Dependency of Calcium Alternans on Ryanodine Receptor Refractoriness
Alvarez-Lacalle, Enric; Cantalapiedra, Inma R.; Peñaranda, Angelina; Cinca, Juan; Hove-Madsen, Leif; Echebarria, Blas
2013-01-01
Background Rapid pacing rates induce alternations in the cytosolic calcium concentration caused by fluctuations in calcium released from the sarcoplasmic reticulum (SR). However, the relationship between calcium alternans and refractoriness of the SR calcium release channel (RyR2) remains elusive. Methodology/Principal Findings To investigate how ryanodine receptor (RyR2) refractoriness modulates calcium handling on a beat-to-beat basis using a numerical rabbit cardiomyocyte model. We used a mathematical rabbit cardiomyocyte model to study the beat-to-beat calcium response as a function of RyR2 activation and inactivation. Bi-dimensional maps were constructed depicting the beat-to-beat response. When alternans was observed, a novel numerical clamping protocol was used to determine whether alternans was caused by oscillations in SR calcium loading or by RyR2 refractoriness. Using this protocol, we identified regions of RyR2 gating parameters where SR calcium loading or RyR2 refractoriness underlie the induction of calcium alternans, and we found that at the onset of alternans both mechanisms contribute. At low inactivation rates of the RyR2, calcium alternans was caused by alternation in SR calcium loading, while at low activation rates it was caused by alternation in the level of available RyR2s. Conclusions/Significance We have mapped cardiomyocyte beat-to-beat responses as a function of RyR2 activation and inactivation, identifying domains where SR calcium load or RyR2 refractoriness underlie the induction of calcium alternans. A corollary of this work is that RyR2 refractoriness due to slow recovery from inactivation can be the cause of calcium alternans even when alternation in SR calcium load is present. PMID:23390511
CaSR-mediated interactions between calcium and magnesium homeostasis in mice.
Quinn, Stephen J; Thomsen, Alex R B; Egbuna, Ogo; Pang, Jian; Baxi, Khanjan; Goltzman, David; Pollak, Martin; Brown, Edward M
2013-04-01
Calcium (Ca) and magnesium (Mg) homeostasis are interrelated and share common regulatory hormones, including parathyroid hormone (PTH) and vitamin D. However, the role of the calcium-sensing receptor (CaSR) in Mg homeostasis in vivo is not well understood. We sought to investigate the interactions between Mg and Ca homeostasis using genetic mouse models with targeted inactivation of PTH (PTH KO) or both PTH and the calcium-sensing receptor (CaSR) (double knockout, DKO). Serum Mg is lower in PTH KO and DKO mice than in WT mice on standard chow, whereas supplemental dietary Ca leads to equivalent Mg levels for all three genotypes. Mg loading increases serum Mg in all genotypes; however, the increase in serum Mg is most pronounced in the DKO mice. Serum Ca is increased with Mg loading in the PTH KO and DKO mice but not in the WT mice. Here, too, the hypercalcemia is much greater in the DKO mice. Serum and especially urinary phosphate are reduced during Mg loading, which is likely due to intestinal chelation of phosphate by Mg. Mg loading decreases serum PTH in WT mice and increases serum calcitonin in both WT and PTH KO mice but not DKO mice. Furthermore, Mg loading elevates serum 1,25-dihydroxyvitamin D in all genotypes, with greater effects in PTH KO and DKO mice, possibly due to reduced levels of serum phosphorus and FGF23. These hormonal responses to Mg loading and the CaSR's role in regulating renal function may help to explain changes in serum Mg and Ca found during Mg loading.
Paydar, Mehrak Javadi; Pousti, Abbas; Farsam, Hasan; Amanlou, Massoud; Mehr, Shahram Ejtemaei; Dehpour, Ahmad Reza
2005-11-01
The purpose of this study was to determine the effects of 2 Ca2+ channel blockers, verapamil and diltiazem, on calcium loading (active Ca2+ uptake) and the following Ca2+ release induced by silver ion (Ag+) and Ca2+ from the membrane of heavy sarcoplasmic reticulum (SR) of chicken skeletal muscle. A fluorescent probe technique was employed to determine the calcium movement through the SR. Pretreatment of the medium with diltiazem and verapamil resulted in a significant decrease in the active Ca2+ uptake, with IC50 of about 290 micromol/L for verapamil and 260 micromol/L for diltiazem. Inhibition of Ca2+ uptake was not due to the development of a substantial drug-dependent leak of Ca2+ from the SR. It might, in part, have been mediated by a direct inhibitory effect of these drugs on the Ca2+ ATPase activity of the SR Ca2+ pump. We confirmed that Ca2+ channel blockers, administered after SR Ca2+ loading and before induction of Ca2+ release, caused a dose-dependent inhibition of both Ca2+- and Ag+-induced Ca2+ release rate. Moreover, if Ca2+ channel blockers were administered prior to SR Ca2+ loading, in spite of Ca2+ uptake inhibition the same reduction in Ca2+- and Ag+-induced Ca2+ release rate was seen. We showed that the inhibition of Ag+-induced Ca2+ release by L-channel blockers is more sensitive than Ca2+-induced Ca2+ release inhibition, so the IC50 for Ag+- and Ca2+-induced Ca2+ release was about 100 and 310 micromol/L for verapamil and 79 and 330 micromol/L for diltiazem, respectively. Our results support the evidence that Ca2+ channel blockers affect muscle microsome of chicken skeletal muscle by 2 independent mechanisms: first, reduction of Ca2+ uptake rate and Ca2+-ATPase activity inhibition, and second, inhibition of both Ag+- and Ca2+-induced Ca2+ release by Ca2+ release channels. These findings confirm the direct effect of Ca2+ channel blockers on calcium release channels. Our results suggest that even if the SR is incompletely preloaded with Ca2+ because of inhibition of Ca2+ uptake by verapamil and diltiazem, no impairment in Ca2+ release occurs.
The contractile adaption to preload depends on the amount of afterload
Schotola, Hanna; Sossalla, Samuel T.; Renner, André; Gummert, Jan; Danner, Bernhard C.; Schott, Peter
2017-01-01
Abstract Aims The Frank–Starling mechanism (rapid response (RR)) and the secondary slow response (SR) are known to contribute to increases contractile performance. The contractility of the heart muscle is influenced by pre‐load and after‐load. Because of the effect of pre‐load vs. after‐load on these mechanisms in not completely understood, we studied the effect in isolated muscle strips. Methods and results Progressive stretch lead to an increase in shortening/force development under isotonic (only pre‐load) and isometric conditions (pre‐ and after‐load). Muscle length with maximal function was reached earlier under isotonic (L max‐isotonic) compared with isometric conditions (L max‐isometric) in nonfailing rabbit, in human atrial and in failing ventricular muscles. Also, SR after stretch from slack to L max‐isotonic was comparable under isotonic and isometric conditions (human: isotonic 10 ± 4%, isometric 10 ± 4%). Moreover, a switch from isotonic to isometric conditions at L max‐isometric showed no SR proving independence of after‐load. To further analyse the degree of SR on the total contractile performance at higher pre‐load muscles were stretched from slack to 98% L max‐isometric under isotonic conditions. Thereby, the SR was 60 ± 9% in rabbit and 51 ± 14% in human muscle strips. Conclusions This work shows that the acute contractile response largely depends on the degree and type of mechanical load. Increased filling of the heart elevates pre‐load and prolongs the isotonic part of contraction. The reduction in shortening at higher levels of pre‐load is thereby partially compensated by the pre‐load‐induced SR. After‐load shifts the contractile curve to a better ‘myofilament function’ by probably influencing thin fibers and calcium sensitivity, but has no effect on the SR. PMID:29154423
Maruyama, Yutaka; Yasuda, Reiko; Kuroda, Motonaka; Eto, Yuzuru
2012-01-01
Recently, we reported that calcium-sensing receptor (CaSR) is a receptor for kokumi substances, which enhance the intensities of salty, sweet and umami tastes. Furthermore, we found that several γ-glutamyl peptides, which are CaSR agonists, are kokumi substances. In this study, we elucidated the receptor cells for kokumi substances, and their physiological properties. For this purpose, we used Calcium Green-1 loaded mouse taste cells in lingual tissue slices and confocal microscopy. Kokumi substances, applied focally around taste pores, induced an increase in the intracellular Ca2+ concentration ([Ca2+]i) in a subset of taste cells. These responses were inhibited by pretreatment with the CaSR inhibitor, NPS2143. However, the kokumi substance-induced responses did not require extracellular Ca2+. CaSR-expressing taste cells are a different subset of cells from the T1R3-expressing umami or sweet taste receptor cells. These observations indicate that CaSR-expressing taste cells are the primary detectors of kokumi substances, and that they are an independent population from the influenced basic taste receptor cells, at least in the case of sweet and umami. PMID:22511946
Steenbergen, J M; Fay, F S
1996-01-26
Calcium release from intracellular stores occurs in a graded manner in response to increasing concentrations of either inositol 1,4,5-trisphosphate or caffeine. To investigate the mechanism responsible for this quantal release phenomenon, [Ca2+] changes inside intracellular stores in isolated single smooth muscle cells were monitored with mag-fura 2. Following permeabilization with saponin or alpha-toxin the dye, loaded via its acetoxymethyl ester, was predominantly trapped in the sarcoplasmic reticulum (SR). Low caffeine concentrations in the absence of ATP induced only partial Ca2+ release; however, after inhibiting the calcium pump with thapsigargin the same stimulus released twice as much Ca2+. When the SR Ca(2+)-ATPase was rendered non-functional by depleting its "ATP pool," submaximal caffeine doses almost fully emptied the stores of Ca2+. We conclude that quantal release of Ca2+ in response to caffeine in these smooth muscle cells is largely due to the activity of the SR Ca(2+)-ATPase, which appears to return a portion of the released Ca2+ back to the SR, even in the absence of ATP. Apparently the SR Ca(2+)-ATPase is fueled by ATP, which is either compartmentalized or bound to the SR.
CA-45 AND Sr-85 METABOLISM IN MAN. Progress Report for June 15, 1959- May 20, 1960
DOE Office of Scientific and Technical Information (OSTI.GOV)
None
1960-10-31
Bone formation rate in a normal, healthy, young adult was observed to be 0.521 g calcium/day. Calcium balance and bone formation and destruction rates were studied in patients with disuse osetoporosis associated with quadriplegia secondary to poliomyelitis and patients with senile and posmenopausal osteoporosis. Renal strontium/calcium discrimination, studied for nine cases, was given by a mean factor of 4.3. This factor means that, exposed to trace amounts of strontium and normal calcium loads, the human kidney will produce a urine containing 4.3 atoms of strontium per unit filtered strontium for each atom calcium per unit filtered calcium. The mean valuemore » for gastrointestinal discrimination between endogenously secreted Sr/sup 85/ and Ca/sup 45/ was 1.4. The ratio of strontium-determined pool to calcium- determined pool was 1.04 plus or minus 0.13 (1 S.D.) and the corresponding ratio for bone formation values was 1.04 plus or minus 0.32 (1 S.D.) for nine patients studied. (C.J.G.)« less
Masaeli, Reza; Jafarzadeh Kashi, Tahereh Sadat; Dinarvand, Rassoul; Rakhshan, Vahid; Shahoon, Hossein; Hooshmand, Behzad; Mashhadi Abbas, Fatemeh; Raz, Majid; Rajabnejad, Alireza; Eslami, Hossein; Khoshroo, Kimia; Tahriri, Mohammadreza; Tayebi, Lobat
2016-12-01
The purpose of this multi-phase explorative in vivo animal/surgical and in vitro multi-test experimental study was to (1) create a 3wt%-nanostrontium hydroxyapatite-enhanced calcium phosphate cement (Sr-HA/CPC) for increasing bone formation and (2) creating a simvastatin-loaded poly(lactic-co-glycolic acid) (SIM-loaded PLGA) microspheres plus CPC composite (SIM-loaded PLGA+nanostrontium-CPC). The third goal was the extensive assessment of multiple in vitro and in vivo characteristics of the above experimental explorative products in vitro and in vivo (animal and surgical studies). Physical and chemical properties of the prepared Sr-HA/CPC were evaluated. MTT assay and alkaline phosphatase activities, and radiological and histological examinations of Sr-HA/CPC, CPC and negative control were compared. X-ray diffraction (XRD) indicated that crystallinity of the prepared cement increased by increasing the powder-to-liquid ratio. Incorporation of Sr-HA into CPC increased MTT assay (biocompatibility) and ALP activity (P<0.05). Histomorphometry showed greater bone formation after 4weeks, after implantation of Sr-HA/CPC in 10 rats compared to implantations of CPC or empty defects in the same rats (n=30, ANOVA P<0.05). METHODS AND RESULTS PERTAINING TO SIM-LOADED PLGA MICROSPHERES+NANOSTRONTIUM-CPC COMPOSITE: After SEM assessment, the produced composite of microspheres and enhanced CPC were implanted for 8weeks in 10 rabbits, along with positive and negative controls, enhanced CPC, and enhanced CPC plus SIM (n=50). In the control group, only a small amount of bone had been regenerated (localized at the boundary of the defect); whereas, other groups showed new bone formation within and around the materials. A significant difference was found in the osteogenesis induced by the groups sham control (16.96±1.01), bone materials (32.28±4.03), nanostrontium-CPC (24.84±2.6), nanostrontium-CPC-simvastatin (40.12±3.29), and SIM-loaded PLGA+nanostrontium-CPC (44.8±6.45) (ANOVA P<0.001). All the pairwise comparisons were significant (Tukey P<0.01), except that of nanostrontium-CPC-simvastatin and SIM-loaded PLGA+nanostrontium-CPC. This confirmed the efficacy of the SIM-loaded PLGA+nanostrontium-CPC composite, and its superiority over all materials except SIM-containing nanostrontium-CPC. Copyright © 2016 Elsevier B.V. All rights reserved.
Kabbara, Akram A; Allen, David G
2001-01-01
Single fibres from the lumbrical muscles of the cane toad (Bufo marinus) were incubated in fluo-5N AM for 2 h at 35 °C in order to load the indicator into the sarcoplasmic reticulum. Fluo-5N is a low-affinity calcium indicator (KCa 90 μm). Successful sarcoplasmic reticulum (SR) loading was indicated by a fluorescence signal that declined during contraction. Confocal microscopy showed that the dye loaded principally in lines perpendicular to the long axis of the fibre that repeated each sarcomere. This is consistent with much of the dye residing in the SR. To establish the site of loading, fibres were exposed to 30 mm caffeine in the presence of 20 μm 2,5-di(tert-butyl)1,4-hydroquinone (TBQ, an SR pump inhibitor) which should release most Ca2+ from the SR; this procedure reduced the fluorescence to 46 ± 4 % of the control value. To determine how much indicator was in the myoplasm, fibres were exposed to 100 μg ml−1 saponin which permeabilizes the surface membrane; saponin treatment reduced the fluorescence to 51 ± 2 % of the control value. During maximally activated tetani (100 Hz stimulation rate, 22 °C) the component of signal from the SR declined by 33 ± 4 %. During relaxation the SR signal recovered in two phases with time constants of 0.38 ± 0.14 s and 10.1 ± 1.7 s. Partially activated tetani (30 Hz stimulation rate) showed a smaller SR signal. Application of the SR Ca2+ pump inhibitor TBQ slowed the rate of recovery of the SR signal. Muscle fatigue was produced by repeated short tetani until tension was reduced to 50 %. The SR signal during the periods between tetani declined steadily and the SR Ca2+ signal was eventually reduced to 71 ± 8 % of the control signal. This signal recovered in two phases when the muscle was rested. An initial phase had a time constant of 1.7 ± 0.2 s so that by 20 s of recovery the SR Ca2+ signal was 86 ± 7 % of control; the second phase was slower and by 5 min the SR Ca2+ signal was back to control values (98 ± 5 % control). In addition the magnitude of the SR signal decline associated with each tetanus (Δ[Ca2+]SR) declined monotonically throughout fatigue and returned to control after 5 min recovery. This approach can monitor the SR Ca2+ concentration in normally functioning muscle fibres with good time resolution. The method confirms other approaches that show that the free Ca2+ available for release in the SR declines during fatigue. This reduction in [Ca2+]SR will contribute to the failure of Ca2+ delivery to the myofilaments which is an important cause of muscle fatigue. PMID:11432994
Kabbara, A A; Allen, D G
2001-07-01
1. Single fibres from the lumbrical muscles of the cane toad (Bufo marinus) were incubated in fluo-5N AM for 2 h at 35 degrees C in order to load the indicator into the sarcoplasmic reticulum. Fluo-5N is a low-affinity calcium indicator (K(Ca) 90 microM). Successful sarcoplasmic reticulum (SR) loading was indicated by a fluorescence signal that declined during contraction. 2. Confocal microscopy showed that the dye loaded principally in lines perpendicular to the long axis of the fibre that repeated each sarcomere. This is consistent with much of the dye residing in the SR. 3. To establish the site of loading, fibres were exposed to 30 mM caffeine in the presence of 20 microM 2,5-di(tert-butyl)1,4-hydroquinone (TBQ, an SR pump inhibitor) which should release most Ca(2+) from the SR; this procedure reduced the fluorescence to 46 +/- 4 % of the control value. To determine how much indicator was in the myoplasm, fibres were exposed to 100 microg ml(-1) saponin which permeabilizes the surface membrane; saponin treatment reduced the fluorescence to 51 +/- 2 % of the control value. 4. During maximally activated tetani (100 Hz stimulation rate, 22 degrees C) the component of signal from the SR declined by 33 +/- 4 %. During relaxation the SR signal recovered in two phases with time constants of 0.38 +/- 0.14 s and 10.1 +/- 1.7 s. Partially activated tetani (30 Hz stimulation rate) showed a smaller SR signal. Application of the SR Ca(2+) pump inhibitor TBQ slowed the rate of recovery of the SR signal. 5. Muscle fatigue was produced by repeated short tetani until tension was reduced to 50 %. The SR signal during the periods between tetani declined steadily and the SR Ca(2+) signal was eventually reduced to 71 +/- 8 % of the control signal. This signal recovered in two phases when the muscle was rested. An initial phase had a time constant of 1.7 +/- 0.2 s so that by 20 s of recovery the SR Ca(2+) signal was 86 +/- 7 % of control; the second phase was slower and by 5 min the SR Ca(2+) signal was back to control values (98 +/- 5 % control). In addition the magnitude of the SR signal decline associated with each tetanus (Delta[Ca(2+)](SR)) declined monotonically throughout fatigue and returned to control after 5 min recovery. 6. This approach can monitor the SR Ca(2+) concentration in normally functioning muscle fibres with good time resolution. The method confirms other approaches that show that the free Ca(2+) available for release in the SR declines during fatigue. This reduction in [Ca(2+)](SR) will contribute to the failure of Ca(2+) delivery to the myofilaments which is an important cause of muscle fatigue.
Cabello, Nuria; Llach, Anna; Vallmitjana, Alexander; Benítez, Raúl; Badimon, Lina; Cinca, Juan; Llorente-Cortés, Vicenta; Hove-Madsen, Leif
2013-01-01
The damaging effects of high plasma levels of cholesterol in the cardiovascular system are widely known, but little attention has been paid to direct effects on cardiomyocyte function. We therefore aimed at testing the hypothesis that Low Density Lipoprotein (LDL) cholesterol affects calcium dynamics and signal propagation in cultured atrial myocytes. For this purpose, mRNA and protein expression levels were determined by real time PCR and western blot analysis, respectively, and intracellular calcium was visualized in fluo-4 loaded atrial HL-1 myocyte cultures subjected to field stimulation. At low stimulation frequencies all cultures had uniform calcium transients at all tested LDL concentrations. However, 500 µg LDL/mL maximally reduced the calcium transient amplitude by 43% from 0.30±0.04 to 0.17±0.02 (p<0.05). Moreover, LDL-cholesterol dose-dependently increased the fraction of alternating and irregular beat-to-beat responses observed when the stimulation interval was shortened. This effect was linked to a concurrent reduction in SERCA2, RyR2, IP3RI and IP3RII mRNA levels. SERCA2 protein levels were also reduced by 43% at 200 µg LDL/mL (p<0.05) and SR calcium loading was reduced by 38±6% (p<0.001). By contrast, HDL-cholesterol had no significant effect on SERCA expression or SR calcium loading. LDL-cholesterol also slowed the conduction velocity of the calcium signal from 3.2+0.2 mm/s without LDL to 1.7±0.1 mm/s with 500 µg LDL/mL (p<0.05). This coincided with a reduction in Cx40 expression (by 44±3%; p<0.05 for mRNA and by 79±2%; p<0.05 for Cx40 protein at 200 µg/ml LDL) whereas the Cx-43 expression did not significantly change. In conclusion, LDL-cholesterol destabilizes calcium handling in cultured atrial myocytes subjected to rapid pacing by reducing SERCA2 and Cx40 expression and by slowing the conduction velocity of the calcium signal. PMID:23516438
Mamillapalli, Ramanaiah; VanHouten, Joshua; Dann, Pamela; Bikle, Daniel; Chang, Wenhan; Brown, Edward
2013-01-01
To meet the demands for milk calcium, the lactating mother adjusts systemic calcium and bone metabolism by increasing dietary calcium intake, increasing bone resorption, and reducing renal calcium excretion. As part of this adaptation, the lactating mammary gland secretes PTHrP into the maternal circulation to increase bone turnover and mobilize skeletal calcium stores. Previous data have suggested that, during lactation, the breast relies on the calcium-sensing receptor (CaSR) to coordinate PTHrP secretion and milk calcium transport with calcium availability. To test this idea genetically, we bred BLG-Cre mice with CaSR-floxed mice to ablate the CaSR specifically from mammary epithelial cells only at the onset of lactation (CaSR-cKO mice). Loss of the CaSR in the lactating mammary gland did not disrupt alveolar differentiation or milk production. However, it did increase the secretion of PTHrP into milk and decreased the transport of calcium from the circulation into milk. CaSR-cKO mice did not show accelerated bone resorption, but they did have a decrease in bone formation. Loss of the mammary gland CaSR resulted in hypercalcemia, decreased PTH secretion, and increased renal calcium excretion in lactating mothers. Finally, loss of the mammary gland CaSR resulted in decreased calcium accrual by suckling neonates, likely due to the combination of increased milk PTHrP and decreased milk calcium. These results demonstrate that the mammary gland CaSR coordinates maternal bone and calcium metabolism, calcium transport into milk, and neonatal calcium accrual during lactation. PMID:23782944
Dubinin, M V; Adakeeva, S I; Samartsev, V N
2013-04-01
Long-chain saturated monocarboxylic fatty acids can induce nonspecific permeability of the inner membrane (open pores) of liver mitochondria loaded with Ca2+ or Sr(2+) by the mechanism insensitive to cyclosporin A. In this work we investigated the effect of their metabolites - α,ω-dioic (dicarboxylic) acids - as potential inducers of pore opening by a similar mechanism. It was established that the addition of α,ω-hexadecanedioic acid (HDA) at a concentration of 10-30 µM to liver mitochondria loaded with Ca2+ or Sr(2+) leads to swelling of the organelles and release of these ions from the matrix. The maximum effect of HDA is observed at 50 µM Ca2+ concentration. Cyclosporin A at a concentration of 1 µM, previously added to the mitochondria, did not inhibit the observed processes. The calcium uniporter inhibitor ruthenium red, which blocks influx of Ca2+ and Sr(2+) to the matrix of mitochondria, prevented HDA-induced swelling. The effect of HDA as inducer of swelling of mitochondria was compared with similar effects of α,ω-tetradecanedioic and α,ω-dodecanedioic acids whose acyl chains are two and four carbon atoms shorter than HDA, respectively. It was found that the efficiency of these α,ω-dioic acids decreases with reducing number of carbon atoms in their acyl chains. It was concluded that in the presence of Ca2+ or Sr(2+) long-chain saturated α,ω-dioic acids can induce a cyclosporin A-insensitive permeability of the inner membrane (open pores) of liver mitochondria as well as their monocarboxylic analogs.
Cheng, Hao; Xiong, Wei; Fang, Zhong; Guan, Hanfeng; Wu, Wei; Li, Yong; Zhang, Yong; Alvarez, Mario Moisés; Gao, Biao; Huo, Kaifu; Xu, Jiangwen; Xu, Na; Zhang, Chengcheng; Fu, Jijiang; Khademhosseini, Ali; Li, Feng
2016-02-01
Two frequent problems are associated with the titanium surfaces of bone/dental implants: lack of native tissue integration and associated infection. These problems have prompted a significant body of research regarding the modification of these surfaces. The present study describes a hydrothermal treatment for the fabrication of strontium (Sr) and silver (Ag) loaded nanotubular structures with different tube diameters on titanium surfaces. The Sr loading from a Sr(OH)2 solution was regulated by the size of the inner diameter of the titanium nanotubes (NT) (30nm or 80nm, formed at 10V or 40V, respectively). The quantity of Ag was adjusted by immersing the samples in 1.5 or 2.0M AgNO3 solutions. Sr and Ag were released in a controllable and prolonged matter from the NT-Ag.Sr samples, with negligible cytotoxicity. Prominent antibacterial activity was observed due to the release of Ag. Sr incorporation enhanced the initial cell adhesion, migration, and proliferation of preosteoblast MC3T3-E1 cells. Sr release also up-regulated the expression of osteogenic genes and induced mineralization, as suggested by the presence of more mineralized calcium nodules in cells cultured on NT-Ag.Sr surfaces. In vivo experiments showed that the Sr-loaded samples accelerated the formation of new bone in both osteoporosis and bone defect models, as confirmed by X-ray, Micro-CT evaluation, and histomorphometric analysis of rats implanted with NT-Ag.Sr samples. The antibacterial activity and outstanding osteogenic properties of NT-Ag.Sr samples highlight their excellent potential for use in clinical applications. Two frequent problems associated with Ti surfaces, widely used in orthopedic and dental arenas, are their lack of native tissue integration and risk of infection. We describe a novel approach for the fabrication of strontium (Sr) and silver (Ag) loaded nanotubular structures on titanium surfaces. A relevant aspect of this work is the demonstration of long-lasting and controllable Ag release, leading to excellent antibacterial and anti-adherent properties against methicillin-resistant Staphylococcus aureus (MRSA), and Gram-negative bacteria such as Escherichia coli. The extended release of Sr accelerates the filling of bone defects by improving the repair of damaged cortical bone and increasing trabecular bone microarchitecture. Our results highlight the potential of Sr and Ag loaded nanotubular structures for use in clinical applications. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Suzuki, M; Aso, T; Sato, T; Michimata, M; Kazama, I; Saiki, H; Hatano, R; Ejima, Y; Miyama, N; Sato, A; Matsubara, M
2005-06-01
The calcium-sensing receptor (CaSR) regulates the extracellular calcium level, mainly by controlling parathyroid hormon secretion and renal calcium reabsorption. In gain-of-function CaSR mutations, the genetic abnormalities increase CaSR activity leading to the development of such clinical manifestations as hypercalciuric hypocalcemia and hypoparathyroidism. We report a Japanese case of CaSR gain-of-function mutation and represent a therapeutic intervention based on the functional characteristics of CaSR in renal tubule. DNA sequence analysis revealed a heterozygous G to T mutation identified in a 12-year-old Japanese girl presenting with sporadic onset of hypercalciuric hypocalcemia and hypoparathyroidism. The mutation is located in the N-terminal extracellular domain of the CaSR gene, one of the most important parts for the three-dimensional construction of the receptor, resulting in the substitution of phenylalanine for cysteine at amino acid 131 (C131F) in exon 3. Based on the diagnosis of the gain-of-function mutation in the CaSR, oral hydrochlorothiazide administration and supplemental hydration were started in addition to calcium supplementation. The combination therapy of thiazide and supplemental hydration markedly reduced both renal calcium excretion and urinary calcium concentration from 0.4-0.7 to less than 0.1 mg/mg (urinary calcium/creatinine ratio) and from 10-15 to 3-5 mg/dl (urinary calcium concentration), respectively. This therapy stopped the progression of renal calcification during the follow-up period. Supplemental hydration should be considered essential for the following reasons: (1) calcium supplementation activates the CaSR in the kidney and suppresses renal urinary concentrating ability, (2) the thiazide has a diuretic effect, (3) as calcium supplementation increases renal calcium excretion, the supplemental hydration decreases urinary calcium concentration by increasing urinary volume, thereby diminishing the risk of intratubular crystallization of calcium ion.
Quinn, Stephen J.; Thomsen, Alex R. B.; Pang, Jian L.; Kantham, Lakshmi; Bräuner-Osborne, Hans; Pollak, Martin; Goltzman, David
2013-01-01
Calcium and phosphorus homeostasis are highly interrelated and share common regulatory hormones, including FGF23. However, little is known about calcium's role in the regulation of FGF23. We sought to investigate the regulatory roles of calcium and phosphorus in FGF23 production using genetic mouse models with targeted inactivation of PTH (PTH KO) or both PTH and the calcium-sensing receptor (CaSR; PTH-CaSR DKO). In wild-type, PTH KO, and PTH-CaSR DKO mice, elevation of either serum calcium or phosphorus by intraperitoneal injection increased serum FGF23 levels. In PTH KO and PTH-CaSR DKO mice, however, increases in serum phosphorus by dietary manipulation were accompanied by severe hypocalcemia, which appeared to blunt stimulation of FGF23 release. Increases in dietary phosphorus in PTH-CaSR DKO mice markedly decreased serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] despite no change in FGF23, suggesting direct regulation of 1,25(OH)2D3 synthesis by serum phosphorus. Calcium-mediated increases in serum FGF23 required a threshold level of serum phosphorus of about 5 mg/dl. Analogously, phosphorus-elicited increases in FGF23 were markedly blunted if serum calcium was less than 8 mg/dl. The best correlation between calcium and phosphorus and serum FGF23 was found between FGF23 and the calcium × phosphorus product. Since calcium stimulated FGF23 production in the PTH-CaSR DKO mice, this effect cannot be mediated by the full-length CaSR. Thus the regulation of FGF23 by both calcium and phosphorus appears to be fundamentally important in coordinating the serum levels of both mineral ions and ensuring that the calcium × phosphorus product remains within a physiological range. PMID:23233539
Evans, A Mark; Fameli, Nicola; Ogunbayo, Oluseye A; Duan, Jingxian; Navarro-Dorado, Jorge
2016-08-01
Calcium signals determine, for example, smooth muscle contraction and changes in gene expression. How calcium signals select for these processes is enigmatic. We build on the "panjunctional sarcoplasmic reticulum" hypothesis, describing our view that different calcium pumps and release channels, with different kinetics and affinities for calcium, are strategically positioned within nanojunctions of the SR and help demarcate their respective cytoplasmic nanodomains. SERCA2b and RyR1 are preferentially targeted to the sarcoplasmic reticulum (SR) proximal to the plasma membrane (PM), i.e., to the superficial buffer barrier formed by PM-SR nanojunctions, and support vasodilation. In marked contrast, SERCA2a may be entirely restricted to the deep, perinuclear SR and may supply calcium to this sub-compartment in support of vasoconstriction. RyR3 is also preferentially targeted to the perinuclear SR, where its clusters associate with lysosome-SR nanojunctions. The distribution of RyR2 is more widespread and extends from this region to the wider cell. Therefore, perinuclear RyR3s most likely support the initiation of global calcium waves at L-SR junctions, which subsequently propagate by calcium-induced calcium release via RyR2 in order to elicit contraction. Data also suggest that unique SERCA and RyR are preferentially targeted to invaginations of the nuclear membrane. Site- and function-specific calcium signals may thus arise to modulate stimulus-response coupling and transcriptional cascades.
Superresolution Modeling of Calcium Release in the Heart
Walker, Mark A.; Williams, George S.B.; Kohl, Tobias; Lehnart, Stephan E.; Jafri, M. Saleet; Greenstein, Joseph L.; Lederer, W.J.; Winslow, Raimond L.
2014-01-01
Stable calcium-induced calcium release (CICR) is critical for maintaining normal cellular contraction during cardiac excitation-contraction coupling. The fundamental element of CICR in the heart is the calcium (Ca2+) spark, which arises from a cluster of ryanodine receptors (RyR). Opening of these RyR clusters is triggered to produce a local, regenerative release of Ca2+ from the sarcoplasmic reticulum (SR). The Ca2+ leak out of the SR is an important process for cellular Ca2+ management, and it is critically influenced by spark fidelity, i.e., the probability that a spontaneous RyR opening triggers a Ca2+ spark. Here, we present a detailed, three-dimensional model of a cardiac Ca2+ release unit that incorporates diffusion, intracellular buffering systems, and stochastically gated ion channels. The model exhibits realistic Ca2+ sparks and robust Ca2+ spark termination across a wide range of geometries and conditions. Furthermore, the model captures the details of Ca2+ spark and nonspark-based SR Ca2+ leak, and it produces normal excitation-contraction coupling gain. We show that SR luminal Ca2+-dependent regulation of the RyR is not critical for spark termination, but it can explain the exponential rise in the SR Ca2+ leak-load relationship demonstrated in previous experimental work. Perturbations to subspace dimensions, which have been observed in experimental models of disease, strongly alter Ca2+ spark dynamics. In addition, we find that the structure of RyR clusters also influences Ca2+ release properties due to variations in inter-RyR coupling via local subspace Ca2+ concentration ([Ca2+]ss). These results are illustrated for RyR clusters based on super-resolution stimulated emission depletion microscopy. Finally, we present a believed-novel approach by which the spark fidelity of a RyR cluster can be predicted from structural information of the cluster using the maximum eigenvalue of its adjacency matrix. These results provide critical insights into CICR dynamics in heart, under normal and pathological conditions. PMID:25517166
Determining the sources of calcium for migratory songbirds using stable strontium isotopes.
Blum, Joel D; Taliaferro, E Hank; Holmes, Richard T
2001-02-01
We investigated natural variations in the stable isotopic composition of strontium (a surrogate for calcium) in the bones of a single species of breeding migratory songbird, as well as in their eggshells, egg contents, and food sources. We use this information to determine the sources of calcium to these migratory songbirds and their offspring. Samples were collected from two locations in the northeastern USA (Hubbard Brook, NH, and Downer Forest, VT.) that differed in soil geochemistry. The mean 87 Sr/ 86 Sr ratios of food items (caterpillars and snails), eggshells, and egg contents were indistinguishable within each site, but significantly different between the two sites. Mean 87 Sr/ 86 Sr ratios for the bones of adult females were significantly different between the two sites, but values were significantly lower than those of food items and eggshells at each site. Two of four adult individuals studied at each site had 87 Sr/ 86 Sr ratios lower than the entire range of values for local food sources. Mixing calculations indicate that up to 60% of skeletal strontium and calcium was derived from foods consumed in the winter grounds where lower 87 Sr/ 86 Sr ratios predominate. At each study site, the 87 Sr/ 86 Sr ratio of eggshells differed significantly between clutches, but the mean clutch 87 Sr/ 86 Sr ratios were unrelated to the skeletal 87 Sr/ 86 Sr ratio of the laying adult. These findings suggest that strontium (and hence calcium) for eggshell production in this species is derived predominantly from local food sources in breeding areas. Thus, reductions in available calcium in northern temperate ecosystems due to the influences of acid deposition could be potentially harmful to this and other species of migratory bird.
[The functions of calcium-sensing receptor in regulating mineral metabolism.
Kinoshita, Yuka
Calcium-sensing receptor(CaSR)which belongs to a G protein-coupled receptor family is one of the key elements in regulating calcium homeostasis. CaSR has been identified as a receptor to control parathyroid hormone(PTH)secretion in parathyroid glands according to serum calcium ion(Ca2+)levels. It has also been shown that CaSR controls reabsorption of water and several cations including Ca2+and magnesium ion(Mg2+)in renal tubular cells. This review summarizes the functions and roles of CaSR in mineral metabolism that are exerted in parathyroid glands, kidney, and intestine.
Extracellular Calcium Has Multiple Targets to Control Cell Proliferation.
Capiod, Thierry
2016-01-01
Calcium channels and the two G-protein coupled receptors sensing extracellular calcium, calcium-sensing receptor (CaSR) and GPRC6a, are the two main means by which extracellular calcium can signal to cells and regulate many cellular processes including cell proliferation, migration and invasion of tumoral cells. Many intracellular signaling pathways are sensitive to cytosolic calcium rises and conversely intracellular signaling pathways can modulate calcium channel expression and activity. Calcium channels are undoubtedly involved in the former while the CaSR and GPRC6a are most likely to interfere with the latter. As for neurotransmitters, calcium ions use plasma membrane channels and GPCR to trigger cytosolic free calcium concentration rises and intracellular signaling and regulatory pathways activation. Calcium sensing GPCR, CaSR and GPRC6a, allow a supplemental degree of control and as for metabotropic receptors, they not only modulate calcium channel expression but they may also control calcium-dependent K+ channels. The multiplicity of intracellular signaling pathways involved, their sensitivity to local and global intracellular calcium increase and to CaSR and GPRC6a stimulation, the presence of membrane signalplex, all this confers the cells the plasticity they need to convert the effects of extracellular calcium into complex physiological responses and therefore determine their fate.
NASA Astrophysics Data System (ADS)
Sternitzke, Vanessa; Janousch, Markus; Heeb, Michèle B.; Hering, Janet G.; Johnson, C. Annette
2014-06-01
The heterogeneous precipitation of calcium-phosphates on calcium hydroxyapatite (Ca10(PO4)6(OH)2 or HAP) in the presence and absence of fluoride is important in the formation of bone and teeth, protection against tooth decay, dental and skeletal fluorosis and defluoridation of drinking water. Strontium hydroxyapatite (Sr10(PO4)6(OH)2 or SrHAP) and strontium carbonate (SrCO3) were used as calcium-free seed templates in precipitation experiments conducted with varying initial calcium-to-phosphate (Ca/P) or calcium-to-phosphate-to-fluoride (Ca/P/F) ratios. Suspensions of SrHAP or SrCO3 seed templates (which were calcium-limited for both templates and phosphate-limited in the case of SrCO3) were reacted at pH 7.3 (25 °C) over 3 days. The resulting solids were examined with Scanning Transmission Electron Microscopy (STEM), X-ray Diffraction (XRD), Fourier Transform Infrared (FTIR), and X-ray Photoelectron Spectroscopy (XPS), X-ray Absorption Near Edge Structure (XANES), and Extended X-ray Absorption Fine Structure spectroscopy (EXAFS). Calcium apatite was the predominant phase identified by all techniques independent of the added Ca/P ratios and of the presence of fluoride. It was not possible to make an unambiguous distinction between HAP and fluorapatite (Ca10(PO4)6F2, FAP). The apatite was calcium-deficient and probably contained some strontium.
Modeling CICR in rat ventricular myocytes: voltage clamp studies
2010-01-01
Background The past thirty-five years have seen an intense search for the molecular mechanisms underlying calcium-induced calcium-release (CICR) in cardiac myocytes, with voltage clamp (VC) studies being the leading tool employed. Several VC protocols including lowering of extracellular calcium to affect Ca2+ loading of the sarcoplasmic reticulum (SR), and administration of blockers caffeine and thapsigargin have been utilized to probe the phenomena surrounding SR Ca2+ release. Here, we develop a deterministic mathematical model of a rat ventricular myocyte under VC conditions, to better understand mechanisms underlying the response of an isolated cell to calcium perturbation. Motivation for the study was to pinpoint key control variables influencing CICR and examine the role of CICR in the context of a physiological control system regulating cytosolic Ca2+ concentration ([Ca2+]myo). Methods The cell model consists of an electrical-equivalent model for the cell membrane and a fluid-compartment model describing the flux of ionic species between the extracellular and several intracellular compartments (cell cytosol, SR and the dyadic coupling unit (DCU), in which resides the mechanistic basis of CICR). The DCU is described as a controller-actuator mechanism, internally stabilized by negative feedback control of the unit's two diametrically-opposed Ca2+ channels (trigger-channel and release-channel). It releases Ca2+ flux into the cyto-plasm and is in turn enclosed within a negative feedback loop involving the SERCA pump, regulating[Ca2+]myo. Results Our model reproduces measured VC data published by several laboratories, and generates graded Ca2+ release at high Ca2+ gain in a homeostatically-controlled environment where [Ca2+]myo is precisely regulated. We elucidate the importance of the DCU elements in this process, particularly the role of the ryanodine receptor in controlling SR Ca2+ release, its activation by trigger Ca2+, and its refractory characteristics mediated by the luminal SR Ca2+ sensor. Proper functioning of the DCU, sodium-calcium exchangers and SERCA pump are important in achieving negative feedback control and hence Ca2+ homeostasis. Conclusions We examine the role of the above Ca2+ regulating mechanisms in handling various types of induced disturbances in Ca2+ levels by quantifying cellular Ca2+ balance. Our model provides biophysically-based explanations of phenomena associated with CICR generating useful and testable hypotheses. PMID:21062495
Control of calcium release and the effect of ryanodine in skinned muscle fibres of the toad.
Lamb, G D; Stephenson, D G
1990-01-01
1. Skinned muscle fibres from the toad were used to investigate the roles of T-system membrane potential and Ca2+ in controlling the calcium release channels of the sarcoplasmic reticulum (SR). 2. Replacement of K+ in the bathing solution with Na+ produced a large contraction which could last for 30 s or more under certain circumstances. This prolonged contraction could be quickly and completely terminated by repolarizing the fibre in the K+ solution and then immediately re-initiated by returning to the Na+ solution. These data indicate that the membrane potential tightly controlled the substantial and prolonged release of calcium. 3. T-system depolarization in the presence of 10 mM-free EGTA (pCa greater than 9) markedly depleted the SR of Ca2+. This implies that depolarization of the T-system can still trigger substantial release of Ca2+ from the SR even when the myoplasmic [Ca2+] is very low and very heavily buffered by EGTA. 4. When the SR was heavily loaded with Ca2+, substitution of a weakly buffered high [Ca2+] solution (pCa 5.4, 50 microM-EGTA) could produce a small to moderate, transient contraction taking between 3 and 12 s to reach a peak and lasting 30 s or more. 5. This contraction may be produced at least partly by 'calcium-induced calcium release' as ruthenium red (2 microM) completely blocked the responses. Moreover, repeated substitutions produced successively smaller responses in parallel with the 'run-down' of the depolarization-induced contractions. 6. Depolarization could always produce an additional large and fast response at any stage during a 'Ca2(+)-induced' response. 7. In the presence of 25 microM-ryanodine, the rapid contraction produced by T-system depolarization was prolonged and could not be stopped by repolarization. During and after this contraction no depolarizing stimulus could induce a further contraction, even though in some fibres addition of 30 mM-caffeine produced a maximum response which indicated that there was still a substantial amount of calcium in the SR. 8. At pCa 6.4, 25 microM-ryanodine could itself induce a substantial slow contracture in a normally polarized fibre within 30-60 s, after which little or no response could be induced by T-system depolarization. At higher concentrations (25 microM) ryanodine produced a near-maximum contraction in only a few seconds.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2167367
Regulation of axonal and dendritic growth by the extracellular calcium-sensing receptor (CaSR)
Vizard, Thomas N.; O'Keeffe, Gerard W.; Gutierrez, Humberto; Kos, Claudine H.; Riccardi, Daniela; Davies, Alun M.
2009-01-01
The extracellular calcium-sensing receptor (CaSR) monitors the systemic extracellular free ionized calcium level ([Ca2+]o) in organs involved in systemic [Ca2+]o homeostasis. However, the CaSR is also expressed in the nervous system where its role is unknown. Here we find high levels of the CaSR in perinatal mouse sympathetic neurons when their axons are innervating and branching extensively in their targets. Manipulating CaSR function in these neurons by varying [Ca2+]o, using CaSR agonists and antagonists or expressing a dominant-negative CaSR markedly affects neurite growth in vitro Sympathetic neurons lacking the CaSR have smaller neurite arbors in vitro, and sympathetic innervation density is reduced in CaSR-deficient mice in vivo. Hippocampal pyramidal neurons, which also express the CaSR, have smaller dendrites when transfected with dominant-negative CaSR in postnatal organotypic cultures. Our findings reveal a crucial role for the CaSR in regulating the growth of neural processes in the peripheral and central nervous systems. PMID:18223649
Regulation of Bicarbonate Secretion in Marine Fish Intestine by the Calcium-Sensing Receptor.
Gregório, Sílvia F; Fuentes, Juan
2018-04-04
In marine fish, high epithelial intestinal HCO₃ − secretion generates luminal carbonate precipitates of divalent cations that play a key role in water and ion homeostasis. The present study was designed to expose the putative role for calcium and the calcium-sensing receptor (CaSR) in the regulation of HCO₃ − secretion in the intestine of the sea bream ( Sparus aurata L.). Effects on the expression of the CaSR in the intestine were evaluated by qPCR and an increase was observed in the anterior intestine in fed fish compared with unfed fish and with different regions of intestine. CaSR expression reflected intestinal fluid calcium concentration. In addition, anterior intestine tissue was mounted in Ussing chambers to test the putative regulation of HCO₃ − secretion in vitro using the anterior intestine. HCO₃ − secretion was sensitive to varying calcium levels in luminal saline and to calcimimetic compounds known to activate/block the CaSR i.e., R 568 and NPS-2143. Subsequent experiments were performed in intestinal sacs to measure water absorption and the sensitivity of water absorption to varying luminal levels of calcium and calcimimetics were exposed as well. It appears, that CaSR mediates HCO₃ − secretion and water absorption in marine fish as shown by responsiveness to calcium levels and calcimimetic compounds.
SR/ER-mitochondrial local communication: Calcium and ROS
Csordás, György; Hajnóczky, György
2009-01-01
Mitochondria form junctions with the sarco/endoplasmic reticulum (SR/ER), which support signal transduction and biosynthetic pathways and affect organellar distribution. Recently, these junctions have received attention because of their pivotal role in mediating calcium signal propagation to the mitochondria, which is important for both ATP production and mitochondrial cell death. Many of the SR/ER-mitochondrial calcium transporters and signaling proteins are sensitive to redox regulation and are directly exposed to the reactive oxygen species (ROS) produced in the mitochondria and SR/ER. Although ROS has been emerging as a novel signaling entity, the redox signaling of the SR/ER-mitochondrial interface is yet to be elucidated. We describe here possible mechanisms of the mutual interaction between local Ca2+ and ROS signaling in the control of SR/ER-mitochondrial function. PMID:19527680
NASA Astrophysics Data System (ADS)
Cosentino, N. J.; Jordan, T. E.; Derry, L. A.; Morgan, J. P.
2015-12-01
An elevation-dependent relationship of the 87Sr/86Sr ratio of Holocene surface accumulations of sulfate salts is demonstrated for a continental margin hyperarid setting. In the Atacama Desert of northern Chile, gypsum and anhydrite of multiple origins exist widely on superficial materials that originated during the last 10,000 years. An important source of calcium sulfate is from offshore-generated stratocumulus clouds that are advected onto the continent, where they generate fog that transfers water droplets to the ground surface which, upon evaporation, leaves calcium sulfate crystals. Meteorological measurements of the cloud base and top altitudes average ˜400 m and ˜1100 m above sea level (masl), respectively. The seawater ratio of 87Sr/86Sr (0.70917) is distinctively higher than that reported for weathered mean Andean rock (less than 0.70750). Samples of 28 modern surface salt accumulations for locations between 200 and 2950 masl and between ˜19°30' and ˜21°30'S verify that 87Sr/86Sr varies as a function of site altitude. Sites below 1075 masl and above 225 masl display calcium sulfate 87Sr/86Sr of mean value 0.70807 ± 0.00004, while the ratio outside this altitudinal domain is 0.70746 ± 0.00010. Thus, the 87Sr/86Sr ratio of Holocene salt accumulations differentiates two altitudinal domains.
RADIOACTIVE STRONTIUM IN SOIL, CROPS, FOOD-STUFFS AND HUMAN BONES IN THE NETHERLANDS. PART 2
DOE Office of Scientific and Technical Information (OSTI.GOV)
Barendsen, G.W.; Beusker, T.L.J.; Bleichrodt, J.F.
1959-12-01
Results are presented for 1958 and 1959 on Sr/sup 89/ and Sr/sup 90/ analyses on various biological materials. First Sr/sup 89/ and Sr/sup 90/ concentrations are given of soil, grass, and milk obtained from different localities, selected for high and respectively low calcium contents of the soils. Comparison with the results of 1957 shows a relativeiy small increase of Sr/sup 90/ in the soil, about 10%, but much larger increases up to 150% of Sr/sup 90/ concentrations per gram of calcium in milk. The December 1957 milk data reflect levels present in winter fodder while the May 1958 data reflectmore » levels occurring in the pastures. Samples of grass taken in May 1958 contained less Sr/sup 90/ per gram of calcium than grass taken in December 1957. (auth)« less
Letz, Saskia; Haag, Christine; Schulze, Egbert; Frank-Raue, Karin; Raue, Friedhelm; Hofner, Benjamin; Mayr, Bernhard; Schöfl, Christof
2014-01-01
Introduction Activating calcium sensing receptor (CaSR) mutations cause autosomal dominant hypocalcemia (ADH) characterized by low serum calcium, inappropriately low PTH and relative hypercalciuria. Four activating CaSR mutations cause additional renal wasting of sodium, chloride and other salts, a condition called Bartter syndrome (BS) type 5. Until today there is no specific medical treatment for BS type 5 and ADH. We investigated the effects of different allosteric CaSR antagonists (calcilytics) on activating CaSR mutants. Methods All 4 known mutations causing BS type 5 and five ADH mutations were expressed in HEK 293T cells and receptor signalling was studied by measurement of intracellular free calcium in response to extracellular calcium ([Ca2+]o). To investigate the effect of calcilytics, cells were stimulated with 3 mM [Ca2+]o in the presence or absence of NPS-2143, ATF936 or AXT914. Results All BS type 5 and ADH mutants showed enhanced signalling activity to [Ca2+]o with left shifted dose response curves. In contrast to the amino alcohol NPS-2143, which was only partially effective, the quinazolinone calcilytics ATF936 and AXT914 significantly mitigated excessive cytosolic calcium signalling of all BS type 5 and ADH mutants studied. When these mutants were co-expressed with wild-type CaSR to approximate heterozygosity in patients, ATF936 and AXT914 were also effective on all mutants. Conclusion The calcilytics ATF936 and AXT914 are capable of attenuating enhanced cytosolic calcium signalling activity of CaSR mutations causing BS type 5 and ADH. Quinazolinone calcilytics might therefore offer a novel treatment option for patients with activating CaSR mutations. PMID:25506941
Ravikumar, Krishnan; Sadacharan, Dhalapathy; Muthukumar, Sankaran; Sundarram, Thalavai; Periyasamy, Selladurai; Suresh, R V
2017-01-01
Postoperative transient hypocalcemia is sequelae of total thyroidectomy (TT), which is observed in up to 50% of patients. Routine oral calcium and Vitamin D supplementation have been proposed to prevent symptomatic hypocalcemia preventing morbidity and facilitating early discharge. A total of 208 patients with nontoxic benign thyroid disorders, undergoing TT, were serially randomized into four groups: Group A (no supplements were given), Group B (oral calcium - 2 g/day given), Group C (calcium and calcitriol - 1 mcg/day are given), and Group D (calcium, calcitriol, and cholecalciferol - 60,000 IU/day are given). Patients were monitored for clinical and biochemical hypocalcemia (serum calcium, [Sr. Ca] <8 mg/dl), along with serum intact parathormone (Sr. PTH) and magnesium 6 h after surgery and Sr. Ca every 24 h. Intravenous (IV) calcium infusion was started, if any of the above four groups exhibit frank hypocalcemia. Patients are followed up with Sr. Ca and Sr. PTH at 3 and 6 months. All groups were age and sex matched. Hypocalcemia was observed in 72/208 (34.61%) cases. Incidence of hypocalcemia was higher in Group A (57.69%) and Group B (50%) compared to Group C (15.38%) and Group D (15.38%). Hypocalcemia necessitating IV calcium occurred in 31/208 (14.90%) patients. IV calcium requirement exceeded in Group A (26.92%) and Group B (23.07%) compared to Group C (5.76%) and Group D (3.84%). There was no statistical difference in basal levels of serum Vitamin D, calcium, magnesium, intact PTH, and 6 h after surgery. Permanent hypoparathyroidism developed in five patients on follow-up. Routine postoperative supplementation of oral calcium and Vitamin D will help in the prevention of postthyroidectomy transient hypocalcemia significantly. Preoperative Vitamin D levels do not predict postoperative hypocalcemia.
2012-01-01
Background Fruit ripening is a complicated development process affected by a variety of external and internal cues. It is well established that calcium treatment delays fruit ripening and senescence. However, the underlying molecular mechanisms remain unclear. Results Previous studies have shown that calcium/calmodulin-regulated SR/CAMTAs are important for modulation of disease resistance, cold sensitivity and wounding response in vegetative tissues. To study the possible roles of this gene family in fruit development and ripening, we cloned seven SR/CAMTAs, designated as SlSRs, from tomato, a model fruit-bearing crop. All seven genes encode polypeptides with a conserved DNA-binding domain and a calmodulin-binding site. Calmodulin specifically binds to the putative targeting site in a calcium-dependent manner. All SlSRs were highly yet differentially expressed during fruit development and ripening. Most notably, the expression of SlSR2 was scarcely detected at the mature green and breaker stages, two critical stages of fruit development and ripening; and SlSR3L and SlSR4 were expressed exclusively in fruit tissues. During the developmental span from 10 to 50 days post anthesis, the expression profiles of all seven SlSRs were dramatically altered in ripening mutant rin compared with wildtype fruit. By contrast, only minor alterations were noted for ripening mutant nor and Nr fruit. In addition, ethylene treatment of mature green wildtype fruit transiently stimulated expression of all SlSRs within one to two hours. Conclusions This study indicates that SlSR expression is influenced by both the Rin-mediated developmental network and ethylene signaling. The results suggest that calcium signaling is involved in the regulation of fruit development and ripening through calcium/calmodulin/SlSR interactions. PMID:22330838
Decomposition pathways of polytetrafluoroethylene by co-grinding with strontium/calcium oxides.
Qu, Jun; He, Xiaoman; Zhang, Qiwu; Liu, Xinzhong; Saito, Fumio
2017-06-01
Waste polytetrafluoroethylene (PTFE) could be easily decomposed by co-grinding with inorganic additive such as strontium oxide (SrO), strontium peroxide (SrO 2 ) and calcium oxide (CaO) by using a planetary ball mill, in which the fluorine was transformed into nontoxic inorganic fluoride salts such as strontium fluoride (SrF 2 ) or calcium fluoride (CaF 2 ). Depending on the kind of additive as well as the added molar ratio, however, the reaction mechanism of the decomposition was found to change, with different compositions of carbon compounds formed. CO gas, the mixture of strontium carbonate (SrCO 3 ) and carbon, only SrCO 3 were obtained as reaction products respectively with equimolar SrO, excess SrO and excess SrO 2 to the monomer unit CF 2 of PTFE were used. Excess amount of CaO was needed to effectively decompose PTFE because of its lower reactivity compared with strontium oxide, but it promised practical applications due to its low cost.
2012-01-01
The calcium-sensing receptor (CaSR) regulates organismal Ca2+ homeostasis. Dysregulation of CaSR expression or mutations in the CASR gene cause disorders of Ca2+ homeostasis and contribute to the progression or severity of cancers and cardiovascular disease. This brief review highlights recent findings that define the CaSR life cycle, which controls the cellular abundance of CaSR and CaSR signaling. A novel mechanism, termed agonist-driven insertional signaling (ADIS), contributes to the unique hallmarks of CaSR signaling, including the high degree of cooperativity and the lack of functional desensitization. Agonist-mediated activation of plasma membrane-localized CaSR increases the rate of insertion of CaSR at the plasma membrane without altering the constitutive endocytosis rate, thereby acutely increasing the maximum signaling response. Prolonged CaSR signaling requires a large intracellular ADIS-mobilizable pool of CaSR, which is maintained by signaling-mediated increases in biosynthesis. This model provides a rational framework for characterizing the defects caused by CaSR mutations and the altered functional expression of wild-type CaSR in disease states. Mechanistic dissection of ADIS of CaSR should lead to optimized pharmacological approaches to normalize CaSR signaling in disorders of Ca2+ homeostasis. PMID:22745192
Calsequestrin mediates changes in spontaneous calcium release profiles.
Tania, Nessy; Keener, James P
2010-08-07
Calsequestrin (CSQ) is the primary calcium buffer within the sarcoplasmic reticulum (SR) of cardiac cells. It has also been identified as a regulator of Ryanodine receptor (RyR) calcium release channels by serving as a SR luminal sensor. When calsequestrin is free and unbound to calcium, it can bind to RyR and desensitize the channel from cytoplasmic calcium activation. In this paper, we study the role of CSQ as a buffer and RyR luminal sensor using a mechanistic model of RyR-CSQ interaction. By using various asymptotic approximations and mean first exit time calculation, we derive a minimal model of a calcium release unit which includes CSQ dependence. Using this model, we then analyze the effect of changing CSQ expression on the calcium release profile and the rate of spontaneous calcium release. We show that because of its buffering capability, increasing CSQ increases the spark duration and size. However, because of luminal sensing effects, increasing CSQ depresses the basal spark rate and increases the critical SR level for calcium release termination. Finally, we show that with increased bulk cytoplasmic calcium concentration, the CRU model exhibits deterministic oscillations.
Liou, Alice P.; Sei, Yoshitatsu; Zhao, Xilin; Feng, Jianying; Lu, Xinping; Thomas, Craig; Pechhold, Susanne; Raybould, Helen E.
2011-01-01
The extracellular calcium-sensing receptor (CaSR) has recently been recognized as an l-amino acid sensor and has been implicated in mediating cholecystokinin (CCK) secretion in response to aromatic amino acids. We investigated whether direct detection of l-phenylalanine (l-Phe) by CaSR results in CCK secretion in the native I cell. Fluorescence-activated cell sorting of duodenal I cells from CCK-enhanced green fluorescent protein (eGFP) transgenic mice demonstrated CaSR gene expression. Immunostaining of fixed and fresh duodenal tissue sections confirmed CaSR protein expression. Intracellular calcium fluxes were CaSR dependent, stereoselective for l-Phe over d-Phe, and responsive to type II calcimimetic cinacalcet in CCK-eGFP cells. Additionally, CCK secretion by an isolated I cell population was increased by 30 and 62% in response to l-Phe in the presence of physiological (1.26 mM) and superphysiological (2.5 mM) extracellular calcium concentrations, respectively. While the deletion of CaSR from CCK-eGFP cells did not affect basal CCK secretion, the effect of l-Phe or cinacalcet on intracellular calcium flux was lost. In fact, both secretagogues, as well as superphysiological Ca2+, evoked an unexpected 20–30% decrease in CCK secretion compared with basal secretion in CaSR−/− CCK-eGFP cells. CCK secretion in response to KCl or tryptone was unaffected by the absence of CaSR. The present data suggest that CaSR is required for hormone secretion in the specific response to l-Phe by the native I cell, and that a receptor-mediated mechanism may inhibit hormone secretion in the absence of a fully functional CaSR. PMID:21252045
Macías-García, Beatriz; Rocha, Antonio; González-Fernández, Lauro
2016-03-01
Protein tyrosine phosphorylation (PY), a hallmark of sperm capacitation, is inhibited by extracellular calcium in stallion sperm. The objective of this study was to determine the presence and influence of the calcium-sensing receptor (CaSR) in this phenomenon. First, the presence of the CaSR was demonstrated in stallion sperm. We then tested its function in these gametes using its inhibitor NPS2143 or its agonist AC34356. Sperm were capacitated for 4 hr in modified Whitten's medium with 25 mM bicarbonate plus NPS2143 and 2.4 mM calcium or AC34356 alone, followed by analysis of PY. Inhibition of CaSR with NPS2143 prevented the calcium-dependent PY inhibition in a dose-dependent manner (5, 10, and 15 μM) whereas AC34356 (100 μM) inhibited PY similarly to calcium. Stallion sperm motility and viability significantly decreased in presence of 15 μM of NPS2143 whereas only sperm motility decreased with 100 μM of AC34356. CaSR function was also studied in the complete absence of calcium by including 2 mM ethylene glycol tetraacetic acid (EGTA); under these conditions, AC34356 again inhibited PY, but this time induced a significant increase in sperm motility. Inhibition of calmodulin by W-7 did not recover the AC34356-mediated PY inhibition. When stallion sperm were incubated under capacitating conditions (calcium, bicarbonate, plus bovine serum albumin) at elevated pH (7.9 or 8.5) AC34356 did not block PY. These results thus elucidate the effect of extracellular conditions on the regulation of CaSR, and point to its modulatory role on stallion sperm PY, motility, and viability. Mol. Reprod. Dev. 83: 236-245, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Using Strontium Isotopes in Arid Agricultural Soils to Determine a Sink or Source of CO2
NASA Astrophysics Data System (ADS)
Ortiz, A. C.; Jin, L.
2014-12-01
Arid and semi-arid regions of the world are predicted to continue to expand through land degradation and prolonged drought events. Agricultural practices in these drylands degrade soils through elevated salinity, sodicity and alkalinity. Indeed, flood irrigation loads salts onto the soils including carbonate minerals in the form of calcite. Alfalfa and Pecan are salt tolerant and commonly grown in the arid El Paso region, but need irrigation using Rio Grande water with little to no contribution from local ground waters. We hypothesize that the irrigation is loading extra Ca and bicarbonate to soils and anthropogenically enhancing the precipitation of carbonates. We intend to monitor soil CO2 efflux after irrigation, characterize soil minerals, and combine them to isotopic data of soil, irrigation, and drainage waters to link the sources of Ca and C, kinetics of calcite precipitation, to irrigation events. This will include strontium isotopic analysis to determine the source of calcium in the agricultural fields, U-disequilibrium isotopes to estimate the carbonate ages, and CO2 efflux to monitor atmosphere-soil exchange. Carbon dioxide emissions are expected to change during flood irrigation when soils are saturated. After irrigation events, evaporative effects increase Ca and dissolved inorganic carbon concentration in soil waters leading to precipitation of calcite and thus elevated CO2efflux. Preliminary measurements in the pecan field show a marginally significant difference in CO2 fluxes before and after irrigation (p=0.07, t-test). Carbon dioxide emissions are lower during moist conditions (0.6 g m-2hr-1 CO2) than those in dry conditions (1.0 g m-2hr-1 CO2). Future C isotope data are needed to identify the source of extra CO2, biogenic or calcite-precipitation related. A water leachable extraction of alfalfa soils shows 87Sr/86Sr ratios ranged from 0.7101 to 0.7103, indicating Rio Grande river as a dominant calcium source. Further Sr isotopic analysis of sequential extractions from both alfalfa soils (for calcite fraction), pore waters, irrigation waters, and drainage waters will allow us to quantitatively evaluate the source of calcium in calcite therefore, defining if anthropogenic sources of calcium lead to enhanced CO2 production in agricultural fields.
Ravikumar, Krishnan; Sadacharan, Dhalapathy; Muthukumar, Sankaran; Sundarram, Thalavai; Periyasamy, Selladurai; Suresh, R. V.
2017-01-01
Background: Postoperative transient hypocalcemia is sequelae of total thyroidectomy (TT), which is observed in up to 50% of patients. Routine oral calcium and Vitamin D supplementation have been proposed to prevent symptomatic hypocalcemia preventing morbidity and facilitating early discharge. Patients and Methods: A total of 208 patients with nontoxic benign thyroid disorders, undergoing TT, were serially randomized into four groups: Group A (no supplements were given), Group B (oral calcium – 2 g/day given), Group C (calcium and calcitriol – 1 mcg/day are given), and Group D (calcium, calcitriol, and cholecalciferol – 60,000 IU/day are given). Patients were monitored for clinical and biochemical hypocalcemia (serum calcium, [Sr. Ca] <8 mg/dl), along with serum intact parathormone (Sr. PTH) and magnesium 6 h after surgery and Sr. Ca every 24 h. Intravenous (IV) calcium infusion was started, if any of the above four groups exhibit frank hypocalcemia. Patients are followed up with Sr. Ca and Sr. PTH at 3 and 6 months. Results: All groups were age and sex matched. Hypocalcemia was observed in 72/208 (34.61%) cases. Incidence of hypocalcemia was higher in Group A (57.69%) and Group B (50%) compared to Group C (15.38%) and Group D (15.38%). Hypocalcemia necessitating IV calcium occurred in 31/208 (14.90%) patients. IV calcium requirement exceeded in Group A (26.92%) and Group B (23.07%) compared to Group C (5.76%) and Group D (3.84%). There was no statistical difference in basal levels of serum Vitamin D, calcium, magnesium, intact PTH, and 6 h after surgery. Permanent hypoparathyroidism developed in five patients on follow-up. Conclusion: Routine postoperative supplementation of oral calcium and Vitamin D will help in the prevention of postthyroidectomy transient hypocalcemia significantly. Preoperative Vitamin D levels do not predict postoperative hypocalcemia. PMID:28670529
Perni, Stefano; Iyer, V Ramesh; Franzini-Armstrong, Clara
2012-06-01
It is known that cardiac myocytes contain three categories of calcium release units (CRUs) all bearing arrays of RyR2: peripheral couplings, constituted of an association of the junctional SR (jSR) with the plasmalemma; dyads, associations between jSR and T tubules; internal extended junctional jSR (EjSR)/corbular jSR that is not associated with plasmalemma/T tubules. The bird hearts, even if fast beating (e.g., in finch and hummingbird) have no T tubules, despite fiber sizes comparable to those of mammalian ventricle, but are rich in EjSR/corbular SR. The heart of small lizard also lacks T tubule, but it has only peripheral couplings and compensates for lack of internal CRUs by the small diameter of its cells. We have extended previous information on chicken heart to finch and lizard by establishing a spatial relationship between RyR2 clusters in jSR of peripheral couplings and clusters of intra-membrane particles identifiable as voltage sensitive calcium channels (CaV1.2) in the adjacent plasmalemma. This provides the structural basis for initiation of the heart beat in all three species. Further we evaluated the distances separating peripheral couplings from each other and between EjSR/corbular SR sites within the bird muscles in all three hearts. The distances suggest that peripheral coupling sites are most likely to act independently of each other and that a calcium wave-front propagation from one internal CRU site to the other across the level of the Z line, may be marginally successful in the chicken, but certainly very effective in the finch.
Yarova, Polina L.; Stewart, Alecia L.; Sathish, Venkatachalem; Britt, Rodney D; Thompson, Michael A.; Lowe, Alexander P. P.; Freeman, Michelle; Aravamudan, Bharathi; Kita, Hirohito; Brennan, Sarah C.; Schepelmann, Martin; Davies, Thomas; Yung, Sun; Cholisoh, Zakky; Kidd, Emma J.; Ford, William R.; Broadley, Kenneth J.; Rietdorf, Katja; Chang, Wenhan; Khayat, Mohd E. Bin; Ward, Donald T.; Corrigan, Christopher J.; Ward, Jeremy P. T.; Kemp, Paul J.; Pabelick, Christina M.; Prakash, Y. S.; Riccardi, Daniela
2016-01-01
Airway hyperresponsiveness and inflammation are fundamental hallmarks of allergic asthma that are accompanied by increases in certain polycations, such as eosinophil cationic protein. Levels of these cations in body fluids correlate with asthma severity. We show that polycations and elevated extracellular calcium activate the human recombinant and native calcium-sensing receptor (CaSR), leading to intracellular calcium mobilization, cyclic adenosine monophosphate breakdown, and p38 mitogen-activated protein kinase phosphorylation in airway smooth muscle (ASM) cells. These effects can be prevented by CaSR antagonists, termed calcilytics. Moreover, asthmatic patients and allergen-sensitized mice expressed more CaSR in ASMs than did their healthy counterparts. Indeed, polycations induced hyper-reactivity in mouse bronchi, and this effect was prevented by calcilytics and absent in mice with CaSR ablation from ASM. Calcilytics also reduced airway hyperresponsiveness and inflammation in allergen-sensitized mice in vivo. These data show that a functional CaSR is up-regulated in asthmatic ASM and targeted by locally produced polycations to induce hyperresponsiveness and inflammation. Thus, calcilytics may represent effective asthma therapeutics. PMID:25904744
Kaplan, Mehmet Mahsum; Sultana, Nasreen; Benedetti, Ariane; Obermair, Gerald J; Linde, Nina F; Papadopoulos, Symeon; Dayal, Anamika; Grabner, Manfred; Flucher, Bernhard E
2018-06-26
Formation of synapses between motor neurons and muscles is initiated by clustering of acetylcholine receptors (AChRs) in the center of muscle fibers prior to nerve arrival. This AChR patterning is considered to be critically dependent on calcium influx through L-type channels (Ca V 1.1). Using a genetic approach in mice, we demonstrate here that either the L-type calcium currents (LTCCs) or sarcoplasmic reticulum (SR) calcium release is necessary and sufficient to regulate AChR clustering at the onset of neuromuscular junction (NMJ) development. The combined lack of both calcium signals results in loss of AChR patterning and excessive nerve branching. In the absence of SR calcium release, the severity of synapse formation defects inversely correlates with the magnitude of LTCCs. These findings highlight the importance of activity-dependent calcium signaling in early neuromuscular junction formation and indicate that both LTCC and SR calcium release individually support proper innervation of muscle by regulating AChR patterning and motor axon outgrowth. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
Constraints on Ca/Sr as a Proxy for Calcium in Forest Ecosystems
NASA Astrophysics Data System (ADS)
Hoff, C. J.; Hobbie, E. A.; Hallett, R.; Colpaert, J.; Bryce, J. G.
2004-05-01
Calcium is a key plant nutrient and important base cation in ecosystems. Our current efforts to quantify Ca cycling in ecosystems rely on indirect proxies, e.g., Ca/Sr or Sr isotopic systems (1). An important assumption in these applications is that the elemental ratio of calcium to strontium faithfully represents calcium cycling and that little fractionation occurs through biogeochemical and physiological processes. However, several researchers have reported variations in Ca/Sr, e.g. among different tree tissues (2) and during weathering processes (3), raising doubts about the suitability of the proxy. To address the question of reliability, we measured Ca/Sr values in a culture study in which Scots pines were grown at low or high nutrient supply rates (3% per day or 5% per day). Because mycorrhizal fungi are intimately involved in plant nutrient supply, plants were also grown either uncolonized or colonized with one of two different species of mycorrhizal fungi (Suillus luteus and Thelephora terrestris). Our preliminary results indicate that Ca/Sr values differ between high and low nutrient treatments, root and foliage, and mycorrhizal treatments. In individual seedlings, roots have lower Ca/Sr than foliage by absolute factors of 2-5. The magnitude of the effect is apparently determined by a combination of environmental factors including both the nutrient and mycorrhizal treatments. These results indicate that Ca and Sr are partitioned differently between nutrient and mycorrhizal treatments and between plant fractions despite the common nutrient broth and substrate. Thus, Ca/Sr values alone are not reliable tracers of Ca within an ecosystem because of partitioning of Ca and Sr during nutrient transport within the plant-mycorrhizal system. We are presently refining analytical techniques and conducting leachate experiments to improve the quantification of this Ca/Sr fractionation. We are also exploring the use of isotopic tracers to study calcium biogeochemical cycling in forest ecosystems. (1) Blum, J.D., et al. 2002. Nature 417: 729-731. (2) Bailey, S.W., et al. 1996. Water Resources Research 32: 707-719. (3) Vitousek, P.M., et al. 1999. Oecologia 121: 255- 259.
The Calcium-Sensing Receptor and Integrins in Cellular Differentiation and Migration
Tharmalingam, Sujeenthar; Hampson, David R.
2016-01-01
The calcium-sensing receptor (CaSR) is a widely expressed homodimeric G-protein coupled receptor structurally related to the metabotropic glutamate receptors and GPRC6A. In addition to its well characterized role in maintaining calcium homeostasis and regulating parathyroid hormone release, evidence has accumulated linking the CaSR with cellular differentiation and migration, brain development, stem cell engraftment, wound healing, and tumor growth and metastasis. Elevated expression of the CaSR in aggressive metastatic tumors has been suggested as a potential novel prognostic marker for predicting metastasis, especially to bone tissue where extracellular calcium concentrations may be sufficiently high to activate the receptor. Recent evidence supports a model whereby CaSR-mediated activation of integrins promotes cellular migration. Integrins are single transmembrane spanning heterodimeric adhesion receptors that mediate cell migration by binding to extracellular matrix proteins. The CaSR has been shown to form signaling complexes with the integrins to facilitate both the movement and differentiation of cells, such as neurons during normal brain development and tumor cells under pathological circumstances. Thus, CaSR/integrin complexes may function as a universal cell migration or homing complex. Manipulation of this complex may be of potential interest for treating metastatic cancers, and for developmental disorders pertaining to aberrant neuronal migration. PMID:27303307
Strontium biokinetic model for the pregnant woman and fetus: application to Techa River studies.
Shagina, N B; Fell, T P; Tolstykh, E I; Harrison, J D; Degteva, M O
2015-09-01
A biokinetic model for strontium (Sr) for the pregnant woman and fetus (Sr-PWF model) has been developed for use in the quantification of doses from internal radiation exposures following maternal ingestion of Sr radioisotopes before or during pregnancy. The model relates in particular to the population of the Techa River villages exposed to significant amounts of ingested Sr radioisotopes as a result of releases of liquid radioactive wastes from the Mayak plutonium production facility (Russia) in the early 1950s. The biokinetic model for Sr metabolism in the pregnant woman was based on a biokinetic model for the adult female modified to account for changes in mineral metabolism during pregnancy. The model for non-pregnant females of all ages was developed earlier with the use of extensive data on (90)Sr-body measurements in the Techa Riverside residents. To determine changes in model parameter values to take account of changing mineral metabolism during pregnancy, data from longitudinal studies of calcium homeostasis during human pregnancy were analysed and applied. Exchanges between maternal and fetal circulations and retention in fetal skeleton and soft tissues were modelled as adaptations of previously published models, taking account of data on Sr and calcium (Ca) metabolism obtained in Russia (Southern Urals and Moscow) relating to dietary calcium intakes, calcium contents in maternal and fetal skeletons and strontium transfer to the fetus. The model was validated using independent data on (90)Sr in the fetal skeleton from global fallout as well as unique data on (90)Sr-body burden in mothers and their still-born children for Techa River residents. While the Sr-PWF model has been developed specifically for ingestion of Sr isotopes by Techa River residents, it is also more widely applicable to maternal ingestion of Sr radioisotopes at different times before and during pregnancy and different ages of pregnant women in a general population.
Schumacher, M; Lode, A; Helth, A; Gelinsky, M
2013-12-01
In the present study, the in vitro effects of novel strontium-modified calcium phosphate bone cements (SrCPCs), prepared using two different approaches on human-bone-marrow-derived mesenchymal stem cells (hMSCs), were evaluated. Strontium ions, known to stimulate bone formation and therefore already used in systemic osteoporosis therapy, were incorporated into a hydroxyapatite-forming calcium phosphate bone cement via two simple approaches: incorporation of strontium carbonate crystals and substitution of Ca(2+) by Sr(2+) ions during cement setting. All modified cements released 0.03-0.07 mM Sr(2+) under in vitro conditions, concentrations that were shown not to impair the proliferation or osteogenic differentiation of hMSCs. Furthermore, strontium modification led to a reduced medium acidification and Ca(2+) depletion in comparison to the standard calcium phosphate cement. In indirect and direct cell culture experiments with the novel SrCPCs significantly enhanced cell proliferation and differentiation were observed. In conclusion, the SrCPCs described here could be beneficial for the local treatment of defects, especially in the osteoporotic bone. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Maxwell, Joshua T; Blatter, Lothar A
2012-12-01
The widely accepted paradigm for cytosolic Ca(2+) wave propagation postulates a 'fire-diffuse-fire' mechanism where local Ca(2+)-induced Ca(2+) release (CICR) from the sarcoplasmic reticulum (SR) via ryanodine receptor (RyR) Ca(2+) release channels diffuses towards and activates neighbouring release sites, resulting in a propagating Ca(2+) wave. A recent challenge to this paradigm proposed the requirement for an intra-SR 'sensitization' Ca(2+) wave that precedes the cytosolic Ca(2+) wave and primes RyRs from the luminal side to CICR. Here, we tested this hypothesis experimentally with direct simultaneous measurements of cytosolic ([Ca(2+)](i); rhod-2) and intra-SR ([Ca(2+)](SR); fluo-5N) calcium signals during wave propagation in rabbit ventricular myocytes, using high resolution fluorescence confocal imaging. The increase in [Ca(2+)](i) at the wave front preceded depletion of the SR at each point along the calcium wave front, while during this latency period a transient increase of [Ca(2+)](SR) was observed. This transient elevation of [Ca(2+)](SR) could be identified at individual release junctions and depended on the activity of the sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA). Increased SERCA activity (β-adrenergic stimulation with 1 μM isoproterenol (isoprenaline)) decreased the latency period and increased the amplitude of the transient elevation of [Ca(2+)](SR), whereas inhibition of SERCA (3 μM cyclopiazonic acid) had the opposite effect. In conclusion, the data provide experimental evidence that local Ca(2+) uptake by SERCA into the SR facilitates the propagation of cytosolic Ca(2+) waves via luminal sensitization of the RyR, and supports a novel paradigm of a 'fire-diffuse-uptake-fire' mechanism for Ca(2+) wave propagation in cardiac myocytes.
Maxwell, Joshua T; Blatter, Lothar A
2012-01-01
The widely accepted paradigm for cytosolic Ca2+ wave propagation postulates a ‘fire-diffuse-fire’ mechanism where local Ca2+-induced Ca2+ release (CICR) from the sarcoplasmic reticulum (SR) via ryanodine receptor (RyR) Ca2+ release channels diffuses towards and activates neighbouring release sites, resulting in a propagating Ca2+ wave. A recent challenge to this paradigm proposed the requirement for an intra-SR ‘sensitization’ Ca2+ wave that precedes the cytosolic Ca2+ wave and primes RyRs from the luminal side to CICR. Here, we tested this hypothesis experimentally with direct simultaneous measurements of cytosolic ([Ca2+]i; rhod-2) and intra-SR ([Ca2+]SR; fluo-5N) calcium signals during wave propagation in rabbit ventricular myocytes, using high resolution fluorescence confocal imaging. The increase in [Ca2+]i at the wave front preceded depletion of the SR at each point along the calcium wave front, while during this latency period a transient increase of [Ca2+]SR was observed. This transient elevation of [Ca2+]SR could be identified at individual release junctions and depended on the activity of the sarco-endoplasmic reticulum Ca2+-ATPase (SERCA). Increased SERCA activity (β-adrenergic stimulation with 1 μm isoproterenol (isoprenaline)) decreased the latency period and increased the amplitude of the transient elevation of [Ca2+]SR, whereas inhibition of SERCA (3 μm cyclopiazonic acid) had the opposite effect. In conclusion, the data provide experimental evidence that local Ca2+ uptake by SERCA into the SR facilitates the propagation of cytosolic Ca2+ waves via luminal sensitization of the RyR, and supports a novel paradigm of a ‘fire-diffuse-uptake-fire’ mechanism for Ca2+ wave propagation in cardiac myocytes. PMID:22988145
Balghi, Haouaria; Sebille, Stéphane; Constantin, Bruno; Patri, Sylvie; Thoreau, Vincent; Mondin, Ludivine; Mok, Elise; Kitzis, Alain; Raymond, Guy; Cognard, Christian
2006-01-01
We present here evidence for the enhancement of an inositol 1,4,5-trisphosphate (IP3) mediated calcium signaling pathway in myotubes from dystrophin-deficient cell lines (SolC1(−)) as compared to a cell line from the same origin but transfected with mini-dystrophin (SolD(+)). With confocal microscopy, we demonstrated that calcium rise, induced by the perifusion of a solution containing a high potassium concentration, was higher in SolC1(−) than in SolD(+) myotubes. The analysis of amplitude and kinetics of the calcium increase in SolC1(−) and in SolD(+) myotubes during the exposure with SR Ca2+ channel inhibitors (ryanodine and 2-APB) suggested the presence of two mechanisms of SR calcium release: (1) a fast SR calcium release that depended on ryanodine receptors and (2) a slow SR calcium release mediated by IP3 receptors. Detection analyses of mRNAs (reverse transcriptase [RT]-PCR) and proteins (Western blot and immunolocalization) demonstrated the presence of the three known isoforms of IP3 receptors in both SolC1(−) and SolD(+) myotubes. Furthermore, analysis of the kinetics of the rise in calcium revealed that the slow IP3-dependent release may be increased in the SolC1(−) as compared to the SolD(+), suggesting an inhibitory effect of mini-dystrophin in this signaling pathway. Upon incubation with pertussis toxin (PTX), an inhibitory effect similar to that of the IP3R inhibitor (2-APB) was observed on K+-evoked calcium release. This result suggests the involvement of a Gi protein upstream of the IP3 pathway in these stimulation conditions. A hypothetical model is depicted in which both Gi protein and IP3 production could be involved in K+-evoked calcium release as well as a possible interaction with mini-dystrophin. Our findings demonstrate the existence of a potential relationship between mini-dystrophin and SR calcium release as well as a regulatory role of mini-dystrophin on intracellular signaling. PMID:16446505
Bouschet, Tristan; Martin, Stéphane; Kanamarlapudi, Venkateswarlu; Mundell, Stuart; Henley, Jeremy M
2007-08-01
G-protein-coupled receptors (GPCRs) transduce the binding of extracellular stimuli into intracellular signalling cascades that can lead to morphological changes. Here, we demonstrate that stimulation of the calcium-sensing receptor (CaSR), a GPCR that promotes chemotaxis by detecting increases in extracellular calcium, triggers plasma membrane (PM) ruffling via a pathway that involves beta-arrestin 1, Arf nucleotide binding site opener (ARNO), ADP-ribosylating factor 6 (ARF6) and engulfment and cell motility protein (ELMO). Expression of dominant negative beta-arrestin 1 or its knockdown with siRNA impaired the CaSR-induced PM ruffling response. Expression of a catalytically inactive ARNO also reduced CaSR-induced PM ruffling. Furthermore, beta-arrestin 1 co-immunoprecipitated with the CaSR and ARNO under resting conditions. Agonist treatment did not markedly alter beta-arrestin 1 binding to the CaSR or to ARNO but it did elicit the translocation and colocalisation of the CaSR, beta-arrestin 1 and ARNO to membrane protrusions. Furthermore, ARF6 and ELMO, two proteins known to couple ARNO to the cytoskeleton, were required for CaSR-dependent morphological changes and translocated to the PM ruffles. These data suggest that cells ruffle upon CaSR stimulation via a mechanism that involves translocation of beta-arrestin 1 pre-assembled with the CaSR or ARNO, and that ELMO plays an essential role in this CaSR-signalling-induced cytoskeletal reorganisation.
Peterlik, Meinrad; Kállay, Enikoe; Cross, Heide S.
2013-01-01
Through a systematic search in Pubmed for literature, on links between calcium malnutrition and risk of chronic diseases, we found the highest degree of evidence for osteoporosis, colorectal and breast cancer, as well as for hypertension, as the only major cardiovascular risk factor. Low calcium intake apparently has some impact also on cardiovascular events and disease outcome. Calcium malnutrition can causally be related to low activity of the extracellular calcium-sensing receptor (CaSR). This member of the family of 7-TM G-protein coupled receptors allows extracellular Ca2+ to function as a “first messenger” for various intracellular signaling cascades. Evidence demonstrates that Ca2+/CaSR signaling in functional linkage with vitamin D receptor (VDR)-activated pathways (i) promotes osteoblast differentiation and formation of mineralized bone; (ii) targets downstream effectors of the canonical and non-canonical Wnt pathway to inhibit proliferation and induce differentiation of colorectal cancer cells; (iii) evokes Ca2+ influx into breast cancer cells, thereby activating pro-apoptotic intracellular signaling. Furthermore, Ca2+/CaSR signaling opens Ca2+-sensitive K+ conductance channels in vascular endothelial cells, and also participates in IP3-dependent regulation of cytoplasmic Ca2+, the key intermediate of cardiomyocyte functions. Consequently, impairment of Ca2+/CaSR signaling may contribute to inadequate bone formation, tumor progression, hypertension, vascular calcification and, probably, cardiovascular disease. PMID:23340319
Choi, Keun Hee; Shin, Choong Ho; Yang, Sei Won; Cheong, Hae Il
2015-04-01
The calcium sensing receptor (CaSR) plays an important role in calcium homeostasis. Activating mutations of CaSR cause autosomal dominant hypocalcemia by affecting parathyroid hormone secretion in parathyroid gland and calcium resorption in kidney. They can also cause a type 5 Bartter syndrome by inhibiting the apical potassium channel in the thick ascending limb of the loop of Henle in the kidney. This study presents a patient who had autosomal dominant hypocalcemia with Bartter syndrome due to an activating mutation Y829C in the transmembrane domain of the CaSR. Symptoms of hypocalcemia occurred 12 days after birth and medication was started immediately. Medullary nephrocalcinosis and basal ganglia calcification were found at 7 years old and at 17 years old. Three hypercalcemic episodes occurred, one at 14 years old and two at 17 years old. The Bartter syndrome was not severe while the serum calcium concentration was controlled, but during hypercalcemic periods, the symptoms of Bartter syndrome were aggravated.
Choi, Keun Hee; Yang, Sei Won; Cheong, Hae Il
2015-01-01
The calcium sensing receptor (CaSR) plays an important role in calcium homeostasis. Activating mutations of CaSR cause autosomal dominant hypocalcemia by affecting parathyroid hormone secretion in parathyroid gland and calcium resorption in kidney. They can also cause a type 5 Bartter syndrome by inhibiting the apical potassium channel in the thick ascending limb of the loop of Henle in the kidney. This study presents a patient who had autosomal dominant hypocalcemia with Bartter syndrome due to an activating mutation Y829C in the transmembrane domain of the CaSR. Symptoms of hypocalcemia occurred 12 days after birth and medication was started immediately. Medullary nephrocalcinosis and basal ganglia calcification were found at 7 years old and at 17 years old. Three hypercalcemic episodes occurred, one at 14 years old and two at 17 years old. The Bartter syndrome was not severe while the serum calcium concentration was controlled, but during hypercalcemic periods, the symptoms of Bartter syndrome were aggravated. PMID:25932037
Gorvin, Caroline M; Babinsky, Valerie N; Malinauskas, Tomas; Nissen, Peter H; Schou, Anders J; Hanyaloglu, Aylin C; Siebold, Christian; Jones, E Yvonne; Hannan, Fadil M; Thakker, Rajesh V
2018-02-20
The calcium-sensing receptor (CaSR) is a G protein-coupled receptor (GPCR) that signals through G q/11 and G i/o to stimulate cytosolic calcium (Ca 2+ i ) and mitogen-activated protein kinase (MAPK) signaling to control extracellular calcium homeostasis. Studies of loss- and gain-of-function CASR mutations, which cause familial hypocalciuric hypercalcemia type 1 (FHH1) and autosomal dominant hypocalcemia type 1 (ADH1), respectively, have revealed that the CaSR signals in a biased manner. Thus, some mutations associated with FHH1 lead to signaling predominantly through the MAPK pathway, whereas mutations associated with ADH1 preferentially enhance Ca 2+ i responses. We report a previously unidentified ADH1-associated R680G CaSR mutation, which led to the identification of a CaSR structural motif that mediates biased signaling. Expressing CaSR R680G in HEK 293 cells showed that this mutation increased MAPK signaling without altering Ca 2+ i responses. Moreover, this gain of function in MAPK activity occurred independently of G q/11 and G i/o and was mediated instead by a noncanonical pathway involving β-arrestin proteins. Homology modeling and mutagenesis studies showed that the R680G CaSR mutation selectively enhanced β-arrestin signaling by disrupting a salt bridge formed between Arg 680 and Glu 767 , which are located in CaSR transmembrane domain 3 and extracellular loop 2, respectively. Thus, our results demonstrate CaSR signaling through β-arrestin and the importance of the Arg 680 -Glu 767 salt bridge in mediating signaling bias. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Schoutteten, M K; Bravenboer, B; Seneca, S; Stouffs, K; Velkeniers, B
2017-07-01
Regulation of calcium is mediated by parathyroid hormone (PTH) and 1.25-dihydroxyvitamine D3. The calcium-sensing receptor (CaSR) regulates PTH release by a negative feedback system. Gain-of-function mutations in the CaSR gene reset the calcium-PTH axis, leading to hypocalcaemia. We analysed a family with hypocalcaemia. The proband was a 47-year-old man (index, patient I1), who presented with paraesthesias in both limbs. He has two sons (patient II1 a nd I I2). The probands' lab results showed: serum calcium of 1.95 mmol/l, albumin 41 g/l, phosphate 0.81 mmol/l and PTH 6.6 ng/l (normal 15-65 ng/l). Based on this analysis, we suspected a hereditary form of hypocalcaemia and performed genetic testing by polymerase chain reaction and Sanger sequencing of the coding regions and intron boundaries of the CaSR gene. Genetic analysis revealed a new heterozygous mutation: c.2195A>G, p.(Asn732Ser) in exon 7. The lab results of patient II1 showed: serum calcium of 1.93 mmol/l, phosphate 1.31 mmol/l, albumin 41 g/l, and PTH 24.3 ng/l. His genotype revealed the same activating mutation and, like his father, he also lost his scalp hair at an early adolescent age. Patient II2 is asymptomatic, and has neither biochemical abnormalities, nor the familial CaSR gene mutation. He still has all his scalp hair. 1) The c.2195A>G, p.(Asn732Ser) mutation in exon 7 of the CaSR gene leads to hypocalcaemia, and has not been reported before in the medical literature. 2) Possibly, this mutation is linked to premature baldness.
Involvement of the Calcium-sensing Receptor in Human Taste Perception
Ohsu, Takeaki; Amino, Yusuke; Nagasaki, Hiroaki; Yamanaka, Tomohiko; Takeshita, Sen; Hatanaka, Toshihiro; Maruyama, Yutaka; Miyamura, Naohiro; Eto, Yuzuru
2010-01-01
By human sensory analyses, we found that various extracellular calcium-sensing receptor (CaSR) agonists enhance sweet, salty, and umami tastes, although they have no taste themselves. These characteristics are known as “kokumi taste” and often appear in traditional Japanese cuisine. Although GSH is a typical kokumi taste substance (taste enhancer), its mode of action is poorly understood. Here, we demonstrate how the kokumi taste is enhanced by the CaSR, a close relative of the class C G-protein-coupled receptors T1R1, T1R2, and T1R3 (sweet and umami receptors). We identified a large number of CaSR agonist γ-glutamyl peptides, including GSH (γ-Glu-Cys-Gly) and γ-Glu-Val-Gly, and showed that these peptides elicit the kokumi taste. Further analyses revealed that some known CaSR agonists such as Ca2+, protamine, polylysine, l-histidine, and cinacalcet (a calcium-mimetic drug) also elicit the kokumi taste and that the CaSR-specific antagonist, NPS-2143, significantly suppresses the kokumi taste. This is the first report indicating a distinct function of the CaSR in human taste perception. PMID:19892707
Reich, Christopher D.; Kuffner, Ilsa B.; Hickey, T. Don; Morrison, Jennifer M.; Flannery, Jennifer A.
2013-01-01
Strontium-to-calcium ratios (Sr/Ca) were measured on the skeletal matrix of a core sample from a colony of the massive coral Siderastrea siderea collected in Coral Bay, St. John, U.S. Virgin Islands. Strontium and calcium are incorporated into the coral skeleton during the precipitation of aragonite by the coral polyps and their ratio is highly temperature dependent. The robustness of this temperature dependence makes Sr/Ca a reliable proxy for sea surface temperature (SST). Details presented from the St. John S. siderea core indicate that terrestrial inputs of sediment and freshwater can disrupt the chemical balance and subsequently complicate the utility of Sr/Ca in reconstructing historical SST. An approximately 44-year-long record of Sr/Ca shows that an annual SST signal is recorded but with an increasing Sr/Ca trend from 1980 to present, which is likely the result of runoff from the mountainous terrain of St. John. The overwhelming influence of the terrestrial fingerprint on local seawater chemistry makes utilizing Sr/Ca as a SST proxy in nearshore environments very difficult.
Weber, P.K.; Bacon, C.R.; Hutcheon, I.D.; Ingram, B.L.; Wooden, J.L.
2005-01-01
The ion microprobe has the capability to generate high resolution, high precision isotopic measurements, but analysis of the isotopic composition of strontium, as measured by the 87Sr/ 86Sr ratio, has been hindered by isobaric interferences. Here we report the first high precision measurements of 87Sr/ 86Sr by ion microprobe in calcium carbonate samples with moderate Sr concentrations. We use the high mass resolving power (7000 to 9000 M.R.P.) of the SHRIMP-RG ion microprobe in combination with its high transmission to reduce the number of interfering species while maintaining sufficiently high count rates for precise isotopic measurements. The isobaric interferences are characterized by peak modeling and repeated analyses of standards. We demonstrate that by sample-standard bracketing, 87Sr/86Sr ratios can be measured in inorganic and biogenic carbonates with Sr concentrations between 400 and 1500 ppm with ???2??? external precision (2??) for a single analysis, and subpermil external precision with repeated analyses. Explicit correction for isobaric interferences (peak-stripping) is found to be less accurate and precise than sample-standard bracketing. Spatial resolution is ???25 ??m laterally and 2 ??m deep for a single analysis, consuming on the order of 2 ng of material. The method is tested on otoliths from salmon to demonstrate its accuracy and utility. In these growth-banded aragonitic structures, one-week temporal resolution can be achieved. The analytical method should be applicable to other calcium carbonate samples with similar Sr concentrations. Copyright ?? 2005 Elsevier Ltd.
