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Medial vascular calcification, associated with enhanced mortality in chronic kidney disease (CKD), is fostered by osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs). Here, we describe that serum- and glucocorticoid-inducible kinase 1 (SGK1) was upregulated in VSMCs under calcifying conditions. In primary human aortic VSMCs, overexpression of constitutively active [SGK1.sup.S422D], but not inactive [SGK1.sup.K127N], upregulated osteo-/chondrogenic marker expression and activity, effects pointing to increased osteo-/chondrogenic transdifferentiation. [SGK1.sup.S422D] induced nuclear translocation and increased transcriptional activity of NF-[kappa]B. Silencing or pharmacological inhibition of IKK abrogated the osteoinductive effects of [SGK1.sup.S422D]. Genetic deficiency, silencing, and pharmacological inhibition of SGK1 dissipated phosphate-induced calcification and osteo-/chondrogenic transdifferentiation of VSMCs. Aortic calcification, stiffness, and osteo-/chondrogenic transdifferentiation in mice following cholecalciferol overload were strongly reduced by genetic knockout or pharmacological inhibition of Sgk1 by EMD638683. Similarly, Sgk1 deficiency blunted vascular calcification in apolipoprotein E-deficient mice after subtotal nephrectomy. Treatment of human aortic smooth muscle cells with serum from uremic patients induced osteo-/chondrogenic transdifferentiation, effects ameliorated by EMD638683. These observations identified SGK1 as a key regulator of vascular calcification. SGK1 promoted vascular calcification, at least partly, via NF-[kappa]B activation. Inhibition of SGK1 may, thus, reduce the burden of vascular calcification in CKD.

Human patients carrying PAPP‐A2 inactivating mutations have low bone mineral density. The underlying mechanisms for this reduced calcification are poorly understood. Using a zebrafish model, we report that Papp-aa regulates bone calcification by promoting Ca2+-transporting epithelial cell (ionocyte) quiescence-proliferation transition. Ionocytes, which are normally quiescent, re-enter the cell cycle under low [Ca2+] stress. Genetic deletion of Papp-aa, but not the closely related Papp-ab, abolished ionocyte proliferation and reduced calcified bone mass. Loss of Papp-aa expression or activity resulted in diminished IGF1 receptor-Akt-Tor signaling in ionocytes. Under low Ca2+ stress, Papp-aa cleaved Igfbp5a. Under normal conditions, however, Papp-aa proteinase activity was suppressed and IGFs were sequestered in the IGF/Igfbp complex. Pharmacological disruption of the IGF/Igfbp complex or adding free IGF1 activated IGF signaling and promoted ionocyte proliferation. These findings suggest that Papp-aa-mediated local Igfbp5a cleavage functions as a [Ca2+]-regulated molecular switch linking IGF signaling to bone calcification by stimulating epithelial cell quiescence-proliferation transition under low Ca2+ stress.

Ocean acidification is considered a major threat to marine ecosystems and may particularly affect calcifying organisms such as corals, foraminifera and coccolithophores. Here we investigate the impact of elevated pCO2 and lowered pH on growth and calcification in the common calcareous dinoflagellate Thoracosphaera heimii. We observe a substantial reduction in growth rate, calcification and cyst stability of T. heimii under elevated pCO2. Furthermore, transcriptomic analyses reveal CO2 sensitive regulation of many genes, particularly those being associated to inorganic carbon acquisition and calcification. Stable carbon isotope fractionation for organic carbon production increased with increasing pCO2 whereas it decreased for calcification, which suggests interdependence between both processes. We also found a strong effect of pCO2 on the stable oxygen isotopic composition of calcite, in line with earlier observations concerning another T. heimii strain. The observed changes in stable oxygen and carbon isotope composition of T. heimii cysts may provide an ideal tool for reconstructing past seawater carbonate chemistry, and ultimately past pCO2. Although the function of calcification in T. heimii remains unresolved, this trait likely plays an important role in the ecological and evolutionary success of this species. Acting on calcification as well as growth, ocean acidification may therefore impose a great threat for T. heimii.

Calciprotein particles (CPPs) may play an important role in the calcification process. The calcification propensity of serum (T50) is highly predictive of all-cause mortality in chronic kidney disease patients. Whether T50 is therapeutically improvable, by high-flux hemodialysis (HD) or hemodiafiltration (HDF), has not been studied yet. We designed a cross-sectional single center study, and included stable prevalent in-center dialysis patients on HD or HDF. Patients were divided into two groups based on dialysis modality, were on a thrice-weekly schedule, had a dialysis vintage of > 3 months and vascular access providing a blood flow rate > 300 ml/min. Calcification propensity of serum was measured by the time of transformation from primary to secondary CPP (T50 test), by time-resolved nephelometry. We included 64 patients, mean convective volume was 21.7L (SD 3.3L). In the pooled analysis, T50 levels increased in both the HD and HDF group with pre- and post-dialysis (mean (SD)) of 244(64) - 301(57) and 253(55) - 304(61) min respectively (P = 0.43(HD vs. HDF)). The mean increase in T50 was 26.29% for HD and 21.97% for HDF patients (P = 0.61 (HD vs. HDF)). The delta values (Δ) of calcium, phosphate and serum albumin were equal in both groups. Baseline T50 was negatively correlated with phosphate, and positively correlated with serum magnesium and fetuin-A. The ΔT50 was mostly influenced by Δ phosphate (r = -0.342; P = 0.002 HD and r = -0.396; P<0.001 HDF) in both groups. HD and HDF patients present with same baseline T50 calcification propensity values pre-dialysis. Calcification propensity is significantly improved during both HD and HDF sessions without significant differences between both modalities.

