Correction to: Accelerating Reactive Transport Modeling: On-Demand Machine Learning Algorithm for Chemical Equilibrium Calculations

Transport in Porous Media - In the original publication of the article, Table 2 was published incorrectly.     

Electron transport in corona charged 12 μm teflon FEP with saturable deep traps

Surface-potential measurements carried out in negatively corona charged 12 m samples of fluorethylenepropylene (Teflon FEP) showed the following characteristics: 1) with a constant charging current, the potential initially rises linearly, and then sublinearly; 2) the potential saturates irrespectively of the charging process and 3) practically no potential decay is observed after switching off the corona. These results have been interpreted in terms of an usual model (field-independent trapping time) for charge transport in insulators, with saturable deep traps in both surface and bulk of the sample and a relatively high electron mobility in order to prevent free-space charge accumulation. The partial differential equations derived from the model are numerically solved and it was found that only the product of the mobility with the trapping time is relevant to the fitting of experimental results, provided that >10^–8 cm²/Vs. A field-dependent trapping time model leads to poorer fittings.     

Phase separation of p53 precedes aggregation and is affected by oncogenic mutations and ligands

Mutant p53 tends to form aggregates with amyloid properties, especially amyloid oligomers inside the nucleus, which are believed to cause oncogenic gain-of-function (GoF). The mechanism of the formation of the aggregates in the nucleus remains uncertain. The present study demonstrated that the DNA-binding domain of p53 (p53C) underwent phase separation (PS) on the pathway to aggregation under various conditions. p53C phase separated in the presence of the crowding agent polyethylene glycol (PEG). Similarly, mutant p53C (M237I and R249S) underwent PS; however, the process evolved to a solid-like phase transition faster than that in the case of wild-type p53C. The data obtained by microscopy of live cells indicated that transfection of mutant full-length p53 into the cells tended to result in PS and phase transition (PT) in the nuclear compartments, which are likely the cause of the GoF effects. Fluorescence recovery after photobleaching (FRAP) experiments revealed liquid characteristics of the condensates in the nucleus. Mutant p53 tended to undergo gel- and solid-like phase transitions in the nucleus and in nuclear bodies demonstrated by slow and incomplete recovery of fluorescence after photobleaching. Polyanions, such as heparin and RNA, were able to modulate PS and PT in vitro. Heparin apparently stabilized the condensates in a gel-like state, and RNA apparently induced a solid-like state of the protein even in the absence of PEG. Conditions that destabilize p53C into a molten globule conformation also produced liquid droplets in the absence of crowding. The disordered transactivation domain (TAD) modulated both phase separation and amyloid aggregation. In summary, our data provide mechanistic insight into the formation of p53 condensates and conditions that may result in the formation of aggregated structures, such as mutant amyloid oligomers, in cancer. The pathway of mutant p53 from liquid droplets to gel-like and solid-like (amyloid) species may be a suitable target for anticancer therapy.

Mutant p53 tends to form aggregates with amyloid properties, especially amyloid oligomers inside the nucleus, which are believed to cause oncogenic gain-of-function (GoF).     

Sexual attraction in the silkworm moth: structure of the pheromone-binding-protein-bombykol complex

BACKGROUND: Insects use volatile organic molecules to communicate messages with remarkable sensitivity and specificity. In one of the most studied systems, female silkworm moths (Bombyx mori) attract male mates with the pheromone bombykol, a volatile 16-carbon alcohol. In the male moth's antennae, a pheromone-binding protein conveys bombykol to a membrane-bound receptor on a nerve cell. The structure of the pheromone-binding protein, its binding and recognition of bombykol, and its full role in signal transduction are not known. RESULTS: The three-dimensional structure of the B. mori pheromone-binding protein with bound bombykol has been determined by X-ray diffraction at 1.8 A resolution. CONCLUSIONS: The pheromone binding protein of B. mori has six helices, and bombykol binds in a completely enclosed hydrophobic cavity formed by four antiparallel helices. Bombykol is bound in this cavity through numerous hydrophobic interactions, and sequence alignments suggest critical residues for specific pheromone binding.     