Chu, Yingying; Wang, Rong; Chen, Mengjun
2015-01-01
¹³⁷Cs⁺/⁹⁰Sr²⁺-containing radioactive wastewater is one of the most important problems that the world has been facing with. A by-product, activated porous calcium silicate, is generated at high levels by the pre-desiliconizing and soda-lime-sintering processes for producing Al₂O₃from high-alumina fly ash. In order to examine if this by-product could be used as an absorbent for removal of ¹³⁷Cs⁺/⁹⁰Sr²⁺ from radioactive wastewater, various parameters, such as pH, adsorbent dose, contact time, and initial concentration, were discussed. Results indicated that the equilibrium reached in about 2 hr. Activated porous calcium silicate was highly pH sensitive and able to remove Cs(+)/Sr²⁺ in a near-neutral environment. The adsorption equilibrium was best described by Freundlich isotherm equations, and the adsorption of Cs⁺/Sr²⁺ was a physical process. The adsorption kinetic data could be better fitted by the pseudo-second-order model, and the adsorption was controlled by multidiffusion. Current study showed that activated porous calcium silicate has a good adsorption of Cs⁺/Sr²⁺ for their removal. However, other characteristics, such as selectivity because of coexisting cations, elution and regeneration, thermal stability, and acid resistance, should be discussed carefully before using it in an actual field.
Sarcoplasmic Reticulum Calcium Release Channels in Ventricles of Older Adult Hamsters
ERIC Educational Resources Information Center
Nicholl, Peter A.; Howlett, Susan E.
2006-01-01
Whether the density of sarcoplasmic reticulum (SR) calcium release channels/ryanodine receptors in the heart declines with age is not clear. We investigated age-related changes in the density of [3H]-ryanodine receptors in crude ventricular homogenates, which contained all ligand binding sites in heart and in isolated junctional SR membranes.…
NASA Astrophysics Data System (ADS)
Yang, Shih-Ping; Lee, Tzer-Min; Lui, Truan-Sheng
2015-08-01
An implant requires a suitable surface to trigger osteointegration. The surface characteristics and chemical composition are important factors in this process. Plasma spraying and micro-arc oxidation can be used to fabricate rough and porous structures for medical applications. Strontium (Sr) has been shown to prevent osteoporosis in vitro and in vivo. However, few scientists have evaluated the biological response of Sr-containing coatings on different surface treatments. In this study, a sand-blasted (SB) surface (as the control), plasma-sprayed hydroxyapatite (HA) and Sr-substituted HA coatings (HAPS and SrHAPS, respectively), calcium phosphate and Sr-containing calcium phosphate micro-arc oxidation surface (CPM and SrCPM, respectively) were analyzed in terms of human osteoblastic cell (MG63) response. Sr was confirmed to be incorporated into the surface. SrHAPS and SrCPM specimens had higher cell responses than those of the HAPS and CPM groups, respectively. The cells cultured on SrCPM and SrHAPS specimens exhibited high proliferation and differentiation. However, CPM and SrCPM specimens stimulated more ECM-like structures than other specimens. The results show that Sr-containing coatings have good characteristics that enhance cell response. The SrCPM coating is a suitable implant surface treatment for clinical applications.
Lamboley, C R; Murphy, R M; McKenna, M J; Lamb, G D
2014-03-15
The Ca(2+) uptake properties of the sarcoplasmic reticulum (SR) were compared between type I and type II fibres of vastus lateralis muscle of young healthy adults. Individual mechanically skinned muscle fibres were exposed to solutions with the free [Ca(2+)] heavily buffered in the pCa range (-log10[Ca(2+)]) 7.3-6.0 for set times and the amount of net SR Ca(2+) accumulation determined from the force response elicited upon emptying the SR of all Ca(2+). Western blotting was used to determine fibre type and the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) isoform present in every fibre examined. Type I fibres contained only SERCA2 and displayed half-maximal Ca(2+) uptake rate at ∼pCa 6.8, whereas type II fibres contained only SERCA1 and displayed half-maximal Ca(2+) uptake rate at ∼pCa 6.6. Maximal Ca(2+) uptake rate was ∼0.18 and ∼0.21 mmol Ca(2+) (l fibre)(-1) s(-1) in type I and type II fibres, respectively, in good accord with previously measured SR ATPase activity. Increasing free [Mg(2+)] from 1 to 3 mM had no significant effect on the net Ca(2+) uptake rate at pCa 6.0, indicating that there was little or no calcium-induced calcium release occurring through the Ca(2+) release channels during uptake in either fibre type. Ca(2+) leakage from the SR at pCa 8.5, which is thought to occur at least in part through the SERCA, was ∼2-fold lower in type II fibres than in type I fibres, and was little affected by the presence of ADP, in marked contrast to the larger SR Ca(2+) leak observed in rat muscle fibres under the same conditions. The higher affinity of Ca(2+) uptake in the type I human fibres can account for the higher relative level of SR Ca(2+) loading observed in type I compared to type II fibres, and the SR Ca(2+) leakage characteristics of the human fibres suggest that the SERCAs are regulated differently from those in rat and contribute comparatively less to resting metabolic rate.
Dong, Bingzi; Endo, Itsuro; Ohnishi, Yukiyo; Kondo, Takeshi; Hasegawa, Tomoka; Amizuka, Norio; Kiyonari, Hiroshi; Shioi, Go; Abe, Masahiro; Fukumoto, Seiji; Matsumoto, Toshio
2015-11-01
Activating mutations of calcium-sensing receptor (CaSR) cause autosomal dominant hypocalcemia (ADH). ADH patients develop hypocalcemia, hyperphosphatemia, and hypercalciuria, similar to the clinical features of hypoparathyroidism. The current treatment of ADH is similar to the other forms of hypoparathyroidism, using active vitamin D3 or parathyroid hormone (PTH). However, these treatments aggravate hypercalciuria and renal calcification. Thus, new therapeutic strategies for ADH are needed. Calcilytics are allosteric antagonists of CaSR, and may be effective for the treatment of ADH caused by activating mutations of CaSR. In order to examine the effect of calcilytic JTT-305/MK-5442 on CaSR harboring activating mutations in the extracellular and transmembrane domains in vitro, we first transfected a mutated CaSR gene into HEK cells. JTT-305/MK-5442 suppressed the hypersensitivity to extracellular Ca(2+) of HEK cells transfected with the CaSR gene with activating mutations in the extracellular and transmembrane domains. We then selected two activating mutations locating in the extracellular (C129S) and transmembrane (A843E) domains, and generated two strains of CaSR knock-in mice to build an ADH mouse model. Both mutant mice mimicked almost all the clinical features of human ADH. JTT-305/MK-5442 treatment in vivo increased urinary cAMP excretion, improved serum and urinary calcium and phosphate levels by stimulating endogenous PTH secretion, and prevented renal calcification. In contrast, PTH(1-34) treatment normalized serum calcium and phosphate but could not reduce hypercalciuria or renal calcification. CaSR knock-in mice exhibited low bone turnover due to the deficiency of PTH, and JTT-305/MK-5442 as well as PTH(1-34) increased bone turnover and bone mineral density (BMD) in these mice. These results demonstrate that calcilytics can reverse almost all the phenotypes of ADH including hypercalciuria and renal calcification, and suggest that calcilytics can become a novel therapeutic agent for ADH. © 2015 American Society for Bone and Mineral Research.
Tyler Miller, R
2013-06-01
Through regulation of excretion, the kidney shares responsibility for the metabolic balance of calcium (Ca(2+)) with several other tissues including the GI tract and bone. The balances of Ca(2+) and phosphate (PO4), magnesium (Mg(2+)), sodium (Na(+)), potassium (K(+)), chloride (Cl(-)), and water (H2O) are linked via regulatory systems with overlapping effects and are also controlled by systems specific to each of them. Cloning of the calcium-sensing receptor (CaSR) along with the recognition that mutations in the CaSR gene are responsible for two familial syndromes characterized by abnormalities in the regulation of PTH secretion and Ca(2+) metabolism (Familial Hypocalciuric Hypercalcemia, FHH, and Autosomal Dominant Hypocalcemia, ADH) made it clear that extracellular Ca(2+) (Ca(2+)o) participates in its own regulation via a specific, receptor-mediated mechanism. Demonstration that the CaSR is expressed in the kidney as well as the parathyroid glands combined with more complete characterizations of FHH and ADH established that the effects of elevated Ca(2+) on the kidney (wasting of Na(+), K(+), Cl(-), Ca(2+), Mg(2+) and H2O) are attributable to activation of the CaSR. The advent of positive and negative allosteric modulators of the CaSR along with mouse models with global or tissue-selective deletion of the CaSR in the kidney have allowed a better understanding of the functions of the CaSR in various nephron segments. The biology of the CaSR is more complicated than originally thought and difficult to define precisely owing to the limitations of reagents such as anti-CaSR antibodies and the difficulties inherent in separating direct effects of Ca(2+) on the kidney mediated by the CaSR from associated CaSR-induced changes in PTH. Nevertheless, renal CaSRs have nephron-specific effects that contribute to regulating Ca(2+) in the circulation and urine in a manner that assures a narrow range of Ca(2+)o in the blood and avoids excessively high concentrations of Ca(2+) in the urine. Published by Elsevier Ltd.
Relationship between serum calcium and CA 19-9 levels in colorectal cancer
Fuszek, Peter; Lakatos, Peter; Tabak, Adam; Papp, Janos; Nagy, Zsolt; Takacs, Istvan; Horvath, Henrik Csaba; Lakatos, Peter Laszlo; Speer, Gabor
2004-01-01
AIM: To examine the calcium metabolism of colorectal cancer (CRC) in patients with colorectal cancer and control patients. METHODS: Seventy newly diagnosed CRC patients were included. The healthy control group was age and gender matched (n = 32). Particular attention was devoted to the relationship between serum calcium of patients, and levels of AFP, CEA, carbohydrate antigen 19-9 (CA 19-9) (that could be considered as prognostic factors). Furthermore, the Ca-sensing receptor (CaSR) gene A986S polymorphism was investigated in these patients, as well as the relationship between different CaSR genotypes and the data stated above. RESULTS: A lower level of ionized calcium (also corrected for albumin) was found in the serum of CRC patients with normal 25 (OH) vitamin D levels. The ionized calcium concentration was inversely correlated with the serum level of CA 19-9. There was no difference in the distribution of CaSR genotypes, between CRC patients and general population. The genotypes did not correlate with other data examined. CONCLUSION: Based on these results, lower levels of serum calcium might be a pathogenic and prognostic factor in colorectal cancer. PMID:15222030
Synthesis of highly phase pure (Bi, Pb)-Sr-Ca-Cu-O superconductor
Dorris, Stephen E.; Poeppel, Roger B.; Prorok, Barton C.; Lanagan, Michael T.; Maroni, Victor A.
1994-01-01
An article and method of manufacture of (Bi,Pb)-Sr-Ca-Cu-O superconductor. The superconductor is manufactured by preparing a first powdered mixture of bismuth oxide, lead oxide, strontium carbonate, calcium carbonate and copper oxide. A second powdered mixture is then prepared of strontium carbonate, calcium carbonate and copper oxide. The mixtures are calcined separately with the two mixtures then combined. The resulting combined mixture is then subjected to a powder in tube deformation and thermal processing to produce a substantially phase pure (Bi,Pb)-Sr-Ca-Cu-O superconductor.
Yang, Tianbao; Peng, Hui; Whitaker, Bruce D; Jurick, Wayne M
2013-07-01
Calcium has been shown to enhance stress tolerance, maintain firmness and reduce decay in fruits. Previously we reported that seven tomato SlSRs encode calcium/calmodulin-regulated proteins, and that their expressions are developmentally regulated during fruit development and ripening, and are also responsive to ethylene. To study their expressions in response to stresses encountered during postharvest handling, tomato fruit at the mature-green stage was subjected to chilling and wounding injuries, infected with Botrytis cinerea and treated with salicylic acid or methyl jasmonate. Gene expression studies revealed that the seven SlSRs differentially respond to different stress signals. SlSR2 was the only gene upregulated by all the treatments. SlSR4 acted as a late pathogen-induced gene; it was upregulated by salicylic acid and methyl jasmonate, but downregulated by cold treatment. SlSR3L was cold- and wound-responsive and was also induced by salicylic acid. SlSR1 and SlSR1L were repressed by cold, wounding and pathogen infection, but were upregulated by salicylic acid and methyl jasmonate. Overall, results of these expression studies indicate that individual SlSRs have distinct roles in responses to the specific stress signals, and SlSRs may act as a coordinator(s) connecting calcium-mediated signaling with other stress signal transduction pathways during fruit ripening and storage. © 2013 Scandinavian Plant Physiology Society.
Calcium-sensing receptor (CaSR): pharmacological properties and signaling pathways.
Conigrave, Arthur D; Ward, Donald T
2013-06-01
In this article we consider the mechanisms by which the calcium-sensing receptor (CaSR) induces its cellular responses via the control (activation or inhibition) of signaling pathways. We consider key features of CaSR-mediated signaling including its control of the heterotrimeric G-proteins Gq/11, Gi/o and G12/13 and the downstream consequences recognizing that very few CaSR-mediated cell phenomena have been fully described. We also consider the manner in which the CaSR contributes to the formation of specific signaling scaffolds via peptide recognition sequences in its intracellular C-terminal along with the origins of its high level of cooperativity, particularly for Ca(2+)o, and its remarkable resistance to desensitization. We also consider the nature of the mechanisms by which the CaSR controls oscillatory and sustained Ca(2+)i mobilizing responses and inhibits or elevates cyclic adenosine monophosphate (cAMP) levels dependent on the cellular and signaling context. Finally, we consider the diversity of the receptor's ligands, ligand binding sites and broader compartment-dependent physiological roles leading to the identification of pronounced ligand-biased signaling for agonists including Sr(2+) and modulators including l-amino acids and the clinically effective calcimimetic cinacalcet. We note the implications of these findings for the development of new designer drugs that might target the CaSR in pathophysiological contexts beyond those established for the treatment of disorders of calcium metabolism. Copyright © 2013 Elsevier Ltd. All rights reserved.
Synthesis of highly phase pure (Bi, Pb)-Sr-Ca-Cu-O superconductor
Dorris, S.E.; Poeppel, R.B.; Prorok, B.C.; Lanagan, M.T.; Maroni, V.A.
1994-10-11
An article and method of manufacture of (Bi,Pb)-Sr-Ca-Cu-O superconductor are disclosed. The superconductor is manufactured by preparing a first powdered mixture of bismuth oxide, lead oxide, strontium carbonate, calcium carbonate and copper oxide. A second powdered mixture is then prepared of strontium carbonate, calcium carbonate and copper oxide. The mixtures are calcined separately with the two mixtures then combined. The resulting combined mixture is then subjected to a powder in tube deformation and thermal processing to produce a substantially phase pure (Bi,Pb)-Sr-Ca-Cu-O superconductor. 5 figs.
ATP utilization for calcium uptake and force production in skinned muscle fibres of Xenopus laevis.
Stienen, G J; Zaremba, R; Elzinga, G
1995-01-01
1. A method has been developed to discriminate between the rate of ATP hydrolysis associated with calcium uptake into the sarcoplasmic reticulum (SR) and force development of the contractile apparatus in mechanically or saponin-skinned skeletal muscle fibres. The rate of ATP hydrolysis was determined in fibres of different types from the iliofibularis muscle of Xenopus laevis by enzymatic coupling of ATP re-synthesis to the oxidation of NADH. 2. The ATPase activity was determined before and after exposure of the preparations for 30 min to a solution containing 0.5% Triton X-100, which effectively abolishes the SR ATPase activity. The fibres were activated in a solution containing 5 mM caffeine to ensure that calcium uptake into the SR was maximal. 3. At saturating Ca2+ concentrations the actomyosin (AM) and SR ATPase activities in fast-twitch fibres, at 4.3 degrees C, amounted to 1.52 +/- 0.07 and 0.58 +/- 0.10 mumol s-1 (g dry wt)-1, respectively (means +/- S.E.M.; n = 25). The SR ATPase activity was 25% of the total ATPase activity. At submaximal calcium concentrations the AM ATPase activity varied in proportion to the isometric force. 4. The calcium sensitivity of the SR ATPase was larger than that of the AM ATPase and its dependence on [Ca2+] was less steep. The AM ATPase activity was half-maximal at a pCa of 6.11 (pCa = -log [Ca2+]) whereas the SR ATPase activity was half-maximal at a pCa of 6.62. 5. In Triton X-100-treated fibres, at different 2,3-butanedione monoxime (BDM) concentrations, the AM ATPase activity and isometric force varied proportionally. The SR ATPase activity determined by extrapolation of the total ATPase activity in mechanically skinned or saponin-treated fibres to zero force, was independent of the BDM concentration in the range studied (0-20 mM). The values obtained for the SR ATPase activity in this way were similar to those obtained with Triton X-100 treatment. 6. The AM ATPase activity in slow-twitch fibres amounted to 0.74 +/- 0.13 mumol s-1 (g dry wt)-1, i.e. about a factor of two smaller than in fast-twitch fibres. The SR ATPase activity amounted to 0.47 +/- 0.07 mumol s-1 (g dry wt)-1, i.e. rather similar to the value in fast-twitch fibres. The proportion of the total ATPase activity that was due to SR ATPase (40%) was larger than in fast-twitch fibres. 7. The temperature dependence of the AM and SR ATPase activities in fast-twitch fibres differed. In the temperature range 5-10 degrees C, the relative changes in AM and SR ATPase activities for a 10 degrees C temperature change (Q10) were 3.9 +/- 0.3 and 7.2 +/- 1.5, respectively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7730976
Nivala, Michael; Song, Zhen; Weiss, James N.; Qu, Zhilin
2015-01-01
In heart failure (HF), T-tubule (TT) disruption contributes to dyssynchronous calcium (Ca) release and impaired contraction, but its role in arrhythmogenesis remains unclear. In this study, we investigate the mechanisms of TT disruption and other HF remodeling factors on Ca alternans in ventricular myocytes using computer modeling. A ventricular myocyte model with detailed spatiotemporal Ca cycling modeled by a coupled Ca release unit (CRU) network was used, in which the L-type Ca channels and the ryanodine receptor (RyR) channels were simulated by random Markov transitions. TT disruption, which removes the L-type Ca channels from the associated CRUs, results in “orphaned” RyR clusters and thus provides increased opportunity for spark-induced Ca sparks to occur. This effect combined with other HF remodeling factors promoted alternans by two distinct mechanisms: 1) for normal sarco-endoplasmic reticulum Ca ATPase (SERCA) activity, alternans was caused by both CRU refractoriness and coupling. The increased opportunity for spark-induced sparks by TT disruption combined with the enhanced CRU coupling by Ca elevation in the presence or absence of increased RyR leakiness facilitated spark synchronization on alternate beats to promote Ca alternans; 2) for down-regulated SERCA, alternans was caused by the sarcoplasmic reticulum (SR) Ca load-dependent mechanism, independent of CRU refractoriness. TT disruption and increased RyR leakiness shifted and steepened the SR Ca release-load relationship, which combines with down-regulated SERCA to promote Ca alternans. In conclusion, the mechanisms of Ca alternans for normal and down-regulated SERCA are different, and TT disruption promotes Ca alternans by both mechanisms, which may contribute to alternans at different stages of HF. PMID:25450613
Nivala, Michael; Song, Zhen; Weiss, James N; Qu, Zhilin
2015-02-01
In heart failure (HF), T-tubule (TT) disruption contributes to dyssynchronous calcium (Ca) release and impaired contraction, but its role in arrhythmogenesis remains unclear. In this study, we investigate the effects of TT disruption and other HF remodeling factors on Ca alternans in ventricular myocytes using computer modeling. A ventricular myocyte model with detailed spatiotemporal Ca cycling modeled by a coupled Ca release unit (CRU) network was used, in which the L-type Ca channels and the ryanodine receptor (RyR) channels were simulated by random Markov transitions. TT disruption, which removes the L-type Ca channels from the associated CRUs, results in "orphaned" RyR clusters and thus provides increased opportunity for spark-induced Ca sparks to occur. This effect combined with other HF remodeling factors promoted alternans by two distinct mechanisms: 1) for normal sarco-endoplasmic reticulum Ca ATPase (SERCA) activity, alternans was caused by both CRU refractoriness and coupling. The increased opportunity for spark-induced sparks by TT disruption combined with the enhanced CRU coupling by Ca elevation in the presence or absence of increased RyR leakiness facilitated spark synchronization on alternate beats to promote Ca alternans; 2) for down-regulated SERCA, alternans was caused by the sarcoplasmic reticulum (SR) Ca load-dependent mechanism, independent of CRU refractoriness. TT disruption and increased RyR leakiness shifted and steepened the SR Ca release-load relationship, which combines with down-regulated SERCA to promote Ca alternans. In conclusion, the mechanisms of Ca alternans for normal and down-regulated SERCA are different, and TT disruption promotes Ca alternans by both mechanisms, which may contribute to alternans at different stages of HF. Copyright © 2014 Elsevier Ltd. All rights reserved.
The Calcium-Sensing Receptor in Health and Disease.
Díaz-Soto, G; Rocher, A; García-Rodríguez, C; Núñez, L; Villalobos, C
2016-01-01
The extracellular calcium-sensing receptor (CaSR) is a unique G protein-coupled receptor (GPCR) activated by extracellular Ca 2+ and by other physiological cations including Mg 2+ , amino acids, and polyamines. CaSR is the most important master controller of the extracellular Ca 2+ homeostatic system being expressed at high levels in the parathyroid gland, kidney, gut and bone, where it regulates parathyroid hormone (PTH) secretion, vitamin D synthesis, and Ca 2+ absorption and resorption, respectively. Gain and loss of function mutations in the CaSR are responsible for severe disturbances in extracellular Ca 2+ metabolism. CaSR agonists (calcimimetics) and antagonists (calcilytics) are in use or under intense research for treatment of hyperparathyroidism secondary to kidney failure and hypocalcemia with hypercalciuria, respectively. Expression of the CaSR extends to other tissues and systems beyond the extracellular Ca 2+ homeostatic system including the cardiovascular system, the airways, and the nervous system where it may play physiological functions yet to be fully understood. As a consequence, CaSR has been recently involved in different pathologies including uncontrolled blood pressure, vascular calcification, asthma, and Alzheimer's disease. Finally, the CaSR has been shown to play a critical role in cancer either contributing to bone metastasis and/or acting as a tumor suppressor in some forms of cancer (parathyroid cancer, colon cancer, and neuroblastoma) and as oncogene in others (breast and prostate cancers). Here we review the role of CaSR in health and disease in calciotropic tissues and others beyond the extracellular calcium homeostatic system. Copyright © 2016 Elsevier Inc. All rights reserved.
Bihuniak, Jessica D; Sullivan, Rebecca R; Simpson, Christine A; Caseria, Donna M; Huedo-Medina, Tania B; O'Brien, Kimberly O; Kerstetter, Jane E; Insogna, Karl L
2014-03-01
Increasing dietary protein within a physiologic range stimulates intestinal calcium absorption, but it is not known if specific amino acids or dietary protein as a whole are responsible for this effect. Therefore, we selectively supplemented a low-protein (0.7 g/kg) diet with either the calcium-sensing receptor-activating amino acids (CaSR-AAAs) L-tryptophan, L-phenylalanine, and L-histidine, or the dibasic amino acids (DAAs) L-arginine and L-lysine, to achieve intakes comparable to the content of a high-protein diet (2.1 g/kg) and measured intestinal calcium absorption. Fourteen young women took part in a placebo-controlled, double-blind, crossover feeding trial in which each participant ingested a 6-d low-protein diet supplemented with CaSR-AAAs, DAAs, or methylcellulose capsules (control) after an 11-d adjustment period. All participants ingested all 3 diets in random order. Intestinal calcium absorption was measured between days 5 and 6 using dual-stable calcium isotopes ((42)Ca, (43)Ca, and (44)Ca). There was no difference in calcium absorption between the diet supplemented with CaSR-AAAs (22.9 ± 2.0%) and the control diet (22.3 ± 1.4%) (P = 0.64). However, calcium absorption tended to be greater during the DAA supplementation period (25.2 ± 1.4%) compared with the control diet period (22.3 ± 1.4%) (P < 0.10). Larger and longer clinical trials are needed to clarify the possible benefit of arginine and lysine on calcium absorption.
Flux pinning by precipitates in the Bi-Sr-Ca-Cu-O system
Shi, Donglu
1992-01-01
A fundamental pinning mechanism has been identified in the Bi-Sr-Ca-Cu-O system. The pinning strength has been greatly increased by the introduction of calcium- and copper-rich precipitates into the sample matrix. The calcium and copper are supersaturated in the system by complete melting, and the fine calcium and copper particles precipitated during subsequent crystallization anneal to obtain the superconducting phases. The intragrain critical current density has been increased from the order of 10.sup.5 A/cm.sup.2 to 10.sup.7 A/cm.sup.2 at 5 T.
The Incredible, Embryological Egg: Calcium and Strontium Isotopes Recapitulate Ontogeny
NASA Astrophysics Data System (ADS)
Gordon, G. W.; Skulan, J. L.
2011-12-01
Embryological development reflects evolutionary history. Understanding the processes of fetal growth is important for curing human birth defects and predicting damage to ecosystems from environmental insults. Tracing enzymatic and hormonal gradients during development, and correlating them to genetic cues dominate modern embryology. Previous work done tracing the mass transfer of elements has generally been limited to isotope spikes in vitro. Natural mass-dependent Ca and Sr isotopic ratios and radiogenic Sr isotopes have the potential to reveal both source and biochemical mechanism information about processes in vivo, but have not previously been extensively explored. The process when a hen lays a fertilized egg that becomes a chick includes formation and dissolution of calcium phosphate (bone) and calcium carbonate (shell). Skulan and DePaolo (1999) showed that chickens have 2% δ44/42Ca between a hen's bones and an egg white; this span represents more than 80% of the entire range of natural Ca isotope variation and illustrates there is significant variation to investigate. A striking feature of archosaurian development that also occurs in many mammals, including humans, is mass transfer of calcium from mother to embryo. The yolk of the domestic hen matures over 7-9 days, but the albumen, shell membranes and shell form in less than 20 hours. Domestic laying hens are at the physiological limit of egg production and selective breeding is no longer an effective method of increasing egg production. 60-75% of the shell's ~1.5 g of calcium comes from dietary sources, while 25-40% comes from the hen's medullary bone. Medullary bone is spicules formed in the marrow of long bones, and is a store of dietary calcium rapidly available for eggshell secretion. During in ovo development, the embryo's skeleton is formed from calcium in the yolk and by bulk dissolution of the eggshell's inner aspect via carbonic anhydrase in a process that has an effect on bone density similar to that caused by osteoporosis in humans. For both mass-dependent Ca and Sr isotopes, the isotopic value of the albumen is the highest natural value yet measured. The offset between the δ88/86Sr values of the albumen and shell is 0.45%, less than half that of the δ44/42Ca offset value (1.29%), as predicted by the relative mass differences. However, the yolk is 0.35% heavier than the shell in δ44/42Ca but 0.70% lighter in δ88/86Sr. In addition, the 87Sr/86Sr value of the shell (0.70854 ±0.000012, 2σ) is statistically the same as the albumen (0.70856 ±0.000018), but slightly offset from the yolk (0.70830 ±0.000014). The apparent decoupling of Ca and Sr, and the radiogenic offset between yolk and shell, may reflect differences in the residence time of calcium and strontium in different reproductive organs, as well as the contribution of medullary bone to shell formation. In addition, it may also reflect differential discrimination against Sr versus Ca in oviduct and uterus. Further studies could extend to thinning eggshells in wild avian populations, biochemical mechanisms of bone formation, and the mechanism of strontium ranelate in the treatment of osteoporosis.
DOE Office of Scientific and Technical Information (OSTI.GOV)
None
1963-12-01
Separate abstracts were prepared for twenty-eight of the thirty-three papers. The other papers deal with whole-rock Rb- Sr ages of Ontario norite and micropegmatite and the Southern Rhodesia Great Dyke, Sr isotopes in vein type mineral deposits, whole-rock Rb-- Sr studies of volcanics, and accuracy in Sr / sup 87//Sr/sup 86/ measurements. (D.C.W.)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sol-Rolland, J.; Joseph, M.; Rinaldi-Carmona, M.
1991-05-01
A procedure for the isolation of primate skeletal microsomal membranes was initiated. Membranes exhibited specific enzymatic markers such as 5'-nucleotidase, Ca{sup 2}{sup +},Mg({sup 2}{sup +})-adenosine triphosphatase and an ATP-dependent calcium uptake. Baboon skeletal microsomes bound specifically with high-affinity potent Ca{sup 2}{sup +} channel blockers such as dihydropyridine, phenylalkylamine and benzothiazepine derivatives. Scatchard analysis of equilibrium binding assays with ({sup 3}H)(+)-PN 200-110, ({sup 3}H)(-)-desmethoxyverapamil (( {sup 3}H)(-)-D888) and ({sup 3}H)-d-cis-dilitiazem were consistent with a single class of binding sites for the three radioligands. The pharmacological profile of SR 33557, an original compound with calcium antagonist properties, was investigated using radioligand bindingmore » studies. SR 33557 totally inhibited the specific binding of the three main classes of Ca{sup 2}{sup +} channel effectors and interacted allosterically with them. In addition, SR 33557 bound with high affinity to a homogeneous population of binding sites in baboon skeletal muscle.« less
Silver, R B
1986-06-01
Monospecific antibodies to the calcium transport enzyme (alpha-Ca pump) inhibit mitosis when microinjected into sand dollar embryos. Immunoglobulins were raised against the calcium transport enzyme (Ca pump) of sarcoplasmic reticulum (SR) from rat skeletal muscle and guinea pig ileum smooth muscle. Specific antibodies were further isolated from IgG fractions by using electrophoretically purified SR Ca-pump protein as the immobilized ligand for immunoaffinity chromatography. ELISA demonstrated that common antigenic determinants are shared by SR, SR Ca pump (of rat skeletal and guinea pig ileum smooth muscle), and isolated membrane containing "native" mitotic apparatus (MA). Preimmune sera gave negative results in identical control assays. Triton X-100 extraction of MA removes the Ca-pump antigen. SR Ca pump and the MA Ca pump have nearly identical molecular masses as determined by NaDodSO4/PAGE. These alpha-SR Ca-pump IgGs inhibit ATP-dependent Ca2+ sequestration by purified SR and MA membranes. Indirect immunofluorescence of isolated native MA demonstrated coincident localization of the MA Ca pump, sequestered calcium, and membrane vesicles. Fluorescent foci were regionally concentrated within the volumes of the asters and spindle. Microinjection of the anti-Ca-pump IgGs into one of two sister blastomeres at second metaphase resulted in mitotic arrest of the injected cell accompanied by a rapid loss of spindle birefringence. Karyomeres formed and fused to form nuclei either at the site of the metaphase plate or at the position the chromosomes occupied during anaphase A. The cleavage furrow did not develop in the injected cell, while the sister and neighbor cells continued normal mitotic cycling. Injection later in mitosis yielded cells with two nuclei whose cleavage furrow relaxed completely. Routine control injections of boiled immune IgG, preimmune IgG, Wesson oil, buffer, or goat anti-rabbit IgG did not affect mitosis, birefringence of the MA, or cleavage furrow activity.
Silver, R B
1986-01-01
Monospecific antibodies to the calcium transport enzyme (alpha-Ca pump) inhibit mitosis when microinjected into sand dollar embryos. Immunoglobulins were raised against the calcium transport enzyme (Ca pump) of sarcoplasmic reticulum (SR) from rat skeletal muscle and guinea pig ileum smooth muscle. Specific antibodies were further isolated from IgG fractions by using electrophoretically purified SR Ca-pump protein as the immobilized ligand for immunoaffinity chromatography. ELISA demonstrated that common antigenic determinants are shared by SR, SR Ca pump (of rat skeletal and guinea pig ileum smooth muscle), and isolated membrane containing "native" mitotic apparatus (MA). Preimmune sera gave negative results in identical control assays. Triton X-100 extraction of MA removes the Ca-pump antigen. SR Ca pump and the MA Ca pump have nearly identical molecular masses as determined by NaDodSO4/PAGE. These alpha-SR Ca-pump IgGs inhibit ATP-dependent Ca2+ sequestration by purified SR and MA membranes. Indirect immunofluorescence of isolated native MA demonstrated coincident localization of the MA Ca pump, sequestered calcium, and membrane vesicles. Fluorescent foci were regionally concentrated within the volumes of the asters and spindle. Microinjection of the anti-Ca-pump IgGs into one of two sister blastomeres at second metaphase resulted in mitotic arrest of the injected cell accompanied by a rapid loss of spindle birefringence. Karyomeres formed and fused to form nuclei either at the site of the metaphase plate or at the position the chromosomes occupied during anaphase A. The cleavage furrow did not develop in the injected cell, while the sister and neighbor cells continued normal mitotic cycling. Injection later in mitosis yielded cells with two nuclei whose cleavage furrow relaxed completely. Routine control injections of boiled immune IgG, preimmune IgG, Wesson oil, buffer, or goat anti-rabbit IgG did not affect mitosis, birefringence of the MA, or cleavage furrow activity. Images PMID:2940599
Manno, Carlo; Sztretye, Monika; Figueroa, Lourdes; Allen, Paul D; Ríos, Eduardo
2013-01-15
The buffering power, B, of the sarcoplasmic reticulum (SR), ratio of the changes in total and free [Ca(2+)], was determined in fast-twitch mouse muscle cells subjected to depleting membrane depolarization. Changes in total SR [Ca(2+)] were measured integrating Ca(2+) release flux, determined with a cytosolic [Ca(2+)] monitor. Free [Ca(2+)](SR) was measured using the cameleon D4cpv-Casq1. In 34 wild-type (WT) cells average B during the depolarization (ON phase) was 157 (SEM 26), implying that of 157 ions released, 156 were bound inside the SR. B was significantly greater when BAPTA, which increases release flux, was present in the cytosol. B was greater early in the pulse - when flux was greatest - than at its end, and greater in the ON than in the OFF. In 29 Casq1-null cells, B was 40 (3.6). The difference suggests that 75% of the releasable calcium is normally bound to calsequestrin. In the nulls the difference in B between ON and OFF was less than in the WT but still significant. This difference and the associated decay in B during the ON were not artifacts of a slow SR monitor, as they were also found in the WT when [Ca(2+)](SR) was tracked with the fast dye fluo-5N. The calcium buffering power, binding capacity and non-linear binding properties of the SR measured here could be accounted for by calsequestrin at the concentration present in mammalian muscle, provided that its properties were substantially different from those found in solution. Its affinity should be higher, or K(D) lower than the conventionally accepted 1 mm; its cooperativity (n in a Hill fit) should be higher and the stoichiometry of binding should be at the higher end of the values derived in solution. The reduction in B during release might reflect changes in calsequestrin conformation upon calcium loss.
Zhang, Na; Zhai, Dong; Chen, Lei; Zou, Zhaoyong; Lin, Kaili; Chang, Jiang
2014-04-01
In the absence of any organic surfactants and solvents, the silicon (Si) and strontium (Sr) co-substituted hydroxyapatite [Ca10(PO4)6(OH)2, Si/Sr-HAp] nanowires were synthesized via hydrothermal treatment of the Sr-containing calcium silicate (Sr-CS) powders as the precursors in trisodium phosphate (Na3PO4) aqueous solution. The morphology, phase, chemical compositions, lattice constants and the degradability of the products were characterized. The Si/Sr-HAp nanowires with diameter of about 60nm and up to 2μm in length were obtained after hydrothermal treatment of the Sr-CS precursors. The Sr and Si substitution amount of the HAp nanowires could be well regulated by facile tailoring the Sr substitution level of the precursors and the reaction ratio of the precursor/solution, respectively. The SiO4 tetrahedra and Sr(2+) ions occupied the crystal sites of the HAp, and the lattice constants increased apparently with the increase of the substitution amount. EDS mapping also suggested the uniform distribution of Si and Sr in the synthetic nanowires. Moreover, the Si/Sr-substitution apparently improved the degradability of the HAp materials. Our study suggested that the precursor transformation method provided a facile approach to synthesize the Si/Sr co-substituted HAp nanowires with controllable substitution amount, and the synthetic Si/Sr-HAp nanowires might be used as bioactive materials for hard tissue regeneration applications. Copyright © 2014 Elsevier B.V. All rights reserved.
Putting out the fire: what terminates calcium-induced calcium release in cardiac muscle?
Stern, Michael D; Cheng, Heping
2004-06-01
The majority of contractile calcium in cardiac muscle is released from stores in the sarcoplasmic reticulum (SR), by a process of calcium-induced calcium release (CICR) through ryanodine receptors. Because CICR is intrinsically self-reinforcing, the stability of and graded regulation of cardiac EC coupling appear paradoxical. It is now well established that this gradation results from the stochastic recruitment of varying numbers of elementary local release events, which may themselves be regenerative, and which can be directly observed as calcium sparks. Ryanodine receptors (RyRs) are clustered in dense lattices, and most calcium sparks are now believed to involve activation of multiple RyRs. This implies that local CICR is regenerative, requiring a mechanism to terminate it. It was initially assumed that this mechanism was inactivation of the RyR, but during the decade since the discovery of sparks, no sufficiently strong inactivation mechanism has been demonstrated in vitro and all empirically determined gating schemes for the RyR give unstable EC coupling in Monte Carlo simulations. We consider here possible release termination mechanisms. Stochastic attrition is the spontaneous decay of active clusters due to random channel closure; calculations show that it is much too slow unless assisted by another process. Calcium-dependent RyR inactivation involving third-party proteins remains a viable but speculative mechanism; current candidates include calmodulin and sorcin. Local depletion of SR release terminal calcium could terminate release, however calculations and measurements leave it uncertain whether a sufficient diffusion resistance exists within the SR to sustain such depletion. Depletion could be assisted by dependence of RyR activity on SR lumenal [Ca(2+)]. There is substantial evidence for such lumenal activation, but it is not clear if it is a strong enough effect to account for the robust termination of sparks. The existence of direct interactions among clustered RyRs might account for the discrepancy between the inactivation properties of isolated RyRs and intact clusters. Such coupled gating remains controversial. Determining the mechanism of release termination is the outstanding unsolved problem of cardiac EC coupling, and will probably require extensive genetic manipulation of the EC coupling apparatus in its native environment to unravel the solution.
Curran, Jerry; Tang, Lifei; Roof, Steve R; Velmurugan, Sathya; Millard, Ashley; Shonts, Stephen; Wang, Honglan; Santiago, Demetrio; Ahmad, Usama; Perryman, Matthew; Bers, Donald M; Mohler, Peter J; Ziolo, Mark T; Shannon, Thomas R
2014-01-01
Spontaneous calcium waves in cardiac myocytes are caused by diastolic sarcoplasmic reticulum release (SR Ca(2+) leak) through ryanodine receptors. Beta-adrenergic (β-AR) tone is known to increase this leak through the activation of Ca-calmodulin-dependent protein kinase (CaMKII) and the subsequent phosphorylation of the ryanodine receptor. When β-AR drive is chronic, as observed in heart failure, this CaMKII-dependent effect is exaggerated and becomes potentially arrhythmogenic. Recent evidence has indicated that CaMKII activation can be regulated by cellular oxidizing agents, such as reactive oxygen species. Here, we investigate how the cellular second messenger, nitric oxide, mediates CaMKII activity downstream of the adrenergic signaling cascade and promotes the generation of arrhythmogenic spontaneous Ca(2+) waves in intact cardiomyocytes. Both SCaWs and SR Ca(2+) leak were measured in intact rabbit and mouse ventricular myocytes loaded with the Ca-dependent fluorescent dye, fluo-4. CaMKII activity in vitro and immunoblotting for phosphorylated residues on CaMKII, nitric oxide synthase, and Akt were measured to confirm activity of these enzymes as part of the adrenergic cascade. We demonstrate that stimulation of the β-AR pathway by isoproterenol increased the CaMKII-dependent SR Ca(2+) leak. This increased leak was prevented by inhibition of nitric oxide synthase 1 but not nitric oxide synthase 3. In ventricular myocytes isolated from wild-type mice, isoproterenol stimulation also increased the CaMKII-dependent leak. Critically, in myocytes isolated from nitric oxide synthase 1 knock-out mice this effect is ablated. We show that isoproterenol stimulation leads to an increase in nitric oxide production, and nitric oxide alone is sufficient to activate CaMKII and increase SR Ca(2+) leak. Mechanistically, our data links Akt to nitric oxide synthase 1 activation downstream of β-AR stimulation. Collectively, this evidence supports the hypothesis that CaMKII is regulated by nitric oxide as part of the adrenergic cascade leading to arrhythmogenesis.
Fénelon, Karine; Lamboley, Cédric R.H.; Carrier, Nicole
2012-01-01
Experiments were performed to characterize the properties of the intrinsic Ca2+ buffers in the sarcoplasmic reticulum (SR) of cut fibers from frog twitch muscle. The concentrations of total and free calcium ions within the SR ([CaT]SR and [Ca2+]SR) were measured, respectively, with the EGTA/phenol red method and tetramethylmurexide (a low affinity Ca2+ indicator). Results indicate SR Ca2+ buffering was consistent with a single cooperative-binding component or a combination of a cooperative-binding component and a linear binding component accounting for 20% or less of the bound Ca2+. Under the assumption of a single cooperative-binding component, the most likely resting values of [Ca2+]SR and [CaT]SR are 0.67 and 17.1 mM, respectively, and the dissociation constant, Hill coefficient, and concentration of the Ca-binding sites are 0.78 mM, 3.0, and 44 mM, respectively. This information can be used to calculate a variable proportional to the Ca2+ permeability of the SR, namely d[CaT]SR/dt ÷ [Ca2+]SR (denoted release permeability), in experiments in which only [CaT]SR or [Ca2+]SR is measured. In response to a voltage-clamp step to −20 mV at 15°C, the release permeability reaches an early peak followed by a rapid decline to a quasi-steady level that lasts ∼50 ms, followed by a slower decline during which the release permeability decreases by at least threefold. During the quasi-steady level of release, the release amplitude is 3.3-fold greater than expected from voltage activation alone, a result consistent with the recruitment by Ca-induced Ca2+ release of 2.3 SR Ca2+ release channels neighboring each channel activated by its associated voltage sensor. Release permeability at −60 mV increases as [CaT]SR decreases from its resting physiological level to ∼0.1 of this level. This result argues against a release termination mechanism proposed in mammalian muscle fibers in which a luminal sensor of [Ca2+]SR inhibits release when [CaT]SR declines to a low level. PMID:23008434
Fénelon, Karine; Lamboley, Cédric R H; Carrier, Nicole; Pape, Paul C
2012-10-01
Experiments were performed to characterize the properties of the intrinsic Ca(2+) buffers in the sarcoplasmic reticulum (SR) of cut fibers from frog twitch muscle. The concentrations of total and free calcium ions within the SR ([Ca(T)](SR) and [Ca(2+)](SR)) were measured, respectively, with the EGTA/phenol red method and tetramethylmurexide (a low affinity Ca(2+) indicator). Results indicate SR Ca(2+) buffering was consistent with a single cooperative-binding component or a combination of a cooperative-binding component and a linear binding component accounting for 20% or less of the bound Ca(2+). Under the assumption of a single cooperative-binding component, the most likely resting values of [Ca(2+)](SR) and [Ca(T)](SR) are 0.67 and 17.1 mM, respectively, and the dissociation constant, Hill coefficient, and concentration of the Ca-binding sites are 0.78 mM, 3.0, and 44 mM, respectively. This information can be used to calculate a variable proportional to the Ca(2+) permeability of the SR, namely d[Ca(T)](SR)/dt ÷ [Ca(2+)](SR) (denoted release permeability), in experiments in which only [Ca(T)](SR) or [Ca(2+)](SR) is measured. In response to a voltage-clamp step to -20 mV at 15°C, the release permeability reaches an early peak followed by a rapid decline to a quasi-steady level that lasts ~50 ms, followed by a slower decline during which the release permeability decreases by at least threefold. During the quasi-steady level of release, the release amplitude is 3.3-fold greater than expected from voltage activation alone, a result consistent with the recruitment by Ca-induced Ca(2+) release of 2.3 SR Ca(2+) release channels neighboring each channel activated by its associated voltage sensor. Release permeability at -60 mV increases as [Ca(T)](SR) decreases from its resting physiological level to ~0.1 of this level. This result argues against a release termination mechanism proposed in mammalian muscle fibers in which a luminal sensor of [Ca(2+)](SR) inhibits release when [Ca(T)](SR) declines to a low level.
Grant, Michael P.; Stepanchick, Ann
2012-01-01
Calcium-sensing receptors (CaSRs) regulate systemic Ca2+ homeostasis. Loss-of-function mutations cause familial benign hypocalciuric hypercalcemia (FHH) or neonatal severe hyperparathyroidism (NSHPT). FHH/NSHPT mutations can reduce trafficking of CaSRs to the plasma membrane. CaSR signaling is potentiated by agonist-driven anterograde CaSR trafficking, leading to a new steady state level of plasma membrane CaSR, which is maintained, with minimal functional desensitization, as long as extracellular Ca2+ is elevated. This requirement for CaSR signaling to drive CaSR trafficking to the plasma membrane led us to reconsider the mechanism(s) contributing to dysregulated trafficking of FHH/NSHPT mutants. We simultaneously monitored dynamic changes in plasma membrane levels of CaSR and intracellular Ca2+, using a chimeric CaSR construct, which allowed explicit tracking of plasma membrane levels of mutant or wild-type CaSRs in the presence of nonchimeric partners. Expression of mutants alone revealed severe defects in plasma membrane targeting and Ca2+ signaling, which were substantially rescued by coexpression with wild-type CaSR. Biasing toward heterodimerization of wild-type and FHH/NSHPT mutants revealed that intracellular Ca2+ oscillations were insufficient to rescue plasma membrane targeting. Coexpression of the nonfunctional mutant E297K with the truncation CaSRΔ868 robustly rescued trafficking and Ca2+ signaling, whereas coexpression of distinct FHH/NSHPT mutants rescued neither trafficking nor signaling. Our study suggests that rescue of FHH/NSHPT mutants requires a steady state intracellular Ca2+ response when extracellular Ca2+ is elevated and argues that Ca2+ signaling by wild-type CaSRs rescues FHH mutant trafficking to the plasma membrane. PMID:23077345
Long, Chao-liang; Zhang, Yan-fang; Yin, Zhao-yun; Wang, Hai
2005-08-01
To study the effect of acute hypoxia and hypoxic acclimatization on myocardial function of rats. Eighteen male Wistar rats were randomly divided into three groups: normoxic control, acute hypoxia and intermittent hypoxic acclimatization group (n=6). After being exposed to hypoxia (8000 m) for 4 h before and after intermittent hypoxic acclimatization (3000 m and 5000 m, 14 d respectively, 4 h/d), the rats were decapitated and then myocardial sarcoplasmic reticulum (SR) were derived from cardiac muscles. Activities of Na+, K(+)-ATPase, Ca2+, Mg2(+)-ATPase in SR, phosphorylation of phospholamban (PLB) and the ability of 45Ca2+ uptake in SR were observed in all these three groups. 1) Hypoxia had no effects on the activity of Na+, K(+)-ATPase in rats myocardial SR of rats. 2) Compared with normoxic control rats, the activity of Ca2+, Mg2(+)-ATPase in myocardial SR of rats after acute hypoxia was reduced significantly (P<0.01). After intermittent hypoxic acclimatization, its activity increased significantly as compared with that of acute hypoxic rats (P<0.01). 3) The phosphorylation of PLB in acute hypoxic rats was reduced significantly compared with normoxic control rats. After intermittent hypoxic acclimatization, its phosphorylation was increased significantly compared with that of acute hypoxic rats. It suggests that hypoxic acclimatization could alleviate the inhibition of calcium pump. 4) The ability of 45Ca2+ uptake of SR in acute hypoxic rats was decreased significantly. After hypoxic acclimatization, its ability was strengthened significantly. These results suggest that the increased function of myocardial SR calcium pump, the strengthened phosphorylation of PLB to alleviate the inhibition of calcium pump and the increased function of Ca2+ transport in SR are the mechanisms of hypoxic acclimatization protecting cardiac functions from injury induced by severe hypoxia.
The role of Sr2+ on the structure and reactivity of SrO-CaO-ZnO-SiO2 ionomer glasses.
Boyd, Daniel; Towler, Mark R; Watts, Sally; Hill, Robert G; Wren, Anthony W; Clarkin, Owen M
2008-02-01
The suitability of Glass Polyalkenoate Cements (GPCs) for use in orthopaedics is retarded by the presence in the glass phase of aluminium, a neurotoxin. Unfortunately, the aluminium ion plays an integral role in the setting process of GPCs and its absence is likely to hinder cement formation. However, the authors have previously shown that aluminium free GPCs may be formulated based on calcium zinc silicate glasses and these novel materials exhibit significant potential as hard tissue biomaterials. To further improve their potential, and given that Strontium (Sr) based drugs have had success in the treatment of osteoporosis, the authors have substituted Calcium (Ca) with Sr in the glass phase of a series of aluminium free GPCs. However to date little data exists on the effect SrO has on the structure and reactivity of SrO-CaO-ZnO-SiO(2) glasses. The objective of this work was to characterise the effect of the Ca/Sr substitution on the structure of such glasses, and evaluate the subsequent reactivity of these glasses with an aqueous solution of Polyacrylic acid (PAA). To this end (29)Si MAS-NMR, differential scanning calorimetry (DSC), X-ray diffraction, and network connectivity calculations, were used to characterize the structure of four strontium calcium zinc silicate glasses. Following glass characterization, GPCs were produced from each glass using a 40 wt% solution of PAA (powder:liquid = 2:1.5). The working times and setting times of the GPCs were recorded as per International standard ISO9917. The results acquired as part of this research indicate that the substitution of Ca for Sr in the glasses examined did not appear to significantly affect the structure of the glasses investigated. However it was noted that increasing the amount of Ca substituted for Sr did result in a concomitant increase in setting times, a feature that may be attributable to the higher basicity of SrO over CaO.
Burgess, Kevin M N; Xu, Yang; Leclerc, Matthew C; Bryce, David L
2014-01-06
A series of calcium and strontium complexes featuring aryl carboxylate ligands has been prepared and characterized by alkaline-earth ((43)Ca and (87)Sr) solid-state NMR experiments in a magnetic field of 21.1 T. In the 11 compounds studied as part of this work, a range of coordination motifs are observed including nitrogen atom binding to Ca(2+) and Sr(2+), a binding mode which has not been investigated previously by (43)Ca or (87)Sr solid-state NMR. (43)Ca isotopic enrichment has enabled the full characterization of the (43)Ca electric field gradient (EFG) and chemical shift tensors of the two calcium sites in calcium p-aminosalicylate (Ca(pams)), where both NMR interactions are affected by the presence of a nitrogen atom in the first coordination sphere of one of the metal sites. The (43)Ca isotropic chemical shift is sensitive to the Ca-N distance as exemplified by the NMR parameters of a second form of Ca(pams) and density functional theory (DFT) calculations. Studies of the strontium analogue, Sr(pams), confirm a similar sensitivity of the (87)Sr EFG tensor to the presence or absence of nitrogen in the first coordination sphere. To our knowledge, this is the first systematic (87)Sr NMR study of strontium complexes featuring organic ligands. The |CQ((87)Sr)| values are found to be sensitive to the coordination number about Sr(2+). In general, this work has also established a larger data set of reliable experimental |CQ((43)Ca)| values which correlate well with those obtained using gauge-including projector-augmented-wave (GIPAW) DFT calculations. It is found that the use of a recently recommended quadrupole moment for (43)Ca, -44.4 mbarn, improves the agreement with experimental values. This contribution lays the groundwork for the interpretation of (43)Ca and (87)Sr NMR spectra of more challenging systems, particularly where nitrogen-alkaline earth metal bonding is occurring.
Launikonis, B S; Stephenson, D G
1997-01-01
1. Mechanically skinned fibres from skeletal muscles of the rat, toad and yabby were used to investigate the effect of saponin treatment on sarcoplasmic reticulum (SR) Ca2+ loading properties. The SR was loaded submaximally under control conditions before and after treatment with saponin and SR Ca2+ was released with caffeine. 2. Treatment with 10 micrograms ml-1 saponin greatly reduced the SR Ca2+ loading ability of skinned fibres from the extensor digitorum longus muscle of the rat with a rate constant of 0.24 min-1. Saponin concentrations up to 150 micrograms ml-1 and increased exposure time up to 30 min did not further reduce the SR Ca2+ loading ability of the SR, which indicates that the inhibitory action of 10-150 micrograms ml-1 saponin is not dose dependent. The effect of saponin was also not dependent on the state of polarization of the transverse-tubular system. 3. Treatment with saponin at concentrations up to 100 micrograms ml-1 for 30 min did not affect the Ca2+ loading ability of SR in skinned skeletal muscle fibres from the twitch portion of the toad iliofibularis muscle but SR Ca2+ loading ability decreased markedly with a time constant of 0.22 min-1 in the presence of 150 micrograms ml-1 saponin. 4. The saponin dependent increase in permeability could be reversed in both rat and toad fibres by short treatment with 6 microM Ruthenium Red, a potent SR Ca2+ channel blocker, suggesting that saponin does affect the SR Ca2+ channel properties in mammalian and anuran skeletal muscle. 5. Treatment of skinned fibres of long sarcomere length (> 6 microns) from the claw muscle of the yabby (a freshwater decapod crustacean) with 10 micrograms ml-1 saponin for 30 min abolished the ability of the SR to load Ca2+, indicating that saponin affects differently the SR from skeletal muscles of mammals, anurans and crustaceans. 6. It is concluded that at relatively low concentrations, saponin causes inhibition of the skeletal SR Ca2+ loading ability in a species dependent manner, probably by increasing the Ca2+ loss through SR Ca2+ release channels. PMID:9365915
Launikonis, B S; Stephenson, D G
1997-10-15
1. Mechanically skinned fibres from skeletal muscles of the rat, toad and yabby were used to investigate the effect of saponin treatment on sarcoplasmic reticulum (SR) Ca2+ loading properties. The SR was loaded submaximally under control conditions before and after treatment with saponin and SR Ca2+ was released with caffeine. 2. Treatment with 10 micrograms ml-1 saponin greatly reduced the SR Ca2+ loading ability of skinned fibres from the extensor digitorum longus muscle of the rat with a rate constant of 0.24 min-1. Saponin concentrations up to 150 micrograms ml-1 and increased exposure time up to 30 min did not further reduce the SR Ca2+ loading ability of the SR, which indicates that the inhibitory action of 10-150 micrograms ml-1 saponin is not dose dependent. The effect of saponin was also not dependent on the state of polarization of the transverse-tubular system. 3. Treatment with saponin at concentrations up to 100 micrograms ml-1 for 30 min did not affect the Ca2+ loading ability of SR in skinned skeletal muscle fibres from the twitch portion of the toad iliofibularis muscle but SR Ca2+ loading ability decreased markedly with a time constant of 0.22 min-1 in the presence of 150 micrograms ml-1 saponin. 4. The saponin dependent increase in permeability could be reversed in both rat and toad fibres by short treatment with 6 microM Ruthenium Red, a potent SR Ca2+ channel blocker, suggesting that saponin does affect the SR Ca2+ channel properties in mammalian and anuran skeletal muscle. 5. Treatment of skinned fibres of long sarcomere length (> 6 microns) from the claw muscle of the yabby (a freshwater decapod crustacean) with 10 micrograms ml-1 saponin for 30 min abolished the ability of the SR to load Ca2+, indicating that saponin affects differently the SR from skeletal muscles of mammals, anurans and crustaceans. 6. It is concluded that at relatively low concentrations, saponin causes inhibition of the skeletal SR Ca2+ loading ability in a species dependent manner, probably by increasing the Ca2+ loss through SR Ca2+ release channels.
Desai, Aditya J.; Roberts, David J.
2014-01-01
The Calcium Sensing Receptor (CaSR) plays a role in calcium homeostasis by sensing minute changes in serum Ca2+ and modulating secretion of calciotropic hormones. It has been shown in transfected cells that accessory proteins known as Receptor Activity Modifying Proteins (RAMPs), specifically RAMPs 1 and 3, are required for cell-surface trafficking of the CaSR. These effects have only been demonstrated in transfected cells, so their physiological relevance is unclear. Here we explored CaSR/RAMP interactions in detail, and showed that in thyroid human carcinoma cells, RAMP1 is required for trafficking of the CaSR. Furthermore, we show that normal RAMP1 function is required for intracellular responses to ligands. Specifically, to confirm earlier studies with tagged constructs, and to provide the additional benefit of quantitative stoichiometric analysis, we used fluorescence resonance energy transfer to show equal abilities of RAMP1 and 3 to chaperone CaSR to the cell surface, though RAMP3 interacted more efficiently with the receptor. Furthermore, a higher fraction of RAMP3 than RAMP1 was observed in CaSR-complexes on the cell-surface, suggesting different ratios of RAMPs to CaSR. In order to determine relevance of these findings in an endogenous expression system we assessed the effect of RAMP1 siRNA knock-down in medullary thyroid carcinoma TT cells, (which express RAMP1, but not RAMP3 constitutively) and measured a significant 50% attenuation of signalling in response to CaSR ligands Cinacalcet and neomycin. Blockade of RAMP1 using specific antibodies induced a concentration-dependent reduction in CaSR-mediated signalling in response to Cinacalcet in TT cells, suggesting a novel functional role for RAMP1 in regulation of CaSR signalling in addition to its known role in receptor trafficking. These data provide evidence that RAMPs traffic the CaSR as higher-level oligomers and play a role in CaSR signalling even after cell surface localisation has occurred. PMID:24454825
Desai, Aditya J; Roberts, David J; Richards, Gareth O; Skerry, Timothy M
2014-01-01
The Calcium Sensing Receptor (CaSR) plays a role in calcium homeostasis by sensing minute changes in serum Ca(2+) and modulating secretion of calciotropic hormones. It has been shown in transfected cells that accessory proteins known as Receptor Activity Modifying Proteins (RAMPs), specifically RAMPs 1 and 3, are required for cell-surface trafficking of the CaSR. These effects have only been demonstrated in transfected cells, so their physiological relevance is unclear. Here we explored CaSR/RAMP interactions in detail, and showed that in thyroid human carcinoma cells, RAMP1 is required for trafficking of the CaSR. Furthermore, we show that normal RAMP1 function is required for intracellular responses to ligands. Specifically, to confirm earlier studies with tagged constructs, and to provide the additional benefit of quantitative stoichiometric analysis, we used fluorescence resonance energy transfer to show equal abilities of RAMP1 and 3 to chaperone CaSR to the cell surface, though RAMP3 interacted more efficiently with the receptor. Furthermore, a higher fraction of RAMP3 than RAMP1 was observed in CaSR-complexes on the cell-surface, suggesting different ratios of RAMPs to CaSR. In order to determine relevance of these findings in an endogenous expression system we assessed the effect of RAMP1 siRNA knock-down in medullary thyroid carcinoma TT cells, (which express RAMP1, but not RAMP3 constitutively) and measured a significant 50% attenuation of signalling in response to CaSR ligands Cinacalcet and neomycin. Blockade of RAMP1 using specific antibodies induced a concentration-dependent reduction in CaSR-mediated signalling in response to Cinacalcet in TT cells, suggesting a novel functional role for RAMP1 in regulation of CaSR signalling in addition to its known role in receptor trafficking. These data provide evidence that RAMPs traffic the CaSR as higher-level oligomers and play a role in CaSR signalling even after cell surface localisation has occurred.
Cesium and strontium loads into a combined sewer system from rainwater runoff.
Kamei-Ishikawa, Nao; Yoshida, Daiki; Ito, Ayumi; Umita, Teruyuki
2016-12-01
In this study, combined sewage samples were taken with time in several rain events and sanitary sewage samples were taken with time in dry weather to calculate Cs and Sr loads to sewers from rainwater runoff. Cs and Sr in rainwater were present as particulate forms at first flush and the particulate Cs and Sr were mainly bound with inorganic suspended solids such as clay minerals in combined sewage samples. In addition, multiple linear regression analysis showed Cs and Sr loads from rainwater runoff could be estimated by the total amount of rainfall and antecedent dry weather days. The variation of the Sr load from rainwater to sewers was more sensitive to total amount of rainfall and antecedent dry weather days than that of the Cs load. Copyright © 2016 Elsevier Ltd. All rights reserved.
Kubalova, Zuzana; Györke, Inna; Terentyeva, Radmila; Viatchenko-Karpinski, Serge; Terentyev, Dmitry; Williams, Simon C; Györke, Sandor
2004-01-01
Waves of Ca2+-induced Ca2+ release occur in various cell types and are involved in the pathology of certain forms of cardiac arrhythmia. These arrhythmias include catecholaminergic polymorphic ventricular tachycardia (CPVT), certain cases of which are associated with mutations in the cardiac calsequestrin gene (CASQ2). To explore the mechanisms of Ca2+ wave generation and unravel the underlying causes of CPVT, we investigated the effects of adenoviral-mediated changes in CASQ2 protein levels on the properties of cytosolic and sarcoplasmic reticulum (SR) Ca2+ waves in permeabilized rat ventricular myocytes. The free [Ca2+] inside the sarcoplasmic reticulum ([Ca2+]SR) was monitored by fluo-5N entrapped into the SR, and cytosolic Ca2+ was imaged using fluo-3. Overexpression of CASQ2 resulted in significant increases in the amplitude of Ca2+ waves and interwave intervals, whereas reduced CASQ2 levels caused drastic reductions in the amplitude and period of Ca2+ waves. CASQ2 abundance had no impact on resting diastolic [Ca2+]SR or on the amplitude of the [Ca2+]SR depletion signal during the Ca2+ wave. However, the recovery dynamics of [Ca2+]SR following Ca2+ release were dramatically altered as the rate of [Ca2+]SR recovery increased ∼3-fold in CASQ2-overexpressing myocytes and decreased to 30% of control in CASQ2-underexpressing myocytes. There was a direct linear relationship between Ca2+ wave period and the half-time of basal [Ca2+]SR recovery following Ca2+ release. Loading the SR with the low affinity exogenous Ca2+ buffer citrate exerted effects quantitatively similar to those observed on overexpressing CASQ2. We conclude that free intra-SR [Ca2+] is a critical determinant of cardiac Ca2+ wave generation. Our data indicate that reduced intra-SR Ca2+ binding activity promotes the generation of Ca2+ waves by accelerating the dynamics of attaining a threshold free [Ca2+]SR required for Ca2+ wave initiation, potentially accounting for arrythmogenesis in CPVT linked to mutations in CASQ2. PMID:15486014
Localized intracellular calcium signaling in muscle: calcium sparks and calcium quarks.
Niggli, E
1999-01-01
Subcellularly localized Ca2+ signals in cardiac and skeletal muscle have recently been identified as elementary Ca2+ signaling events. The signals, termed Ca2+ sparks and Ca2+ quarks, represent openings of Ca2+ release channels located in the membrane of the sarcoplasmic reticulum (SR). In cardiac muscle, the revolutionary discovery of Ca2+ sparks has allowed the development of a fundamentally different concept for the amplification of Ca2+ signals by Ca(2+)-induced Ca2+ release. In such a system, a graded amplification of the triggering Ca2+ signal entering the myocyte via L-type Ca2+ channels is accomplished by a recruitment process whereby individual SR Ca2+ release units are locally controlled by L-type Ca2+ channels. In skeletal muscle, the initial SR Ca2+ release is governed by voltage-sensors but subsequently activates additional Ca2+ sparks by Ca(2+)-induced Ca2+ release from the SR. Results from studies on elementary Ca2+ release events will improve our knowledge of muscle Ca2+ signaling at all levels of complexity, from the molecule to normal cellular function, and from the regulation of cardiac and skeletal muscle force to the pathophysiology of excitation-contraction coupling.
NASA Astrophysics Data System (ADS)
Bui, Duc-Nguyen; Mu, Jin; Wang, Lei; Kang, Shi-Zhao; Li, Xiangqing
2013-06-01
Cu-loaded SrTiO3 nanoparticles (Cu-SrTiO3) were prepared using a simple in situ photo-deposition method and their photocatalytic activity for hydrogen evolution from methanol aqueous solution was evaluated. The results characterized with XRD, TEM, XPS and EDX indicated that the as-synthesized sample was composed of metallic Cu and cubic SrTiO3, and the metallic Cu was homogeneously loaded on the surface of SrTiO3 nanoparticles. Under UV light irradiation, Cu-SrTiO3 displayed much higher photocatalytic activity for hydrogen evolution and excellent stability in comparison with pure SrTiO3 nanoparticles. The results further confirmed that the efficient separation of photogenerated electron/hole pairs was critical for the enhanced photocatalytic activity of Cu-SrTiO3. Moreover, the rate of hydrogen evolution of 0.5 wt.% Cu-SrTiO3 is comparable with that of 0.5 wt.% Pt-SrTiO3 photocatalyst under optimum conditions, implying that the metallic Cu is an efficient alternative to Pt as a co-catalyst on SrTiO3. The high photocatalytic activity, low cost and chemical stability mean that the Cu-loaded SrTiO3 is a potential catalyst for the photocatalytic hydrogen evolution from methanol aqueous solution.
Voltage Dependence of a Neuromodulator-Activated Ionic Current.
Gray, Michael; Golowasch, Jorge
2016-01-01
The neuromodulatory inward current (IMI) generated by crab Cancer borealis stomatogastric ganglion neurons is an inward current whose voltage dependence has been shown to be crucial in the activation of oscillatory activity of the pyloric network of this system. It has been previously shown that IMI loses its voltage dependence in conditions of low extracellular calcium, but that this effect appears to be regulated by intracellular calmodulin. Voltage dependence is only rarely regulated by intracellular signaling mechanisms. Here we address the hypothesis that the voltage dependence of IMI is mediated by intracellular signaling pathways activated by extracellular calcium. We demonstrate that calmodulin inhibitors and a ryanodine antagonist can reduce IMI voltage dependence in normal Ca(2+), but that, in conditions of low Ca(2+), calmodulin activators do not restore IMI voltage dependence. Further, we show evidence that CaMKII alters IMI voltage dependence. These results suggest that calmodulin is necessary but not sufficient for IMI voltage dependence. We therefore hypothesize that the Ca(2+)/calmodulin requirement for IMI voltage dependence is due to an active sensing of extracellular calcium by a GPCR family calcium-sensing receptor (CaSR) and that the reduction in IMI voltage dependence by a calmodulin inhibitor is due to CaSR endocytosis. Supporting this, preincubation with an endocytosis inhibitor prevented W7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride)-induced loss of IMI voltage dependence, and a CaSR antagonist reduced IMI voltage dependence. Additionally, myosin light chain kinase, which is known to act downstream of the CaSR, seems to play a role in regulating IMI voltage dependence. Finally, a Gβγ-subunit inhibitor also affects IMI voltage dependence, in support of the hypothesis that this process is regulated by a G-protein-coupled CaSR.
Voltage Dependence of a Neuromodulator-Activated Ionic Current123
2016-01-01
Abstract The neuromodulatory inward current (IMI) generated by crab Cancer borealis stomatogastric ganglion neurons is an inward current whose voltage dependence has been shown to be crucial in the activation of oscillatory activity of the pyloric network of this system. It has been previously shown that IMI loses its voltage dependence in conditions of low extracellular calcium, but that this effect appears to be regulated by intracellular calmodulin. Voltage dependence is only rarely regulated by intracellular signaling mechanisms. Here we address the hypothesis that the voltage dependence of IMI is mediated by intracellular signaling pathways activated by extracellular calcium. We demonstrate that calmodulin inhibitors and a ryanodine antagonist can reduce IMI voltage dependence in normal Ca2+, but that, in conditions of low Ca2+, calmodulin activators do not restore IMI voltage dependence. Further, we show evidence that CaMKII alters IMI voltage dependence. These results suggest that calmodulin is necessary but not sufficient for IMI voltage dependence. We therefore hypothesize that the Ca2+/calmodulin requirement for IMI voltage dependence is due to an active sensing of extracellular calcium by a GPCR family calcium-sensing receptor (CaSR) and that the reduction in IMI voltage dependence by a calmodulin inhibitor is due to CaSR endocytosis. Supporting this, preincubation with an endocytosis inhibitor prevented W7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride)-induced loss of IMI voltage dependence, and a CaSR antagonist reduced IMI voltage dependence. Additionally, myosin light chain kinase, which is known to act downstream of the CaSR, seems to play a role in regulating IMI voltage dependence. Finally, a Gβγ-subunit inhibitor also affects IMI voltage dependence, in support of the hypothesis that this process is regulated by a G-protein-coupled CaSR. PMID:27257619
Attenuated response of L-type calcium current to nitric oxide in atrial fibrillation.
Rozmaritsa, Nadiia; Christ, Torsten; Van Wagoner, David R; Haase, Hannelore; Stasch, Johannes-Peter; Matschke, Klaus; Ravens, Ursula
2014-03-01
Nitric oxide (NO) synthesized by cardiomyocytes plays an important role in the regulation of cardiac function. Here, we studied the impact of NO signalling on calcium influx in human right atrial myocytes and its relation to atrial fibrillation (AF). Right atrial appendages (RAAs) were obtained from patients in sinus rhythm (SR) and AF. The biotin-switch technique was used to evaluate endogenous S-nitrosylation of the α1C subunit of L-type calcium channels. Comparing SR to AF, S-nitrosylation of Ca(2+) channels was similar. Direct effects of the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) on L-type calcium current (ICa,L) were studied in cardiomyocytes with standard voltage-clamp techniques. In SR, ICa,L increased with SNAP (100 µM) by 48%, n/N = 117/56, P < 0.001. The SNAP effect on ICa,L involved activation of soluble guanylate cyclase and protein kinase A. Specific inhibition of phosphodiesterase (PDE)3 with cilostamide (1 µM) enhanced ICa,L to a similar extent as SNAP. However, when cAMP was elevated by PDE3 inhibition or β-adrenoceptor stimulation, SNAP reduced ICa,L, pointing to cGMP-cAMP cross-regulation. In AF, the stimulatory effect of SNAP on ICa,L was attenuated, while its inhibitory effect on isoprenaline- or cilostamide-stimulated current was preserved. cGMP elevation with SNAP was comparable between the SR and AF group. Moreover, the expression of PDE3 and soluble guanylate cyclase was not reduced in AF. NO exerts dual effects on ICa,L in SR with an increase of basal and inhibition of cAMP-stimulated current, and in AF NO inhibits only stimulated ICa,L. We conclude that in AF, cGMP regulation of PDE2 is preserved, but regulation of PDE3 is lost.
NASA Astrophysics Data System (ADS)
Gussone, Nikolaus; Filipsson, Helena L.; Kuhnert, Henning
2016-01-01
We analysed Mg/Ca, Sr/Ca and Ca isotope ratios of benthonic foraminifers from sediment core tops retrieved during several research cruises in the Atlantic Ocean, in order to improve the understanding of isotope fractionation and element partitioning resulting from biomineralisation processes and changes in ambient conditions. Species include foraminifers secreting tests composed of hyaline low magnesium calcite, porcelaneous high magnesium calcite as well as aragonite. Our results demonstrate systematic isotope fractionation and element partitioning patterns specific for these foraminiferal groups. Calcium isotope fractionation is similar in porcelaneous and hyaline calcite tests and both groups demonstrate the previously described anomaly with enrichment of heavy isotopes around 3-4 °C (Gussone and Filipsson, 2010). Calcium isotope ratios of the aragonitic species Hoeglundina elegans, on the other hand, are about 0.4‰ lighter compared to the calcitic species, which is in general agreement with stronger fractionation in inorganic aragonite compared to calcite. However, the low and strongly variable Sr content suggests additional processes during test formation, and we propose that transmembrane ion transport or a precursor phase to aragonite may be involved. Porcelaneous tests, composed of high Mg calcite, incorporate higher amounts of Sr compared to hyaline low Mg calcite, in agreement with inorganic calcite systematics, but also porcelaneous tests with reduced Mg/Ca show high Sr/Ca. While calcium isotopes, Sr/Ca and Mg/Ca in benthonic foraminifers primarily appear to fractionate and partition with a dominant inorganic control, δ44/40Ca temperature and growth rate dependencies of benthonic foraminifer tests favour a dominant contribution of light Ca by transmembrane transport relative to unfractionated seawater Ca to the calcifying fluid, thus controlling the formation of foraminiferal δ44/40Ca and Sr/Ca proxy signals.
Rodríguez, Mariano; Goodman, William G; Liakopoulos, Vassilios; Messa, Piergiorgio; Wiecek, Andrzej; Cunningham, John
2015-01-01
Until the discovery of calcimimetics, the management of secondary hyperparathyroidism (SHPT) relied exclusively on treatment with phosphate binders, vitamin D derivatives or surgical parathyroidectomy with limited success. The therapeutic use of calcimimetic agents, together with a better understanding of the pivotal role of the calcium-sensing receptor (CaSR) in the physiological regulation of parathyroid gland function, substantially advanced the management of hyperparathyroidism in dialysis practice. Calcimimetics bind selectively to the CaSR receptor in parathyroid tissue and enhance the inhibitory effect of extracellular calcium ions on parathyroid hormone (PTH) secretion, thereby reducing PTH levels even when serum calcium concentrations are normal or low. The availability of calcimimetic agents for clinical use has opened a new era in the management of patients with SHPT. Indeed, calcimimetic compounds have been shown to reduce PTH levels and to lower serum calcium concentrations in all forms of hyperparathyroidism, including primary hyperparathyroidism (PHPT) and parathyroid carcinoma. Such findings underscore the critical importance of the CaSR as a therapeutic target in this family of clinical disorders. New calcimimetic agents are being developed that have the potential to offer improved efficacy and safety compared with currently available calcimimetic compounds. © 2015 Wiley Periodicals, Inc.
Intracellular calcium buffering capacity in isolated squid axons
Brinley, FJ; Tiffert, T; Scarpa, A; Mullins, LJ
1977-01-01
Changes in ionized calcium were studied in axons isolated from living squid by measuring absorbance of the Ca binding dye Arsenazo III using multiwavelength differential absorption spectroscopy. Absorption changes measured in situ were calibrated in vitro with media of ionic composition similar to axoplasm containing CaEGTA buffers. Calcium loads of 50-2,500 μmol/kg axoplasm were induced by microinjection, by stimulation in 112 mM Ca seawater, or by soaking in choline saline with 1-10 mM Ca. Over this range of calcium loading of intact axoplasm, the ionized calcium in the axoplasm rose about 0.6 nM/μM load. Similar loading in axons preteated with carbonyl cyanide 4- trifluoromethoxyphenylhydrazone (FCCP) to inhibit the mitochondrial proton gradient increased ionized calcium by 5-7 percent of the imposed load, i.e. 93-95 percent of the calcium load was buffered by a process insensitive to FCCP. This FCCP- insensitive buffer system was not saturated by the largest calcium loads imposed, indicating a capacity of at least several millimolar. Treatment of previously loaded axons with FCCP or apyrase plus cyanide produced rises in ionized calcium which could be correlated with the extent of the load. Analysis of results indicated that, whereas only 6 percent of the endogenous calcium in fresh axons is stored in the FCCP-sensitive (presumably mitochondrial) buffer system, about 30 percent of an imposed exogenous load in the range of 50-2,500 μM is taken up by this system. PMID:894260
Robin, Gaëlle; Berthier, Christine
2012-01-01
Under resting conditions, external Ca2+ is known to enter skeletal muscle cells, whereas Ca2+ stored in the sarcoplasmic reticulum (SR) leaks into the cytosol. The nature of the pathways involved in the sarcolemmal Ca2+ entry and in the SR Ca2+ leak is still a matter of debate, but several lines of evidence suggest that these Ca2+ fluxes are up-regulated in Duchenne muscular dystrophy. We investigated here SR calcium permeation at resting potential and in response to depolarization in voltage-controlled skeletal muscle fibers from control and mdx mice, the mouse model of Duchenne muscular dystrophy. Using the cytosolic Ca2+ dye Fura2, we first demonstrated that the rate of Ca2+ increase in response to cyclopiazonic acid (CPA)–induced inhibition of SR Ca2+-ATPases at resting potential was significantly higher in mdx fibers, which suggests an elevated SR Ca2+ leak. However, removal of external Ca2+ reduced the rate of CPA-induced Ca2+ increase in mdx and increased it in control fibers, which indicates an up-regulation of sarcolemmal Ca2+ influx in mdx fibers. Fibers were then loaded with the low-affinity Ca2+ dye Fluo5N-AM to measure intraluminal SR Ca2+ changes. Trains of action potentials, chloro-m-cresol, and depolarization pulses evoked transient Fluo5N fluorescence decreases, and recovery of voltage-induced Fluo5N fluorescence changes were inhibited by CPA, demonstrating that Fluo5N actually reports intraluminal SR Ca2+ changes. Voltage dependence and magnitude of depolarization-induced SR Ca2+ depletion were found to be unchanged in mdx fibers, but the rate of the recovery phase that followed depletion was found to be faster, indicating a higher SR Ca2+ reuptake activity in mdx fibers. Overall, CPA-induced SR Ca2+ leak at −80 mV was found to be significantly higher in mdx fibers and was potentiated by removal of external Ca2+ in control fibers. The elevated passive SR Ca2+ leak may contribute to alteration of Ca2+ homeostasis in mdx muscle. PMID:22371362
Stepanchick, Ann; Breitwieser, Gerda E.
2010-01-01
The calcium sensing receptor (CaSR) is a Family 3/C G protein-coupled receptor with slow and partial targeting to the plasma membrane in both native and heterologous cells. We identified cargo receptor family member p24A in yeast two-hybrid screens with the CaSR carboxyl terminus. Interactions were confirmed by immunoprecipitation of either p24A or CaSR in transiently transfected HEK293 cells. Only the immaturely glycosylated form of CaSR interacts with p24A. Dissociation likely occurs in the endoplasmic reticulum Golgi intermediate compartment (ERGIC) or cis-Golgi, since only the uncleaved form of a CaSR mutant sensitive to the trans-Golgi enzyme furin was coimmunoprecipitated with p24A. p24A and p24A(ΔGOLD) significantly increased total and plasma membrane CaSR protein but p24A(FF/AA) did not. The CaSR carboxyl terminus distal to T868 is required for differential sensitivity to p24A and its mutants. Interaction with p24A therefore increases CaSR stability in the ER and enhances plasma membrane targeting. Neither wt Sar1p or the T39N mutant increased CaSR maturation or abundance while the H79G mutant increased abundance but prevented maturation of CaSR. These results suggest that p24A is the limiting factor in CaSR trafficking in the early secretory pathway, and that cycling between the ER and ERGIC protects CaSR from degradation. PMID:20361938
Active Calcium and Strontium Transport in Human Erythrocyte Ghosts
Olson, Erik J.; Cazort, Ralph J.
1969-01-01
Both calcium and strontium could be transported actively from erythrocytes if adenosine triphosphate, guanosine triphosphate, or inosine triphosphate were included in the hypotonic medium used to infuse calcium or strontium into the cells. Acetyl phosphate and pyrophosphate were not energy sources for the transport of either ion. Neither calcium nor strontium transport was accompanied by magnesium exchange, and the addition of Mg++ to the reaction medium in a final concentration of 3.0 mmoles/liter did not promote the transport of either ion. In the absence of nucleotide triphosphates, the addition of 1.5 mmoles/liter of Sr++ to the reaction solution did not bring about active calcium transport and similarly 1.5 mmoles/liter of Ca++ did not bring about active strontium transport. The inclusion of 1.5 mmoles/liter of Ca++ or Sr++ in the reaction medium did not interfere with the transport of the other ion when the erythrocytes were infused with adenosine triphosphate. PMID:4304202
Greenwood, K B; Ko, D; Vander Griend, D A; Sarjeant, G M; Milgram, J W; Garrity, E S; DeLoach, D I; Poeppelmeier, K R; Salvador, P A; Mason, T O
2000-07-24
Substitution of calcium for strontium in LnSr2-xCaxCu2GaO7 (Ln = La, Pr, Nd, Gd, Ho, Er, Tm, and Yb) materials at ambient pressure and 975 degrees C results in complete substitution of calcium for strontium in the lanthanum and praseodymium systems and partial substitution in the other lanthanide systems. The calcium saturation level depends on the size of the Ln cation, and in all cases, a decrease in the lattice parameters with calcium concentration was observed until a common, lower bound, average A-cation size is reached. Site occupancies from X-ray and neutron diffraction experiments for LnSr2-xCaxCu2GaO7 (x = 0 and x = 2) confirm that the A-cations distribute between the two blocking-layer sites and the active-layer site based on size. A quantitative link between cation distribution and relative site-specific cation enthalpy for calcium, strontium, and lanthanum within the gallate structure is derived. The cation distribution in other similar materials can potentially be modeled.
Wang, Li; Widatalla, Sarrah E; Whalen, Diva S; Ochieng, Josiah; Sakwe, Amos M
2017-08-02
Breast cancer (BC) patients with late-stage and/or rapidly growing tumors are prone to develop high serum calcium levels which have been shown to be associated with larger and aggressive breast tumors in post and premenopausal women respectively. Given the pivotal role of the calcium sensing receptor (CaSR) in calcium homeostasis, we evaluated whether polymorphisms of the CASR gene at rs1801725 and rs1801726 SNPs in exon 7, are associated with circulating calcium levels in African American and Caucasian control subjects and BC cases. In this retrospective case-control study, we assessed the mean circulating calcium levels, the distribution of two inactivating CaSR SNPs at rs1801725 and rs1801726 in 199 cases and 384 age-matched controls, and used multivariable regression analysis to determine whether these SNPs are associated with circulating calcium in control subjects and BC cases. We found that the mean circulating calcium levels in African American subjects were higher than those in Caucasian subjects (p < 0.001). As expected, the mean calcium levels were higher in BC cases compared to control subjects (p < 0.001), but the calcium levels in BC patients were independent of race. We also show that in BC cases and control subjects, the major alleles at rs1801725 (G/T, A986S) and at rs1801726 (C/G, Q1011E) were common among Caucasians and African Americans respectively. Compared to the wild type alleles, polymorphisms at the rs1801725 SNP were associated with higher calcium levels (p = 0.006) while those at rs1801726 were not. Using multivariable linear mixed-effects models and adjusting for age and race, we show that circulating calcium levels in BC cases were associated with tumor grade (p = 0.009), clinical stage (p = 0.003) and more importantly, with inactivating mutations of the CASR at the rs1801725 SNP (p = 0.038). These data suggest that decreased sensitivity of the CaSR to calcium due to inactivating polymorphisms at rs1801725, may predispose up to 20% of BC cases to high circulating calcium-associated larger and/or aggressive breast tumors.
SR-80 and US-191 oversize load study.
DOT National Transportation Integrated Search
2013-11-01
The purpose of the SR-80 and US-191 Oversize Load Study is to identify roadway conditions that restrict travel by oversize vehicles on the SR-80 and US-191 study routes. The study also recommends infrastructure and related improvements that will elim...
Behind the curtain: cellular mechanisms for allosteric modulation of calcium-sensing receptors
Cavanaugh, Alice; Huang, Ying; Breitwieser, Gerda E
2012-01-01
Calcium-sensing receptors (CaSR) are integral to regulation of systemic Ca2+ homeostasis. Altered expression levels or mutations in CaSR cause Ca2+ handling diseases. CaSR is regulated by both endogenous allosteric modulators and allosteric drugs, including the first Food and Drug Administration-approved allosteric agonist, Cinacalcet HCl (Sensipar®). Recent studies suggest that allosteric modulators not only alter function of plasma membrane-localized CaSR, but regulate CaSR stability at the endoplasmic reticulum. This brief review summarizes our current understanding of the role of membrane-permeant allosteric agonists in cotranslational stabilization of CaSR, and highlights additional, indirect, signalling-dependent role(s) for membrane-impermeant allosteric drugs. Overall, these studies suggest that allosteric drugs act at multiple cellular organelles to control receptor abundance and hence function, and that drug hydrophobicity can bias the relative contributions of plasma membrane and intracellular organelles to CaSR abundance and signalling. LINKED ARTICLES This article is part of a themed section on the Molecular Pharmacology of G Protein-Coupled Receptors (GPCRs). To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-6. To view the 2010 themed section on the same topic visit http://onlinelibrary.wiley.com/doi/10.1111/bph.2010.159.issue-5/issuetoc PMID:21470201
Transcription factor CREB is involved in CaSR-mediated cytoskeleton gene expression.
Huang, Shuaishuai; Ren, Yu; Wang, Ping; Li, Yanyuan; Wang, Xue; Zhuang, Haihui; Fang, Rong; Wang, Yuduo; Liu, Ningsheng; Hehir, Michael; Zhou, Jeff X
2015-03-01
Our previous studies illustrated that a steady increase of intracellular calcium concentration ([Ca2+]i) was important for maintaining microtubules (MTs) rearrangement in apoptotic cells. However, little is known about the effect of calcium sensing receptor (CaSR)-mediated increase in [Ca2+]i on cytoskeleton gene expression. We examined the impact of taxol or CaSR agonist/antagonist on the regulation of [Ca2+]i concentration, cytoskeleton arrangement, phosphorylated CREB and cytoskeleton gene expressions in HeLa cells with dominant negative plasmid of CREB (PM). This study demonstrated that Gdcl3 (a specific CaSR agonist) evoked a rapid increase of [Ca2+]i, formed a rigid bundle of MTs which surrounded the nucleus and decreased the cytoskeleton gene expressions in HeLa cells. These effects were rescued by addition of NPS2390 (a specific CaSR antagonist). Moreover, CaSR activity affected cytoskeleton gene expression through transcription factor CREB. Histoscores of pCREB immunoreactivity in tissues of cervical adenocarcinoma, renal clear cell carcinoma, and diffuse large B-cell lymphoma were markedly increased compared with non malignant tissue. These data demonstrate, for the first time, that CaSR-mediated increase in [Ca2+]i probably modulate cytoskeleton organization and gene expression via transcription factor. © 2014 Wiley Periodicals, Inc.
Zimmerman, C.E.
2005-01-01
Analysis of otolith strontium (Sr) or strontium-to-calcium (Sr:Ca) ratios provides a powerful tool to reconstruct the chronology of migration among salinity environments for diadromous salmonids. Although use of this method has been validated by examination of known individuals and translocation experiments, it has never been validated under controlled experimental conditions. In this study, incorporation of otolith Sr was tested across a range of salinities and resulting levels of ambient Sr and Ca concentrations in juvenile chinook salmon (Oncorhynchus tshawytscha), coho salmon (Oncorhynchus kisutch), sockeye salmon (Oncorhynchus nerka), rainbow trout (Oncorhynchus rnykiss), and Arctic char (Salvelinus alpinus). Experimental water was mixed, using stream water and seawater as end members, to create experimental salinities of 0.1, 6.3, 12.7, 18.6, 25.5, and 33.0 psu. Otolith Sr and Sr:Ca ratios were significantly related to salinity for all species (r2 range: 0.80-0.91) but provide only enough predictive resolution to discriminate among fresh water, brackish water, and saltwater residency. These results validate the use of otolith Sr:Ca ratios to broadly discriminate salinity histories encountered by salmonids but highlight the need for further research concerning the influence of osmoregulation and physiological changes associated with smoking on otolith microchemistry.
Rodrat, Mayuree; Wongdee, Kannikar; Panupinthu, Nattapon; Thongbunchoo, Jirawan; Teerapornpuntakit, Jarinthorn; Krishnamra, Nateetip; Charoenphandhu, Narattaphol
2018-02-15
Overdose of oral calcium supplement and excessive intestinal calcium absorption can contribute pathophysiological conditions, e.g., nephrolithiasis, vascular calcification, dementia, and cardiovascular accident. Since our previous investigation has indicated that fibroblast growth factor (FGF)-23 could abolish the 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ]-enhanced calcium absorption, we further hypothesized that FGF-23 produced locally in the enterocytes might be part of a local negative feedback loop to regulate calcium absorption. Herein, 1,25(OH) 2 D 3 was found to enhance the transcellular calcium transport across the epithelium-like Caco-2 monolayer, and this stimulatory effect was diminished by preceding prolonged exposure to high-dose 1,25(OH) 2 D 3 or high concentration of apical ionized calcium. Pretreatment with a neutralizing antibody for FGF-23 prevented this negative feedback regulation of calcium hyperabsorption induced by 1,25(OH) 2 D 3 . FGF-23 exposure completely abolished the 1,25(OH) 2 D 3 -enhanced calcium transport. Western blot analysis revealed that FGF-23 expression was upregulated in a dose-dependent manner by 1,25(OH) 2 D 3 or apical calcium exposure. Finally, calcium-sensing receptor (CaSR) inhibitors were found to prevent the apical calcium-induced suppression of calcium transport. In conclusion, prolonged exposure to high apical calcium and calcium hyperabsorption were sensed by CaSR, which, in turn, increased FGF-23 expression to suppress calcium transport. This local negative feedback loop can help prevent unnecessary calcium uptake and its detrimental consequences. Copyright © 2018 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Balter, Vincent; Person, Alain; Labourdette, Nathalie; Drucker, Dorothée; Renard, Maurice; Vandermeersch, Bernard
2001-01-01
Strontium-calcium (Sr/Ca) and barium-calcium (Ba/Ca) ratios are reduced constantly between diet and bioapatite in mammal organisms. This phenomenon leads to a reduction in the Sr/Ca and Ba/Ca ratios at higher trophic level in predator-prey mammalian communities, and is applied here to the reconstruction of a castelperronian food web, which includes a Neanderthal specimen. Adapted chemical pretreatment allows to isolate bioapatite from diagenetic compounds for analysis of Ca, Sr and Ba. Sr/Ca and Ba/Ca results of the fauna are consistent with trophic predictions. Initial results for the Neandertal suggest that he was mostly carnivorous. Distribution of Ba/Ca values of bones of herbivorous taxa reveals that ruminant animals can be distinguished from non-ruminants. The biosegregation model predicts that the diet of the Neandertal was composed by about 97 % in weight of meat with a weak contribution of vegetable or fish, and that the association of fish and plant is excluded in any proportion.
Synthesis of highly phase pure BSCCO superconductors
Dorris, S.E.; Poeppel, R.B.; Prorok, B.C.; Lanagan, M.T.; Maroni, V.A.
1995-11-21
An article and method of manufacture (Bi, Pb)-Sr-Ca-Cu-O superconductor are disclosed. The superconductor is manufactured by preparing a first powdered mixture of bismuth oxide, lead oxide, strontium carbonate, calcium carbonate and copper oxide. A second powdered mixture is then prepared of strontium carbonate, calcium carbonate and copper oxide. The mixtures are calcined separately with the two mixtures then combined. The resulting combined mixture is then subjected to a powder in tube deformation and thermal processing to produce a substantially phase pure (Bi, Pb)-Sr-Ca-Cu-O superconductor. 5 figs.
Synthesis of highly phase pure BSCCO superconductors
Dorris, Stephen E.; Poeppel, Roger B.; Prorok, Barton C.; Lanagan, Michael T.; Maroni, Victor A.
1995-01-01
An article and method of manufacture of (Bi, Pb)-Sr-Ca-Cu-O superconductor. The superconductor is manufactured by preparing a first powdered mixture of bismuth oxide, lead oxide, strontium carbonate, calcium carbonate and copper oxide. A second powdered mixture is then prepared of strontium carbonate, calcium carbonate and copper oxide. The mixtures are calcined separately with the two mixtures then combined. The resulting combined mixture is then subjected to a powder in tube deformation and thermal processing to produce a substantially phase pure (Bi, Pb)-Sr-Ca-Cu-O superconductor.
Nagano, Nobuo; Tsutsui, Takaaki
2016-06-01
Calcimimetics act as positive allosteric modulators of the calcium-sensing receptor (CaSR), thereby decreasing parathyroid hormone (PTH) secretion from the parathyroid glands. On the other hand, negative allosteric modulators of the CaSR with stimulatory effect on PTH secretion are termed calcilytics. The calcimimetic cinacalcet hydrochloride (cinacalcet) is the world's first allosteric modulator of G protein-coupled receptor to enter the clinical market. Cinacalcet just tunes the physiological effects of Ca(2+), an endogenous ligand, therefore, shows high selectivity and low side effects. Calcimimetics also increase cell surface CaSR expression by acting as pharmacological chaperones (pharmacoperones). It is considered that the cinacalcet-induced upper gastrointestinal problems are resulted from enhanced physiological responses to Ca(2+) and amino acids via increased sensitivity of digestive tract CaSR by cinacalcet. While clinical developments of calcilytics for osteoporosis were unfortunately halted or terminated due to paucity of efficacy, it is expected that calcilytics may be useful for the treatment of patients with activating CaSR mutations, asthma, and idiopathic pulmonary artery hypertension.
Zhang, Chen; Zhang, Tuo; Zou, Juan; Miller, Cassandra Lynn; Gorkhali, Rakshya; Yang, Jeong-Yeh; Schilmiller, Anthony; Wang, Shuo; Huang, Kenneth; Brown, Edward M; Moremen, Kelley W; Hu, Jian; Yang, Jenny J
2016-05-01
Ca(2+)-sensing receptors (CaSRs) modulate calcium and magnesium homeostasis and many (patho)physiological processes by responding to extracellular stimuli, including divalent cations and amino acids. We report the first crystal structure of the extracellular domain (ECD) of human CaSR bound with Mg(2+) and a tryptophan derivative ligand at 2.1 Å. The structure reveals key determinants for cooperative activation by metal ions and aromatic amino acids. The unexpected tryptophan derivative was bound in the hinge region between two globular ECD subdomains, and represents a novel high-affinity co-agonist of CaSR. The dissection of structure-function relations by mutagenesis, biochemical, and functional studies provides insights into the molecular basis of human diseases arising from CaSR mutations. The data also provide a novel paradigm for understanding the mechanism of CaSR-mediated signaling that is likely shared by the other family C GPCR [G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor] members and can facilitate the development of novel CaSR-based therapeutics.
