A ZEB1-miR-375-YAP1 pathway regulates epithelial plasticity in prostate cancer.

MicroRNA-375 (miR-375) is frequently elevated in prostate tumors and cell-free fractions of patient blood, but its role in genesis and progression of prostate cancer is poorly understood. In this study, we demonstrated that miR-375 is inversely correlated with epithelial-mesenchymal transition signatures (EMT) in clinical samples and can drive mesenchymal-epithelial transition (MET) in model systems. Indeed, miR-375 potently inhibited invasion and migration of multiple prostate cancer lines. The transcription factor YAP1 was found to be a direct target of miR-375 in prostate cancer. Knockdown of YAP1 phenocopied miR-375 overexpression, and overexpression of YAP1 rescued anti-invasive effects mediated by miR-375. Furthermore, transcription of the miR-375 gene was shown to be directly repressed by the EMT transcription factor, ZEB1. Analysis of multiple patient cohorts provided evidence for this ZEB1-miR-375-YAP1 regulatory circuit in clinical samples. Despite its anti-invasive and anti-EMT capacities, plasma miR-375 was found to be correlated with circulating tumor cells in men with metastatic disease. Collectively, this study provides new insight into the function of miR-375 in prostate cancer, and more broadly identifies a novel pathway controlling epithelial plasticity and tumor cell invasion in this disease.

Impact of synthetic antioxidants on lipid peroxidation of distiller's dried grains with solubles and distiller's corn oil stored under high temperature and humidity conditions.

This experiment evaluated the effect of antioxidants, oil content in distiller's dried grains with solubles (DDGS), quality of distiller's corn oil, and storage time on lipid peroxidation. A source of low-oil DDGS (LO-DDGS; 5.0% ether extract [EE], as-fed basis), high-oil DDGS (HO-DDGS; 13.0% EE, as-fed basis), and 2 sources of distiller's corn oil (DCO; 1.20, 0.08, and 0.48% moisture, insoluble impurities, and unsaponifiables [MIU], respectively [DCO-1], and 1.20, 0.01, and 0.10% MIU, respectively [DCO-2]) were obtained. Each of the 4 ingredients was divided into 18 representative subsamples (approximately 908 g for DDGS or 2 kg of DCO). Six subsamples of each ingredient were mixed with either no supplemental antioxidants (CON), Rendox-CQ (REN; 1,000 mg/kg EE; Kemin, Industries, Des Moines, IA), or Santoquin-Q4T (SAN; 1,500 mg/kg EE; Novus International, St. Louis, MO). Each mixture ( = 72) was split into thirds, and 1 portion was immediately frozen at -20°C (d 0). Two portions were stored under hot (38.6 ± 0.1°C) and humid conditions (94.0 ± 0.3% relative humidity) for 14 or 28 d. The MIXED procedure of SAS was used to evaluate the effects of ingredient, antioxidant, storage time, and interactions, with d-0 values used as a covariate. From d 14 to 28, peroxide value (PV), -anisidine value (AnV), and thiobarbituric acid reactive substances (TBARS) of DCO and DDGS increased by 3- to 4-fold ( < 0.05). Over the entire storage period, PV of DCO-1 and HO-DDGS (12.3 ± 0.3 and 12.6 ± 0.3 mEq O/kg oil, respectively) exceeded ( < 0.05) that of DCO-2 and LO-DDGS (9.6 ± 0.3 and 9.3 ± 0.3 mEq O/kg oil, respectively). Adding REN or SAN ( < 0.05) reduced TBARS and AnV relative to CON (TBARS = 11.0 ± 0.2 mg malondialdehyde Eq/kg oil and AnV = 6.5 ± 0.2) over the entire period (mean of d 14 and 28), but TBARS and AnV did not differ ( > 0.05) between antioxidants (TBARS = 6.1 ± 0.2 and 5.9 ± 0.2 mg malondialdehyde Eq/kg oil, respectively, and AnV = 1.9 ± 0.2 and 1.8 ± 0.2 for REN and SAN, respectively). The PV on d 14 and 28 and overall was less ( < 0.05) when either antioxidant was added relative to CON (16.0 mEq O/kg) and was greater for ingredients treated with SAN ( < 0.05) compared with REN (8.8 ± 0.2 and 8.0 ± 0.2 mEq O/kg oil for SAN and REN, respectively). In summary, antioxidants reduced peroxidation of DDGS and DCO by approximately 50% during 28 d of storage at 38.6°C and 94.0% relative humidity, but neither antioxidant completely stabilized the ingredients.

Effect of feeding peroxidized dried distillers grains with solubles to sows and progeny on growth performance and metabolic oxidative status of nursery pigs.

