Calcium isotope fractionation by intracellular amorphous calcium carbonate (ACC) forming cyanobacteria.

The formation of intracellular amorphous calcium carbonate (ACC) by various cyanobacteria is a widespread biomineralization process, yet its mechanism and importance in past and modern environments remain to be fully comprehended. This study explores whether calcium (Ca) isotope fractionation, linked to ACC-forming cyanobacteria, can serve as a reliable tracer for detecting these microorganisms in modern and ancient settings. Accordingly, we measured stable Ca isotope fractionation during Ca uptake by the intracellular ACC-forming cyanobacterium Cyanothece sp. PCC 7425. Our results show that Cyanothece sp. PCC 7425 cells are enriched in lighter Ca isotopes relative to the solution. This finding is consistent with the kinetic isotope effects observed in the Ca isotope fractionation during biogenic carbonate formation by marine calcifying organisms. The Ca isotope composition of Cyanothece sp. PCC 7425 was accurately modeled using a Rayleigh fractionation model, resulting in a Ca isotope fractionation factor (Δ44Ca) equal to -0.72 ± 0.05‰. Numerical modeling suggests that Ca uptake by these cyanobacteria is primarily unidirectional, with minimal back reaction observed over the duration of the experiment. Finally, we compared our Δ44Ca values with those of other biotic and abiotic carbonates, revealing similarities with organisms that form biogenic calcite. These similarities raise questions about the effectiveness of using the Ca isotope fractionation factor as a univocal tracer of ACC-forming cyanobacteria in the environment. We propose that the use of Δ44Ca in combination with other proposed tracers of ACC-forming cyanobacteria such as Ba and Sr isotope fractionation factors and/or elevated Ba/Ca and Sr/Ca ratios may provide a more reliable approach.

Calcium isotopes as a biomarker for vascular calcification in chronic kidney disease.

Calcium balance is abnormal in adults with chronic kidney disease (CKD) and is associated with the development of vascular calcification. It is currently not routine to screen for vascular calcification in CKD patients. In this cross-sectional study, we investigate whether the ratio of naturally occurring calcium (Ca) isotopes, 44Ca and 42Ca, in serum could be used as a noninvasive marker of vascular calcification in CKD. We recruited 78 participants from a tertiary hospital renal center: 28 controls, 9 subjects with mild-moderate CKD, 22 undertaking dialysis and 19 who received a kidney transplant. For each participant, systolic blood pressure, ankle brachial index, pulse wave velocity, and estimated glomerular filtration rate were measured, along with serum markers. Calcium concentrations and isotope ratios were measured in urine and serum. While we found no significant association between urine Ca isotope composition (noted δ44/42Ca) between the different groups, δ44/42Ca values in serum were significantly different between healthy controls, subjects with mild-moderate CKD and those undertaking dialysis (P < 0.01). Receiver operative characteristic curve analysis shows that the diagnostic utility of serum δ44/42Ca for detecting medial artery calcification is very good (AUC = 0.818, sensitivity 81.8% and specificity 77.3%, P < 0.01), and performs better than existing biomarkers. Although our results will need to be verified in prospective studies across different institutions, serum δ44/42Ca has the potential to be used as an early screening test for vascular calcification.

Calcium isotope ratio in kidney stones: preliminary exploration of mechanism from the geochemical perspective.

Stable calcium (Ca) isotope ratios are sensitive and radiation-free biomarkers in monitoring biological processes in human bodies. Recently, the Ca isotope ratios of bone, blood, and urine have been widely reported to study bone mineral balance. However, as a pure Ca crystallization product, there is no report on the Ca isotope ratios of kidney stones, even though the prevalence of kidney stones is currently on the rise. Here, we measured Ca isotope data of 21 kidney stone samples collected in Beijing, China. The δ44/42CaNIST 915a values ranged from 0.25‰ to 2.85‰ for calcium oxalate, and from 0.38‰ to 3.00‰ and 0.61‰ to 0.69‰ for carbonate apatite and uric acid, respectively. Kidney stones have heavier Ca isotope ratios than bone or blood, which is probably because complexed Ca contains more heavy Ca isotopes than free Ca2+. Ca isotope evidence suggests that magnesium (Mg) affects kidney stone formation, as the δ44/42CaNIST 915a value is inversely correlated with the Ca/Mg ratio. This study provides important preliminary reference values on the Ca isotopic composition of kidney stones and proposes a factor influencing Ca isotope fractionation in biological processes for future research.

