Ca Load Research Articles

Mechanistic link between CaM-RyR2 interactions and the genesis of cardiac arrhythmia

In this study, we develop a computational model of the interaction between ryanodine receptor type 2 (RyR2) and calmodulin (CaM) to explore the mechanistic link between CaM-RyR2 interactions and cardiac arrhythmia. Our starting point is a biophysically based computational model of CaM binding to a single RyR2 subunit, which reproduces single-channel RyR2 measurements in lipid bilayers. We then integrate this CaM-RyR2 model into a spatially distributed whole-cell model of Ca cycling, which is used to investigate the relationship between CaM and Ca cycling homeostasis. We show that a reduction in CaM concentration leads to a substantial increase in the rate of spontaneous Ca sparks, and this induces a marked reduction in sarcoplasmic reticulum Ca load during steady-state pacing. Also, we show that a reduction in CaM modifies the RyR2 open probability, which makes the cell more prone to Ca wave propagation. These results indicate that aberrant Ca cycling activity during pacing is determined by the interplay between sarcoplasmic reticulum load reduction and the threshold for Ca wave propagation. Based on these results, we show that when CaM is reduced, Ca waves can occur in a cell and induce action potential perturbations that are arrhythmogenic. Thus, this study outlines a novel, to our knowledge, mechanistic link between CaM-RyR2 binding kinetics and the induction of arrhythmias in the heart.

The dissolution of simulant UK Ca/Zn-modified nuclear waste glass: the effect of increased waste loading

The influence of increasing the waste loading of Ca- and Zn-containing MW high-level-waste glass, from 20 to 35 wt%, on the chemical durability was investigated using 112-day PCT-B tests at 90 °C in ultra-high-quality water. During the initial stage of dissolution, from 0 to 3 days, increased waste loadings corresponded to reduced boron dissolution rates. By 112 days, however, there was no difference in the normalised mass loss of boron as a function of waste loading, within experimental uncertainty. In comparison to literature values obtained for traditional MW high-level-waste glasses, containing no Ca and Zn, the boron dissolution rates of CaZn MW glasses in the residual stage of dissolution, > 28 days, were greater by at least an order of magnitude. Analysis of secondary phases, combined with geochemical modelling of the solutions, indicate that the dual formation of Mg- and Zn-smectite phyllosilicate clays, potentially saponite (Ca0.2Mg3(Si,Al)4O10(OH)2·4H2O) and sauconite (Na0.3Zn3(Si, Al)4O10(OH)2·nH2O), respectively, may be the cause of this enhanced dissolution.

Chemical looping gasification of biochar to produce hydrogen-rich syngas using Fe/Ca-based oxygen carrier prepared by coprecipitation

Biochar chemical looping gasification (CLG) is a novel technology to obtain hydrogen-rich syngas, high gasification efficiency and low carbon deposition. This study investigates the effect of preparation methods, Fe loadings, active components, Ca loadings and steam/biochar (S/C) to achieve the optimal oxygen carrier. The results show that coprecipitation is the best preparation method to gain highest efficiency, redox activity and dispersion. H2 production increases visibly with the increase of Fe loading, while efficiencies increase firstly and then decrease. There is an evident effect of active component on CLG. Oxygen carrier based on Fe/Ca performs a lower carbon deposition, higher H2 production and efficiency. With the increase of Ca loading, H2 production and efficiencies increase firstly and then decrease. S/C has an obvious effect on CLG performance. 1.5 is the optimal S/C to achieve high H2 concentration of 67.35%, the highest gas production of 1.34 Nm3/kg and gasification efficiency of 96.93%.

