Influence of the ABCG2 gout risk 141?K allele on urate metabolism during a fructose challenge

Introduction

Both genetic variation in ATP-binding cassette sub-family G member 2 (ABCG2) and intake of fructose-containing beverages are major risk factors for hyperuricemia and gout. This study aimed to test the hypothesis that the ABCG2 gout risk allele 141 K promotes the hyperuricaemic response to fructose loading.

Methods

Healthy volunteers (n = 74) provided serum and urine samples immediately before and 30, 60, 120 and 180 minutes after ingesting a 64 g fructose solution. Data were analyzed based on the presence or absence of the ABCG2 141 K gout risk allele.

Results

The 141 K risk allele was present in 23 participants (31%). Overall, serum urate (SU) concentrations during the fructose load were similar in those with and without the 141 K allele (P_SNP = 0.15). However, the 141 K allele was associated with a smaller increase in SU following fructose intake (P_SNP <0.0001). Those with the 141 K allele also had a smaller increase in serum glucose following the fructose load (P_SNP = 0.002). Higher fractional excretion of uric acid (FEUA) at baseline and throughout the fructose load was observed in those with the 141 K risk allele (P_SNP <0.0001). However, the change in FEUA in response to fructose was not different in those with and without the 141 K risk allele (P_SNP = 0.39). The 141 K allele effects on serum urate and glucose were more pronounced in Polynesian participants and in those with a body mass index ≥25 kg/m².

Conclusions

In contrast to the predicted responses for a hyperuricemia/gout risk allele, the 141 K allele is associated with smaller increases in SU and higher FEUA following a fructose load. The results suggest that ABCG2 interacts with extra-renal metabolic pathways in a complex manner to regulate SU and gout risk.

Clinical Trials Registration

The study was registered by the Australian Clinical Trials Registry (ACTRN12610001036000).     

Nutrient resorption of two evergreen shrubs in response to long-term fertilization in a bog

Plant resorption of multiple nutrients during leaf senescence has been established but stoichiometric changes among N, P and K during resorption and after fertilization are poorly understood. We anticipated that increased N supply would lead to further P limitation or co-limitation with N or K [i.e. P-(co)limitation], decrease N resorption and increase P and K resorption, while P and K addition would decrease P and K resorption and increase N resorption. Furthermore, Ca would accumulate while Mg would be resorbed during leaf senescence, irrespective of fertilization. We investigated the effect of N, P and K addition on resorption in two evergreen shrubs (Chamaedaphne calyculata and Rhododendron groenlandicum) in a long-term fertilization experiment at Mer Bleue bog, Ontario, Canada. In general, N addition caused further P-(co)limitation, increased P and K resorption efficiency but did not affect N resorption. P and K addition did not shift the system to N limitation and affect K resorption, but reduced P resorption proficiency. C. calyculata resorbed both Ca and Mg while R. groenlandicum resorbed neither. C. calyculata showed a higher resorption than R. groenlandicum, suggesting it is better adapted to nutrient deficiency than R. groenlandicum. Resorption during leaf senescence decreased N:P, N:K and K:P ratios. The limited response of N and K and the response of P resorption to fertilization reflect the stoichiometric coupling of nutrient cycling, which varies among the two shrub species; changes in species composition may affect nutrient cycling in bogs.     

Constitutively expressed rat mRNA encoding a 70-kilodalton heat-shock-like protein.

A nearly full-length cDNA clone isolated from the rat pheochromocytoma cell line, PC12, revealed extensive nucleotide sequence similarity between the rat cDNA and the Drosophila melanogaster hsp70 gene. The rat recombinant clone encodes a 71,000-dalton protein that is 70% identical with the dipteran hsp70 protein. Remarkably, a truncated segment of this cDNA clone was originally isolated by immunoreactivity with antisera raised to catecholamine-synthesizing enzymes, suggesting that this heat shock protein and these catecholamine enzymes shared antigenic determinants. The rat hsp70-related mRNA is responsible for the production of a constitutive hsp70 protein, because it is present in abundant amounts in various tissues at normal growth temperatures and is only minimally induced by hyperthermia. The rat hsp70-related sequence is part of a multigene family that extends across species to mice and humans.     