Linked fire activity and climate whiplash in California during the early Holocene.

Recent wildfire activity in semi-arid regions like western North America exceeds the range of historical records. High-resolution paleoclimate archives such as stalagmites could illuminate the link between hydroclimate, vegetation change, and fire activity in pre-anthropogenic climate states beyond the timescale of existing tree-ring records. Here we present an analysis of levoglucosan, a combustion-sensitive anhydrosugar, and lignin oxidation products (LOPs) in a stalagmite, reconstructing fire activity and vegetation composition in the California Coast Range across the 8.2 kyr event. Elevated levoglucosan concentrations suggest increased fire activity while altered LOP compositions indicate a shift toward more woody vegetation during the event. These changes are concurrent with increased hydroclimate volatility as shown by carbon and calcium isotope proxies. Together, these records suggest that climate whiplash (oscillations between extreme wetness and aridity) and fire activity in California, both projected to increase with anthropogenic climate change, were tightly coupled during the early Holocene.

Natural stable calcium isotope ratios: a new gold standard for bone balance?

Bone calcium balance is the net gain, loss, or equilibrium of calcium moving to and from bone, which reflects bone balance. There are currently no clinically available tools for measuring real-time bone balance. In this issue, Shroff et al. demonstrate the use of natural stable calcium isotope ratios as a novel biomarker of bone balance in children with chronic kidney disease on dialysis that is highly repeatable and associated with radiological and biochemical markers of bone metabolism.

Nutritional Calcium Supply Dependent Calcium Balance, Bone Calcification and Calcium Isotope Ratios in Rats.

Serum calcium isotopes (δ44/42Ca) have been suggested as a non-invasive and sensitive Ca balance marker. Quantitative δ44/42Ca changes associated with Ca flux across body compartment barriers relative to the dietary Ca and the correlation of δ44/42CaSerum with bone histology are unknown. We analyzed Ca and δ44/42Ca by mass-spectrometry in rats after two weeks of standard-Ca-diet (0.5%) and after four subsequent weeks of standard- and of low-Ca-diet (0.25%). In animals on a low-Ca-diet net Ca gain was 61 ± 3% and femur Ca content 68 ± 41% of standard-Ca-diet, bone mineralized area per section area was 68 ± 15% compared to standard-Ca-diet. δ44/42Ca was similar in the diets, and decreased in feces and urine and increased in serum in animals on low-Ca-diet. δ44/42CaBone was higher in animals on low-Ca-diet, lower in the diaphysis than the metaphysis and epiphysis, and unaffected by gender. Independent of diet, δ44/42CaBone was similar in the femora and ribs. At the time of sacrifice, δ44/42CaSerum inversely correlated with intestinal Ca uptake and histological bone mineralization markers, but not with Ca content and bone mineral density by µCT. In conclusion, δ44/42CaBone was bone site specific, but mechanical stress and gender independent. Low-Ca-diet induced marked changes in feces, serum and urine δ44/42Ca in growing rats. δ44/42CaSerum inversely correlated with markers of bone mineralization.

Naturally occurring stable calcium isotope ratios are a novel biomarker of bone calcium balance in chronic kidney disease.