Abstract 12877: Magnesium Deficiency Causes Reversible Metabolic Diastolic and Systolic Cardiomyopathies

Introduction: Low circulating magnesium (Mg) level is associated with increased cardiovascular mortality, and conversely, dietary Mg intake is associated with a decreased risk of developing heart failure. Hypothesis: We investigated whether Mg deficiency alone could cause cardiomyopathy. Methods: C57BL/6J mice were fed with a low-Mg diet (low-Mg, 15-30 mg/kg Mg) or a normal diet (nl-Mg, 600 mg/kg Mg) for 6 weeks. To test reversibility, half of the low-Mg mice were fed then with normal diet for another 6 weeks (low→nl-Mg group). Results: Mg deficiency increased mortality, especially in female mice. After 6 weeks of low-Mg diet, surviving mice showed significantly decreased serum Mg (0.9±0.1 vs. 2.8±0.1 mg/dL for nl-Mg) and a reciprocal increase in serum Ca, K, and Na. Low-Mg mice exhibited a decreased cardiac ejection fraction (EF%, 39.8±1.9% vs. 52.0±1.7% of nl-Mg) and impaired relaxation (E/e’: 21.1±1.1 vs. 15.4±0.4 of nl-Mg) in echocardiography. At the cellular level, ATP, Ca transient amplitude, sarcoplasmic reticulum (SR) Ca load, resting sarcomere length, and sarcomere shortening were all decreased significantly in low-Mg hearts and cardiomyocytes. These changes were accompanied by evidence of mitochondrial dysfunction with significantly increased mitochondrial ROS production and mitochondrial membrane depolarization. Mg repletion normalized electrolytes, contraction, relaxation, and cellular changes. The SR Ca pump (SERCA) was decreased, the SR Ca channel RyR2 oxidized, and cardiac myosin binding protein C S-glutathionylated in low-Mg mouse hearts. These changes were normalized with Mg repletion. In vivo , mitoTEMPO treatment during low Mg diet improved the cardiac relaxation and increased cellular ATP levels without improving contraction. Conclusions: Mg deficiency caused a reversible diastolic and systolic cardiomyopathy associated with mitochondrial dysfunction. This cardiomyopathy may explain the relationship of hypomagnesemia and worsening heart failure. Mg intake could reverse these changes, reinforcing the known correlation of increased Mg intake and reduced heart failure symptoms and mortality. In deficiency states, Mg supplementation may represent a novel treatment for systolic and diastolic heart failure.

Improved gel synthesis enables routes to Al-rich chabazite

Abstract Phase pure Al-rich CHA(1.6–2.0) was prepared both from seed-assisted and non-seeded gel routes. Two different gel composition spaces were explored and both cation composition and the addition of seeds had a large effect on the product phase. A working hypothesis that guided the initial synthesis work is that the product phase and SAR is a strong function of the SiO2 solubility for the given gel system and addition of a seed would nucleate a CHA phase. Adsorption studies on pure and mixed alkali/alkaline earth CHA(2.0) showed homogeneous isosteric heats and low N2 Henry's constants for the pure Na and Li forms as well as Ca2Li8CHA(2.0); whereas a heterogenous heat and significant increase in Henry's constant were observed for higher Ca loadings in this mixed Ca/Li system. This behavior strongly suggests that in the dehydrated form,

Cellular mechanisms of early tachycardia-induced ventricular dysfunction in the human heart

