The luciferase-based in vivo protein-protein interaction assay revealed that CHK1 promotes PP2A and PME-1 interaction.

Protein phosphatase 2A (PP2A) is an essential serine/threonine protein phosphatase, and its dysfunction is involved in the onset of cancer and neurodegenerative disorders. PP2A functions as a trimeric holoenzyme whose composition is regulated by the methyl-esterification (methylation) of the PP2A catalytic subunit (PP2Ac). Protein phosphatase methylesterase-1 (PME-1) is the sole PP2Ac methylesterase, and the higher PME-1 expression is observed in various cancer and neurodegenerative diseases. Apart from serving as a methylesterase, PME-1 acts as a PP2A inhibitory protein, binding directly to PP2Ac and suppressing its activity. The intricate function of PME-1 hinders drug development by targeting the PME-1/PP2Ac axis. This study applied the NanoBiT system, a bioluminescence-based protein interaction assay, to elucidate the molecular mechanism that modulates unknown PME-1/PP2Ac protein-protein interaction (PPI). Compound screening identified that the CHK1 inhibitors inhibited PME-1/PP2Ac association without affecting PP2Ac methylation levels. CHK1 directly phosphorylates PP2Ac to promote PME-1 association. Phospho-mass spectrometry identified multiple phospho-sites on PP2Ac, including the Thr219, that affect PME-1 interaction. An anti-phospho-Thr219 PP2Ac antibody was generated and showed that CHK1 regulates the phosphorylation levels of this site in cells. On the contrary, in vitro phosphatase assay showed that CHK1 is the substrate of PP2A, and PME-1 hindered PP2A-mediated dephosphorylation of CHK1. Our data provides novel insights into the molecular mechanisms governing the PME-1/PP2Ac PPI and the triad relationship between PP2A, PME-1, and CHK1.

Targeted insertion of conditional expression cassettes into the mouse genome using the modified i-PITT.

BACKGROUND: Transgenic (Tg) mice are widely used in biomedical research, and they are typically generated by injecting transgenic DNA cassettes into pronuclei of one-cell stage zygotes. Such animals often show unreliable expression of the transgenic DNA, one of the major reasons for which is random insertion of the transgenes. We previously developed a method called "pronuclear injection-based targeted transgenesis" (PITT), in which DNA constructs are directed to insert at pre-designated genomic loci. PITT was achieved by pre-installing so called landing pad sequences (such as heterotypic LoxP sites or attP sites) to create seed mice and then injecting Cre recombinase or PhiC31 integrase mRNAs along with a compatible donor plasmid into zygotes derived from the seed mice. PITT and its subsequent version, improved PITT (i-PITT), overcome disadvantages of conventional Tg mice such as lack of consistent and reliable expression of the cassettes among different Tg mouse lines, and the PITT approach is superior in terms of cost and labor. One of the limitations of PITT, particularly using Cre-mRNA, is that the approach cannot be used for insertion of conditional expression cassettes using Cre-LoxP site-specific recombination. This is because the LoxP sites in the donor plasmids intended for achieving conditional expression of the transgene will interfere with the PITT recombination reaction with LoxP sites in the landing pad. RESULTS: To enable the i-PITT method to insert a conditional expression cassette, we modified the approach by simultaneously using PhiC31o and FLPo mRNAs. We demonstrate the strategy by creating a model containing a conditional expression cassette at the Rosa26 locus with an efficiency of 13.7%. We also demonstrate that inclusion of FLPo mRNA excludes the insertion of vector backbones in the founder mice. CONCLUSIONS: Simultaneous use of PhiC31 and FLP in i-PITT approach allows insertion of donor plasmids containing Cre-loxP-based conditional expression cassettes.

Functional AGXT2 SNP rs180749 variant and depressive symptoms: Baseline data from the Aidai Cohort Study in Japan.

