Showing papers by "University of Basel published in 1986"

The nuclear lamina is a meshwork of intermediate-type filaments.

Abstract: The nuclear lamina, a protein meshwork lining the nucleoplasmic surface of the inner nuclear membrane, is thought to provide a framework for organizing nuclear envelope structure and an anchoring site at the nuclear periphery for interphase chromatin. In several higher eukaryotic cells, the lamina appears to be a polymer comprised mainly of one to three immunologically related polypeptides of relative molecular mass (Mr) 60,000-75,000 (60-70K) termed lamins. Three lamins (A, B, and C) are typically present in mammalian somatic cells. Previous studies on nuclear envelopes of rat liver and Xenopus oocytes suggested that the lamina has a fibrillar or filamentous substructure. Interestingly, protein sequences recently deduced for human lamins A and C from complementary DNA clones indicate that both of these polypeptides contain a region of approximately 350 amino acids very similar in sequence to the coiled-coil alpha-helical rod domain that characterizes all intermediate-type filament (IF) proteins. Here we analyse the supramolecular organization of the native nuclear lamina and the structure and assembly properties of purified lamins, and show that the lamins constitute a previously unrecognized class of IF polypeptides.

Plant chitinases are potent inhibitors of fungal growth

Abstract: The antimicrobial arsenal of plants is thought to consist mainly of secondary metabolites, among which the phytoalexins are the best-studied1–3. But plants may also possess antimicrobial proteins4,5: it has been reported that wheat-germ agglutinin, a chitin-binding lectin from wheat embryos, inhibits growth of the fungus Trichoderma viride4. This has led to the notion that plant lectins, with their intriguing biochemical similarity to animal antibodies, have an antibody-like antimicrobial function4,6,7. We report here that the main proteinaceous inhibitor of fungal growth in bean leaves is chitinase, an enzyme that can be induced by the plant hormone ethylene, or by pathogen attack. Among commercial preparations of purified chitin-binding lectins (from wheat germ, tomato, potato, pokeweed and gorse), only those containing contaminating chitinase activity inhibit fungal growth. Our data indicate that plant chitinases, but not chitin-binding lectins, are important antifungal proteins in plants.

Binding of a specific ligand inhibits import of a purified precursor protein into mitochondria

Abstract: Methotrexate, a folate antagonist, blocks import into mitochondria of mouse dihydrofolate reductase fused to a mitochondrial presequence. Methotrexate does not mask the presequence, but stabilizes the dihydrofolate reductase moiety. It does not inhibit import of the authentic precursor from which the presequence is derived. This suggests that dihydrofolate reductase must at least partly unfold in order to be transported across mitochondrial membranes.

Haematogenous metastastic patterns in colonic carcinoma: An analysis of 1541 necropsies

Abstract: The sequence of events in haematogenous metastasis from colonic carcinoma was analysed, using 1541 necropsy reports from 16 centres. The findings are consistent with the cascade hypothesis that metastases develop in discrete steps, first in the liver, next in the lungs and finally, in other sites. Deviations of necropsy findings from the cascade model are largely explained on the basis of false negative reports. In only 216 of 1194 cases was there suggestive evidence that metastatic patterns (excluding lymph nodes) were causally related to lymphatic or non-haematogenous pathways. The incidence of metastatic involvement in 'other' (quaternary) sites correlated with target organ blood-flow (ml min-) per g, only when bone marrow and thyroid were excluded. In the thyroid the incidence was lower than expected on the basis of blood flow per g tissue; this may indicate that the thyroid is an unfavourable site for metastatic growth of colonic carcinoma. In the bone marrow it is higher; the latter may be due to delivery of cancer cells via both arterial blood and the vertebral venous plexus. Recognition of this pattern of metastases in the bone marrow could be important with respect of diagnosis and therapy, in patients with colonic carcinoma.

Three-dimensional structure of the adenovirus major coat protein hexon.

Abstract: The three-dimensional crystal structure of the adenovirus major coat protein is presented. Adenovirus type 2 hexon, at 967 residues, is now the longest polypeptide whose structure has been determined crystallographically. Taken with our model for hexon packing, which positions the 240 trimeric hexons in the capsid, the structure defines 60% of the protein within the 150 X 10(6) dalton virion. The assembly provides the first details of a DNA-containing animal virus that is 20 times larger than the spherical RNA viruses previously described. Unexpectedly, the hexon subunit contains two similar beta-barrels whose topology is identical to those of the spherical RNA viruses, but whose architectural role in adenovirus is very different. The hexon structure reveals several distinctive features related to its function as a stable protective coat, and shows that the type-specific immunological determinants are restricted to the virion surface.