Abstract Background Tachycardia-induced cardiomyopathy (TCM) is a reversible form of ventricular dysfunction caused by persistent tachycardia. Characterization of TCM is mainly based on artificially RV paced animal models. Moreover, the underlying mechanisms and time course from compensation to failure remain unclear. This study aimed to investigate early cellular remodeling of tachycardia-induced myocardial dysfunction in human myocardium. Methods and results To elucidate early cellular electrophysiological targets mediating the transition to TCM, we chronically paced (120bpm vs 60bpm control) human induced pluripotent stem cell cardiomyocytes (hiPS-CM) for up to 7d. As a major substrate of cellular myocardial dysfunction, we investigated the influence of chronic tachycardia on cellular Ca cycling. After 24h of persistent tachycardia we detected a significant decrease in Ca transient (CaT) amplitude and reduced diastolic Ca levels (Fura-2). Meanwhile, Ca elimination time (RT80) was unchanged compared to control (n=44/42 cells / 8 diff.). Caffeine application was performed to evaluate sarcoplasmic reticulum (SR) Ca load. We found a shortening of caffeine-induced CaT relaxation time, whereas SR Ca load was unchanged (n=12/13 /8). Further illustrating the transition to TCM, CaT amplitude was progressively decreased after 7d of chronic tachycardia. In contrast to 24h of tachycardia, 7d persistent stimulation resulted in slowed relaxation (RT80, n=75/65 /7). These findings could be explained by a significant reduction of SERCA activity (Ksys-Kcaff) and SR Ca load (n=14/12 / 7). Diastolic Ca concentration remained reduced (n=75/65 /7), in total suggesting a shift to transsarcolemmal Ca elimination. Sodium measurements (SBFI) revealed a significant increase of intracellular sodium concentration (n=69/69 /5) after 7d of tachycardia. In patch clamp experiments we detected a prolongation of action potential duration as early as 24h after onset of tachycardia (n=26/21 /4), which persisted throughout 7d of pacing (n=8/12 /3). Resting membrane potential and action potential amplitude were not changed. Finally, we investigated tachycardia-mediated effects on pre-existing human heart failure (HF). 8h tachycardic stimulation (120bpm) of human HF ventricular trabeculae compromised systolic force, while diastolic tension and relaxation time were markedly increased compared to control (60bpm) (n=7/6 trabeculae /6 human hearts). The extensive molecular characterization of involved ion channels and pathways mediating transition to TCM is currently under investigation. Conclusion This study demonstrates that a persistent tachycardia adversely alters cardiomyocyte excitation-contraction coupling via early electrophysiological cellular remodeling. In pre-existing HF persistent tachycardia strongly aggravates ventricular dysfunction. Our first translational investigation in human myocardium may help to understand the pathophysiology of an underrated and very prevalent disease. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Else-Kröner-Fresenius-Stiftung

Hydrogeochemical characterization and quality evaluation of groundwater suitability for domestic and agricultural uses in the state of Qatar

This study aims to investigate the groundwater (GW) quality in Qatar to be utilized in domestic and agricultural uses. The integrated physiochemical analysis along with hydrochemical faces analysis, geochemical modeling, statistical and geostatistical analysis was conducted. The results showed that the GW samples mainly have the following cations Na+ > Ca2+ > Mg2+ >K+ abundantly, while Cl− > SO42− > HCO3− > NO3− were the main anions. The obtained analytical values of the GW samples were plotted on Piper, Schoeller, Ternary, Ludwig Langelier, Giggenbach Triangle, Durov, and stiff graphs. The hydrogeochemical facies and the obtained graphs confirmed that most of the analyzed GW samples fall into two types of water namely calcium-chloride-type (SO4–Cl and Ca–Mg) and sodium-chloride-type (SO4–Cl and Na–K). Three principal components were yielded from the principal component analysis (PCA), which are the first principal component (PC1), second principal component (PC2), and third principal component (PC3) with ≥1 Eigenvalues, and total variance of 49, 31, and 19.9%, respectively. A positive loading of Mg, Th, Sr, Ca, TDS, SO4, Li, Cl, F, Br, Cd, K, Ba, and Na has been shown by the PC1; representing the factors which are contributing to the high salinity of the GW due to the salt water intrusion and the mineralization of rocks and soil which is supported by the water type classification and saturation indices. The PC2 showed a negative loading of U, Al, Se, Mo, Mg, and temperature, which could be associated with a localized sedimentary depositional or hydrogeochemical environment. The PC3 showed a positive loading of Ni, Zn, Be, pH, Cu, Co, Fe, B, V, and TOC, which indicates the dissolution and precipitation (reducing and oxidizing factor) such as iron which is a redox-sensitive variable.

Therapeutic effect of cinnamaldehyde on ulcerative colitis in mice induced by dextran sulfate sodium with Candida albicans colonization and its effect on dectin-1/TLRs/NF-κB signaling pathway

