The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling

The mammalian target of rapamycin (mTOR) protein kinase is a master growth promoter that nucleates two complexes, mTORC1 and mTORC2. Despite the diverse processes controlled by mTOR, few substrates are known. We defined the mTOR-regulated phosphoproteome by quantitative mass spectrometry and characterized the primary sequence motif specificity of mTOR using positional scanning peptide libraries. We found that the phosphorylation response to insulin is largely mTOR dependent and that mTOR exhibits a unique preference for proline, hydrophobic, and aromatic residues at the +1 position. The adaptor protein Grb10 was identified as an mTORC1 substrate that mediates the inhibition of phosphoinositide 3-kinase typical of cells lacking tuberous sclerosis complex 2 (TSC2), a tumor suppressor and negative regulator of mTORC1. Our work clarifies how mTORC1 inhibits growth factor signaling and opens new areas of investigation in mTOR biology.     

Effects of Culture Area,Stocking Density,and Shrimp and Fish Polyculture on the Cost Efficiency of Hard Clam,Meretrix meretrix,Culture: A Case Study of Hard Clam Farms in Yunlin,Taiwan

Using the hard clam farms in Yunlin, Taiwan as examples, this study analyzes the effects of culture area, stocking density, and shrimp and fish polyculture on the cost efficiency (CE) of hard clam farming. A data envelopment analysis (DEA) is used to estimate the farms' technical efficiency (TE), allocative efficiency (AE), and CE values. The findings show that the mean TE, AE, and CE values of hard clam farms are 0.74, 0.57, and 0.43, respectively. The TE value is higher than the AE value, which indicates that cost inefficiency is mainly attributable to poor AE. Tobit regression results suggest that there are positive relationships between CE and both culture area and operator experience. Hard clam stocking density and age of the operators have negative effects on CE. Hard clam culture areas larger than 2 ha and a stocking density of 1.1–1.2 million hard clams per hectare have higher CEs than smaller culture areas and smaller or larger stocking densities. The use of sand shrimp, white shrimp, kuruma shrimp, and grass shrimp for polyculture and the use of milkfish and silver sea bream for polyculture are both associated with high CEs.     

Genetic Diversity and Population Structure in the Heavily Exploited Korean Rockfish,Sebastes schlegeli,in Korea

The Korean rockfish, Sebastes schlegeli, is a valuable and intensively exploited species in Korea. We discuss the genetic diversity and genetic structure of four Korean rockfish populations using eight microsatellite loci. In total, 161 different alleles from 138 individuals were observed. Average allele number per locus ranged from 2.5 to 23 and allelic richness varied from 13.38 to 14.63 within a population. Despite a long history of stocking practices, we found very high levels of polymorphism (mean heterozygosity = 0.810), which is comparable to other congeneric species. No significant difference in genetic diversity and molecular genetic variance (F_ST and R_ST) was observed among four local samples (P > 0.1). Little indication of contemporary inbreeding (F_IS= 0.051) or population structure (K = 1) was detected. This absence of differentiation may reflect high levels of gene flow along the coast of Korea. Our study demonstrates that rockfish in Korea should be managed as a single unit. Currently, the species does not appear to be genetically threatened, but the potential for a rapid loss of genetic diversity remains. This information on the genetic characteristics of Korean rockfish populations has important implications for fisheries management and conservation efforts, and will aid in the sustainable exploitation of the fishing resources and the preservation of biodiversity.     

Effect of dopamine on excretory urographic image quality and the prevention of contrast-induced nephropathy in dogs

The effect of low dose dopamine on the excretory urographic image quality and contrast media-induced nephropathy in normal dogs (experiment 1) and the dogs with decreased renal function (experiment 2) were assessed. In experiment 2, decreased renal function was induced by gentamicin overdose. In each experiment, animals were divided into 3 groups. In group 1, only contrast medium (iohexol) was administered. In group 2, contrast medium plus intravenous fluid (0.9% saline) were administered. And in group 3, contrast medium plus intravenous fluid and low dose dopamine were administered. Investigated parameters included intrarenal resistive index (RI), serum BUN and creatinine concentrations, contrast medium elimination time and radiographic image quality. In experiment 1, RI of group I increased at 80 min after contrast medium administration (p<0.05), but RI of group 3 decreased at 48 and 72 hr (p<0.05). Serum BUN concentration of group 1 was higher than that of group 2 and 3 (p<0.05); in radiographic examination, contrast medium elimination time decreased in group 2 and 3, but image quality of group 2 was inferior to that of group 3. In experiment 2, image quality of group 3 only provided adequate visualization of renal structures. The formula of contrast medium plus low dose dopamine was found to provide good nephrogram and pyelogram image quality without supplemental contrast medium, and to protect renal tubules from prolonged exposure to concentrated contrast medium.     

Metabolism of flupyrazofos in the isolated perfused rat liver

To investigate the hepatic metabolism of the new insecticide flupyrazofos [O,O-diethyl O-(1-phenyl-3-trifluoromethylpyrazol-5-yl) phosphorothioate], isolated rat liver was perfused with flupyrazofos under single-pass conditions. In outflow perfusate and bile, 1-phenyl-3-trifluoromethyl-5-hydroxyprazole (PTMHP), PTMHP-sulfate and PTMHP-glucuronide conjugates were identified as the metabolites of flupyrazofos. However, O,O-diethyl O-(1-phenyl-3-trifluoromethylpyrazol-5-yl) phosphate (flupyrazofos oxon) was not detected. A HPLC method with UV detection was used to investigate the hepatic disposition of flupyrazofos and its metabolite PTMHP. The concentrations of flupyrazofos, PTMHP and PTMHP conjugates in outflow perfusate reached steady-state levels within 20 min after commencing perfusion of 7.3 microM flupyrazofos. At steady state, the mean extraction ratio of flupyrazofos was 0.93 (+/- 0.01) and clearance was 26.1 (+/- 0.2) ml min-1 which nearly approached perfusate flow rate (28 ml min-1). PTMHP accounted for 55.7 (+/- 5.8)% of eliminated flupyrazofos and was recovered as unchanged PTMHP, PTMHP-sulfate and PTMHP-glucuronide in the bile as well as the outflow perfusate.     

ULTRASONOGRAPHIC DIAGNOSIS—PYLOROGASTRIC INTUSSUSCEPTION IN A DOG

A 7-year-old female Maltese presented for evaluation of severe vomiting. A diagnosis of pylorogastric intussusception was made during ultrasonographic examination. The intussusception spontaneously underwent reduction by the following morning.     

Rye and wheat in piglet rations supplemented by bisergon

In a feeding experiment (54 piglets) and a slaughtering test for the registration of tract and digesta properties (15 piglets) the influence of rations with 69% rye (R) or wheat (W) with and without a supplement of 200 mg of the chinoxalin derivate Bisergon/kg DM (rations RB and WB) was studied. In the sequence R, RB, W and WB the feed intake in the test period of 3 weeks after weaning amounted to 581, 651, 583 and 764 g, weight gain to 314, 365, 319 and 424 g per animal and day. In the same sequence the concentration of organic acids in the stomach amounted to 41, 5, 25 and 18 mmol per 100 g dry matter and in the colon to 106, 83, 64 and 62. Bisergon caused a redistribution of the digesta from the stomach to the large intestine and a more rapid emptying of the stomach as well. Rye caused extreme fermentation processes in the front part of the tract and Bisergon clearly has ergotropic qualities for the stabilization of the intestinal flora.