This experiment evaluated the effects of including peroxidized corn dried distillers grains with solubles (DDGS) in diets for sows and nursery pigs on growth performance, vitamin E (VE), and Se status, and the incidence of mulberry heart disease (MHD) of nursery pigs. Sows (n = 12) were fed corn-soybean meal diets (C-SBM) or C-SBM diets with DDGS (40% and 20% in gestation and lactation, respectively) for 3 parities. In the third parity, 108 weaned pigs (BW = 6.6 ± 0.36 kg) were blocked by BW within litter, assigned to pens (2 pigs/pen; 5 and 4 pens per litter for groups 1 and 2, respectively), and pens were assigned 1 of 3 nursery diets: 1) corn-soybean meal (CON), 2) 30% peroxidized DDGS (Ox-D), and 3) 30% Ox-D with 5 × NRC (1998) level of VE (Ox-D+5VE) for 7 wk, in a 2 × 3 factorial arrangement of sow and nursery diets (n = 9 pens/treatment). The peroxidized DDGS source in nursery diets contained concentrations of thiobarbituric acid reactive substances (TBARS) and peroxide values that were 25 and 27 times greater than a reference corn sample. Sow colostrum, milk, and serum, as well as pig serum and liver samples, were analyzed for α-tocopherol and Se concentrations. Pig serum was analyzed for glutathione peroxidase activity (GPx), TBARS, and sulfur-containing AA (SAA). Pig hearts were evaluated for gross and histopathological lesions indicative of MHD, but none were detected. Pigs from sows fed DDGS tended to have reduced (P = 0.07) VE in serum during lactation and reduced VE at weaning (P < 0.01; 5.6 vs. 6.7 ± 0.1 µg/mL) compared with pigs from sows fed C-SBM. Inclusion of DDGS in sow diets reduced the VE status of pigs during lactation, but not in the nursery when MHD can be a concern. Pigs fed Ox-D+5VE (P = 0.08) tended to have, and those fed Ox-D (P = 0.04) had greater ADFI than pigs fed CON, but ADG was not affected (P > 0.1) by nursery diet. Feeding Ox-D or Ox-D+5VE increased (P < 0.05) serum α-tocopherol compared with CON (2.5, 2.8, and 3.4 ± 0.09 µg/mL, respectively), but TBARS and GPx were not affected by nursery diet. Serum concentration of SAA was 40% to 50% greater (P < 0.01) for pigs fed Ox-D or Ox-D+5VE compared with those fed C-SBM, which was likely due to greater (P < 0.01) SAA intake for pigs fed Ox-D. The antioxidant properties of SAA may have spared VE and Se and masked any effect of Ox-D on metabolic oxidation status. Therefore, increasing the dietary VE concentration was unnecessary in nursery diets containing Ox-D.

Space allowance and high fiber diet impact performance and behavior of group-kept gestating sows.

Identifying and optimizing housing and management systems that improve the well-being of the gestating sow is essential to sustaining animal agriculture. Therefore, the impact of 2 floor-space allowances and a high-fiber gestation diet on dry group-housed sows were evaluated using multiple measures of well-being. Groups of 10 multiparous sows/pen (n = 221) were assigned randomly to treatments in a 2 × 2 factorial arrangement to either a corn-soybean meal diet (CTL) or corn-soybean meal diet supplemented with soybean hulls and wheat middlings (FBR), and floor-space allowance of either 1.7 or 2.3 m(2)/sow. Sow BW, backfat (BF), and body condition score (BCS) were all recorded on d 34, 65, 90, and 110 of gestation, whereas skin lesions were scored on d 34, every 2 d for the first 2-wk postmixing, and then biweekly throughout gestation. Blood sample was collected only on d 34 for cortisol (baseline), and samples were collected on d 90 of gestation for other measures including cortisol. Behavior was registered on multiple days throughout gestation. Sows fed FBR and kept at 1.7 m(2) produced heavier litter and weaning weights and greater number of piglets born alive, compared to sows fed FBR but kept at 2.3 m(2) of floor space (diet × floor space, P ≤ 0.04). Sows fed FBR and kept at 1.7 m(2) performed fewer oral-nasal-facial and sham-chew behaviors than sows fed CTL and kept at the same floor space (diet × floor space, P ≤ 0.044). Sows kept at 1.7 m(2) of floor space had a greater (P < 0.05) total lesion severity score than sows kept at 2.3 m(2)/sow, and vulva lesion scores were more (P < 0.02) severe among CTL-fed sows than FBR-fed sows. Parities 2 and 3 sows fed FBR and kept at 1.7 m(2) of floor space were heavier (P < 0.001) than sows fed the same diet but kept at 2.3 m(2). These results indicate that keeping small groups of pregnant sows at a minimum floor-space allowance of 1.7 m(2)/sow and floor feeding these sows a high-fiber diet can improve short-term sow well-being.

Studies in global and local histogram-guided relaxation algorithms.

An image segmentation algorithm based on histogram clustering and probabilistic relaxation labeling is explored. The algorithm is evaluated by means of a set of artificially generated test images with known parameters. Two sources of pixel labeling errors are revealed. The first derives from distribution overlap in the histogram and leads to fragmented or missing regions in a segmentation. The second derives from the gloal nature of the compatibility coefficients used in the relaxation process. The coefficients are shown to be insufficient to correct certain labeling errors and can even cause the destruction of fine image details during the course of the relaxation updating process. A potential solution to these problems is shown to be obtainable by using orientation dependent compatibility coefficients and localizing the scope of the algorithm to small subimages followed by a merging of the segmented subimages.