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<jats:p> Two cumulene carbenes, H <jats:sub>2</jats:sub> C <jats:sub>5</jats:sub> and H <jats:sub>2</jats:sub> C <jats:sub>6</jats:sub> , were detected in a supersonic molecular beam by Fourier transform microwave spectroscopy. Their rotational and leading centrifugal distortion constants were determined with high accuracy, such that the entire radio spectrum can now be calculated. Like the known carbenes H <jats:sub>2</jats:sub> C <jats:sub>3</jats:sub> and H <jats:sub>2</jats:sub> C <jats:sub>4</jats:sub> , both molecules have singlet electronic ground states and linear carbon-chain backbones. They can be produced in sufficiently high concentrations in the laboratory that their electronic spectra, expected to lie in the visible, should be readily detectable by laser spectroscopy. The microwave spectra of other, more exotic isomers may be detectable as well. </jats:p>

<jats:p> Niobium/uranium ratios in greenstone-belt basalts and gabbros indicate that parts of the Late Archean mantle beneath Western Australia underwent a level of melt extraction, resulting in formation of the continental crust, comparable to that seen in the present mantle. The implication is either that (i) the amount of continental crust that formed before 2.7 × 10 <jats:sup>9</jats:sup> years ago was much greater than generally thought or (ii) crustal growth occurred by severe depletion of small volumes of the mantle rather than by moderate depletion of a large volume of mantle. </jats:p>

<jats:p>The nuclear factor κB (NF-κB) transcription factor is responsive to specific cytokines and stress and is often activated in association with cell damage and growth arrest in eukaryotes. NF-κB is a heterodimeric protein, typically composed of 50- and 65-kilodalton subunits of the Rel family, of which RelA(p65) stimulates transcription of diverse genes. Specific cyclin-dependent kinases (CDKs) were found to regulate transcriptional activation by NF-κB through interactions with the coactivator p300. The transcriptional activation domain of RelA(p65) interacted with an amino-terminal region of p300 distinct from a carboxyl-terminal region of p300 required for binding to the cyclin E-Cdk2 complex. The CDK inhibitor p21 or a dominant negative Cdk2, which inhibited p300-associated cyclin E-Cdk2 activity, stimulated κB-dependent gene expression, which was also enhanced by expression of p300 in the presence of p21. The interaction of NF-κB and CDKs through the p300 and CBP coactivators provides a mechanism for the coordination of transcriptional activation with cell cycle progression.</jats:p>

<jats:p> Development of the <jats:italic>Rhizobium</jats:italic> -legume symbiosis is controlled by the host plant, although the underlying mechanisms have remained obscure. A mutant in the annual legume <jats:italic>Medicago truncatula</jats:italic> exhibits an increase of more than an order of magnitude in the number of persistent rhizobial infections. Physiological and genetic analyses indicate that this same mutation confers insensitivity to the plant hormone ethylene for multiple aspects of plant development, including nodulation. These data support the hypothesis that ethylene is a component of the signaling pathway controlling rhizobial infection of legumes. </jats:p>

<jats:p> Tryptophan and serotonin were imaged with infrared illumination by three-photon excitation (3PE) of their native ultraviolet (UV) fluorescence. This technique, established by 3PE cross section measurements of tryptophan and the monoamines serotonin and dopamine, circumvents the limitations imposed by photodamage, scattering, and indiscriminate background encountered in other UV microscopies. Three-dimensionally resolved images are presented along with measurements of the serotonin concentration (∼50 mM) and content (up to ∼5 × 10 <jats:sup>8</jats:sup> molecules) of individual secretory granules. </jats:p>

<jats:p> Heterotrimeric GTP-binding proteins (G proteins) participate in cellular signaling and regulate a variety of physiological processes. Disruption of the gene encoding the G protein subunit α <jats:sub>13</jats:sub> (Gα <jats:sub>13</jats:sub> ) in mice impaired the ability of endothelial cells to develop into an organized vascular system, resulting in intrauterine death. In addition, Gα <jats:sub>13</jats:sub> (−/−) embryonic fibroblasts showed greatly impaired migratory responses to thrombin. These results demonstrate that Gα <jats:sub>13</jats:sub> participates in the regulation of cell movement in response to specific ligands, as well as in developmental angiogenesis. </jats:p>

<jats:p> Apoptosis, a form of cellular suicide, involves the activation of CED-3-related cysteine proteases (caspases). The regulation of caspases by apoptotic signals and the precise mechanism by which they kill the cell remain unknown. In <jats:italic>Drosophila</jats:italic> , different death-inducing stimuli induce the expression of the apoptotic activator <jats:italic>reaper</jats:italic> . Cell killing by <jats:italic>reaper</jats:italic> and two genetically linked apoptotic activators, <jats:italic>hid</jats:italic> and <jats:italic>grim</jats:italic> , requires caspase activity. A <jats:italic>Drosophila</jats:italic> caspase, named <jats:italic>Drosophila</jats:italic> caspase-1 (DCP-1), was identified and found to be structurally and biochemically similar to <jats:italic>Caenorhabditis elegans</jats:italic> CED-3. Loss of zygotic DCP-1 function in <jats:italic>Drosophila</jats:italic> caused larval lethality and melanotic tumors, showing that this gene is essential for normal development. </jats:p>

<jats:p>Lymphocyte-specific interferon regulatory factor (LSIRF) (now called IRF4) is a transcription factor expressed only in lymphocytes. Mice deficient in IRF4 showed normal distribution of B and T lymphocyes at 4 to 5 weeks of age but developed progressive generalized lymphadenopathy. IRF4-deficient mice exhibited a profound reduction in serum immunoglobulin concentrations and did not mount detectable antibody responses. T lymphocyte function was also impaired in vivo; these mice could not generate cytotoxic or antitumor responses. Thus, IRF4 is essential for the function and homeostasis of both mature B and mature T lymphocytes.</jats:p>

<jats:p> The morphology of axon terminals changes with differentiation into mature synapses. A molecule that might regulate this process was identified by a screen of <jats:italic>Drosophila</jats:italic> mutants for abnormal motor activities. The <jats:italic>still life</jats:italic> ( <jats:italic>sif</jats:italic> ) gene encodes a protein homologous to guanine nucleotide exchange factors, which convert Rho-like guanosine triphosphatases (GTPases) from a guanosine diphosphate-bound inactive state to a guanosine triphosphate-bound active state. The SIF proteins are found adjacent to the plasma membrane of synaptic terminals. Expression of a truncated SIF protein resulted in defects in neuronal morphology and induced membrane ruffling with altered actin localization in human KB cells. Thus, SIF proteins may regulate synaptic differentiation through the organization of the actin cytoskeleton by activating Rho-like GTPases. </jats:p>

<jats:p>Selective occlusion of tumor vasculature was tested as a therapy for solid tumors in a mouse model. The formation of blood clots (thrombosis) within the tumor vessels was initiated by targeting the cell surface domain of human tissue factor, by means of a bispecific antibody, to an experimentally induced marker on tumor vascular endothelial cells. This truncated form of tissue factor (tTF) had limited ability to initiate thrombosis when free in the circulation, but became an effective and selective thrombogen when targeted to tumor endothelial cells. Intravenous administration of the antibody-tTF complex to mice with large neuroblastomas resulted in complete tumor regressions in 38 percent of the mice.</jats:p>