13 research outputs found

    Loss of AND-34/BCAR3 Expression in Mice Results in Rupture of the Adult Lens

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    PURPOSE. AND-34/BCAR3 (Breast Cancer Anti-Estrogen Resistance 3) associates with the focal adhesion adaptor protein, p130CAS/BCAR1. Expression of AND-34 regulates epithelial cell growth pattern, motility, and growth factor dependence. We sought to establish the effects of the loss of AND-34 expression in a mammalian organism. METHODS. AND-34−/− mice were generated by homologous recombination. Histopathology, in situ hybridization, and western blotting were performed on murine tissues. RESULTS. Western analyses confirmed total loss of expression in AND-34−/− splenic lymphocytes. Mice lacking AND-34 are fertile and have normal longevity. While AND-34 is widely expressed in wild type mice, histologic analysis of multiple organs in AND-34−/− mice is unremarkable and analyses of lymphocyte development show no overt changes. A small percentage of AND-34−/− mice show distinctive small white eye lesions resulting from the migration of ruptured cortical lens tissue into the anterior chamber. Following initial vacuolization and liquefaction of the lens cortex first observed at postnatal day three, posterior lens rupture occurs in all AND-34−/− mice, beginning as early as three weeks and seen in all mice at three months. Western blot analysis and in situ hybridization confirmed the presence of AND-34 RNA and protein in lens epithelial cells, particularly at the lens equator. Prior data link AND-34 expression to the activation of Akt signaling. While Akt Ser 473 phosphorylation was readily detectable in AND-34+/+ lens epithelial cells, it was markedly reduced in the AND-34−/− lens epithelium. Basal levels of p130Cas phosphorylation were higher in AND-34+/+ than in AND-34−/− lens epithelium. CONCLUSIONS. These results demonstrate the loss of AND-34 dysregulates focal adhesion complex signaling in lens epithelial cells and suggest that AND-34-mediated signaling is required for maintenance of the structural integrity of the adult ocular lens.National Institutes of Health (RO1 CA114094); Logica Foundatio

    Inversion of the slow-wave frequency gradient in symptomatic patients with Roux-en-Y anastomoses.

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    Patients with Roux-en-Y anastomoses may have chronic symptoms of nausea, vomiting, epigastric fullness, and abdominal pain. To investigate the mechanism of these symptoms, the electrical activity of the Roux limb was studied in five symptomatic and four asymptomatic patients with Roux-en-Y anastomoses. Slow-wave and spike activity in the Roux limb were recorded using six bipolar suction electrodes positioned 10 cm apart. Ten healthy volunteers were studied as a control. In the control subjects, the mean slow-wave frequency decreased from 11.27 +/- 0.2 cycles/min at 30 cm below the ligament of Treitz to 10.96 +/- 0.2 cycles/min at 80 cm past Treitz. By contrast, in five patients the slow-wave frequency in the Roux limb increased from 11.12 +/- 0.2 cycles/min 10 cm below the gastrojejunal anastomosis to 11.42 +/- 0.4 cycles/min 50 cm more distally. Four of these five patients had severe symptoms. In the other four patients, of whom three were completely symptom-free, an aborally decreasing slow-wave frequency was observed. In both the controls and the patients with Roux-en-Y anastomoses, the direction of propagation of phase 3 spike bursts of the migrating motor complex was always aboral. During phase 2, most spike bursts were uncoordinated at adjacent recording sites. Propagated spike bursts, single or repetitive, were rare. The propagation direction of these spike bursts was always aboral in healthy controls. In symptomatic patients with inverted slow wave frequency gradients, however, the rare propagated spike bursts always propagated orally. The observed electrical abnormalities may in part be responsible for the symptoms of patients with the Roux-en-Y syndrome

    Inversion of the slow-wave frequency gradient in symptomatic patients with Roux-en-Y anastomoses.

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    Patients with Roux-en-Y anastomoses may have chronic symptoms of nausea, vomiting, epigastric fullness, and abdominal pain. To investigate the mechanism of these symptoms, the electrical activity of the Roux limb was studied in five symptomatic and four asymptomatic patients with Roux-en-Y anastomoses. Slow-wave and spike activity in the Roux limb were recorded using six bipolar suction electrodes positioned 10 cm apart. Ten healthy volunteers were studied as a control. In the control subjects, the mean slow-wave frequency decreased from 11.27 +/- 0.2 cycles/min at 30 cm below the ligament of Treitz to 10.96 +/- 0.2 cycles/min at 80 cm past Treitz. By contrast, in five patients the slow-wave frequency in the Roux limb increased from 11.12 +/- 0.2 cycles/min 10 cm below the gastrojejunal anastomosis to 11.42 +/- 0.4 cycles/min 50 cm more distally. Four of these five patients had severe symptoms. In the other four patients, of whom three were completely symptom-free, an aborally decreasing slow-wave frequency was observed. In both the controls and the patients with Roux-en-Y anastomoses, the direction of propagation of phase 3 spike bursts of the migrating motor complex was always aboral. During phase 2, most spike bursts were uncoordinated at adjacent recording sites. Propagated spike bursts, single or repetitive, were rare. The propagation direction of these spike bursts was always aboral in healthy controls. In symptomatic patients with inverted slow wave frequency gradients, however, the rare propagated spike bursts always propagated orally. The observed electrical abnormalities may in part be responsible for the symptoms of patients with the Roux-en-Y syndrome

    An integrated micromorphological and phytolith study of urban soils and sediments from the Gallo‐Roman town Atuatuca Tungrorum, Belgium

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    Tongeren is the only Roman administrative capital within the borders of present-day Belgium. It developed in the first century A.D. and became an important civitas. Many excavations in the center of town have uncovered complex stratigraphic sequences, including dark earths, dating to Roman as well as early medieval times. Their interpretation, based on traditional archaeological methods, often remains problematic. A large-scale excavation at Vermeulenstraat in 2014 is the first occasion where a geoarchaeological study was conducted using both micromorphology and the study of phytoliths in thin sections. The aim was to evaluate the impact of depositional and post-depositional processes, to gain an understanding of the formation of the dark earths encountered on the site, to characterize the deposits between and underneath them, and to identify and differentiate human activities and natural phenomena. The results show a range of different activities and events, such as cultivation, construction (including floor preparation), destruction, waste dumping, and gardening. Their different formation histories illustrate the evolution of the area, and their analysis provides an important precedent for the further geoarchaeological study of this town.SCOPUS: ar.jDecretOANoAutActifinfo:eu-repo/semantics/publishe

    Immunotherapy for advanced thyroid cancers — rationale, current advances and future strategies

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