Relation between Red Cell Distribution Width and Fibroblast Growth Factor 23 Cleaving in Patients with Chronic Kidney Disease and Heart Failure

Objective

In chronic kidney disease (CKD), both anemia and deregulated phosphate metabolism are common and predictive of adverse outcome. Previous studies suggest that iron status influences phosphate metabolism by modulating proteolytic cleavage of FGF23 into C-terminal fragments. Red cell distribution width (RDW) was recently identified as a strong prognostic determinant for cardiovascular morbidity and mortality, independently of iron status. We assessed whether RDW is associated with FGF23 cleaving in CKD patients with heart failure.

Materials and Methods

The associations between RDW and either intact FGF23 (iFGF23), C-terminal FGF23 (cFGF23, reflecting iFGF23 and C-terminal fragments together) and the iFGF23/cFGF23 ratio were analyzed in 52 patients with CKD (eGFR 34,9 ± 13.9 ml/min/1.73m²) and chronic heart failure (CHF). Associations between RDW and FGF23 forms were studied by linear regression analysis adjusted for parameters of renal function, iron metabolism, phosphate metabolism and inflammation.

Results

Median cFGF23 levels were 197.5 [110–408.5] RU/ml, median iFGF23 levels were 107.3 [65.1–162.2] pg/ml and median FGF23 ratio was 0.80 [0.37–0.86]. Mean RDW was 14.1 ± 1.2%. cFGF23 and RDW were associated (β = 1.63x10^-3, P <0.001), whereas iFGF23 and RDW were not (β = -1.38x10^-3, P = 0.336). The iFGF23/cFGF23 ratio was inversely associated with RDW. The difference between cFGF23 and iFGF23 (cFGF23- iFGF23) was positively associated with RDW (β = 1.74x10^-3, P< 0.001). The association between cFGF23 and RDW persisted upon multivariable linear regression analysis, adjusted for parameters of renal function, phosphate metabolism, iron metabolism and inflammation (β = 0.97x10^-3, P = 0.047).

Conclusion

RDW is associated with cFGF23 but not with iFGF23 levels in patients with CKD and CHF. This suggests a connection between RDW and FGF23 catabolism, independent of iron status and inflammation. Future studies are needed to unravel underlying mechanisms and whether these pertain to the link between RDW and outcome.     

Differences in Body Fat Distribution Play a Role in the Lower Levels of Elevated Fasting Glucose amongst Ghanaian Migrant Women Compared to Men

Background

Despite higher levels of obesity, West African migrant women appear to have lower rates of type 2 diabetes than their male counterparts. We investigated the role of body fat distribution in these differences.

Methods

Cross-sectional study of Ghanaian migrants (97 men, 115 women) aged 18–60 years in Amsterdam, the Netherlands. Weight, height, waist and hip circumferences were measured. Logistic regression was used to explore the association of BMI, waist and hip measurements with elevated fasting glucose (glucose≥5.6 mmol/L). Linear regression was used to study the association of the same parameters with fasting glucose.

Results

Mean BMI, waist and hip circumferences were higher in women than men while the prevalence of elevated fasting glucose was higher in men than in women, 33% versus 19%. With adjustment for age only, men were non-significantly more likely than women to have an elevated fasting glucose, odds ratio (OR) 1.81, 95% CI: 0.95, 3.46. With correction for BMI, the higher odds among men increased and were statistically significant (OR 2.84, 95% CI: 1.32, 6.10), but with consideration of body fat distribution (by adding both hip and waist in the analysis) differences were no longer significant (OR 1.56 95% CI: 0.66, 3.68). Analysis with fasting glucose as continuous outcome measure showed somewhat similar results.

Conclusion

Compared to men, the lower rates of elevated fasting glucose observed among Ghanaian women may be partly due to a more favorable body fat distribution, characterized by both hip and waist measurements.     

Oxygen mass transfer characteristics in a membrane-aerated biofilm reactor

Immobilization of pollutant-degrading microorganisms on oxygen-permeable membranes provides a novel method of increasing the oxidation capacity of wastewater treatment bioreactors. Oxygen mass transfer characteristics during continuous-flow steady-state experiments were investigated for biofilms supported on tubular silicone membranes. An analysis of oxygen mass transport and reaction using an established mathematical model for dual-substrate limitation supported the experimental results reported. In thick biofilms, an active layer of biomass where both carbon substrate and oxygen are available was found to exist. The location of this active layer varies depending on the ratio of the carbon substrate loading rate to the intramembrane oxygen pressure. The thickness of a carbon-substrate-starved layer was found to greatly influence the mass transport of oxygen into the active biomass layer, which was located close to, but not in contact with, the biofilm-liquid interface. The experimental results demonstrated that oxygen uptake rates as high as 20 g m-2 d-1 bar-1 can be achieved, and the model predicts that, for an optimized biofilm thickness, oxygen uptake rates of more than 30 g m-2 d-1 bar-1 should be possible. This would allow membrane-aerated biofilm reactors to operate with much greater thicknesses of active biomass than can conventional biofilm reactors as well as offering the further advantage of close to 100% oxygen conversion efficiencies for the treatment of high-strength wastewaters. In the case of dual- substrate-limited biofilms, the potential to increase the oxygen flux does not necessarily increase the substrate (acetate) removal rate.     

Molecular characterization of a cystathionine beta-synthase gene,CBS1, in Magnaporthe grisea

CBS1 from Magnaporthe grisea is a structural and functional homolog of the cystathionine β-synthase (CBS) gene from Saccharomyces cerevisiae. Our studies indicated that M. grisea can utilize homocysteine and methionine through a CBS-independent pathway. The results also revealed responses of M. grisea to homocysteine that are reminiscent of human homocystinuria.     

