On the tertiary structure of the extracellular domains of the epidermal growth factor and insulin receptors

Alignment of the sequences, the identification of conserved residue patterns and secondary structure predictions indicate that the extra-cellular regions of the human and Drosophila epidermal growth factor (EGF), c-erb-B2 and human insulin receptors each contain two large, homologous domains (L) which are probably comprised of at least four short alpha-helices followed by turns of conserved length and beta-strands. In the human and Drosophila EGF and c-erb-B2 receptors these homologous domains are each followed by a series of smaller cystine-rich domains (S) to give a gene-duplicated structure of L1S11S12S13L2S21S22S23. In the human insulin receptor, the second series of cystine domains is replaced by a different sequence. These duplicated structures are probably organised as a pseudo-symmetrical dimer. There are two 'hyper-variable' regions, one at the end of the large domains and one in the cystine-rich sequences, which are candidates for hormone or growth-factor binding.     

HISTORICAL VERSUS SELECTIONIST EXPLANATIONS IN EVOLUTIONARY BIOLOGY

Abstract— Evolutionary changes require historical explanations, yet these are limited by the evolutionary processes we entertain and investigate. Using phylogenetic analysis, adaptation and natural selection can be tested as historical claims, but this is appropriate only in those special cases where change follows the scheme of one character-one function, singled out in new environmental circumstances. Systematic treatment of the evolutionary origin of characters (in particular, origin through ecological and developmental flexibility) lies outside the scope of selectionist explanations. Structural hypotheses about regularities in the directions of change, also analyzed phylogenetically, expand the scope of historical explanation to include the origin of characters, yet retain the view of organisms as passive and constrained objects of evolutionary change. Historical biology needs to encompass both the active responses of organisms and the construction by organisms of their own environments. For this to be realized will require changes in the concepts and practices of evolutionary biology, including a re-examination of the Lamarckian theme that the active responses of organisms have evolutionary significance—the rarity of individual-to-individual transmission of "acquired" characters does not disprove the possibility of their frequency increasing in a population.     

Clinical hypersensitivity to specific aerosol challenge in parenterally immunized calves.

This paper reports an experiment designed to demonstrate that the calf lung can be sensitized to a specific respirable challenge following parenteral immunization with a nonliving antigen (human serum albumin). The possibility that immune-mediated injury could subsequently interfere with nonspecific mucosal defenses was also investigated by infecting calves with Pasteurella haemolytica after the antigen challenge and assessing pulmonary clearance of the organism. The results indicated that specific aerosol challenge produces reversible signs of respiratory hypersensitivity and that persistence of incidental infection in the upper respiratory tract is potentiated. Since the calves were sensitized by an immunization regime which imitated conventional vaccination, this study highlights the potential dangers of inactivated parenteral respiratory vaccines.     

Metabolism of the mutagen MeIQx in vivo: metabolite screening by liquid chromatography-thermospray mass spectrometry

2-Amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx) is a potent mutagen found in cooked food. MeIQx and its isotopically labelled (13C, 15N2 and 14C) analogues were synthesised and used for metabolic studies in vivo. An equimolar mixture of MeIQx and its 13C, 15N2 stable isotope labelled analogue (containing tracer amounts of 14C-MeIQx) was given intraperitoneally to mice. Some 67% of the radioactivity was eliminated in urine and faeces within 24h. Four radiolabelled species were observed when urine was analysed by HPLC, corresponding to unchanged MeIQx and three more polar metabolites. Urine was analysed directly by HPLC-thermospray mass spectrometry. Four signals were observed containing the characteristic 1:1 isotopic doublet, corresponding to unchanged MeIQx, an MeIQx glucuronide, and two uncharacterized metabolites.     

Chromosome organisation in polyploid mouse trophoblast nuclei

At least one-third of mouse trophoblast cells undergo endoreduplication during the first half of gestation. It has been suggested that the endoreduplicated chromosomes may be polytenised. Here it is shown, using in situ hybridisation to the -1 antitrypsin genes, which map at a unique site, that while there is a tendency for duplicated chromosomes to cluster, this does not involve the complete fusion of replicated chromatids found in fully polytene chromosomes, and in a substantial proportion of homologues the sites on the chromosome arms corresponding to these genes are widely separated. The centromeres do not fuse into a single chromocentre but the possibility is not ruled out that individual chromosomes may be polytenised in the centromeric region. Evidence is also presented showing that endoreduplication in trophoblast nuclei is not accompanied by the formation of new prekinetochore structures, in contrast to the situation in polyploid mouse liver and C127 cells.     

The beta 1----2-D-xylose and alpha 1----3-L-fucose substituted N-linked oligosaccharides from Erythrina cristagalli lectin. Isolation, characterisation and comparison with other legume lectins

The carbohydrate moieties of Erythrina cristagalli lectin were released as oligosaccharides by hydrazinolysis, followed by N-acetylation and reduction with NaB3H4. Fractionation of the tritium-labelled oligosaccharide mixture by Bio-Gel P-4 column chromatography and high-voltage borate electrophoresis revealed that it is composed of five neutral oligosaccharides. Structural studies by sequential exoglycosidase digestion in combination with methylation analysis and two-dimensional 1H-NMR showed that the major component was the fucose-containing heptasaccharide Man alpha 3(Man alpha 6)(Xyl beta 2)Man beta 4GlcNAc beta 4(Fuc alpha 3)GlcNAcol. This is the first report of such a structure in plant lectins. Small amounts of the corresponding afucosyl hexasaccharide were also identified, as well as three other minor components. The structure of the heptasaccharide shows the twin characteristics of a newly established family of N-linked glycans, found to date only in plants. The characteristics are substitution of the common pentasaccharide core [Man alpha 3(Man alpha 6)Man beta 4GlcNAc beta 4GlcNAc] by a D-xylose residue linked beta 1----2 to the beta-mannosyl residue and an L-fucose residue linked alpha 1----3 to the reducing terminal N-acetylglucosamine residue. The oligosaccharide heterogeneity pattern for Erythrina cristagalli lectin was also found for the lectins from four other Erythrina species and the lectins of two other legumes, Sophora japonica and Lonchocarpus capassa.