Gonzalez, Daniel R.; Treuer, Adriana V.; Lamirault, Guillaume; Mayo, Vera; Cao, Yenong; Dulce, Raul A.
2014-01-01
Duchenne muscular dystrophy may affect cardiac muscle, producing a dystrophic cardiomyopathy in humans and the mdx mouse. We tested the hypothesis that oxidative stress participates in disrupting calcium handling and contractility in the mdx mouse with established cardiomyopathy. We found increased expression (fivefold) of the NADPH oxidase (NOX) 2 in the mdx hearts compared with wild type, along with increased superoxide production. Next, we tested the impact of NOX2 inhibition on contractility and calcium handling in isolated cardiomyocytes. Contractility was decreased in mdx myocytes compared with wild type, and this was restored toward normal by pretreating with apocynin. In addition, the amplitude of evoked intracellular Ca2+ concentration transients that was diminished in mdx myocytes was also restored with NOX2 inhibition. Total sarcoplasmic reticulum (SR) Ca2+ content was reduced in mdx hearts and normalized by apocynin treatment. Additionally, NOX2 inhibition decreased the production of spontaneous diastolic calcium release events and decreased the SR calcium leak in mdx myocytes. In addition, nitric oxide (NO) synthase 1 (NOS-1) expression was increased eightfold in mdx hearts compared with wild type. Nevertheless, cardiac NO production was reduced. To test whether this paradox implied NOS-1 uncoupling, we treated cardiac myocytes with exogenous tetrahydrobioterin, along with the NOX inhibitor VAS2870. These agents restored NO production and phospholamban phosphorylation in mdx toward normal. Together, these results demonstrate that, in mdx hearts, NOX2 inhibition improves the SR calcium handling and contractility, partially by recoupling NOS-1. These findings reveal a new layer of nitroso-redox imbalance in dystrophic cardiomyopathy. PMID:25015966
Kanchana, Ponnusamy; Sekar, Chinnathambi
2010-01-01
Biphasic calcium phosphate (BCP) ceramics are suitable for synthetic bone applications. The strontium substituted calcium phosphate ceramics have potential for use in orthopedic surgeries. Aim of the present work is to introduce strontium into BCP (composed of hydroxyapatite and tricalcium phosphate) ceramics and to study their bioactivity and mechanical properties. BCP ceramics have been synthesized at room temperature under the physiological pH of 7.4 by gel method in the presence of strontium (5, 10 M %). The appropriate choice of anhydrous CaCl₂ as precursor solution has promoted the formation of BCP instead of pure HA for CaCl₂.2H₂O. Powder X-ray diffraction analysis confirmed the formation of BCP with different HA and ß -TCP ratios depending upon the Sr content. The presence of Sr has reduced the nucleation and growth rate of BCP when compared to pure system. The SEM micrographs showed that the microstructural morphology of BCP changes from fibrous to platelet. Nanoindentation studies indicate a significant decrease in the hardness and elastic modulus values of BCP ceramics due to Sr doping. In vitro bioactivity study has revealed the formation of apatite layer on the Sr doped BCP samples and the doping enhanced its bioactivity.
Federico, Marilen; Portiansky, Enrique L; Sommese, Leandro; Alvarado, Francisco J; Blanco, Paula G; Zanuzzi, Carolina N; Dedman, John; Kaetzel, Marcia; Wehrens, Xander H T; Mattiazzi, Alicia; Palomeque, Julieta
2017-06-15
Spontaneous sarcoplasmic reticulum (SR) Ca 2+ release events increased in fructose-rich diet mouse (FRD) myocytes vs. control diet (CD) mice, in the absence of significant changes in SR Ca 2+ load. In HEK293 cells, hyperglycaemia significantly enhanced [ 3 H]ryanodine binding and Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) phosphorylation of RyR2-S2814 residue vs. normoglycaemia. These increases were prevented by CaMKII inhibition. FRD significantly augmented cardiac apoptosis in WT vs. CD-WT mice, which was prevented by co-treatment with the reactive oxygen species scavenger Tempol. Oxidative stress was also increased in FRD-SR-autocamide inhibitory peptide (AIP) mice, expressing the SR-targeted CaMKII inhibitor AIP, without any significant enhancement of apoptosis vs. CD-SR-AIP mice. FRD produced mitochondrial swelling and membrane depolarization in FRD-WT mice but not in FRD-S2814A mice, in which the CaMKII site on ryanodine receptor 2 was ablated. FRD decreased mitochondrial area, mean Feret diameter and the mean distance between SR and the outer mitochondrial membrane vs. CD hearts. This remodelling was prevented in AC3I mice, with cardiac-targeted CaMKII inhibition. The impact of cardiac apoptosis in pre-diabetic stages of diabetic cardiomyopathy is unknown. We show that myocytes from fructose-rich diet (FRD) animals exhibit arrhythmias produced by exacerbated Ca 2+ /calmodulin-protein kinase (CaMKII) activity, ryanodine receptor 2 (RyR2) phosphorylation and sarcoplasmic reticulum (SR) Ca 2+ leak. We tested the hypothesis that this mechanism also underlies cardiac apoptosis in pre-diabetes. We generated a pre-diabetic model in FRD mice. FRD mice showed an increase in oxidative stress, hypertrophy and systolic dysfunction. FRD myocytes exhibited enhanced SR Ca 2+ spontaneous events in the absence of SR Ca 2+ load alterations vs. control-diet (CD) myocytes. In HEK293 cells, hyperglycaemia significantly enhanced [ 3 H]ryanodine binding and CaMKII phosphorylation of RyR2-S2814 residue vs. normoglycaemia. CaMKII inhibition prevented hyperglycaemia-induced alterations. FRD also evoked cardiac apoptosis in WT mice vs. CD-WT mice. Co-treatment with the reactive oxygen species scavenger Tempol prevented FRD-induced apoptosis in WT mice. In contrast, FRD enhanced oxidative stress but not apoptosis in FRD-SR-AIP mice, in which a CaMKII inhibitor is targeted to the SR. FRD produced mitochondrial membrane depolarization in WT mice but not in S2814A mice, in which the CaMKII phosphorylation site on RyR2 was ablated. Furthermore, FRD decreased mitochondrial area, mean Feret diameter and mean SR-mitochondrial distance vs. CD-WT hearts. This remodelling was prevented in AC3I mice, with cardiac-targeted CaMKII inhibition. CaMKII phosphorylation of RyR2, SR Ca 2+ leak and mitochondrial membrane depolarization are critically involved in the apoptotic pathway of the pre-diabetic heart. The FRD-induced decrease in SR-mitochondrial distance is likely to additionally favour Ca 2+ transit between the two organelles. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.
Cooper, Leroy L; Li, Weiyan; Lu, Yichun; Centracchio, Jason; Terentyeva, Radmila; Koren, Gideon; Terentyev, Dmitry
2013-01-01
Ageing is associated with a blunted response to sympathetic stimulation and an increased risk of arrhythmia and sudden cardiac death. Aberrant calcium (Ca2+) handling is an important contributor to the electrical and contractile dysfunction associated with ageing. Yet, the specific molecular mechanisms underlying abnormal Ca2+ handling in ageing heart remain poorly understood. In this study, we used ventricular myocytes isolated from young (5–9 months) and old (4–6 years) rabbit hearts to test the hypothesis that changes in Ca2+ homeostasis are caused by post-translational modification of ryanodine receptors (RyRs) by mitochondria-derived reactive oxygen species (ROS) generated in the ageing heart. Changes in parameters of Ca2+ handling were determined by measuring cytosolic and intra-sarcoplasmic reticulum (SR) Ca2+ dynamics in intact and permeabilized ventricular myocytes using confocal microscopy. We also measured age-related changes in ROS production and mitochondria membrane potential using a ROS-sensitive dye and a mitochondrial voltage-sensitive fluorescent indicator, respectively. In permeablized myocytes, ageing did not change SERCA activity and spark frequency but decreased spark amplitude and SR Ca2+ load suggesting increased RyR activity. Treatment with the antioxidant dithiothreitol reduced RyR-mediated SR Ca2+ leak in permeabilized myocytes from old rabbit hearts to the level comparable to young. Moreover, myocytes from old rabbits had more depolarized mitochondria membrane potential and increased rate of ROS production. Under β-adrenergic stimulation, Ca2+ transient amplitude, SR Ca2+ load, and latency of pro-arrhythmic spontaneous Ca2+ waves (SCWs) were decreased while RyR-mediated SR Ca2+ leak was increased in cardiomyocytes from old rabbits. Additionally, with β-adrenergic stimulation, scavenging of mitochondrial ROS in myocytes from old rabbit hearts restored redox status of RyRs, which reduced SR Ca2+ leak, ablated most SCWs, and increased latency to levels comparable to young. These data indicate that an age-associated increase of ROS production by mitochondria leads to the thiol-oxidation of RyRs, which underlies the hyperactivity of RyRs and thereby shortened refractoriness of Ca2+ release in cardiomyocytes from the ageing heart. This mechanism probably plays an important role in the increased incidence of arrhythmia and sudden death in the ageing population. PMID:24042501
Saniewski, Michał; Zalewska, Tamara
2016-01-01
In the period 2005-2011 total atmospheric fallout and the riverine input to the Gulf of Gdańsk was 1168.8 GBq of (90)Sr and 424.1 GBq (137)Cs. The major source of both radionuclides to the Gulf of Gdańsk is the Vistula river; its contribution reached 99.7% in the case of (90)Sr and 95.8% regarding (137)Cs. The atmospheric load of (137)Cs, 18.1 GBq, was nearly 4 times bigger than in the case of (90)Sr (3.75 GBq). In the period 2005-2010, the average annual atmospheric load were at the levels 2-3 GBq for (137)Cs and 0.4-0.6 GBq for (90)Sr, while in 2011, due to the Fukuchima Dai-ichi power plant break down, an increase of annual atmospheric loads was noted to 5.3 GBq of (137)Cs and to 0.87 GBq of (90)Sr. The additional loads did not have an increasing effect on the activity concentrations of (137)Cs and (90)Sr in seawater of the Gulf of Gdańsk, where mean activity concentrations in seawater were equal to 31.1 Bq m(-3) and 7.6 Bq m(-3) in the case of (137)Cs and (90)Sr respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.
Royer, Leandro; Pouvreau, Sandrine; Ríos, Eduardo
2008-01-01
Intracellular calcium signals regulate multiple cellular functions. They depend on release of Ca2+ from cellular stores into the cytosol, a process that in many types of cells appears to be tightly controlled by changes in [Ca2+] within the store. In contrast with cardiac muscle, where depletion of Ca2+ in the sarcoplasmic reticulum is a crucial determinant of termination of Ca2+ release, in skeletal muscle there is no agreement regarding the sign, or even the existence of an effect of SR Ca2+ level on Ca2+ release. To address this issue we measured Ca2+ transients in mouse flexor digitorum brevis (FDB) skeletal muscle fibres under voltage clamp, using confocal microscopy and the Ca2+ monitor rhod-2. The evolution of Ca2+ release flux was quantified during long-lasting depolarizations that reduced severely the Ca2+ content of the SR. As in all previous determinations in mammals and non-mammals, release flux consisted of an early peak, relaxing to a lower level from which it continued to decay more slowly. Decay of flux in this second stage, which has been attributed largely to depletion of SR Ca2+, was studied in detail. A simple depletion mechanism without change in release permeability predicts an exponential decay with time. In contrast, flux decreased non-exponentially, to a finite, measurable level that could be maintained for the longest pulses applied (1.8 s). An algorithm on the flux record allowed us to define a quantitative index, the normalized flux rate of change (NFRC), which was shown to be proportional to the ratio of release permeability P and inversely proportional to Ca2+ buffering power B of the SR, thus quantifying the ‘evacuability’ or ability of the SR to empty its content. When P and B were constant, flux then decayed exponentially, and NFRC was equal to the exponential rate constant. Instead, in most cases NFRC increased during the pulse, from a minimum reached immediately after the early peak in flux, to a time between 200 and 250 ms, when the index was no longer defined. NFRC increased by 111% on average (in 27 images from 18 cells), reaching 300% in some cases. The increase may reflect an increase in P, a decrease in B, or both. On experimental and theoretical grounds, both changes are to be expected upon SR depletion. A variable evacuability helps maintain a constant Ca2+ output under conditions of diminishing store Ca2+ load. PMID:18687715
Zimmerman, Christian E.; Nielsen, Roger L.
2003-01-01
The use of strontium-to-calcium (Sr/Ca) ratios in otoliths is becoming a standard method to describe life history type and the chronology of migrations between freshwater and seawater habitats in teleosts (e.g. Kalish, 1990; Radtke et al., 1990; Secor, 1992; Rieman et al., 1994; Radtke, 1995; Limburg, 1995; Tzeng et al. 1997; Volk et al., 2000; Zimmerman, 2000; Zimmerman and Reeves, 2000, 2002). This method provides critical information concerning the relationship and ecology of species exhibiting phenotypic variation in migratory behavior (Kalish, 1990; Secor, 1999). Methods and procedures, however, vary among laboratories because a standard method or protocol for measurement of Sr in otoliths does not exist. In this note, we examine the variations in analytical conditions in an effort to increase precision of Sr/Ca measurements. From these findings we argue that precision can be maximized with higher beam current (although there is specimen damage) than previously recommended by Gunn et al. (1992).
A process for the development of strontium hydroxyapatite
NASA Astrophysics Data System (ADS)
Zahra, N.; Fayyaz, M.; Iqbal, W.; Irfan, M.; Alam, S.
2014-06-01
A procedure for the preparation of Strontium Hydroxyapatite is adapted to produce high purity and better homogeneity ceramic with good Crystallinity. The strontium substituted bone cement has potential for use in orthopedic surgeries. Ionic Strontium (Sr) in humans shares the same physiological pathway as calcium and can be deposited in the mineral structure of the bone. In the present study, a novel concept of preparing Sr-contained Hydroxyapatite bone cement by using a precipitation method is proposed to get an ideal biomaterial that possesses potential degradability and more excellent pharmacological effect. Chemical analysis, Fourier Transform Infra Red analysis and Thermogravimetric/ Differential Scanning Calorimetric studies were conducted on prepared Strontium Hydroxyapatite sample to characterize the incorporation of 15% Sr2+ into the crystal lattice of Hydroxyapatite. Strontium was quantitatively incorporated into Hydroxyapatite where its substitution for calcium provoked a linear shift of the infrared absorption bands of the hydroxyl and phosphate groups. Thus, the formation of Sr-HAp was confirmed by Chemical Analysis, FT-IR and TGA/DSC results.
Selective labeling of retinal ganglion cells with calcium indicators by retrograde loading in vitro
Behrend, Matthew R.; Ahuja, Ashish K.; Humayun, Mark S.; Weiland, James D.; Chow, Robert H.
2012-01-01
Here we present a retrograde loading technique that makes it possible for the first time to rapidly load a calcium indicator in the majority of retinal ganglion cells (RGCs) in salamander retina, and then to observe physiological activity of these dye-loaded cells. Dextran-conjugated calcium indicator, dissolved in water, was applied to the optic nerve stump. Following dye loading, the isolated retina was mounted on a microelectrode array to demonstrate that electrical activity and calcium activity were preserved, as the retina responded to electrical stimuli. PMID:19428523
Tang, Lieqi; Cheng, Catherine Y.; Sun, Xiangrong; Pedicone, Alexandra J.; Mohamadzadeh, Mansour; Cheng, Sam X.
2016-01-01
Different from other epithelia, the intestinal epithelium has the complex task of providing a barrier impeding the entry of toxins, food antigens, and microbes, while at the same time allowing for the transfer of nutrients, electrolytes, water, and microbial metabolites. These molecules/organisms are transported either transcellularly, crossing the apical and basolateral membranes of enterocytes, or paracellularly, passing through the space between enterocytes. Accordingly, the intestinal epithelium can affect energy metabolism, fluid balance, as well as immune response and tolerance. To help accomplish these complex tasks, the intestinal epithelium has evolved many sensing receptor mechanisms. Yet, their roles and functions are only now beginning to be elucidated. This article explores one such sensing receptor mechanism, carried out by the extracellular calcium-sensing receptor (CaSR). In addition to its established function as a nutrient sensor, coordinating food digestion, nutrient absorption, and regulating energy metabolism, we present evidence for the emerging role of CaSR in the control of intestinal fluid homeostasis and immune balance. An additional role in the modulation of the enteric nerve activity and motility is also discussed. Clearly, CaSR has profound effects on many aspects of intestinal function. Nevertheless, more work is needed to fully understand all functions of CaSR in the intestine, including detailed mechanisms of action and specific pathways involved. Considering the essential roles CaSR plays in gastrointestinal physiology and immunology, research may lead to a translational opportunity for the development of novel therapies that are based on CaSR's unique property of using simple nutrients such as calcium, polyamines, and certain amino acids/oligopeptides as activators. It is possible that, through targeting of intestinal CaSR with a combination of specific nutrients, oral solutions that are both inexpensive and practical may be developed to help in conditioning the gut microenvironment and in maintaining digestive health. PMID:27458380
Tang, Lieqi; Cheng, Catherine Y; Sun, Xiangrong; Pedicone, Alexandra J; Mohamadzadeh, Mansour; Cheng, Sam X
2016-01-01
Different from other epithelia, the intestinal epithelium has the complex task of providing a barrier impeding the entry of toxins, food antigens, and microbes, while at the same time allowing for the transfer of nutrients, electrolytes, water, and microbial metabolites. These molecules/organisms are transported either transcellularly, crossing the apical and basolateral membranes of enterocytes, or paracellularly, passing through the space between enterocytes. Accordingly, the intestinal epithelium can affect energy metabolism, fluid balance, as well as immune response and tolerance. To help accomplish these complex tasks, the intestinal epithelium has evolved many sensing receptor mechanisms. Yet, their roles and functions are only now beginning to be elucidated. This article explores one such sensing receptor mechanism, carried out by the extracellular calcium-sensing receptor (CaSR). In addition to its established function as a nutrient sensor, coordinating food digestion, nutrient absorption, and regulating energy metabolism, we present evidence for the emerging role of CaSR in the control of intestinal fluid homeostasis and immune balance. An additional role in the modulation of the enteric nerve activity and motility is also discussed. Clearly, CaSR has profound effects on many aspects of intestinal function. Nevertheless, more work is needed to fully understand all functions of CaSR in the intestine, including detailed mechanisms of action and specific pathways involved. Considering the essential roles CaSR plays in gastrointestinal physiology and immunology, research may lead to a translational opportunity for the development of novel therapies that are based on CaSR's unique property of using simple nutrients such as calcium, polyamines, and certain amino acids/oligopeptides as activators. It is possible that, through targeting of intestinal CaSR with a combination of specific nutrients, oral solutions that are both inexpensive and practical may be developed to help in conditioning the gut microenvironment and in maintaining digestive health.
Spalding, B P; Spalding, I R
2001-01-15
Strontium-90 is a major hazardous contaminant of radioactive wastewater and its processing sludges at many Department of Energy (DOE) facilities. In the past, such contaminated wastewater and sludge have been disposed in soil seepage pits, lagoons, or cribs often under highly perturbed alkaline conditions (pH > 12) where 90Sr solubility is low and its adsorption to surrounding soil is high. As natural weathering returns these soils to near-neutral or slightly acidic conditions, the adsorbed and precipitated calcium and magnesium phases, in which 90Sr is carried, change significantly in both nature and amounts. No comprehensive computational method has been formulated previously to quantitatively simulate the dynamics of 90Sr in the soil-groundwater environment under such dynamic and wide-ranging conditions. A computational code, the Hydrologic Utility Model for Demonstrating Integrated Nuclear Geochemical Environmental Responses (HUMDINGER), was composed to describe the changing equilibria of 90Sr in soil based on its causative chemical reactions including soil buffering, pH-dependent cation-exchange capacity, cation selectivity, and the precipitation/dissolution of calcium carbonate, calcium hydroxide, and magnesium hydroxide in response to leaching groundwater characteristics including pH, acid-neutralizing capacity, dissolved cations, and inorganic carbonate species. The code includes a simulation of one-dimensional transport of 90Sr through a soil column as a series of soil mixing cells where the equilibrium soluble output from one cell is applied to the next cell. Unamended soil leaching and highly alkaline soil treatments, including potassium hydroxide, sodium silicate, and sodium aluminate, were simulated and compared with experimental findings using large (10 kg) soil columns that were leached with 90Sr-contaminated groundwater after treatment. HUMDINGER's simulations were in good agreement with dynamic experimental observations of soil exchange capacity, exchangeable cations, total 90Sr, and pH values of layers within the soil columns and of column effluents.
Tess E. Busch,; Flannery, Jennifer A.; Richey, Julie N.; Stathakopoulos, Anastasios
2015-11-13
An inverse relationship has been demonstrated between water temperature and the ratio of strontium to calcium (Sr/Ca) in coral aragonite for a number of Pacific species of the genus Porites. This empirically determined relationship has been used to reconstruct past sea-surface temperature (SST) from modern and Holocene age coral archives. A study was conducted to investigate this relationship for Porites astreoides to determine the potential for using these corals as a paleotemperature archive in the Caribbean and western tropical Atlantic Ocean. Skeletal aragonite from a P. astreoides colony growing offshore of the southeast coast of Florida was subsampled with a mean temporal resolution of 14 samples per year and analyzed for Sr/Ca. The resulting Sr/Ca time series yielded well-defined annual cycles that correspond to annual growth bands in the coral. Sr/Ca was regressed against a monthly SST record from C-MAN buoy station FWYF1 (located at Fowey Rocks, Florida), resulting in the following Sr/Ca-SST relationship: Sr/Ca = –0.040*SST + 10.128 (R = –0.77). A 10-year time series of Sr/Ca-derived SST yields annual cycles with a 10–12 degree Celsius seasonal amplitude, consistent with available local instrumental records. We conclude that Sr/Ca in Porites astreoides from the Caribbean/Atlantic region has high potential for developing subannually resolved modern and recent Holocene SST records.
Bioactive Polymeric Nanoparticles for Periodontal Therapy
Alfonso-Rodríguez, Camilo Andrés; Medina-Castillo, Antonio L.; Alaminos, Miguel; Toledano, Manuel
2016-01-01
Aims to design calcium and zinc-loaded bioactive and cytocompatible nanoparticles for the treatment of periodontal disease. Methods PolymP-nActive nanoparticles were zinc or calcium loaded. Biomimetic calcium phosphate precipitation on polymeric particles was assessed after 7 days immersion in simulated body fluid, by scanning electron microscopy attached to an energy dispersive analysis system. Amorphous mineral deposition was probed by X-ray diffraction. Cell viability analysis was performed using oral mucosa fibroblasts by: 1) quantifying the liberated deoxyribonucleic acid from dead cells, 2) detecting the amount of lactate dehydrogenase enzyme released by cells with damaged membranes, and 3) by examining the cytoplasmic esterase function and cell membranes integrity with a fluorescence-based method using the Live/Dead commercial kit. Data were analyzed by Kruskal-Wallis and Mann-Whitney tests. Results Precipitation of calcium and phosphate on the nanoparticles surfaces was observed in calcium-loaded nanoparticles. Non-loaded nanoparticles were found to be non-toxic in all the assays, calcium and zinc-loaded particles presented a dose dependent but very low cytotoxic effect. Conclusions The ability of calcium-loaded nanoparticles to promote precipitation of calcium phosphate deposits, together with their observed non-toxicity may offer new strategies for periodontal disease treatment. PMID:27820866
Xiang, J Z; Kentish, J C
1995-03-01
The aim was to investigate whether, and how, increases in inorganic phosphate (Pi) and ADP, similar to those occurring intracellularly during early myocardial ischaemia, affect the calcium handling of the sarcoplasmic reticulum. Rat ventricular trabeculae were permeabilised with saponin. The physiological process of calcium induced calcium release (CICR) from the muscle sarcoplasmic reticulum was triggered via flash photolysis of the "caged Ca2+", nitr-5. Alternatively, calcium release was induced by rapid application of caffeine to give an estimate of sarcoplasmic reticular calcium loading. The initial rate of sarcoplasmic reticular calcium pumping was also assessed by photolysis of caged ATP at saturating [Ca2+]. Myoplasmic [Ca2+] (using fluo-3) and isometric force were measured. Pi (2-20 mM) significantly depressed the magnitude of CICR and the associated force transient. Sarcoplasmic reticular calcium loading was inhibited even more than CICR by Pi, suggesting that reduced calcium loading could account for all of the inhibitory effect of Pi on CICR and that Pi may slightly activate the calcium release mechanism. The reduced sarcoplasmic reticular calcium loading seemed to be due to a fall in the free energy of ATP hydrolysis (delta GATP) available for the calcium pump, since equal decreases in delta GATP produced by adding both Pi and ADP in various ratios caused similar falls in the calcium loading of the sarcoplasmic reticulum. The caged ATP experiments indicated that Pi (20 mM) did not affect the rate constant of sarcoplasmic reticular calcium uptake. ADP (10 mM) alone, or with 1 mM Pi, inhibited calcium loading. In spite of this, ADP (10 mM) did not alter CICR and, when 1 mM Pi was added, ADP increased CICR above control. An increase in intracellular Pi reduces sarcoplasmic reticular calcium loading and thus depresses the CICR. This could be an important contributing factor in the hypoxic or ischaemic contractile failure of the myocardium. However the detrimental effect of Pi may be offset to some extent by a stimulatory action of ADP on the calcium release mechanism of CICR.
Properties of Ca2+ sparks evoked by action potentials in mouse ventricular myocytes
Bridge, John H B; Ershler, Philip R; Cannell, Mark B
1999-01-01
Calcium sparks were examined in enzymatically dissociated mouse cardiac ventricular cells using the calcium indicator fluo-3 and confocal microscopy. The properties of the mouse cardiac calcium spark are generally similar to those reported for other species.Examination of the temporal relationship between the action potential and the time course of calcium spark production showed that calcium sparks are more likely to occur during the initial repolarization phase of the action potential. The latency of their occurrence varied by less than 1·4 ms (s.d.) and this low variability may be explained by the interaction of the gating of L-type calcium channels with the changes in driving force for calcium entry during the action potential.When fixed sites within the cell are examined, calcium sparks have relatively constant amplitude but the amplitude of the sparks was variable among sites. The low variability of the amplitude of the calcium sparks suggests that more than one sarcoplasmic reticulum (SR) release channel must be involved in their genesis. Noise analysis (with the assumption of independent gating) suggests that > 18 SR calcium release channels may be involved in the generation of the calcium spark. At a fixed site, the response is close to ‘all-or-none’ behaviour which suggests that calcium sparks are indeed elementary events underlying cardiac excitation-contraction coupling.A method for selecting spark sites for signal averaging is presented which allows the time course of the spark to be examined with high temporal and spatial resolution. Using this method we show the development of the calcium spark at high signal-to-noise levels. PMID:10381593
NASA Astrophysics Data System (ADS)
Possenti, Elena; Colombo, Chiara; Conti, Claudia; Gigli, Lara; Merlini, Marco; Plaisier, Jasper Rikkert; Realini, Marco; Gatta, G. Diego
2018-05-01
Diammonium hydrogen phosphate (DAP)-based consolidating treatments react with carbonatic stones and form calcium phosphates phases, whose composition depends on the availability of free calcium ions. In this work, an innovative non-destructive approach based on grazing incidence X-ray diffraction (GIXRD) with synchrotron radiation (SR) is used to investigate DAP-treated Carrara marble specimens and to study the influence of the substrate composition on the crystallization of calcium phosphate phases. The outcomes indicate that the presence of compositional micro-heterogeneity of Carrara marble favours the formation of specific phases. Dicalcium phosphate dihydrate, a calcium phosphate with a low Ca/P molar ratio, is formed on carbonatic phases with a low Ca amount, such as dolomite grains and Mg-containing veins. Furthermore, this study highlights the potentialities of SR-GIXRD as a powerful non-destructive tool for the diagnostic of Cultural Heritage objects since it allows investigating the conservation history of stone materials and their interaction with the environment.
Del Buffa, Stefano; Bonini, Massimo; Ridi, Francesca; Severi, Mirko; Losi, Paola; Volpi, Silvia; Al Kayal, Tamer; Soldani, Giorgio; Baglioni, Piero
2015-06-15
This paper reports on the preparation, characterization, and cytotoxicity of a hybrid nanocomposite material made of Sr(II)-loaded Halloysite nanotubes included within a biopolymer (3-polyhydroxybutyrate-co-3-hydroxyvalerate) matrix. The Sr(II)-loaded inorganic scaffold is intended to provide mechanical resistance, multi-scale porosity, and to favor the in-situ regeneration of bone tissue thanks to its biocompatibility and bioactivity. The interaction of the hybrid system with the physiological environment is mediated by the biopolymer coating, which acts as a binder, as well as a diffusional barrier to the Sr(II) release. The degradation of the polymer progressively leads to the exposure of the Sr(II)-loaded Halloysite scaffold, tuning its interaction with osteogenic cells. The in vitro biocompatibility of the composite was demonstrated by cytotoxicity tests on L929 fibroblast cells. The results indicate that this composite material could be of interest for multiple strategies in the field of bone tissue engineering. Copyright © 2015 Elsevier Inc. All rights reserved.
Biotic Nitrogen Enrichment Regulates Calcium Sources to Forests
NASA Astrophysics Data System (ADS)
Pett-Ridge, J. C.; Perakis, S. S.; Hynicka, J. D.
2015-12-01
Calcium is an essential nutrient in forest ecosystems that is susceptible to leaching loss and depletion. Calcium depletion can affect plant and animal productivity, soil acid buffering capacity, and fluxes of carbon and water. Excess nitrogen supply and associated soil acidification are often implicated in short-term calcium loss from soils, but the long-term role of nitrogen enrichment on calcium sources and resupply is unknown. Here we use strontium isotopes (87Sr/86Sr) as a proxy for calcium to investigate how soil nitrogen enrichment from biological nitrogen fixation interacts with bedrock calcium to regulate both short-term available supplies and the long-term sources of calcium in montane conifer forests. Our study examines 22 sites in western Oregon, spanning a 20-fold range of bedrock calcium on sedimentary and basaltic lithologies. In contrast to previous studies emphasizing abiotic control of weathering as a determinant of long-term ecosystem calcium dynamics and sources (via bedrock fertility, climate, or topographic/tectonic controls) we find instead that that biotic nitrogen enrichment of soil can strongly regulate calcium sources and supplies in forest ecosystems. For forests on calcium-rich basaltic bedrock, increasing nitrogen enrichment causes calcium sources to shift from rock-weathering to atmospheric dominance, with minimal influence from other major soil forming factors, despite regionally high rates of tectonic uplift and erosion that can rejuvenate weathering supply of soil minerals. For forests on calcium-poor sedimentary bedrock, we find that atmospheric inputs dominate regardless of degree of nitrogen enrichment. Short-term measures of soil and ecosystem calcium fertility are decoupled from calcium source sustainability, with fundamental implications for understanding nitrogen impacts, both in natural ecosystems and in the context of global change. Our finding that long-term nitrogen enrichment increases forest reliance on atmospheric calcium helps explain reports of greater ecological calcium limitation in an increasingly nitrogen-rich world.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, Yuwen; Wang, Xiyao; Liang, Xiaohui
Hyperhomocysteinemia induces the proliferation of vascular smooth muscle cells (VSMCs). Hydrogen sulfide (H{sub 2}S) inhibits the phenotype switch of VSMCs and calcium-sensing receptor (CaSR) regulated the production of endogenous H{sub 2}S. However, whether CaSR inhibits the proliferation of VSMCs by regulating the endogenous cystathionine-gamma-lyase (CSE, a major enzyme that produces H{sub 2}S) pathway in high homocysteine (HHcy) has not been previously investigated. The intracellular calcium concentration, the concentration of H{sub 2}S, the cell viability, the proliferation and the expression of proteins of cultured VSMCs from rat thoracic aortas were measured, respectively. The results showed that the [Ca{sup 2+}]{sub i} andmore » the expression of p-CaMK and CSE increased upon treatment with CaSR agonist. In HHcy, the H{sub 2}S concentration decrease, the proliferation and migration rate increased, the expression of Cyclin D1, PCNA, Osteopontin and p-Erk1/2 increased while the α-SM actin, P21{sup Cip/WAK−1} and Calponin decreased. The CaSR agonist or exogenous H{sub 2}S significantly reversed the changes of VSMCs caused by HHcy. In conclusion, our results demonstrated that CaSR regulate the endogenous CSE/H{sub 2}S is related to the PLC-IP{sub 3} receptor and CaM signal pathways which inhibit the proliferation of VSMCs, and the latter is involved in the Erk1/2 dependent signal pathway in high homocysteine. - Highlights: • CaSR activation increased the production of endogenous H{sub 2}S in high homocysteine VSMCs. • CaSR modulated the CSE/H{sub 2}S are related to the PLC-IP{sub 3}R and Ca{sup 2+}-CaM signal pathways. • Inhibition of H{sub 2}S on the proliferation of VSMCs is involved in the Erk1/2 pathway. • Explore the potential roles of CaSR in regulating VSMCs proliferation in high homocysteine.« less
Effect of hydrocortisone on total body calcium in rats. [/sup 47/Ca and /sup 85/Sr tracer techniques
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yasumura, S.; Ellis, K.J.; Cohn, S.H.
Administration of 5 mg. of hydrocortisone acetate to rats every other day for 2 weeks resulted in growth retardation and weight loss as indicated by body weights of experimental animals, which averaged 33 percent lower than those of the controls, and a significant decrease in the length of the tibiae and femurs (p less than 0.01 for treated vs controls). However, despite the smaller size of the treated animals, the values for total body calcium (TBCa) and the calcium in the tibia and femur did not differ significantly from control values. Thus, there was more calcium per unit length ofmore » bone, resulting in an increase in the skeletal density of treated rats. This finding was confirmed by x-ray examination of these bones. The net intestinal absorption of calcium (rate of initial entry) calculated from plasma levels following an oral and intravenous dose of /sup 47/Ca and /sup 85/Sr, respectively, was not significantly different in hydrocortisone-treated rats compared to controls. This would indicate that the rate of intestinal absorption of calcium is unimpaired despite the administration of massive doses of corticosteroids. When the animals were placed on a calcium-deficient diet, both TBCa and tibia and femur calcium levels were decreased. Subsequent administration of hydrocortisone did not alter the calcium values. The results of this study are compatible with the hypothesis that hydrocortisone promotes weight loss, retards growth, but inhibits the rate of bone resorption.« less
Identification of Global and Ligand-Specific Calcium Sensing Receptor Activation Mechanisms.
Keller, Andrew N; Kufareva, Irina; Josephs, Tracy M; Diao, Jiayin; Mai, Vyvyan T; Conigrave, Arthur D; Christopoulos, Arthur; Gregory, Karen J; Leach, Katie
2018-06-01
Calcium sensing receptor (CaSR) positive allosteric modulators (PAMs) are therapeutically important. However, few are approved for clinical use, in part due to complexities in assessing allostery at a receptor where the endogenous agonist (extracellular calcium) is present in all biologic fluids. Such complexity impedes efforts to quantify and optimize allosteric drug parameters (affinity, cooperativity, and efficacy) that dictate PAM structure-activity relationships (SARs). Furthermore, an underappreciation of the structural mechanisms underlying CaSR activation hinders predictions of how PAM SAR relates to in vitro and in vivo activity. Herein, we combined site-directed mutagenesis and calcium mobilization assays with analytical pharmacology to compare modes of PAM binding, positive modulation, and agonism. We demonstrate that 3-(2-chlorophenyl)- N -((1 R )-1-(3-methoxyphenyl)ethyl)-1-propanamine (NPS R568) binds to a 7 transmembrane domain (7TM) cavity common to class C G protein-coupled receptors and used by ( αR )-(-)- α -methyl- N -[3-[3-[trifluoromethylphenyl]propyl]-1-napthalenemethanamine (cinacalcet) and 1-benzothiazol-2-yl-1-(2,4-dimethylphenyl)-ethanol (AC265347); however, there are subtle distinctions in the contribution of select residues to the binding and transmission of cooperativity by PAMs. Furthermore, we reveal some common activation mechanisms used by different CaSR activators, but also demonstrate some differential contributions of residues within the 7TM bundle and extracellular loops to the efficacy of the PAM-agonist, AC265347, versus cooperativity. Finally, we show that PAMS potentiate the affinity of divalent cations. Our results support the existence of both global and ligand-specific CaSR activation mechanisms and reveal that allosteric agonism is mediated in part via distinct mechanisms to positive modulation. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.
Plasma Retention and Systemic Kinetics of 90Sr Intramuscularly Injected in Female Nonhuman Primates
Poudel, Deepesh; Klumpp, John A.; Bertelli, Luiz; ...
2017-08-01
Thirteen female Rhesus macaques were intramuscularly injected with 90Sr(NO 3) 2 diluted in sodium citrate solution. The biokinetic data from these animals were compared against the predictions of the NCRP 156 wound models combined with the ICRP systemic models. We observed observed that the activities measured in plasma of these nonhuman primates (NHPs) were consistently lower than those predicted by the default human biokinetic models. The urinary excretion from the NHPs at times immediately after injection was much greater than that in humans. The fecal excretion rates were found to be in relatively better agreement with humans. Similarly, the activitiesmore » retained in the skeleton of the NHPs were lower than that in humans. These differences were attributed to the higher calcium diet of the NHPs (0.03 to 0.12 g/d/kg body weight) compared to that of humans. These observations were consistent with the early animal and human studies that showed the effect of calcium on strontium metabolism, specifically urinary excretion. Strontium is preferentially filtered at a much higher rate in kidneys than calcium because it is less completely bound to protein than is calcium. Furthermore, these differences, along with large inter-animal variability, should be considered when estimating the behavior of Sr in humans from the metabolic data in animals or vice-versa.« less
Plasma Retention and Systemic Kinetics of 90Sr Intramuscularly Injected in Female Nonhuman Primates
DOE Office of Scientific and Technical Information (OSTI.GOV)
Poudel, Deepesh; Klumpp, John A.; Bertelli, Luiz
Thirteen female Rhesus macaques were intramuscularly injected with 90Sr(NO 3) 2 diluted in sodium citrate solution. The biokinetic data from these animals were compared against the predictions of the NCRP 156 wound models combined with the ICRP systemic models. We observed observed that the activities measured in plasma of these nonhuman primates (NHPs) were consistently lower than those predicted by the default human biokinetic models. The urinary excretion from the NHPs at times immediately after injection was much greater than that in humans. The fecal excretion rates were found to be in relatively better agreement with humans. Similarly, the activitiesmore » retained in the skeleton of the NHPs were lower than that in humans. These differences were attributed to the higher calcium diet of the NHPs (0.03 to 0.12 g/d/kg body weight) compared to that of humans. These observations were consistent with the early animal and human studies that showed the effect of calcium on strontium metabolism, specifically urinary excretion. Strontium is preferentially filtered at a much higher rate in kidneys than calcium because it is less completely bound to protein than is calcium. Furthermore, these differences, along with large inter-animal variability, should be considered when estimating the behavior of Sr in humans from the metabolic data in animals or vice-versa.« less
Lu, Luyao; Xia, Ling; Ye, Xuesong; Cheng, Heping
2010-05-26
Calcium homeostasis is considered to be one of the most important factors for the contraction and relaxation of the heart muscle. However, under some pathological conditions, such as heart failure (HF), calcium homeostasis is disordered, and spontaneous waves may occur. In this study, we developed a mathematical model of formation and propagation of a calcium wave based upon a governing system of diffusion-reaction equations presented by Izu et al (2001 Biophys. J. 80 103-20) and integrated non-clustered or 'rogue' ryanodine receptors (rogue RyRs) into a two-dimensional (2D) model of ventricular myocytes isolated from failing hearts in which sarcoplasmic reticulum (SR) Ca(2+) pools are partially unloaded. The model was then used to simulate the effect of rogue RyRs on initiation and propagation of the calcium wave in ventricular myocytes with HF. Our simulation results show that rogue RyRs can amplify the diastolic SR Ca(2+) leak in the form of Ca(2+) quarks, increase the probability of occurrence of spontaneous Ca(2+) waves even with smaller SR Ca(2+) stores, accelerate Ca(2+) wave propagation, and hence lead to delayed afterdepolarizations (DADs) and cardiac arrhythmia in the diseased heart. This investigation suggests that incorporating rogue RyRs in the Ca(2+) wave model under HF conditions provides a new view of Ca(2+) dynamics that could not be mimicked by adjusting traditional parameters involved in Ca(2+) release units and other ion channels, and contributes to understanding the underlying mechanism of HF.
Cytoplasmic calcium levels in protoplasts from the cap and elongation zone of maize roots
NASA Technical Reports Server (NTRS)
Kiss, H. G.; Evans, M. L.; Johnson, J. D.
1991-01-01
Calcium has been implicated as a key component in the signal transduction process of root gravitropism. We measured cytoplasmic free calcium in protoplasts isolated from the elongation zone and cap of primary roots of light-grown, vertically oriented seedlings of Zea mays L. Protoplasts were loaded with the penta-potassium salts of fura-2 and indo-1 by incubation in acidic solutions of these calcium indicators. Loading increased with decreasing pH but the pH dependence was stronger for indo-1 than for fura-2. In the case of fura-2, loading was enhanced only at the lowest pH (4.5) tested. Dyes loaded in this manner were distributed predominantly in the cytoplasm as indicated by fluorescence patterns. As an alternative method of loading, protoplasts were incubated with the acetoxymethylesters of fura-2 and indo-1. Protoplasts loaded by this method exhibited fluorescence both in the cytoplasm and in association with various organelles. Cytoplasmic calcium levels measured using spectrofluorometry, were found to be 160 +/- 40 nM and 257 +/- 27 nM, respectively, in populations of protoplasts from the root cap and elongation zone. Cytoplasmic free calcium did not increase upon addition of calcium to the incubation medium, indicating that the passive permeability to calcium was low.
Tuzuner, T; Sencan, I; Ozdemir, D; Alper, M; Duman, S; Yavuz, T; Yildirim, M
2006-12-01
The objective of this study was to evaluate the efficacy of teicoplanin- and calcium sulphate-loaded polymethylmethacrylate (PMMA) bone cements in preventing experimental implant-related osteomyelitis in rats. Four groups of antibiotic-loaded rods were prepared and were implanted into the lateral condylus of the rat femur after inoculation of Staphylococcus aureus. The effectiveness of these were assessed microbiologically, radiographically, and histopathologically. Radiographic evaluation revealed a significant reduction of periostal reaction and osteolysis in rats that received calcium sulphate- and teicoplanin-loaded rods. Histopathological evaluation confirmed these results. Acute infection and bone necrosis were found to be significantly lower in rats that had received calcium sulphate- and teicoplanin-loaded rods. The addition of calcium sulfate to teicoplanin-loaded PMMA bone cement appeared satisfactory as an antibiotic-carrying system for prophylaxis of experimental implant-related osteomyelitis, but further investigations are needed to reach definitive statements for clinical applications.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sugavaneshwar, Ramu Pasupathi, E-mail: r.p.sugavaneshwar@nims.go.jp, E-mail: NAGAO.Tadaaki@nims.go.jp; Chen, Kai; Lakshminarayana, Gandham
2015-11-01
Thin films of SrTiO{sub 3} (STO) and Rh-doped SrTiO{sub 3} (Rh-STO) were synthesized by sol-gel method and loaded with Ag nanoparticles. Pristine STO films exhibited anodic photocurrent while Rh-STO exhibited cathodic photocurrent. An enhancement in the overall cathodic photocurrent is observed with Ag nanoparticle loading and an additional enhancement in the visible light range is seen from the incident photon-to-current efficiency spectrum due to synergetic effect of Rh doping and Ag loading in STO.
Medina, Johan; Nakagawa, Yuko; Nagasawa, Masahiro; Fernandez, Anny; Sakaguchi, Kazushige; Kitaguchi, Tetsuya; Kojima, Itaru
2016-01-01
The calcium-sensing receptor (CaSR) is activated by various cations, cationic compounds, and amino acids. In the present study we investigated the effect of glucose on CaSR in HEK293 cells stably expressing human CaSR (HEK-CaSR cells). When glucose concentration in the buffer was raised from 3 to 25 mm, a rapid elevation of cytoplasmic Ca2+ concentration ([Ca2+]c) was observed. This elevation was immediate and transient and was followed by a sustained decrease in [Ca2+]c. The effect of glucose was detected at a concentration of 4 mm and reached its maximum at 5 mm. 3-O-Methylglucose, a non-metabolizable analogue of glucose, reproduced the effect of glucose. Sucrose also induced an elevation of [Ca2+]c in HEK-CaSR cells. Similarly, sucralose was nearly as effective as glucose in inducing elevation of [Ca2+]c. Glucose was not able to increase [Ca2+]c in the absence of extracellular Ca2+. The effect of glucose on [Ca2+]c was inhibited by NPS-2143, an allosteric inhibitor of CaSR. In addition, NPS-2143 also inhibited the [Ca2+]c responses to sucralose and sucrose. Glucose as well as sucralose decreased cytoplasmic cAMP concentration in HEK-CaSR cells. The reduction of cAMP induced by glucose was blocked by pertussis toxin. Likewise, sucralose reduced [cAMP]c. Finally, glucose increased [Ca2+]c in PT-r parathyroid cells and in Madin-Darby canine kidney cells, both of which express endogenous CaSR. These results indicate that glucose acts as a positive allosteric modulator of CaSR. PMID:27613866
Role of the Calcium-Sensing Receptor (CaSR) in bovine gametes and during in vitro fertilization.
Macías-García, Beatriz; Lopes, Graça; Rocha, Antonio; González-Fernández, Lauro
2017-06-01
Calcium Sensing Receptor (CaSR) is a G-protein coupled receptor which senses extracellular calcium and activates diverse intracellular pathways. The objective of our work was to demonstrate the presence of CaSR in bovine gametes and its possible role in fertilization and embryo development. The location of CaSR was demonstrated by immunofluorescence in bovine gametes; additionally bovine sperm were incubated with 5, 10 and 15 μM of the specific CaSR inhibitor NPS2143 in a Tyrode's Albumin Lactate Pyruvate medium (4 h). Sperm viability was maintained for all concentrations tested while total motility decreased significantly at 10 and 15 μM. Addition of 15 μM of NPS2143 during oocyte in vitro maturation did not alter the maturation rate. When NPS2143 (15 μM) was added to the fertilization medium during sperm-oocyte co-incubation the cleavage, morula and blastocyst rates remained unchanged. To confirm if 15 μM of NPS2143 exerted any effect on embryo development, NPS2143 was added to the embryo culture medium. Cleavage rates remained unchanged when 15 μM of NPS2143 was added to the culture medium (79.1 ± 6.8 vs. 73.7 ± 5.3; mean % ± SEM; p > 0.05, control vs. inhibitor). By contrast, development to the morula (46.6 ± 7.3 vs. 24.3 ± 4.3; mean % ± SEM; p < 0.05) and blastocyst stages (29.9 ± 9.0 vs. 9.9 ± 3.6; mean % ± SEM; p < 0.05) decreased (control vs. inhibitor). Our results demonstrate a key role of CaSR on sperm motility and embryo development but not on oocyte maturation or fertilization in the bovine species. Copyright © 2017 Elsevier Inc. All rights reserved.
Lin, Kaili; Xia, Lunguo; Li, Haiyan; Jiang, Xinquan; Pan, Haobo; Xu, Yuanjin; Lu, William W; Zhang, Zhiyuan; Chang, Jiang
2013-12-01
The regeneration capacity of the osteoporotic bones is generally lower than that of the normal bones. Current methods of bone defect treatment for osteoporosis are not always satisfactory. Recent studies have shown that the silicate based biomaterials can stimulate osteogenesis and angiogenesis due to the silicon (Si) ions released from the materials, and enhance bone regeneration in vivo. Other studies showed that strontium (Sr) plays a distinct role on inhibiting bone resorption. Based on the hypothesis that the combination of Si and Sr may have synergetic effects on osteoporotic bone regeneration, the porous Sr-substituted calcium silicate (SrCS) ceramic scaffolds combining the functions of Sr and Si elements were developed with the goals to promote osteoporotic bone defect repair. The effects of the ionic extract from SrCS on osteogenic differentiation of bone marrow mesenchymal stem cells derived from ovariectomized rats (rBMSCs-OVX), angiogenic differentiation of human umbilical vein endothelial cells (HUVECs) were investigated. The in vitro results showed that Sr and Si ions released from SrCS enhanced cell viability, alkaline phosphatase (ALP) activity, and mRNA expression levels of osteoblast-related genes of rBMSCs-OVX and expression of vascular endothelial growth factor (VEGF) without addition of extra osteogenic and angiogenic reagents. The activation in extracellular signal-related kinases (ERK) and p38 signaling pathways were observed in rBMSCs-OVX cultured in the extract of SrCS, and these effects could be blocked by ERK inhibitor PD98059, and P38 inhibitor SB203580, respectively. Furthermore, the ionic extract of SrCS stimulated HUVECs proliferation, differentiation and angiogenesis process. The in vivo experiments revealed that SrCS dramatically stimulated bone regeneration and angiogenesis in a critical sized OVX calvarial defect model, and the enhanced bone regeneration might be attributed to the modulation of osteogenic differentiation of endogenous mesenchymal stem cells (MSCs) and the inhibition of osteoclastogenesis, accompanying with the promotion of the angiogenic activity of endothelial cells (ECs). Copyright © 2013 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Khare, A.; Kilbourne, K. H.; Schijf, J.
2017-12-01
Standard methods of reconstructing past sea surface temperatures (SSTs) with coral skeletal Sr/Ca ratios assume the seawater Sr/Ca ratio is constant. However, there is little data to support this assumption, in part because analytical techniques capable of determining seawater Sr/Ca with sufficient accuracy and precision are expensive and time consuming. We demonstrate a method to measure seawater Sr/Ca using inductively coupled plasma atomic emission spectrometry where we employ an intensity ratio calibration routine that reduces the self- matrix effects of calcium and cancels out the matrix effects that are common to both calcium and strontium. A seawater standard solution cross-calibrated with multiple instruments is used to correct for long-term instrument drift and any remnant matrix effects. The resulting method produces accurate seawater Sr/Ca determinations rapidly, inexpensively, and with a precision better than 0.2%. This method will make it easier for coral paleoclimatologists to quantify potentially problematic fluctuations in seawater Sr/Ca at their study locations. We apply our method to test for variability in surface seawater Sr/Ca along the Florida Keys Reef Tract. We are collecting winter and summer samples for two years in a grid with eleven nearshore to offshore transects across the reef, as well as continuous samples collected by osmotic pumps at four locations adjacent to our grid. Our initial analysis of the grid samples indicates a trend of decreasing Sr/Ca values offshore potentially due to a decreasing groundwater influence. The values differ by as much as 0.05 mmol/mol which could lead to an error of 1°C in mean SST reconstructions. Future work involves continued sampling in the Florida Keys to test for seasonal and interannual variability in seawater Sr/Ca, as well as collecting data from small reefs in the Virgin Islands to test the stability of seawater Sr/Ca under different geologic, hydrologic and hydrographic environments.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fredriksson, L.; Eriksson, B.; Eriksson, A.
1961-03-01
The influence of liming on the accurnulation of Sr/sup 89/ in the aerial parte of a number of weed species, grown on a natnralla calcium deficient soil in pot experiments, was studied. Liming decreased the accumulation of Sr/sup 89/ in all of the weed species used. At one and the same Ca content in soil great differences were found in Sr/sup 89/ activity in the dry matter of the different weed species. (auth)
Lorbach, Olaf; Kieb, Matthias; Raber, Florian; Busch, Lüder C; Kohn, Dieter; Pape, Dietrich
2012-02-01
To compare the biomechanical properties and footprint coverage of a single-row (SR) repair using a modified suture configuration versus a double-row (DR) suture-bridge repair in small to medium and medium to large rotator cuff tears. We created 25- and 35-mm artificial defects in the rotator cuff of 24 human cadaveric shoulders. The reconstructions were performed as either an SR repair with triple-loaded suture anchors (2 to 3 anchors) and a modified suture configuration or a modified suture-bridge DR repair (4 to 6 anchors). Reconstructions were cyclically loaded from 10 to 60 N. The load was increased stepwise up to 100, 180, and 250 N. Cyclic displacement and load to failure were determined. Furthermore, footprint widths were quantified. In the 25-mm rupture, ultimate load to failure was 533 ± 107 N for the SR repair and 681 ± 250 N for the DR technique (P ≥ .21). In the 35-mm tear, ultimate load to failure was 792 ± 122 N for the SR reconstruction and 891 ± 174 N for the DR reconstruction (P ≥ .28). There were no statistically significant differences for both tested rupture sizes. Cyclic displacement showed no significant differences between the tested configurations at 60 N (P = .563), 100 N (P = .171), 180 N (P = .211), and 250 N (P = .478) for the 25-mm tear. For the 35-mm tear, cyclic displacement showed significantly lower gap formation for the SR reconstruction at 180 N (P = .037) and 250 N (P = .020). No significant differences were found at 60 N (P = .296) and 100 N (P = .077). A significantly greater footprint width (P = .028) was seen for the DR repair (16.2 mm) compared with the SR repair (13.8 mm). However, both reconstructions were able to achieve complete footprint coverage compared with the initial footprint. The tested SR repair using a modified suture configuration was similar in load to failure and cyclic displacement to the DR suture-bridge technique independent of the tested initial sizes of the rupture. The tested DR repair consistently restored a larger footprint than the SR method. However, both constructs achieved complete footprint coverage. SR repairs with modified suture configurations might combine the biomechanical advantages and increased footprint coverage that are described for DR repairs without increasing the overall costs of the reconstruction. Copyright © 2012 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.
Measurements of Sr/Ca in bones to evaluate differences in temperature
NASA Astrophysics Data System (ADS)
Santos, P. R.; Added, N.; Aburaya, J. H.; Rizzutto, M. A.
2008-04-01
Analysis of aragonite from sea shells and coral skeletons showed a clear correlation between the strontium and calcium concentrations for these crystals (Sr/Ca ratio) and seawater temperature obtained by satellites and ship readings. In this work we present the results of a study that correlates Sr/Ca ratio with formation temperature of another calcium crystal, the hydroxyapatite (Ca10(PO4)6(OH)2), main mineral compound of teeth and bones from vertebrates. These animals, independent of its thermoregulation pattern (endothermic or ectothermic) have variations of internal temperature along the body. One interesting application of this work is to differentiate warm-blooded animals from cold-blooded ones just by measuring Sr/Ca ratio in their bones. Bones from a crocodile from Caiman yacare species and two dogs, a poodle and a non defined race, were analyzed using PIXE technique and thick target correction. A 1.78 (18) MeV external proton beam was used in LAMFI-USP with an accumulated charge of about 10 μC for probing the samples. Emitted X-rays were collected using Si-PIN detectors (140 keV for Fe). As in coral skeletons, the Sr/Ca ratio of animals is lower in the body's warmer parts and higher in colder parts.
Cinco, Roehl M.; Robblee, John H.; Messinger, Johannes; Fernandez, Carmen; Holman, Karen L. McFarlane; Sauer, Kenneth; Yachandra, Vittal K.
2014-01-01
The oxygen-evolving complex of photosystem II (PS II) in green plants and algae contains a cluster of four Mn atoms in the active site, which catalyzes the photoinduced oxidation of water to dioxygen. Along with Mn, calcium and chloride ions are necessary cofactors for proper functioning of the complex. The current study using polarized Sr EXAFS on oriented Sr-reactivated samples shows that Fourier peak II, which fits best to Mn at 3.5 Å rather than lighter atoms (C, N, O, or Cl), is dichroic, with a larger magnitude at 10° (angle between the PS II membrane normal and the X-ray electric field vector) and a smaller magnitude at 80°. Analysis of the dichroism of the Sr EXAFS yields a lower and upper limit of 0° and 23° for the average angle between the Sr–Mn vectors and the membrane normal and an isotropic coordination number (number of Mn neighbors to Sr) of 1 or 2 for these layered PS II samples. The results confirm the contention that Ca (Sr) is proximal to the Mn cluster and lead to refined working models of the heteronuclear Mn4Ca cluster of the oxygen-evolving complex in PS II. PMID:15491134
Lefeuvre, Benjamin; Minoletti, Fabrice; de Rafélis, Marc
2017-01-01
The formation of the coccolith biominerals by a group of marine algae (the Coccolithophores) offers fascinating research avenues both from the biological and geological sides. It is surprising how biomineralisation by a key phytoplanktonic group remains underconstrained, yet is influential on ocean alkalinity and responsible for the built up of our paleoclimatic archive over the last 200 Myrs. Here, we report two close relative coccolith taxa exhibiting substantial bioaccumulation of strontium: Scyphosphaera and Pontosphaera grown in the laboratory or retrieved from Pliocene sediments. This strontium enrichment relative to calcium is one order of magnitude greater than reported in other coccoliths of the orders Isochrysidales and Coccolithales, and extends well beyond established controls on Sr/Ca ratios by temperature and growth rate. We discuss this prominent vital effect in relation with possible specific uptake of strontium relative to calcium from the extracellular environment to the coccolith vesicle in coccolithophores excreting very large scale coccoliths. The report of Sr-rich biominerals challenges our current understanding of the cellular acquisition and intracellular trafficking of alkaline earth cations in phytoplanktonic calcifying eukaryotic algae. The presence of Sr-rich coccolith species in the geological record has to be quantitatively considered in future Sr/Ca-based palaeoceanographic reconstruction. PMID:29036179
Alcalai, Ronny; Wakimoto, Hiroko; Arad, Michael; Planer, David; Konno, Tetsuo; Wang, Libin; Seidman, Jon G; Seidman, Christine E; Berul, Charles I
2011-03-01
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial arrhythmic syndrome caused by mutations in genes encoding the calcium-regulation proteins cardiac ryanodine receptor (RyR2) or calsequestrin-2 (CASQ2). Mechanistic studies indicate that CPVT is mediated by diastolic Ca(2+) overload and increased Ca(2+) leak through the RyR2 channel, implying that treatment targeting these defects might be efficacious in CPVT. CPVT mouse models that lack CASQ2 were treated with Ca(2+) -channel inhibitors, β-adrenergic inhibitors, or Mg(2+) . Treatment effects on ventricular arrhythmia, sarcoplasmic reticulum (SR) protein expression and Ca(2+) transients of isolated myocytes were assessed. Each study agent reduced the frequency of stress-induced ventricular arrhythmia in mutant mice. The Ca(2+) channel blocker verapamil was most efficacious and completely prevented arrhythmia in 85% of mice. Verapamil significantly increased the SR Ca(2+) content in mutant myocytes, diminished diastolic Ca(2+) overload, increased systolic Ca(2+) amplitude, and prevented Ca(2+) oscillations in stressed mutant myocytes. Ca(2+) channel inhibition by verapamil rectified abnormal calcium handling in CPVT myocytes and prevented ventricular arrhythmias. Verapamil-induced partial normalization of SR Ca(2+) content in mutant myocytes implicates CASQ2 as modulator of RyR2 activity, rather than or in addition to, Ca(2+) buffer protein. Agents such as verapamil that attenuate cardiomyocyte calcium overload are appropriate for assessing clinical efficacy in human CPVT. © 2010 Wiley Periodicals, Inc.
Alcalai, Ronny; Wakimoto, Hiroko; Arad, Michael; Planer, David; Konno, Tetsuo; Wang, Libin; Seidman, Jon G.; Seidman, Christine E.; Berul, Charles I
2010-01-01
Background Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial arrhythmic syndrome caused by mutations in genes encoding the calcium-regulation proteins cardiac ryanodine receptor (RyR2) or calsequestrin-2 (CASQ2). Mechanistic studies indicate that CPVT is mediated by diastolic Ca2+ overload and increased Ca2+ leak through the RyR2 channel, implying that treatment targeting these defects might be efficacious in CPVT. Method and results CPVT mouse models that lack CASQ2 were treated with Ca2+-channel inhibitors, β-adrenergic inhibitors, or Mg2+. Treatment effects on ventricular arrhythmia, sarcoplasmic reticulum (SR) protein expression and Ca2+ transients of isolated myocytes were assessed. Each study agent reduced the frequency of stress-induced ventricular arrhythmia in mutant mice. The Ca2+ channel blocker verapamil was most efficacious and completely prevented arrhythmia in 85% of mice. Verapamil significantly increased the SR Ca2+ content in mutant myocytes, diminished diastolic Ca2+ overload, increased systolic Ca2+ amplitude, and prevented Ca2+ oscillations in stressed mutant myocytes. Conclusions Ca2+ channel inhibition by verapamil rectified abnormal calcium handling in CPVT myocytes and prevented ventricular arrhythmias. Verapamil-induced partial normalization of SR Ca2+ content in mutant myocytes implicates CASQ2 as modulator of RyR2 activity, rather than or in addition to, Ca2+ buffer protein. Agents such as verapamil that attenuate cardiomyocyte calcium overload are appropriate for assessing clinical efficacy in human CPVT. PMID:20807279
Effects of a micro/nano rough strontium-loaded surface on osseointegration
Li, Yongfeng; Qi, Yaping; Gao, Qi; Niu, Qiang; Shen, Mingming; Fu, Qian; Hu, Kaijin; Kong, Liang
2015-01-01
We developed a hierarchical hybrid micro/nanorough strontium-loaded Ti (MNT-Sr) surface fabricated through hydrofluoric acid etching followed by magnetron sputtering and evaluated the effects of this surface on osseointegration. Samples with a smooth Ti (ST) surface, micro Ti (MT) surface treated with hydrofluoric acid etching, and strontium-loaded nano Ti (NT-Sr) surface treated with SrTiO3 target deposited via magnetron sputtering technique were investigated in parallel for comparison. The results showed that MNT-Sr surfaces were prepared successfully and with high interface bonding strength. Moreover, slow Sr release could be detected when the MNT-Sr and NT-Sr samples were immersed in phosphate-buffered saline. In in vitro experiments, the MNT-Sr surface significantly improved the proliferation and differentiation of osteoblasts compared with the other three groups. Twelve weeks after the four different surface implants were inserted into the distal femurs of 40 rats, the bone–implant contact in the ST, MT, NT-Sr, and MNT-Sr groups were 39.70%±6.00%, 57.60%±7.79%, 46.10%±5.51%, and 70.38%±8.61%, respectively. In terms of the mineral apposition ratio, the MNT-Sr group increased by 129%, 58%, and 25% compared with the values of the ST, MT, and NT-Sr groups, respectively. Moreover, the maximal pullout force in the MNT-Sr group was 1.12-, 0.31-, and 0.69-fold higher than the values of the ST, MT, and NT-Sr groups, respectively. These results suggested that the MNT-Sr surface has a synergistic effect of hierarchical micro/nano-topography and strontium for enhanced osseointegration, and it may be a promising option for clinical use. Compared with the MT surface, the NT-Sr surface significantly improved the differentiation of osteoblasts in vitro. In the in vivo animal experiment, the MT surface significantly enhanced the bone-implant contact and maximal pullout force than the NT-Sr surface. PMID:26213468
Quigley, Ryan J; Gupta, Akash; Oh, Joo-Han; Chung, Kyung-Chil; McGarry, Michelle H; Gupta, Ranjan; Tibone, James E; Lee, Thay Q
2013-08-01
The transosseous-equivalent (TOE) rotator cuff repair technique increases failure loads and contact pressure and area between tendon and bone compared to single-row (SR) and double-row (DR) repairs, but no study has investigated if this translates into improved healing in vivo. We hypothesized that a TOE repair in a rabbit chronic rotator cuff tear model would demonstrate a better biomechanical profile than SR and DR repairs after 12 weeks of healing. A two-stage surgical procedure was performed on 21 New Zealand White Rabbits. The right subscapularis tendon was transected and allowed to retract for 6 weeks to simulate a chronic tear. Repair was done with the SR, DR, or TOE technique and allowed to heal for 12 weeks. Cyclic loading and load to failure biomechanical testing was then performed. The TOE repair showed greater biomechanical characteristics than DR, which in turn were greater than SR. These included yield load (p < 0.05), energy absorbed to yield (p < 0.05), and ultimate load (p < 0.05). For repair of a chronic, retracted rotator cuff tear, the TOE technique was the strongest biomechanical construct after healing followed by DR with SR being the weakest. Copyright © 2013 Orthopaedic Research Society.
NASA Astrophysics Data System (ADS)
Myojo, Kunihiro; Yokoyama, Tetsuya; Okabayashi, Satoki; Wakaki, Shigeyuki; Sugiura, Naoji; Iwamori, Hikaru
2018-01-01
Nucleosynthetic isotope anomalies in meteorites are useful for investigating the origin of materials in the protoplanetary disk and dynamical processes of planetary formation. In particular, calcium and aluminum-rich inclusions (CAIs) found in chondrites are key minerals for decoding the initial conditions of the solar system before the accretion of small planetary bodies. In this study, we report isotopic analyses for three Allende CAIs, fluffy type A (FTA), type B, and fine-grained spinel rich (FS) inclusions, with a specific emphasis on the measurements of 84Sr/86Sr ratios. It was found that the average μ 84Sr values (106 relative deviations from a standard material) were 175, 129, and 56 ppm for the samples of FTA, type B, and FS inclusions, respectively. Additionally, the FTA samples exhibited heterogeneous μ 84Sr values, while those for the type B and FS inclusions were homogeneous within individual inclusions. The elevated μ 84Sr values were most likely explained by the relative enrichment of r-process nuclides in the CAI formation region. The variation of μ 84Sr values between the FTA and type B inclusions, as well as within the FTA inclusion, suggests the presence of multiple CAI source reservoirs with distinct isotopic compositions, which is either inherited from isotopic heterogeneity in the molecular cloud or caused by the selective destruction of r-process-enriched supernova grains via nebular thermal processing. On the other hand, the reaction between a refractory precursor of the FS inclusion and a gaseous reservoir enriched in Mg, Si, and 16O resulted in the lowest μ 84Sr values for the FS inclusion.
Calcium-Sensing Receptor Tumor Expression and Lethal Prostate Cancer Progression.
Ahearn, Thomas U; Tchrakian, Nairi; Wilson, Kathryn M; Lis, Rosina; Nuttall, Elizabeth; Sesso, Howard D; Loda, Massimo; Giovannucci, Edward; Mucci, Lorelei A; Finn, Stephen; Shui, Irene M
2016-06-01
Prostate cancer metastases preferentially target bone, and the calcium-sensing receptor (CaSR) may play a role in promoting this metastatic progression. We evaluated the association of prostate tumor CaSR expression with lethal prostate cancer. A validated CaSR immunohistochemistry assay was performed on tumor tissue microarrays. Vitamin D receptor (VDR) expression and phosphatase and tensin homolog tumor status were previously assessed in a subset of cases by immunohistochemistry. Cox proportional hazards models adjusting for age and body mass index at diagnosis, Gleason grade, and pathological tumor node metastasis stage were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of CaSR expression with lethal prostate cancer. The investigation was conducted in the Health Professionals Follow-up Study and Physicians' Health Study. We studied 1241 incident prostate cancer cases diagnosed between 1983 and 2009. Participants were followed up or cancer-specific mortality or development of metastatic disease. On average, men were followed up 13.6 years, during which there were 83 lethal events. High CaSR expression was associated with lethal prostate cancer independent of clinical and pathological variables (HR 2.0; 95% CI 1.2-3.3). Additionally, there was evidence of effect modification by VDR expression; CaSR was associated with lethal progression among men with low tumor VDR expression (HR 3.2; 95% CI 1.4-7.3) but not in cases with high tumor VDR expression (HR 0.8; 95% CI 0.2-3.0). Tumor CaSR expression is associated with an increased risk of lethal prostate cancer, particularly in tumors with low VDR expression. These results support further investigating the mechanism linking CaSR with metastases.
The Calcium-Sensing Receptor Increases Activity of the Renal NCC through the WNK4-SPAK Pathway.
Bazúa-Valenti, Silvana; Rojas-Vega, Lorena; Castañeda-Bueno, María; Barrera-Chimal, Jonatan; Bautista, Rocío; Cervantes-Pérez, Luz G; Vázquez, Norma; Plata, Consuelo; Murillo-de-Ozores, Adrián R; González-Mariscal, Lorenza; Ellison, David H; Riccardi, Daniela; Bobadilla, Norma A; Gamba, Gerardo
2018-05-30
Background Hypercalciuria can result from activation of the basolateral calcium-sensing receptor (CaSR), which in the thick ascending limb of Henle's loop controls Ca 2+ excretion and NaCl reabsorption in response to extracellular Ca 2+ However, the function of CaSR in the regulation of NaCl reabsorption in the distal convoluted tubule (DCT) is unknown. We hypothesized that CaSR in this location is involved in activating the thiazide-sensitive NaCl cotransporter (NCC) to prevent NaCl loss. Methods We used a combination of in vitro and in vivo models to examine the effects of CaSR on NCC activity. Because the KLHL3-WNK4-SPAK pathway is involved in regulating NaCl reabsorption in the DCT, we assessed the involvement of this pathway as well. Results Thiazide-sensitive 22 Na + uptake assays in Xenopus laevis oocytes revealed that NCC activity increased in a WNK4-dependent manner upon activation of CaSR with Gd 3+ In HEK293 cells, treatment with the calcimimetic R-568 stimulated SPAK phosphorylation only in the presence of WNK4. The WNK4 inhibitor WNK463 also prevented this effect. Furthermore, CaSR activation in HEK293 cells led to phosphorylation of KLHL3 and WNK4 and increased WNK4 abundance and activity. Finally, acute oral administration of R-568 in mice led to the phosphorylation of NCC. Conclusions Activation of CaSR can increase NCC activity via the WNK4-SPAK pathway. It is possible that activation of CaSR by Ca 2+ in the apical membrane of the DCT increases NaCl reabsorption by NCC, with the consequent, well known decrease of Ca 2+ reabsorption, further promoting hypercalciuria. Copyright © 2018 by the American Society of Nephrology.
Banta, J.R.; Clark, Allan K.
2012-01-01
In general, the water-quality data indicated that the samples were representative of a calcium carbonate dominated system. The major ion chemistry and relations between magnesium to calcium molar ratios and 87Sr/86Sr isotopic ratios of samples collected from sites H and I indicated that the groundwater from these sites was most geochemically similar to groundwater collected from site B (State well AY-68-36-134), which is representative of groundwater in the Edwards aquifer. Of the sites sampled in this study, there appears to be varying hydrologic connectivity between groundwater from wells completed in the Austin Group and the Edwards aquifer.
Stehno-Bittel, L; Sturek, M
1992-01-01
1. We tested the hypothesis that the Ca(2+)-loaded sarcoplasmic reticulum (SR) of coronary artery smooth muscle spontaneously releases Ca2+ preferentially toward the sarcolemma to be extruded from the cell without increasing the average free myoplasmic [Ca2+] (Ca(im)) concentration. 2. The SR of bovine cells was Ca(2+)-loaded by depolarization-induced Ca2+ influx. Release (unloading) of Ca2+ from the SR during recovery from depolarization was determined by Fura-2 microfluorometry of Ca(im). The SR Ca2+ unloading was maximal following a long (14 min) recovery from depolarization, as shown by the 66% decrease in the peak caffeine-induced Ca(im) transient compared to the Ca(im) transient after a short (2 min) recovery. No increase in Ca(im) occurred during the long recovery. No unloading of the SR Ca2+ store was noted in porcine cells. 3. Approximately 80% of the outward K+ current in bovine and porcine cells was sensitive to subsarcolemmal Ca2+ (Ca(is)) concentrations. Whole-cell voltage clamp using pipette solutions with Ca2+ concentrations clamped between 0 and 1000 nM with Ca(2+)-EGTA or Ca(2+)-BAPTA buffers showed increasing K+ currents (normalized for cell membrane surface area) as a function of both membrane potential and Ca(is). Clamping of Ca(im) and Ca(is) was verified by the lack of changes in K+ current and Fura-2 ratio in response to Ca2+ influx, Ca(2+)-free external solution, or caffeine-induced Ca2+ release. At +30 to +50 mV the K+ current amplitude showed a similar sensitivity to Ca2+ as Fura-2. These data indicate that in this experimental preparation Ca(2+)-activated K+ current is a valid estimate of Ca(is). 4. Simultaneous Ca(im) and Ca(is) measurements in bovine cells which were not Ca(2+)-clamped (2 x 10(-4) M-EGTA pipette solution) showed that during the long recovery period the K+ current (reflecting Ca(is)) increased 55%, while Ca(im) did not change. 5. In quiescent bovine cells the Ca(is) was higher than Ca(im), while the higher resting Ca(is) gradient was not apparent in porcine cells. 6. The Ca(is) concentration was directly related to the amount of Ca2+ in the SR in bovine, but not porcine cells. Depletion of the SR in bovine cells by caffeine resulted in a 58% decrease in K+ current compared to the resting K+ current. 7. Caffeine-induced Ca2+ release caused an increase in Ca(is) which preceded the increase in Ca(im) by approximately 2 s.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1403820
NASA Astrophysics Data System (ADS)
Lu, Hongbin; Chen, Can; Wang, Zhanwen; Qu, Jin; Xu, Daqi; Wu, Tianding; Cao, Yong; Zhou, Jingyong; Zheng, Cheng; Hu, Jianzhong
2015-09-01
Tendon attaches to bone through a functionally graded fibrocartilage zone, including uncalcified fibrocartilage (UF), tidemark (TM) and calcified fibrocartilage (CF). This transition zone plays a pivotal role in relaxing load transfer between tendon and bone, and serves as a boundary between otherwise structurally and functionally distinct tissue types. Calcium and zinc are believed to play important roles in the normal growth, mineralization, and repair of the fibrocartilage zone of bone-tendon junction (BTJ). However, spatial distributions of calcium and zinc at the fibrocartilage zone of BTJ and their distribution-function relationship are not totally understood. Thus, synchrotron radiation-based micro X-ray fluorescence analysis (SR-μXRF) in combination with backscattered electron imaging (BEI) was employed to characterize the distributions of calcium and zinc at the fibrocartilage zone of rabbit patella-patellar tendon complex (PPTC). For the first time, the unique distributions of calcium and zinc at the fibrocartilage zone of the PPTC were clearly mapped by this method. The distributions of calcium and zinc at the fibrocartilage zone of the PPTC were inhomogeneous. A significant accumulation of zinc was exhibited in the transition region between UF and CF. The highest zinc content (3.17 times of that of patellar tendon) was found in the TM of fibrocartilage zone. The calcium content began to increase near the TM and increased exponentially across the calcified fibrocartilage region towards the patella. The highest calcium content (43.14 times of that of patellar tendon) was in the transitional zone of calcified fibrocartilage region and the patella, approximately 69 μm from the location with the highest zinc content. This study indicated, for the first time, that there is a differential distribution of calcium and zinc at the fibrocartilage zone of PPTC. These observations reveal new insights into region-dependent changes across the fibrocartilage zone of BTJ and will serve as critical benchmark parameters for current efforts in BTJ repair.
Effects of temperature and calcium availability on ventricular myocardium from rainbow trout.
Coyne, M D; Kim, C S; Cameron, J S; Gwathmey, J K
2000-06-01
We studied the mechanical and electrophysiological properties of ventricular myocardium from rainbow trout (Oncorhynchus mykiss) in vitro at 4, 10, and 18 degrees C from fish acclimated at 10 degrees C. Temperature alone did not significantly alter the contractile force of the myocardium, but the time to peak tension and time to 80% relaxation were prolonged at 4 degrees C and shortened at 18 degrees C. The duration of the action potential was also prolonged at 4 degrees C and progressively shortened at higher temperatures. An alteration of the stimulation frequency did not affect contraction amplitude at any temperature. Calcium influx via L-type calcium channels was increased by raising extracellular calcium concentration (¿Ca(2+)(o)) or including Bay K 8644 (Bay K) and isoproterenol in the bathing medium. These treatments significantly enhanced the contractile force at all temperatures. Calcium channel blockers had a reverse-negative inotropic effect. Unexpectedly, the duration of the action potential at 10 degrees C was shortened as ¿Ca(2+)(o) increased. However, Bay K prolonged the plateau phase at 4 degrees C. Caffeine, which promotes the release of sarcoplasmic reticulum (SR) calcium, increased contractile force eightfold at all three temperatures, but the SR blocker ryanodine was only inhibitory at 4 degrees C. Our results suggest that contractile force in ventricular myocardium from Oncorhynchus mykiss is primarily regulated by sarcolemmal calcium influx and that ventricular contractility is maintained during exposure to a wide range of temperatures.
Role of claudins in renal calcium handling.
Negri, Armando Luis
2015-01-01
Paracellular channels occurring in tight junctions play a major role in transepithelial ionic flows. This pathway includes a high number of proteins, such as claudins. Within renal epithelium, claudins result in an ionic selectivity in tight junctions. Ascending thick limb of loop of Henle (ATLH) is the most important segment for calcium reabsorption in renal tubules. Its cells create a water-proof barrier, actively transport sodium and chlorine through a transcellular pathway, and provide a paracellular pathway for selective calcium reabsorption. Several studies have led to a model of paracellular channel consisting of various claudins, particularly claudin-16 and 19. Claudin-16 mediates cationic paracellular permeability in ATLH, whereas claudin-19 increases cationic selectivity of claudin-16 by blocking anionic permeability. Recent studies have shown that claudin-14 promoting activity is only located in ATLH. When co-expressed with claudin-16, claudin-14 inhibits the permeability of claudin-16 and reduces paracellular permeability to calcium. Calcium reabsorption process in ATLH is closely regulated by calcium sensor receptor (CaSR), which monitors circulating Ca levels and adjusts renal excretion rate accordingly. Two microRNA, miR-9 and miR-374, are directly regulated by CaSR. Thus, miR-9 and miR-374 suppress mRNA translation for claudin-14 and induce claudin-14 decline. Copyright © 2015 The Author. Published by Elsevier España, S.L.U. All rights reserved.
Strontium and Trace Metals in the Mississippi River Mixing Zone
NASA Astrophysics Data System (ADS)
Xu, Y.; Marcantonio, F.
2001-12-01
Strontium is generally believed to be a conservative element, i.e., it is assumed that dissolved Sr moves directly from rivers through estuaries to the ocean. More recently, however, detailed sampling of rivers suggests a weak non-conservative behavior for Sr. Here, we present dissolved and suspended load Sr and trace metal data for samples retrieved along salinity transects in the estuarine mixing zone of the Mississippi River. Our cruises took place during times representing high, falling, and low Mississippi River discharge. Sr concentration and isotopic composition were analyzed for both dissolved particulate loads. Selected particle-reactive or redox-sensitive trace metals (Mn, Fe, U, V, Mo, Ti, and Pb) were analyzed simultaneously. In the dissolved load, Sr showed conservative behavior in both high- and low- discharge periods. Non-conservative behavior of Sr predominated during falling discharge in the summer. Significant positive correlations were found between Sr, Mo and Ti. U and V distributions were found to be essentially controlled by mixing of river water and seawater, but with significantly lower riverine concentrations during high-flow stage. Particulate element concentrations can be quite variable and heterogeneous. In this study, strong correlations were found between particulate Mn (and Fe) concentrations and particulate concentrations of Ti, U, V, and Pb. No such correlations with Mn (or Fe) were found for particulate Sr and Mo. There is a vast hypoxic zone along the coast of Louisiana in the Gulf of Mexico that exists during the summer months. Based on the Sr isotope systematics and the relationships between Sr and trace metals, we believe that this eutrophication may contribute to the non-conservative behaviors of Sr and other trace metals. We discuss the potential implications of this hypothesis on the Sr mass balance of present-day and past seawater.
Yachandra, Vittal K.; Yano, Junko
2011-01-01
This review describes the results from X-ray absorption spectroscopy studies that have contributed to an understanding of the role of Ca in the photosynthetic water oxidation reaction. The results include the first Mn, Ca and Sr X-ray spectroscopy studies using Ca or Sr-substituted PS II samples that established the presence of a MnCa heteronuclear structure and its orientation, and the most recent Sr X-ray spectroscopy study using biosynthetically prepared Sr-containing PS II in the various S-states that provide important insights into the requirement for Ca in the mechanism of the Mn4Ca catalytic center. PMID:21524917
Calcium inputs and transport in a base-poor forest ecosystem as interpreted by Sr isotopes
Scott W. Bailey; James W. Hornbeck; Charles T. Driscoll; Henri E. Gaudette
1996-01-01
Depletion of Ca in forests and its effects on forest health are poorly quantified. Depletion has been difficult to document due to limitations in determining rates at which Ca becomes available for ecosystem processes through weathering, and difficulty in determining changes in ecosystem storage. We coupled a detailed analysis of Sr isotopic composition with a mass...
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chen, Min, E-mail: chenminyx@gmail.com; Yunnan Centers for Diseases Prevention and Control, Kunming 650022; Wang, Yanru
2010-06-11
Energy metabolism and Ca{sup 2+} handling serve critical roles in cardiac physiology and pathophysiology. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1{alpha}) is a multi-functional coactivator that is involved in the regulation of cardiac mitochondrial functional capacity and cellular energy metabolism. However, the regulation of PGC-1{alpha} in cardiac Ca{sup 2+} signaling has not been fully elucidated. To address this issue, we combined confocal line-scan imaging with off-line imaging processing to characterize calcium signaling in cultured adult rat ventricular myocytes expressing PGC-1{alpha} via adenoviral transduction. Our data shows that overexpressing PGC-1{alpha} improved myocyte contractility without increasing the amplitude of Ca{sup 2+}more » transients, suggesting that myofilament sensitivity to Ca{sup 2+} increased. Interestingly, the decay kinetics of global Ca{sup 2+} transients and Ca{sup 2+} waves accelerated in PGC-1{alpha}-expressing cells, but the decay rate of caffeine-elicited Ca{sup 2+} transients showed no significant change. This suggests that sarcoplasmic reticulum (SR) Ca{sup 2+}-ATPase (SERCA2a), but not Na{sup +}/Ca{sup 2+} exchange (NCX) contribute to PGC-1{alpha}-induced cytosolic Ca{sup 2+} clearance. Furthermore, PGC-1{alpha} induced the expression of SERCA2a in cultured cardiac myocytes. Importantly, overexpressing PGC-1{alpha} did not disturb cardiac Ca{sup 2+} homeostasis, because SR Ca{sup 2+} load and the propensity for Ca{sup 2+} waves remained unchanged. These data suggest that PGC-1{alpha} can ameliorate cardiac Ca{sup 2+} cycling and improve cardiac work output in response to physiological stress. Unraveling the PGC-1{alpha}-calcium handing pathway sheds new light on the role of PGC-1{alpha} in the therapy of cardiac diseases.« less
Experimental study of the effects of installation on singleand counter-rotation propeller noise
NASA Technical Reports Server (NTRS)
Block, P. J. W.
1986-01-01
Measurements which are required to define the directivity and the level of propeller noise were studied. The noise radiation pattern for various single-rotation (SR) propeller and counter-rotation (CR) propeller installations were mapped. The measurements covered + or - 60 deg from the propeller disk plane and + or - 60 deg in the cross-stream direction. Configurations examined included SR and CR propellers at angle of attack and an SR pusher installation. The increases in noise that arise from an unsteady loading operation such as an SR pusher or a CR exceeded 15 dB in the forward axial direction. Most of the additional noise radiates in the axial directions for unsteady loading operations of both the SR pusher and the CR tractor.
Huang, Baolin; Tian, Yu; Zhang, Wenjing; Ma, Yifan; Yuan, Yuan; Liu, Changsheng
2017-11-01
Preserving and improving osteogenic activity of bone morphogenetic protein-2 (BMP-2) upon implants remains one of the key limitations in bone regeneration. With calcium phosphate cement (CPC) as model, we have developed a series of strontium (Sr)-doped CPC (SCPC) to address this issue. The effects of fixed Sr on the bioactivity of recombinant human BMP-2 (rhBMP-2) as well as the underlying mechanism were investigated. The results suggested that the rhBMP-2-induced osteogenic activity was significantly promoted upon SCPCs, especially with a low amount of fixed Sr (SrCO 3 content <10wt%). Further studies demonstrated that the Sr-induced enhancement of bioactivity of rhBMP-2 was related to an elevated recognition of bone morphogenetic protein receptor-IA (BMPR-IA) to rhBMP-2 and an increased expression of BMPR-IA in C2C12 model cells. As a result, the activations of BMP-induced signaling pathways were different in C2C12 cells incubated upon CPC/rhBMP-2 and SCPCs/rhBMP-2. These findings explicitly decipher the mechanism of SCPCs promoting osteogenic bioactivity of rhBMP-2 and signify the promising application of the SCPCs/rhBMP-2 matrix in bone regeneration implants. Copyright © 2017 Elsevier B.V. All rights reserved.
Strontium-based glass polyalkenoate cements for luting applications in the skeleton.
Clarkin, O; Boyd, D; Towler, M R
2010-02-01
Glass Polyalkenoate Cements (GPCs) based on strontium calcium zinc silicate (Sr-Ca-Zn-SiO2) glasses and high molecular weight poly(acrylic acid) (PAA) have been shown to exhibit suitable mechanical properties for orthopaedic arthroplasty applications, however for vertebroplasty and other medical luting applications these cements have working and setting times which are unsuitable for such applications. In this study GPCs based on Sr-Ca-Zn-SiO2 glasses and low molecular weight PAA were evaluated for orthopaedic luting applications. GPCs based on four different glasses; BT100 (0.16CaO, 0.36ZnO, 0.48SiO2), BT101 (0.04SrO, 0.12CaO, 0.36ZnO, 0.48SiO2), BT102 (0.08SrO 0.08CaO, 0.36ZnO, 0.48SiO2) and BT103 (0.12SrO 0.04CaO, 0.36ZnO, 0.48SiO2) and two PAAs (MW; 12,700 and 25,700) were examined. These cement formulations exhibited handling properties potentially suitable for luting applications as well as mechanical strengths which were similar to those of trabecular bone. Upon immersion in simulated body fluid, the GPCs showed sustained growth of a calcium phosphate layer on the surface of the cement indicating that these cements were bioactive in nature.
Kaiser, Jozef; Holá, Markéta; Galiová, Michaela; Novotný, Karel; Kanický, Viktor; Martinec, Petr; Sčučka, Jiří; Brun, Francesco; Sodini, Nicola; Tromba, Giuliana; Mancini, Lucia; Kořistková, Tamara
2011-08-01
The outcomes from the feasibility study on utilization of synchrotron radiation X-ray microtomography (SR-μCT) to investigate the texture and the quantitative mineralogical composition of selected calcium oxalate-based urinary calculi fragments are presented. The comparison of the results obtained by SR-μCT analysis with those derived from current standard analytical approaches is provided. SR-μCT is proved as a potential effective technique for determination of texture, 3D microstructure, and composition of kidney stones.
Stepanchick, Ann; McKenna, Jennifer; McGovern, Olivia; Huang, Ying; Breitwieser, Gerda E.
2010-01-01
Calcium sensing receptor (CaSR) mutations implicated in familial hypocalciuric hypercalcemia, pancreatitis and idiopathic epilepsy syndrome map to an extended arginine-rich region in the proximal carboxyl terminus. Arginine-rich motifs mediate endoplasmic reticulum retention and/or retrieval of multisubunit proteins so we asked whether these mutations, R886P, R896H or R898Q, altered CaSR targeting to the plasma membrane. Targeting was enhanced by all three mutations, and Ca2+-stimulated ERK1/2 phosphorylation was increased for R896H and R898Q. To define the role of the extended arginine-rich region in CaSR trafficking, we independently determined the contributions of R890/R891 and/or R896/K897/R898 motifs by mutation to alanine. Disruption of the motif(s) significantly increased surface expression and function relative to wt CaSR. The arginine-rich region is flanked by phosphorylation sites at S892 (protein kinase C) and S899 (protein kinase A). The phosphorylation state of S899 regulated recognition of the arginine-rich region; S899D showed increased surface localization. CaSR assembles in the endoplasmic reticulum as a covalent disulfide-linked dimer and we determined whether retention requires the presence of arginine-rich regions in both subunits. A single arginine-rich region within the dimer was sufficient to confer intracellular retention comparable to wt CaSR. We have identified an extended arginine-rich region in the proximal carboxyl terminus of CaSR (residues R890 - R898) which fosters intracellular retention of CaSR and is regulated by phosphorylation. Mutation(s) identified in chronic pancreatitis and idiopathic epilepsy syndrome therefore increase plasma membrane targeting of CaSR, likely contributing to the altered Ca2+ signaling characteristic of these diseases. PMID:20798521
Lamboley, C R; Murphy, R M; McKenna, M J; Lamb, G D
2013-12-01
The relationship between sarcoplasmic reticulum (SR) Ca(2+) content and calsequestrin (CSQ) isoforms was investigated in human skeletal muscle. A fibre-lysing assay was used to quantify the endogenous Ca(2+) content and maximal Ca(2+) capacity of the SR in skinned segments of type I and type II fibres from vastus lateralis muscles of young healthy adults. Western blotting of individual fibres showed the great majority contained either all fast or all slow isoforms of myosin heavy chain (MHC), troponins C and I, tropomyosin and SERCA, and that the strontium sensitivity of the force response was closely indicative of the troponin C isoform present. The endogenous SR Ca(2+) content was slightly lower in type I compared to type II fibres (0.76 ± 0.03 and 0.85 ± 0.02 mmol Ca(2+) per litre of fibre, respectively), with virtually all of this Ca(2+) evidently being in the SR, as it could be rapidly released with a caffeine-low [Mg(2+)] solution (only 0.08 ± 0.01 and <0.07 mmol l(-1), respectively, remaining). The maximal Ca(2+) content that could be reached with SR Ca(2+) loading was 1.45 ± 0.04 and 1.79 ± 0.03 mmol l(-1) in type I and type II fibres, respectively (P < 0.05). In non-lysed skinned fibres, where the SR remained functional, repeated cycles of caffeine-induced Ca(2+) release and subsequent Ca(2+) reloading similarly indicated that (i) maximal SR Ca(2+) content was lower in type I fibres than in type II fibres (P < 0.05), and (ii) the endogenous Ca(2+) content represented a greater percentage of maximal content in type I fibres compared to type II fibres (∼59% and 41%, respectively, P < 0.05). Type II fibres were found on average to contain ∼3-fold more CSQ1 and ∼5-fold less CSQ2 than type I fibres (P < 0.001). The findings are consistent with the SR Ca(2+) content characteristics in human type II fibres being primarily determined by the CSQ1 abundance, and in type I fibres by the combined amounts of both CSQ1 and CSQ2.
Lamboley, C R; Murphy, R M; McKenna, M J; Lamb, G D
2013-01-01
The relationship between sarcoplasmic reticulum (SR) Ca2+ content and calsequestrin (CSQ) isoforms was investigated in human skeletal muscle. A fibre-lysing assay was used to quantify the endogenous Ca2+ content and maximal Ca2+ capacity of the SR in skinned segments of type I and type II fibres from vastus lateralis muscles of young healthy adults. Western blotting of individual fibres showed the great majority contained either all fast or all slow isoforms of myosin heavy chain (MHC), troponins C and I, tropomyosin and SERCA, and that the strontium sensitivity of the force response was closely indicative of the troponin C isoform present. The endogenous SR Ca2+ content was slightly lower in type I compared to type II fibres (0.76 ± 0.03 and 0.85 ± 0.02 mmol Ca2+ per litre of fibre, respectively), with virtually all of this Ca2+ evidently being in the SR, as it could be rapidly released with a caffeine-low [Mg2+] solution (only 0.08 ± 0.01 and <0.07 mmol l−1, respectively, remaining). The maximal Ca2+ content that could be reached with SR Ca2+ loading was 1.45 ± 0.04 and 1.79 ± 0.03 mmol l−1 in type I and type II fibres, respectively (P < 0.05). In non-lysed skinned fibres, where the SR remained functional, repeated cycles of caffeine-induced Ca2+ release and subsequent Ca2+ reloading similarly indicated that (i) maximal SR Ca2+ content was lower in type I fibres than in type II fibres (P < 0.05), and (ii) the endogenous Ca2+ content represented a greater percentage of maximal content in type I fibres compared to type II fibres (∼59% and 41%, respectively, P < 0.05). Type II fibres were found on average to contain ∼3–fold more CSQ1 and ∼5–fold less CSQ2 than type I fibres (P < 0.001). The findings are consistent with the SR Ca2+ content characteristics in human type II fibres being primarily determined by the CSQ1 abundance, and in type I fibres by the combined amounts of both CSQ1 and CSQ2. PMID:24127619
Pape, Paul C.; Carrier, Nicole
1998-01-01
Cut muscle fibers from Rana temporaria (sarcomere length, 3.5–3.9 μm; 14–16°C) were mounted in a double Vaseline-gap chamber and equilibrated with an external solution that contained tetraethyl ammonium– gluconate and an internal solution that contained Cs as the principal cation, 20 mM EGTA, and 0 Ca. Fibers were stimulated with a voltage-clamp pulse protocol that consisted of pulses to −70, −65, −60, −45, and −20 mV, each separated by 400-ms periods at −90 mV. The change in total Ca that entered into the myoplasm (Δ[CaT]) and the Ca content of the SR ([CaSR]) were estimated with the EGTA/phenol red method (Pape, P.C., D.-S. Jong, and W.K. Chandler. 1995. J. Gen. Physiol. 106:259–336). Fibers were stimulated with the pulse protocol, usually every 5 min, so that the resting value of [CaSR] decreased from its initial value of 1,700–2,300 μM to values near or below 100 μM after 18–30 stimulations. Three main findings for the voltage pulses to −70, −65, and −60 mV are: (a) the depletion-corrected rate of Ca release (release permeability) showed little change when [CaSR] decreased from its highest level (>1,700 μM) to ∼1,000 μM; (b) as [CaSR] decreased below 1,000 μM, the release permeability increased to a maximum level when [CaSR] was near 300 μM that was on average about sevenfold larger than the values observed for [CaSR] > 1,000 μM; and (c) as [CaSR] decreased from ∼300 μM to <100 μM, the release permeability decreased, reaching half its maximum value when [CaSR] was ∼110 μM on average. It was concluded that finding b was likely due to a decrease in Ca inactivation, while finding c was likely due to a decrease in Ca-induced Ca release. PMID:9689025
Hermeling, Evelien; Delhaas, Tammo; Prinzen, Frits W; Kuijpers, Nico H L
2012-01-01
In the ECG, T- and R-wave are concordant during normal sinus rhythm (SR), but discordant after a period of ventricular pacing (VP). Experiments showed that the latter phenomenon, called T-wave memory, is mediated by a mechanical stimulus. By means of a mathematical model, we investigated the hypothesis that slow acting mechano-electrical feedback (MEF) explains T-wave memory. In our model, electromechanical behavior of the left ventricle (LV) was simulated using a series of mechanically and electrically coupled segments. Each segment comprised ionic membrane currents, calcium handling, and excitation-contraction coupling. MEF was incorporated by locally adjusting conductivity of L-type calcium current (g(CaL)) to local external work. In our set-up, g(CaL) could vary up to 25%, 50%, 100% or unlimited amount around its default value. Four consecutive simulations were performed: normal SR (with MEF), acute VP, sustained VP (with MEF), and acutely restored SR. MEF led to T-wave concordance in normal SR and to discordant T-waves acutely after restoring SR. Simulated ECGs with a maximum of 25-50% adaptation closely resembled those during T-wave memory experiments in vivo and also provided the best compromise between optimal systolic and diastolic function. In conclusion, these simulation results indicate that slow acting MEF in the LV can explain a) the relatively small differences in systolic shortening and mechanical work during SR, b) the small dispersion in repolarization time, c) the concordant T-wave during SR, and d) T-wave memory. The physiological distribution in electrophysiological properties, reflected by the concordant T-wave, may serve to optimize cardiac pump function. Copyright © 2012 Elsevier Ltd. All rights reserved.
