Effect of urine pH on uric acid excretion by manipulating food materials

A potential utilization of dietary intervention for reducing hyperuricemia was tested by managing food materials. Within the framework of the Japanese Government's health promotion program, we made recipes that consisted of more protein-rich and less vegetable/fruit-rich materials for the acidic diet and others composed of less protein-rich and more vegetable/fruit-rich materials for the alkaline diet. We have shown that urine alkalization facilitates uric acid excretion. In this study, it has been clarified with simultaneous measurements of both serum and urine uric acid concentration that acidic diets increase serum uric acid together with a decrease of uric acid excretion. The ratio (R) of uric acid clearance/creatinine clearance was calculated. On the third experimental day, the relative R, referring to that of the first day for the acidic diet, became smaller than that for the alkaline diet, indicating that in acidic urine, uric acid excretion is limited by more active reabsorption, compared with that in alkaline urine. Taken together, we tentatively conclude that dietary intervention may well be the safest and the most economical way for the prevention of hyperuricemia.     

Inorganic phosphate homeostasis in sodium-dependent phosphate cotransporter Npt2b⁺/⁻ mice

An inorganic phosphate (P(i))-restricted diet is important for patients with chronic kidney disease and patients on hemodialysis. Phosphate binders are essential for preventing hyperphosphatemia and ectopic calcification. The sodium-dependent P(i) (Na/P(i)) transport system is involved in intestinal P(i) absorption and is regulated by several factors. The type II sodium-dependent P(i) transporter Npt2b is expressed in the brush-border membrane in intestinal epithelial cells and transports P(i). In the present study, we analyzed the phenotype of Npt2b(-/-) and hetero(+/-) mice. Npt2b(-/-) mice died in utero soon after implantation, indicating that Npt2b is essential for early embryonic development. At 4 wk of age, Npt2b(+/-) mice showed hypophosphatemia and low urinary P(i) excretion. Plasma fibroblast growth factor 23 levels were significantly decreased and 1,25(OH)(2)D(3) levels were significantly increased in Npt2b(+/-) mice compared with Npt2b(+/+) mice. Npt2b mRNA levels were reduced to 50% that in Npt2b(+/+) mice. In contrast, renal Npt2a and Npt2c transporter protein levels were significantly increased in Npt2b(+/-) mice. At 20 wk of age, Npt2b(+/-) mice showed hypophosphaturia and reduced Na/P(i) cotransport activity in the distal intestine. Npt2b(+/+) mice with adenine-induced renal failure had hyperphosphatemia and high plasma creatinine levels. Npt2b(+/-) mice treated with adenine had significantly reduced plasma P(i) levels compared with Npt2b(+/+) mice. Intestinal Npt2b protein and Na(+)/P(i) transport activity levels were significantly lower in Npt2b(+/-) mice than in the Npt2b(+/+) mice. The findings of the present studies suggest that Npt2b is an important target for the prevention of hyperphosphatemia.     

Craniofacial morphology of Homo floresiensis: description, taxonomic affinities, and evolutionary implication

This paper describes in detail the external morphology of LB1/1, the nearly complete and only known cranium of Homo floresiensis. Comparisons were made with a large sample of early groups of the genus Homo to assess primitive, derived, and unique craniofacial traits of LB1 and discuss its evolution. Principal cranial shape differences between H. floresiensis and Homo sapiens are also explored metrically. The LB1 specimen exhibits a marked reductive trend in its facial skeleton, which is comparable to the H. sapiens condition and is probably associated with reduced masticatory stresses. However, LB1 is craniometrically different from H. sapiens showing an extremely small overall cranial size, and the combination of a primitive low and anteriorly narrow vault shape, a relatively prognathic face, a rounded oval foramen that is greatly separated anteriorly from the carotid canal/jugular foramen, and a unique, tall orbital shape. Whereas the neurocranium of LB1 is as small as that of some Homo habilis specimens, it exhibits laterally expanded parietals, a weak suprameatal crest, a moderately flexed occipital, a marked facial reduction, and many other derived features that characterize post-habilis Homo. Other craniofacial characteristics of LB1 include, for example, a relatively narrow frontal squama with flattened right and left sides, a marked frontal keel, posteriorly divergent temporal lines, a posteriorly flexed anteromedial corner of the mandibular fossa, a bulbous lateral end of the supraorbital torus, and a forward protruding maxillary body with a distinct infraorbital sulcus. LB1 is most similar to early Javanese Homo erectus from Sangiran and Trinil in these and other aspects. We conclude that the craniofacial morphology of LB1 is consistent with the hypothesis that H. floresiensis evolved from early Javanese H. erectus with dramatic island dwarfism. However, further field discoveries of early hominin skeletal remains from Flores and detailed analyses of the finds are needed to understand the evolutionary history of this endemic hominin species.     

