ALBERT

Description: Saliva, as a biofluid, is inexpensive and non-invasive to obtain, and provides a vital tool to investigate oral health and its interaction with systemic health conditions. There is growing interest in salivary biomarkers for systemic diseases, notably cardiovascular disease. Whereas hundreds of genetic loci have been shown to be involved in the regulation of blood metabolites, leading to significant insights into the pathogenesis of complex human diseases, little is known about the impact of host genetics on salivary metabolites. Here we report the first genome-wide association study exploring 476 salivary metabolites in 1419 subjects from the TwinsUK cohort (discovery phase), followed by replication in the Study of Health in Pomerania (SHIP-2) cohort. A total of 14 distinct locus-metabolite associations were identified in the discovery phase, most of which were replicated in SHIP-2. While only a limited number of the loci that are known to regulate blood metabolites were also associated with salivary metabolites in our study, we identified several novel saliva-specific locus-metabolite associations, including associations for the AGMAT (with the metabolites 4-guanidinobutanoate and beta-guanidinopropanoate), ATP13A5 (with the metabolite creatinine) and DPYS (with the metabolites 3-ureidopropionate and 3-ureidoisobutyrate) loci. Our study suggests that there may be regulatory pathways of particular relevance to the salivary metabolome. In addition, some of our findings may have clinical significance, such as the utility of the pyrimidine (uracil) degradation metabolites in predicting 5-fluorouracil toxicity and the role of the agmatine pathway metabolites as biomarkers of oral health.

Description: Coccolithophores contribute significantly to marine primary productivity and play a unique role in ocean biogeochemistry by using carbon for photosynthesis (soft-tissue pump) and for calcification (carbonate counter pump). Despite the importance of including coccolithophores in Earth system models to allow better predictions of the climate system's responses to planetary change, the reconstruction of coccolithophore productivity mostly relied on proxies dependent on accumulation and sedimentation rates and preservation conditions. In this study we used an independent proxy, based on the coccolith fraction (CF) Sr∕Ca ratio, to reconstruct coccolithophore productivity. We studied the marine sediment core MD03-2699 from the western Iberian margin (IbM), concentrating on glacial–interglacial cycles of Marine Isotopic Stage (MIS) 12 to MIS 9. We found that IbM coccolithophore productivity was controlled by changes in the oceanographic conditions, such as in sea surface temperature (SST) and nutrient availability, and by competition with other phytoplankton groups. Long-term coccolithophore productivity was primarily affected by variations in the dominant surface water mass. Polar and subpolar surface waters during glacial substages were associated with decreased coccolithophore productivity, with the strongest productivity minima concomitant with Heinrich-type events (HtEs). Subtropical, nutrient-poorer waters, increased terrigenous input, and moderate to strong upwelling during the deglaciation and early MIS11 are hypothesized to have attributed a competitive advantage to diatoms to the detriment of coccolithophores, resulting in intermediate coccolithophore productivity levels. During the progression towards full glacial conditions an increasing presence of nutrient-richer waters, related to the growing influence of transitional surface waters and/or intensified upwelling, probably stimulated coccolithophore productivity to maxima following the rapid depletion of silica by diatoms. We present conceptual models of the carbon and carbonate cycle components for the IbM in different time slices that might serve as a basis for further investigation and modelling experiments.