Phase Of Ca2 Research Articles

Identification and pharmacological characterization of the prostaglandin FP receptor and FP receptor variant complexes

Background and purpose: A prostamide analogue, bimatoprost, has been shown to be effective in reducing intraocular pressure, but its precise mechanism of action remains unclear. Hence, to elucidate the molecular mechanisms of this effect of bimatoprost, we focused on pharmacologically characterizing prostaglandin FP receptor (FP) and FP receptor variant (altFP) complexes.Experimental approach: FP receptor mRNA variants were identified by reverse transcription-polymerase chain reaction. The FP-altFP4 heterodimers were established in HEK293/EBNA cells co-expressing FP and altFP4 receptor variants. A fluorometric imaging plate reader was used to study Ca2+ mobilization. Upregulation of cysteine-rich angiogenic protein 61 (Cyr61) mRNA was measured by Northern blot analysis, and phosphorylation of myosin light chain (MLC) by western analysis.Key results: Six splicing variants of FP receptor mRNA were identified in human ocular tissues. Immunoprecipitation confirmed that the FP receptor is dimerized with altFP4 receptors in HEK293/EBNA cells co-expressing FP and altFP4 receptors. In the studies of the kinetic profile for Ca2+ mobilization, prostaglandin F2α (PGF2α) elicited a rapid increase in intracellular Ca2+ followed by a steady state phase. In contrast, bimatoprost elicited an immediate increase in intracellular Ca2+ followed by a second phase. The prostamide antagonist, AGN211335, selectively and dose-dependently inhibited the bimatoprost-initiated second phase of Ca2+ mobilization, Cyr61 mRNA upregulation and MLC phosphorylation, but did not block the action of PGF2α.Conclusion and implications: Bimatoprost lacks effects on the FP receptor but may interact with the FP-altFP receptor heterodimer to induce alterations in second messenger signalling. Hence, FP-altFP complexes may represent the underlying basis of bimatoprost pharmacology.

Microstructure, mechanical properties and bio-corrosion properties of Mg–Zn–Mn–Ca alloy for biomedical application

Microstructure, mechanical properties and bio-corrosion properties of as-cast Mg–Zn–Mn–Ca alloys were investigated for biomedical application in detail by optical microscopy, scanning electronic microscopy (SEM), mechanical properties testing and electrochemical measurement. SEM and optical microscopy observation indicated that the grain size of the as-cast alloys significantly decreased with the increasing of Ca content up to 0.5 wt.%. Further increasing of Ca content did not refine the grain more. The phase constitute was mainly controlled by the atomic ratio of Zn to Ca. When the ratio was more than 1.0–1.2, the alloy was mainly composed of primary Mg and lamellar eutectic (α-Mg + Ca 2Mg 6Zn 3), while the alloy was composed of primary Mg and divorced eutectic (α-Mg + Mg 2Ca + Ca 2Mg 6Zn 3) when the atomic ratio was less than 1.0–1.2. The yield strength of the as-cast alloy increased but the elongation and the tensile strength increased first and then decreased with the increasing of Ca content. It was thought that Mg 2Ca phase deteriorated the tensile strength and ductility. Electrochemical measurements indicated that Mg 2Ca phase improved the corrosion resistance of the as-cast alloy.

Influence of Ca on the corrosion properties of magnesium for biomaterials

The corrosion properties of a Mg alloy with Ca in Hank's solution were investigated by the hydrogen evolution test. In the test results, the hydrogen evolution rate increased with increasing Ca content. This phenomenon was caused by the precipitation of Mg 2Ca phase in large amounts on the Mg matrix. In the case of Mg–Ca alloy, the formation of a micro-galvanic cell between the Mg 2Ca phase and Mg matrix accelerated the preferred dissolution of the matrix. These results demonstrated that the corrosion resistance and hydrogen evolution rate are controlled by the Mg 2Ca phase distribution in the Mg–Ca alloy system.

Microstructure and superplasticity of Mg–Al–Ca electromagnetic casting alloys after hot extrusion

Microstructure and superplastic properties of the plates extruded from the Ca containing Mg alloy (1wt.% Ca–AZ31) billets fabricated by electromagnetic casting (EMC) without and with electromagnetic stirring (EMS) were examined. The linear intercept grain sizes of the extruded materials were 3.7μm and 2.1μm, respectively. The material extruded from the EMC+EMS billet exhibited good superplasticity at low temperatures as well as at high strain rates, including the tensile elongations of 370% at 1×10−3s−1, −523K and 550% at 1×10−2s−1, −673K. These values largely exceeded those of the AZ31 alloys with the similar grain sizes. The superior superplasticity of the extruded EMC+EMS billet could be attributed to fine grains and high grain stability at elevated temperatures by the presence of finely dispersed particles of thermally stable (Al,Mg)2Ca phase. The constitutive equations were developed for describing the high-temperature deformation behavior of the fine-grained 1wt.% Ca–AZ31 alloys with different grain sizes in wide range of temperature and strain rate.