Dysregulated calcium homeostasis is common in chronic kidney disease and causally associated with disorders of bone mineralization. However, radiological measures and biomarkers do not allow accurate evaluation of bone calcium balance. Non-radioactive calcium isotopes, 42Ca and 44Ca, are present in our diet and sequestered into body compartments following principles of kinetic isotope fractionation. Isotopically light 42Ca is preferentially incorporated into bone, while heavier 44Ca is excreted. The ratio (44/42Caserum) increases when bone formation exceeds resorption and vice versa, reflecting bone calcium balance. We measured these calcium isotopes by inductively coupled plasma mass-spectrometry in blood, urine and feces of 42 children with chronic kidney disease and 92 receiving dialysis therapy. We compared the isotope ratios with bone biomarkers and determined total bone mineral content by dual-energy x-ray absorptiometry and peripheral quantitative CT expressed as age-adjusted z-scores. The 44/42Caserum ratio positively correlated with serum calcium, 25-hydroxyvitamin D and alkaline phosphatases and inversely with serum parathyroid hormone and other bone resorption markers. The 44/42Caserum ratio positively correlated with age-adjusted z-scores of tibial trabecular bone mineral density and total bone mineral content measured by peripheral quantitative CT, and hip bone mineral density measured by dual-energy X-ray absorptiometry. Significant and independent predictors of total bone mineral content, measured by, were the 44/42Caserum ratio and parathyroid hormone. The 44/42Caserum ratio, repeated after four weeks, highly correlated with baseline values. When adjusted for calcium-containing medications and kidney impairment, the 44/42Caserum ratio in patients receiving dialysis was 157% lower than that of age-matched children and 29% lower than levels in elderly women with osteoporosis, implying significantly lower bone mineral content. Thus, calcium isotope ratios may provide a novel, sensitive and non-invasive method of assessing bone calcium balance in chronic kidney disease.

Calcium isotopes tracing secondary mineral formation in the high-relief Yalong River Basin, Southeast Tibetan Plateau.

Calcium is a critical element in the global carbon cycle due to its role in carbon sequestration via silicate weathering and carbonate formation. Here we apply calcium (δ44/40Ca) and strontium (87Sr/86Sr) isotopes to explore such chemical weathering processes in a river system draining a diverse range of geologic and climatic environments: the Yalong River, China, and its tributaries. This river originates on the Tibetan Plateau and represents one of the upper reaches of the Changjiang River, China. The Ca isotopic composition of the dissolved load of the Yalong River ranges from 0.60‰ to 1.02‰ (relative to the NIST standard SRM 915a). Higher δ44/40Ca values were found in the plateau and lowland rivers, with lower values in the mountainous rivers. Correlations between riverine dissolved δ44/40Ca values, Sr/Ca ratios, and calcite saturation index indicate that the precipitation of secondary carbonates governs the Ca isotopic composition and carbon transformation in most of this river system. However, such correlations are not seen in the lowland tributaries, where the relationship between δ44/40Ca and lithium (Li) isotopes instead suggests a control by topography and climate, via secondary clay mineral formation. Specifically, heavy rainfall in the lowland regions lowers the pH of the soil solution, which inhibits the precipitation of secondary carbonates. In addition, the flat terrain and thick soils increase the time for water-rock interaction, which favours the formation of secondary clay minerals that preferentially incorporate the lighter Ca isotopes. Overall, this study highlights the potential of stable Ca isotopes, when used in combination with other isotope systems (e.g. Sr and Li isotopes), to quantify secondary mineral formation processes in large river basins.

Adapting automated instrumentation for high-throughput calcium isotope measurements by multi-collector inductively coupled plasma mass spectrometry.

RATIONALE: Large, efficiently generated datasets of calcium isotope ratios offer tremendous utility in an increasing number of scientific disciplines. Modern analytical capabilities in mass spectrometry present unique challenges to previously established sample preparation techniques, the extent of which must be thoroughly examined before these data are interpreted and reported. This study addresses key methodological challenges in the determination of calcium isotopes using state-of-the-art, commercially available instruments. METHODS: Automated ion chromatography was used to isolate calcium from carbonate- and seawater-like samples prior to analysis by multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS). A new, membrane-bearing desolvator (Apex-Ω) is implemented and achieves enhanced sensitivity, yet necessitates an update to established sample preparation techniques due to previously unobserved matrix effects. Performance of this method was assessed through analyses of multiple standard reference materials (SRM 915b, USGS EN-1, and seawater) and several in-house standards using a Neptune MC-ICP-MS instrument. RESULTS: The enhanced sensitivity afforded by the Apex-Ω also yields pronounced matrix effects during mass spectrometry, resulting specifically from heightened sample Na and Sr content and deviations in sample [Ca] from their bracketing standards. While the latter can be addressed by a concentration correction, the first two matrix effects are mitigated using a modified chromatography technique that implements unique rinsing protocols. CONCLUSIONS: This precise (0.14‰ 2σ), high-throughput method is very reproducible for small sample amounts and, at optimal efficiency, can generate approximately 140 sample δ44/40 Ca values per week with 5 h of in-person effort per day. Documented matrix effects are successfully mitigated through corrections and modified chromatographic techniques. Additionally, this method may be permuted to accommodate most major cations.