No study has shown the relationship between alanine-glyoxylate aminotransferase 2 (AGXT2) single nucleotide polymorphisms (SNPs) and depressive symptoms. The present case-control study examined this relationship in Japanese adults. Cases and control participants were selected from those who participated in the baseline survey of the Aidai Cohort Study, which is an ongoing cohort study. Cases comprised 280 participants with depressive symptoms based on a Center for Epidemiologic Studies Depression Scale (CES-D) score ≥ 16. Control participants comprised 2034 participants without depressive symptoms based on the CES-D who had not been diagnosed by a physician as having depression or who had not been currently taking medication for depression. Adjustment was made for age, sex, smoking status, alcohol consumption, leisure time physical activity, education, body mass index, hypertension, dyslipidemia, and diabetes mellitus. Compared with the GG genotype of rs180749, both the GA and AA genotypes were significantly positively associated with the risk of depressive symptoms assessed by the CES-D: the adjusted odds ratios for the GA and AA genotypes were 2.83 (95% confidence interval [CI] 1.23-8.24) and 3.10 (95% CI 1.37-8.92), respectively. The TGC haplotype of rs37370, rs180749, and rs16899974 was significantly inversely related to depressive symptoms (crude OR 0.67; 95% CI 0.49-0.90), whereas the TAC haplotype was significantly positively associated with depressive symptoms (crude OR 1.24; 95% CI 1.01-1.52). This is the first study to show significant associations between AGXT2 SNP rs180749, the TGC haplotype, and the TAC haplotype and depressive symptoms.

Nut consumption during pregnancy is associated with decreased risk of peer problems in 5-year-old Japanese children.

OBJECTIVES: Nuts are nutrient-dense foods rich in unsaturated fatty acids, protein, dietary fiber, vitamins, and minerals. The present prebirth cohort study examined the association between maternal nut intake during pregnancy and the risk of childhood behavioral problems in 5-year-old Japanese children. METHODS: Study subjects were 1199 mother-child pairs. Dietary intake was assessed using a diet history questionnaire. Emotional problems, conduct problems, hyperactivity problems, peer problems, and low prosocial behavior were assessed using the parent-reported version of the Strengths and Difficulties Questionnaire. Adjustments were made for a priori-selected nondietary confounders and potentially related dietary factors. RESULTS: Compared with mothers who had not eaten nuts during pregnancy, mothers who had eaten nuts had a significantly reduced risk of peer problems in children; the adjusted odds ratio was 0.64 (95% confidence interval: 0.42-0.97). There were no measurable associations between maternal consumption of nuts during pregnancy and the risk of childhood emotional problems, conduct problems, hyperactivity problems, and low prosocial behavior. CONCLUSIONS: Maternal consumption of nuts during pregnancy may be associated with a decreased risk of peer problems in 5-year-old children.

Coffee and caffeine intake reduces risk of ulcerative colitis: a case-control study in Japan.

BACKGROUND AND AIM: Although diet is one of the potential environmental factors affecting ulcerative colitis (UC), evidence is not sufficient to draw definitive conclusions. This Japanese case-control study examined the association between the consumption of coffee, other caffeine-containing beverages and food, and total caffeine and the risk of UC. METHODS: The study involved 384 UC cases and 665 control subjects. Intake of coffee, decaffeinated coffee, black tea, green tea, oolong tea, carbonated soft drinks, and chocolate snacks was measured with a semiquantitative food-frequency questionnaire. Adjustments were made for sex, age, pack-years of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, body mass index, and intake of vitamin C, retinol, and total energy. RESULTS: Higher consumption of coffee and carbonated soft drinks was associated with a reduced risk of UC with a significant dose-response relationship (P for trend for coffee and carbonated soft drinks were <0.0001 and 0.01, respectively), whereas higher consumption of chocolate snacks was significantly associated with an increased risk of UC. No association was observed between consumption of decaffeinated coffee, black tea, green tea, or oolong tea and the risk of UC. Total caffeine intake was inversely associated with the risk of UC; the adjusted odds ratio between extreme quartiles was 0.44 (95% confidence interval: 0.29-0.67; P for trend <0.0001). CONCLUSIONS: We confirmed that intake of coffee and caffeine is also associated with a reduced risk of UC in Japan where people consume relatively low quantities of coffee compared with Western countries.

