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Heterogametic sex chromosomes have evolved independently in various lineages of vertebrates. Such sex chromosome pairs often contain nonrecombining regions, with one of the chromosomes harboring a master sex-determining (SD) gene. It is hypothesized that these sex chromosomes evolved from a pair of autosomes that diverged after acquiring the SD gene. By linkage and association mapping of the SD locus in fugu (Takifugu rubripes), we show that a SNP (C/G) in the anti-Müllerian hormone receptor type II (Amhr2) gene is the only polymorphism associated with phenotypic sex. This SNP changes an amino acid (His/Asp384) in the kinase domain. While females are homozygous (His/His384), males are heterozygous. Sex in fugu is most likely determined by a combination of the two alleles of Amhr2. Consistent with this model, the medaka hotei mutant carrying a substitution in the kinase domain of Amhr2 causes a female phenotype. The association of the Amhr2 SNP with phenotypic sex is conserved in two other species of Takifugu but not in Tetraodon. The fugu SD locus shows no sign of recombination suppression between X and Y chromosomes. Thus, fugu sex chromosomes represent an unusual example of proto-sex chromosomes. Such undifferentiated X-Y chromosomes may be more common in vertebrates than previously thought.

In a previous study, we demonstrated that the carotenoid neoxanthin was contained in young leafy vegetables including spinach and showed a fat accumulation inhibitory effect in vitro . To evaluate the bioavailability of neoxanthin, a raw young spinach leaf (100 g day –1 for 4 weeks) intake test was performed on 14 participants (36.5 ± 8.0 years; male:female ratio = 9:5). Neoxanthin, neochrome, β–carotene, and lutein concentration in the spinach and blood of participants (before and after the test) was measured using high performance liquid chromatography. Neither neoxanthin nor neochrome was detected in the blood samples, whereas β–carotene and lutein concentration significantly increased (1.4– and 1.9–fold, respectively) during testing. Neoxanthin bioavailability in humans is low; thus, it is unlikely to have a fat accumulation inhibitory effect in vivo , contrary to the result in vitro . Ingesting the leafy vegetables raw can help maintain high neoxanthin levels, but it is not beneficial for neoxanthin bioavailability.

Epidemiological studies in humans have suggested that tomato consumption and the compositional ratios of Prevotella , Megamonas, and Streptococcus in the intestinal microbiota are related to intestinal permeability. In this study, we investigated the causal relationship using Caenorhabditis ( C .) elegans . We cultured Escherichia coli OP50 (the standard C . elegans food), Prevotella ( P .) copri JCM 13464 T , Megamonas funiformis JCM 14723 T , and Streptococcus salivarius JCM 5707 T in either normal medium or medium containing 1% (v/v) tomato juice (TJ medium), fed these bacteria to C. elegans for three days, and evaluated intestinal permeability using the Smurf assay. The proportion of Smurf individuals was significantly lower in C. elegans fed P. copri cultured in TJ medium than in those fed the same bacteria cultured in normal medium, while other strains showed no such medium-dependent differences. Interestingly, heat-killed P. copri grown in normal medium also reduced the proportion of Smurf individuals. Furthermore, P. copri grown in TJ medium exhibited a lower survival rate after seeding on nematode growth medium, an effect not observed in other strains. Liquid chromatography-tandem mass spectrometry analysis revealed that P. copri cultured in TJ medium accumulated L-(-)-3-phenyllactic acid (L-(-)-3-PLA), a compound known for its antibacterial properties through oxidative stress and its protective effects on the intestinal barrier. In contrast, the levels of known antioxidants such as 2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid and Cyclo(phenylalanyl-prolyl) were decreased. Culturing P. copri in normal medium supplemented with L-(-)-3-PLA alone did not reduce survival, suggesting that both L-(-)-3-PLA accumulation and the depletion of antioxidants contribute to reduced viability. Additionally, L-(-)-3-PLA directly suppressed intestinal permeability in C. elegans . In conclusion, the results of this study suggest that TJ may inhibit increased intestinal permeability through both rendering P. copri vulnerable and the direct effects of L-(-)-3-PLA. Further studies are needed to determine the relevance of these findings to humans.