Meibom, A.; Stage, M.; Wooden, J.; Constantz, B.R.; Dunbar, R.B.; Owen, A.; Grumet, N.; Bacon, C.R.; Chamberlain, C.P.
2003-01-01
In thermodynamic equilibrium with sea water the Sr/Ca ratio of aragonite varies predictably with temperature and the Sr/Ca ratio in coral have thus become a frequently used proxy for past Sea Surface Temperature (SST). However, biological effects can offset the Sr/Ca ratio from its equilibrium value. We report high spatial resolution ion microprobe analyses of well defined skeletal elements in the reef-building coral Porites lutea that reveal distinct monthly oscillations in the Sr/Ca ratio, with an amplitude in excess of ten percent. The extreme Sr/Ca variations, which we propose result from metabolic changes synchronous with the lunar cycle, introduce variability in Sr/Ca measurements based on conventional sampling techniques well beyond the analytical precision. These variations can limit the accuracy of Sr/Ca paleothermometry by conventional sampling techniques to about 2??C. Our results may help explain the notorious difficulties involved in obtaining an accurate and consistent calibration of the Sr/Ca vs. SST relationship.
Noble, Debbie; Borysova, Lyudmyla; Wray, Susan; Burdyga, Theodor
2014-09-01
In the myometrium SR Ca(2+) depletion promotes an increase in force but unlike several other smooth muscles, there is no Ca(2+) sparks-STOCs coupling mechanism to explain this. Given the importance of the control of contractility for successful parturition, we have examined, in pregnant rat myometrium, the effects of SR Ca(2+)-ATPase (SERCA) inhibition on the temporal relationship between action potentials, Ca(2+) transients and force. Simultaneous recording of electrical activity, calcium and force showed that SERCA inhibition, by cyclopiazonic acid (CPA 20 μM), caused time-dependent changes in excitability, most noticeably depolarization and elevations of baseline [Ca(2+)]i and force. At the onset of these changes there was a prolongation of the bursts of action potentials and a corresponding series of Ca(2+) spikes, which increased the amplitude and duration of contractions. As the rise of baseline Ca(2+) and depolarization continued a point was reached when electrical and Ca(2+) spikes and phasic contractions ceased, and a maintained, tonic force and Ca(2+) was produced. Lanthanum, a non-selective blocker of store-operated Ca(2+) entry, but not the L-type Ca(2+) channel blocker nifedipine (1-10 μM), could abolish the maintained force and calcium. Application of the agonist, carbachol, produced similar effects to CPA, i.e. depolarization, elevation of force and calcium. A brief, high concentration of carbachol, to cause SR Ca(2+) depletion without eliciting receptor-operated channel opening, also produced these results. The data obtained suggest that in pregnant rats SR Ca(2+) release is coupled to marked Ca(2+) entry, via store operated Ca(2+) channels, leading to depolarization and enhanced electrical and mechanical activity. Copyright © 2014. Published by Elsevier Ltd.
Maltsev, Alexander V.; Maltsev, Victor A.; Stern, Michael D.
2017-01-01
Intracellular Local Ca releases (LCRs) from sarcoplasmic reticulum (SR) regulate cardiac pacemaker cell function by activation of electrogenic Na/Ca exchanger (NCX) during diastole. Prior studies demonstrated the existence of powerful compensatory mechanisms of LCR regulation via a complex local cross-talk of Ca pump, release and NCX. One major obstacle to study these mechanisms is that LCR exhibit complex Ca release propagation patterns (including merges and separations) that have not been characterized. Here we developed new terminology, classification, and computer algorithms for automatic detection of numerically simulated LCRs and examined LCR regulation by SR Ca pumping rate (Pup) that provides a major contribution to fight-or-flight response. In our simulations the faster SR Ca pumping accelerates action potential-induced Ca transient decay and quickly clears Ca under the cell membrane in diastole, preventing premature releases. Then the SR generates an earlier, more synchronized, and stronger diastolic LCR signal activating an earlier and larger inward NCX current. LCRs at higher Pup exhibit larger amplitudes and faster propagation with more collisions to each other. The LCRs overlap with Ca transient decay, causing an elevation of the average diastolic [Ca] nadir to ~200 nM (at Pup = 24 mM/s). Background Ca (in locations lacking LCRs) quickly decays to resting Ca levels (<100 nM) at high Pup, but remained elevated during slower decay at low Pup. Release propagation is facilitated at higher Pup by a larger LCR amplitude, whereas at low Pup by higher background Ca. While at low Pup LCRs show smaller amplitudes, their larger durations and sizes combined with longer transient decay stabilize integrals of diastolic Ca and NCX current signals. Thus, the local interplay of SR Ca pump and release channels regulates LCRs and Ca transient decay to insure fail-safe pacemaker cell operation within a wide range of rates. PMID:28792496
The role of working memory in spatial S-R correspondence effects.
Wühr, Peter; Biebl, Rupert
2011-04-01
This study investigates the impact of working memory (WM) load on response conflicts arising from spatial (non) correspondence between irrelevant stimulus location and response location (Simon effect). The dominant view attributes the Simon effect to automatic processes of location-based response priming. The automaticity view predicts insensitivity of the Simon effect to manipulations of processing load. Four experiments investigated the role of spatial and verbal WM in horizontal and vertical Simon tasks by using a dual-task approach. Participants maintained different amounts of spatial or verbal information in WM while performing a horizontal or vertical Simon task. Results showed that high load generally decreased, and sometimes eliminated, the Simon effect. It is interesting to note that spatial load had a larger impact than verbal load on the horizontal Simon effect, whereas verbal load had a larger impact than spatial load on the vertical Simon effect. The results highlight the role of WM as the perception-action interface in choice-response tasks. Moreover, the results suggest spatial coding of horizontal stimulus-response (S-R) tasks, and verbal coding of vertical S-R tasks.
High speed turboprop aeroacoustic study (single rotation). Volume 1: Model development
NASA Technical Reports Server (NTRS)
Whitfield, C. E.; Gliebe, P. R.; Mani, R.; Mungur, P.
1989-01-01
A frequency-domain noncompact-source theory for the steady loading and volume-displacement (thickness) noise of high speed propellers has been developed and programmed. Both near field and far field effects have been considered. The code utilizes blade surface pressure distributions obtained from three-dimensional nonlinear aerodynamic flow field analysis programs as input for evaluating the steady loading noise. Simplified mathematical models of the velocity fields induced at the propeller disk by nearby wing and fuselage surfaces and by angle-of-attack operation have been developed to provide estimates of the unsteady loading imposed on the propeller by these potential field type interactions. These unsteady blade loadings have been coupled to a chordwise compact propeller unsteady loading noise model to provide predictions of unsteady loading noise caused by these installation effects. Finally, an analysis to estimate the corrections to be applied to the free-field noise predictions in order to arrive at the measurable fuselage sound pressure levels has been formulated and programmed. This analysis considers the effects of fuselage surface reflection and diffraction together with surface boundary layer refraction. The steady loading and thickness model and the unsteady loading model have been verified using NASA-supplied data for the SR-2 and SR-3 model propfans. In addition, the steady loading and thickness model has been compared with data from the SR-6 model propfan. These theoretical models have been employed in the evaluation of the SR-7 powered Gulfstream aircraft in terms of noise characteristics at representative takeoff, cruise, and approach operating conditions. In all cases, agreement between theory and experiment is encouraging.
Calcium carbonate precipitation rate as a function of ion ratio in the presence & absence of Sr2+
NASA Astrophysics Data System (ADS)
Gebrehiwet, T.; Beig, M. S.; Fujita, Y.; Redden, G. D.; Smith, R. W.
2010-12-01
Tsigabu Gebrehiwet 1*, Mikala Beig 2, Yoshiko Fujita 3, George Redden 3 and Robert W. Smith 1 1University of Idaho, 1776 Science Center Dr, Idaho Falls,ID, 83402 (*tgebrehiwet@uidaho.edu; smithbob@uidaho.edu ) 27963 Grasmere Dr.Boulder, CO 80301(mbeig@alumni.rice.edu) 3Idaho National Laboratory, MS 2208, Idaho Falls, ID 83415 (Yoshiko.Fujita@inl.gov; George.Redden@inl.gov) Engineered in situ precipitation of calcium carbonate is a proposed strategy for remediating toxic or radioactive metals (e.g., Sr2+)in subsurface environments as well as for modifying the physical properties (e.g., stiffness, permeability) of geomedia. Inducing the precipitation reaction will likely involve manipulating the geochemical conditions by adding calcium, (bi)carbonate, or both, and relying on mixing of the two reactants. Under these conditions, the ratio of Ca2+ to CO32- will vary with distance from the mixing interface, and for most or all of the porous medium, a 1:1 stoichiometry between calcium and carbonate is unlikely to be achieved. Indeed, in engineered systems where rapid treatment is an important objective, very steep ion concentration gradients may be generated, which would result in local reactant ratios varying from very small to very large over short distances, depending on the mixing geometry and particular chemical composition of the mixing fluids. This in turn has an impact on the rate of mineral precipitation. Typically, the rate of calcium carbonate precipitation is expressed with an affinity-based rate law of the type: Rate = k(Ω-1)n, where k is a rate constant, Ω is the saturation state for the mineral (e.g., calcite), and n is an empirical reaction order. The saturation state Ω is defined as the ratio of the ion activity product to the mineral solubility product. In this expression, the rate is simply dependent on the value of Ω; the actual activities of the individual ions (Ca2+ and CO32-) do not appear in the expression. In support of the development of engineered calcite precipitation schemes for contaminant immobilization, we have conducted experiments on CaCO3 precipitation kinetics under constant composition conditions where the supersaturation state (Ω) with respect to calcite is held constant at 12.8, but the ion activity ratio (Ca2+:CO32-) is varied. The objective is to examine the effect of the ion ratio on the mineral precipitation rate and on the distribution coefficient for co-precipitated Sr (DexSr). Our results to date indicate that precipitation rates vary by up to a factor of two with the maximum rate occurring at r=0.23, where r is carbonate to calcium ions ratio. In addition, although the extent of variation in the DexSr values is similar to that for the calcite precipitation rate, we have observed low correlation between strontium distribution coefficients and precipitation rates.
Weiffert, Tanja; Ní Mhurchú, Niamh; O’Connell, David; Linse, Sara
2016-01-01
Secretagogin is a calcium-sensor protein with six EF-hands. It is widely expressed in neurons and neuro-endocrine cells of a broad range of vertebrates including mammals, fishes and amphibia. The protein plays a role in secretion and interacts with several vesicle-associated proteins. In this work, we have studied the contribution of calcium binding and disulfide-bond formation to the stability of the secretagogin structure towards thermal and urea denaturation. SDS-PAGE analysis of secretagogin in reducing and non-reducing conditions identified a tendency of the protein to form dimers in a redox-dependent manner. The denaturation of apo and Calcium-loaded secretagogin was studied by circular dichroism and fluorescence spectroscopy under conditions favoring monomer or dimer or a 1:1 monomer: dimer ratio. This analysis reveals significantly higher stability towards urea denaturation of Calcium-loaded secretagogin compared to the apo protein. The secondary and tertiary structure of the Calcium-loaded form is not completely denatured in the presence of 10 M urea. Reduced and Calcium-loaded secretagogin is found to refold reversibly after heating to 95°C, while both oxidized and reduced apo secretagogin is irreversibly denatured at this temperature. Thus, calcium binding greatly stabilizes the structure of secretagogin towards chemical and heat denaturation. PMID:27812162
Serum calcium and incident type 2 diabetes: the Atherosclerosis Risk in Communities (ARIC) study.
Rooney, Mary R; Pankow, James S; Sibley, Shalamar D; Selvin, Elizabeth; Reis, Jared P; Michos, Erin D; Lutsey, Pamela L
2016-10-01
Elevated serum calcium has been associated with a variety of metabolic abnormalities and may be associated with a greater risk of diabetes. The purpose of this study was to test the hypothesis that serum calcium concentration is positively and independently associated with the incidence of diabetes and to evaluate the association of calcium-sensing receptor (CaSR) gene single nucleotide polymorphism (SNP) rs1801725 with incident diabetes. Atherosclerosis Risk in Communities study participants free of diabetes at baseline (n = 12,800; mean age: 53.9 y; 22.6% black) were studied for incident diabetes. Serum calcium was measured at baseline and corrected for serum albumin. Diabetes was defined by use of glucose concentrations, self-report, or medication use. Cox proportional hazards regression was used. During a mean 8.8 y of follow-up, 1516 cases of diabetes were reported. Participants in the highest compared with lowest calcium quintile were at greater risk of incident diabetes after adjustment for demographic and lifestyle factors [HR (95% CI): 1.34 (1.14, 1.57); P-trend across quintiles <0.0001] and with further adjustment for waist circumference and body mass index [1.26 (1.07, 1.48); P-trend = 0.004]. Additional adjustment for biomarkers on the metabolic pathway (e.g., 25-hydroxyvitamin D, parathyroid hormone, phosphorus) had little impact. The calcium-diabetes association was statistically significant in blacks [1.48 (1.11, 1.98); P-trend = 0.002] but not whites [1.17 (0.96, 1.43); P-trend = 0.17] after adjustment for adiposity. In whites, CaSR gene SNP rs1801725 was associated with serum calcium but not with risk of diabetes. Consistent with 3 previous cohort studies, elevated serum calcium was found to be associated with a greater risk of type 2 diabetes. Further research is needed to understand the role, if any, that calcium plays in the pathogenesis of diabetes. © 2016 American Society for Nutrition.
NASA Astrophysics Data System (ADS)
Cosentino, Nicolas Juan
The lithosphere-scale geodynamic mechanisms that control forearc topography are still contentious. In northern Chile, this is in part due to a lack of paleoelevation constraints. In order to rectify this lack of data, this thesis carries out a series of studies. First, a new paleoaltimetry proxy for the hyperarid Atacama Desert was developed, based on the elevation-dependent relationship of the 87Sr/86Sr ratio of Holocene surface accumulations of salts. Here, an important source of calcium sulfate comes from stratocumulus clouds that generate fog on the continent, transferring water droplets to the ground surface which, upon evaporation, precipitate calcium sulfate. The seawater ratio of 87Sr/86Sr (0.70917) is distinctly higher than that of weathered mean Andean rock (<0.70750). Sites below 1075 m.a.s.l. and above 225 m.a.s.l. display Holocene calcium sulfate 87Sr/86Sr of mean value 0.70807 ± 0.00004, while the ratio outside this altitudinal domain is 0.70746 ± 0.00010. Based on these results for Holocene materials, Pliocene-Pleistocene paleoelevations of the forearc surface were inferred. We measured 87Sr/86Sr of dated ancient gypsic soils and applied appropriate corrections to the paleo-fog zone top and bottom. The results show that the magnitudes of paleo-elevation changes are small compared to the elevation of the study area: more than 45% of the 1000 m.a.s.l. average elevation of the Central Depression and more than 70% of the 900 m.a.s.l. average elevation of the westernmost Coastal Cordillera were achieved by pre-early Pliocene regional scale tectonic processes. Finally, the response of the forearc surface to 2D viscoelastic flow in a subduction channel was characterized numerically. 800-1100-m-thick subduction channels with viscosities of 5-10 x1018 Pa s best fit the elevations of the Central Depression after steady-state topography is reached in less than 6 myr. The onset of hyperaridity at 25 Ma starved the trench and subduction channel of sediments, raising shear stresses at the plate interface and uplifting the forearc. Short-lived phases of less aridity may have affected forearc topography transiently. The models predict that in order to accord with available Central Depression paleoelevation constraints, these phases translated to pulses of “weaker” subduction channels with viscosities between 2-7 x1018 Pa s.
NASA Astrophysics Data System (ADS)
Jordan, T. E.; Cosentino, N. J.
2014-12-01
We have developed a new altimeter proxy based on the 87Sr/86Sr ratio of surficial accumulations of salts in hyperarid settings. Under hyperarid conditions like in the Andean forearc in northern Chile at altitudes below ~3000 m.a.s.l., gypsum and other soluble salts form saline soils. The altimeter is based on the first-order topographic control on the extent of inland incursion of fog-transported marine aerosols derived from the Pacific Ocean. Once this fog is evaporated it deposits calcium sulfates with a marine 87Sr/86Sr signal. At positions in the landscape not reached by marine aerosols, calcium sulfates have no marine source, except by eolian reworking, and have a lower 87Sr/86Sr. 87Sr/86Sr values for Holocene accumulations of salts show a bimodal distribution: high values between 225-1075 m.a.s.l. (0.70807 ± 0.00004) and low values below and above those altitude thresholds (0.70746 ± 0.00010). We sampled dated gypsic relict soils and Gypsisols to study post-5 Ma surface height evolution using this method, after correcting for changes in the altitudinal structure of the paleo-fog zone with time. Locations spanning ~250 km strike-parallel distance within the forearc and at elevations between 450-1650 m.a.s.l. display moderate amounts of altitudinal change during the Pliocene, Pleistocene and Quaternary. Site results include two in the northern zone (19.5ºS and 19.65ºS) that experienced maximum net surface uplifts of ~350 m and ~600 m since 2.5 ± 0.5 Ma and ~2.6 Ma, respectively. Locations at ~21.4°S display an estimated minimum net decline in altitude of ~250 m since 3.4 ± 1.1 Ma and ~200 m since 1.1 ± 0.4 Ma. These constraints will shed light on the geodynamic processes responsible for surface elevation change, by acting as boundary conditions to numerical models of the Andean forearc.
Calcium-dependent phosphodiesterase 1C inhibits renin release from isolated juxtaglomerular cells
Ortiz-Capisano, M. Cecilia; Liao, Tang-Dong; Ortiz, Pablo A.
2009-01-01
Renin release from the juxtaglomerular (JG) cell is stimulated by the second messenger cAMP and inhibited by calcium. We previously showed JG cells contain a calcium sensing receptor (CaSR), which, when stimulated, decreases cAMP formation and inhibits renin release. We hypothesize CaSR activation decreases cAMP and renin release, in part, by stimulating a calcium calmodulin-activated phosphodiesterase 1 (PDE1). We incubated our primary culture of JG cells with two selective PDE1 inhibitors [8-methoxymethil-IBMX (8-MM-IBMX; 20 μM) and vinpocetine (40 μM)] and the calmodulin inhibitor W-7 (10 μM) and measured cAMP and renin release. Stimulation of the JG cell CaSR with the calcimimetic cinacalcet (1 μM) resulted in decreased cAMP from a basal of 1.13 ± 0.14 to 0.69 ± 0.08 pM/mg protein (P < 0.001) and in renin release from 0.89 ± 0.16 to 0.38 ± 0.08 μg ANG I/ml·h−1·mg protein−1 (P < 0.001). However, the addition of 8-MM-IBMX with cinacalcet returned both cAMP (1.10 ± 0.19 pM/mg protein) and renin (0.57 ± 0.16 μg ANG I/ml·h−1·mg protein−1) to basal levels. Similar results were obtained with vinpocetine, and also with W-7. Combining 8-MM-IBMX and W-7 had no additive effect. To determine which PDE1 isoform is involved, we performed Western blot analysis for PDE1A, B, and C. Only Western blot analysis for PDE1C showed a characteristic band apparent at 80 kDa. Immunofluorescence showed cytoplasmic distribution of PDE1C and renin in the JG cells. In conclusion, PDE1C is expressed in isolated JG cells, and contributes to calcium's inhibitory modulation of renin release from JG cells. PMID:19741056
DOE Office of Scientific and Technical Information (OSTI.GOV)
Choudhary, V.R.; Mulla, S.A.R.; Uphade, B.S.
1998-06-01
The influence of catalyst carrier or support (with different chemical compositions and surface properties), catalyst deposition method (viz., impregnation and coating), precursor for strontium oxide (SrO; Sr-nitrate, acetate, hydroxide, and carbonate), and loading of SrO and lanthanum oxide (La{sub 2}O{sub 3}; 0--25 wt%) on the surface properties and performance of catalyst in oxidative coupling of methane (OCM; at 850 C, gas hourly space velocity = 1.02 {times} 10{sup 5} cm{sup 3}/g{center_dot}h and CH{sub 4}/O{sub 2} = 4 or 16) was thoroughly investigated. The basicity, acidity, and O{sub 2} chemisorption of the catalysts were studied by the temperature programmed desorption (TPD)more » of CO{sub 2}, NH{sub 3}, and O{sub 2}, respectively, from 50 to 950 C. The total and strong basic sites, acidity, and OCM activity of the supported catalyst were strongly influenced by the support used and also by the La{sub 2}O{sub 3} loading on the support. The catalyst with a sintered low surface area porous silica-Alumina support and high (20 wt%) La{sub 2}O{sub 3} and SrO loadings showed the best performance in the OCM process. The OCM activity was influenced by SrO loading, but to a smaller extent, and also by the method of SrO deposition. The OCM activity of the supported catalysts could be related to their strong basic sites (measured in terms of the CO{sub 2} desorbed between 500 and 950 C).« less
The extracellular calcium-sensing receptor regulates human fetal lung development via CFTR
Brennan, Sarah C.; Wilkinson, William J.; Tseng, Hsiu-Er; Finney, Brenda; Monk, Bethan; Dibble, Holly; Quilliam, Samantha; Warburton, David; Galietta, Luis J.; Kemp, Paul J.; Riccardi, Daniela
2016-01-01
Optimal fetal lung growth requires anion-driven fluid secretion into the lumen of the developing organ. The fetus is hypercalcemic compared to the mother and here we show that in the developing human lung this hypercalcaemia acts on the extracellular calcium-sensing receptor, CaSR, to promote fluid-driven lung expansion through activation of the cystic fibrosis transmembrane conductance regulator, CFTR. Several chloride channels including TMEM16, bestrophin, CFTR, CLCN2 and CLCA1, are also expressed in the developing human fetal lung at gestational stages when CaSR expression is maximal. Measurements of Cl−-driven fluid secretion in organ explant cultures show that pharmacological CaSR activation by calcimimetics stimulates lung fluid secretion through CFTR, an effect which in humans, but not mice, was also mimicked by fetal hypercalcemic conditions, demonstrating that the physiological relevance of such a mechanism appears to be species-specific. Calcimimetics promote CFTR opening by activating adenylate cyclase and we show that Ca2+-stimulated type I adenylate cyclase is expressed in the developing human lung. Together, these observations suggest that physiological fetal hypercalcemia, acting on the CaSR, promotes human fetal lung development via cAMP-dependent opening of CFTR. Disturbances in this process would be expected to permanently impact lung structure and might predispose to certain postnatal respiratory diseases. PMID:26911344
METHOD OF REMOVING STRONTIUM IONS
Rhodes, D.W.; McHenry, J.R.; Ames, L.L. Jr.
1962-05-01
A method is given for removing trace amounts of Sr/sup 90/ from solutions. Phosphate ion is added to the solution and it is then brought into contact with a solid salt such as calcium carbonate which will react methathetically with the phosphate ion to form a salt such as calcium phosphate. During this reaction, strontium will be absorbed to a high degree within the newly formed lattice. (AEC)
Ca4As3 – a new binary calcium arsenide
Hoffmann, Andrea V.; Hlukhyy, Viktor; Fässler, Thomas F.
2015-01-01
The crystal structure of the binary compound tetracalcium triarsenide, Ca4As3, was investigated by single-crystal X-ray diffraction. Ca4As3 crystallizes in the Ba4P3 structure type and is thus a homologue of isotypic Sr4As3. The unit cell contains 32 Ca2+ cations, 16 As3− isolated anions and four centrosymmetric [As2]4– dumbbells. The As atoms in each of the dumbbells are connected by a single bond, thus this calcium arsenide is a Zintl phase. PMID:26870427
Reinforced fluropolymer nanocomposites with high-temperature superconducting Bi2Sr2CaCu2Oy
NASA Astrophysics Data System (ADS)
Jayasree, T. K.
2014-10-01
Bismuth Strontium Calcium Copper Oxide (Bi2Sr2CaCu2Oy)/Polyvinylidene fluoride (PVDF) nanocomposite was prepared and their thermal properties were analyzed. The composite consists of the polyvinylidene fluoride (PVDF) as an insulating polymer matrix, and homogenously distributed Bismuth strontium calcium copperoxide (2212) nanoparticles. SEM data shows flaky grains of the superconductor coated and linked by polymer. Differential scanning calorimetry (DSC) results indicated that the melting point was not affected significantly by the addition of BSCCO. However, the addition of superconducting ceramic resulted in an extra melting peak at a lower temperature (145°C). Thermogravimetric analysis of the samples shows that the onset decomposition temperature of the PVDF matrix was decreased by the addition of SC filler.
Alsaleh, Nasser B.; Persaud, Indushekhar; Brown, Jared M.
2016-01-01
Engineered nanomaterial (ENM)-mediated toxicity often involves triggering immune responses. Mast cells can regulate both innate and adaptive immune responses and are key effectors in allergic diseases and inflammation. Silver nanoparticles (AgNPs) are one of the most prevalent nanomaterials used in consumer products due to their antimicrobial properties. We have previously shown that AgNPs induce mast cell degranulation that was dependent on nanoparticle physicochemical properties. Furthermore, we identified a role for scavenger receptor B1 (SR-B1) in AgNP-mediated mast cell degranulation. However, it is completely unknown how SR-B1 mediates mast cell degranulation and the intracellular signaling pathways involved. In the current study, we hypothesized that SR-B1 interaction with AgNPs directs mast cell degranulation through activation of signal transduction pathways that culminate in an increase in intracellular calcium signal leading to mast cell degranulation. For these studies, we utilized bone marrow-derived mast cells (BMMC) isolated from C57Bl/6 mice and RBL-2H3 cells (rat basophilic leukemia cell line). Our data support our hypothesis and show that AgNP-directed mast cell degranulation involves activation of PI3K, PLCγ and an increase in intracellular calcium levels. Moreover, we found that influx of extracellular calcium is required for the cells to degranulate in response to AgNP exposure and is mediated at least partially via the CRAC channels. Taken together, our results provide new insights into AgNP-induced mast cell activation that are key for designing novel ENMs that are devoid of immune system activation. PMID:27907088
Handling of induced hypercalcaemia in hyperthyroidism
Lim, P.; Jacob, E.; Khoo, O. T.
1969-01-01
The mean serum calcium of 13 hyperthyroid patients was found to be significantly higher than that of controls matched for sex and age, though none of the patients' values were outside the normal range. Nevertheless, these patients responded very promptly to hypercalcaemia (induced by an intravenous calcium load), and their serum calcium returned to normal much more rapidly compared with the matched controls. There was also increased retention of intravenous calcium load, possibly owing to increased calcitonin production. Calcium infusion may be useful in treating bone diseases in which increased bone resorption exceeds bone accretion. PMID:5354875
NASA Astrophysics Data System (ADS)
Cherepy, N. J.; Payne, S. A.; Sturm, B. W.; O'Neal, S. P.; Seeley, Z. M.; Drury, O. B.; Haselhorst, L. K.; Rupert, B. L.; Sanner, R. D.; Thelin, P. A.; Fisher, S. E.; Hawrami, R.; Shah, K. S.; Burger, A.; Ramey, J. O.; Boatner, L. A.
2011-09-01
Recently discovered scintillators for gamma ray spectroscopy - single-crystal SrI2(Eu), GYGAG(Ce) transparent ceramic and Bismuth-loaded plastics - offer resolution and fabrication advantages compared to commercial scintillators, such as NaI(Tl) and standard PVT plastic. Energy resolution at 662 keV of 2.7% is obtained with SrI2(Eu), while 4.5% is obtained with GYGAG(Ce). A new transparent ceramic scintillator for radiographic imaging systems, GLO(Eu), offers high light yield of 70,000 Photons/MeV, high stopping, and low radiation damage. Implementation of single-crystal SrI2(Eu), Gd-based transparent ceramics, and Bi-loaded plastic scintillators can advance the state-of-the art in ionizing radiation detection systems.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cherepy, N J; Payne, S A; Sturm, B W
2011-08-30
Recently discovered scintillators for gamma ray spectroscopy, single crystal SrI{sub 2}(Eu), GYGAG(Ce) transparent ceramic and Bismuth-loaded plastics, offer resolution and fabrication advantages compared to commercial scintillators, such as NaI(Tl) and standard PVT plastic. Energy resolution at 662 keV of 2.7% is obtained with SrI{sub 2}(Eu), while 4.5% is obtained with GYGAG(Ce). A new transparent ceramic scintillator for radiographic imaging systems, GLO(Eu) offers high light yield of 70,000 Photons/MeV, high stopping, and low radiation damage. Implementation of single crystal SrI{sub 2}(Eu), Gd-based transparent ceramics, and Bi-loaded plastic scintillators can advance the state-of-the art in ionizing radiation detection systems.
Zhao, Ming; He, Xi; Yang, Yong-Hua; Yu, Xiao-Jiang; Bi, Xue-Yuan; Yang, Yang; Xu, Man; Lu, Xing-Zhu; Sun, Qiang; Zang, Wei-Jin
2015-04-01
The Ca(2+)-sensing receptor (CaSR) plays an important role in regulating vascular tone. In the present study, we investigated the positive effects of the vagal neurotransmitter acetylcholine by suppressing CaSR activation in mesenteric arteries exposed to hypoxia/reoxygenation (H/R). The artery rings were exposed to a modified 'ischemia mimetic' solution and an anaerobic environment to simulate an H/R model. Our results showed that acetylcholine (10(-6) mol/L) significantly reduced the contractions induced by KCl and phenylephrine and enhanced the endothelium-dependent relaxation induced by acetylcholine. Additionally, acetylcholine reduced CaSR mRNA expression and activity when the rings were subjected to 4 h of hypoxia and 12 h of reoxygenation. Notably, the CaSR antagonist NPS2143 significantly reduced the contractions but did not improve the endothelium-dependent relaxation. When a contractile response was achieved with extracellular Ca(2+), both acetylcholine and NPS2143 reversed the H/R-induced abnormal vascular vasoconstriction, and acetylcholine reversed the calcimimetic R568-induced abnormal vascular vasoconstriction in the artery rings. In conclusion, this study suggests that acetylcholine ameliorates the dysfunctional vasoconstriction of the arteries after H/R, most likely by decreasing CaSR expression and activity, thereby inhibiting the increase in intracellular calcium concentration. Our findings may be indicative of a novel mechanism underlying ACh-induced vascular protection. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.
Studies on Inhibition of Intestinal Absorption of Radioactive Strontium
Skoryna, Stanley C.; Paul, T. M.; Edward, Deirdre Waldron
1964-01-01
A method is reported which permits selective suppression of absorption of radioactive strontium from ingested food material, permitting the calcium to be available to the body. Studies were carried out in vivo by injection of Sr89 and Ca45 in the presence of inert carrier into ligated intestinal segments in rats, and the amount of absorption was measured by standard monitoring techniques. The pattern of absorption of both ions is very similar but the rate of absorption is different. It was found that the polyelectrolyte, sodium alginate, obtained from brown algae (Phaeophyceae), injected simultaneously with radiostrontium effectively reduces the absortion of Sr89 from all segments of the intestine by as much as 50-80% of the control values. No significant reduction in absorption of Ca45 was observed in equivalent concentrations. The reduction in blood levels of Sr89 and in bone uptake corresponded to the absorption pattern. The difference in the effect on strontium and calcium absorption may be due to differences in the binding capacity of sodium alginate from the two metal ions under the conditions present in vivo. PMID:14180534
Structural mechanism of ligand activation in human calcium-sensing receptor
DOE Office of Scientific and Technical Information (OSTI.GOV)
Geng, Yong; Mosyak, Lidia; Kurinov, Igor
2016-07-19
Human calcium-sensing receptor (CaSR) is a G-protein-coupled receptor (GPCR) that maintains extracellular Ca 2+homeostasis through the regulation of parathyroid hormone secretion. It functions as a disulfide-tethered homodimer composed of three main domains, the Venus Flytrap module, cysteine-rich domain, and seven-helix transmembrane region. Here, we present the crystal structures of the entire extracellular domain of CaSR in the resting and active conformations. We provide direct evidence that L-amino acids are agonists of the receptor. In the active structure, L-Trp occupies the orthosteric agonist-binding site at the interdomain cleft and is primarily responsible for inducing extracellular domain closure to initiate receptor activation.more » Our structures reveal multiple binding sites for Ca 2+and PO 4 3-ions. Both ions are crucial for structural integrity of the receptor. While Ca 2+ions stabilize the active state, PO 4 3-ions reinforce the inactive conformation. The activation mechanism of CaSR involves the formation of a novel dimer interface between subunits.« less
Measurement of Intracellular Ionized Calcium in a Free-living Soil Nematode, Caenorhabditis elegans.
Kawaii, S; Yoshizawa, Y; Mizutani, J
1993-01-01
A calcium chelating fluorescence indicator, fura-2, was used to measure intracellular ionized calcium in Caenorhabditis elegans. The indicator loading process was harmless to the nematode, and completed within 2-3 h. Fura-2 was loaded mainly at its intestinal tract. The effects of DOPA on locomotion and the level of intracellular calcium were investigated and measured by using a microfluorometer. The addition of DOPA temporarily increased [Ca(2+)]i for several minutes.
Use of Chelex-100 for selectively removing Y-90 from its parent Sr-90
Huntley, Mark W.
1996-01-01
A method for selectively removing yttrium-90 from its parent strontium-90 contained in an environmental sample includes loading the sample onto a column containing a chelating ion-exchange resin capable of retaining yttrium-90; washing the column with a solution capable of removing strontium, calcium, and other contaminants from the yttrium-90 fraction retained on the column; removing excess acetate salts from the column; eluting yttrium-90 solution from the column and adjusting the pH of this solution to about 2.7; filtering the yttrium-90 solution and weighing this solution for gravimetric yield; and, counting the yttrium-90 containing solution with a radiological counter for a time sufficient to achieve the statistical accuracy desired. It is preferred that the chelating ion-exchange resin is a bidente ligand having the chemical name iminodiacetic acid mounted on a divinyl benzene substrate, converted from sodium form to ammonia form.
Use of Chelex-100 for selectively removing Y-90 from its parent Sr-90
Huntley, M.W.
1996-02-27
A method for selectively removing yttrium-90 from its parent strontium-90 contained in an environmental sample includes loading the sample onto a column containing a chelating ion-exchange resin capable of retaining yttrium-90; washing the column with a solution capable of removing strontium, calcium, and other contaminants from the yttrium-90 fraction retained on the column; removing excess acetate salts from the column; eluting yttrium-90 solution from the column and adjusting the pH of this solution to about 2.7; filtering the yttrium-90 solution and weighing this solution for gravimetric yield; and, counting the yttrium-90 containing solution with a radiological counter for a time sufficient to achieve the statistical accuracy desired. It is preferred that the chelating ion-exchange resin is a ligand having the chemical name iminodiacetic acid mounted on a divinyl benzene substrate, converted from sodium form to ammonia form.
Calcium Isotope Fractionation during Carbonate Weathering in the Northern Guangdong, South China
NASA Astrophysics Data System (ADS)
Liu, F.; Mao, G.; Wei, G.; Zhang, Z.
2017-12-01
CO2 is consumed during the weathering of carbonates, whereas carbonates are precipitated rapidly in the oceans, which are pivotal to modulate atmospheric CO2, oceanic pH and climate. Calcium carbonate in limestone is one of the largest reservoirs of carbon at the Earth's surface, so calcium is an important element that links the lithosphere, hydrosphere, biosphere, and the atmosphere. Compared with silicate rocks, carbonate rocks have more rapid rates of physical and chemical erosions, so the carbonate weathering will respond more quickly to the climatic changes. In the southeast of China, enormous of carbonate rocks are widely distributed. Due to the influence of the subtropical monsoon climate, the rocks experienced strong chemical weathering and pedogenic process, resulting in red weathering crust of carbonate rocks. This type of weathering crust is geochemistry-sensitive and ecology-vulnerable, which can provide important insights into the recycle of supergene geochemistry in the karst areas. In this study, we report calcium isotopic compositions of saprolites from a weathering profile developed on argillaceous carbonate rocks in northern Guangdong, South China. The acid-leachable fraction, which was extracted by 1N hydrochloride acid, showed limited variation of δ44/40Ca(NIST 915a) spanning from 0.55 ± 0.06‰ (2SD) to 0.72 ± 0.05‰ (2SD) despite CaO content ranging from 0.01 wt.% to 45.7 wt.%, implying that Ca isotope didn't fractionate much which may due to the congruent dissolution of limestone minerals. In contrast, radiogenic 87Sr/86Sr ratios of the whole rocks changed with depth from 0.710086 ± 6 (2SE) at the base rock to 0.722164± 8 (2SE) at the top-soil, which are possibly attributed to the mixing effect between carbonate and silicate fractions. Sr is an analogue for Ca due to its similar ionic size and charge; however, these two systems can differ in certain respects. The coupled study of Ca and Sr will be helpful to verify sources of Ca and the global Ca and C cycles.
Clarke, Jessica D.; Caldwell, Jessica L.; Horn, Margaux A.; Bode, Elizabeth F.; Richards, Mark A.; Hall, Mark C.S.; Graham, Helen K.; Briston, Sarah J.; Greensmith, David J.; Eisner, David A.; Dibb, Katharine M.; Trafford, Andrew W.
2015-01-01
Heart failure (HF) is commonly associated with reduced cardiac output and an increased risk of atrial arrhythmias particularly during β-adrenergic stimulation. The aim of the present study was to determine how HF alters systolic Ca2 + and the response to β-adrenergic (β-AR) stimulation in atrial myocytes. HF was induced in sheep by ventricular tachypacing and changes in intracellular Ca2 + concentration studied in single left atrial myocytes under voltage and current clamp conditions. The following were all reduced in HF atrial myocytes; Ca2 + transient amplitude (by 46% in current clamped and 28% in voltage clamped cells), SR dependent rate of Ca2 + removal (kSR, by 32%), L-type Ca2 + current density (by 36%) and action potential duration (APD90 by 22%). However, in HF SR Ca2 + content was increased (by 19%) when measured under voltage-clamp stimulation. Inhibiting the L-type Ca2 + current (ICa-L) in control cells reproduced both the decrease in Ca2 + transient amplitude and increase of SR Ca2 + content observed in voltage-clamped HF cells. During β-AR stimulation Ca2 + transient amplitude was the same in control and HF cells. However, ICa-L remained less in HF than control cells whilst SR Ca2 + content was highest in HF cells during β-AR stimulation. The decrease in ICa-L that occurs in HF atrial myocytes appears to underpin the decreased Ca2 + transient amplitude and increased SR Ca2 + content observed in voltage-clamped cells. PMID:25463272
Stuss, Michał; Sewerynek, Ewa; Król, Iwona; Stępień-Kłos, Wioletta; Jędrzejczyk, Sławomir
2016-01-01
The aim of this study was to evaluate quantitative changes in OPG and RANKL proteins after treatment with strontium ranelate (SR) and ibandronate in patients with postmenopausal osteoporosis. A total of 89 women with postmenopausal osteoporosis (PO), aged 51-85 years, patients of the Outpatient Clinic of Osteoporosis of the Military Teaching Hospital in Lodz, were enrolled in the study. The patients were randomly assigned to different therapies: ibandronate and (SR). Patients of the control group received only calcium and vitamin D3 supplements. The patients' visits were repeated after three and six months. Measurements of beta-CTX (C-terminal Telopeptide of type 1 collagen), osteocalcin, RANKL, osteoprotegerin (OPG), alkaline phosphatase concentrations in serum, as well as of total 24-hour calcium and phosphate levels in serum and urine, were carried out in material collected at baseline and after three and six months of therapy. Left hip and lumbar spine densitometry was done twice (at baseline visit and after six months). In all three groups there were no significant differences noted in the concentrations of OPG and RANKL serum protein levels during the study period. Both negative and positive correlations or tendencies of correlations were found between OPG serum concentrations and BMD changes in the SR group. Both ibandronate and SR do not seem to cause any significant changes in OPG and RANKL protein serum levels during the first six months of treatment. OPG may play a role in osteoclast activity suppression in the course of treatment with ibandronate in patients with PO. OPG may play an important role in the mechanism of SR therapy and may be viewed as a potentially valuable parameter for monitoring and predicting the course of treatment with SR in PO.
Bullen, T.D.; Bailey, S.W.
2005-01-01
Depletion of calcium from forest soils has important implications for forest productivity and health. Ca is available to fine feeder roots from a number of soil organic and mineral sources, but identifying the primary source or changes of sources in response to environmental change is problematic. We used strontium isotope and alkaline earth element concentration ratios of trees and soils to discern the record of Ca sources for red spruce at a base-poor, acid deposition-impacted watershed. We measured 87Sr/86Sr and chemical compositions of cross-sectional stemwood cores of red spruce, other spruce tissues and sequential extracts of co-located soil samples. 87Sr/86Sr and Sr/Ba ratios together provide a tracer of alkaline earth element sources that distinguishes the plant-available fraction of the shallow organic soils from those of deeper organic and mineral soils. Ca/Sr ratios proved less diagnostic, due to within-tree processes that fractionate these elements from each other. Over the growth period from 1870 to 1960, 87Sr/86Sr and Sr/Ba ratios of stemwood samples became progressively more variable and on average trended toward values that considered together are characteristic of the uppermost forest floor. In detail the stemwood chemistry revealed an episode of simultaneous enhanced uptake of all alkaline earth elements during the growth period from 1930 to 1960, coincident with reported local and regional increases in atmospheric inputs of inorganic acidity. We attribute the temporal trends in stemwood chemistry to progressive shallowing of the effective depth of alkaline earth element uptake by fine roots over this growth period, due to preferential concentration of fine roots in the upper forest floor coupled with reduced nutrient uptake by roots in the lower organic and upper mineral soils in response to acid-induced aluminum toxicity. Although both increased atmospheric deposition and selective weathering of Ca-rich minerals such as apatite provide possible alternative explanations of aspects of the observed trends, the chemical buffering capacity of the forest floor-biomass pool limits their effectiveness as causal mechanisms. ?? Springer 2005.
Viviano, Jeffrey; Krishnan, Anuradha; Scully, Jenna; Wu, Hao; Venkataraman, Venkat
2016-06-01
In this data article we show the specificity of the Ca(2+)-induced mobility shift in three proteins that belong to the neuronal calcium sensor (NCS) protein family: Hippocalcin, GCAP1 and GCAP2. These proteins did not display a shift in mobility in native gels when incubated with divalent cations other than Ca(2+) - such as Mg(2+), Ba(2+), and Sr(2+), even at 10× concentrations. The data is similar to that obtained with another NCS protein, neurocalcin delta (Viviano et al., 2016, "Electrophoretic Mobility Shift in Native Gels Indicates Calcium-dependent Structural Changes of Neuronal Calcium Sensor Proteins", [1]).
NASA Technical Reports Server (NTRS)
Ito, K.; Yan, X.; Tajima, M.; Su, Z.; Barry, W. H.; Lorell, B. H.; Schneider, M. (Principal Investigator)
2000-01-01
Mouse myocyte contractility and the changes induced by pressure overload are not fully understood. We studied contractile reserve in isolated left ventricular myocytes from mice with ascending aortic stenosis (AS) during compensatory hypertrophy (4-week AS) and the later stage of early failure (7-week AS) and from control mice. Myocyte contraction and [Ca(2+)](i) transients with fluo-3 were measured simultaneously. At baseline (0.5 Hz, 1.5 mmol/L [Ca(2+)](o), 25 degrees C), the amplitude of myocyte shortening and peak-systolic [Ca(2+)](i) in 7-week AS were not different from those of controls, whereas contraction, relaxation, and the decline of [Ca(2+)](i) transients were slower. In response to the challenge of high [Ca(2+)](o), fractional cell shortening was severely depressed with reduced peak-systolic [Ca(2+)](i) in 7-week AS compared with controls. In response to rapid pacing stimulation, cell shortening and peak-systolic [Ca(2+)](i) increased in controls, but this response was depressed in 7-week AS. In contrast, the responses to both challenge with high [Ca(2+)](o) and rapid pacing in 4-week AS were similar to those of controls. Although protein levels of Na(+)-Ca(2+) exchanger were increased in both 4-week and 7-week AS, the ratio of SR Ca(2+)-ATPase to phospholamban protein levels was depressed in 7-week AS compared with controls but not in 4-week AS. This was associated with an impaired capacity to increase sarcoplasmic reticulum Ca(2+) load during high work states in 7-week AS myocytes. In hypertrophied failing mouse myocytes, depressed contractile reserve is related to an impaired augmentation of systolic [Ca(2+)](i) and SR Ca(2+) load and simulates findings in human failing myocytes.
Calcium homeostasis during oral glucose load in healthy women.
D'Erasmo, E; Pisani, D; Ragno, A; Raejntroph, N; Vecci, E; Acca, M
1999-04-01
It has been demonstrated that in healthy subjects during oral glucose tolerance test, serum calcium declines, while urinary calcium excretion increases, even if there is not a general agreement in this regard. The study was carried out in order to evaluate the effects of glucose oral load on calcium homeostasis in eight healthy adult women, also considering ionized calcium, plasma insulin and parathyroid hormone changes. The results showed a decline of total and ionized serum calcium (p < 0.05 and p < 0.01, respectively; maximum of the decrease at time 120'), in parallel with the increase of urinary calcium/ creatinine ratio (p < 0.05). Serum glucose and insulin increase (p < 0.0001 and p < 0.0005 respectively; maximum value at time 60'), while the parathyroid hormone level decreases (maximum decline at time 120', p < 0.01). No changes were observed in fasting control subjects for all parameters considered. The changes of these parameters with time suggest that the effects of glucose oral load on calcium metabolism in healthy adult women may be the consequence of parathyroid hormone suppression induced by acute hyperglycemia/hyperinsulinemia. The results confirm in vivo the PTH behaviour in vitro, on cultured bovine parathyroid cells, with high glucose concentration.
Xiang, Xiao-Dong; Chang, Hauyee; Takeuchi, Ichiro
2000-01-01
A dielectric thin-film material for microwave applications, including use as a capacitor, the thin-film comprising a composition of barium strontium calcium and titanium of perovskite type (Ba.sub.x Sr.sub.y Ca.sub.1-x-y)TiO.sub.3. Also provided is a method for making a dielectric thin film of that formula over a wide compositional range through a single deposition process.
Mathiesen, Claus; Brazhe, Alexey; Thomsen, Kirsten; Lauritzen, Martin
2013-02-01
Glial calcium (Ca(2+)) waves constitute a means to spread signals between glial cells and to neighboring neurons and blood vessels. These waves occur spontaneously in Bergmann glia (BG) of the mouse cerebellar cortex in vivo. Here, we tested three hypotheses: (1) aging and reduced blood oxygen saturation alters wave activity; (2) glial Ca(2+) waves change cerebral oxygen metabolism; and (3) neuronal and glial wave activity is correlated. We used two-photon microscopy in the cerebellar cortexes of adult (8- to 15-week-old) and aging (48- to 80-week-old) ketamine-anesthetized mice after bolus loading with OGB-1/AM and SR101. We report that the occurrence of spontaneous waves is 20 times more frequent in the cerebellar cortex of aging as compared with adult mice, which correlated with a reduction in resting brain oxygen tension. In adult mice, spontaneous glial wave activity increased on reducing resting brain oxygen tension, and ATP-evoked glial waves reduced the tissue O(2) tension. Finally, although spontaneous Purkinje cell (PC) activity was not associated with increased glia wave activity, spontaneous glial waves did affect intracellular Ca(2+) activity in PCs. The increased wave activity during aging, as well as low resting brain oxygen tension, suggests a relationship between glial waves, brain energy homeostasis, and pathology.
Dissolved strontium and calcium levels in the tropical Indian Ocean
NASA Astrophysics Data System (ADS)
Steiner, Zvi; Sarkar, Amit; Turchyn, Alexandra
2017-04-01
Measurements of seawater alkalinity and dissolved calcium concentrations along oceanic transects are often used to calculate calcium carbonate precipitation and dissolution rates. Given that the distribution coefficient of strontium in CaCO3 varies greatly between different groups of organisms, adding precise measurements of dissolved strontium concentrations provides opportunities to also track relative contributions of these different groups to the regional CaCO3 cycle. However, there are several obstacles to this approach. These obstacles include unresolved systematic discrepancies between seawater calcium and alkalinity data, very large analytical noise around the calcium concentration measurements and the unconstrained role of acantharia (radiolarian precipitating SrSO4 skeletons) in the marine strontium cycle. During the first cruise of the second International Indian Ocean Expedition (IIOE-2) water samples were collected along 67°E from 9°N to 5°S to explore the dissolution rate of calcium carbonate in the water. The dissolution rate can be calculated by combining measurements of water column potential alkalinity with calcium and strontium concentrations measured by ICP-OES and calcium concentration measurements using isotope dilution thermal ionization mass spectrometry (ID-TIMS). CaCO3 mineral saturation state calculated using pH and total alkalinity suggests that along 67°E, the aragonite saturation horizon lays at depth of 500 m on both sides of the equator. Across the cruise transect, dissolved strontium concentrations increase by 2-3% along the thermocline suggesting rapid recycling of strontium rich phases. This is particularly evident just below the thermocline at 8-9°N and below 1000 m water depth, south of the equator. The deep, southern enrichment in strontium does not involve a change in the Sr/Ca ratio, suggesting that this strontium enrichment is related to CaCO3 dissolution. In contrast, in the intermediate waters of the northern part of the section Sr/Ca ratios increase significantly. This finding is opposite to expectations based on plankton net tows collected during the cruise, where we found high abundance of acantharia in the southern parts of the section, while the preferential enrichment in strontium is in the northern part of the section. When potential alkalinity is calculated by correcting the normalized total alkalinity for the effects of nutrient accumulation below the thermocline, we observe that the increase in alkalinity begins at 100 m, well above the aragonite saturation horizon. The total change in dissolved calcium concentrations between 0 and 2000 m is similar to the total change in potential alkalinity yet their profiles do not overlap; calcium concentrations increase faster than total alkalinity between 100-1000 m and the gap is closed between 1000-1500 m. This suggests an additional, unaccounted process that is likely occurring in the Red Sea and Persian Gulf, the intermediate water sources of this region.
Ma, Hongtao; Harris, Samuel; Rahmani, Redi; Lacefield, Clay O.; Zhao, Mingrui; Daniel, Andy G. S.; Zhou, Zhiping; Bruno, Randy M.; Berwick, Jason; Schwartz, Theodore H.
2014-01-01
Abstract. In vivo calcium imaging is an incredibly powerful technique that provides simultaneous information on fast neuronal events, such as action potentials and subthreshold synaptic activity, as well as slower events that occur in the glia and surrounding neuropil. Bulk-loading methods that involve multiple injections can be used for single-cell as well as wide-field imaging studies. However, multiple injections result in inhomogeneous loading as well as multiple sites of potential cortical injury. We used convection-enhanced delivery to create smooth, continuous loading of a large area of the cortical surface through a solitary injection site and demonstrated the efficacy of the technique using confocal microscopy imaging of single cells and physiological responses to single-trial events of spontaneous activity, somatosensory-evoked potentials, and epileptiform events. Combinations of calcium imaging with voltage-sensitive dye and intrinsic signal imaging demonstrate the utility of this technique in neurovascular coupling investigations. Convection-enhanced loading of calcium dyes may be a useful technique to advance the study of cortical processing when widespread loading of a wide-field imaging is required. PMID:25525611
Ma, Hongtao; Harris, Samuel; Rahmani, Redi; Lacefield, Clay O; Zhao, Mingrui; Daniel, Andy G S; Zhou, Zhiping; Bruno, Randy M; Berwick, Jason; Schwartz, Theodore H
2014-07-24
In vivo calcium imaging is an incredibly powerful technique that provides simultaneous information on fast neuronal events, such as action potentials and subthreshold synaptic activity, as well as slower events that occur in the glia and surrounding neuropil. Bulk-loading methods that involve multiple injections can be used for single-cell as well as wide-field imaging studies. However, multiple injections result in inhomogeneous loading as well as multiple sites of potential cortical injury. We used convection-enhanced delivery to create smooth, continuous loading of a large area of the cortical surface through a solitary injection site and demonstrated the efficacy of the technique using confocal microscopy imaging of single cells and physiological responses to single-trial events of spontaneous activity, somatosensory-evoked potentials, and epileptiform events. Combinations of calcium imaging with voltage-sensitive dye and intrinsic signal imaging demonstrate the utility of this technique in neurovascular coupling investigations. Convection-enhanced loading of calcium dyes may be a useful technique to advance the study of cortical processing when widespread loading of a wide-field imaging is required.
Gravinese, Philip M.; Flannery, Jennifer A.; Toth, Lauren T.
2016-11-23
The larvae of the Florida stone crab, Menippe mercenaria, migrate through a variety of habitats as they develop and, therefore, experience a broad range of environmental conditions through ontogeny. Environmental variability experienced by the larvae may result in distinct elemental signatures within the exoskeletons, which could provide a tool for tracking the environmental history of larval stone crab populations. A method was developed to examine trace-element ratios, specifically magnesium-to-calcium (Mg/Ca) and strontium-to-calcium (Sr/Ca) ratios, in the exoskeletons of M. mercenaria larvae. Two developmental stages of stone crab larvae were analyzed—stage III and stage V. Specimens were reared in a laboratory environment under stable conditions to quantify the average ratios of Mg/Ca and Sr/Ca of larval stone crab exoskeletons and to determine if the ratios differed through ontogeny. The elemental compositions (Ca, Mg, and Sr) in samples of stage III larvae (n = 50 per sample) from 11 different broods (mean Sr/Ca = 5.916 ± 0.161 millimole per mole [mmol mol−1]; mean Mg/Ca = 218.275 ± 59.957 mmol mol−1) and stage V larvae (n = 10 per sample) from 12 different broods (mean Sr/Ca = 6.110 ± 0.300 mmol mol−1; mean Mg/Ca = 267.081 ± 67.211 mmol mol–1) were measured using inductively coupled plasma optical emission spectrometry (ICP–OES). The ratio of Sr/Ca significantly increased from stage III to stage V larvae, suggesting an ontogenic shift in Sr/Ca ratios between larval stages. The ratio of Mg/Ca did not change significantly between larval stages, but variability among broods was high. The method used to examine the trace-element ratios provided robust, highly reproducible estimates of Sr/Ca and Mg/Ca ratios in the larvae of M. mercenaria, demonstrating that ICP–OES can be used to determine the trace-element composition of chitinous organisms like the Florida stone crab.
Nivala, Michael; de Lange, Enno; Rovetti, Robert; Qu, Zhilin
2012-01-01
Intracellular calcium (Ca) cycling dynamics in cardiac myocytes is regulated by a complex network of spatially distributed organelles, such as sarcoplasmic reticulum (SR), mitochondria, and myofibrils. In this study, we present a mathematical model of intracellular Ca cycling and numerical and computational methods for computer simulations. The model consists of a coupled Ca release unit (CRU) network, which includes a SR domain and a myoplasm domain. Each CRU contains 10 L-type Ca channels and 100 ryanodine receptor channels, with individual channels simulated stochastically using a variant of Gillespie’s method, modified here to handle time-dependent transition rates. Both the SR domain and the myoplasm domain in each CRU are modeled by 5 × 5 × 5 voxels to maintain proper Ca diffusion. Advanced numerical algorithms implemented on graphical processing units were used for fast computational simulations. For a myocyte containing 100 × 20 × 10 CRUs, a 1-s heart time simulation takes about 10 min of machine time on a single NVIDIA Tesla C2050. Examples of simulated Ca cycling dynamics, such as Ca sparks, Ca waves, and Ca alternans, are shown. PMID:22586402
DOE Office of Scientific and Technical Information (OSTI.GOV)
Walser, M.; Robinson, B.H.B.
The ratio of excreted (Sr/sub u/) to filtered (Sr/sub o/) radiostrontium (Sr/sup 85/) was compared with the ratio of excreted (Ca/sub u/) to filtered (Ca/ sub o/) calcium in human subjects and dogs undergoing a variety of diuretic procedures. The relation Sr/sub u//Sr/sub o/ = (Ca/sub u/,/Ca/sub o//sup 0.7/ serves to predict Sr/sub u//Sr/sub o/ from Ca/su b u//Ca/sub o/with a standard error of estimate of 15% over a wide range of variation (30- to 200-fold) in the 2 quantities. The equation can be derived from the assumptions that the 2 ions are reabsorbed at rates proportional to the localmore » concentrations in the tubular fluid, and that the rate constant for Sr reabsorption is always 0.7 times that for Ca reabsorption. This relation was not affected by adrenocortical activity (in man), parathyroid activity, hypercalcemia, acid-base balance, Mg clearance, or diuretics (chlorothiazide or hydrochlorothiazide). Sulfate or ferrocyanide infusion was also without effect, presumably because the affinity of each of the 2 anions for Ca is similar to its affinity for Sr. Citrate, which binds Ca more strongly, diminishes renal discrimination between Ca and Sr. Although this relation has high predictive value (r* = 0.98), it does not establish that the reabsorption of Ca and Sr are first-order processes nor that the 2 ions share a common mechanism. (H.H.D.)« less
NASA Astrophysics Data System (ADS)
Guo, Xiaoxuan; Wang, Zhiqiang; Wu, Jin; Wang, Jian; Zhu, Ying-Jie; Sham, Tsun-Kong
2015-04-01
Imaging is one of the most direct and ideal ways to track drug loading distributions in drug carriers on the molecular level, which will facilitate the optimization of drug carriers and drug loading capacities. Herein, we report the mapping of an individual mesoporous calcium silicate hydrate (CSH) microsphere before and after the loading of ibuprofen (IBU) and the interactions between drug carriers and drug molecules simultaneously by scanning transmission X-ray microscopy (STXM). Nanoscaled X-ray absorption near edge structure (XANES) spectroscopy clearly indicates that IBU is bonded to calcium and silicate sites via carboxylic acid groups. More importantly, STXM has been successfully used to determine the absolute thickness of IBU, revealing its distribution in the CSH microsphere.Imaging is one of the most direct and ideal ways to track drug loading distributions in drug carriers on the molecular level, which will facilitate the optimization of drug carriers and drug loading capacities. Herein, we report the mapping of an individual mesoporous calcium silicate hydrate (CSH) microsphere before and after the loading of ibuprofen (IBU) and the interactions between drug carriers and drug molecules simultaneously by scanning transmission X-ray microscopy (STXM). Nanoscaled X-ray absorption near edge structure (XANES) spectroscopy clearly indicates that IBU is bonded to calcium and silicate sites via carboxylic acid groups. More importantly, STXM has been successfully used to determine the absolute thickness of IBU, revealing its distribution in the CSH microsphere. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr07471h
Synchrotron Study of Strontium in Modern and Ancient Human Bones
NASA Astrophysics Data System (ADS)
Pingitore, N. E.; Cruz-Jimenez, G.
2001-05-01
Archaeologists use the strontium in human bone to reconstruct diet and migration in ancient populations. Because mammals discriminate against strontium relative to calcium, carnivores show lower bone Sr/Ca ratios than herbivores. Thus, in a single population, bone Sr/Ca ratios can discriminate a meat-rich from a vegetarian diet. Also, the ratio of 87-Sr to 86-Sr in soils varies with the underlying geology; incorporated into the food chain, this local signature becomes embedded in our bones. The Sr isotopic ratio in the bones of individuals or populations which migrate to a different geologic terrane will gradually change as bone remodels. In contrast, the isotopic ratio of tooth enamel is fixed at an early age and is not altered later in life. Addition of Sr to bone during post-mortem residence in moist soil or sediment compromises application of the Sr/Ca or Sr-isotope techniques. If this post-mortem Sr resides in a different atomic environment than the Sr deposited in vivo, x-ray absorption spectroscopy could allow us to distinguish pristine from contaminated, and thus unreliable, samples. Initial examination of a suite of modern and ancient human and animal bones by extended x-ray absorption fine structure (EXAFS) showed no obvious differences between the fresh and buried materials. We note, with obvious concern, that the actual location of Sr in modern bone is controversial: there is evidence both that Sr substitutes for Ca and that Sr is sorbed on the surfaces of bone crystallites. Additional material is being studied.
Calcium Imaging of AM Dyes Following Prolonged Incubation in Acute Neuronal Tissue
Morley, John W.; Tapson, Jonathan; Breen, Paul P.; van Schaik, André
2016-01-01
Calcium-imaging is a sensitive method for monitoring calcium dynamics during neuronal activity. As intracellular calcium concentration is correlated to physiological and pathophysiological activity of neurons, calcium imaging with fluorescent indicators is one of the most commonly used techniques in neuroscience today. Current methodologies for loading calcium dyes into the tissue require prolonged incubation time (45–150 min), in addition to dissection and recovery time after the slicing procedure. This prolonged incubation curtails experimental time, as tissue is typically maintained for 6–8 hours after slicing. Using a recently introduced recovery chamber that extends the viability of acute brain slices to more than 24 hours, we tested the effectiveness of calcium AM staining following long incubation periods post cell loading and its impact on the functional properties of calcium signals in acute brain slices and wholemount retinae. We show that calcium dyes remain within cells and are fully functional >24 hours after loading. Moreover, the calcium dynamics recorded >24 hrs were similar to the calcium signals recorded in fresh tissue that was incubated for <4 hrs. These results indicate that long exposure of calcium AM dyes to the intracellular cytoplasm did not alter the intracellular calcium concentration, the functional range of the dye or viability of the neurons. This data extends our previous work showing that a custom recovery chamber can extend the viability of neuronal tissue, and reliable data for both electrophysiology and imaging can be obtained >24hrs after dissection. These methods will not only extend experimental time for those using acute neuronal tissue, but also may reduce the number of animals required to complete experimental goals. PMID:27183102
DOE Office of Scientific and Technical Information (OSTI.GOV)
Singer, D.M.; Johnson, S.B.; Catalano, J.G.
Calcium oxalate monohydrate (CaC{sub 2}O{sub 4}{center_dot}H{sub 2}O -- abbreviated as CaOx) is produced by two-thirds of all plant families, comprising up to 80 wt.% of the plant tissue and found in many surface environments. It is unclear, however, how CaOx in plants and soils interacts with metal ions and possibly sequesters them. This study examines the speciation of Sr(II){sub aq} following its reaction with CaOx. Batch uptake experiments were conducted over the pH range 4--10, with initial Sr solution concentrations, [Sr]{sub aq}, ranging from 1 x 10{sup -4} to 1 x 10{sup -3} M and ionic strengths ranging of 0.001--0.1more » M, using NaCl as the background electrolyte. Experimental results indicate that Sr uptake is independent of pH and ionic strength over these ranges. After exposure of CaOx to Sr{sub aq} for two days, the solution Ca concentration, [Ca]{sup aq}, increased for all samples relative to the control CaOx suspension (with no Sr added). The amount of Sr{sub aq} removed from solution was nearly equal to the total [Ca]{sup aq} after exposure of CaOx to Sr. These results suggest that nearly 90% of the Sr is removed from solution to a solid phase as Ca is released into solution. We suggest that the other 10% is sequestered through surface adsorption on a solid phase, although we have no direct evidence for this. Extended X-ray absorption fine structure (EXAFS) spectroscopy was used to determine the molecular-level speciation of Sr in the reaction products. Deconvolutions of the Sr K-edge EXAFS spectra were performed to identify multi-electron excitation (MEE) features. MEE effects were found to give rise to low-frequency peaks in the Fourier transform before the first shell of oxygen atoms and do not affect EXAFS fitting results. Because of potential problems caused by asymmetric distributions of Sr-O distances when fitting Sr K-edge EXAFS data using the standard harmonic model, we also employed a cumulant expansion model and an asymmetric analytical model to account for anharmonic effects in the EXAFS data. For Sr-bearing phases with low to moderate first-shell (Sr-O pair correlation) anharmonicity, the cumulant expansion model is sufficient for EXAFS fitting; however, for higher degrees of anharmonicity, an analytical model is required. Based on batch uptake results and EXAFS analyses of reaction products, we conclude that Sr is dominantly sequestered by a solid phase at the CaOx surface, likely the result of a dissolution-reprecipitation mechanism, to form SrC{sub 2}O{sub 4} of mixed hydration state (i.e. SrO{sub x}{center_dot}nH{sub 2}O, where n = 0, 1, or 2). Surprisingly, no spectroscopic or XRD evidence was found for a (Sr,Ca)Ox solid solution or for a separate SrCO3 phase. In addition, we found no evidence for Sr(II) inner-sphere sorption complexes on CaOx surfaces based on lack of Sr-Ca second-neighbor pair correlations in the EXAFS spectra, although some type of Sr(II) surface complex (perhaps a type B Sr-oxalate ternary complex or an outer-sphere Sr(II) complex) or some as yet undetected Sr-bearing solid phases are needed to account for approximately 10% of Sr uptake by CaOx. The formation of a hydrated SrOx phase in environments under conditions similar to those of our experiments should retard Sr mobility and could be a significant factor in the biogeochemical cycling of Sr in soils and sediments or in plants and plant litter where CaOx is present.« less
Faria, Thaís de Oliveira; Costa, Gustavo Pinto; Almenara, Camila Cruz Pereira; Angeli, Jhuli Keli; Vassallo, Dalton Valentim; Stefanon, Ivanita; Vassallo, Paula Frizera
2014-01-01
Right ventricle systolic dysfunction is a major risk factor for death and heart failure after myocardial infarction (MI). Heavy metal exposure has been associated with the development of several cardiovascular diseases, such as MI. The aim of this study was to investigate whether chronic exposure to low doses of mercury chloride (HgCl2) enhances the functional deterioration of right ventricle strips after MI. Male Wistar rats were divided into four groups: Control (vehicle); HgCl2 (exposure during 4 weeks- 1st dose 4.6 µg/kg, subsequent dose 0.07 µg/kg/day, i.m. to cover daily loss); MI surgery induced and HgCl2-MI groups. One week after MI, the morphological and hemodynamic measurements and isometric tension of right ventricle strips were investigated. The chronic HgCl2 exposure did not worsen the injury compared with MI alone in the morphological or hemodynamic parameters evaluated. At basal conditions, despite similar maximum isometric force at L-max, relaxation time was increased in the MI group but unaffected in the HgCl2-MI compared to the Control group. Impairment of the sarcoplasmic reticulum (SR) function and reduction in the sarcolemmal calcium influx were observed in MI group associated with SERCA2a reduction and increased PLB protein expression. Induction of MI in chronic HgCl2 exposed rats did not cause any alteration in the developed force at L-max, lusitropic function or −dF/dt except for a tendency of a reduction SR function. These findings could be partially explained by the normalization in the sarcolemmal calcium influx and the increase in NCX protein expression observed only in this group. These results suggest that chronic exposure to low doses of HgCl2 prevents the impaired SR function and the reduced sarcolemmal calcium influx observed in MI likely by acting on NCX, PLB and SERCA2a protein expression. PMID:24748367
Late INa increases diastolic SR-Ca2+-leak in atrial myocardium by activating PKA and CaMKII
Fischer, Thomas H.; Herting, Jonas; Mason, Fleur E.; Hartmann, Nico; Watanabe, Saera; Nikolaev, Viacheslav O.; Sprenger, Julia U.; Fan, Peidong; Yao, Lina; Popov, Aron-Frederik; Danner, Bernhard C.; Schöndube, Friedrich; Belardinelli, Luiz; Hasenfuss, Gerd; Maier, Lars S.; Sossalla, Samuel
2015-01-01
Aims Enhanced cardiac late Na current (late INa) and increased sarcoplasmic reticulum (SR)-Ca2+-leak are both highly arrhythmogenic. This study seeks to identify signalling pathways interconnecting late INa and SR-Ca2+-leak in atrial cardiomyocytes (CMs). Methods and results In murine atrial CMs, SR-Ca2+-leak was increased by the late INa enhancer Anemonia sulcata toxin II (ATX-II). An inhibition of Ca2+/calmodulin-dependent protein kinase II (Autocamide-2-related inhibitory peptide), protein kinase A (H89), or late INa (Ranolazine or Tetrodotoxin) all prevented ATX-II-dependent SR-Ca2+-leak. The SR-Ca2+-leak induction by ATX-II was not detected when either the Na+/Ca2+ exchanger was inhibited (KBR) or in CaMKIIδc-knockout mice. FRET measurements revealed increased cAMP levels upon ATX-II stimulation, which could be prevented by inhibition of adenylyl cyclases (ACs) 5 and 6 (NKY 80) but not by inhibition of phosphodiesterases (IBMX), suggesting PKA activation via an AC-dependent increase of cAMP levels. Western blots showed late INa-dependent hyperphosphorylation of CaMKII as well as PKA target sites at ryanodine receptor type-2 (-S2814 and -S2808) and phospholamban (-Thr17, -S16). Enhancement of late INa did not alter Ca2+-transient amplitude or SR-Ca2+-load. However, upon late INa activation and simultaneous CaMKII inhibition, Ca2+-transient amplitude and SR-Ca2+-load were increased, whereas PKA inhibition reduced Ca2+-transient amplitude and load and additionally slowed Ca2+ elimination. In atrial CMs from patients with atrial fibrillation, inhibition of late INa, CaMKII, or PKA reduced the SR-Ca2+-leak. Conclusion Late INa exerts distinct effects on Ca2+ homeostasis in atrial myocardium through activation of CaMKII and PKA. Inhibition of late INa represents a potential approach to attenuate CaMKII activation and decreases SR-Ca2+-leak in atrial rhythm disorders. The interconnection with the cAMP/PKA system further increases the antiarrhythmic potential of late INa inhibition. PMID:25990311
Platelet-independent adhesion of calcium-loaded erythrocytes to von Willebrand factor
Bierings, Ruben; Meems, Henriet; Mul, Frederik P. J.; Geerts, Dirk; Vlaar, Alexander P. J.; Voorberg, Jan; Hordijk, Peter L.
2017-01-01
Adhesion of erythrocytes to endothelial cells lining the vascular wall can cause vaso-occlusive events that impair blood flow which in turn may result in ischemia and tissue damage. Adhesion of erythrocytes to vascular endothelial cells has been described in multiple hemolytic disorders, especially in sickle cell disease, but the adhesion of normal erythrocytes to endothelial cells has hardly been described. It was shown that calcium-loaded erythrocytes can adhere to endothelial cells. Because sickle erythrocyte adhesion to ECs can be enhanced by ultra-large von Willebrand factor multimers, we investigated whether calcium loading of erythrocytes could promote binding to endothelial cells via ultra-large von Willebrand factor multimers. We used (immunofluorescent) live-cell imaging of washed erythrocytes perfused over primary endothelial cells at venular flow rate. Using this approach, we show that calcium-loaded erythrocytes strongly adhere to histamine-stimulated primary human endothelial cells. This adhesion is mediated by ultra-large von Willebrand factor multimers. Von Willebrand factor knockdown or ADAMTS13 cleavage abolished the binding of erythrocytes to activated endothelial cells under flow. Platelet depletion did not interfere with erythrocyte binding to von Willebrand factor. Our results reveal platelet-independent adhesion of calcium-loaded erythrocytes to endothelium-derived von Willebrand factor. Erythrocyte adhesion to von Willebrand factor may be particularly relevant for venous thrombosis, which is characterized by the formation of erythrocyte-rich thrombi. PMID:28249049
NASA Astrophysics Data System (ADS)
Liu, Yuan; Wang, Mingqiang; Ning, Xingyao
2018-02-01
Spinning reserve (SR) should be scheduled considering the balance between economy and reliability. To address the computational intractability cursed by the computation of loss of load probability (LOLP), many probabilistic methods use simplified formulations of LOLP to improve the computational efficiency. Two tradeoffs embedded in the SR optimization model are not explicitly analyzed in these methods. In this paper, two tradeoffs including primary tradeoff and secondary tradeoff between economy and reliability in the maximum LOLP constrained unit commitment (UC) model are explored and analyzed in a small system and in IEEE-RTS System. The analysis on the two tradeoffs can help in establishing new efficient simplified LOLP formulations and new SR optimization models.
Pathogenesis of hypokalemia in autosomal dominant hypocalcemia type 1.
Kamiyoshi, Naohiro; Nozu, Kandai; Urahama, Yoshimichi; Matsunoshita, Natsuki; Yamamura, Tomohiko; Minamikawa, Shogo; Ninchoji, Takeshi; Morisada, Naoya; Nakanishi, Koichi; Kaito, Hiroshi; Iijima, Kazumoto
2016-04-01
Autosomal dominant hypocalcemia type 1 (ADH1) is a relatively rare endocrine disorder characterized by hypocalcemia and inadequate parathyroid hormone secretion. ADH is caused by activating mutations in the calcium-sensing receptor (CaSR) gene, CASR. CaSR plays a crucial role in calcium and magnesium homeostasis in the kidney. ADH may be accompanied by hypokalemia and metabolic alkalosis when it is classified as type V Bartter syndrome. However, the mechanism underlying hypokalemia in this disease is unclear. We investigated a 33-year-old woman with hypocalcemia and hypoparathyroidism since childhood, whose mother also had hypocalcemia and hypoparathyroidism, but with no clinical symptoms. Blood examinations showed hypokalemia and metabolic alkalosis in the patient, but not her mother. We conducted mutation analysis and diuretic tests to clarify the patient's and her mother's diagnosis and to investigate the onset mechanism of hypokalemia in ADH1. We also determined the localization of CaSR in the kidney by immunohistochemistry. We detected a known gain-of-function mutation in CASR in both the patient and her mother. Diuretic tests revealed a response to furosemide and no reaction to thiazide in the patient, although the mother responded well to both diuretics. CaSR co-localized with the Na(+)-Cl(-) cotransporter (NCCT) on distal tubular epithelial cells. These results indicate that the NCCT in the distal convoluted tubule was secondarily affected in this patient. We conclude that the main pathogenesis of secondary hypokalemia in ADH1 in this patient was secondary NCCT dysfunction.
NASA Astrophysics Data System (ADS)
Abdelghany, A. M.; Ouis, M. A.; Azooz, M. A.; ElBatal, H. A.; El-Bassyouni, G. T.
2016-01-01
Borate glasses containing SrO substituting both CaO and NaO were prepared and characterized for their bioactivity or bone bonding ability. Glass ceramic derivatives were prepared by thermal heat treatment process. FTIR, XRD and SEM measurements for the prepared glass and glass-ceramics before and after immersion in sodium phosphate solution for one and two weeks were carried out. The appearance of two IR peaks within the range 550-680 cm-1 after immersion in phosphate solution indicates the formation of hydroxyapatite or equivalent Sr phosphate layer. X-ray diffraction data agree with the FTIR spectral analysis. The solubility test was carried out for both glasses and glass ceramics derivatives in the same phosphate solution. The introduction of SrO increases the solubility for both glasses and glass ceramics and this is assumed to be due to the formation of Sr phosphate which is more soluble than calcium phosphate (hydroxyapatite). SEM images reveal varying changes in the surfaces of glass ceramics after immersion according to the SrO content.
Abdelghany, A M; Ouis, M A; Azooz, M A; ElBatal, H A; El-Bassyouni, G T
2016-01-05
Borate glasses containing SrO substituting both CaO and NaO were prepared and characterized for their bioactivity or bone bonding ability. Glass ceramic derivatives were prepared by thermal heat treatment process. FTIR, XRD and SEM measurements for the prepared glass and glass-ceramics before and after immersion in sodium phosphate solution for one and two weeks were carried out. The appearance of two IR peaks within the range 550-680cm(-1) after immersion in phosphate solution indicates the formation of hydroxyapatite or equivalent Sr phosphate layer. X-ray diffraction data agree with the FTIR spectral analysis. The solubility test was carried out for both glasses and glass ceramics derivatives in the same phosphate solution. The introduction of SrO increases the solubility for both glasses and glass ceramics and this is assumed to be due to the formation of Sr phosphate which is more soluble than calcium phosphate (hydroxyapatite). SEM images reveal varying changes in the surfaces of glass ceramics after immersion according to the SrO content. Copyright © 2015 Elsevier B.V. All rights reserved.
Biological removal of cationic fission products from nuclear wastewater.
Ngwenya, N; Chirwa, E M N
2011-01-01
Nuclear energy is becoming a preferred energy source amidst rising concerns over the impacts of fossil fuel based energy on global warming and climate change. However, the radioactive waste generated during nuclear power generation contains harmful long-lived fission products such as strontium (Sr). In this study, cationic strontium uptake from solution by microbial cultures obtained from mine wastewater is evaluated. A high strontium removal capacity (q(max)) with maximum loading of 444 mg/g biomass was achieved by a mixed sulphate reducing bacteria (SRB) culture. Sr removal in SRB was facilitated by cell surface based electrostatic interactions with the formation of weak ionic bonds, as 68% of the adsorbed Sr(2+) was easily desorbed from the biomass in an ion exchange reaction with MgCl₂. To a lesser extent, precipitation reactions were also found to account for the removal of Sr from aqueous solution as about 3% of the sorbed Sr was precipitated due to the presence of chemical ligands while the remainder occurred as an immobile fraction. Further analysis of the Sr-loaded SRB biomass by scanning electron microscopy (SEM) coupled to energy dispersive X-ray (EDX) confirmed extracellular Sr(2+) precipitation as a result of chemical interaction. In summary, the obtained results demonstrate the prospects of using biological technologies for the remediation of industrial wastewaters contaminated by fission products.
Assanasen, Chatchawin; Mineo, Chieko; Seetharam, Divya; Yuhanna, Ivan S.; Marcel, Yves L.; Connelly, Margery A.; Williams, David L.; de la Llera-Moya, Margarita; Shaul, Philip W.; Silver, David L.
2005-01-01
The binding of HDL to scavenger receptor–BI (SR-BI) mediates cholesterol movement. HDL also induces multiple cellular signals, which in endothelium occur through SR-BI and converge to activate eNOS. To determine the molecular basis of a signaling event induced by HDL, we examined the proximal mechanisms in HDL activation of eNOS. In endothelial cells, HDL and methyl-β-cyclodextrin caused comparable eNOS activation, whereas cholesterol-loaded methyl-β-cyclodextrin had no effect. Phosphatidylcholine-loaded HDL caused greater stimulation than native HDL, and blocking antibody against SR-BI, which prevents cholesterol efflux, prevented eNOS activation. In a reconstitution model in COS-M6 cells, wild-type SR-BI mediated eNOS activation by both HDL and small unilamellar vesicles (SUVs), whereas the SR-BI mutant AVI, which is incapable of efflux to SUV, transmitted signal by only HDL. In addition, eNOS activation by methyl-β-cyclodextrin was SR-BI dependent. Studies of mutant and chimeric class B scavenger receptors revealed that the C-terminal cytoplasmic PDZ-interacting domain and the C-terminal transmembrane domains of SR-BI are both necessary for HDL signaling. Furthermore, we demonstrated direct binding of cholesterol to the C-terminal transmembrane domain using a photoactivated derivative of cholesterol. Thus, HDL signaling requires cholesterol binding and efflux and C-terminal domains of SR-BI, and SR-BI serves as a cholesterol sensor on the plasma membrane. PMID:15841181
Synthesis of BiPbSrCaCuO superconductor
Hults, W.L.; Kubat-Martin, K.A.; Salazar, K.V.; Phillips, D.S.; Peterson, D.E.
1994-04-05
A process and a precursor composition for preparing a lead-doped bismuth-strontium-calcium-copper oxide superconductor of the formula Bi[sub a]Pb[sub b]Sr[sub c]Ca[sub d]Cu[sub e]O[sub f] wherein a is from about 1.7 to about 1.9, b is from about 0.3 to about 0.45, c is from about 1.6 to about 2.2, d is from about 1.6 to about 2.2, e is from about 2.97 to about 3.2 and f is 10[+-]z by reacting a mixture of Bi[sub 4]Sr[sub 3]Ca[sub 3]Cu[sub 4]O[sub 16[+-]z], an alkaline earth metal cuprate, e.g., Sr[sub 9]Ca[sub 5]Cu[sub 24]O[sub 41], and an alkaline earth metal plumbate, e.g., Ca[sub 2[minus]x]Sr[sub x]PbO[sub 4] wherein x is about 0.5, is disclosed.
Synthesis of BiPbSrCaCuO superconductor
Hults, William L.; Kubat-Martin, Kimberly A.; Salazar, Kenneth V.; Phillips, David S.; Peterson, Dean E.
1994-01-01
A process and a precursor composition for preparing a lead-doped bismuth-strontium-calcium-copper oxide superconductor of the formula Bi.sub.a Pb.sub.b Sr.sub.c Ca.sub.d Cu.sub.e O.sub.f wherein a is from about 1.7 to about 1.9, b is from about 0.3 to about 0.45, c is from about 1.6 to about 2.2, d is from about 1.6 to about 2.2, e is from about 2.97 to about 3.2 and f is 10.+-.z by reacting a mixture of Bi.sub.4 Sr.sub.3 Ca.sub.3 Cu.sub.4 O.sub.16.+-.z, an alkaline earth metal cuprate, e.g., Sr.sub.9 Ca.sub.5 Cu.sub.24 O.sub.41, and an alkaline earth metal plumbate, e.g., Ca.sub.2-x Sr.sub.x PbO.sub.4 wherein x is about 0.5, is disclosed.
Leaching Characteristics of Calcium and Strontium from Phosphogypsum Under Acid Rain.
Wang, Mei; Luo, Houqiao; Chen, Yong; Yang, Jinyan
2018-02-01
Phosphogypsum (PG) stored close to phosphorus chemical plants has caused worldwide environmental problems. Column leaching experiments were conducted to evaluate Ca and Sr leaching from PG under simulated acid rain at pH levels typical for rain in the study region (Shifang, China). High concentrations of Ca and Sr in leachates in the first five leaching events could pollute the soil and groundwater around the PG. Leachates pH was lower than and had no correlation with simulated rain pH. No correlations between simulated rain pH and cumulative Ca and Sr content in leachates were noted. Around 2.0%-2.2% of Ca and 0.5%-0.6% of Sr were leached out from PG by the simulated summer rainfall in Shifang. Electrical conductivity values, Ca and Sr concentrations at bottom sections of PG columns were higher than those of top sections, while pH values showed a reverse trend. More precautions should be taken to protect the environment around PG stacks.
NASA Astrophysics Data System (ADS)
AlKhatib, Mahmoud; Eisenhauer, Anton
2017-07-01
In order to study Strontium (Sr) partitioning and isotope fractionation of Sr and Calcium (Ca) in calcite we performed precipitation (T) experiments decoupling temperature and precipitation rate (R∗). Calcite was precipitated at 12.5, 25.0 and 37.5 °C by diffusing NH3 and CO2 gases into aqueous solutions closely following the experimental setup of Lemarchand et al. (2004). The precipitation rate (R∗) for every sample was determined applying the initial rate method and from the specific surface area of almost all samples for each reaction. The order of reaction with respect to Ca2+ ions was determined to be one and independent of T. However, the order of reaction with respect to HCO3- changed from three to one as temperature increases from 12.5, 25 °C and 37.5 °C. Strontium incorporated into calcite (expressed as DSr = [Sr/Ca]calcite/[Sr/Ca]solution) was found to be R∗ and T dependent. As a function of increasing R∗ the Δ88/86Sr-values become more negative and as temperature increases the Δ88/86Sr values also increase at constant R∗. The DSr and Δ88/86Sr-values are correlated to a high degree and depend only on R∗ being independent of temperature, complexation and varying initial ratios. Latter observation may have important implications for the study of diagenesis, the paleo-sciences and the reconstruction of past environmental conditions. Calcium isotope fractionation (Δ44/40Ca) was also found to be R∗ and T dependent. For 12.5 and 25.0 °C we observe a general increase of the Δ44/40Ca values as a function of R∗ (Lemarchand et al. type behavior, Lemarchand et al. (2004)). Whereas at 37.5 °C a significant decreasing Δ44/40Ca is observed relative to increasing R∗ (Tang et al. type behavior, Tang et al. (2008)). In order to reconcile the discrepant observations we suggest that the temperature triggered change from a Ca2+-NH3-aquacomplex covalent controlled bonding to a Ca2+-H2O-aquacomplex van-der-Waals controlled bonding caused the change in sign of the R∗ - Δ44/40Ca slope due to the switch of an equilibrium type of isotope fractionation related to the covalent bonding during lower temperatures to a kinetic type of isotope fractionation at higher temperatures. This is supported by the observation that the Δ44/40Ca ratios tend to depend on the [Ca]:[DIC] ratio at 12.5 and 25 °C but is highly independent at 37.5 °C. Our observations imply the chemical fluid composition and temperature dependent complexation controls the amount and direction of Ca isotope fractionation in contrast to the Sr isotopes which do not show any change of its fractionation behavior as a function of complexation in the liquid phase.
NASA Astrophysics Data System (ADS)
Debastiani, Rafaela; Simon, Rolf; Goettlicher, Joerg; Heissler, Stefan; Steininger, Ralph; Batchelor, David; Fiederle, Michael; Baumbach, Tilo
2016-10-01
Roman mural green pigment painting fragments from three Roman sites in the north of the Roman province Germania Superior: Koblenz Stadtwald Remstecken (KOSR), Weißenthurm " Am guten Mann" (WEIS) and Mendig Lungenkärchen (MELU), dating from second and third centuries AD were analyzed. The experiments were performed nondestructively using synchrotron-based scanning macro-X-ray fluorescence (SR-MA-XRF), synchrotron-based scanning micro-X-ray fluorescence (SR-μ-XRF), synchrotron-based X-ray diffraction (SR-XRD) and Raman spectroscopy. Correlation between SR-MA-XRF, SR-μ-XRF elemental map distributions and optical images of scanned areas was mainly found for the elements Ca, Fe and K. With XRF, Fe and K were identified correlated with green pigment, but in samples from two sites, Mendig Lungenkärchen and Weißenthurm " Am guten Mann", also Cu was detected in minor concentration. The results of SR-XRD and Raman spectroscopy were limited to one sample from Weißenthurm " Am guten Mann". In this sample, green earth and calcium carbonate were identified by SR-XRD and, additionally, malachite by Raman spectroscopy.
Singh, Navneet; Chakrabarty, Subhas
2013-11-15
We recently reported on the isolation and characterization of calcium sensing receptor (CaSR) null human colon cancer cells (Singh et al., Int J Cancer 2013; 132: 1996-2005). CaSR null cells possess a myriad of molecular features that are linked to a highly malignant and drug resistant phenotype of colon cancer. The CaSR null phenotype can be maintained in defined human embryonic stem cell culture medium. We now show that the CaSR null cells can be induced to differentiate in conventional culture medium, regained the expression of CaSR with a concurrent reversal of the cellular and molecular features associated with the null phenotype. These features include cellular morphology, expression of colon cancer stem cell markers, expression of survivin and thymidylate synthase and sensitivity to fluorouracil. Other features include the expression of epithelial mesenchymal transition linked molecules and transcription factors, oncogenic miRNAs and tumor suppressive molecule and miRNA. With the exception of cancer stem cell markers, the reversal of molecular features, upon the induction of CaSR expression, is directly linked to the expression and function of CaSR because blocking CaSR induction by shRNA circumvented such reversal. We further report that methylation and demethylation of the CaSR gene promoter underlie CaSR expression. Due to the malignant nature of the CaSR null cells, inclusion of the CaSR null phenotype in disease management may improve on the mortality of this disease. Because CaSR is a robust promoter of differentiation and mediates its action through diverse mechanisms and pathways, inactivation of CaSR may serve as a new paradigm in colon carcinogenesis. Copyright © 2013 UICC.
Bouhlel, Aicha; Joumaa, Wissam H; Léoty, Claude
2003-09-01
The effects of anabolic-androgenic steroid administration on the function of the sarcoplasmic reticulum (SR) pump were investigated in chemically skinned fibres from the extensor digitorum longus (EDL) and soleus muscles of sedentary rats. Twenty male rats were divided into two groups, one group received an intramuscular injection of nandrolone decanoate (15 mg x kg(-1)) weekly for 8 weeks, the second received similar weekly doses of vehicle (sterile peanut oil). Compared with control muscles, nandrolone decanoate treatment reduced SR Ca(2+) loading in EDL and soleus fibres by 49% and 29%, respectively. In control and treated muscles, the rate of Ca(2+) leakage depended on the quantity of Ca(2+) loaded. Furthermore, for similar SR Ca(2+) contents, the Ca(2+) leakage rate was not significantly modified by nandrolone decanoate treatment. Nandrolone decanoate treatment thus affects Ca (2+) uptake by the SR in a fibre-type dependent manner.
Large-scale imaging of cortical network activity with calcium indicators.
Ikegaya, Yuji; Le Bon-Jego, Morgane; Yuste, Rafael
2005-06-01
Bulk loading of calcium indicators has provided a unique opportunity to reconstruct the activity of cortical networks with single-cell resolution. Here we describe the detailed methods of bulk loading of AM dyes we developed and have been improving for imaging with a spinning disk confocal microscope.