Maternal fat intake in pregnancy and risk of depressive symptoms in Japanese adolescents: the Kyushu Okinawa Maternal and Child Health Study.

The current prebirth cohort study investigated the association between maternal intake of specific types of fatty acids during pregnancy and adolescent depressive symptoms based on the Center for Epidemiologic Studies Depression Scale. Subjects were 873 mother-child pairs. Dietary intake during the preceding month was assessed using a self-administered diet history questionnaire. The risk of depressive symptoms was 23.3% among the 873 adolescents at 13 years of age. Higher maternal saturated fatty acid intake during pregnancy was independently associated with a reduced risk of depressive symptoms in adolescents. Maternal intake of total fat, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid and cholesterol during pregnancy was not significantly related to depressive symptoms in adolescents. Higher maternal intake of saturated fatty acids during pregnancy may be inversely associated with adolescent depressive symptoms.

Clinical Features and Prognostic Factors in Anti-Myelin Oligodendrocyte Glycoprotein Antibody Positive Optic Neuritis.

In order to review the clinical features of anti-myelin oligodendrocyte glycoprotein antibody positive optic neuritis (MOGON), we investigated the clinical characteristics, visual function, optical coherence tomography findings, and magnetic resonance imaging of 31 patients (44 eyes). MOGON was more common in middle age without sex difference and was characterised by pain on eye movement and optic disc swelling. Magnetic resonance imaging lesions tended to be long with inflammation around the optic nerve sheath; longer lesions were associated with worse visual acuities at onset. Recurrence was significantly associated with retinal nerve fibre layer thinning, and thus, it is important to reduce recurrence as much as possible.

Sex differences in the association between smoking exposure and prevalence of wheeze and asthma in 3-year-old children.

OBJECTIVE: We examined independent and joint associations between prenatal and postnatal smoking exposure and the prevalence of wheeze and asthma among 3-year-old Japanese children. Sex differences were also investigated. METHODS: Smoking exposure, allergic symptoms, and potential confounding factor data were collected using a self-administered questionnaire. Wheeze was defined on the basis of the International Study of Asthma and Allergies in Childhood criteria. Physician-diagnosed asthma was considered to be present if a physician had diagnosed the child with asthma any time before the survey was administered. RESULTS: There were 6402 pediatric participants in this study. Maternal smoking throughout pregnancy and household smoking exposure during the first year of life were associated with an increased prevalence of wheeze among girls but not boys (adjusted odds ratio (OR) [95% CI] = 2.00 [1.13-3.42] and 1.34 [1.07-1.68], respectively). Girls exposed to both prenatal maternal smoking and postnatal household smoking exposure had a significantly higher prevalence of wheeze and physician-diagnosed asthma compared with girls without these exposures (adjusted OR [95% CI] = 2.06 [1.39-3.01] and 1.86 [1.01-3.26], respectively). No association was observed between perinatal smoking exposure and the prevalence of wheeze or asthma among boys. Significant interactions between sex and smoking exposure affecting wheeze and asthma were also found (p for interaction = 0.0003 and 0.01, respectively). CONCLUSION: We found a positive association between perinatal smoking exposure and the prevalence of wheeze and asthma only among girls. Effects of perinatal smoking exposure on wheeze and asthma might be sex specific. Further research is required.

The safety of plasma apheresis from donors recovering from COVID-19 infection in Japan.

PURPOSE: Since 2020, the novel coronavirus infection (COVID-19) has spread globally. A few studies have investigated the safety of COVID-19 convalescent plasma (CCP) apheresis from COVID-19. This study was the first retrospective observational study of CCP in Japan. METHODS: We recruit donors from April 2020 to November 2021 and plasmapheresis in our center (NCGM: national center for global health and medicine). We set the primary endpoint as the Donors Adverse Event (DAE) occurrence at the time of the CCP collection. Variable selection was used to explore the determinants of DAE. RESULTS: Mean and SD age was 50.5 (10.6) years old. Seventy-three (42.2 %) were female, and 87 (33.3 %) were multiple-times donors. Twelve (6.97 % by donors and 4.6 % in total collections) adverse events occurred. The DAEs were VVR (Vaso Vagal Reaction), paresthesia, hypotension, agitation, dizziness, malaise, and hearing impairment/paresthesia. Half of them were VVR during apheresis. DAE occurred only in first-time donors and more in severe illnesses such as using ventilation and ECMO. From the donor characteristics and variable selection, the risk factors are as follows: younger age, female, the severity of disease at the time of the disease, and lower SBP before initiation. Our DAE incidence did not differ from previous studies. DAEs were more likely to occur in CCP apheresis than in healthy donors. CONCLUSION: We confirm the safety of CCP apheresis in this study, although DAEs were more than healthy donors. More caution should be exercised in the plasma collection for future outbreaks of emerging infectious diseases.

