Weak cubic CaSiO3 perovskite in the Earth's mantle.

Cubic CaSiO3 perovskite is a major phase in subducted oceanic crust, where it forms at a depth of about 550 kilometres from majoritic garnet1,2,28. However, its rheological properties at temperatures and pressures typical of the lower mantle are poorly known. Here we measured the plastic strength of cubic CaSiO3 perovskite at pressure and temperature conditions typical for a subducting slab up to a depth of about 1,200 kilometres. In contrast to tetragonal CaSiO3, previously investigated at room temperature3,4, we find that cubic CaSiO3 perovskite is a comparably weak phase at the temperatures of the lower mantle. We find that its strength and viscosity are substantially lower than that of bridgmanite and ferropericlase, possibly making cubic CaSiO3 perovskite the weakest lower-mantle phase. Our findings suggest that cubic CaSiO3 perovskite governs the dynamics of subducting slabs. Weak CaSiO3 perovskite further provides a mechanism to separate subducted oceanic crust from the underlying mantle. Depending on the depth of the separation, basaltic crust could accumulate at the boundary between the upper and lower mantle, where cubic CaSiO3 perovskite may contribute to the seismically observed regions of low shear-wave velocities in the uppermost lower mantle5,6, or sink to the core-mantle boundary and explain the seismic anomalies associated with large low-shear-velocity provinces beneath Africa and the Pacific7-9.

An improved setup for radial diffraction experiments at high pressures and high temperatures in a resistive graphite-heated diamond anvil cell.

We present an improved setup for the experimental study of deformation of solids at simultaneous high pressures and temperatures by radial x-ray diffraction. This technique employs a graphite resistive heated Mao-Bell type diamond anvil cell for radial x-ray diffraction in combination with a water-cooled vacuum chamber. The new chamber has been developed by the sample environment group at PETRA III and implemented at the Extreme Conditions Beamline P02.2 at PETRA III, DESY (Hamburg, Germany). We discuss applications of the new setup to study deformation of a variety of materials, including ferropericlase, calcium perovskite, bridgmanite, and tantalum carbide, at high-pressure/temperature.

Poroelastic theory of transcapillary flow: effects of endothelial glycocalyx deterioration.

The luminal surface of endothelial cells is lined with a carbohydrate-rich layer known as the endothelial glycocalyx. Identification of the structural properties of the glycocalyx has led investigators to examine its various functions and it has since been recognized as playing a role in many physiological processes, one of which is the regulation of fluid and protein exchange across the capillary wall. Experimental observations in which the glycocalyx was degraded in rat myocardial capillaries showed fluid accumulation in the tissue, suggesting that the glycocalyx acts as a protective barrier against edema. In this work we seek to quantify the observed edema formation by using our earlier poroelastic model to examine the consequences of glycocalyx deterioration on transcapillary filtration. Upon enzymatic treatment the properties of the glycocalyx, such as its thickness and permeability, will be modified, and our purpose here is to investigate quantitatively how changes in these parameters affect the magnitude of the fluid filtration through the capillary wall. We compare our results with both experimental data as well as other theoretical models where applicable, discussing the implications of the models as well as the limitations of comparison. This work provides the basis for further experiments that may better characterise many of the parameters involved in this process.

Deformation experiments in the diamond-anvil cell: texture in copper to 30 GPa.

The combination of the diamond-anvil cell, synchrotron x-ray diffraction in radial geometry and simultaneous Rietveld refinement with texture analysis allows us to quantitatively investigate the plastic deformation behaviour of materials at very high pressures. Our study of copper to 30 GPa shows in ideal experimental geometry a [110] fibre texture component, as is typical for axial compression of soft face centred cubic metals. Locally a plane strain texture develops which is energetically favoured (curling). A transition from compressional to plane strain/pure shear texture can be monitored by analysing individual images taken at different positions in the diamond cell.

Deformation textures produced in diamond anvil experiments, analysed in radial diffraction geometry.

Diamond anvil cells may not only impose pressure upon a sample but also a compressive stress that produces elastic and plastic deformation of polycrystalline samples. The plastic deformation may result in texture development if the material deforms by slip or mechanical twinning, or if grains have a non-equiaxed shape. In radial diffraction geometry, texture is revealed by variation of intensity along Debye rings relative to the compression direction. Diffraction images (obtained by CCD or image plate) can be used to extract quantitative texture information. Currently the most elegant and powerful method is a modified Rietveld technique as implemented in the software package MAUD. From texture data one can evaluate the homogeneity of strain in a diamond anvil cell, the strain magnitude and deformation mechanisms, the latter by comparing observed texture patterns with results from polycrystal plasticity simulations. Some examples such as olivine, magnesiowuestite, MgSiO(3) perovskite and ε-iron are discussed.

