Display-control relationships for Chinese subjects using three controls.

Display-control stereotypes for direction of motion were tested using a paper-and-pencil test. Seven hundred and eight-three Yunnan Province Chinese subjects of both sexes from a wide range of ages and backgrounds were asked to indicate the control movement they would make to move a display dot in a given direction. Three types of controls and three different planes for the controls were used. The results indicated that although there were some similarities between Western and Chinese stereotypes, the Chinese exhibited stereotypes not generally found in Western subjects.     

Leucine aminopeptidase activity in the digestive tract of perch, Perca fluviatilis L.

The distribution of the enzyme leucine aminopeptidase (LAP, EC 3.4.1.1) in the digestive tract of perch, Perca fluviatilis L., was investigated histochemically. The enzyme was present in the mucosa of the entire intestine and was absent in the oesophagus, stomach and pyloric sphincter. In the intestine, the enzyme was localized in the supranuclear cytoplasm of the columnar cells and was strongest in the brush border area. Enzyme activity was also present in the lumen of the intestine. The activity of the enzyme in the intestine decreased slightly towards the rectum. In perch, the final digestion of peptides and aminopeptides is both extracellular and intracellular and takes place along the entire length of the intestine.     

Amino acid sequence of chicken fibrinopeptide A

Chicken fibrinopeptide A was isolated and the complete amino acid sequence was established. It is a pentadecapeptide with the sequence of Gln(Pyr)-Asp-Gly-Lys-Thr-Thr-Phe-Glu-Lys-Glu-Gly-Gly-Gly-Gly-Arg and is homologous with mammalian fibrinopeptide A. Two peptides which appear to be derivatives of fibrinopeptide A were also isolated. One of these appeared to be fibrinopeptide A with NH2-terminal pyroglutamic acid; the other was fibrinopeptide A which lacked the COOH-terminal arginine residue.     

Differential expression of cytochrome P-450 1 and related forms in rabbit liver and kidney

Monoclonal antibodies developed to cytochrome P-450 1, some of which react with proteins in addition to P-450 1, were used to investigate the differential expression of P-450 1 dependent 21-hydroxylase activity in renal tissue of rabbits exhibiting differences in hepatic 21-hydroxylase activity. Using immunohistochemical techniques, the monoclonal antibodies, 2F5 and 3C3, localized protein in the S2 and S3 segments of the proximal tubule in the renal cortex. These two monoclonal antibodies, 2F5 and 3C3, reacted with a kidney protein that migrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a relative electrophoretic mobility that did not correspond to known rabbit hepatic isozymes and was termed P-450 K. Antibodies specific for P-450 1 and 3b, 1F11 and 8-27, respectively, produced no staining in kidney. The protein recognized by the 2F5 and 3C3 antibodies is immunologically distinct from cytochrome P-450s 1, 2, and 3b. The rate of 21-hydroxylation of progesterone was shown to be approximately 100-fold less in kidney than liver microsomes where this pathway is largely catalyzed by P-450 1. The activity of the kidney microsomes was not inhibited by antibodies directed to P-450 1. In addition, the variation observed for the 21-hydroxylase activity in the hepatic microsomal fraction of outbred New Zealand white rabbits was not evident in kidney microsomes from these same animals. The 2F5 antibody was found, however, to be inhibitory (about 50%) of the 11-hydroxylation of lauric acid in kidney microsomes. This suggests that P-450 K participates in lauric acid 11-hydroxylase activity. The treatment of rabbits with phenobarbital, but not 2,3,7,8-tetrachlorodibenzo-p-dioxin, was found to induce the levels of P-450 K.     

Hepatitis C virus-induced cancer stem cell-like signatures in cell culture and murine tumor xenografts

