Skeletal Calcification Research Articles

Tertiary Hyperparathyroidism and Extra Skeletal Calcification in End Stage Kidney Disease Patients: Case-series and Literature Review

Background:: Tertiary hyperparathyroidism (THPT) is a well-known complication of end-stage kidney disease (ESKD), resulting from a loss of functional renal tissue with subsequent alterations in calcium and phosphate metabolism. Tertiary hyperparathyroidism reflects severe parathyroid hyperplasia with autonomous excessive secretion of parathyroid hormone (PTH) that is no longer responsive to the concentration of plasma calcium and leads to abnormal bone remodelling, soft tissue calcifications, vasculopathy, and other systemic complications. Case Presentation:: The authors, hereby, highlight varied presentations of tertiary hyperparathyroidism (THPT) by presenting 3 interesting cases, describing their clinical course and outcomes. Through sharing these experiences and insights, we hope to contribute to a better understanding of THPT and its optimal management in patients with ESKD. Conclusion:: THPT can have a significant impact on patient health and quality of life. Despite the widespread use of interventions, such as vitamin D analogues, calcimimetics and parathyroidectomy, THPT remains a significant clinical challenge for patients with ESKD.

Chromosome-level genome assembly of hadal snailfish reveals mechanisms of deep-sea adaptation in vertebrates

As the deepest vertebrate in the ocean, the hadal snailfish (Pseudoliparis swirei), which lives at a depth of 6,000–8,000 m, is a representative case for studying adaptation to extreme environments. Despite some preliminary studies on this species in recent years, including their loss of pigmentation, visual and skeletal calcification genes, and the role of trimethylamine N-oxide in adaptation to high-hydrostatic pressure, it is still unknown how they evolved and why they are among the few vertebrate species that have successfully adapted to the deep-sea environment. Using genomic data from different trenches, we found that the hadal snailfish may have entered and fully adapted to such extreme environments only in the last few million years. Meanwhile, phylogenetic relationships show that they spread into different trenches in the Pacific Ocean within a million years. Comparative genomic analysis has also revealed that the genes associated with perception, circadian rhythms, and metabolism have been extensively modified in the hadal snailfish to adapt to its unique environment. More importantly, the tandem duplication of a gene encoding ferritin significantly increased their tolerance to reactive oxygen species, which may be one of the important factors in their adaptation to high-hydrostatic pressure.

Chromosome-level genome assembly of hadal snailfish reveals mechanisms of deep-sea adaptation in vertebrates.

As the deepest vertebrate in the ocean, the hadal snailfish (Pseudoliparis swirei), which lives at a depth of 6,000-8,000 m, is a representative case for studying adaptation to extreme environments. Despite some preliminary studies on this species in recent years, including their loss of pigmentation, visual and skeletal calcification genes, and the role of trimethylamine N-oxide in adaptation to high-hydrostatic pressure, it is still unknown how they evolved and why they are among the few vertebrate species that have successfully adapted to the deep-sea environment. Using genomic data from different trenches, we found that the hadal snailfish may have entered and fully adapted to such extreme environments only in the last few million years. Meanwhile, phylogenetic relationships show that they spread into different trenches in the Pacific Ocean within a million years. Comparative genomic analysis has also revealed that the genes associated with perception, circadian rhythms, and metabolism have been extensively modified in the hadal snailfish to adapt to its unique environment. More importantly, the tandem duplication of a gene encoding ferritin significantly increased their tolerance to reactive oxygen species, which may be one of the important factors in their adaptation to high-hydrostatic pressure.

Skeletal calcification patterns of batoid, teleost, and mammalian models: Calcified cartilage versus bone matrix.