Comparison of the choice effect and the distance effect in a number-comparison task by FMRI

Behavioral and neurophysiological studies of numerical comparisons have shown a "distance effect," whereby smaller numerical distances between two digits are associated with longer response times and higher activity in the parietal region. In this experiment, we introduced a two-choice condition (between either the smaller/lower or the larger/higher of two digits) and examined its effect on brain activity by fMRI. We observed longer response times and greater activity with the choice of smaller numbers ("choice effect") in several brain regions including the right temporo-parietal region, (pre)cuneus, superior temporal sulcus, precentral gyrus, superior frontal gyrus, bilateral insula, and anterior cingulate cortex. These regions correspond to areas that have been suggested to play a role in attentional shift and response conflict. However, brain activity associated with the distance effect disappeared even though the behavioral distance effect remained. Despite the absence of the distance effect on brain activity, several areas changed activity in relation to response time, including regions that were reported to change activity in both a distance effect and a reaction-time-related manner. The result suggested that the level of task load may change the activity of regions that are responsible for magnitude detection.     

Relationship between seasonal cold acclimatization and mtDNA haplogroup in Japanese

Background

The purpose of this study was to elucidate the interaction between mtDNA haplogroup and seasonal variation that contributes to cold adaptation.

Methods

There were 15 subjects (seven haplotype D subjects and eight haplotype non-D subjects). In summer and winter, the subjects were placed in an environment where the ambient temperature dropped from 27 °C to 10 °C in 30 minutes. After that, they were exposed to cold for 60 minutes.

Results

In summer, the decrease in rectal temperature and increase in oxygen consumption was smaller and cold tolerance was higher in the haplotype non-D group than in the haplotype D group. In winter, no significant differences were seen in rectal temperature or oxygen consumption, but the respiratory exchange ratio decreased in the haplotype D group.

Conclusions

The results of the present study suggest that haplogroup D subjects are a group that changes energy metabolism more, and there appears to be a relationship between differences in cold adaptability and mtDNA polymorphism within the population. Moreover, group differences in cold adaptability seen in summer may decrease in winter due to supplementation by seasonal cold acclimatization.     

A single nucleotide polymorphism of the neuropeptide B/W receptor-1 gene influences the evaluation of facial expressions

Neuropeptide B/W receptor-1 (NPBWR1) is expressed in discrete brain regions in rodents and humans, with particularly strong expression in the limbic system, including the central nucleus of the amygdala. Recently, Nagata-Kuroiwa et al. reported that Npbwr1(-/-) mice showed changes in social behavior, suggesting that NPBWR1 plays important roles in the emotional responses of social interactions.The human NPBWR1 gene has a single nucleotide polymorphism at nucleotide 404 (404A>T; SNP rs33977775). This polymorphism results in an amino acid change, Y135F. The results of an in vitro experiment demonstrated that this change alters receptor function. We investigated the effect of this variation on emotional responses to stimuli of showing human faces with four categories of emotional expressions (anger, fear, happiness, and neutral). Subjects' emotional levels on seeing these faces were rated on scales of hedonic valence, emotional arousal, and dominance (V-A-D). A significant genotype difference was observed in valence evaluation; the 404AT group perceived facial expressions more pleasantly than did the 404AA group, regardless of the category of facial expression. Statistical analysis of each combination of [V-A-D and facial expression] also showed that the 404AT group tended to feel less submissive to an angry face than did the 404AA group. Thus, a single nucleotide polymorphism of NPBWR1 seems to affect human behavior in a social context.     

Human hematopoietic prostaglandin D synthase inhibitor complex structures

In mast and Th2 cells, hematopoietic prostaglandin (PG) D synthase (H-PGDS) catalyses the isomerization of PGH(2) in the presence of glutathione (GSH) to produce the allergic and inflammatory mediator PGD(2). We determined the X-ray structures of human H-PGDS inhibitor complexes with 1-amino-4-{4-[4-chloro-6-(2-sulpho-phenylamino)-[1,3,5]triazin-2-ylmethyl]-3-sulpho-phenylamino}-9,10-dioxo-9,10-dihydro-anthracene-2-sulphonic acid (Cibacron Blue) and 1-amino-4-(4-aminosulphonyl) phenyl-anthraquinone-2-sulphonic acid (APAS) at 2.0 ? resolution. When complexed with H-PGDS, Cibacron Blue had an IC(50) value of 40 nM and APAS 2.1 μM. The Cibacron Blue molecule was stabilized by four hydrogen bonds and π-π stacking between the anthraquinone ring and Trp104, the ceiling of the active site H-PGDS pocket. Among the four hydrogen bonds, the Cibacron Blue terminal sulphonic group directly interacted with conserved residues Lys112 and Lys198, which recognize the PGH(2) substrate α-chain. In contrast, the APAS anthraquinone ring was inverted to interact with Trp104, while its benzenesulphonic group penetrated the GSH-bound region at the bottom of the active site. Due to the lack of extended aromatic rings, APAS could not directly hydrogen bond with the two conserved lysine residues, thus decreasing the total number of hydrogen bond from four to one. These factors may contribute to the 50-fold difference in the IC(50) values obtained for the two inhibitors.