Sugar-sweetened beverage consumption may modify associations between genetic variants in the CHREBP (carbohydrate responsive element binding protein) locus and HDL-C (high-density lipoprotein cholesterol) and triglyceride concentrations

BACKGROUND: ChREBP (carbohydrate responsive element binding protein) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the CHREBP locus have separately been linked to HDL-C (high-density lipoprotein cholesterol) and triglyceride concentrations. We hypothesized that SSB consumption would modify the association between genetic variants in the CHREBP locus and dyslipidemia.METHODS: Data from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (N=63599) and the UK Biobank (N=59220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and triglyceride concentrations using linear regression models. A total of 1606 single nucleotide polymorphisms within or near CHREBP were considered. SSB consumption was estimated from validated questionnaires, and participants were grouped by their estimated intake.RESULTS: In a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers (beta, 2.12 [95% CI, 1.16-3.07] mg/dL per allele; P<0.0001), but not significantly among the lowest SSB consumers (P=0.81; P-Diff<0.0001). Similar results were observed for 2 additional variants (rs35709627 and rs71556736). For triglyceride, rs55673514 was positively associated with triglyceride concentrations only among the highest SSB consumers (beta, 0.06 [95% CI, 0.02-0.09] In-mg/dL per allele, P=0.001) but not the lowest SSB consumers (P=0.84; P-Diff=0.0005).CONCLUSIONS: Our results identified genetic variants in the CHREBP locus that may protect against SSB-associated reductions in HDL-C and other variants that may exacerbate SSB-associated increases in triglyceride concentrations.Clinical epidemiolog

Long-Baseline Neutrino Facility (LBNF) and Deep Underground Neutrino Experiment (DUNE) Conceptual Design Report Volume 2: The Physics Program for DUNE at LBNF

The Physics Program for the Deep Underground Neutrino Experiment (DUNE) at the Fermilab Long-Baseline Neutrino Facility (LBNF) is described

Synthesis and anti-melanoma activity of analogues of N-acetyl-4-S-cysteaminylphenol substituted with two methyl groups alpha to the nitrogen

Synthesis and anti-melanoma activity of analogues of N-acetyl-4-S-cysteaminylphenol substituted with two methyl groups alpha to the nitrogen. N-Acetyl-4-S-cysteaminylphenol 1 is an analogue of a biosynthetic intermediate in the pathway to melanin. It is probably oxidized to an o-quinone which can alkylate cellular nucleophiles resulting in interference with cell growth and proliferation. It is reported to have useful anti-melanoma activity. We previously synthesized a range of analogues of 1 by varying the acyl portion of the amide. A modest increase in melanoma activity against six melanoma cell lines for these analogues could be correlated with increased lipophilicity. Thirteen new analogues of 1 containing two methyl groups at the cf.-position of the amino component and various acyl groups have now been prepared and assessed for anti-melanoma activity against six human melanoma cell lines. Most of the new compounds displayed greater cytotoxicity than the lead compound 1. The highest cytotoxicity against the cell lines was observed for the cyclohexylacetamide 11 followed by the cyclohexylcarboxamide 10 and the 2,2-dimethylpropanamide 6. The IC50 values of the most cytotoxic compound 11 against the cell lines were comparable with those of cisplatin. Small variations in the acyl components of these analogues, such as reducing the ring size, lengthening the carbon chain and reducing the amount of chain branching, resulted in a considerable loss of cytotoxicity. The moderate activity of 6, 10 and 11 against SK- Mel-24 cells (non-tyrosinase containing) and an ovarian cell line suggests that interference with the melanin pathway may not be their only mode of action

Phylogeny of the Sepia officinalis species complex in the eastern Atlantic extends the known distribution of Sepia vermiculata across the Benguela upwelling region

Accurate species identification and biogeographic characterisation are fundamental for appropriate management of expanding cephalopod fisheries. This study  addresses this topic within the common cuttlefish Sepia officinalis species complex (S. officinalis, S. hierredda and S. vermiculata), with an emphasis on occurrence in African waters. Tissue samples from the currently presumed distributions of S. vermiculata and S. hierredda (from South Africa and Ghana/Angola, respectively) were sequenced for the cytochrome c oxidase subunit I (COI) and the cytochrome b (cytb) genes of the mitochondrial genome and then compared to existing S.  officinalis sequences. Three highly divergent and reciprocally monophyletic clades, corresponding to S. officinalis, S. hierredda and S. vermiculata, were resolved,  representing the first molecular confirmation of the distinct species status of S. hierredda and S. vermiculata. The sequences also revealed that, contrary to  expectations based on presently published information, all samples from southern Angola were S. vermiculata. These results indicate that the range of S. vermiculata extends beyond the currently described northern limit and that S. hierredda and S. vermiculata may be indiscriminately harvested in Angolan waters. Finer-scale patterns within S. vermiculata phylogeography also indicate that the Benguela Current System and/or other environmental factors serve to isolate northern andsouthern stocks.Keywords: biogeography, cephalopods, cuttlefish, dispersal, ecosystem-compatible exploitation, fisheries management, indiscriminate harvesting, mtDNA sequencing, phylogenetic