The development of binary Mg–Ca alloys for use as biodegradable materials within bone

Binary Mg–Ca alloys with various Ca contents were fabricated under different working conditions. X-ray diffraction (XRD) analysis and optical microscopy observations showed that Mg– xCa ( x = 1–3 wt%) alloys were composed of two phases, α(Mg) and Mg 2Ca. The results of tensile tests and in vitro corrosion tests indicated that the mechanical properties could be adjusted by controlling the Ca content and processing treatment. The yield strength (YS), ultimate tensile strength (UTS) and elongation decreased with increasing Ca content. The UTS and elongation of as-cast Mg–1Ca alloy (71.38 ± 3.01 MPa and 1.87 ± 0.14%) were largely improved after hot rolling (166.7 ± 3.01 MPa and 3 ± 0.78%) and hot extrusion (239.63 ± 7.21 MPa and 10.63 ± 0.64%). The in vitro corrosion test in simulated body fluid (SBF) indicated that the microstructure and working history of Mg– xCa alloys strongly affected their corrosion behaviors. An increasing content of Mg 2Ca phase led to a higher corrosion rate whereas hot rolling and hot extrusion could reduce it. The cytotoxicity evaluation using L-929 cells revealed that Mg–1Ca alloy did not induce toxicity to cells, and the viability of cells for Mg–1Ca alloy extraction medium was better than that of control. Moreover, Mg–1Ca alloy pins, with commercial pure Ti pins as control, were implanted into the left and right rabbit femoral shafts, respectively, and observed for 1, 2 and 3 months. High activity of osteoblast and osteocytes were observed around the Mg–1Ca alloy pins as shown by hematoxylin and eosin stained tissue sections. Radiographic examination revealed that the Mg–1Ca alloy pins gradually degraded in vivo within 90 days and the newly formed bone was clearly seen at month 3. Both the in vitro and in vivo corrosion suggested that a mixture of Mg(OH) 2 and hydroxyapatite formed on the surface of Mg–1Ca alloy with the extension of immersion/implantation time. In addition, no significant difference ( p > 0.05) of serum magnesium was detected at different degradation stages. All these results revealed that Mg–1Ca alloy had the acceptable biocompatibility as a new kind of biodegradable implant material. Based on the above results, a solid alloy/liquid solution interface model was also proposed to interpret the biocorrosion process and the associated hydroxyapatite mineralization.

The Effects of Yttrium Element on Microstructure and Mechanical Properties of Mg-5 mass%Al-3 mass%Ca Based Alloys Fabricated by Gravity Casting and Extrusion Process

The as-cast microstructure of Mg-5Al-3Ca-xY alloy consists of dendritic α-Mg matrix, (Mg, Al)2Ca eutectic phase and Al2Y intermetallic compounds. These two kind of (Mg, Al)2Ca compounds were observed: coarse irregular-shape structure at grain boundary and fine needle-shape structure in the α-Mg matrix grain. This (Mg, Al)2Ca phase of the extruded alloys was elongated to extrusion direction and size of this phase was refined comparing with that of as-cast alloys because of severe deformation during hot extrusion. Maximum yield and ultimate strength value of extruded alloys was 326 and 331 MPa at Mg-5Al-3Ca-3Y alloy, respectively. From these results, it is conclusively demonstrated that Y additions on Mg-5Al-3Ca alloy have more effect to improve mechanical properties.

Sequential phases of Ca2+ alterations in pre-apoptotic cells

The very early events of the intrinsic, damage-induced apoptotic pathway, i.e., upstream to Bax activation, probably consist of physico-chemical alterations (i.e., redox, pH or Ca2+ changes) rather then subtle molecular interactions, and in spite of many studies they remain unclear. One problem is that cells undergo apoptosis in an asynchronous way, leading to heterogeneity in the cell population that impairs the results of bulk analyses. In this study, we present a flow cytometric approach for studying Ca2+ alteration in apoptosis at the single cell level. By means of a multiparametric analysis, we could discriminate different sub-populations, i.e., viable and apoptotic cells and cells in secondary necrosis, and separately analyse static as well as dynamic Ca2+ parameters in each sub-population. With this approach, we have identified a set of sequential Ca2+ changes; two very early ones occur prior to any other apoptotic alterations, whereas a later change coincides with the appearance of apoptosis. Interestingly, the two pre-apoptotic changes occur simultaneously in all treated cells, i.e., at fixed times post-treatment, whereas the later one occurs at varying times, i.e., within a wide time range, concomitantly with the other apoptotic events.

