Fibulin-5, an integrin-binding matricellular protein: its function in development and disease

Interactions between the extracellular matrix (ECM) and cells are critical in embryonic development, tissue homeostasis, physiological remodeling, and tumorigenesis. Matricellular proteins, a group of ECM components, mediate cell-ECM interactions. One such molecule, Fibulin-5 is a 66-kDa glycoprotein secreted by various cell types, including vascular smooth muscle cells (SMCs), fibroblasts, and endothelial cells. Fibulin-5 contributes to the formation of elastic fibers by binding to structural components including tropoelastin and fibrillin-1, and to cross-linking enzymes, aiding elastic fiber assembly. Mice deficient in the fibulin-5 gene (Fbln5) exhibit systemic elastic fiber defects with manifestations of loose skin, tortuous aorta, emphysematous lung and genital prolapse. Although Fbln5 expression is down-regulated after birth, following the completion of elastic fiber formation, expression is reactivated upon tissue injury, affecting diverse cellular functions independent of its elastogenic function. Fibulin-5 contains an evolutionally conserved arginine-glycine-aspartic acid (RGD) motif in the N-terminal region, which mediates binding to a subset of integrins, including α5β1, αvβ3, and αvβ5. Fibulin-5 enhances substrate attachment of endothelial cells, while inhibiting migration and proliferation in a cell type- and context-dependent manner. The antagonistic function of fibulin-5 in angiogenesis has been demonstrated in vitro and in vivo; fibulin-5 may block angiogenesis by inducing the anti-angiogenic molecule thrompospondin-1, by antagonizing VEGF165-mediated signaling, and/or by antagonizing fibronectin-mediated signaling through directly binding and blocking the α5β1 fibronectin receptor. The overall effect of fibulin-5 on tumor growth depends on the balance between the inhibitory property of fibulin-5 on angiogenesis and the direct effect of fibulin-5 on proliferation and migration of tumor cells. However, the effect of tumor-derived versus host microenvironment-derived fibulin-5 remains to be evaluated

Leonides VII and his family

Kapetanopoulos Élias A. Leonides VII and his family. In: Bulletin de correspondance hellénique. Volume 92, livraison 2, 1968. pp. 493-518

Flavius Hiérophantes Paianieus and Lucius Verus

The genealogical table of Flavius Hierophantes' family is reconstructed and new identifications are proposed for the family's members. Also, the initiation of the emperor Lucius Verus into the Eleusinian Mysteries is placed in A.D. 162 (A.D. 161/2).Kapetanopoulos Élias A. Flavius Hiérophantes Paianieus and Lucius Verus. In: Revue des Études Grecques, tome 83, fascicule 394-395, Janvier-juin 1970. pp. 63-69

Attic Inscriptions : Notes

Kapetanopoulos Élias A. Attic Inscriptions : Notes. In: Revue belge de philologie et d'histoire, tome 52, fasc. 1, 1974. Antiquité - Oudheid. pp. 59-71

Klea and Leontis : two ladies from Delphi

Kapetanopoulos Élias A. Klea and Leontis : two ladies from Delphi. In: Bulletin de correspondance hellénique. Volume 90, livraison 1, 1966. pp. 119-130

Effects of mate separation in female and social isolation in male free-living Greylag geese on behavioural and physiological measures

The presence of a social partner may significantly contribute to coping with stressful events, whereas dyadic separation generally increases glucocorticoid levels and, thereby, might also affect immune function and health. To study the covariation between social factors, immuno-reactive corticosterone metabolites, haematology and parasite product excretion patterns in a free-living, long-term monogamous bird, we separated pair mates in Greylag geese (Anser anser). We isolated the males of eight pairs for 48 hours to examine behavioural, adrenocortical, haematological and parasitological responses to mate removal in the female partners, and to social isolation in the males. Females showed no elevated levels of corticosterone metabolites in their droppings, but their haematocrit decreased during mate removal, whereas leucocyte number and heterophil/lymphocyte (H/L) ratio remained unchanged. In contrast, the socially isolated males excreted significantly elevated levels of corticosterone metabolites compared to baseline and showed a decrease in haematocrit as well as elevated leucocyte number and H/L ratio. In both sexes, the excretion of coccidian oocysts increased within 48 hours of the start of the separation, remained high one week after separation, and returned to baseline four weeks later. Described effects were generally more pronounced in males than in females. Our results suggest relatively swift potential health effects of mate loss and social isolation in an unfamiliar confinement in free-living geese

