LDLs stimulate p38 MAPKs and wound healing through SR-BI independently of Ras and PI3 kinase.

Intracellular signals elicited by LDLs are likely to play a role in the pathogenesis associated with increased LDL blood levels. We have previously determined that LDL stimulation of human skin fibroblasts, used as a model system for adventitial fibroblasts, activates p38 mitogen-activated protein kinases (MAPKs), followed by IL-8 production and increased wound-healing capacity of the cells. The proximal events triggering these responses had not been characterized, however. Here we show that MAPK kinases MKK3 and MKK6, but not MKK4, are the upstream kinases responsible for the activation of the p38 MAPKs and stimulation of wound closure in response to LDLs. Phosphoinositide 3 kinases (PI3Ks) and Ras have been suggested to participate in lipoprotein-induced MAPK activation. However, specific PI3K inhibitors or expression of a dominant-negative form of Ras failed to blunt LDL-induced p38 MAPK activation. The classical LDL receptor does not participate in LDL signaling, but the contribution of other candidate lipoprotein receptors has not been investigated. Using cells derived from scavenger receptor class B type I (SR-BI) knockout mice or the BLT-1 SR-BI inhibitor, we now show that this receptor is required for LDLs to stimulate p38 MAPKs and to promote wound healing. Identification of MKK3/6 and SR-BI as cellular relays in LDL-mediated p38 activation further defines the signaling events that could participate in LDL-mediated pathophysiological responses.

Mg/Ca and Sr/Ca ratios of ostracod valves from living species of Lake Geneva

The Mg/Ca and Sr/Ca ratios of living ostracods belonging to 15 different species and sampled monthly over a one year-cycle at five sites (2, 5, 13, 33, and 70 m water depths) in western Lake Geneva (Switzerland) are compared to the oxygen and carbon isotope compositions measured on the same samples as well as to the temperature and chemical composition of the water (δ18OH2O, δ13CDIC, Mg/CaH2O, and Sr/CaH2O) at the time of ostracod calcification. The results indicate that trace element incorporation varied at the species level, mainly because of the ecological and biological differences between the different species (life-cycle, (micro-)habitat preference, biomineralisation processes) and the control thereof on trace element incorporation of the ostracods. In littoral zones, the Mg/Ca and Sr/Ca of ostracod valves increase as temperature and Mg/Ca and Sr/Ca of water increase during spring and summer, hence reflecting mainly seasonal variations. However, given that for Lake Geneva the Mg/Ca and Sr/Ca of water also vary with temperature, it is not possible to distinguish the effects of temperature from those of changes in chemical composition of water on the trace element content in ostracod valves. Results support that both water temperature and water Mg/Ca and Sr/Ca ratios control the final trace element content of Cyprididae valves. In contrast, the trace element content of species living in deeper zones of the basin is influenced by variations in the chemical composition of the pore water for the infaunal species. Trace element content measured for these specimens cannot, therefore, be used to reconstruct the compositions of the water lake bottom. In addition, incorporation of Mg and Sr into the shell differs from one family, sub-family, or even species to the other. This suggests that the distinctive Mg and Sr partition coefcients for the analysed taxa result from different valve calcification strategies that may be phylogenetic.

Morphologic and electroretinographic phenotype of SR-BI knockout mice after a long-term atherogenic diet.

PURPOSE: To evaluate functional and ultrastructural changes in the retina of scavenger receptor B1 (SR-BI) knockout (KO) mice consuming a high fat cholate (HFC) diet. METHODS: Three-month-old male KO and wild-type (WT) mice were fed an HFC diet for 30 weeks. After diet supplementation, plasma cholesterol levels and electroretinograms were analyzed. Neutral lipids were detected with oil red O, and immunohistochemistry was performed on cryostat ocular tissue sections. The retina, Bruch's membrane (BM), retinal pigment epithelium (RPE), and choriocapillaris (CC) were analyzed by transmission electron microscopy. RESULTS: Using the WT for reference, ultrastructural changes were recorded in HFC-fed SR-BI KO mice, including lipid inclusions, a patchy disorganization of the photoreceptor outer segment (POS) and the outer nuclear layer (ONL), and BM thickening with sparse sub-RPE deposits. Within the CC, there was abnormal disorganization of collagen fibers localized in ectopic sites with sparse and large vacuolization associated with infiltration of macrophages in the subretinal space, reflecting local inflammation. These lesions were associated with electroretinographic abnormalities, particularly increasing implicit time in a- and b-wave scotopic responses. Abnormal vascular endothelial growth factor (VEGF) staining was detected in the outer nuclear layer. CONCLUSIONS: HFC-fed SR-BI KO mice thus presented sub-RPE lipid-rich deposits and functional and morphologic alterations similar to some features observed in dry AMD. The findings lend further support to the hypothesis that atherosclerosis causes retinal and subretinal damage that increases susceptibility to some forms of AMD.

Estats de l'Empire des Turqs en Europe, subdivisés suivant l'estendüe des Beglerbeglicz, ou Gouvernements dans lesquels sont marquées les résidences des Sangiacz qui en dépendent. ou sont encor la Transilvanie, la Valaquie, la Moldavie, la Petite Tartarie, &c. Tributaires des Turqs. Dressé sur les Memoires les plus Nouveaux / Par le Sr. Sanson, ... ; Dedié au roy ; Par... Hubert Iaillot, ... ; Cordier Sculpsit

Échelle(s) : [1:4 100 000 environ], Mille Pas Geometriques, ou Mille d'Italie 180 [= 8 cm]

Estats de l'Empire des Turqs en Europe, subdivisés suivant l'estendüe des Beglerbeglicz, ou Gouvernements dans lesquels sont marquées les résidences des Sangiacz qui en dépendent. ou sont encor la Transilvanie, la Valaquie, la Moldavie, la Petite Tartarie, &c. Tributaires des Turqs. Dressé sur les Memoires les plus Nouveaux / Par le Sr. Sanson, ... ; Dedié au roy ; Par... Hubert Iaillot, ... ; Cordier Sculpsit

Échelle(s) : [1:4 100 000 environ], Mille Pas Geometriques, ou Mille d'Italie 180 [= 8 cm]

Partie méridionale de la Turquie d'Europe où sont les Beglerbeglicz de Romélie et de la Mer dans lesquels sont remarquées les Résidences des Sangiacs qui en dépendent : ou sont encor l'Isle et Royaume de Candie, et les Isles de Corfou, Céphalonie, Zante et autres Places sur les Costes qui appartiennent aux Vénitiens / par le Sr. Sanson

Échelle(s) : [1:2 921 000 environ], Lieües Commes de France 25 [= 3,8 cm]

Jugement... de la capitainerie royale de Senart, qui condamne le Sr Le Paige, seigneur de Quincy, en 100 livres d'amende, pour avoir tiré et chassé aux lapins dans son parc de Quincy, nonobstant les défenses à lui faites

[Acte. 1778-08-24. Montgeron]