346 research outputs found
Laboratory study of spectral induced polarization responses of magnetite - Fe2+ redox reactions in porous media
Spectral Induced Polarization (SIP) phase anomalies in field surveys at contaminated sites have previously been shown to correlate with the occurrence of chemically reducing conditions and/or semiconductive minerals, but the reasons for this are not fully understood. We report a systematic laboratory investigation of the role of the semiconductive mineral magnetite and its interaction with redoxactive versus redox-inactive ions in producing such phase anomalies. The SIP responses of quartz sand with 5% magnetite in solutions containing redox-inactive Ca2+, and Ni2+, versus redox-active Fe2+ were measured across the pH ranges corresponding to adsorption of these metals to magnetite. With redox inactive ions Ca2+ and Ni2+, SIP phase response showed no changes across the pH range 4 to10, corresponding to their adsorption, showing ~30 mrad anomalies peaking at ~59 to 74 Hz. These large phase anomalies are probably caused by polarization of the magnetite-solution interfaces. With the redox-active ion Fe2+, frequency of peak phase res onse decreased progressively from ~46 to ~3 Hz as effluent pH increased from 4 to 7, corresponding to progressive adsorption of Fe2+ to the magnetite surface. The latter frequency (3 Hz) corresponds approximately with those of phase anomalies detected in field surveys reported elsewhere. We conclude that pH sensitivity arises from redox reactions between Fe2+ and magnetite surfaces, with transfer of electrical charge through the bulk mineral, as reported in other laboratory investigations. Our results confirm that SIP measurements are sensitive to redox reactions involving charge transfers between adsorbed ions and semiconductive minerals. Phase anomalies seen in field surveys of groundwater contamination and biostimulation may therefore be indicative of iron-reducing conditions, when semiconductive iron minerals such as magnetite are present
How Short-Lived Ikaite Affects Calcite Crystallization
The pathways of CaCO₃ crystallization are manifold, often involving one or several metastable amorphous or nanocrystalline intermediate phases. The presence of such intermediates is often overlooked, because they are short-lived and/or occur at small molar fractions. However, their occurrence does not just impact the mechanisms and pathways of formation of the final stable CaCO₃ phase, but also affects their crystal size, shape, and structure. Here we document the presence of a short-lived intermediate through in situ and time-resolved small and wide-angle X-ray scattering combined with high resolution electron microscope observations. When ikaite forms concomitant with the dissolution of amorphous calcium carbonate (ACC) but prior to calcite formation, fairly large glendonite-type calcite crystals grow despite the presence of citrate ligands that usually reduce crystal size. These were ideal seeding crystals for further crystallization from supersaturated ions in solution. In contrast, in the absence of ikaite the crystallization of calcite proceeds through transformation from ACC, resulting in fine-grained spherulitic calcite with sizes ∼8 times smaller than when ikaite was present. Noteworthy is that the formation of the intermediate ikaite, although it consumes less than 3 mol % of the total precipitated CaCO₃, still clearly affected the calcite formation mechanism
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Biomineralisation by earthworms: an investigation into the stability and distribution of amorphous calcium carbonate
Background
Many biominerals form from amorphous calcium carbonate (ACC), but this phase is highly unstable when synthesised in its pure form inorganically. Several species of earthworm secrete calcium carbonate granules which contain highly stable ACC. We analysed the milky fluid from which granules form and solid granules for amino acid (by liquid chromatography) and functional group (by Fourier transform infrared (FTIR) spectroscopy) compositions. Granule elemental composition was determined using inductively coupled plasma-optical emission spectroscopy (ICP-OES) and electron microprobe analysis (EMPA). Mass of ACC present in solid granules was quantified using FTIR and compared to granule elemental and amino acid compositions. Bulk analysis of granules was of powdered bulk material. Spatially resolved analysis was of thin sections of granules using synchrotron-based μ-FTIR and EMPA electron microprobe analysis.