Requirement for cell-bound proteases in the mechanism of human neutrophil activation with various stimuli.

A cell membrane-associated protease/esterase has been implicated in the mechanism of "stimulus-secretion coupling" described for human neutrophil degranulation. In this regard, a broad spectrum of protease inhibitors were evaluated for their effects on granule enzyme release from neutrophils exposed to soluble, surface-active stimuli. The serine protease inhibitors, L-1-tosylamide-2-phenylethyl-chloromethyl ketone (TPCK) and N-alpha-p-tosyl-L-lysine-chloromethyl ketone (TLCK) and a thiol protease inhibitor, p-hydroxymercuribenzoate (PHMB), caused a concentration-related suppression of neutrophil degranulation elicited with 1-O-hexadecyl/octadecyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine (AGEPC), ionophore A23187, phorbol myristate acetate (PMA), and 5(S), 12(R)-dihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid (LTB4). However, other inhibitors, such as aprotinin and p-hydroxyphenylpyruvic acid, were inactive. The maximum inhibitory effect with TPCK, TLCK, and PHMB was observed when neutrophils were exposed to these inhibitors prior to contact with the respective stimuli. In addition, the magnitude of inhibition increased in proportion to the preincubation time of protease inhibitor with stimulus. The results of these studies implicate proteases in the sequence of events underlying activation of the human neutrophil secretory process in response to structurally and chemically dissimilar stimuli.

Characteristics of aggregated immunoglobulin G as an immunologic phagocytic stimulus for granule enzyme release from human neutrophils.

Aggregated immunoglobulin G (AggIgG) induced a time- and concentration-dependent phagocytic release of granule-associated lysozyme and myeloperoxidase (MPO) from human neutrophils. Degranulation was significantly enhanced in the presence of calcium or magnesium, and maximum granule exocytosis was observed when both divalent cations were present. AggIgG-stimulated enzyme release was inhibited with the intracellular calcium antagonist, TMB-8[8-(N,N-diethylamino)-octyl-(3,4,5-trimethoxy)benzoate] in the absence of extracellular calcium. DIDS (4,4'-diisothiocyano-2,2'-disulfonic acid stilbene), a permeant anion channel blocker, also suppressed AggIgG-induced degranulation. Cycloheximide, an inhibitor of protein synthesis, enhanced granule exocytosis from AggIgG-treated neutrophils. Two inhibitors of transmethylation reactions, 3-deazaadenosine (3-DZA) and homocysteine thiolactone (HCTL) in combination, suppressed AggIgG-elicited granule enzyme release. These data indicate that AggIgG is a useful probe for investigating the requirements for phagocytic enzyme release from human neutrophils.

Yttrium and lanthanides in human lung fluids, probing the exposure to atmospheric fallout.

Inhalation of airborne particles can produce crystallization of phosphatic microcrysts in intraaveolar areas of lungs, sometimes degenerating into pulmonary fibrosis. Results of this study indicate that these pathologies are induced by interactions between lung fluids and inhaled atmospheric dust in people exposed to volcanic dust ejected from Mount Etna in 2001. Here, the lung solid-liquid interaction is evaluated by the distribution of yttrium and lanthanides (YLn) in fluid bronchoalveolar lavages on selected individuals according the classical geochemical approaches. We found that shale-normalised patterns of yttrium and lanthanides have a 'V shaped' feature corresponding to the depletion of elements from Nd to Tb when compared to the variable enrichments of heavy lanthanides, Y, La and Ce. These features and concurrent thermodynamic simulations suggest that phosphate precipitation can occur in lungs due to interactions between volcanic particles and fluids. We propose that patterns of yttrium and lanthanides can represent a viable explanation of some pathology observed in patients after prolonged exposure to atmospheric fallout and are suitable to become a diagnostic parameter of chemical environmental stresses.

A poroelastic model of transcapillary flow in normal tissue.