This study compares the skeletal calcification pattern of batoid Raja asterias with the endochondral ossification model of mammalians Homo sapiens and teleost Xiphias gladius. Skeletal mineralization serves to stiffen the mobile elements for locomotion. Histology, histochemistry, heat deproteination, scanning electron microscopy (SEM)/EDAX analysis, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and Fourier transform infrared spectrometry (FTIR) have been applied in the study. H. sapiens and X. gladius bone specimens showed similar profiles, R. asterias calcified cartilage diverges for higher water release and more amorphous bioapatite. In endochondral ossification, fetal calcified cartilage is progressively replaced by bone matrix, while R. asterias calcified cartilage remains un-remodeled throughout the life span. Ca2+ and PO4 3- concentration in extracellular matrix is suggested to reach the critical salts precipitation point through H2 O recall from extracellular matrix into both chondroblasts or osteoblasts. Cartilage organic phase layout and incomplete mineralization allow interstitial fluids diffusion, chondrocytes survival, and growth in a calcified tissue lacking of a vascular and canalicular system. HIGHLIGHTS: Comparative physico-chemical characterization (TGA, DTG and DSC) testifies the mass loss due to water release, collagen and carbonate decomposition of the three tested matrices. R. asterias calcified cartilage water content is higher than that of H. sapiens and X. gladius, as shown by the respectively highest dehydration enthalpy values. Lower crystallinity degree of R. asterias calcified cartilage can be related to the higher amount of collagen in amorphous form than in bone matrix. These data can be discussed in terms of the mechanostat theory (Frost, 1966) or by organic/inorganic phase transformation in the course evolution from fin to limbs. Mineral analysis documented different charactersof R. asterias vs H. sapiens and X. gladius calcified matrix.

Effects of Dietary Phosphorus Deficiency and High Phosphorus Content on the Growth Performance, Serum Variables, and Tibia Development in Goslings

Understanding how dietary phosphorus (P) regulates the growth and skeletal development of goslings is essential for fully utilizing P in the production of geese. We aimed to study the effects of dietary P deficiency and high P content on growth performance, serum variables, tibia quality, and mRNA expression of osteogenesis-related genes in tibia to reveal how dietary P regulates bone development in goslings. Two hundred and sixteen one-day-old Jiangnan White male geese were fed corn-soybean meal diets for 14 days. The diets were set with the same calcium (Ca) level (0.80%) and three non-phytate P (NPP) levels: 0.08% (P deficiency), 0.38% (P control), and 0.80% (P high content). Each treatment consisted of six replicates with 12 goslings in each replicate. The P deficient group had a high cumulative mortality of 26.67% with lower body weight (BW), average daily feed intake (ADFI), average daily gain (ADG), serum P contents, tibia width, tibia length, tibia fresh weight at d 14 as compared with the control and high P content group (p ≤ 0.05). Dietary P deficiency caused a reduction in the goslings’ tibia strength, tibia ash content, tibia Ca content, and tibia P content during d 4–d 14 (p < 0.05). The P deficiency reduced tibia mRNA expression of osteoprotegerin (OPG) and runt-related transcription factor 2 (Runx2) on d 7 (p < 0.05), whereas up-regulated serum alkaline phosphatase (ALP) activity, calcitonin (CT) content, and the tibia mRNA ratio of receptor activator of NF-κB ligand (RNAKL)/OPG during d 7–d 14 (p < 0.05). The serum 1,25-(OH2)D3 content, serum bone Gla-protein (BGP), and the mRNA relative expression of RNAKL and BGP in tibia were decreased in the NPP 0.08% and 0.80% groups compared with the control on d 14 (p < 0.05). In conclusion, dietary P deficiency induced acute rickets in goslings as early as the fourth day. A P deficiency hindered the tibia and body growth partly due to poor skeletal calcification caused by a down-expression of osteogenesis-related genes regulated by high serum ALP activity and calcitonin contents and lower serum BGP and skeletal P contents.

