Correlation between molecular structure and helicity of induced chiral nematics in terms of short-range and electrostatic-induction interactions. The case of chiral biphenyls.

The helical structure of the chiral nematic phases induced by chiral dopants in nematic solvents provides a macroscopic image of the molecular chirality of the dopant promoted by the orientational order. Chiral biphenyls are challenging systems because their twisting ability shows a strong dependence on the molecular structure, which does not conform to empirical correlation rules. This points out the need for adequate interpretative tools, able to establish a link between molecular properties and macroscopic response. In this paper the twisting ability of chiral biphenyls is reviewed, by reporting examples taken from the literature together with some new experimental results. The microscopic origin of the observed behavior is explained in terms of chirality and anisotropy of short-range and electrostatic-induction interactions. These are described, respectively, by a shape model and a reaction field method, having the common characteristics of a realistic representation of the structure and properties of the chiral dopants in terms of molecular surface, atom charges, and distributed polarizabilities.

Streptomyces genes involved in biosynthesis of the peptide antibiotic valinomycin.

We have identified genes from Streptomyces levoris A-9 involved in the biosynthesis of the peptide antibiotic valinomycin. Two segments of chromosomal DNA were recovered from genomic libraries, constructed by using the low-copy-number plasmid pIJ922, by complementation of valinomycin-deficient (vlm) mutants of S. levoris A-9. One set of plasmids restored valinomycin production to only one mutant, that carrying vlm-1, whereas a second set of plasmids restored productivity to seven vlm mutants, those carrying vlm-2 through vlm-8. Additional complementation studies using subcloned restriction enzyme fragments showed that the vlm-1+ gene was contained within a 2.5-kilobase (kb) DNA region, whereas alleles vlm-2+ through vlm-8+ were contained in a 12-kb region, representing at least three genes. Physical mapping experiments based on the isolation of cosmid clones showed that the two vlm loci were 50 to 70 kb apart. Southern hybridization experiments demonstrated that the vlm-2+ gene cluster was highly conserved among other valinomycin-producing Streptomyces strains, whereas the vlm-1+ gene was ubiquitous among Streptomyces species tested. Increasing the copy number of the vlm-2+ gene cluster in S. levoris A-9 by the introduction of low-copy-number recombinant plasmids resulted in a concomitant increase in the level of valinomycin production.

Structure, regulatory polymorphisms, and allelic hypervariability regions in murine I-A alpha.

Class II major histocompatibility complex (MHC) molecules, the Ia antigens, are intimately involved in regulating the intensity and specificity of the cellular and humoral responses to T cell-dependent antigens. One approach to understanding the mechanism of this regulation is to analyze the structure and allelic polymorphism of Ia molecules. In addition there are regulatory polymorphisms in the expression of the I-E alpha and I-E beta class II MHC polypeptide chains. Analysis of the cDNA sequence indicates that I-A and I-E alpha chains are similar with short stretches of homology and other regions of nonhomology. Analysis of Northern blots of mRNA indicates that at least three separate types of regulatory polymorphisms result in failure of expression of I-E alpha. Comparison of allelic sequences of six alleles of the I-A alpha chain shows that almost all of the allelic polymorphism is in the first domain and that within the first domain it is clustered in three allelic hypervariable regions within the first domain of I-A alpha. The structural and functional implications of these findings are discussed.

Regions of allelic hypervariability in the murine A alpha immune response gene.

The murine Ia antigens, a group of cell surface glycoproteins, are involved in the control of the immune response. The structure of one of these class II major histocompatibility complex molecules, A alpha, was recently deduced from sequence analysis of a cDNA clone produced from k haplotype mice. We have now isolated and sequenced A alpha cDNA clones from five other mouse haplotypes: d, b, f, u, and q. Sequence comparison revealed a surprisingly high degree of allelic polymorphism. Interestingly, amino acid substitutions were clustered within the first external domain of this polypeptide chain, particularly at a few highly variable positions. Functional implications of A alpha polymorphism and possible mechanisms for its generation are discussed.

The murine E alpha immune response gene.

We have isolated and sequenced cDNA and genomic clones of the murine E alpha gene, one of the immune response genes of the major histocompatibility complex. Comparison of our data with those recently reported for the human homolog DR alpha shows an identical intron-exon structure, and a good conservation of the protein-coding sequences, including the amino acids potentially involved in organizing the second external protein domain into an immunoglobulin-like fold. Noncoding sequences are less conserved, with the exception of the promoter region. Finally, we show that differential expression of the gene in various cell types appears to be transcriptionally regulated, and that genomic rearrangements do not seem necessary for expression.

Several mechanisms can account for defective E alpha gene expression in different mouse haplotypes.

The murine Ia antigens, encoded by the I region of the major histocompatibility complex, are cell-surface glyco-proteins (consisting of alpha and beta polypeptides) thought to be involved in the control of immune responsiveness. Mice of haplotypes b, s, q, and f fail to express one of the Ia antigen complexes, the E complex, on the cell surface. We have attempted to determine at the molecular level how such a defect (or defects) might be generated. By using I-region E alpha and A alpha gene probes for analyses of RNA and DNA structure, it was possible to conclude that at least three mechanisms can operate. Mice of haplotypes b and s bear a deletion in the E alpha gene, f haplotype mice synthesize predominantly an E alpha mRNA of aberrant size, and mice of the q haplotype seem to have a defect in RNA processing or a problem with mRNA stability, or both.

The murine Ia alpha chains, E alpha and A alpha, show a surprising degree of sequence homology.

The I region of the murine major histocompatibility complex codes for a group of glycoproteins, the Ia antigens, thought to be involved in the control of immune responsiveness. Each Ia antigen complex contains a "heavy chain," a "light chain," and the "invariant chain." We describe here the isolation and characterization of genomic and cDNA clones for one of the heavy chains, Ak alpha. The complete nucleotide sequence of the cDNA clone is presented, and the predicted amino acid sequence is compared with that of another alpha chain, Ek alpha. About 50% of the amino acids are identical, a finding somewhat unexpected on the basis of preliminary protein sequence data.

Monoclonal antibodies reacting with murine teratocarcinoma cells.

Monoclonal antibodies were produced in vitro by fusing mouse myeloma cells with spleen cells from a rat immunized with the C3H mouse teratocarcinoma C86-S1. After the fusion two clones were chosen for further analysis. The first clone, 3C4-10, produced an antibody recognizing an antigen with a distribution restricted to teratocarcinoma cell lines, an endoderm cell line, and a neuroblastoma. The second clone, 4A1-9, produced an antibody that reacted with all cultured murine cells tested and adult brain. Neither antibody reacted with preimplantation embryos. The 3C4-10 antibody recognized an antigen associated with proteins. The apparent molecular weight of the 3C4-10 antigen was greater than 100,000.