Starling's seminal work on the absorption of fluids from connective tissue spaces (and Starling's hypothesis that the energy for transcapillary flow lies in the difference between hydrostatic and osmotic pressures across the capillary wall) has long formed the basis of much of experimental physiology. Related recent experimental evidence points to a more active role of the interstitium in controlling interstitial fluid pressure (IFP) which has significant implications for clinical oncology. In light of these considerations, it is clearly of importance to reconsider the relationship between IFP and transcapillary transport, in addition to the regulation of IFP in normal tissue. In this paper, we adopt the Michel-Weinbaum viewpoint on the locality of Starling forces and model the capillary wall as a poroelastic solid using Biot's consolidation theory. However, the incorporation of the Michel-Weinbaum hypothesis requires an extension of Darcy's law to include the effects of oncotic pressure in the mechanism of filtration through the capillary wall. A unique feature of the model of transcapillary flow developed here is its ability to predict the stress and strain distribution across the capillary wall, which to our knowledge has not been attempted previously. We are optimistic that, with rapidly advancing technological capabilities, experimentalists will soon be able to test many of the model predictions.

Iron spin transition in Earth's mantle.

High-pressure Mössbauer spectroscopy on several compositions across the (Mg,Fe)O magnesiowüstite solid solution confirms that ferrous iron (Fe(2+)) undergoes a high-spin to low-spin transition at pressures and for compositions relevant to the bulk of the Earth's mantle. High-resolution x-ray diffraction measurements document a volume change of 4-5% across the pressure-induced spin transition, which is thus expected to cause seismological anomalies in the lower mantle. The spin transition can lead to dissociation of Fe-bearing phases such as magnesiowüstite, and it reveals an unexpected richness in mineral properties and phase equilibria for the Earth's deep interior.

Effects of soluble stimuli on human monocyte secretion.

We report here that the chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP), and the mitogenic phorbol ester, phorbol myristate acetate (PMA) cause a time- and concentration-dependent, selective, extracellular release of N-acetyl-beta-glucosaminidase and lysozyme from freshly isolated, adherent human peripheral blood monocytes. The inability of the protein synthesis inhibitor, cycloheximide, to influence enzyme release indicates that these enzymes are constitutive secretory products. 1-O-Hexadecyl-/octadecyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine demonstrated moderate secretory activity, whereas pepstatin A, concanavalin A, and leukotriene B4 were essentially inactive. FMLP- and PMA-induced enzyme release were inhibited with the intracellular calcium antagonist, 8-(N,N-diethylamino)-octyl-(3,4,5-trimethoxy)benzoate hydrochloride and the anion channel blocker, 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene. These results demonstrate the capacity of soluble, surface-active stimuli to activate the human monocyte secretory process.

Interleukin-1 stimulates granule exocytosis from human neutrophils.

The interaction of human polymorphonuclear neutrophilic leukocytes (neutrophils) with interleukin-1 (IL-1) resulted in a time- and concentration-dependent, selective, release of azurophil (myeloperoxidase, lysozyme) and specific (lysozyme, vitamin B12-binding protein) granule constituents. Myeloperoxidase (MPO) and lysozyme secretion was markedly attenuated if neutrophils were not exposed to cytochalasin B (CB) prior to contact with IL-1. Degranulation was significantly enhanced in the presence of extracellular calcium. IL-1-elicited granule exocytosis was inhibited by the intracellular calcium antagonist, 8-(N,N-diethylamino)-octyl-(3,4,5-trimethoxy) benzoate hydrochloride (TMB-8), a calmodulin antagonist, trifluoperazine (TFP), and an anion channel blocker, 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene (DIDS). An evaluation of the role of arachidonic acid metabolites in IL-1-induced neutrophil activation revealed a suppressive effect on enzyme release exerted by the lipoxygenase inhibitors, piriprost potassium (6,9,deepoxy-6,9-(phenylimino)-delta 6,8 -prostaglandin I1, U-60,257B) and NDGA (nordihydroguaiaretic acid), and a cyclooxygenase/lipoxygenase inhibitor, ETYA (5,8,11,14-eicosatetraynoic acid). These data describe the characteristics of IL-1 as a human neutrophil secretagogue, and enhance our insight into the mechanism of inflammatory cell activation with this monokine.

Properties of interleukin-1 as a complete secretagogue for human neutrophils.

Human monocyte-derived Interleukin-1 (IL-1) stimulated a concentration-dependent extracellular release of azurophil (myeloperoxidase) and specific (vitamin B12-binding protein) granule constituents from cytochalasin B-treated human neutrophils. The serine protease inhibitors, L-1-tosylamide-2-phenylethyl-chloromethyl ketone (TPCK) and N-alpha-p-tosyl-L-lysine-chloromethyl ketone (TPCK) as well as an inhibitor of thiol protease activity, p-hydroxymercuribenzoate (PHMB), suppressed granule enzyme release from neutrophils activated with IL-1. Cycloheximide, an inhibitor of protein synthesis, had no effect on IL-1-induced neutrophil degranulation. Neutrophils pretreated with IL-1 were rendered unresponsive to subsequent exposure to this stimulus. IL-1-elicited granule exocytosis appears to be stimulus specific in that N-formyl-methionyl-leucyl-phenylalanine (FMLP), 1-0-hexadecyl/octadecyl-2-0-acetyl-sn-glyceryl-3-phosphorycholine (AGEPC), and 5(S),12(R)-dihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid (LTB4) were capable of eliciting a secretory response from IL-1-pretreated cells.