To evaluate the relationships between coral calcification, thermal stress, and sedimentation and eutrophication linked to human impact (hereafter referred to as \"land development\") by river discharge, we analyzed growth characteristics in the context of a paleoenvironment that was reconstructed from geochemical signals in modern and fossil (1.2 cal kyr BP and 3.5 cal kyr BP, respectively) massive Porites corals from Nagura Bay (\"Nagura\") and from modern Porites corals from the estuary of the Todoroki River, Shiraho Reef (\"Todoroki\"). Both sites are on Ishigaki Island, Japan, and Nagura is located approximately 12 km west of Todoroki. At Nagura, the individual corals provide time windows of 13 (modern), 10 (1.2 cal kyr BP), and 38 yr in length (3.5 cal kyr BP). Here, we present the coral annual calcification for Nagura and Todoroki, and (bi) monthly resolved records of Sr/Ca (a proxy of sea surface temperature (SST)) and Ba/Ca (a proxy of sedimentation and nutrients related to land development) for Nagura. At Nagura, the winter SST was cooler by 2.8°C in the 1.2 cal kyr BP, and the annual and winter SSTs in the 3.5 cal kyr BP were cooler by 2.6°C and 4.6°C, respectively. The annual periodicity of Ba/Ca in modern coral is linked to river discharge and is associated with land development including sugar cane cultivation. Modern coral calcification also has declined with SST warming and increasing Ba/Ca peaks in winter. However, calcification of fossil corals does not appear to have been influenced by variations in Sr/Ca and Ba/Ca. Modern coral growth characteristics at Nagura and Todoroki indicate that coral growth is both spatially and temporally influenced by river discharge and land development. At Nagura, our findings suggest that land development induces negative thermal sensitivity for calcification in winter due to sugar cane harvest, which is a specifically modern phenomenon.

Renal interstitial fibrosis and arterial lesions predict loss of function in chronic kidney disease. Noninvasive estimation of interstitial fibrosis and vascular lesions is currently not available. The aim of the study was to determine whether phosphocalcic markers are associated with, and can predict, renal chronic histological changes. We included 129 kidney allograft recipients with an available transplant biopsy in a retrospective study. We analyzed the associations and predictive values of phosphocalcic markers and serum calcification propensity (T50) for chronic histological changes (interstitial fibrosis and vascular lesions). PTH, T50 and vitamin D levels were independently associated to interstitial fibrosis. PTH elevation was associated with increasing interstitial fibrosis severity (r = 0.29, p = 0.001), while T50 and vitamin D were protective (r = -0.20, p = 0.025 and r = -0.23, p = 0.009 respectively). On the contrary, fibroblast growth factor 23 (FGF23) and Klotho correlated only modestly with interstitial fibrosis (p = 0.045) whereas calcium and phosphate did not. PTH, vitamin D and T50 were predictors of extensive fibrosis (AUC: 0.73, 0.72 and 0.68 respectively), but did not add to renal function prediction. PTH, FGF23 and T50 were modestly predictive of low fibrosis (AUC: 0.63, 0.63 and 0.61) but did not add to renal function prediction. T50 decreased with increasing arterial lesions (r = -0.21, p = 0.038). The discriminative performance of T50 in predicting significant vascular lesions was modest (AUC 0.61). In summary, we demonstrated that PTH, vitamin D and T50 are associated to interstitial fibrosis and vascular lesions in kidney allograft recipients independently of renal function. Despite these associations, mineral metabolism indices do not show superiority or additive value to fibrosis prediction by eGFR and proteinuria in kidney allograft recipients, except for vascular lesions where T50 could be of relevance.

Bryozoans are colonial benthic marine invertebrate calcifiers, important and especially abundant and diverse in southern hemisphere shelf environments. Large heavily calcified colonies can be up to 50 years old, but most longer-lived bryozoans are limited to 10–20 y. Many smaller species are annual. Radial extension in flat encrusting bryozoans is generally on the order of 1–5 mm/y. Erect calcified species generally grow vertically 2–15 mm/y, though articulated species such as Cellaria may reach rates of 40 mm/y. Corresponding calcification rates are generally 101–102 mg/y, but there can be an order of magnitude variation in rate among years in high-latitude bryozoans. Multi-branched bryozoans produce up to 24 g of CaCO3/y. The carbonate produced by bryozoans varies from calcite to aragonite and mixtures of both. Skeletal carbonate mineralogy of bryozoans is complex and appears to be strongly genetically controlled. Global climate change, leading to increasing water temperatures, will generally increase marine bryozoan metabolic rates, and may increase Mg in calcite. On the other hand, decreasing pH (ocean acidification) causes corrosion, changes in mineralogy, and decreased survival. This review of bryozoan growth and calcification allows a general perspective, but also reveals gaps in our knowledge which need to be addressed.

