RESUMEN
Male Tsumura-Suzuki Obese Diabetes (TSOD) mice, a spontaneous metabolic syndrome model, develop non-alcoholic steatohepatitis and liver tumors by feeding on a standard mouse diet. Nearly 70% of liver tumors express glutamine synthetase (GS), a marker of hepatocellular carcinoma. In contrast, approximately 30% are GS-negative without prominent nuclear or structural atypia. In this study, we examined the characteristics of the GS-negative tumors of TSOD mice. Twenty male TSOD mice were sacrificed at 40 weeks and a total of 21 tumors were analyzed by HE staining and immunostaining of GS, liver fatty acid-binding protein (L-FABP), serum amyloid A (SAA), and beta-catenin. With immunostaining for GS, six (29%) tumors were negative. Based on the histological and immunohistological characteristics, six GS-negative tumors were classified into several subtypes of human hepatocellular adenoma (HCA). One large tumor showed generally similar findings to inflammatory HCA, but contained small atypical foci with GS staining and partial nuclear beta-catenin expression suggesting malignant transformation. GS-negative tumors of TSOD mice contained features similar to various subtypes of HCA. Different HCA subtypes occurring in the same liver have been reported in humans; however, the diversity of patient backgrounds limits the ability to conduct a detailed, multifaceted analysis. TSOD mice may share similar mechanisms of HCA development as in humans. It is timely to review the pathogenesis of HCA from both genetic and environmental perspectives, and it is expected that TSOD mice will make further contributions in this regard.
Asunto(s)
Adenoma de Células Hepáticas , Carcinoma Hepatocelular , Diabetes Mellitus , Neoplasias Hepáticas , Síndrome Metabólico , Enfermedad del Hígado Graso no Alcohólico , Adenoma de Células Hepáticas/etiología , Adenoma de Células Hepáticas/metabolismo , Animales , Carcinoma Hepatocelular/metabolismo , Proteínas de Unión a Ácidos Grasos/metabolismo , Glutamato-Amoníaco Ligasa/genética , Glutamato-Amoníaco Ligasa/metabolismo , Humanos , Inmunohistoquímica , Neoplasias Hepáticas/metabolismo , Masculino , Síndrome Metabólico/complicaciones , Ratones , Ratones Obesos , Enfermedad del Hígado Graso no Alcohólico/etiología , Proteína Amiloide A Sérica/metabolismo , beta Catenina/genética , beta Catenina/metabolismoRESUMEN
Prion diseases are a group of fatal neurodegenerative disorders caused by prions, which consist mainly of the abnormally folded isoform of prion protein, PrPSc. A pivotal pathogenic event in prion disease is progressive accumulation of prions, or PrPSc, in brains through constitutive conformational conversion of the cellular prion protein, PrPC, into PrPSc. However, the cellular mechanism by which PrPSc is progressively accumulated in prion-infected neurons remains unknown. Here, we show that PrPSc is progressively accumulated in prion-infected cells through degradation of the VPS10P sorting receptor sortilin. We first show that sortilin interacts with PrPC and PrPSc and sorts them to lysosomes for degradation. Consistently, sortilin-knockdown increased PrPSc accumulation in prion-infected cells. In contrast, overexpression of sortilin reduced PrPSc accumulation in prion-infected cells. These results indicate that sortilin negatively regulates PrPSc accumulation in prion-infected cells. The negative role of sortilin in PrPSc accumulation was further confirmed in sortilin-knockout mice infected with prions. The infected mice had accelerated prion disease with early accumulation of PrPSc in their brains. Interestingly, sortilin was reduced in prion-infected cells and mouse brains. Treatment of prion-infected cells with lysosomal inhibitors, but not proteasomal inhibitors, increased the levels of sortilin. Moreover, sortilin was reduced following PrPSc becoming detectable in cells after infection with prions. These results indicate that PrPSc accumulation stimulates sortilin degradation in lysosomes. Taken together, these results show that PrPSc accumulation of itself could impair the sortilin-mediated sorting of PrPC and PrPSc to lysosomes for degradation by stimulating lysosomal degradation of sortilin, eventually leading to progressive accumulation of PrPSc in prion-infected cells.