Long-term transition of antibody titers in healthcare workers following the first to fourth doses of mRNA COVID-19 vaccine: Comparison of two automated SARS-CoV-2 immunoassays.

Anti-spike receptor binding domain (S-RBD) antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which best correlates with virus-neutralizing antibody is useful for estimating the period of protection and identifying the timing of additional booster doses. Long-term transition of the S-RBD antibody titer and the antibody responses among healthy individuals remain unclear. In the present study, therefore, we monitored the S-RBD antibody titers of 16 healthcare workers every 4 weeks for 76 weeks after vaccination with a fourth dose of mRNA-1273 (Moderna) following three doses of BNT162b2 (Pfizer/BioNTech) using two commercial automated immunoassays (Roche and Abbott). Two antibody responses to the vaccine were similar with an up-down change before and after the second (weeks 3), third (weeks 40) and fourth (week 72) vaccinations, but the titer did not fall below the assay's positivity threshold in any individual. The peak level of the geometric mean titer (GMT) in the Roche assay was highest after the third vaccination, and that in Abbott assay was highest after the fourth vaccination but almost equal to that after the third vaccination. Both the geometric mean fold rise (GMFR) demonstrated by the Roche and Abbott assays were highest after the third vaccination. Antibody titers determined by the Roche and Abbott assays showed a positive strong correlation (correlation coefficient: 0.70 to 0.99), but the ratio (Roche/Abbott) of antibodies demonstrated by both assays increased 0.46- to 8.26-fold between weeks 3 and 76. These findings will be helpful for clinicians when interpreting results for SARS-CoV-2 antibody levels and considering future vaccination strategies.

Pathogenesis, Clinical Features, and Treatment of Patients with Myelin Oligodendrocyte Glycoprotein (MOG) Autoantibody-Associated Disorders Focusing on Optic Neuritis with Consideration of Autoantibody-Binding Sites: A Review.

Although there is a substantial amount of data on the clinical characteristics, diagnostic criteria, and pathogenesis of myelin oligodendrocyte glycoprotein (MOG) autoantibody-associated disease (MOGAD), there is still uncertainty regarding the MOG protein function and the pathogenicity of anti-MOG autoantibodies in this disease. It is important to note that the disease characteristics, immunopathology, and treatment response of MOGAD patients differ from those of anti-aquaporin 4 antibody-positive neuromyelitis optica spectrum disorders (NMOSDs) and multiple sclerosis (MS). The clinical phenotypes of MOGAD are varied and can include acute disseminated encephalomyelitis, transverse myelitis, cerebral cortical encephalitis, brainstem or cerebellar symptoms, and optic neuritis. The frequency of optic neuritis suggests that the optic nerve is the most vulnerable lesion in MOGAD. During the acute stage, the optic nerve shows significant swelling with severe visual symptoms, and an MRI of the optic nerve and brain lesion tends to show an edematous appearance. These features can be alleviated with early extensive immune therapy, which may suggest that the initial attack of anti-MOG autoantibodies could target the structures on the blood-brain barrier or vessel membrane before reaching MOG protein on myelin or oligodendrocytes. To understand the pathogenesis of MOGAD, proper animal models are crucial. However, anti-MOG autoantibodies isolated from patients with MOGAD do not recognize mouse MOG efficiently. Several studies have identified two MOG epitopes that exhibit strong affinity with human anti-MOG autoantibodies, particularly those isolated from patients with the optic neuritis phenotype. Nonetheless, the relations between epitopes on MOG protein remain unclear and need to be identified in the future.