Aplicación del análisis de isótopos de estroncio en la identificación humana en Colombia / Application of strontium isotope analysis for human identification in Colombia

El artículo presenta una revisión de las investigaciones realizadas a la fecha en Colombia relacionadas con la aplicación de los análisis de isótopos en la identificación humana. En especial, hace énfasis en la utilidad de las relaciones isotópicas de estroncio (87Sr/86Sr) para rastrear el lugar de origen de un cuerpo en condición no identificada (CNI). Dentro de la revisión se resalta la importancia de la variabilidad geológica colombiana, la cual puede incidir en la diversidad del estroncio biodisponible, en un espacio y un periodo determinados. Esta diversidad del estroncio biodisponible puede verse reflejada en la distribución espacial de la composición isotópica de estroncio en diferentes tejidos humanos (dientes, huesos, cabello y uñas) de los pobladores del territorio colombiano. Esto es debido a la transferencia de la señal isotópica del estroncio biodisponible a los tejidos humanos. Dentro de las conclusiones de la revisión bibliográfica realizada se menciona la importancia del uso del estroncio (Sr) en la identificación humana en el contexto colombiano, su aplicación forense y sus posibles limitantes respecto al uso de esta metodología en el país.

Calcium isotope fractionation by osteoblasts and osteoclasts, across endothelial and epithelial cell barriers, and with binding to proteins.

Timely and accurate diagnosis of osteoporosis is essential for adequate therapy. Calcium isotope ratio (δ44/42Ca) determination has been suggested as a sensitive, noninvasive, and radiation-free biomarker for the diagnosis of osteoporosis, reflecting bone calcium balance. The quantitative diagnostic is based on the calculation of the δ44/42Ca difference between blood, urine, and bone. The underlying cellular processes, however, have not been studied systematically. We quantified calcium transport and δ44/42Ca fractionation during in vitro bone formation and resorption by osteoblasts and osteoclasts and across renal proximal tubular epithelial cells (HK-2), human vein umbilical endothelial cells (HUVECs), and enterocytes (Caco-2) in transwell systems and determined transepithelial electrical resistance characteristics. δ44/42Ca fractionation was furthermore quantified with calcium binding to albumin and collagen. Calcified matrix formed by osteoblasts was isotopically lighter than culture medium by -0.27 ± 0.03‰ within 5 days, while a consistent effect of activated osteoclasts on δ44/42Ca could not be demonstrated. A transient increase in δ44/42Ca in the apical compartment by 0.26‰ occured across HK-2 cells, while δ44/42Ca fractionation was small across the HUVEC barrier and absent with Caco-2 enterocytes, and with binding of calcium to albumin and collagen. In conclusion, δ44/42Ca fractionation follows similar universal principles as during inorganic mineral precipitation; osteoblast activity results in δ44/42Ca fractionation. δ44/42Ca fractionation also occurs across the proximal tubular cell barrier and needs to be considered for in vivo bone mineralization modeling. In contrast, the effect of calcium transport across endothelial and enterocyte barriers on blood δ44/42Ca should be low and is absent with physiochemical binding of calcium to proteins.

Lactation and gestation controls on calcium isotopic compositions in a mammalian model.

