Complex reactions catalyzed by cytochrome P450 enzymes

Cytochrome P450 (P450) enzymes are some of the most versatile redox proteins known. The basic P450 reactions include C-hydroxylation, heteroatom oxygenation, heteroatom release (dealkylation), and epoxide formation. Mechanistic explanations for these reactions have been advanced. A number of more complex P450 reactions also occur, and these can be understood largely in the context of the basic chemical mechanisms and subsequent rearrangements. The list discussed here updates a 2001 review and includes chlorine oxygenation, aromatic dehalogenation, formation of diindole products, dimer formation via Diels-Alder reactions of products, ring coupling and also ring formation, reductive activation (e.g., aristolochic acid), ring contraction (piperidine nitroxide radical), oxidation of troglitazone, cleavage of amino oxazoles and a 1,2,4-oxadiazole ring, bioactivation of a dihydrobenzoxathiin, and oxidative aryl migration.     

Radiosensitization effects by bismuth oxide nanorods of different sizes in megavoltage external beam radiotherapy

BackgroundNanotechnology application has successfully reached numerous scientific breakthroughs including in radiotherapy. However, the clinical application of nanoparticles requires more diligent research primarily on the crucial parameters such as nanoparticle sizes. This study is aimed to investigate the influence of bismuth oxide nanorod (Bi₂O₃-NR) sizes on radiosensitization effects on MCF-7 and HeLa cell lines for megavoltage photon and electron beam radiotherapy.Materials and methodsMCF-7 and HeLa cells were treated with and without 0.5 μMol/L of Bi₂O₃-NR of varying sizes (60, 70, 80, and 90 nm). The samples, including the control groups, were exposed to different radiation doses (0–10 Gy), using photon (6 MV and 10 MV), and electron beam (6 MeV and 12 MeV) radiotherapy. Clonogenic assay was performed, and sensitization enhancement ratio (SER) was determined from linear quadratic based cell survival curves.ResultsThe results depicted that 60 nm Bi₂O₃-NR yields the most excellent SER followed by 70 nm Bi₂O₃-NR. Meanwhile, the 80 and 90 nm Bi₂O₃-NR showed an insignificant difference between treated and untreated cell groups. This study also found that MCF-7 was subjected to more cell death compared to HeLa.Conclusion60 nm Bi₂O₃-NR was the optimal Bi₂O₃-NR size to induce radiosensitization effects for megavoltage external beam radiotherapy. The SER in photon beam radiotherapy marked the highest compared to electron beam radiotherapy due to decreased primary radiation energy from multiple radiation interaction and higher Compton scattering.     

A membrane-bound hemoglobin from gills of the green shore crab Carcinus maenas

Most hemoglobins serve for the transport or storage of O(2). Although hemoglobins are widespread in "entomostracan" Crustacea, malacostracans harbor the copper-containing hemocyanin in their hemolymph. Usually, only one type of respiratory protein occurs within a single species. Here, we report the identification of a hemoglobin of the shore crab Carcinus maenas (Malacostraca, Brachyura). In contrast to the dodecameric hemocyanin of this species, C. maenas hemoglobin does not reside in the hemolymph but is restricted to the gills. Immunofluorescence studies and cell fractioning showed that C. maenas hemoglobin resides in the membrane of the chief cells of the gill. To the best of our knowledge, this is the first time that a membrane-bound hemoglobin has been identified in eukaryotes. Bioinformatic evaluation suggests that C. maenas hemoglobin is anchored in the membrane by N-myristoylation. Recombinant C. maenas hemoglobin has a hexacoordinate binding scheme at the Fe(2+) and an oxygen affinity of P(50) = 0.5 Torr. A rapid autoxidation rate precludes a function as oxygen carrier. We rather speculate that, analogous to prokaryotic membrane-globins, C. maenas hemoglobin carries out enzymatic functions to protect the lipids in cell membrane from reactive oxygen species. Sequence comparisons and phylogenetic studies suggested that the ancestral arthropod hemoglobin was most likely an N-myristoylated protein that did not have an O(2) supply function. True respiratory hemoglobins of arthropods, however, evolved independently in chironomid midges and branchiopod crustaceans.     