Cellular adaptations leading to coral fragment attachment on artificial substrates in Acropora millepora (Am-CAM)

Reproductive propagation by asexual fragmentation in the reef-building coral Acropora millepora depends on (1) successful attachment to the reef substrate through modification of soft tissues and (2) a permanent bond with skeletal encrustation. Despite decades of research examining asexual propagation in corals, the initial response, cellular reorganisation, and development leading to fragment substrate attachment via a newly formed skeleton has not been documented in its entirety. Here, we establish the first "coral attachment model" for this species ("Am-CAM") by developing novel methods that allow correlation of fluorescence and electron microscopy image data with in vivo microscopic time-lapse imagery. This multi-scale imaging approach identified three distinct phases involved in asexual propagation: (1) the contact response of the coral fragment when contact with the substrate, followed by (2) fragment stabilisation through anchoring by the soft tissue, and (3) formation of a "lappet-like appendage" structure leading to substrate bonding of the tissue for encrustation through the onset of skeletal calcification. In developing Am-CAM, we provide new biological insights that can enable reef researchers, managers and coral restoration practitioners to begin evaluating attachment effectiveness, which is needed to optimise species-substrate compatibility and achieve effective outplanting.

The role of phosphate on non-skeletal carbonate production in a Cretaceous alkaline lake

Alkaline carbonate-rich systems may, under some circumstances, result in significant accumulation of aqueous phosphorus. Additionally, the geochemistry of modern alkaline lakes, combined with current understanding of CaCO3 precipitation kinetics, indicates that the establishment of high alkalinity, high dissolved inorganic carbon (DIC), and CaCO3 supersaturation require compounds that inhibit or interfere with CaCO3 precipitation. Furthermore, the interplay between these factors may potentially affect fabric development in non-skeletal carbonates. In order to understand how these interlinked processes may have regulated PO4 concentrations and the processes and products of non-skeletal CaCO3 precipitation in the distant past, we conducted a detailed geological and geochemical study in two cores drilled in different portions of the Santos Basin, offshore southeastern Brazil, consisting of lacustrine carbonate rocks from the Lower Cretaceous Barra Velha Formation. We find that phosphorus in the sediments comes from two main products, phosphatic bioclasts and authigenic phosphate (of both primary and diagenetic origins). We also find that phosphorus occurs in concentrations of up to several thousand ppm in some intervals and is preferentially associated with some calcite textures potentially reflecting the primary sedimentary depositional conditions (e.g., upward-radiating aggregates of fibrous calcite, or “shrubs” and spherulitic aggregates of fibrous calcite, or “spherulites”). Microanalytical data from selected samples and high-Mg CaCO3 textures show median P values can be particularly high in crusts, shrubs and spherulitic calcite minerals interpreted here to have formed as primary to early diagenetic deposits, and roughly vary between 1000 and 2000 ppm (10.5–21.1 mmol/kg). The average P/(Ca + Mg) molar ratio values based on the same data for these three calcite textures are 1.45 ± 0.98, 1.13 ± 0.97 and 1.09 ± 0.90 mmol/mol, respectively, being as high as 4.80 mmol/mol in specific spots in “shrubby” textures. Although multiple source-to-sink mechanisms were likely involved in the P budget in lake waters and in the sediments, such as recycling and remobilisation of skeletal- and organic-bound phosphate, high alkalinity may have enhanced its accumulation in the lake’s waters. In light of current understanding of CaCO3 precipitation kinetics, we hypothesise that phosphate may have played a central role in maintaining high calcium carbonate saturation (14–45 < Ωcalcite ≤ 100–180). These conditions would have favoured growth of calcite crystals on pre-existing substrates over nucleation of finely particulate carbonate sediment. By combining these observations with theoretical geochemical considerations, we propose that phosphate inhibition of calcium carbonate precipitation was enhanced by high alkalinity, further sustaining CaCO3 supersaturation and favouring distinctive carbonate growth textures. This unique and relatively well-preserved example of non-skeletal carbonate production implies that similar regulation of CaCO3 precipitation kinetics and PO4 concentrations may have operated across other intervals of time in Earth’s history, both in non-marine and marine environments that pre-date the emergence of skeletal calcification.