Pre- and postnatal maternal hair dye use and risk of wheeze and asthma in 5-year-old Japanese children: the Kyushu Okinawa Maternal and Child Health Study.

The present study investigated the association between pre- and postnatal maternal hair dye use and the risk of wheeze and asthma in Japanese children aged 5 years. Study participants were 1199 mother-child pairs. Information on the variables under study was obtained using repeated questionnaires completed by parents. Prenatal maternal hair dye use was associated with an increased risk of current wheeze and ever doctor-diagnosed asthma; the adjusted odds ratios (ORs) (95% confidence intervals [CIs]) were 1.44 (1.02-2.02) and 1.51 (1.00-2.25), respectively. Postnatal maternal hair dye use was related to the risk of doctor-diagnosed asthma; the adjusted OR (95% CI) was 1.58 (1.03-2.40). Children who were exposed to maternal hair dye use both prenatally and postnatally had an increased risk of childhood current wheeze and ever doctor-diagnosed asthma; the adjusted ORs (95% CIs) were 1.59 (1.03-2.42) and 1.76 (1.06-2.88), respectively. Our findings suggest that perinatal maternal hair dye use is associated with the risk of wheeze and asthma in children.

Incomplete Hydrogenation by Geranylgeranyl Reductase from a Proteobacterial Phototroph Halorhodospira halochloris, Resulting in the Production of Bacteriochlorophyll with a Tetrahydrogeranylgeranyl Tail.

Light harvesting and charge separation are functions of chlorophyll and bacteriochlorophyll pigments. While most photosynthetic organisms use (bacterio)chlorophylls with a phytyl (2-phytenyl) group as the hydrophobic isoprenoid tail, Halorhodospira halochloris, an anoxygenic photosynthetic bacterium belonging to Gammaproteobacteria, produces bacteriochlorophylls with a unique 6,7,14,15-tetrahydrogeranylgeranyl (2,10-phytadienyl) tail. Geranylgeranyl reductase (GGR), encoded by the bchP gene, catalyzes hydrogenation at three unsaturated C=C bonds of a geranylgeranyl group, giving rise to the phytyl tail. In this study, we discovered that H. halochloris GGR exhibits only partial hydrogenation activities, resulting in the tetrahydrogeranylgeranyl tail formation. We hypothesized that the hydrogenation activity of H. halochloris GGR differed from that of Chlorobaculum tepidum GGR, which also produces a pigment with partially reduced hydrophobic tails (2,6-phytadienylated chlorophyll a). An engineered GGR was also constructed and demonstrated to perform only single hydrogenation, resulting in the dihydrogeranylgeranyl tail formation. H. halochloris original and variant GGRs shed light on GGR catalytic mechanisms and offer prospective bioengineering tools in the microbial production of isoprenoid compounds. IMPORTANCE Geranylgeranyl reductase (GGR) catalyzes the hydrogenation of carbon-carbon double bonds of unsaturated hydrocarbons of isoprenoid compounds, including α-tocopherols, phylloquinone, archaeal cell membranes, and (bacterio)chlorophyll pigments in various organisms. GGRs in photosynthetic organisms, including anoxygenic phototrophic bacteria, cyanobacteria, and plants perform successive triple hydrogenation to produce chlorophylls and bacteriochlorophylls with a phytyl chain. Here, we demonstrated that the GGR of a gammaproteobacterium Halorhodospira halochloris catalyzed unique double hydrogenation to produce bacteriochlorophylls with a tetrahydrogeranylgeranyl tail. We also constructed a variant enzyme derived from H. halochloris GGR that performs only single hydrogenation. The results of this study provide new insights into catalytic mechanisms of multiposition reductions by a single enzyme.

Podocytes are lost from glomeruli before completing apoptosis.

