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Abnormal phosphate levels result in several pathological conditions such as rickets/osteomalacia and ectopic calcification indicating that there must be a system that regulates phosphate level within a narrow range. FGF23 has been shown to be an essential hormone regulating serum phosphate level. FGF23 binds to Klotho-FGF receptor complex to reduce serum phosphate level. Several reports suggested that FGF receptor is involved in the regulation of FGF23 production. It has been also shown that high extracellular phosphate can activate several intracellular signaling pathways. However, it has been unclear whether and how phosphate regulates FGF23 production in vivo. Our recent results indicate that high extracellular phosphate directly activates FGF receptor 1 and the downstream intracellular signaling enhances FGF23 production. Thus, there is a negative feedback system for the regulation of serum phosphate level involving FGF receptor and FGF23. We propose that FGF receptor works at least as one of phosphate sensors in the maintenance of serum phosphate level. [ABSTRACT FROM AUTHOR]

Background: Inorganic phosphate (Pi) is used extensively as a preservative and a flavor enhancer in the Western diet. Physical inactivity, a common feature of Western societies, is associated with increased cardiovascular morbidity and mortality. It is unknown whether dietary Pi excess contributes to exercise intolerance and physical inactivity.Methods: To determine an association between Pi excess and physical activity in humans, we assessed the relationship between serum Pi and actigraphy-determined physical activity level, as well as left ventricular function by cardiac magnetic resonance imaging, in DHS-2 (Dallas Heart Study phase 2) participants after adjusting for relevant variables. To determine direct effects of dietary Pi on exercise capacity, oxygen uptake, serum nonesterified fatty acid, and glucose were measured during exercise treadmill test in C57/BL6 mice fed either a high-Pi (2%) or normal-Pi (0.6%) diet for 12 weeks. To determine the direct effect of Pi on muscle metabolism and expression of genes involved in fatty acid metabolism, additional studies in differentiated C2C12 myotubes were conducted after subjecting to media containing 1 to 3 mmol/L Pi (pH 7.0) to simulate in vivo phosphate conditions.Results: In participants of the DHS-2 (n=1603), higher serum Pi was independently associated with reduced time spent in moderate to vigorous physical activity ( P=0.01) and increased sedentary time ( P=0.004). There was no association between serum Pi and left ventricular ejection fraction or volumes. In animal studies, compared with the control diet, consumption of high-Pi diet for 12 weeks did not alter body weight or left ventricular function but reduced maximal oxygen uptake, treadmill duration, spontaneous locomotor activity, fat oxidation, and fatty acid levels and led to downregulation of genes involved in fatty acid synthesis, release, and oxidation, including Fabp4, Hsl, Fasn, and Pparγ, in muscle. Similar results were recapitulated in vitro by incubating C2C12 myotubes with high-Pi media.Conclusions: Our data demonstrate a detrimental effect of dietary Pi excess on skeletal muscle fatty acid metabolism and exercise capacity that is independent of obesity and cardiac contractile function. Dietary Pi may represent a novel and modifiable target to reduce physical inactivity associated with the Western diet. [ABSTRACT FROM AUTHOR]

Highlights • Gelation of myofibrillar protein-Na 4 P 2 O 7 ·10H 2 O or Na 5 P 3 O 10 (MP-SPP or STP) was studied. • Phosphate weakened MP network as instantaneous and retarded compliance rose at 4 and 40 °C. • MP changed from weak gel into concentrated sol as 280 mg/kg SPP or 440 mg/kg STP added. • Phosphate contributed to smaller pore size and finer structure for MP gel network. • Phosphate more tightly trapped immobile water into smaller-sized pores of MP network. Abstract Effect of phosphates on the heat-induced gel characteristics of myofibrillar protein (MP) from grass carp was investigated. Both heating and phosphates exerted significant influences. Heating induced more elastic, water-holding and less flowing gel. But phosphates had diverse effects at different temperatures. At 4 °C and 40 °C, phosphate as a dominant factor reduced the gel elasticity and resistance and increased flowability with increasing levels of phosphates. Furthermore, 280 mg/kg sodium pyrophosphate (SPP) or 440 mg/kg sodium triphosphates (STP) transformed MP from weak gel into concentrated solution. It clarified phosphates disentangled MP macromolecules and inhibited their aggregation and pre-gelation at low temperature. At 80 °C, heating accompanied with phosphates governed MP gelation. The appropriate level of phosphates (SPP superior to STP) endowed MP-phosphate gels with the lowest flowability and greatest elasticity, textural properties as well as finest microstructures. Besides, phosphates entrapped a portion of weak immobile water more tightly into smaller-sized pores of protein network. [ABSTRACT FROM AUTHOR]

Phosphate is a common ingredient in many healthy foods but, it is also present in foods containing additives and preservatives. When found in foods, phosphate is absorbed in the intestines and filtered from the blood by the kidneys. Generally, any excess is excreted in the urine. In renal pathologies, however, such as chronic kidney disease, a reduced renal ability to excrete phosphate can result in excess accumulation in the body. This accumulation can be a catalyst for widespread damage to the cellular components, bones, and cardiovascular structures. This in turn can reduce mortality. Because of an incomplete understanding of the mechanism for phosphate homeostasis, and the multiple organ systems that can modulate it, treatment strategies designed to minimize phosphate burden are limited. The Recommended Dietary Allowance (RDA) for phosphorous is around 700 mg/day for adults, but the majority of healthy adult individuals consume far more phosphate (almost double) than the RDA. Studies suggest that low-income populations are particularly at risk for dietary phosphate overload because of the higher amounts of phosphate found in inexpensive, processed foods. Education in nutrition, as well as access to inexpensive healthy food options may reduce risks for excess consumption as well as a wide-range of disorders, ranging from cardiovascular diseases to kidney diseases to tumor formation. Pre-clinical and clinical studies suggest that dietary phosphate overload has toxic and prolonged adverse health effects. Improved regulations for reporting of phosphate concentrations on food labels are necessary so that people can make more informed choices about their diets and phosphate consumption. This is especially the case given the lack of treatments available to mitigate the short and long-term effects of dietary phosphate overload-related toxicity. Phosphate toxicity is quickly becoming a global health concern. Without measures in place to reduce dietary phosphate intake, the conditions associated with phosphate toxicity will likely to cause untold damage to the wellbeing of individuals around the world. [ABSTRACT FROM AUTHOR]

Abstract Organophosphate flame retardants (OPFRs) have been commonly observed in indoor dust, food, and drinking water in China, but little is known about their exposure levels or factors leading to exposure in Chinese children. In this study, we measured eight metabolites of OPFRs (mOPFRs) in 227 urine samples collected from 0- to 5-year-old children in China. The high detection rates of mOPFRs (60%–100%) in the collected urine samples demonstrated the widespread exposure of this population to OPFRs. The median concentrations indicated that bis(2-chloroethyl)phosphate (BCEP, 0.85 ng/mL) and diphenyl phosphate (DPHP, 0.27 ng/mL) were the dominant chlorinated mOPFRs and nonchlorinated mOPFRs, respectively. Interestingly, the median urinary levels of bis(1-chloro-2-propyl)phosphate (BCIPP, 6.48 ng/mL) and bis(2-butoxyethyl)phosphate (BBOEP, 0.31 ng/mL) in inpatient infants were one order of magnitude higher (p < 0.01) than those observed in outpatient infants. For home-stay participants, furthermore, infants (0–1 year) had the highest median levels of BCIPP (0.72 ng/mL) and dibutyl phosphate (DBP, 0.14 ng/mL) among the three age groups (i.e., 0–1, >1–3, and >3–5 years), and significantly (p < 0.05) negative age-related relationships were found for both urinary mOPFRs. Two set of data on estimated daily intakes (EDIs) were calculated based on the fraction of OPFR excreted as the corresponding mOPFR (F UE) in human liver microsomes (EDI HLM) and S9 fraction (EDI S9) system, respectively. In general, children have relatively high EDIs of tris(2-chloroethyl)phosphate (TCEP: EDI HLM = 485 ng/kg bw/day, EDI S9 = 261 ng/kg bw/day). Furthermore, 17% or 21% of inpatient infants had EDIs that exceeded the reference dose, whereas this value was reduced to 13% in outpatient infants; and this value decreased with age among all home-stay children (0–5 years). Our results indicated that inpatient and home-stay infants had a higher potential risk of OPFR exposure. To our knowledge, this is the first study to identify the elevated urinary levels of mOPFRs in inpatients. Graphical abstract Image 1 Highlights • The first assessment of OPFR exposure in children aged 0–5 was conducted in China. • Urinary BCIPP and BBOEP levels were significantly higher in inpatients than those in outpatients. • Inpatients and home-stay infants had high potential risk of OPFR exposure. Inpatient and home-stay infants had a higher potential risk of OPFR exposure. [ABSTRACT FROM AUTHOR]

