The interaction of actinide and lanthanide ions with hemoglobin and its relevance to human and environmental toxicology
Contributors: Amit Kumar, Manjoor Ali, Raghumani S. Ningthoujam, Pallavi Gaikwad, Mukesh Kumar, Bimalendu B. Nath, Badri N. Pandey
... Due to increasing use of lanthanides/actinides in nuclear and civil applications, understanding the impact of these metal ions on human health and environment is a growing concern. Hemoglobin (Hb), which occurs in all the kingdom of living organism, is the most abundant protein in human blood. In present study, effect of lanthanides and actinides [thorium: Th(IV), uranium: U(VI), lanthanum: La(III), cerium: Ce(III) and (IV)] on the structure and function of Hb has been investigated. Results showed that these metal ions, except Ce(IV) interacted with carbonyl and amide groups of Hb, which resulted in the loss of its alpha-helix conformation. However, beyond 75μM, these ions affected heme moiety. Metal–heme interaction was found to affect oxygen-binding of Hb, which seems to be governed by their closeness with the charge-to-ionic-radius ratio of iron(III). Consistently, Ce(IV) being closest to iron(III), exhibited a greater effect on heme. Binding constant and binding stoichiometry of Th(IV) were higher than that of U(VI). Experiments using aquatic midge Chironomus (possessing human homologous Hb) and human blood, further validated metal–Hb interaction and associated toxicity. Thus, present study provides a biochemical basis to understand the actinide/lanthanide-induced interference in heme, which may have significant implications for the medical and environmental management of lanthanides/actinides toxicity.
Contributors: Dongjie Jiang, Nathan J. Bechle, Chad M. Landis, Stelios Kyriakides
... Experiment and analysis are used to investigate the buckling and recovery of pseudoelastic NiTi tubes with a diameter-to-thickness ratio of 23.6 under compression and the associated energy absorption. At a stress level corresponding to the onset of transformation to martensite, the tube initially buckles into a periodic axisymmetric wrinkling mode. The wrinkled structure remains stable despite the loss in stiffness, but at larger strain levels wrinkling gives way to an unstable non-axisymmetric buckling mode, characterized by three circumferential waves. With the load decreasing, this mode localizes first into a single lobe followed progressively by others. Unlike elastoplastic material behavior, transformation terminates into a stiff, saturation-type response with the linear elastic modulus of the M-phase. This stiffening of the material limits the growth of deformation in the mode-3 lobes preventing them from folding up. As a consequence, this progressive collapse occurs at a much higher stress level relative to that at the onset of collapse, than in concertina folding observed in typical structural metal energy absorbers. Even more importantly, on unloading the material transforms back to the A-phase resulting in recovery of deformation, erasure of the buckles, and a nearly closed hysteresis. The buckling and recovery phenomena are simulated numerically using a finite element model coupled to a J2-type nonlinear kinematic hardening model. The model is customized to the primarily compressive stress state of the problem at hand and is calibrated to the compressive hysteresis of the material. The analysis captures the onset of wrinkling, the switch to mode-3, and its localization first into a single lobe followed by a second and subsequent ones. The recovery on unloading is also reproduced by the analysis resulting in a completely closed hysteresis. Idealizations made in the present version of the constitutive model resulted in an unloading stress that is at a higher level than that observed in the experiment. Despite this discrepancy, the results demonstrate the overall veracity of the constitutive model developed.
A magnetic-based dispersive micro-solid-phase extraction method using the metal-organic framework HKUST-1 and ultra-high-performance liquid chromatography with fluorescence detection for determining polycyclic aromatic hydrocarbons in waters and fruit tea infusions
Contributors: Priscilla Rocío-Bautista, Verónica Pino, Juan H. Ayala, Jorge Pasán, Catalina Ruiz-Pérez, Ana M. Afonso
... A hybrid material composed by the metal-organic framework (MOF) HKUST-1 and Fe3O4 magnetic nanoparticles (MNPs) has been synthetized in a quite simple manner, characterized, and used in a magnetic-assisted dispersive micro-solid-phase extraction (M-d-μSPE) method in combination with ultra-high-performance liquid chromatography (UHPLC) and fluorescence detection (FD). The application was devoted to the determination of 8 heavy polycyclic aromatic hydrocarbons (PAHs) in different aqueous samples, specifically tap water, wastewaters, and fruit tea infusion samples. The overall M-d-μSPE-UHPLC-FD method was optimized and validated. The method is characterized by: its simplicity in both the preparation of the hybrid material (simple mixing) and the magnetic-assisted approach (∼10min extraction time), the use of low sorbent amounts (20mg of HKUST-1 and 5mg of Fe3O4 MNPs), and the low organic solvent consumption in the overall M-d-μSPE-UHPLC-FD method (1.5mL of acetonitrile in the M-d-μSPE method and 2.8mL of acetonitrile in the UHPLC-FD run). The resulting method has high sensitivity, with LODs down to 0.8ngL−1; adequate intermediate precision, with relative standard deviation values (RSD) always lower than 6.3% (being the range 5.9–9.0% in tap water for a spiked level of 45ngL−1, 6.1–14% in wastewaters for a spiked level of 45ngL−1, and 7.2–17% in fruit tea infusion samples for a spiked level of 45ngL−1); and adequate relative recoveries, with average values of 82% in tap water, and 94% and 75% in wastewater and fruit tea infusion samples, respectively, if using the proper matrix-matched calibration.