Lamb, G D; Stephenson, D G
1990-04-01
1. Skeletal muscle fibres from the toad were mechanically skinned under paraffin oil and then bathed in a potassium HDTA solution (HDTA: hexamethylenediamine-tetraacetate) which mimicked the ionic composition of the myoplasm. 2. Rapid transient contractions could be triggered by substitution of K+ with Na+ (with no change of anion), which should have virtually no direct effect on the electrical polarization of the sarcoplasmic reticulum (SR) membrane. Up to thirty or more contractions could be evoked by repeated substitutions if there was sufficient 'repriming' time (about 30 s) between them; these rapid contractions were analagous to potassium contractures in intact fibres. 3. When the SR was not heavily loaded, substitution of potassium HDTA with choline chloride also produced a rapid, brief contraction. 4. All treatments designed to 'inactivate' the voltage sensor in the T-system invariably abolished the rapid contractions. Thus, rapid contractions were absent if (i) the T-system was permanently depolarized by pre-soaking the muscle in a high potassium solution with ouabain before skinning, (ii) a fibre was split rather than skinned, (iii) the T-system was temporarily depolarized by Na+ substitution immediately before choline chloride substitution, or vice versa, (iv) a skinned fibre was briefly exposed to saponin (50 micrograms/ml) to selectively disrupt the T-system membrane or (v) the muscle was pre-soaked in a solution with 1 mM-EGTA and no Ca2+ or Mg2+ before skinning. In contrast to (v), if 10 mM-Mg2+ was present in the EGTA solution before skinning, rapid contractions could be elicited, presumably because the presence of Mg2+ prevented the inactivation of the T-system voltage sensor in low [Ca2+]. 5. These results unequivocally demonstrate that (a) the T-system reseals and repolarizes after mechanical skinning under oil and (b) the fast contractions are produced by activation of the voltage sensor in the T-system. 6. When the SR had been heavily loaded, choline chloride substitution (but not Na+ substitution) could also induce an unphysiological, slow contraction ('second component'). In total contrast to the fast contraction, this slow component was unaffected by any of the treatments (i-v) above, indicating that it did not depend on activation of the voltage sensor in the T-system but resulted from a direct action of choline chloride on the SR.(ABSTRACT TRUNCATED AT 400 WORDS)
Lamb, G D; Stephenson, D G
1990-01-01
1. Skeletal muscle fibres from the toad were mechanically skinned under paraffin oil and then bathed in a potassium HDTA solution (HDTA: hexamethylenediamine-tetraacetate) which mimicked the ionic composition of the myoplasm. 2. Rapid transient contractions could be triggered by substitution of K+ with Na+ (with no change of anion), which should have virtually no direct effect on the electrical polarization of the sarcoplasmic reticulum (SR) membrane. Up to thirty or more contractions could be evoked by repeated substitutions if there was sufficient 'repriming' time (about 30 s) between them; these rapid contractions were analagous to potassium contractures in intact fibres. 3. When the SR was not heavily loaded, substitution of potassium HDTA with choline chloride also produced a rapid, brief contraction. 4. All treatments designed to 'inactivate' the voltage sensor in the T-system invariably abolished the rapid contractions. Thus, rapid contractions were absent if (i) the T-system was permanently depolarized by pre-soaking the muscle in a high potassium solution with ouabain before skinning, (ii) a fibre was split rather than skinned, (iii) the T-system was temporarily depolarized by Na+ substitution immediately before choline chloride substitution, or vice versa, (iv) a skinned fibre was briefly exposed to saponin (50 micrograms/ml) to selectively disrupt the T-system membrane or (v) the muscle was pre-soaked in a solution with 1 mM-EGTA and no Ca2+ or Mg2+ before skinning. In contrast to (v), if 10 mM-Mg2+ was present in the EGTA solution before skinning, rapid contractions could be elicited, presumably because the presence of Mg2+ prevented the inactivation of the T-system voltage sensor in low [Ca2+]. 5. These results unequivocally demonstrate that (a) the T-system reseals and repolarizes after mechanical skinning under oil and (b) the fast contractions are produced by activation of the voltage sensor in the T-system. 6. When the SR had been heavily loaded, choline chloride substitution (but not Na+ substitution) could also induce an unphysiological, slow contraction ('second component'). In total contrast to the fast contraction, this slow component was unaffected by any of the treatments (i-v) above, indicating that it did not depend on activation of the voltage sensor in the T-system but resulted from a direct action of choline chloride on the SR.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1696987
Seppel, Gernot; Saier, Tim; Martetschläger, Frank; Plath, Johannes E; Guevara-Alvarez, Alberto; Henschel, Julia; Winkler, Martin; Augat, Peter; Imhoff, Andreas B; Buchmann, Stefan
2017-12-01
Fractures of the humeral greater tuberosity (GT) are a frequent injury progressively treated with arthroscopic suture anchor repair. Yet, no biomechanical study has been performed comparing fixation strength of arthroscopic single- (SR) vs. double row (DR) fixation. Standardized fractures of the greater tuberosity were created in 12 fresh frozen proximal humeri. After random assignation to the SR or DR group the fixed humeri were tested applying cyclic loading to the supraspinatus and infraspinatus tendon. Load to failure and fragment displacement were assessed by means of an electrodynamic material testing machine using an optical tracking system. Load to failure values were higher in the DR group (649 N; ±176) than in the SR group (490 N; ±145) however without statistical significance (p = .12). In greater tuberosity displacement of 3-5 mm surgical treatment is recommended. The fixing constructs in this study did not reach displacement landmarks of 3 or 5 mm before construct failure as shown in previous studies. Thus the applied traction force (N) at 1 mm displacement was analyzed. In the SR group the load at 1 mm displacement was 277 N; ±46 compared to 260 N; ±62 in the DR group (p = .65). The results suggest that both techniques are viable options for refixation of greater tuberosity fractures. Laboratory study.
McConoughey, Stephen J; Howlin, Robert P; Wiseman, Jessica; Stoodley, Paul; Calhoun, Jason H
2015-05-01
Antibiotic-loaded bone cement is a primary option for treatment of orthopedic infections. Poly(methyl methacrylate) (PMMA) is a widely used cement that, when loaded with antibiotics in spacer or bead form, has been shown to reduce infection rates. However, PMMA is not resorbable and requires a second surgery for removal, while also acting as a potential foreign body for bacterial colonization. Alternatively, resorbable bone cements, such as calcium sulfate, have been proposed and present the advantage of being completely reabsorbed. It is unknown whether the antibiotic elution characteristics of absorbable bone cements are similar to PMMA. This study (1) characterized antibiotic elution from synthetic, highly purified calcium sulfate cement beads of varying sizes against pathogenic bacteria both in liquid culture and seeded on agar plates, (2) tested calcium sulfate beads against PMMA beads loaded with the same antibiotics, and (3) analyzed the structural differences between how PMMA and calcium sulfate bind to antibiotics. In every assay, the calcium sulfate beads performed as well as, or better than, the PMMA beads in inhibition of bacterial growth and elution of vancomycin in vitro with complete elution observed from calcium sulfate within three days. These data suggest that calcium sulfate, functions, as well as PMMA in the patient setting for infection control. © 2014 Wiley Periodicals, Inc.
Benthic sulfate reduction along the Chesapeake Bay central channel. II. Temporal controls
Marvin-DiPasquale, M. C.; Boynton, W.R.; Capone, D.G.
2003-01-01
Seasonal and interannual controls of benthic sulfate reduction (SR) were examined at 3 sites (upper [UB], mid- [MB] and lower [LB] bay) along the Chesapeake Bay central channel, from early spring through fall, for 6 yr (1989 to 1994). The combined influences of temperature, sulfate, organic loading and bioturbation affected seasonal SR rates differently in the 3 regions. Consistently low SR rates at UB resulted from low overlying-water sulfate concentrations and the dominance of refractory organic terrestrial material. Combined seasonal variation in temperature and sulfate accounted for 50% of the annual variability in 0 to 2 cm depth interval SR rates, while sediment organic content had no significant seasonal influence. In contrast, MB and LB sites had high rates of SR fostered by high levels of overlying water SO42- and organic input dominated by labile phytoplankton detritus. New organic loading (measured as chl a) stimulated 0 to 2 cm SR during spring at both sites. Combined organic quantity (as particulate C and/or N) and temperature accounted for > 75% of the variability in 0 to 2 cm SR at MB during spring and fall. Molecular diffusion supplied 25 to 45% of the SO 42- needed to fuel 0 to 12 cm depth interval SR at MB, with the balance presumably supplied by S-recycling. Interannual differences in summertime SR rates were linked to the extent of freshwater flow during spring, with high-flow years associated with high SR rates at UB and MB, and low rates at LB. The negative trend between benthic SR and river flow at LB may result from the up-estuary transport of senescing organic matter in bottom water, which increases in the lower reach of the estuary with increasing freshwater inflow.
Alamshah, A; Spreckley, E; Norton, M; Kinsey-Jones, J S; Amin, A; Ramgulam, A; Cao, Y; Johnson, R; Saleh, K; Akalestou, E; Malik, Z; Gonzalez-Abuin, N; Jomard, A; Amarsi, R; Moolla, A; Sargent, P R; Gray, G W; Bloom, S R; Murphy, K G
2017-11-01
High-protein diets (HPDs) are associated with greater satiety and weight loss than diets rich in other macronutrients. The exact mechanisms by which HPDs exert their effects are unclear. However, evidence suggests that the sensing of amino acids produced as a result of protein digestion may have a role in appetite regulation and satiety. We investigated the effects of l-phenylalanine (L-Phe) on food intake and glucose homeostasis in rodents. We investigated the effects of the aromatic amino-acid and calcium-sensing receptor (CaSR) agonist l-phenylalanine (L-Phe) on food intake and the release of the gastrointestinal (GI) hormones peptide YY (PYY), glucagon-like peptide-1 (GLP-1) and ghrelin in rodents, and the role of the CaSR in mediating these effects in vitro and in vivo. We also examined the effect of oral l-Phe administration on glucose tolerance in rats. Oral administration of l-Phe acutely reduced food intake in rats and mice, and chronically reduced food intake and body weight in diet-induced obese mice. Ileal l-Phe also reduced food intake in rats. l-Phe stimulated GLP-1 and PYY release, and reduced plasma ghrelin, and also stimulated insulin release and improved glucose tolerance in rats. Pharmacological blockade of the CaSR attenuated the anorectic effect of intra-ileal l-Phe in rats, and l-Phe-induced GLP-1 release from STC-1 and primary L cells was attenuated by CaSR blockade. l-Phe reduced food intake, stimulated GLP-1 and PYY release, and reduced plasma ghrelin in rodents. Our data provide evidence that the anorectic effects of l-Phe are mediated via the CaSR, and suggest that l-Phe and the CaSR system in the GI tract may have therapeutic utility in the treatment of obesity and diabetes. Further work is required to determine the physiological role of the CaSR in protein sensing in the gut, and the role of this system in humans.
Calcium EXAFS Establishes the Mn-Ca Cluster in the Oxygen-Evolving Complex of Photosystem II†
Cinco, Roehl M.; Holman, Karen L. McFarlane; Robblee, John H.; Yano, Junko; Pizarro, Shelly A.; Bellacchio, Emanuele; Sauer, Kenneth; Yachandra, Vittal K.
2014-01-01
The proximity of Ca to the Mn cluster of the photosynthetic water-oxidation complex is demonstrated by X-ray absorption spectroscopy. We have collected EXAFS data at the Ca K-edge using active PS II membrane samples that contain approximately 2 Ca per 4 Mn. These samples are much less perturbed than previously investigated Sr-substituted samples, which were prepared subsequent to Ca depletion. The new Ca EXAFS clearly shows backscattering from Mn at 3.4 Å, a distance that agrees with that surmised from previously recorded Mn EXAFS. This result is also consistent with earlier related experiments at the Sr K-edge, using samples that contained functional Sr, that show Mn is ~ 3.5 Å distant from Sr. The totality of the evidence clearly advances the notion that the catalytic center of oxygen evolution is a Mn-Ca heteronuclear cluster. PMID:12390018
Márquez-Herrera, Alfredo; Ovando-Medina, Victor Manuel; Castillo-Reyes, Blanca Estela; Zapata-Torres, Martin; Meléndez-Lira, Miguel; González-Castañeda, Jaquelina
2016-01-01
Pyrrole monomer was chemically polymerized onto SrCO3-Sr(OH)2 powders to obtain SrCO3-Sr(OH)2/polypyrrole nanocomposite to be used as a candidate for photocatalytic degradation of methylene blue dye (MB). The material was characterized by Fourier transform infrared (FTIR) spectroscopy, UV/Vis spectroscopy, and X-ray diffraction (XRD). It was observed from transmission electronic microscopy (TEM) analysis that the reported synthesis route allows the production of SrCO3-Sr(OH)2 nanoparticles with particle size below 100 nm which were embedded within a semiconducting polypyrrole matrix (PPy). The SrCO3-Sr(OH)2 and SrCO3-Sr(OH)2/PPy nanocomposites were tested in the photodegradation of MB dye under visible light irradiation. Also, the effects of MB dye initial concentration and the catalyst load on photodegradation efficiency were studied and discussed. Under the same conditions, the efficiency of photodegradation of MB employing the SrCO3-Sr(OH)2/PPy nanocomposite increases as compared with that obtained employing the SrCO3-Sr(OH)2 nanocomposite. PMID:28787830
Inaba, Masaaki; Okuno, Senji; Nagayama, Harumi; Yamada, Shinsuke; Ishimura, Eiji; Imanishi, Yasuo; Shoji, Shigeichi
2015-03-01
Control of phosphate is the most critical in the treatment of chronic kidney disease with mineral and bone disorder (CKD-MBD). Because calcium-containing phosphate binder to CKD patients is known to induce adynamic bone disease with ectopic calcification by increasing calcium load, we examined the effect of lanthanum carbonate (LaC), a non-calcium containing phosphate binder, to restore bone turnover in 27 hemodialysis patients with suppressed parathyroid function (serum intact parathyroid hormone [iPTH] ≦ 150 pg/mL). At the initiation of LaC administration, the dose of calcium-containing phosphate binder calcium carbonate (CaC) was withdrawn or reduced based on serum phosphate. After initiation of LaC administration, serum calcium and phosphate decreased significantly by 4 weeks, whereas whole PTH and iPTH increased. A significant and positive correlation between decreases of serum calcium, but not phosphate, with increases of whole PTH and iPTH, suggested that the decline in serum calcium with reduction of calcium load by LaC might increase parathyroid function. Serum bone resorption markers, such as serum tartrate-resistant acid phosphatase 5b, and N-telopeptide of type I collagen increased significantly by 4 weeks after LaC administration, which was followed by increases of serum bone formation markers including serum bone alkaline phosphatase, intact procollagen N-propeptide, and osteocalcin. Therefore, it was suggested that LaC attenuated CaC-induced suppression of parathyroid function and bone turnover by decreasing calcium load. In conclusion, replacement of CaC with LaC, either partially or totally, could increase parathyroid function and resultant bone turnover in hemodialysis patients with serum iPTH ≦ 150 pg/mL. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
Electronic structure, chemical bonding, and geometry of pure and Sr-doped CaCO3.
Stashans, Arvids; Chamba, Gaston; Pinto, Henry
2008-02-01
The electronic structure, chemical bonding, geometry, and effects produced by Sr-doping in CaCO(3) have been studied on the basis of density-functional theory using the VASP simulation package and molecular-orbital theory utilizing the CLUSTERD computer code. Two calcium carbonate structures which occur naturally in anhydrous crystalline forms, calcite and aragonite, were considered in the present investigation. The obtained diagrams of density of states show similar patterns for both materials. The spatial structures are computed and analyzed in comparison to the available experimental data. The electronic properties and atomic displacements because of the trace element Sr-incorporation are discussed in a comparative manner for the two crystalline structures. (c) 2007 Wiley Periodicals, Inc.
Sr$sup 90$ CONTAMINATION OF MEN CAUSED BY FOOD UPTAKE (in German)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Seidler, H.; Haertig, M.; Siebert, K.
During 1961 in determined periods, the total food of 4 groups of persons was collected and investigated for Sr/sup 90/. Parallel to that, analytical determinations were made of the Sr/sup 90/ contents of the chief foods and the statistically determined consumed amount and the daily Sr/sup 90/ load to various groups of persons were calculated. There was very little difference between the calculated and measured values of Sr/sup 90/ activity in food. For babies and small children it amounted to about 5 pC Sr/sup 90/ per person per day and for children, youths, and adults about 10 pC Sr/sup 90/more » per person per day. (tr- auth)« less
Low loss composition of BaxSryCa1-x-yTiO3: Ba0.12-0.25Sr0.35-0.47Ca0.32-0.53TiO3
Xiang, Xiao-Dong; Chang, Hauyee; Takeuchi, Ichiro
2001-01-01
A dielectric thin-film material for microwave applications, including use as a capacitor, the thin-film comprising a composition of barium strontium calcium and titanium of perovskite type (Ba.sub.x Sr.sub.y Ca.sub.1-x-y)TiO.sub.3. Also provided is a method for making a dielectric thin film of that formula over a wide compositional range through a single deposition process.
Spontaneous calcium waves in Bergman glia increase with age and hypoxia and may reduce tissue oxygen
Mathiesen, Claus; Brazhe, Alexey; Thomsen, Kirsten; Lauritzen, Martin
2013-01-01
Glial calcium (Ca2+) waves constitute a means to spread signals between glial cells and to neighboring neurons and blood vessels. These waves occur spontaneously in Bergmann glia (BG) of the mouse cerebellar cortex in vivo. Here, we tested three hypotheses: (1) aging and reduced blood oxygen saturation alters wave activity; (2) glial Ca2+ waves change cerebral oxygen metabolism; and (3) neuronal and glial wave activity is correlated. We used two-photon microscopy in the cerebellar cortexes of adult (8- to 15-week-old) and aging (48- to 80-week-old) ketamine-anesthetized mice after bolus loading with OGB-1/AM and SR101. We report that the occurrence of spontaneous waves is 20 times more frequent in the cerebellar cortex of aging as compared with adult mice, which correlated with a reduction in resting brain oxygen tension. In adult mice, spontaneous glial wave activity increased on reducing resting brain oxygen tension, and ATP-evoked glial waves reduced the tissue O2 tension. Finally, although spontaneous Purkinje cell (PC) activity was not associated with increased glia wave activity, spontaneous glial waves did affect intracellular Ca2+ activity in PCs. The increased wave activity during aging, as well as low resting brain oxygen tension, suggests a relationship between glial waves, brain energy homeostasis, and pathology. PMID:23211964
Mora, Miguel A.; Taylor, Robert J.; Brattin, Bryan L.
2007-01-01
We investigated the occurrence and potential ecotoxicological significance of elevated concentrations of strontium (Sr) in eggshells of nine passerine birds from four regions in Arizona. Concentrations of Sr in eggshells ranged from 70 to 1360 µg g−1 dry weight (overall mean = 684 ± 345 SD µg g−1 dw) for the four regions. 23% of the eggshells had Sr concentrations greater than 1000 µg g−1 dw. To our knowledge, these are among the highest levels of Sr that have been reported in bird eggshells in North America. Of the nine species, Brown-headed Cowbirds (Molothrus ater) had the greatest concentrations of Sr. There was a significant positive correlation between Sr and calcium (Ca), and between barium (Ba) and Ca. Ca, Sr, and Ba interact with each other and can exert similar chemical and pharmacological effects. Mean (n ≥ 3) eggshell∶egg ratios for Sr varied with species and ranged from 6.1∶1 to 40.2∶1; ratios for individual eggs reached 92.7∶1. Mean Sr/Ca values ranged from 1.3 × 10−3 to 3.0 × 10−3 and mean eggshell thickness ranged from 83 ± 6 to 120 ± 9 µm for all species. Eggshell thickness was not significantly correlated with Sr for any species but tended to increase with Sr concentrations. We postulate that high concentrations of Sr in the shell could affect later-stage embryos by possible interference with Ca metabolism and bone growth, resulting in reduced hatching success and potential minor beak deformities.
NASA Astrophysics Data System (ADS)
Thapa, Mahendra Bahadur
Calbindin D9k (CAB) is a single domain calcium-binding protein and is the smallest members of the calmodulin superfamily, possessing a pair of calcium-binding EF-hands, and structures for all four states have been determined and extensively characterized experimentally. Because of the tremendous advancement in hardware and software computer technologies in recent years, longer and more realistic molecular dynamics (MD) simulations of a protein are possible now in reasonable periods of time. These advances were exploited to generate multiple, all-atom MD simulations of CAB via the AMBER software package, and the resulting trajectories were employed to calculate backbone order parameters of the apo, the singly and the doubly loaded states of calcium in CAB. The results are in very good agreement with corresponding experimental NMR-based (Nuclear Magnetic Resonance spectroscopy) results, and are improved in comparison to those calculated over a decade ago; use of modified force fields played a key role in the observed improvements. The apo state is the most flexible, and the singly loaded and the doubly loaded states are similar, thus supporting positive cooperativity in line with the experimental results. Further, B-factor calculations of backbone atoms for these calcium-binding states of calbindin D9k also support such cooperativity. Although changes in side-chain motions are not necessarily correlated to changes in protein backbone mobility, past studies on the comparison of experimental and simulated methyl side-chain NMR relaxation parameters of CAB for the doubly-loaded state reported significant improvements in the quantitative representation of side-chain motion by MD simulation. In this project, the order parameters for various side chains in apo, singly loaded and doubly loaded states of CAB were calculated. The primary goal of this work was to determine whether or not the allosteric effect of calcium binding, as observed via the backbone order parameters, also extended to the amino acid side chains, and if so, to what extent. Such information could be useful in better understanding the physical basis of cooperative calcium binding in CAB. Most of the residues which provide ligands to bind calcium at the binding sites support positive cooperativity, as observed when Ca-Cß, Cß-C?, C-C bond and C-O bonds of COO groups of aspartic and glutamic acid residues, the C-N bond of the side-chain amide group in asparagine and glutamine residues, and the N-H bonds of amide (NH2) group order parameters were studied. There are only a few residues containing methyl groups that are involved in providing ligands to the calcium, and the studies of order parameters of C-C bond and C-H bond of these methyl groups did not exhibit the cooperativity effect upon calcium binding; the simulated C-C bond order parameter of the methyl group symmetry axis did correlate well with the experimental results for the fully loaded state of CAB (4ICB). Analysis of the MD trajectories using GSATools and MutInf, provided valuable insights into possible pathways for communicating allosteric effects between the two calcium-binding sites of CAB.
Zhang, Huiping; Annich, Gail M; Miskulin, Judiann; Osterholzer, Kathryn; Merz, Scott I; Bartlett, Robert H; Meyerhoff, Mark E
2002-03-01
Nitric oxide (NO) releasing silicone rubbers (SR) are prepared via a three-step reaction scheme. A diamino triaminoalkyltrimethoxysilane crosslinker is used to vulcanize hydroxyl terminated polydimethylsiloxane (PDMS) in the presence of ambient moisture and a dibutyltin dilaurate catalyst so that the respective diamine triamine groups are covalently linked to the cured SR structure. These amine sites are then diazeniumdiolated, in situ, when the cured SR is reacted with NO at elevated pressure (80 psi). Although nitrite species are also formed during the NO addition reaction, in most cases the diazeniumdiolated polymer is the major product within the final SR matrix. Temperature appears to be the major driving force for the dissociation of the attached diazeniumdiolate moieties, whereas the presence of bulk water bathing the SR materials has only minimal effect on the observed NO release rate owing to the low water uptake of the SR matrices. The resulting SR films/coatings release NO at ambient or physiological temperature for up to 20 d with average fluxes of at least 4 x 10(10) mol x cm(-2) x min(-1) (coating thickness > or = 600 microm) over first 4 h, comparable to the NO fluxes observed from stimulated human endothelial cells. The NO loading and concomitant NO release flux of the SR material are readily adjustable by altering the diamine triamine loading and film/coating thickness. The new NO releasing SR materials are shown to exhibit improved thromboresistance in vivo, as demonstrated via reduced platelet activation on the surface of these polymers when used to coat the inner walls of SR tubings employed for extracorporeal circulation in a rabbit model.
Larosa, Claudio; Salerno, Marco; de Lima, Juliana Silva; Merijs Meri, Remo; da Silva, Milena Fernandes; de Carvalho, Luiz Bezerra; Converti, Attilio
2018-08-01
Incorporating enzymes into calcium alginate beads is an effective method to immobilise them and to preserve, at the same time, their catalytic activity. Sodium alginate was mixed with Aspergillus ficuum tannase in aqueous solution, and tannase-loaded calcium alginate beads were prepared using a simple droplet-based microfluidic system. Extensive experimental analysis was carried out to characterise the samples. Microscopic imaging revealed morphological differences between the surfaces of bare alginate matrix and tannase-loaded alginate beads. Thermal analysis allowed assessing the hydration contents of alginate and revealed the presence of tannase entrapped in the loaded beads, which was confirmed by vibrational spectroscopy. X-ray diffraction allowed us to conclude that alginate of tannase-loaded beads is not crystalline, which would make them suitable as carriers for possible controlled release. Moreover, they could be used in food applications to improve tea quality or clarify juices. Copyright © 2018 Elsevier B.V. All rights reserved.
High speed propeller performance and noise predictions at takeoff/landing conditions
NASA Technical Reports Server (NTRS)
Nallasamy, M.; Woodward, R. P.; Groeneweg, J. F.
1988-01-01
The performance and noise of a high speed SR-7A model propeller under takeoff/landing conditions are considered. The blade loading distributions are obtained by solving the three-dimensional Euler equations and the sound pressure levels are computed using a time domain approach. At the nominal takeoff operating point, the blade sections near the hub are lightly or negatively loaded. The chordwise loading distributions are distinctly different from those of cruise conditions. The noise of the SR-7A model propeller at takeoff is dominated by the loading noise, similar to that at cruise conditions. The waveforms of the acoustic pressure signature are nearly sinusoidal in the plane of the propeller. The computed directivity of the blade passing frequency tone agrees fairly well with the data at nominal takeoff blade angle.
High speed propeller performance and noise predictions at takeoff/landing conditions
NASA Technical Reports Server (NTRS)
Nallasamy, M.; Woodward, R. P.; Groeneweg, J. F.
1987-01-01
The performance and noise of a high speed SR-7A model propeller under takeoff/landing conditions are considered. The blade loading distributions are obtained by solving the three-dimensional Euler equations and the sound pressure levels are computed using a time domain approach. At the nominal takeoff operating point, the blade sections near the hub are lightly or negatively loaded. The chordwise loading distributions are distinctly different from those of cruise conditions. The noise of the SR-7A model propeller at takeoff is dominated by the loading noise, similar to that at cruise conditions. The waveforms of the acoustic pressure signature are nearly sinusoidal in the plane of the propeller. The computed directivity of the blade passing frequency tone agrees fairly well with the data at nominal takeoff blade angle.
Zofková, I
2010-05-01
Hypercalcemia and hypophosphatemia are symptoms of two relatively rare hereditary diseases and are extraordinarily important from the standpoint of the differential diagnosis. Mutation in calcium sensing receptor gene (CaSR) clinically manifests as familial hypocalciuric hypercalcemia (FHH) or as the much more serious neonatal hyperparathyreosis. Hypercalciuric hypocalcemia is extremely rare. Prognosis for the most frequent mutations in the CaSR gene FHH is considered benign; nevertheless, if overlooked it can lead to an incorrect diagnosis of primary hyperparathyreosis, which has a fundamentally different prognosis and treatment. Familial hypophosphatemia sometimes occurs as hereditary rickets, which is a consequence of insufficient production of vitamin D-hormone or abnormal function of vitamin D receptors (VDR). The disease manifests as X-linked dominant hypophosphatemic rickets or autosomal dominant hypophosphatemic rickets. Autosomal recessive form is very rare. Oncogenic hypophosphatemia should be excluded in differential diagnosis. In this review the issues of pathogenesis, differential diagnosis and treatment of FHH and hypophosphatemic rickets are discussed.
Abeele, Fabien Vanden; Lotteau, Sabine; Ducreux, Sylvie; Dubois, Charlotte; Monnier, Nicole; Hanna, Amy; Gkika, Dimitra; Romestaing, Caroline; Noyer, Lucile; Flourakis, Matthieu; Tessier, Nolwenn; Al-Mawla, Ribal; Chouabe, Christophe; Lefai, Etienne; Lunardi, Joël; Hamilton, Susan; Fauré, Julien; Van Coppenolle, Fabien; Prevarskaya, Natalia
2018-06-21
Malignant hyperthermia (MH) is a pharmacogenetic disorder arising from uncontrolled muscle calcium release due to an abnormality in the sarcoplasmic reticulum (SR) calcium-release mechanism triggered by halogenated inhalational anesthetics. However, the molecular mechanisms involved are still incomplete. We aimed to identify transient receptor potential vanilloid 1 (TRPV1) variants within the entire coding sequence in patients who developed sensitivity to MH of unknown etiology. In vitro and in vivo functional studies were performed in heterologous expression system, trpv1 -/- mice, and a murine model of human MH. We identified TRPV1 variants in two patients and their heterologous expression in muscles of trpv1 -/- mice strongly enhanced calcium release from SR upon halogenated anesthetic stimulation, suggesting they could be responsible for the MH phenotype. We confirmed the in vivo significance by using mice with a knock-in mutation (Y524S) in the type I ryanodine receptor (Ryr1), a mutation analogous to the Y522S mutation associated with MH in humans. We showed that the TRPV1 antagonist capsazepine slows the heat-induced hypermetabolic response in this model. We propose that TRPV1 contributes to MH and could represent an actionable therapeutic target for prevention of the pathology and also be responsible for MH sensitivity when mutated.
Malone, Shane; Owen, Adam; Mendes, Bruno; Hughes, Brian; Collins, Kieran; Gabbett, Tim J
2018-03-01
This study investigated the association between high-speed running (HSR) and sprint running (SR) and injuries within elite soccer players. The impact of intermittent aerobic fitness as measured by the end speed of the 30-15 intermittent fitness test (30-15V IFT ) and high chronic workloads (average 21-day) as potential mediators of injury risk were also investigated. Observational Cohort Study. 37 elite soccer players from one elite squad were involved in a one-season study. Training and game workloads (session-RPE×duration) were recorded in conjunction with external training loads (using global positioning system technology) to measure the HSR (>14.4kmh -1 ) and SR (>19.8kmh -1 ) distance covered across weekly periods during the season. Lower limb injuries were also recorded. Training load and GPS data were modelled against injury data using logistic regression. Odds ratios (OR) were calculated with 90% confidence intervals based on 21-day chronic training load status (sRPE), aerobic fitness, HSR and SR distance with these reported against a reference group. Players who completed moderate HSR (701-750-m: OR: 0.12, 90%CI: 0.08-0.94) and SR distances (201-350-m: OR: 0.54, 90%CI: 0.41-0.85) were at reduced injury risk compared to low HSR (≤674-m) and SR (≤165-m) reference groups. Injury risk was higher for players who experienced large weekly changes in HSR (351-455-m; OR: 3.02; 90%CI: 2.03-5.18) and SR distances (between 75-105-m; OR: 6.12, 90%CI: 4.66-8.29). Players who exerted higher chronic training loads (≥2584 AU) were at significantly reduced risk of injury when they covered 1-weekly HSR distances of 701-750m compared to the reference group of <674m (OR=0.65, 90% CI 0.27-0.89). When intermittent aerobic fitness was considered based on 30-15V IFT performance, players with poor aerobic fitness had a greater risk of injury than players with better-developed aerobic fitness. Exposing players to large and rapid increases in HSR and SR distances increased the odds of injury. However, higher chronic training loads (≥2584 AU) and better intermittent aerobic fitness off-set lower limb injury risk associated with these running distances in elite soccer players. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.
Regional and interspecific variation in Sr, Ca, and Sr/Ca ratios in avian eggshells from the USA.
Mora, Miguel A; Brattin, Bryan; Baxter, Catherine; Rivers, James W
2011-08-01
To examine regional variation in strontium (Sr), which at high concentrations may reduce eggshell quality, increase egg breakage and reproductive failure, we analyzed Sr, and calcium (Ca) concentrations and Sr/Ca ratios in eggshells from 20 avian species from California, Texas, Idaho, Kansas, and Michigan. In addition, we included data previously reported from Arizona to expand the regional comparisons and to better establish patterns of Sr, and Sr/Ca ratios in bird species across the United States. We found Sr concentrations varied significantly among regions, among species, and among foraging guilds; this variability is strongly influenced by the Sr/Ca ratios in surface water from locations close to the region where the eggshells were collected. Sr concentrations and Sr/Ca ratios were significantly higher in bird eggshells from the Volta wildlife region in the San Joaquin Valley, California and in various locales from Arizona. Sr concentrations and Sr/Ca ratios in bird eggshells from other locations in the USA were lower than those detected in these two regions. Among foraging guilds, invertivores had the highest Sr concentrations and Sr/Ca ratios and carnivores had the lowest. In general, the Sr/Ca ratio increased strongly with increasing Sr concentrations (R(2) = 0.99, P < 0.0001). There was a significant correlation (R(2) = 0.58, P < 0.0001) between Sr/Ca ratios in water and the average Sr/Ca ratios in eggshells suggesting that these values could be determined from Sr/Ca ratios in water. Eggshell thickness was poorly correlated with Sr (R(2) = 0.03) but had a significant and positive correlation with Ca and was more properly correlated by a quadratic equation (R(2) = 0.50, Thickness = 2.13 - 0.02Ca - 3.07 * 10(-5)Ca(2)). Our study provides further evidence that Sr accumulates significantly in the avian eggshell, in some regions at concentrations which could be of concern for potential negative effects on reproduction. We suggest that when assessing the effects of metals on avian reproduction in regions with high Sr deposits in rock and soil, Sr concentrations in the eggshell also should be measured to evaluate additional effects on thickness and reproduction.
Adams, Julie E; O'Brien, Virginia; Magnusson, Erik; Rosenstein, Benjamin; Nuckley, David J
2018-01-01
Therapy programs to treat thumb carpometacarpal (CMC) arthritis may engage selective activation and reeducation of thenar muscles, particularly the first dorsal interosseous (FDI) and opponens pollicis (OP) to reduce subluxation of the joint. We describe the effect of simulated selective activation of the FDI and OP muscles upon radiographic subluxation of the thumb CMC joint. In a cadaver model of CMC subluxation, loads were applied to the FDI, the OP, and then concomitantly at 0%, 25%, 50%, 75%, and 100% maximal loads and radial subluxation of the joint and reduction in subluxation was measured. Selective activation of the OP, alone, improved the subluxation ratio (SR) in a dose-dependent manner. Selective activation of FDI, alone, demonstrated minimal effects on SR. Concomitant activation of OP and FDI improved the SR across all loading states, and activation of 75% and greater, when compared with FDI activation alone, resulted in a statistically significant improvement in SR to within 10% of the presubluxed joint. Concomitant activation of the FDI and OP acts to reduce subluxation of the thumb CMC joint in a dose-dependent fashion. The OP is likely the predominant reducing force. Hand therapy programs that focus on selective strengthening programs likely function in part to encourage patients to activate the easily palpable and easily understood FDI. Concomitant coactivation of the OP may be the major reducing force to elicit clinical and radiographic reduction of subluxation, improved thumb positioning, and reduction of pain and arthritic symptoms.
Indirect evidence of calcitonin secretion in man.
Caniggia, A; Gennari, C; Vattimo, A; Nardi, P; Nuti, R
1976-09-01
1. The effect of calcitonin, a large amount of calcium given orally, pentagastrin and glucagon on plasma 47Ca radioactivity curves in subjects pretreated with 47Ca was examined. 2. A sudden increase of plasma radioactivity after intravenous administration of calcitonin and pentagastrin and after the oral calcium load was observed in normal subjects; the intravenous infusion of glucagon was less effective. 3. Two thyroparathyroidectomized patients who responded to the calcitonin infusion did not respond to the oral calcium load. 4. These data may be considered to offer indirect evidence of endogenous calcitonin secretion in man.
Jiménez, W; Gal, C S; Ros, J; Cano, C; Cejudo, P; Morales-Ruiz, M; Arroyo, V; Pascal, M; Rivera, F; Maffrand, J P; Rodés, J
2000-10-01
Water retention in experimental cirrhosis can be reversed by blocking V(2)-vasopressin (AVP) receptors with the nonpeptide antagonist OPC-31260 or by using the kappa-opioid receptor agonist niravoline, a compound inhibiting central AVP release. However, reluctance to use these drugs in human beings has emerged because the former loses aquaretic efficacy in rats after 2 days of treatment and the latter may have adverse effects in humans. Recently, a new potent and selective nonpeptide V(2)-AVP receptor antagonist, SR121463, has been developed that could be useful for the treatment of dilutional hyponatremia in human cirrhosis. The current study assessed the aquaretic efficacy of 10-day chronic oral administration of SR121463 (0.5 mg/kg/day) in cirrhotic rats with ascites and impaired water excretion after a water load (minimum urinary osmolality >160 mOsm/kg and percentage of water load excreted <60%). Urine volume (UV), osmolality (U(Osm)V), and sodium excretion (U(Na)V) were measured daily. At the end of the 10-day treatment, mean arterial pressure also was measured. In basal conditions cirrhotic rats showed ascites, sodium retention, and impaired water excretion. UV, U(Osm)V, and U(Na)V did not change throughout the study in cirrhotic rats receiving the vehicle. In contrast, SR121463 increased UV and reduced U(Osm)V during the 10-day treatment. This resulted in a greater renal ability to excrete a water load and normalization in serum sodium and osmolality. During the first 6 days of treatment, SR121463 also increased U(Na)V without affecting mean arterial pressure. These data suggest that SR121463 could be of therapeutical value for chronic management of human cirrhosis.
M, Bindu; G, Unnikrishnan
2017-09-27
We report the transport characteristics of silicone rubber/nano-hydroxylapatite (SR/n-HA) systems at room temperature with reference to the effects of n-HA loading, morphology and penetrant nature, using toluene, xylene, ethyl acetate and butyl acetate in the liquid phase and methanol, ethanol, 1-propanol, 2-propanol and butanol in the vapour phase as probe molecules. The interaction between the n-HA particles and SR matrix has been confirmed by FTIR analysis. As the n-HA content in the SR matrix increased, the penetrant uptake has been found to decrease. The observations have been correlated with the density and void content of the systems. Scanning electron microscopy images have been found to be complementary to the observed transport features. The reinforcement effect of n-HA particles on the SR matrix has been verified by Kraus equation. Molecular mass between the cross links has been observed to decrease with an increase in n-HA loading. The results have been compared with affine, phantom network, parallel, series and Maxwell models. The transport data have been complemented by observations on biological fluid uptake with urea, d-glucose, KI, saline water, phosphate buffer and artificial urine as the media.
NASA Astrophysics Data System (ADS)
Bylyku, Elida
2009-04-01
In Albania in recent years it has been of increasing interest to determine various pollutants in the environment and their possible effects on human health. The radiochemical procedure used to identify Pu, Am, U, Th, and Sr radioisotopes in soil, sediment, water, coal, and milk samples is described. The analysis is carried out in the presence of respective tracer solutions and combines the procedure for Pu analysis based on anion exchange, the selective method for Sr isolation based on extraction chromatography using Sr-Spec resin, and the application of the TRU-Spec column for separation of Am fraction. An acid digestion method has been applied for the decomposition of samples. The radiochemical procedure involves the separation of Pu from Th, Am, and Sr by anion exchange, followed by the preconcentration of Am and Sr by coprecipitation with calcium oxalate. Am is separated from Sr by extraction chromatography. Uranium is separated from the bulk elements by liquid-liquid extraction using UTEVA® resin. Thin sources for alpha spectrometric measurements are prepared by microprecipitation with NdF3. Two International Atomic Energy Agency reference materials were analyzed in parallel with the samples.
NASA Astrophysics Data System (ADS)
Ding, W.; Chen, Y.
2016-12-01
Eighteen calcium carbonate veins within the igneous basement recovered close to the fossil spreading ridge of the South China Sea during the Integrated Ocean Drilling Program (IODP) Expedition 349 were investigated. These carbonates are of primarily either calcite or aragonite, or some mixed aragonite and calcite, with rarely ankerite. The chemical (Ca, Mg, Sr, Mn, Fe) contents and isotopic (87Sr/86Sr, δ18O, δ18C) compositions of the veins were determined to study the evolving chemistry of hydrothermal fluids and to constrain the timing of vein formation. The carbonate δ18O values range from -5.0 to -0.2 ‰ PDB, indicating these are typical low temperature basement carbonates. Chemical analyses show distinct Mg/Ca and Sr/Ca ratios for aragonite and calcite. 87Sr/86Sr ratios show negative correlations with both the depth and δ18O-calculated formation temperature, and are independent of mineralogy with both aragonite and calcite, indicating more geochemically evolved carbonated have precipitated from warmer fluids. The hightest 87Sr/86Sr ratios of vein samples at each drill site are believed to reflect the contemporaneous seawater compositions when carbonates precipitated. No unambiguous precipitation ages can be constrained by correlating 87Sr/86Sr ratios with the global seawater Sr isotope evolution. However, based on correlations of vein chemical composition with depth and formation temperature, as well as the Neogene post-spreading magmatism, we hypothesize 10 Ma is a particular time favoring the formation of carbonate veins in our study area.
NASA Astrophysics Data System (ADS)
Radermacher, Pascal; Schöne, Bernd R.; Nunn, Elizabeth V.; Zengjie, Zhang
2010-05-01
Quantifiable paleotemperature data can help to verify predictions made by numerical climate models. Traditionally, paleotemperature estimates are based on δ18O values of biogenic hard parts. However, oxygen isotope values not only reflect changes in ambient temperature, but also changes in δ18Owater, i.e. driven by freshwater influx, evaporation etc. Information regarding the δ18Owater value of past environments is limited for the geological past. The validity of published δ18O paleotemperature data can be tested using element-to-calcium ratios of bivalve shells such as the long-lived ocean quahog, Arctica islandica. Preliminary investigations suggest that Sr/Ca ratios of this species may provide more reliable paleotemperature data. However, contemporaneously deposited shell portions within the outer shell layer demonstrate at least a 30% variability in the Sr/Ca value. This study presents Sr/Ca ratios measured by ICP-OES wet-chemical analyses. Significantly different distributions of Sr/Ca ratios were recorded from the shell surface (over 1330 ppm), through the interior (850 ppm) and to the inner shell surface (1860 ppm). Furthermore, this study showed that different shell crystal fabrics incorporate different amounts of Sr into the CaCO3 lattice of the A. islandica shell. Disparate Sr distribution could potentially be explained either by postdepositional diagenetic processes or syndepositional processes during biomineralization (i.e. different amounts of Sr incorporated into the shell). Understanding the mechanism of the observed Sr heterogeneity is essential if Sr/Ca ratios are to be used confidently in paleotemperature reconstructions.
NASA Astrophysics Data System (ADS)
Cai, Lili; Ma, Wen; Ma, Bole; Guo, Feng; Chen, Weidong; Dong, Hongying; Shuang, Yingchai
2017-08-01
La2Zr2O7-SrZrO3 composite thermal barrier coatings (TBCs) were prepared by air plasma spray (APS). The La2Zr2O7-SrZrO3 composite TBCs covered with calcium-magnesium-aluminum-silicate (CMAS) powder, as well as the powder mixture of CMAS and spray-dried La2Zr2O7-SrZrO3 composite powder, were heat-treated at 1250 °C in air for 1, 4, 8, and 12 h. The phase constituents and microstructures of the reaction products were characterized by x-ray diffraction, scanning electron microscopy, and energy-dispersive spectroscopy. Experimental results showed that the La2Zr2O7-SrZrO3 composite TBCs had higher CMAS resistance than 8YSZ coating. A dense new layer developed between CMAS and La2Zr2O7-SrZrO3 composite TBCs during interaction, and this new layer consisted mostly of apatite (Ca2La8(SiO4)6O2) and c-ZrO2. The newly developed layer effectively protected the La2Zr2O7-SrZrO3 composite TBCs from further CMAS attack.
Ding, Guan-Jun; Zhu, Ying-Jie; Qi, Chao; Sun, Tuan-Wei; Wu, Jin; Chen, Feng
2015-06-26
A facile and environmentally friendly approach has been developed to prepare yolk-shell porous microspheres of calcium phosphate by using calcium L-lactate pentahydrate (CL) as the calcium source and adenosine 5'-triphosphate disodium salt (ATP) as the phosphate source through the microwave-assisted hydrothermal method. The effects of the concentration of CL, the microwave hydrothermal temperature, and the time on the morphology and crystal phase of the product are investigated. The possible formation mechanism of yolk-shell porous microspheres of calcium phosphate is proposed. Hemoglobin from bovine red cells (Hb) and ibuprofen (IBU) are used to explore the application potential of yolk-shell porous microspheres of calcium phosphate in protein/drug loading and delivery. The experimental results indicate that the as-prepared yolk-shell porous microspheres of calcium phosphate have relatively high protein/drug loading capacity, sustained protein/drug release, favorable pH-responsive release behavior, and a high biocompatibility in the cytotoxicity test. Therefore, the yolk-shell porous microspheres of calcium phosphate have promising applications in various biomedical fields such as protein/drug delivery. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
The role of wall calcium in the extension of cell walls of soybean hypocotyls
NASA Technical Reports Server (NTRS)
Virk, S. S.; Cleland, R. E.
1990-01-01
Calcium crosslinks are load-bearing bonds in soybean (Glycine max (L.) Merr.) hypocotyl cell walls, but they are not the same load-bearing bonds that are broken during acid-mediated cell elongation. This conclusion is reached by studying the relationship between wall calcium, pH and the facilitated creep of frozen-thawed soybean hypocotyl sections. Supporting data include the following observations: 1) 2-[(2-bis-[carboxymethyl]amino-5-methylphenoxy)methyl]-6-methoxy-8-bis[car boxymethyl]aminoquinoline (Quin 2) and ethylene glycol-bis(2-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) caused only limited facilitated creep as compared with acid, despite removal of comparable or larger amounts of wall calcium; 2) the pH-response curves for calcium removal and acid-facilitated creep were different; 3) reversible acid-extension occurred even after removal of almost all wall calcium with Quin 2; and 4) growth of abraded sections did not involve a proportional loss of wall calcium. Removal of wall calcium, however, increased the capacity of the walls to undergo acid-facilitated creep. These data indicate that breakage of calcium crosslinks is not a major mechanism of cell-wall loosening in soybean hypocotyl tissues.
Structural diversity of alkaline-earth 2,5-thiophenedicarboxylates
NASA Astrophysics Data System (ADS)
Balendra; Ramanan, Arunachalam
2017-03-01
Exploration of the structural landscape of the system containing divalent alkaline-earth metal ion (Mg, Ca and Sr) with the rigid 2,5-thiophenedicarboxylic acid (TDC) under varying solvothermal condition (DMF, DMA and DEF) yielded five new crystals: [Mg(TDC) (DEF)2(H2O)1/2] (1), [Ca(TDC) (DMA)] (2), [Ca(TDC) (DMA) (H2O)] (3), [Sr(TDC) (DMA)] (4) and [Sr(TDC) (DMA) (H2O)] (5) and two known solids. Single crystal structures of all the solids are characteristic of extended coordination interaction between metal and carboxylate ions. While the smaller magnesium ion crystallized into a 2D coordination polymer, the larger calcium and strontium compounds resulted into the growth of 3D metal organic frameworks. All the solids show blue emission arising from intra ligand charge transfer.
Damasceno, A; Santos, A; Serrão, P; Caupers, P; Soares-da-Silva, P; Polónia, J
1999-12-01
To evaluate the involvement of the renal dopaminergic system in the natriuretic responses to acute saline load in salt-resistant (SR) and salt-sensitive (SS) black normotensive (NT) and hypertensive (HT) subjects. We studied the relationship between the urinary excretion of dopa, dopamine (DA) and its metabolite DOPAC and the natriuretic responses to acute volume expansion (2 l NaCl 0.9% over 2 h) in 20 black NT subjects (12 SR and 8 SS) and 19 black HT subjects (10 SS and 9 SR). Subjects received a low salt (LS) diet (40 mmol sodium/day) for 1 week and a high salt (HS) diet (300 mmol sodium/day) for 1 week; the sequence of the dietary regimens was randomized. Comparisons were made between the results before the saline infusion (baseline) and the results 2 h after the infusion. In all the groups saline infusion induced significant increases in urinary volume (ml/4 h) of two- to three-fold and in urinary sodium excretion (mmol/4 h) of three- to ten-fold; these increases were significantly greater during the HS diet than during the LS diet. Saline infusion significantly increased the mean arterial pressure (MAP) by 5 mmHg in HT-SS subjects and by 4-5 mmHg in NT-SS subjects, but the MAP did not changed in the NT-SR and HT-SR groups. Under the LS diet, saline infusion changed the DA excretion (in nmol/4 h) by -49+/-89 in HT-SS subjects, by 17+/-52 in NT-SS subjects, by 235+/-72 in HT-SR subjects and by 220+/-86 in NT-SR subjects (P < 0.05 between SR and SS subjects). The saline infusion-induced changes in DA excretion correlated significantly with the increases in urinary sodium excretion (r = 0.71, P < 0.01) in the NT-SR and HT-SR subjects under the LS diet, but not in the SR groups on the HS diet nor in the SS groups (HT and NT) on either diet. Saline infusion significantly reduced the DA/dopa ratio in SS (NT and HT) but not SR (NT and HT) subjects, whereas the DA/DOPAC (dihydroxyphenylacetic acid) ratios were similar in all the groups. The urinary dopaminergic system may participate in the natriuretic responses to acute sodium load only in SR subjects (NT and HT) and only under LS diets, but not in SS subjects (NT and HT). This strongly suggests that black NT- and HT-SS subjects have an underlying impairment in the activity of the renal dopaminergic system which may be associated with a reduced decarboxylation of dopa into DA.
Palacios, Cristina; Wigertz, Karin; Braun, Michelle; Martin, Berdine R; McCabe, George P; McCabe, Linda; Pratt, J Howard; Peacock, Munro; Weaver, Connie M
2013-01-01
Background: Previously, we showed that black girls retained more calcium than white girls did and that salt loading negatively affected calcium retention. Racial differences likely exist in other bone minerals also, such as magnesium, in response to salt loading during growth. Objective: We studied racial differences in magnesium metabolism in response to dietary sodium and calcium during rapid bone growth. Design: Twenty-seven white and 40 black girls (11–15 y old) were studied for 3 wk while they consumed low-sodium (1.3 g/d) and high-sodium (3.8 g/d) diets by using a randomized-order, crossover metabolic study with 3 dietary calcium intakes; the magnesium dietary intake was fixed at 230 mg/d. Urine and feces were collected during each 3-wk period in 24-h pools and analyzed for magnesium. A mixed-model ANOVA was used to determine the effect of race and dietary sodium with calcium intake as a covariate. Results: Salt loading or calcium intake had no significant effect on urinary magnesium excretion. Blacks excreted significantly less urinary magnesium (mean ± SD: 83.8 ± 25.6 mg/d) than did whites (94.9 ± 27.3 mg/d; P < 0.05). No effects were observed in fecal magnesium excretion. Magnesium retention was higher with the low-sodium diet (50.1 ± 44.0 mg/d) than with the high-sodium diet (39.3 ± 49.8 mg/d) (P < 0.05), with no effects of race or calcium intake. Salt loading had no effect on biomarkers. Whites had higher 25-hydroxyvitamin D and insulin-like growth factor binding protein 3 but lower 1,25-dihydroxyvitamin D and parathyroid hormone concentrations. Conclusions: Blacks excreted less urinary magnesium than did whites. Magnesium retention was similar between races but higher with the low-sodium diet. Kinetic studies are needed to fully explain magnesium homeostasis. This trial was registered at clinicaltrials.gov as NCT01564238. PMID:23553157
Binding of Dissolved Strontium by Micrococcus luteus
Faison, Brendlyn D.; Cancel, Carmen A.; Lewis, Susan N.; Adler, Howard I.
1990-01-01
Resting cells of Micrococcus luteus have been shown to remove strontium (Sr) from dilute aqueous solutions of SrCl2 at pH 7. Loadings of 25 mg of Sr per g of cell dry weight were achieved by cells exposed to a solution containing 50 ppm (mg/liter) of Sr. Sr binding occurred in the absence of nutrients and did not require metabolic activity. Initial binding was quite rapid (<0.5 h), although a slow, spontaneous release of Sr was observed over time. Sr binding was inhibited in the presence of polyvalent cations but not monovalent cations. Ca and Sr were bound preferentially over all other cations tested. Sr-binding activity was localized on the cell envelope and was sensitive to various chemical and physical pretreatments. Bound Sr was displaced by divalent ions or by H+. Other monovalent ions were less effective. Bound Sr was also removed by various chelating agents. It was concluded that Sr binding by M. luteus is a reversible equilibrium process. Both ion exchange mediated by acidic cell surface components and intracellular uptake may be involved in this activity. PMID:16348370
Stroup, Bridget M.; Sawin, Emily A.; Murali, Sangita G.; Binkley, Neil; Hansen, Karen E.
2017-01-01
Background. Skeletal fragility is a complication of phenylketonuria (PKU). A diet containing amino acids compared with glycomacropeptide reduces bone size and strength in mice. Objective. We tested the hypothesis that amino acid medical foods (AA-MF) provide a high dietary acid load, subsequently increasing urinary excretion of renal net acid, calcium, and magnesium, compared to glycomacropeptide medical foods (GMP-MF). Design. In a crossover design, 8 participants with PKU (16–35 y) provided food records and 24-hr urine samples after consuming a low-Phe diet in combination with AA-MF and GMP-MF for 1–3 wks. We calculated potential renal acid load (PRAL) of AA-MF and GMP-MF and determined bone mineral density (BMD) measurements using dual X-ray absorptiometry. Results. AA-MF provided 1.5–2.5-fold higher PRAL and resulted in 3-fold greater renal net acid excretion compared to GMP-MF (p = 0.002). Dietary protein, calcium, and magnesium intake were similar. GMP-MF significantly reduced urinary excretion of calcium by 40% (p = 0.012) and magnesium by 30% (p = 0.029). Two participants had low BMD-for-age and trabecular bone scores, indicating microarchitectural degradation. Urinary calcium with AA-MF negatively correlated with L1–L4 BMD. Conclusion. Compared to GMP-MF, AA-MF increase dietary acid load, subsequently increasing urinary calcium and magnesium excretion, and likely contributing to skeletal fragility in PKU. The trial was registered at clinicaltrials.gov as NCT01428258. PMID:28546877
Stiber, Jonathan; Hawkins, April; Zhang, Zhu-Shan; Wang, Sunny; Burch, Jarrett; Graham, Victoria; Ward, Cary C.; Seth, Malini; Finch, Elizabeth; Malouf, Nadia; Williams, R. Sanders; Eu, Jerry P.; Rosenberg, Paul
2009-01-01
It is now well established that stromal interaction molecule 1 (STIM1) is the calcium sensor of endoplasmic reticulum (ER) stores required to activate store-operated calcium entry (SOC) channels at the surface of non-excitable cells. Yet little is known about STIM1 in excitable cells such as striated muscle where the complement of calcium regulatory molecules is rather disparate from that of non-excitable cells. Here, we show that STIM1 is expressed in both myotubes and adult skeletal muscle. Myotubes lacking functional STIM1 fail to exhibit SOC and fatigue rapidly. Moreover, mice lacking functional STIM1 die perinatally from a skeletal myopathy. In addition, STIM1 haploinsufficiency confers a contractile defect only under conditions where rapid refilling of stores would be needed. These findings provide novel insight to the role of STIM1 in skeletal muscle and suggest that STIM1 has a universal role as an ER/SR calcium sensor in both excitable and non-excitable cells. PMID:18488020
NASA Astrophysics Data System (ADS)
Sahoo, Sarata Kumar; Kavasi, Norbert; Sorimachi, Atsuyuki; Arae, Hideki; Tokonami, Shinji; Mietelski, Jerzy Wojciech; Łokas, Edyta; Yoshida, Satoshi
2016-04-01
The radioactive fission product 90Sr has a long biological half-life (˜18 y) in the human body. Due to its chemical similarity to calcium it accumulates in bones and irradiates the bone marrow, causing its high radio-toxicity. Assessing 90Sr is therefore extremely important in case of a nuclear disaster. In this work 16 soil samples were collected from the exclusion zone (<30 km) of the earthquake-damaged Fukushima Daiichi nuclear power plant, to measure 90Sr activity concentration using liquid scintillation counting. 137Cs activity concentration was also measured with gamma-spectroscopy in order to investigate correlation with 90Sr. The 90Sr activity concentrations ranged from 3.0 ± 0.3 to 23.3 ± 1.5 Bq kg-1 while the 137Cs from 0.7 ± 0.1 to 110.8 ± 0.3 kBq kg-1. The fact that radioactive contamination originated from the Fukushima nuclear accident was obvious due to the presence of 134Cs. However, 90Sr contamination was not confirmed in all samples although detectable amounts of 90Sr can be expected in Japanese soils, as a background, stemming from global fallout due to the atmospheric nuclear weapon tests. Correlation analysis between 90Sr and 137Cs activity concentrations provides a potentially powerful tool to discriminate background 90Sr level from its Fukushima contribution.
Sahoo, Sarata Kumar; Kavasi, Norbert; Sorimachi, Atsuyuki; Arae, Hideki; Tokonami, Shinji; Mietelski, Jerzy Wojciech; Łokas, Edyta; Yoshida, Satoshi
2016-04-06
The radioactive fission product (90)Sr has a long biological half-life (˜18 y) in the human body. Due to its chemical similarity to calcium it accumulates in bones and irradiates the bone marrow, causing its high radio-toxicity. Assessing (90)Sr is therefore extremely important in case of a nuclear disaster. In this work 16 soil samples were collected from the exclusion zone (<30 km) of the earthquake-damaged Fukushima Daiichi nuclear power plant, to measure (90)Sr activity concentration using liquid scintillation counting. (137)Cs activity concentration was also measured with gamma-spectroscopy in order to investigate correlation with (90)Sr. The (90)Sr activity concentrations ranged from 3.0 ± 0.3 to 23.3 ± 1.5 Bq kg(-1) while the (137)Cs from 0.7 ± 0.1 to 110.8 ± 0.3 kBq kg(-1). The fact that radioactive contamination originated from the Fukushima nuclear accident was obvious due to the presence of (134)Cs. However, (90)Sr contamination was not confirmed in all samples although detectable amounts of (90)Sr can be expected in Japanese soils, as a background, stemming from global fallout due to the atmospheric nuclear weapon tests. Correlation analysis between (90)Sr and (137)Cs activity concentrations provides a potentially powerful tool to discriminate background (90)Sr level from its Fukushima contribution.
Sahoo, Sarata Kumar; Kavasi, Norbert; Sorimachi, Atsuyuki; Arae, Hideki; Tokonami, Shinji; Mietelski, Jerzy Wojciech; Łokas, Edyta; Yoshida, Satoshi
2016-01-01
The radioactive fission product 90Sr has a long biological half-life (˜18 y) in the human body. Due to its chemical similarity to calcium it accumulates in bones and irradiates the bone marrow, causing its high radio-toxicity. Assessing 90Sr is therefore extremely important in case of a nuclear disaster. In this work 16 soil samples were collected from the exclusion zone (<30 km) of the earthquake-damaged Fukushima Daiichi nuclear power plant, to measure 90Sr activity concentration using liquid scintillation counting. 137Cs activity concentration was also measured with gamma-spectroscopy in order to investigate correlation with 90Sr. The 90Sr activity concentrations ranged from 3.0 ± 0.3 to 23.3 ± 1.5 Bq kg−1 while the 137Cs from 0.7 ± 0.1 to 110.8 ± 0.3 kBq kg−1. The fact that radioactive contamination originated from the Fukushima nuclear accident was obvious due to the presence of 134Cs. However, 90Sr contamination was not confirmed in all samples although detectable amounts of 90Sr can be expected in Japanese soils, as a background, stemming from global fallout due to the atmospheric nuclear weapon tests. Correlation analysis between 90Sr and 137Cs activity concentrations provides a potentially powerful tool to discriminate background 90Sr level from its Fukushima contribution. PMID:27048779
Knot, Harm J; Standen, Nicholas B; Nelson, Mark T
1998-01-01
The effects of inhibitors of ryanodine-sensitive calcium release (RyR) channels in the sarcoplasmic reticulum (SR) and Ca2+-dependent potassium (KCa) channels on the membrane potential, intracellular [Ca2+], and diameters of small pressurized (60 mmHg) cerebral arteries (100–200 μm) were studied using digital fluorescence video imaging of arterial diameter and wall [Ca2+], combined with microelectrode measurements of arterial membrane potential. Ryanodine (10 μm), an inhibitor of RyR channels, depolarized by 9 mV, increased intracellular [Ca2+] by 46 nm and constricted pressurized (to 60 mmHg) arteries with myogenic tone by 44 μm (∼22 %). Iberiotoxin (100 nm), a blocker of KCa channels, under the same conditions, depolarized the arteries by 10 mV, increased arterial wall calcium by 51 nm, and constricted by 37 μm (∼19 %). The effects of ryanodine and iberiotoxin were not additive and were blocked by inhibitors of voltage-dependent Ca2+ channels. Caffeine (10 mm), an activator of RyR channels, transiently increased arterial wall [Ca2+] by 136 ± 9 nm in control arteries and by 158 ± 12 nm in the presence of iberiotoxin. Caffeine was relatively ineffective in the presence of ryanodine, increasing [calcium] by 18 ± 5 nm. In the presence of blockers of voltage-dependent Ca2+ channels (nimodipine, diltiazem), ryanodine and inhibitors of the SR calcium ATPase (thapsigargin, cyclopiazonic acid) were without effect on arterial wall [Ca2+] and diameter. These results suggest that local Ca2+ release originating from RyR channels (Ca2+ sparks) in the SR of arterial smooth muscle regulates myogenic tone in cerebral arteries solely through activation of KCa channels, which regulate membrane potential through tonic hyperpolarization, thus limiting Ca2+ entry through L-type voltage-dependent Ca2+ channels. KCa channels therefore act as a negative feedback control element regulating arterial diameter through a reduction in global intracellular free [Ca2+]. PMID:9490841
Zhang, Qian; Huang, Yu; Xu, Lifeng; Cao, Jun-ji; Ho, Wingkei; Lee, Shun Cheng
2016-02-17
Harnessing inexhaustible solar energy for photocatalytic disposal of nitrogen oxides is of great significance nowadays. In this study, Ag-SrTiO3 nanocomposites (Ag-STO) were synthesized via one-pot solvothermal method for the first time. The deposition of Ag nanoparticles incurs a broad plasmonic resonance absorption in the visible light range, resulting in enhanced visible light driven activity on NO removal in comparison with pristine SrTiO3. The Ag loading amount has a significant influence on light absorption properties of Ag-STO, which further affects the photocatalytic efficiency. It was shown that 0.5% Ag loading onto SrTiO3 (in mass ratio) could remove 30% of NO in a single reaction path under visible light irradiation, which is twice higher than that achieved on pristine SrTiO3. Most importantly, the generation of harmful intermediate (NO2) is largely inhibited over SrTiO3 and Ag-STO nanocomposites, which can be ascribed to the basic surface property of strontium sites. As identified by electron spin resonance (ESR) spectra,·O2(-) and ·OH radicals are the major reactive species for NO oxidation. Essentially speaking, the abundance of reactive oxygen radicals produced over Ag-STO nanocomposites are responsible for the improved photocatalytic activity. This work provides a facile and controllable route to fabricate plasmonic Ag-SrTiO3 nanocomposite photocatalyst featuring high visible light activity and selectivity for NO abatement.
Prejac, J; Višnjević, V; Skalny, A A; Grabeklis, A R; Mimica, N; Momčilović, B
2017-07-01
Strontium (Sr) is a trace element that closely resembles calcium metabolism. At the present time there is no available long-term biological indicator tissue for assessing the human Sr nutritional status. Here we have presented a novel concept on how to assess the Sr nutritional status by studying the frequency distribution properties of hair Sr ( Sr H) concentration. In this prospective, observational, cross-sectional, and exploratory epidemiological study, we analyzed Sr H in 311 apparently healthy adult Croatians (123 men, 188 women). Hair strontium was analyzed by the ICP-MS. The natural frequency distribution of Sr H followed the Power law, so that the data were analyzed by fitting the logistic bioassay sigmoid curve (ogive) of median derivatives. Women tend to accumulate three and a half time more Sr H than men (median men 867ngg -1 vs. median women 3120ngg -1 ). The normal (adequate) linear physiological response range of the sigmoid curve was 351-3489ngg -1 for men and 846-8457ngg -1 for women. Values below that linear range are considered to indicate deficient Sr nutritional status, whereas values above that linear range indicate excessive strontium exposure. Hair, as a long-term, and whole blood as a short-term biological indicator tissues were not commensurable entities. Similarly, Sr H accumulation was not age dependent in either men or women. Hair strontium is a reliable long-term biological indicator tissue for assessing the strontium nutritional status. Copyright © 2017 Elsevier GmbH. All rights reserved.
Transformation of Strontium during formation of biogenic calcium carbonate
NASA Astrophysics Data System (ADS)
Ohnuki, T.; Kozai, N.; Sakamoto, F.; Yamashita, M.; Horiieke, T.; Utsunomiya, S.
2016-12-01
Some amounts of radionuclides contaminated water containing 90Sr generated in the Fukushima Daiichi Nuclear Power Plant were leaked to sea water in the port. One of the possible method to eliminate 90Sr is co-precipitated with biogenic carbonates minerals (CCM). Specific bacteria are known to form biogenic CCM in groundwater. In the present study, we have screened specific bacterium to form CCM in saline water, and studied transformation of Sr during biogenic CCM. A marine microbe of strain TK2d, which is screened from Tokyo bay to form CCM in saline solution, was grown in the medium solution contained urea and Sr. The concentratuion of Sr2+ in the solution was monitored by ICP-OES (ICP-OES; 720 Agilent Technologies, Inc., USA) during the formation of biogenic CCM. The precipitates were analyzed by SEM, TEM, and XAFS. When 1.0 mM Sr was dissolved in the medium solution, the concentration of Sr decreased up to 0.02 mM within 10 days, indicating that most of Sr in the solution was eliminated within 10 days. SEM and TEM analyses showed that needle shaped CCM containing Ca and Sr were formed. The CCM was not single crystalline, but poly-crystalline of calcite and aragonite. The elemental mapping showed that Sr was present at the same position of Ca, indicating that Sr was coprecipitated with Ca. The XANES analysis of Sr in the precipitates showed that the XANES spectrum was not the same as that of Sr coprecipitated with an abiotic Ca carbonates. Linear combination fitting of XANES spectra by those of SrCl2 and SrCO3 showed that both Sr2+ and SrCO3 were present in CCM. Longer contact time resulted in higher content of SrCO3, indicating that Sr was incorporated gradually with time into CCM structure. Thus, Sr was changed its chemical species from adsorbed one to the incorporated one in biogenic CCM in saline solution. This work was partially supported by a research grant from the Japan Science and Technology Agency, Japan (research grant No. 260502).
Full-Scale and Bench-Scale Studies on the Removal of Strontium from Water (abstract)
Strontium (Sr) is a natural and commonly occurring alkaline earth metal which has an oxidation state of +2 under normal environmental conditions. Stable strontium is suspended in water and is dissolved after water runs through rocks and soil. It behaves very similar to calcium. G...
NASA Astrophysics Data System (ADS)
Schmitt, Anne-Désirée; Gangloff, Sophie; Labolle, François; Chabaux, François; Stille, Peter
2017-09-01
Calcium (Ca) is the fourth most abundant element in mineral nutrition and plays key physiological and structural roles in plant metabolism. At the soil-water-plant scale, stable Ca isotopes are a powerful tool for the identification of plant-mineral interactions and recycling via vegetation. Radiogenic Sr isotopes are often used as tracers of Ca sources and mixtures of different reservoirs. In this study, stable Ca and radiogenic Sr are combined and analysed in several organs from two beech trees that were collected in June and September in the Strengbach critical zone observatory (CZO) (NE France) and in corresponding soil solutions. At the beech-tree scale, this study confirms the field Ca adsorption (i.e., physico-chemical mechanism and not vital effects) on carboxyl acid groups of pectin in the apoplasm of small roots. The analysis of the xylem sap and corresponding organs shows that although the Strengbach CZO is nutrient-poor, Ca seems to be non-limiting for tree-growth. Different viscosities of xylem sap between the stemwood and branches or leaves can explain δ44/40Ca values in different tree-organs. The bark and phloem 40Ca-enrichments could be due to Ca-oxalate precipitation in the bark tissues and in the phloem. The results from this study regarding the combination of these two isotopic systems show that the isotopic signatures of the roots are dominated by Ca fractionation mechanisms and Sr, and thus Ca, source variations. In contrast, translocation mechanisms are only governed by Ca fractionation processes. This study showed that at the root-soil solution interface, litter degradation was not the main source of Ca and Sr and that the soil solutions are not the complement of uptake by roots for samples from the 2011/2013 period. The opposite is observed for older samples. These observations indicate the decreasing contribution of low radiogenic Sr fluxes, such as recycling, alimenting the soil solutions. Such reduced importance of nutrient uptake and biomass production by the trees could be because the Strengbach trees are ageing and probably weakened by repeated storm events and drought episodes.
Gwynne, Rachel M; Ly, Kenny D K N; Parry, Laura J; Bornstein, Joel C
2017-01-01
Amino acids applied to the mucosa evoke inhibitory reflexes in guinea-pig jejunum, but the receptors involved in sensory transduction are still unclear. One promising candidate is the extracellular calcium sensing receptor (CaSR), which is expressed by mucosal enteroendocrine cells and is preferentially activated by aromatic L-amino acids. We tested this by applying various amino acids to the mucosa and recording the resulting inhibitory junction potentials (IJPs) in nearby circular smooth muscle via intracellular recording. The CaSR is stereospecific and L-Phenylalanine evoked a significantly larger response than D-Phenylalanine when both were applied to the same site. The same pattern was seen with L- and D-Tryptophan, another aromatic amino acid. The CaSR is preferentially activated by aromatic amino acids and responses to L-Leucine and L-Lysine were significantly lower than those to L-Phenylalanine applied to the same site. Responses to L-Phenylalanine were dose-dependently suppressed by blockade of the CaSR with NPS2143, a CaSR antagonist, and mimicked by mucosal application of cinacalcet, a CaSR agonist. Responses to cinacalcet had similar pharmacology to that of responses to L-Phenylalanine, in that each requires both P2 purinoreceptors and 5-HT receptors. L-Glutamate evoked IJPs similar to those produced by L-Phenylalanine and these were depressed by blockade of P2 receptors and 5-HT 3 plus 5-HT 4 receptors, but NPS2143 was ineffective. The AMPA receptor antagonists DNQX (10 μM) and CNQX (10 μM) reduced IJPs evoked by L-Glutamate by 88 and 79% respectively, but neither BAY367260 (mGluR5 antagonist) nor 2APV (NMDA antagonist) affected IJPs evoked by L-Glutamate. We conclude that local inhibitory reflexes evoked by aromatic L-amino acids in guinea pig jejunum involve activation of CaSRs which triggers release of ATP and 5-HT from the mucosa. L-Glutamate also evokes inhibitory reflexes, via a pathway that does not involve CaSRs. It is likely there are multiple receptors acting as sensory transducers for different luminal amino acids.
Dulce, Raul A; Mayo, Vera; Rangel, Erika B; Balkan, Wayne; Hare, Joshua M
2015-01-02
Although nitric oxide (NO) signaling modulates cardiac function and excitation-contraction coupling, opposing results because of inconsistent experimental conditions, particularly with respect to temperature, confound the ability to elucidate NO signaling pathways. Here, we show that temperature significantly modulates NO effects. To test the hypothesis that temperature profoundly affects nitroso-redox equilibrium, thereby affecting sarcoplasmic reticulum (SR) calcium (Ca(2+)) leak. We measured SR Ca(2+) leak in cardiomyocytes from wild-type (WT), NO/redox imbalance (neuronal nitric oxide synthase-deficient mice-1 [NOS1(-/-)]), and hyper S-nitrosoglutathione reductase-deficient (GSNOR(-/-)) mice. In WT cardiomyocytes, SR Ca(2+) leak increased because temperature decreased from 37°C to 23°C, whereas in NOS1(-/-) cells, the leak suddenly increased when the temperature surpassed 30°C. GSNOR(-/-) cardiomyocytes exhibited low leak throughout the temperature range. Exogenously added NO had a biphasic effect on NOS1(-/-) cardiomyocytes; reducing leak at 37°C but increasing it at subphysiological temperatures. Oxypurinol and Tempol diminished the leak in NOS1(-/-) cardiomyocytes. Cooling from 37°C to 23°C increased reactive oxygen species generation in WT but decreased it in NOS1(-/-) cardiomyocytes. Oxypurinol further reduced reactive oxygen species generation. At 23°C in WT cells, leak was decreased by tetrahydrobiopterin, an essential NOS cofactor. Cooling significantly increased SR Ca(2+) content in NOS1(-/-) cells but had no effect in WT or GSNOR(-/-). Ca(2+) leak and temperature are normally inversely proportional, whereas NOS1 deficiency reverses this effect, increasing leak and elevating reactive oxygen species production because temperature increases. Reduced denitrosylation (GSNOR deficiency) eliminates the temperature dependence of leak. Thus, temperature regulates the balance between NO and reactive oxygen species which in turn has a major effect on SR Ca(2+). © 2014 American Heart Association, Inc.
Glass-ceramic route of BSCCO superconductors - Fabrication of amorphous precursor
NASA Astrophysics Data System (ADS)
Nilsson, Andreas; Gruner, Wolfgang; Acker, Jörg; Wetzig, Klaus
2007-09-01
It is well known that many Bi-Sr-Ca-Cu-O compositions are glass-forming and some Bi-based glasses such as Bi 2Sr 2CaCu 2O x and Bi 2Sr 2Ca 2Cu 3O x are converted into high critical temperature superconductors after proper annealing. In order to fabricate superconductors having high- Tc and high critical current density using the glass-ceramic route, it is necessary to clarify the total chemical composition of the quenched glasses prepared in most cases by rapid quenching of melts from around 1200 °C in air. The total oxygen content measured directly reflects a significant oxygen deficit due to the melting process. We have also investigated the cation content in quenched Bi 2Sr 2Ca 2Cu 3O x precursors and found that there are substantial differences from the nominal composition to the quenched materials especially for calcium. Such glasses also show some CaO crystalline reflexes in the XRD patterns.
Hu, Wei; Yan, Yan; Tie, Weiwei; Ding, Zehong; Wu, Chunlai; Ding, Xupo; Wang, Wenquan; Xia, Zhiqiang; Guo, Jianchun; Peng, Ming
2018-04-19
Calcium (Ca 2+ ) plays a crucial role in plant development and responses to environmental stimuli. Currently, calmodulins (CaMs), calmodulin-like proteins (CMLs), and calcineurin B-like proteins (CBLs), such as Ca 2+ sensors, are not well understood in cassava ( Manihot esculenta Crantz), an important tropical crop. In the present study, 8 CaMs, 48 CMLs, and 9 CBLs were genome-wide identified in cassava, which were divided into two, four, and four groups, respectively, based on evolutionary relationship, protein motif, and gene structure analyses. Transcriptomic analysis revealed the expression diversity of cassava CaMs-CMLs-CBLs in distinct tissues and in response to drought stress in different genotypes. Generally, cassava CaMs-CMLs-CBLs showed different expression profiles between cultivated varieties (Arg7 and SC124) and wild ancestor (W14) after drought treatment. In addition, numerous CaMs-CMLs-CBLs were significantly upregulated at 6 h, 12 h, and 48 h after harvest, suggesting their possible role during storage roots (SR) deterioration. Further interaction network and co-expression analyses suggested that a CBL-mediated interaction network was widely involved in SR deterioration. Taken together, this study provides new insights into CaMs-CMLs-CBLs-mediated drought adaption and SR deterioration at the transcription level in cassava, and identifies some candidates for the genetic improvement of cassava.
Williams, Hywel D; Anby, Mette U; Sassene, Philip; Kleberg, Karen; Bakala-N'Goma, Jean-Claude; Calderone, Marilyn; Jannin, Vincent; Igonin, Annabel; Partheil, Anette; Marchaud, Delphine; Jule, Eduardo; Vertommen, Jan; Maio, Mario; Blundell, Ross; Benameur, Hassan; Carrière, Frédéric; Müllertz, Anette; Pouton, Colin W; Porter, Christopher J H
2012-11-05
The LFCS Consortium was established to develop standardized in vitro tests for lipid-based formulations (LBFs) and to examine the utility of these tests to probe the fundamental mechanisms that underlie LBF performance. In this publication, the impact of bile salt (sodium taurodeoxycholate, NaTDC) concentration and drug loading on the ability of a range of representative LBFs to generate and sustain drug solubilization and supersaturation during in vitro digestion testing has been explored and a common driver of the potential for drug precipitation identified. Danazol was used as a model poorly water-soluble drug throughout. In general, increasing NaTDC concentrations increased the digestion of the most lipophilic LBFs and promoted lipid (and drug) trafficking from poorly dispersed oil phases to the aqueous colloidal phase (AP(DIGEST)). High NaTDC concentrations showed some capacity to reduce drug precipitation, although, at NaTDC concentrations ≥3 mM, NaTDC effects on either digestion or drug solubilization were modest. In contrast, increasing drug load had a marked impact on drug solubilization. For LBFs containing long-chain lipids, drug precipitation was limited even at drug loads approaching saturation in the formulation and concentrations of solubilized drug in AP(DIGEST) increased with increased drug load. For LBFs containing medium-chain lipids, however, significant precipitation was evident, especially at higher drug loads. Across all formulations a remarkably consistent trend emerged such that the likelihood of precipitation was almost entirely dependent on the maximum supersaturation ratio (SR(M)) attained on initiation of digestion. SR(M) defines the supersaturation "pressure" in the system and is calculated from the maximum attainable concentration in the AP(DIGEST) (assuming zero precipitation), divided by the solubility of the drug in the colloidal phases formed post digestion. For LBFs where phase separation of oil phases did not occur, a threshold value for SR(M) was evident, regardless of formulation composition and drug solubilization reduced markedly above SR(M) > 2.5. The threshold SR(M) may prove to be an effective tool in discriminating between LBFs based on performance.
NASA Astrophysics Data System (ADS)
Naik, Parvaiz Ahmad; Pardasani, Kamal Raj
2013-11-01
Oocyte is a female gametocyte or germ cell involved in reproduction. Calcium ions (Ca2+) impact nearly all aspects of cellular life as they play an important role in a variety of cellular functions. Calcium ions contributes to egg activation upon fertilization. Since it is the internal stores which provide most of the calcium signal, much attention has been focused on the intracellular channels. There are mainly two types of calcium channels which release calcium from the internal stores to the cytoplasm in many cell types. These channels are IP3-Receptor and Ryanodine Receptor (RyR). Further it is essential to maintain low cytosolic calcium concentration, the cell engages the Serco/Endoplasmic reticulum Ca2+ ATPases (SERCA) present on the ER or SR membrane for the re-uptake of cytosolic calcium at the expense of ATP hydrolysis. In view of above an attempt has been made to study the effect of the Ryanodine receptor (RyR) and the SERCA pump on the calcium distribution in oocytes. The main aim of this paper is to study the calcium concentration in absence and presence of these parameters. The FEM is used to solve the proposed Mathematical model under appreciate initial and boundary conditions. The program has been developed in MATLAB 7.10 for the entire problem to get numerical results.
CALCIUM BINDING TO INTESTINAL MEMBRANES
Oschman, James L.; Wall, Betty J.
1972-01-01
Flame photometry reveals that glutaraldehyde and buffer solutions in routine use for electron microscopy contain varying amounts of calcium. The presence of electron-opaque deposits adjacent to membranes in a variety of tissues can be correlated with the presence of calcium in the fixative. In insect intestine (midgut), deposits occur adjacent to apical and lateral plasma membranes. The deposits are particularly evident in tissues fixed in glutaraldehyde without postosmication. They are also observed in osmicated tissue if calcium is added to wash and osmium solutions. Deposits are absent when calcium-free fixatives are used, but are present when traces of CaCl2 (as low as 5 x 10-5 M) are added. The deposits occur at regular intervals along junctional membranes, providing images strikingly similar to those obtained by other workers who have used pyroantimonate in an effort to localize sodium. Other divalent cations (Mg++, Sr++, Ba++, Mn++, Fe++) appear to substitute for calcium, while sodium, potassium, lanthanum, and mercury do not. After postfixing with osmium with calcium added, the deposits can be resolved as patches along the inner leaflet of apical and lateral plasma membranes. The dense regions may thus localize membrane constituents that bind calcium. The results are discussed in relation to the role of calcium in control of cell-to-cell communication, intestinal calcium uptake, and the pyroantimonate technique for ion localization. PMID:4569411
Structure and properties of strontium-doped phosphate-based glasses
Abou Neel, Ensanya A.; Chrzanowski, Wojciech; Pickup, David M.; O'Dell, Luke A.; Mordan, Nicola J.; Newport, Robert J.; Smith, Mark E.; Knowles, Jonathan C.
2008-01-01
Owing to similarity in both ionic size and polarity, strontium (Sr2+) is known to behave in a comparable way to calcium (Ca2+), and its role in bone metabolism has been well documented as both anti-resorptive and bone forming. In this study, novel quaternary strontium-doped phosphate-based glasses, containing 1, 3 and 5 mol% SrO, were synthesized and characterized. 31P magic angle spinning (MAS) nuclear magnetic resonance results showed that, as the Sr2+ content is increased in the glasses, there is a slight increase in disproportionation of Q2 phosphorus environments into Q1 and Q3 environments. Moreover, shortening and strengthening of the phosphorus to bridging oxygen distance occurred as obtained from FTIR. The general broadening of the spectral features with Sr2+ content is most probably due to the increased variation of the phosphate–cation bonding interactions caused by the introduction of the third cation. This increased disorder may be the cause of the increased degradation of the Sr-containing glasses relative to the Sr-free glass. As confirmed from elemental analysis, all Sr-containing glasses showed higher Na2O than expected and this also could be accounted for by the higher degradation of these glasses compared with Sr-free glasses. Measurements of surface free energy (SFE) showed that incorporation of strontium had no effect on SFE, and samples had relatively higher fractional polarity, which is not expected to promote high cell activity. From viability studies, however, the incorporation of Sr2+ showed better cellular response than Sr2+-free glasses, but still lower than the positive control. This unfavourable cellular response could be due to the high degradation nature of these glasses and not due to the presence of Sr2+. PMID:18826914
Wang, Bing; Wen, Aiping; Feng, Chengmin; Niu, Lijing; Xiao, Xin; Luo, Le; Shen, Chengyi; Zhu, Jiang; Lei, Jun; Zhang, Xiaoming
2018-06-01
In present study, the apoptosis induction and proliferation suppression effects of l-phenylalanine (l-Phe) on fibroblasts were confirmed. The action sites of l-Phe on fibroblasts suppression were deduced to be calcium sensitive receptor (CaSR) which could cause the release of endoplasmic reticulum (ER) Ca 2+ stores; disruption of intracellular Ca 2+ homeostasis triggers cell apoptosis via the ER or mitochondrial pathways. The down-regulation of CaSR were observed after the application of l-Phe, and the results those l-Phe triggered the increasing of intracellular Ca 2+ concentration and calcineurin expression, and then the apoptosis and increasing G1 fraction of fibroblasts have verified our deduction. Hence, l-Phe could be seen as a kind of anti-fibrotic drugs for the crucial participation of fibroblast in the occurrence of fibrosis. And then, poly(p-dioxanone-co-l-phenylalanine) (PDPA) which could prolong the in-vivo anti-fibrotic effect of l-Phe for the sustained release of l-Phe during its degradation could be treated as anti-fibrotic polymer prodrugs. Based on the above, the in vivo anti-fibrotic function of PDPA was evaluated in rabbit ear scarring, rat peritoneum lipopolysaccharide, and rat sidewall defect/cecum abrasion models. PDPA reduced skin scarring and suppressed peritoneal fibrosis and post operation adhesion as well as secretion of transforming growth factor-β1 in injured tissue. These results indicate that PDPA is an effective agent for preventing fibrosis following tissue injury. We have previously demonstrated that poly(p-dioxanone-co-l-phenylalanine) (PDPA) could induce apoptosis to fibroblast and deduced that the inhibitory effect comes from l-phenylalanine. In present study, the inhibition mechanism of l-phenylalanine on fibroblast proliferation was demonstrated. The calcium sensitive receptor (CaSR) was found to be the action site. The CaSR was downregulated after the application of l-phenylalanine, and then the ER Ca 2+ stores were released. The released Ca 2+ can simultaneously activate Ca 2+ /calcineurin and then trigger apoptosis and G1 arrest of fibroblast. Hence, l-phenylalanine could be seen as anti-fibrosis drug and PDPA which conjugate l-phenylalanine by hydrolytic covalent bonds could be seen as l-phenylalanine polymer prodrug. Based above, the in vivo anti-fibrotic function of PDPA were verified in three different animal models. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Hamon, B; Heinemann, U
1986-01-01
Decreases in extracellular free calcium ([Ca2+]o) and concomitant field potentials were recorded from the dendritic and cell body layers of the CA1 field in transverse hippocampal slices. They were elicited by tetanic stimulation of Schaffer collaterals and commissural fibers or by iontophoretic application of the excitatory amino acids N-methyl-D-aspartate (NMDA) and quisqualate (Quis). Under control conditions, decreases in [Ca2+]o were found to be maximal in stratum pyramidale (SP). In stratum radiatum (SR), 100 micron away from SP, decreases in [Ca2+]o were half the size of those observed in SP. Bicuculline methiodide, bath-applied at concentrations of 10-100 microM, enhanced the reductions in [Ca2+]o, increased the field potentials in all layers and also induced "spontaneous" epileptiform activity. In the presence of bicuculline, the decreases in [Ca2+]o were particularly enhanced in SR and were often greater than those recorded in SP. This was the case for changes in [Ca2+]o induced either by repetitive electrical stimulation or by application of NMDA and Quis. When synaptic transmission was blocked by perfusing the slices with a low Ca2+ medium, all NMDA and Quis-induced changes in [Ca2+]o were predictably reduced but there was a relative enhancement of changes in [Ca2+]o in SR with respect to those in SP. We propose that, under normal conditions, an inhibitory control mediated by GABA limits the reductions of [Ca2+]o particularly in SR. In support of this proposal, we found that bath-applied GABA had a depressant action on changes in [Ca2+]o.
Vasopressin regulates renal calcium excretion in humans
Hanouna, Guillaume; Haymann, Jean-Philippe; Baud, Laurent; Letavernier, Emmanuel
2015-01-01
Antidiuretic hormone or arginine vasopressin (AVP) increases water reabsorption in the collecting ducts of the kidney. Three decades ago, experimental models have shown that AVP may increase calcium reabsorption in rat kidney. The objective of this study was to assess whether AVP modulates renal calcium excretion in humans. We analyzed calcium, potassium, and sodium fractional excretion in eight patients affected by insipidus diabetes (nephrogenic or central) under acute vasopressin receptor agonist action and in 10 patients undergoing oral water load test affected or not by inappropriate antidiuretic hormone secretion (SIADH). Synthetic V2 receptor agonist (dDAVP) reduced significantly calcium fractional excretion from 1.71% to 0.58% (P < 0.05) in patients with central diabetes insipidus. In patients with nephrogenic diabetes insipidus (resistant to AVP), calcium fractional excretion did not change significantly after injection (0.48–0.68%, P = NS). In normal subjects undergoing oral water load test, calcium fractional excretion increased significantly from 1.02% to 2.54% (P < 0.05). Patients affected by SIADH had a high calcium fractional excretion at baseline that remained stable during test from 3.30% to 3.33% (P = NS), possibly resulting from a reduced calcium absorption in renal proximal tubule. In both groups, there was a significant correlation between urine output and calcium renal excretion. In humans, dDAVP decreases calcium fractional excretion in the short term. Conversely, water intake, which lowers AVP concentration, increases calcium fractional excretion. The correlation between urine output and calcium excretion suggests that AVP-related antidiuresis increases calcium reabsorption in collecting ducts. PMID:26620256
NASA Astrophysics Data System (ADS)
Paytan, A.; Eisenhauer, A.; Wallmann, K. J. G.; Griffith, E. M.; Ridgwell, A.
2017-12-01
The radiogenic Sr-isotopic signature (87Sr/86Sr) of seawater fluctuates primarily in response to changes in the inputs of Sr from weathering and hydrothermal activity, which have distinct 87Sr/86Sr values. Changes in the isotopic ratio of the weathered terrain also contribute to observed changes in 87Sr/86Sr. The stable Sr-isotope ratios in seawater (mass dependent isotopic fractionation; δ88/86Sr) fluctuate primarily in response to the rate of calcium carbonate (CaCO3) accumulation at the seafloor. Together the radiogenic and stable Sr can constrain the coupling between weathering and sedimentation and shed light on the relation between weathering, CaCO3 deposition, the global carbon (C) cycle and climate. Reconstruction of the coupled stable and radiogenic Sr seawater curves over the past 35 Ma of Earth history indicates that the location and rate of CaCO3 burial in the ocean fluctuated considerably over the past 35 Ma. Between 35 to 18 Ma a reduction in neritic CaCO3 burial and increased burial in pelagic settings is observed. The trend was reversed between 20 and 3 Ma and finally over the last 3 million years a rapid change from neritic to pelagic burial is seen. The lack of continues increase of pelagic CaCO3 burial rates suggests that silicate weathering rates have not increased monotonically over the past 35 Ma implying strong feedbacks operating in the climate system - lower atmospheric pCO2 and cooling trends (which control chemical weathering as seen from carbonate deposition in the ocean) countered the effects of uplift (which controls physical weathering) - modulating weathering rates and preventing a runaway ice-house. In addition the data suggests considerable fluctuations in seawater Sr concentrations over time. These data demonstrate how using multiple isotope proxies can help constrain interpretations of the geological record.
Watmough, Shaun
2018-06-01
There is increasing concern over the negative ecological impacts caused by falling calcium (Ca) concentrations in lakes, particularly in central Ontario, Canada. Forecasting regional changes in lake Ca concentrations relies on accurate estimates of mineral weathering rates that are not widely available. In this study, bulk atmospheric deposition, surface water and soil chemistry along with 87 Sr/ 86 Sr isotope measurements were used to provide regional insight into weathering controls on Ca concentrations in lakes. Regionally, Ca concentrations in 90% of 129 lakes sampled in central Ontario were <0.1 mmol L -1 and the Ca/Sr ratio in lakes increased and the K/Sr ratio decreased with increasing Sr concentration, which is indicative of greater Ca sources from calcite or apatite in the higher Ca lakes. Significant relationships between 87 Sr/ 86 Sr ratios and Ca/Sr rations in dilute acid (0.1 M HCl) soil extracts are also indicative of the presence of trace amounts of calcite or apatite in surficial soils. Within the low (<0.7 mmol L -1 ) Ca lakes, defined in this study that are considered most at risk from falling Ca concentrations, 87 Sr/ 86 Sr ratios fell within the range observed in weak acid soil extracts and were also significantly related to Ca/Na and K/Sr ratios in surface waters. There were large inconsistencies however, between Ca/Na ratios and Ca/Sr in surface waters and soil acid extracts that suggest differences in 87 Sr/ 86 Sr ratios in surface waters of the low Ca lakes do not simply reflect differences in Ca derived from non-silicate minerals in surficial soils and that that Ca sources from deeper soil or bedrock are also important contributors to surface water Ca in these low Ca lakes. Copyright © 2018 Elsevier B.V. All rights reserved.
Babo, Pedro S; Carvalho, Pedro P; Santo, Vítor E; Faria, Susana; Gomes, Manuela E; Reis, Rui L
2016-11-01
Injectable calcium phosphate cements have been used as a valid alternative to autologous bone grafts for bone augmentation with the additional advantage of enabling minimally invasive implantation procedures and for perfectly fitting the tissue defect. Nevertheless, they have low biodegradability and lack adequate biochemical signaling to promote bone healing and remodeling. In previous in vitro studies, we observed that the incorporation of platelet lysate directly into the cement paste or loaded in hyaluronic acid microspheres allowed to modulate the cement degradation and the in vitro expression of osteogenic markers in seeded human adipose derived stem cells. The present study aimed at investigating the possible effect of this system in new bone formation when implanted in calvarial bilateral defects in rats. Different formulations were assessed, namely plain calcium phosphate cements, calcium phosphate cements loaded with human platelet lysate, hybrid injectable formulations composed of the calcium phosphate cement incorporating hyaluronin acid non-loaded microparticles (20% hyaluronin acid) or with particles loaded with platelet lysate. The degradability and new bone regrowth were evaluated in terms of mineral volume in the defect, measured by micro-computed tomography and histomorphometric analysis upon 4, 8 and 12 weeks of implantation. We observed that the incorporation of hyaluronin acid microspheres induced an overly rapid cement degradation, impairing the osteoconductive properties of the cement composites. Moreover, the incorporation of platelet lysate induced higher bone healing than the materials without platelet lysate, up to four weeks after surgery. Nevertheless, this effect was not found to be significant when compared to the one observed in the sham-treated group. © The Author(s) 2016.
Preparation and characterization of strontium-fluorapatite nanopowders by sol-gel method
NASA Astrophysics Data System (ADS)
Kamaei, Maryam; Fathi, Mohammad Hossein
2018-01-01
Biomaterials based on calcium orthophosphate are especially attractive for use in medicine, for bone and teeth implants due to their biological properties, such as biocompatibility and bioactivity. Among them, hydroxyapatite (HAP; Ca10(PO4)6(OH)2) is used particularly because of its similarities to the inorganic component of bone. Hydroxyapatite has been widely used for biomedical applications. Despite desirable properties such as bioactivity, biocompatibility, solubility and adsorption, synthetic HA is limited in application due to poor thermostability and poor mechanical properties. Properties of HA can be tailored over a wide range by incorporating different ions into HA lattice. Use of the sol-gel technique is technically simple, cost effective and beneficial for fabrication biomaterials. This research aimed to prepare and characterize Sr-doped FA nanopowders (Sr-FA). Sr-FA with different Sr contents was prepared by sol-gel method. The designated degree of substitution of Ca by Sr in the mixture was determined by the x value in the general formula of (Ca10-x Srx(PO4)6F2), where x=0,0.5,1. X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) techniques were utilized to characterize the obtained nano powders. Results showed that Sr ions entered into the fluorapatite lattice and occupied Ca sites. The incorporation of Sr ions into the fluorapatite resulted in the increase of the lattice parameters.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chatelain, P.; Beaufort, P.; Meysmans, L.
1991-01-01
SR 33557 represents a new class of compounds (indolizine sulfone) that inhibit L-type Ca2+ channels. ({sup 3}H)SR 33557 has been shown to bind with high affinity (Kd congruent to 0.36 nM, calculated from saturation isotherms and association/dissociation kinetics) to a single class of sites in a purified preparation of rat cardiac sarcolemmal membranes. The binding was found to be saturable and reversible. The maximal binding capacity was in approximately 1:1 stoichiometry with that of other Ca2+ channel antagonists. Various divalent cations (Mg2+, Mn2+, Ca2+, Ba2+, and Cd2+) were shown to inhibit specific ({sup 3}H)SR 33557 binding, with Cd2+ being themore » most potent. Among several receptor or channel ligands (including omega-conotoxin and Na+ and K+ channel modulators), only the L-type Ca2+ channel antagonists were found to displace ({sup 3}H)SR 33557. However, dihydropyridines, phenylalkylamines, benzothiazepines, and diphenylbutylpiperidines were found to inhibit ({sup 3}H)SR 33557 in a noncompetitive manner as demonstrated by displacement and saturation experiments in addition to dissociation kinetics. From these results, we suggest that SR 33557 binds with high affinity to a unique site on the L-type Ca2+ channel found in rat cardiac sarcolemmal membranes.« less
Synthesis and thermal properties of strontium and calcium peroxides
NASA Technical Reports Server (NTRS)
Philipp, Warren H.; Kraft, Patricia A.
