Role of the Netrin-like Domain of Procollagen C-Proteinase Enhancer-1 in the Control of Metalloproteinase Activity

The netrin-like (NTR) domain is a feature of several extracellular proteins, most notably the N-terminal domain of tissue inhibitors of metalloproteinases (TIMPs), where it functions as a strong inhibitor of matrix metalloproteinases and some other members of the metzincin superfamily. The presence of a C-terminal NTR domain in procollagen C-proteinase enhancers (PCPEs), proteins that stimulate the activity of astacin-like tolloid proteinases, raises the possibility that this might also have inhibitory activity. Here we show that both long and short forms of the PCPE-1 NTR domain, the latter beginning at the N-terminal cysteine known to be critical for TIMP activity, show no inhibition, at micromolar concentrations, of several members of the metzincin superfamily, including matrix metalloproteinase-2, bone morphogenetic protein-1 (a tolloid proteinase), and different ADAMTS (a disintegrin and a metalloproteinase with thrombospondin motifs) proteinases from the adamalysin family. In contrast, we report that the NTR domain within PCPE-1 leads to superstimulation of bone morphogenetic protein-1 activity in the presence of heparin and heparan sulfate. These observations point to a new mechanism whereby binding to cell surface-associated or extracellular heparin-like sulfated glycosaminoglycans might provide a means to accelerate procollagen processing in specific cellular and extracellular microenvironments

The energy calibration of LEP in the 1993 scan

This report summarizes the procedure for providing the absolute energy calibration of the LEP beams during the energy scan in 1993. The average beam energy around the LEP ring was measured in 25 calibrations with the resonant depolarization technique. The time variation of this average beam energy is well described by a model of the accelerator based on monitored quantities. The absolute calibration of the centre of mass energies of the off-peak points is determined with a precision of 2 parts in 10(5) resulting in a systematic error on the Z-mass of about 1.4 MeV and on the Z-width of about 1.5 MeV

Periodontal Ehlers-Danlos Syndrome Is Caused by Mutations in C1R and C1S, which Encode Subcomponents C1r and C1s of Complement

Periodontal Ehlers-Danlos syndrome (pEDS) is an autosomal-dominant disorder characterized by early-onset periodontitis leading to premature loss of teeth, joint hypermobility, and mild skin findings. A locus was mapped to an approximately 5.8 Mb region at 12p13.1 but no candidate gene was identified. In an international consortium we recruited 19 independent families comprising 107 individuals with pEDS to identify the locus, characterize the clinical details in those with defined genetic causes, and try to understand the physiological basis of the condition. In 17 of these families, we identified heterozygous missense or in-frame insertion/deletion mutations in C1R (15 families) or C1S (2 families), contiguous genes in the mapped locus that encode subunits C1r and C1s of the first component of the classical complement pathway. These two proteins form a heterotetramer that then combines with six C1q subunits. Pathogenic variants involve the subunit interfaces or inter-domain hinges of C1r and C1s and are associated with intracellular retention and mild endoplasmic reticulum enlargement. Clinical features of affected individuals in these families include rapidly progressing periodontitis with onset in the teens or childhood, a previously unrecognized lack of attached gingiva, pretibial hyperpigmentation, skin and vascular fragility, easy bruising, and variable musculoskeletal symptoms. Our findings open a connection between the inflammatory classical complement pathway and connective tissue homeostasis

Global link between deformation and volcanic eruption quantified by satellite imagery

A key challenge for volcanological science and hazard management is that few of the world’s volcanoes are effectively monitored. Satellite imagery covers volcanoes globally throughout their eruptive cycles, independent of ground-based monitoring, providing a multidecadal archive suitable for probabilistic analysis linking deformation with eruption. Here we show that, of the 198 volcanoes systematically observed for the past 18 years, 54 deformed, of which 25 also erupted. For assessing eruption potential, this high proportion of deforming volcanoes that also erupted (46%), together with the proportion of non-deforming volcanoes that did not erupt (94%), jointly represent indicators with ‘strong’ evidential worth. Using a larger catalogue of 540 volcanoes observed for 3 years, we demonstrate how this eruption–deformation relationship is influenced by tectonic, petrological and volcanic factors. Satellite technology is rapidly evolving and routine monitoring of the deformation status of all volcanoes from space is anticipated, meaning probabilistic approaches will increasingly inform hazard decisions and strategic development

Surface motion of mountain glaciers derived from satellite optical imagery

A complete and detailed map of the ice-velocity field on mountain glaciers is obtained by cross-correlating SPOT5 optical images. This approach offers an alternative to SAR interferometry, because no present or planned RADAR satellite mission provides data with a temporal separation short enough to derive the displacements of glaciers. The methodology presented in this study does not require ground control points (GCPs). The key step is a precise relative orientation of the two images obtained by adjusting the stereo model of one "slave" image assuming that the other "master" image is well georeferenced. It is performed with numerous precisely-located homologous points extracted automatically. The strong ablation occurring during summer time on the glaciers requires a correction to obtain unbiased displacements. The accuracy of our measurement is assessed based on a comparison with nearly simultaneous differential GPS surveys performed on two glaciers of the Mont Blanc area (Alps). If the images have similar incidence angles and correlate well, the accuracy is on the order of 0.5 m, or 1/5 of the pixel size. Similar results are also obtained without GCPs. An acceleration event, observed in early August for the Mer de Glace glacier, is interpreted in term of an increase in basal sliding. Our methodology, applied to SPOT5 images, can potentially be used to derive the displacements of the Earth's surface caused by landslides, earthquakes, and volcanoes. (c) 2004 Elsevier Inc. All rights reserved