Bacteriophage‐induced aggregation of oil sands tailings

Very large quantities of tailings are produced as a result of processing oil sands. After the sand particles settle out, a dense stable mixture of clay, silt, water with residual bitumen, salts, and organics called mature fine tailings (MFT) can remain in suspension for decades. Research into developing methods that would allow consolidation and sedimentation of the suspended particles is ongoing. We have studied the ability of a filamentous bacteriophage (called VP12 bearing the peptide DSQKTNPS at the N‐terminus of the major coat protein pVIII) to aggregate MFT. To understand the biophysical basis of the aggregation, phage‐induced aggregation of diluted MFT was measured at room temperature under varying conditions of pH, salt, detergent. Phage at concentrations of 5.0 × 10¹¹/mL to 10¹²/mL induced rapid settling of the diluted MFT. The addition of sodium chloride (10 mM) lowered the concentration of phage required to induce aggregation. Since the non‐ionic detergents Triton‐X 100 and Tween‐20, and the ionic detergent sodium deoxycholate had little effect, hydrophobic interactions do not appear to be a major contributor to the phage‐induced aggregation of MFT. However, aggregation was prevented at pH values higher than 9.0 suggesting that positively charged amino acid residues are required for MFT aggregation by phage. Genetic engineering of the pVIII peptide sequence indicated that hydrogen bonding also contributes to phage‐induced aggregation. In addition, replacing the basic residue lysine with an alanine in the recombinant peptide of VP12 completely prevented phage‐induced aggregation. Three other phage displaying different amino acid sequences but all containing a lysine in the same position had variable aggregation efficiencies, ranging from no aggregation to rapid aggregation. We conclude that not only are the functional groups of the amino acids important, but the conformation that is adopted by the variable pVIII peptide is also important for phage‐induced MFT aggregation. Biotechnol. Bioeng. 2013; 110: 803–811. © 2012 Wiley Periodicals, Inc.     

Ossification in the hand and foot of the pigtail macaque (Macaca nemestrina). II. Order of appearance of centers and variability in sequence

The order of appearance of the carpals, tarsals and secondary epiphyseal centers in the hand-wrist and foot-ankle regions of the fetal and infant pigtail macaque (Macaca nemestrina) was reconstructed using a cross-sectional sample of 127 animals and a longitudinal one of 14 animals. Comparison of the most common sequence in the monkey with that described in the human studies showed major interspecific differences in the order of appearance of several groups of centers, particularly those involving the thumb and great toe. The monkey displays a degree of sequence variability equivalent to that documented by the human longitudinal data, with certain centers markedly variable in timing and/or order of appearance. The evidence from related animals suggests a strong genetic component underlying some of the variable sequences observed, as has been reported in the human studies. The demonstrated variability in both timing and sequence precludes the use of specific centers in the determination of gestational age in fetuses of unknown conception date.     

A bis-[N-3-(1-hydroxy-1-methyl-ethyl)-benzyl)-cyclic urea as a HIV protease inhibitor

Synthetic efforts to overcome the metabolic oxidative degradation of the HIV protease inhibitory cyclic urea DMP323, a benzyl alcohol, have led to the discovery of a tertiary carbinol with superior affinity for the viral protease and more potent inhibitory activity against viral replication. Synthetic approaches to this new carbinol and comparative analysis of its pharmacology and pharmacokinetics are presented.