In situ analysis of garnet inclusion in diamond using single-crystal X-ray diffraction and X-ray micro-tomography

none9A single crystal of garnet enclosed in a diamond from the Jericho kimberlite (Slave Craton, Canada) has been investigated using X-ray diffraction and X-ray micro-tomography. The novel experimental approach allowed us to determine the crystal structure of the garnet. The unit-cell edge a and fractional atomic coordinates of oxygen were used to determine the composition via an updated Margules model for garnets. The composition is Pyr(0.41(5))Alm(0.36(7))Gro(0.22(1))Uva(0.01(1)), which is indistinguishable from the eclogitic garnets found in other Jericho diamonds. We also demonstrated that residual pressures on the inclusion of up to 1 GPa do not affect significantly the determination of the garnet composition by structure refinement.noneFABRIZIO NESTOLA;M. MERLI;PAOLO NIMIS;M. PARISATTO;M. KOPYLOVA;A. DE;M. LONGO;L. ZIBERNA;M. MANGHNANINestola, Fabrizio; M., Merli; Nimis, Paolo; Parisatto, Matteo; M., Kopylova; A., De; Longo, Micaela; Ziberna, Luca; M., Manghnan

Relatively oxidized conditions for diamond formation at Udachnaya (Siberia)

Thanks to the physical strength of diamonds and their relatively unreactive chemical nature, their mineral inclusions may remain exceptionally preserved from alteration processes and chemical exchanges with surrounding minerals, fluids and/or melts following diamond formation. Cr-bearing spinels are relatively common inclusions found in peridotitic diamonds and important oxybarometers providing information about the oxygen fugacity (fO2) of their source mantle rocks. Here, we investigated a magnesiochromite-olivine touching pair in a diamond from the Udachnaya kimberlite (Siberia) by in situ single-crystal X-ray diffraction and energy-domain synchrotron Mossbauer spectroscopy, aiming to constrain the physical-chemical conditions of diamond formation and to explore the redox state of this portion of the Siberian craton when the diamond was formed. The P-T-fO(2) entrapment conditions of the inclusion pair, determined by thermo- and oxybarometric analyses, are similar to 5.7(0.4) GPa and similar to 1015(50) ? (although entrapment at higher T and re-equilibration during subsequent mantle storage are also possible) and fO(2) near the enstatite-magnesite-olivine-diamond (EMOD) buffer. The determined fO(2) is similar to, or slightly more oxidized than, those of xenoliths from Udachnaya, but whilst the xenoliths last equilibrated with the surrounding mantle just prior to their entrainment in the kimberlite at similar to 360 Ma, the last equilibration of the inclusion pair is much older, occurring at 3.5-3.1, similar to 2 or similar to 1.8 Ga before final encapsulation in its host diamond. Hence, the similarity between xenoliths and inclusion fO(2) values indicates that the modern redox state of this portion of the Siberian lithosphere was likely attained relatively early after its formation and may have persisted for billions of years after diamond formation, at least at the local scale. Moreover, the oxygen fugacity determination for the inclusion pair provides direct evidence of diamond formation near the EMOD buffer and is consistent with recent models suggesting relatively oxidized, water-rich CHO fluids as the most likely parents for lithospheric diamonds

Structural Analysis of a Peptide Fragment of Transmembrane Transporter Protein Bilitranslocase

Using a combination of genomic and post-genomic approaches is rapidly altering the number of identified human influx carriers. A transmembrane protein bilitranslocase (TCDB 2.A.65) has long attracted attention because of its function as an organic anion carrier. It has also been identified as a potential membrane transporter for cellular uptake of several drugs and due to its implication in drug uptake, it is extremely important to advance the knowledge about its structure. However, at present, only the primary structure of bilitranslocase is known. In our work, transmembrane subunits of bilitranslocase were predicted by a previously developed chemometrics model and the stability of these polypeptide chains were studied by molecular dynamics (MD) simulation. Furthermore, sodium dodecyl sulfate (SDS) micelles were used as a model of cell membrane and herein we present a high-resolution 3D structure of an 18 amino acid residues long peptide corresponding to the third transmembrane part of bilitranslocase obtained by use of multidimensional NMR spectroscopy. It has been experimentally confirmed that one of the transmembrane segments of bilitranslocase has alpha helical structure with hydrophilic amino acid residues oriented towards one side, thus capable of forming a channel in the membrane

Toxicological aspects of the use of phenolic compounds in disease prevention

The consumption of a diet low in fat and enhanced by fruits and vegetables, especially rich in phenolic compounds, may reduce risks of many civilization diseases. The use of traditional medicines, mainly derived from plant sources, has become an attractive segment in the management of many lifestyle diseases. Concerning the application of dietary supplements (based on phenolic compounds) in common practice, the ongoing debate over possible adverse effects of certain nutrients and dosage levels is of great importance. Since dietary supplements are not classified as drugs, their potential toxicities and interactions have not been thoroughly evaluated. First, this review will introduce phenolic compounds as natural substances beneficial for human health. Second, the potential dual mode of action of flavonoids will be outlined. Third, potential deleterious impacts of phenolic compounds utilization will be discussed: pro-oxidant and estrogenic activities, cancerogenic potential, cytotoxic effects, apoptosis induction and flavonoid-drug interaction. Finally, future trends within the research field will be indicated

Bioavailability of flavonoids: in vitro methods for assessing bilitranslocase-mediated membrane transport