Phase clustering in globally coupled photochemical oscillators

We experimentally investigate the formation of clusters in a population of globally coupled photochemical oscillators. The system consists of catalytic micro-particles in Belousov-Zhabotinsky solution and the coupling exploits the excitatory properties of light; an increase in the light intensity leads to excitation ("firing") of an oscillator. As the coupling strength is increased, a transition occurs from incoherence to clustering, whereby the oscillators split into synchronised groups, to complete synchronisation. Multistability is observed between a one-phase cluster (fully synchronised group) and two-phase clusters (two groups with the same frequency but different phases). The results are reproduced in simulations and we demonstrate that the heterogeneity of the population as well as the relaxational nature of the oscillators is important in the observation of clusters. We also examine the exploitation of the phase model for the prediction of clusters in experiments. © EDP Sciences and Springer 2008

Acute resting myocardial perfusion imaging in patients with diabetes mellitus: Results from the Emergency Room Assessment of Sestamibi for Evaluation of Chest Pain (ERASE Chest Pain) trial

Resting myocardial perfusion imaging (MPI) improves the triage of patients presenting to the emergency department (ED) with symptoms suggestive of acute cardiac ischemia (ACI). In the ED setting the presence of diabetes mellitus (DM) is a predictor of ACI and hospitalization, but the role of resting MPI in patients with DM is unknown. A secondary data analysis of a prospective, multicenter, randomized, controlled trial of ED evaluation strategies in patients with symptoms suggestive of ACI and normal or nondiagnostic electrocardiograms was performed. In the main trial 2475 patients were randomized to receive either the usual ED evaluation strategy (n = 1260) or the usual strategy supplemented by results from resting MPI by use of single photon emission computed tomography (SPECT) technetium 99m sestamibi (n = 1215). Patients with diabetes (n = 341) were evaluated separately. Imaging results, final diagnoses, effect on triage, and prognostic value of the SPECT imaging were compared between diabetic and nondiabetic patients. Of the 341 patients with diabetes, 153 (45%) were randomized to the imaging strategy. Patients with DM had higher rates of hospitalization (66% vs 49.6%, P = .0001) and ACI (21.1% vs 12.0%, P < .001) than patients without DM. Among diabetic patients without ACI, the admission rate was 63% in the usual strategy group versus 54% in the imaging strategy group (relative risk [RR] = 0.91 [95% CI, 0.76-1.06]; P = .24). There was no difference in the magnitude of this reduced risk of admission compared with patients without DM (RR = 0.84 [95% CI, 0.77-0.92]; P = .0002 for patients without DM and P = .35 for interaction of diabetes and RR reduction). Acute resting MPI with Tc-99m sestamibi is associated with improved triage decision making in symptomatic ED patients with diabetes

Fibulin-5 initiates epithelial–mesenchymal transition (EMT) and enhances EMT induced by TGF-β in mammary epithelial cells via a MMP-dependent mechanism

Epithelial–mesenchymal transition (EMT) is a normal physiological process that regulates tissue development, remodeling and repair; however, aberrant EMT also elicits disease development in humans, including lung fibrosis, rheumatoid arthritis and cancer cell metastasis. Transforming growth factor-β (TGF-β) is a master regulator of EMT in normal mammary epithelial cells (MECs), wherein this pleiotropic cytokine also functions as a potent suppressor of mammary tumorigenesis. In contrast, malignant MECs typically evolve resistance to TGF-β-mediated cytostasis and develop the ability to proliferate, invade and metastasize when stimulated by TGF-β. It therefore stands to reason that establishing how TGF-β promotes EMT may offer new insights into targeting the oncogenic activities of TGF-β in human breast cancers. By monitoring alterations in the actin cytoskeleton and various markers of EMT, we show here that the TGF-β gene target, fibulin-5 (FBLN5), initiates EMT and enhances that induced by TGF-β. Whereas normal MECs contain few FBLN5 transcripts, those induced to undergo EMT by TGF-β show significant upregulation of FBLN5 messenger RNA, suggesting that EMT and the dedifferentiation of MECs override the repression of FBLN5 expression in polarized MECs. We also show that FBLN5 stimulated matrix metalloproteinase expression and activity, leading to MEC invasion and EMT, to elevated Twist expression and to reduced E-cadherin expression. Finally, FBLN5 promoted anchorage-independent growth in normal and malignant MECs, as well as enhanced the growth of 4T1 tumors in mice. Taken together, these findings identify a novel EMT and tumor-promoting function for FBLN5 in developing and progressing breast cancers