In this study, phosphate and vanadate were used as additives in the NaCl electrolyte in Mg-air batteries. The inhibiting effect of these additives on the corrosion of the AZ31 Mg alloy was investigated through electrochemical tests and the battery performance was evaluated through constant-current discharging tests. The phosphate had a more pronounced inhibiting effect than the vanadate. The corrosion current densities of AZ31 in the blank, phosphate-containing, and vanadate-containing electrolytes were 79.43, 1.98, and 22.38 μA cm −2 , respectively. However, both the presence of the phosphate and vanadate significantly improved the battery performance, especially under intermittent discharging. Under constant-current continuous discharging, the anodic efficiencies of the Mg-air batteries with the blank, phosphate-containing, and vanadate-containing electrolytes were 65.5%, 73.1%, and 69.9%, respectively, while those under constant-current intermittent discharging were 59.7%, 72.5%, and 68.8%, respectively. Moreover, the addition of the phosphate and the vanadate resulted in the formation of a loosely packed film of the discharging products on the Mg anode, which also helped improve the battery performance. [ABSTRACT FROM AUTHOR]

The detection of phosphate (Pi) under physiological conditions is a very important issue in environmental and biological sciences. Herein, a unique fluorescent probe {[EuL(H2O)1.35(DMF)0.65]·1.9DMF}n (1) was prepared through the organic–inorganic hybridization between asymmetrical tricarboxylate ligands and Eu2O2 clusters under solvothermal conditions. The as-prepared sample 1 exhibited excellent fluorescence properties and could be designed as a self-calibrating fluorescent probe for sensitively and selectively detecting Pi which served as an essential substance in aquatic ecosystems and biological systems. The different responses of the two emission peaks caused by the addition of Pi resulted in a continuous fluorescence color change, which could be clearly observed with the naked eye under UV light lamp illumination at 302 nm. Typically, a good linearity existed between the ratio of dual fluorescence intensities and the Pi contents ranging from 0.1 μM to 15 μM with a low detection limit of 52 nM (S/N = 3). It is noteworthy that the prepared self-calibrating fluorescent probe displayed specific recognition towards Pi anions with satisfactory recovery ranging from 92.8% to 100.6% in water samples and biological fluids. Thus, we can envision that this work may open a new avenue for the detection of many other bioactive ions in environmental and biological samples. [ABSTRACT FROM AUTHOR]

Abstract: This study aimed to investigate the risk factors for PHPT in children with stable renal function who received KT. We retrospectively analyzed the clinical findings and laboratory results of patients who underwent KT below 19 years of age, between 1996 and 2016 at our hospital. Patients were followed up for more than 1 year after KT. We calculated the mean ± standard deviation or median [minimum – maximum] for each parameter. We included a total of 46 patients (male:female = 26:20). Twelve patients (26.1%) were included in the PHPT group, and 34 (73.9%) were in the nPTH group. The dialysis duration was 57.1 ± 49.9, 44 [0‐145] months in the PHPT group and 23.5 ± 25.8, 15 [1‐121] months in the nPTH group (P = .040). The post‐KT total CO2 level was significantly higher in the PHPT group (P = .022). The pre‐ (P = .021) and post‐KT (P = .005) and 3‐month average (P = .018) iPTH levels were also significantly higher in PHPT group. The height z‐score showed a negative correlation, and the pre‐KT, 3‐month average phosphorus and alkaline phosphate levels showed positive correlations with iPTH levels, at 1 year after KT. Patients who undergo prolonged durations of dialysis, have increased iPTH levels before and after KT, and have low bicarbonate levels after KT are at risk of PHPT and should be monitored carefully. [ABSTRACT FROM AUTHOR]

Phosphate (Pi) is one of the major nutrients for crop growth and yield. Although several studies have revealed a global view of Pi starvation responses in rice, the detailed features were not well-addressed. To identify differentially expressed genes associated with phosphate starvation on a genome scale, we analyzed transcriptome data of roots from 2-week old seedlings that were grown on Pi-sufficient or -deficient media for 7 and 21 days. Using publicly available RNA-sequencing data, we subsequently identified 820 up-regulated genes in roots under Pi starvation. Gene ontology enrichment analysis of these genes indicated that secondary metabolic processes are most significantly enriched under Pi starvation, and Pi transport and defense to biotic stress also play significant roles in response against Pi deficiency. Functional classification analysis using MapMan emphasizes the significance of transcription factors, such as MYB, WRKY, and bHLH, various transporters, and genes in secondary metabolic processes. Use of promoter trap lines or transgenic plants expressing the GUS reporter gene under the control of Pi starvation-inducible gene promoters confirmed the meta-expression patterns of two genes stimulated by Pi starvation, suggesting novel promoters for enhancing Pi use efficiency. In addition to the identification of two novel promoters for Pi starvation response, cis-regulatory elements for the regulation of Pi starvation are suggested. Overall, our study provides a global view of Pi starvation response based on transcriptome data and novel tools for improving PUE and Pi uptake in rice, a model crop plant. [ABSTRACT FROM AUTHOR]

LP533401 is an orally bioavailable small molecule that inhibits tryptophan hydroxylase-1, an enzyme responsible for the synthesis of gut-derived serotonin (GDS). Recently, we showed that increased GDS in rats with chronic kidney disease (CKD) affected bone strength and metabolism. We tested the hypothesis that treatment with LP533401 could reverse CKD-induced bone loss in uremia. Sixteen weeks after 5/6 nephrectomy, rats were randomized into untreated (CKD), treated with vehicle (VEH) and LP533401 at a dose of 30 or 100 mg/kg daily for 8 weeks. Treatment with LP533401 decreased serotonin turnover and restored bone mineral status, microarchitecture, and strength in CKD rats to the values observed in the controls. In parallel with the reduction of serotonin, serum phosphate levels also decreased, particularly in the LP533401, 100 mg/kg group. The mechanism underlying this phenomenon resulted from decreased expression of the renal VDR/FGF1R/Klotho/Npt2a/Npt2c axis, leading to elevated phosphate excretion in the kidneys. The elevated urinary phosphate excretion resulted in improved bone mineral status and strength in LP533401-treated rats. Unexpectedly, the standard VEH used in this model was able to reduce renal VDR/FGF1R/Klotho/Npt2a expression, leading to a compensatory increase in Npt2c mRNA levels, secondary disturbances in phosphate-regulated hormones and partial improvement in the mineral status of the trabecular bone. The decrease of serotonin synthesis together with the simultaneous reduction of renal Npt2a and Npt2c expression in rats treated with LP533401, 100 mg/kg led to an increase in 1,25(OH) 2 D 3 levels; this mechanism seems to be particularly beneficial in relation to the mineral status of cortical bone. [ABSTRACT FROM AUTHOR]

Summary: Prasinophytes are widespread marine algae for which responses to nutrient limitation and viral infection are not well understood. We studied the picoprasinophyte, Micromonas pusilla, grown under phosphate‐replete (0.65 ± 0.07 d−1) and 10‐fold lower (low)‐phosphate (0.11 ± 0.04 d−1) conditions, and infected by the phycodnavirus MpV‐SP1. Expression of 17% of Micromonas genes in uninfected cells differed by >1.5‐fold (q < 0.01) between nutrient conditions, with genes for P‐metabolism and the uniquely‐enriched Sel1‐like repeat (SLR) family having higher relative transcript abundances, while phospholipid‐synthesis genes were lower in low‐P than P‐replete. Approximately 70% (P‐replete) and 30% (low‐P) of cells were lysed 24 h post‐infection, and expression of ≤5.8% of host genes changed relative to uninfected treatments. Host genes for CAZymes and glycolysis were activated by infection, supporting importance in viral production, which was significantly lower in slower growing (low‐P) hosts. All MpV‐SP1 genes were expressed, and our analyses suggest responses to differing host‐phosphate backgrounds involve few viral genes, while the temporal program of infection involves many more, and is largely independent of host‐phosphate background. Our study (i) identifies genes previously unassociated with nutrient acclimation or viral infection, (ii) provides insights into the temporal program of prasinovirus gene expression by hosts and (iii) establishes cell biological aspects of an ecologically important host‐prasinovirus system that differ from other marine algal‐virus systems. [ABSTRACT FROM AUTHOR]

Object: To present and evaluate a fast phosphorus magnetic resonance spectroscopic imaging (MRSI) sequence using echo planar spectroscopic imaging with flyback readout gradient trajectories.Materials and Methods: Waveforms were designed and implemented using a 3 Tesla MRI system. 31P spectra were acquired with 2 × 2 cm2 and 3 × 3 cm2 resolution over a 20- and 21-cm field of view and spectral bandwidths up to 1923 Hz. The sequence was first tested using a 20-cm-diameter phosphate phantom, and subsequent in vivo tests were performed on healthy human calf muscles and brains from five volunteers.Results: Flyback EPSI achieved 10× and 7× reductions in acquisition time, with 68.0 ± 1.2 and 69.8 ± 2.2% signal-to-noise ratio (SNR) per unit of time efficiency (theoretical SNR efficiency was 74.5 and 76.4%) for the in vivo experiments, compared to conventional phase-encoded MRSI for the 2 × 2 cm2 and 3 × 3 cm2 resolution waveforms, respectively. Statistical analysis showed no difference in the quantification of most metabolites. Time savings and SNR comparisons were consistent across phantom, leg and brain experiments.Conclusion: EPSI using flyback readout trajectories was found to be a reliable alternative for acquiring 31P-MRSI data in a shorter acquisition time. [ABSTRACT FROM AUTHOR]

