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<jats:p>For the past decade the immune system has been exploited as a rich source of de novo catalysts. Catalytic antibodies have been shown to have chemoselectivity, enantioselectivity, large rate accelerations, and even an ability to reroute chemical reactions. In many instances catalysts have been made for reactions for which there are no known natural or man-made enzymes. Yet, the full power of this combinatorial system can only be exploited if there was a system that allows for the direct selection of a particular function. A method that allows for the direct chemical selection for catalysis from antibody libraries was so devised, whereby the positive aspects of hybridoma technology were preserved and re-formatted in the filamentous phage system to allow direct selection of catalysis. This methodology is based on a purely chemical selection process, making it more general than biologically based selection systems because it is not limited to reaction products that perturb cellular machinery.</jats:p>

<jats:p> A cytochrome c oxidase model that consists of a cobalt(II) porphyrin with a copper(I) triazacyclononane macrocycle fastened on the distal face and an imidazole covalently attached to the proximal face has been synthesized and characterized. Redox titrations with molecular oxygen (O <jats:sub>2</jats:sub> ) and cobaltocene were carried out, and O <jats:sub>2</jats:sub> was found to bind irreversibly in a 1:1 ratio to the model compound. This O <jats:sub>2</jats:sub> adduct (a bridged peroxide) can be fully reduced to the deoxygenated form with four equivalents of cobaltocene. The model compound was adsorbed on an edge-plane graphite electrode, and rotating ring-disk voltammetry was used to monitor the electrocatalytic reduction of O <jats:sub>2</jats:sub> . Four-electron reduction of O <jats:sub>2</jats:sub> was observed at physiological pH. </jats:p>

<jats:p> Gas chromatographic-mass spectral analyses of the four stereoisomers of 2-amino-2,3-dimethylpentanoic acid (DL-α-methylisoleucine and DL-α-methylalloisoleucine) obtained from the Murchison meteorite show that the L enantiomer occurs in excess (7.0 and 9.1%, respectively) in both of the enantiomeric pairs. Similar results were obtained for two other α-methyl amino acids, isovaline and α-methylnorvaline, although the α hydrogen analogs of these amino acids, α-amino- <jats:italic>n</jats:italic> -butyric acid and norvaline, were found to be racemates. With the exception of α-amino- <jats:italic>n</jats:italic> -butyric acid, these amino acids are either unknown or of limited occurrence in the biosphere. Because carbonaceous chondrites formed 4.5 billion years ago, the results are indicative of an asymmetric influence on organic chemical evolution before the origin of life. </jats:p>

<jats:p>A three-dimensional molecular dynamics simulation of shock wave loading was undertaken to investigate the Hugoniot equation of state at the transition of argon from solid to liquid. The simulated data agree with shock wave and static high-pressure experimental data. The melting transition in this simulation occurs without overshooting the argon melting temperature. There are two discontinuities that may bracket a mixed-phase region of solid and liquid along the simulated argon Hugoniot. This is an intrinsic feature of the Hugoniot crossing the argon melting curve and does not require the addition of any solid-solid phase transition.</jats:p>

<jats:p>An analysis of historical sea surface temperatures provides evidence for global warming since 1900, in line with land-based analyses of global temperature trends, and also shows that over the same period, the eastern equatorial Pacific cooled and the zonal sea surface temperature gradient strengthened. Recent theoretical studies have predicted such a pattern as a response of the coupled ocean-atmosphere system to an exogenous heating of the tropical atmosphere. This pattern, however, is not reproduced by the complex ocean-atmosphere circulation models currently used to simulate the climatic response to increased greenhouse gases. Its presence is likely to lessen the mean 20th-century global temperature change in model simulations.</jats:p>

<jats:p>The mechanisms responsible for thyrocyte destruction in Hashimoto's thyroiditis (HT) are poorly understood. Thyrocytes from HT glands, but not from nonautoimmune thyroids, expressed Fas. Interleukin-1β (IL-1β), abundantly produced in HT glands, induced Fas expression in normal thyrocytes, and cross-linking of Fas resulted in massive thyrocyte apoptosis. The ligand for Fas (FasL) was shown to be constitutively expressed both in normal and HT thyrocytes and was able to kill Fas-sensitive targets. Exposure to IL-1β induced thyrocyte apoptosis, which was prevented by antibodies that block Fas, suggesting that IL-1β-induced Fas expression serves as a limiting factor for thyrocyte destruction. Thus, Fas-FasL interactions among HT thyrocytes may contribute to clinical hypothyroidism.</jats:p>

<jats:p>Putative endothelial cell (EC) progenitors or angioblasts were isolated from human peripheral blood by magnetic bead selection on the basis of cell surface antigen expression. In vitro, these cells differentiated into ECs. In animal models of ischemia, heterologous, homologous, and autologous EC progenitors incorporated into sites of active angiogenesis. These findings suggest that EC progenitors may be useful for augmenting collateral vessel growth to ischemic tissues (therapeutic angiogenesis) and for delivering anti- or pro-angiogenic agents, respectively, to sites of pathologic or utilitarian angiogenesis.</jats:p>

<jats:p> Cancers of the microsatellite mutator phenotype (MMP) show exaggerated genomic instability at simple repeat sequences. More than 50 percent (21 out of 41) of human MMP <jats:sup>+</jats:sup> colon adenocarcinomas examined were found to have frameshift mutations in a tract of eight deoxyguanosines [(G) <jats:sub>8</jats:sub> ] within <jats:italic>BAX</jats:italic> , a gene that promotes apoptosis. These mutations were absent in MMP <jats:sup>−</jats:sup> tumors and were significantly less frequent in (G) <jats:sub>8</jats:sub> repeats from other genes. Frameshift mutations were present in both <jats:italic>BAX</jats:italic> alleles in some MMP <jats:sup>+</jats:sup> colon tumor cell lines and in primary tumors. These results suggest that inactivating <jats:italic>BAX</jats:italic> mutations are selected for during the progression of colorectal MMP <jats:sup>+</jats:sup> tumors and that the wild-type <jats:italic>BAX</jats:italic> gene plays a suppressor role in a p53-independent pathway for colorectal carcinogenesis. </jats:p>

<jats:p> Posttetanic potentiation (PTP) is a common form of short-term synaptic plasticity that is generally thought to be entirely presynaptic. Consistent with that idea, PTP of evoked excitatory postsynaptic potentials at <jats:italic>Aplysia</jats:italic> sensory-motor neuron synapses in cell culture was reduced by presynaptic injection of a slow calcium chelator and was accompanied by an increase in the frequency but not the amplitude of spontaneous excitatory postsynaptic potentials. However, PTP was also reduced by postsynaptic injection of a rapid calcium chelator or postsynaptic hyperpolarization. Thus, PTP at these synapses is likely to involve a postsynaptic induction mechanism in addition to the known presynaptic mechanisms. </jats:p>

<jats:p> The telomerase ribonucleoprotein catalyzes the addition of new telomeres onto chromosome ends. A gene encoding a mammalian telomerase homolog called TP1 (telomerase-associated protein 1) was identified and cloned. TP1 exhibited extensive amino acid similarity to the <jats:italic>Tetrahymena</jats:italic> telomerase protein p80 and was shown to interact specifically with mammalian telomerase RNA. Antiserum to TP1 immunoprecipitated telomerase activity from cell extracts, suggesting that TP1 is associated with telomerase in vivo. The identification of TP1 suggests that telomerase-associated proteins are conserved from ciliates to humans. </jats:p>