Microstructure and Mechanical Properties of Mg-Al-Ca Alloys with Yttrium Addition

The aims of this study are to investigate the effect of Y (yttrium) addition in the Mg-Al- Ca alloys on microstructure and mechanical properties. In additions, the alloys were solution treated in order to achieve a better understanding of the precipitation mechanisms. The as-cast microstructure of Mg-5Al-3Ca alloy and Mg-5Al-3Ca-xY alloys contains dendritic α-Mg matrix and eutectic intermetallic compound at grain boundary. The hardness values of Mg-Al-Ca alloy with Y additions were slightly increased than that of Mg-Al-Ca with no Y addition. It is because of reduction of α-Mg phase and presence of (Mg,Al)2Ca and Al-Y rich intermetallic phase at grain boundary and α-Mg matrix grains. Also, hardness value of yttrium (Y) containing alloys was increased with increasing Y contents. Compared to Mg-5Al-3Ca alloy, maximum strength and yield strength of the alloys with Y additions have slightly increased with increasing Y additions in the case of as-cast samples.

Muscle sarcoplasmic reticulum calcium regulation in humans during consecutive days of exercise and recovery

The study investigated the hypothesis that three consecutive days of prolonged cycle exercise would result in a sustained reduction in the Ca(2+)-cycling properties of the vastus lateralis in the absence of changes in the sarcoplasmic (endoplasmic) reticulum Ca(2+)-ATPase (SERCA) protein. Tissue samples were obtained at preexercise (Pre) and postexercise (Post) on day 1 (E1) and day 3 (E3) and during recovery day 1 (R1), day 2 (R2), and day 3 (R3) in 12 active but untrained volunteers (age 19.2 +/- 0.27 yr; mean +/- SE) and analyzed for changes (nmol.mg protein(-1).min(-1)) in maximal Ca(2+)-ATPase activity (V(max)), Ca(2+) uptake and Ca(2+) release (phase 1 and phase 2), and SERCA isoform expression (SERCA1a and SERCA2a). At E1, reductions (P < 0.05) from Pre to Post in V(max) (150 +/- 7 vs. 121 +/- 7), Ca(2+) uptake (7.79 +/- 0.28 vs. 5.71 +/- 0.33), and both phases of Ca(2+) release (phase 1, 20.3 +/- 1.3 vs. 15.2 +/- 1.1; phase 2, 7.70 +/- 0.60 vs. 4.99 +/- 0.48) were found. In contrast to V(max), which recovered at Pre E3 and then remained stable at Post E3 and throughout recovery, Ca(2+) uptake remained depressed (P < 0.05) at E3 Pre and Post and at R1 as did phase 2 of Ca(2+) release. Exercise resulted in an increase (P < 0.05) in SERCA1a (14% at R2) but not SERCA2a. It is concluded that rapidly adapting mechanisms protect V(max) following the onset of regular exercise but not Ca(2+) uptake and Ca(2+) release.

Effect of Ca additions on microstructure and microhardness of an as-cast Mg–5.0 wt.% Al alloy

The effects of Ca additions (0.5–2.0 wt.%) on the microstructure and the microhardness of an as-cast Mg–5.0 wt.% Al alloy have been investigated. The coarse microstructure of the base alloy can be refined through adding Ca. DSC and TEM results showed that, as Ca additions increased up to 1.5 wt.% Ca, the β-Mg17Al12 phase was completely replaced by a (Al, Mg)2Ca phase. The Vickers microhardness of the as-cast Mg–Al–Ca alloys increased with increasing Ca content. Tests on the Mg–5.0Al–2.0Ca (wt.%) alloy showed an indentation size effect, which was well described by Meyer's Law.

A first-principles study on the structural stability of Al 2Ca Al 4Ca and Mg 2Ca phases

Energetics and electronic structures have been determined from first-principles calculations for Al 2Ca Al 4Ca Mg 2Ca phases. These calculations show that Al 2Ca phase has the strongest alloying ability as well as the highest structural stability, next Al 4Ca, finally Mg 2Ca, which is also well explained through the densities of states (DOS) of these compounds.