Lactation and gestation are among the physiological events that trigger the most intense changes in body calcium (Ca) fluxes. Along with the composition of the animal 2021 diet, these events are suspected to impact the Ca isotopic composition of Ca body reservoirs but their dynamics are poorly understood. In this study, we monitored a group of domestic sows across a full reproduction cycle. We collected tissues and fluids (blood, urine, milk, colostrum, umbilical blood, adult and piglet bones) at different steps of gestation and lactation, and analyzed their Ca isotopic compositions (i.e. δ44/42Ca) by means of multi-collector inductively coupled plasma mass spectrometry. Among other results, we report the first observations of Ca isotopic fractionation between maternal and umbilical blood (Δ44/42Caumbilical blood-sow blood = -0.18 ± 0.11‰, n = 3). Our data also highlight that gestation and lactation periods are characterized by small diet-bone Ca isotopic offsets (Δ44/42Cabone-diet = -0.28 ± 0.11‰, n = 3), with 44Ca-enriched blood compositions during nursing (Δ44/42Canursing blood-gestation blood = $+ 0.42{\rm{\,\,}}_{ - 0.12}^{ + 0.11}$‰, n = 3). Under the light of an up-to-date mammalian box model, we explored different scenarios of gestation and lactation Ca fluxes experienced by a sow-like animal. These simulations suggest that gestation changes on body δ44/42Ca values may result from the intensification of Ca absorption by the animal, whereas the production of 44Ca-depleted milk is the main driver for the 44Ca enrichment in blood during lactation. In addition, our results also support that bone mineralization could be associated with a more restricted Ca isotopic fractionation than previously envisioned. Together, these results refine the framework of Ca isotope applications, notably regarding the monitoring of human bone balance and the study of species and ecosystems from the present and the past.

Sex-Specific Classification of Drug-Induced Torsade de Pointes Susceptibility Using Cardiac Simulations and Machine Learning.

Torsade de Pointes (TdP), a rare but lethal ventricular arrhythmia, is a toxic side effect of many drugs. To assess TdP risk, safety regulatory guidelines require quantification of hERG channel block in vitro and QT interval prolongation in vivo for all new therapeutic compounds. Unfortunately, these have proven to be poor predictors of torsadogenic risk, and are likely to have prevented safe compounds from reaching clinical phases. Although this has stimulated numerous efforts to define new paradigms for cardiac safety, none of the recently developed strategies accounts for patient conditions. In particular, despite being a well-established independent risk factor for TdP, female sex is vastly under-represented in both basic research and clinical studies, and thus current TdP metrics are likely biased toward the male sex. Here, we apply statistical learning to synthetic data, generated by simulating drug effects on cardiac myocyte models capturing male and female electrophysiology, to develop new sex-specific classification frameworks for TdP risk. We show that (i) TdP classifiers require different features in females vs. males; (ii) male-based classifiers perform more poorly when applied to female data; and (iii) female-based classifier performance is largely unaffected by acute effects of hormones (i.e., during various phases of the menstrual cycle). Notably, when predicting TdP risk of intermediate drugs on female simulated data, male-biased predictive models consistently underestimate TdP risk in women. Therefore, we conclude that pipelines for preclinical cardiotoxicity risk assessment should consider sex as a key variable to avoid potentially life-threatening consequences for the female population.

Isotopic calcium biogeochemistry of MIS 5 fossil vertebrate bones: application to the study of the dietary reconstruction of Regourdou 1 Neandertal fossil.

The calcium isotopic composition (δ44/42Ca) of bone and tooth enamel can be used for dietary reconstructions of extant and extinct mammals. In natural conditions, the δ44/42Ca value of bone and teeth varies according to dietary intake with a constant isotopic offset of about -0.6‰. Owing to the poor conservation of collagen, carbon (C), and nitrogen (N) isotopic compositions of the Regourdou Mousterian site (MIS 5, Dordogne, France) previously failed to provide any paleodietary information. Therefore, to reconstruct the trophic chain, we have measured calcium (Ca) isotopes from fossil bone samples of the fauna from the Regourdou site, as well as from three bone samples of the Regourdou 1 Neandertal specimen. The results show a taxon-dependent patterning of the Ca isotopic compositions: herbivores generally have higher δ44/42Ca values than carnivores. All the δ44/42Ca values of Regourdou 1 are low (<-1.6‰), placing this specimen amid carnivores. Using a bone-muscle Ca isotopic offset determined on extant animals, we further show that the δ44/42Ca value of the Regourdou 1 diet, and that of most carnivores, cannot be accounted for by the consumption of meat only, as plants and meat have indistinguishable δ44/42Ca values. Mass balance calculations indicate that the low δ44/42Ca values of the Neandertal's carnivorous diet are explained by the ingestion of bone marrow containing as little as 1% trabecular bone. Our results show that the Regourdou 1 Neanderthal consumed a mixture of various herbivorous prey, as well as trabecular bone, which probably occurred when marrow was ingested, by accident or intentionally.

