Aim
We performed a birth cohort study involving 124 mother–infant pairs to investigate whether placental DNA methylation is associated with maternal choline status and fetal development.
Methods
...Plasma choline concentration was assayed longitudinally in the 1st and 3rd trimesters and at term‐pregnancy in mothers and cord blood. Placental DNA methylation was measured for 12 target candidate genes that are related to fetal growth, adipogenesis, lipid and energy metabolism, or long interspersed nuclear elements.
Results
Higher maternal plasma and cord blood choline levels at term tended to associate with lower birthweight (r = −0.246, P < 0.013; r = −0.290, P < 0.002) and body mass index (BMI) at birth (r = 0.344, P < 1E−3; r = −0.360, P < 1E−3). The correlation between maternal plasma choline level and cord blood choline level was relatively modest (r = 0.049, P = 0.639). There was an inverse correlation between placental DNA methylation at the retinoid X receptor alpha (RXRA) gene and maternal plasma choline level (r = −0.188 to r = −0.452, P = 0.043 to P < 1E−3 at three points). RXRA methylation level was positively associated with birthweight and BMI at birth (r = 0.306, P = 0.001; r = 0.390, P < 1E−3). Further, RXRA methylation was inversely correlated with RXRA gene expression level (r = 0.333, P < 1E−3).
Conclusion
Our results suggest that the association between maternal choline status and placental RXRA methylation represents a potential fetal programing mechanism contributing to fetal growth.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Ploidy is relevant to numerous biological phenomena, including development, metabolism, and tissue regeneration. Single-cell RNA-seq and other omics studies are revolutionizing our understanding of ...biology, yet they have largely overlooked ploidy. This is likely due to the additional assay step required for ploidy measurement. Here, we developed a statistical method to infer ploidy from single-cell ATAC-seq data, addressing this gap. When applied to data from human and mouse cell atlases, our method enabled systematic detection of polyploidy across diverse cell types. This method allows for the integration of ploidy analysis into single-cell studies. Additionally, this method can be adapted to detect the proliferating stage in the cell cycle and copy number variations in cancer cells. The software is implemented as the scPloidy package of the R software and is freely available from CRAN.
The cooling water systems are used to remove heat generated in the various industries. Biofouling of the cooling water systems causes blocking of condenser pipes and the heat exchanger tubes. In many ...Gram-negative bacteria, N-acylhomoserine lactone (AHL) are used as quorum-sensing signal molecule and associated with biofilm formation. To investigate the relationship between quorum sensing and biofouling in the cooling water system, we isolated a total of 192 bacterial strains from the five cooling water systems, and screened for AHL production. Seven isolates stimulated AHL-mediated purple pigment production in AHL reporter strain Chromobacterium violaceum CV026 or VIR07. Based on their 16S rRNA gene sequences, AHL-producing isolates were assigned to Aeromonas hydrophila, Lysobacter sp., Methylobacterium oryzae, and Bosea massiliensis. To the best of our knowledge, B. massiliensis and Lysobacter sp. have not been reported as AHL-producing species in the previous researches. AHLs extracted from the culture supernatants of B. massiliensis and Lysobacter sp. were identified by liquid chromatography-mass spectrometry. AHLs produced by B. massiliensis were assigned as N-hexanoyl-L-homoserine lactone (C6-HSL), N-(3-oxohexanoyl)-L-homoserine lactone (3-oxo-C6-HSL), and N-(3-oxooctanoyl)-L-homoserine lactone (3-oxo-C8-HSL). AHLs produced by Lysobacter sp. were assigned as N-decanoyl-L-homoserine lactone (C10-HSL) and N-(3-oxodecanoyl)-L-homoserine lactone (3-oxo-C10-HSL). This is the first report of identification of AHLs produced by B. massiliensis and Lysobacter sp. isolated from the cooling water system.