Structural organization and sequence of the homeotic gene Antennapedia of Drosophila melanogaster

Abstract: The structure of the Drosophila melanogaster Antennapedia (Antp) gene has been investigated by the isolation and sequencing of different cDNAs and genomic clones. Northern analysis, S1 mapping and primer extension experiments reveal a complex and unusual gene structure. The gene is composed of two promoters, eight exons spanning >100 kb, and two termination processing regions. Four major polyadenylated transcripts were found, two of them starting at a second internal promoter in front of exon 3. All four transcripts have extremely long untranslated leader and trailer sequences in the range of 1-2 kb. Despite the complex transcriptional organization, the open reading frame is the same in all transcripts, and starts in exon 5 giving rise to a protein of mol. wt. 42 800. The putative protein is rich in glutamine (18%) and proline (10%). The homeobox, a region which previously has been shown to be highly conserved among homeotic genes, is contained in the open reading frame and located in the last exon. Functional implications of the complex structure with respect to development and its relation to the mutant phenotypes are discussed.

Isolation of the paired gene of Drosophila and its spatial expression during early embryogenesis

Abstract: We have cloned the paired gene of Drosophila melanogaster, a pair-rule gene required for the establishment of proper segmentation. The transcriptional pattern in young embryos shows developmental polarities along the antero-posterior and dorso-ventral axes. Transcripts, initially expressed with a double-segment periodicity, switch to a single-segment repeat during syncytial blastoderm.

Identification of the O-linked sialyloligosaccharides of glycophorin A as the erythrocyte receptors for S-fimbriated Escherichia coli.

Abstract: The erythrocyte receptors for S-fimbriated Escherichia coli, which causes sepsis and meningitis in newborn infants, were investigated. Neuraminidase and trypsin treatments of erythrocytes abolished the hemagglutination ability of the bacteria. To identify the receptor glycoproteins, we separated erythrocyte membrane proteins by gel electrophoresis, blotted them to nitrocellulose, and incubated them with 125I-labeled bacteria. The only bacterium-binding bands identified corresponded to glycophorin A dimer and monomer, and the binding was abolished by neuraminidase treatment of the blot. Radiolabeled bacteria also bound to purified glycophorin A adsorbed to polyvinyl chloride microwells, and the binding was inhibited by other sialoglycoproteins and isolated sialyloligosaccharides containing the NeuAc alpha 2-3Gal sequence. Oligosaccharides which contain the NeuAc alpha 2-3Gal beta 1-3GalNAc and NeuAc alpha 2-3Gal beta 1-3(NeuAc alpha 2-6)GalNAc sequence and which are identical to the O-linked saccharides of glycophorin A were twofold more effective inhibitors of binding than were other oligosaccharides containing the NeuAc alpha 2-3Gal sequence. The replacement of sialic acid in asialoerythrocytes with a purified Gal beta 1-3GalNAc alpha 2-3 sialyltransferase, which forms the O-linked NeuAc alpha 2-3Gal beta 1-3GalNAc sequence in asialoglycophorins, restored bacterial hemagglutination. These results indicated that the major erythrocyte receptor for S-fimbriated E. coli is the NeuAc alpha 2-3Gal beta 1-3GalNAc sequence of the O-linked oligosaccharide chains of glycophorin A.

The cleavable pre-sequence of an imported chloroplast protein directs attached polypeptides into yeast mitochondria.

Abstract: The cleavable pre-sequences of imported chloroplast and mitochondrial proteins have several features in common This structural similarity prompted us to test whether a chloroplast pre-sequence (;transit peptide') can also be decoded by the mitochondrial import machinery In the green alga, Chlamydomonas reinhardtii, the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) (a chloroplast protein) is nuclear-encoded and synthesized in the cytosol with a transient pre-sequence of 45 residues The 31 amino-terminal residues of this chloroplast pre-sequence were fused to mouse dihydrofolate reductase (a cytosolic protein) and to yeast cytochrome oxidase subunit IV (an imported mitochondrial protein) from which the authentic pre-sequence had been removed The chloroplast pre-sequence transported both attached proteins into the yeast mitochondrial matrix or inner membrane, although it functioned less efficiently than an authentic mitochondrial pre-sequence We conclude that mitochondrial and chloroplast pre-sequences perform their function by a similar mechanism

Regulation of Fructan Metabolism in Leaves of Barley (Hordeum vulgare L. cv Gerbel).

Abstract: Excised primary leaf blades of barley (Hordeum vulgare L. cv Gerbel) rapidly synthesized large quantities of fructan in the light and, upon transfer to the dark, they rapidly degraded it again. In the course of such a light/dark cycle the activities of sucrose-sucrose-fructosyltransferase (SST), fructan hydrolase, and invertase were measured in cell-free extracts of the blades. SST activity increased 20-fold within 24 hours in the light and disappeared again upon transfer to the dark during a similar period of time. Cycloheximide inhibited the increase of SST activity in the light indicating de novo synthesis. The loss of SST activity in the dark, however, was unaffected by cycloheximide. No SST activity appeared in the light if photosynthesis was inhibited by lowering the CO(2) concentration in the atmosphere. However, SST activity and fructan synthesis were induced even in the dark and at a low CO(2) concentration when the leaf blades were immersed in a solution of sucrose. Several other sugars, maltose and fructose in particular, had the same effect. Trehalose induced SST activity but no fructan synthesis occurred. The activities of fructan hydrolase and invertase changed little during the light/dark cycle. It is suggested that the control of SST activity in conjunction with the supply of photosynthates plays a key role in the regulation of fructan metabolism.