Molecular dynamics simulations of a nucleoside analogue of 1,4-dihydro-4-oxoquinoline-3-carboxylic acid synthesized as a potential antiviral agent: Conformational studies in vacuum and in water

Conformational analysis of nucleosides may have direct applications to the structure–activity relationship (SAR) studies and in the design of new drug candidates. Although conformational analysis may be accessed in many different ways, in this work it was performed using molecular dynamics (MD) simulation in order to study the dynamic behavior of a nucleoside derivative of 1,4-dihydro-4-oxoquinoline-3-carboxylic acid, synthesized by our group as a potential antiviral agent. The MD simulation was carried out during 10 ns in vacuum and in a box of water at two different temperatures (i.e., 300 and 600 K) using the AMBER force field. The in vacuum MD simulation results are in agreement with the crystallographic structure and with the DFT calculations of the nucleoside, revealing the anti conformer as the more stable one. The simulation in water, however, shows that both conformers may exist at 300 K, the temperature of the in vivo and in vitro assays, revealing that both the syn and anti conformers should be considered in a MD simulation study of the inhibitor–enzyme complex. Simulations are also in agreement with the NOE experiment, which shows that the anti conformer is the preferential one in DMSO-d6 solution at 298 K.     

A rapid and sensitive method for simultaneous determination of lamivudine and zidovudine in human serum by on-line solid-phase extraction coupled to liquid chromatography/tandem mass spectrometry detection

A method based on solid-phase extraction (SPE) coupled to high-performance liquid chromatography (HPLC) with positive ion electrospray ionization tandem mass spectrometry (ESI-MS/MS) detection was developed for the simultaneous determination of lamivudine (3TC) and zidovudine (AZT) in human serum, using didanosine (ddI) as internal standard. The acquisition was performed in multiple reaction monitoring (MRM) mode, monitoring the transitions m/z 230.0 --> 111.8 for 3TC, m/z 268.1 --> 126.8 for AZT, and m/z 237.2 --> 136.8 for ddI. The limits of detection and quantitation were 3 and 10 ng/mL for 3TC, and 5 and 15 ng/mL for AZT. The method was linear in the studied ranges (10-1500 ng/mL for 3TC and 15-3000 ng/mL for AZT), with r(2) > 0.99 for each drug, and the run time was 4 min. The intra-assay precisions (%) were in the ranges 1.9-8.7 (3TC) and 2.2-8.9 (AZT), the inter-assay precisions were in the ranges 2.6-9.0 (3TC) and 4.2-8.1 (AZT), and the intra- and inter-assay accuracies were >97% for both drugs. The absolute recoveries were 95-99% for 3TC (45, 600 and 1200 ng/mL) and 104-112% for AZT (45, 1000 and 2400 ng/mL). The analytical method was applied to a bioequivalence study in which 24 healthy adult volunteers received single oral doses of the reference formulation and two test combined AZT/3TC tablets, in an open, three-period, balanced, randomized, crossover protocol. Based on the 90% confidence interval of the individual ratios (test formulation/reference formulation) for C(max) (peak serum concentration) and AUC(0-inf) (extrapolated area under the serum concentration vs. time curve from time zero to infinity), it was concluded that the two test formulations are bioequivalent to the reference formulation with respect to the rate and extent of absorption of both 3TC and AZT.     

Labelling of organotin compounds for fluorimetric detection

A systematic study of the fluorescence of complexes of some flavone derivatives with organotin compounds in hexane and in an aqueous micellar medium on Triton X-100 is reported. Some relationships between fluorescence intensity and the structure of the fluorogenic reagent or that of the organotin compound can be deduced, and the most suitable reagent for each organotin species can be chosen on the basis of sensitivity and selectivity. Results point out that flavone derivatives are appropriate post-column derivatization reagents for organotin compounds in liquid chromatography.