Elevated levels of the metabolic by-products, including acidosis (i.e., high [H+]) and phosphate (Pi) are putative agents of muscle fatigue; however, the mechanism through which they affect myosin’s function remain unclear. To elucidate these mechanisms, we directly examined the effect of acidosis (pH 6.5 vs. 7.4), alone and in combination with elevated levels of Pi on the force-generating capacity of a mini-ensemble of myosin using a laser trap assay. Acidosis decreased myosin’s average force-generating capacity by 20% (p < 0.05). The reduction was due to both a decrease in the force generated during each actomyosin interaction, as well as an increase in the number of binding events generating negative forces. Adding Pi to the acidic condition resulted in a quantitatively similar decrease in force but was solely due to an elimination of all high force-generating events (>2 pN), resulting from an acceleration of the myosin’s rate of detachment from actin. Acidosis and Pi also had distinct effects on myosin’s steady state ATPase rate with acidosis slowing it by ∼90% (p > 0.05), while the addition of Pi under acidic conditions caused a significant recovery in the ATPase rate. These data suggest that these two fatigue agents have distinct effects on myosin’s cross-bridge cycle that may underlie the synergistic effect that they have muscle force. Thus these data provide novel molecular insight into the mechanisms underlying the depressive effects of Pi and H+ on muscle contraction during fatigue. [ABSTRACT FROM AUTHOR]

Organophosphate esters (OPEs) are often used as flame retardants and plasticizers. Animal data suggest exposure to OPEs could impact children's growth and development, yet impacts on human birth outcomes are understudied. We evaluate impacts of OPE exposure on the timing of delivery and infant's birthweight in the Pregnancy Infection and Nutrition Study (PIN). North Carolina women enrolled in PIN in early pregnancy and participated in follow-up through delivery. Analyses were limited to mothers recruited from 2002 to 2005, whose children participated in additional follow-up in early childhood ( n  = 349). Mothers collected urine samples in which OPE metabolites were assessed and birth outcomes were abstracted from medical records. Bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), isopropyl-phenyl phenyl phosphate (ip-PPP), bis(1-chloro-2-propyl) 1-hydroxy-2-propyl phosphate (BCIPHIPP) were detected in >80% of samples. Average birthweight and gestational age were 3326 g and 39.1 weeks, respectively. As data suggest that the mechanisms of action by which OPEs impact birth outcomes may be fetal sex dependent, we conducted sex-stratified statistical analyses. Women with the highest ip-PPP concentrations delivered girls 1 week earlier than women with lower levels (95% Confidence Interval (CI): −1.85, −0.15). Women with BDCIPP levels above the median had 3.99 (95% CI: 1.08, 14.78) times the odds of delivering their daughters preterm. Similarly, higher ip-PPP levels were associated with lower birthweight, but not after standardizing for gestational age. Among males, maternal ip-PPP was associated with decreased odds of preterm birth (OR = 0.21, 95% CI: 0.06, 0.68). DPHP and BCIPHIPP levels were not associated with outcomes in either sex. Results indicate that prenatal OPE exposure may impact timing of birth, though results are imprecise. Given widespread OPE exposure and the urgent need to identify and mitigate causes of preterm birth, further investigation is warranted. [ABSTRACT FROM AUTHOR]

Abstract: Notch signaling is a highly conserved pathway existed in multicellular organisms. It plays roles in normal human body development, human cancer initiation, progression and metastasis. The Notch negative regulatory region (NRR) is critical for Notch signaling, and cleavage at the S2 site in the NRR ultimately leads to the activation of Notch signaling. To study the function of human NRR1, we expressed the recombinant human NRR1 (rhNRR1) domain in Escherichia coli. After purification, rhNRR1 was obtained with approximately 94% purity according to SDS‐PAGE analysis. Furthermore, the polyclonal anti‐rhNRR1 serum raised by immunizing mouse with the purified rhNRR1 was able to reduce the generation of active form of Notch1 intracellular domain in HeLa cells, which implied the raised antibody could recognize and bind the natural conformation of Notch1 NRR. Preparation of rhNRR1 by this way is convenient, time‐consuming, and could be used to the preparation of anti‐NRR1 therapeutic antibody. [ABSTRACT FROM AUTHOR]

Phosphorus magnetic resonance spectroscopy (31P MRS) has been employed before to assess phosphocreatine (PCr) and other high-energy phosphates in the visual cortex during visual stimulation with inconsistent results. We performed functional 31P MRS imaging in the visual cortex and control regions during a visual stimulation paradigm at an unprecedented sensitivity, exploiting a dedicated RF coil design at a 7 T MR system. Visual stimulation in a 3 min 24 s on-off paradigm in eight young healthy adults generated a clear BOLD effect with traditional 1H functional MRI in the visual cortex (average z score 9.9 ± 0.2). However, no significant event-related changes in any of the 31P metabolite concentrations, linewidths (7.9 ± 1.8 vs 7.8 ± 1.9 Hz) or tissue pH (7.07 ± 0.13 vs 7.06 ± 0.07) were detectable. Overall, our study of 31P MRSI in 15 cm3 voxels had a detection threshold for changes in PCr, Pi and γ-ATP between stimulation and rest of 5, 17 and 10%, respectively. In individual subjects, the mean coefficients of variance for PCr and Pi levels of control voxels were 6 ± 3 and 19 ± 8% (three time point average of 3 min 24 s). Altogether this indicates that energy supply for neuronal activation at this temporal resolution does not drain global PCr resources. [ABSTRACT FROM AUTHOR]

Introduction: Maternal urinary levels of dialkyl phosphate (DAP) metabolites of organophosphate pesticides (OP) during pregnancy are associated with adverse outcomes in the offspring. Between 2012 and 2014, eighteen active OP ingredients were restricted or banned in Israel for agricultural use.Aim: We aimed to study trends of urinary DAP metabolites among pregnant women and their offspring in the era of the new regulations.Methods: Pregnant women were recruited at 11-18 weeks of gestation and provided spot urine samples (n = 273). Soon after birth, neonatal urine samples were collected (n = 107). All urine specimens analyzed for DAP metabolites. Trends in DAP metabolites were tested using Mann-Kendall trend statistic (M-K S) and linear regression models were constructed to estimate the association between calendar period and DAP levels between September 2012 and March 2016.Results: Over the study period, median maternal ∑DAP levels decreased from 248 nmol/L to 148 nmol/L. Time of recruitment was associated with a statistically significant decrease in DAP metabolites, which remained significant after multivariate adjustment. Overall, the results for the analysis of before and after June 2014 showed a significant decrease in ∑DAP of -0.198 log10 nmol/L (95%CI: -0.311,-0.084) which corresponds with a decrease of 36.6% in ∑DAP. A similar trend was found for DAP metabolites in neonatal urine. Compared to other studies, pregnant women in Jerusalem had higher ∑DAP levels, even at the end of the study period.Conclusion: We observed significant reductions in maternal and neonatal DAP urinary levels during the period of 2012-2016. Regulations restricting agricultural use of OP seem to be effective in reducing population exposure to OP, in an era when residential use of OP is banned. [ABSTRACT FROM AUTHOR]

Isochoric (constant volume) freezing has been recently suggested as a new method for cell and organ preservation. As a first step in studying the effect of isochoric freezing on mammalian cells, Madin-Darby canine kidney epithelial cells (MDCK), were frozen in an isochoric system, in a simple extracellular phosphate buffered solution to −10 °C (96.5 MPa), - 15 °C (162 MPa) and −20 °C (205 MPa) for 60 and 120 min. Cell membrane integrity and cell metabolism were studied with a Live/Dead cell vitality assay and flow cytometry. We found that cell survival decreases with an increase in pressure (lower temperatures) and time of exposure. For example, 60% of cells survived 60 min at – 10 °C and only 18% survived 120 min at this temperature. Negligible survival was measured at – 20 °C . This study may serve as the baseline towards further research on techniques to optimize the effects of isochoric freezing on living biological matter. [ABSTRACT FROM AUTHOR]

Tris (1, 3-dichloro-2-propyl) phosphate (TDCIPP), an extensively used organophosphorus flame retardant, is frequently detected in various environmental media and biota, and has been demonstrated as neurotoxic. Autophagy has been proposed as a protective mechanism against toxicant-induced neurotoxicity. The purpose of the present study was to investigate the effect of TDCIPP exposure on autophagy, and its role in TDCIPP-induced developmental neurotoxicity. Zebrafish embryos (2–120 h post-fertilization [hpf]) were exposed to TDCIPP (0, 5, 50 and 500 μg/l) and a model neurotoxic chemical, chlorpyrifos (CPF, 100 μg/l). The developmental endpoints, locomotive behavior, cholinesterase activities, gene and protein expression related to neurodevelopment and autophagy were measured in the larvae. Our results demonstrate that exposure to TDCIPP (500 μg/l) and CPF causes developmental toxicity, including reduced hatching and survival rates and increased malformation rate (e.g., spinal curvature), as well as altered locomotor behavior. The expression of selected neurodevelopmental gene and protein markers (e.g., mbp , syn2a , and α 1-tubulin ) was significantly down-regulated in CPF and TDCIPP exposed zebrafish larvae. Treatment with CPF significantly inhibits AChE and BChE, while TDCIPP (0–500 μg/l) exerts no effects on these enzymes. Furthermore, the conversion of microtubule-associated protein I (LC3 I) to LC3 II was significantly increased in TDCIPP exposed zebrafish larvae. In addition, exposure to TDCIPP also activates transcription of several critical genes in autophagy (e.g. Becn1, atg3, atg5, map1lc3b and sqstm1 ). To further investigate the role of autophagy in TDCIPP induced developmental neurotoxicity, an autophagy inducer (rapamycin, Rapa, 1 nM) and inhibitor (chloroquine, CQ, 1 μM) were used. The results demonstrate that the hatching rate, survival rate, and the expression of mbp and а 1-tubulin proteins were all significantly increased in larvae treated with TDCIPP (500 μg/l) and Rapa compared to TDCIPP alone. In contrast, co-treatment with the autophagy inhibitor CQ results in exacerbated neurodevelopmental toxicity. Taken together, our results confirm that exposure to TDCIPP induces autophagy, which plays a protective role in TDCIPP-induced developmental neurotoxicity in zebrafish embryos and larvae. [ABSTRACT FROM AUTHOR]

