Analysis of the flavonoid component of bioactive New Zealand mānuka (Leptospermum scoparium) honey and the isolation, characterisation and synthesis of an unusual pyrrole

The flavonoid components of New Zealand mānuka (Leptospermum scoparium) honey have been quantified in a series of 31 honeys of varying non-peroxide antibacterial activity to clarify discrepancies between previous studies reported in the literature. Total flavonoid content was 1.16 mg/100 g honey. The principal flavonoids present were pinobanksin, pinocembrin, luteolin and chrysin and together these represented 61% of the total flavonoid content. 1, 2-formyl-5-(2-methoxyphenyl)-pyrrole, which was weakly correlated with the non-peroxide antibacterial activity, was isolated from the flavonoid fraction and separately synthesised. 1 did not display inhibitory activity against Staphylococcus aureus in vitro and thus the origin of the correlation, which is still unknown, is not a direct contribution

Attention Drives Synchronization of Alpha and Beta Rhythms between Right Inferior Frontal and Primary Sensory Neocortex

The right inferior frontal cortex (rIFC) is specifically associated with attentional control via the inhibition of behaviorally irrelevant stimuli and motor responses. Similarly, recent evidence has shown that alpha (7–14 Hz) and beta (15–29 Hz) oscillations in primary sensory neocortical areas are enhanced in the representation of non-attended stimuli, leading to the hypothesis that allocation of these rhythms plays an active role in optimal inattention. Here, we tested the hypothesis that selective synchronization between rIFC and primary sensory neocortex occurs in these frequency bands during inattention. We used magnetoencephalography to investigate phase synchrony between primary somatosensory (SI) and rIFC regions during a cued-attention tactile detection task that required suppression of response to uncertain distractor stimuli. Attentional modulation of synchrony between SI and rIFC was found in both the alpha and beta frequency bands. This synchrony manifested as an increase in the alpha-band early after cue between non-attended SI representations and rIFC, and as a subsequent increase in beta-band synchrony closer to stimulus processing. Differences in phase synchrony were not found in several proximal control regions. These results are the first to reveal distinct interactions between primary sensory cortex and rIFC in humans and suggest that synchrony between rIFC and primary sensory representations plays a role in the inhibition of irrelevant sensory stimuli and motor responses.National Institutes of Health (U.S.) (Grant P41RR14075)National Institutes of Health (U.S.) (Grant K25MH072941)National Institutes of Health (U.S.) (Grant K01AT003459)National Institutes of Health (U.S.) (Grant K24AT004095)National Institutes of Health (U.S.) (Grant RO1-NS045130-01)National Institutes of Health (U.S.) (Grant T32GM007484)National Science Foundation (U.S.) (Grant 0316933)National Science Foundation (U.S.). Graduate Research Fellowship Program (Grant DGE-1147470

Prevalence of Cataract Surgery and Visual Outcomes in Indian Immigrants in Singapore: The Singapore Indian Eye Study

10.1371/journal.pone.0075584PLoS ONE810-POLN

Glucuronidation by UGT1A1 Is the Dominant Pathway of the Metabolic Disposition of Belinostat in Liver Cancer Patients

10.1371/journal.pone.0054522PLoS ONE81

Genome-Wide Association Study of Retinopathy in Individuals without Diabetes

10.1371/journal.pone.0054232PLoS ONE82

Are C-Reactive Protein Associated Genetic Variants Associated with Serum Levels and Retinal Markers of Microvascular Pathology in Asian Populations from Singapore?

