Structure, flame retarding and smoke suppressing properties of Zn-Mg-Al-CO3 layered double hydroxides

Zn-Mg-Al-CO3 layered double hydroxides (LDHs) have been synthesized by a new method involving separate nucleation and aging steps. The Zn-Mg-Al-CO3 LDHs were characterized by XRD, FT-IR, ICP and TG-DTA. The limiting oxygen index and smoke density of composites of the LDHs with EVA-28 were determined. Incorporation of Zn^2 in the layers of the LDHs was found promoting material charring and smoke suppression. The mechanism of flame retardation and smoke suppression is discussed. The results show that Zn-Mg-Al-CO3 LDHs have better flam eretarding and smoke suppressing effects than Mg-Al-CO3 LDHs.     

Germline mutations in RAD51D confer susceptibility to ovarian cancer

Recently, RAD51C mutations were identified in families with breast and ovarian cancer. This observation prompted us to investigate the role of RAD51D in cancer susceptibility. We identified eight inactivating RAD51D mutations in unrelated individuals from 911 breast-ovarian cancer families compared with one inactivating mutation identified in 1,060 controls (P = 0.01). The association found here was principally with ovarian cancer, with three mutations identified in the 59 pedigrees with three or more individuals with ovarian cancer (P = 0.0005). The relative risk of ovarian cancer for RAD51D mutation carriers was estimated to be 6.30 (95% CI 2.86-13.85, P = 4.8 × 10(-6)). By contrast, we estimated the relative risk of breast cancer to be 1.32 (95% CI 0.59-2.96, P = 0.50). These data indicate that RAD51D mutation testing may have clinical utility in individuals with ovarian cancer and their families. Moreover, we show that cells deficient in RAD51D are sensitive to treatment with a PARP inhibitor, suggesting a possible therapeutic approach for cancers arising in RAD51D mutation carriers.     

Dynamic evolution of the innate immune system in Drosophila

The availability of complete genome sequence from 12 Drosophila species presents the opportunity to examine how natural selection has affected patterns of gene family evolution and sequence divergence among different components of the innate immune system. We have identified orthologs and paralogs of 245 Drosophila melanogaster immune-related genes in these recently sequenced genomes. Genes encoding effector proteins, and to a lesser extent genes encoding recognition proteins, are much more likely to vary in copy number across species than genes encoding signaling proteins. Furthermore, we can trace the apparent recent origination of several evolutionarily novel immune-related genes and gene families. Using codon-based likelihood methods, we show that immune-system genes, and especially those encoding recognition proteins, evolve under positive darwinian selection. Positively selected sites within recognition proteins cluster in domains involved in recognition of microorganisms, suggesting that molecular interactions between hosts and pathogens may drive adaptive evolution in the Drosophila immune system.     

Social networks and private spaces in economic forecasting

The outputs of economic forecasting—predictions for national economic indicators such as GDP, unemployment rates and inflation—are all highly visible. The production of these forecasts is a much more private affair, however, typically being thought of as the work of individual forecasters or forecast teams using their economic model to produce a forecast that is then made public. This conception over-emphasises the individual and the technical whilst silencing the broader social context through which economic forecasters develop the expertise that is essential for the credibility of their predictions. In particular, economic forecasts are given meaning and fine-tuned through the social and institutional networks that give forecasters access to the expertise of a heterogeneous mix of academics, policy-makers and business people. Within these broader groups, individual forecasters often create private forecast ‘clubs’, where subscribers have privileged access to the expertise of the economist, but where the forecasters also have privileged access to their clients’ own expert knowledge. In examining these aspects of the forecasters’ work I show that the visible and audible activities of modelling and forecasting are made possible and plausible by virtue of the modeller’s invisible interaction with a wider network.     

Karyotypic abnormalities create discordance of germline genotype and cancer cell phenotypes

The nature of mendelian inheritance assumes that all tissues in which a phenotype of interest is expressed have a uniform diploid karyotype, which is often not the case in cancer cells. Owing to nonrandom gains of chromosomes, trisomies are present in many cases of leukemia and other malignances. We used polymorphisms in the genes encoding thiopurine S-methyltransferase (TPMT), gamma-glutamyl hydrolase (GGH) and the reduced folate carrier (SLC19A1) to assess the nature of chromosomal acquisition and its influence on genotype-phenotype concordance in cancer cells. TPMT and GGH activities in somatic cells were concordant with germline genotypes, whereas activities in leukemia cells were determined by chromosomal number and whether the acquired chromosomes contained a wild-type or variant allele. Leukemia cells that had acquired an additional chromosome containing a wild-type TPMT or GGH allele had significantly lower accumulation of thioguanine nucleotides or methotrexate polyglutamates, respectively. Among these genes, there was a comparable number of acquired chromosomes with wild-type and variant alleles. Therefore, chromosomal gain can alter the concordance of germline genotype and cancer cell phenotypes, indicating that allele-specific quantitative genotyping may be required to define cancer pharmacogenomics unequivocally.     

Identification of the T-cell and Ia contact residues of a T-cell antigenic epitope

The precise molecular structure of the antigenic determinant recognized by the T-cell receptor of the CD4-positive cell has not been completely resolved. A major advance in our understanding of this issue has been made by our demonstration of a direct association between an immunogenic peptide and a purified Ia molecule. The most likely and economical hypothesis is that antigen binds directly to an Ia molecule creating the antigenic determinant and that this antigen-Ia complex is recognized by the T-cell receptor. We examined in detail a determinant of hen egg-white lysozyme (HEL) contained in the tryptic fragment HEL(46-61), recognized by T cells in H-2k strains of mice. This peptide binds with a Kd of approximately 3 microM to I-Ak molecules. We have already ascertained that (1) the 10-mer HEL(52-61) is the shortest stimulatory peptide; (2) the Leu56 residue, the only residue different from mouse lysozyme, is responsible for the immunogenicity; (3) the Leu56 and Tyr53 residues are critical for recognition by the T-cell receptor and (4) HEL(46-61) generates multiple determinants when it associated with the I-Ak molecule. If antigen and Ia interact, the antigen must have two features: it must bind to an Ia molecule and also interact with the T-cell receptor. The two sites do not appear to be laterally separable in this peptide and are therefore probably composed of distinct but interspersed amino-acid residues. We have now identified the three residues of HEL(52-61) that contact the T-cell receptor and three other residues that contact the I-Ak molecule. From modelling studies we also propose that HEL(52-61) assumes an alpha-helical conformation as it is bound to I-Ak and recognized by the T-cell receptor.