Results
The milky fluid from which granules form is amino acid-rich (≤ 136 ± 3 nmol mg−1 (n = 3; ± std dev) per individual amino acid); the CaCO3 phase present is ACC. Even four years after production, granules contain ACC. No correlation exists between mass of ACC present and granule elemental composition. Granule amino acid concentrations correlate well with ACC content (r ≥ 0.7, p ≤ 0.05) consistent with a role for amino acids (or the proteins they make up) in ACC stabilisation. Intra-granule variation in ACC (RSD = 16%) and amino acid concentration (RSD = 22–35%) was high for granules produced by the same earthworm. Maps of ACC distribution produced using synchrotron-based μ-FTIR mapping of granule thin sections and the relative intensity of the ν2: ν4 peak ratio, cluster analysis and component regression using ACC and calcite standards showed similar spatial distributions of likely ACC-rich and calcite-rich areas. We could not identify organic peaks in the μ-FTIR spectra and thus could not determine whether ACC-rich domains also had relatively high amino acid concentrations. No correlation exists between ACC distribution and elemental concentrations determined by EMPA.
Conclusions
ACC present in earthworm CaCO3 granules is highly stable. Our results suggest a role for amino acids (or proteins) in this stability. We see no evidence for stabilisation of ACC by incorporation of inorganic components
A candidate gene approach identifies an IL33 genetic variant as a novel genetic risk factor for GCA
INTRODUCTION:
Increased expression of IL-33 and its receptor ST2, encoded by the IL1RL1 gene, has been detected in the inflamed arteries of giant cell arteritis (GCA) patients. The aim of the present study was to investigate for the first time the potential influence of the IL33 and IL1RL1 loci on GCA predisposition.
METHODS:
A total of 1,363 biopsy-proven GCA patients and 3,908 healthy controls from four European cohorts (Spain, Italy, Germany and Norway) were combined in a meta-analysis. Six genetic variants: rs3939286, rs7025417 and rs7044343, within the IL33 gene, and rs2058660, rs2310173 and rs13015714, within the IL1RL1 gene, previously associated with immune-related diseases, were genotyped using predesigned TaqMan assays.
RESULTS:
A consistent association between the rs7025417 polymorphism and GCA was evident in the overall meta-analysis, under both allele (P(MH) = 0.041, OR = 0.88, CI 95% 0.78-0.99) and recessive (P(MH) = 3.40E-03, OR = 0.53, CI 95% 0.35-0.80) models. No statistically significant differences between allele or genotype frequencies for the other IL33 and IL1RL1 genetic variants were detected in this pooled analysis.
CONCLUSIONS:
Our results clearly evidenced the implication of the IL33 rs7025417 polymorphism in the genetic network underlying GCA
Dual FGF-2 and Intergrin α5β1 Signaling Mediate GRAF-Induced RhoA Inactivation in a Model of Breast Cancer Dormancy
Interactions with the bone marrow stroma regulate dormancy and survival of breast cancer micrometastases. In an in vitro model of dormancy in the bone marrow, we previously demonstrated that estrogen-dependent breast cancer cells are partially re-differentiated by FGF-2, re-express integrin α5β1 lost with malignant transformation and acquire an activated PI3K/Akt pathway. Ligation of integrin α5β1 by fibronectin and activation of the PI3K pathway both contribute to survival of these dormant cells. Here, we investigated mechanisms responsible for the dormant phenotype. Experiments demonstrate that integrin α5β1 controls de novo cytoskeletal rearrangements, cell spreading, focal adhesion kinase rearrangement to the cell perimeter and recruitment of a RhoA GAP known as GRAF. This results in the inactivation of RhoA, an effect which is necessary for the stabilization of cortical actin. Experiments also demonstrate that activation of the PI3K pathway by FGF-2 is independent of integrin α5β1 and is also required for cortical actin reorganization, GRAF membrane relocalization and RhoA inactivation. These data suggest that GRAF-mediated RhoA inactivation and consequent phenotypic changes of dormancy depend on dual signaling by FGF-2-initiated PI3K activation and through ligation of integrin α5β1 by fibronectin
Essential Role of TGF-β/Smad Pathway on Statin Dependent Vascular Smooth Muscle Cell Regulation