Abstract P573: The Interplay Between Mineral and Skeletal Metabolism Biomarkers and Intracranial Internal Carotid Artery Calcifications in Stroke Patients

Background: Intracranial internal carotid artery calcifications (IICAC), considered a phenomenon within the spectrum of atherosclerosis and vascular aging, are frequently encountered in ischemic stroke patients. While intimal IICAC directly contributes to ischemic stroke pathophysiology, the medial counterpart is generally deemed as a risk factor for vascular end-points. Apart from aging and cardiovascular risk factors, the underlying pathophysiology that contributes to development of IICAC is not well understood; herein we studied the interplay between mineral and skeletal metabolism biomarkers, and IICAC presence and pattern. Methods: In a prospective series of 194 ischemic stroke patients (mean±SD age: 69±14 yr), blood samples were collected to determine calcium, phosphorus, magnesium, osteocalcin, parathyroid hormone, and vitamin D levels within 72 hours of symptom onset. IICAC presence and type was determined on admission CT-angiography source images; a medial or intimal type of IICAC category was assigned according to Kockelkoren criteria. Results: A total of 45 (23%) patients had no calcifications, while 95 (49%) had an intimal pattern and 54 (28%) had non-intimal (or medial) pattern. Apart from the well-known factors related with IICAC, such as age, lower glomerular filtration rate (GFR), history of hypertension, diabetes mellitus, coronary artery disease and atrial fibrillation, we identified admission magnesium levels to be associated with IICAC presence and pattern (no calcification: 1.96±0.18 mEq/L, intimal calcification 1.93±0.19 mEq/L, medial calcification: 1.81±0.28 mEq/L; p=0.006). None of the other biomarkers had any significant relationship to IICAC. In multivariate models, a lower magnesium level was significantly associated with medial calcification (each 0.1 mEq/L drop increased the odds by 1.2 (95% CI 1.0-1.4; p=0.046)), in addition to older age, history of diabetes mellitus and lower GFR. Conclusion: Hypomagnesemia is one of the factors well-known to be associated with vascular calcifications in the body. Our findings, extend this relationship to the intracranial vascular bed. No similar association was observed for other biomarkers related to mineral and skeletal metabolism. (Funding: TUBITAK grant 218S753)

A severe case of thrombocytopenia, anasarca, fever, renal insufficiency or reticulin fibrosis, and organomegaly syndrome with myocardial and skeletal muscle calcification despite hypocalcemia: a case report

BackgroundTAFRO (thrombocytopenia, anasarca, fever, renal insufficiency or reticulin fibrosis, and organomegaly) syndrome is a recently recognized disease with a variety of presentations of variable severity. In acute settings, this disease also involves organ dysfunction because of the associated systemic inflammation. However, cases of TAFRO syndrome with myocardial and/or skeletal muscle calcification have never been reported.Case presentationA 24-year-old healthy young Asian man was admitted with intermittent epigastric pain and fever for 2 weeks. Computed tomography revealed pleural effusion, ascites and systemic lymphadenopathy. Laboratory tests showed thrombocytopenia, elevated C-reactive protein, hypoalbuminemia, anemia and renal dysfunction. Based on these findings and bone marrow biopsy, we diagnosed his disease as TAFRO syndrome and commenced hemodialysis for the renal dysfunction. However, he developed refractory hypocalcemia with unstable vital signs, for which we administered calcium gluconate hydrate. Thereafter, myocardial and skeletal muscle calcification was revealed radiologically, with the myocardial calcification causing sick sinus syndrome. He was treated with tocilizumab and finally discharged in an ambulatory condition after prolonged hospitalization, with residual calcific lesions.ConclusionThis is the first report of a patient with TAFRO syndrome and the complication of organ calcification. The etiology of calcification in this case is not clear. Systemic inflammation with possible hypercytokinemia might have been involved in the unexpected complication of systemic calcification. It is important to carefully handle the general management of TAFRO syndrome because of the possibility of various complications.

Synthetic amorphous calcium phosphates (ACPs): preparation, structure, properties, and biomedical applications.

