Developmental Trajectories of Body Mass Index Among Japanese Children and Impact of Maternal Factors during Pregnancy

Background

The aims of this study were to 1) determine the distinct patterns of body mass index (BMI) trajectories in Japanese children, and 2) elucidate the maternal factors during pregnancy, which contribute to the determination of those patterns.

Methodology/Principal Findings

All of the children (1,644 individuals) born in Koshu City, Japan, between 1991 and 1998 were followed in a longitudinal study exploring the subjects’ BMI. The BMI was calculated 11 times for each child between birth and 12 years of age. Exploratory latent class growth analyses were conducted to identify trajectory patterns of the BMI z-scores. The distribution of BMI trajectories were best characterized by a five-group model for boys and a six-group model for girls. The groups were named “stable thin,” “stable average,” “stable high average,” “progressive overweight,” and “progressive obesity” in both sexes; girls were allocated to an additional group called “progressive average.” Multinomial logistic regression found that maternal weight, smoking, and skipping breakfast during pregnancy were associated with children included in the progressive obesity pattern rather than the stable average pattern. These associations were stronger for boys than for girls.

Conclusions/Significance

Multiple developmental patterns in Japanese boys and girls were identified, some of which have not been identified in Western countries. Maternal BMI and some unfavorable behaviors during early pregnancy may impact a child’s pattern of body mass development. Further studies to explain the gender and regional differences that were identified are warranted, as these may be important for early life prevention of weight-associated health problems.     

Aligned genetic linkage maps of apple rootstock cultivar ‘JM7’ and Malus sieboldii ‘Sanashi 63’ constructed with novel EST-SSRs

Identification of markers associated with genes of interest and quantitative trait loci (QTLs), combined with high-density genetic linkage maps, can help reduce labor and costs by enabling marker-assisted selection (MAS). In this study, a dwarfing apple rootstock cultivar ??JM7?? (Malus prunifolia × Malus pumila ??Malling 9??) and wild apple Malus sieboldii ??Sanashi 63?? (section Sorbomalus) were used for constructing genetic linkage maps. Here, a species from section Sorbomalus was used for the first time as a target species in a genome-wide mapping study. We also developed and mapped 137 novel-expressed sequence tag-simple sequence repeat (EST-SSR) markers. The genetic linkage maps of ??JM7?? and ??Sanashi 63?? consisted of 415 and 310 loci and spanned 998.0 and 981.8?cM, respectively, comparable to the reference map of Malus × domestica ??Discovery??. A BLASTN search revealed that all of the EST-SSR sequences used in this study exhibited very high homology to one or more previously characterized apple genome contigs. Although the most homologous contigs of 89 EST-SSRs were located within the same linkage groups (LGs) identified by mapping analysis, the other 48 EST-SSRs were aligned into contigs positioned in different LGs than those identified by mapping. When search criteria were expanded to include the five most homologous contigs of each EST-SSR, at least one of the top five contigs for 15 of these 48 EST-SSRs corresponded to the LG obtained by mapping. The maps of ??JM7?? and ??Sanashi 63?? may be useful for analyzing important rootstock characteristics and identifying markers for MAS.     

Vasohibin-2 expressed in human serous ovarian adenocarcinoma accelerates tumor growth by promoting angiogenesis

Vasohibin-1 (VASH1) is a VEGF-inducible endothelium-derived angiogenesis inhibitor and VASH2 is its homolog. Our previous analysis revealed that VASH1 is expressed in endothelial cells to terminate angiogenesis, whereas VASH2 is expressed in infiltrating mononuclear cells mobilized from bone marrow to promote angiogenesis in a mouse model of hypoxia-induced subcutaneous angiogenesis. To test the possible involvement of VASH2 in the tumor, we examined human ovarian cancer cells for the presence of VASH2. Immunohistochemical analysis revealed that VASH2 protein was preferentially detected in cancer cells of serous ovarian adenocarcinoma. We then used SKOV-3 and DISS, two representative human serous adenocarcinoma cell lines, and examined the role of VASH2 in the tumor. The knockdown of VASH2 showed little effect on the proliferation of cancer cells in vitro but notably inhibited tumor growth, peritoneal dissemination, and tumor angiogenesis in a murine xenograft model. Next, we stably transfected the human VASH2 gene into two types of murine tumor cells, EL-4 and MLTC-1, in which endogenous VASH2 was absent. When either EL-4 or MLTC-1 cells were inoculated into VASH2 (-/-) mice, the VASH2 transfectants formed bigger tumors when compared with the controls, and the tumor microvessel density was significantly increased. VASH2 stimulated the migration of endothelial cells, and its increased expression in cancer cells is related to the decrease of mir-200b. These results indicate that VASH2 expressed in serous ovarian carcinoma cells promoted tumor growth and peritoneal dissemination by promoting angiogenesis. Mol Cancer Res; 10(9); 1135-46. ?2012 AACR.     