The model yeast Saccharomyces cerevisiae elicits a transcriptional response to phosphate (P i ) depletion. To determine the origins of the phosphate response (PHO) system, we bioinformatically identified putative PHO components in the predicted proteomes of diverse fungi. Our results suggest that the PHO system is ancient; however, components have been expanded or lost in different fungal lineages. To show that a similar physiological response is present in deeply-diverging fungi we examined the transcriptional and physiological response of PHO genes to P i depletion in the blastocladiomycete Blastocladiella emersonii . Our physiological experiments indicate that B. emersonii relies solely on high-affinity Na + -independent Pho84-like transporters. In response to P i depletion, Be Pho84 paralogues were 4–8-fold transcriptionally upregulated, whereas several other PHO homologues like phosphatases and vacuolar transporter chaperone (VTC) complex components show 2–3-fold transcriptional upregulation. Since P i has been shown to be important during the development of B. emersonii, we sought to determine if PHO genes are differentially regulated at different lifecycle stages. We demonstrate that a similar set of PHO transporters and phosphatases are upregulated at key points during B. emersonii development. Surprisingly, some genes upregulated during P i depletion, including VTC components, are repressed at these key stages of development indicating that PHO genes are regulated by different pathways in different developmental and environmental situations. Overall, our findings indicate that a complex PHO network existed in the ancient branches of the fungi, persists in diverse extant fungi, and that this ancient network is likely to be involved in development and cell cycle regulation. [ABSTRACT FROM AUTHOR]

Strain Serratia sp. S119 is a peanut native bacterium with high phosphate solubilizing activity that promotes the growth of peanut and maize in the cultivation area of Córdoba in Argentina. The aims of this study were to obtain and analyze the genome sequence of Serratia sp. S119 to understand the genetic basis of its beneficial properties on plant growth, and to demonstrate phosphate solubilizing ability in early stages of bacterial growth. Results obtained indicated that soluble P and gluconic acid were detected during exponential growth phase in bacterial supernatant. Analysis of the genome sequence of Serratia sp. S119 obtained from this study showed the presence of genes related to several plant growth promoting traits. The genome sequence of this strain is a valuable source of information to study bacterial response to phosphate starvation and to investigate interaction between this bacterium with host plants under nutritional deficient environments. [ABSTRACT FROM AUTHOR]

A steady-state absorption and emission spectroscopy was used to create a comprehensive work and to study the interaction of the wild type Escherichia coli purine nucleoside phosphorylase and its mutants, PNPF159Y and PNPF159A, with a potent E. coli PNP inhibitor - formycin A. The absorption and emission spectra were recorded in the presence and absence of the phosphate at the 50 mM concentration. From the collected sets of data dissociation constants ( K d ), apparent dissociation constants (K app ) and Hill's coefficients ( h ) were calculated. Additionally, the temperature dependence of the enzymes emission quenching at two temperatures, 10 °C and 25 °C, was examined. To verify the calculations, total difference absorption spectra were computed for all types of the complexes. A prominent quenching of the PNPF159Y emission indicates a complex formation, with the strongest association in the phosphate buffer, pH 7, relative to the wild type enzyme. On the other hand, results testify to a deterioration of the interactions in the E. coli PNP/PNPF159Y and formycin A complexes in the presence of the phosphate, pH 8.3. Moreover, data obtained for the PNPF159A-FA complexes confirm a weak association of the FA to the mutant's active center. [ABSTRACT FROM AUTHOR]

Polyhexamethylene guanidine phosphate (PHMG-phosphate), an active component of humidifier disinfectant, is suspected to be a major cause of pulmonary fibrosis. Fibrosis, induced by recurrent epithelial damage, is significantly affected by epigenetic regulation, including microRNAs (miRNAs). The aim of this study was to investigate the fibrogenic mechanisms of PHMG-phosphate through the profiling of miRNAs and their target genes. A549 cells were treated with 0.75 μg/mL PHMG-phosphate for 24 and 48 h and miRNA microarray expression analysis was conducted. The putative mRNA targets of the miRNAs were identified and subjected to Gene Ontology analysis. After exposure to PHMG-phosphate for 24 and 48 h, 46 and 33 miRNAs, respectively, showed a significant change in expression over 1.5-fold compared with the control. The integrated analysis of miRNA and mRNA microarray results revealed the putative targets that were prominently enriched were associated with the epithelial-mesenchymal transition (EMT), cell cycle changes, and apoptosis. The dose-dependent induction of EMT by PHMG-phosphate exposure was confirmed by western blot. We identified 13 putative EMT-related targets that may play a role in PHMG-phosphate-induced fibrosis according to the Comparative Toxicogenomic Database. Our findings contribute to the comprehension of the fibrogenic mechanism of PHMG-phosphate and will aid further study on PHMG-phosphate-induced toxicity. [ABSTRACT FROM AUTHOR]

Calciprotein particles (CPP) have emerged as nanoscale mediators of phosphate-induced toxicity in Chronic Kidney Disease (CKD). Uraemia favors ripening of the particle mineral content from the amorphous (CPP-I) to the crystalline state (CPP-II) but the pathophysiological significance of this transformation is uncertain. Clinical studies suggest an association between CPP ripening and inflammation, vascular dysfunction and mortality. Although ripening has been modelled in vitro , it is unknown whether particles synthesised in serum resemble their in vivo counterparts. Here we show that in vitro formation and ripening of CPP in uraemic serum is characterised by extensive physiochemical rearrangements involving the accretion of mineral, loss of surface charge and transformation of the mineral phase from a spherical arrangement of diffuse domains of amorphous calcium phosphate to densely-packed lamellar aggregates of crystalline hydroxyapatite. These physiochemical changes were paralleled by enrichment with small soluble apolipoproteins, complement factors and the binding of fatty acids. In comparison, endogenous CPP represent a highly heterogeneous mixture of particles with characteristics mostly intermediate to synthetic CPP-I and CPP-II, but are also uniquely enriched for carbonate-substituted apatite, DNA fragments, small RNA and microbe-derived components. Pathway analysis of protein enrichment predicted the activation of cell death and pro-inflammatory processes by endogenous CPP and synthetic CPP-II alike. This comprehensive characterisation validates the use of CPP-II generated in uraemic serum as in vitro equivalents of their endogenous counterparts and provides insight into the nature and pathological significance of CPP in CKD, which may act as vehicles for various bioactive ligands. [ABSTRACT FROM AUTHOR]

Background: In this study, we coordinated a network meta-analysis to establish the efficacy and safety of different agents used in the treatment of hyperphosphatemia patients with chronic kidney disease.Methods: PubMed, CNKI, and Embase were systematically searched to retrieve relevant studies. Outcomes were presented by mean differences, odds ratios, and corresponding 95% credible intervals for continuous outcomes and binary outcomes, respectively. Each therapy was ranked according to the value of surface under the cumulative ranking curve. Consistencies between direct and indirect comparisons were assessed with a node-splitting plot.Results: In terms of efficacy end points (including levels of serum phosphate, serum calcium, serum intact parathyroid hormone, and serum calcium × phosphorus product), all 7 kinds of agents outperformed or performed at least equally to placebo, with iron-based phosphate-binding agents being potentially the most effective. As for safety end points (including mortality, adverse events, and all-cause discontinuation), almost all agents were equivalent in term of mortality and all-cause discontinuation except in the comparison between iron-based phosphate-binding agents and placebo. Meanwhile, iron-based phosphate-binding agents colestilan and nicotinic acid performed poorly compared with placebo in terms of adverse events. Furthermore, iron-based phosphate-binding agents were potentially the safest agents followed sequentially by calcium-based phosphate-binding agents and placebo.Conclusion: Iron-based phosphate-binding agents were the preferable agents when considering efficacy and safety simultaneously. [ABSTRACT FROM AUTHOR]

Multifunctional ecosystem of narrow grasslands located between croplands and streams slowly disappears from the agricultural landscape in Poland despite its importance to reduce the impact of land-based nutrients on freshwater ecosystems. We studied the effects of five extensive grasslands on nitrate and phosphate reduction in the catchment scale. During our 4-year monitoring, we did not observe the saturation effect in case of the two buffer zones that were receiving high nitrate load via subsurface flow. Highest nitrate concentration exceeded twice the level of 50 mg NO 3 /L, which is considered a threshold level of water pollution status by the EU Nitrates Directive. Concentrations above 100 mg NO 3 /L were reduced by 68% and 99% passing through the 25 m and 45 m of grassland, respectively. The efficiency of buffer zone to mitigate phosphate losses varied depending on the input load. The results obtained for high concentrations (above 1.5 mg PO 4 /L) showed 81% and 76% effectiveness of 45 m and 47 m grassland, respectively. However, the release of phosphates was reported as well and occurred at the buffer zones characterized by low inflow P concentrations when assimilation-decomposition processes dominated ecotone P dynamics. The analysis of nutrient retention in vegetation showed that harvesting of grassland removed 131 kg N/ha/yr and 19.4 kg P/ha/yr. Furthermore, the amount of nitrate and phosphate removed by buffer zones were statistically and positively correlated (r = 0.62, p < 0.05 and r = 0.52, p < 0.05, for NO 3 and PO 4 respectively) with the biodiversity (expressed as Shannon index), which underlines the importance of marginal parts of buffer zones. [ABSTRACT FROM AUTHOR]

