β‐catenin is the major effector of the canonical Wnt signaling pathway. Mutations in components of the pathway that stabilize β‐catenin result in augmented gene transcription and play a major role in ...many human cancers. We employed microarrays to identify transcriptional targets of deregulated β‐catenin in a human epithelial cell line (293) engineered to produce mutant β‐catenin and in ovarian endometrioid adenocarcinomas characterized with respect to mutations affecting the Wnt/β‐catenin pathway. Two genes strongly induced in both systems—FGF20 and DKK1—were studied in detail. Elevated levels of FGF20 RNA were also observed in adenomas from mice carrying the ApcMinallele. Both XFGF20 and Xdkk‐1 are expressed early in Xenopus embryogenesis under the control of the Wnt signaling pathway. Furthermore, FGF20 and DKK1 appear to be direct targets for β‐catenin/TCF transcriptional regulation via LEF/TCF‐binding sites. Finally, by using small inhibitory RNAs specific for FGF20, we show that continued expression of FGF20 is necessary for maintenance of the anchorage‐independent growth state in RK3E cells transformed by β‐catenin, implying that FGF‐20 may be a critical element in oncogenesis induced by the Wnt signaling pathway.
Breast cancer is a genetically and clinically heterogeneous disease, and the contributions of different target cells and different oncogenic mutations to this heterogeneity are not well understood. ...Here we report that mammary tumors induced by components of the Wnt signaling pathway contain heterogeneous cell types and express early developmental markers, in contrast to tumors induced by other signaling elements. Expression of the Wnt-1 protooncogene in mammary glands of transgenic mice expands a population of epithelial cells expressing progenitor cell markers, keratin 6 and Sca-1; subsequent tumors express these markers and contain luminal epithelial and myoepithelial tumor cells that share a secondary mutation, loss of Pten, implying that they arose from a common progenitor. Mammary tumors arising in transgenic mice expressing β-catenin and c-Myc, downstream components of the canonical Wnt signaling pathway, also contain a significant proportion of myoepithelial cells and cells expressing keratin 6. Progenitor cell markers and myoepithelial cells, however, are lacking in mammary tumors from transgenic mice expressing Neu, H-Ras, or polyoma middle T antigen. These results suggest that mammary stem cells and/or progenitors to mammary luminal epithelial and myoepithelial cells may be the targets for oncogenesis by Wnt-1 signaling elements. Thus, the developmental heterogeneity of different breast cancers is in part a consequence of differential effects of oncogenes on distinct cell types in the breast.
El presente artículo es el resultado de la investigación denominada Reconocimiento del cuerpo en niños, jóvenes y adultos, que fue realizada con la población del Colegio Sagrado Corazón de Jesús ...Hermanas Bethlemitas en la ciudad de San Juan de Pasto. Esta población de estudio se clasificó de la siguiente manera: niños y niñas de grado transición y primero de primaria; adolescentes mujeres y hombres de grados décimo y once en básica media; y adultos de género femenino y masculino, los padres de familia de los escolares. Este proceso investigativo se desarrolló a partir de una metodología de carácter cualitativo y crítico, que permitió identificar, reconocer y configurar, por medio de los relatos escritos y las representaciones gráficas realizadas por la población de estudio, los significados del cuerpo en cada una de las etapas generacionales. Como resultado de la investigación, se logró establecer unas categorías que llevaron a configurar las diferentes concepciones del cuerpo: 1) corporeidad, 2) percepción del cuerpo, 3) sensaciones del cuerpo, 4) subjetividades del cuerpo e 5) intersubjetividades del cuerpo.
El presente artículo es el resultado de la investigación denominada Reconocimiento del cuerpo en niños, jóvenes y adultos, que fue realizada con la población del Colegio Sagrado Corazón de Jesús ...Hermanas Bethlemitas en la ciudad de San Juan de Pasto. Esta población de estudio se clasificó de la siguiente manera: niños y niñas de grado transición y primero de primaria; adolescentes mujeres y hombres de grados décimo y once en básica media; y adultos de género femenino y masculino, los padres de familia de los escolares. Este proceso investigativo se desarrolló a partir de una metodología de carácter cualitativo y crítico, que permitió identificar, reconocer y configurar, por medio de los relatos escritos y las representaciones gráficas realizadas por la población de estudio, los significados del cuerpo en cada una de las etapas generacionales. Como resultado de la investigación, se logró establecer unas categorías que llevaron a configurar las diferentes concepciones del cuerpo: 1) corporeidad, 2) percepción del cuerpo, 3) sensaciones del cuerpo, 4) subjetividades del cuerpo e 5) intersubjetividades del cuerpo.