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Left ventricular noncompaction cardiomyopathy (LVNC) is a heart muscle disorder morphologically characterized by reticulated trabeculations and intertrabecular recesses in the left ventricular (LV) ...cavity. LVNC is a genetically and phenotypically heterogeneous condition, which has been increasingly recognized with the accumulation of evidence provided by genotype-phenotype correlation analyses. Here, we report 2 sporadic adult cases of LVNC; both developed acute heart failure as an initial clinical manifestation and harbored causal sarcomere gene mutations. One case was a 57-year-old male with digenic heterozygote mutations, p.R1344Q in myosin heavy chain 7 (MYH7) and p.R144W in troponin T2, cardiac type (TNNT2), who showed morphological characteristics of LVNC in the lateral to apical regions of the LV together with a comorbidity of non-transmural myocardial infarction, resulting from a coronary artery stenosis. After the removal of ischemic insult and standard heart failure treatment, LVNC became less clear, and LV function gradually improved. The other case was a 36-year-old male with a heterozygote mutation, p.E334K in myosin binding protein C3 (MYBPC3), who exhibited cardiogenic shock on admission with morphological characteristics of LVNC being most prominent in the apical segment of the LV. The dosage of beta-blocker was deliberately increased in an outpatient clinic over 6 months following hospitalization, which remarkably improved the LV ejection fraction from 21% to 54.3%. Via a combination of imaging and histopathological and genetic tests, we have found that these cases are not compatible with a persistent phenotype of primary cardiomyopathy, but their morphological features are changeable in response to treatment. Thus, we point out phenotypic plasticity or undulation as a noticeable element of LVNC in this case report.
Background & Aims Solute carrier family 15 (SLC15) A4 is a proton-coupled histidine and oligopeptide cotransporter expressed by the immune and nervous systems and associated with disorders such as ...inflammatory bowel diseases and systemic lupus erythematosus. High levels of SLC15A4 transcripts were observed in human antigen-presenting cells, including dendritic cells, activated macrophages, and B cells. However, the roles of SLC15A4 in the immune regulation are not known. We investigated the function of SLC15A4 in the innate immune system. Methods We created SLC15A4-deficient ( SLC15A4 −/− ) mice and compared Toll-like receptor 9 and NOD1-dependent innate immune responses between SLC15A4 −/− and control ( SLC15A4 +/+ ) mice. Results SLC15A4 deficiency impaired CpG-induced production of interleukin-12, interleukin-15, and interleukin-18 by dendritic cells. Correspondingly, SLC15A4 −/− mice developed a less severe form of Th1-dependent colitis than SLC15A4 +/+ mice. Increased lysosomal histidine, in the absence of SLC15A4, appears to negatively regulate Toll-like receptor 9 function by inhibiting the proteolytic activities of cathepsins B and L. SLC15A4 −/− mice also had a severe defect in NOD1-dependent cytokine production, indicating that SLC15A4 functions as a transporter of the NOD1 ligand. Conclusions SLC15A4 promotes colitis through Toll-like receptor 9 and NOD1-dependent innate immune responses. Histidine homeostasis within intracellular compartments is important for eliciting effective innate immune responses.
Aim: It is challenging to identify causal (or target) genes at individual loci detected using genome-wide association studies (GWAS). In order to follow up GWAS loci, we investigated functional genes ...at homologous loci identified using human lipid GWAS that responded to a high-fat, high-cholesterol diet (HFD) intervention in an animal model. Methods: The HFD intervention was carried out for four weeks in male rats of the spontaneously hypertensive rat strain. The liver and adipose tissues were subsequently excised for analyses of changes in the gene expression as compared to that observed in rats fed normal rat chow (n=8 per group). From 98 lipid-associated loci reported in previous GWAS, 280 genes with rat orthologs were initially selected as targets for the two-staged analysis involving screening with DNA microarray and validation with quantitative PCR (qPCR). Consequently, genes showing a differential expression due to HFD were examined for changes in the expression induced by atorvastatin, which was independently administered to the rats. Results: Using the HFD intervention in the rats, seven known (Abca1, Abcg5, Abcg8, Lpl, Nr1h3, Pcsk9 and Pltp) and three novel (Madd, Stac3 and Timd4) genes were identified as potential significant targets, with an additional list of 23 suggestive genes. Among these 33 genes, Stac3, Fads1 and six known genes exhibited nominally significant expression changes following treatment with atorvastatin. Six (of 33) genes overlapped with those previously detected in the expression QTL studies. Conclusions: Our experimental in vivo approach increases the ability to identify target gene(s), when combined with other functional studies, thus improving understanding of the mechanisms by which GWAS variants act.
