CMG2/ANTXR2 regulates extracellular collagen VI which accumulates in hyaline fibromatosis syndrome.

Loss-of-function mutations in capillary morphogenesis gene 2 (CMG2/ANTXR2), a transmembrane surface protein, cause hyaline fibromatosis syndrome (HFS), a severe genetic disorder that is characterized by large subcutaneous nodules, gingival hypertrophy and severe painful joint contracture. Here we show that CMG2 is an important regulator of collagen VI homoeostasis. CMG2 loss of function promotes accumulation of collagen VI in patients, leading in particular to nodule formation. Similarly, collagen VI accumulates massively in uteri of Antxr2 <sup>-/-</sup> mice, which do not display changes in collagen gene expression, and leads to progressive fibrosis and sterility. Crossing Antxr2 <sup>-/-</sup> with Col6a1 <sup>-/-</sup> mice leads to restoration of uterine structure and reversion of female infertility. We also demonstrate that CMG2 may act as a signalling receptor for collagen VI and mediates its intracellular degradation

Temporal evolution of stable water isotopologues in cloud droplets in a hill cap cloud in central Europe (HCCT-2010)

In this work, we present the first study resolving the temporal evolution of δ2H and δ18O values in cloud droplets during 13 different cloud events. The cloud events were probed on a 937 m high mountain chain in Germany in the framework of the Hill Cap Cloud Thuringia 2010 campaign (HCCT-2010) in September and October 2010. The δ values of cloud droplets ranged from −77‰ to −15‰ (δ2H) and from −12.1‰ to −3.9‰ (δ18O) over the whole campaign. The cloud water line of the measured δ values was δ2H=7.8×δ18O+13×10−3, which is of similar slope, but with higher deuterium excess than other Central European Meteoric Water Lines. Decreasing δ values in the course of the campaign agree with seasonal trends observed in rain in central Europe. The deuterium excess was higher in clouds developing after recent precipitation revealing episodes of regional moisture recycling. The variations in δ values during one cloud event could either result from changes in meteorological conditions during condensation or from variations in the δ values of the water vapor feeding the cloud. To test which of both aspects dominated during the investigated cloud events, we modeled the variation in δ values in cloud water using a closed box model. We could show that the variation in δ values of two cloud events was mainly due to changes in local temperature conditions. For the other eleven cloud events, the variation was most likely caused by changes in the isotopic composition of the advected and entrained vapor. Frontal passages during two of the latter cloud events led to the strongest temporal changes in both δ2H (≈ 6‰ per hour) and δ18O (≈ 0.6‰ per hour). Moreover, a detailed trajectory analysis for the two longest cloud events revealed that variations in the entrained vapor were most likely related to rain out or changes in relative humidity and temperature at the moisture source region or both. This study illustrates the sensitivity of stable isotope composition of cloud water to changes in large scale air mass properties and regional recycling of moisture

Podoplanin Associates with CD44 to Promote Directional Cell Migration

Podoplanin, a cancer-associated glycoprotein, interacts with CD44. Both glycoproteins are coordinately upregulated during tumor progression. Podoplanin–CD44 interaction in the cell membrane occurs mainly in migrating cells, and it seems to be required for podoplanin-mediated cell migration and directionality

Abnormal macular pigment distribution in type 2 idiopathic macular telangiectasia

PURPOSE: To determine the distribution of macular pigment in type 2 idiopathic macular telangiectasia (IMT). METHODS: Twenty-two eyes of 12 patients with type 2 IMT were examined by means of best-corrected visual acuity testing, fundus biomicroscopy, fundus photography, fluorescein angiography, and optical coherence tomography. Macular pigment optical density (MPOD) was assessed using a modified confocal scanning laser ophthalmoscope whereby MPOD was calculated from fundus autofluorescence images acquired at two different excitation wavelengths (488 and 514 nm). The results were verified with a method that provides density maps after digital subtraction of log fundus reflectance maps (four patients) and by means of heterochromatic flicker photometry (four patients). RESULTS: MOPD distribution showed an abnormal pattern for all patients with type 2 IMT. In correspondence to the late-phase hyperfluorescent areas shown by fluorescein angiography, MPOD was reduced in the macular area, while there was preserved MPOD at 5 degrees to 7 degrees eccentricity. CONCLUSIONS: The central depletion of macular pigment represents a novel phenotypic characteristic of type 2 IMT. Recording of macular pigment distribution may prove useful in the diagnosis of type 2 IMT and implicates an impaired trafficking or storage of lutein and zeaxanthin in the disease process