Contributors: Kathryn Grandfield, Ralf-Peter Herber, Ling Chen, Sabra Djomehri, Caleb Tam, Ji-Hyun Lee, Evan Brown, Wood R. Woolwine III, Don Curtis, Mark Ryder
... The objective of this study was to investigate the effect of mechanical strain by mapping physicochemical properties at periodontal ligament (PDL)–bone and PDL–cementum attachment sites and within the tissues per se.
Contributors: Diego Lopez-Torres, Cesar Elosua, Miguel Hernaez, Javier Goicoechea, Francisco J. Arregui
... In this paper a nanocoating that shows a superhydrophilic behavior (with a contact angle close to 0°) is transformed into a superhydrophobic nanofilm (whose contact angle is 165°) following a procedure that needs no nanoparticles to generate the nano-roughness required for superhydrophobicity. The superhydrophilic nanocoating was fabricated using poly (allylamine hydrochloride) (PAH) and poly (sodium phosphate) (PSP) combined by means of the Layer-by-Layer (LbL) technique. Seven different nanocoatings were constructed with different number of bilayers (4, 8, 12, 16, 20, 30 and 40) being the concentration of both polymers 10−3M. The analysis was conducted studying three different features: roughness, thickness and contact angle. The results show that initially, the contact angle of the nanofilms above 20 bilayers is close to 0°, that is, the minimum value for a superhydrophilic coating. These surfaces were functionalized using 1H,1H,2H,2H-Perfluorodecyltriethoxsilane to transform them into hydrophobic coatings by Chemical Vapor Disposition (CVD). Thereafter, the nanofilms showed a superhydrophobic behavior with a contact angle of 165° for the 40 bilayers films. The results of roughness and the images of AFM prove that the morphology of the nanocoating is preserved.
Contributors: O. Kovalchuk Ben-Zaken, I. Nissan, S. Tzaban, A. Taraboulos, E. Zcharia, S. Matzger, I. Shafat, I. Vlodavsky, Y. Tal
... Cellular heparan sulfate (HS) has a dual role in scrapie pathogenesis; it is required for PrPSc (scrapie prion protein) formation and facilitates infection of cells, mediating cellular uptake of prions. We examined the involvement of heparanase, a mammalian endoglycosidase degrading HS, in scrapie infection. In cultured cells, heparanase treatment or over-expression resulted in a profound decrease in PrPSc. Moreover, disease onset and progression were dramatically delayed in scrapie infected transgenic mice over-expressing heparanase. Together, our results provide direct in vivo evidence for the involvement of intact HS in the pathogenesis of prion disease and the protective role of heparanase both in terms of susceptibility to infection and disease progression.
Contributors: Vadim S. Kamenetsky, Gregory M. Yaxley
... Kimberlite is a rare volcanic rock renowned as the major host of diamonds and originated at the base of the subcontinental lithospheric mantle. Although kimberlite magmas are dense in crystals and deeply-derived rock fragments, they ascend to the surface extremely rapidly, enabling diamonds to survive. The unique physical properties of kimberlite magmas depend on the specific compositions of their parental melts that, in absence of historical eruptions and due to pervasive alteration of kimberlite rocks, remain highly debatable. We explain exceptionally rapid ascent of kimberlite magma from mantle depths by combining empirical data on the essentially carbonatite composition of the kimberlite primary melts and experimental evidence on interaction of the carbonate liquids with mantle minerals. Our experimental study shows that orthopyroxene is completely dissolved in a Na2CO3 melt at 2.0–5.0GPa and 1000–1200°C. The dissolution of orthopyroxene results in homogeneous silicate–carbonate melt at 5.0GPa and 1200°C, and is followed by unmixing of carbonate and carbonated silicate melts and formation of stable magmatic emulsion at lower pressures and temperatures. The dispersed silicate melt has a significant capacity for storing a carbonate component in the deep mantle (13 wt% CO2 at 2.0GPa). We envisage that this component reaches saturation and is gradually released as CO2 bubbles, as the silicate melt globules are transported upwards through the lithosphere by the carbonatite magma. The globules of unmixed, CO2-rich silicate melt are continuously produced upon further reaction between the natrocarbonatite melt and mantle peridotite. On decompression the dispersed silicate melt phase ensures a continuous supply of CO2 bubbles that decrease density and increase buoyancy and promote rapid ascent of the magmatic emulsion.