Amorphous calcium phosphates (ACPs) represent a metastable amorphous state of other calcium orthophosphates (abbreviated as CaPO4) possessing variable compositional but rather identical glass-like physical properties, in which there are neither translational nor orientational long-range orders of the atomic positions. In nature, ACPs of a biological origin are found in the calcified tissues of mammals, some parts of primitive organisms, as well as in the mammalian milk. Manmade ACPs can be synthesized in a laboratory by various methods including wet-chemical precipitation, in which they are the first solid phases, precipitated after a rapid mixing of aqueous solutions containing dissolved ions of Ca2+ and PO43- in sufficient amounts. Due to the amorphous nature, all types of synthetic ACPs appear to be thermodynamically unstable and, unless stored in dry conditions or doped by stabilizers, they tend to transform spontaneously to crystalline CaPO4, mainly to ones with an apatitic structure. This intrinsic metastability of the ACPs is of a great biological relevance. In particular, the initiating role that metastable ACPs play in matrix vesicle biomineralization raises their importance from a mere laboratory curiosity to that of a reasonable key intermediate in skeletal calcifications. In addition, synthetic ACPs appear to be very promising biomaterials both for manufacturing artificial bone grafts and for dental applications. In this review, the current knowledge on the occurrence, structural design, chemical composition, preparation, properties, and biomedical applications of the synthetic ACPs have been summarized.

Uptake of groundwater nitrogen by a near-shore coral reef community on Bermuda

Nutrient enrichment can slow growth, enhance bioerosion rates, and intensify algal competition for reef-building corals. In areas of high human population density and/or limited waste management, submarine groundwater discharge can transfer anthropogenic nutrients from polluted groundwater to coastal reefs. In this case study, we investigate the impact of submarine groundwater discharge on a near-shore reef in Bermuda, where over 60% of sewage generated by the island’s 64,000 residents enters the groundwater through untreated cesspits. Temperature, salinity, pH, and alkalinity were monitored at a groundwater discharge vent, three locations across the adjacent coral reef (0–30 m from shore), and a comparison patch reef site 2 km from shore. Groundwater discharge was characterized by low salinity, low aragonite saturation state (Ωar), high alkalinity, elevated nitrate + nitrite (NO3– + NO2–; hereafter, “NO3–”) concentrations (> 400 µM), and an elevated 15N/14N ratio of NO3– (δ15N = 10.9 ± 0.02‰ vs. air, mean ± SD). Rainfall and tidal cycles strongly impacted groundwater discharge, with maximum discharge during low tide. NO3– concentrations on the near-shore reef averaged 4 µM, ten times higher than that found at the control site 2 km away, and elevated NO3– δ15N at the near-shore reef indicated sewage-contaminated groundwater as a significant nitrogen source. Tissue δ15N of Porites astreoides, a dominant reef-building coral, was elevated by ~ 3‰ on the near-shore reef compared to the control site, indicating that corals across the near-shore reef were assimilating groundwater-derived nitrogen. In addition, coral skeletal density and calcification rates across the near-shore reef were inversely correlated with NO3– concentration and δ15N, indicating a negative coral health response to groundwater-borne nutrient inputs. P. astreoides bioerosion rates, in contrast, did not show an effect from the groundwater input.

Effects of turbidity and depth on the bioconstruction of the Abrolhos reefs

Turbidity increase is one of the main stressors to coral reefs. It affects light availability and will act together with global sea level rise to reduce potential photosynthesis that is important to light-enhanced calcification in corals. Corals are the main contributors to the morphological complexity of reefs through skeletal calcification. Bioconstruction by corals is a multifactorial process that is controlled by physical (e.g., irradiance and turbidity) and biological factors such as photoacclimation process. In this paper, we intend to show how turbidity and photobiology might interplay to produce a coral species distribution that controls reef growth and structural complexity. The Abrolhos complex is composed by a group of reefs closer to the coastline characterized by a high light attenuation value (Kd490 = 0.11), and another one about 60 km far from the coast characterized by a light attenuation coefficient of Kd490 = 0.08. In these reefs, different coral communities produce bioconstruction potential accordingly. We used data collected for 7 yrs, with the AGRRA (Atlantic and Gulf rapid reef assessment) Protocol. Coral species cover and distribution data were used to estimate reef bioconstruction [sensu Done (1995)] rates. A field experiment examined the metabolic function of five species (Mussismilia braziliensis, Mussismilia hispida, Mussismilia harttii, Montastraea cavernosa and Siderastrea stellata) through respirometry and rapid light curves (RLC). Bioconstruction potential and primary gross productivity demonstrated a substantial variability between reefs and species. In combination, these functional responses meant that coral species distribution is controlled by local factors and acclimation process. Therefore, our results suggest that these functional responses are useful tools to understand photoacclimation process and its consequences, species distribution and the space occupation on Abrolhos bank. We highlight the deleterious effect of turbidity in bioconstruction. This suggests that the local processes that increase sediment runoff is an immediate impact and must be controlled.