To observe the efficacy of cinnamaldehyde on dextran sulfate sodium(DSS)-induced ulcerative colitis(UC) with Can-dida albicans(Ca) colonization and its effect on dectin-1/TLRs/NF-κB signaling pathway in mice. C57 BL/6 mice were randomly divided into normal group, DSS group, DSS+Ca group, cinnamaldehyde group and mesalazine group. Mice in DSS+Ca group were given Ca(1×10~8 CFU per mouse) through intragastrical administration for 4 consecutive days and then distilled water with 3.0% DSS for 7 consecutive days. In cinnamaldehyde group and mesalazine group, in addition to the induction method of the DSS+Ca group, mice were given 75 mg·kg~(-1) cinnamaldehyde and 200 mg·kg~(-1) mesalazine accompanied with 3.0% DSS for 7 consecutive days, respectively. Mice in normal group and DSS group were correspondingly administered with distilled water. The general conditions of the mice were observed daily, the diseased activity index(DAI) score was calculated, and fungal loads of feces were detected by plate method. The mice were sacrificed on day 12, colon length was measured, colon mucosa damage index(CMDI) score was calculated, and histopathological analysis was carried out by HE staining. Anti-saccharomces cerevisiae antibody(ASCA) and β-1,3-glucan in serum, and TNF-α, IL-1β, IL-6, IL-8, IL-10 in serum and colon tissue were detected by ELISA. The contents of β-1,3-glucan and macrophage infiltration in colon tissues were examined by immunofluorescence staining. The protein expressions of dectin-1, TLR2, TLR4 and NF-κB were detected by Western blot and immunohistochemistry staining. The results showed that cinnamaldehyde could significantly improve the general conditions of UC mice with Ca colonization, decrease DAI and histopathological scores, reduce intestinal mucosal congestion, erosion and colon shortening, decrease Ca load in mouse feces and tissues, down-regulate the contents of ASCA and β-1,3-glucan in serum, reduce the contents of TNF-α, IL-1β, IL-6, IL-8 and increase IL-10 in serum and colon tissues, inhibit macrophages infiltration and down-regulate the protein expression of dectin-1, TLR2, TLR4 and NF-κB in colon tissue. These results suggested that cinnamaldehyde had a therapeutic effect on UC mice with Ca colonization, which might be related to the inhibition of Ca proliferation, the regulation of dectin-1/TLRs/NF-κB signaling pathways and the coordination of the balance between pro-inflammatory and anti-inflammatory factors.

Producing elemental sulfur from SO2 by calcium loaded activated coke: Enhanced activity and selectivity

SO2 carbothermal reduction is one of the promising strategies to convert SO2 to elemental sulfur, while the long-term challenge is to simultaneously improve the reactivity and selectivity. In this work, we demonstrate an effective approach for enhancing both the activity and selectivity of activated coke (AC) for SO2 carbothermal reduction by controllably loading catalytic Ca species. Ca-loaded ACs were prepared via a simple ultrasound assisted liquid phase impregnation method, in which the pore structure as well as CaCl2 distribution in Ca-loaded ACs can be optimized by tuning CaCl2 loading content. Dynamic experiments show that CaCl2-loaded ACs exhibit much higher SO2 removal rates as compared with pure AC, indicating the promoting role of Ca loading in SO2 carbothermal reduction activity. Such enhanced activity of CaCl2-loaded ACs is attributed to the decrease of activation energy according to the kinetic parameters calculated from Random Pore Model (RPM). By calculating and correlating the amounts of consumed reactants and reaction products, AC loaded with 30- wt% CaCl2 can achieve a record-high elemental sulfur production selectivity of 80%, which should be contributed by both the reactions of SO2 + C → CO2 + S and 2CO + SO2 → 2CO2 + S. Chemical environment investigations and density functional theory (DFT) calculations further demonstrate that the C-O-Ca structure in Ca-loaded AC can weaken the C-O bond in reaction intermediates and thereby reduce the energy needed for O transfer, making SO2 reduction feasible to occur. In addition, we also evaluate the recyclability of catalyst CaCl2 that is proven to be easily recovered and recirculated. This work provides a facile strategy to improve the reactivity and selectivity for SO2 carbothermal reduction, holding great application potentials in flue gas desulfurization.