Although apoptosis of podocytes has been widely reported in in vitro studies, it has been less frequently and less definitively documented in in vivo situations. To investigate this discrepancy, we analyzed the dying process of podocytes in vitro and in vivo using LMB2, a human (h)CD25-directed immunotoxin. LMB2 induced cell death within 2 days in 56.8 ± 13.6% of cultured podocytes expressing hCD25 in a caspase-3, Bak1, and Bax-dependent manner. LMB2 induced typical apoptotic features, including TUNEL staining and fragmented nuclei without lactate dehydrogenase leakage. In vivo, LMB2 effectively eliminated hCD25-expressing podocytes in NEP25 mice. Podocytes injured by LMB2 were occasionally stained for cleaved caspase-3 and cleaved lamin A but never for TUNEL. Urinary sediment contained TUNEL-positive podocytes. To examine the effect of glomerular filtration, we performed unilateral ureteral obstruction in NEP25 mice treated with LMB2 1 day before euthanasia. In the obstructed kidney, glomeruli contained significantly more cleaved lamin A-positive podocytes than those in the contralateral kidney (50.1 ± 5.4% vs. 29.3 ± 4.1%, P < 0.001). To further examine the dying process without glomerular filtration, we treated kidney organoids generated from nephron progenitor cells of NEP25 mice with LMB2. Podocytes showed TUNEL staining and nuclear fragmentation. These results indicate that on activation of apoptotic caspases, podocytes are detached and lost in the urine before nuclear fragmentation and that the physical force of glomerular filtration facilitates detachment. This phenomenon may be the reason why definitive apoptosis is not observed in podocytes in vivo.NEW & NOTEWORTHY This report clarifies why morphologically definitive apoptosis is not observed in podocytes in vivo. When caspase-3 is activated in podocytes, these cells are immediately detached from the glomerulus and lost in the urine before DNA fragmentation occurs. Detachment is facilitated by glomerular filtration. This phenomenon explains why podocytes in vivo rarely show TUNEL staining and never apoptotic bodies.

Multispecies Populations of Methanotrophic Methyloprofundus and Cultivation of a Likely Dominant Species from the Iheya North Deep-Sea Hydrothermal Field.

The Methyloprofundus clade is represented by uncultivated methanotrophic bacterial endosymbionts of deep-sea bathymodiolin mussels, but only a single free-living species has been cultivated to date. This study reveals the existence of free-living Methyloprofundus variants in the Iheya North deep-sea hydrothermal field in the mid-Okinawa Trough. A clade-targeted amplicon analysis of the particulate methane monooxygenase gene (pmoA) detected 647 amplicon sequence variants (ASVs) of the Methyloprofundus clade in microbial communities newly formed in in situ colonization systems. Such systems were deployed at colonies of bathymodiolin mussels and a galatheoid crab in diffuse-flow areas. These ASVs were classified into 161 species-like groups. The proportion of the species-like groups representing endosymbionts of mussels was unexpectedly low. A methanotrophic bacterium designated INp10, a likely dominant species in the Methyloprofundus population in this field, was enriched in a biofilm formed in a methane-fed cultivation system operated at 10°C. Genomic characterization with the gene transcription data set of INp10 from the biofilm suggested traits advantageous to niche competition in environments, such as mobility, chemotaxis, biofilm formation, offensive and defensive systems, and hypoxia tolerance. The notable metabolic traits that INp10 shares with some Methyloprofundus members are the use of lanthanide-dependent XoxF as the sole methanol dehydrogenase due to the absence of the canonical MxaFI, the glycolytic pathway using fructose-6-phosphate aldolase instead of fructose-1,6-bisphosphate aldolase, and the potential to perform partial denitrification from nitrate under oxygen-limited conditions. These findings help us better understand the ecological strategies of this possibly widespread marine-specific methanotrophic clade. IMPORTANCE The Iheya North deep-sea hydrothermal field in the mid-Okinawa Trough is characterized by abundant methane derived from organic-rich sediments and diverse chemosynthetic animal species, including those harboring methanotrophic bacterial symbionts, such as bathymodiolin mussels Bathymodiolus japonicus and "Bathymodiolus" platifrons and a galatheoid crab, Shinkaia crosnieri. Symbiotic methanotrophs have attracted significant attention, and yet free-living methanotrophs in this environment have not been studied in detail. We focused on the free-living Methyloprofundus spp. that thrive in this hydrothermal field and identified an unexpectedly large number of species-like groups in this clade. Moreover, we enriched and characterized a methanotroph whose genome sequence indicated that it corresponds to a new species in the genus Methyloprofundus. This species might be a dominant member of the indigenous Methyloprofundus population. New information on free-living Methyloprofundus populations suggests that the hydrothermal field is a promising locale at which to investigate the adaptive capacity and associated genetic diversity of Methyloprofundus spp.