Muscle RING-finger protein-1 (MuRF1) as a connector of muscle energy metabolism and protein synthesis

During pathophysiological muscle wasting, a family of ubiquitin ligases, including muscle RING-finger protein-1 (MuRF1), has been proposed to trigger muscle protein degradation via ubiquitination. Here, we characterized skeletal muscles from wild-type (WT) and MuRF1 knockout (KO) mice under amino acid (AA) deprivation as a model for physiological protein degradation, where skeletal muscles altruistically waste themselves to provide AAs to other organs. When WT and MuRF1 KO mice were fed a diet lacking AA, MuRF1 KO mice were less susceptible to muscle wasting, for both myocardium and skeletal muscles. Under AA depletion, WT mice had reduced muscle protein synthesis, while MuRF1 KO mice maintained nonphysiologically elevated levels of skeletal muscle protein de novo synthesis. Consistent with a role of MuRF1 for muscle protein turnover during starvation, the concentrations of essential AAs, especially branched-chain AAs, in the blood plasma significantly decreased in MuRF1 KO mice under AA deprivation. To clarify the molecular roles of MuRF1 for muscle metabolism during wasting, we searched for MuRF1-associated proteins using pull-down assays and mass spectrometry. Muscle-type creatine kinase (M-CK), an essential enzyme for energy metabolism, was identified among the interacting proteins. Coexpression studies revealed that M-CK interacts with the central regions of MuRF1 including its B-box domain and that MuRF1 ubiquitinates M-CK, which triggers the degradation of M-CK via proteasomes. Consistent with MuRF1's role of adjusting CK activities in skeletal muscles by regulating its turnover in vivo, we found that CK levels were significantly higher in the MuRF1 KO mice than in WT mice. Glucocorticoid modulatory element binding protein-1 and 3-hydroxyisobutyrate dehydrogenase, previously identified as potential MuRF1-interacting proteins, were also ubiquitinated MuRF1-dependently. Taken together, these data suggest that, in a multifaceted manner, MuRF1 participates in the regulation of AA metabolism, including the control of free AAs and their supply to other organs under catabolic conditions, and in the regulation of ATP synthesis under metabolic-stress conditions where MuRF1 expression is induced.     

Structures of dimeric nonstandard nucleotide triphosphate pyrophosphatase from Pyrococcus horikoshii OT3: functional significance of interprotomer conformational changes

Nonstandard nucleotide triphosphate pyrophosphatase (NTPase) can efficiently hydrolyze nonstandard purine nucleotides in the presence of divalent cations. The crystal structures of the NTPase from Pyrococcus horikoshii OT3 (PhNTPase) have been determined in two unliganded forms and in three liganded forms with inosine 5′-monophosphate (IMP), ITP and Mn²⁺, which visualize the recognition of these ligands unambiguously. The overall structure of PhNTPase is similar to that of previously reported crystal structures of the NTPase from Methanococcus jannaschii and the human ITPase. They share a similar protomer folding with two domains and a similar homodimeric quaternary structure. The dimeric interface of NTPase is well conserved, and the dimeric state might be important to constitute the active site of this enzyme. A conformational analysis of the five snapshots of PhNTPase structures using the multiple superposition method reveals that IMP, ITP and Mn²⁺ bind to the active site without inducing large local conformational changes, indicating that a combination of interdomain and interprotomer rigid-body shifts mainly describes the conformational change of PhNTPase. The interdomain and interprotomer conformations of the ITP liganded form are essentially the same as those observed in the unliganded form 1, indicating that ITP binding to PhNTPase in solution may follow the selection mode in which ITP binds to the subunit that happens to be in the conformation observed in the unliganded form 1. In contrast to the human ITPase inducing a large domain closure upon ITP binding, the interdomain active site cleft is generally closed in PhNTPase and only the IMP binding form shows a remarkable domain opening by 14° only in the B subunit. The interprotomer rigid-body rotation of PhNTPase has a tendency to keep the dimeric 2-fold symmetry, which is also true in human ITPase, thereby suggesting its relevance to the positive cooperativity of the dimeric NTPases. The exception of this rule is observed in the IMP liganded form in which the dimeric 2-fold symmetry is broken by a 3° interprotomer rotation in an unusual direction. A combination of the exceptional interdomain and interprotomer relocations is most likely the reason for the observed asymmetric IMP binding that might be necessary for PhNTPase to release the reaction product IMP.     

The visual pigments of a deep-sea myctophid fish Myctophum nitidulum Garman; an HPLC and spectroscopic description of a non-paired rhodopsin–porphyropsin system

Unusually for a deep-sea fish, the retina of the myctophid (lanternfish) Myctophum nitidulum was found to contain two visual pigments, shown by extract spectrophotometry to be maximally sensitive at 468 and 522 nm, respectively, giving this species one of the broadest spectral ranges of all deep-sea fishes. High performance liquid chromatography (HPLC) indicated that the retina contained both A₁- and A₂-based chromophores. Surprisingly, the maximum absorbance (λ_max) values of the two visual pigments were too far apart to form a rhodopsin–porphyropsin 'pigment pair', suggesting they were based on distinct opsins each linked to a different chromophore. This might be an adaptation to the detection of both long-wave bioluminescence and residual shorter-wave surface illumination, and could be related to this animal's tendency to migrate towards surface waters at night.     

The continuous public goods game and the evolution of cooperative sex ratios

Some animals, such as Melittobia wasps and surface-living mites, have extremely female-biased sex ratios that cannot be explained by the existing local mate competition (LMC) theories. The restricted production of sons may entail cooperation among mothers, enabling the production of more daughters and avoiding severe competition among sons for insemination access. These unusual examples are characterized by the long-term cohabitation of egg-layers (foundresses) on resource patches and possible contact with oviposited eggs. By applying the logic of mutual policing, we develop a novel game theoretical model for the evolution of cooperation in sex-ratio traits. This is the first attempt to model the evolution of sex ratios based on iterated games. We assumed that foundresses have two abilities to enable mutual policing: they can monitor the sex ratio in the resource patch, and they can punish defectors that produce an overabundance of males. Numerical analysis and evolutionary simulations demonstrate that cooperative low sex ratios can evolve when the number of foundresses per patch is sufficiently small. Our model predicts a slight, but steady increase in oviposition sex ratios with an increase in the number of foundresses, which mimics the phenomenon observed in several animals with extremely female-biased sex ratios. We also discuss the relationship between our model and other models of sex-ratio evolution.