Molecular evolution of the sex peptide network in Drosophila

Successful reproduction depends on interactions between numerous proteins beyond those involved directly in gamete fusion. Although such reproductive proteins evolve in response to sexual selection pressures, how networks of interacting proteins arise and evolve as reproductive phenotypes change remains an open question. Here, we investigated the molecular evolution of the ‘sex peptide network’ of Drosophila melanogaster, a functionally well‐characterized reproductive protein network. In this species, the peptide hormone sex peptide (SP) and its interacting proteins cause major changes in female physiology and behaviour after mating. In contrast, females of more distantly related Drosophila species do not respond to SP. In spite of these phenotypic differences, we detected orthologs of all network proteins across 22 diverse Drosophila species and found evidence that most orthologs likely function in reproduction throughout the genus. Within SP‐responsive species, we detected the recurrent, adaptive evolution of several network proteins, consistent with sexual selection acting to continually refine network function. We also found some evidence for adaptive evolution of several proteins along two specific phylogenetic lineages that correspond with increased expression of the SP receptor in female reproductive tracts or increased sperm length, respectively. Finally, we used gene expression profiling to examine the likely degree of functional conservation of the paralogs of an SP network protein that arose via gene duplication. Our results suggest a dynamic history for the SP network in which network members arose before the onset of robust SP‐mediated responses and then were shaped by both purifying and positive selection.     

Linking root production to aboveground plant characteristics and water table in a temperate bog

To develop agronomic application rates for alum-amended poultry litter, nutrient and Al availability of this particular organic fertilizer were examined using long-term field weathering studies. It was revealed that concentrations of N, P, K⁺, and Al³⁺ in the poultry litter leachate ranged from 5 to 6,503 mg L^-1, 2 to 84 mg L^-1, 2 to 5135 mg L^-1, and 0.05 to 4.6 mg L^-1, respectively. Release of nutrients occurred principally in the first growing season and would last for years. During 19 months of field weathering, 10.5 kg N, 1.1 kg P, 34.5 kg K⁺, and 0.031 kg Al³⁺ were released per ton of the poultry litter and recovered in the leachate. The results suggest that no Al toxicity would be generated to crops if alum-amended poultry litter is used as a fertilizer. If applied at 13.3 ton ha^-1, the poultry litter will supply 150.0 kg ha^-1 N, 15.2 kg ha^-1 P, and 456.2 kg ha^-1 K⁺ to seasonal crops. Application of alum-amended poultry litter at available N-based rates will meet crop nutrient requirements while minimizing nutrient runoff losses.     

Neutralizing anti-IL-10 antibody blocks the protective effect of tapeworm infection in a murine model of chemically induced colitis

There is increasing evidence that parasitic helminth infection has the ability to ameliorate other disease conditions. In this study the ability of the rat tapeworm, Hymenolepis diminuta, to modulate dinitrobenzene sulfonic acid (DNBS)-induced colitis in mice is assessed. Mice receiving DNBS (3 mg intrarectally) developed colitis by 72 h after treatment. Mice infected 8 days before DNBS with five H. diminuta larvae were significantly protected from the colitis, as gauged by reduced clinical disease, histological damage scores, and myeloperoxidase levels. This anticolitic effect was dependent on a viable infection and helminth rejection, because no benefit was observed in mice given killed larvae or in infected STAT6 knockout mice or rats, neither of which eliminate H. diminuta. The anticolitic effect of H. diminuta was associated with increased colonic IL-10 mRNA and stimulated splenocytes from H. diminuta- plus DNBS-treated mice produced more IL-10 than splenocytes from DNBS-only treated mice. Coadministration of an anti-IL-10 Ab blocked the anticolitic effect of prophylactic H. diminuta infection. Also, mice infected 48 h after DNBS treatment showed an enhanced recovery response. Finally, using a model of OVA hypersensitivity, we found no evidence of concomitant H. diminuta infection enhancing enteric responsiveness to subsequent ex vivo OVA challenge. The data show that a viable infection of H. diminuta in a nonpermissive system exerts a profound anticolitic effect (both prophylactically and as a treatment) that is mediated at least in part via IL-10 and does not predispose to enhanced sensitivity to bystander proteins.