1989-01-01
A practical synthesis and a discussion of some chemical properties of pure strontium peroxide and calcium peroxide are presented. The general synthesis of these peroxides involves precipitation of their octahydrates by addition of H2O2 to aqueous ammoniacal Sr(NO3)2 or CaCl2. The octahydrates are converted to the anhydrous peroxides by various dehydration techniques. A new x-ray diffraction powder pattern for CaO2 x 8H2O is given from which lattice parameters a=6.212830 and c=11.0090 were calculated on the basis of the tetragonal crystal system.
Lee, Jung-Hwan; Mandakhbayar, Nandin; El-Fiqi, Ahmed; Kim, Hae-Won
2017-09-15
Inducing differentiation and maturation of resident multipotent stem cells (MSCs) is an important strategy to regenerate hard tissues in mal-calcification conditions. Here we explore a co-delivery approach of therapeutic molecules comprised of ion and drug through a mesoporous bioglass nanoparticle (MBN) for this purpose. Recently, MBN has offered unique potential as a nanocarrier for hard tissues, in terms of high mesoporosity, bone bioactivity (and possibly degradability), tunable delivery of biomolecules, and ionic modification. Herein Sr ion is structurally doped to MBN while drug Phenamil is externally loaded as a small molecule activator of BMP signaling, for the stimulation of osteo/odontogenesis and mineralization of human MSCs derived from dental pulp. The Sr-doped MBN (85Si:10Ca:5Sr) sol-gel processed presents a high mesoporosity with a pore size of ∼6nm. In particular, Sr ion is released slowly at a daily rate of ∼3ppm per mg nanoparticles for up to 7days, a level therapeutically effective for cellular stimulation. The Sr-MBN is internalized to most MSCs via an ATP dependent macropinocytosis within hours, increasing the intracellular levels of Sr, Ca and Si ions. Phenamil is loaded maximally ∼30% into Sr-MBN and then released slowly for up to 7days. The co-delivered molecules (Sr ion and Phenamil drug) have profound effects on the differentiation and maturation of cells, i.e., significantly enhancing expression of osteo/odontogenic genes, alkaline phosphatase activity, and mineralization of cells. Of note, the stimulation is a result of a synergism of Sr and Phenamil, through a Trb3-dependent BMP signaling pathway. This biological synergism is further evidenced in vivo in a mal-calcification condition involving an extracted tooth implantation in dorsal subcutaneous tissues of rats. Six weeks post operation evidences the osseous-dentinal hard tissue formation, which is significantly stimulated by the Sr/Phenamil delivery, based on histomorphometric and micro-computed tomographic analyses. The bioactive nanoparticles releasing both Sr ion and Phenamil drug are considered to be a promising therapeutic nanocarrier platform for hard tissue regeneration. Furthermore, this novel ion/drug co-delivery concept through nanoparticles can be extensively used for other tissues that require different therapeutic treatment. This study reports a novel design concept in inorganic nanoparticle delivery system for hard tissues - the co-delivery of therapeutic molecules comprised of ion (Sr) and drug (Phenamil) through a unique nanoparticle of mesoporous bioactive glass (MBN). The physico-chemical and biological properties of MBN enabled an effective loading of both therapeutic molecules and a subsequently sustained/controlled release. The co-delivered Sr and Phenamil demonstrated significant stimulation of adult stem cell differentiation in vitro and osseous/dentinal regeneration in vivo, through BMP signaling pathways. We consider the current combination of Sr ion with Phenamil is suited for the osteo/odontogenesis of stem cells for hard tissue regeneration, and further, this ion/drug co-delivery concept can extend the applications to other areas that require specific cellular and tissue functions. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Xie, Xiaolong; Zhu, Tiebing; Chen, Lulu; Ding, Shuang; Chu, Han; Wang, Jing; Yao, Honghong; Chao, Jie
2018-01-29
Monocyte chemotactic protein-1-induced protein 1 (MCPIP1) plays a important role in ischemia/reperfusion (I/R) injury. Autophagy is involved in activating endothelial cells in response to I/R. However, researchers have not clearly determined whether MCPIP1 mediates I/R injury in endothelial cells via autophagy, and its downstream mechanism remains unclear. Western blotting analyses and immunocytochemistry were applied to detect protein levels were detected in HUVECs. An in vitro scratch assay was used to detect cell migration. Cells were transfected with siRNAs to knockdown MCPIP1 and high mobility group box 1 (HMGB1) expression. The pharmacological activator of autophagy rapamycin and the specific calcium-sensing receptor (CaSR) inhibitor NPS-2143 were used to confirm the roles of autophagy and CaSR in I/R injury. I/R induced HMGB1 and CaSR expression, which subsequently upreguated the migration and apoptosis of HUVECs and coincided with the increase of autophagy. HMGB1 was involved in cell migration, whereas CaSR specifically participated in I/R-induced HUVEC apoptosis. Based on these findings, I/R-induced MCPIP1 expression regulates the migration and apoptosis of HUVECs via HMGB1 and CaSR, respectively, suggesting a new therapeutic targetof I/R injury.
Hori, Masako; Sano, Yuji; Ishida, Akizumi; Takahata, Naoto; Shirai, Kotaro; Watanabe, Tsuyoshi
2015-01-01
Insolation is an important component of meteorological data because solar energy is the primary and direct driver of weather and climate. Previous analyses of cultivated giant clam shells revealed diurnal variation in the Sr/Ca ratio, which might reflect the influence of the daily light cycle. We applied proxy method to sample from prehistoric era, a fossil giant clam shell collected at Ishigaki Island in southern Japan. The specimen was alive during the middle Holocene and thus exposed to the warmest climate after the last glacial period. This bivalve species is known to form a growth line each day, as confirmed by the analysis of the Sr enrichment bands using EPMA and facilitated age-model. We analyzed the Sr/Ca, Mg/Ca and Ba/Ca ratios along the growth axis, measuring a 2-μm spot size at 2-μm interval using NanoSIMS. The Sr/Ca ratios in the winter layers are characterized by a striking diurnal cycle consisting of narrow growth lines with high Sr/Ca ratios and broad growth bands with low Sr/Ca ratios. These variations, which are consistent with those of the cultivated clam shell, indicate the potential for the reconstruction of the variation in solar insolation during the middle Holocene at a multi-hourly resolution. PMID:25736488
Physicochemical Properties and Cellular Responses of Strontium-Doped Gypsum Biomaterials
Pouria, Amir; Bandegani, Hadis; Pourbaghi-Masouleh, Milad; Hesaraki, Saeed; Alizadeh, Masoud
2012-01-01
This paper describes some physical, structural, and biological properties of gypsum bioceramics doped with various amounts of strontium ions (0.19–2.23 wt%) and compares these properties with those of a pure gypsum as control. Strontium-doped gypsum (gypsum:Sr) was obtained by mixing calcium sulfate hemihydrate powder and solutions of strontium nitrate followed by washing the specimens with distilled water to remove residual salts. Gypsum was the only phase found in the composition of both pure and gypsum:Sr, meanwhile a shift into lower diffraction angles was observed in the X-ray diffraction patterns of doped specimens. Microstructure of all gypsum specimens consisted of many rod-like small crystals entangled to each other with more elongation and higher thickness in the case of gypsum:Sr. The Sr-doped sample exhibited higher compressive strength and lower solubility than pure gypsum. A continuous release of strontium ions was observed from the gypsum:Sr during soaking it in simulated body fluid for 14 days. Compared to pure gypsum, the osteoblasts cultured on strontium-doped samples showed better proliferation rate and higher alkaline phosphatase activity, depending on Sr concentration. These observations can predict better in vivo behavior of strontium-doped gypsum compared to pure one. PMID:22719270
Hodkin, David J; Stewart, Douglas I; Graham, James T; Burke, Ian T
2016-08-15
This study investigated the simultaneous removal of Sr(2+) and (14)CO3(2-) from pH>12 Ca(OH)2 solution by the precipitation of calcium carbonate. Initial Ca(2+):CO3(2-) ratios ranged from 10:1 to 10:100 (mM:mM). Maximum removal of (14)C and Sr(2+) both occurred in the system containing 10mM Ca(2+) and 1mM CO3(2-) (99.7% and 98.6% removal respectively). A kinetic model is provided that describes (14)C and Sr removal in terms of mineral dissolution and precipitation reactions. The removal of (14)C was achieved during the depletion of the initial TIC in solution, and was subsequently significantly affected by recrystallization of the calcite precipitate from an elongate to isotropic morphology. This liberated >46% of the (14)C back to solution. Sr(2+) removal occurred as Ca(2+) became depleted in solution and was not significantly affected by the recrystallization process. The proposed reaction could form the basis for low cost remediation scheme for (90)Sr and (14)C in radioactively contaminated waters (<$0.25 reagent cost per m(3) treated). Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.
Frasnelli, Matteo; Cristofaro, Francesco; Sglavo, Vincenzo M; Dirè, Sandra; Callone, Emanuela; Ceccato, Riccardo; Bruni, Giovanna; Cornaglia, Antonia Icaro; Visai, Livia
2017-02-01
The production of stable suspensions of strontium-substituted hydroxyapatite (Sr-HA) nanopowders, as Sr ions vector for bone tissue regeneration, was carried out in the present work. Sr-HA nanopowders were synthesized via aqueous precipitation methods using Sr 2+ amount from 0 to 100mol% and were characterized by several complementary techniques such as solid-state Nuclear Magnetic Resonance spectroscopy, X-ray diffraction, Infrared spectroscopy, N 2 physisorption and Transmission Electron Microscopy. The substitution of Ca 2+ with Sr 2+ in HA is always isomorphic with gradual evolution between the two limit compositions (containing 100% Ca and 100% Sr), this pointing out the homogeneity of the synthesized nanopowders and the complete solubility of strontium in HA lattice. Strontium addition is responsible for an increasing c/a ratio in the triclinic unit cell. A significant variation of the nanopowders shape and dimension is also observed, a preferential growth along the c-axis direction being evident at higher strontium loads. Modifications in the local chemical environment of phosphate and hydroxyl groups in the apatite lattice are also observed. Stable suspensions were produced by dispersing the synthesized nanopowders in bovine serum albumin. Characterization by Dynamic Light Scattering and ζ-potential determination allowed to show that Ca 2+ →Sr 2+ substitution influences the hydrodynamic diameter, which is always twice the particles size determined by TEM, the nanoparticles being always negatively charged as a result from the albumin rearrangement upon the interaction with nanoparticles surface. The biocompatibility of the suspensions was studied in terms of cell viability, apoptosis, proliferation and morphology, using osteosarcoma cell line SAOS-2. The data pointed out an increased cell proliferation for HA nanoparticles containing larger Sr 2+ load, the cells morphology remaining essentially unaffected. Copyright © 2016 Elsevier B.V. All rights reserved.
Iammarino, Marco; dell’Oro, Daniela; Bortone, Nicola
2015-01-01
90Sr is considered as a dangerous contaminant of agri-food supply chains due to its chemical affinity with Calcium, which makes its absorption in bones easy. 90Sr accumulation in raw materials and then in final products is particularly significant in relationship to its ability to transfer into animal source products. The radionuclides transfer (137Cs and 90Sr) from environment to forages and then to products of animal origin (milk, cow and pork meats) was studied and evaluated in different studies, which were carried out in contaminated areas, from Chernobyl disaster until today. In the present work, the development and validation of a radiochemical method for the detection of 90Sr in different types of animal feed, and the application of this technique for routinely control activities, are presented. Liquid scintillation counting was the employed analytical technique, since it is able to determine very low activity concentrations of 90Sr (<0.01 Bq Kg–1). All samples analysed showed a 90Sr contamination much higher than method detection limit (0.008 Bq kg–1). In particular, the highest mean activity concentration was registered in hay samples (2.93 Bq kg–1), followed by silage samples (2.07 Bq kg–1) and animal feeds (0.77 Bq kg–1). In fact, all samples were characterized by 90Sr activity concentrations much lower than reference limits. This notwithstanding, the necessity to monitor these levels was confirmed, especially considering that 90Sr is a possible carcinogen for human. PMID:27800378
Conceptual design of high speed supersonic aircraft: A brief review on SR-71 (Blackbird) aircraft
NASA Astrophysics Data System (ADS)
Xue, Hui; Khawaja, H.; Moatamedi, M.
2014-12-01
The paper presents the conceptual design of high-speed supersonic aircraft. The study focuses on SR-71 (Blackbird) aircraft. The input to the conceptual design is a mission profile. Mission profile is a flight profile of the aircraft defined by the customer. This paper gives the SR-71 aircraft mission profile specified by US air force. Mission profile helps in defining the attributes the aircraft such as wing profile, vertical tail configuration, propulsion system, etc. Wing profile and vertical tail configurations have direct impact on lift, drag, stability, performance and maneuverability of the aircraft. A propulsion system directly influences the performance of the aircraft. By combining the wing profile and the propulsion system, two important parameters, known as wing loading and thrust to weight ratio can be calculated. In this work, conceptual design procedure given by D. P. Raymer (AIAA Educational Series) is applied to calculate wing loading and thrust to weight ratio. The calculated values are compared against the actual values of the SR-71 aircraft. Results indicates that the values are in agreement with the trend of developments in aviation.
Adaptive Wiener filter super-resolution of color filter array images.
Karch, Barry K; Hardie, Russell C
2013-08-12
Digital color cameras using a single detector array with a Bayer color filter array (CFA) require interpolation or demosaicing to estimate missing color information and provide full-color images. However, demosaicing does not specifically address fundamental undersampling and aliasing inherent in typical camera designs. Fast non-uniform interpolation based super-resolution (SR) is an attractive approach to reduce or eliminate aliasing and its relatively low computational load is amenable to real-time applications. The adaptive Wiener filter (AWF) SR algorithm was initially developed for grayscale imaging and has not previously been applied to color SR demosaicing. Here, we develop a novel fast SR method for CFA cameras that is based on the AWF SR algorithm and uses global channel-to-channel statistical models. We apply this new method as a stand-alone algorithm and also as an initialization image for a variational SR algorithm. This paper presents the theoretical development of the color AWF SR approach and applies it in performance comparisons to other SR techniques for both simulated and real data.
Domeier, Timothy L; Maxwell, Joshua T; Blatter, Lothar A
2012-01-01
β-Adrenergic signalling induces positive inotropic effects on the heart that associate with pro-arrhythmic spontaneous Ca2+ waves. A threshold level of sarcoplasmic reticulum (SR) Ca2+ ([Ca2+]SR) is necessary to trigger Ca2+ waves, and whether the increased incidence of Ca2+ waves during β-adrenergic stimulation is due to an alteration in this threshold remains controversial. Using the low-affinity Ca2+ indicator fluo-5N entrapped within the SR of rabbit ventricular myocytes, we addressed this controversy by directly monitoring [Ca2+]SR and Ca2+ waves during β-adrenergic stimulation. Electrical pacing in elevated extracellular Ca2+ ([Ca2+]o= 7 mm) was used to increase [Ca2+]SR to the threshold where Ca2+ waves were consistently observed. The β-adrenergic agonist isoproterenol (ISO; 1 μm) increased [Ca2+]SR well above the control threshold and consistently triggered Ca2+ waves. However, when [Ca2+]SR was subsequently lowered in the presence of ISO (by lowering [Ca2+]o to 1 mm and partially inhibiting sarcoplasmic/endoplasmic reticulum calcium ATPase with cyclopiazonic acid or thapsigargin), Ca2+ waves ceased to occur at a [Ca2+]SR that was higher than the control threshold. Furthermore, for a set [Ca2+]SR level the refractoriness of wave occurrence (Ca2+ wave latency) was prolonged during β-adrenergic stimulation, and was highly dependent on the extent that [Ca]SR exceeded the wave threshold. These data show that acute β-adrenergic stimulation increases the [Ca2+]SR threshold for Ca2+ waves, and therefore the primary cause of Ca2+ waves is the robust increase in [Ca2+]SR above this higher threshold level. Elevation of the [Ca2+]SR wave threshold and prolongation of wave latency represent potentially protective mechanisms against pro-arrhythmogenic Ca2+ release during β-adrenergic stimulation. PMID:22988136
Low-Sulfate Seawater Injection into Oil Reservoir to Avoid Scaling Problem
NASA Astrophysics Data System (ADS)
Merdhah, Amer Badr Bin; Mohd Yassin, Abu Azam
This study presents the results of laboratory experiments carried out to investigate the formation of calcium, strontium and barium sulfates from mixing Angsi seawater or low sulfate seawater with the following sulfate contents (75, 50, 25, 5 and 1%) and formation water contain high concentration of calcium, strontium and barium ions at various temperatures (40-90°C) and atmospheric pressure. The knowledge of solubility of common oil field scale formation and how their solubilities are affected by changes in salinity and temperatures is also studied. Results show a large of precipitation occurred in all jars containing seawater while the amount of precipitation decreased when the low sulfate seawater was used. At higher temperatures the mass of precipitation of CaSO4 and SrSO4 scales increases and the mass of precipitation of BaSO4 scale decreases since the solubilities of CaSO4 and SrSO4 scales decreases and the solubility of BaSO4 increases with increasing temperature. It can be concluded that even at sulfate content of 1% there may still be a scaling problem.
NASA Technical Reports Server (NTRS)
Nechay, Bohdan R.
1989-01-01
During the 1988 NASA Summer Faculty Fellowship Program, it was proposed that the loss of skeletal calcium upon prolonged exposure to microgravity could be explained, in part, by a renal maladjustment characterized by an increased urinary excretion of calcium. It was theorized that because the conservation of body fluids and electrolytes depends upon the energy of adenosine triphosphate and enzymes that control the use of its energy for renal ion transport, an induction of renal sodium and potassium-dependent adenosine triphosphatase (Na + K ATPase) by oral loading with potassium would increase the reabsorption of sodium directly and that of calcium indirectly, leading to improved hydration and to reduced calcium loss. Preliminary studies showed the following. Rats drinking water containing 0.2 M potassium chloride for six to 13 days excreted in urine 22 muEq of calcium and 135 muEq of sodium per 100 grams of body weight per day. The corresponding values for control rats drinking tap water were 43 muEq and 269 muEq respectively. Renal Na + K ATPase activity in potassium loaded rats was higher than in controls. Thus, oral potassium loading resulted in increased Na + K ATPase activity and diminished urinary excretion of calcium and of sodium as predicted by the hypothesis. An extension of these studies to humans has the potential of resulting in development of harmless, non-invasive, drug-free, convenient measures to reduce bone loss and other electrolyte and fluid problems in space travelers exposed to prolonged periods of microgravity.
Lippert, Frank
2012-10-01
This study investigated the effects of lesion baseline characteristics and different strontium (Sr) to calcium (Ca) ratios in plaque fluid-like solutions (PF) on lesion de- and remineralization. Caries lesions were formed in enamel using three protocols: methylcellulose acid gel (MeC) and partially saturated lactic acid solutions containing carboxymethylcellulose (CMC) or not (SOLN). Lesions were exposed to PF with four distinct Sr:Ca molar ratios (0:1/3:1:3), but otherwise identical composition and total Sr+Ca molarity, for seven days. Lesions were characterized using transverse microradiography (TMR) at baseline and post-treatment. At baseline, MeC and CMC had similar integrated mineral loss values, whereas SOLN lesions were more demineralized. All lesions showed significant differences in their mineral distributions, with CMC and SOLN having lower R values (integrated mineral loss to lesion depth ratio) than MeC. Post-PF exposure, no interaction was found between lesion type and Sr:Ca ratio. Within lesion type, MeC demineralized, whereas CMC and SOLN exhibited some remineralization, with the differences between MeC and the other lesion types being of statistical significance. Within Sr:Ca ratio, the 1:3 ratio exhibited some remineralization whereas other groups tended to demineralize. Only the difference between groups SrCa1/3 and SrCa0 was of statistical significance. In summary, both lesion baseline characteristics and Sr:Ca ratio were shown to effect lesion de- and remineralization. Under the conditions of the study, high-R lesions are more prone to demineralize under PF-like conditions than low-R lesions. In addition, partial Sr substitution for Ca in PF was shown to enhance lesion remineralization. Copyright © 2012 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Kumam, Nandini; Singh, Ningthoujam Premananda; Singh, Laishram Priyobarta; Srivastava, Sri Krishna
2015-09-01
Synthesis of lanthanide-doped fluoride SrF2:3Dy and SrF2:3Dy@CaF2 nanoparticles with different ratios of core to shell (1:0.5, 1:1 and 1:2) has been carried out by employing ethylene glycol route. X-ray diffraction (XRD) patterns reveal that the structure of the prepared nanoparticles was of cubical shape, which is also evident in TEM images. The size of the nanoparticles for core (SrF2:3Dy) is found to increase when core is covered by shell (CaF2). It is also evident from Fourier transform infrared spectroscopy (FTIR) that ethylene glycol successfully controls the growth and acts as a shape modifier by regulating growth rate. In the photoluminescence investigation, emission spectra of SrF2:3Dy is found to be highly enhanced when SrF2:3Dy is covered by CaF2 due to the decrease of cross relaxation amongst the Dy3+-Dy3+ ions. Such type of enhancement of luminescence in homonanostructure SrF2:3Dy@CaF2 (core@shell) has not been studied so far, to the best of the authors' knowledge. This luminescent material exhibits prominently white light emitting properties as shown by the Commission Internationale d'Eclairage (CIE) chromaticity diagram. The calculated correlate colour temperature (CCT) values for SrF2:3Dy, SrF2:3Dy@CaF2 (1:0.05), SrF2:3Dy@CaF2 (1:1) and SrF2:3Dy@CaF2 (1:2) are 5475, 5476, 5384 and 5525 K, respectively, which lie in the cold white region.
NASA Astrophysics Data System (ADS)
Hissler, Christophe; Stille, Peter; Pfister, Laurent
2017-04-01
The sustainable management of water resources is one of the greatest challenges of the 21st century. Water is a vital resource that is increasingly put under pressure from multiple perspectives. While the global population is on the rise, socio-economic development makes equally rapid progress - eventually compromising access to clean water bodies. Multiple pollution sources constitute an immediate threat to aquatic ecosystems and are likely to cause long lasting contaminations of water bodies that are critical for drinking and/or irrigation water production. There is a pressing need for an adequate quantification of anthropogenic impacts on the critical zone of river basins and the identification of the temporal dynamics of these impacts. As an example, despite the work done to assess the environmental impact of REE pollutions in larger river systems, we are still lacking information on the dynamics of these anthropogenic compounds in relation to rapid hydrological changes. Filling these knowledge gaps is a pre-requisite for the design and implementation of sustainable water resources management strategies. In order to better constrain the relative contributions of both anthropogenic and geogenic trace element sources we propose using a multitracer approach combining elemental and 87Sr/86Sr, 143Nd/144Nd, and 206Pb/207Pb isotopic ratios. The use of these three separate isotopic systems together with REE concentrations is new in the field of anthropogenic source identification in river systems. We observed enrichments in Anthropogenic Rare Earth Elements (AREE) for dissolved Gd and suspended Nd loads of river water. With increasing discharge, AREE anomalies progressively disappeared and gave way to the geogenic chemical signature of the basin in both dissolved and suspended loads. The isotopic data confirm these observations and shed new light on the trace elements sources. On the one hand, dissolved loads have peculiar isotopic characteristics and carry mainly limestone-derived and anthropogenic Sr and Nd as well as significant amounts of anthropogenic Pb. On the other hand, the results clearly indicate that anthropogenic contributions impact the suspended loads in all hydrological conditions. This study demonstrates that (i) the composition of the AREE pool is characteristic of a given river basin and controlled by the different anthropogenic contributions located in a specific study area and (ii) the anthropogenic contributions to the river may change not only Pb, but also Sr and Nd isotopic compositions in both dissolved and suspended loads. This is of importance for future provenance studies in the critical zone of polluted river basins.
Radioecological study of the Charophytes
DOE Office of Scientific and Technical Information (OSTI.GOV)
Marciulioninene, D.P.; Dusauskiene-Duz, R.F.; Cibiraite, N.A.
1976-01-01
The accumulation of Sr/sup 90/, Ce/sup 144/, Cs/sup 137/ and Ru/sup 106/ in Charophyta depends on the species, while accumulation of Sr/sup 90/ and Cs/sup 137/ depends on sampling time and vegetative period. The accumulation and excretion of Sr/sup 90/ and Cs/sup 137/ in Charophyta depend both on the exchangeable calcium and potassium in these algae and on the concentration of these elements in water. The Sr/sup 90/ and Cs/sup 137/ are taken up by the Charophyta during short-term experiments not only via absorption on a cell membrane but also via high-rate ion exchange between the environment and cellular components.more » The Ce/sup 144/ and Ru/sup 106/ uptake by Charophyta cells in short-term experiments occurs via absorption on cellular membrane. The uptake coefficients for aquatic plants notable for high mineralization (Charophyta) appear to be approximately 16 times as high under natural conditions as those under laboratory conditions, while the accumulation factors for Sr/sup 90/ in aquatic plants with fairly low mineralization (phytoplankton, Cladospora, Elodea and duckweed) were the same both under laboratory and natural conditions.« less
NASA Astrophysics Data System (ADS)
Nikolaev, Anton; Kuz'mina, Maria; Frank-Kamenetskaya, Olga; Zorina, Maina
2015-06-01
The study of the influence of carbonate ions in a solution to Sr-distribution in system «solution-crystal» and to ion substitutions and the non-stoichiometry of formed CaHA-SrHA solid solutions was carried out. The CaHA-SrHA solid solutions were synthesized by precipitation from aqueous solutions with the atomic C/P ratio equal to 0, 0.05 and 0.1 at T = 90 °C. Resulting precipitates were studied using various methods including X-ray powder diffraction, infrared spectroscopy and different chemical analyses. The results of the study have shown that in the range of values of (Ca + Sr)/P in the water solution from 40% to 85%, the presence of carbonate ions (C/P = 0.05-0.1) promotes the incorporation of strontium in the apatite. Crystalline apatite solid solutions formed from water solutions of such composition are more defective compared to apatites that are mainly calcium or strontium. They are characterized by a smaller size coherence scattering domain length along [0 0 1] direction and a greater number of carbonate ions, water molecules and vacancies at the Ca-sites.
Reeve, J; Hesp, R
1976-12-22
1. A method has been devised for comparing the impulse response functions of the skeleton for two or more boneseeking tracers, and for estimating the contribution made by measurement errors to the differences between any pair of impulse response functions. 2. Comparisons were made between the calculated impulse response functions for 47Ca and 85Sr obtained in simultaneous double tracer studies in sixteen subjects. Collectively the differences between the 47Ca and 85Sr functions could be accounted for entirely by measurement errors. 3. Because the calculation of an impulse response function requires fewer a priori assumptions than other forms of mathematical analysis, and automatically corrects for differences induced by recycling of tracer and non-identical rates of excretory plasma clearance of tracer, it is concluded that differences shown in previous in vivo studies between the fluxes of Ca and Sr into bone can be fully accounted for by undetermined oversimplifications in the various mathematical models used to analyse the results of those studies. 85Sr is therefore an adequate tracer for bone calcium in most in vivo studies.
NASA Astrophysics Data System (ADS)
Gulothungan, G.; Malathi, R.
2018-04-01
Disturbed sodium (Na+) and calcium (Ca2+) handling is known to be a major predisposing factor for life-threatening cardiac arrhythmias. Cardiac contractility in ventricular tissue is prominent by Ca2+ channels like voltage dependent Ca2+ channels, sodium-calcium exchanger (Na+-Ca2+x) and sacroplasmicrecticulum (SR) Ca2+ pump and leakage channels. Experimental and clinical possibilities for studying cardiac arrhythmias in human ventricular myocardium are very limited. Therefore, the use of alternative methods such as computer simulations is of great importance. Our aim of this article is to study the impact on action potential (AP) generation and propagation in single ventricular myocyte and ventricular tissue under different dysfunction Ca2+ channels condition. In enhanced activity of Na+-Ca2+x, single myocyte produces AP duration (APD90) and APD50 is significantly smaller (266 ms and 235 ms). Its Na+-Ca2+x current at depolarization is increases 60% from its normal level and repolarization current goes more negative (nonfailing= -0.28 pA/pF and failing= -0.47 pA/pF). Similarly, same enhanced activity of Na+-Ca2+x in 10 mm region of ventricular sheet, raises the plateau potential abruptly, which ultimately affects the diastolic repolarization. Compare with normal ventricular sheet region of 10 mm, 10% of ventricular sheet resting state is reduces and ventricular sheet at time 250 ms is goes to resting state very early. In hypertrophy condition, single myocyte produces APD90 and APD50 is worthy of attention smaller (232 mS and 198 ms). Its sodium-potassium (Na+-K+) pump current is 75% reduces from its control conditions (0.13 pA/pF). Hypertrophy condition, 50% of ventricular sheet is reduces to minimum plateau potential state, that starts the repolarization process very early and reduces the APD. In a single failing SR Ca2+ channels myocyte, recovery of Ca2+ concentration level in SR reduces upto 15% from its control myocytes. At time 290 ms, 70% of ventricular sheet is in dysfunction resting potential state in the range -83 mV and ventricular sheet at time 295 ms is goes to 65% dysfunction resting state. Therefore we concluded that shorter APD, instability resting potential and affected calcium induced calcium release (CICR) due to dysfunction Ca2+ channels is potentially have a substantial effect on cardiac contractility and relaxation. Computational study on ventricular tissue AP and its underlying ionic channel currents could help to elucidate possible arrhythmogenic mechanism on a cellular level.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ciceri, Paola; Volpi, Elisa; Brenna, Irene
2012-02-24
Highlights: Black-Right-Pointing-Pointer Lanthanum reduces the progression of high phosphate-induced calcium deposition. Black-Right-Pointing-Pointer Calcium receptor agonists and the calcimimetic calindol reduce calcium deposition. Black-Right-Pointing-Pointer Lanthanum and calindol cooperate on reducing calcium deposition. Black-Right-Pointing-Pointer Lanthanum and calindol may interact with the same receptor. -- Abstract: Phosphate (Pi)-binders are commonly used in dialysis patients to control high Pi levels, that associated with vascular calcification (VC). The aim of this study was to investigate the effects of lanthanum chloride (LaCl{sub 3}) on the progression of high Pi-induced VC, in rat vascular smooth muscle cells (VSMCs). Pi-induced Ca deposition was inhibited by LaCl{sub 3}, withmore » a maximal effect at 100 {mu}M (59.0 {+-} 2.5% inhibition). Furthermore, we studied the effects on VC of calcium sensing receptor (CaSR) agonists. Gadolinium chloride, neomycin, spermine, and the calcimimetic calindol significantly inhibited Pi-induced VC (55.9 {+-} 2.2%, 37.3 {+-} 4.7%, 30.2 {+-} 5.7%, and 63.8 {+-} 5.7%, respectively). To investigate the hypothesis that LaCl{sub 3} reduces the progression of VC by interacting with the CaSR, we performed a concentration-response curve of LaCl{sub 3} in presence of a sub-effective concentration of calindol (10 nM). Interestingly, this curve was shifted to the left (IC{sub 50} 9.6 {+-} 2.6 {mu}M), compared to the curve in the presence of LaCl{sub 3} alone (IC{sub 50} 19.0 {+-} 4.8 {mu}M). In conclusion, we demonstrated that lanthanum chloride effectively reduces the progression of high phosphate-induced vascular calcification. In addition, LaCl{sub 3} cooperates with the calcimimetic calindol in decreasing Ca deposition in this in vitro model. These results suggest the potential role of lanthanum in the treatment of VC induced by high Pi.« less
Amano, Hikaru; Sakamoto, Hideaki; Shiga, Norikatsu; Suzuki, Kaori
2016-06-01
A screening method for measuring (90)Sr in edible plant samples by focusing on (90)Y in equilibrium with (90)Sr is reported. (90)Y was extracted from samples with acid, co-precipitated with iron hydroxide, and precipitated with oxalic acid. The dissolved oxalate precipitate was loaded on an extraction chromatography resin, and the (90)Y-enriched eluate was analyzed by Cherenkov counting with a TDCR liquid scintillation counter. (90)Sr ((90)Y) concentration was determined in plant samples collected near the damaged Fukushima Daiichi Nuclear Power Plants with this method. Copyright © 2016 Elsevier Ltd. All rights reserved.
Sharma, Kritika; Hallan, Supandeep Singh; Lal, Bharat; Bhardwaj, Ankur; Mishra, Neeraj
2016-09-01
The obejctive of the present study was to investigate the potential use of floating spheroids of Atorvastatin Calcium (ATS) Loaded nanostructured lipid carriers (NLCs). The final formula of floating spheroids was optimized on the basis of shape (spherical), diameter (0.47 mm), lag time (20 s), and floating time (> 32 h). The results were further confirmed by different pharmacokinetic parameters-it was observed that the developed optimized floating ATS spheroid-loaded NLCs formulation has significantly improved relative bioavailability, that is, 3.053-folds through oral route in comparison to marketed formulation.
Jayasinghe, Isuru D; Munro, Michelle; Baddeley, David; Launikonis, Bradley S; Soeller, Christian
2014-10-06
Localization microscopy is a fairly recently introduced super-resolution fluorescence imaging modality capable of achieving nanometre-scale resolution. We have applied the dSTORM variation of this method to image intracellular molecular assemblies in skeletal muscle fibres which are large cells that critically rely on nanoscale signalling domains, the triads. Immunofluorescence staining in fixed adult rat skeletal muscle sections revealed clear differences between fast- and slow-twitch fibres in the molecular organization of ryanodine receptors (RyRs; the primary calcium release channels) within triads. With the improved resolution offered by dSTORM, abutting arrays of RyRs in transverse view of fast fibres were observed in contrast to the fragmented distribution on slow-twitch muscle that were approximately 1.8 times shorter and consisted of approximately 1.6 times fewer receptors. To the best of our knowledge, for the first time, we have quantified the nanometre-scale spatial association between triadic proteins using multi-colour super-resolution, an analysis difficult to conduct with electron microscopy. Our findings confirm that junctophilin-1 (JPH1), which tethers the sarcoplasmic reticulum ((SR) intracellular calcium store) to the tubular (t-) system at triads, was present throughout the RyR array, whereas JPH2 was contained within much smaller nanodomains. Similar imaging of the primary SR calcium buffer, calsequestrin (CSQ), detected less overlap of the triad with CSQ in slow-twitch muscle supporting greater spatial heterogeneity in the luminal Ca2+ buffering when compared with fast twitch muscle. Taken together, these nanoscale differences can explain the fundamentally different physiologies of fast- and slow-twitch muscle. © 2014 The Author(s) Published by the Royal Society. All rights reserved.
Jayasinghe, Isuru D.; Munro, Michelle; Baddeley, David; Launikonis, Bradley S.; Soeller, Christian
2014-01-01
Localization microscopy is a fairly recently introduced super-resolution fluorescence imaging modality capable of achieving nanometre-scale resolution. We have applied the dSTORM variation of this method to image intracellular molecular assemblies in skeletal muscle fibres which are large cells that critically rely on nanoscale signalling domains, the triads. Immunofluorescence staining in fixed adult rat skeletal muscle sections revealed clear differences between fast- and slow-twitch fibres in the molecular organization of ryanodine receptors (RyRs; the primary calcium release channels) within triads. With the improved resolution offered by dSTORM, abutting arrays of RyRs in transverse view of fast fibres were observed in contrast to the fragmented distribution on slow-twitch muscle that were approximately 1.8 times shorter and consisted of approximately 1.6 times fewer receptors. To the best of our knowledge, for the first time, we have quantified the nanometre-scale spatial association between triadic proteins using multi-colour super-resolution, an analysis difficult to conduct with electron microscopy. Our findings confirm that junctophilin-1 (JPH1), which tethers the sarcoplasmic reticulum ((SR) intracellular calcium store) to the tubular (t-) system at triads, was present throughout the RyR array, whereas JPH2 was contained within much smaller nanodomains. Similar imaging of the primary SR calcium buffer, calsequestrin (CSQ), detected less overlap of the triad with CSQ in slow-twitch muscle supporting greater spatial heterogeneity in the luminal Ca2+ buffering when compared with fast twitch muscle. Taken together, these nanoscale differences can explain the fundamentally different physiologies of fast- and slow-twitch muscle. PMID:25100314
A Study for Tooth Bleaching via Carbamide Peroxide-Loaded Hollow Calcium Phosphate Spheres.
Qin, Tao; Mellgren, Torbjörn; Jefferies, Steven; Xia, Wei; Engqvist, Håkan
2016-12-26
The objective of this study was to investigate if a prolonged bleaching effect of carbamide peroxide-loaded hollow calcium phosphate spheres (HCPS) can be achieved. HCPS was synthesized via a hydrothermal reaction method. Carbamide peroxide (CP) was-loaded into HCPS by mixing with distilled water as solvent. We developed two bleaching gels containing CP-loaded HCPS: one gel with low HP concentration as at-home bleaching gel, and one with high HP concentration as in-office gel. Their bleaching effects on stained human permanent posterior teeth were investigated by measuring the color difference before and after bleaching. The effect of gels on rhodamine B degradation was also studied. To investigate the potential effect of remineralization of using HCPS, bleached teeth were soaked in phosphate buffer solution (PBS) containing calcium and magnesium ions. Both bleaching gels had a prolonged whitening effect, and showed a strong ability to degrade rhodamine B. After soaking in PBS for 3 days, remineralization was observed at the sites where HCPS attached to the teeth surface. CP-loaded HCPS could prolong the HP release behavior and improve the bleaching effect. HCPS was effective in increasing the whitening effect of carbamide peroxide and improving remineralization after bleaching process.
Bovo, Elisa; Huke, Sabine; Blatter, Lothar A; Zima, Aleksey V
2017-03-01
Functional impact of cardiac ryanodine receptor (type 2 RyR or RyR2) phosphorylation by protein kinase A (PKA) remains highly controversial. In this study, we characterized a functional link between PKA-mediated RyR2 phosphorylation level and sarcoplasmic reticulum (SR) Ca 2+ release and leak in permeabilized rabbit ventricular myocytes. Changes in cytosolic [Ca 2+ ] and intra-SR [Ca 2+ ] SR were measured with Fluo-4 and Fluo-5N, respectively. Changes in RyR2 phosphorylation at two PKA sites, serine-2031 and -2809, were measured with phospho-specific antibodies. cAMP (10μM) increased Ca 2+ spark frequency approximately two-fold. This effect was associated with an increase in SR Ca 2+ load from 0.84 to 1.24mM. PKA inhibitory peptide (PKI; 10μM) abolished the cAMP-dependent increase of SR Ca 2+ load and spark frequency. When SERCA was completely blocked by thapsigargin, cAMP did not affect RyR2-mediated Ca 2+ leak. The lack of a cAMP effect on RyR2 function can be explained by almost maximal phosphorylation of RyR2 at serine-2809 after sarcolemma permeabilization. This high RyR2 phosphorylation level is likely the consequence of a balance shift between protein kinase and phosphatase activity after permeabilization. When RyR2 phosphorylation at serine-2809 was reduced to its "basal" level (i.e. RyR2 phosphorylation level in intact myocytes) using kinase inhibitor staurosporine, SR Ca 2+ leak was significantly reduced. Surprisingly, further dephosphorylation of RyR2 with protein phosphatase 1 (PP1) markedly increased SR Ca 2+ leak. At the same time, phosphorylation of RyR2 at serine 2031 did not significantly change under identical experimental conditions. These results suggest that RyR2 phosphorylation by PKA has a complex effect on SR Ca 2+ leak in ventricular myocytes. At an intermediate level of RyR2 phosphorylation SR Ca 2+ leak is minimal. However, complete dephosphorylation and maximal phosphorylation of RyR2 increases SR Ca 2+ leak. Copyright © 2017 Elsevier Ltd. All rights reserved.
Mangano, Kelsey M; Walsh, Stephen J; Kenny, Anne M; Insogna, Karl L; Kerstetter, Jane E
2014-02-01
High dietary acid load (DAL) may be detrimental to bone mineral density (BMD). The objectives of the study were to: (1) evaluate the cross-sectional relation between DAL and BMD; and (2) determine whether calcium intake modifies this association. Men (n = 1218) and women (n = 907) aged ≥60 years were included from the National Health and Nutrition Examination Survey 2005-2008. Nutrient intake from 2, 24-hour recalls was used to calculate net endogenous acid production (NEAP) and potential renal acid load (PRAL) (mEq/d). PRAL was calculated from dietary calcium (PRALdiet ) and diet + supplemental calcium (PRALtotal ). Tests for linear trend in adjusted mean BMD of the hip and lumbar spine were performed across energy-adjusted NEAP and PRAL quartiles. Modification by calcium intake (dietary or total) above or below 800 mg/d was assessed by interaction terms. Overall, mean age was 69 ± 0.3 years. Among women, there was no association between NEAP and BMD. PRALdiet was positively associated with proximal femur BMD (p trend = 0.04). No associations were observed with PRALtotal at any BMD site (p range, 0.38-0.82). Among men, no significant associations were observed between BMD and NEAP or PRAL. However, an interaction between PRALdiet and calcium intake was observed with proximal femur BMD (p = 0.08). An inverse association between PRALdiet and proximal femur BMD was detected among men with <800 mg/d dietary calcium (p = 0.02); no associations were found among men with ≥800 mg/d (p = 0.98). A significant interaction with PRALtotal was not observed. In conclusion, when supplemental calcium is considered, there is no association between DAL and BMD among adults. Men with low dietary calcium showed an inverse relation with PRAL at the proximal femur; in women no interaction was observed. This study highlights the importance of calcium intake in counteracting the adverse effect of DAL on bone health. Further research should determine the relation between DAL and change in BMD with very low calcium intake. © 2014 American Society for Bone and Mineral Research.
High Dietary Protein Intake and Protein-Related Acid Load on Bone Health.
Cao, Jay J
2017-12-01
Consumption of high-protein diets is increasingly popular due to the benefits of protein on preserving lean mass and controlling appetite and satiety. The paper is to review recent clinical research assessing dietary protein on calcium metabolism and bone health. Epidemiological studies show that long-term, high-protein intake is positively associated with bone mineral density and reduced risk of bone fracture incidence. Short-term interventional studies demonstrate that a high-protein diet does not negatively affect calcium homeostasis. Existing evidence supports that the negative effects of the acid load of protein on urinary calcium excretion are offset by the beneficial skeletal effects of high-protein intake. Future research should focus on the role and the degree of contribution of other dietary and physiological factors, such as intake of fruits and vegetables, in reducing the acid load and further enhancing the anabolic effects of protein on the musculoskeletal system.
NASA Astrophysics Data System (ADS)
Minami, M.; Goto, A.; Suzuki, K.; Kato, T.; Watanabe, K.; Hasegawa, T.
2007-12-01
Strontium enters the human body through the food chain as nutrients pass from bedrock through soil and water to plants and animals. Strontium substitutes for calcium in the hydroxyapatite mineral of skeletal tissue, and is stored there. 87Sr/86Sr ratios in an individual's bone and teeth could directly reflect the isotopic ratios found in the plants and animals that she or he consumed, which reflect the isotope ratios found in the soil and bedrock of that geologic region. Therefore, 87Sr/86Sr ratios of human skeletons could be useful tools for assessing human residential mobility in prehistory, and many studies on them have been often made. In this study, to evaluate whether the 87Sr/86Sr ratio of a bone or teeth really reflects the isotopic ratios of its birth and growth places, several bone and teeth samples were measured for 87Sr/86Sr ratios, compared with 87Sr/86Sr ratios of geological samples in their growth-places. Bone and teeth samples were leached with 5% acetic acid. After drying, samples were ashed in a muffle furnace at 825°C for 8h, and then digested in nitric acid, followed by cation exchange chromatography with 2.4M hydrochloric acid. 87Sr/86Sr ratios were measured using a thermal ionization mass Spectrometer (VG Sector 54) or an inductively coupled plasma mass spectrometer (Finnigan ELEMENT2). A modern boar bone collected at Asuke, Toyota City, Aichi prefecture, Japan showed a 87Sr/86Sr of 0.71001±0.00002 (2 σ), while stream sediments in the Asuke area showed around 0.710 (Asahara et al., 2006). The 87Sr/86Sr ratio of a modern black bass bone collected from Lake Biwa, Shiga prefecture, Japan was 0.71215±0.00002, while those of surface water in Lake Biwa was 0.71233±0.00002. The similar 87Sr/86Sr ratios between bone and its provenance geology could indicate that the 87Sr/86Sr ratios of bones reflect the isotopic ratios of the birth- and growth-places. The more results of modern and fossil skeletons will be shown in our presentation.
Suntornsaratoon, Panan; Charoenphandhu, Narattaphol; Krishnamra, Nateetip
2018-03-01
Breastfeeding leads to bone calcium loss for milk production, resulting in progressive maternal osteopenia. Calcium supplement from natural sources has been postulated to be more beneficial to bone health than purified CaCO 3 because natural sources also contain other nutrients such as certain amino acids that might enhance calcium metabolism. Herein, we examined the effect of calcium supplementation from tuna bone powder and CaCO 3 on bones of dams and the offspring. Both forms of calcium supplement, i.e. tuna bone powder and CaCO 3 , increased maternal bone mineral density (BMD). However, bone histomorphometry revealed that only tuna bone had beneficial effect on maternal bone microstructure, i.e. increased bone formation, decreased bone resorption and increased in bone volume. Regarding the mechanical properties, the decreased ultimate load in non-supplement lactating mothers was restored to the load seen in nulliparous animals by calcium supplementation. Moreover, both tuna bone and CaCO 3 supplementation in mothers led to increased milk calcium concentration and consequently increased BMD in the growing offspring. Calcium supplement from tuna bone powder was effective in preventing maternal osteopenia. Tuna bone, which is a readily available fishing industrial waste, is a good alternative source of calcium supplement that increases BMD in both lactating mothers and the neonates. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Khan, M.A.; Khan, S.A.
Sorption studies of cesium, strontium, and cobalt (Cs, Sr, and Co) on bentonite under various experimental conditions, such as contact time, pH, sorbent and sorbate concentration, and temperature, have been performed. The sorption data for all these metals have been interpreted in terms of Freundlich, Langmuir, and Dubinin-Radushkevich equations. Thermodynamics parameters, such as heat of sorption {Delta}H{degrees}, free energy change {Delta}G{degrees}, and entropy change {Delta}S{degrees}, for the sorption of these metals on bentonite have been calculated. The value of {Delta}H{degrees} shows that the sorption of Cs was exothermic, while the sorption of Sr and Co on bentonite were endothermic inmore » nature. The value of {Delta}G{degrees} for their sorption was negative, showing the spontaneity of the process. The maximum loading capacity of Cs, Sr, and Co were 75.5, 22, and 27.5 meq, respectively, for 100 g of bentonite. The mean free energy E of Cs, Sr, and Co sorption on bentonite was 14.5, 9, and 7.7 kJ/mol, respectively. The value of E indicates that ion exchange may be the predominant mode of sorption for these radionuclides. The desorption studies with 0.01 M CaCl{sub 2} and groundwater at low-metal loading on bentonite showed that about 95% of Cs, 85-90% of Sr, and 97% of Co were irreversibly sorbed. Bentonite could be effectively used for the decontamination of wastewater effluent containing low concentrations of radioactive nuclides of Cs, Sr, and Co. 16 refs., 7 figs., 3 tabs.« less
Lalli, M J; Yong, J; Prasad, V; Hashimoto, K; Plank, D; Babu, G J; Kirkpatrick, D; Walsh, R A; Sussman, M; Yatani, A; Marbán, E; Periasamy, M
2001-07-20
Ectopic expression of the sarcoplasmic reticulum (SR) Ca(2+) ATPase (SERCA) 1a pump in the mouse heart results in a 2.5-fold increase in total SERCA pump level. SERCA1a hearts show increased rates of contraction/relaxation and enhanced Ca(2+) transients; however, the cellular mechanisms underlying altered Ca(2+) handling in SERCA1a transgenic (TG) hearts are unknown. In this study, using confocal microscopy, we demonstrate that SERCA1a protein traffics to the cardiac SR and structurally substitutes for the endogenous SERCA2a isoform. SR Ca(2+) load measurements revealed that TG myocytes have significantly enhanced SR Ca(2+) load. Confocal line-scan images of field-stimulated SR Ca(2+) release showed an increased rate of Ca(2+) removal in TG myocytes. On the other hand, ryanodine receptor binding activity was decreased by approximately 30%. However, TG myocytes had a greater rate of spontaneous ryanodine receptor opening as measured by spark frequency. Whole-cell L-type Ca(2+) current density was reduced by approximately 50%, whereas the time course of inactivation was unchanged in TG myocytes. These studies provide important evidence that SERCA1a can substitute both structurally and functionally for SERCA2a in the heart and that SERCA1a overexpression can be used to enhance SR Ca(2+) transport and cardiac contractility.
Anthrax and the geochemistry of soils in the contiguous United States
Griffin, Dale W.; Silvestri, Erin E.; Bowling, Charlena Y.; Boe, Timothy; Smith, David B.; Nichols, Tonya L.
2014-01-01
Soil geochemical data from sample sites in counties that reported occurrences of anthrax in wildlife and livestock since 2000 were evaluated against counties within the same states (MN, MT, ND, NV, OR, SD and TX) that did not report occurrences. These data identified the elements, calcium (Ca), manganese (Mn), phosphorus (P) and strontium (Sr), as having statistically significant differences in concentrations between county type (anthrax occurrence versus no occurrence). Tentative threshold values of the lowest concentrations of each of these elements (Ca = 0.43 wt %, Mn = 142 mg/kg, P = 180 mg/kg and Sr = 51 mg/kg) and average concentrations (Ca = 1.3 wt %, Mn = 463 mg/kg, P = 580 mg/kg and Sr = 170 mg/kg) were identified from anthrax-positive counties as prospective investigative tools in determining whether an outbreak had “potential” or was “likely” at any given geographic location in the contiguous United States.
Launikonis, B S; Stephenson, D G
2000-07-15
1. The role of myoplasmic [Mg2+] on Ca2+ release from the sarcoplasmic reticulum (SR) was examined in the two major types of crustacean muscle fibres, the tonic, long sarcomere fibres and the phasic, short sarcomere fibres of the fresh water decapod crustacean Cherax destructor (yabby) and in the fast-twitch rat muscle fibres using the mechanically skinned muscle fibre preparation. 2. A robust Ca2+-induced Ca2+-release (CICR) mechanism was present in both long and short sarcomere fibres and 1 mM Mg2+ exerted a strong inhibitory action on the SR Ca2+ release in both fibre types. 3. The SR displayed different properties with respect to Ca2+ loading in the long and the short sarcomere fibres and marked functional differences were identified with respect to Mg2+ inhibition between the two crustacean fibre types. Thus, in long sarcomere fibres, the submaximally loaded SR was able to release Ca2+ when [Mg2+] was lowered from 1 to 0.01 mM in the presence of 8 mM ATPtotal and in the virtual absence of Ca2+ (< 5 nM) even when the CICR was suppressed. In contrast, negligible Ca2+ was released from the submaximally loaded SR of short sarcomere yabby fibres when [Mg2+] was lowered from 1 to 0.01 mM under the same conditions as for the long sarcomere fibres. Nevertheless, the rate of SR Ca2+ release in short sarcomere fibres increased markedly when [Mg2+] was lowered in the presence of [Ca2+] approaching the normal resting levels (50-100 nM). 4. Rat fibres were able to release SR Ca2+ at a faster rate than the long sarcomere yabby fibres when [Mg2+] was lowered from 1 to 0. 01 mM in the virtual absence of Ca2+ but, unlike with yabby fibres, the net rate of Ca2+ release was actually increased for conditions that were considerably less favourable to CICR. 5. In summary, it is concluded that crustacean skeletal muscles have more that one functional type of Ca2+-release channels, that these channels display properties that are intermediate between those of mammalian skeletal and cardiac isoforms, that the inhibition exerted by Mg2+ at rest on the crustacean SR Ca2+-release channels must be removed during excitation-contraction coupling and that, unlike in crustacean fibres, CICR cannot play the major role in the activation of SR Ca2+-release channels in the rat skeletal muscle.
Effect of SrO content on Zeolite Structure
NASA Astrophysics Data System (ADS)
Widiarti, N.; Sari, U. S.; Mahatmanti, F. W.; Harjito; Kurniawan, C.; Prasetyoko, D.; Suprapto
2018-04-01
The aims of current studies is to investigate the effect of strontium oxide content (SrO) on synthesized zeolite. Zeolite was synthesized from Tetraethyl orthosilicate (TEOS) as precursors of SiO2 and aluminum isopropoxide (AIP) precursors. The mixture was aged for 3 days and hydrothermally treated for 6 days. The SrO content was added by impregnation method. The products were then characterized using X-Ray Diffraction (XRD), Fourier Transform Infrared (FTIR), and Surface Area Analyzer (SAA). The diffractogram confirmed the formation of Faujasite-like zeolite. However, after the addition of SrO, the crystallinity of zeolite was deformed. The diffractograms shows the amorphous phase of zeolite were decrease as the SrO content is increase. The structural changes was also observed from FTIR spectra which shows the shifting and peak formation. The surface area analysis showed that the increasing loading of SrO/Zeolites reduced the catalyst surface area.
Evaluation of Limb Load Asymmetry Using Two New Mathematical Models
Kumar, Senthil NS; Omar, Baharudin; Joseph, Leonard H.; Htwe, Ohnmar; Jagannathan, K.; Hamdan, Nor M Y; Rajalakshmi, D.
2015-01-01
Quantitative measurement of limb loading is important in orthopedic and neurological rehabilitation. In current practice, mathematical models such as Symmetry index (SI), Symmetry ratio (SR), and Symmetry angle (SA) are used to quantify limb loading asymmetry. Literatures have identified certain limitations with the above mathematical models. Hence this study presents two new mathematical models Modified symmetry index (MSI) and Limb loading error (LLE) that would address these limitations. Furthermore, the current mathematical models were compared against the new model with the goal of achieving a better model. This study uses hypothetical data to simulate an algorithmic preliminary computational measure to perform with all numerical possibilities of even and uneven limb loading that can occur in human legs. Descriptive statistics are used to interpret the limb loading patterns: symmetry, asymmetry and maximum asymmetry. The five mathematical models were similar in analyzing symmetry between limbs. However, for asymmetry and maximum asymmetry data, the SA and SR values do not give any meaningful interpretation, and SI gives an inflated value. The MSI and LLE are direct, easy to interpret and identify the loading patterns with the side of asymmetry. The new models are notable as they quantify the amount and side of asymmetry under different loading patterns. PMID:25716372
TRPV3 channels mediate strontium-induced mouse egg activation
Carvacho, Ingrid; Lee, Hoi Chang; Fissore, Rafael A.; Clapham, David E.
2014-01-01
SUMMARY In mammals, calcium influx is required for oocyte maturation and egg activation. The molecular identities of the calcium-permeant channels that underlie the initiation of embryonic development are not established. Here, we describe a Transient Receptor Potential (TRP) ion channel current activated by TRP agonists that is absent in TrpV3−/− eggs. TRPV3 current is differentially expressed during oocyte maturation, reaching a peak of maximum density and activity at metaphase of meiosis II (MII), the stage of fertilization. Selective activation of TRPV3 channels provokes egg activation by mediating massive calcium entry. Widely used to activate eggs, strontium application is known to yield normal offspring in combination with somatic cell nuclear transfer. We show that TRPV3 is required for strontium influx, as TrpV3−/− eggs failed to permeate Sr2+ or undergo strontium-induced activation. We propose that TRPV3 is the major mediator of calcium influx in mouse eggs and is a putative target for artificial egg activation. PMID:24316078
Parent, Marianne; Baradari, Hiva; Champion, Eric; Damia, Chantal; Viana-Trecant, Marylène
2017-04-28
Effective treatment of critical-size defects is a key challenge in restorative surgery of bone. The strategy covers the implantation of biocompatible, osteoconductive, bioactive and biodegradable devices which (1) well interact with native tissue, mimic multi-dimensional and hierarchical structure of bone and (2) are able to enhance bone repair, treating post implantation pathologies or bone diseases by local delivery of therapeutic agents. Among different options, calcium phosphate biomaterials are found to be attractive choices, due to their excellent biocompatibility, customisable bioactivity and biodegradability. Several approaches have been established to enhance this material ability to be loaded with a therapeutic agent, in order to obtain an in situ controlled release that meets the clinical needs. This article reviews the most important factors influencing on both drug loading and release capacity of porous calcium phosphate bone substitutes. Characteristics of the carrier, drug/carrier interactions, experimental conditions of drug loading and evaluation of drug delivery are considered successively. Copyright © 2017 Elsevier B.V. All rights reserved.
Si, Fengzhan; Zhang, Guoguang; Huang, Kevin
2016-04-09
Here, the present study investigates the mass loading effect of an infiltrated La 0.6Sr 0.4Co 0.2Fe 0.8O 3-δ (LSCF) nanoparticles (NPs) catalyst on the area-specific polarization resistance (Rp) of a screen-printed porous LSCF cathode for solid oxide fuel cells. The results show that R p of the LSCF-NPs decorated LSCF cathode can be substantially reduced by as much as 89.3% after a single-step impregnation of 1.5 M nitrate solution containing La:Sr:Co:Fe = 0.6:0.4:0.2:0.8 with a mass loading of 3 wt%.
NASA Astrophysics Data System (ADS)
Vandevenne, Niels; Iacobescu, Remus Ion; Pontikes, Yiannis; Carleer, Robert; Thijssen, Elsy; Gijbels, Katrijn; Schreurs, Sonja; Schroeyers, Wouter
2018-05-01
Minimizing harmful effects to the environment in waste-management practices requires continuous innovation. This is especially important in the field of radioactive waste management. Alternatives to the commonly used ordinary Portland cement matrices are being increasingly studied for improved immobilisation purposes. The development of inorganic polymers (IP) from industrial residues has been successfully studied for the immobilisation of caesium (Cs+) and strontium (Sr2+). However, knowledge of the effect of these introduced elements on the IP-matrix is scarce, especially considering that studied effects are dependent on the IP-precursor characteristics and the form in which the Cs+ and Sr2+ are introduced. In this study, IPs containing varying amounts of CsNO3 and Sr(NO3)2 were developed to study the effect of the introduced elements on the IP-characteristics. IP-samples were developed from ground granulated blast furnace slag (GGBFS) and 6 M NaOH activating solution. Cs+ and Sr2+ were added to account for 0.5, 1 and 2 wt% of the total IP-mass. Throughout the entire study, Cs+-addition showed no significant effects on the studied parameters. Calorimetric results showed that Sr2+ severely affects reaction kinetics, consuming hydroxide ions necessary for the alkali activation reaction. Sr2+-addition also caused a severe decrease in compressive strength, increased calcium leaching, and decreased sodium and hydroxide leaching. Micro-chemical analyses showed that Cs+ is almost fully incorporated in the formed IP-matrix, while Sr2+ mainly precipitates as Sr(OH)2 in concentrated regions throughout the IP-structure. The findings presented in this paper give insights on the effect of contaminant elements on the immobilising matrix.
Kuffner, Ilsa; Jokiel, Paul L.; Rodgers, Kuulei; Andersson, Andreas; Mackenzie, Fred T.
2012-01-01
Measuring the strontium to calcium ratio in coral skeletons reveals information on seawater temperatures during skeletal deposition, but studies have shown additional variables may affect the ratio. Here we measured Sr/Ca in the reef coral, Montipora capitata, grown in six mesocosms continuously supplied with seawater from the adjacent reef flat. Three mesocosms were ambient controls, and three had seawater chemistry simulating "ocean acidification" (OA). We found that Sr/Ca was not affected by the OA treatment, and neither was coral calcification for these small colonies (larger colonies did show an OA effect). The lack of OA effects allowed us to test the hypothesis that coral growth rate can affect Sr/Ca using the natural range in calcification rates of the corals grown at the same temperature. We found that Sr/Ca was inversely related to calcification rate (Sr/Ca = 9.39 - 0.00404 mmol/mol * mg day-1 cm-2, R2 = 0.32). Using a previously published calibration curve for this species, a 22 mg day-1 colony-1 increase in calcification rate introduced a 1°C warmer temperature estimate, with the 27 corals reporting "temperatures" ranging from 24.9 to 28.9, with mean 26.6 ± 0.9°C SD. Our results lend support to hypotheses invoking kinetic processes and growth rate to explain vital effects on Sr/Ca. However, uncertainty in the slope of the regression of Sr/Ca on calcification and a low R-squared value lead us to conclude that Sr/Ca could still be a useful proxy in this species given sufficient replication or by including growth rate in the calibration.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Paton, Chad; Schiller, Martin; Bizzarro, Martin, E-mail: chadpaton@gmail.com, E-mail: schiller@snm.ku.dk, E-mail: bizzarro@snm.ku.dk
2013-02-01
The existence of correlated nucleosynthetic heterogeneities in solar system reservoirs is now well demonstrated for numerous nuclides. However, it has proven difficult to discriminate between the two disparate processes that can explain such correlated variability: incomplete mixing of presolar material or secondary processing of a well-mixed disk. Using stepwise acid-leaching of the Ivuna CI-chondrite, we show that unlike other nuclides such as {sup 54}Cr and {sup 50}Ti, Sr-isotope variability is the result of a carrier depleted in {sup 84}Sr. The carrier is most likely presolar SiC, which is known to have both high Sr-concentrations relative to solar abundances and extremelymore » depleted {sup 84}Sr compositions. Thus, variability in {sup 84}Sr in meteorites and their components can be attributed to varying contributions from presolar SiC. The observed {sup 84}Sr excesses in calcium-aluminum refractory inclusions (CAIs) suggest their formation from an SiC-free gaseous reservoir, whereas the {sup 84}Sr depletions present in differentiated meteorites require their formation from material with an increased concentration of SiC relative to CI chondrites. The presence of a positive correlation between {sup 84}Sr and {sup 54}Cr, despite being hosted in carriers of negative and positive anomalies, respectively, is not compatible with incomplete mixing of presolar material but instead suggests that the solar system's nucleosynthetic heterogeneity reflects selective thermal processing of dust. Based on vaporization experiments of SiC under nebular conditions, the lack of SiC material in the CAI-forming gas inferred from our data requires that the duration of thermal processing of dust resulting in the vaporization of CAI precursors was extremely short-lived, possibly lasting only hours to days.« less
Strontium-rich injectable hybrid system for bone regeneration.
Neves, Nuno; Campos, Bruno B; Almeida, Isabel F; Costa, Paulo C; Cabral, Abel Trigo; Barbosa, Mário A; Ribeiro, Cristina C
2016-02-01
Current challenges in the development of scaffolds for bone regeneration include the engineering of materials that can withstand normal dynamic physiological mechanical stresses exerted on the bone and provide a matrix capable of supporting cell migration and tissue ingrowth. The objective of the present work was to develop and characterize a hybrid polymer–ceramic injectable system that consists of an alginate matrix crosslinked in situ in the presence of strontium(Sr), incorporating a ceramic reinforcement in the form of Sr-rich microspheres. The incorporation of Sr in the microspheres and in the vehicle relies on the growing evidence that Sr has beneficial effects in bone remodeling and in the treatment of osteopenic disorders and osteoporosis. Sr-rich porous hydroxyapatite microspheres with a uniform size and a mean diameter of 555 μm were prepared, and their compression strength and friability tested. A 3.5% (w/v) ultrapure sodium alginate solution was used as the vehicle and its in situ gelation was promoted by the addition of calcium (Ca) or Sr carbonate and Glucone-δ-lactone. Gelation times varied with temperature and crosslinking agent, being slower for Sr than for Ca, but adequate for injection in both cases. Injectability was evaluated using a device employed in vertebroplasty surgical procedures, coupled to a texture analyzer in compression mode. Compositions with 35%w of microspheres presented the best compromise between injectability and compression strength of the system, the force required to extrude it being lower than 100 N.Micro CT analysis revealed a homogeneous distribution of the microspheres inside the vehicle, and a mean inter-microspheres space of 220 μm. DMA results showed that elastic behavior of the hybrid is over the viscous one and that the higher storage modulus was obtained for the 3.5%Alg–35%Sr-HAp-Sr formulation.
Jain, Roshan A; Wolman, Marc A; Marsden, Kurt C; Nelson, Jessica C; Shoenhard, Hannah; Echeverry, Fabio A; Szi, Christina; Bell, Hannah; Skinner, Julianne; Cobbs, Emilia N; Sawada, Keisuke; Zamora, Amy D; Pereda, Alberto E; Granato, Michael
2018-05-07
Animals continuously integrate sensory information and select contextually appropriate responses. Here, we show that zebrafish larvae select a behavioral response to acoustic stimuli from a pre-existing choice repertoire in a context-dependent manner. We demonstrate that this sensorimotor choice is modulated by stimulus quality and history, as well as by neuromodulatory systems-all hallmarks of more complex decision making. Moreover, from a genetic screen coupled with whole-genome sequencing, we identified eight mutants with deficits in this sensorimotor choice, including mutants of the vertebrate-specific G-protein-coupled extracellular calcium-sensing receptor (CaSR), whose function in the nervous system is not well understood. We demonstrate that CaSR promotes sensorimotor decision making acutely through Gα i/o and Gα q/11 signaling, modulated by clathrin-mediated endocytosis. Combined, our results identify the first set of genes critical for behavioral choice modulation in a vertebrate and reveal an unexpected critical role for CaSR in sensorimotor decision making. Copyright © 2018 Elsevier Ltd. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nagy, B.; Bercz, J.P.
CentrifiChem System 400 general-purpose spectrophotometric analyzer which can process simultaneously 30 samples and reads the reactions within milliseconds was used for toxicity studies. Organic and inorganic chemicals were screened for inhibitory action of the hydrolytic activity of sarcoplasmic reticulum (SR) Ca,Mg-ATPase and that of the sacrolemmal (SL) Na,K-ATPase, or mitochondrial ATPase (M). SR and SL were prepared from rabbit muscles, Na,K-ATPase from pig kidneys, M from pig hearts. Pseudosubstrates of paranitrophenyl phosphate and 2,4-dinitrophenyl phosphate, both proven high energy phosphate substitutes for ATPase coupled ion transfer were used. The reaction rates were followed spectrophotometrically at 405 nm measuring the accumulationmore » of yellow nitrophenolate ions. The reported calcium transfer coupling ratio to hydrolysis of 2:1 was ascertained with use of /sup 45/Ca in case of SR. Inhibition constants (pI) on SR, SL, and M for the pseudosubstrate hydrolysis will be given for over 20 chemicals tested. The applicability of the system to general toxicity testing and to general cardio-effective drug screening will be presented.« less
Ph-activated nano-amorphous calcium phosphate-based cement to reduce dental enamel demineralization.
Melo, Mary A S; Weir, Michael D; Passos, Vanara F; Powers, Michael; Xu, Hockin H K
2017-12-01
Enamel demineralization is destructive, esthetically compromised, and costly complications for orthodontic patients. Nano-sized amorphous calcium phosphate (NACP) has been explored to address this challenge. The 20% NACP-loaded ortho-cement notably exhibited favorable behavior on reducing demineralization of enamel around brackets in a caries model designed to simulate the carious attack. The 20% NACP-loaded ortho-cement markedly promotes higher calcium and phosphate release at a low pH, and the mineral loss was almost two fold lower and carious lesion depth decreased the by 1/3. This novel approach is promising co-adjuvant route for prevention of dental caries dissemination in millions of patients under orthodontic treatment.
Anderson, Collin; MacKay, Mark
2016-11-01
Calcium and phosphate precipitation is an ongoing concern when compounding pediatric parenteral nutrition (PN) solutions. Considerable effort has been expended in producing graphs, tables, and equations to guide the practitioner in prescribing PN that will remain stable. Calcium gluconate is preferred over calcium chloride when compounding PN because of its superior compatibility with inorganic phosphates. PN solutions containing calcium gluconate carry a higher aluminum load than equivalent solutions compounded with calcium chloride, leading to increased potential for aluminum toxicity. This study tested the solubility of calcium chloride in PN solutions compounded with an organic phosphate component, sodium glycerophosphate (NaGP), in place of sodium phosphate. Five PN solutions were compounded by adding calcium chloride at 10, 20, 30, 40, and 50 mEq/L and corresponding concentrations of NaGP at 10, 20, 30, 40, and 50 mmol/L. Each of the 5 solutions was compounded using 1.5% and 4% amino acids, cysteine, and lipids. The physical stability was evaluated by visual inspection (precipitation, haze, and color change). Solutions were evaluated microscopically for any microcrystals using U.S. Pharmacopeia <788> standards. Compatibility testing showed no changes in the PN solution in any of the concentrations tested. Calcium chloride was found to be physically compatible with NaGP in PN at the tested concentrations. Utilization of NaGP in PN solutions would eliminate the need for precipitation curves and allow for the use of calcium chloride. Compounding with NaGP and calcium chloride allows the practitioner a mechanism for reducing the aluminum load in PN. © 2015 American Society for Parenteral and Enteral Nutrition.
Synthesis of Silver-Strontium Titanate Hybrid Nanoparticles by Sol-Gel-Hydrothermal Method.
Ueno, Shintaro; Nakashima, Kouichi; Sakamoto, Yasunao; Wada, Satoshi
2015-03-24
Silver (Ag) nanoparticle-loaded strontium titanate (SrTiO₃) nanoparticles were attempted to be synthesized by a sol-gel-hydrothermal method. We prepared the titanium oxide precursor gels incorporated with Ag⁺ and Sr 2+ ions with various molar ratios, and they were successfully converted into the Ag-SrTiO₃ hybrid nanoparticles by the hydrothermal treatment at 230 °C in strontium hydroxide aqueous solutions. The morphology of the SrTiO₃ nanoparticles is dendritic in the presence and absence of Ag⁺ ions. The precursor gels, which act as the high reactive precursor, give rise to high nucleation and growth rates under the hydrothermal conditions, and the resultant diffusion-limited aggregation phenomena facilitate the dendritic growth of SrTiO₃. From the field-emission transmission electron microscope observation of these Ag-SrTiO₃ hybrid nanoparticles, the Ag nanoparticles with a size of a few tens of nanometers are distributed without severe agglomeration, owing to the competitive formation reactions of Ag and SrTiO₃.
Paul, Kallyanashis; Padalhin, Andrew R.; Linh, Nguyen Thuy Ba; Kim, Boram; Sarkar, Swapan Kumar; Lee, Byong Taek
2016-01-01
A bipotential polyelectrolyte complex with biphasic calcium phosphate (BCP) powder dispersion provides an excellent option for protein adsorption and cell attachment and can facilitate enhanced bone regeneration. Application of the bipotential polyelectrolyte complex embedded in a spongy scaffold for faster healing of large segmental bone defects (LSBD) can be a promising endeavor in tissue engineering application. In the present study, a hollow scaffold suitable for segmental long bone replacement was fabricated by the sponge replica method applying the microwave sintering process. The fabricated scaffold was coated with calcium alginate at the shell surface, and genipin-crosslinked chitosan with biphasic calcium phosphate (BCP) dispersion was loaded at the central hollow core. The chitosan core was subsequently loaded with BMP-2. The electrolytic complex was characterized using SEM, porosity measurement, FTIR spectroscopy and BMP-2 release for 30 days. In vitro studies such as MTT, live/dead, cell proliferation and cell differentiation were performed. The scaffold was implanted into a 12 mm critical size defect of a rabbit radius. The efficacy of this complex is evaluated through an in vivo study, one and two month post implantation. BV/TV ratio for BMP-2 loaded sample was (42±1.76) higher compared with hollow BCP scaffold (32±0.225). PMID:27711142
Dotsuta, Yuma; Nakano, Yuriko; Ochiai, Asumi; Utsunomiya, Satoshi; Ohnuki, Toshihiko
2017-01-01
ABSTRACT Radioactive strontium (90Sr) leaked into saline environments, including the ocean, from the Fukushima Daiichi Nuclear Power Plant after a nuclear accident. Since the removal of 90Sr using general adsorbents (e.g., zeolite) is not efficient at high salinity, a suitable alternative immobilization method is necessary. Therefore, we incorporated soluble Sr into biogenic carbonate minerals generated by urease-producing microorganisms from a saline solution. An isolate, Bacillus sp. strain TK2d, from marine sediment removed >99% of Sr after contact for 4 days in a saline solution (1.0 × 10−3 mol liter−1 of Sr, 10% marine broth, and 3% [wt/vol] NaCl). Transmission electron microscopy and energy-dispersive X-ray spectroscopy showed that Sr and Ca accumulated as phosphate minerals inside the cells and adsorbed at the cell surface at 2 days of cultivation, and then carbonate minerals containing Sr and Ca developed outside the cells after 2 days. Energy-dispersive spectroscopy revealed that Sr, but not Mg, was present in the carbonate minerals even after 8 days. X-ray absorption fine-structure analyses showed that a portion of the soluble Sr changed its chemical state to strontianite (SrCO3) in biogenic carbonate minerals. These results indicated that soluble Sr was selectively solidified into biogenic carbonate minerals by the TK2d strain in highly saline environments. IMPORTANCE Radioactive nuclides (134Cs, 137Cs, and 90Sr) leaked into saline environments, including the ocean, from the Fukushima Daiichi Nuclear Power Plant accident. Since the removal of 90Sr using general adsorbents, such as zeolite, is not efficient at high salinity, a suitable alternative immobilization method is necessary. Utilizing the known concept that radioactive 90Sr is incorporated into bones by biomineralization, we got the idea of removing 90Sr via incorporation into biominerals. In this study, we revealed the ability of the isolated ureolytic bacterium to remove Sr under high-salinity conditions and the mechanism of Sr incorporation into biogenic calcium carbonate over a longer duration. These findings indicated the mechanism of the biomineralization by the urease-producing bacterium and the possibility of the biomineralization application for a new purification method for 90Sr in highly saline environments. PMID:28802269
Effect of three nanobiomaterials on the surface roughness of bleached enamel
Khoroushi, Maryam; Shirban, Farinaz; Doustfateme, Samaneh; Kaveh, Sara
2015-01-01
Background: The ever-increasing demand for enhanced esthetic appearance has resulted in significant developments in bleaching products. However, the enamel surface roughness (SR) might be negatively affected by bleaching agents. This in vitro study was undertaken to compare the effects of three nanobiomaterials on the enamel SR subsequent to bleaching. Materials and Methods: The crowns of six extracted intact nonerupted human third molars were sectioned. Five dental blocks measuring 2 mm × 3 mm × 4 mm were prepared from each tooth and placed in colorless translucent acrylic resin. The enamel areas from all the specimens were divided into five groups (n = 6): Group 1 did not undergo any bleaching procedures; Group 2 was bleached with a 40% hydrogen peroxide (HP) gel; Groups 3, 4, and 5 were bleached with a 40% HP gel modified by bioactive glass (BAG), amorphous calcium phosphate, and hydroxyapatite, respectively. The enamel SR was evaluated before and after treatment by atomic force microscopy. The data were analyzed by Kruskal–Wallis and Mann–Whitney tests. Results: SR increased significantly in the HP group. SR decreased significantly in the HP gel modified by BAG group as compared to other groups. Conclusions: Within the limitations of this study, incorporation of each one of the three test biomaterials proved effective in decreasing enamel SR subsequent to in-office bleaching technique. PMID:26681849
Influence of SrO substitution for CaO on the properties of bioactive glass S53P4.
Massera, Jonathan; Hupa, Leena
2014-03-01
Commercial melt-quenched bioactive glasses consist of the oxides of silicon, phosphorus, calcium and sodium. Doping of the glasses with oxides of some other elements is known to affect their capability to support hydroxyapatite formation and thus bone tissue healing but also to modify their high temperature processing parameters. In the present study, the influence of gradual substitution of SrO for CaO on the properties of the bioactive glass S53P4 was studied. Thermal analysis and hot stage microscopy were utilized to measure the thermal properties of the glasses. The in vitro bioactivity and solubility was measured by immersing the glasses in simulated body fluid for 6 h to 1 week. The formation of silica rich and hydroxyapatite layers was assessed from FTIR spectra analysis and SEM images of the glass surface. Increasing substitution of SrO for CaO decreased all characteristic temperatures and led to a slightly stronger glass network. The initial glass dissolution rate increased with SrO content. Hydroxyapatite layer was formed on all glasses but on the SrO containing glasses the layer was thinner and contained also strontium. The results suggest that substituting SrO for CaO in S53P4 glass retards the bioactivity. However, substitution greater than 10 mol% allow for precipitation of a strontium substituted hydroxyapatite layer.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zook, M.N.; Rush, J.S.; Kuc, J.A.
Calcium and strontium ions enhanced rishitin but not lubimin accumulation in tuber tissue of potato (Solanum tuberosum cv Kennebec) treated with arachidonic acid (AA). The same cations in the presence of poly-L-lysine (PL) enhanced the accumulation of lubimin more than rishitin. In contrast, Mg/sup 2 +/ did not affect AA-elicited rishitin and lubimin accumulation and inhibited the accumulation of these compounds following application of PL. AA-elicited potato tuber tissue remained sensitive to the stimulatory effects of Ca/sup 2 +/ and Sr/sup 2 +/ up to 24 h after application of AA, but PL-elicited tuber tissue was sensitive to Ca/sup 2more » +/ and Sr/sup 2 +/ for only 6 hours after PL application. Etyleneglycol-bis (..beta..-aminoethyl ether)-N,N'-tetraacetic acid and La/sup 3 +/ both inhibited rishitin and lubimin accumulation elicited by AA. The inhibition by either agent was overcome by the addition of Ca/sup 2 +/. Calcium was more effective in overcoming lanthanum inhibition when applied simultaneously than when applied 12 hours later. Lanthanum was only effective in inhibiting rishitin and lubimin accumulation when applied within 3 hours of the application of AA. Inhibition of phytoalexin accumulation was greater when La/sup 3 +/ was greater when La/sup 3 +/ was applied simultaneously with AA compared to La/sup 3 +/ application after AA aplication to discs. These observations suggest that the mobilization of calcium may play a central regulatory role in the expression of phytoalexin accumulation following elicitation in potato tissue.« less
NASA Astrophysics Data System (ADS)
Shao, Kunjuan; Wang, Yanjie; Iqbal, Muzaffar; Lin, Lin; Wang, Kai; Zhang, Xuehua; He, Meng; He, Tao
2018-03-01
Modification of a wide-bandgap semiconductor with noble metals that can exhibit surface plasmon effect is an effective approach to make it responsive to the visible light. In this work, a series of cubic and all-edge-truncated SrTiO3 with and without thermal pretreatment in air are modified by Ag nanoparticles via photodeposition method. The crystal structure, morphology, loading amount of Ag nanoparticles, and optical properties of the obtained Ag-SrTiO3 nanomaterials are well characterized by powder X-ray diffraction, scanning microscope, transmission electron microscope, energy disperse X-ray spectroscopy, ICP-MS and UV-vis diffuse-reflection spectroscopy. The loading amount and size of the Ag nanoparticles can be controlled to some extent by tuning the photodeposition time via growth-dissolution mechanism. The Ag nanoparticles are inclined to deposit on different locations on the surface of cubic and truncated SrTiO3 with and without thermal pretreatment. The resultant SrTiO3 modified by Ag nanoparticles exhibits visible light activity for photocatalytic reduction of CO2, which is closely related to the oxygen vacancy induced by thermal pretreatment, size and amount of Ag nanoparticles. Accordingly, there is an optimized photodeposition time for the synthesis of the photocatalyst that exhibits the highest photocatalytic activity.
1993-01-01
Cut fibers from Rana temporaria and Rana pipiens (striation spacing, 3.9-4.2 microns) were mounted in a double Vaseline-gap chamber and studied at 14 degrees C. The Ca indicator purpurate-3,3' diacetic acid (PDAA) was introduced into the end pools and allowed to diffuse into the optical recording site. When the concentration at the site exceeded 2 mM, step depolarizations to 10 mV were applied and the [Ca] transient measured with PDAA was used to estimate Ca release from the sarcoplasmic reticulum (SR) (Baylor, S. M., W. K. Chandler, and M. W. Marshall. 1983. Journal of Physiology. 344:625-666). With depolarization, the rate of SR Ca release increased to an early peak and then rapidly decreased several-fold to a quasi-steady level. The total amount of Ca released from the SR at the time of peak rate of release appeared to be independent of SR Ca content, consistent with the idea that a single activated channel might pass, on average, a fixed number of ions, independent of the magnitude of the single channel flux. A possible explanation of this property is given in terms of locally induced Ca inactivation of Ca release. The solution in the end pools was then changed to one with PDAA plus fura-2. SR Ca release was estimated from the [Ca] transient, as before, and from the delta [Cafura-2] signal. On average, 2-3 mM fura-2 increased the quasi-steady level of the rate of SR Ca release by factors of 6.6 and 3.8, respectively, in three fibers from Rana temporaria and three fibers from Rana pipiens. The peak rate of release was increased in five of the six fibers but to a lesser extent than the quasi-steady level. In all fibers, the amplitude of the free [Ca] transient was markedly reduced. These increases in the rate of SR Ca release are consistent with the idea that Ca inactivation of Ca release develops during a step depolarization to 10 mV and that 2-3 mM fura-2 is able to reduce this inactivation by complexing Ca and thereby reducing free [Ca]. Once the concentration of fura-2 becomes sufficiently large, a further increase reduces the rate of SR Ca release. On average, 5-6 mM fura-2 increased the quasi-steady rate of release, compared with 0 mM fura-2, by 6.5 and 2.9, respectively, in four fibers from Rana temporaria and three from Rana pipiens.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:8228914
Raman-Spektren der Hexathiohypodiphosphate des NH4, Mg, Ca, Sr und Ba
NASA Astrophysics Data System (ADS)
Pätzmann, Ulrich; Brockner, Wolfgang
1987-06-01
The title compounds have been prepared and their Raman spectra recorded. The observed frequencies of (NH4)4P2S6 and Mg2P2S6 are assigned on the basis of P2S64- units with D3d symmetry. The Raman spectra of the Calcium, Strontium and Barium compounds indicate symmetry splitting, therefore the P2S64- frequencies are assigned with C2h symmetry. This assignment is supported by the correlation D3d → C2h. It is concluded that Sr2P2S6 and Ba2P2S6 crystallize in the monoclinic modification II.
Fisher, Donald W.
1967-01-01
A 2-year study of precipitation composition over eastern North Carolina and southeastern Virginia has been completed. Chemical analyses were made of the major ions in monthly rainfall samples from each of 12 sampling locations. Areal and seasonal distributions were determined for chloride, calcium, magnesium, sodium, potassium, sulfate, and nitrate. Annual changes in loads and in geographical distribution of sulfate and of nitrate are small. Yearly rainfall sulfate loads amount to approximately 7 tons per square mile, whereas deposition of nitrate is about 2 tons per square mile per year in the interior of the network and less near the coast. Areal patterns of chloride content are consistent with the assumption that the ocean is the only major source of rainfall chloride in the area. Chloride loads were 2.1 and 1.8 tons per square mile per year; the difference can be attributed to meteorological conditions. Cation concentrations in network precipitation appear to depend on localized sources, probably soil dust. Annual loads of the major cations are approximately 2 tons per square mile of calcium, 1.8 tons per square mile of sodium, 0.5 ton per square mile of magnesium, and 0.3 ton per square mile of potassium; considerable year-to-year differences were noted in these values. Bicarbonate and hydrogen ion in network rainfall are closely related to the relative concentrations of sulfate and calcium. Apparently, reaction of an acidic sulfur-containing aerosol with an alkaline calcium source is one of the principal controls on precipitation alkalinity and pH. Ions in precipitation contribute substantially to the quality of surface water in the network area. Comparisons between precipitation input and stream export of ions for four North Carolina rivers show that rainfall sulfate is equal to sulfate discharged, whereas nitrate in rain slightly exceeds stream nitrate. Contributions of cations to the streams by way of precipitation range from about 20 percent for potassium to almost 50 percent for calcium. Chloride deposited by precipitation amounts to about one-fourth of the stream load. Additions of manufactured salt may account for much of the remainder of the surface-water load.
Calcium-independent metal-ion catalytic mechanism of anthrax edema factor
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shen, Yuequan; Zhukovskaya, Natalia L.; Guo, Qing
2009-11-18
Edema factor (EF), a key anthrax exotoxin, has an anthrax protective antigen-binding domain (PABD) and a calmodulin (CaM)-activated adenylyl cyclase domain. Here, we report the crystal structures of CaM-bound EF, revealing the architecture of EF PABD. CaM has N- and C-terminal domains and each domain can bind two calcium ions. Calcium binding induces the conformational change of CaM from closed to open. Structures of the EF-CaM complex show how EF locks the N-terminal domain of CaM into a closed conformation regardless of its calcium-loading state. This represents a mechanism of how CaM effector alters the calcium affinity of CaM andmore » uncouples the conformational change of CaM from calcium loading. Furthermore, structures of EF-CaM complexed with nucleotides show that EF uses two-metal-ion catalysis, a prevalent mechanism in DNA and RNA polymerases. A histidine (H351) further facilitates the catalysis of EF by activating a water to deprotonate 3'OH of ATP. Mammalian adenylyl cyclases share no structural similarity with EF and they also use two-metal-ion catalysis, suggesting the catalytic mechanism-driven convergent evolution of two structurally diverse adenylyl cyclases.« less
Uskoković, Vuk; Batarni, Samir Shariff; Schweicher, Julien; King, Andrew; Desai, Tejal A.
2013-01-01
Powders composed of four morphologically different calcium phosphate particles were prepared by precipitation from aqueous solutions: flaky, brick-like, elongated orthogonal, and spherical. The particles were then loaded with either clindamycin phosphate as the antibiotic of choice, or fluorescein, a model molecule used to assess the drug release properties. A comparison was carried out of the comparative effect of such antibiotic-releasing materials on: sustained drug release profiles; Staphylococcus aureus growth inhibition; and osteogenic propensities in vitro. Raman spectroscopic analysis indicated the presence of various calcium phosphate phases, including monetite (flaky and elongated orthogonal particles), octacalcium phosphate (brick-shaped particles) and hydroxyapatite (spherical particles). Testing the antibiotic-loaded calcium phosphate powders for bacterial growth inhibition demonstrated satisfying antibacterial properties both in broths and on agar plates. All four calcium-phosphate-fluorescein powders exhibited sustained drug release over 21 days. The calcium phosphate sample with the highest specific surface area and the smallest, spherical particle size was the most effective in both drug loading and release, consequently having the highest antibacterial efficiency. Moreover, the highest cell viability, the largest gene expression upregulation of three different osteogenic markers – osteocalcin, osteopontin and Runx2 - as well as the least disrupted cell cytoskeleton and cell morphologies were also noticed for the calcium phosphate powder composed of smallest, spherical nanosized particles. Still, all four powders exerted a viable effect on osteoblastic MC3T3-E1 cells in vitro, as evidenced by both morphological assessments on fluorescently stained cells and measurements of their mitochondrial activity. The obtained results suggest that the nanoscale particle size and the corresponding coarseness of the surface of particle conglomerates as the cell attachment points may present a favorable starting point for the development of calcium-phosphate-based osteogenic drug delivery devices. PMID:23484624
Direct Imaging of ER Calcium with Targeted-Esterase Induced Dye Loading (TED)
Samtleben, Samira; Jaepel, Juliane; Fecher, Caroline; Andreska, Thomas; Rehberg, Markus; Blum, Robert
2013-01-01
Visualization of calcium dynamics is important to understand the role of calcium in cell physiology. To examine calcium dynamics, synthetic fluorescent Ca2+ indictors have become popular. Here we demonstrate TED (= targeted-esterase induced dye loading), a method to improve the release of Ca2+ indicator dyes in the ER lumen of different cell types. To date, TED was used in cell lines, glial cells, and neurons in vitro. TED bases on efficient, recombinant targeting of a high carboxylesterase activity to the ER lumen using vector-constructs that express Carboxylesterases (CES). The latest TED vectors contain a core element of CES2 fused to a red fluorescent protein, thus enabling simultaneous two-color imaging. The dynamics of free calcium in the ER are imaged in one color, while the corresponding ER structure appears in red. At the beginning of the procedure, cells are transduced with a lentivirus. Subsequently, the infected cells are seeded on coverslips to finally enable live cell imaging. Then, living cells are incubated with the acetoxymethyl ester (AM-ester) form of low-affinity Ca2+ indicators, for instance Fluo5N-AM, Mag-Fluo4-AM, or Mag-Fura2-AM. The esterase activity in the ER cleaves off hydrophobic side chains from the AM form of the Ca2+ indicator and a hydrophilic fluorescent dye/Ca2+ complex is formed and trapped in the ER lumen. After dye loading, the cells are analyzed at an inverted confocal laser scanning microscope. Cells are continuously perfused with Ringer-like solutions and the ER calcium dynamics are directly visualized by time-lapse imaging. Calcium release from the ER is identified by a decrease in fluorescence intensity in regions of interest, whereas the refilling of the ER calcium store produces an increase in fluorescence intensity. Finally, the change in fluorescent intensity over time is determined by calculation of ΔF/F0. PMID:23685703
Direct imaging of ER calcium with targeted-esterase induced dye loading (TED).
Samtleben, Samira; Jaepel, Juliane; Fecher, Caroline; Andreska, Thomas; Rehberg, Markus; Blum, Robert
2013-05-07
Visualization of calcium dynamics is important to understand the role of calcium in cell physiology. To examine calcium dynamics, synthetic fluorescent Ca(2+) indictors have become popular. Here we demonstrate TED (= targeted-esterase induced dye loading), a method to improve the release of Ca(2+) indicator dyes in the ER lumen of different cell types. To date, TED was used in cell lines, glial cells, and neurons in vitro. TED bases on efficient, recombinant targeting of a high carboxylesterase activity to the ER lumen using vector-constructs that express Carboxylesterases (CES). The latest TED vectors contain a core element of CES2 fused to a red fluorescent protein, thus enabling simultaneous two-color imaging. The dynamics of free calcium in the ER are imaged in one color, while the corresponding ER structure appears in red. At the beginning of the procedure, cells are transduced with a lentivirus. Subsequently, the infected cells are seeded on coverslips to finally enable live cell imaging. Then, living cells are incubated with the acetoxymethyl ester (AM-ester) form of low-affinity Ca(2+) indicators, for instance Fluo5N-AM, Mag-Fluo4-AM, or Mag-Fura2-AM. The esterase activity in the ER cleaves off hydrophobic side chains from the AM form of the Ca(2+) indicator and a hydrophilic fluorescent dye/Ca(2+) complex is formed and trapped in the ER lumen. After dye loading, the cells are analyzed at an inverted confocal laser scanning microscope. Cells are continuously perfused with Ringer-like solutions and the ER calcium dynamics are directly visualized by time-lapse imaging. Calcium release from the ER is identified by a decrease in fluorescence intensity in regions of interest, whereas the refilling of the ER calcium store produces an increase in fluorescence intensity. Finally, the change in fluorescent intensity over time is determined by calculation of ΔF/F0.
Jing, Da; Baik, Andrew D.; Lu, X. Lucas; Zhou, Bin; Lai, Xiaohan; Wang, Liyun; Luo, Erping; Guo, X. Edward
2014-01-01
Osteocytes have been hypothesized to be the major mechanosensors in bone. How in situ osteocytes respond to mechanical stimuli is still unclear because of technical difficulties. In vitro studies have shown that osteocytes exhibited unique calcium (Ca2+) oscillations to fluid shear. However, whether this mechanotransduction phenomenon holds for in situ osteocytes embedded within a mineralized bone matrix under dynamic loading remains unknown. Using a novel synchronized loading/imaging technique, we successfully visualized in real time and quantified Ca2+ responses in osteocytes and bone surface cells in situ under controlled dynamic loading on intact mouse tibia. The resultant fluid-induced shear stress on the osteocyte in the lacunocanalicular system (LCS) was also quantified. Osteocytes, but not surface cells, displayed repetitive Ca2+ spikes in response to dynamic loading, with spike frequency and magnitude dependent on load magnitude, tissue strain, and shear stress in the LCS. The Ca2+ oscillations were significantly reduced by endoplasmic reticulum (ER) depletion and P2 purinergic receptor (P2R)/phospholipase C (PLC) inhibition. This study provides direct evidence that osteocytes respond to in situ mechanical loading by Ca2+ oscillations, which are dependent on the P2R/PLC/inositol trisphosphate/ER pathway. This study develops a novel approach in skeletal mechanobiology and also advances our fundamental knowledge of bone mechanotransduction.—Jing, D., Baik, A. D., Lu, X. L., Zhou, B., Lai, X., Wang, L., Luo, E., Guo, X. E. In situ intracellular calcium oscillations in osteocytes in intact mouse long bones under dynamic mechanical loading. PMID:24347610
Age and gender specific biokinetic model for strontium in humans
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shagina, N. B.; Tolstykh, E. I.; Degteva, M. O.
A biokinetic model for strontium in humans is necessary for quantification of internal doses due to strontium radioisotopes. The ICRP-recommended biokinetic model for strontium has limitation for use in a population study, because it is not gender specific and does not cover all age ranges. The extensive Techa River data set on 90Sr in humans (tens of thousands of measurements) is a unique source of data on long-term strontium retention for men and women of all ages at intake. These, as well as published data, were used for evaluation of age- and gender-specific parameters for a new compartment biokinetic modelmore » for strontium (Sr-AGe model). The Sr-AGe model has similar structure as the ICRP model for the alkaline earth elements. The following parameters were mainly reevaluated: gastro-intestinal absorption and parameters related to the processes of bone formation and resorption defining calcium and strontium transfers in skeletal compartments. The Sr-AGe model satisfactorily describes available data sets on strontium retention for different kinds of intake (dietary and intravenous) at different ages (0–80 years old) and demonstrates good agreement with data sets for different ethnic groups. The Sr-AGe model can be used for dose assessment in epidemiological studies of general population exposed to ingested strontium radioisotopes.« less
NASA Astrophysics Data System (ADS)
Gioncada, A.; Petrini, R.; Bosio, G.; Gariboldi, K.; Collareta, A.; Malinverno, E.; Bonaccorsi, E.; Di Celma, C.; Pasero, M.; Urbina, M.; Bianucci, G.