Growth and survival of Pocillopora damicornis (Scleractinia: Pocilloporidae) coral fragments and their potential for coral reef restoration in the Tropical Eastern Pacific

ABSTRACTTransplantation of coral fragments is a common procedure for the restoration of degraded coral reefs. In the Tropical Eastern Pacific (TEP), the branching coral Pocillopora damicornis is the main reef-builder, and it frequently propagates through natural fragmentation; it is therefore a candidate for restoration efforts in this region. To evaluate the usefulness of P. damicornis for reef restoration in the TEP, fragments of three lengths were used: small (1–2 cm), medium (4 cm) and large (7 cm). Fragments of these three sizes were attached on the back-reef, reef flat and reef crest of La Azufrada reef (Gorgona Island, Colombian Pacific). Coral length, width, weight, and survival were followed during 119 days. Furthermore, skeletal density, linear extension and calcification rates of each coral fragment were obtained to evaluate the growth rates as a function of initial size and position on the reef. The overall fragment survival rate was 83.5%, but small fragments survived less, particularly on the back reef, than medium or large fragments. Fragment growth was greatest on the reef flat, whereas medium and large fragments grew faster than small ones. The overall mean of skeletal density, linear extension and calcification rates were 1.70 gCaCO3 cm−3, 1.89 cm yr−1 and 3.16 gCaCO3 cm−2 yr−1, respectively. These growth rates were comparable to those of other reef-building coral species in the world. Growth and survival rates of P. damicornis coral fragments found in this study, suggest that successful and low-cost restoration of TEP coral reefs is feasible using this species.

Correlation of Parathyroid Hormone Levels with Mineral Status in End-stage Renal Disease Patients.

Parathyroid hormone (PTH) is the main regulator of calcium, phosphate, magnesium, sodium, and potassium homeostasis. Therefore, this study was conducted to evaluate the relationship between PTH and aforementioned minerals in end-stage renal disease (ESRD) patients.Aim:The aim of this study was to estimate serum intact parathormone (iPTH) and other biochemical parameters in ESRD patients and to find correlation between serum iPTH and biochemical parameters in the study group.Results:This cross-sectional study included 60 clinically diagnosed patients of ESRD of age (>18 years), either sex. Disordered mineral metabolism is common complications of ESRD patients. The mean value of calcium, phosphorus, and magnesium was 7.90 ± 1.16 mg/dL, 6.44 ± 1.72 mg/dL, and 2.57 ± 0.62 mg/dL, respectively, indicating hypocalcemia, hyperphosphatemia, and hypermagnesemia in ESRD patients. To compensate the deranged mineral status, increased levels of PTH were seen in ESRD patients with mean value of 173.93 ± 62.62 pg/mL. There was a statistically significant positive correlation found between PTH and S. creatinine (P ≤ 0.001; r = 0.596), whereas the statistically significant negative correlation found between PTH and eGFR (P ≤ 0.001; r = −0.525). A significant positive correlation found between PTH and phosphorous (P = 0.003; r = 0.378) and potassium (P ≤ 0.001; r = 0.421). On the other hand, significant negative correlation found with calcium (P ≤ 0.001; r = −0.805) and corrected calcium (P = <0.001; r = −0.769). But nonsignificant association was found with magnesium, sodium, and calcium × phosphorous (P > 0.05).Conclusion:It was concluded that PTH is playing crucial role in mineral metabolism; it should be frequently assessed in order to prevent any untoward mineral decompensation and to prevent complications like bone disease and extra skeletal calcification, and decrease cardiac disease risk in ESRD patients.