Coral reefs worldwide are affected by increasing dissolved inorganic carbon (DIC) and organic carbon (DOC) concentrations due to ocean acidification (OA) and coastal eutrophication. These two stressors can occur simultaneously, particularly in near-shore reef environments with increasing anthropogenic pressure. However, experimental studies on how elevated DIC and DOC interact are scarce and fundamental to understanding potential synergistic effects and foreseeing future changes in coral reef function. Using an open mesocosm experiment, the present study investigated the impact of elevated DIC (pHNBS: 8.2 and 7.8; pCO2: 377 and 1076 μatm) and DOC (added as 833 μmol L-1 of glucose) on calcification and photosynthesis rates of two common calcifying green algae, Halimeda incrassata and Udotea flabellum, in a shallow reef environment. Our results revealed that under elevated DIC, algal photosynthesis decreased similarly for both species, but calcification was more affected in H. incrassata, which also showed carbonate dissolution rates. Elevated DOC reduced photosynthesis and calcification rates in H. incrassata, while in U. flabellum photosynthesis was unaffected and thalus calcification was severely impaired. The combined treatment showed an antagonistic effect of elevated DIC and DOC on the photosynthesis and calcification rates of H. incrassata, and an additive effect in U. flabellum. We conclude that the dominant sand dweller H. incrassata is more negatively affected by both DIC and DOC enrichments, but that their impact could be mitigated when they occur simultaneously. In contrast, U. flabellum can be less affected in coastal eutrophic waters by elevated DIC, but its contribution to reef carbonate sediment production could be further reduced. Accordingly, while the capacity of environmental eutrophication to exacerbate the impact of OA on algal-derived carbonate sand production seems to be species-specific, significant reductions can be expected under future OA scenarios, with important consequences for beach erosion and coastal sediment dynamics.

Background Data on the relationship between the triglyceride glucose (TyG) index and coronary artery calcification (CAC) progression is limited. This longitudinal study evaluated the association of TyG index with CAC progression in asymptomatic adults. Methods We enrolled 12,326 asymptomatic Korean adults who had at least two CAC evaluations. The TyG index was determined using ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). CAC progression was defined as a difference ≥ 2.5 between the square roots (√) of the baseline and follow-up coronary artery calcium score (CACS) (Δ√transformed CACS). Annualized Δ√transformed CACS was defined as Δ√transformed CACS divided by the inter-scan period. Results During a mean 3.3 years, the overall incidence of CAC progression was 30.6%. The incidence of CAC progression (group I [lowest]: 22.7% versus [vs.] group II: 31.7% vs. group III [highest]: 37.5%, P < 0.001) and annualized Δ√transformed CACS (group I: 0.46 ± 1.44 vs. group II: 0.71 ± 2.02 vs. group III: 0.87 ± 1.75, P < 0.001) were markedly elevated with increasing TyG index tertiles. Multivariate linear regression analysis showed that TyG index was associated with annualized Δ√transformed CACS (β = 0.066, P = 0.036). In multivariate logistic regression analysis, the TyG index was significantly associated with CAC progression in baseline CACS ≤ 100. Conclusion The TyG index is an independent predictor of CAC progression, especially in adults without heavy baseline CAC.

Malnutrition and inflammation are closely linked to vascular calcification (VC), the severity of which correlate with adverse outcome. However, there were few studies on the interplay between malnutrition, inflammation and VC progression, rather than VC presence per se. We aimed to determine the relationship of malnutrition, inflammation, abdominal aortic calcification (AAC) progression with survival in hemodialysis (HD) patients. Malnutrition and inflammation were defined as low serum albumin (< 40 g/L) and high hs-CRP (≥ 28.57 nmol/L), respectively. We defined AAC progression as an increase in AAC score using lateral lumbar radiography at both baseline and one year later. Patients were followed up to investigate the impact of AAC progression on all-cause and cardiovascular mortality. AAC progressed in 54.6% of 97 patients (mean age 58.2±11.7 years, 41.2% men) at 1-year follow-up. Hypoalbuminemia (Odds ratio 3.296; 95% confidence interval 1.178-9.222), hs-CRP (1.561; 1.038-2.348), low LDL-cholesterol (0.976; 0.955-0.996), and the presence of baseline AAC (10.136; 3.173-32.386) were significant risk factors for AAC progression. During the mean follow-up period of 5.9 years, 38(39.2%) patients died and 27(71.0%) of them died of cardiovascular disease. Multivariate Cox regression analysis adjusted for old age, diabetes, cardiovascular history, and hypoalbuminemia determined that AAC progression was an independent predictor of all-cause mortality (2.294; 1.054-4.994). Malnutrition and inflammation were significantly associated with AAC progression. AAC progression is more informative than AAC presence at a given time-point as a predictor of all-cause mortality in patients on maintenance HD.