Quantification of reduced macular pigment optical density in the central retina in macular telangiectasia type 2

Recently, a unique distribution, namely a reduction of macular pigment optical density (MPOD) within the central retina with a surrounding ring-like structure of preserved MPOD at about 6 degrees eccentricity was suggested to be a common finding in macular telangiectasia (MacTel) type 2. In order to quantify this reduced MPOD, 28 eyes of 14 patients with MacTel type 2 were investigated by fundus reflectometry and two wavelengths fundus autofluorescence (FAF; at 488nm and 514nm). Fundus reflectometry showed a reduced MPOD within the central 4 degrees eccentricity that was most absent temporal to the foveola. At 6 degrees, MP density was not different from normative values. Two wavelengths FAF was in accordance with these findings. Fundus reflectometry also allowed separate determination of lutein and zeaxanthin. The patients with MacTel type 2 showed a disproportionally high zeaxanthin reduction. The study suggests that in MacTel type 2, there might be an inability to accumulate MP in the central retina. This disease might serve as a model to further study abnormalities of MP distribution in retinal disorders and to elucidate the mechanisms of MP disposition in the retina

Stable water isotopologue ratios in fog and cloud droplets of liquid clouds are not size-dependent

In this work, we present the first observations of stable water isotopologue ratios in cloud droplets of different sizes collected simultaneously. We address the question whether the isotope ratio of droplets in a liquid cloud varies as a function of droplet size. Samples were collected from a ground intercepted cloud (= fog) during the Hill Cap Cloud Thuringia 2010 campaign (HCCT-2010) using a three-stage Caltech Active Strand Cloud water Collector (CASCC). An instrument test revealed that no artificial isotopic fractionation occurs during sample collection with the CASCC. Furthermore, we could experimentally confirm the hypothesis that the δ values of cloud droplets of the relevant droplet sizes (μm-range) were not significantly different and thus can be assumed to be in isotopic equilibrium immediately with the surrounding water vapor. However, during the dissolution period of the cloud, when the supersaturation inside the cloud decreased and the cloud began to clear, differences in isotope ratios of the different droplet sizes tended to be larger. This is likely to result from the cloud's heterogeneity, implying that larger and smaller cloud droplets have been collected at different moments in time, delivering isotope ratios from different collection times

Le foot au féminin

Une initiative innovante : la création, au lycée Louis Pergaud de Besançon, d'une section sportive académique de football féminin, structure d'accueuil pour l'élite régionale. Organisation de la section sports-études, programme de l'année, présentation de quelques situations pédagogiques

Supplementary Material for: Altered Global 5-Hydroxymethylation Status in Hidradenitis Suppurativa: Support for an Epigenetic Background

<p><b><i>Background:</i></b> The pathogenesis of hidradenitis suppurativa (HS), with its complex inflammatory network, is still elusive. Imbalances in DNA methylation can lead to genome destabilization and have been assumed to play a role in inflammatory diseases. Global DNA methylation and hydroxymethylation have not been studied in HS yet. <b><i>Objective:</i></b> We conducted this study to investigate the global DNA methylation and hydroxymethylation status in lesional and perilesional HS skin compared to healthy controls. <b><i>Methods:</i></b> Immunohistochemical analysis was performed for 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in 30 lesional and 30 corresponding healthy-appearing perilesional HS tissue samples. We included 30 healthy subjects as an interindividual control group. <b><i>Results:</i></b> 5-hmC levels were significantly lower in healthy-appearing perilesional (<i>p</i> < 0.0001) and lesional HS skin (<i>p</i> < 0.0001) when compared to healthy controls. There was no significant difference between lesional HS skin and perilesional HS skin regarding 5-hmC levels (<i>p</i> = 0.6654). In contrast to 5-hmC, 5-mC staining showed no significant changes between the 3 groups. Univariate analysis revealed no significant association between patients' characteristics, disease severity, and the levels of 5-mC and 5-hmC. <b><i>Conclusion:</i></b> Our findings indicate that imbalances in DNA hydroxymethylation may play a role in the pathogenesis of HS rather than DNA methylation. Further studies are warranted to investigate the significance of DNA hydroxymethylation and the regulating enzymes in HS in order to advance our knowledge of the inflammatory network in this disease.</p