Effects of lectins and tunicamycin on IL-1 binding to YT cells.

Specific binding of iodinated-interleukin-1 alpha or beta to YT cells could be inhibited by the lectins wheat germ agglutinin (WGA) and concanavalin A (Con A). WGA and Con A inhibition of IL-1 binding was abrogated by previous exposure of these plant proteins to the lectin-specific sugars N-acetylglucosamine (GlcNAc) and methyl glucoside (MG), respectively. Tunicamycin, an inhibitor of glycosylation, decreased interleukin-1 (IL-1) binding to YT cells, but also reduced total protein synthesis. These observations suggest that carbohydrate moieties on or near the interleukin-1 receptor may be important for optimal receptor binding of IL-1 to intact YT cells.

A possible requirement for arachidonic acid lipoxygenation in the mechanism of phagocytic degranulation by human neutrophils stimulated with aggregated immunoglobulin G.

Aggregated immunoglobulin G (AggIgG) caused a concentration-dependent extracellular release of granule-associated lysozyme and myeloperoxidase (MPO) from human neutrophils. Generation of the 5-lipoxygenase product of arachidonic acid (AA) metabolism, 5(S),12(R)-dihydroxy-6,14-cis,8,10-trans-eicosatetraenoic acid [leukotriene B4 (LTB4)], by neutrophils is exposed to AggIgG occurred in the presence but not absence of exogenous AA. U-60,257B (piriprost potassium), an inhibitor of leukotriene synthesis, caused a dose-related suppression of LTB4 production and granule exocytosis by AggIgG-treated cells. These data suggest that a lipoxygenase product of AA metabolism may mediate AggIgG-induced phagocytic release of granule constituents from neutrophils.

Sound velocity and elasticity of tetragonal lysozyme crystals by Brillouin spectroscopy.

Quasilongitudinal sound velocities and the second-order elastic moduli of tetragonal hen egg-white lysozyme crystals were determined as a function of relative humidity (RH) by Brillouin scattering. In hydrated crystals the measured sound velocities in the [110] plane vary between 2.12 +/- 0.03 km/s along the [001] direction and 2.31 +/- 0.08 km/s along the [110] direction. Dehydration from 98% to 67% RH increases the sound velocities and decreases the velocity anisotropy in (110) from 8.2% to 2.0%. A discontinuity in velocity and an inversion of the anisotropy is observed with increasing dehydration providing support for the existence of a structural transition below 88% RH. Brillouin linewidths can be described by a mechanical model in which the phonon is coupled to a relaxation mode of hydration water with a single relaxation time of 55 +/- 5 ps. At equilibrium hydration (98% RH) the longitudinal moduli C(11) + C(12) + 2C(66) = 12.81 +/- 0.08 GPa, C(11) = 5.49 +/- 0.03 GPa, and C(33) = 5.48 +/- 0.05 GPa were directly determined. Inversion of the measured sound velocities in the [110] plane constrains the combination C(44) + (1/2)C(13) to 2.99 +/- 0.05 GPa. Further constraints on the elastic tensor are obtained by combining the Brillouin quasilongitudinal results with axial compressibilities determined from high-pressure x-ray diffraction. We constrain the adiabatic bulk modulus to the range 2.7-5.3 GPa.

Soybean trypsin inhibitor. An IL-1-like protein?

Soybean trypsin inhibitor (SBTI) shares some structural homology with interleukin-1 (IL-1) and was tested for IL-1 bioactivity. Human T-cells proliferated maximally when stimulated with PMA and SBTI but failed to respond to either stimulus alone. This response was abrogated by neutralizing antibodies to IL-1 beta but not to IL-1 alpha. However, immunoblots showed no cross-reactivity between SBTI and anti-IL-1 antibodies. Furthermore, SBTI did not bind to IL-1 receptors on YT cells and did not activate a murine T-lymphoma or human T-hybridoma. Supernantants from monocytes stimulated with SBTI contained significant levels of IL-1 activity. The data show that SBTI has no direct IL-1 activity but can stimulate T-cells indirectly through an IL-1 dependent mechanism.