IL12B rs6887695 polymorphism and interaction with alcohol intake in the risk of ulcerative colitis in Japan.

BACKGROUND: The interleukin (IL)-23/Th17 pathway plays a critical role in ulcerative colitis (UC). The IL-12p40 subunit, which is shared by IL-23 and IL-12, is encoded by the IL12B gene. The current case-control study investigated the association between IL12B SNP rs6887695 and the UC risk. METHODS: There were 384 cases within 4 years of UC diagnosis and 661 controls who were enrolled. Adjustments were made for sex, age, pack-years of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, and body mass index. RESULTS: Subjects with the GG IL12B SNP rs6887695 genotype had a significantly increased risk of UC compared with those with the CC genotype (adjusted odds ratio [AOR], 1.60; 95% confidence interval [CI], 1.08-2.36). This positive association was also significant using the additive and recessive models (AOR, 1.25; 95% CI, 1.03-1.52; AOR, 1.50; 95% CI, 1.08-2.09, respectively). An independent inverse relationship was observed between ever alcohol consumption and the UC risk in those with the CC genotype while no significant association was found in those with at least one G allele (P for interaction = 0.0008). CONCLUSIONS: IL12B SNP rs6887695 was significantly associated with UC. The influence of alcohol consumption might rely on rs6887695.

Perinatal maternal depressive symptoms and risk of behavioral problems at five years.

BACKGROUND: Evidence on the association between perinatal maternal depression and children's behavioral development is limited. We investigated the association between maternal depressive symptoms during pregnancy and postpartum and the risk of childhood behavioral problems using data from a birth cohort study. METHODS: Study subjects were 1199 mother-child pairs. Maternal depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale during pregnancy and the Edinburgh Postnatal Depression Scale at 4 months postpartum. Children's behavioral development at 5 years of age was assessed with the Strengths and Difficulties Questionnaire. RESULTS: Compared with children whose mothers did not experience depressive symptoms during pregnancy, those whose mothers did experience depressive symptoms during pregnancy had increased risk of emotional symptoms, conduct problems, hyperactivity, peer problems, and low prosocial behavior. Maternal depressive symptoms at around 4 months postpartum were associated with increased risk of childhood emotional problems. Compared with children whose mothers did not experience depressive symptoms during the perinatal period, those whose mothers did experience depressive symptoms both during pregnancy and postpartum had a fivefold increased risk of childhood emotional symptoms and a threefold increased risk of peer problems. CONCLUSIONS: Our findings suggest that perinatal maternal depression is associated with behavioral problems in children. IMPACT: Several epidemiological studies in Western countries have examined the association between perinatal maternal depression and children's behavioral development, yet the results are conflicting and inconclusive. There is limited evidence on this topic in Asia. In our study using data from a prospective pregnancy birth cohort, maternal depressive symptoms around 4 months postpartum were associated with an increased risk of emotional symptoms in children aged 5 years. Children whose mothers had exhibited depressive symptoms both during pregnancy and postpartum had a fivefold increased risk of childhood emotional symptoms and a threefold increased risk of peer problems.

Identification of Chitin Allomorphs in Poorly Crystalline Samples Based on the Complexation with Ethylenediamine.