Acute Genetic Ablation of Cardiac Sodium-Calcium Exchange Suppresses Arrhythmogenic Delayed after Depolarizations

Sodium-calcium exchange (NCX) is the dominant calcium (Ca) efflux mechanism in cardiac myocytes. As an electrogenic transporter, NCX is thought to generate the inward current responsible for Ca-dependent arrhythmogenic delayed afterdepolarizations (DADs). To test this hypothesis, we patch-clamped ventricular myocytes isolated from our novel tamoxifen-inducible cardiac-specific NCX knockout (KO) mouse (αMHC-MerCreMer promotor). Tamoxifen (40mg/kg/day IP) was injected for 5 consecutive days in 10 to 12-week-old mice. 4 weeks after injection, we found a 96% decrease of NCX protein expression and an 87% reduction of caffeine-induced NCX current (p< 0.001), with 25% of cells showing no NCX current whatsoever. Sarcoplasmic reticulum Ca load was similar to control. Transient outward current (ITO) and Kv4.2 protein expression were significantly increased (by 60 and 34% respectively, p < 0.01) and ICa was reduced by 47% (p < 0.001). The action potential duration (APD) was shortened when measured at either 10 % (8.6 ± 0.7 ms in control vs 5.5 ± 0.5 ms in KO, p < 0.05) or 90 % (43.9 ± 4.9 ms in control vs 11.1 ± 0.9 ms in KO, p < 0.001) repolarization. In response to a pro-arrhythmic stimulation protocol, spontaneous APs triggered by DADs occurred in 95% of control cells, but only in 35% of NCX KO myocytes, even though we observed no change in the mean number of DADs per cell. Notably, DAD amplitude was significantly reduced in NCX KO mice: 14% of KO cells exhibited DADs with an amplitude ≥ 3mV versus 78 % in control cells. In the 25% of KO cells with no detectable DADs, there were no spontaneous APs. Most likely these were the cells with no NCX activity. Thus, acute genetic reduction/ablation of NCX suppresses DAD frequency/amplitude and subsequent spontaneous AP generation.

Catecholaminergic Polymorphic Ventricular Tachycardia.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare congenital arrhythmogenic disorder induced by physical or emotional stress. It mainly affects children and younger adults and is characterized by rapid polymorphic and bidirectional ventricular tachycardia. Symptoms can include dizziness, palpitations, and presyncope, which may progress to syncope, hypotonia, convulsive movements, and sudden cardiac death. CPVT is the result of perturbations in Ca ion handling in the sarcoplasmic reticulum of cardiac myocytes. Mutations in the cardiac ryanodine receptor gene and the calsequestrin isoform 2 gene are most commonly seen in familial CPVT patients. Under catecholaminergic stimulation, either mutation can result in an excess Ca load during diastole resulting in delayed after depolarization and subsequent arrhythmogenesis. The current first-line treatment for CPVT is β-blocker therapy. Other therapeutic interventions that can be used in conjunction with β-blockers include moderate exercise training, flecainide, left cardiac sympathetic denervation, and implantable cardioverter-defibrillators. Several potential therapeutic interventions, including verapamil, dantrolene, JTV519, and gene therapy, are also discussed.

Investigation of Ni─Ca binary catalystic activities for production of light aromatics from catalytic pyrolysis of brown coal

AbstractThe pyrolysis behavior of Ni─Ca‐loaded Yunnan brown coals (Shi Caoxing [SCX] and Guo Jiashan [GJS]) was studied in a fixed‐bed reactor to investigate the effects of Ni, Ca, and Ni─Ca loading on the yields of the obtained liquids and light aromatic hydrocarbons. Structural variations of the prepared coal chars were characterized by the scanning electron microscope–energy dispersion X‐ray, Fourier‐transform infrared spectroscopy, X‐ray diffractometer, Brunauer–Emmett–Teller analysis, and elemental analysis. The effects of the Ni, Ca, and Ni─Ca loadings on the tar yield and upgradation of pyrolysis tar were evaluated. The results revealed that the use of the Ni─Ca catalyst affords improved yields of the liquid products and tar. Furthermore, the light hydrocarbon liquids contents in the coal tar was improved with the use of the Ni─Ca catalyst. The heavy components and polycyclic aromatic hydrocarbons in the coal tar could be easy to convert into light hydrocarbon liquids (phenol, cresol, xylenols, and naphthalene) with the SCX brown coal pyrolysis. In contrast, the catalytic pyrolysis of GJS brown coal was inhibited by the Ni─Ca catalyst. The study revealed that the catalytic activity of the Ni─Ca catalyst greatly depends on the type of the coal substrate and was promoted or inhibited depending on the type of the brown coal.