Introduction:C-reactive protein (CRP) levels are associated with cardiovascular disease and systemic inflammation. We assessed whether CRP-associated loci were associated with serum CRP and retinal markers of microvascular disease, in Asian populations.Methods:Genome-wide association analysis (GWAS) for serum CRP was performed in East-Asian Chinese (N = 2,434) and Malays (N = 2,542) and South-Asian Indians (N = 2,538) from Singapore. Leveraging on GWAS data, we assessed, in silico, association levels among the Singaporean datasets for 22 recently identified CRP-associated loci. At loci where directional inconsistencies were observed, quantification of inter-ethnic linkage disequilibrium (LD) difference was determined. Next, we assessed association for a variant at CRP and retinal vessel traits [central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE)] in a total of 24,132 subjects of East-Asian, South-Asian and European ancestry.Results:Serum CRP was associated with SNPs in/near APOE, CRP, HNF1A and LEPR (p-values ≤4.7×10-8) after meta-analysis of Singaporean populations. Using a candidate-SNP approach, we further replicated SNPs at 4 additional loci that had been recently identified to be associated with serum CRP (IL6R, GCKR, IL6 and IL1F10) (p-values ≤0.009), in the Singaporean datasets. SNPs from these 8 loci explained 4.05% of variance in serum CRP. Two SNPs (rs2847281 and rs6901250) were detected to be significant (p-value ≤0.036) but with opposite effect directions in the Singaporean populations as compared to original European studies. At these loci we did not detect significant inter-population LD differences. We further did not observe a significant association between CRP variant and CRVE or CRAE levels after meta-analysis of all Singaporean and European datasets (p-value >0.058).Conclusions:Common variants associated with serum CRP, first detected in primarily European studies, are also associated with CRP levels in East-Asian and South-Asian populations. We did not find a causal link between CRP and retinal measures of microvascular disease

A study assessing the association of glycated hemoglobin a1C (HbA1C) associated variants with HbA1C, chronic kidney disease and diabetic retinopathy in populations of asian ancestry

10.1371/journal.pone.0079767PLoS ONE811-POLN

Regulation of shear-induced nuclear translocation of the Nrf2 transcription factor in endothelial cells

<p>Abstract</p> <p>Background</p> <p>Vascular endothelial cells (ECs) constantly experience fluid shear stresses generated by blood flow. Laminar flow is known to produce atheroprotective effects on ECs. Nrf2 is a transcription factor that is essential for the antioxidant response element (ARE)-mediated induction of genes such as heme-oxygenase 1 (HO-1). We previously showed that fluid shear stress increases intracellular reactive oxygen species (ROS) in ECs. Moreover, oxidants are known to stimulate Nrf2. We thus examined the regulation of Nrf2 in cultured human ECs by shear stress.</p> <p>Results</p> <p>Exposure of human umbilical vein endothelial cells (HUVECs) to laminar shear stress (12 dyne/cm²) induced Nrf2 nuclear translocation, which was inhibited by a phosphatidylinositol 3-kinase (PI3K) inhibitor, a protein kinase C (PKC) inhibitor, and an antioxidant agent N-acetyl cysteine (NAC), but not by other protein kinase inhibitors. Therefore, PI3K, PKC, and ROS are involved in the signaling pathway that leads to the shear-induced nuclear translocation of Nrf2. We also found that shear stress increased the ARE-binding activity of Nrf2 and the downstream expression of HO-1.</p> <p>Conclusion</p> <p>Our data suggest that the atheroprotective effect of laminar flow is partially attributed to Nrf2 activation which results in ARE-mediated gene transcriptions, such as HO-1 expression, that are beneficial to the cardiovascular system.</p

Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer.

Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.BCAC is funded by Cancer Research UK (C1287/A10118, C1287/A12014) and by the European Community's Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS). Meetings of the BCAC have been funded by the European Union COST programme (BM0606). Genotyping on the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710, C8197/A16565), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer program and the Ministry of Economic Development, Innovation and Export Trade of Quebec, grant PSR-SIIRI-701. Combination of the GWAS data was supported in part by the US National Institutes of Health (NIH) Cancer Post-Cancer GWAS initiative, grant 1 U19 CA148065-01 (DRIVE, part of the GAME-ON initiative). For a full description of funding and acknowledgments, see the Supplementary Note.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ng.324