Pancreatic lesions and hormonal profile of pancreatic tumors in multiple endocrine neoplasia type I. An immunocytochemical study of nine patients.

Abstract: Pancreatic specimens of nine patients suffering from multiple endocrine neoplasia type I (MEN I) were investigated with regard to tumor frequency and growth pattern, islet hyperplasia and endocrine cell neoformation, immunocytochemical hormone profile of the tumors, and correlation to clinical symptoms. The majority of the 201 tumors were microadenomas (diameter less than 0.5 cm), which frequently displayed a trabecular growth pattern. Microadenomatosis was considered the most distinct feature of the MEN I pancreas. Additional larger tumors (diameter greater than 1.0 cm) were found in five patients. Whereas islet hyperplasia appears not to belong to the spectrum of the pancreatic lesions in MEN I, nesidioblastosis was occasionally observed. Immunocytochemical screening revealed that among hormone-positive tumors (approximately 80% of the tumors), pancreatic polypeptide tumors (PPomas), glucagonomas, and insulinomas were the most frequent. The high incidence of PPomas in these pancreases probably accounts for the elevated serum PP levels found in many MEN I patients. Somatostatinomas, gastrinomas, vasoactive intestinal polypeptide tumors (VIPomas), and neurotensinomas were rare. Clinically overt hyperinsulinism, observed in two patients and associated with a large insulinoma, was cured by tumor resection. Eight of nine patients presented a Zollinger-Ellison's syndrome (ZES), but only in two patients were gastrin-producing tumors found. The source of gastrin in MEN I patients with a ZES, in whom no gastrinoma could be detected, remains unclear.

The molecular mechanisms of two common polymorphisms of drug oxidation-evidence for functional changes in cytochrome P-450 isozymes catalysing bufuralol and mephenytoin oxidation

Abstract: 1. Using the stereospecific metabolism of (+)- and (-)-bufuralol and (+)- and (-)metoprolol as model reactions, we have characterized the enzymic deficiency of the debrisoquinelsparteine-type polymorphism by comparing kinetic data of subjects in wiwo with their microsomal activities in uitro and with reconstituted activities of cytochrome P4SO isozymes purified from human liver. 2. The metabolism of bufuralol in liver microsomes of in viuo phenotyped ‘poor metabolizers’ of debrisoquine and/or sparteine is characterized by a marked increase in K,, a decrease in V,. and a virtual loss of the stereoselectivity of the reaction. These parameters apparently allow the ‘phenotyping’ of microsomes in uitro.

Epidermis and Dermis

Abstract: The first detailed histological report on reptilian skin was published well over 100 years ago (Leydig 1873). In the following 60 years a large number of studies has been accumulated and reviewed by Lange (1931). However, due to the piecemeal nature of the information available at this time, many misinterpretations occurred and no general patterns of differentiation could be demonstrated in this article.

Three descending interneurons reporting deviation from course in the locust. II. Physiology.

Abstract: The DNI, DNM and DNC descending interneurons all have very similar properties and are each at the convergence of visual, ocellar, wind-hair and other mechanoreceptor inputs. The 3 neurons respond almost exclusively to movement of the animal in space about its three axes of rotation. All are spatially and directionally selective. Movements in the preferred sense produce increasingly strong responses with amplitude and absolute position, while movements in the antipreferred sense usually elicit no response at all. Movements in the preferred sense, but towards, rather than away from, the normal flying position start to produce responses only as the animal approaches the normal flight position. The neurons function as feature detectors, responding only to specific sorts of deviation from course. DNI, DNM and DNC differ from one another principally in their directionality. DNI responds optimally to a diving banked turn to the ipsilateral side, DNM to downwards pitch, and the DNC to a diving banked turn to the contralateral side. The DN neurons contribute to the production of steering manoeuvres. They appear to be representatives of a larger class of descending interneurons bringing exteroceptive sensory input to the thoracic locomotory neuropil. The occurrence of this class of units in locusts and other insects is discussed.

Economics of chemical defense in chrysomelinae

Abstract: Chemical defense in chrysomelid larvae (subtribe Chrysomelina and Phyllodectina) is reviewed. Most species secrete autogenous monoterpenes. The diversity of their secretion is interpreted as a mechanism to reduce adaptation by predacious arthropods. The consequences of a host plant shift to the Salicacae are explored. Salicin from these host plants is used as a precursor for the salicylaldehyde secreted by the larvae of many species. This offers several advantages. It provides the larvae with an inexpensive and efficient defense. The recovery of the glucose moiety of the salicin contributes significantly to the larval energy budget. Adults sequester salicin in the eggs at concentrations which are toxic to ants. Owing to this maternal provisioning, neonate larvae produce salicylaldehyde from hatching onwards, whereas other species secreting monoterpenes are not protected at hatching. The secretion of salicylaldehyde by different species is considered to be chemical mimicry reinforcing visual aposematic signals.