Asunto(s)
Proteínas Adaptadoras del Transporte Vesicular/metabolismo , Proteínas PrPC/metabolismo , Proteínas PrPSc/metabolismo , Priones/metabolismo , Animales , Lisosomas/metabolismo , Ratones , Neuronas/metabolismo , Enfermedades por Prión/metabolismo , Transporte de Proteínas/fisiologíaRESUMEN
Unusual lung adenocarcinoma with morule-like components is characterized by uniform, tightly packed spindle-shaped cells filling the lumens of neoplastic glandular structures. We present a case of a 78-year-old woman who presented with a part-solid ground-glass nodule in the upper lobe of the right lung. Following right upper lobectomy, histological examination revealed adenocarcinoma in-situ with multiple morule-like intra-alveolar proliferative nests of epithelial cells. Immunostaining was positive for thyroid-transcription factor 1 in the tumor cells and morule-like components. The tumor was also positive for an epidermal growth factor receptor mutation. This case provides valuable insights about lung adenocarcinoma in-situ with morule-like components.
RESUMEN
In the presence of phenylsilane and a catalytic amount of indium(III) acetate, organic iodides added to electron-deficient alkenes in ethanol at room temperature. Both simple and functionalized organic iodides were applicable to this reaction. A plausible reaction mechanism involves the formation of indium hydride species by hydride transfer from silicon to indium and an indium hydride-mediated radical chain process.
Asunto(s)
Acetatos/química , Alquenos/síntesis química , Hidrocarburos Yodados/química , Indio/química , Alquenos/química , Catálisis , Estructura MolecularRESUMEN
The pseudo-response regulators (PRRs) are the circadian clock component proteins in the model dicot Arabidopsis thaliana. They contain a receiver-like domain (RLD) similar to the receiver domains of the RRs in the His-Asp phosphorelay system, but the RLDs lack the phosphoacceptor aspartic acid residue invariably conserved in the receiver domains. To study the evolution of PRR genes in plants, here we characterize their homologue genes, PpPRR1, PpPRR2, PpPRR3 and PpPRR4, from the moss Physcomitrella patens. In the phylogenetic analysis, PpPRRs cluster together, sister to an angiosperm PRR gene subfamily, illustrating their close relationships with the angiosperm PRRs. However, distinct from the angiosperm sequences, the RLDs of PpPRR2/3/4 exhibit a potential phosphoacceptor aspartic acid-aspartic acid-lysine (DDK) motif. Consistently, the PpPRR2 RLD had phosphotransfer ability in vitro, suggesting that PpPRR2 functions as an RR. The PpPRR1 RLD, on the other hand, shows a partially diverged DDK motif, and it did not show phosphotransfer ability. All PpPRRs were expressed in a circadian and light-dependent manner, with differential regulation between PpPRR2/4 and PpPRR1/3. Altogether, our results illustrate that PRRs originated from an RR(s) and that there are intraspecific divergences among PpPRRs. Finally, we offer scenarios for the evolution of the PRR family in land plants.
Asunto(s)
Bryopsida/genética , Evolución Molecular , Proteínas de Plantas/genética , Plantas/genética , Factores de Transcripción/genética , Datos de Secuencia MolecularRESUMEN
Acid-base bifunctional heterogeneous catalysts were prepared by the reaction of an acidic silica-alumina (SA) surface with silane-coupling reagents possessing amino functional groups. The obtained SA-supported amines (SA-NR2) were characterized by solid-state 13C and 29Si NMR spectroscopy, FT-IR spectroscopy, and elemental analysis. The solid-state NMR spectra revealed that the amines were immobilized by acid-base interactions at the SA surface. The interactions between the surface acidic sites and the immobilized basic amines were weaker than the interactions between the SA and free amines. The catalytic performances of the SA-NR2 catalysts for various carbon-carbon bond-forming reactions, such as cyano-ethoxycarbonylation, the Michael reaction, and the nitro-aldol reaction, were investigated and compared with those of homogeneous and other heterogeneous catalysts. The SA-NR2 catalysts showed much higher catalytic activities for the carbon-carbon bond-forming reactions than heterogeneous amine catalysts using other supports, such as SiO2 and Al2O3. On the other hand, homogeneous amines hardly promoted these reactions under similar reaction conditions, and the catalytic behavior of SA-NR2 was also different from that of MgO, which was employed as a typical heterogeneous base. An acid-base dual-activation mechanism for the carbon-carbon bond-forming reactions is proposed.
RESUMEN
The In(OAc)3-catalyzed reaction of bromo- and iodoalkanes with PhSiH3 in THF at 70 degrees C gave dehalogenated alkanes in good to high yields. In the presence of Et3B and air, the reduction proceeded smoothly at 30 degrees C. When 2,6-lutidine and air were used as additives, the In(OAc)3-catalyzed system enabled an efficient reduction of simple and functionalized iodoalkanes in EtOH. Catalytic use of GaCl3 was found to be effective in the reduction of haloalkanes with poly(methylhydrosiloxane) (PMHS). These catalytic reductions probably involve a radical chain mechanism in which indium or gallium hydride species work as the actual reductants.