Background and Aim
Non‐alcoholic fatty liver disease (NAFLD) is linked to metabolic syndrome, and is known to be associated with impaired fasting glycemia and diabetes mellitus. This prospective ...community‐based study was conducted to determine the association between NAFLD and incidence of diabetes mellitus in an urban adult population in Sri Lanka.
Methods
Participants of the Ragama Health Study cohort were assessed for NAFLD using established ultrasound criteria in 2007. Those who were free of diabetes at baseline were followed up for 3 years. Incidence rates of diabetes mellitus were compared between subjects with and without NAFLD at baseline.
Results
Out of 2984 subjects, 926 had NAFLD and 676 had diabetes in 2007. Of the 2276 subjects who were free of diabetes in 2007, 1914 were re‐assessed in 2010. After 3 years, 104 out of 528 subjects with NAFLD and 138 out of 1314 subjects without NAFLD had developed diabetes mellitus de novo. Incidence rates of diabetes were respectively 64.2 and 34 per 1000 person‐years of follow up for those with and without NAFLD. NAFLD was an independent predictor of developing diabetes mellitus. Other independent predictors were impaired fasting glycemia and dyslipidemia.
Conclusions
Subjects with ultrasonically diagnosed NAFLD have an increased risk of developing diabetes mellitus. Intervention for NAFLD through lifestyle modification may prevent progression of the current diabetes epidemic.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
N-Acylhomoserine lactones (AHLs) are used as quorum-sensing (QS) signals by gram-negative bacteria. We have reported that the cyclic oligosaccharides known as cyclodextrins (CDs) form inclusion ...complexes with AHLs and disrupt QS signaling. In this study, a series of CD derivatives were designed and synthesized to improve the QS inhibitory activity over that of native CDs. The production of the red pigment prodigiosin by Serratia marcescens AS-1, which is regulated by AHL-mediated QS, was drastically decreased by adding 10 mg/ml 6-alkylacylamino-β-CD with an alkyl chain ranging from C7 to C12. An improvement in the QS inhibitory activity was also observed for 6-alkylamino-α- or γ-CDs and 2-alkylamino-CDs. Furthermore, 6,6′-dioctylamino-β-CD, which contains two octylamino groups, exhibited greater inhibitory activity than 6-monooctylamino-β-CD. The synthesized CD derivatives also had strong inhibitory effects on QS by other gram-negative bacteria, including Chromobacterium violaceum and Pseudomonas aeruginosa. The synthetic alkylamine-modified CD derivatives had higher equilibrium binding constants for binding with AHL than the native CDs did, consistent with the improved QS inhibition. 1H NMR measurements suggested that the alkyl side chains of 6-alkylacylamino-β-CDs with alkyl chains up to 6 carbon atoms long could form self-inclusion complexes with the CD unit.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background The impact of psychosocial states, such as depression or anxiety, and social support on the outcomes of stable outpatients with mild heart failure (HF) has not been evaluated in the "real ...world" clinical practice. Methods and Results In the present study, 139 patients with a prior history of admission for HF provided the baseline demographic, clinical, socio-environmental, and psychosocial information. Cardiac death or re-admission because of worsening of HF was monitored during the follow-up period of 1 year. The prevalence of depression and anxiety were 37% and 37%, respectively, in HF patients. Depression was independently associated with male (sβ=-0.36, P=0.01), social ties (sβ=0.22, P=0.04) and low social support (sβ=-0.39, P<0.01). Anxiety was associated with alcohol drinking (sβ=0.22, P=0.04), brain natriuretic peptide ≥200 pg/dl (sβ=0.35, P<0.01), and low social support (sβ=-0.28, P=0.01). Kaplan-Meier analysis demonstrated that patients with anxiety (log-lank test; P<0.01) and lower scores of social support (P<0.01) had a higher rate of HF-related re-admission. Conclusions Anxiety and low social support were independently associated with HF-related re-admission, which indicates the need for their inclusion in the assessment and management of HF. (Circ J 2009; 73: 280 - 287)
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