Calibration of a Linear Free Energy Estimation Approach for Estimating Stability Constants for Metal-Bacterial Surface Complexes

In this study, we use the measured extent of metal adsorption onto bacterial cells to constrain a linear free energy relationship that allows estimation of unknown stability constants for metal-bacterial surface complexes based on the value of corresponding aqueous metal-acetate stability constants. A previous study (Fein et al., 2001 Fein, J B, Martin, A M and Wightman, P G. 2001. Metal adsorption onto bacterial surface: Development of a predictive approach. Geochim Cosmochim Acta, 65: 4267–4273. [Crossref], [Web of Science ®] , [Google Scholar]) used metal adsorption experiments to constrain a similar relationship, but the experiments were conducted using acid-washed bacteria, and subsequent evidence (Borrok et al., 2004a Borrok, D, Fein, J B, Tischler, M, O'Loughlin, E, Meyer, H, Liss, M and Kemner, K M. 2004a. The effect of acidic solutions and growth conditions on the adsorptive properties of bacterial surfaces. Chem Geol, 209: 107–119. [Crossref], [Web of Science ®] , [Google Scholar]) shows that the acid-washing step affects the extent of adsorption of a number of metals onto bacterial surfaces. We measured the adsorption of Zn, Ni, Co, Sr, and Nd onto Bacillus subtilis in 0.1 M NaClO₄ as a function of pH and metal:bacterial site ratio, using a non-electrostatic discrete four-site model of the bacterial protonation reactions as a basis for the metal adsorption modeling. The adsorption of the divalent cations (Zn, Ni, Co, and Sr) could best be modeled by considering adsorption reactions involving three sites on the bacterial surface; we used a one-site model to account for the Nd data that covered a more restricted pH range. The calculated stability constants for metal-Site 2 bacterial surface complexes are used to re-calibrate the linear free energy relationship previously defined by Fein et al. (2001) Fein, J B, Martin, A M and Wightman, P G. 2001. Metal adsorption onto bacterial surface: Development of a predictive approach. Geochim Cosmochim Acta, 65: 4267–4273. [Crossref], [Web of Science ®] , [Google Scholar]. There is a significant difference between the original and the re-calibrated lines for weakly binding cations such as Sr^{2 +}, but the difference becomes negligible for the stronger-binding cations. Because the linear free energy relationship defined in this study was calibrated from experiments that involved bacteria that were not exposed to acidic conditions, the estimated stability constant values that result from using this relationship are likely to reasonably reflect bacterial adsorption behaviors that occur in realistic geologic settings.     

Involvement of CYP3A4 and CYP2D6 in the Metabolism of Haloperidol

1. Human cytochrome P450 (CYP) isoenzymes expressed in a human cell line were used to elucidate their involvement in the metabolism of haloperidol (HAL).2. It was found that CYP3A4 catalyzes the metabolism of HAL to HAL 1,2,3,6-tetrahydropyridine (HTP). HTP is further metabolized to HAL pyridinium (HP⁺) by both CYP3A4 and CYP2D6.3. CYP3A4 and CYP2D6 are also responsible for the N-dealkylation of HAL. The N-dealkylation of reduced HAL (RH) was observed, which is catalyzed by CYP3A4. In addition, CYP3A4 also catalyzes the oxidation of RH back to HAL.4. These results are discussed in terms of the metabolic interactions of HAL with other drugs and how this knowledge may be used to reduce the movement disorders induced by HAL.     

Diversity of Mitochondrial DNA Haplogroups in Ethnic Populations of the Volga–Ural Region

The mtDNA polymorphism was analyzed in eight ethnic groups (N = 979) of the Volga–Ural region. Most mtDNA variants belonged to haplogroups H, U, T, J, W, I, R, and N1 characteristic of West Eurasian populations. The most frequent were haplogroups H (12–42%) and U (18–44%). East Eurasian mtDNA types (A, B, Y, F, M, N9) were also observed. Genetic diversity was higher in Turkic than in Finno-Ugric populations. The frequency of mtDNA types characteristic of Siberian and Central Asian populations substantially increased in the ethnic groups living closer to the Urals, a boundary between Europe and Asia. Geographic distances, rather than linguistic barriers, were assumed to play the major role in distribution of mtDNA types in the Volga–Ural region. Thus, as concerns the maternal lineage, the Finno-Ugric populations of the region proved to be more similar to their Turkic neighbors rather than to linguistically related Balto-Finnish ethnic groups.     