2018-01-01
The late Miocene Pisco Formation of Peru is an outstanding example of richness and high-quality preservation of fossil marine vertebrates. In order to reconstruct the fossilization path, we present new textural, mineralogical and Sr-isotope data of diagenetic minerals formed in correspondence of fossil specimens such as marine vertebrates and mollusks. These fossil specimens were found at Cerro los Quesos, in the Ica Desert, within the diatomaceous strata of the Pisco Formation. Dolomite, gypsum, anhydrite and Mn minerals are the main phases found, while the calcium carbonate originally forming the mollusk valves is replaced by gypsum. An early formation of dolomite and of Mn minerals, triggered by the modifications of the geochemical environment due to organic matter degradation, is suggested by the textural relationships and is confirmed by the Sr isotopic ratio of dolomite, which agrees with that of seawater at the time of sedimentation. Instead, gypsum Sr isotopic ratios indicate a pre-Miocene seawater-derived brine circulating within the sedimentary sequence as a source for Sr. Oxidation of diagenetic sulfide causing a lowering of the pH of porewater is proposed as an explanation for Ca-carbonate dissolution. The diagenetic chemical environment was, nevertheless, favorable to bone preservation.
NASA Astrophysics Data System (ADS)
Hale, C. A.; Carling, G. T.; Fernandez, D. P.; Nelson, S.; Aanderud, Z.; Tingey, D. G.; Dastrup, D.
2017-12-01
Water chemistry in mountain streams is variable during spring snowmelt as shallow groundwater flow paths are activated in the watershed, introducing solutes derived from soil water. Sr isotopes and other tracers can be used to differentiate waters that have interacted with soils and dust (shallow groundwater) and bedrock (deep groundwater). To investigate processes controlling water chemistry during snowmelt, we analyzed 87Sr/86Sr ratios, Sr and other trace element concentrations in bulk snowpack, dust, soil, soil water, ephemeral channels, and river water during snowmelt runoff in the upper Provo River watershed in northern Utah, USA, over four years (2014-2017). Strontium concentrations in the river averaged 20 ppb during base flow and decreased to 10 ppb during snowmelt runoff. 87Sr/86Sr ratios were around 0.717 during base flow and decreased to 0.715 in 2014 and 0.713 in 2015 and 2016 during snowmelt, trending towards less radiogenic values of mineral dust inputs in the Uinta Mountain soils. Ephemeral channels, representing shallow flow paths with soil water inputs, had Sr concentrations between 7-20 ppb and 87Sr/86Sr ratios between 0.713-0.716. Snowpack Sr concentrations were generally <2 ppb with 87Sr/86Sr ratios between 0.710-711, similar to atmospheric dust inputs. The less radiogenic 87Sr/86Sr ratios and lower Sr concentrations in the river during snowmelt are likely a result of activating shallow groundwater flow paths, which allows melt water to interact with shallow soils that contain accumulated dust deposits with a less radiogenic 87Sr/86Sr ratio. These results suggest that flow paths and atmospheric dust are important to consider when investigating variable solute loads in mountain streams.
Engineering analysis of lightweight high-opacity newsprint production by fiber loading
John H. Klungness; Matthew L. Stroika; Marguerite S. Sykes; Said M. Abubakr; Werner Witek; Oliver U. Heise
1999-01-01
We estimated the capital effectiveness of fiber loading in regard to producing lightweight high-opacity newsprint. Fiber loading enhances fiber bonding at increased precipitated calcium carbonate levels without significant loss in Canadian standard freeness or additional use of energy. We investigated the return on investment (ROI) for fiber loading precipitated...
Heavy metal cations permeate the TRPV6 epithelial cation channel.
Kovacs, Gergely; Danko, Tamas; Bergeron, Marc J; Balazs, Bernadett; Suzuki, Yoshiro; Zsembery, Akos; Hediger, Matthias A
2011-01-01
TRPV6 belongs to the vanilloid family of the transient receptor potential channel (TRP) superfamily. This calcium-selective channel is highly expressed in the duodenum and the placenta, being responsible for calcium absorption in the body and fetus. Previous observations have suggested that TRPV6 is not only permeable to calcium but also to other divalent cations in epithelial tissues. In this study, we tested whether TRPV6 is indeed also permeable to cations such as zinc and cadmium. We found that the basal intracellular calcium concentration was higher in HEK293 cells transfected with hTRPV6 than in non-transfected cells, and that this difference almost disappeared in nominally calcium-free solution. Live cell imaging experiments with Fura-2 and NewPort Green DCF showed that overexpression of human TRPV6 increased the permeability for Ca(2+), Ba(2+), Sr(2+), Mn(2+), Zn(2+), Cd(2+), and interestingly also for La(3+) and Gd(3+). These results were confirmed using the patch clamp technique. (45)Ca uptake experiments showed that cadmium, lanthanum and gadolinium were also highly efficient inhibitors of TRPV6-mediated calcium influx at higher micromolar concentrations. Our results suggest that TRPV6 is not only involved in calcium transport but also in the transport of other divalent cations, including heavy metal ions, which may have toxicological implications. Copyright © 2010 Elsevier Ltd. All rights reserved.
Modulation of cardiac contractility by the phospholamban/SERCA2a regulatome.
Kranias, Evangelia G; Hajjar, Roger J
2012-06-08
Heart disease remains the leading cause of death and disability in the Western world. Current therapies aim at treating the symptoms rather than the subcellular mechanisms, underlying the etiology and pathological remodeling in heart failure. A universal characteristic, contributing to the decreased contractile performance in human and experimental failing hearts, is impaired calcium sequestration into the sarcoplasmic reticulum (SR). SR calcium uptake is mediated by a Ca(2+)-ATPase (SERCA2), whose activity is reversibly regulated by phospholamban (PLN). Dephosphorylated PLN is an inhibitor of SERCA and phosphorylation of PLN relieves this inhibition. However, the initial simple view of a PLN/SERCA regulatory complex has been modified by our recent identification of SUMO, S100 and the histidine-rich Ca-binding protein as regulators of SERCA activity. In addition, PLN activity is regulated by 2 phosphoproteins, the inhibitor-1 of protein phosphatase 1 and the small heat shock protein 20, which affect the overall SERCA-mediated Ca-transport. This review will highlight the regulatory mechanisms of cardiac contractility by the multimeric SERCA/PLN-ensemble and the potential for new therapeutic avenues targeting this complex by using small molecules and gene transfer methods.
Han, Yong; Zhou, Jianhong; Zhang, Lan; Xu, Kewei
2011-07-08
We report here, for the first time, a novel multi-scaled hybrid orthopedic implant material consisting of a macroporous Ti scaffold, whose macropores' walls have a microporous titania layer which is fully covered with nanofibers of Sr-doped hydroxyapatite (Sr-HA). The microporous titania layer is formed on and within the Ti scaffold by micro-arc oxidation, which firmly binds to the Ti substrate and contains Ca2+, Sr2+ and PO4(3-) ions. It is then hydrothermally treated to form Sr-HA nanofibers. During the hydrothermal treatment, Sr-HA nanoprisms nucleate from Ca0.5Sr0.5TiO3 pre-formed on the TiO2 and grow in length to nanofibers at the expense of Ca2+, Sr2+ and PO4(3-) ions that migrate from the TiO2. These Sr-HA nanofibers construct a network structure similar to the hierarchical organization of bone extracellular matrix (ECM), and the resulting nanofibrous surface displays a firm adhesion to substrate, superhydrophilicity and apatite-inducing ability. The induced apatite prefers to nucleate on the basal-faceted surfaces of Sr-HA nanofibers. The nanofiber-walled scaffold has a great potential for load-bearing orthotopic use.
NASA Astrophysics Data System (ADS)
Han, Yong; Zhou, Jianhong; Zhang, Lan; Xu, Kewei
2011-07-01
We report here, for the first time, a novel multi-scaled hybrid orthopedic implant material consisting of a macroporous Ti scaffold, whose macropores' walls have a microporous titania layer which is fully covered with nanofibers of Sr-doped hydroxyapatite (Sr-HA). The microporous titania layer is formed on and within the Ti scaffold by micro-arc oxidation, which firmly binds to the Ti substrate and contains Ca2 + , Sr2 + and PO43 - ions. It is then hydrothermally treated to form Sr-HA nanofibers. During the hydrothermal treatment, Sr-HA nanoprisms nucleate from Ca0.5Sr0.5TiO3 pre-formed on the TiO2 and grow in length to nanofibers at the expense of Ca2 + , Sr2 + and PO43 - ions that migrate from the TiO2. These Sr-HA nanofibers construct a network structure similar to the hierarchical organization of bone extracellular matrix (ECM), and the resulting nanofibrous surface displays a firm adhesion to substrate, superhydrophilicity and apatite-inducing ability. The induced apatite prefers to nucleate on the basal-faceted surfaces of Sr-HA nanofibers. The nanofiber-walled scaffold has a great potential for load-bearing orthotopic use.
Dielectric response of high permittivity polymer ceramic composite with low loss tangent
DOE Office of Scientific and Technical Information (OSTI.GOV)
Subodh, G.; 1.Physikalisches Institut, Universitat Stuttgart, Pfaffenwaldring 57, Stuttgart 70550; Deepu, V.
2009-08-10
The present communication investigates the dielectric response of the Sr{sub 9}Ce{sub 2}Ti{sub 12}O{sub 36} ceramics loaded high density polyethylene and epoxy resin. Sr{sub 9}Ce{sub 2}Ti{sub 12}O{sub 36} ceramic filled polyethylene and epoxy composites were prepared using hot blending and mechanical mixing, respectively. 40 vol % ceramic loaded polyethylene has relative permittivity of 12.1 and loss tangent of 0.004 at 8 GHz, whereas the corresponding composite using epoxy as matrix has permittivity and loss tangent of 14.1 and 0.022, respectively. The effective medium theory fits relatively well for the observed permittivity of these composites.
Typical tropospheric aerosol backscatter profiles for Southern Ireland: The Cork Raman lidar
NASA Astrophysics Data System (ADS)
McAuliffe, Michael A. P.; Ruth, Albert A.
2013-02-01
A Raman lidar instrument (UCLID) was established at the University College Cork as part of the European lidar network EARLINET. Raman backscatter coefficients, extinction coefficients and lidar ratios were measured within the period 28/08/2010 and 24/04/2011. Typical atmospheric scenarios over Southern Ireland in terms of the aerosol load in the planetary boundary layer are outlined. The lidar ratios found are typical for marine atmospheric condition (lidar ratio ca. 20-25 sr). The height of the planetary boundary layer is below 1000 m and therefore low in comparison to heights found at other lidar sites in Europe. On the 21st of April a large aerosol load was detected, which was assigned to a Saharan dust event based on HYSPLIT trajectories and DREAM forecasts along with the lidar ratio (70 sr) for the period concerned. The dust was found at two heights, pure dust at 2.5 km and dust mixing with pollution from 0.7 to 1.8 km with a lidar ratio of 40-50 sr.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hawkins, C.; Dietz, M.; Kaminski, M.
2016-03-01
A technical program to support the Centers of Disease Control and Prevention is being developed to provide an analytical method for rapid extraction of Sr-90 from urine, with the intent of assessing the general population’s exposure during an emergency response to a radiological terrorist event. Results are presented on the progress in urine sample preparation and chemical separation steps that provide an accurate and quantitative detection of Sr-90 based upon an automated column separation sequence and a liquid scintillation assay. Batch extractions were used to evaluate the urine pretreatment and the column separation efficiency and loading capacity based upon commercial,more » extractant-loaded resins. An efficient pretreatment process for decolorizing and removing organics from urine without measurable loss of radiostrontium from the sample was demonstrated. In addition, the Diphonix® resin shows promise for the removal of high concentrations of common strontium interferents in urine as a first separation step for Sr-90 analysis.« less
Risitano, Salvatore; Sabatini, Luigi; Atzori, Francesco; Massè, Alessandro; Indelli, Pier Francesco
2018-06-01
Periprosthetic joint infection (PJI) is a serious complication in total knee arthroplasty (TKA) and represents one of the most common causes of revision. The challenge for surgeons treating an infected TKA is to quickly obtain an infection-free joint in order to re-implant, when possible, a new TKA. Recent literature confirms the role of local antibiotic-loaded beads as a strong bactericidal, allowing higher antibiotic elution when compared with antibiotic loaded spacers only. Unfortunately, classical Polymethylmethacrylate (PMMA) beads might allow bacteria adhesion, secondary development of antibiotic resistance and eventually surgical removal once antibiotics have eluted. This article describes a novel surgical technique using static, custom-made antibiotic loaded spacers augmented by calcium sulphate antibiotic-impregnated beads to improve the success rate of revision TKA in a setting of PJI. The use of calcium sulphate beads has several potential benefits, including a longer sustained local antibiotic release when compared with classical PMMA beads and, being resorbable, not requiring accessory surgical interventions.
Kanter, Ulrike; Hauser, Andreas; Michalke, Bernhard; Dräxl, Stephan; Schäffner, Anton R.
2010-01-01
Due to the physico-chemical similarities of caesium (Cs+) to potassium (K+) on the one hand and strontium (Sr2+) to calcium (Ca2+) on the other hand, both elements can easily be taken up by plants and thus enter the food chain. This could be detrimental when radionuclides such as 137Cs and 90Sr are involved. In this study, both genetic and physiological aspects of Cs+ and Sr2+ accumulation in Arabidopsis thaliana were investigated using 86 Arabidopsis accessions and a segregating F2 population of the low Cs+ accumulating Sq-1 (Ascot, UK) crossed with the high uptaking Sorbo (Khurmatov, Tajikistan). Hydroponically grown plants were exposed to subtoxic levels of Cs+ and Sr2+ using radioactive isotopes as tracers. In the natural accessions shoot concentration of Cs+ as well as Sr2+ varied about 2-fold, whereas its heritability ranged for both ions between 0.60 and 0.73. Shoot accumulation of Cs+ and Sr2+ could be compromised by increasing concentrations of their essential analogues K+ and Ca2+, respectively, causing a reduction of up to 80%. In the case of the segregating F2/F3 population Sq-1×Sorbo, this study identified several QTL for the trait Cs+ and Sr2+ accumulation, with main QTL on chromosomes 1 and 5. According to the correlation and discrimination surveys combined with QTL-analysis Cs+ and Sr2+ uptake seemed to be mediated mostly via non-selective cation channels. A polymorphism, affecting amino acids close to the K+-pore of one candidate, CYCLIC-NUCLEOTIDE-GATED CHANNEL 1 (CNGC1), was identified in Sorbo and associated with high Cs+ concentrating accessions. PMID:20624763
Koua, Faisal Hammad Mekky; Umena, Yasufumi; Kawakami, Keisuke; Shen, Jian-Ren
2013-03-05
Oxygen-evolving complex of photosystem II (PSII) is a tetra-manganese calcium penta-oxygenic cluster (Mn4CaO5) catalyzing light-induced water oxidation through several intermediate states (S-states) by a mechanism that is not fully understood. To elucidate the roles of Ca(2+) in this cluster and the possible location of water substrates in this process, we crystallized Sr(2+)-substituted PSII from Thermosynechococcus vulcanus, analyzed its crystal structure at a resolution of 2.1 Å, and compared it with the 1.9 Å structure of native PSII. Our analysis showed that the position of Sr was moved toward the outside of the cubane structure of the Mn4CaO5-cluster relative to that of Ca(2+), resulting in a general elongation of the bond distances between Sr and its surrounding atoms compared with the corresponding distances in the Ca-containing cluster. In particular, we identified an apparent elongation in the bond distance between Sr and one of the two terminal water ligands of Ca(2+), W3, whereas that of the Sr-W4 distance was not much changed. This result may contribute to the decrease of oxygen evolution upon Sr(2+)-substitution, and suggests a weak binding and rather mobile nature of this particular water molecule (W3), which in turn implies the possible involvement of this water molecule as a substrate in the O-O bond formation. In addition, the PsbY subunit, which was absent in the 1.9 Å structure of native PSII, was found in the Sr-PSII structure.
Strategic Positioning and Biased Activity of the Mitochondrial Calcium Uniporter in Cardiac Muscle*
De La Fuente, Sergio; Fernandez-Sanz, Celia; Vail, Caitlin; Agra, Elorm J.; Holmstrom, Kira; Sun, Junhui; Mishra, Jyotsna; Williams, Dewight; Finkel, Toren; Murphy, Elizabeth; Joseph, Suresh K.; Sheu, Shey-Shing; Csordás, György
2016-01-01
Control of myocardial energetics by Ca2+ signal propagation to the mitochondrial matrix includes local Ca2+ delivery from sarcoplasmic reticulum (SR) ryanodine receptors (RyR2) to the inner mitochondrial membrane (IMM) Ca2+ uniporter (mtCU). mtCU activity in cardiac mitochondria is relatively low, whereas the IMM surface is large, due to extensive cristae folding. Hence, stochastically distributed mtCU may not suffice to support local Ca2+ transfer. We hypothesized that mtCU concentrated at mitochondria-SR associations would promote the effective Ca2+ transfer. mtCU distribution was determined by tracking MCU and EMRE, the proteins essential for channel formation. Both proteins were enriched in the IMM-outer mitochondrial membrane (OMM) contact point submitochondrial fraction and, as super-resolution microscopy revealed, located more to the mitochondrial periphery (inner boundary membrane) than inside the cristae, indicating high accessibility to cytosol-derived Ca2+ inputs. Furthermore, MCU immunofluorescence distribution was biased toward the mitochondria-SR interface (RyR2), and this bias was promoted by Ca2+ signaling activity in intact cardiomyocytes. The SR fraction of heart homogenate contains mitochondria with extensive SR associations, and these mitochondria are highly enriched in EMRE. Size exclusion chromatography suggested for EMRE- and MCU-containing complexes a wide size range and also revealed MCU-containing complexes devoid of EMRE (thus disabled) in the mitochondrial but not the SR fraction. Functional measurements suggested more effective mtCU-mediated Ca2+ uptake activity by the mitochondria of the SR than of the mitochondrial fraction. Thus, mtCU “hot spots” can be formed at the cardiac muscle mitochondria-SR associations via localization and assembly bias, serving local Ca2+ signaling and the excitation-energetics coupling. PMID:27637331
Endotrophic Calcium, Strontium, and Barium Spores of Bacillus megaterium and Bacillus cereus1
Foerster, Harold F.; Foster, J. W.
1966-01-01
Foerster, Harold F. (The University of Texas, Austin), and J. W. Foster. Endotrophic calcium, strontium, and barium spores of Bacillus megaterium and Bacillus cereus. J. Bacteriol. 91:1333–1345. 1966.—Spores were produced by washed vegetative cells suspended in deionized water supplemented with CaCl2, SrCl2, or BaCl2. Normal, refractile spores were produced in each case; a portion of the barium spores lost refractility and darkened. Thin-section electron micrographs revealed no apparent anatomical differences among the three types of spores. Analyses revealed that the different spore types were enriched specifically in the metal to which they were exposed during sporogenesis. The calcium content of the strontium and the barium spores was very small. From binary equimolar mixtures of the metal salts, endotrophic spores accumulated both metals to nearly the same extent. Viability of the barium spores was considerably less than that of the other two types. Strontium and barium spores were heat-resistant; however, calcium was essential for maximal heat resistance. Significant differences existed in the rates of germination; calcium spores germinated fastest, strontium spores were slower, and barium spores were slowest. Calcium-barium and calcium-strontium spores germinated readily. Endotrophic calcium and strontium spores germinated without the prior heat activation essential for growth spores. Chemical germination of the different metal-type spores with n-dodecylamine took place at the same relative rates as physiological germination. Heat-induced release of dipicolinic acid occurred much faster with barium and strontium spores than with calcium spores. The washed “coat fraction” from disrupted spores contained little of the spore calcium but most of the spore barium. The metal in this fraction was released by dilute acid. The demineralized coats reabsorbed calcium and barium at neutral pH. Images PMID:4956334
Douglas, Timothy E L; Dziadek, Michal; Gorodzha, Svetlana; Lišková, Jana; Brackman, Gilles; Vanhoorne, Valérie; Vervaet, Chris; Balcaen, Lieve; Del Rosario Florez Garcia, Maria; Boccaccini, Aldo R; Weinhardt, Venera; Baumbach, Tilo; Vanhaecke, Frank; Coenye, Tom; Bačáková, Lucie; Surmeneva, Maria A; Surmenev, Roman A; Cholewa-Kowalska, Katarzyna; Skirtach, Andre G
2018-06-01
Mineralization of hydrogel biomaterials is desirable to improve their suitability as materials for bone regeneration. In this study, gellan gum (GG) hydrogels were formed by simple mixing of GG solution with bioactive glass microparticles of 45S5 composition, leading to hydrogel formation by ion release from the amorphous bioactive glass microparticles. This resulted in novel injectable, self-gelling composites of GG hydrogels containing 20% bioactive glass. Gelation occurred within 20 min. Composites containing the standard 45S5 bioactive glass preparation were markedly less stiff. X-ray microcomputed tomography proved to be a highly sensitive technique capable of detecting microparticles of diameter approximately 8 μm, that is, individual microparticles, and accurately visualizing the size distribution of bioactive glass microparticles and their aggregates, and their distribution in GG hydrogels. The widely used melt-derived 45S5 preparation served as a standard and was compared with a calcium-rich, sol-gel derived preparation (A2), as well as A2 enriched with zinc (A2Zn5) and strontium (A2Sr5). A2, A2Zn, and A2Sr bioactive glass particles were more homogeneously dispersed in GG hydrogels than 45S5. Composites containing all four bioactive glass preparations exhibited antibacterial activity against methicillin-resistant Staphylococcus aureus. Composites containing A2Zn5 and A2Sr5 bioactive glasses supported the adhesion and growth of osteoblast-like cells and were considerably more cytocompatible than 45S5. All composites underwent mineralization with calcium-deficient hydroxyapatite upon incubation in simulated body fluid. The extent of mineralization appeared to be greatest for composites containing A2Zn5 and 45S5. The results underline the importance of the choice of bioactive glass when preparing injectable, self-gelling composites. Copyright © 2018 John Wiley & Sons, Ltd.
Simulating the Transfer of Strontium-90 from Soil to Leafy Vegetables by Using Strontium-88.
Kuke, Ding; Shujuan, Liu; Yingxue, He; Dong, Yan; Fengshou, Zhang; Shuifeng, Wang; Jinghua, Guo; Wei, Zhang; Xin, Wang; Xiaoyan, Jiang
The transfer, from soil to Chinese cabbage and spinach, of radioactive strontium-90 released as a result of accidents in nuclear power stations was studied using a stable isotope of strontium, namely nuclide strontium-88 ( 88 Sr). The study led to an experimental model for assessing the hazard of radionuclide strontium-90 ( 90 Sr) entering the food chain and for predicting the risk to food safety. Chinese cabbage and spinach were grown in pots in a greenhouse and irrigated with deionized water containing known quantities of strontium. Based on the strontium content of that water, the plants were divided into five groups (treatments) and strontium content of the soil, and 30-day-old plants were determined by inductively coupled plasma atomic emission spectroscopy instrument (ICP-AES). Data on the strontium content of soil and plants enabled the development of a model using MATLAB, a mathematical software package, which included curve fitting and problem solving using regression equations and differential equations. Although strontium curves for leaves, stems, and roots of Chinese cabbage were not exactly the same, all showed a non-linear increase when compared with the increase in the content of strontium in soil. Strontium curves for leaves, stems, and roots of spinach were very similar and showed an initial increase followed by a decrease. Strontium concentrations in both Chinese cabbage and spinach were initially related to the concentrations of sodium and sulfur, the next two relevant nuclides being calcium and magnesium. The relationship between calcium and strontium in Chinese cabbage was different from that in spinach. By using 88 Sr to simulate the transfer of radionuclide 90 Sr from soil to a crop, the relevant data required to deal with accidental release of strontium can be obtained using a fitting curve and regression equations, thereby providing some experimental basis for evaluating the potential hazards posed by such accidents to the food chain.
Sulfur Cycling Mediates Calcium Carbonate Geochemistry in Modern Marine Stromatolites
NASA Technical Reports Server (NTRS)
Visscher, P. T.; Hoeft, S. E.; Bebout, B. M.; Reid, R. P.
2004-01-01
Modem marine stromatolites forming in Highborne Cay, Exumas (Bahamas), contain microbial mats dominated by Schizothrix. Although saturating concentrations of Ca2+ and CO32- exist, microbes mediate CaCO3 precipitation. Cyanobacterial photosynthesis in these stromatolites aids calcium carbonate precipitation by removal of HS+ through CO2 use. Photorespiration and exopolymer production predominantly by oxygenic phototrophs fuel heterotrophic activity: aerobic respiration (approximately 60 umol/sq cm.h) and sulfate reduction (SR; 1.2 umol SO42-/sq cm.h) are the dominant C- consuming processes. Aerobic microbial respiration and the combination of SR and H2S oxidation both facilitate CaCO3 dissolution through H+ production. Aerobic respiration consumes much more C on an hourly basis, but duel fluctuating O2 and H2 depth profiles indicate that overall, SR consumes only slightly less (0.2-0.5) of the primary production. Moreover, due to low O2 concentrations when SR rates are peaking, reoxidation of the H2S formed is incomplete: both thiosulfate and polythionates are formed. The process of complete H2S oxidation yields H+. However, due to a low O2 concentration late in the day and relatively high O2 concentrations early in the following morning, a two-stage oxidation takes place: first, polythionates are formed from H2S, creating alkalinity which coincides with CaCO3 precipitation; secondly, oxidation of polythionates to sulfate yields acidity, resulting in dissolution, etc. Vertical profiles confirmed that the pH peaked late in the afternoon (greater than 8.8) and had the lowest values (less than 7.4) early in the morning. Thus, the effect of this S-cycling through alkalinity production, followed by acidification during H2S oxidation, results in a six times stronger fluctuation in acidity than photosynthesis plus aerobic respiration accomplish. This implies that anaerobic processes play a pivotal role in stromatolite formation.
NASA Astrophysics Data System (ADS)
Li, Mei; He, Peng; Wu, Yuanhao; Zhang, Yu; Xia, Hong; Zheng, Yufeng; Han, Yong
2016-09-01
The influence of Mg-1Ca-xwt.% Sr (x = 0.2, 0.5, 1.0, 2.0) alloys on the osteogenic differentiation and mineralization of pre-osteoblast MC3T3-E1 were studied through typical differentiation markers, such as intracellular alkaline phosphatase (ALP) activity, extracellular collagen secretion and calcium nodule formation. It was shown that Mg-1Ca alloys with different content of Sr promoted cell viability and enhanced the differentiation and mineralization levels of osteoblasts, and Mg-1Ca-2.0Sr alloy had the most remarkable and significant effect among all. To further investigate the underlying mechanisms, RT-PCR and Western Blotting assays were taken to analyze the mRNA expression level of osteogenesis-related genes and intracellular signaling pathways involved in osteogenesis, respectively. RT-PCR results showed that Mg-1Ca-2.0Sr alloy significantly up-regulated the expressions of the transcription factors of Runt-related transcription factor 2 (RUNX2) and Osterix (OSX), Integrin subunits, as well as alkaline phosphatase (ALP), Bone sialoprotein (BSP), Collagen I (COL I), Osteocalcin (OCN) and Osteopontin (OPN). Western Blotting results suggested that Mg-1Ca-2.0Sr alloy rapidly induced extracellular signal-regulated kinase (ERK) activation but showed no obvious effects on c-Jun N terminal kinase (JNK) and p38 kinase of MAPK. Taken together, our results demonstrated that Mg-1Ca-2.0Sr alloy had excellent biocompatibility and osteogenesis via the ERK pathway and is expected to be promising as orthopedic implants and bone repair materials.
Taylor, Howard E.; Antweiler, Ronald C.; Brinton, Terry I.; Roth, David A.; Moody, John A.
1994-01-01
Extensive flooding in the upper Mississippi River Basin during summer 1993 had a significant effect on the water quality of the Mississippi River. To evaluate the change in temporal distribution and transport of dissolved constituents in the Mississippi River, six water samples were collected by a discharge-weighted method from July through September 1993 near Thebes, Illinois. Sampling at this location provided water-quality information from the upper Mississippi, the Missouri, and the Illinois River Basins. Dissolved major constituents that were analyzed in each of the samples included bicarbonate, calcium (Ca), carbonate (C03), chloride (Cl), dissolved organic carbon, magnesium (Mg), potassium (K), silica NOD, sodium (Na), and sulfate (S04). Dissolved nutrients included ammonium ion (NH4), nitrate (N03), nitrite (N02), and orthophosphate (P04) . Dissolved trace elements included aluminum (Al), arsenic (As), barium (Ba), boron (B), beryllium (Be), bromide (Br), cadmium (Cd), chromium (Cr), cobalt, (Co), copper (Cu), fluoride (F), iron (Fe), lead, lithium (Li), manganese (Mn), mercury (Hg), molybdenum (Mo), nickel (Ni), strontium (Sr), thallium, uranium (U), vanadium (V), and zinc (Zn). Other physical properties of water that were measured included specific conductance, pH and suspended-sediment concentration (particle size, less than 63 micrometers). Results of this study indicated that large quantities of dissolved constituents were transported through the river system. Generally, pH, alkalinity, and specific conductance and the concentrations of B, Br, Ca, Cl, Cr, K, Li, Mg, Mo, Na, S04, Sr, U, and V increased as water discharge decreased, while concentrations of F, Hg, and suspended sediment sharply decreased as water discharge decreased after the crest of the flood. Concentrations of other constituents, such as Al, As, Ba, Be, Co, Cu, Ni, N03, N02, NH4, P04, and Si02, varied with time as discharge decreased after the crest of the flood. For most constituents, the load transported during floods generally is much greater than that transported during low-flow conditions. How ever, for Cd, Cr, Fe, Mn, V, and Zn, loads increased substantially as water discharge decreased after the crest of the flood.
NASA Astrophysics Data System (ADS)
Alqadami, Abdulrahman Shueai Mohsen; Jamlos, Mohd Faizal; Soh, Ping Jack; Rahim, Sharul Kamal Abdul; Narbudowicz, Adam
2017-01-01
A compact coplanar waveguide-fed multiple-input multiple-output antenna array based on the left-handed wire loaded spiral resonators (SR) is presented. The proposed antenna consists of a 2 × 2 wire SR with two symmetrical microstrip feed lines, each line exciting a 1 × 2 wire SR. Left-handed metamaterial unit cells are placed on its reverse side and arranged in a 2 × 3 array. A reflection coefficient of less than -16 dB and mutual coupling of less than -28 dB are achieved at 5.15 GHz WLAN band.
Shahnazari, M; Lang, D H; Fosmire, G J; Sharkey, N A; Mitchell, A D; Leach, R M
2007-03-01
Genetic selection for rapid body growth in broiler chickens has resulted in adverse effects on the skeletal system exemplified by a higher rate of cortical fractures in leg bones. Strontium (Sr) has been reported to have beneficial effects on bone formation and strength. We supplemented the diet of 300-day-old chicks with increasing dosages of Sr (0%, 0.12%, or 0.24%) to study the capacity of the element to improve bone quality and mechanical integrity. Treatment with Sr increased cortical bone volume and reduced bone porosity as measured by micro-computed tomography. The higher level of Sr significantly reduced bone Ca content (34.7%) relative to controls (37.2%), suggesting that Sr replaced some of the Ca in bone. Material properties determined by the three-point bending test showed that bone in the Sr-treated groups withstood greater deformation prior to fracture. Load to failure and ultimate stress were similar across groups. Our results indicate that Sr treatment in rapidly growing chickens induced positive effects on bone volume but did not improve the breaking strength of long bones.
Ag loading induced visible light photocatalytic activity for pervoskite SrTiO3 nanofibers
NASA Astrophysics Data System (ADS)
Wu, Yeqiu; He, Tao
2018-06-01
The synthesis and photocatalytic activities of Ag-SrTiO3 nanofibers were reported in this work. The fabricated Ag-SrTiO3 nanofibers were characterized by TG-DSC, XRD, IR, XPS, SEM, TEM, DRS and ESR techniques. The XRD and IR results show that Ag-SrTiO3 nanofibers have a perovskite structure after the heat treatment at 700 °C. The XPS result shows that Ag element exists as Ag0 in the fabricated Ag-SrTiO3 nanofibers. The SEM and TEM images indicate the obtaining of nanofibers with porous structure. The photocatalytic activity of Ag-SrTiO3 nanofibers was evaluated by degrading RhB and MB under visible light irradiation. The Ag-SrTiO3 nanofibers show excellent photocatalytic activity under visible light irradiation because of the surface plasmon resonance effect of Ag0. In the photocatalysis process of RhB and MB, lots of hydroxyl radicals were generated, which plays the key role in the decomposition of organic pollutants.
Ag loading induced visible light photocatalytic activity for pervoskite SrTiO3 nanofibers.
Wu, Yeqiu; He, Tao
2018-06-15
The synthesis and photocatalytic activities of Ag-SrTiO 3 nanofibers were reported in this work. The fabricated Ag-SrTiO 3 nanofibers were characterized by TG-DSC, XRD, IR, XPS, SEM, TEM, DRS and ESR techniques. The XRD and IR results show that Ag-SrTiO 3 nanofibers have a perovskite structure after the heat treatment at 700°C. The XPS result shows that Ag element exists as Ag 0 in the fabricated Ag-SrTiO 3 nanofibers. The SEM and TEM images indicate the obtaining of nanofibers with porous structure. The photocatalytic activity of Ag-SrTiO 3 nanofibers was evaluated by degrading RhB and MB under visible light irradiation. The Ag-SrTiO 3 nanofibers show excellent photocatalytic activity under visible light irradiation because of the surface plasmon resonance effect of Ag 0 . In the photocatalysis process of RhB and MB, lots of hydroxyl radicals were generated, which plays the key role in the decomposition of organic pollutants. Copyright © 2018 Elsevier B.V. All rights reserved.
An anomalous subdiffusion model for calcium spark in cardiac myocytes
NASA Astrophysics Data System (ADS)
Tan, Wenchang; Fu, Chaoqi; Fu, Ceji; Xie, Wenjun; Cheng, Heping
2007-10-01
The elementary events of excitation-contraction coupling in heart muscle are Ca2+ sparks, which arise from ryanodine receptors in the sarcoplasmic reticulum (SR). Here, an anomalous subdiffusion model is developed to explore Ca2+ spark formation in cardiac myocytes. Numerical simulations reproduce the brightness, the time course, and spatial size of a typical cardiac Ca2+ spark. It is suggested that the diffusion of Ca2+ spark in the cytoplasm may no longer obey Fickian second law, but the anomalous space subdiffusion. The physical reason is perhaps due to the effects of the electric field of the calcium ions and the viscoelasticity of the cytoplasm and its complex structures.
Lamboley, C R; Wyckelsma, V L; Dutka, T L; McKenna, M J; Murphy, R M; Lamb, G D
2015-01-01
This study examined the contractile properties and sarcoplasmic reticulum (SR) Ca2+ content in mechanically skinned vastus lateralis muscle fibres of Old (70 ± 4 years) and Young (22 ± 3 years) humans to investigate whether changes in muscle fibre properties contribute to muscle weakness in old age. In type II fibres of Old subjects, specific force was reduced by ∼17% and Ca2+ sensitivity was also reduced (pCa50 decreased ∼0.05 pCa units) relative to that in Young. S-Glutathionylation of fast troponin I (TnIf) markedly increased Ca2+ sensitivity in type II fibres, but the increase was significantly smaller in Old versus Young (+0.136 and +0.164 pCa unit increases, respectively). Endogenous and maximal SR Ca2+ content were significantly smaller in both type I and type II fibres in Old subjects. In fibres of Young, the SR could be nearly fully depleted of Ca2+ by a combined caffeine and low Mg2+ stimulus, whereas in fibres of Old the amount of non-releasable Ca2+ was significantly increased (by > 12% of endogenous Ca2+ content). Western blotting showed an increased proportion of type I fibres in Old subjects, and increased amounts of calsequestrin-2 and calsequestrin-like protein. The findings suggest that muscle weakness in old age is probably attributable in part to (i) an increased proportion of type I fibres, (ii) a reduction in both maximum specific force and Ca2+ sensitivity in type II fibres, and also a decreased ability of S-glutathionylation of TnIf to counter the fatiguing effects of metabolites on Ca2+ sensitivity, and (iii) a reduction in the amount of releasable SR Ca2+ in both fibre types. Key points Muscle weakness in old age is due in large part to an overall loss of skeletal muscle tissue, but it remains uncertain how much also stems from alterations in the properties of the individual muscle fibres. This study examined the contractile properties and amount of stored intracellular calcium in single muscle fibres of Old (70 ± 4 years) and Young (22 ± 3 years) adults. The maximum level of force production (per unit cross-sectional area) in fast twitch fibres in Old subjects was lower than in Young subjects, and the fibres were also less sensitive to activation by calcium. The amount of calcium stored inside muscle fibres and available to trigger contraction was also lower in both fast- and slow-twitch muscle fibres in the Old subjects. These findings indicate that muscle weakness in old age stems in part from an impaired capacity for force production in the individual muscle fibres. PMID:25809942
Lamboley, C R; Wyckelsma, V L; Dutka, T L; McKenna, M J; Murphy, R M; Lamb, G D
2015-06-01
Muscle weakness in old age is due in large part to an overall loss of skeletal muscle tissue, but it remains uncertain how much also stems from alterations in the properties of the individual muscle fibres. This study examined the contractile properties and amount of stored intracellular calcium in single muscle fibres of Old (70 ± 4 years) and Young (22 ± 3 years) adults. The maximum level of force production (per unit cross-sectional area) in fast twitch fibres in Old subjects was lower than in Young subjects, and the fibres were also less sensitive to activation by calcium. The amount of calcium stored inside muscle fibres and available to trigger contraction was also lower in both fast- and slow-twitch muscle fibres in the Old subjects. These findings indicate that muscle weakness in old age stems in part from an impaired capacity for force production in the individual muscle fibres. This study examined the contractile properties and sarcoplasmic reticulum (SR) Ca(2+) content in mechanically skinned vastus lateralis muscle fibres of Old (70 ± 4 years) and Young (22 ± 3 years) humans to investigate whether changes in muscle fibre properties contribute to muscle weakness in old age. In type II fibres of Old subjects, specific force was reduced by ∼17% and Ca(2+) sensitivity was also reduced (pCa50 decreased ∼0.05 pCa units) relative to that in Young. S-Glutathionylation of fast troponin I (TnIf ) markedly increased Ca(2+) sensitivity in type II fibres, but the increase was significantly smaller in Old versus Young (+0.136 and +0.164 pCa unit increases, respectively). Endogenous and maximal SR Ca(2+) content were significantly smaller in both type I and type II fibres in Old subjects. In fibres of Young, the SR could be nearly fully depleted of Ca(2+) by a combined caffeine and low Mg(2+) stimulus, whereas in fibres of Old the amount of non-releasable Ca(2+) was significantly increased (by > 12% of endogenous Ca(2+) content). Western blotting showed an increased proportion of type I fibres in Old subjects, and increased amounts of calsequestrin-2 and calsequestrin-like protein. The findings suggest that muscle weakness in old age is probably attributable in part to (i) an increased proportion of type I fibres, (ii) a reduction in both maximum specific force and Ca(2+) sensitivity in type II fibres, and also a decreased ability of S-glutathionylation of TnIf to counter the fatiguing effects of metabolites on Ca(2+) sensitivity, and (iii) a reduction in the amount of releasable SR Ca(2+) in both fibre types. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.
Synhaeve, Nicholas; Wade-Gueye, Ndéye Marième; Musilli, Stefania; Stefani, Johanna; Grandcolas, Line; Gruel, Gaëtan; Souidi, Maâmar; Dublineau, Isabelle; Bertho, Jean-Marc
2014-01-01
The aim of this work was to delineate the effects of chronic ingestion of strontium 90 ((90) Sr) at low concentrations on the hematopoiesis and the bone physiology. A mouse model was used for that purpose. Parent animals ingested water containing 20 kBq l(-1) of (90) Sr two weeks before mating. Offspring were then continuously contaminated with (90) Sr through placental transfer during fetal life, through lactation after birth and through drinking water after weaning. At various ages between birth and 20 weeks, animals were tested for hematopoietic parameters such as blood cell counts, colony forming cells in spleen and bone marrow and cytokine concentrations in the plasma. However, we did not find any modification in (90) Sr ingesting animals as compared with control animals. By contrast, the analysis of bone physiology showed a modification of gene expression towards bone resorption. This was confirmed by an increase in C-telopeptide of collagen in the plasma of (90) Sr ingesting animals as compared with control animals. This modification in bone metabolism was not linked to a modification of the phosphocalcic homeostasis, as measured by calcium, phosphorus, vitamin D and parathyroid hormone in the blood. Overall these results suggest that the chronic ingestion of (90) Sr at low concentration in the long term may induce modifications in bone metabolism but not in hematopoiesis. Copyright © 2012 John Wiley & Sons, Ltd.
Almog, Orna; González, Ana; Godin, Noa; de Leeuw, Marina; Mekel, Marlene J; Klein, Daniela; Braun, Sergei; Shoham, Gil; Walter, Richard L
2009-02-01
We determine and compare the crystal structure of two proteases belonging to the subtilisin superfamily: S41, a cold-adapted serine protease produced by Antarctic bacilli, at 1.4 A resolution and Sph, a mesophilic serine protease produced by Bacillus sphaericus, at 0.8 A resolution. The purpose of this comparison was to find out whether multiple calcium ion binding is a molecular factor responsible for the adaptation of S41 to extreme low temperatures. We find that these two subtilisins have the same subtilisin fold with a root mean square between the two structures of 0.54 A. The final models for S41 and Sph include a calcium-loaded state of five ions bound to each of these two subtilisin molecules. None of these calcium-binding sites correlate with the high affinity known binding site (site A) found for other subtilisins. Structural analysis of the five calcium-binding sites found in these two crystal structures indicate that three of the binding sites have two side chains of an acidic residue coordinating the calcium ion, whereas the other two binding sites have either a main-chain carbonyl, or only one acidic residue side chain coordinating the calcium ion. Thus, we conclude that three of the sites are of high affinity toward calcium ions, whereas the other two are of low affinity. Because Sph is a mesophilic subtilisin and S41 is a psychrophilic subtilisin, but both crystal structures were found to bind five calcium ions, we suggest that multiple calcium ion binding is not responsible for the adaptation of S41 to low temperatures. Copyright 2008 Wiley-Liss, Inc.
Studies on the Inhibition of Intestinal Absorption of Radioactive Strontium
Waldron-Edward, Deirdre; Paul, T. M.; Skoryna, Stanley C.
1964-01-01
A method is reported which permits selective suppression of absorption of radioactive strontium from ingested food material, permitting calcium to be available to the body. Studies were carried out by measuring bone uptake of Sr89 and Ca45 when various amounts of sodium alginate were fed with the diet. Long-term studies were made in which two different levels of radioactivity were used, to determine the pattern of Sr89 deposition with continuous intake of binding agent. It was found that administration of sodium alginate as a jelly overcomes the problem of constipation and effectively reduces Sr89 uptake, up to 83%. This fact represents a significant finding with respect to the use of the compound in human subjects. Addition of sodium alginate to drinking water is effective with low levels of Sr89 intake. This naturally occurring water-soluble macromolecular substance possesses several advantages in use for the suppression of absorption of radioactive strontium when compared with synthetic ion exchange resins: there is no disturbance of electrolyte balance; efficiency is not reduced by treatment over a prolonged period of time; and finally, the product is palatable. PMID:14222668
NASA Astrophysics Data System (ADS)
Schmitt, Anne-Désirée; Gangloff, Sophie; Labolle, François; Chabaux, François; Stille, Peter
2017-04-01
Stable calcium and radiogenic Sr are analysed in several organs from two beech trees that were collected in June and September in the Strengbach CZO (NE France) and in corresponding soil solutions. The combination of these two isotopic systems shows that the isotopic signatures of roots are dominated by Ca fractionation mechanisms and Sr, and thus Ca, source variations. In contrast, translocation mechanisms are only governed by Ca fractionation processes. This study also confirms in the field that the Ca uptake mechanisms from nutritive solutions are controlled by adsorption processes in small roots because of physico-chemical mechanisms. Similarly, a study of surface soil solutions suggests that recent soil waters are less affected by vegetation uptake than in the past, probably because of a decline in the growth of the vegetation that is linked to climate warming, which causes drought episodes. Thus, soil solutions reflect the role of soil components in addition to nutrient uptake by vegetation. This isotopic Ca-Sr study also helps to identify one-time events that are caused by snow cover melting and/or dry episodes that release cations.
Xiang, Liang; Kong, Wei; Su, Jingtan; Liang, Jian; Zhang, Guiyou; Xie, Liping; Zhang, Rongqing
2014-01-01
The growth of molluscan shell crystals is generally thought to be initiated from the extrapallial fluid by matrix proteins, however, the cellular mechanisms of shell formation pathway remain unknown. Here, we first report amorphous calcium carbonate (ACC) precipitation by cellular biomineralization in primary mantle cell cultures of Pinctada fucata. Through real-time PCR and western blot analyses, we demonstrate that mantle cells retain the ability to synthesize and secrete ACCBP, Pif80 and nacrein in vitro. In addition, the cells also maintained high levels of alkaline phosphatase and carbonic anhydrase activity, enzymes responsible for shell formation. On the basis of polarized light microscopy and scanning electron microscopy, we observed intracellular crystals production by mantle cells in vitro. Fourier transform infrared spectroscopy and X-ray diffraction analyses revealed the crystals to be ACC, and de novo biomineralization was confirmed by following the incorporation of Sr into calcium carbonate. Our results demonstrate the ability of mantle cells to perform fundamental biomineralization processes via amorphous calcium carbonate, and these cells may be directly involved in pearl oyster shell formation. PMID:25405357
Strong G-Protein-Mediated Inhibition of Sodium Channels.
Mattheisen, Glynis B; Tsintsadze, Timur; Smith, Stephen M
2018-05-29
Voltage-gated sodium channels (VGSCs) are strategically positioned to mediate neuronal plasticity because of their influence on action potential waveform. VGSC function may be strongly inhibited by local anesthetic and antiepileptic drugs and modestly modulated via second messenger pathways. Here, we report that the allosteric modulators of the calcium-sensing receptor (CaSR) cinacalcet, calindol, calhex, and NPS 2143 completely inhibit VGSC current in the vast majority of cultured mouse neocortical neurons. This form of VGSC current block persisted in CaSR-deficient neurons, indicating a CaSR-independent mechanism. Cinacalcet-mediated blockade of VGSCs was prevented by the guanosine diphosphate (GDP) analog GDPβs, indicating that G-proteins mediated this effect. Cinacalcet inhibited VGSCs by increasing channel inactivation, and block was reversed by prolonged hyperpolarization. Strong cinacalcet inhibition of VGSC currents was also present in acutely isolated mouse cortical neurons. These data identify a dynamic signaling pathway by which G-proteins regulate VGSC current to indirectly modulate central neuronal excitability. Published by Elsevier Inc.
Mechanisms of intragastric pH sensing.
Goo, Tyralee; Akiba, Yasutada; Kaunitz, Jonathan D
2010-12-01
Luminal amino acids and lack of luminal acidity as a result of acid neutralization by intragastric foodstuffs are powerful signals for acid secretion. Although the hormonal and neural pathways underlying this regulatory mechanism are well understood, the nature of the gastric luminal pH sensor has been enigmatic. In clinical studies, high pH, tryptic peptides, and luminal divalent metals (Ca(2+) and Mg(2+)) increase gastrin release and acid production. The calcium-sensing receptor (CaSR), first described in the parathyroid gland but expressed on gastric G cells, is a logical candidate for the gastric acid sensor. Because CaSR ligands include amino acids and divalent metals, and because extracellular pH affects ligand binding in the pH range of the gastric content, its pH, metal, and nutrient-sensing functions are consistent with physiologic observations. The CaSR is thus an attractive candidate for the gastric luminal sensor that is part of the neuroendocrine negative regulatory loop for acid secretion.
NASA Astrophysics Data System (ADS)
Vereshchagina, Tatiana A.; Vereshchagin, Sergei N.; Shishkina, Nina N.; Vasilieva, Nataly G.; Solovyov, Leonid A.; Anshits, Alexander G.
2013-06-01
Hollow microsphere zeolite materials with a bilayered zeolite/glass crystalline shell bearing NaP1 zeolite were synthesized by the hydrothermal treatment of coal fly ash cenospheres (Si/Al = 2.7) in an alkaline medium. Cs+ and/or Sr2+ forms of zeolitized cenospheres with the different Cs+ and/or Sr2+ loading were prepared by the ion exchange from nitrate solutions. The resulted (Cs,Na)P1, (Sr,Na)P1 and (Cs,Sr,Na)P1 bearing microsphere zeolites were converted to glass ceramics by heating at 900-1000 °C. The differential scanning calorimetry and quantitative phase analysis were used to monitor the solid-phase transformation of the initial and ion exchanged zeolite materials. It was established that the final solidified forms of Cs+ and/or Sr2+ are glass-crystalline ceramic materials based on pollucite-nepheline, Sr-feldspar-nepheline and Sr-feldspar-pollucite composites including ˜60 wt.% of the major host phases (pollucite, Sr-feldspar) and 10-20 wt.% of glass. The 137Cs leaching rate of 4.1 × 10-7 g cm-2 day-1 was determined for the pollucite glass-ceramic according to Russian State Standard (GOST) No. 52126 P-2003 (7 day, 25 °C, distilled water).
Diet and renal stone formation.
Trinchieri, A
2013-02-01
The relationship between diet and the formation of renal stones is demonstrated, but restrictive diets do not take into account the complexity of metabolism and the complex mechanisms that regulate the saturation and crystallization processes in the urine. The restriction of dietary calcium can reduce the urinary excretion of calcium but severe dietary restriction of calcium causes hyperoxaluria and a progressive loss of bone mineral component. Furthermore urinary calcium excretion is influenced by other nutrients than calcium as sodium, potassium, protein and refined carbohydrates. Up to 40% of the daily excretion of oxalate in the urine is from dietary source, but oxalate absorption in the intestine depends linearly on the concomitant dietary intake of calcium and is influenced by the bacterial degradation by several bacterial species of intestinal flora. A more rational approach should be based on the cumulative effects of foods and different dietary patterns on urinary saturation rather than on the effect of single nutrients. A diet based on a adequate intake of calcium (1000-1200 mg per day) and containment of animal protein and salt can decrease significantly urinary supersaturation for calcium oxalate and reduce the relative risk of stone recurrence in hypercalciuric renal stone formers. The DASH-style diet that is high in fruits and vegetables, moderate in low-fat dairy products and low in animal proteins and salt is associated with a lower relative supersaturation for calcium oxalate and a marked decrease in risk of incident stone formation. All the diets above mentioned have as a common characteristic the reduction of the potential acid load of the diet that can be correlated with a higher risk of recurrent nephrolithiasis, because the acid load of diet is inversely related to urinary citrate excretion. The restriction of protein and salt with an adequate calcium intake seem to be advisable but should be implemented with the advice to increase the intake of vegetables that can carry a plentiful supply of alkali that counteract the acid load coming from animal protein. New prospective studies to evaluate the effectiveness of the diet for the prevention of renal stones should be oriented to simple dietary advices that should be focused on a few specific goals easily controlled by means of self-evaluation tools, such as the LAKE food screener.
NASA Technical Reports Server (NTRS)
Morgan, P. E. D.; Ratto, J. J.; Housley, R. M.; Porter, J. R.
1988-01-01
EDXS performed on isolated particles of the Bi-Ca-Sr-Cu-O high-temperature ceramic superconductor has verified the presence of significant elemental exchange between the Ca and Sr, and, to a lesser extent, between Cu and Bi. Two primary preparations, identified as primarily 24.4 A and 30.6 A, respectively, are identified. The Cu:Bi ratio in the 30.6 A material is approximately 1:1 for most particles, although only a few particles of the nominally 24.4 A material have the expected 1:2 ratio. No unequivocal assignment of atomic composition to the predominantly 24.4 A or 30.6 A appears possible, if major syntactic problems are present.
Investigating the role of smooth muscle cells in large elastic arteries: a finite element analysis.
Murtada, Sae-Il; Holzapfel, Gerhard A
2014-10-07
Physiological loading in large elastic arteries is considered to be mainly carried by the passive components of the media but it is not known how much the contraction of the smooth muscle cells is actually involved in the load carrying. Smooth muscle contraction is considered to occur in a relatively slow time domain but the contraction is able to produce significant tension. In the present work the role of smooth muscle contraction in large elastic arteries is investigated by analyzing how changes in the intracellular calcium, and thereby the active tone of smooth muscle cells, influence the deformation and stress behavior; different intracellular calcium functions and medial wall thicknesses with cycling internal pressure are studied. In particular, a recently proposed mechanochemical model (Murtada et al., 2012. J. Theor. Biol. 297, 176-186), which links intracellular calcium with mechanical contraction and an anisotropic model representing the elastin/collagen composite, was implemented into a 3D finite element framework. Details of the implementation procedure are described and a verification of the model implementation is provided by means of the isometric contraction/relaxation analysis of a medial strip at optimal muscle length. In addition, numerically obtained pressure-radius relationships of arterial rings modeled with one and two layers are analyzed with different geometries and at different calcium levels; a comparison with the Laplace equation is provided. Finally, a two-layer arterial ring is loaded with a realistic pressure wave and with various intracellular calcium functions (different amplitudes and mean values) and medial wall thicknesses; residual stresses are considered. The finite element results show that changes in the calcium amplitudes hardly have an influence on the current inner ring radius and the circumferential stress. However, an increase in the mean intracellular calcium value and the medial wall thickness leads to a clear influence on the deformation and the stress behavior. Copyright © 2014 Elsevier Ltd. All rights reserved.
Federal Register 2010, 2011, 2012, 2013, 2014
2012-05-15
... have a novel or unusual design feature(s) associated with Tamarack Aerospace Group's modification. The... the control system. (b) The design of the load alleviation system or of any other automatic system...) Each detail of the Tamarack Active Control Surface (TACS) must be designed and installed to prevent...
Federal Register 2010, 2011, 2012, 2013, 2014
2013-02-13
... with Tamarack Aerospace Group's modification. The design change will install winglets and an Active... not aware of the failure. Warning systems must not activate the control system. (b) The design of the... abrupt Tamarack Active Control Surface (TACS) operation. (b) The load alleviation system must be designed...
Trace elements in lake sediments measured by the PIXE technique
NASA Astrophysics Data System (ADS)
Gatti, Luciana V.; Mozeto, Antônio A.; Artaxo, Paulo
1999-04-01
Lakes are ecosystems where there is a great potential of metal accumulation in sediments due to their depositional characteristics. Total concentration of trace elements was measured on a 50 cm long sediment core from the Infernão Lake, that is an oxbow lake of the Moji-Guaçu River basin, in the state of São Paulo, Brazil. Dating of the core shows up to 180 yrs old sediment layers. The use of the PIXE technique for elemental analysis avoids the traditional acid digestion procedure common in other techniques. The multielemental characteristic of PIXE allows a simultaneous determination of about 20 elements in the sediment samples, such as, Al, Si, P, S, Cl, K, Ca, Ti, V, Cr, Mn, Fe, Ni, Cu, Zn, Rb, Sr, Zr, Ba, and Pb. Average values for the elemental composition were found to be similar to the bulk crustal composition. The lake flooding pattern strongly influences the time series of the elemental profiles. Factor analysis of the elemental variability shows five factors. Two of the factors represent the mineralogical matrix, and others represent the organic component, a factor with lead, and another loaded with chromium. The mineralogical component consists of elements such as, Fe, Al, V, Ti, Mn, Ni, K, Zr, Sr, Cu and Zn. The variability of Si is explained by two distinct factors, because it is influenced by two different sources, aluminum-silicates and quartz, and the effect of inundation are different for each other. The organic matter is strongly associated with calcium, and also bounded with S, Zn, Cu and P. Lead and chromium appears as separated factors, although it is not clear the evidences for their anthropogenic origin. The techniques developed for sample preparation and PIXE analysis was proven as advantageous and provided very good reproducibility and accuracy.
NASA Astrophysics Data System (ADS)
Dicus, C. M.; Snyder, G. T.; Dickens, G. R.
2004-12-01
Site 1230 of the Ocean Drilling Program targeted the chemistry and microbiology of an active deep-water gas hydrate system in the Peru Trench. The site is noteworthy because, at nearly 6000 m water depth, it lies well below the carbonate compensation depth and the sediments comprise mostly terrigenous clays and biogenic silica. Shipboard work at this site delineated a prominent sulfate-methane transition (SMT) at 8-10 m below seafloor (mbsf) as well as some carbonate horizons. In this study, we present calcium and strontium data for pore waters and sediments at this site, including across the SMT. Concentration profiles show that dissolved Ca2+ diffuses downward from the seafloor toward the SMT, where a sharp inflection indicates consumption of Ca2+ into an authigenic phase. Dissolved Sr2+, on the other hand, diffuses upward from depth toward the SMT. Again, however, a prominent inflection suggests removal of Sr2+ to sediment. The inferences from pore water profiles are borne out by sediment chemistry. Large peaks in the calcium and strontium content of sediment mark the SMT. The calcium and strontium fronts reach ˜2700 and ˜5 mmol/kg, respectively, at 9 mbsf, which are much greater than average background values of ˜10 and ˜1 mmol/kg. These authigenic fronts are primarily composed of carbonate minerals, as determined by acetic acid extractions and x-ray diffraction. Because the calcium and strontium fronts coincide with both the SMT and changes in dissolved chemistry, it is proposed that the carbonates are currently forming as follows: methane rising from the underlying gas hydrate system reacts with dissolved sulfate through anaerobic oxidation of methane which releases HCO3- and alkalinity and causes carbonate precipitation. The overall process has been observed elsewhere; the Peru Trench is interesting, however, because the process leads to carbonate in sediments otherwise devoid of carbonate.
NASA Astrophysics Data System (ADS)
Li, Kai; Hu, Dandan; Xie, Youtao; Huang, Liping; Zheng, Xuebin
2018-02-01
Biomedical coatings for orthopedic implants should facilitate osseointegration and mitigate implant-induced inflammatory reactions. In our study, Ca-Si coatings with Sr-containing nanowire-like structures (NW-Sr-CS) were achieved via hydrothermal treatment. In order to identify the effect of nanowire-like topography and Sr dopant on the biological properties of Ca-Si-based coatings, the original Ca-Si coating, Ca-Si coatings modified with nanoplate (NP-CS) and similar nanowire-like structure (NW-CS) were fabricated as the control. Surface morphology, phase composition, surface area, zeta potential and ion release of these coatings were characterized. The in vitro osteogenic activities and immunomodulatory properties were evaluated with bone marrow stromal cells (BMSCs) and RAW 264.7 cells, a mouse macrophage cell line. Compared with the CS and NP-CS coatings, the NW-CS coating possessed a larger surface area and pore volume, beneficial protein adsorption, up-regulated the expression levels of integrin β1, Vinculin and focal adhesion kinase and promoted cell spreading. Furthermore, the NW-CS coating significantly enhanced the osteogenic differentiation and mineralization as indicated by the up-regulation of ALP activity, mineralized nodule formation and osteoblastogenesis-related gene expression. With the introduction of Sr, the NW-Sr-CS coatings exerted a greater effect on the BMSC proliferation rate, calcium sensitive receptor gene expression as well as PKC and ERK1/2 phosphorylation. In addition, the Sr-doped coatings significantly up-regulated the ratio of OPG/RANKL in the BMSCs. The NW-Sr-CS coatings could modulate the polarization of macrophages towards the wound-healing M2 phenotype, reduce the mRNA expression levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and enhance anti-inflammatory cytokines (IL-1ra, IL-10). The Sr-doped nanowire modification may be a valuable approach to enhance osteogenic activities and reduce inflammatory reactions.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dezerald, Lucile; Kohanoff, Jorge J.; Correa, Alfredo A.
One of the main challenges faced by the nuclear industry is the long-term confinement of nuclear waste. Because it is inexpensive and easy to manufacture, cement is the material of choice to store large volumes of radioactive materials, in particular the low-level medium-lived fission products. It is therefore of utmost importance to assess the chemical and structural stability of cement containing radioactive species. Here, we use ab initio calculations based on density functional theory (DFT) to study the effects of 90Sr insertion and decay in C–S–H (calcium-silicate-hydrate) in order to test the ability of cement to trap and hold thismore » radioactive fission product and to investigate the consequences of its β-decay on the cement paste structure. We show that 90Sr is stable when it substitutes the Ca 2+ ions in C–S–H, and so is its daughter nucleus 90Y after β-decay. Interestingly, 90Zr, daughter of 90Y and final product in the decay sequence, is found to be unstable compared to the bulk phase of the element at zero K but stable when compared to the solvated ion in water. Furthermore, cement appears as a suitable waste form for 90Sr storage.« less
Spatial distribution of the trace elements zinc, strontium and lead in human bone tissue☆
Pemmer, B.; Roschger, A.; Wastl, A.; Hofstaetter, J.G.; Wobrauschek, P.; Simon, R.; Thaler, H.W.; Roschger, P.; Klaushofer, K.; Streli, C.
2013-01-01
Trace elements are chemical elements in minute quantities, which are known to accumulate in the bone. Cortical and trabecular bones consist of bone structural units (BSUs) such as osteons and bone packets of different mineral content and are separated by cement lines. Previous studies investigating trace elements in bone lacked resolution and therefore very little is known about the local concentration of zinc (Zn), strontium (Sr) and lead (Pb) in BSUs of human bone. We used synchrotron radiation induced micro X-ray fluorescence analysis (SR μ-XRF) in combination with quantitative backscattered electron imaging (qBEI) to determine the distribution and accumulation of Zn, Sr, and Pb in human bone tissue. Fourteen human bone samples (10 femoral necks and 4 femoral heads) from individuals with osteoporotic femoral neck fractures as well as from healthy individuals were analyzed. Fluorescence intensity maps were matched with BE images and correlated with calcium (Ca) content. We found that Zn and Pb had significantly increased levels in the cement lines of all samples compared to the surrounding mineralized bone matrix. Pb and Sr levels were found to be correlated with the degree of mineralization. Interestingly, Zn intensities had no correlation with Ca levels. We have shown for the first time that there is a differential accumulation of the trace elements Zn, Pb and Sr in BSUs of human bone indicating different mechanisms of accumulation. PMID:23932972
Dezerald, Lucile; Kohanoff, Jorge J.; Correa, Alfredo A.; ...
2015-10-29
One of the main challenges faced by the nuclear industry is the long-term confinement of nuclear waste. Because it is inexpensive and easy to manufacture, cement is the material of choice to store large volumes of radioactive materials, in particular the low-level medium-lived fission products. It is therefore of utmost importance to assess the chemical and structural stability of cement containing radioactive species. Here, we use ab initio calculations based on density functional theory (DFT) to study the effects of 90Sr insertion and decay in C–S–H (calcium-silicate-hydrate) in order to test the ability of cement to trap and hold thismore » radioactive fission product and to investigate the consequences of its β-decay on the cement paste structure. We show that 90Sr is stable when it substitutes the Ca 2+ ions in C–S–H, and so is its daughter nucleus 90Y after β-decay. Interestingly, 90Zr, daughter of 90Y and final product in the decay sequence, is found to be unstable compared to the bulk phase of the element at zero K but stable when compared to the solvated ion in water. Furthermore, cement appears as a suitable waste form for 90Sr storage.« less
2011-01-01
Background Modern diets have been suggested to increase systemic acid load and net acid excretion. In response, alkaline diets and products are marketed to avoid or counteract this acid, help the body regulate its pH to prevent and cure disease. The objective of this systematic review was to evaluate causal relationships between dietary acid load and osteoporosis using Hill's criteria. Methods Systematic review and meta-analysis. We systematically searched published literature for randomized intervention trials, prospective cohort studies, and meta-analyses of the acid-ash or acid-base diet hypothesis with bone-related outcomes, in which the diet acid load was altered, or an alkaline diet or alkaline salts were provided, to healthy human adults. Cellular mechanism studies were also systematically examined. Results Fifty-five of 238 studies met the inclusion criteria: 22 randomized interventions, 2 meta-analyses, and 11 prospective observational studies of bone health outcomes including: urine calcium excretion, calcium balance or retention, changes of bone mineral density, or fractures, among healthy adults in which acid and/or alkaline intakes were manipulated or observed through foods or supplements; and 19 in vitro cell studies which examined the hypothesized mechanism. Urine calcium excretion rates were consistent with osteoporosis development; however calcium balance studies did not demonstrate loss of whole body calcium with higher net acid excretion. Several weaknesses regarding the acid-ash hypothesis were uncovered: No intervention studies provided direct evidence of osteoporosis progression (fragility fractures, or bone strength as measured using biopsy). The supporting prospective cohort studies were not controlled regarding important osteoporosis risk factors including: weight loss during follow-up, family history of osteoporosis, baseline bone mineral density, and estrogen status. No study revealed a biologic mechanism functioning at physiological pH. Finally, randomized studies did not provide evidence for an adverse role of phosphate, milk, and grain foods in osteoporosis. Conclusions A causal association between dietary acid load and osteoporotic bone disease is not supported by evidence and there is no evidence that an alkaline diet is protective of bone health. PMID:21529374
Fenton, Tanis R; Tough, Suzanne C; Lyon, Andrew W; Eliasziw, Misha; Hanley, David A
2011-04-30
Modern diets have been suggested to increase systemic acid load and net acid excretion. In response, alkaline diets and products are marketed to avoid or counteract this acid, help the body regulate its pH to prevent and cure disease. The objective of this systematic review was to evaluate causal relationships between dietary acid load and osteoporosis using Hill's criteria. Systematic review and meta-analysis. We systematically searched published literature for randomized intervention trials, prospective cohort studies, and meta-analyses of the acid-ash or acid-base diet hypothesis with bone-related outcomes, in which the diet acid load was altered, or an alkaline diet or alkaline salts were provided, to healthy human adults. Cellular mechanism studies were also systematically examined. Fifty-five of 238 studies met the inclusion criteria: 22 randomized interventions, 2 meta-analyses, and 11 prospective observational studies of bone health outcomes including: urine calcium excretion, calcium balance or retention, changes of bone mineral density, or fractures, among healthy adults in which acid and/or alkaline intakes were manipulated or observed through foods or supplements; and 19 in vitro cell studies which examined the hypothesized mechanism. Urine calcium excretion rates were consistent with osteoporosis development; however calcium balance studies did not demonstrate loss of whole body calcium with higher net acid excretion. Several weaknesses regarding the acid-ash hypothesis were uncovered: No intervention studies provided direct evidence of osteoporosis progression (fragility fractures, or bone strength as measured using biopsy). The supporting prospective cohort studies were not controlled regarding important osteoporosis risk factors including: weight loss during follow-up, family history of osteoporosis, baseline bone mineral density, and estrogen status. No study revealed a biologic mechanism functioning at physiological pH. Finally, randomized studies did not provide evidence for an adverse role of phosphate, milk, and grain foods in osteoporosis. A causal association between dietary acid load and osteoporotic bone disease is not supported by evidence and there is no evidence that an alkaline diet is protective of bone health.
A coral Sr/Ca calibration and replication study of two massive corals from the Gulf of Mexico
DeLong, Kristine L.; Flannery, Jennifer A.; Maupin, Christopher R.; Poore, Richard Z.; Quinn, Terrence M.
2011-01-01
This study examined the variations in the ratio of strontium-to-calcium (Sr/Ca) for two Atlantic corals (Montastraea faveolata and Siderastrea siderea) from the Dry Tortugas National Park (centered on 24.7°N, 82.8°W) in the Gulf of Mexico. Cores from coral colonies in close proximity (10s of meters) and with the same environmental conditions (i.e., depth and water chemistry) were micro-sampled with approximately monthly resolution and the resulting Sr/Ca variations were calibrated with local sea surface temperature (SST) records. Replication tests for coral Sr/Ca variations found high agreement between intra-colony variations and between individual colonies of S. siderea (a single M. faveolata colony was sampled). Regression analysis of monthly variations in coral Sr/Ca and local SST revealed significant correlation on monthly and inter-annual timescales. Verification of the calibration on different timescales found coral Sr/Ca–SST reconstructions in S. siderea were more accurate than those from M. faveolata, especially on inter-annual timescales. Sr/Ca–SST calibration equations for the two species are significantly different (cf., Sr/Ca = -0.042 SST + 10.070, S. siderea; Sr/Ca = -0.027 SST + 9.893, M. faveolata). Mean linear extension for M. faveolata is approximately twice that of S. siderea (4.63, 4.31, and 8.31 mm year−1, A1, F1, and B3, respectively); however, seasonal Sr/Ca variability in M. faveolata is less than S. siderea (0.323, 0.353, and 0.254 mmol mol−1, A1, F1, and B3, respectively). The reduced slope for M. faveolata is attributed to physical sampling issues associated with complex time-skeletal structure of M. faveolata, i.e., a sampling effect, and not a growth effect since the faster growing M. faveolata has the reduced Sr/Ca variability.
NASA Astrophysics Data System (ADS)
Willmes, Malte; James, Hannah; Boel, Ceridwen; Courtaud, Patrice; Chancerel, Antoine; McMorrow, Linda; Armstrong, Richard; Kinsley, Les; Aubert, Maxime; Eggins, Stephen; Moffat, Ian; Grün, Rainer
2014-05-01
Oxygen (δ18O) and strontium (87Sr/86Sr) isotopes were used as tools to investigate human migration at the early Bell Beaker site (2500-2000 BC) Le Tumulus des Sables, Saint-Laurent-Médoc, south-west France. The O and Sr isotope ratios measured in tooth enamel record the average dietary isotope signature ingested by that individual during their childhood. When this data is compared to the isotope signature of the burial site it can be used to indicate if the individual migrated into this area during their lifetime. The O isotopic composition of meteoric water changes depending on climate, temperature and quantity of precipitation. O isotope ratios in skeletal and dental remains are related to body water, which in turn is influenced by diet, physiology and climate. Most of the water consumed by large mammals comes from drinking water, typically sourced locally. Sr isotope ratios on the other hand vary between different geologic regions, depending on their age and composition. Sr is released through weathering and transported into the soil, ground and surface water, where it becomes available for uptake by plants, enters the food cycle and eventually ends up in skeletal and dental tissue where it substitutes for calcium. We analysed the teeth of 18 adult and 8 juvenile disarticulated skeletons from Le Tumulus des Sables. O isotopes were analysed in-situ by Sensitive High Resolution Ion Micro Probe (SHRIMP).The Sr isotope analysis involved drilling a 0.2-0.5 mg sample of enamel from the tooth. The Sr was then chemically separated and analysed by Thermal Ionization Mass Spectrometry (TIMS). These results were then compared to the O isoscape of Europe and bioavailable Sr isotope data (fauna, plants, soils) from the IRHUM database. We found that most of the individuals at Le Tumulus des Sables show O and Sr isotope ratios corresponding to the local environmental signal and we interpret these as part of the local population. 3 adults however show slightly higher 87Sr/86Sr ratios, which correspond to a clay and limestone unit in close proximity (
Diagenesis in tephra-rich sediments from the Lesser Antilles Volcanic Arc: Pore fluid constraints
NASA Astrophysics Data System (ADS)
Murray, Natalie A.; McManus, James; Palmer, Martin R.; Haley, Brian; Manners, Hayley
2018-05-01
We present sediment pore fluid and sediment solid phase results obtained during IODP Expedition 340 from seven sites located within the Grenada Basin of the southern Lesser Antilles Volcanic Arc region. These sites are generally characterized as being low in organic carbon content and rich in calcium carbonate and volcanogenic material. In addition to the typical reactions related to organic matter diagenesis, pore fluid chemistry indicates that the diagenetic reactions fall within two broad categories; (1) reactions related to chemical exchange with volcanogenic material and (2) reactions related to carbonate dissolution, precipitation, or recrystallization. For locations dominated by reaction with volcanogenic material, these sites exhibit increases in dissolved Ca with coeval decreases in Mg. We interpret this behavior as being driven by sediment-water exchange reactions from the alteration of volcanic material that is dispersed throughout the sediment package, which likely result in formation of Mg-rich secondary authigenic clays. In contrast to this behavior, sediment sequences that exhibit decreases in Ca, Mg, Mn, and Sr with depth suggest that carbonate precipitation is an active diagenetic process affecting solute distributions. The distributions of pore fluid 87Sr/86Sr reflect these competitive diagenetic reactions between volcanic material and carbonate, which are inferred by the major cation distributions. From one site where we have solid phase 87Sr/86Sr (site U1396), the carbonate fraction is found to be generally consistent with the contemporaneous seawater isotope values. However, the 87Sr/86Sr of the non-carbonate fraction ranges from 0.7074 to 0.7052, and these values likely represent a mixture of local arc volcanic sources and trans-Atlantic eolian sources. Even at this site where there is clear evidence for diagenesis of volcanogenic material, carbonate diagenesis appears to buffer pore fluid 87Sr/86Sr from the larger changes that might be expected given the high abundance of tephra in these sediments. Part of this carbonate buffering, at this site as well as throughout the region, derives from the fact that the Sr concentration in the non-carbonate fraction is generally low (<200 ppm), whereas the carbonate fraction has Sr concentrations approaching ∼1000 ppm.
Trinchieri, Alberto; Lizzano, Renata; Marchesotti, Federica; Zanetti, Giampaolo
2006-02-01
The aim of this study was to investigate the influence of the potential renal acid load (PRAL) of the diet on the urinary risk factors for renal stone formation. The present series comprises 187 consecutive renal calcium stone patients (114 males, 73 females) who were studied in our stone clinic. Each patient was subjected to an investigation including a 24-h dietary record and 24-h urine sample taken over the same period. Nutrients and calories were calculated by means of food composition tables using a computerized procedure. Daily PRAL was calculated considering the mineral and protein composition of foods, the mean intestinal absorption rate for each nutrient and the metabolism of sulfur-containing amino acids. Sodium, potassium, calcium, magnesium, phosphate, oxalate, urate, citrate, and creatinine levels were measured in the urine. The mean daily PRAL was higher in male than in female patients (24.1+/-24.0 vs 16.1+/-20.1 mEq/day, P=0.000). A significantly (P=0.01) negative correlation (R=-0.18) was found between daily PRAL and daily urinary citrate, but no correlation between PRAL and urinary calcium, oxalate, and urate was shown. Daily urinary calcium (R=0.186, P=0.011) and uric acid (R=0.157, P=0.033) were significantly related to the dietary intake of protein. Daily urinary citrate was significantly related to the intakes of copper (R=0.178, P=0.015), riboflavin (R=0.20, P=0.006), piridoxine (R=0.169, P=0.021) and biotin (R=0.196, P=0.007). The regression analysis by stepwise selection confirmed the significant negative correlation between PRAL and urinary citrate (P=0.002) and the significant positive correlation between riboflavin and urinary citrate (P=0.000). Urinary citrate excretion of renal stone formers (RSFs) is highly dependent from dietary acid load. The computation of the renal acid load is advisable to investigate the role of diet in the pathogenesis of calcium stone disease and it is also a useful tool to evaluate the lithogenic potential of the diet of the individual patient.
The Role of Nutrition in the Changes in Bone and Calcium Metabolism During Space Flight
NASA Technical Reports Server (NTRS)
Morey-Holton, Emily R.; Arnaud, Sara B.
1995-01-01
On Earth, the primary purpose of the skeleton is provide structural support for the body. In space, the support function of the skeleton is reduced since, without gravity, structures have only mass and no weight. The adaptation to space flight is manifested by shifts in mineral distribution, altered bone turnover, and regional mineral deficits in weight-bearing bones. The shifts in mineral distribution appear to be related to the cephalic fluid shift. The redistribution of mineral from one bone to another or to and from areas in the same bone in response to alterations in gravitational loads is more likely to affect skeletal function than quantitative whole body losses and gains. The changes in bone turnover appear dependent upon changes in body weight with weight loss tending to increase bone resorption as well as decrease bone formation. During bedrest, the bone response to unloading varies depending upon the routine activity level of the subjects with more active subjects showing a greater suppression of bone formation in the iliac crest with inactivity. Changes in body composition during space flight are predicted by bedrest studies on Earth which show loss of lean body mass and increase tn body fat in adult males after one month. In ambulatory studies on Earth, exercising adult males of the same age, height, g weight, body mass index, and shoe size show significantly higher whole body mineral and lean body mass. than non-exercising subjects. Nutritional preference appears to change with activity level. Diet histories in exercisers and nonexercisers who maintain identical body weights show no differences in nutrients except for slightly higher carbohydrate intake in the exercisers. The absence of differences in dietary calcium in men with higher total body calcium is noteworthy. In this situation, the increased bone mineral content was facilitated by the calcium endocrine system. This regulatory system can be by-passed by raising dietary calcium. Increased calcium intake can increase the calcium content in normally loaded bone. However, bone with a higher calcium content still decreases proportionally to normal bone during unloading. Nutritional requirements in space should be reevaluated with respect to these adaptive changes to loading and physical activity.
Recovery Act. Advanced Load Identification and Management for Buildings
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yang, Yi; Casey, Patrick; Du, Liang
2014-02-12
In response to the U.S. Department of Energy (DoE)’s goal of achieving market ready, net-zero energy residential and commercial buildings by 2020 and 2025, Eaton partnered with the Department of Energy’s National Renewable Energy Laboratory (NREL) and Georgia Institute of Technology to develop an intelligent load identification and management technology enabled by a novel “smart power strip” to provide critical intelligence and information to improve the capability and functionality of building load analysis and building power management systems. Buildings account for 41% of the energy consumption in the United States, significantly more than either transportation or industrial. Within the buildingmore » sector, plug loads account for a significant portion of energy consumption. Plug load consumes 15-20% of building energy on average. As building managers implement aggressive energy conservation measures, the proportion of plug load energy can increase to as much as 50% of building energy leaving plug loads as the largest remaining single source of energy consumption. This project focused on addressing plug-in load control and management to further improve building energy efficiency accomplished through effective load identification. The execution of the project falls into the following three major aspects; An intelligent load modeling, identification and prediction technology was developed to automatically determine the type, energy consumption, power quality, operation status and performance status of plug-in loads, using electric waveforms at a power outlet level. This project demonstrated the effectiveness of the developed technology through a large set of plug-in loads measurements and testing; A novel “Smart Power Strip (SPS) / Receptacle” prototype was developed to act as a vehicle to demonstrate the feasibility of load identification technology as a low-cost, embedded solution; and Market environment for plug-in load control and management solutions, in particular, advanced power strips (APSs) was studied. The project evaluated the market potential for Smart Power Strips (SPSs) with load identification and the likely impact of a load identification feature on APS adoption and effectiveness. The project also identified other success factors required for widespread APS adoption and market acceptance. Even though the developed technology is applicable for both residential and commercial buildings, this project is focused on effective plug-in load control and management for commercial buildings, accomplished through effective load identification. The project has completed Smart Receptacle (SR) prototype development with integration of Load ID, Control/Management, WiFi communication, and Web Service. Twenty SR units were built, tested, and demonstrated in the Eaton lab; eight SR units were tested in the National Renewable Energy Lab (NREL) for one-month of field testing. Load ID algorithm testing for extended load sets was conducted within the Eaton facility and at local university campuses. This report is to summarize the major achievements, activities, and outcomes under the execution of the project.« less
Ding, Yunfei; Lin, Jixing; Wen, Cuie; Zhang, Dongmei; Li, Yuncang
2016-01-01
Our previous studies have demonstrated that Mg-Zr-Sr alloys can be anticipated as excellent biodegradable implant materials for load-bearing applications. In general, rare earth elements (REEs) are widely used in magnesium (Mg) alloys with the aim of enhancing the mechanical properties of Mg-based alloys. In this study, the REE holmium (Ho) was added to an Mg-1Zr-2Sr alloy at different concentrations of Mg1Zr2SrxHo alloys (x = 0, 1, 3, 5 wt. %) and the microstructure, mechanical properties, degradation behaviour and biocompatibility of the alloys were systematically investigated. The results indicate that the addition of Ho to Mg1Zr2Sr led to the formation of the intermetallic phases MgHo3, Mg2Ho and Mg17Sr2 which resulted in enhanced mechanical strength and decreased degradation rates of the Mg-Zr-Sr-Ho alloys. Furthermore, Ho addition (≤5 wt. %) to Mg-Zr-Sr alloys led to enhancement of cell adhesion and proliferation of osteoblast cells on the Mg-Zr-Sr-Ho alloys. The in vitro biodegradation and the biocompatibility of the Mg-Zr-Sr-Ho alloys were both influenced by the Ho concentration in the Mg alloys; Mg1Zr2Sr3Ho exhibited lower degradation rates than Mg1Zr2Sr and displayed the best biocompatibility compared with the other alloys. PMID:27553403
Arachidonate-Regulated Ca2+ Influx in Human Airway Smooth Muscle
Thompson, Michael A.; Prakash, Y. S.
2014-01-01
Plasma membrane Ca2+ influx, especially store-operated Ca2+ entry triggered by sarcoplasmic reticulum (SR) Ca2+ release, is a key component of intracellular calcium concentration ([Ca2+]i) regulation in airway smooth muscle (ASM). Agonist-induced Ca2+ oscillations in ASM that involve both influx and SR mechanisms have been previously demonstrated. In nonexcitable cells, [Ca2+]i oscillations involve Ca2+ influx via arachidonic acid (AA) –stimulated channels, which show similarities to store-operated Ca2+ entry, although their molecular identity remains undetermined. Little is known about AA-regulated Ca2+ channels or their regulation in ASM. In enzymatically dissociated human ASM cells loaded with the Ca2+ indicator, fura-2, AA (1–10 μM) triggered [Ca2+]i oscillations that were inhibited by removal of extracellular Ca2+. Other fatty acids, such as the diacylglycerol analog, 1-oleoyl-2-acetyl-SN-glycerol, oleic acid, and palmitic acid (10 μM each), failed to elicit similar [Ca2+]i responses. Preincubation with LaCl3 (1 μM or 1 mM) inhibited AA-induced oscillations. Inhibition of receptor-operated channels (SKF96,365 [10 μM]), lipoxygenase (zileuton [10 μM]), or cyclooxygenase (indomethacin [10 μM]) did not affect oscillation parameters. Inhibition of SR Ca2+ release (ryanodine [10 μM] or inositol 1,4,5-trisphosphate receptor inhibitor, xestospongin C [1 μM]) decreased [Ca2+]i oscillation frequency and amplitude. Small interfering RNA against caveolin-1, stromal interaction molecule 1, or Orai3 (20 nM each) reduced the frequency and amplitude of AA-induced [Ca2+]i oscillations. In ASM cells derived from individuals with asthma, AA increased oscillation amplitude, but not frequency. These results are highly suggestive of a novel AA-mediated Ca2+–regulatory mechanism in human ASM, reminiscent of agonist-induced oscillations. Given the role of AA in ASM intracellular signaling, especially with inflammation, AA-regulated Ca2+ channels could potentially contribute to increased [Ca2+]i in diseases such asthma. PMID:24471656
Sun, Xiangrong; Tang, Lieqi; Winesett, Steven; Chang, Wenhan; Cheng, Sam Xianjun
2018-02-01
Calcium-sensing receptor (CaSR) is expressed on neurons of both submucosal and myenteric plexuses of the enteric nervous system (ENS) and the CaSR agonist R568 inhibited Cl - secretion in intestine. The purpose of this study was to localize the primary site of action of R568 in the ENS and to explore how CaSR regulates secretion through the ENS. Two preparations of rat proximal and distal colon were used. The full-thickness preparation contained both the submucosal and myenteric plexuses, whereas for the "stripped" preparation the myenteric plexus with the muscle layers was removed. Both preparations were mounted onto Ussing chambers and Cl - secretory responses were compared by measuring changes in short circuit current (I sc ). Two tissue-specific CaSR knockouts (i.e., neuron-specific vs. enterocyte-specific) were generated to compare the effect of R568 on expression of c-fos protein in myenteric neurons by immunocytochemistry. In full-thickness colons, tetrodotoxin (TTX) inhibited I sc , both in proximal and distal colons. A nearly identical inhibition was produced by R568. However, in stripped preparations, while the effect of TTX on I sc largely remained, the effect of R568 was nearly completely eliminated. In keeping with this, R568 reduced c-fos protein expression only in myenteric neurons of wild type mice and mutant mice that contained CaSR in neurons (i.e., villin Cre/Casr flox/flox mice), but not in myenteric neurons of nestin Cre/Casr flox/flox mice in which neuronal cell CaSR was eliminated. These results indicate that R568 exerts its anti-secretory effects predominantly via CaSR-mediated inhibition of neuronal activity in the myenteric plexus. Published by Elsevier Inc.
Reduction of greenhouse gases by fiber-loaded lightweight, high-opacity newsprint production
John H. Klungness; Matthew L. Stroika; Said M. Abubakr
1999-01-01
We estimated the effectiveness of fiber loading in reducing greenhouse gas emissions for producing lightweight high-opacity newsprint. Fiber loading enhances fiber bonding at increased precipitated calcium carbonate levels without significant loss in Canadian Standard Freeness or additional energy use. We investigated the reduction of greenhouse gas emissions for a...
Sambudi, Nonni Soraya; Kim, Minjeong G; Park, Seung Bin
2016-03-01
The electrospun fibers consist of backbone fibers and nano-branch network are synthesized by loading of ellipsoidal calcium carbonate in the mixture of chitosan/poly(vinyl alcohol) (PVA) followed by electrospinning. The synthesized ellipsoidal calcium carbonate is in submicron size (730.7±152.4 nm for long axis and 212.6±51.3 nm for short axis). The electrospun backbone fibers experience an increasing in diameter by loading of calcium carbonate from 71.5±23.4 nm to 281.9±51.2 nm. The diameters of branch fibers in the web-network range from 15 nm to 65 nm with most distributions of fibers are in 30-35 nm. Calcium carbonate acts as reinforcing agent to improve the mechanical properties of fibers. The optimum value of Young's modulus is found at the incorporation of 3 wt.% of calcium carbonate in chitosan/PVA fibers, which is enhanced from 15.7±3 MPa to 432.4±94.3 MPa. On the other hand, the ultimate stress of fibers experiences a decrease. This result shows that the fiber network undergoes changes from flexible to more stiff by the inclusion of calcium carbonate. The thermal analysis results show that the crystallinity of polymer is changed by the existence of calcium carbonate in the fiber network. The immersion of fibers in simulated body fluid (SBF) results in the formation of apatite on the surface of fibers. Copyright © 2015 Elsevier B.V. All rights reserved.
Temperature-induced labelling of Fluo-3 AM selectively yields brighter nucleus in adherent cells
DOE Office of Scientific and Technical Information (OSTI.GOV)
Meng, Guixian; Pan, Leiting, E-mail: plt@nankai.edu.cn; Li, Cunbo
2014-01-17
Highlights: •We detailedly examine temperature effects of Fluo-3 AM labelling in adherent cells. •4 °C Loading and 20 °C de-esterification of Fluo-3 AM yields brighter nuclei. •Brighter nuclei labelling by Fluo-3 AM also depends on cell adhesion quality. •A qualitative model of the brighter nucleus is proposed. -- Abstract: Fluo-3 is widely used to study cell calcium. Two traditional approaches: (1) direct injection and (2) Fluo-3 acetoxymethyl ester (AM) loading, often bring conflicting results in cytoplasmic calcium ([Ca{sup 2+}]{sub c}) and nuclear calcium ([Ca{sup 2+}]{sub n}) imaging. AM loading usually yields a darker nucleus than in cytoplasm, while direct injectionmore » always induces a brighter nucleus which is more responsive to [Ca{sup 2+}]{sub n} detection. In this work, we detailedly investigated the effects of loading and de-esterification temperatures on the fluorescence intensity of Fluo-3 in response to [Ca{sup 2+}]{sub n} and [Ca{sup 2+}]{sub c} in adherent cells, including osteoblast, HeLa and BV2 cells. Interestingly, it showed that fluorescence intensity of nucleus in osteoblast cells was about two times larger than that of cytoplasm when cells were loaded with Fluo-3 AM at 4 °C and allowed a subsequent step for de-esterification at 20 °C. Brighter nuclei were also acquired in HeLa and BV2 cells using the same experimental condition. Furthermore, loading time and adhesion quality of cells had effect on fluorescence intensity. Taken together, cold loading and room temperature de-esterification treatment of Fluo-3 AM selectively yielded brighter nucleus in adherent cells.« less
Mori, Michela; Rossi, Silvia; Bonferoni, Maria Cristina; Ferrari, Franca; Sandri, Giuseppina; Riva, Federica; Del Fante, Claudia; Perotti, Cesare; Caramella, Carla
2014-01-30
The aim of the present work was the development of a powder formulation for the combined delivery of platelet lysate and of a model antibiotic drug, vancomycin hydrochloride (VCM), in chronic skin ulcers. Calcium alginate particles were prepared by freeze-drying beads obtained by ionic gelation method. The experimental conditions adopted permitted the complete loading of VCM and of PDGF AB, the growth factor chosen as representative of those contained in PL. Such particles where able to absorb PBS (mimicking wound exudate), to form a gel and to modulate the release of VCM and of PDGF AB. They are characterized by enhancement properties of human fibroblast proliferation due to PL presence. In particular, PL, when loaded in alginate particles, was able not only to increase the number of viable cells, but also the number of cells in proliferative phase. Such properties were comparable to those of fresh PL indicating the capability of calcium alginate particles to load PL bioactive substances without altering their activity. The formulation developed is characterized by an easier and a less painful administration with respect to traditional gauzes and semisolid preparations and permits the loading in the same dosage form of active substances of different nature avoiding eventual incompatibility problems. Copyright © 2013 Elsevier B.V. All rights reserved.
Kasina, M; Kleyböcker, A; Michalik, M; Würdemann, H
2015-01-01
In a co-digestion system running with rapeseed oil and sewage sludge, an extremely fast increase in the organic loading rate was studied to develop a procedure to allow for flexible and demand-driven energy production. The over-acidification of the digestate was successfully prevented by calcium oxide dosage, which resulted in granule formation. Mineralogical analyses revealed that the granules were composed of insoluble salts of long chain fatty acids and calcium and had a porous structure. Long chain fatty acids and calcium formed the outer cover of granules and offered interfaces on the inside thereby enhancing the growth of biofilms. With granule size and age, the pore size increased and indicated degradation of granular interfaces. A stable biogas production up to the organic loading rate of 10.4 kg volatile solids m(-3) d(-1) was achieved although the hydrogen concentration was not favorable for propionic acid degradation. However, at higher organic loading rates, unbalanced granule formation and degradation were observed. Obviously, the adaption time for biofilm growth was too short to maintain the balance, thereby resulting in a low methane yield.
NASA Astrophysics Data System (ADS)
Tarlani, Aliakbar; Zarabadi, Mir Pouyan
2013-02-01
In a new approach, strong basic sites has been successfully prepared by loading of calcium nitrate (Ca) on organized nano-porous alumina (ONPA). The prepared CaONPAs were characterized by low-angle X-ray diffraction (XRD), N2 adsorption-desorption isotherms (Brunauer-Emmett-Teller (BET)-Barret-Joyner-Halenda (BJH)), transmission electron microscopy (TEM) and thermogravimetric analysis (TGA). Measuring of the amount of the basic sites and the basicity was carried out by titration method, temperature-programmed desorption (TPD-CO2) and Hammett indicators. Resistance of the basic sites was also tested by washing with water. N2 sorption measurements showed that supporting of the calcium nitrate on ONPA can lead to the bimodal porosity at lower loading. BET surface area of the bare ONPA was 212 m2/g which decreased to 111 m2/g for the 25% of loading of Ca (25CaONPA). The results pointed out that CaONPA samples have basicity between 18.4 < H_ < 22 for 15 and 25% of loadings and well-preserved of the basicity after washing with water especially for 5 and 15% samples. Also no crystalline phase of CaO was observed for 25CaONPA which was calcined at 600 °C.
Balaji Raghavendran, Hanumantha Rao; Pingguan-Murphy, Belinda; Abbas, Azlina A.; Merican, Azhar M.; Kamarul, Tunku
2017-01-01
The role for mechanical stimulation in the control of cell fate has been previously proposed, suggesting that there may be a role of mechanical conditioning in directing mesenchymal stromal cells (MSCs) towards specific lineage for tissue engineering applications. Although previous studies have reported that calcium signalling is involved in regulating many cellular processes in many cell types, its role in managing cellular responses to tensile loading (mechanotransduction) of MSCs has not been fully elucidated. In order to establish this, we disrupted calcium signalling by blocking stretch-activated calcium channel (SACC) in human MSCs (hMSCs) in vitro. Passaged-2 hMSCs were exposed to cyclic tensile loading (1 Hz + 8% for 6, 24, 48, and 72 hours) in the presence of the SACC blocker, gadolinium. Analyses include image observations of immunochemistry and immunofluorescence staining from extracellular matrix (ECM) production, and measuring related tenogenic and apoptosis gene marker expression. Uniaxial tensile loading increased the expression of tenogenic markers and ECM production. However, exposure to strain in the presence of 20 μM gadolinium reduced the induction of almost all tenogenic markers and ECM staining, suggesting that SACC acts as a mechanosensor in strain-induced hMSC tenogenic differentiation process. Although cell death was observed in prolonged stretching, it did not appear to be apoptosis mediated. In conclusion, the knowledge gained in this study by elucidating the role of calcium in MSC mechanotransduction processes, and that in prolonged stretching results in non-apoptosis mediated cell death may be potential useful for regenerative medicine applications. PMID:28654695
Polymer Nanocarriers for Dentin Adhesion
Osorio, R.; Osorio, E.; Medina-Castillo, A.L.; Toledano, M.