Calcium and phosphate are vital for the organism and constitute essential components of the skeleton. Serum levels are tightly hormonally regulated and maintained by exchange with three major sources: the intestines, the kidney and the bone. The effects of sex steroids on the bone have been extensively studied and it is well known that sex steroid deficiency induces bone loss, indirectly influencing renal calcium and phosphate homeostasis. However, it is unknown whether sex steroids also directly regulate renal calcium and phosphate handling, hereby potentially indirectly impacting on bone. The presence of androgen receptors (AR) and estrogen receptors (ER) in both human and rodent kidney, although their exact localization within the kidney remains debated, supports direct effects. Estrogens stimulate renal calcium reabsorption as well as phosphate excretion, while the effects of androgens are less clear. Many of the studies performed with regard to renal calcium and/or phosphate homeostasis do not correct for the calcium and phosphate fluxes from the bone and intestines, which complicates the differentiation between the direct effects of sex steroids on renal calcium and phosphate handling and the indirect effects via the bone and intestines. The objective of this study is to review the literature and current insight of the role of sex steroids in calcium and phosphate handling in the kidney. [ABSTRACT FROM AUTHOR]

Background Spray polyurethane foam (SPF) is a highly effective thermal insulation material that has seen considerable market growth in the past decade. Organophosphate flame retardants (PFRs) are added to SPF formulations to meet fire code requirements. A common flame retardant used in SPF formulations is tris 1-chloro 2-propyl phosphate (TCIPP), a suspected endocrine disruptor. Exposure monitoring efforts during SPF applications have focused primarily on the isocyanate component, a potent respiratory and dermal sensitizer. However, to our knowledge, there is no monitoring data for TCIPP. Objective To characterize occupational exposures to TCIPP and other flame retardants during SPF insulation. Methods Workers at four SPF insulation sites and one foam removal site (total n  = 14) were recruited as part of this pilot study. Personal inhalation exposure to TCIPP was monitored with a CIP-10MI inhalable sampler and potential dermal exposure was assessed through the use of a glove dosimeter. Biomarkers of TCIPP and three other PFRs were measured in urine collected from workers pre-and post-shift. Linear mixed effect models were used to analyze associations of urinary biomarkers with inhalation and dermal exposures and paired t -tests were used to examine the difference on the means of urinary biomarkers pre-and post-shift. Chemical analysis of all species was performed with liquid chromatography-electrospray ionization tandem mass spectrometry. Results Geometric mean (GM) concentrations of TCIPP in personal air monitors and glove dosimeters collected from SPF applicators, 294.7 μg/m 3 and 18.8 mg/pair respectively. Overall, GM concentrations of the two TCIPP urinary biomarkers BCIPP and BCIPHIPP and (6.2 and 88.8 μg/mL) were 26–35 times higher than reported in the general population. Post-shift levels of TCIPP biomarkers were higher than pre-shift even though workers at insulation sites wore supplied air respirators, gloves and coveralls. The urinary biomarkers for the other PFRs were not elevated post shift. Concentrations of TCIPP on glove dosimeters were positively associated with post-shift urinary TCIPP biomarkers ( p  < 0.05) whereas concentrations in personal air samples were not. Conclusions High levels of urinary biomarkers for TCIPP among SPF applicators, including post-shift, points to absorption of TCIPP during the work shift, in spite of the use of best industry exposure control practices. Dermal exposure appears to be an important, if not the primary exposure pathway for TCIPP, although inhalation or incidental ingestion of foam particles post-SPF application cannot be ruled out in this pilot study. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (AgNPs) have many medical and commercial applications, but their effects on human health are poorly understood. The aim of this study was to assess the effect of AgNPs on the human neuroblastoma cell line SH-SY5Y and to explore their potential mechanisms of action. We found that AgNPs decreased SH-SY5Y cell viability in a dose- and time-dependent manner. Exposure to AgNPs activated endoplasmic reticulum (ER) stress, as reflected by upregulated expression of glucose-regulated protein 78 (GRP78), phosphorylated PKR-like endoplasmic reticulum kinase (p-PERK), phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α), C/EBP homology protein (CHOP), spliced X-box binding protein-1 (XBP1), and phosphorylated inositol-requiring enzyme (p-IRE), all of which are involved in the cellular unfolded protein response. Prolonged exposure of cells to AgNPs damaged calcium (Ca 2+ ) homeostasis, increased the length of contact sites between the ER and mitochondria, altered IP 3 R function by the increased levels of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in the ER and enhanced mitochondrial Ca 2+ uptake. Finally, Ca 2+ overload and disrupted homeostasis in the mitochondria triggered apoptotic cell death. Our results suggest that caution should be exercised in the use of AgNPs in humans. [ABSTRACT FROM AUTHOR]

We tested the legacy of the farming system (conventional or organic) on the interactions among phosphate solubilizing bacteria (PSB) and phosphate (Pi) solubilisation. We determined the in vitro Pi solubilisation and production of organic acids by nine PSB (four from conventional and five from organic farming) isolated from the rhizospheres of Carica papya , grown in monoculture or in pairs (66 combinations). When grown in monoculture, PSB isolated from conventional farming solubilised more Pi, but when grown in pairs, these PSB solubilised the least Pi. Furthermore, when the pairs included only PSB isolated from conventional farming, no Pi-solubilising cooperation was observed, that is, Pi solubilisation by pairs was lower than in monoculture. When PSB isolated from organic farming were present in the pairs, ∼40% of the combinations resulted in Pi solubilising cooperation. Organic acid production was not related with Pi solubilisation. Our work demonstrated the existence of a farming system legacy influencing the biotic interactions among PSB, and that the output of the interactions (cooperation or antagonism) was not phylogenetically determined. Data highlighted that biotic interactions should be considered when screening for potential plant growth promoting bacteria. [ABSTRACT FROM AUTHOR]

A systematic DFT conformational studies of four building blocks of TNA with cytosine attached to the C1′ atom of the α-L-threofuranose moiety are presented. Structures bearing 2′-OR and 3′-OR substituents, where R represents H, CH 3 and phosphate groups, were used in the studies using a B3LYP functional in the gas phase. The χ angle ( C2-N1-C1′-O4′ ), the ν 0 - ν 4 endocyclic torsion angles and the exocyclic torsion angles ε ( X-O2′-C2′-C1′ ) and γ ( X-O3′-C3′-C2′ ) geometry parameter variations were taken into consideration. Three energy minima, high-anti, anti and syn , were found for the rotation about the C1′-N1 bond. The high-anti orientation of the base with respect to the sugar moiety, turned out to be preferred, regardless of the substituents at the C2′ and C3′ positions. Other orientations are at least 1.65 kcal/mol higher in Gibbs free energy than the high-anti one. It has been shown that intramolecular H-bonds and the anomeric effect of phosphate groups strongly affect the conformational preferences of the studied compounds. Further, the structure of substituents attached to the sugar moiety influence the pucker of the furanoid ring. The furanoid ring in the global minima of the compound with two OH groups ( TC1 ) in the 2′ and 3′ positions, and the compound having a 3′-phosphate group ( TC2 ), adopt roughly the same conformation located at the southern range of the pseudorotation wheel, and thus are close to those found in the B type DNA helix. The low-energy high-anti rotamers of the geometry with the phosphate group attached to the sugar ring in the 2′ position ( TC3 ) and the geometry with two methoxyl groups ( TC4 ) have their furanoid rings in conformations resembling those found in A DNA and RNA helices (the northern range of the pseudorotation wheel). [ABSTRACT FROM AUTHOR]

Tri- n -butyl phosphate (TBP) is widely used in various industrial processes and has been detected in all environmental matrices. So far, little work has been done regarding the metabolism of TBP on terrestrial invertebrates. We investigated the metabolism of TBP in the earthworm, Perionyx excavatus , after acute exposure to TBP for one and two days in filter paper contact test, as well as after chronic exposure for 28 days in soil experiment. Biotransformation products were identified by using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry, and by exploiting the information dependent acquisition in tandem mass spectrometry. TBP exhibited low accumulation in earthworm-soil ecosystem at 10 mg/kg and 50 mg/kg. The presence of earthworms significantly enhanced TBP degradation at 50 mg/kg in soil. Dibutyl phosphate and hydroxylated TBP were the major phase I metabolites. Three novel phase II metabolites were identified: ethanol dibutyl phosphate and its sulfate conjugate, and the phosphate conjugate of hydroxylated TBP. Hydroxylation and further phosphorylation dominated metabolism in chronic exposure. An extensive metabolic pathway of TBP in earthworm was proposed. This is the first report of TBP metabolism in terrestrial invertebrates and highlights the necessity to identify metabolites of contaminants when evaluating their bioaccumulation and toxicity. [ABSTRACT FROM AUTHOR]