BACKGROUND: The 3-hydroxy-3-methylglutaryl CoA reductase inhibitors (also called statins) exert proven beneficial effects on cardiovascular diseases. Recent data suggest a protective role for Transforming Growth Factor-beta (TGF-beta) in atherosclerosis by regulating the balance between inflammation and extracellular matrix accumulation. However, there are no studies about the effect of statins on TGF-beta/Smad pathway in atherosclerosis and vascular cells. METHODOLOGY: In cultured vascular smooth muscle cells (VSMCs) statins enhanced Smad pathway activation caused by TGF-beta. In addition, statins upregulated TGF-beta receptor type II (TRII), and increased TGF-beta synthesis and TGF-beta/Smad-dependent actions. In this sense, statins, through Smad activation, render VSMCs more susceptible to TGF-beta induced apoptosis and increased TGF-beta-mediated ECM production. It is well documented that high doses of statins induce apoptosis in cultured VSMC in the presence of serum; however the precise mechanism of this effect remains to be elucidated. We have found that statins-induced apoptosis was mediated by TGF-beta/Smad pathway. Finally, we have described that RhoA inhibition is a common intracellular mechanisms involved in statins effects. The in vivo relevance of these findings was assessed in an experimental model of atherosclerosis in apolipoprotein E deficient mice: Treatment with Atorvastatin increased Smad3 phosphorylation and TRII overexpression, associated to elevated ECM deposition in the VSMCs within atheroma plaques, while apoptosis was not detected. CONCLUSIONS: Statins enhance TGF-beta/Smad pathway, regulating ligand levels, receptor, main signaling pathway and cellular responses of VSMC, including apoptosis and ECM accumulation. Our findings show that TGF-beta/Smad pathway is essential for statins-dependent actions in VSMCs
Transcriptional Activity and Nuclear Localization of Cabut, the Drosophila Ortholog of Vertebrate TGF-β-Inducible Early-Response Gene (TIEG) Proteins
BackgroundCabut (Cbt) is a C2H2-class zinc finger transcription factor involved in embryonic dorsal closure, epithelial regeneration and other developmental processes in Drosophila melanogaster. Cbt orthologs have been identified in other Drosophila species and insects as well as in vertebrates. Indeed, Cbt is the Drosophila ortholog of the group of vertebrate proteins encoded by the TGF-ß-inducible early-response genes (TIEGs), which belong to Sp1-like/Krüppel-like family of transcription factors. Several functional domains involved in transcriptional control and subcellular localization have been identified in the vertebrate TIEGs. However, little is known of whether these domains and functions are also conserved in the Cbt protein.Methodology/Principal FindingsTo determine the transcriptional regulatory activity of the Drosophila Cbt protein, we performed Gal4-based luciferase assays in S2 cells and showed that Cbt is a transcriptional repressor and able to regulate its own expression. Truncated forms of Cbt were then generated to identify its functional domains. This analysis revealed a sequence similar to the mSin3A-interacting repressor domain found in vertebrate TIEGs, although located in a different part of the Cbt protein. Using β-Galactosidase and eGFP fusion proteins, we also showed that Cbt contains the bipartite nuclear localization signal (NLS) previously identified in TIEG proteins, although it is non-functional in insect cells. Instead, a monopartite NLS, located at the amino terminus of the protein and conserved across insects, is functional in Drosophila S2 and Spodoptera exigua Sec301 cells. Last but not least, genetic interaction and immunohistochemical assays suggested that Cbt nuclear import is mediated by Importin-α2.Conclusions/SignificanceOur results constitute the first characterization of the molecular mechanisms of Cbt-mediated transcriptional control as well as of Cbt nuclear import, and demonstrate the existence of similarities and differences in both aspects of Cbt function between the insect and the vertebrate TIEG proteins
Heart Rate Variability Dynamics for the Prognosis of Cardiovascular Risk
Statistical, spectral, multi-resolution and non-linear methods were applied to heart rate variability (HRV) series linked with classification schemes for the prognosis of cardiovascular risk. A total of 90 HRV records were analyzed: 45 from healthy subjects and 45 from cardiovascular risk patients. A total of 52 features from all the analysis methods were evaluated using standard two-sample Kolmogorov-Smirnov test (KS-test). The results of the statistical procedure provided input to multi-layer perceptron (MLP) neural networks, radial basis function (RBF) neural networks and support vector machines (SVM) for data classification. These schemes showed high performances with both training and test sets and many combinations of features (with a maximum accuracy of 96.67%). Additionally, there was a strong consideration for breathing frequency as a relevant feature in the HRV analysis
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