Naturally Occurring Stable Calcium Isotope Ratios in Body Compartments Provide a Novel Biomarker of Bone Mineral Balance in Children and Young Adults.

Serum calcium (Ca), bone biomarkers, and radiological imaging do not allow accurate evaluation of bone mineral balance (BMB), a key determinant of bone mineral density (BMD) and fracture risk. We studied naturally occurring stable (non-radioactive) Ca isotopes in different body pools as a potential biomarker of BMB. 42 Ca and 44 Ca are absorbed from our diet and sequestered into different body compartments following kinetic principles of isotope fractionation; isotopically light 42 Ca is preferentially incorporated into bone, whereas heavier 44 Ca preferentially remains in blood and is excreted in urine and feces. Their ratio (δ44/42 Ca) in serum and urine increases during bone formation and decreases with bone resorption. In 117 healthy participants, we measured Ca isotopes, biomarkers, and BMD by dual-energy X-ray absorptiometry (DXA) and tibial peripheral quantitative CT (pQCT). 44 Ca and 42 Ca were measured by multi-collector ionization-coupled plasma mass-spectrometry in serum, urine, and feces. The relationship between bone Ca gain and loss was calculated using a compartment model. δ44/42 Caserum and δ44/42 Caurine were higher in children (n = 66, median age 13 years) compared with adults (n = 51, median age 28 years; p < 0.0001 and p = 0.008, respectively). δ44/42 Caserum increased with height in boys (p < 0.001, R2 = 0.65) and was greatest at Tanner stage 4. δ44/42 Caserum correlated positively with biomarkers of bone formation (25-hydroxyvitaminD [p < 0.0001, R2 = 0.37] and alkaline phosphatase [p = 0.009, R2 = 0.18]) and negatively with bone resorption marker parathyroid hormone (PTH; p = 0.03, R2 = 0.13). δ44/42 Caserum strongly positively correlated with tibial cortical BMD Z-score (n = 62; p < 0.001, R2 = 0.39) but not DXA. Independent predictors of tibial cortical BMD Z-score were δ44/42 Caserum (p = 0.004, ß = 0.37), 25-hydroxyvitaminD (p = 0.04, ß = 0.19) and PTH (p = 0.03, ß = -0.13), together predicting 76% of variability. In conclusion, naturally occurring Ca isotope ratios in different body compartments may provide a novel, non-invasive method of assessing bone mineralization. Defining an accurate biomarker of BMB could form the basis of future studies investigating Ca dynamics in disease states and the impact of treatments that affect bone homeostasis. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Experimental evidence refuting the assumption of phosphorus-31 nuclear-spin entanglement-mediated consciousness.

Phosphorus-31 nuclear-spin entanglements within Ca9(PO4)6 molecules (Posner molecules) have been proposed to be central for neural processing. However, this has yet to be proven experimentally. Relatedly, increasing calcium ion concentration in the cerebrospinal fluid has been proposed to enhance consciousness by accelerating Posner molecules' creation. A dependence on calcium isotope is also expected. Here we test these predictions experimentally by measuring the loss of righting reflex ED50 for mice to sevoflurane - an increase in loss of righting reflex ED50 indicates a higher level of consciousness and vice versa. Our mice's findings demonstrate that intracerebroventricular injection of EGTA enhances the sevoflurane-induced loss of righting reflex ED50 while injecting calcium-40 chloride or calcium-43 chloride causes an opposite effect. Further, the identical effects of calcium-40 and calcium-43 indicate an absence of calcium isotope dependence. Here, our findings disprove conventional proposals that calcium ion concentration correlates with consciousness.