A study on natural and synthetic humic acids and their complexing ability towards cadmium

The natural and synthetic humic acids were characterised by potentiometric titrations, viscosity and surface tension measurements, as well as visible spectometry The results have been correlated with coiling-decoiling behaviour and aliphatic–aromatic balance of these acids. The stability constant of complexes formed by these humic acids with Cd²⁺ ions in aqueous phase was evaluated by the ion-exchange method. Results tend to suggest that humic phenolic –OH group was involved in the formation of Cd²⁺–humic complex, leading to it the given stability in a manner as for the analogous metal–oxine complexation. The hydrophobic moiety of the synthetic humic acid may also provide a cage-type conformation around Cd²⁺ ion, imparting to the Cd²⁺–humic complex the desired stability.     

Structure and Function of RecQ DNA Helicases

RecQ family helicases play important roles in coordinating genome maintenance pathways in living cells. In the absence of functional RecQ proteins, cells exhibit a variety of phenotypes, including increased mitotic recombination, elevated chromosome missegregation, hypersensitivity to DNA-damaging agents, and defects in meiosis. Mutations in three of the five human RecQ family members give rise to genetic disorders associated with a predisposition to cancer and premature aging, highlighting the importance of RecQ proteins and their cellular activities for human health. Current evidence suggests that RecQ proteins act at multiple steps in DNA replication, including stabilization of replication forks and removal of DNA recombination intermediates, in order to maintain genome integrity. The cellular basis of RecQ helicase function may be explained through interactions with multiple components of the DNA replication and recombination machinery. This review focuses on biochemical and structural aspects of the RecQ helicases and how these features relate to their known cellular function, specifically in preventing excessive recombination.     

Enantioselective inhibitory effect of nicardipine on the hepatic clearance of propranolol in man

The influence of a single oral dose of 30 mg nicardipine on the pharmacokinetics of (R)- and (S)-propranolol, given orally as rac-propranolol 80 mg, was studied in 12 healthy volunteers. The plasma concentrations were higher for the (S)-enantiomer than for the (R)-enantiomer. The Cl_o and the Cl′_intr of (S)-propranolol were significantly lower than the Cl_o and Cl′_intr of (R)-propranolol. The unbound fraction of (R)-propranolol was significantly higher than that of (S)-propranolol. Coadministration of nicardipine significantly increased the AUC and C_max and significantly decreased the Cl_o and Cl′_intr for unbound drug of (R)- and (S)-propranolol. These changes were more important for (R)- than for (S)-propranolol. The protein binding was not altered by nicardipine. The enantioselective effect of nicardipine on the metabolic clearance of propranolol appears to be due to an interaction at the level of the metabolizing enzymes. The effect on blood pressure of rac-propranolol was little affected when nicardipine was coadministered with rac-propranolol, and its bradycardic effect was reduced. © 1994 Wiley-Liss, Inc.     

Nucleosomal locations of dominant DNA sequence motifs for histone-DNA interactions and nucleosome positioning

DNA sequence is an important determinant of the positioning, stability, and activity of nucleosomes, yet the molecular basis of these effects remains elusive. A "consensus DNA sequence" for nucleosome positioning has not been reported and, while certain DNA sequence preferences or motifs for nucleosome positioning have been discovered, how they function is not known. Here, we report that an unexpected observation concerning the reassembly of nucleosomes during salt gradient dialysis has allowed a breakthrough in our efforts to identify the nucleosomal locations of the DNA sequence motifs that dominate histone-DNA interactions and nucleosome positioning. We conclude that a previous selection experiment for high-affinity, nucleosome-forming DNA sequences exerted selective pressure chiefly on the central stretch of the nucleosomal DNA. This observation implies that algorithms for aligning the selected DNA sequences should seek to optimize the alignment over much less than the full 147 bp of nucleosomal DNA. A new alignment calculation implemented these ideas and successfully aligned 19 of the 41 sequences in a non-redundant database of selected high-affinity, nucleosome-positioning sequences. The resulting alignment reveals strong conservation of several stretches within a central 71 bp of the nucleosomal DNA. The alignment further reveals an inherent palindromic symmetry in the selected DNAs; it makes testable predictions of nucleosome positioning on the aligned sequences and for the creation of new positioning sequences, both of which are upheld experimentally; and it suggests new signals that may be important in translational nucleosome positioning.