Contributors: Qingsen Li, Ekta Makhija, F.M. Hameed, G.V. Shivashankar
... Cells sense physical cues at the level of focal adhesions and transduce them to the nucleus by biochemical and mechanical pathways. While the molecular intermediates in the mechanical links have been well studied, their dynamic coupling is poorly understood. In this study, fibroblast cells were adhered to micropillar arrays to probe correlations in the physical coupling between focal adhesions and nucleus. For this, we used novel imaging setup to simultaneously visualize micropillar deflections and EGFP labeled chromatin structure at high spatial and temporal resolution. We observed that micropillar deflections, depending on their relative positions, were positively or negatively correlated to nuclear and heterochromatin movements. Our results measuring the time scales between micropillar deflections and nucleus centroid displacement are suggestive of a strong elastic coupling that mediates differential force transmission to the nucleus.
Contributors: John B. Bührdel, Sofia Hirth, Mirjam Keßler, Sören Westphal, Monika Forster, Linda Manta, Gerhard Wiche, Benedikt Schoser, Joachim Schessl, Rolf Schröder
... Myofibrillar myopathies (MFM) are progressive diseases of human heart and skeletal muscle with a severe impact on life quality and expectancy of affected patients. Although recently several disease genes for myofibrillar myopathies could be identified, today most genetic causes and particularly the associated mechanisms and signaling events that lead from the mutation to the disease phenotype are still mostly unknown. To assess whether the zebrafish is a suitable model system to validate MFM candidate genes using targeted antisense-mediated knock-down strategies, we here specifically inactivated known human MFM disease genes and evaluated the resulting muscular and cardiac phenotypes functionally and structurally. Consistently, targeted ablation of MFM genes in zebrafish led to compromised skeletal muscle function mostly due to myofibrillar degeneration as well as severe heart failure. Similar to what was shown in MFM patients, MFM gene-deficient zebrafish showed pronounced gene-specific phenotypic and structural differences. In summary, our results indicate that the zebrafish is a suitable model to functionally and structurally evaluate novel MFM disease genes in vivo.
Contributors: Julie A. Rytlewski, M. Alejandra Aldon, Evan W. Lewis, Laura J. Suggs
... Stem cell-based therapies are a promising new avenue for treating ischemic disease and chronic wounds. Mesenchymal stem cells (MSCs) have a proven ability to augment the neovascularization processes necessary for wound healing and are widely popular as an autologous source of progenitor cells. Our lab has previously reported on PEGylated fibrin as a unique hydrogel that promotes spontaneous tubulogenesis of encapsulated MSCs without exogenous factors. However, the mechanisms underlying this process have remained unknown. To better understand the therapeutic value of PEGylated fibrin delivery of MSCs, we sought to clarify the relationship between biomaterial properties and cell behavior. Here we find that fibrin PEGylation does not dramatically alter the macroscopic mechanical properties of the fibrin-based matrix (less than 10% difference). It does, however, dramatically reduce the rate of diffusion through the gel matrix. PEGylated fibrin enhances the tubulogenic growth of encapsulated MSCs demonstrating fluid-filled lumens by interconnected MSCs. Image analysis gave a value of 4320±1770μm total network length versus 618±443μm for unmodified fibrin. PEGylation promotes the endothelial phenotype of encapsulated MSCs—compared to unmodified fibrin—as evidenced by higher levels of endothelial markers (von Willebrand factor, 2.2-fold; vascular endothelial cadherin, 1.8-fold) and vascular endothelial growth factor (VEGF, up to 1.8-fold). Prospective analysis of underlying molecular pathways demonstrated that this endothelial-like MSC behavior is sensitively modulated by hypoxic stress, but not VEGF supplementation as evidenced by a significant increase in VEGF and MMP-2 secretion per cell under hypoxia. Further gain-of-function studies under hypoxic stress demonstrated that hypoxia culture of MSCs in unmodified fibrin could increase both vWF and VE-cadherin levels to values that were not significantly different than cells cultured in PEGylated fibrin. This result corroborated our hypothesis that the diffusion-limited environment of PEGylated fibrin is augmenting endothelial differentiation cues provided by unmodified fibrin. However, MSC networks lack platelet endothelial cell adhesion molecule-1 (PECAM-1) expression, which indicates incomplete differentiation towards an endothelial cell type. Collectively, the data here supports a revised understanding of MSC-derived neovascularization that contextualizes their behavior and utility as a hybrid endothelial–stromal cell type, with mixed characteristics of both populations.