Facile Preparative Access to Bioactive Silicon Oxycarbides with Tunable Porosity.

In the present work, Ca-containing silicon oxycarbides (SiCaOC) with varying Ca content have been synthesized via sol-gel processing and thermal treatment in inert gas atmosphere (pyrolysis). It has been shown that the as-prepared SiCaOC materials with low Ca loadings (Ca/Si molar ratios = 0.05 or 0.12) were X-ray amorphous; their glassy network contains Q3 sites, indicating the presence of Ca2+ at non-bridging-oxygen sites. SiCaOC with high Ca content (i.e., Ca/Si molar ratio = 0.50) exhibits the presence of crystalline calcium silicate (mainly pseudowollastonite). Furthermore, it has been shown that the incorporation of Ca into the SiOC glassy network has a significant effect on its porosity and specific surface area. Thus, the as-prepared Ca-free SiOC material is shown to be non-porous and having a specific surface area (SSA) of 22.5 m2/g; whereas SiCaOC with Ca/Si molar ratio of 0.05 exhibits mesoporosity and a SSA value of 123.4 m2/g. The further increase of Ca content leads to a decrease of the SSA and the generation of macroporosity in SiCaOC; thus, SiCaOC with Ca/Si molar ratio of 0.12 is macroporous and exhibits a SSA value of 39.5 m2/g. Bioactivity assessment in simulated body fluid (SBF) confirms the hydroxyapatite formation on all SiCaOC samples after seven days soaking, unlike the relatively inert ternary silicon oxycarbide reference. In particular, SiCaOC with a Ca/Si molar ratio of 0.05 shows an increased apatite forming ability compared to that of SiCaOC with Ca/Si molar ratio of 0.12; this difference is considered to be a direct consequence of the significantly higher SSA of the sample with the Ca/Si ratio of 0.05. The present work indicates two effects of Ca incorporation into the silicon oxycarbide glassy network on its bioactivity: Firstly, Ca2+ is shown to contribute to the slight depolymerization of the network, which clearly triggers the hydroxyapatite formation (compare the bioactive behavior of SiOC to that of SiCaOC with Ca/Si molar ratio 0.12 upon SBF exposure); secondly, the Ca2+ incorporation seems to strongly affect the porosity and SSA in the prepared SiCaOC materials. There is an optimum of Ca loading into the silicon oxycarbide glassy network (at a Ca/Si molar ration of 0.05), which provides mesoporosity and reaches maximum SSA, both highly beneficial for the bioactive behavior of the materials. An increase of the Ca loading leads, in addition to the crystallization of calcium silicates, to a coarsening of the pores (i.e., macroporosity) and a significant decrease of the SSA, both negatively affecting the bioactivity.

Control of cardiac contraction by sodium: Promises, reckonings, and new beginnings

Several generations of cardiac physiologists have verified that basal cardiac contractility depends strongly on the transsarcolemmal Na gradient, and the underlying molecular mechanisms that link cardiac excitation-contraction coupling (ECC) to the Na gradient have been elucidated in good detail for more than 30 years. In brief, small increases of cytoplasmic Na push cardiac (NCX1) Na/Ca exchangers to increase contractility by increasing the myocyte Ca load. Accordingly, basal cardiac contractility is expected to be physiologically regulated by pathways that modify the cardiac Na gradient and the function of Na transporters. Assuming that this expectation is correct, it remains to be elucidated how in detail signaling pathways affecting the cardiac Na gradient are controlled in response to changing cardiac output requirements. Some puzzle pieces that may facilitate progress are outlined in this short review. Key open issues include (1) whether the concept of local Na gradients is viable, (2) how in detail Na channels, Na transporters and Na/K pumps are regulated by lipids and metabolic processes, (3) the physiological roles of Na/K pump inactivation, and (4) the possibility that key diffusible signaling molecules remain to be discovered.