Hepatitis C virus (HCV) infection is a prominent risk factor for the development of hepatocellular carcinoma (HCC). Similar to most solid tumors, HCCs are believed to contain poorly differentiated cancer stem cell-like cells (CSCs) that initiate tumorigenesis and confer resistance to chemotherapy. In these studies, we demonstrate that the expression of an HCV subgenomic replicon in cultured cells results in the acquisition of CSC traits. These traits include enhanced expression of doublecortin and CaM kinase-like-1 (DCAMKL-1), Lgr5, CD133, α-fetoprotein, cytokeratin-19 (CK19), Lin28, and c-Myc. Conversely, curing of the replicon from these cells results in diminished expression of these factors. The putative stem cell marker DCAMKL-1 is also elevated in response to the overexpression of a cassette of pluripotency factors. The DCAMKL-1-positive cells isolated from hepatoma cell lines by fluorescence-activated cell sorting (FACS) form spheroids in Matrigel. The HCV RNA abundance and NS5B levels are significantly reduced by the small interfering RNA (siRNA)-led depletion of DCAMKL-1. We further demonstrate that HCV replicon-expressing cells initiate distinct tumor phenotypes compared to the tumors initiated by parent cells lacking the replicon. This HCV-induced phenotype is characterized by high-level expression/coexpression of DCAMKL-1, CK19, α-fetoprotein, and active c-Src. The results obtained by the analysis of liver tissues from HCV-positive patients and liver tissue microarrays reiterate these observations. In conclusion, chronic HCV infection appears to predispose cells toward the path of acquiring cancer stem cell-like traits by inducing DCAMKL-1 and hepatic progenitor and stem cell-related factors. DCAMKL-1 also represents a novel cellular target for combating HCV-induced hepatocarcinogenesis.     

Photosynthetic photon flux density and phytochrome B interact to regulate branching in Arabidopsis

Branching is regulated by environmental signals including phytochrome B (phyB)-mediated responses to the ratio of red to far red light. While the mechanisms associated with phytochrome regulation of branching are beginning to be elucidated, there is little information regarding other light signals, including photosynthetic photon flux density (PPFD) and how it influences phytochrome-mediated responses. This study shows that Arabidopsis (Arabidopsis thaliana) branching is modified by both varying PPFD and phyB status and that significant interactions occur between these variables. While phyB deficiency decreased branching when the PPFD was low, the effect was suppressed by high PPFD and some branching aspects were actually promoted. Photosynthesis measurements showed that PPFD may influence branching in phyB-deficient plants at least partially through a specific signalling pathway rather than directly through energy effects on the shoot. The expression of various genes in unelongated buds of phyB-deficient and phyB-sufficient plants grown under high and low PPFD demonstrated potential roles for several hormones, including auxin, cytokinins and ABA, and also showed imperfect correlation between expression of the branching regulators BRC1 and BRC2 and bud fate. These results may implicate additional undiscovered bud autonomous mechanisms and/or components contributing to bud outgrowth regulation by environmental signals.     

mTORC1 inhibition increases neurotensin secretion and gene expression through activation of the MEK/ERK/c-Jun pathway in the human endocrine cell line BON

The mammalian target of rapamycin (mTOR) signaling exists in two complexes: mTORC1 and mTORC2. Neurotensin (NT), an intestinal hormone secreted by enteroendocrine (N) cells in the small bowel, has important physiological effects in the gastrointestinal tract. The human endocrine cell line BON abundantly expresses the NT gene and synthesizes and secretes NT in a manner analogous to that of N cells. Here, we demonstrate that the inhibition of mTORC1 by rapamycin (mTORC1 inhibitor), torin1 (both mTORC1 and mTORC2 inhibitor) or short hairpin RNA-mediated knockdown of mTOR, regulatory associated protein of mTOR (RAPTOR), and p70 S6 kinase (p70S6K) increased basal NT release via upregulating NT gene expression in BON cells. c-Jun activity was increased by rapamycin or torin1 or p70S6K knockdown. c-Jun overexpression dramatically increased NT promoter activity, which was blocked by PD98059, an mitogen-activated protein kinase kinase (MEK) inhibitor. Furthermore, overexpression of MEK1 or extracellular signal-regulated kinase 1 (ERK1) increased c-Jun expression and NT promoter activity. More importantly, PD98059 blocked rapamycin- or torin1-enhanced NT secretion. Consistently, rapamycin and torin1 also increased NT gene expression in Hep3B cells, a human hepatoma cell line that, similar to BON, expresses high levels of NT. Phosphorylation of c-Jun and ERK1/2 was also increased by rapamycin and torin1 in Hep3B cells. Finally, we showed activation of mTOR in BON cells treated with amino acids, high glucose, or serum and, concurrently, the attenuation of ERK1/2 and c-Jun phosphorylation and NT secretion. Together, mTORC1, as a nutrient sensor, negatively regulates NT secretion via the MEK/ERK/c-Jun signaling pathway. Our results identify a physiological link between mTORC1 and MEK/ERK signaling in controlling intestinal hormone gene expression and secretion.