Cytotoxic effects of digitoxin.

<p>A: Cytotoxic effects of digitoxin (0.1 µM) expressed as Survival Index % (<i>vs.</i> untreated control cells) in the various leukaemia types (T-ALL, B precursor ALL, AML and CLL) and PBMC using the standard 72 h assay. B: Effects of therapeutically achievable digitoxin concentrations against leukaemic cells from patients and CCRF-CEM cell line over six days with daily medium change.</p

Cytotoxic IC₅₀ values.

<p>Cytotoxic IC₅₀ values (µM) for digitoxin (A) and oubain (B) in primary cultures of human leukaemia cells (T-ALL, B-precursor ALL, AML and CLL) and PBMCs.</p

Comparison between colorectal and leukaemic cell lines.

<p>For comparative purposes the effects of digitoxin on DNA and protein synthesis (A and B respectively) were also monitored in the colorectal adenocarcinoma cell line Hct116. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0015718#pone-0015718-g004" target="_blank">Figure 4C</a> shows differences in cytotoxic activity of digitoxin in the Hct116 cell line and the leukaemic cell lines (CCRF-CEM and SUP-B15) used in the present study. In <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0015718#pone-0015718-g004" target="_blank">Figure 4D</a> the effects on survival (at 72 h, measured by FMCA) and protein synthesis at 24 hours at digitoxin concentrations slightly exceeding the IC₅₀ values in HT29 and SUP-B15 cells are shown.</p

Effects of digitoxin on DNA synthesis in leukaemic cell lines.

<p>Effects of digitoxin exposure on DNA synthesis (i.e. thymidine incorporation) in CCRF-CEM (A) and SUP-B15 (B) cells. The DNA polymerase inhibitor aphidicolin (15 µM) was used as a positive control. Effects of digitoxin exposure on protein synthesis (i.e. leucine incorporation) in CCRF-CEM (C) and SUP-B15 (D) cells. The ribosomal inhibitor cycloheximide (36 µM) was used as a positive control.</p

IC₅₀ (µM) regarding the effects of digitoxin and ouabain on primary leukaemic cells and PBMCs.

<p>*Never reached IC 50%.</p

Althusser and the Critique of Political Economy

Two disulfide-containing peptides, barrettides A (<b>1</b>) and B (<b>2</b>), from the cold-water marine sponge <i>Geodia barretti</i> are described. Those 31 amino acid residue long peptides were sequenced using mass spectrometry methods and structurally characterized using NMR spectroscopy. The structure of <b>1</b> was confirmed by total synthesis using the solid-phase peptide synthesis approach that was developed. The two peptides were found to differ only at a single position in their sequence. The three-dimensional structure of <b>1</b> revealed that these peptides possess a unique fold consisting of a long β-hairpin structure that is cross-braced by two disulfide bonds in a ladder-like arrangement. The peptides are amphipathic in nature with the hydrophobic and charged residues clustered on separate faces of the molecule. The barrettides were found not to inhibit the growth of either <i>Escherichia coli</i> or <i>Staphylococcus aureus</i> but displayed antifouling activity against barnacle larvae (<i>Balanus improvisus</i>) without lethal effects in the concentrations tested