The possibility of whether tRNAs with and without a highly modified base in their anticodon loop may influence the level of retroviral ribosomal frameshifting was examined. Rabbit reticulocyte ...lysates were programmed with mRNA encoding UUU or AAC at the frameshift site and the corresponding Phe tRNA with or without the highly modified wyebutoxine (Y) base on the 3′ side of its anticodon or Asn tRNA with or without the highly modified queuine (Q) base in the wobble position of its anticodon added. Phe and Asn tRNAs without the Y or Q base, respectively, stimulated the level of frameshifting, suggesting that the frameshift event is influenced by tRNA modification status. In addition, when AAU occurred immediately upstream of UUU as the penultimate frameshift site codon, addition of tRNAAsnwithout the Q base reduced the stimulatory effect of tRNAPhewithout the Y base, whereas addition of tRNAAsnwith the Q base did not alter the stimulatory effect. The addition of tRNAAsnwithout the Q base and tRNAPhewith the Y base inhibited frameshifting. The latter studies suggest an interplay between the tRNAs decoded at the penulimate frameshift and frameshift site codons that is also influenced by tRNA modification status. These data may be intrepreted as indicating that a hypomodified isoacceptor modulates frameshifting in an upward manner when utilized at the frameshift site codon, but modulates frameshifting in a downward manner when utilized at the penultimate frameshift site codon.
The Tec family kinases are implicated in signaling from lymphocyte antigen receptors and are activated following phosphorylation by Src kinases. For most Tec kinases, this activation requires an ...interaction between their pleckstrin homology (PH) domains and the products of phosphoinositide 3-Kinase, which localizes Tec kinases to membrane RAFTs. Rlk/Txk is a Tec related kinase expressed in T cells that lacks a pleckstrin homology domain, having instead a palmitoylated cysteine-string motif. To evaluate Rlk's function in T cell receptor signaling cascades, we examined the requirements for Rlk localization and activation by Src family kinases.
We demonstrate that Rlk is also associated with RAFTs, despite its lack of a pleckstrin homology domain. Rlk RAFT association requires the cysteine-string motif and is independent of PI3 Kinase activity. We further demonstrate that Rlk can be phosphorylated and activated by Src kinases, leading to a decrease in its half-life. A specific tyrosine in the activation loop of Rlk, Y420, is required for phosphorylation and activation, as well as for decreased stability, but is not required for lipid RAFT association. Mutation of this tyrosine also prevents increased tyrosine phosphorylation of Rlk after stimulation of the T cell receptor, suggesting that Rlk is phosphorylated by Src family kinases in response to T cell receptor engagement.
Like the other related Tec kinases, Rlk is associated with lipid RAFTs and can be phosphorylated and activated by Src family kinases, supporting a role for Rlk in signaling downstream of Src kinases in T cell activation.
Theiler's virus is a picornavirus responsible for a persistent, demyelinating infection of mouse central nervous system. We examined the nature of infected cells during the course of this disease ...using a simultaneous immunoperoxidase-in situ hybridization assay. Cell types were identified with antigenic markers and infected cells were recognized by the presence of viral RNA. We found that, depending on the animal, approximately 10% of infected cells were migroglia-macrophages, 5 to 10% were astrocytes and 25 to 40% were oligodendrocytes. Approximately half of the infected cells could not be identified.
Disky bulges in spiral galaxies are commonly thought to form out of disk materials (mainly) via bar-driven secular processes. They are structurally and dynamically distinct from "classical bulges," ...which are built in violent merger events. We use high-resolution GTC/MEGARA integral-field unit spectroscopic observations of the Sa galaxy NGC 7025, obtained during the MEGARA commissioning run, together with detailed 1D and 2D decompositions of this galaxy's Sloan Digital Sky Survey i-band data to investigate the formation of its disky (bulge) component, which makes up ∼30% of the total galaxy light. With a Sérsic index , a half-light radius , and stellar mass , this bulge dominates the galaxy light distribution in the inner (∼4.7 kpc). Measuring the spins (λ) and ellipticities (ϵ) enclosed within nine different circular apertures with radii , we show that the bulge, which exhibits a spin track of outwardly rising λ and ϵ, is a fast rotator for all the apertures considered. Our findings suggest that this inner disky component is a pseudo-bulge, consistent with the stellar and dust spiral patterns seen in the galaxy down to the innermost regions but in contrast to the classical bulge interpretation favored in the past. We propose that a secular process involving the tightly wound stellar spiral arms of NGC 7025 may be driving gas and stars out of the disk into the inner regions of the galaxy, building up the massive pseudo-bulge.
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