Nitisinone Arrests but Does Not Reverse Ochronosis in Alkaptonuric Mice.

Alkaptonuria (AKU) is an ultrarare autosomal recessive disorder resulting from a deficiency of homogentisate 1,2 dioxygenase (HGD), an enzyme involved in the catabolism of phenylalanine and tyrosine. Loss of HGD function prevents metabolism of homogentisic acid (HGA), leading to increased levels of plasma HGA and urinary excretion. Excess HGA becomes deposited in collagenous tissues and subsequently undergoes polymerisation, principally in the cartilages of loaded joints, in a process known as ochronosis. This results in an early-onset, devastating osteoarthropathy for which there is currently no effective treatment. We recently described the natural history of ochronosis in a murine model of AKU, demonstrating that deposition of ochronotic pigment begins very early in life and accumulates with age. Using this model, we were able to show that lifetime treatment with nitisinone, a potential therapy for AKU, was able to completely prevent deposition of ochronotic pigment. However, although nitisinone has been shown to inhibit ochronotic deposition, whether it can also facilitate removal of existing pigment has not yet been examined. We describe here that midlife administration of nitisinone to AKU mice arrests further deposition of ochronotic pigment in the tibiofemoral joint, but does not result in the clearance of existing pigment. We also demonstrate the dose-dependent response of plasma HGA to nitisinone, highlighting its efficacy for personalised medicine, where dosage can be tailored to the individual AKU patient

Carbon sequestration in the deep Atlantic enhanced by Saharan dust

Enhanced atmospheric input of dust-borne nutrients and minerals to the remote surface ocean can potentially increase carbon uptake and sequestration at depth. Nutrients can enhance primary productivity, and mineral particles act as ballast, increasing sinking rates of particulate organic matter. Here we present a two-year time series of sediment trap observations of particulate organic carbon flux to 3,000 m depth, measured directly in two locations: the dust-rich central North Atlantic gyre and the dust-poor South Atlantic gyre. We find that carbon fluxes are twice as high and a higher proportion of primary production is exported to depth in the dust-rich North Atlantic gyre. Low stable nitrogen isotope ratios suggest that high fluxes result from the stimulation of nitrogen fixation and productivity following the deposition of dust-borne nutrients. Sediment traps in the northern gyre also collected intact colonies of nitrogen-fixing Trichodesmium species. Whereas ballast in the southern gyre is predominantly biogenic, dust-derived mineral particles constitute the dominant ballast element during the enhanced carbon fluxes in the northern gyre. We conclude that dust deposition increases carbon sequestration in the North Atlantic gyre through the fertilization of the nitrogen-fixing community in surface waters and mineral ballasting of sinking particles

Plant DNA Barcoding Principles and Limits: A Case Study in the Genus Vanilla

International audiencePowerful DNA barcodes have been much more difficult to define in plants than in animals. In 2009, the international Consortium for the Barcoding Of Life (CBOL) chose the combination of the chloroplast genes (rbcL + matK) as the proposed official barcode for plants. However, this system has got important limits. First, any barcode system will only be useful if there is a clear barcode gap and if species are monophyletic. Second, chloroplast and mitochondrial (COI gene used for animals) barcodes will not be usable for discriminating hybrid species. Moreover, it was also shown that, using chloroplast regions, maximum species discrimination would be around 70% and very variable among plant groups. This is why many authors have more recently advocated for the addition of the nuclear ITS region to this barcode because it reveals more variations and allows the resolution of hybrid or closely related species. We tested different chloroplast genes (rbcL, matK, psaB, psbC) and the nuclear ITS region in the genus Vanilla, a taxonomically complex group and therefore a good model to test for the efficiency of different barcode systems. We found that the CBOL official barcode system performed relatively poorly in Vanilla (76% species discrimination), and we demonstrate that adding ITS to this barcode system allows to increase resolution (for closely related species and to the subspecies level) and to identify hybrid species. The best species discrimination attained was 96.2% because of one paraphyletic species that could not be resolved

The influence of regional circulation patterns on wet and dry mineral dust and sea salt deposition over Greenland

Annually resolved ice core records from different regions over the Greenland ice sheet (GrIS) are used to investigate the spatial and temporal vari- ability of calcium (Ca2+, mainly from mineral dust) and sodium (Na+, mainly from sea salt) deposition. Cores of high common inter-annual variability are grouped with an EOF analysis, resulting in regionally representative Ca2+ and Na+ records for northeastern and central Greenland. Utilizing a regression and validation method with ERA-40 reanalysis data, these common records are associated with distinct regional atmospheric circulation patterns over the North American Arctic, Greenland, and Central to Northern Europe. These patterns are interpreted in terms of transport and deposition of the impurities. In the northeastern part of the GrIS sea salt records reflect the intrusion of marine air masses from southeasterly flow. A large fraction of the Ca2+, variability in this region is connected to a circulation pattern suggesting transport from the west and dry deposition. This pattern is consistent with the current understanding of a predominantly Asian source of the dust deposited over the GrIS. However, our results also indicate that a significant fraction of the inter-annual dust variability in NE and Central Greenland is determined by the frequency and intensity of wet deposition during the season of high atmospheric dust loading, rather than representing the variability of the Asian dust source and/or long-range transport to Greenland. The variances in the regional proxy records explained by the streamfunction patterns are high enough to permit reconstructions of the corresponding regional deposition regimes and the associated circulation patterns