B ilitranslocase (TC 2.A.65.1.1) is a plasma membrane transporter expressed in the gastro-intestinal epithelium (luminal side), the liver and kidney (vascular side) (1) and in the vascular endothelium (2). It transports bilirubin, flavonoids and other organic anions. By using specific anti-sequence bilitranslocase antibodies targeting extracellular epitopes critical for the carrier function, we can investigate both the tissue and cellular localisation of the protein and its function in absorption and tissue distribution of flavonoids, by a system of in vitro methods featured by increasing structural complexity: i) plasma membrane vesicles, ii) cell cultures, iii) tissue fragments, and iv) isolated organs. The best example of implementation of this chain of in vitro methods is the cardiovascular system, where consistent observations were obtained throughout the chain. It can be concluded that the first method, i.e. a bilitranslocase-specific functional assay (3) in membrane vesicles where potential ligands (competitive and non-competitive inhibitors) are identified, yields data predictive of bilitranslocase function in organs. This approach can be helpful for exploiting bilitranslocase as a membrane transporter in drug targeting and development. 1 Passamonti S, Terdoslavich M, Franca R, Vanzo A, Tramer F, Braidot E, et al. Curr Drug Metab. 2009 May;10(4):369-94. 2 Maestro A, Terdoslavich M, Vanzo A, Kuku A, Tramer F, Nicolin V, et al.. Cardiovasc Res. 2009 Aug 25. 3 Passamonti S, Tramer F, Petrussa E, Braidot E, Vianello A. In: FettNeto AG, editor. Plant Secondary Metabolism Engineering Methods and Applications. Totowa, NJ: Humana Press Inc.; 2010

Dietary anthocyanins: are they micronutrients?

Dietary anthocyanins might be seen as micronutrients. Even though they are abundant in fruits and vegetables, and thus also in our diet, they occur in plasma and tissues only in trace amounts. However, they profoundly af ect cellular metabolism, organ functioning, and have strong clinical-epidemiological evidence supporting their health-promoting ef ects

Cellular antioxidant activity of bilirubin in the human endothelial cell line EA.hy 926 is mediated by bilitranslocase

Background Oxidative stress plays an important role in the pathogenesis of cardiovascular degenerative diseases. Bilirubin is known to be a potent endogenous antioxidant, both in in vitro and in vivo. The latter can be ascribed to an efficient amplification cycle whereby bilirubin, acting as antioxidant, is itself oxidized to biliverdin and then recycled back to bilirubin by NADPH-dependent biliverdin reductase. Bilitranslocase, a bilirubin-specific membrane carrier that mediates cellular uptake of bilirubin, has recently been found in the vascular endothelium. However, the levels of albumin-free bilirubin in plasma and tissues are only 10 to 50 nM. Therefore, the objective of this study was to elucidate the antioxidant activity of low concentrations of bilirubin and the involvement of bilitranslocase-mediated plasma membrane transport in human endothelial cells. Methods In this study we used the cellular antioxidant activity (CAA) assay developed by Wolfe and Liu [1]. Briefly, the assay is designed to trigger an acute oxidative stress into cells (by adding the radical initiator ABAP to the cell medium) and to fluorimetrically follow the subsequent increase of an intracellular radical-sensitive fluorescent dye. Substances with antioxidative properties that have free oxygen radical scavenging properties have been found to decrease the formation of fluorescence. By using the CAA assay, we have quantitatively evaluated the antioxidant activity of bilirubin in the endothelial cell line EA.hy 926. In our experiments, the cells were pre-incubated with anti-bilitranslocase antibodies (studied group) or bovine IgG (control group) before starting the CAA assay with bilirubin (0.5-100 nM). Results The intra-cellular antioxidant activity of bilirubin was concentration-dependent with an apparent saturation obtained at higher concentrations. The half-maximal effect was obtained at concentrations as low as 5 nM. The pre-incubation of the cells with anti-bilitranslocase antibodies reduced the antioxidant activity by about 50%. Conclusion Bilirubin has a potent intracellular antioxidant activity if applied to cells at concentrations close to its albumin-free plasma levels. The observed cellular antioxidant activity depends on bilitranslocase-mediated plasma membrane transport and therefore confirms the functional role of bilitranslocase as a membrane transporter in the endothelium

Transport and bioactivity of cyanidin 3-glucoside into the vascular endothelium

Flavonoids are dietary components involved in decreasing oxidative stress in the vascular endothelium, and thus the risk of endothelial dysfunction. However, their very low concentrations in plasma place this role in doubt. Thus, a relationship between the effective intracellular concentration of flavonoids and their bioactivity needs to be assessed. This study examined the uptake of physiological concentrations of cyanidin 3-glucoside, a widespread dietary flavonoid, into the human vascular endothelial cells. Furthermore, the involvement of the membrane transporter bilitranslocase (TC #2.A.65.1.1) as the key underlying molecular mechanism for membrane transport was investigated by using purified anti-sequence antibodies binding at the extracellular domain of the protein. The experimental observations were carried out in isolated plasma membrane vesicles and intact endothelial cells from human endothelial cells (EA.hy926), and on the ischemia-reperfusion model in the isolated rat hearts. Cyanidin 3-glucoside was transported via bilitranslocase into endothelial cells, where it acted as a powerful intracellular antioxidant and a cardioprotective agent in the reperfusion phase after ischemia. These findings suggest that dietary flavonoids, in spite of their limited oral bioavailability and very low post-absorption plasma concentrations, may provide protection against oxidative stress-based cardiovascular diseases. Bilitranslocase, by mediating the cellular uptake of some flavonoids, is thus a key factor for their protective activity on the endothelial function