Background: The Tohoku Medical Megabank Project (TMM) was established to realize personalized healthcare and medicine using genomic and omics data. This study evaluated the validity and reproducibility of food group intakes derived from a self-administered food frequency questionnaire (TMM-FFQ) that included the response option “constitutionally unable to eat/drink it” among community-dwelling Japanese adults.Methods: Participants comprised 89 men and 124 women aged ≥20 years from Miyagi Prefecture. Participants completed weighed food records (WFRs) for 3 consecutive days per season as reference intake and FFQs in 2019 (FFQ1) and 2021 (FFQ3). Spearman’s rank correlation coefficients (CCs) were calculated for correlations between food group intakes estimated from the 12-day WFR and FFQ3 (validity), and for correlations between those estimated from the FFQ1 and FFQ3 (reproducibility). Cross-classification according to quintiles using FFQ and WFR data was also performed.Results: The percentage of participants who chose the “constitutionally unable to eat/drink it” option was non-negligible for some food groups. In the validity analysis, CCs were >0.40 for many food groups; the median across 21 food groups was 0.49 in men and 0.45 in women. The median percentages of cross-classification into exact plus adjacent quintiles were 73.0% in men and 66.9% in women. In the reproducibility analysis, CCs were >0.50 for many food groups; the median across 21 food groups was 0.60 in men and 0.51 in women.Conclusion: The validity of the TMM-FFQ compared with 12-day WFR and the reproducibility of the TMM-FFQ were reasonable for food groups in the TMM cohort studies.

Background: More research is needed to clarify the health effects of dietary carotenoid intakes, and this requires the use of high-quality assessments of habitual dietary intake. Cohort studies from the Tohoku Medical Megabank Organization included a self-administered food frequency questionnaire (TMM-FFQ) for community-dwelling adults. This study evaluated the validity of carotenoid intakes derived from the TMM-FFQ using serum carotenoid concentrations as the gold standard.Methods: In Miyagi Prefecture, 88 men and 124 women aged ≥20 years voluntarily agreed to participate in the study and provided completed TMM-FFQs and blood samples in 2019 and 2021. Carotenoids examined included α-carotene, β-carotene, β-cryptoxanthin, and lycopene. Intraclass correlation coefficients (ICCs) were calculated to assess correlations between serum concentrations in 2019 and 2021. Spearman’s rank correlation coefficients were calculated to evaluate the correlations between energy-adjusted dietary carotenoid intakes from the TMM-FFQ in 2021 and the average serum carotenoid concentrations in 2019 and 2021, with correction for the attenuating effect of random within-individual variation.Results: The ICCs between serum concentrations over the 2 years were >0.50 for all carotenoids. Among men, correlation coefficients were 0.33 for α-carotene, 0.42 for β-carotene, 0.50 for β-cryptoxanthin, and −0.09 for lycopene. Among women, the coefficients were lower than those for men, except for lycopene: 0.11 for α-carotene, 0.23 for β-carotene, 0.21 for β-cryptoxanthin, and 0.28 for lycopene.Conclusion: The TMM-FFQ demonstrated reasonable validity for assessing intakes of α-carotene, β-carotene, and β-cryptoxanthin among men, but not among women, in the TMM cohort studies when using serum concentrations as the gold standard.

Background: The Tohoku Medical Megabank Project has initiated the Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study) including genomic and omics investigations and conducted a self-administered food frequency questionnaire with the response option “constitutionally unable to eat or drink it” for individual food items (TMM-FFQ) for pregnant women. This study evaluated the validity of the TMM-FFQ among pregnant women.Methods: Participants comprised 122 pregnant women aged ≥20 years residing in Miyagi Prefecture who completed weighed food records (WFRs) for 3 days as reference intake and the TMM-FFQ during mid-pregnancy. Correlations between nutrient or food group intakes based on the WFR and the TMM-FFQ were calculated using Spearman’s rank correlation coefficients (CCs), adjusting for energy intake and correcting for random within-individual variation of WFR. Cross-classification was also conducted according to quintiles using the WFR and TMM-FFQ data.Results: The percentages of participants who chose the “constitutionally unable to eat or drink it” option were >3% for seven food and drink items. CCs were >0.30 for 31 nutrients; the median across energy and 44 nutrients was 0.41. CCs were >0.30 for 14 food groups; the median across 20 food groups was 0.35. The median percentages of cross-classification into exact plus adjacent quintiles and extreme quintiles were 63.1% and 3.3% for energy and nutrients and 61.9% and 4.1% for food groups, respectively.Conclusion: The validity of the TMM-FFQ compared with the WFR was reasonable for certain nutrients and food groups among pregnant women in the TMM BirThree Cohort Study.

Background Associations of fruit and vegetable consumption before and during pregnancy with birth weight of new-borns and the risk of low birth weight (LBW) remain unclear. Methods Between July 2013 and March 2017, we recruited 23,406 pregnant women in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study). Fruit and vegetable consumption before and during pregnancy was calculated using food frequency questionnaires. Information regarding birth weight was obtained from medical records, and LBW was defined as < 2500 g. We used a multivariable linear regression model and a multivariate logistic regression model to assess associations between fruit and vegetable consumption and birth weight/risk of LBW. Results In total, 17,610 women were included in the analysis. Mean birth weight was 3061.8 ± 354.1 g, and 5.4% of the new-borns had LBW. Compared to women in the lowest quartile of fruit consumption between pre- and early pregnancy, women in the highest quartile had heavier new-borns (β = 49.4; 95% CI: 34.1–64.7) and lower risk of LBW (OR: 0.79; 95% CI: 0.65–0.95). Women in the highest quartile of fruit consumption from early to mid-pregnancy also had heavier new-borns (β = 32.3; 95% CI: 17.1–47.6), and they tended to have lower risk of LBW (OR: 0.83; 95% CI: 0.69–1.01). Results of analysing the association between changes in fruit consumption from pre- to mid-pregnancy and birth outcomes revealed that women with continuous high fruit consumption from pre- to mid-pregnancy had heavier new-borns (β = 37.6; 95% CI: 25.0–50.3), but they did not have lower risk of LBW (OR: 0.90; 95% CI: 0.77–1.06). Associations involving vegetable consumption and birth weight/risk of LBW were not observed. Conclusions Fruit consumption before and during pregnancy was positively associated with birth weight of new-borns and negatively associated with risk of LBW.