Structural stability of intermetallic compounds of Mg-Al-Ca alloy

A first-principles plane-wave pseudopotential method based on the density functional theory was used to investigate the energetic and electronic structures of intermetallic compounds of Mg-Al-Ca alloy, such as Al 2Ca, Al 4Ca and Mg 2Ca. The negative formation heat, the cohesive energies and Gibbs energies of these compounds were estimated from the electronic structure calculations, and their structural stability was also analyzed. The results show that Al 2Ca phase has the strongest alloying ability as well as the highest structural stability, next Al 4Ca, finally Mg 2Ca. After comparing the density of states of Al 2Ca, Al 4Ca and Mg 2Ca phases, it is found that the highest structural stability of Al 2Ca is attributed to an increase in the bonding electron numbers in lower energy range below Fermi level, which mainly originates from the contribution of valence electron numbers of Ca(s) and Ca(p) orbits, while the lowest structural stability of Mg 2Ca is resulted from the least bonding electron numbers near Fermi level.

Microstructure and nano-scale mechanical behavior of Mg–Al and Mg–Al–Ca alloys

The microstructure of magnesium alloys containing aluminum (AM50) and calcium (AC51 and AC52) cast by high-pressure die casting (DC) or permanent mold casting (PM) were characterized by SEM and TEM, and the influence of these microstructural features on the local mechanical properties was investigated. The presence of (Al, Mg) 2Ca phase was identified in PM AC51 and AC52 alloys, which has a high melting temperature, was thermally more stable than the Mg 17Al 12 phase. A nanoindentation technique using a Berkovich indenter was used to characterize the nano-scale mechanical behavior of the α-Mg grains of the alloys at room temperature. The results of nanoindentation testing show that the hardness and composite modulus of the alloys vary with penetration depth. Ca addition to the alloy gives rise to an increase in the hardness and modulus, which can be attributed to solid solution strengthening. A regression analysis of the experimental nanoindentation data reveals a linear correlation between the contact stiffness and the penetration depth for all the tested alloys. The established correlations were used to calculate the continuous hardness and the composite modulus. Both the experimental and calculated data show that hardness values exhibit peak load dependence, i.e. indentation size effect (ISE) on all the tested alloys, while composite modulus was insensitive to peak load. Upon reaching a peak value of hardness at the beginning of the indentation test, the hardness of all the tested alloys decreases considerably by six times from around 1.2 to 0.2 GPa with increasing the penetration depth during the course of testing. However, the composite modulus of the alloy is much less dependent on the penetration depth only changing from 35 to 25 GPa during the tests. The comparison of the calculated results with experimental measurements indicates that they are in good agreement.

Effect of Sr Additions on the Microstructure and Strength of a Mg-Al-Ca Ternary Alloy

The effect of Sr additions on the microstructure and strength of a Mg-5Al-3Ca alloy was investigated by replacing Ca with Sr. In the as-cast alloys, the major intermetallic compound observed at the α-Mg dendrite cell boundary region changes from the Al-rich (Mg, Al)2Ca phase to the Mg-rich Mg17Sr2 phase with increasing Sr content. This results in an increased Al solute content in the α-Mg phase in the high-Sr containing alloys. More than 1 wt pct of Sr enhances the solid-solution strength of the α-Mg phase, resulting in the increased compression strength of the alloys.

Behavior of CaO and Calcium in pure Magnesium

Mg alloys exhibit a number of good properties such as low density, good castability and high specific strength. However, molten Mg and Mg alloys are ignited without the melt protective gases during melting and casting process due to their high reactivity. The purpose of this study is to investigate effects of Ca and CaO on pure Mg through microstructure observation, ignition test and phase analysis. With increasing Ca and CaO contents, the ignition resistance of Ca or CaO added pure Mg is increased and the grains are refined. As results of XRD and EDS, CaO is reduced to Ca in CaO added pure Mg. Mg 2Ca phase is formed even in 0.1 wt.% CaO added pure Mg by reduction mechanism, while Mg 2Ca phase is formed over 1.35 wt.% Ca added pure Mg.

Requirement of biphasic calcium release from the endoplasmic reticulum for Fas-mediated apoptosis

Fas receptor is a member of the tumor necrosis factor-α family of death receptors that mediate physiologic apoptotic signaling. To investigate the molecular mechanisms regulating calcium mobilization during Fas-mediated apoptosis, we have analyzed the sequential steps leading to altered calcium homeostasis and cell death in response to activation of the Fas receptor. We show that Fas-mediated apoptosis requires endoplasmic reticulum–mediated calcium release in a mechanism dependent on phospholipase C-γ1 (PLC-γ1) activation and Ca2+ release from inositol 1,4,5-trisphosphate receptor (IP3R) channels. The kinetics of Ca2+ release were biphasic, demonstrating a rapid elevation caused by PLC-γ1 activation and a delayed and sustained increase caused by cytochrome c binding to IP3R. Blocking either phase of Ca2+ mobilization was cytoprotective, highlighting PLC-γ1 and IP3R as possible therapeutic targets for disorders associated with Fas signaling.