Mathematical Modeling and Optimization of Active Calcium Absorption in Human Body

Active calcium (Ca) absorption is the first process in Ca metabolism, which regulates the whole Ca absorption. There are a few notable models which depict the mechanism of active Ca absorption; it is still required to update it for human metabolism and optimal conditions to propose an adequate amount of absorbed Ca. In this study, we were to develop a mathematical model describing the active Ca absorption and optimized the active Ca absorption. The developed model explained the active Ca absorption with 3 steps: Ca entry by electrochemical diffusion, intracellular Ca diffusion in cell by facilitated diffusion, and Ca extrusion in Ca pump by Michaelis–Menten equation. Model simulation was validated by showing similar responses with a previous model; then, the model was applied to simulate the active Ca absorption with parameters estimated based on human studies. In addition, the simulated Ca absorption was optimized as a function of Ca load in intestine and regulatory molecule, i.e., Ca-binding protein. This study provides a mechanistic point of view in human active Ca absorption and is expected to be a useful tool for analyzing the whole Ca metabolism and for designing Ca-related clinical experiment.

Metabolic Calcium Balance in Rats with Chronic Renal Failure Assessed Using 42Ca Tracer

Objective: This study's objective is to explore the effect of venous calcium (Ca) load on Ca metabolism using an isotope tracer in both healthy rats and rats with chronic renal failure (CRF). Materials and Methods: The methods included inducing CRF by feeding rats with food that containing 0.75% adenine. Both the rats in the control and CRF group received an intravenous injection of 100 mg/kg CaCl2 mixed with 0.5 mg/kg 42Ca for over 2 minutes in order to induce hypercalcemia. Blood samples, urine, and feces were collected for Ca kinetics and metabolism testing before and 24 hours after the injection. Results: Peak blood Ca levels were presented at 5 minutes in both groups but returned to baseline levels differently: within 3 hours in the CRF group and 1 hour in the control group. 24-hour hypercalciuria and a higher weight-corrected fecal Ca loss were consistently detected in the CRF rats before and after the injection, along with a decrease in the percent fractional Ca absorption and true fractional calcium absorption compared to the control group. The increased fecal Ca in the CRF rats primarily resulted from changes in decreased absorption rate, which indirectly lead to an increase in endogenous fecal Ca (EFC). Body weightcorrected EFC levels in the CRF group were significantly higher than those in the control group (207.58 ± 107.18 mg/kg/day vs. 62.44 ± 20.49 mg/kg/day). In addition, EFC was 22.6% and 26.02% of the total fecal Ca in the CRF group and the control group. Conclusion: These results may be useful in the evaluation of calcium metabolism and may have important implications for stable isotopes that are widely used in exploring calcification studies in the CRF.

Ammonium Sorption from Landfill Leachates Using Natural and Modified Zeolites: Pre-Tests for a Novel Application of the Ion Exchanger Loop Stripping Process

Ammonium (NH4+) is a main constituent of landfill leachates (50–2200 mg L−1) which has to be removed prior to indirect (&lt;200 mg L−1) or direct discharge (&lt;10 mg L−1) during landfill operation and aftercare, i.e., for more than 100 years after the end of waste disposal. In this study, lab-scale experiments regarding the sorption of NH4+ from landfill leachates using natural and modified clinoptilolite (Ca0.5,Na,K)6(Al6Si30)O72·20H2O) were conducted to assess the applicability of the innovative ion exchanger loop stripping (ILS) process for ammonium recovery. Samples of 20 g clinoptilolite after different pre-treatments (Ca loading, Na loading, natural loading) were shaken with 500 mL of each leachate from ten Austrian landfills (75 mg L−1 &lt; c(NH4+) &lt; 2805 mg L−1; 7.7 &lt; pH &lt; 8.7) for 24 h. Between 13% and 61% of the dissolved NH4+ was adsorbed to the clinoptilolite, which remained stable during the experiment. In summary, our study indicates that the ILS process is highly promising with respect to NH4+ recovery from landfill leachates, but further research is needed to reach threshold values for direct discharge.