Exposure to elevated sea-surface temperatures below the bleaching threshold impairs coral recovery and regeneration following injury.

Elevated sea surface temperatures (SSTs) are linked to an increase in the frequency and severity of bleaching events due to temperatures exceeding corals’ upper thermal limits. The temperatures at which a breakdown of the coral-Symbiodinium endosymbiosis (coral bleaching) occurs are referred to as the upper thermal limits for the coral species. This breakdown of the endosymbiosis results in a reduction of corals’ nutritional uptake, growth, and tissue integrity. Periods of elevated sea surface temperature, thermal stress and coral bleaching are also linked to increased disease susceptibility and an increased frequency of storms which cause injury and physical damage to corals. Herein we aimed to determine the capacity of corals to regenerate and recover from injuries (removal of apical tips) sustained during periods of elevated sea surface temperatures which result in coral stress responses, but which do not result in coral bleaching (i.e., sub-bleaching thermal stress events). In this study, exposure of the species Acropora aspera to an elevated SST of 32 °C (2 °C below the bleaching threshold, 34 °C) was found to result in reduced fluorescence of green fluorescent protein (GFP), reduced skeletal calcification and a lack of branch regrowth at the site of injury, compared to corals maintained under ambient SST conditions (26 °C). Corals maintained under normal, ambient, sea surface temperatures expressed high GFP fluorescence at the injury site, underwent a rapid regeneration of the coral branch apical tip within 12 days of sustaining injury, and showed extensive regrowth of the coral skeleton. Taken together, our results have demonstrated that periods of sustained increased sea surface temperatures, below the corals’ bleaching threshold but above long-term summertime averages, impair coral recovery from damage, regardless of the onset or occurrence of coral bleaching.

Delayed osteogenesis and calcification in a large true toad with a comparative survey of the timing of skeletal ossification in anurans

Postembryonic skeletogenesis in anuran amphibians has been widely studied, yet less than one percent of the extant diversity has been covered and relatively few comparative studies exist. Here we document the sequence and timing of ossification of the Common Toad Rhinella arenarum, a large true toad (Bufonidae) from South America that is a model organism for varied ongoing research. We study histological sections and cleared-and-stained specimens of an ontogenetic series ranging from early larval stages to juveniles, documenting the ossification sequence of the entire skeleton. To diminish potential environmental biases we also study the skeletogenesis of the frog Leptodactylus latinasus (Leptodactylidae) from the same pond and season. We summarize comparative data from numerous anuran species to contextualize our results in a broad phylogenetic context. Histological data shows that skeletal calcification in R. arenarum is temporally dissociated from osteoid matrix formation and occurs later than in most other anurans, which is unexpected given its generalized pond-type larva and heavily ossified adult skeleton. At the onset of metamorphosis, exoccipitals, parasphenoid, and frontoparietals are the only ossified skull elements, whereas most of the postcranium has already started ossification. This pattern is rare among anurans but is shared by other bufonids, in which it has been previously linked to rapid development. Our comparative survey, however, suggests that the delayed bufonid pattern is not related to fast-developing larvae but instead might be a distinctive feature of true toads.

Two Centuries of Coral Skeletons from the Northern South China Sea Record Mercury Emissions from Modern Chinese Wars.

The contemporary mercury (Hg) cycle in the world's oceans has been greatly affected by human activities. However, we are still lacking reliable, long-term, and continuous records of Hg in seawater. Here, we report for the first time on using annually banded Porites coral skeletons from the northern South China Sea (SCS) as an archive for recording changes of seawater dissolved Hg spanning the past two centuries. We developed a combustion-trapping method to preconcentrate ultratrace Hg concentrations from coral aragonitic skeletons for highly accurate total Hg measurements. Results show that Hg in the coral skeletons ranges from 0.3 to 5.1 pmol/g and is discriminated against Ca during coral skeletal calcification. Preindustrial (1798-1832) Hg levels in coral skeletons were found to be approximately 0.5 pmol/g. The highest Hg concentrations (3-5 pmol/g) were observed during the WWII period (1933-1942). Other distinct Hg maxima (∼3 pmol/g) are observed for the periods 1833-1847, 1858-1862, 1918-1927, 1978-1982, and 1988-1992, with the first four coinciding with contemporary Chinese wars. Our study suggests that the production and use of ammunitions in those wars likely account for the primary Hg emission sources in the northern SCS before 1950, and coral is potentially a robust indicator of historical, regional Hg contamination events.