Calcium isotopic ecology of Turkana Basin hominins.

Diet is a major driver of hominin evolution, but most of the geochemical evidence relies on carbon isotopes (δ13C). Here, we report enamel stable calcium isotope (δ44/42Ca) values against δ13C values for several hominins and co-existing primates in the Turkana Basin area, circa 4 to 2 Ma. Australopithecus anamensis clusters with mammal browsers, Kenyanthropus platyops is distinct from A. anamensis in foraging into more open environments and the coexisting Theropithecus brumpti encompasses both the grazer and omnivore/carnivore domains. Early Homo is remarkable for its wide distribution in δ44/42Ca values, possibly reflecting omnivorous and opportunistic preferences. Paranthropus boisei is uniquely distributed in the δ13C versus δ44/42Ca iso-space being distinct from all other hominins from the Turkana Basin area as well as from the co-existing Theropithecus oswaldi. Several hypotheses are explored to discuss the unique δ44/42Ca values of Paranthropus boisei including significant differences observed with δ44/42Ca values recently reported for P. robustus from South Africa, questioning the monophyly of this genus.

Modeling and simulation of excitation- contraction coupling of fast-twitch skeletal muscle fibers.

BACKGROUND: The current excitation-contraction coupling model of fast-twitch skeletal muscle fibers cannot completely simulate the excitation-contraction process. OBJECTIVE: To solve this problem, this study proposes an excitation-contraction model of fast-twitch skeletal muscle fibers based on the physiological structure and contractile properties of half-sarcomeres. METHODS: The model includes the action potential model of fast-twitch fiber membranes and transverse tubule membranes, the cycle model of 𝐶𝑎2+ in myofibril, the cross-bridge cycle model, and the fatigue model of metabolism. RESULTS: Finally, detailed analyses of the results from the simulation are conducted using the Simulink toolbox in MATLAB. Two conditions, non-coincidence and coincidence, are analyzed for both the thick and thin myofilaments. CONCLUSIONS: The simulation results of two groups of models are the same as the previous research results, which validates the accuracy of models.

Use of Calcium Isotopic Tracers To Determine Factors That Perturb Calcium Metabolism.

Calcium plays an important role in maintaining bone health. Ensuring adequate calcium intake throughout life is essential for reaching greater peak bone mass in young adulthood and lowering osteoporotic fracture risk when aging. Calcium homeostasis involves a complex interaction between three organ systems: intestine, kidney, and bone. Metabolic balance plus kinetic studies using calcium isotopic tracers can estimate calcium metabolism parameters and pinpoint how organs and processes are perturbed by internal and external modifiers. Both modifiable factors (e.g., vitamin D supplementations and dietary bioactives) and non-modifiable factors (e.g., age, sex, and race) influence calcium utilization. Current evidence suggests that prebiotic fibers may offer an alternative approach to enhance calcium absorption through altering gut microbiota to ultimately improve bone health.

High-resolution 13 C and 43 Ca solid-state NMR and computational studies of the ethylene glycol solvate of atorvastatin calcium.

We report 43 Ca and 13 C solid-state nuclear magnetic resonance (NMR) spectroscopic studies of the ethylene glycol solvate of atorvastatin calcium. The 13 C and 43 Ca chemical shift and 43 Ca quadrupolar coupling tensor parameters are reported. The results are interpreted in terms of the reported X-ray diffraction crystal structure of the solvate and are compared with the NMR parameters of atorvastatin calcium trihydrate, the active pharmaceutical ingredient in Lipitor®. Hartree-Fock and density functional theory calculations of the NMR parameters based on a cluster model derived from the optimized X-ray diffraction crystal structure of the ethylene glycol solvate of atorvastatin calcium are in reasonable agreement with the experimental 43 Ca and 13 C NMR measurables.