Post-Prandial Protein Handling: You Are What You Just Ate

Background

Protein turnover in skeletal muscle tissue is highly responsive to nutrient intake in healthy adults.

Objective

To provide a comprehensive overview of post-prandial protein handling, ranging from dietary protein digestion and amino acid absorption, the uptake of dietary protein derived amino acids over the leg, the post-prandial stimulation of muscle protein synthesis rates, to the incorporation of dietary protein derived amino acids in de novo muscle protein.

Design

12 healthy young males ingested 20 g intrinsically [1-¹³C]-phenylalanine labeled protein. In addition, primed continuous L-[ring-²H₅]-phenylalanine, L-[ring-²H₂]-tyrosine, and L-[1-¹³C]-leucine infusions were applied, with frequent collection of arterial and venous blood samples, and muscle biopsies throughout a 5 h post-prandial period. Dietary protein digestion, amino acid absorption, splanchnic amino acid extraction, amino acid uptake over the leg, and subsequent muscle protein synthesis were measured within a single in vivo human experiment.

Results

55.3±2.7% of the protein-derived phenylalanine was released in the circulation during the 5 h post-prandial period. The post-prandial rise in plasma essential amino acid availability improved leg muscle protein balance (from -291±72 to 103±66 μM·min^-1·100 mL leg volume^-1; P<0.001). Muscle protein synthesis rates increased significantly following protein ingestion (0.029±0.002 vs 0.044±0.004%·h^-1 based upon the muscle protein bound L-[ring-²H₅]-phenylalanine enrichments (P<0.01)), with substantial incorporation of dietary protein derived L-[1-¹³C]-phenylalanine into de novo muscle protein (from 0 to 0.0201±0.0025 MPE).

Conclusion

Ingestion of a single meal-like amount of protein allows ~55% of the protein derived amino acids to become available in the circulation, thereby improving whole-body and leg protein balance. About 20% of the dietary protein derived amino acids released in the circulation are taken up in skeletal muscle tissue following protein ingestion, thereby stimulating muscle protein synthesis rates and providing precursors for de novo muscle protein synthesis.

Trial Registration

trialregister.nl 3638     

Role of two dileucine-like motifs in insulin receptor anchoring to microvilli

In the absence of ligand, the insulin receptor is maintained on microvilli on the cell surface. A dileucine motif (LL(986-987)) is necessary but not sufficient for this anchoring, which also required the presence of additional sequence(s) downstream of position 1000. The aim of the present study was to identify this (these) additional sequence(s). First, exons 16 or 17 were fused to the extracellular and transmembrane domains of complement receptor 1 and stably expressed in Chinese hamster ovary cells. Results obtained indicate that exon 17 is sufficient for anchoring to microvilli. Second, analysis of insulin receptor mutants truncated within exon 17 demonstrated that whereas receptors truncated at position 1000 showed no preferential association with microvilli, receptors truncated at position 1012 displayed a level of association identical to that of the full-length insulin receptor. Third, mutation of a diisoleucine motif (II(1006-1007)) present within this 12-amino acid stretch abrogated the preferential association of the receptor with microvilli. These results indicate that the domain required for association of insulin receptor with microvilli is contained within the region encoded by exon 17 and that, within this sequence, two dileucine-like motifs (LL(986-987) and II(1006-1007)) play a crucial role.     

Impacts of logging and conversion of rainforest to oil palm on the functional diversity of birds in Sundaland

Commercial selective logging and the conversion of primary and degraded forests to agriculture are the biggest threats to tropical biodiversity. Our understanding of the impacts of these disturbances and the resulting local extinctions on the functional roles performed by the remaining species is limited. We address this issue by examining functional diversity (FD), which quantifies a range of traits that affect a species' ecological role in a community as a single continuous metric. We calculated FD for birds across a gradient of disturbance from primary forest through intensively logged forest to oil palm plantations on previously forested land in Borneo, Southeast Asia, a hotspot of imperilled biodiversity. Logged rainforest retained similar levels of FD to unlogged rainforest, even after two logging rotations, but the conversion of logged forest to oil palm resulted in dramatic reductions in FD. The few remaining species in oil palm filled a disproportionately wide range of functional roles but showed very little clustering in terms of functional traits, suggesting that any further extinctions from oil palm would reduce FD even further. Determining the extent to which the changes we recorded were due to under‐utilization of resources within oil palm or a reduction in the resources present is an important next step. Nonetheless our study improves our understanding of the stability and resilience of functional diversity in these ecosystems and of the implications of land‐use changes for ecosystem functioning.     

Population structure of the black seabream Spondyliosoma cantharus along the south-west Portuguese coast inferred from otolith chemistry

The chemistry of black seabream Spondyliosoma cantharus otoliths from three main fishery grounds (Olhão, Sagres and Sesimbra) located along c. 400 km of the Portuguese south and west coasts was examined. Element:Ca ratios were determined in whole otoliths and otolith cores of young adult specimens of 2–3 years of age. Using the data from whole otoliths, it was possible to discriminate among S. cantharus from the three fishing grounds with an average accuracy of 91%. Differences among fishing grounds were significant for all element:Ca ratios, and otoliths from Sagres had significantly higher levels of all ratios compared to the other fishing grounds. In contrast, the chemical composition of the otolith core, representative of the larval stage, showed limited variation among the fishing grounds, with an average discrimination accuracy of only 44%, although the Mg:Ca ratio of the otolith cores was also significantly higher for the Sagres samples. The data suggest that larval stages experienced a homogenous environment consistent with an offshore oceanic spawning. Juveniles appeared to display local residency on the inshore fishing grounds, areas probably characterized by greater environmental heterogeneity. Spondyliosoma cantharus population structure is consistent with distinct local population units that share a spawning ground providing recruits to different coastal fishery areas.