Treatment for CKD-MBD(Chronic Kidney Disease-Mineral and Bone Disorder)

CKD is a common disease that is estimated to develop one in eight persons in Japan. The CKD itself is highly risk factor on the cardiac/vascular mortality. In addition,a new concept has been proposed "CKD-MBD". CKD-MBD is composed of a combination of abnormal mineral metabolism, abnormal bone, and extra skeletal calcification with cardiovascular high mortality. Treatment for CKD-MBD is a wide-ranging. We aim to decline cardiovascular event, fracture, and mortality rate of patients with CKD. The main therapeutic target for CKD-MBD becomes the phosphate control. Today, we can use of the VRDA, Calcimimetics and muti-phosphate binders as a lot of pharmacological intervention.

Molecular footprinting of skeletal tissues in the catshark Scyliorhinus canicula and the clawed frog Xenopus tropicalis identifies conserved and derived features of vertebrate calcification.

Understanding the evolutionary emergence and subsequent diversification of the vertebrate skeleton requires a comprehensive view of the diverse skeletal cell types found in distinct developmental contexts, tissues, and species. To date, our knowledge of the molecular nature of the shark calcified extracellular matrix, and its relationships with osteichthyan skeletal tissues, remain scarce. Here, based on specific combinations of expression patterns of the Col1a1, Col1a2, and Col2a1 fibrillar collagen genes, we compare the molecular footprint of endoskeletal elements from the chondrichthyan Scyliorhinus canicula and the tetrapod Xenopus tropicalis. We find that, depending on the anatomical location, Scyliorhinus skeletal calcification is associated to cell types expressing different subsets of fibrillar collagen genes, such as high levels of Col1a1 and Col1a2 in the neural arches, high levels of Col2a1 in the tesserae, or associated to a drastic Col2a1 downregulation in the centrum. We detect low Col2a1 levels in Xenopus osteoblasts, thereby revealing that the osteoblastic expression of this gene was significantly reduced in the tetrapod lineage. Finally, we uncover a striking parallel, from a molecular and histological perspective, between the vertebral cartilage calcification of both species and discuss the evolutionary origin of endochondral ossification.

Effects of etidronate on the Enpp1⁻/⁻ mouse model of generalized arterial calcification of infancy.

Generalized arterial calcification of infancy (GACI) is an autosomal recessive disorder of spontaneous infantile arterial and periarticular calcification which is attributed to mutations in the ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1) gene. Whilst the bisphosphonate, etidronate, is currently used off-label for the treatment for GACI, recent studies have highlighted its detrimental effects on bone mineralisation. In the present study, we used the Enpp1−/− mouse model of GACI to examine the effects of etidronate treatment (100 µg/kg), on vascular and skeletal calcification. Micro-computed tomography (µCT) analysis revealed a significant decrease in trabecular bone mass, as reflected by the decrease in trabecular bone volume/tissue volume (BV/TV; %), trabecular thickness, trabecular separation, trabecular number and pattern factor (P<0.05) in the Enpp1−/− mice in comparison to the wild-type (WT) mice. Mechanical testing revealed that in the WT mice, treatment with etidronate significantly improved work to fracture and increased work post-failure (P<0.05, in comparison to the vehicle-treated WT mice). This significant increase, however, was not observed in the Enpp1−/− mice. Treatment with etidronate had no effect on bone parameters in the WT mice; however, the Enpp1−/− mice displayed an increased structural model index (SMI; P<0.05). We used a recently developed 3D µCT protocol to reconstruct and quantify the extensive aortic calcification in Enpp1−/− mice in comparison to the WT mice. However, treatment with etidronate did not prevent de novo calcification, and did not arrest the progression of established calcification of the aorta.