Effects of reduction of graphene oxide on the hydrogen storage capacities of metal graphene nanocomposite

Light-weight materials such as graphene have attracted a great interest for hydrogen storage applications. In this study, a metal-on graphene nanocomposite was synthesized for hydrogen storage for on-board applications. The graphene used as support was obtained from precursor graphite oxide, which was synthesized using the Improved Tours method and later reduced by L-Ascorbic acid and ammonia. The precursor graphite flakes used in the synthesis of graphite oxide were 100 μm in size. The XRD patterns depicted a low angle shift in GO, 11.3° from graphite 30° proved successful oxidation of graphite. The FTIR and Raman band showed L-Ascorbic reduced the GO better than ammonia through the observed decrease on the functional bands after reduction. The elemental analysis carried out using XRF showed the successful loading of Ca on the graphene matrix and TEM images also confirmed this. The hydrogen storage capacity of the nanocomposite was tested using TGA and TPD equipped with Mass Spectrometer. The Ca/graphene nanocomposite reduced by ammonia exhibited a large hydrogen storage uptake at 4.98 wt. % compared to L-Ascorbic acid.

Mechanisms of Calcium Leak from Cardiac Sarcoplasmic Reticulum Revealed by Statistical Mechanics

Heart muscle contraction is normally activated by a synchronized Ca release from sarcoplasmic reticulum (SR), a major intracellular Ca store. However, under abnormal conditions, Ca leaks from the SR, decreasing heart contraction amplitude and increasing risk of life-threatening arrhythmia. The mechanisms and regimes of SR operation generating the abnormal Ca leak remain unclear. Here, we employed both numerical and analytical modeling to get mechanistic insights into the emergent Ca leak phenomenon. Our numerical simulations using a detailed realistic model of the Ca release unit reveal sharp transitions resulting in Ca leak. The emergence of leak is closely mapped mathematically to the Ising model from statistical mechanics. The system steady-state behavior is determined by two aggregate parameters: the analogs of magnetic field (h) and the inverse temperature (β) in the Ising model, for which we have explicit formulas in terms of SR [Ca] and release channel opening and closing rates. The classification of leak regimes takes the shape of a phase β-h diagram, with the regime boundaries occurring at h = 0 and a critical value of β (β∗) that we estimate using a classical Ising model and mean field theory. Our theory predicts that a synchronized Ca leak will occur when h > 0 and β >β∗, and a disordered leak occurs when β <β∗ and h is not too negative. The disorder leak is distinguished from synchronized leak (in long-lasting sparks) by larger Peierls contour lengths, an output parameter reflecting degree of disorder. Thus, in addition to our detailed numerical model approach, we also offer an instantaneous computational tool using analytical formulas of the Ising model for respective ryanodine receptor parameters and SR Ca load that describe and classify phase transitions and leak emergence.

The contribution of the pericanalicular matrix to mineral content in human osteonal bone.

The osteocyte lacunar-canalicular network (LCN) penetrates bone and houses the osteocytes and their processes. Despite its rather low volume fraction, the LCN represents an outstanding large surface that is possibly used by the osteocytes to interact with the surrounding mineralized bone matrix thereby contributing to mineral homeostasis. The aim of this study was to quantitatively describe such contributions by spatially correlating the local density of the LCN with the mineral content at the same location in micrometer-sized volume elements in human osteons. For this purpose, 65 osteons from the femur midshaft from healthy adults (n = 4) and children (n = 2) were structurally characterized with two different techniques. The 3D structure of the LCN in the osteons was imaged with confocal laser scanning microscopy after staining the bone samples with rhodamine. Subsequent image analysis provided the canalicular length density, i.e. the total length of the canaliculi per unit volume (μm/μm3). Quantitative information on the mineral content (wt%Ca) from the identical regions was obtained using quantitative backscattered electron imaging. As the LCN-porosity lowers the mineral content, a negative correlation between Ca content and network density was expected. Calculations predict a reduction of around -0.97 fmol Ca per μm of network. However, the experiment revealed for 62 out of 65 osteons a positive correlation resulting in an average additional Ca loading of +1.15 fmol per μm of canalicular network, i.e. an accumulation of mineral has occurred at dense network regions. We hypothesize that this accumulation happens in the close vicinity of canaliculi forming mineral reservoirs that can be utilized by osteocytes. Significant differences found between individuals indicate that the extent of mineral loading of the reservoir zone reflects an important parameter for mineral homeostasis.