Demonstration of retinoic acid isomers in human urine under physiological conditions

Summary Untransformed retinoic acid has never been demonstrated in human excreta under normal physiological conditions. We have developed a two-step liquid chromatographic system for the demonstration of subnanogram amounts of this compound in human urine without administration of any precursor.The work was supported by a grant of the N.F.S.R. to W.L.     

Effect of ouabain on volume regulation of rabbit kidney cortex slices in hypo-osmotic media

The volume regulation process at work in rabbit kidney cortex slices submitted to hypo-osmotic media show both a swelling limitation and a volume readjustment phase. Swelling limitation is Na+ dependent and is blocked by ouabain 10(-3) M. There is, however, no need to implicate the activity of a ouabain sensitive Na+ /K+ pump in this process.     

Structure of porphobilinogen deaminase reveals a flexible multidomain polymerase with a single catalytic site.

The three-domain structure of porphobilinogen deaminase, a key enzyme in the biosynthetic pathway of tetrapyrroles, has been defined by X-ray analysis at 1.9 A resolution. Two of the domains structurally resemble the transferrins and periplasmic binding proteins. The dipyrromethane cofactor is covalently linked to domain 3 but is bound by extensive salt-bridges and hydrogen-bonds within the cleft between domains 1 and 2, at a position corresponding to the binding sites for small-molecule ligands in the analogous proteins. The X-ray structure and results from site-directed mutagenesis provide evidence for a single catalytic site. Interdomain flexibility may aid elongation of the polypyrrole product in the active-site cleft of the enzyme.     

Dust-climate couplings over the past 800,000 years from the EPICA Dome C ice core

Dust can affect the radiative balance of the atmosphere by absorbing or reflecting incoming solar radiation; it can also be a source of micronutrients, such as iron, to the ocean. It has been suggested that production, transport and deposition of dust is influenced by climatic changes on glacial-interglacial timescales. Here we present a high-resolution record of aeolian dust from the EPICA Dome C ice core in East Antarctica, which provides an undisturbed climate sequence over the past eight climatic cycles. We find that there is a significant correlation between dust flux and temperature records during glacial periods that is absent during interglacial periods. Our data suggest that dust flux is increasingly correlated with Antarctic temperature as the climate becomes colder. We interpret this as progressive coupling of the climates of Antarctic and lower latitudes. Limited changes in glacial-interglacial atmospheric transport time suggest that the sources and lifetime of dust are the main factors controlling the high glacial dust input. We propose that the observed approximately 25-fold increase in glacial dust flux over all eight glacial periods can be attributed to a strengthening of South American dust sources, together with a longer lifetime for atmospheric dust particles in the upper troposphere resulting from a reduced hydrological cycle during the ice ages.     

Effect of ouabain on volume regulation of rabbit kidney cortex slices in hypo-osmotic media

Summary The volume regulation process at work in rabbit kidney cortex slices submitted to hypo-osmotic media show both a swelling limitation and a volume readjustment phase. Swelling limitation is Na⁺ dependent and is blocked by ouabain 10^–3 M. There is, however, no need to implicate the activity of a ouabain sensitive Na⁺/K⁺ pump in this process.This work has been aided by a grant 1.5.422.82F from the FNRS to R.G. We wish to thank Mr J.M. Theate for his skilful assitance.     

Bone marrow-derived mesenchymal cells and MMP13 contribute to experimental choroidal neovascularization

In this study, we evaluate the potential involvement of collagenase-3 (MMP13), a matrix metalloproteinase (MMP) family member, in the exudative form of age-related macular degeneration characterized by a neovascularisation into the choroid. RT-PCR analysis revealed that human neovascular membranes issued from patients with AMD expressed high levels of Mmp13. The contribution of MMP13 in choroidal neovascularization (CNV) formation was explored by using a murine model of laser-induced CNV and applying it to wild-type mice (WT) and Mmp13-deficient mice (Mmp13 ^?/? mice). Angiogenic and inflammatory reactions were explored by immunohistochemistry. The implication of bone marrow (BM)-derived cells was determined by BM engraftment into irradiated mice and by injecting mesenchymal stem cells (MSC) isolated from WT BM. The deficiency of Mmp13 impaired CNV formation which was fully restored by WT BM engraftment and partially rescued by several injections of WT MSC. The present study sheds light on a novel function of MMP13 during BM-dependent choroidal vascularization and provides evidence for a role for MSC in the pathogenesis of CNV.