Asphaltene nanoaggregates from three diverse source materialscoal-derived asphaltenes dominated by aromatic carbon, petroleum asphaltenes with comparable abundances of aromatic and aliphatic carbon, and immature source-rock asphaltenes dominated by aliphatic carbonare examined by means of surface-assisted laser desorption ionization mass spectrometry (SALDI-MS) coupled with laser desorption laser ionization mass spectrometry (L2MS). All three types of asphaltenes form nanoaggregates with aggregation numbers close to 7. Molecular dynamics calculations for proposed island molecular structures show the important roles that π-stacking and alkane steric hindrance play in nanoaggregate formation and structure. These results are discussed in terms of entropy and enthalpy changes. All results are consistent with the Yen-Mullins model, which bodes well for its expanded use in oilfield reservoir evaluations.

We recently reported a real-time method to measure heparin in human whole blood based on the photoacoustic change of methylene blue (MB). Intriguingly, the MB behaved unlike other “turn on” photoacoustic probesthe absorbance decreased as the photoacoustic signal increased. The underlying mechanism was not clear and motivated this study. We studied the binding mechanism of MB and heparin in water and phosphate buffer saline (PBS) with both experimental and computational methods. We found that the photoacoustic enhancement of the MB–heparin mixture was a result of MB–heparin aggregation due to charge neutralization and resulting sequestration of MB in these aggregates. The sequestration of MB in the MB–heparin aggregates led to decreased absorbancethere was simply less free dye in solution to absorb light. The highest photoacoustic signal and aggregation occurred when the number of negatively charged sulfate groups on heparin was approximately equal to the number of positively charged MB molecule. The MB–heparin aggregates dissociated when there were more sulfated groups from heparin than MB molecules because of the electrostatic repulsion between negatively charged sulfate groups. PBS facilitated MB dimer formation regardless of heparin concentration and reprecipitated free MB in aggregates due to ionic strength and ionic shielding. Further molecular dynamics experiments found that binding of heparin occurred at the sulfates and glucosamines in heparin. Phosphate ions could interact with the heparin via sodium ions to impair the MB–heparin binding. Finally, our model found 3.7-fold more MB dimerization upon addition of heparin in MB solution confirming that heparin facilitates MB aggregation. We conclude that the addition of heparin in MB decreases the absorbance of the sample because of MB–heparin aggregation leading to fewer MB molecules in solution; however, the aggregation also increases the PA intensity because the MB molecules in the MB–heparin aggregate have reduced degrees of freedom and poor heat transfer to solvent.

Optimizing DNA polymerases for a broad range of tasks requires an understanding of the factors influencing polymerase fidelity, but many details of polymerase behavior remain unknown, especially in the presence of mismatched nascent base pairs. Using molecular dynamics, the large fragment of Bacillus stearothermophilus DNA polymerase I is simulated in the presence of all 16 possible standard nucleoside triphosphate-template (dNTP-dN) pairs, including four Watson-Crick pairs and 12 mismatches. The precatalytic steps of nucleotide addition from nucleotide insertion to immediately preceding catalysis are explored using three starting structures representing different stages of nucleotide addition. From these simulations, interactions between dNTPs and the DNA-protein complex formed by the polymerase are elucidated. Patterns of large-scale conformational shifts, classification of nucleotide pairs based on composition, and investigation of the roles of residues interacting with dNTPs are completed on 50+ μs of simulation. The role of molecular dynamics in studies of polymerase behavior is discussed.

A 58-year-old man presented with necrotising fasciitis and septic shock requiring urgent surgical debridement. Idarucizumab was used preoperatively to reverse the effects of dabigatran, which he was taking for chronic atrial fibrillation. He developed multiorgan failure including an oliguric acute kidney injury and was given continuous venovenous haemodiafiltration. Adjunctive intravenous immunoglobulin therapy was used in addition to his antibiotic therapy for necrotising fasciitis. Significant clinical and laboratory coagulopathy continued for over 12 days with evidence of a persistent dabigatran effect. Here, we discuss the potential impact of the immunoglobulin therapy, the patient’s weight on the degree of redistribution of dabigatran seen and the oliguria in the context of an acute kidney injury on the apparent lack of the effectiveness of idarucizumab.

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