Association of DNA Methylation at CPT1A Locus with Metabolic Syndrome in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study

In this study, we conducted an epigenome-wide association study of metabolic syndrome (MetS) among 846 participants of European descent in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). DNA was isolated from CD4+ T cells and methylation at ~470,000 cytosine-phosphate-guanine dinucleotide (CpG) pairs was assayed using the Illumina Infinium HumanMethylation450 BeadChip. We modeled the percentage methylation at individual CpGs as a function of MetS using linear mixed models. A Bonferroni-corrected P-value of 1.1 x 10⁻⁷ was considered significant. Methylation at two CpG sites in CPT1A on chromosome 11 was significantly associated with MetS (P for cg00574958 = 2.6x10^-14 and P for cg17058475 = 1.2x10^-9). Significant associations were replicated in both European and African ancestry participants of the Bogalusa Heart Study. Our findings suggest that methylation in CPT1A is a promising epigenetic marker for MetS risk which could become useful as a treatment target in the future.     

Vascular Multiplicity Should Not Be a Contra-Indication for Live Kidney Donation and Transplantation

BackgroundWhether vascular multiplicity should be considered as contraindication and therefore ‘extended donor criterion’ is still under debate.MethodsData from all live kidney donors from 2006–2013 (n = 951) was retrospectively reviewed. Vascular anatomy as imaged by MRA, CTA or other modalities was compared with intraoperative findings. Furthermore, the influence of vascular multiplicity on outcome of donors and recipients was studied.ResultsIn 237 out of 951 donors (25%), vascular multiplicity was present. CTA had the highest accuracy levels regarding vascular anatomy assessment. Regarding outcome of donors with vascular multiplicity, warm ischemia time (WIT) and skin-to-skin time were significantly longer if arterial multiplicity (AM) was present (5.1 vs. 4.0 mins and 202 vs. 178 mins). Skin-to-skin time was significantly longer, and complication rates were higher in donors with venous multiplicity (203 vs. 180 mins and 17.2% vs. 8.4%). Outcome of renal transplant recipients showed a significantly increased WIT (30 vs. 26.7 minutes), higher rate of DGF (13.9% vs. 6.9%) and lower rate of BPAR (6.9% vs. 13.9%) in patients receiving a kidney with AM compared to kidneys with singular anatomy.ConclusionsWe conclude that vascular multiplicity should not be a contra-indication, since it has little impact on clinical outcome in the donor as well as in renal transplant recipients.     

Supply- and Demand-Side Factors Influencing Utilization of Infant and Young Child Feeding Counselling Services in Viet Nam

Adequate utilization of services is critical to maximize the impact of counselling on infant and young child feeding (IYCF), but little is known about factors affecting utilization. Our study examined supply- and demand-side factors associated with the utilization of IYCF counselling services in Viet Nam. We used survey data from mothers with children <2y (n = 1,008) and health staff (n = 60) from the evaluation of a program that embedded IYCF counseling into the existing government health system. The frequency of never users, one-time users, repeat users, and achievers of the recommended minimum number of visits at health facilities were 45.1%, 13.0%, 28.4% and 13.5%, respectively. Poisson regression showed that demand-generation strategies, especially invitation cards, were the key factors determining one-time use (Prevalence ratio, PR 3.0, 95% CI: 2.2–4.2), repeated use (PR 3.2, 95% CI: 2.4–4.2), and achievement of minimum visits (PR 5.5, 95% CI: 3.6–8.4). Higher maternal education was associated with higher utilization both for one-time and repeated use. Being a farmer, belonging to an ethnic minority, and having a wasted child were associated with greater likelihood of achieving the minimum recommended number of visits, whereas child stunting or illness were not. Distance to health center was a barrier to repeated visits. Among supply-side factors, good counselling skills (PR: 1.3–1.8) was the most important factor associated with any service use, whereas longer employment duration and greater work pressure of health center staff were associated with lower utilization. Population attributable risk estimations showed that an additional 25% of the population would have achieved the minimum number of visits if exposed to three demand-generation strategies, and further increased to 49% if the health staff had good counseling skills and low work pressure. Our study provides evidence that demand-generation strategies are essential to increase utilization of facility-based IYCF counselling services in Viet Nam, and may be relevant for increasing and sustaining use of nutrition services in similar contexts.     