It remains unclear how the various environmental factors are combined in practice to influence vegetable preferences in school-aged children. This study aimed to clarify the environmental factors during infancy and their association with vegetable preference in school-aged children. To find clusters of early childhood environmental factors, we conducted a factor analysis on 58 items related to early childhood environmental factors and a k-means cluster analysis using the factors obtained. The association of the extracted factors and clusters with vegetable preferences was assessed by multiple regression analysis. Twelve factors relating to vegetable eating, cooking and harvesting experience, and parental attitudes were extracted by factor analysis. Three clusters, “low awareness of experiences”, “high awareness” and “low positive encouragement”, were then extracted. In the multiple regression analysis, all 12 factors were found to be associated with vegetable preferences. Furthermore, it was found that the “high awareness” group had a significantly higher score for vegetable preference than the “low awareness of experiences” group (β = 0.56, 95% CI: 0.37–0.74). Thus, the study found that environmental factors during infancy, in isolation and combination, influenced vegetable preferences in school-aged children. Assessing the combination of various environmental factors during infancy may contribute to a better understanding of future vegetable preferences.

The association between fruit and vegetable consumption before and during pregnancy and offspring’s physical growth has been well reported, but no study has focused on offspring’s neurological development. We aimed to explore the association between maternal fruit and vegetable consumption before and during pregnancy and developmental delays in their offspring aged 2 years. Between July 2013 and March 2017, 23 406 women were recruited for the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Fruit and vegetable consumption was calculated using FFQ, and offspring’s developmental delays were evaluated by the Ages & Stages Questionnaires, Third Edition (ASQ-3) for infants aged 2 years. Finally, 10 420 women and 10 543 infants were included in the analysis. Totally, 14·9 % of children had developmental delay when screened using the ASQ-3. Women in the highest quartile of vegetable consumption from pre-pregnancy to early pregnancy and from early to mid-pregnancy had lower odds of offspring’s developmental delays (OR 0·74; 95 % CI 0·63, 0·89 and OR 0·70; 95 % CI 0·59, 0·84, respectively) than women in the lowest quartile. Women in the highest quartile of fruit consumption from early to mid-pregnancy had lower odds of offspring’s developmental delays (OR 0·78; 95 % CI 0·66, 0·92) than women in the lowest quartile. In conclusion, high fruit and vegetable consumption before and during pregnancy was associated with a lower risk of developmental delays in offspring aged 2 years.

Background Oral health has a significant effect on longevity and quality of life. Periodontal diseases and dental caries are the primary causes of tooth loss, with the former being more prevalent than the latter. Antioxidants are associated with periodontal diseases. However, comprehensive analyses of this association are limited in literature, especially when focusing on circulating antioxidants. This study analyzed the association between antioxidant levels in the blood and skin along with periodontal diseases in populations with normal occlusion. Methods This cross-sectional study was conducted as part of the Iwaki Health Promotion Project in 2022. Overall, 456 individuals aged ≥ 20 years with healthy occlusion were included. Multivariate logistic regression analyses were performed, with periodontal disease defined as the primary outcome variable, circulating antioxidant levels as the exposure, and the following covariates: age, sex, smoking and drinking status, sugar intake, educational background, and oral care habits. In addition, the potential causal direction between antioxidant levels and periodontal diseases were explored using Bayesian network analysis. Results Individuals with the fifth quintile of blood and skin carotenoid levels had a lower odds ratio (OR) for periodontal diseases compared with those with the first quintile (blood: adjusted OR = 0.32 [95% confidence interval (CI), 0.16–0.64], skin: adjusted OR = 0.45 [95% CI, 0.23–0.88]). In particular, blood lutein and lycopene levels, but not vitamin A, C, and E levels, were significantly associated with periodontal diseases. Bayesian network analysis suggested that carotenoid levels may be a potential causal factor for periodontal diseases, and this association may be mediated by salivary immunoglobulin A and oral dysbiosis. Conclusions Blood and skin carotenoid levels are associated with the prevalence of periodontal diseases.