2014-01-01
To obtain more durable adhesion to dentin, and to protect collagen fibrils of the dentin matrix from degradation, calcium- and phosphate-releasing particles have been incorporated into the dental adhesive procedure. The aim of the present study was to incorporate zinc-loaded polymeric nanocarriers into a dental adhesive system to facilitate inhibition of matrix metalloproteinases (MMPs)-mediated collagen degradation and to provide calcium ions for mineral deposition within the resin-dentin bonded interface. PolymP-nActive nanoparticles (nanoMyP) were zinc-loaded through 30-minute ZnCl2 immersion and tested for bioactivity by means of 7 days’ immersion in simulated body fluid solution (the Kokubo test). Zinc-loading and calcium phosphate depositions were examined by scanning and transmission electron microscopy, elemental analysis, and x-ray diffraction. Nanoparticles in ethanol solution infiltrated into phosphoric-acid-etched human dentin and Single Bond (3M/ESPE) were applied to determine whether the nanoparticles interfered with bonding. Debonded sticks were analyzed by scanning electron microscopy. A metalloproteinase collagen degradation assay was also performed in resin-infiltrated dentin with and without nanoparticles, measuring C-terminal telopeptide of type I collagen (ICTP) concentration in supernatants, after 4 wk of immersion in artificial saliva. Numerical data were analyzed by analysis of variance (ANOVA) and Student-Newman-Keuls multiple comparisons tests (p < .05). Nanoparticles were effectively zinc-loaded and were shown to have a chelating effect, retaining calcium regardless of zinc incorporation. Nanoparticles failed to infiltrate demineralized intertubular dentin and remained on top of the hybrid layer, without altering bond strength. Calcium and phosphorus were found covering nanoparticles at the hybrid layer, after 24 h. Nanoparticle application in etched dentin also reduced MMP-mediated collagen degradation. Tested nanoparticles may be incorporated into dental adhesive systems to provide the appropriate environment in which dentin MMP collagen degradation is inhibited and mineral growth can occur. PMID:25227634
Spherical nanoindentation stress-strain analysis, Version 1
DOE Office of Scientific and Technical Information (OSTI.GOV)
Weaver, Jordan S.; Turner, David; Miller, Calvin
Nanoindentation is a tool that allows the mechanical response of a variety of materials at the nano to micron length scale to be measured. Recent advances in spherical nanoindentation techniques have allowed for a more reliable and meaningful characterization of the mechanical response from nanoindentation experiments in the form on an indentation stress-strain curve. This code base, Spin, is written in MATLAB (The Mathworks, Inc.) and based on the analysis protocols developed by S.R. Kalidindi and S. Pathak [1, 2]. The inputs include the displacement, load, harmonic contact stiffness, harmonic displacement, and harmonic load from spherical nanoindentation tests in themore » form of an Excel (Microsoft) spreadsheet. The outputs include indentation stress-strain curves and indentation properties as well their variance due to the uncertainty of the zero-point correction in the form of MATLAB data (.mat) and figures (.png). [1] S. Pathak, S.R. Kalidindi. Spherical nanoindentation stress–strain curves, Mater. Sci. Eng R-Rep 91 (2015). [2] S.R. Kalidindi, S. Pathak. Determination of the effective zero-point and the extraction of spherical nanoindentation stress-strain curves, Acta Materialia 56 (2008) 3523-3532.« less
NASA Astrophysics Data System (ADS)
Chabaux, François; Riotte, Jean; Clauer, Norbert; France-Lanord, Christian
2001-10-01
U activity ratios have been measured in the dissolved loads of selected rivers from the Himalayan range, in Central Nepal, and from the Bangladesh, as well as in some rain waters. A few European and Asian rivers have also been analyzed for their U activity ratios. The data confirm the negligible effect of rainwater on the budget of dissolved U in river waters. The results also indicate that rivers on each Himalayan structural unit have homogeneous and specific U isotope compositions: i) (234U/238U) activity ratios slightly lower than unity in the dissolved load of the streams draining the Tethyan Sedimentary Series (TSS); ii) values slightly higher than unity for waters from the High Himalaya Crystalline (HHC) and the Lesser Himalaya (LH); iii) systematically higher (234U/238U) activity ratios for waters from the Siwaliks. Thus, U activity ratios, in association with Sr isotopic ratios, can be used to trace the sources of dissolved fluxes carried by these rivers. Coupling of U with Sr isotope data shows (1) that the U carried by the dissolved load of the Himalayan rivers mainly originates from U-rich lithologies of the TSS in the northern formations of the Tibetan plateau; and (2) that the elemental U and Sr fluxes carried by the Himalayan rivers at the outflow of the highlands are fairly homogeneous at the scale of the Himalayan chain. Rivers flowing on the Indian plain define a different trend from that of the Himalayan rivers in the U-Sr isotopic diagram, indicating the contribution of a specific floodplain component to the U and Sr budgets of the Ganges and the Brahmaputra. The influence of this component remains limited to 10 to 15 percent for the U flux, but can contribute 35 to 55% of the Sr flux. The variations of the Sr and U fluxes of the Ganges-Brahmaputra river system in response to climatic variations have been estimated by assuming a temporary cut off of the chemical fluxes from high-altitude terrains during glacial episodes. This scenario would significantly decrease the dissolved U flux of the Ganges-Brahmaputra river system and increase its U activity ratio. Such a climatic dependence of the Himalayan U flux could induce a periodic variation of the mean U activity ratio of the world rivers on glacial-interglacial timescales
Miura, Yuki; Naka, Masamitsu; Matsuki, Norio; Nomura, Hiroshi
2012-10-31
Action potential-independent transmitter release, or spontaneous release, is postulated to produce multiple postsynaptic effects (e.g., maintenance of dendritic spines and suppression of local dendritic protein synthesis). Potentiation of spontaneous release may contribute to the precise modulation of synaptic function. However, the expression mechanism underlying potentiated spontaneous release remains unclear. In this study, we investigated the involvement of extracellular and intracellular calcium in basal and potentiated spontaneous release. Miniature excitatory postsynaptic currents (mEPSCs) of the basolateral amygdala neurons in acute brain slices were recorded. Forskolin, an adenylate cyclase activator, increased mEPSC frequency, and the increase lasted at least 25 min after washout. Removal of the extracellular calcium decreased mEPSC frequency in both naïve and forskolin-treated slices. On the other hand, chelation of intracellular calcium by BAPTA-AM decreased mEPSC frequency in naïve, but not in forskolin-treated slices. A blockade of the calcium-sensing receptor (CaSR) resulted in an increase in mEPSC frequency in forskolin-treated, but not in naïve slices. These findings indicate that forskolin-induced potentiation is accompanied by changes in the mechanisms underlying Ca(2+)-dependent spontaneous release. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
The role of calcium in excitation-contraction coupling of lobster muscle.
Gainer, H
1968-07-01
Potassium contractures were induced in lobster muscle bundles under conditions which produced varying KCl fluxes into the fibers. The presence or absence of chloride fluxes during depolarization by high concentrations of potassium, had no effect on the tensions developed. The curve relating tension to the membrane potential had a typical sigmoid shape with an apparent "threshold" for tension at -60 mv. Soaking the muscles in low (0.1 mM) calcium salines for 30 min completely eliminated the potassium contractures but the caffeine contractures were only slightly reduced under these conditions. The potassium contracture could be completely restored in less than 2 min by return of the calcium ions to the saline. Evidence is presented for independent, superficial, and deep calcium sites; the superficial sites appear to be involved in the coupling mechanisms associated with potassium contractures. These sites are highly selective for Ca(++), and attempts to substitute either Cd(++), Co(++), Mg(++), Ba(++), or Sr(++) for Ca(++) were unsuccessful. However, K(+) appeared to compete with Ca(++) for these sites, and the evoked tension could be reduced by prestimulation of the muscle fibers with high K(+) salines. The results of studies on the influx of (45)Ca during potassium contractures were compatible with the view of muscle activation by the entry of extracellular calcium.
The SR-71 Test Bed Aircraft: A Facility for High-Speed Flight Research
NASA Technical Reports Server (NTRS)
Corda, Stephen; Moes, Timothy R.; Mizukami, Masashi; Hass, Neal E.; Jones, Daniel; Monaghan, Richard C.; Ray, Ronald J.; Jarvis, Michele L.; Palumbo, Nathan
2000-01-01
The SR-71 test bed aircraft is shown to be a unique platform to flight-test large experiments to supersonic Mach numbers. The test bed hardware mounted on the SR-71 upper fuselage is described. This test bed hardware is composed of a fairing structure called the "canoe" and a large "reflection plane" flat plate for mounting experiments. Total experiment weights, including the canoe and reflection plane, as heavy as 14,500 lb can be mounted on the aircraft and flight-tested to speeds as fast as Mach 3.2 and altitudes as high as 80,000 ft. A brief description of the SR-71 aircraft is given, including details of the structural modifications to the fuselage, modifications to the J58 engines to provide increased thrust, and the addition of a research instrumentation system. Information is presented based on flight data that describes the SR-71 test bed aerodynamics, stability and control, structural and thermal loads, the canoe internal environment, and reflection plane flow quality. Guidelines for designing SR-71 test bed experiments are also provided.
Carr, Lynn; Bardet, Sylvia M; Arnaud-Cormos, Delia; Leveque, Philippe; O'Connor, Rodney P
2018-02-01
Cytosolic, synthetic chemical calcium indicators are typically used to visualise the rapid increase in intracellular calcium ion concentration that follows nanosecond pulsed electric field (nsPEF) application. This study looks at the application of genetically encoded calcium indicators (GECIs) to investigate the spatiotemporal nature of nsPEF-induced calcium signals using fluorescent live cell imaging. Calcium responses to 44kV/cm, 10ns pulses were observed in U87-MG cells expressing either a plasma membrane targeted GECI (GCaMP5-G), or one cytosolically expressed (GCaMP6-S), and compared to the response of cells loaded with cytosolic or plasma membrane targeted chemical calcium indicators. Application of 100 pulses, to cells containing plasma membrane targeted indicators, revealed a wave of calcium across the cell initiating at the cathode side. A similar spatial wave was not observed with cytosolic indicators with mobile calcium buffering properties. The speed of the wave was related to pulse application frequency and it was not propagated by calcium induced calcium release. Copyright © 2017 Elsevier B.V. All rights reserved.
The alkaline earth intercalates of molybdenum disulfide
NASA Technical Reports Server (NTRS)
Somoano, R. B.; Hadek, V.; Rembaum, A.; Samson, S.; Woollam, J. A.
1975-01-01
Molybdenum disulfide has been intercalated with calcium and strontium by means of the liquid ammonia technique. Chemical, X-ray, and superconductivity data are presented. The X-ray data reveal a lowering of crystal symmetry and increase of complexity of the structure upon intercalation with the alkaline earth metals. The Ca and Sr intercalates start to superconduct at 4 and 5.6 K, respectively, and show considerable anisotropy regarding the critical magnetic field.
NASA Astrophysics Data System (ADS)
Heinemann, Agnes; Fietzke, Jan; Eisenhauer, Anton; Zumholz, Karsten
2008-01-01
In this study we present the first combined investigation into the composition of the major matrices involved in calcification processes (surrounding water, extrapallial fluid, aragonite, and calcite) of Mytilus edulis with respect to their calcium isotope (δ44/40Ca) and elemental compositions (Sr/Ca and Mg/Ca). Our aim was to examine the suitability of Mytilus edulis as a proxy archive and to contribute to the understanding of the process of biomineralization. Mytilus edulis specimens were live collected from the Schwentine Estuary, Kiel Fjord, and North Sea (Sylt). δ44/40Ca was determined by thermal ionization mass spectrometry (TIMS) accompanied by measurements of Mg/Ca and Sr/Ca using inductively coupled plasma-optical emission spectroscopy (ICP-OES). The elemental and isotopic compositions of the investigated matrices showed systematic offsets. The carbonates are strongly depleted in their magnesium and strontium concentrations and fractionated toward lighter calcium isotope compositions relative to the surrounding Schwentine Estuary water. The opposite is observed for the extrapallial fluid (EPF). Our findings extend the results of previous studies reporting a strong biological control and the interaction of different environmental conditions influencing biomineralization. Future studies should focus on the temporal development of the interrelation between the different matrices.
NASA Astrophysics Data System (ADS)
Gopi, D.; Nithiya, S.; Shinyjoy, E.; Kavitha, L.
Synthetic calcium hydroxyapatite (HAP,Ca10(PO4)6(OH)2) is a well-known bioceramic material used in orthopaedic and dental applications because of its excellent biocompatibility and bone-bonding ability. Substitution of trace elements, such as Sr, Mg and Zn ions into the structure of calcium phosphates is the subject of widespread investigation. In this paper, we have reported the synthesis of Sr, Mg and Zn co-substituted nanohydroxyapatite by soft solution freezing method. The effect of pH on the morphology of bioceramic nanomaterial was also discussed. The in vitro bioactivity of the as-synthesized bioceramic nanomaterial was determined by soaking it in SBF for various days. The as-synthesized bioceramic nanomaterial was characterized by Fourier transform infrared spectroscopy, X- ray diffraction analysis, Scanning electron microscopy and Energy dispersive X-ray analysis and Transmission electron microscopic techniques respectively. The results obtained in our study have revealed that pH 10 was identified to induce the formation of mineralized nanohydroxyapatite. It is observed that the synthesis of bioceramic nanomaterial not only support the growth of apatite layer on its surface but also accelerate the growth which is evident from the in vitro studies. Therefore, mineralized nanohydroxyapatite is a potential candidate in bone tissue engineering.
Maxwell, Joshua T; Blatter, Lothar A
2017-06-15
In atrial myocytes excitation-contraction coupling is strikingly different from ventricle because atrial myocytes lack a transverse tubule membrane system: Ca 2+ release starts in the cell periphery and propagates towards the cell centre by Ca 2+ -induced Ca 2+ release from the sarcoplasmic reticulum (SR) Ca 2+ store. The cytosolic Ca 2+ sensitivity of the ryanodine receptor (RyRs) Ca 2+ release channel is low and it is unclear how Ca 2+ release can be activated in the interior of atrial cells. Simultaneous confocal imaging of cytosolic and intra-SR calcium revealed a transient elevation of store Ca 2+ that we termed 'Ca 2+ sensitization signal'. We propose a novel paradigm of atrial ECC that is based on tandem activation of the RyRs by cytosolic and luminal Ca 2+ through a 'fire-diffuse-uptake-fire' (or FDUF) mechanism: Ca 2+ uptake by SR Ca 2+ pumps at the propagation front elevates Ca 2+ inside the SR locally, leading to luminal RyR sensitization and lowering of the cytosolic Ca 2+ activation threshold. In atrial myocytes Ca 2+ release during excitation-contraction coupling (ECC) is strikingly different from ventricular myocytes. In many species atrial myocytes lack a transverse tubule system, dividing the sarcoplasmic reticulum (SR) Ca 2+ store into the peripheral subsarcolemmnal junctional (j-SR) and the much more abundant central non-junctional (nj-SR) SR. Action potential (AP)-induced Ca 2+ entry activates Ca 2+ -induced Ca 2+ release (CICR) from j-SR ryanodine receptor (RyR) Ca 2+ release channels. Peripheral elevation of [Ca 2+ ] i initiates CICR from nj-SR and sustains propagation of CICR to the cell centre. Simultaneous confocal measurements of cytosolic ([Ca 2+ ] i ; with the fluorescent Ca 2+ indicator rhod-2) and intra-SR ([Ca 2+ ] SR ; fluo-5N) Ca 2+ in rabbit atrial myocytes revealed that Ca 2+ release from j-SR resulted in a cytosolic Ca 2+ transient of higher amplitude compared to release from nj-SR; however, the degree of depletion of j-SR [Ca 2+ ] SR was smaller than nj-SR [Ca 2+ ] SR . Similarly, Ca 2+ signals from individual release sites of the j-SR showed a larger cytosolic amplitude (Ca 2+ sparks) but smaller depletion (Ca 2+ blinks) than release from nj-SR. During AP-induced Ca 2+ release the rise of [Ca 2+ ] i detected at individual release sites of the nj-SR preceded the depletion of [Ca 2+ ] SR , and during this latency period a transient elevation of [Ca 2+ ] SR occurred. We propose that Ca 2+ release from nj-SR is activated by cytosolic and luminal Ca 2+ (tandem RyR activation) via a novel 'fire-diffuse-uptake-fire' (FDUF) mechanism. This novel paradigm of atrial ECC predicts that Ca 2+ uptake by sarco-endoplasmic reticulum Ca 2+ -ATPase (SERCA) at the propagation front elevates local [Ca 2+ ] SR , leading to luminal RyR sensitization and lowering of the activation threshold for cytosolic CICR. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.
Thakkar, Hetal Paresh; Baser, Amit Kumar; Parmar, Mayur Prakashbhai; Patel, Ketul Harshadbhai; Ramachandra Murthy, Rayasa
2012-06-01
Vincristine-sulfate-loaded liposomes were prepared with an aim to improve stability, reduce drug leakage during systemic circulation, and increase intracellular uptake. Liposomes were prepared by the thin-film hydration method, followed by coating with calcium phosphate, using the sequential addition approach. Prepared formulations were characterized for size, zeta potential, drug-entrapment efficiency, morphology by transmission electron microscopy (TEM), in vitro drug-release profile, and in vitro cell cytotoxicity study. Effect of formulation variables, such as drug:lipid ratio as well as nature and volume of hydration media, were found to affect drug entrapment, and the concentration of calcium chloride in coating was found to affect size and coating efficiency. Size, zeta potential, and TEM images confirmed that the liposomes were effectively coated with calcium phosphate. The calcium phosphate nanoshell exhibited pH-dependent drug release, showing significantly lower release at pH 7.4, compared to the release at pH 4.5, which is the pH of the tumor interstitium. The in vitro cytotoxicity study done on the lung cancer cell line indicated that coated liposomes are more cytotoxic than plain liposomes and drug solution, indicating their potential for intracellular drug delivery. The cell-uptake study done on the lung cancer cell line indicated that calcium-phosphate-coated liposomes show higher cell uptake than uncoated liposomes.
Williams, C P; Child, D F; Hudson, P R; Soysa, L D; Davies, G K; Davies, M G; De Bolla, A R
1996-01-01
AIMS: To present experimental evidence in support of a proposed common cause for absorptive hypercalciuria, renal hypercalciuria, renal phosphate leak and enhancement of 1,25-(OH)2-vitamin D concentrations in patients presenting with renal stone disease; and to suggest further investigation with a view to new management. METHODS: An oral calcium loading test was administered to 15 patients with renal stones and 10 normal controls in the fasting state: urine and blood were collected hourly. After the second urine sample, 400 mg calcium dissolved in water was administered orally. Serum calcium, albumin, parathyroid hormone (PTH), and phosphate were measured together with urine calcium clearance and urinary phosphate from which the TmPO4/glomerular filtration rate (GFR) ratio was calculated. Serum 1,25-(OH)2-vitamin D was measured in the first serum sample. In addition, 24 hour urine calcium results were collected retrospectively from the patients' case notes over the previous 18 months. RESULTS: In the basal state, renal stone patients had an overall greater phosphaturia (lower TmPO4/GFR: median 1.72 compared with 2.10 in controls) and increased calcium clearance. Serum corrected calcium and PTH concentrations did not differ between the groups. After calcium loading, serum calcium and urine calcium clearance rose in both groups, with patients with renal stones experiencing a greater percentage fall in phosphaturia. In both groups TmPO4/GFR fell (greater phosphaturia) with increased serum corrected calcium, with the patients showing notably greater phosphaturia for any given calcium concentration. Patients also had notably greater phosphaturia compared with the serum calcium concentration for any given PTH value. Serum 1,25-(OH)2-vitamin D was higher in patients than controls and for any 1,25-(OH)2-vitamin D concentration phosphaturia measured against serum calcium was greater in patients than controls. 1,25-(OH)2-vitamin D did not correlate with phosphaturia relative to serum calcium concentrations within the patient and control groups. CONCLUSIONS: It is proposed that patients with idiopathic hypercalciuria have an "inappropriately' high phosphate excretion for any given serum calcium concentration. Loss of phosphate may induce increased activation of 1,25-(OH)2-vitamin D. Some of the commonly described causes of stone formation may be manifestations of a single mechanism. PMID:8944605
Photoreduction of CO2 on TiO2/SrTiO3 Heterojunction Network Film
NASA Astrophysics Data System (ADS)
Bi, Yongsheng; Zong, Lanlan; Li, Chen; Li, Qiuye; Yang, Jianjun
2015-08-01
Nanotube titanic acid (NTA) network film has a porous structure and large BET surface area, which lead them to possessing high utilization of the incident light and strong adsorption ability. We used NTA as the precursor to fabricate a TiO2/ SrTiO3 heterojunction film by the hydrothermal method. In the process of the reaction, part of NTA reacted with SrCl2 to form SrTiO3 nanocubes, and the remainder dehydrated to transform to the rutile TiO2. The ratio of TiO2 and SrTiO3 varied with the hydrothermal reaction time. SEM and TEM images indicated that SrTiO3 nanocubes dispersed uniformly on TiO2 film, and the particle size and crystallinity of SrTiO3 nanocubes increased with the reaction time prolonging. The TiO2/SrTiO3 heterojunction obtained by 1 h showed the best activity for CO2 photoreduction, where the mole ratio of TiO2 and SrTiO3 was 4:1. And the photo-conversion efficiency of CO2 to CH4 improved remarkably after the foreign electron traps of Pt and Pd nanoparticles were loaded. The highest photocatalytic production rate of CH4 reached 20.83 ppm/h cm2. In addition, the selectivity of photoreduction product of CO2 was also increased apparently when Pd acted as the cocatalyst on TiO2/SrTiO3 heterojunction film.
NASA Technical Reports Server (NTRS)
Okubo, Tsutomo; Yonemochi, Osamu; Nakamura, Kazuo; Maeda, Minoru
1988-01-01
Chemical compounds SrZrO3, CaZrO3, and BaZrO3 were synthesized by solid reaction and arc fusion, and their properties examined. Results were as follows: (1) in the synthesis of CaZrO3 by solid reaction, ZrO2 solid solution with cubic form was produced, which then changed into CaZrO3; (2) the BaZrO3 was a cubic form and did not show any transformation, while SrZrO3 and CaZrO3 with an orthorhombic form transformed to a cubic form at high temperature; and (3) the solubility of BaZrO3 in acid and its vaporization rate at a high temperature were greater than those of zirconates.
RAPID METHOD FOR DETERMINATION OF RADIOSTRONTIUM IN EMERGENCY MILK SAMPLES
DOE Office of Scientific and Technical Information (OSTI.GOV)
Maxwell, S.; Culligan, B.
2008-07-17
A new rapid separation method for radiostrontium in emergency milk samples was developed at the Savannah River Site (SRS) Environmental Bioassay Laboratory (Aiken, SC, USA) that will allow rapid separation and measurement of Sr-90 within 8 hours. The new method uses calcium phosphate precipitation, nitric acid dissolution of the precipitate to coagulate residual fat/proteins and a rapid strontium separation using Sr Resin (Eichrom Technologies, Darien, IL, USA) with vacuum-assisted flow rates. The method is much faster than previous method that use calcination or cation exchange pretreatment, has excellent chemical recovery, and effectively removes beta interferences. When a 100 ml samplemore » aliquot is used, the method has a detection limit of 0.5 Bq/L, well below generic emergency action levels.« less
Allometric constraints on Sr/Ca and Ba/Ca partitioning in terrestrial mammalian trophic chains.
Balter, Vincent
2004-03-01
In biological systems, strontium (Sr) and barium (Ba) are two non-essential elements, in comparison to calcium (Ca) which is essential. The Sr/Ca and Ba/Ca ratios tend to decrease in biochemical pathways which include Ca as an essential element, and these processes are termed biopurification of Ca. The quantitative pathway of the biopurification of Ca in relation to Sr and Ba between two biological reservoirs ( Rn and R(n -1)) is measured with an observed ratio (OR) expressed by the (Sr/Ca) Rn /(Sr/Ca)( Rn-1) and (Ba/Ca) Rn /(Ba/Ca)( Rn-1) ratios. For a mammalian organism, during the whole biopurification of Ca starting with the diet to the ultimate reservoir of Ca which is the bone, the mean values for ORSr and ORBa are 0.25 and 0.2, respectively. In this study, published Sr/Ca and Ba/Ca ratios are used for three sets of soils, plants, and bones of herbivorous and carnivorous mammals, each comprising a trophic chain, to illustrate the biopurification of Ca at the level of trophic chains. Calculated ORSr and ORBa of herbivore bones in relation to plants and of bones of carnivores in relation to bones of herbivores give ORSr=0.30+/-0.08 and ORBa=0.16+/-0.08, thus suggesting that trophic chains reflect the Sr/Ca and Ba/Ca fluxes that are prevalent at the level of a mammalian organism. The slopes of the three regression equations of log(Sr/Ca) vs. log(Ba/Ca) are similar, indicating that the process of biopurification of Ca with respect to Sr and Ba is due to biological processes and is independent of the geological settings. Modifications of the logarithmic expression of the Sr/Ca and Ba/Ca relationship allow a new formula of the biopurification process to be deduced, leading to the general equation ORBa=ORSr(1.79+/-0.33), where the allometric coefficient is the mean of the slopes of the three regression equations. Some recent examples are used to illustrate this new analysis of predator-prey relations between mammals. This opens up new possibilities for the utilization of Ba/Ca and Sr/Ca in addition to stable isotope ratios (delta13C and delta15N) for the determination of the relative contribution of different food sources to an animal's diet.
Epitaxial Relationships between Calcium Carbonate and Inorganic Substrates
Yang, Taewook; Jho, Jae Young; Kim, Il Won
2014-01-01
The polymorph-selective crystallization of calcium carbonate has been studied in terms of epitaxial relationship between the inorganic substrates and the aragonite/calcite polymorphs with implication in bioinspired mineralization. EpiCalc software was employed to assess the previously published experimental results on two different groups of inorganic substrates: aragonitic carbonate crystals (SrCO3, PbCO3, and BaCO3) and a hexagonal crystal family (α-Al2O3, α-SiO2, and LiNbO3). The maximum size of the overlayer (aragonite or calcite) was calculated for each substrate based on a threshold value of the dimensionless potential to estimate the relative nucleation preference of the polymorphs of calcium carbonate. The results were in good agreement with previous experimental observations, although stereochemical effects between the overlayer and substrate should be separately considered when existed. In assessing the polymorph-selective nucleation, the current method appeared to provide a better tool than the oversimplified mismatch parameters without invoking time-consuming molecular simulation\\. PMID:25226539
NASA Astrophysics Data System (ADS)
Cirino, M.; Dunbar, R. B.; Tangri, N.; Mehta, A.
2014-12-01
We investigated the use of synchrotron radiation for elemental imaging within the skeleton of a Porites coral from American Samoa to explore the fine-scale structure of strontium to calcium (Sr/Ca) variability. The use of a synchrotron for coral paleoclimate analysis is relatively new. The method provides a high resolution, two-dimensional elemental map of a coral surface. The aragonitic skeleton of Porites sp. colonies has been widely used for paleoclimate reconstruction as the oxygen isotope ratio (δ18O) signal varies with both sea surface temperature (SST) and sea surface salinity (SSS). Sr/Ca has been used in previous studies in conjunction with δ18O to deconvolve SST from SSS, as Sr/Ca in the coral skeleton varies with SST, but not SSS. However, recent studies suggest that in some cases Sr/Ca variability in coral does not reliably reflect changes in SST. We sought to address this puzzle by investigating Sr/Ca variability in Porites corals at a very fine spatial scale while also demonstrating the suitability of the synchrotron as a coral analysis tool. We also considered Sr/Ca variability as it pertains to the coral's structural elements. The Stanford Linear Accelerator Center synchrotron station generates collimated x-rays in the energy range of 4500-45000 eV with beam diameters as small as 20 μm. Synchrotron imaging allows faster and higher-resolution Sr/Ca analysis than does inductively coupled plasma mass spectrometry (ICP-MS). It also is capable of mapping spatial distributions of many elements, which aids in the development of a multiproxy approach to paleoclimate reconstruction. Imaging and analysis of the Porites coral using synchrotron radiation revealed an intricate sub-seasonal Sr/Ca signal, possibly correlating to a sub-monthly resolution. This signal, which seems unrelated to SST, dominates the annual signal.
The Biological Nature of Geochemical Proxies: algal symbionts affect coral skeletal chemistry
NASA Astrophysics Data System (ADS)
Owens, K.; Cohen, A. L.; Shimizu, N.
2001-12-01
The strontium-calcium ratio (Sr/Ca) of reef coral skeleton is an important ocean temperature proxy that has been used to address some particularly controversial climate change issues. However, the paleothermometer has sometimes proven unreliable and there are indications that the temperature-dependence of Sr/Ca in coral aragonite is linked to the photosynthetic activity of algal symbionts (zooxanthellae) in coral tissue. We examined the effect of algal symbiosis on skeletal chemistry using Astrangia danae, a small colonial temperate scleractinian that occurs naturally with and without zooxanthellae. Live symbiotic (deep brown) and asymbiotic (white) colonies of similar size were collected in Woods Hole where water temperatures fluctuate seasonally between -2oC and 23oC. We used a microbeam technique (Secondary Ion Mass Spectrometry) and a 30 micron diameter sampling beam to construct high-resolution Sr/Ca profiles, 2500 microns long, down the growth axes of the outer calical (thecal) walls. Profiles generated from co-occuring symbiotic and asymbiotic colonies are remarkably different despite their exposure to identical water temperatures. Symbiotic coral Sr/Ca displays four large-amplitude annual cycles with high values in the winter, low values in the summer and a temperature dependence similar to that of tropical reef corals. By comparison, Sr/Ca profiles constructed from asymbiotic coral skeleton display little variability over the same time period. Asymbiont Sr/Ca is relatively insensitive to the enormous temperature changes experienced over the year; the temperature dependence is similar to that of nighttime skeletal deposits in tropical reef corals and non-biological aragonite precipitates. We propose that the large variations in skeletal Sr/Ca observed in all symbiont-hosting coral species are not related to SST variability per se but are driven primarily by large seasonal variations in skeletal calcification rate associated with symbiont photosynthesis. Our model provides a framework for understanding the role of biology in determining coral skeletal chemistry and an explanation for anomalous Sr/Ca-based paleotemperature derivations.
USDA-ARS?s Scientific Manuscript database
Despite some beneficial effects on bone, high protein diets are conventionally considered a primary dietary risk factor for osteoporosis and bone fracture due to the acid load associated with protein catabolism. To test the hypothesis that high dietary protein diets do not negatively affect calcium ...
Magnesium stable isotope ecology using mammal tooth enamel
NASA Astrophysics Data System (ADS)
Martin, Jeremy E.; Vance, Derek; Balter, Vincent
2015-01-01
Geochemical inferences on ancient diet using bone and enamel apatite rely mainly on carbon isotope ratios (δ13C) and to a lesser extent on strontium/calcium (Sr/Ca) and barium/calcium (Ba/Ca) elemental ratios. Recent developments in nontraditional stable isotopes provide an unprecedented opportunity to use additional paleodietary proxies to disentangle complex diets such as omnivory. Of particular relevance for paleodietary reconstruction are metals present in large quantity in bone and enamel apatite, providing that biologically mediated fractionation processes are constrained. Calcium isotope ratios (δ44Ca) meet these criteria but exhibit complex ecological patterning. Stable magnesium isotope ratios (δ26Mg) also meet these criteria but a comprehensive understanding of its variability awaits new isotopic data. Here, 11 extant mammal species of known ecology from a single locality in equatorial Africa were sampled for tooth enamel and, together with vegetation and feces, analyzed for δ26Mg, δ13C, Sr/Ca, and Ba/Ca ratios. The results demonstrate that δ26Mg incorporated in tooth enamel becomes heavier from strict herbivores to omnivores/faunivores. Using data from experimentally raised sheep, we suggest that this 26Mg enrichment up the trophic chain is due to a 26Mg enrichment in muscle relative to bone. Notably, it is possible to distinguish omnivores from herbivores, using δ26Mg coupled to Ba/Ca ratios. The potential effects of metabolic and dietary changes on the enamel δ26Mg composition remain to be explored but, in the future, multiproxy approaches would permit a substantial refinement of dietary behaviors or enable accurate trophic reconstruction despite specimen-limited sampling, as is often the case for fossil assemblages.
Zimmerman, C.E.; Reeves, G.H.
2002-01-01
Comparisons of strontium:calcium (Sr:Ca) ratios in otolith primordia and freshwater growth regions were used to identify the progeny of steelhead Oncorhynchus mykiss (anadromous rainbow trout) and resident rainbow trout in the Deschutes River, Oregon. We cultured progeny of known adult steelhead and resident rainbow trout to confirm the relationship between Sr:Ca ratios in otolith primordia and the life history of the maternal parent. The mean (??SD) Sr:Ca ratio was significantly higher in the otolith primordia of the progeny of steelhead (0.001461 ?? 0.00029; n = 100) than in those of the progeny of resident rainbow trout (0.000829 ?? 0.000012; n = 100). We used comparisons of Sr:Ca ratios in the primordia and first-summer growth regions of otoliths to determine the maternal origin of unknown O. mykiss juveniles (n = 272) collected from rearing habitats within the main-stem Deschutes River and tributary rearing habitats and thus to ascertain the relative proportion of each life history morph in each rearing habitat. Resident rainbow trout fry dominated the bi-monthly samples collected from main-stem rearing habitats between May and November 1995. Steelhead fry dominated samples collected from below waterfalls on two tributaries in 1996 and 1998.
Wei, Wei-Chun; Jacobs, Benjamin; Becker, Esther B. E.; Glitsch, Maike D.
2015-01-01
G protein-coupled receptors (GPCRs) are cell surface receptors that detect a wide range of extracellular messengers and convey this information to the inside of cells. Extracellular calcium-sensing receptor (CaSR) and ovarian cancer gene receptor 1 (OGR1) are two GPCRs that sense extracellular Ca2+ and H+, respectively. These two ions are key components of the interstitial fluid, and their concentrations change in an activity-dependent manner. Importantly, the interstitial fluid forms part of the microenvironment that influences cell function in health and disease; however, the exact mechanisms through which changes in the microenvironment influence cell function remain largely unknown. We show that CaSR and OGR1 reciprocally inhibit signaling through each other in central neurons, and that this is lost in their transformed counterparts. Furthermore, strong intracellular acidification impairs CaSR function, but potentiates OGR1 function. Thus, CaSR and OGR1 activities can be regulated in a seesaw manner, whereby conditions promoting signaling through one receptor simultaneously inhibit signaling through the other receptor, potentiating the difference in their relative signaling activity. Our results provide insight into how small but consistent changes in the ionic microenvironment of cells can significantly alter the balance between two signaling pathways, which may contribute to disease progression. PMID:26261299
Cement As a Waste Form for Nuclear Fission Products: The Case of (90)Sr and Its Daughters.
Dezerald, Lucile; Kohanoff, Jorge J; Correa, Alfredo A; Caro, Alfredo; Pellenq, Roland J-M; Ulm, Franz J; Saúl, Andrés
2015-11-17
One of the main challenges faced by the nuclear industry is the long-term confinement of nuclear waste. Because it is inexpensive and easy to manufacture, cement is the material of choice to store large volumes of radioactive materials, in particular the low-level medium-lived fission products. It is therefore of utmost importance to assess the chemical and structural stability of cement containing radioactive species. Here, we use ab initio calculations based on density functional theory (DFT) to study the effects of (90)Sr insertion and decay in C-S-H (calcium-silicate-hydrate) in order to test the ability of cement to trap and hold this radioactive fission product and to investigate the consequences of its β-decay on the cement paste structure. We show that (90)Sr is stable when it substitutes the Ca(2+) ions in C-S-H, and so is its daughter nucleus (90)Y after β-decay. Interestingly, (90)Zr, daughter of (90)Y and final product in the decay sequence, is found to be unstable compared to the bulk phase of the element at zero K but stable when compared to the solvated ion in water. Therefore, cement appears as a suitable waste form for (90)Sr storage.
Justen, Gisele C; Espinoza-Quiñones, Fernando R; Módenes, Aparecido Nivaldo; Bergamasco, Rosangela
2012-01-01
In this work the analysis of elements concentration in groundwater was performed using the synchrotron radiation total-reflection X-ray fluorescence (SR-TXRF) technique. A set of nine tube-wells with serious risk of contamination was chosen to monitor the mean concentration of elements in groundwater from the North Serra Geral aquifer in Santa Helena, Brazil, during 1 year. Element concentrations were determined applying a SR-TXRF methodology. The accuracy of SR-TXRF technique was validated by analysis of a certified reference material. As the groundwater composition in the North Serra Geral aquifer showed heterogeneity in the spatial distribution of eight major elements, a hierarchical clustering to the data was performed. By a similarity in their compositions, two of the nine wells were grouped in a first cluster, while the other seven were grouped in a second cluster. Calcium was the major element in all wells, with higher Ca concentration in the second cluster than in the first cluster. However, concentrations of Ti, V, Cr in the first cluster are slightly higher than those in the second cluster. The findings of this study within a monitoring program of tube-wells could provide a useful assessment of controls over groundwater composition and support management at regional level.
Matsumura, M; Mashima, H
1976-01-01
Ca ions were ionophoretically injected through an intracellular microelectrode into the single muscle fiber of a crayfish, and the resulting contraction sphere was observed under a microscope and photographed with a movie camera. The minimum contraction produced by the threshold current involved usually three or four, sometimes two, sarcomers on both sides of the injecting pipette but contraction involving only one sarcomere was not observered. The rheobase of the Ca-injecting current was 3.2 X 10(-9) A. The strength-duration curves were determined for Ca-, Sr-, and Ba-injecting currents; all fitted a similar hyperbolic equation. The threshold amount of Ca above rheobasic injection was 2.1 X 10(-15)mol, and the ratios between threshold amounts were Ca: Sr: Ba=1: 1.9: 3.0. The effects of Ca and Sr were additive for the contraction. More current was required for the Ca-injection to produce the contraction in the K-depolarized-or 15mM-procaine-treated muscle, although less current was sufficient for the muscle treated with 0.5-1.0 mM of caffeine. The participation of the Ca-induced Ca release mechanism in the contraction produced by Ca injection and the role of Sr or Ba as a substitute for Ca were discussed.
Effect of Microgravity on Bone Tissue and Calcium Metabolism
NASA Technical Reports Server (NTRS)
1997-01-01
Session TA4 includes short reports concerning: (1) Human Bone Tissue Changes after Long-Term Space Flight: Phenomenology and Possible Mechanics; (2) Prediction of Femoral Neck Bone Mineral Density Change in Space; (3) Dietary Calcium in Space; (4) Calcium Metabolism During Extended-Duration Space Flight; (5) External Impact Loads on the Lower Extremity During Jumping in Simulated Microgravity and the Relationship to Internal Bone Strain; and (6) Bone Loss During Long Term Space Flight is Prevented by the Application of a Short Term Impulsive Mechanical Stimulus.
NASA Astrophysics Data System (ADS)
Brázda, Petr; Mutombo, Pingo; Ondráček, Martin; Corrêa, Cinthia Antunes; Kopeček, Jaromír; Palatinus, Lukáš
2018-05-01
The bulk and surface structures of calcium and strontium disilicides are investigated by computational methods using density functional theory. The investigated structures are R6, R3 and P1-CaSi2 and P1-SrSi2. The investigated properties are the cleavage energy at the silicene sheet, buckling of the bulk and surface silicene layers, charge transfer from calcium to silicon, band structure of bulk and surface-terminated structures and adsorption energies on H atoms and H2 molecules on the silicene-terminated surface of the R3 phase. The cleavage energy at the silicene surface is low in all cases. Structures P1-CaSi2 and R3-CaSi2 contain silicene sheets with different coordination to Ca, while R6-CaSi2 contains both types of the sheets. It is shown that the properties of the two types of silicene-like sheets in R6-CaSi2 are similar to those of the corresponding sheets in P1-CaSi2 and R3-CaSi2, and the thermodynamically stable R6 phase is a good candidate for experimental investigation of silicene-terminated surface in calcium disilicide.
Estoppey, Nicolas; Schopfer, Adrien; Fong, Camille; Delémont, Olivier; De Alencastro, Luiz F; Esseiva, Pierre
2016-12-01
This study firstly aims to assess the field performances of low density polyethylene (LDPE) and silicone rubber (SR) samplers for the monitoring of polychlorinated biphenyls (PCBs) in water regarding the uptake, the sampling rate (R S ) estimated by using performance reference compounds (PRCs) and the time-weighted average (TWA) concentrations. The second aim is to evaluate the efficiency of these samplers to investigate PCB sources (localization and imputation steps) using methods with and without PRCs to correct for the impact of water velocity on the uptake. Samplers spiked with PRCs were deployed in the outfalls of two PCB sources and at 8 river sites situated upstream and downstream of the outfalls. After 6weeks, the uptake of PCBs in the linear phase was equivalent in LDPE and SR but 5 times lower in LDPE for PCBs approaching equilibrium. PRC-based R S and water velocity (0.08 to 1.21ms -1 ) were well correlated in river (LDPE: R 2 =0.91, SR: R 2 =0.96) but not in outfalls (higher turbulences and potential release of PRCs to air). TWA concentrations obtained with SR were slightly higher than those obtained with LDPE (factor 1.4 to 2.6 in river) likely because of uncertainty in sampler-water partition coefficient values. Concentrations obtained through filtration and extraction of water samples (203L) were 1.6 and 5.1 times higher than TWA concentrations obtained with SR and LDPE samplers, respectively. PCB sources could efficiently be localized when PRCs were used (increases of PCB loads in river) but the impact of high differences of water velocity was overcorrected (leading sometimes to false positives and negatives). Increases of PCB loads in the river could not be entirely imputed to the investigated sources (underestimation of PCBs contributing to the load increases). A method without PRCs (relationship between uptake and water velocity) appeared to be a good complementary method for LDPE. Copyright © 2016. Published by Elsevier B.V.
Effect of ADP on slow-twitch muscle fibres of the rat: implications for muscle fatigue.
Macdonald, W A; Stephenson, D G
2006-05-15
Slow-twitch mechanically skinned fibres from rat soleus muscle were bathed in solutions mimicking the myoplasmic environment but containing different [ADP] (0.1 microm to 1.0 mm). The effect of ADP on sarcoplasmic reticulum (SR) Ca2+-content was determined from the magnitude of caffeine-induced force responses, while temporal changes in SR Ca2+-content allowed determination of the effective rates of the SR Ca2+-pump and of the SR Ca2+-leak. The SR Ca2+-pump rate, estimated at pCa (-log10[Ca2+]) 7.8, was reduced by 20% as the [ADP] was increased from 0.1 to 40 microm, with no further alteration when the [ADP] was increased to 1.0 mm. The SR Ca2+-leak rate constant was not altered by increasing [ADP] from 0.1 to 40 microm, but was increased by 26% when the [ADP] was elevated to 1.0 mm. This ADP-induced SR Ca2+-leak was insensitive to ruthenium red but was abolished by 2,5-di(tert-butyl)-1,4-hydroquinone (TBQ), indicating that the leak pathway is via the SR Ca2+-pump and not the SR Ca2+-release channel. The decrease in SR Ca2+-pump rate and SR Ca2+-leak rate when [ADP] was increased led to a 40% decrease in SR Ca2+-loading capacity. Elevation of [ADP] had only minor direct effects on the contractile apparatus of slow-twitch fibres. These results suggest that ADP has only limited depressing effects on the contractility of slow-twitch muscle fibres. This is in contrast to the marked effects of ADP on force responses in fast-twitch muscle fibres and may contribute to the fatigue-resistant nature of slow-twitch muscle fibres.
Zhu, Yuan; Wang, Miaomiao; Zhang, Ya; Zeng, Jin; Omari-Siaw, E; Yu, Jiangnan; Xu, Ximing
2016-10-01
Developing a promising carrier for the delivery of poorly water-soluble drugs, such as silybin, to improve oral absorption has become a very worthy of consideration. The goal of this study was to prepare a novel porous calcium phosphate microparticle using povidone-mixed micelles as template while evaluating its in vitro and in vivo properties with silybin as a model drug. The particle characterization, in vitro drug release behavior, and pharmacokinetic parameters of the prepared silybin-loaded calcium phosphate microparticle were investigated. The mean particle size was found to be 3.54 ± 0.32 μm with a rough surface porous structure. Additionally, the silybin-loaded calcium phosphate microparticle compared with the free silybin showed a prolonged 72-h release in vitro and a higher C max (418.5 ± 23.7 ng mL(-1)) with 167.5% oral relative bioavailability. A level A in vitro-in vivo correlation (IVIVC), established for the first time, demonstrated an excellent IVIVC of the formulated silybin in oral administration. In conclusion, this povidone-mixed micelle-based microparticle was successfully prepared to enhance the oral bioavailability of silybin. Therefore, application of this novel porous calcium phosphate microparticle holds a significant potential for the development of poorly water-soluble drugs.
Dixon, P B; Hahn, D W
2005-01-15
The detection and identification of individual bioaerosols using laser-induced breakdown spectroscopy (LIBS) is investigated using aerosolized Bacillus spores. Spores of Bacillus atrophaeous, Bacillus pumilus, and Bacillus stearothemophilus were introduced into an aerosol flow stream in a prescribed manner such that single-particle LIBS detection was realized. Bacillus spores were successfully detected based on the presence of the 393.4- and 396.9-nm calcium atomic emission lines. Statistical analyses based on the aerosol number density, the LIBS-based spore sampling frequency, and the distribution of the resulting calcium mass loadings support the conclusion of individual spore detection within single-shot laser-induced plasmas. The average mass loadings were in the range of 2-3 fg of calcium/Bacillus spore, which corresponds to a calcium mass percentage of approximately 0.5%. While individual spores were detected based on calcium emission, the resulting Bacillus spectra were free from CN emission bands, which has implications for the detection of elemental carbon, and LIBS-based detection of single spores based on the presence of magnesium or sodium atomic emission was unsuccessful. Based on the current instrumental setup and analyses, real-time LIBS-based detection and identification of single Bacillus spores in ambient (i.e., real life) conditions appears unfeasible.
Aggarwal, Abhishek; Schulz, Herbert; Manhardt, Teresa; Bilban, Martin; Thakker, Rajesh V; Kallay, Enikö
2017-06-01
Colorectal cancer is one of the most common cancers in industrialised societies. Epidemiological studies, animal experiments, and randomized clinical trials have shown that dietary factors can influence all stages of colorectal carcinogenesis, from initiation through promotion to progression. Calcium is one of the factors with a chemoprophylactic effect in colorectal cancer. The aim of this study was to understand the molecular mechanisms of the anti-tumorigenic effects of extracellular calcium ([Ca 2+ ] o ) in colon cancer cells. Gene expression microarray analysis of colon cancer cells treated for 1, 4, and 24h with 2mM [Ca 2+ ] o identified significant changes in expression of 1571 probe sets (ANOVA, p<10 -5 ). The main biological processes affected by [Ca 2+ ] o were DNA replication, cell division, and regulation of transcription. All factors involved in DNA replication-licensing were significantly downregulated by [Ca 2+ ] o . Furthermore, we show that the calcium-sensing receptor (CaSR), a G protein-coupled receptor is a mediator involved in this process. To test whether these results were physiologically relevant, we fed mice with a standard diet containing low (0.04%), intermediate (0.1%), or high (0.9%) levels of dietary calcium. The main molecules regulating replication licensing were inhibited also in vivo, in the colon of mice fed high calcium diet. We show that among the mechanisms behind the chemopreventive effect of [Ca 2+ ] o is inhibition of replication licensing, a process often deregulated in neoplastic transformation. Our data suggest that dietary calcium is effective in preventing replicative stress, one of the main drivers of cancer and this process is mediated by the calcium-sensing receptor. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
Optimizing pressurized contact area in rotator cuff repair: the diamondback repair.
Burkhart, Stephen S; Denard, Patrick J; Obopilwe, Elifho; Mazzocca, Augustus D
2012-02-01
The purpose of this study was to compare tendon-bone footprint contact area over time under physiologic loads for 4 different rotator cuff repair techniques: single row (SR), triangle double row (DR), chain-link double row (CL), and diamondback double row (DBK). A supraspinatus tear was created in 28 human cadavers. Tears were fixed with 1 of 4 constructs: SR, DR, CL, or DBK. Immediate post-repair measurements of pressurized contact area were taken in neutral rotation and 0° of abduction. After a static tensile load, pressurized contact area was observed over a 160-minute period after repair. Cyclic loading was then performed. The DBK repair had the highest pressurized contact area initially, as well as the highest pressurized contact area and lowest percentage decrease in pressurized contact area after 160 minutes of testing. The DBK repair had significantly larger initial pressurized contact than CL (P = .003) and SR (P = .004) but not DR (P = .06). The DBK technique was the only technique that produced a pressurized contact area that exceeded the native footprint both at initial repair (P = .01) and after 160 minutes of testing (P = .01). DBK had a significantly larger mean pressurized contact area than all the repairs after 160 minutes of testing (P = .01). DBK had a significantly larger post-cyclic loading pressurized contact area than CL (P = .01) and SR (P = .004) but not DR (P = .07). This study showed that a diamondback repair (a modification of the transosseous repair) can significantly increase the rotator cuff pressurized contact area in comparison with other standard rotator cuff repair constructs when there is sufficient tendon mobility to perform a double-row repair without excessive tension on the repair site. The persistent pressurized contact area of a DBK repair may be desirable to enhance healing potential when there is sufficient tendon mobility to perform a double-row repair, particularly for large or massive rotator cuff tears where it is important to optimize footprint area and contact to encourage biologic healing. Copyright © 2012 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.
Kiyak, Gorkem; Balikci, Tevfik; Heydar, Ahmed Majid; Bezer, Murat
2018-02-01
Mechanical study. To compare the pullout strength of different screw designs and augmentation techniques in an osteoporotic bone model. Adequate bone screw pullout strength is a common problem among osteoporotic patients. Various screw designs and augmentation techniques have been developed to improve the biomechanical characteristics of the bone-screw interface. Polyurethane blocks were used to mimic human osteoporotic cancellous bone, and six different screw designs were tested. Five standard and expandable screws without augmentation, eight expandable screws with polymethylmethacrylate (PMMA) or calcium phosphate augmentation, and distal cannulated screws with PMMA and calcium phosphate augmentation were tested. Mechanical tests were performed on 10 unused new screws of each group. Screws with or without augmentation were inserted in a block that was held in a fixture frame, and a longitudinal extraction force was applied to the screw head at a loading rate of 5 mm/min. Maximum load was recorded in a load displacement curve. The peak pullout force of all tested screws with or without augmentation was significantly greater than that of the standard pedicle screw. The greatest pullout force was observed with 40-mm expandable pedicle screws with four fins and PMMA augmentation. Augmented distal cannulated screws did not have a greater peak pullout force than nonaugmented expandable screws. PMMA augmentation provided a greater peak pullout force than calcium phosphate augmentation. Expandable pedicle screws had greater peak pullout forces than standard pedicle screws and had the advantage of augmentation with either PMMA or calcium phosphate cement. Although calcium phosphate cement is biodegradable, osteoconductive, and nonexothermic, PMMA provided a significantly greater peak pullout force. PMMA-augmented expandable 40-mm four-fin pedicle screws had the greatest peak pullout force.
Thounaojam, Menaka C; Jadeja, Ravirajsinh N; Salunke, Sunita P; Devkar, Ranjitsinh V; Ramachandran, A V
2012-10-01
The present study evaluates efficacy of Sida rhomboidea.Roxb (SR) leaves extract in ameliorating experimental atherosclerosis using in vitro and in vivo experimental models. Atherogenic (ATH) diet fed rats recorded significant increment in the serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), very LDL (VLDL), autoantibody against oxidized LDL (Ox-LDL), markers of LDL oxidation and decrement in high-density lipoprotein (HDL) along with increment in aortic TC and TG. The ex vivo LDL oxidation assay revealed an increased susceptibility of LDL isolated from ATH rats to undergo copper mediated oxidation. These set of changes were minimized by simultaneous co-supplementation of SR extract to ATH diet fed rats. Histopathology of aorta and immunolocalization studies recorded pronounced atheromatous plaque formation, vascular calcification, significant elastin derangements and higher expression of macrophage surface marker (F4/80), vascular cell adhesion molecule-1 (VCAM-1) and p-selectin in ATH rats. Whereas, ATH+SR rats depicted minimal evidence of atheromatous plaque formation, calcium deposition, distortion/defragmentation of elastin and accumulation of macrophages along with lowered expression of VCAM-1 and P-selectin compared to ATH rats. Further, monocyte to macrophage differentiation and in vitro foam cell formation were significantly attenuated in presence of SR extract. In conclusion, SR extract has the potency of controlling experimental atherosclerosis and can be used as promising herbal supplement in combating atherosclerosis.
Lipogenesis mitigates dysregulated sarcoplasmic reticulum calcium uptake in muscular dystrophy.
Paran, Christopher W; Zou, Kai; Ferrara, Patrick J; Song, Haowei; Turk, John; Funai, Katsuhiko
2015-12-01
Muscular dystrophy is accompanied by a reduction in activity of sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) that contributes to abnormal Ca(2+) homeostasis in sarco/endoplasmic reticulum (SR/ER). Recent findings suggest that skeletal muscle fatty acid synthase (FAS) modulates SERCA activity and muscle function via its effects on SR membrane phospholipids. In this study, we examined muscle's lipid metabolism in mdx mice, a mouse model for Duchenne muscular dystrophy (DMD). De novo lipogenesis was ~50% reduced in mdx muscles compared to wildtype (WT) muscles. Gene expressions of lipogenic and other ER lipid-modifying enzymes were found to be differentially expressed between wildtype (WT) and mdx muscles. A comprehensive examination of muscles' SR phospholipidome revealed elevated phosphatidylcholine (PC) and PC/phosphatidylethanolamine (PE) ratio in mdx compared to WT mice. Studies in primary myocytes suggested that defects in key lipogenic enzymes including FAS, stearoyl-CoA desaturase-1 (SCD1), and Lipin1 are likely contributing to reduced SERCA activity in mdx mice. Triple transgenic expression of FAS, SCD1, and Lipin1 (3TG) in mdx myocytes partly rescued SERCA activity, which coincided with an increase in SR PE that normalized PC/PE ratio. These findings implicate a defect in lipogenesis to be a contributing factor for SERCA dysfunction in muscular dystrophy. Restoration of muscle's lipogenic pathway appears to mitigate SERCA function through its effects on SR membrane composition. Copyright © 2015. Published by Elsevier B.V.
Spatial distribution of the trace elements zinc, strontium and lead in human bone tissue.
Pemmer, B; Roschger, A; Wastl, A; Hofstaetter, J G; Wobrauschek, P; Simon, R; Thaler, H W; Roschger, P; Klaushofer, K; Streli, C
2013-11-01
Trace elements are chemical elements in minute quantities, which are known to accumulate in the bone. Cortical and trabecular bones consist of bone structural units (BSUs) such as osteons and bone packets of different mineral content and are separated by cement lines. Previous studies investigating trace elements in bone lacked resolution and therefore very little is known about the local concentration of zinc (Zn), strontium (Sr) and lead (Pb) in BSUs of human bone. We used synchrotron radiation induced micro X-ray fluorescence analysis (SR μ-XRF) in combination with quantitative backscattered electron imaging (qBEI) to determine the distribution and accumulation of Zn, Sr, and Pb in human bone tissue. Fourteen human bone samples (10 femoral necks and 4 femoral heads) from individuals with osteoporotic femoral neck fractures as well as from healthy individuals were analyzed. Fluorescence intensity maps were matched with BE images and correlated with calcium (Ca) content. We found that Zn and Pb had significantly increased levels in the cement lines of all samples compared to the surrounding mineralized bone matrix. Pb and Sr levels were found to be correlated with the degree of mineralization. Interestingly, Zn intensities had no correlation with Ca levels. We have shown for the first time that there is a differential accumulation of the trace elements Zn, Pb and Sr in BSUs of human bone indicating different mechanisms of accumulation. © 2013. Published by Elsevier Inc. All rights reserved.
Tranquille, C A; Walker, V A; Hernlund, E; Egenvall, A; Roepstorff, L; Peterson, M L; Murray, R C
2015-01-01
A recent epidemiological study identified various aspects of arena surfaces and arena surface maintenance that were related to risk of injury in horses and that arena maintenance is important in reducing injury risk. However, there has been little research into how properties of arena surfaces change with harrowing. This study aimed to compare the properties of different arena surface types pre- and post-harrowing. The Orono Biomechanical Surface Tester fitted with accelerometers and a single- and a three-axis load cell was used to test 11 arenas with two different surfaces types, sand with rubber (SR) and waxed-sand with fibre (WSF). Three drop tests were carried out at 10 standardised locations on each arena. Mixed models were created to assess the effect of surface type, pre- or post-harrowing, and drop number on the properties of the surface, including maximum horizontal deceleration, maximum vertical deceleration, maximum vertical load and maximum horizontal load. Post-harrowing, none of the parameters were altered significantly on SR. On WSF, maximum vertical deceleration and maximum vertical load significantly decreased post-harrowing. The differences in the effects of superficial harrowing on SR and WSF could be attributed to the different compositions and sizes of the surface material. The results suggest that different maintenance techniques may be more suitable for different surface types and that the effects of superficial harrowing are short-lived due to the rapid re-compaction of the surface with repeated drops on WSF. Further work is required to determine the effects of other maintenance techniques, and on other surface types. Copyright © 2014 Elsevier Ltd. All rights reserved.
Migration of Sakhalin taimen (Parahucho perryi): Evidence of freshwater resident life history types
Zimmerman, C.E.; Rand, P.S.; Fukushima, M.; Zolotukhin, S.F.
2012-01-01
Sakhalin taimen (Parahucho perryi) range from the Russian Far East mainland along the Sea of Japan coast, and Sakhalin, Kuril, and Hokkaido Islands and are considered to primarily be an anadromous species. We used otolith strontium-to-calcium ratios (Sr/Ca) to determine the chronology of migration between freshwater and saltwater and identify migratory contingents of taimen collected from the Koppi River, Russia. In addition, we examined taimen from the Sarufutsu River, Japan and Tumnin River, Russia that were captured in marine waters. Transects of otolith Sr/Ca for the Sarufutsu River fish were consistent with patterns observed in anadromous salmonids. Two fish from the Tumnin River appeared to be recent migrants to saltwater and one fish was characterized by an otolith Sr/Ca transect consistent with marine migration. Using these transects as benchmarks, all Koppi River taimen were classified as freshwater residents. These findings suggest more work is needed to assess life history variability among locations and the role of freshwater productivity in controlling migratory behavior in taimen. ?? 2011 Springer Science+Business Media B.V. (outside the USA).
Tong, Fei; Chai, Rongkui; Jiang, Haiying; Dong, Bo
2018-01-01
The objective of this study was to survey the therapeutic function of curcumin-encapsulated poly(gamma-benzyl l-glutamate)-poly(ethylene glycol)-poly(gammabenzyl l-glutamate) (PBLG-PEG-PBLG) (P) on diabetic cardiomyopathy (DCM) via cross regulation effect of calcium-sensing receptor (CaSR) and endogenous cystathionine-γ-lyase (CSE)/hydrogen sulfide (H 2 S). Diabetic rats were preconditioned with 20 mg/kg curcumin or curcumin/P complex continuously for 8 weeks. The blood and myocardiums were collected, the level of serum H 2 S was observed, and the [Ca 2+ ] i content was measured in myocardial cells, and hematoxylin-eosin, CaSR, CSE, and calmodulin (CaM) expression were detected. Both curcumin and curcumin/P pretreatment alleviated pathological morphological damage of myocardium, increased H 2 S and [Ca 2+ ] i levels, and upregulated the expression of CaSR, CSE, and CaM as compared to DCM group, while curcumin/P remarkably augmented this effect. PBLG-PEG-PBLG could improve water-solubility and bioactivity of curcumin and curcumin/PBLG-PEG-PBLG significantly alleviated diabetic cardiomyopathy.
Maleki Dizaj, Solmaz; Lotfipour, Farzaneh; Barzegar-Jalali, Mohammad; Zarrintan, Mohammad-Hossein; Adibkia, Khosro
2017-05-01
Ciprofloxacin HCl-loaded calcium carbonate (CaCO 3 ) nanoparticles were prepared via a w/o microemulsion method and characterized by dynamic light scattering, scanning electron microscopy, X-ray powder diffraction (XRPD) analysis, differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). The in vitro drug release profiles as well as antimicrobial effect against Staphylococcus aureus (S. aureus) were also evaluated. The antibacterial effect was studied using serial dilution technique to determine the minimum inhibitory concentration (MIC) of the nanoparticles and was confirmed by streak cultures. The mean particle size, drug loading and entrapment efficiency were calculated to be 116.09 nm, 20.49% and 44.05%, respectively. PXRD and FTIR studies confirmed that both vaterite and calcite polymorphs of CaCO 3 were formed during the preparation process. In vitro release profiles of the nanoparticles showed slow release pattern for 12 h. The drug-loaded nanoparticles showed similar MICs against S. aureus compared to untreated drug. However, a preserved antimicrobial effect was observed for drug-loaded nanoparticles compared to untreated drug after 2 days of incubation.
The role of low acid load in vegetarian diet on bone health: a narrative review.
Burckhardt, Peter
2016-01-01
Vegetarian and vegan diets contain low amounts of protein and calcium. For this reason they are supposed to cause low bone mineral density (BMD) and osteoporosis. But this is not the case, except for vegans with a particularly low calcium intake. The absence of osteoporosis or low BMD can be explained by the low acid load of these diets. Nutritional acid load is negatively correlated with bone mineral density (BMD) and positively with fracture risk. Low acid load is correlated with lower bone resorption and higher BMD. It is linked to high intake of potassium-rich nutrients, such as fruits and vegetables, as found in vegetarian diets. The total nutritional acid load, which not only depends on the potassium content of the nutrition, was recently assessed in several studies on vegetarian and vegan diets and was found to be very low or absent, while the diet of Western-style omnivores produces daily 50 to 70 mEq of acid. This might be an important factor for the protection of vegetarians from osteoporosis.
Ehrich, Marion; Wu, Xiaohua; Werre, Stephen R; Major, Michael A; McCain, Wilfred C; Reddy, Gunda
2009-01-01
Cyclotrimethylenetrinitramine (RDX) has been used extensively as an explosive in military munitions. Mechanisms for seizure production, seen in past animal studies, have not been described. Increased calcium levels contribute to excitotoxicity, so in this study neuroblastoma cells are loaded with calcium-indicating dye before application of 1.5 microM to 7.5 mM RDX, with fluorescence recorded for 30 cycles of 11 seconds each. The lowest concentration of RDX increases calcium fluorescence significantly above baseline for cycles 2 to 8; millimolar concentrations increase calcium fluorescence significantly above baseline for cycles 2 to 30. Increases in calcium, like those of 200 nM carbachol, are prevented with 10 mM of calcium chelator ethylene glycol-bis(beta-aminoethyl ether)-N,N,N,N tetra-acetic acid (EGTA, tetrasodium salt). Calcium channel blocker verapamil (20 microM), Ca(2+)-ATPase inhibitor thapsigargin (5 microM), and general membrane stabilizer lidocaine (10 mM) partially attenuate carbachol- and RDX-induced increases in calcium, suggesting that RDX transiently increases intracellular calcium by multiple mechanisms.
Calcitonin control of calcium metabolism during weightlessness
NASA Technical Reports Server (NTRS)
Soliman, Karam F. A.
1993-01-01
The main objective of this proposal is to elucidate calcitonin role in calcium homeostasis during weightlessness. In this investigation our objectives are to study: the effect of weightlessness on thyroid and serum calcitonin, the effect of weightlessness on the circadian variation of calcitonin in serum and the thyroid gland, the role of light as zeitgeber for calcitonin circadian rhythm, the circadian pattern of thyroid sensitivity to release calcitonin in response to calcium load, and the role of serotonin and norepinephrine in the control of calcitonin release. The main objective of this research/proposal is to establish the role of calcitonin in calcium metabolism during weightlessness condition. Understanding the mechanism of these abnormalities will help in developing therapeutic means to counter calcium imbalance in spaceflights.
Esmaeili, Alireza; Stewart, Andrew M; Hopkins, William G; Elias, George P; Lazarus, Brendan H; Rowell, Amber E; Aughey, Robert J
2018-01-01
Aim: The sit and reach test (S&R), dorsiflexion lunge test (DLT), and adductor squeeze test (AST) are commonly used in weekly musculoskeletal screening for athlete monitoring and injury prevention purposes. The aim of this study was to determine the normal week to week variability of the test scores, individual differences in variability, and the effects of training load on the scores. Methods: Forty-four elite Australian rules footballers from one club completed the weekly screening tests on day 2 or 3 post-main training (pre-season) or post-match (in-season) over a 10 month season. Ratings of perceived exertion and session duration for all training sessions were used to derive various measures of training load via both simple summations and exponentially weighted moving averages. Data were analyzed via linear and quadratic mixed modeling and interpreted using magnitude-based inference. Results: Substantial small to moderate variability was found for the tests at both season phases; for example over the in-season, the normal variability ±90% confidence limits were as follows: S&R ±1.01 cm, ±0.12; DLT ±0.48 cm, ±0.06; AST ±7.4%, ±0.6%. Small individual differences in variability existed for the S&R and AST (factor standard deviations between 1.31 and 1.66). All measures of training load had trivial effects on the screening scores. Conclusion: A change in a test score larger than the normal variability is required to be considered a true change. Athlete monitoring and flagging systems need to account for the individual differences in variability. The tests are not sensitive to internal training load when conducted 2 or 3 days post-training or post-match, and the scores should be interpreted cautiously when used as measures of recovery.
NASA Astrophysics Data System (ADS)
AlKhatib, Mahmoud; Eisenhauer, Anton
2017-07-01
In order to study Strontium (Sr) partitioning and isotope fractionation of Sr and Calcium (Ca) in aragonite we performed precipitation experiments decoupling temperature and precipitation rates (R∗, μmol/m2 h) in the interval of about 2.3-4.5 μmol/m2 h. Aragonite is the only pure solid phase precipitated from a stirred solutions exposed to an atmosphere of NH3 and CO2 gases throughout the spontaneous decomposition of (NH4)2CO3. The order of reaction with respect to Ca ions is one and independent of temperature. However, the order of reaction with respect to the dissolved inorganic carbon (DIC) is temperature dependent and decreases from three via two to one as temperature increases from 12.5 and 25.0 to 37.5 °C, respectively. Strontium distribution coefficient (DSr) increases with decreasing temperature. However, R∗ responds differently depending on the initial Sr/Ca concentration and temperature: at 37.5 °C DSr increase as a function of increasing R∗ but decrease for 12.5 and 25 °C. Not seen at 12.5 and 37.5 °C but at 25 °C the DSr-R∗ gradient is also changing sign depending on the initial Sr/Ca ratio. Magnesium (Mg) adsorption coefficient between aragonite and aqueous solution (DMg) decreases with temperature but increases with R∗ in the range of 2.4-3.8 μmol/m2 h. Strontium isotope fractionation (Δ88/86Sraragonite-aq) follows the kinetic type of fractionation and become increasingly negative as a function of R∗ for all temperatures. In contrast Ca isotope fractionation (Δ44/40Caaragonite-aq) shows a different behavior than the Sr isotopes. At low temperatures (12.5 and 25 °C) Ca isotope fractionation (Δ44/40Caaragonite-aq) becomes positive as a function of R∗. In contrast, at 37.5 °C and as a function of increasing R∗ the Δ44/40Caaragonite-aq show a Sr type like behavior and becomes increasingly negative. Concerning both the discrepant behavior of DSr as a function of temperature as well as for the Ca isotope fractionation as a function of temperature we infer that the switch of sign in the trace element partitioning as well as in the direction of the Ca isotope fractionation is probably due to the switch of complexation from a Ca2+-NH3 complexation at and below 25 °C to an Ca2+-H2O aquacomplex at 37.5 °C. The DSr-Δ88/86Srcalcite-aq correlation for calcite is independent of temperature in contrast to aragonite. We interpreted the strong DSr-temperature dependency of aragonite, the smaller range of Sr isotope fractionation as well as the shallower Δ88/86Srcalcite-aq-R∗ gradients to be a consequence of the increased aragonite solubility and the "Mg blocking effect". In contrast to Sr the Ca isotope fractionation values in calcite and aragonite depend both on the complexation in solution and independent on polymorphism.
Lightweight, high-opacity Bible paper by fiber loading
Klaus Doelle; Oliver Heise; John H. Klungness; Said M. AbuBakr
2000-01-01
This paper has been prepared in order to discuss Fiber Loading⢠for lightweight, high-opacity bible paper. Incorporating fillers within pulp fibers has been subject to research since 1960 (Green et al. 1962, Scallan et al. 1985, Allen et al. 1992). Fiber Loading⢠is a method for manufacturing precipitated calcium carbonate (PCC) directly within the pulp processing...
Marguerite Sykes; John Klungness; Freya Tan; Mathew Stroika; Said Abubakr
1999-01-01
Production of a lightweight, high opacity printing paper is a common goal of papermakers using virgin or recycled fibers. Fiber loading is an innovative, commercially viable process that can substantially upgrade and extend most types of wood fibers. Fiber loading, a process carried out at high consistency and high alkalinity, precipitates calcium carbonate (PCC) in...
Loewen, Anisa; Chan, Benny; Li-Chan, Eunice C Y
2018-02-01
The objectives of this study were to apply response surface methodology to optimize fat-soluble vitamin loading in re-assembled casein micelles, and to evaluate vitamin D stability of dry formulations during ambient or accelerated storage and in fortified fluid skim milk stored under refrigeration. Optimal loading of vitamin A (1.46-1.48mg/100mgcasein) was found at 9.7mM phosphate, 5.5mM citrate and 30.0mM calcium, while optimal loading of vitamin D (1.38-1.46mg/100mg casein) was found at 4.9mM phosphate, 4.0mM citrate and 26.1mM calcium. In general, more vitamin D was retained in vitamin D-re-assembled casein micelles than control powders during storage, while vitamin D loss was not different for vitamin D-re-assembled casein micelles and control fortified milks after 21days of refrigerated storage with light exposure. In conclusion, re-assembled casein micelles with high loading efficiency show promise for improving vitamin D stability during dry storage. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Effect of UV irradiation on different types of luminescence of SrAl2 O4 :Eu,Dy phosphors.
Jha, Piyush
2016-11-01
This paper reports the luminescence behavior of Sr 0.097 Al 2 O 4 :Eu 0.01 ,Dy 0.02 phosphors under UV-irradiation. The effect of UV-irradiation on afterglow (AG), thermoluminescence (TL) and mechanoluminescence (ML) of Sr 0.097 Al 2 O 4 :Eu 0.01 ,Dy 0.02 phosphors is investigated. The space group of Sr 0.097 Al 2 O 4 :Eu 0.01 ,Dy 0.02 phosphors is monoclinic P2 1 . The prepared phosphors exhibit a long AG, intense TL and ML. It is found that the AG, ML intensity and TL increase with increasing duration of irradiation time. The ML intensity decreases with successive impact of the load onto the phosphors, whereby the diminished ML intensity can be recovered by UV-irradiation. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
Some queuing network models of computer systems
NASA Technical Reports Server (NTRS)
Herndon, E. S.
1980-01-01
Queuing network models of a computer system operating with a single workload type are presented. Program algorithms are adapted for use on the Texas Instruments SR-52 programmable calculator. By slightly altering the algorithm to process the G and H matrices row by row instead of column by column, six devices and an unlimited job/terminal population could be handled on the SR-52. Techniques are also introduced for handling a simple load dependent server and for studying interactive systems with fixed multiprogramming limits.
1998-09-01
1 .AND. ICOUNT .GT. ISTRAIN )GOTO 55 Add additional terms in equations for interface nodes If radial loading is applied, add term BMAT (NTOT-1) = SR...term in bmat Using Bmat , and the L-U decomposition of Amat determine XSOL, the vector of radial and hoop stresses CALL LUBKSB(AMAT,NRA,LDA,IPVT... BMAT ,XSOL) Compute stresses from the XSOL solution vector Use Boundary conditions S(1,NTOT2) = SR S(2,1) = S(1,1) Compute total axial
Cardiac microvascular endothelial cells express a functional Ca+ -sensing receptor.
Berra Romani, Roberto; Raqeeb, Abdul; Laforenza, Umberto; Scaffino, Manuela Federica; Moccia, Francesco; Avelino-Cruz, Josè Everardo; Oldani, Amanda; Coltrini, Daniela; Milesi, Veronica; Taglietti, Vanni; Tanzi, Franco
2009-01-01
The mechanism whereby extracellular Ca(2+) exerts the endothelium-dependent control of vascular tone is still unclear. In this study, we assessed whether cardiac microvascular endothelial cells (CMEC) express a functional extracellular Ca(2+)-sensing receptor (CaSR) using a variety of techniques. CaSR mRNA was detected using RT-PCR, and CaSR protein was identified by immunocytochemical analysis. In order to assess the functionality of the receptor, CMEC were loaded with the Ca(2+)-sensitive fluorochrome, Fura-2/AM. A number of CaSR agonists, such as spermine, Gd(3+), La(3+) and neomycin, elicited a heterogeneous intracellular Ca(2+) signal, which was abolished by disruption of inositol 1,4,5-trisphosphate (InsP(3)) signaling and by depletion of intracellular stores with cyclopiazonic acid. The inhibition of the Na(+)/Ca(2+) exchanger upon substitution of extracellular Na(+) unmasked the Ca(2+) signal triggered by an increase in extracellular Ca(2+) levels. Finally, aromatic amino acids, which function as allosteric activators of CaSR, potentiated the Ca(2+) response to the CaSR agonist La(3+). These data provide evidence that CMEC express CaSR, which is able to respond to physiological agonists by mobilizing Ca(2+) from intracellular InsP(3)-sensitive stores. Copyright 2008 S. Karger AG, Basel.
Ludwar, Bjoern Ch; Evans, Colin G; Cropper, Elizabeth C
2012-07-15
It has been suggested that changes in intracellular calcium mediate the induction of a number of important forms of synaptic plasticity (e.g., homosynaptic facilitation). These hypotheses can be tested by simultaneously monitoring changes in intracellular calcium and alterations in synaptic efficacy. We demonstrate how this can be accomplished by combining calcium imaging with intracellular recording techniques. Our experiments are conducted in a buccal ganglion of the mollusc Aplysia californica. This preparation has a number of experimentally advantageous features: Ganglia can be easily removed from Aplysia and experiments use adult neurons that make normal synaptic connections and have a normal ion channel distribution. Due to the low metabolic rate of the animal and the relatively low temperatures (14-16 °C) that are natural for Aplysia, preparations are stable for long periods of time. To detect changes in intracellular free calcium we will use the cell impermeant version of Calcium Orange which is easily 'loaded' into a neuron via iontophoresis. When this long wavelength fluorescent dye binds to calcium, fluorescence intensity increases. Calcium Orange has fast kinetic properties and, unlike ratiometric dyes (e.g., Fura 2), requires no filter wheel for imaging. It is fairly photo stable and less phototoxic than other dyes (e.g., fluo-3). Like all non-ratiometric dyes, Calcium Orange indicates relative changes in calcium concentration. But, because it is not possible to account for changes in dye concentration due to loading and diffusion, it can not be calibrated to provide absolute calcium concentrations. An upright, fixed stage, compound microscope was used to image neurons with a CCD camera capable of recording around 30 frames per second. In Aplysia this temporal resolution is more than adequate to detect even a single spike induced alteration in the intracellular calcium concentration. Sharp electrodes are simultaneously used to induce and record synaptic transmission in identified pre- and postsynaptic neurons. At the conclusion of each trial, a custom script combines electrophysiology and imaging data. To ensure proper synchronization we use a light pulse from a LED mounted in the camera port of the microscope. Manipulation of presynaptic calcium levels (e.g. via intracellular EGTA injection) allows us to test specific hypotheses, concerning the role of intracellular calcium in mediating various forms of plasticity.
Patel, Amar A; Alhandi, Ali A; Milne, Edward; Dy, Christopher J; Latta, Loren L; Ouellette, E Anne
2016-03-01
To assess ulnocarpal joint stability after treatment of a peripheral triangular fibrocartilage complex (TFCC) injury with all-inside arthroscopic suture repair (SR), extensor retinaculum capsulorrhaphy with the Herbert sling (HS), and a combination of both (SR+HS). Twelve fresh-frozen, age-matched, upper-extremity specimens intact from the distal humerus were prepared. Nondestructive mechanical testing was performed to assess native ulnocarpal joint stability and load-displacement curves were recorded. A peripheral, ulnar-sided TFCC injury was created with arthroscopic assistance, and mechanical testing was performed. Each specimen was treated with SR or HS and testing was repeated. The 6 specimens treated with SR were then treated with HS (SR+HS), and testing was repeated. We used paired Student t tests for statistical analysis within cohorts. For all cohorts, there was an average increase in ulnar translation after the creation of a peripheral TFCC injury and an average decrease after repair. Herbert sling decreased translation by 21%, SR decreased translation by 12%, and SR+HS decreased translation by 26%. Suture repair plus HS and HS reduce ulnar translation the most after a peripheral TFCC injury, followed by SR alone. Ulnocarpal joint stability should be assessed clinically in patients with peripheral TFCC injury, and consideration should be made for using extensor capsulorrhaphy in isolation or as an adjunct to SR as a treatment option. Copyright © 2016 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.
Lau, Kimberly V.; Maher, Kate; Brown, Shaun T.; ...
2017-11-01
The geological calcium cycle is linked to the geological carbon cycle through the weathering and burial of carbonate rocks. As a result, calcium (Ca) isotope ratios ( 44 Ca/ 40 Ca, expressed as δ 44/40 Ca) can help to constrain ancient carbon cycle dynamics if Ca cycle behavior can be reconstructed. But, the δ 44/40 Ca of carbonate rocks is influenced not only by the δ 44/40 Ca of seawater but also by diagenetic processes and fractionation associated with carbonate precipitation. In this study, we investigate the dominant controls on carbonate δ 44/40 Ca in Upper Permian to Middle Triassicmore » limestones (ca. 253 to 244 Ma) from south China and Turkey. This time interval is ideal for assessing controls on Ca isotope ratios in carbonate rocks because fluctuations in seawater δ 44/40 Ca may be expected based on several large carbon isotope (δ 13 C) excursions ranging from -2 to + 8‰. Parallel negative δ 13 C and δ 44/40 Ca excursions were previously identified across the end-Permian extinction horizon. Here, we find a second negative excursion in δ 44/40 Ca of ~ 0.2‰ within Lower Triassic strata in both south China and Turkey; however, this excursion is not synchronous between regions and thus cannot be interpreted to reflect secular change in the δ 44/40 Ca of global seawater. Additionally, δ 44/40 Ca values from Turkey are consistently 0.3‰ lower than contemporaneous samples from south China, providing further support for local or regional influences. By measuring δ 44/40 Ca and Sr concentrations ([Sr]) in two stratigraphic sections located at opposite margins of the Paleo-Tethys Ocean, we can determine whether the data represent global conditions (e.g., secular variations in the δ 44/40 Ca of seawater) versus local controls (e.g., original mineralogy or diagenetic alteration). The [Sr] and δ 44/40 Ca data from this study are best described statistically by a log-linear correlation that also exists in many previously published datasets of various geological ages. By using a model of early marine diagenetic water-rock interaction, we illustrate that this general correlation can be explained by the chemical evolution of bulk carbonate sediment samples with different initial mineralogical compositions that subsequently underwent recrystallization. Although early diagenetic resetting and carbonate mineralogy strongly influence the carbonate δ 44/40 Ca values, the relationship between [Sr] and δ 44/40 Ca holds potential for reconstructing first-order secular changes in seawater δ 44/40 Ca composition.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lau, Kimberly V.; Maher, Kate; Brown, Shaun T.
The geological calcium cycle is linked to the geological carbon cycle through the weathering and burial of carbonate rocks. As a result, calcium (Ca) isotope ratios ( 44 Ca/ 40 Ca, expressed as δ 44/40 Ca) can help to constrain ancient carbon cycle dynamics if Ca cycle behavior can be reconstructed. But, the δ 44/40 Ca of carbonate rocks is influenced not only by the δ 44/40 Ca of seawater but also by diagenetic processes and fractionation associated with carbonate precipitation. In this study, we investigate the dominant controls on carbonate δ 44/40 Ca in Upper Permian to Middle Triassicmore » limestones (ca. 253 to 244 Ma) from south China and Turkey. This time interval is ideal for assessing controls on Ca isotope ratios in carbonate rocks because fluctuations in seawater δ 44/40 Ca may be expected based on several large carbon isotope (δ 13 C) excursions ranging from -2 to + 8‰. Parallel negative δ 13 C and δ 44/40 Ca excursions were previously identified across the end-Permian extinction horizon. Here, we find a second negative excursion in δ 44/40 Ca of ~ 0.2‰ within Lower Triassic strata in both south China and Turkey; however, this excursion is not synchronous between regions and thus cannot be interpreted to reflect secular change in the δ 44/40 Ca of global seawater. Additionally, δ 44/40 Ca values from Turkey are consistently 0.3‰ lower than contemporaneous samples from south China, providing further support for local or regional influences. By measuring δ 44/40 Ca and Sr concentrations ([Sr]) in two stratigraphic sections located at opposite margins of the Paleo-Tethys Ocean, we can determine whether the data represent global conditions (e.g., secular variations in the δ 44/40 Ca of seawater) versus local controls (e.g., original mineralogy or diagenetic alteration). The [Sr] and δ 44/40 Ca data from this study are best described statistically by a log-linear correlation that also exists in many previously published datasets of various geological ages. By using a model of early marine diagenetic water-rock interaction, we illustrate that this general correlation can be explained by the chemical evolution of bulk carbonate sediment samples with different initial mineralogical compositions that subsequently underwent recrystallization. Although early diagenetic resetting and carbonate mineralogy strongly influence the carbonate δ 44/40 Ca values, the relationship between [Sr] and δ 44/40 Ca holds potential for reconstructing first-order secular changes in seawater δ 44/40 Ca composition.« less
Moore, Daniel R; Kelly, Ryan P; Devries, Michaela C; Churchward-Venne, Tyler A; Phillips, Stuart M; Parise, Gianni; Johnston, Adam P
2018-05-14
Age-related sarcopenia is accelerated by physical inactivity. Low-load resistance exercise (LLRE) counters inactivity-induced muscle atrophy in older adults, but changes in muscle fibre morphology are unstudied. We aimed to determine the impact of LLRE during short-term inactivity (step-reduction) on muscle fibre size and capillarity as well as satellite cell (SC) content in older skeletal muscle. Fourteen older (~71 years) male adults underwent 14 days of step reduction (<1500 steps/day) while performing six sessions of LLRE (~30% maximal strength) with one leg (SR + EX) while the contralateral leg served as an untrained control (SR). Seven healthy ambulatory age-matched male adults (~69 years) served as a comparator group (COM). Muscle biopsies were taken from the vastus lateralis after 14 days, and immunohistochemical analysis was performed to determine muscle fibre cross-sectional area (CSA), myonuclear content, SC content (PAX7 + cells), and total (C:F) and fibre type-specific (C:Fi) capillary-to-fibre ratios. Type I and II fibre CSA was greater in SR + EX compared with SR. Whereas there were no differences across fibre types between SR + EX and CON, type II fibre CSA was significantly lower in SR compared with COM. Type II myonuclear domain was greater in SR + EX compared with COM and SR. Pax7 + cells associated with type I and II fibres were lower in SR compared with SR + EX. Type II PAX7+ cells were also lower in SR compared with COM with a similar trend for type I fibres. There were trends for a lower C:Fi in SR compared with SR + EX for both fibre types with no differences for each compared with COM. Minimal LLRE during a period of decreased physical activity is associated with greater muscle fibre CSA, SC content, and capillarization. These results support the use of LLRE as an effective countermeasure to inactivity-induced alterations in muscle morphology with age. © 2018 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.
Calcium-Citrate-Phosphate Solution Injection for In Situ Strontium-90 Immobilization
NASA Astrophysics Data System (ADS)
Fruchter, J. S.; Vermeul, V.; Szecsody, J.; Williams, M. D.; Fritz, B. G.
2010-12-01
Sr-90 present in groundwater and the vadose zone at the Hanford 100N area due to past waste disposal practices has reached the nearby Columbia River, as evidenced by Sr-90 concentrations in near river wells and aquifer tubes and near shore sediments. Sr-90 is currently being remediated by adsorption onto apatite (55 times stronger than Sr-90 adsorption to sediment), followed by incorporation of the Sr-90 into the apatite structure. If the Sr-90 can remain immobilized for 300 years (~ten 29.1-yr half-lives of Sr-90 decay), it will have decayed below regulatory limits to Y-90 and to stable Zr-90. Apatite [Ca10(PO4)6(OH)2] is being precipitated in situ by injection of an aqueous solution of Ca-citrate and Na-phosphate through a series of injection wells spaced 30 ft on center, forming a 300-ft-long permeable reactive barrier. Design criteria for the injection operations were based on 1) amendment volume and mass injected, 2) amendment arrival at adjacent wells, 3) water-level elevation during treatment, and 4) injection rate limitations associated with well plugging. An evaluation of compliance with these injection design criteria was used to assess operational performance and identify candidate wells for supplemental treatment. Injection design criteria were not fully met at 8 of the 16 injection well locations, with the primary deficiency at 4 of 8 locations being the limited vertical extent of Hanford formation treatment due to low-river-stage conditions during the injection. Wells whose extent of treatment did not meet design criteria were recommended for retreatment. Although injection design criteria were not fully met at a significant number of well locations, aqueous performance assessment monitoring data collected to date indicate good barrier performance. Aqueous Sr-90 monitoring in four compliance monitoring wells over a year following the high concentration injections indicates 84% to 95% decrease in Sr-90 concentrations (relative to the low and high end of the baseline range, respectively). In addition, post treatment sediment cores were collected to quantify the amount of apatite that was formed from the barrier-emplacement operations. Results indicate that the processes that account for the observed reduction in aqueous Sr-90 concentrations include: a) incorporation of Sr-90 into apatite (about 39.4% of the total Sr-90 mass in the core), b) ion exchange flushing due to the Ca-citrate-PO4 solution injection (about 47% of the mass), and c) a small increase in Sr-90 adsorbed to sediment and apatite precipitate.
NASA Astrophysics Data System (ADS)
Füllenbach, Christoph S.; Schöne, Bernd R.; Shirai, Kotaro; Takahata, Naoto; Ishida, Akizumi; Sano, Yuji
2017-05-01
It remains a challenging task to reconstruct water temperatures from Sr/Ca ratios of bivalve shells. Although in many aragonitic species, Sr/Ca is negatively correlated to temperature - which is expected based on abiogenic precipitation experiments, the incorporation of Sr into the shell of bivalves is strongly controlled by physiological processes and occurs away from the predicted thermodynamic equilibrium. Strontium-to-calcium ratios of aragonitic shells remain far below that of the ambient water. Moreover, Sr concentrations vary considerably among shell portions consisting of different microstructures and/or organic content. Values observed at annual growth lines and within the intervening shell portions (= annual growth increments) deviate much stronger from each other than expected from a change in temperature or Sr/Cawater. As demonstrated here by ultra-high-resolution chemical analysis (EPMA, NanoSIMS) of a Cerastoderma edule shell, Sr concentrations are also heterogeneously distributed at approximately micrometer resolution. For example, in the outer portion of the outer shell layer, Sr/Ca ratios were statistically significantly (t-, u-tests) higher at circatidal growth lines (irregular simple prismatic structure; arithmetic mean ± 1 standard deviation = 2.86 ± 0.38 mmol/mol; n = 53) than within circatidal increments (nondenticular prismatic structure; 2.42 ± 0.25 mmol/mol; n = 51). S/Cashell, a representative of the concentration of organics, showed the opposite pattern, i.e., significantly higher values in circatidal increments (2.37 ± 0.29 mmol/mol; n = 51) than at circatidal growth lines (2.13 ± 0.47 mmol/mol; n = 53). Overall highest values of Sr/Cashell (3.47 ± 0.65 mmol/mol; n = 3) and S/Cashell (3.98 ± 0.65 mmol/mol; n = 3), however, were typically associated with annual growth lines and larger biomineral units. The intimate link between Sr/Cashell, S/Cashell and shell architecture may indicate that microstructures or the processes controlling their formation exert a strong control over the incorporation of strontium into shells of C. edule. Analytical techniques with lower sampling resolution, e.g., LA-ICP-MS, cannot resolve such fine-scale Sr variations. As a result, the signal-to-noise ratio decreases and the data generated by such techniques may therefore not seem to provide useful paleotemperature data. Future studies should therefore employ a combined analysis of Sr/Cashell and shell microstructures, and interpret Sr/Ca values of shell portions with different microstructures separately.
Osteocyte calcium signals encode strain magnitude and loading frequency in vivo.
Lewis, Karl J; Frikha-Benayed, Dorra; Louie, Joyce; Stephen, Samuel; Spray, David C; Thi, Mia M; Seref-Ferlengez, Zeynep; Majeska, Robert J; Weinbaum, Sheldon; Schaffler, Mitchell B
2017-10-31
Osteocytes are considered to be the major mechanosensory cells of bone, but how osteocytes in vivo process, perceive, and respond to mechanical loading remains poorly understood. Intracellular calcium (Ca 2+ ) signaling resulting from mechanical stimulation has been widely studied in osteocytes in vitro and in bone explants, but has yet to be examined in vivo. This is achieved herein by using a three-point bending device which is capable of delivering well-defined mechanical loads to metatarsal bones of living mice while simultaneously monitoring the intracellular Ca 2+ responses of individual osteocytes by using a genetically encoded fluorescent Ca 2+ indicator. Osteocyte responses are imaged by using multiphoton fluorescence microscopy. We investigated the in vivo responses of osteocytes to strains ranging from 250 to 3,000 [Formula: see text] and frequencies from 0.5 to 2 Hz, which are characteristic of physiological conditions reported for bone. At all loading frequencies examined, the number of responding osteocytes increased strongly with applied strain magnitude. However, Ca 2+ intensity within responding osteocytes did not change significantly with physiological loading magnitudes. Our studies offer a glimpse into how these critical bone cells respond to mechanical load in vivo, as well as provide a technique to determine how the cells encode magnitude and frequency of loading. Published under the PNAS license.
Peng, Xiong-Bo; Sun, Meng-Xiang; Yang, Hong-Yuan
2009-08-01
Double fertilization is a key process of sexual reproduction in higher plants. The role of calcium in the activation of female sex cells through fertilization has recently received a great deal of attention. The establishment of a Ca(2+)-imaging technique for living, single, female sex cells is a difficult but necessary prerequisite for evaluating the role of Ca(2+) in the transduction of external stimuli, including the fusion with the sperm cell, to internal cellular processes. The present study describes the use of Fluo-3 for reporting the Ca(2+) signal in isolated, single, female sex cells, egg cells and central cells, of tobacco plants. A suitable loading protocol was optimized by loading the cells at pH 5.6 with 2 microM Fluo-3 for 30 min at 30 degrees C. Under these conditions, several key factors related to in vitro fertilization were also investigated in order to test their possible effects on the [Ca(2+)](cyt) of the female sex cells. The results indicated that the bovine serum albumin-fusion system was superior to the polyethlene glycol-fusion system for detecting calcium fluctuations in female sex cells during fertilization. The central cell was fertilized with the sperm cell in bovine serum albumin; however, no evident calcium dynamic was detected, implying that a transient calcium rise might be a specific signal for egg cell fertilization.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cau Dit Coumes, Celine; Courtois, Simone; Peysson, Sandrine
Investigations were carried out in order to solidify in cement a low-level radioactive waste of complex chemistry obtained by mixing two process streams, a slurry produced by ultra-filtration and an evaporator concentrate with a salinity of 600 gxL{sup -1}. Direct cementation with Portland cement (OPC) was not possible due to a very long setting time of cement resulting from borates and phosphates contained in the waste. According to a classical approach, this difficulty could be solved by pre-treating the waste to reduce adverse cement-waste interactions. A two-stage process was defined, including precipitation of phosphates and sulfates at 60 deg. Cmore » by adding calcium and barium hydroxide to the waste stream, and encapsulation with a blend of OPC and calcium aluminate cement (CAC) to convert borates into calcium quadriboroaluminate. The material obtained with a 30% waste loading complied with specifications. However, the pre-treatment step made the process complex and costly. A new alternative was then developed: the direct encapsulation of the waste with a blend of OPC and calcium sulfoaluminate cement (CSA) at room temperature. Setting inhibition was suppressed, which probably resulted from the fact that, when hydrating, CSA cement formed significant amounts of ettringite and calcium monosulfoaluminate hydrate which incorporated borates into their structure. As a consequence, the waste loading could be increased to 56% while keeping acceptable properties at the laboratory scale.« less