RESUMEN
The electronic structures of two series of end-capped thiophene oligomers, one set containing the electron-deficient dimesitylboryl end-cap and one containing the electron-rich triaryl amine end-cap, have been modeled using semiempirical quantum chemical calculations and the results used to assign features in the photoemission spectra of the materials in the condensed phase. For the thiophene oligomers end-capped with the electron-deficient dimesitylboryl moieties, the energy of the occupied frontier orbitals is largely governed by pi-type orbitals of the thiophene repeat units in the oligothiophene main chain. Conversely, in oligomers end-capped with electron-rich triarylamine moieties, the occupied frontier orbital energies are largely governed by orbital states of heavily mixed character associated with thiophene pi-type systems and the low-lying nitrogen lone pairs of end capping groups.
Asunto(s)
Simulación por Computador , Modelos Químicos , Teoría Cuántica , Tiofenos/química , Sensibilidad y Especificidad , Espectrofotometría/métodosRESUMEN
The GATA family of transcription factors participates in gastrointestinal (GI) development. Increases in GATA-4 and -5 expression occur in differentiation and GATA-6 expression in proliferation in embryonic and adult settings. We now show that in colorectal cancer (CRC) and gastric cancer promoter hypermethylation and transcriptional silencing are frequent for GATA-4 and -5 but are never seen for GATA-6. Potential antitumor target genes upregulated by GATA-4 and -5, the trefoil factors, inhibinalpha, and disabled-2 (Dab2) are also silenced, in GI cancers, with associated methylation of the promoters. Drug or genetically induced demethylation simultaneously leads to expression, in CRC cells, of all of the GATA-4, -5, and downstream genes. Expression of exogenous GATA-5 overrides methylation at the downstream promoters to activate the target genes. Selection for silencing of both upstream transcription factors and their target genes in GI cancers could indicate that epigenetic silencing of the involved genes provides a summated contribution to tumor progression.
Asunto(s)
Neoplasias Colorrectales/genética , Proteínas de Unión al ADN/genética , Silenciador del Gen , Neoplasias Gástricas/genética , Factores de Transcripción/genética , Línea Celular Tumoral , Neoplasias Colorrectales/etiología , Islas de CpG , Metilación de ADN , ADN de Neoplasias/genética , Epigénesis Genética , Factor de Transcripción GATA4 , Factor de Transcripción GATA5 , Factor de Transcripción GATA6 , Humanos , Oncogenes , Regiones Promotoras Genéticas , Neoplasias Gástricas/etiologíaRESUMEN
We report a compact light collection scheme suitable for retrofitting a scanning tunneling microscope (STM) for STM-induced light emission experiments. The approach uses a pair of optical fibers with large core diameters and high numerical apertures to maximize light collection efficiency and to moderate the mechanical precision required for alignment. Bench tests indicate that efficiency reduction is almost entirely due to reflective losses at the fiber ends, while losses due to fiber misalignment have virtually been eliminated. Photon-map imaging with nanometer features is demonstrated on a stepped Au(111) surface with signal rates exceeding 10(4) counts/s.
Asunto(s)
Tecnología de Fibra Óptica/instrumentación , Aumento de la Imagen/instrumentación , Interpretación de Imagen Asistida por Computador/instrumentación , Microscopía de Túnel de Rastreo/instrumentación , Diseño de Equipo , Análisis de Falla de Equipo , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/métodos , Luz , Microscopía de Túnel de Rastreo/métodos , Fibras Ópticas , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
The tumor suppressor p16INK4a, one protein encoded by the INK4/ARF locus, is frequently absent in multiple cancers, including non-small cell lung cancer (NSCLC). Whereas increased methylation of the encoding gene (CDKN2A) accounts for its loss in a third of patients, no molecular explanation exists for the remainder. We unraveled an alternative mechanism for the silencing of the INK4/ARF locus involving the E3 ubiquitin ligase and transcriptional cofactor E6AP (also known as UBE3A). We found that the expression of three tumor suppressor genes encoded in the INK4/ARF locus (p15INK4b, p16INK4a, and p19ARF) was decreased in E6AP-/- mouse embryo fibroblasts. E6AP induced the expression of the INK4/ARF locus at the transcriptional level by inhibiting CDC6 transcription, a gene encoding a key repressor of the locus. Luciferase assays revealed that E6AP inhibited CDC6 expression by reducing its E2F1-dependent transcription. Chromatin immunoprecipitation analysis indicated that E6AP reduced the amount of E2F1 at the CDC6 promoter. In a subset of NSCLC samples, an E6AP-low/CDC6-high/p16INK4a-low protein abundance profile correlated with low methylation of the gene encoding p16INK4a (CDKN2A) and poor patient prognosis. These findings define a previously unrecognized tumor-suppressive role for E6AP in NSCLC, reveal an alternative silencing mechanism of the INK4/ARF locus, and reveal E6AP as a potential prognostic marker in NSCLC.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Inhibidor p15 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Inhibidor p19 de las Quinasas Dependientes de la Ciclina/genética , Neoplasias Pulmonares/genética , Ubiquitina-Proteína Ligasas/genética , Animales , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Células Cultivadas , Inhibidor p15 de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Inhibidor p19 de las Quinasas Dependientes de la Ciclina/metabolismo , Metilación de ADN , Factor de Transcripción E2F1/genética , Factor de Transcripción E2F1/metabolismo , Embrión de Mamíferos/citología , Fibroblastos/citología , Fibroblastos/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Ratones Noqueados , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Regiones Promotoras Genéticas/genética , Unión Proteica , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
We have investigated the initial stages of vacuum-deposited sexithiophene (alpha-6T) adlayer formation on Au(111) vicinal surfaces at room temperature. The in situ scanning tunneling microscopy (STM) and photoemission spectroscopy (PES) reveal a step edge-driven growth of alpha-6T on the Au(111) vicinal surfaces that first leads to the formation of an ordered monolayer, comprising two phases with the molecular major axes aligned along the step edges. The monolayer formation is then followed by the appearance of a single-phase 2D superstructure at a two-monolayer coverage. The results highlight the potential of using vicinal metal surfaces as templates for generating organized organic nanostructures over macroscopic areas for applications in organic electronics and moletronics.