Effects and mechanism of Ca on refinement of AZ91D alloy

Ca addition into magnesium alloy is one of the most effective ways to improve high temperature and mechanical properties of magnesium alloys. The influence of calcium on refinement of AZ91D alloy was investigated by optical microscopy, scanning electron microscopy and thermal analysis. It was shown that increasing the amount of added Ca (≤1.0 wt.%Ca), the grain refinement tendency of AZ91D alloy intensified. The related refinement mechanism is as follows: Ca possesses a strong segregation ability in melt alloy and forms an intensive constitutional undercooling in a diffusion layer ahead of the advancing solid/liquid interface which restricts grain growth and promotes nucleation in the melt. The higher the amount of added Ca is, the higher the formation temperature of Al 2Ca phase on grain boundary is, which increases the effect of constitutional undercooling, consequently intensifies the refinement tendency. Besides, with the amount of added Ca increases, the eutectic reaction extent becomes depressed lowered which results in the refinement of eutectic structure.

Effect of Al contents on microstructures, tensile and creep properties of Mg–Al–Sr–Ca alloy

Microstructures, tensile and creep properties of Mg–(4–7)Al–1Sr–1Ca (AJC411–711) alloys have been investigated. The as-cast microstructure of Mg–(4–7)Al–1Sr–1Ca alloys consists of the α-Mg matrix and grain boundary intermetallics. In the alloy with 4% of Al addition (AJC411) thin lamellar eutectic Mg 2Ca, coarse eutectic (Mg, Al) 2Ca and a bulky ternary Mg–Al–Sr phase are observed at grain boundaries. With increase of Al content, the volume fraction of the Mg 2Ca and Mg–Al–Sr phase decreases, meanwhile that of the coarse (Mg, Al) 2Ca phase increases. A 7% of Al addition leads to the formation of another thin lamellar eutectic Al 4Sr at grain boundaries besides eutectic (Mg, Al) 2Ca. The bulky ternary phase and Mg 2Ca phase cannot be found in Mg–7Al–1Sr–1Ca (AJC711) alloy. Both strength and ductility increase with the increase of Al concentration in the alloys studied at ambient and elevated temperatures of 175 and 200 °C. At the conditions of 175 °C/70 MPa and 200 °C/70 MPa, the alloys Mg–6Al–1Sr–1Ca (AJC611) and Mg–5Al–1Sr–1Ca (AJC511) show best creep resistance among prepared alloys, respectively. Higher Al concentration results in remarkable reduction of creep properties.

Thermodynamic calculation of intermetallic compounds in AZ91 alloy containing calcium

Based on the Miedema model and Chou model, the activities of different solute components in Mg-Al-Zn, Mg-Ca-Zn and Mg-Al-Ca ternary systems were calculated. The results show that the variety of zinc content has little influence on the activity of Al or Ca, and the interaction of Zn and Al or Ca can be neglected when the mass fraction of Zn is lower than 2% in the AZ91 alloy containing calcium (noted as Mg-Al-Zn-Ca system). Therefore, the possible intermetallic compounds in the Mg-Al-Zn-Ca system can be predicted by directly calculating the Gibbs free energies of the reactions in Mg-Al-Ca system. The calculated Gibbs free energies in the Mg-Al-Ca system indicate that Al 2Ca phase can take priority of depositing, which agrees with the experimental results in references. The consistency of calculation and experiment proves that the intermetallic compounds in the Mg-Al-Zn-Ca system can be predicted by the Miedema model and Chou model.

The effect of Ca and rare earth elements on the microstructure, mechanical properties and corrosion behavior of AZ91D

The microstructure, mechanical properties and corrosion behavior of AZ91 with addition of Ca and rare earth elements (REs) were investigated using tensile tests, X-ray diffraction, SEM, EDX, immersion tests and electrochemical polarization experiments. The addition of 1%Ca led to the formation of reticular Al 2Ca phase, which improved the corrosion resistance of AZ91D alloys. The reticular Al 2Ca phase had a detrimental influence on the mechanical properties of AZ91 alloys; however, the addition of REs improved the ultimate tensile strength of the AZ91 alloy, but the corrosion resistance increased slightly compared with the addition of Ca. With the addition of 1%Ca and 1%REs to AZ91, the ultimate tensile strength increased by 15.9% and the corrosion rate decreased to 0.086 mg cm −2 day −1 due to the formation of the reticular Al 2Ca phase, which acted as an effective barrier against corrosion.