Epigenetic regulation of <Emphasis Type="Italic">MdMYB1</Emphasis> is associated with paper bagging-induced red pigmentation of apples

Main conclusion

Paper-bagging treatment can transform non-transcribed MdMYB1 - 2 and MdMYB1 - 3 alleles into transcribed alleles through epigenetic regulations, resulting in the red pigmentation of a normally non-red apple cultivar ‘Mutsu.’ Anthocyanin biosynthesis in apples is regulated by MdMYB1/A/10, an R2R3-Type MYB gene. ‘Mutsu,’ a triploid apple cultivar harboring non-transcribed MdMYB1-2 and MdMYB1-3 alleles, retains green skin color under field conditions. However, it can show red/pink pigmentation under natural or artificial ultraviolet-B (UV-B) light exposure after paper-bagging and bag removal treatment. In the present study, we found that in ‘Mutsu,’ paper bagging-induced red pigmentation was due to the activation of non-transcribed MdMYB1-2/-3 alleles, which triggered the expression of downstream anthocyanin biosynthesis genes in a UV-B-dependent manner. By monitoring the epigenetic changes during UV-B-induced pigmentation, no significant differences in DNA methylation and histone modifications in the 5′ upstream region of MdMYB1-2/-3 were recorded between the UV-B-treated fruit skin (red) and the fruit skin treated only by white light (green). In contrast, bag treatment lowered the DNA methylation in this region of MdMYB1-2/-3 alleles. Similarly, higher levels of histone H3 acetylation and trimethylation of H3 tail at lysine 4, and lower level of trimethylation of H3 tail at lysine 27 were observed in the 5′ upstream region of MdMYB1-2/-3 in the skin of the fruit immediately after bag removal. These results suggest that bagging treatment can induce epigenetic changes, facilitating the binding of trans factor(s) to MdMYB1-2/-3 alleles, resulting in the activation of these MYBs after bag removal.

     

Inhibition of soluble epoxide hydrolase activity by compounds isolated from the aerial parts of Glycosmis stenocarpa

The aim of this study is to search for soluble epoxide hydrolase (sEH) inhibitors from natural plants, bioassay-guided fractionation of lipophilic n-hexane and chloroform layers of an extract of the aerial parts of Glycosmis stenocarpa led to the isolation of 12 compounds (1–12) including murrayafoline-A (1), isomahanine (2), bisisomahanine (3), saropeptate (4), (24?S)-ergost-4-en-3,6-dione (5), stigmasta-4-en-3,6-dion (6), stigmast-4-en-3-one (7), β-sitosterol (8), 24-methylpollinastanol (9), trans-phytol (10), neosarmentol III (11) and (+)-epiloliolide (12). Their structures were elucidated on the basis of spectroscopic data. Among them, neosarmentol III (11) was isolated from nature for the first time. All the isolated compounds were evaluated for their inhibitory activity against sEH. Among isolated carbazole-type compounds, isomahanine (2) and bisisomahanine (3) were identified as a potent inhibitor of sEH, with IC₅₀ values of 22.5?±?1.7 and 7.7?±?1.2?µM, respectively. Moreover, the inhibitory action of 2 and 3 represented mixed-type enzyme inhibition.     

A large‐scale phylogeny of the lycophyte genus Selaginella (Selaginellaceae: Lycopodiopsida) based on plastid and nuclear loci

The lycophyte genus Selaginella alone constitutes the family Selaginellaceae, the largest of the lycophyte families. The genus is estimated to contain 700–800 species distributed on all continents except Antarctica, with highest species diversity in tropical and subtropical regions. The monophyly of Selaginella in this broad sense has rarely been doubted, whereas its intrageneric classification has been notoriously contentious. Previous molecular studies were based on very sparse sampling of Selaginella (up to 62 species) and often used DNA sequence data from one genome. In the present study, DNA sequences of one plastid (rbcL) and one nuclear (ITS) locus from 394 accessions representing approximately 200 species of Selaginella worldwide were used to infer a phylogeny using maximum likelihood, Bayesian inference and maximum parsimony methods. The study identifies strongly supported major clades and well resolves relationships among them. Major results include: (i) six deep‐level clades are discovered representing the deep splits of Selaginella; and (ii) 20 major clades representing 20 major evolutionary lineages are identified, which differ from one another in molecular, macro‐morphological, ecological and spore features, and/or geographical distribution.