Solution study of engineered quartz binding peptides using replica exchange molecular dynamics

We use replica-exchange molecular dynamics (REMD) to interrogate molecular structures and properties of four engineered dodecapeptides (in solution, in the absence of a surface) that have been shown to bind to quartz with different propensities. We find that all of the strong-binding peptides feature some polyproline type II secondary structure, have less conformational freedom, and feature fewer intrapeptide hydrogen bonds compared with the weak binder. The regions of contiguous proline content in a given sequence appear to play a role in fostering some of these properties of the strong binders. For preliminary insights into quartz binding, we perform lattice-matching studies between a grid corresponding with the quartz (100) surface and the strong-binding peptide REMD structures. Our findings indicate a commonality among the putative contact residues, even for peptide structures with very different backbone conformations. Furthermore, interpeptide interactions in solution are studied. Our preliminary findings indicate that the strong-binder interpeptide contacts are dominated by weak, nonspecific hydrophobic interactions, while the weak-binding peptide shows more variable behavior due to the distribution of charged residues. In summary, the solution structures of peptides appear to be significant. We propose that these differences in their intra- and interpeptide interactions can influence their propensity to bind onto a solid substrate.     

水分胁迫对大果沙枣光合特性及生物量分配的影响

选取大果沙枣1年生幼苗,盆栽于相对含水量分别为70%~75%(CK)、50%~55%(T1)、35%~40%(T2)和15%~20%(T3)的土壤中培养25 d,研究大果沙枣在水分胁迫下的光合特性变化和生物产量积累及其分配规律。结果显示:水分胁迫抑制了大果沙枣的光合作用,与对照相比,T2和T3处理导致净光合速率、叶片蒸腾速率和水分利用效率显著降低,气孔阻力、胞间二氧化碳浓度和叶绿素含量升高,而且光合午休明显,非气孔因素是干旱时大果沙枣净光合速率下降的主要原因;水分胁迫下,大果沙枣的生长受到抑制,地上部分和地下部分的干生物量积累同时降低,但地下干生物量降低的程度低于地上部分;干旱处理中,T3处理显著抑制大果沙枣的生长,但仍保持一定的生物量增加。结果表明:大果沙枣具有一定的自我调节与保护能力,在水分胁迫下大果沙枣趋于将更多的资源分配给根系,以提高根冠比而适应干旱的环境。     

Antimicrobial activity of some sulfonamide derivatives on clinical isolates of Staphylococus aureus

Background

Human infections with non-O1, non-O139 V. cholerae have been described from Laos. Elsewhere, non cholera-toxin producing, non-O1, non-O139 V. cholerae have been described from blood cultures and ascitic fluid, although they are exceedingly rare isolates.

Case presentation

We describe a farmer who died with Vibrio cholerae O21 bacteremia and peritonitis in Vientiane, Laos, after eating partially cooked apple snails (Pomacea canaliculata) and mussels (Ligumia species). The cultured V. cholerae were non-motile. PCR detected ompW and toxR gene regions but not the ctxA, ompU, omp K and TCP gene regions. Although the organisms lacked flagellae on scanning electron microscopy, they possessed the Vibrio flagellin flaA gene.

Conclusion

Severe bacteremic non-O1, non-O139 V. cholerae is reported from Laos. The organisms were unusual in being non-motile. They possessed the Vibrio flagellin flaA gene. Further research to determine the reasons for the non-motility and virulence is required.     

Body fat distribution has no effect on serum visfatin levels in healthy female subjects

Obesity is the presence of either abnormal absolute amount or relative proportion of body fat. Contrary to gluteal obesity, visceral obesity is associated with different metabolic alterations including insulin resistance (IR). A relatively new adipocytokine visfatin is shown to be expressed predominantly in visceral fat and exhibit insulin-mimicking effects in rodents. It is still unclear whether serum visfatin levels are associated with increased total or visceral fat mass in humans. The aim of our study was to investigate the relation between visfatin and obesity parameters namely body mass index (BMI) and waist circumference (WaC) and IR in healthy female subjects. Eighty one female subjects ?20 years of age, having no diagnosis of glucose intolerance or diabetes, hypertension and dyslipidemia were chosen. The patients were divided into four groups according to their BMI and WaC values. Serum visfatin and HOMA-IR levels did not differ among groups. No correlation was detected between serum visfatin levels and obesity and metabolic parameters. In conclusion, we demonstrated that body fat distribution did not affect serum visfatin levels in healthy female subjects. Further studies are needed to clarify the exact factors influencing and determining serum visfatin levels and its clinical reflections.