Purpose: The main purpose of our work lies in a new methodology of fabricating sorptive materials possessing bi-functionality to adsorb both cationic and anionic contaminants. As noted in the manuscript, many contaminated soils tend to contain multiple contaminants, and therefore, single-phase adsorbents cannot adequately address those mixed contaminants in a water body. In this respect, bi- or multi-functional adsorbents capable of removing multiple contaminants have great merits and practical advantages.Materials and methods: Four types of magnetic Fe/Mn oxide composites were prepared using different precipitation methods with or without post-treatment with H2O2: (1) co-precipitation of Fe2+/Mn2+ in alkaline condition (OS-N), (2) co-precipitation with H2O2 (OS-H), (3) two-step precipitation of Fe2+ and Mn2+ in sequential order (TS-N), and (4) two-step precipitation with H2O2 treatment (TS-H). The composites were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), particle size analyzer, and zeta potential analyzer. Cation-exchange capacity (CEC) and oxidation capacity of the composites were also measured using standard tests. The adsorption capacity of the composites toward Zn and PO4 was evaluated by carrying out adsorption kinetics, adsorption isotherm, and pH effect experiments.Results and discussion: The individual composites consisted mainly of Fe/Mn oxide phases significantly differing in particle size, morphology, and mineralogical phases, as well as adsorption capability. Zeta potential and XRD analyses revealed that Zn2+ adsorption (Langmuir adsorption capacity 64.52 mg g−1) of TS-H composite was relatively high among the four composites due to the strong negative charges of birnessite present in the composite. On the other hand, TS-N composite with the greatest point of zero charge (PZC) showed the highest PO43− adsorption. The kinetic data of Zn2+ and PO43− adsorption were fit to the pseudo-second-order reaction rate model reasonably well, which suggests the adsorption process occurred via chemisorption or chemical bonding between composite’s active sites and adsorbates.Conclusions: Four types of Fe/Mn composites were synthesized by different precipitation methods. Zn2+ and PO43− adsorption capacities of the composites varied with the method by which they were synthesized. Post-treatment with H2O2 also yielded composites with enhanced oxidation capacity. The appropriate synthesis method for generating Fe/Mn-based adsorbents depends on the type of contaminants. Lastly, using the multi-functional adsorbents could facilitate removal of both anion and cation, potentially providing cost benefits over conventional adsorption techniques. [ABSTRACT FROM AUTHOR]

Hyperphosphatemia is associated with mortality in patients with chronic kidney disease, and is common in critically ill patients with acute kidney injury (AKI); however, its clinical implication in these patients is unknown. We conducted an observational study in 1144 patients (mean age, 63.2 years; male, 705 [61.6%]) with AKI who received continuous renal replacement therapy (CRRT) between January 2009 and September 2016. Phosphate levels were measured before (0 h) and 24 h after CRRT initiation. We assessed disease severity using various clinical parameters. Phosphate at 0 h positively correlated with the Acute Physiology and Chronic Health Evaluation II (APACHE II; P < 0.001) and Sequential Organ Failure Assessment (SOFA; P < 0.001) scores, and inversely with mean arterial pressure (MAP; P = 0.02) and urine output (UO; P = 0.01). In a fully adjusted linear regression analysis for age, sex, Charlson comorbidity index (CCI), MAP, and estimated glomerular filtration rate (eGFR), higher 0 h phosphate level was significantly associated with high APACHE II (P < 0.001) and SOFA (P = 0.04) scores, suggesting that phosphate represents disease severity. A multivariable Cox model also showed that hyperphosphatemia was significantly associated with increased 28-day (HR 1.05, 95% CI 1.02–1.08, P = 0.001) and 90-day (HR 1.05, 95% CI 1.02–1.08, P = 0.001) mortality. Furthermore, patients with increased phosphate level during 24 h were at higher risk of death than those with stable or decreased phosphate levels. Finally, c-statistics significantly increased when phosphate was added to a model that included age, sex, CCI, body mass index, eGFR, MAP, hemoglobin, serum albumin, C-reactive protein, and APACHE II score. This study shows that phosphate is a potential biomarker that can reflect disease severity and predict mortality in critically ill patients receiving CRRT. [ABSTRACT FROM AUTHOR]

Background Use of organophosphate flame retardants (PFRs) has increased over the past decade following the phase out of some brominated flame retardants, leading to increased human exposure. We recently reported that increasing maternal PFR exposure is associated with poorer pregnancy outcomes among women from a fertility clinic. Because a small epidemiologic study previously reported an inverse association between male PFR exposures and sperm motility, we sought to examine associations of paternal urinary concentrations of PFR metabolites and their partner's pregnancy outcomes. Methods This analysis included 201 couples enrolled in the Environment and Reproductive Health (EARTH) prospective cohort study (2005–2015) who provided one or two urine samples per IVF cycle. In both the male and female partner, we measured five urinary PFR metabolites [bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), isopropylphenyl phenyl phosphate (ip-PPP), tert -butylphenyl phenyl phosphate (tb-PPP) and bis(1-chloro-2-propyl) phosphate (BCIPP)] using negative electrospray ionization liquid chromatography tandem mass spectrometry (LC-MS/MS). The sum of the molar concentrations of the urinary PFR metabolites was calculated. We used multivariable generalized linear mixed models to evaluate the association of urinary concentrations of paternal PFR metabolites with IVF outcomes, accounting for multiple in vitro fertilization (IVF) cycles per couple. Models were adjusted for year of IVF treatment cycle, primary infertility diagnosis, and maternal urinary PFR metabolites as well as paternal and maternal age, body mass index, and race/ethnicity. Results Detection rates were high for paternal urinary concentrations of BDCIPP (84%), DPHP (87%) and ip-PPP (76%) but low for tb-PPP (12%) and zero for BCIPP (0%). We observed a significant 12% decline in the proportion of fertilized oocytes from the first to second quartile of male urinary ΣPFR and a 47% decline in the number of best quality embryos from the first to third quartile of male urinary BDCIPP in our adjusted models. An 8% decline in fertilization was observed for the highest compared to lowest quartile of urinary BDCIPP concentrations (95% CI: 0.01, 0.12, p-trend = 0.06). Conclusions Using IVF as a model to investigate human reproduction and pregnancy outcomes, we found that paternal urinary concentrations of BDCIPP were associated with reduced fertilization. In contrast to previously reported findings for the female partners, the paternal urinary PFR metabolites were not associated with the proportion of cycles resulting in successful implantation, clinical pregnancy, and live birth. These results indicate that paternal preconception exposure to TDCIPP may adversely impact successful oocyte fertilization, whereas female preconception exposure to ΣPFRs may be more relevant to adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Tris(2-butoxyethyl) phosphate (TBOEP; 20 µg/kg b.w.) was orally administered to three female and three male volunteers. In urine samples collected for 39 h three metabolites of TBOEP were quantitated. bis(2-butoxyethyl) phosphate (BBOEP), tris(2-(3-hydroxy)butoxyethyl) phosphate (OH-TBOEP), bis(2-butoxyethyl)-(2-hydroxyethyl) phosphate (BBOEHEP) were observed in all urine samples within the first 7 h with highest concentration for BBOEHEP. Cmax of OH-TBOEP was in the range of 2–4 h and t1/2 was between 1.5 and 6.1 h. Similar results were obtained for BBOEHEP. In contrast BBOEP showed several maxima within 25 h and, therefore, no toxicokinetic data were calculated. As proof of concept 54 urine samples of children staying at day-care centers in Germany were analysed for all 3 biomarkers. Only BBOEP and BBOEHEP were detected in about 80% of the samples with a median of 0.16 µg/l for BBOEP and 0.18 µg/l for BBOEHEP. A recalculation of daily intake (DI) based on BBOEHEP resulted in a clear undercut of the current reference dose of 50 µg/kg per day. As observed in other studies a calculation of the DI based on the dust concentrations and oral uptake of 20 mg of dust for 8 h for young children results in considerably higher DI but would also not exceed the RfD. [ABSTRACT FROM AUTHOR]

The additive flame retardant triphenyl phosphate (TPHP) has been frequently detected in environments and biota. Evidences indicate that TPHP has potential risks to aquatic organisms. Seldom has been reported about its chronic effects to aquatic organism at low trophic levels, such as Cladocera. In the present study, <12 h old Daphnia magna ( D. magna ) were exposed to 0, 5, 50 or 500 μg/L TPHP for 21 days to investigate the chronic effects of TPHP on body length, fecundity and survival. Meanwhile, D. magna PCR arrays were used to evaluate the transcriptional responses of 155 genes involved in 40 pathways. Exposure to 500 μg/L TPHP for 21 days significantly decreased the body lengths of both F0 and F1 generation and inhibited the fecundity of F0 generation. Results of RT-qPCR showed that the expressions of 76 genes involved in 15 pathways were significantly altered after exposure to 500 μg/L TPHP for 21 days. The significantly altered pathways related to genetic information processing, cellular process and metabolism might be responsible for the observed effects of TPHP. Overall, our results showed that chronic exposure to TPHP caused developmental and reproductive toxicities to D. magna . [ABSTRACT FROM AUTHOR]

