marked in red), and gene distributions, in the different assemblies are indicated.</p

Top 100 ranked protein tribes containing putative effector candidates.

<p>Clusters were determined using hierarchical clustering of the top 100 ranked tribes containing putative effector candidates. A. Rank associated with each tribe based on their content of effector features. B. Score for number of members containing a nuclear localization signals (NLS). C. Score for number of members classified as repeat containing (RCPs). D. Score reflecting number of members classified as small and cysteine rich (SCRs). E. Score for number of members not annotated by searches against swissprot. F. Average protein sequence length for tribe members (ranging from 55 to 856 amino acids). Stars indicate tribes that contain members with similarity to the characterised effector SP7.</p