Notch (N) is a receptor for signals that inhibit neural precursor specification [1-6]. As N and its ligand Delta (DI) are expressed homogeneously, other molecules may be differentially expressed or active to permit neural precursor cells to arise intermingled with nonneural cells [7,8]. During Drosophila wing development, the glycosyltransferase encoded by the gene fringe (fng) promotes N signaling in response to DI, but inhibits N signaling in response to Serrate (Ser), which encodes a ligand that is structurally similar to DI. Dorsal expression of Fng protein localizes N signaling to the dorsoventral (DV) wing margin [9-11]. The secreted protein Scabrous (Sca) is a candidate for modulation of N in neural cells. Mutations at the scabrous (sca) locus alter the locations where precursor cells form in the peripheral nervous system [12,13]. Unlike fringe, sca mutations act cell non-autonomously [12]. Here, we report that targeted misexpression of Sca during wing development inhibited N signaling, blocking expression of all N target genes. Sca reduced N activation in response to DI more than in response to Ser. Ligand-independent signaling by overexpression of N protein, or by expression of activated truncated N molecules, was not inhibited by Sca. Our results indicate that Sca can act on N to reduce its availability for paracrine and autocrine interactions with DI and Ser, and can act as an antagonist of N signaling.

Animals↗

PubMedDate not supplied

Augmentation of streptokinase-induced thrombolysis by heparin and prostacyclin.

The ability of heparin and prostacyclin to improve streptokinase-induced recanalization was examined in open-chest dogs subjected to thrombotic occlusion of the left circumflex coronary artery. Vessel injury was produced by electrical stimulation of the intimal surface at the site of a noncircumferential fixed stenosis. Animals were divided into three treatment groups as follows: group 1 received intracoronary streptokinase alone (75,000 units/80 min starting 30 min postocclusion; n = 8); group 2 received streptokinase plus heparin (300 units/kg i.v. at 20 min postocclusion; n = 7); group 3 received streptokinase plus heparin plus prostacyclin (500 ng/kg/min, intracoronary, given intermittently during reperfusion; n = 7). Overall, the groups did not differ with respect to preocclusion coronary blood flow (27 +/- 1 ml/min; +/- SEM), the duration of streptokinase infusion required to achieve reflow (15 +/- 2 min), and the percentage of animals recanalized (85%). They did differ in the average rate of reflow, which was greater in group 2 (16 +/- 2 ml/min) and group 3 (20 +/- 4 ml/min) as compared with group 1 (6 +/- 1 ml/min; p less than 0.05). The intermittent reocclusions which persisted during reperfusion in group 1 and 2 dogs were diminished during the periodic infusions of prostacyclin. Thrombus mass at the site of injury was comparable among groups. In contrast, distal circumflex thrombi, about twice the weight of the proximal mass, were observed in all group 1 dogs and were undetectable in group 2 and 3 animals. Transient improvements in contractile force during reperfusion were observed only with groups 2 and 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