The Urokinase Receptor Is a Major Vitronectin-Binding Protein on Endothelial Cells

We have previously demonstrated that vitronectin (VN), a morphoregulatory protein in the vessel wall, is internalized and translocated to the subendothelial matrix by an integrin-independent mechanism (J. Histochem. Cytochem.41, 1823–1832, 1993). The cell surface component which mediates the initial contact of VN with endothelial cells is defined here. The specific binding of VN to endothelial cells demonstrated the following properties: a threefold increase after phorbol ester treatment; 85% inhibition by pretreatment of cells with phosphatidylinositol–phospholipase C to release glycolipid-anchored surface proteins; a 90% inhibition by urokinase (u-PA) receptor blocking antibody. u-PA increased VN binding to cells due to an eightfold increase in the affinity of VN for the u-PA receptor. Structure–function studies showed that the amino-terminal fragment of u-PA, devoid of any proteolytic activity, mediated this effect. Active plasminogen activator inhibitor-1 (PAI-1), but not inactivated PAI-1, inhibited VN binding to cells and displaced VN that was prebound to endothelial cell monolayers. Similarly, VN binding to purified (immobilized) u-PA receptor, but not to integrin, was enhanced by u-PA and inhibited by PAI-1. Hence, the binding of soluble VN to endothelial cell surfaces is mediated by the u-PA receptor, and the relative concentrations of u-PA and PAI-1 are able to regulate the strength of this interaction. Endothelial cell adhesion to immobilized VN was found to be integrin-mediated without any involvement of the VN–uPA-receptor system. Hence, the interaction of VN with the u-PA receptor may be involved in the regulation of cellular processes necessary for endothelial cell invasion and migration at VN-rich extracellular matrix sites.     

Some heterostrophic gastropods from Triassic St. Cassian Formation with a discussion on the classification of the Allogastropoda

Fifteen species of Heterostropha are described, 12 of them for the first time. All are newly interpreted with regard to their taxonomic relation to fossil and living gastropods. The Streptacidoidea with long Paleozoic history are represented in the Late Triassic St. Cassian Formation by several genera that can be differentiated into four families. The Ebalidae are represented byEbala, with smooth protoconch, Cassianebalidae byCassianebala andLoxebala with axially ornamented protoconch. The Donaldinidae of St. Cassian are represented by one species ofDonaldina and two ofNeodonaldina that stand in the continuation of Paleozoic species ofDonaldina. Architectonicoidea with shells coiled in a plane and Valvatoidea appear in the St. Cassian fauna without known Paleozoic relation. In the former superfamily the Architectonicidae can be recognized in the genusRinaldoconchus with two species. Cassianaxidae withCassianaxis, Amphitomariidae withAmphitomaria, Stuoraxidae withStuoraxis andAmpezzogyra have a sinistral protoconch and planispirally coiled dextral teleconchs. They all resemble different modern species that have similarly small shells. Modern Hyalogyrinidae have withAlexogyra a new representative from the Triassic. The Valvatoidea are represented with the generaCarboninia andBandellina of the Cornirostridae in the Triassic representatives. The relation of described species in the system of the Heterostropha is discussed.     

Stimulus enhancement and spread of a spontaneous tool use in a colony of long-tailed macaques

In a captive group of long-tailed macaques, tool-using behavior by a single competent individual had a significant effect on the synchronous manipulative behavior of naïve animals. Group members engaged in manipulations on the same object class more frequently during times when the model was working than when it was not. The form of their behavior, however, in no way resembled the technique used by the model. All three animals that later became successful tool users were among the few subjects that exhibited a significant increase in manipulations on the same object class while the model was working. Possible causal relationships between this stimulus enhancement and the transmission of the new behavior to other group members are analyzed and discussed.     

Hybrid survival motor neuron genes in patients with autosomal recessive spinal muscular atrophy: new insights into molecular mechanisms responsible for the disease.

Spinal muscular atrophy (SMA) is a frequent autosomal recessive neurodegenerative disorder leading to weakness and atrophy of voluntary muscles. The survival motor-neuron gene (SMN), a strong candidate for SMA, is present in two highly homologous copies (telSMN and cenSMN) within the SMA region. Only five nucleotide differences within the region between intron 6 and exon 8 distinguish these homologues. Independent of the severity of the disease, 90%-98% of all SMA patients carry homozygous deletions in telSMN, affecting either exon 7 or both exons 7 and 8. We present the molecular analysis of 42 SMA patients who carry homozygous deletions of telSMN exon 7 but not of exon 8. The question arises whether in these cases the telSMN is truncated upstream of exon 8 or whether hybrid SMN genes exist that are composed of centromeric and telomeric sequences. By a simple PCR-based assay we demonstrate that in each case the remaining telSMN exon 8 is part of a hybrid SMN gene. Sequencing of cloned hybrid SMN genes from seven patients, as well as direct sequencing and single-strand conformation analysis of all patients, revealed the same composition in all but two patients: the base-pair differences in introns 6 and 7 and exon 7 are of centromeric origin whereas exon 8 is of telomeric origin. Nonetheless, haplotype analysis with polymorphic multicopy markers, Ag1-CA and C212, localized at the 5' end of the SMN genes suggests different mechanisms of occurrence, unequal rearrangements, and gene conversion involving both copies of the SMN genes. In approximately half of all patients, we identified a consensus haplotype, suggesting a common origin. Interestingly, we identified a putative recombination hot spot represented by recombination-stimulating elements (TGGGG and TGAGGT) in exon 8 that is homologous to the human deletion-hot spot consensus sequence in the immunoglobulin switch region, the alpha-globin cluster, and the polymerase alpha arrest sites. This may explain why independent hybrid SMN genes show identical sequences.     

Development of insect resistance in tomato plants expressing the δ-endotoxin gene ofBacillus thuringiensis subsp.tenebrionis

A crystal -endotoxin gene ofBacillus thuringiensis subsp.tenebrionis (B.t.t.) encoding a coleopteran insect-specific toxin was used to construct a chimeric gene which expressed the toxin in plant cells. Via anAgrobacterium tumefaciens binary vector system, the toxin gene was transferred into tomato cells. From leaf disks recombinant plants were regenerated. Hybridization experiments demonstrated that these plants synthesized toxin-specific mRNA of the expected size. Transgenic tomato plants with the chimericB.t.t. toxin gene contained a 74 kDa protein which cross-reacted with toxin antibodies. The expression caused a significant insecticidal activity of the transgenic tomato plants against Colorado potato beetle larvae.