High arsenic (As) concentrations in the soil, water and plant systems can pose a direct health risk to humans and ecosystems. Phosphate (Pi) ions strongly influence As availability in soil, its uptake and toxicity to plants. Better understanding of As(V)-Pi interactions in soils and plants will facilitate a potential remediation strategy for As contaminated soils, reducing As uptake by crop plants and toxicity to human populations via manipulation of soil Pi content. However, the As(V)-Pi interactions in soil-plant systems are complex, leading to contradictory findings among different studies. Therefore, this review investigates the role of soil type, soil properties, minerals, Pi levels in soil and plant, Pi transporters, mycorrhizal association and microbial activities on As-Pi interactions in soils and hydroponics, and uptake by plants, elucidate the key mechanisms, identify key knowledge gaps and recommend new research directions. Although Pi suppresses As uptake by plants in hydroponic systems, in soils it could either increase or decrease As availability and toxicity to plants depending on the soil types, properties and charge characteristics. In soil, As(V) availability is typically increased by the addition of Pi. At the root surface, the Pi transport system has high affinity for Pi over As(V). However, Pi concentration in plant influences the As transport from roots to shoots. Mycorrhizal association may reduce As uptake via a physiological shift to the mycorrhizal uptake pathway, which has a greater affinity for Pi over As(V) than the root epidermal uptake pathway. [ABSTRACT FROM AUTHOR]

Phosphate functionalized graphene oxide (PGO), prepared by covalently bonding triethylphosphite on to the surface of graphene oxide (GO) via Arbuzov reaction has been demonstrated as an efficient catalyst for three component Biginelli condensation reaction with excellent yield (96%) under microwave condition. The PGO nanocatalyst was thoroughly characterized by Fourier transform infrared spectra (FTIR), FT-Raman spectroscopy, Powder X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Field-emission Scanning electron microscopy (FE-SEM), Energy dispersive X-ray spectroscopy (EDS), N 2 adsorption/desorption study, Ammonia temperature-programmed desorption analysis (NH 3 -TPD) and Thermogravimetric analysis (TGA). The presence of acidic groups on PGO which play an important role in the catalytic transformation were measured by NH 3 -TPD analysis. Based on the catalytic results, a feasible catalytic mechanism has been proposed. Besides high catalytic activity, this nanocatalyst showed good recyclability, suggesting its potential applications for the synthesis of other important organic molecules. [ABSTRACT FROM AUTHOR]

In this paper, iron oxide nanoparticles (IONPs) are successfully synthesized using Eucalyptus leaf extract in the presence of cetyltrimethylammonium bromide (CTAB) to enhance the dispersion and reduce aggregation of IONPs. CTAB was used as a stabilizing and capping agent in biosynthesis of IONP was observed. The particle size decreased from 183.9 ± 30.1 nm to 89.8 ± 17.1 nm as the concentration of CTAB increased from 0 to 0.4 mM CTAB, indicating that CTAB reduce the aggregation of IONPs and enhance the reactivity. In addition, the removal efficiency of phosphate declined from 95.13% to 89.58% when the CTAB concentration increased from 0.4 to 10 mM, indicating that a CTAB impacted on micelles and lipophilic biomolecules in Eucalyptus leaf extract, and hence affected the formation of IONPs. Furthermore, SEM image showed that the smaller spherical with some irregularly shaped CTAB-IONPs having a diameter of 80–90 nm in the presence of 0.4 mM CTAB were observed. The date from EDS, FTIR and TGA suggested that the CTAB capped on the surface of CTAB-IONPs, while XRD showed that zero-valent iron and iron oxide were formed. Finally, the formation mechanism of IONPs was proposed. [ABSTRACT FROM AUTHOR]

Brachypodium distachyon is a model plant that has recently emerged in grass research. Although the growth and photochemical efficiency of this species respond strongly to phosphate (Pi) availability, its Pi starvation response mechanism, which controls the Pi homeostasis, remains largely unknown. This study presents the transcriptomic response profiles of Pi-deficient roots at growth stages during which the plants were starved but obvious growth defects were absent. The results identify several phosphate transporters (i.e., PHO1 ), purple acid phosphatases, and SYG1/PHO81/XPR1 (SPX) domain-containing proteins out of a total of 1740 differentially expressed genes (DEGs). In particular, the transcription factor ethylene response factor (ERF), basic helix-loop-helix (bHLH), and WRKY family genes were the three most abundant DEG groups and the latter was significantly enriched. Comparative transcriptome analysis of Brachypodium versus Arabidopsis and rice revealed the presence of several common components in response to Pi fluctuations. Most significantly, jasmonic acid (JA) signaling-related genes were overrepresented in gene ontology (GO) enrichment tests. The presence of a possible link between low Pi response, inositol polyphosphates, and JA signaling is therefore discussed. [ABSTRACT FROM AUTHOR]

Water deficit and phosphate (Pi) deficiency adversely affect growth and biological nitrogen fixation (BNF) of legume crops. In this study, we examined the impact of interaction between soil water conditions and available soil-Pi levels on growth, nodule development and BNF potential of nine cowpea varieties grown on dry savanna soils. In our experimental design, soils with different available soil-Pi levels, i.e., low, moderate, and high soil-Pi levels, collected from various farming fields were used to grow nine cowpea varieties under well-watered and water-deficit conditions. Significant and severe water deficit-damaging effects on BNF, nodulation, growth, levels of plant-nitrogen (N) and -phosphorus (P), as well as shoot relative water content and chlorophyll content of cowpea plants were observed. Under well-watered and high available soil-Pi conditions, cowpea varieties IT07K-304-9 and Dan'Ila exhibited significantly higher BNF potential and dry biomass, as well as plant-N and -P contents compared with other tested ones. Significant genotypic variations among the cowpeas were recorded under low available soil-Pi and water-deficit conditions in terms of the BNF potential. Principal component (PC) analysis revealed that varieties IT04K-339-1, IT07K-188-49, IT07K-304-9, and IT04K-405-5 were associated with PC1, which was better explained by performance for nodulation, plant biomass, plant-N, plant-P, and BNF potential under the combined stress of water deficit and Pi deficiency, thereby offering prospects for development of varieties with high growth and BNF traits that are adaptive to such stress conditions in the region. On another hand, variety Dan'Ila was significantly related to PC2 that was highly explained by the plant shoot/root ratio and chlorophyll content, suggesting the existence of physiological and morphological adjustments to cope with water deficit and Pi deficiency for this particular variety. Additionally, increases in soil-Pi availability led to significant reductions of water-deficit damage on dry biomass, plant-N and -P contents, and BNF potential of cowpea varieties. This finding suggests that integrated nutrient management strategies that allow farmers to access to Pi-based fertilizers may help reduce the damage of adverse water deficit and Pi deficiency caused to cowpea crop in the regions, where soils are predominantly Pi-deficient and drought-prone. [ABSTRACT FROM AUTHOR]

Phosphate-starved plants reduce phosphatidylcholine content presumably to provide an internal phosphate source while replacing membrane phospholipids by galactolipids, a process termed membrane lipid remodeling. However, whether the metabolic fate of released phosphocholine is a phosphate source remains elusive because primary phosphocholine phosphatases in vivo are unknown in seed plants. Here, we show that PECP1 and PS2 are the primary phosphocholine phosphatases in Arabidopsis and function redundantly under phosphate starvation. Under phosphate starvation, the double knockout mutant of PECP1 and PS2 showed reduced content of choline but no severe growth phenotype, which suggests that phosphocholine dephosphorylation is not likely a major source of internal phosphate reserve. We identified primary phosphocholine phosphatases, demonstrated their involvement under phosphate starvation, and updated the metabolic map of membrane lipid remodeling. [ABSTRACT FROM AUTHOR]

Hyperphosphatemia is related to some pathologies, affecting vascular cell behavior. This work analyzes whether high concentration of extracellular phosphate induces endothelial senescence through up-regulation of endothelin-1 ( ET-1), exploring the mechanisms involved. The phosphate donor β-glycerophosphate ( BGP) in human endothelial cells increased ET-1 production, endothelin-converting enzyme-1 ( ECE-1) protein, and mRNA expression, which depend on the AP-1 activation through ROS production. In parallel, BGP also induced endothelial senescence by increasing p16 expression and the senescence-associated β-galactosidase ( SA-ß- GAL) activity. ET-1 itself was able to induce endothelial senescence, increasing p16 expression and SA-ß- GAL activity. In addition, senescence induced by BGP was blocked when different ET-1 system antagonists were used. BGP increased ROS production at short times, and the presence of antioxidants prevented the effect of BGP on AP1 activation, ECE-1 expression, and endothelial senescence. These findings were confirmed in vivo with two animal models in which phosphate serum levels were increased: seven/eight nephrectomized rats as chronic kidney disease models fed on a high phosphate diet and aged mice. Both models showed hyperphosphatemia, higher levels of ET-1, and up-regulation in aortic ECE-1, suggesting a direct relationship between hyperphosphatemia and ET-1. Present results point to a new and relevant role of hyperphosphatemia on the regulation of ET-1 system and senescence induction at endothelial level, both in endothelial cells and aorta from two animal models. The mechanism involved showed a higher ROS production, which probably activates AP-1 transcription factor and, as a result, ECE-1 expression, increasing ET-1 synthesis, which in consequence induces endothelial senescence. [ABSTRACT FROM AUTHOR]