Chitin is a key component of hard parts in many organisms, but the biosynthesis of the two distinctive chitin allomorphs, α- and ß-chitin, is not well understood. The accurate determination of chitin allomorphs in natural biomaterials is vital. Many chitin-secreting living organisms, however, produce poorly crystalline chitin. This leads to spectrums with only broad lines and imprecise peak positions under conventional analytical methods such as X-ray diffraction (XRD), Fourier-transform infrared spectroscopy, and solid-state nuclear magnetic resonance spectroscopy, resulting in inconclusive identification of chitin allomorphs. Here, we developed a novel method for discerning chitin allomorphs based on their different complexation capacity and guest selectivity, using ethylenediamine (EDA) as a complexing agent. From the peak shift observed in XRD profiles of the chitin/EDA complex, the chitin allomorphs can be clearly discerned. By testing this method on a series of samples with different chitin allomorphs and crystallinity, we show that the sensitivity is sufficiently high to detect the chitin allomorphs even in near-amorphous, very poorly crystalline samples. This is a powerful tool for determining the chitin allomorphs in phylogenetically important chitin-producing organisms and will pave the way for clarifying the evolution and mechanism of chitin biosynthesis.

Tryptophan intake is related to a lower prevalence of depressive symptoms during pregnancy in Japan: baseline data from the Kyushu Okinawa Maternal and Child Health Study.

OBJECTIVE: Tryptophan is an essential amino acid wholly derived from diet. While the majority of tryptophan is degraded through the kynurenine pathway into neuroactive metabolites like quinolinic acid and kynurenic acid, a small proportion of ingested tryptophan is metabolized into the neurotransmitter serotonin. The current cross-sectional study in Japan examined the association between tryptophan intake and depressive symptoms during pregnancy. METHODS: Study subjects were 1744 pregnant women. Dietary intake during the preceding month was assessed using a self-administered diet history questionnaire. Depressive symptoms were defined as a score ≥ 16 on the Center for Epidemiologic Studies Depression Scale. Adjustment was made for age, gestation, region of residence, number of children, family structure, history of depression, family history of depression, smoking, secondhand smoke exposure at home and at work, employment, household income, education, body mass index, and intake of saturated fatty acids, eicosapentaenoic acid plus docosahexaenoic acid, calcium, vitamin D, and isoflavones. RESULTS: The prevalence of depressive symptoms during pregnancy was 19.2%. After adjustment for confounding factors, higher tryptophan intake was independently inversely associated with the prevalence of depressive symptoms during pregnancy: the adjusted prevalence ratios (95% confidence intervals) for depressive symptoms during pregnancy in the first, second, third, and fourth quartiles of tryptophan intake were 1 (reference), 0.99 (0.76-1.28), 0.94 (0.71-1.25), and 0.64 (0.44-0.93), respectively (p for trend = 0.04). CONCLUSIONS: Higher estimated tryptophan intake was cross-sectionally independently associated with a lower prevalence of depressive symptoms during pregnancy in Japanese women.

Active and passive smoking and risk of ulcerative colitis: A case-control study in Japan.

BACKGROUND AND AIM: Although an inverse relationship between current smoking and the development of ulcerative colitis (UC) has been shown in North America and Europe, evidence is limited in Asian countries, where the incidence of UC is rapidly increasing. This Japanese case-control study examined the association between active and passive smoking and risk of UC. METHODS: A self-administered questionnaire was used to obtain information on smoking and potential confounding factors in 384 cases with a diagnosis of UC within the past 4 years and 665 controls. RESULTS: Compared with having never smoked, having ever smoked was associated with an increased risk of UC (adjusted odds ratio [OR] = 1.70, 95% confidence interval [CI]: 1.23-2.37). No association was observed between current smoking and risk of UC, but former smokers had a significant elevation in risk (adjusted OR = 2.40, 95% CI: 1.67-3.45). There was a positive dose-response relationship with pack-years smoked (P for trend = 0.006). Among never smokers, passive smoking exposure at home was significantly associated with an increased risk of UC (adjusted OR = 1.90, 95% CI: 1.30-2.79). A significant dose-response gradient was also observed between pack-years of passive smoking at home and risk of UC (P for trend = 0.0003). CONCLUSIONS: We confirmed that former smoking elevated the risk of UC, whereas an inverse association between current smoking and the risk of UC did not reach a statistically significant level. Passive smoking may be associated with an increased risk of UC.