Phosphate regulation of antibiotic biosynthesis in Streptomyces has been studied due to the importance of this genus as a source of secondary metabolites with biological activity. Streptomyces tsukubaensis is the main producer of tacrolimus (or FK506), an immunosuppressant macrolide that generates important benefits for the pharmaceutical market. However, the production of tacrolimus is under a negative control by phosphate and, therefore, is important to know the molecular mechanism of this regulation. Despite its important role, there are no reports about the Pho regulon in S. tsukubaensis . In this work we combined transcriptional studies on the response to phosphate starvation with the search for PHO boxes in the whole genome sequence of S. tsukubaensis . As a result, we identified a set of genes responding to phosphate starvation and containing PHO boxes that include common Pho regulon members but also new species-specific candidates. In addition, we demonstrate for the first time the functional activity of PhoP from S. tsukubaensis through complementation studies in a Streptomyces coelicolor Δ phoP strain. For this purpose, we developed an anhydrotetracycline inducible system that can be applied to the controlled expression of target genes. [ABSTRACT FROM AUTHOR]

Egg yolk phosvitin is one of the most phosphorylated proteins in nature, and the extraordinarily high concentration of phosphate groups in its structure provides a strong metal-binding ability. Phosvitin is known to possess various functional activities, including metal-chelating, antioxidant, emulsifying, antimicrobial, and cytotoxic activities. However, little is known about the immune-enhancing activity of phosvitin. The objective of this study was to evaluate the immune-enhancing activity of phosvitin in murine RAW 264.7 macrophages. Griess reagents and quantitative real-time PCR were used to determine the effect of phosvitin (at 12.5, 25, 50, and 100 µg/mL) on the levels of pro-inflammatory mediators NO and inducible nitric oxide synthase (iNOS), cytokines TNF-a and IL- 1ß in RAW 264.7 macrophages. The effect of phosvitin on the phagocytic activity of RAW 264.7 macrophages was also measured using the Neutral-Red Uptake method. Lipopolysaccharides was used as a positive control. Phosvitin significantly (P < 0.05) increased the production of NO in RAW 264.7 macrophages in a dose-dependent manner, but did not show any cytotoxicity. The amounts of NO produced were 3.47, 7.12, 10.23, and 14.57 µM in 12.5 to 100 µg/mL range of phosvitin (control: 0.46 µM). Compared with the untreated group, phosvitin treatment at a 100 µg/mL level increased the production of NO by 31.67 times. Phosvitin also significantly increased the mRNA expression of the RAW 264.7 macrophages: 100 µg/mL of phosvitin treatment increased the expression of mRNA for iNOS, TNF-a, and IL-1ß by 46.25, 9.09, and 85.18 times of the control, respectively. The phagocytic activity of RAW 264.7 macrophages was also increased significantly by phosvitin treatment. These results demonstrated that phosvitin dramatically improved the immune functions RAW 264.7 macrophages by enhancing the production of immune mediators and increasing phagocytic activity. Therefore, phosvitin has a potential to be used as an immune-enhancing agent by food or nutraceutical industries. [ABSTRACT FROM AUTHOR]

Background. Sucroferric oxyhydroxide is a noncalcium, ironbased phosphate binder that demonstrated sustained serum phosphorus control, good tolerability and lower pill burden compared with sevelamer carbonate (sevelamer) in a Phase 3 study conducted in dialysis patients. This subanalysis examines the efficacy and tolerability of sucroferric oxyhydroxide and sevelamer in the peritoneal dialysis (PD) patient population. Methods. The initial study (NCT01324128) and its extension (NCT01464190) were multicenter, Phase 3, open-label, randomized (2:1), active-controlled trials comparing sucroferric oxyhydroxide (1.0-3.0 g/day) with sevelamer (2.4-14.4 g/day) in dialysis patients over 52 weeks in total. Results. In the overall study, 84/1055 (8.1%) patients received PD and were eligible for efficacy analysis (sucroferric oxyhydroxide, n=56; sevelamer, n=28). The two groups were broadly comparable to each other and to the overall study population. Serum phosphorus concentrations decreased comparably with both phosphate binders by week 12 (mean change from baseline ≤0.6mmol/L). Over 52 weeks, sucroferric oxyhydroxide effectively reduced serum phosphorus concentrations to a similar extent as sevelamer; 62.5% and 64.3% of patients, respectively, were below the Kidney Disease Outcomes Quality Initiative target range (≤1.78mmol/L). This was achieved with a lower pill burden (3.461.3 versus 8.163.7 tablets/day) with sucroferric oxyhydroxide compared with sevelamer. Treatment adherence rates were 91.2% with sucroferric oxyhydroxide and 79.3% with sevelamer. The proportion of patients reporting at least one treatment-emergent adverse event was 86.0% with sucroferric oxyhydroxide and 93.1% with sevelamer. The most common adverse events with both treatments were gastrointestinal: diarrhea and discolored feces with sucroferric oxyhydroxide and nausea, vomiting and constipation with sevelamer. Conclusions. Sucroferric oxyhydroxide is noninferior to sevelamer for controlling serum phosphorus in patients undergoing PD, while providing a relatively low pill burden and a high rate of adherence. [ABSTRACT FROM AUTHOR]

Tris (2-butoxyethyl) phosphate (TBOEP), is used as a flame retardant worldwide. It is an additive in materials and can be easily discharged into the surrounding environment. There is evidence linking TBOEP exposure to abnormal development and growth in zebrafish embryos/larvae. Here, using zebrafish embryo as a model, we investigated toxicological effects on developing zebrafish ( Danio rerio ) caused by TBOEP at concentrations of 0, 20, 200, 1000, 2000 μg/L starting from 2 h post-fertilization (hpf). Our findings revealed that TBOEP exposure caused developmental toxicity, such as malformation, growth delay and decreased heart rate in zebrafish larvae. Correlation analysis indicated that inhibition of growth was possibly due to down-regulation of expression of genes related to the growth hormone/insulin-like growth factor (GH/IGF) axis. Furthermore, exposure to TBOEP significantly increased thyroxine (T4) and 3,5,3′-triiodothyronine (T3) in whole larvae. In addition, changed expression of genes involved in the hypothalamic-pituitary-thyroid (HPT) axis was observed, indicating that perturbation of HPT axis might be responsible for the developmental damage and growth delay induced by TBOEP. The present study provides a new set of evidence that exposure of embryo-larval zebrafish to TBOEP can cause perturbation of GH/IGF axis and HPT axis, which could result in developmental impairment and growth inhibition. [ABSTRACT FROM AUTHOR]

Background. Hyperphosphataemia is an independent risk factor for accelerated cardiovascular disease in chronic kidney disease (CKD), although the mechanism for this is poorly understood. We investigated the effects of sustained exposure to a high-phosphate environment on endothelial function in cellular and preclinical models, as well as in human subjects. Methods. Resistance vessels from rats and humans (6 CKD) were incubated in a normal (1.18 mM) or high (2.5 mM) phosphate concentration solution and cells were cultured in normal- (0.5 mM) or high-phosphate (3 mM) concentration media. A single-blind crossover study was performed in healthy volunteers, receiving phosphate supplements or a phosphate binder (lanthanum), and endothelial function measured was by flowmediated dilatation. Results. Endothelium-dependent vasodilatation was impaired when resistance vessels were exposed to high phosphate; this could be reversed in the presence of a phosphodiesterase-5- inhibitor. Vessels from patients with CKD relaxed normally when incubated in normal-phosphate conditions, suggesting that the detrimental effects of phosphate may be reversible. Exposure to high-phosphate disrupted the whole nitric oxide pathway with reduced nitric oxide and cyclic guanosine monophosphate production and total and phospho endothelial nitric oxide synthase expression. In humans, endothelial function was reduced by chronic phosphate loading independent of serum phosphate, but was associated with higher urinary phosphate excretion and serumfibroblast growth factor 23. Conclusions. These directly detrimental effects of phosphate, independent of other factors in the uraemic environment, may explain the increased cardiovascular risk associated with phosphate in CKD. [ABSTRACT FROM AUTHOR]

Diatoms are important components of marine ecosystems and contribute greatly to the world’s primary production. Despite their important roles in ecosystems, the molecular basis of how diatoms cope with oxidative stress caused by nutrient fluctuations remains largely unknown. Here, an isobaric tags for relative and absolute quantitation (iTRAQ) proteomic method was coupled with a series of physiological and biochemical techniques to explore oxidative stress- and cell fate decision-related cellular and metabolic responses of the diatom Thalassiosira pseudonana to nitrate (N) and inorganic phosphate (P) stresses. A total of 1151 proteins were detected; 122 and 56 were significantly differentially expressed from control under N- and P-limited conditions, respectively. In N-limited cells, responsive proteins were related to reactive oxygen species (ROS) accumulation, oxidative stress responses and cell death, corresponding to a significant decrease in photosynthetic efficiency, marked intracellular ROS accumulation, and caspase-mediated programmed cell death activation. None of these responses were identified in P-limited cells; however, a significant up-regulation of alkaline phosphatase proteins was observed, which could be the major contributor for P-limited cells to cope with ambient P deficiency. These findings demonstrate that fundamentally different metabolic responses and cellular regulations are employed by the diatom in response to different nutrient stresses and to keep the cells viable. [ABSTRACT FROM AUTHOR]